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Joe has looked old since the day he was born, back in 1982. He’s pink and squinty and wrinkly. His teeth are weird: His incisors sit outside his lips to keep the dirt out of his mouth as he digs tunnels for his tube-shaped body.“He looks remarkably the same,” says Rochelle Buffenstein, a comparative biologist who has studied naked mole rats since the 1980s when she was doing her doctoral work in Cape Town, South Africa. That’s where she met Joe. (He doesn’t have an official name, so we’re going with Joe.) A few years later, Buffenstein was starting her own research on vitamin D metabolism in mole rats because they spend all their time in dark tunnels, away from the sun. She moved to Johannesburg with a few subjects to begin her work, leaving Joe behind. He was eventually shipped off to the Cincinnati Zoo. But he and Buffenstein would soon reunite.In the late 1990s, Buffenstein noticed something odd: Her mole rats just wouldn’t die.“They were more than 15 years old, which is by rodent standards extremely long-lived,” Buffenstein says. “So I thought, ‘Wow, they should be only living a maximum of six years; they’re living more than double their maximum life span.’” She pivoted to aging research, knowing that the field was important but understudied. In the early 2000s, Joe’s other half at the zoo passed away, and he needed a new mate. Buffenstein offered to help him start a new colony at her lab in New York and took him in. Since then, he has traveled with Buffenstein to research posts in New York, Texas, and California.Today, Joe is still a wrinkly rodent with a taste for root veggies. But he’s now Buffenstein’s oldest naked mole rat, the oldest ever recorded—Joe turns 39 this year. That’s nine times older than typical mice live, and five times more than other similarly sized rodents.When Buffenstein set out to study how naked mole rats age, she wanted a sort of before and after picture of their biology—to determine when their bones, or organs, or even antioxidant levels change. She waited. Then waited some more. “It was very frustrating," Buffenstein says. "Because you want to see this change happen, so that you can then delve down to what's changed.”Back then, Buffenstein was one of just a few researchers looking at mole rats and aging. Now mole rats are all the rage, and labs around the world are exploring their basic biology with the goal of using those insights to develop drugs that might prevent the ravages of age in people. Because humans and gorillas get hypertension. Mice and zebrafish get cancer. Kangaroos and dogs get arthritis. An endless list of diseases of aging plague an endless list of animals. The “and”s are so prevalent that any “but” makes scientists’ eyes spring open. Joe is a “but.” Mole rats enjoy incredibly long and healthy lives before they expire.“The naked mole rat says it's not inevitable,” says Buffenstein, who now works for Google’s biotech spinoff, Calico Labs, which does R&D to combat aging and associated diseases. "They clearly have a blueprint to stave off aging.”But what is that blueprint? It could be that their cells are teeming with protective molecules; that a large set of genes are unexpectedly switched on or off; or that the very makeup of their immune system, organs, or cell membranes are radically different. (Perhaps even too radically different.) Mole rat researchers haven’t yet managed to harness these shrively fountains of youth. Maybe their unique anti-aging tricks are destined to extend human life—or maybe they’re just an inevitable dead end.Joe barely ages, but you do. As you get older, your cell function deteriorates, making your body more susceptible to disease and—eventually—death. Your DNA accrues damage from oxidizing molecules, which also attack proteins and fats, tearing you apart microscopically from the inside. Old “senescent” cells stop replicating. Reserves of rejuvenating stem cells dry up. Communication between cells breaks down, and inflammation cranks up. There’s no single force that drives cellular aging; it’s a network of feedback loops. Enzymes read genes like a grocery list of different proteins to prepare, and those proteins might protect that enzyme, or that gene, or some body-wide process. Your body is programmed to tolerate these bumps and bruises. “While we are young, that repair actually works almost flawlessly,” says Vera Gorbunova, a biogerontologist who studies mole rats at the University of Rochester. When aging sets in, though, “now damage outpaces repair.” Gene-reading enzymes falter, misfolded proteins gum up the brain, sputtering mitochondria weaken muscles, and cancers bloom.This is Joe. He took a Lufthansa flight from South Africa to the US decades ago, spending a few years in the Cincinnati Zoo before being reunited with an old human friend, Rochelle Buffenstein.
Photograph: Ben Passarelli/Calico Life Sciences, LLCWhat begins life as a balanced merry-go-round of mistakes and repairs, devolves into a creaky wooden roller coaster—thrown off keel by rusted machinery and lackluster repair jobs; more susceptible to gusts of wind, and a brutal hell on your spine.As the damage from aging accumulates, it also accelerates. Your body observes something called the Gompertz mortality law, a mathematical model that quantifies how the intrinsic risk of death increases exponentially as an animal gets older. Although life spans vary for different species, the shape of the Gompertz curve is canon. A lab mouse’s risk of dying doubles every three months or so. For a dog it’s about every three years. Once a human turns 25, their risk of dying doubles every eight years. Naked mole rats don’t play by these rules.In 2018, Buffenstein and her colleagues at Calico published a paper showing that naked mole rats defy the Gompertz mortality law. Even at 35, Joe hadn’t statistically doubled his risk of dying compared to when he was 2. Naked mole rats still die, of course, but the risk stays nearly flat. “They haven't read the textbooks,” Buffenstein says. “They don't know how they’re meant to behave.”Mole rats like Joe certainly exhibit weird behaviors that are (presumably) unrelated to aging. For one thing, they’re eusocial, a rarity among mammals. That means that one queen rules over the entire colony. She mates with up to three males and remains fertile even 30 years after puberty. (For a human that would equate to having babies at 300 years old.) Joe, as it happens, is a rare breeding male. His late mother, like every mole rat's mother, was a queen, and she kept other females reproductively repressed with acts of dominance—pushing and shoving that may sometimes look aggressive, depending on the despot.Joe has seen dynasties rise and fall. He and his colony mates have spent their years cleaning the nest, caring for the queen, and guarding against intruders as designated workers or xenophobic soldiers. Most of them live relatively healthy lives. And because they live in deep desert burrows, mole rats have few natural predators.So what does kill a naked mole rat? “They beat each other up,” says Martha Delaney, a veterinary pathologist at the University of Illinois. Naked mole rats are extreme xenophobes. They’ll attack outsiders, push and bite each other, and banish colony members as outcasts.“They’re lovely, lovely animals,” Melissa Holmes says with great sincerity. Holmes is a behavioral neuroscientist at the University of Toronto who works with more than 1,000 naked mole rats. The inner workings of mole rats’ odd eusocial structure earns them a reputation for aggression. “But for animals that live in such large groups, they are remarkably stable,” she says.Holmes has had her colonies for 12 years. “And in some of my colonies, we’ve never had an injury, ever,” she says. “That's amazing—that animals live together for years with that lack of aggression.”It’s not that naked mole rats never age or get sick. They do. But their bodies somehow slow those processes down. While typical mammals’ bones get more brittle and thin over the years, mole rat bones keep the same mineral content and remain just as solid. People tend to tack on more fat with age. Naked mole rats? Nope.“But the most striking system,” says Buffenstein, “is cardiovascular.” Human veins and arteries normally stiffen with time. The more rigid those walls get, the harder the heart has to pump. Blood pressure goes up. Risk of death goes up. Naked mole rat blood vessels stay springy throughout life. “Every measure that we've looked at in heart function is unchanged from six months to 24 years,” she says.In humans, heart disease is the leading cause of death. Cancer is second. About 40 percent of people in the US develop cancer in their lifetimes. For naked mole rats, the probability is well below 1 percent. In a 2008 study, Buffenstein reported no cancers at all in a group of 800 mole rats. As of 2021, Buffenstein says she’s only found five cancers in over 3,000 necropsies.“They do age very well,” says Delaney “They’re very well adapted, just kind of like a physiological marvel.” Delaney primarily studies naked mole rats in zoos, scanning biopsies and tissue slices to tease out how they died. She has found a couple cancers in two naked mole rats (“after evaluating hundreds and hundreds,” she says). Neither cancer was fatal. Naked mole rats do develop kidney and brain lesions with age, but those rarely turn into disease.This unexpected resilience means there may be something about their biology that we can capture in pill form—or possibly one day as gene therapy—for humans. “And that's why I think they're so popular now,” says Delaney, “As research models for not just cancer, but age related diseases.” But popular or not, the true payoff remains elusive.Scientists want to sort out what to tweak in our biology to mimic the mole rat’s longevity. Take cancer. Mole rats are so great at avoiding cancer that researchers think their cells might be hardwired with protective molecules that stop mutated cells before they take over. For example, naked mole rat cells amass large amounts of a protein called p53, which is known to suppress tumors. Last year, Buffenstein reported that they show 10 times more of it in their connective tissue than in humans and mice—and it’s more stable.And remember how human aging is linked to DNA and other cellular odds and ends falling apart? A protein called NRF2, or nuclear factor erythroid 2-related factor 2, may protect against that descent into disorder. It’s a transcription factor, meaning it sticks to DNA and activates certain genes that protect the cell. NRF2 works as a sort of crossing guard for antioxidants, detoxicants, and proteins that keep other proteins from misfolding. “Every time I look, it seems to be regulating something else that's equally important for aging and longevity,” says Buffenstein. Heart disease, diabetes, depression, she continues, “just about every disease that you can think of seems to have an accompanying low level of NRF2.”All mammals, including people, naturally make this protein, but Buffenstein recently found that the naked mole rat version is more active, either because it’s more abundant or better at binding. Drug developers have also noticed that NRF2 is involved in medications approved to treat specific diseases. For example, metformin, a diabetes drug, also activates NRF2 and is being studied for anti-aging. Rapamycin, an immunosuppressant prescribed after organ transplants, activates NRF2 and extends life span by about 25 percent in male and female mice. Clinical trials are underway to test it against human aging. Perhaps NRF2 helps mole rats escape the onset of multiple aging-related diseases simultaneously.But here’s the thing about putting drugs to new uses: More isn’t always better. NRF2 levels that are too low or too high can lead to cancerous growths. The same is true for p53. “We've always got to be careful, because so many disease states have hijacked the same proteins to make them work in their favor, too,” says Buffenstein. “It's that very fine line of figuring out how this will help you, versus how this could be used to kill you.”It’s unlikely mole rats have only one unique mechanism that mitigates a disease as diffuse as cancer, much less aging. The naked mole rat likely gets its longevity from more than just one gene that protects against DNA damage, or one enzyme that keeps misfolded proteins from gumming up the brain—it emerges from multiple adaptations, each working in tandem to keep the body alive.And many labs are looking into where those adaptations are hiding. A treatment for humans may come from any distinct process they uncover, or even many separate ones. “It's not a single solution,” says Gorbunova. “We have to really study from multiple angles."So mole rats are unquestionably weird, and that might well be useful, but they might also turn out to be too weird. Their isolated, predator-free, underground existence, says Rich Miller, a University of Michigan biogerontologist, might be too unique to translate. “It's not a safe bet,” he says. Miller doesn't study naked mole rats, but he has studied animal aging for over 50 years and is an expert in testing interventions like rapamycin and metformin, leading one of three labs of the National Institute on Aging’s Interventional Testing Program for almost two decades. "They are so weird and, in many ways, so different from the other kinds of slow-aging mammals," he says. For example, levels of one particular antioxidant called thioredoxin reductase 2 are elevated among the long-lived rodents, primates, and birds Miller has studied. But it’s not in naked mole rats.To be sure, they’re still mammals. (“We are fairly similar to rodents,” Gorbunova says. “It's not like they're some kind of sea sponge.”) But while a Tesla is a car, its spare parts won’t fix your cousin’s Ford Pinto. Maybe the really good stuff is built differently—and is irreconcilably untranslatable.Naked mole rats may be full of such "idiosyncrasies," says Steve Austad, a biogerontologist at the University of Alabama Birmingham who has studied aging in animals since the 1980s. But Austad doesn’t dismiss unique lessons as untranslatable. Rather than just focusing on this one species, he suggests that studying a diverse array of long-lived mammals, like bowhead whales and Brandt’s bats, will point out important overlaps. “It could be that there are certain tricks that nature has invented time and time and time again,” he says. “I'd say it's probably something that's more likely to be relevant to humans.”And Gorbunova, who has studied tissue from dozens of species in her lab, says interest in unconventional animal subjects is growing. Now, she says, “people believe in it.”The drugs aren't here yet, but the biotech tools to decode animal secrets have gotten supercharged. Genome analysis is faster and more reliable than ever. Buffenstein's team is reexamining the naked mole rat genome—the published version isn’t adequate for finding new genes, she says. “You don't know if you're not seeing something because it's really lost or because the genome is of poor quality.” Annotating the sequence from scratch will help trace which genes are critically present, and which are critically unusual or absent. Better tech is also giving researchers an intimate look at the mole rat epigenome—the set of molecular ride-alongs that stick to DNA throughout their lives.As biotech tools have gotten more refined, the search for mole rat secrets has split off in every imaginable direction. Gorbunova, the biologist from Rochester, has spent years focused on a starch-like molecule called hyaluronan. Naked mole rat cells churn out tons of the stuff, and her lab has connected it to their sturdiness against osteoarthritis and cancer. Ewan St. John Smith, a neurophysiologist at the University of Cambridge, identified the gene variation and protein that keeps Joe and his conspecifics from feeling stinging pain from acid. Other labs are analyzing the animals’ gut microbiome or tinkering with reprogrammed mole rat stem cells. Their mitochondria churn out tons of a peptide that correlates with long human health span, and their mole rat brains seem impervious to high levels of another that correlates with Alzheimer’s. Their bodies are exceptional at dismantling dysfunctional proteins, and surprisingly tolerant of others. Their taste for living in crowded, low-oxygen burrows makes them less prone to seizures and may have adapted their pain receptors.And on lab benches not far from where Joe’s friends sleep and squeak, Buffenstein has also pinpointed surprising weirdness in their immune systems. Since they fend off disease so well, she expected to find a festival of natural killer cells—the quick-moving hit squad that zaps cancerous cells and pathogens in humans before they can turn into bigger problems. “Again, these little critters drove me crazy,” she says. “We couldn't find natural killer cells at all.” More lethal T cells may pick up the slack, Buffenstein says. They’ve also got a much higher proportion of macrophages and neutrophils—the invader-eating white blood cells that turn into pus. That front line is “ready to pounce on anything that's foreign and destroy it almost instantly,” Buffenstein says. For mole rat (and human) health, there are still many more questions than answers.“I sort of like the fact that the animals are winning,” Buffenstein says, “and we haven't quite got there yet.”Buffenstein and her team will celebrate Joe’s 40th next year. As far as we can tell, he’ll just want a few nibbles of sweet potato, some quality time with his queen, and maybe a little wrinkle cream. He’ll be the first to live so shockingly long. And, perhaps, not the last.More Great WIRED Stories📩 The latest on tech, science, and more: Get our newsletters!The Arecibo Observatory was like family. I couldn't save itIt’s true. Everyone is multitasking in video meetingsThis is your brain under anesthesiaThe best personal safety devices, apps, and alarmsRansomware’s dangerous new trick: double-encrypting data👁️ Explore AI like never before with our new database🎮 WIRED Games: Get the latest tips, reviews, and more🏃🏽♀️ Want the best tools to get healthy? Check out our Gear team’s picks for the best fitness trackers, running gear (including shoes and socks), and best headphones | Biology |
New antibiotic approach proves promising against Lyme bacterium
Using a technique that has shown promise in targeting cancer tumors, a Duke Health team has found a way to deploy a molecular warhead that can annihilate the bacterium that causes Lyme disease.
Tested in cell cultures using the Borrelia burgdoferi bacterium, the approach holds the potential to target not only bacteria, but also fungi such as yeast and viruses. The findings appear in the journal Cell Chemical Biology.
"This transport mechanism gets internalized in the bacterium and brings in a molecule that causes what we've described as a berserker reaction—a programmed death response," said lead author Timothy Haystead, Ph.D., professor in Duke's Department of Pharmacology and Cancer Biology. "It wipes out the bacteria—sterilizes the culture with a single dose of light. And then when you look at what occurs with electron microscopy, you see the collapse of the chromosome."
Haystead and colleagues used a molecular facilitator called high-temperature protein G (HtpG), which is involved in protecting cells that are undergoing heat stress. This family of proteins has been the focus of drug development programs for possible cancer therapies.
Studies of this protein as an antimicrobial have also been encouraging, but the Duke team's work appears to be the first to tether an HtpG inhibitor to a drug that enhances sensitivity to light.
The researchers found that the HtpG inhibitor, armed with the photosensitive drug, was rapidly absorbed into the cells of the Lyme bacteria. When hit with light, the bacteria's cells went into disarray and ultimately collapsed, killing them.
"Our findings point to a new, alternate antibiotic development strategy, whereby one can exploit a potentially vast number of previously unexplored druggable areas within bacteria to deliver cellular toxins," Haystead said.
In addition to Haystead, study authors include Dave L. Carlson, Mark Kowalewski, Khaldon Bodoor, Adam D. Lietzan, Philip Hughes, David Gooden, David L. Loiselle, David Alcorta, Zoey Dingman, Elizabeth A. Mueller, Irnov Irnov, Shannon Modla, Tim Chaya, Jeffrey Caplan, Monica Embers, Jennifer C. Miller, Christine Jacobs-Wagner, Matthew R. Redinbo, and Neil Spector (deceased).
More information: Dave L. Carlson et al, Targeting Borrelia burgdorferi HtpG with a berserker molecule, a strategy for anti-microbial development, Cell Chemical Biology (2023). DOI: 10.1016/j.chembiol.2023.10.004
Journal information: Cell Chemical Biology
Provided by Duke University Medical Center | Biology |
The 70-odd-million-year-old remains were found in southern Mongolia.Illustration: Yusik Choi.Paleontologists discovered a 71-million-year-old carnivorous dinosaur in Southern Mongolia that they believe had a body built for swimming and diving for prey. Though it looks a lot like a modern bird, it’s actually a non-avian dinosaur, meaning it’s likely an example of convergent evolution, a phenomenon in which unrelated creatures evolve similar traits. OffEnglishThe dinosaur is called Natovenator polydontus, or “swimming hunter with many teeth.” Recent analysis of its fossilized remains indicate the animal was bipedal and built for diving. A full description of the newly discovered animal is published in Communications Biology.“Finding semi-aquatic dinosaurs means that the ecological diversity was very high in dinosaurs,” Yuong-Nam Lee, a paleontologist at Seoul National University and the lead author of the study, wrote in an email to Gizmodo. “More than 30 different lineages of tetrapods have independently invaded water ecosystems. Why not for dinosaurs?”An illustration of the recently discovered species.Illustration: Yusik Choi.Besides its many teeth, N. polydontus had a slender body and a long neck. From the rump up, the extinct dinosaur may have looked a lot like a goose or a cormorant, a modern diving bird, but it had a long tail. The skeleton is incomplete—the researchers found its skull, spine, a forelimb, and some of two hindlimbs—but animal’s morphology could be deduced from the found remains.G/O Media may get a commission“The angle between each rib shaft and its associated articulating vertebra is very low, like many diving birds, but in contrast to terrestrial theropods,” Lee said. “Certain extant diving birds–such as alcids and phalacrocoracids–also have posteriorly extending ribs. In these animals, backward-oriented ribs aid swimming by making the body more streamlined.Lee’s team hopes they can find the stomach contents of the bird, to learn more about its diet. That sort of discovery is not without precedent; last year, paleontologists found the fossilized marine equivalent of a turducken in modern-day Germany.Also last year, a different team made up of many of the same researchers behind the new paper announced the discovery of an armored ankylosaur from the same region in Mongolia. They posited that the ankylosaurs may have dug defensive trenches when threatened, much like modern horned lizards.More fossils will need to be found to better test these ideas, but taken together, the fossils are showing the dynamism of biodiversity in the Cretaceous.More: Paleontologists Find Evidence of Dinosaurs Nesting Near the North Pole | Biology |
Spiders are common critters. And, as almost all of Earth's 43,000 known spider species are venomous (opens in new tab), it is likely that most people have encountered a venomous spider at one point or another.
So that's the bad news. The good news, however, is that of these, only 25 species are known to have killed or caused serious harm to humans. But which spider is the deadliest?
The deadliest spiders — or at least those most frequently cited as having caused death or serious injury to humans — are funnel-web spiders (Atrax), redback and black widow spiders (Latrodectus), banana and wandering spiders (Phoneutria) and recluse spiders (Loxosceles).
But even these deadly spiders, with potent venom and fangs primed for piercing skin, are not particularly dangerous to humans. The American Association of Poison Control Centers (opens in new tab) (AAPCC) tracked only one death caused by a spider bite in the U.S. in 2021. Australia, home to some of the most venomous spiders in the world, hasn't reported a single spider bite death since the 1980s (opens in new tab).
"It is incredibly rare to have a deadly spider encounter," said Rick Vetter (opens in new tab), a retired research associate with the Department of Entomology at University of California, Riverside, whose research focused on medically important spiders. "Considering all the bad things that could happen to you, if spiders are your biggest concern, then you are living the good life."
Funnel-web spiders top the list of deadliest spiders, if only for their storied venom. Native to Australia, these spiders boast venom that's so potent their bite can kill within minutes. "The deadliest is probably the funnel-web spider and its relatives. The Sydney funnel web spider (Atrax robustus) can kill a toddler in about 5 minutes and a 5-year-old in about 2 hours," Vetter told Live Science. Although no one has died from these spiders since the advent of antivenom in the 1980s, it is difficult to imagine a toddler receiving treatment soon enough to recover from a funnel-web bite.
Phoneutria spiders, the most common of which are often referred to as banana spiders or wandering spiders, are native to Brazil and have the most neurologically active venom of any spider. But they rank a bit lower on the list of the world's deadliest spiders because their venom works relatively slowly, leaving ample time for treatment. And Loxosceles spiders, the most familiar of which is the brown recluse (L. reclusa) found in the U.S., may be one the most common causes of spider-related injuries, with painful bites that can cause body aches and fever and take months to fully resolve. But they are very rarely deadly.
The only arachnid genus that gives the funnel-web a real run for its money as the deadliest spider is Latrodectus, which includes the Australian redback (Latrodectus hasselti) and the more familiar black widow spider in the U.S. These spiders have a slight edge because they bite humans more frequently than funnel-web spiders, with comparably potent venom. "The most venomous species (Sydney funnel-web spiders, Brazilian wandering spiders) don't kill or impact that many people," Linda Rayor (opens in new tab), a behavioral ecologist at Cornell University who focuses on spiders, told Live Science in an email. "It is the more widely-distributed black widows that are going to be the stars of your story."
It's important to note that, while AAPCC's annual reports (opens in new tab) carve out a section for spider bite statistics, it isn't easy to get a real handle on spider bite mortality or morbidity.
"A number of human deaths each year are attributed to spiders," Rod Crawford (opens in new tab), curator of arachnids at the Burke Museum at the University of Washington in Seattle, told Live Science in an email. "However, from a scientific viewpoint, almost none of these attributions are evidence-based."
It is exceedingly rare, Crawford explained, for a victim to see a spider on their skin, feel a bite, capture that same spider, and then bring the offending spider to a physician (let alone a spider specialist) for analysis. "Practically all of the 'spider bites' you hear about, including those reported to poison centers originate from the belief that if you didn't see what bit you, it was a spider," Crawford said.
Rayor echoed this sentiment. "I have spent a surprising amount of time trying to track down the human mortality rate from spiders and it is miniscule," she said. "This isn't reliably reported, but it is clear that not that many people get killed by spiders."
Keeping in mind the flawed nature of spider bite statistics, The Australian Museum (opens in new tab) claims that about 2,000 people are bitten by redback spiders each year, and that the antivenom to treat funnel-web spider bites has been given to about 100 patients since 1980. AAPCC's annual report tracked about 3,500 spider bites in the U.S. in 2021, with about 40 "major" clinical outcomes. Nine of those serious outcomes were attributed to black widows; 29 major outcomes and the only death that year were attributed to brown recluses. There were no spider bite deaths in AAPCC's 2020 report (opens in new tab), which tracked seven "major" black widow bites and 23 "major" brown recluse bites.
This means that the deadliest spiders are, in fact, not very deadly. "True human spider bites of any kind — dangerous or harmless — are vanishingly rare," Crawford said. "Take me as an example: Over a long career I have handled tens of thousands of live spiders with my bare hands. Only 3 actual bites resulted; none of the 3 had any significant effect. So when people tell me spiders crawl into their beds at night and bite them while they are asleep, I just roll my eyes."
Vetter agreed. "In reality, spiders are way down the list of things to be concerned about."
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Joshua A. Krisch is a freelance science writer. He is particularly interested in biology and biomedical sciences, but he has covered technology, environmental issues, space, mathematics, and health policy, and he is interested in anything that could plausibly be defined as science. Joshua studied biology at Yeshiva University, and later completed graduate work in health sciences at Cornell University and science journalism at New York University. | Biology |
An international team of scientists has published the results of their research into 23 woolly mammoth genomes in Current Biology. As of today, we have even more tantalizing insights into their evolution, including indications that, while the woolly mammoth was already predisposed to life in a cold environment, it continued to make further adaptations throughout its existence.
Years of research, as well as multiple woolly mammoth specimens, enabled the team to build a better picture of how this species adapted to the cold tundra it called home. Perhaps most significantly, they included a genome they had previously sequenced from a woolly mammoth that lived 700,000 years ago, around the time its species initially branched off from other types of mammoth. Ultimately, the team compared that to a remarkable 51 genomes—16 of which are new woolly mammoth genomes: the aforementioned genome from Chukochya, 22 woolly mammoth genomes from the Late Quaternary, one genome of an American mastodon (a relative of mammoths), and 28 genomes from extant Asian and African elephants.
From that dataset, they were able to find more than 3,000 genes specific to the woolly mammoth. And from there, they focused on genes where all the woolly mammoths carried sequences that altered the protein compared to the version found in their relatives. In other words, genes where changes appear to have been naturally selected.
What’s new (gene-wise)?
David Díez-del-Molino is an evolutionary biologist and the lead author on this paper. "What we call ‘highly evolved genes’ are genes that have a lot of these non-synonymous mutations. The more they have, the more highly evolved that we consider them,” he explained in a video interview with Ars. “The truth is (and by the way, we do mention this in the limitations of the study) all mutations are relevant. So genes that have only one of these mutations, they could be very important for the woolly mammoth phenotype. So we use the number of mutations as an indication of how much the gene has changed in the woolly mammoth.”
Some of those highly evolved genes offer intriguing insight into the woolly mammoth’s environment. The team found evidence for genes involved in the immune system, specifically those that might be useful against parasitic worms or pathogens. Other genes might have helped with DNA repair. Two of the genes they identified in this regard (BRCA1 and BRCA2) are involved with breast cancer in humans, acting to suppress tumors. Could woolly mammoths have been, like their extant relatives, cancer-resistant?
Some of the altered genes are involved in fat storage, heat production, and metabolism, all of which could be very useful against the Arctic cold. Other changes indicate that woolly mammoths may have had altered cold sensation, such as the ability to feel pain in reaction to cold temperatures.
Perhaps most intriguing are the genes related to hair. The team found changes in several genes that, in humans, are responsible for genetic disorders. With names like Uncombable Hair Syndrome and the appropriately named “woolly hair syndrome” (Carvajal syndrome), these disorders collectively produce uncombable, bushy, wiry, and frizzy hair. These attributes, however, correspond with what we imagine of woolly mammoth fur: one big bushy, wiry, uncombable coat of hair. And these genes indicate mammoth fur wasn’t the same for all woollies; it may have evolved over the course of their existence such that later species may have had coats that were different from earlier ones.
“It’s so funny,” Díez-del-Molino said, “because all the names were everything that we thought the mammoth hair was! But it’s important to note that we don’t exactly know the function in woolly mammoths because they are not exactly the same mutations [seen in humans].” | Biology |
Researchers at The University of Queensland have found an anti-ageing function in a protein deep within human cells.
Associate Professor Steven Zuryn and Dr Michael Dai at the Queensland Brain Institute have discovered that a protein called ATSF-1 controls a fine balance between the creation of new mitochondria and the repair of damaged mitochondria.
Mitochondria, with their own DNA, produce energy within cells to power biological functions but the toxic by-products of this process contribute to the rate at which the cell ages.
"In conditions of stress, when mitochondrial DNA has been damaged, the ATSF-1 protein prioritises repair which promotes cellular health and longevity," Dr Zuryn said.
As an analogy, Dr Zuryn likened the relationship to a race car needing a pitstop.
"ATSF-1 makes the call that a pitstop is needed for the cell when mitochondria need repairs," he said.
"We studied ATFS-1 in C. elegans, or round worms and saw that enhancing its function promoted cellular health, meaning the worms became more agile for longer.
"They didn't live longer, but they were healthier as they aged."
"Mitochondrial dysfunction lies at the core of many human diseases, including common age-related diseases such as dementias and Parkinson's.
"Our finding could have exciting implications for healthy ageing and for people with inherited mitochondrial diseases."
Understanding how cells promote repair is an important step towards identifying possible interventions to prevent mitochondrial damage.
"Our goal is to prolong the tissue and organ functions that typically decline during ageing by understanding how deteriorating mitochondria contribute to this process," Dr Dai said.
"We may ultimately design interventions that keep mitochondrial DNA healthier for longer, improving our quality of life," Dr Dai said.
This research was published in Nature Cell Biology.
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From our nose to our lungs to our guts, the human body is home to a diverse range of microorganisms. Such rich microbial ecosystems are prime hunting grounds for viruses that infect and kill bacteria. But how these bacteria-killing viruses interact with human cells has remained mysterious.
Past research has shown that human cells can slurp up bacteria-killing viruses when a cell ingests a large amount of the fluid surrounding it. Microbiologist Jeremy Barr wanted to know if the ingested viruses have any effect on the cell’s immune response.
To his surprise, Barr instead found that mammalian cancer cells grown in the lab use the viruses as a food source. The results, published in the Oct. 26 PLOS Biology, show that it’s possible for mammalian cells to use bacteria-killing viruses as fuel — meaning normal, noncancerous cells could do it too, though this remains to be seen.
This nascent line of work upends traditional biological dogma, says Barr of Monash University in Melbourne, Australia. “You’re told that [phages] just do not interact with mammalian cells,” he says. “And that’s completely false. They do.”
Bacteria-killing viruses, called bacteriophages, are ubiquitous in the human body. Cells in our body ingest up to 30 billion phages each day, Barr estimates. To test how the phages interact with mammalian cells, the researchers experimented with human and dog cancer cells, mainly because they are easy to cultivate in the lab. The team grew the cancer cells in an environment flush with bacteriophage T4, a common virus that preys on E. coli.
Barr’s team then used a battery of antibodies, each of which binds to a specific type of protein, to determine the proteins the cells made in response to the phage. Though the researchers expected to see more proteins involved in inflammation, part of the cell’s immune response, they instead saw changes in the amounts of proteins involved in cell growth and division. “Cells that had been given phage were actually growing at a faster rate,” Barr says. This suggests that “they’re using the phages as a food source.”
Because the cells used in this study were grown in a lab and come from established lines of cells used for research, we can’t yet be sure that cells in the bodies of humans and other mammals behave the same way, says Paul Bollyky, an immunologist at Stanford University. “Cell lines are funny creatures,” he says. “They do things energetically that are probably closer to tumor biology than to normal cell biology, so it can be difficult to extrapolate.”
Still, “this is a really exciting and trailblazing study from a group that’s doing excellent work,” Bollyky says. “Like a lot of good science, this study really raises questions.”
Barr says he next wants to investigate whether noncancerous cells derived from a living animal also snack on phages. He also plans to examine more phages, especially viruses that — like T4 — live in our guts, and others that are being used in phage therapy, where viruses are used instead of antibiotics to kill infectious bacteria (SN: 12/14/21). “We know they kill the bacterial hosts, but what are they doing to the human host?” Barr asks. “How do they interact?” | Biology |
Current estimates of Lake Erie algae toxicity may miss the mark
Study suggests harmful algal bloom toxicity varies over the summer
There is more to a harmful algal bloom than the green stuff in water that meets the eye – specifically, a changing hazard level of toxins produced by the microbes that make up the scummy mess.
A new study analyzing toxins produced by Microcystis, the main type of cyanobacteria that compose the annual harmful algal bloom (HAB) in Lake Erie, suggests that the toxicity of the bloom may be overestimated in earlier warm months and underestimated later in the summer.
The research is part of a large project, led by The Ohio State University, designed to develop a more accurate harmful algal bloom toxicity forecast for Lake Erie.
The toxicity relates to the bloom’s concentration of the liver toxin microcystin, of which there are hundreds of varieties called congeners defined by very small molecular differences. The analysis showed that the toxicity level of the most common congeners found in Lake Erie relates strongly to nitrogen – when there is more nitrogen present in early warm months, dominant congeners tend to be of the less toxic variety. Later in the season, when nitrogen is nearly gone, the balance of dominant congeners changes to a more toxic type.
“The different levels of toxins will ultimately affect the toxicity and the human health impacts. We know that different populations are more sensitive to the toxins, especially those who have non-alcohol fatty liver disease,” said Justin Chaffin, senior researcher and research coordinator at Ohio State’s Stone Laboratory and lead author of the study. “Knowing which congeners are around can better inform beach management, better inform water treatment, and better inform those who need to avoid the water when they should avoid it.”
The research was published recently in the journal Harmful Algae.
Lake Erie supplies drinking water to an estimated 11 million people in the United States and Canada, and the project led by Chaffin is geared toward developing toxicity forecasts that best prepare water treatment plant operators for the removal of microcystin. A high concentration of the toxin overwhelmed a Lake Erie water treatment plant in 2014, leading to the three-day Toledo drinking water crisis.
But not all microcystin congeners are alike in terms of toxicity. The most abundant and most studied congener in Lake Erie, known as MC-LR, has been shown in recent research to be somewhere in the middle, in terms of toxicity, compared to other congeners in the lake’s bloom. In this study, Chaffin and colleagues set out to determine the location and abundance of these different congeners to get a better handle on toxicity trends over the busy summer season.
The team collected samples at 15 sites stretching from Maumee Bay to the Central Basin from June through September in 2018 and 2019, focusing on identifying the concentration of specific microcystin congeners present over time and the changing nutrient levels in the water.
Along with the common MC-LR congener, two other congeners were found to dominate the microcystin populations: MC-RR, whose toxicity is about one-fifth of MC-LR, and MC-LA, estimated to be about 2 1/2 times more toxic than MC-LR. MC-RR, which is 17.5% nitrogen, was more dominant early in the season, when the water was rich in nitrogen, and MC-LA, which is 10.8% nitrogen, dominated later in the season, when nitrogen levels had substantially dipped – however, the total microcystin concentration was lower at that time as well, meaning overall toxicity may not have dramatically increased.
Detecting congeners doesn’t come easily – it requires highly sophisticated equipment and is more expensive than the analysis tool ELISA that’s routinely used to measure microcystins in the bloom – which is why current toxicity estimates are probably off, Chaffin said.
“Because ELISA measures overall concentration, basically you’re overestimating the toxicity in early summer when the majority of microcystins are a low-toxicity form, and then as summer progresses, the bloom is making more toxic forms, so you may be underestimating the toxicity,” he said.
An investment in routinely gathering congener data could improve modeling efforts to predict how the toxicity of the HAB in Lake Erie changes each year. Chaffin co-authored another recent study that showed using data on toxin concentrations (from existing ELISA measurements that don’t take congeners into account), water currents and a bloom’s increase in toxin production in a one-week weather map-like simulation improved the accuracy of microcystin forecasting by 79%.
“We took all the data we could find and put it in a hydrodynamic model and ran it under simulations,” Chaffin said. “So if you know where the toxins are today and make a map of the bloom like a weather map, you can watch where it’s going to go in the next seven days. And if you add biology data to the simulation, you can get a better prediction of where the highest toxin concentrations will be.
“The next step would be to merge the bloom location and toxin concentration forecast with different congeners so we could really forecast the toxicity of the bloom. But lab capabilities would need to be improved to make that possible.”
Pengfei Xue, professor of civil, environmental and geospatial engineering at Michigan Technological University, was senior author of the modeling study published in the Journal of Great Lakes Research. Co-authors of the Harmful Algae study include Judy Westrick of Wayne State University, Laura Reitz of Bowling Green State University (now at the University of Michigan) and Thomas Bridgeman of the University of Toledo. | Biology |
Ocean explorer Jon Copley has completed dozens of dives to the darkest corners of the deep sea. Yet he is still amazed every time he encounters the strange life forms that thrive there. Over the past 25 years, Copley has traveled to the world's deepest hydrothermal vents, to Antarctica's icy "midnight zone" and to spectacular undersea mountain chains across the planet.
As a professor of ocean exploration and science communication at the University of Southampton in the U.K., Copley dedicates much of his time to addressing the myriad questions and myths surrounding the deep sea. His new book "Deep Sea: 10 Things You Should Know" (Orion Publishing, 2023) takes a fascinating look at some of the harshest habitats on Earth.
In a video interview with Live Science, Copley described the latest discoveries and where deep sea research is heading in a warming world.
Q: Four years ago, when I was a student sitting in your deep sea ecology lectures, you had just published your first book, "Ask an Ocean Explorer" (Hodder & Stoughton, 2019). That book had 25 chapters, each answering a question that people commonly ask you as a deep sea biologist. What did you set out to do in "Deep Sea: 10 Things You Should Know"?
Copley: This new book answers the top 10 questions that I know people have about the deep sea and also tackles some of the myths and popular misconceptions that we sometimes hear. The shorter format is an opportunity to focus and update the information — there have been quite a few discoveries in lots of different aspects of deep sea biology since I wrote "Ask an Ocean Explorer."
Q: Research has made great strides in recent years, I'm sure. What are some of the most exciting, new discoveries you discuss in the book?
Copley: We're finding out a lot more about how deep sea animals interact with each other and their environment. An area where we've seen a lot of interesting papers over the past five years has been in sensory ecology — realizing how animals perceive their environment, how they respond to that, how they avoid being seen by predators... It was nice to bring some of those together in a couple of the chapters.
Q: Some of the chapters focus on dispelling misconceptions people might have about what's down there in the ocean. What, to your mind, is the biggest, most pervasive myth about the deep sea?
Copley: It's the idea that we know almost nothing about it. There's this very popular idea that we know more about the moon or Mars than the deep ocean. That's only really true for one very specific aspect of knowledge — having a detailed map of the terrain of its solid surface — because the moon and Mars are not covered in seawater, which blocks radar and means we have to use sonar in the deep ocean. Apart from that, we know far more about the deep ocean than those other places.
Q: The deep sea has attracted a lot of attention recently in the advent of deep sea mining. How worried are you about that?
Copley: I think it's great that deep sea mining has made people care more about the deep ocean, but it hasn't actually started yet and research does not support some of the more hyperbolic headlines.
There's a lot of research focused on how we're going to manage mining, if it does go ahead. And there are some habitat types in the deep ocean that we don't need to do further research on, because we know they are so vulnerable. We know that we would risk species extinction at active hydrothermal vents, for example, because they're a tiny habitat globally — just 50 square kilometers [19 square miles] — with more than 400 animal species not found in any other habitat type. But I'm confident that we will see protection for active hydrothermal vents, because we scientists have been saying that for years.
Q: Deep sea mining is perhaps more manageable in terms of its impacts than other human activities. If not mining, what is the biggest human threat to the deep sea?
Copley: To my mind, it's climate change. And it affects the deep ocean in lots of different ways. The one that concerns me particularly is deoxygenation — the reduction in oxygen levels — because deep sea animals need oxygen and they get it from the seawater.
Oxygen is carried down by currents that form in the polar regions and sink and spread throughout the deep ocean. As a result of climate change, the ocean is getting warmer and that means it can't carry as much dissolved oxygen. When water is warmer, the metabolism of things living in the water runs faster and they use up oxygen more quickly, so that makes the problem even worse. And thirdly, we know that the currents carrying oxygen down to the deep ocean are weakening, because melting ice sheets are making the water fresher and blocking the formation of dense water than sinks.
Those currents take centuries to complete their journey, which means the changes we have already made are going to carry on being felt for centuries. The deep ocean is already on track to have 10% less oxygen overall globally than it did in preindustrial times by 2400. It's hard to predict what the knock-on effects are going to be, but they are going to be widespread and they are coming.
Q: You dedicate much of your time to communicating deep sea science with lay audiences. Why is that so important to you?
Copley: I enjoy talking to people about the deep sea because it's not somewhere we think about every day. We can go out at night and if we look at the sky, we might wonder about what's going on up there. But you can't glance into the deep sea in the same way, so it has become a realm of myth and darkness. Even the names of the deepest bits of the deep sea — the abyssal plains and the hadal zone — evoke that kind of underworld. It's nice to be able to shine a light on that for people and to highlight how our lives are connected to it.
Q: Speaking of the sky, how does exploring the deep ocean inform the search for life outside our solar system?
Copley: Deep sea exploration has shown us that the range of conditions under which life can thrive is far greater than we imagined. The idea that chemosynthesis — where life is powered by a form of chemical energy instead of sunlight with photosynthesis — could sustain whole populations of animal species was impossible, until we discovered hydrothermal vents and other, similar habitats.
Deep sea vents also glow very faintly — too faintly for the human eye to see, but bright enough that microbes can use it as an energy source. Again, it expands our notion of what's possible in the cosmos, because you don't necessarily have to be that close to a bright star, potentially, to sustain life.
"Deep Sea: 10 Things You Should Know" is available in the U.K. to order on Amazon.
This interview has been condensed and lightly edited for length.
Deep Sea: 10 Things You Should Know - £10.11 at Amazon U.K.
In ten brief and informative essays, marine biologist and TV science advisor Professor Jon Copley journeys to one of the most mysterious and fascinating environments on Earth, the deep sea. Discover what makes this unique habitat such a challenging environment, the creatures that call it home and how ocean explorers are able to utilise the latest technology to aid their research and travel miles below the ocean surface.
"The Deep Sea: 10 things you should know" is a brilliant guide to one of the most fascinating and curious places known to humankind.
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Sascha is a U.K.-based trainee staff writer at Live Science. She holds a bachelor’s degree in biology from the University of Southampton in England and a master’s degree in science communication from Imperial College London. Her work has appeared in The Guardian and the health website Zoe. Besides writing, she enjoys playing tennis, bread-making and browsing second-hand shops for hidden gems. | Biology |
Beware any rock that’s oblong and cylindrical, like a stubby stone finger. It might not be a rock. It could, very likely, be a coprolite. Yes, that’s another name for fossilized feces.
And if you do find one, call Thanit Nonsrirach. A paleontologist at Mahasarakham University in Thailand, Nonsrirach estimates he’s examined over 500 coprolites. To date, just one has contained a surprise: eggs from not one but two parasite species, indicating that the poop’s host was carrying squatters.
Nonsrirach is the first author of a study published today in the journal PLOS ONE that describes the coprolite, its fossilized eggs, and what it tells us about animals of the distant past.
Old sh*t, new findings
At just over 7 centimeters long (almost 3 inches), this fecal fossil might not be much to look at but has been hardening since the Late Triassic period about 200 million years ago. Inside it, six small, round structures between a mere 50 and 150 micrometers long represent multiple species of parasite that had been dwelling in this lucky host’s belly at once. One specimen, a thick-shelled oval, is the egg of a parasitic nematode worm. The other five are unidentified worm eggs or protozoan cysts. Past studies, the paper notes, have only found instances of single species in coprolites.
“We were very surprised by the discovery of the parasite fossil,” Nonsrirach writes to Inverse. “Parasite fossils are quite rare, especially those from soft-bodied organisms.” Soft tissue decomposes quickly, so it’s difficult to study ancient parasites that inhabited them. A fossilized parasite egg might not be as exciting as a dinosaur bone, but these freeloaders can tell us a good deal about the prehistoric food chain.
Even more exciting, the nematode egg was split open, “unveiling the embryonic structure” of the worm inside, Nonsrirach continues. He writes that when studying worm eggs, scientists typically use chemical techniques that “merely reveal the external surface of the eggs.” This serendipitous finding provides an opportunity for further classifying the species.
This fossil came from the Huai Hin Lat Formation in Chaiyaphum Province in central northeastern Thailand. Residents of Nong Yakong village found a trove of coprolites, including the parasite-infested one.
“The peculiar appearance of these findings intrigued the villagers, who considered them potentially auspicious and capable of bestowing good luck if repurposed as talismans,” Nonsrirach writes to Inverse. “In 2010, our team received word of this discovery and embarked on a field expedition, guiding the villagers to the actual fossil site.”
Paleoscatology 101
So, whose parasite-infested poop was it?
The sample offers a few clues. First, its shape and form intimate the innards of its creator, “specifically reflecting the configuration of their intestines and anus,” Nonsrirach writes. The cylindrical shape suggests a large amphibian or reptile.
Next, its contents signal the predator’s diet and digestive function. This coprolite contained no remnants of a prey skeleton, an indicator that it went through a crocodile’s robust, bone-grinding gut. However, crocodiles emerged 100 million years after this sample’s date, so the culprit is likely a creature akin to crocodiles or one that evolved alongside them, such as the phytosaur.
Indeed, phytosaurs appeared about 240 million years ago during the Middle Triassic period, and there’s evidence they lurked near this particular fossil site. (And if you ever need to identify a shark or fish coprolite, Nonsrirach writes that those tend to be spiral-shaped.)
Everything comes down to poo
Ultimately, this hoary stool is a window into the lives of ancient soft-bodied creatures.
“This new point of view gives us a deeper understanding of how past ecosystems were connected and how they affected the lives of prehistoric animals,” Nonsrirach writes. He wonders about the interactions between predators, prey animals, and parasites or whether the phytosaur happened to swallow infected prey.
“Coprolites can preserve the soft bodies of ancient organisms, which helps us learn more about their biology,” Nonsrirach writes. “It's exciting to think that we might uncover new fossils that have never been seen before.” | Biology |
Scientists see anti-aging potential in an invasive weed
The fruit of the cocklebur plant, which grows worldwide and is often considered a noxious weed, has antioxidant and anti-inflammatory components that could make it useful as a skin protectant, according to new research.
Researchers found that compounds in the species' spiky fruits reduced damage from UVB exposure and sped wound healing in laboratory tests using cells and tissues. The cocklebur extracts also appear to influence the production of collagen, a protein that gives skin its elasticity and prevents wrinkles.
"We found that cocklebur fruit has the potential to protect the skin and help enhance production of collagen," said Eunsu Song, a doctoral candidate at Myongji University in South Korea, who conducted the research with Myongji University Professsor Jinah Hwang. "In this regard, it could be an attractive ingredient for creams or other cosmetic forms. It will likely show a synergistic effect if it is mixed with other effective compounds, such as hyaluronic acid or retinoic acid, against aging."
Song will present the new research at Discover BMB, the annual meeting of the American Society for Biochemistry and Molecular Biology, March 25–28 in Seattle.
Cocklebur is a plant native to Southern Europe, Central Asia and China that has spread worldwide, often found in moist or sandy areas such as roadside ditches and riverbanks. Its distinctive fruits, covered in stiff husks and burrs, have been used for centuries in traditional medicines for headache, stuffy nose, disorders of skin pigmentation, tuberculosis-related illness and rheumatoid arthritis. In recent years scientists have explored its potential use in treatments for rheumatoid arthritis and cancer.
The new study is the first to examine the fruit's properties as a wound-healing agent and skin protectant. Researchers first studied the molecular properties of cocklebur fruit extracts and isolated particular compounds that could contribute to anti-oxidant and anti-inflammatory effects. They then used cell cultures and a 3D tissue model with properties similar to human skin to study how these compounds affect collagen production, wound healing and damage from UVB radiation.
The results showed that the cocklebur fruit extracts encouraged collagen production, sped wound healing and exerted a protective effect against UVB radiation. Comparing the bioactivity of cocklebur fruits grown in different places, the researchers found that fruits grown in South Korea had slightly higher anti-oxidant and anti-inflammatory properties and greater wound-healing activity than those grown in China.
Researchers cautioned that high doses of cocklebur fruit extract can be harmful and further research is needed to determine how to use it safely in cosmetic or pharmaceutical applications.
"In its burrs, cocklebur fruit also has a toxic constituent, carboxyatractyloside, which can damage the liver," said Song. "Cocklebur showed a potential as a cosmetic agent by increasing collagen synthesis; however, it showed negative results with higher concentrations. Therefore, finding the proper concentration seems very important and would be key to commercializing cocklebur fruit extracts in cosmetics."
Moving forward, the researchers plan to further study the biological mechanisms involved and conduct experiments in animal alternatives to explore ways to safely adapt cocklebur fruit extracts for use in cosmetic products.
More information: Eunsu Song will present this research during the poster session from 4–5:30 p.m. PDT on Tuesday, March 28, in the Exhibit Hall of the Seattle Convention Center (Poster Board No. 139). | Biology |
Scientists say they are stunned after discovering sea spiders have the ability to grow new reproductive organs and an anus.
Experts already knew that when the arthropods lose legs, they can regrow them.
But in a development that will no doubt inspire the next generation of Spider-Man stories, a study has found the underwater creatures have regenerative powers which extend to their entire bottom halves."Nobody had expected this," said the lead researcher behind the breakthrough in understanding, Professor Gerhard Scholtz.Other arthropods - invertebrates with no internal skeleton or backbone, but which do have an exoskeleton - such as centipedes and crabs, are also capable of regrowing limbs.
Some creatures can go further, with starfish able to regenerate their entire bodies on occasion - and lizards able to produce a new tail."If you look at the animal kingdom, the capability of regeneration differs very much in various groups of animals," Professor Scholtz told Sky News."Flatworms, for example, can regenerate their whole body from a limited amount of tissue."On the other hand, us - mammals - cannot regenerate much - liver, tissue, skin, but apart from that very little. "For arthropods - crustaceans, insects, myriapods, and types of spider - it was entirely unknown that they could regenerate body parts other than limbs."More science news:'Golden boy' mummy gets 'digitally unwrapped'The real 'zombie fungus' behind The Last Of UsBest time to see 'once-in-a-lifetime' cometThe study, which has been published in the Proceedings of the National Academy of Sciences journal, saw the hind limbs and backends of 23 sea spiders amputated.While four older spiders did not regrow anything, most of the 19 juveniles did.Sixteen of them regenerated at least one lost body part, 14 recovered their posterior, and 90% survived long-term despite the amputations.Until now, it was thought that the spiders' hard exoskeleton prevented any regeneration beyond the limbs, added Professor Scholtz. But his research found the creatures were recreating body parts within "several weeks or months".The regenerations did not always go smoothly - some spiders were a leg or two short.Hope 'always there' for amputation breakthroughProfessor Scholtz, of Humboldt University of Berlin's Institute for Biology, said the findings should inspire further study into different species."One has to look to other arthropods and whether they can do the same," he said.He is planning further research by reproducing the study with insects, crabs and other crustaceans.And the breakthrough could be transformative for health care.Such research could one day advance treatments for human amputees."The hope is always there," said Professor Scholtz."I don't think the sea spiders will play a crucial role, but who knows? The more you know about regeneration in the animal kingdom, the better you might be able to use it for medical treatment." | Biology |
There is a lot of reports that Ray Kurzweil predicted immortality will be achieved by 2030. Here is the section of the September, 2022 interview with Lex Fridman where Ray talked about Longevity Escape velocity starting around 2030.
His belief is based upon going all in with rapidly improving AI to speed the advance of antiaging medicine. I get to the specifics of Ray’s beliefs and statements and the actual work of applying AI to accelerate drug discovery and progress with antiaging work.
Demis Hassabis and Deep Mind developed Alphafold to solve protein folding. This is the leading edge of AI for accelerate drug discovery.
The significance of AlphaFold
AlphaFold has demonstrated significant progress in tackling the protein-folding problem. Hassabis shared, “Prior to us entering the field with AlphaFold 1 in 2018, and then AlphaFold 2 in 2020, if we look at the decade of progress before that, from 2006 to 2016, on the previous CASP editions, you can see that essentially there’d been no progress for pretty much a decade.”
AlphaFold, a system capable of predicting protein structures with remarkable accuracy, could have far-reaching implications for the future of drug discovery and development. Hassabis believes that this groundbreaking technology will usher in a new era of digital biology, saying, “AlphaFold, I think, is that proof of concept.” He added that the system promises to herald “the dawn of a new era of what we like to refer to as ‘digital biology.’”
AlphaFold is not the only system from a tech company focused on proteins. Scientists at Facebook’s parent Meta have also developed an AI language model known as ESMFold to predict the unknown structures of more than 600 million proteins pertaining to viruses, bacteria and other microbes. The researchers repurposed the model, first designed for decoding human languages, to make accurate predictions regarding proteins’ 3D structure.
Virtual Cell
Deepmind is also working on a number of other projects in chemistry and biology to expedite the drug discovery process. Hassabis envisions the development of a “virtual cell” that models all cellular dynamics and can be used to perform in silico experiments. This would streamline the research process, requiring wet lab validation only at the final stage.
Meta and Deepmind could both offer useful approaches. That is, ESMFold’s speed advantage could complement AlphaFold’s higher accuracy. Researchers could potentially use ESMFold for initial predictions or for large-scale projects, and then refine the results using AlphaFold for specific proteins of interest. This combination could optimize the research process and maximize the benefits of both models.
Breakthroughs like AlphaFold and ESMFold have the potential to catalyze progress drug discovery and other scientific fields, potentially helping usher in a new era in digital biology. Hassabis’ presentation showcased DeepMind’s ambitious vision, while stressing the need for safety, responsibility and ethics in AI development.
A Virtual Cell could be achieved by 2030 and it could speed up some work. It could then be expanded to virtual organs and then virtual bodies for fast virtual clinical trials.
Ray believes there is an accelerating pace of technology and the growing power of AI is now widely accepted. The biotechnology revolution has arrived and has begun to radically change the way medical problems are solved. As these concepts become reality, the question of whether we want to live forever is becoming less theoretical and more real. Here is an excerpt from that Singularity University Alumni conversation.
Ray on Simulating Biology – Applying AI to Biology
Ray said — We are now applying AI to life extension. We’re actually simulating biology, so we can now do tests with simulated biology. Take the Moderna vaccine for example. They actually tested several billion different mRNA sequences and found ones that could create a vaccine. They did this in three days and that was the vaccine. They then spent ten months testing it on humans, but it never changed. It remained the same and it’s the same today. Ultimately, we won’t need to test on humans. We will be able to test on a million simulated humans which will be much better than testing on a few hundred real humans.
It is good that we had the vaccine otherwise many more people would have died. I’m not saying we’re there yet but we are beginning to simulate biology and ultimately we’ll find solutions to all the problems we have in medicine using simulated biology. So, we’ve just begun. I think we’ll see that being very prominent by the end of this decade. But people have to want to live forever. If they avoid solutions to problems then they won’t take advantage of these advances. So we’ll have the opportunity, but that doesn’t mean everybody will do it.
Brian Wang is a Futurist Thought Leader and a popular Science blogger with 1 million readers per month. His blog Nextbigfuture.com is ranked #1 Science News Blog. It covers many disruptive technology and trends including Space, Robotics, Artificial Intelligence, Medicine, Anti-aging Biotechnology, and Nanotechnology.
Known for identifying cutting edge technologies, he is currently a Co-Founder of a startup and fundraiser for high potential early-stage companies. He is the Head of Research for Allocations for deep technology investments and an Angel Investor at Space Angels.
A frequent speaker at corporations, he has been a TEDx speaker, a Singularity University speaker and guest at numerous interviews for radio and podcasts. He is open to public speaking and advising engagements. | Biology |
Taurine - a nutrient found in meat, fish and sold as a supplement - extends life and boosts health in a range of animal species, scientists say.
Levels of taurine decline with age in different species, including people.
Experiments on middle-aged animals showed boosting taurine to youthful levels extended life by over 10% and improved physical and brain health.
The researchers say taurine may be an "elixir of life" - but topping up levels in people has not been tested.
So the team, at Columbia University, in New York, recommend against people buying taurine pills or energy drinks packed with taurine in an attempt to live longer.
The animal research is, however, the latest development in the hunt for ways of slowing ageing.
This study started by analysing molecules in the blood of different species - to explore the differences between young and old.
"One of the most dramatically downgraded [molecules] was taurine," researcher Dr Vijay Yadav said. In elderly people, levels were 80% lower than in the young.
Taurine is virtually non-existent in plants. So the nutrient either comes from animal protein in diet or is manufactured by the body.
And for the past 11 years, the research team have been trying to flesh out its role in ageing.
'Improved memory'
A daily dose was given to 14-month-old mice, which is equivalent to about age 45 for humans.
The results, published in the journal Science, showed male mice lived 10% longer, females 12%, and both appeared to be in better health.
"Whatever we checked, taurine-supplemented mice were healthier and appeared younger," Dr Yadav said.
"They were leaner, had an increased energy expenditure, increased bone density, improved memory and a younger-looking immune system."
Increases in lifespan of 10-23% were also recorded in worms.
Then, 15-year-old rhesus monkeys were given a six-month course of taurine - too short to notice a difference in life expectancy but, again, the researchers found improvements in body weight, bone, blood-sugar levels and the immune system.
"I thought this is almost too good to be true," said Prof Henning Wackerhage, who was involved in the research at the Technical University of Munich. "Taurine somehow hits the engine room of ageing."
But many of the big questions remain unanswered:
- Would the same results be possible in people?
- Why do taurine levels fall in the first place, if it is so good for health?
- How does it slow ageing?
- Are there any dangers in taking taurine?
The researchers performed an analysis of 12,000 people and showed those with more taurine in their blood were generally in better health.
If the data from mice applied to people, it would be the equivalent of an extra seven to eight years of life, they say.
But it will take proper clinical trials - where some people are given the nutrient and others a placebo pill - to see if any benefit can be detected.
Differences in human biology may stop taurine from working or there may be some evolutionary reason why levels are meant to fall with age. Current evidence - including energy drinks being on the market for decades - suggests taurine is safe.
Healthy diet
While taurine is in our diet, it would be hard to eat the quantities used in the experiments. The equivalent dose from the animal experiments, scaled up to people would be 3-6g (0.2oz) per day.
Dr Yadav refused to say whether he chose to take taurine supplements himself, for fear of unduly influencing people.
He told BBC News: "Let us wait for the clinical trials to be completed before recommending to the wider population that they go to the shelf in a grocery store and buy taurine."
Prof Wackerhage said rather than rushing for supplements, there were already proven ways of living longer.
"If you want to live a long, healthy and happy life, then you need a healthy diet - that's one of the most important things - and of course, you should exercise," he said.
Power stations
The scientific report suggests taurine plays a role in reducing cellular senescence - where cells in the body stop dividing - a hallmark of ageing.
The nutrient also appeared to keep mitochondria - the power stations in the body's cells - functioning.
But how it does any of this remains unexplored.
Commenting on the findings, Joseph McGaunn and Joseph Baur, both from the University of Pennsylvania, said: "A singular focus on increasing dietary taurine risks driving poor nutritional choices, because plant-rich diets are associated with human health and longevity.
"Thus like any intervention, taurine supplementation with the aim of improving human health and longevity should be approached with caution."
Follow James on Twitter. | Biology |
University of Oxford researchers have contributed to the first successful extraction of ancient DNA from a 2,900 year-old clay brick. The analysis, published today in Nature Scientific Reports, provides a fascinating insight into the diversity of plant species cultivated at that time and place, and could open the way to similar studies on clay material from different sites and time periods.
During a digitalization project at the Museum in 2020, the group of researchers were able to obtain samples from the inner core of the brick - meaning that there was a low risk of DNA contamination since the brick was created. The team extracted DNA from the samples by adapting a protocol previously used for other porous materials, such as bone.
After the extracted DNA had been sequenced, the researchers identified 34 distinct taxonomic groups of plants. The plant families with the most abundant sequences were Brassicaceae (cabbage) and Ericaceae (heather). Other represented families were Betulaceae (birch), Lauraceae (laurels), Selineae (umbellifiers), and Triticeae (cultivated grasses).
With the interdisciplinary team comprising assyriologists, archaeologists, biologists, and geneticists, they were able to compare their findings with modern-day botanical records from Iraq as well as ancient Assyrian plant descriptions.
The brick would have been made primarily of mud collected near the local Tigris river, mixed with material such as chaff or straw, or animal dung. It would have been shaped in a mould before being inscribed with cuneiform script, then left in the sun to dry. The fact that the brick was never burned, but left to dry naturally, would have helped to preserve the genetic material trapped within the clay.
Dr Sophie Lund Rasmussen (Wildlife Conservation Research Unit, Department of Biology, University of Oxford), joint first author of the paper, said: ‘We were absolutely thrilled to discover that ancient DNA, effectively protected from contamination inside a mass of clay, can successfully be extracted from a 2,900-year-old brick. This research project is a perfect example of the importance of interdisciplinary collaboration in science, as the diverse expertise included in this study provided a holistic approach to the investigation of this material and the results it yielded.’
In addition to the fascinating insight this individual brick revealed, the research serves as a proof of concept and method which could be applied to many other archaeological sources of clay from different places and time periods around the world, to identify past flora and fauna. Clay materials are nearly always present in any archaeological site around the world, and their context means they can often be dated with high precision.
‘Because of the inscription on the brick, we can allocate the clay to a relatively specific period of time in a particular region, which means the brick serves as a biodiversity time-capsule of information regarding a single site and its surroundings. In this case, it provides researchers with a unique access to the ancient Assyrians’ said Dr Troels Arbøll, joint first author of the paper and junior research fellow at the Faculty of Asian and Middle Eastern Studies, University of Oxford, when the study was conducted.
The study ‘Revealing the secrets of a 2900‑year‑old clay brick, discovering a time capsule of ancient DNA’ has been published in Nature Scientific Reports.
The research was conducted in collaboration with Troels Pank Arbøll from Department of Cross-Cultural and Regional Studies, University of Copenhagen; Sophie Lund Rasmussen from the Wildlife Conservation Research Unit, Department of Biology, University of Oxford; Anne Haslund Hansen from Modern History and World Cultures, National Museum of Denmark; Nadieh de Jonge, Cino Pertoldi and Jeppe Lund Nielsen from Department of Chemistry and Bioscience, Aalborg University and Aalborg Zoo (CP). | Biology |
Reef-devouring predator survives coral bleaching and feasts on the survivors
Research conducted by marine biologists from the University of Sydney has found juvenile crown-of-thorns starfish can withstand tremendous heat waves well above levels that kill coral. These starfish then develop into carnivorous predators that devour reefs just as they begin to regrow.
Crown-of-thorns starfish are native to the Great Barrier Reef and found in the Indo-Pacific region, but they are classified as a species of concern because the damage large populations cause to coral is more significant than any other species. They fall behind only cyclones and bleaching events in their impact on coral mortality.
The research is published in the journal Global Change Biology, led by Professor Maria Byrne from the School of Life and Environmental Sciences. She is also a member of the Marine Science Institute and Sydney Environment Institute.
Over the course of the experiment, juvenile crown-of-thorns displayed a surprisingly high heat tolerance, higher than that observed in their adult counterparts. This means that even if the coral-eating adult stage declines in climate change-driven ocean warming scenarios, perhaps from a lack of their coral prey or from the heat, their herbivorous young can wait patiently for the opportune moment to grow into carnivores.
Coral bleaching and death can be triggered when waters warm by 1-3 degrees Celsius above the normal summer maximum, depending on how long the temperature lasts.
"We found juvenile crown of thorns starfish can tolerate almost three times the heat intensity that causes coral bleaching, using a model that measures temperature over time," Professor Byrne said.
"This is an important finding that has implications for understanding the impacts of climate change on marine ecosystems, especially the influence of understudied small cryptic species. Juveniles might well benefit from warming waters. The increase in the amount of their rubble habitat, generated by coral bleaching and mortality, allows their numbers to build over time."
The crown-of-thorns starfish is nature's ultimate coral predator, with a circle of life perfectly adapted to warming waters.
During outbreaks of their carnivorous adult phase, crown-of-thorns starfish dine pervasively on stony coral, leaving lifeless skeletons across the reef. These skeletons eventually become home to algae before crumbling. Bleaching induced coral mortality has a similar effect.
The remains of dead coral may provide the perfect habitat for the starfish's tiny, algae-eating offspring. According to previous research by Professor Byrne, the juveniles can survive, and wait, for at least six years for the reef to come back to life, and given the opportunity as coral recovers these juveniles can grow into coral-eating predators and start the cycle again.
"The heat resistance and potential for the juveniles to gradually buildup in the reef infrastructure in coral rubble over years might be a phenomenon contributing to the initiation of adult crown-of-thorns starfish outbreaks," said Matt Clements, Ph.D. student and co-author of the study.
"Loss of natural predators due to overfishing and the buildup of nutrients in the water have been suspected to contribute to outbreaks of crown-of-thorns starfish. Now we have evidence that bleaching induced coral mortality could aid the sea floor-dwelling juveniles, leading to subsequent large waves of adults in reefs which exacerbate the ravages of climate change."
The researchers also identified factors that contribute to the juveniles' ability to survive in warming conditions. They include small size, which may reduce physiological requirements, and their ability to feed on a variety of food sources, despite preferring a diet of coralline algae.
More information: Juvenile waiting stage crown‐of‐thorns sea stars are resilient in heatwave conditions that bleach and kill corals, Global Change Biology (2023). DOI: 10.1111/gcb.16946
Journal information: Global Change Biology
Provided by University of Sydney | Biology |
Snakes are fascinating creatures, forming about one-eighth of vertebrate animals found on land. They come in a wide range of forms and sizes and have adjusted to different ways of life, such as living underground, on the land, in water, and up in trees. However, the early evolution of snakes and the changes in their morphologies over time has been long debated in the field of biology.
To help unravel this mystery, researchers from the HiLIFE Institute of Biotechnology, University of Helsinki used a different way of studying snake evolution.
“Instead of relying on rare, old fossil remains to learn about the history of snakes, we looked at the brains of living reptiles and traveled back in time, thanks to modern imaging and analysis tools” says the first author of the study, Postdoctoral Researcher Simone Macrì.
By using high-definition 3D models of modern lizard and snake brains, researchers reconstructed the brain shape of early snakes and discovered that they were fully adapted for underground living. Nevertheless, early snakes also displayed versatile behaviors, as evidenced by the mixture of different features and complex patterns in their brain morphologies, which may reflect differences in what they eat, how they use different environments both below and above the ground, and their ability to search for food.
Understanding animal evolution beyond fossils
“What's really exciting is that this study is not only about snakes! It's also showing us a way to learn about other animals whose history is a bit of a mystery because we lack fossils for studying them”, describes Principal Investigator Nicolas Di-Poï, Research Director at the Institute of Biotechnology, University of Helsinki.
By examining both present-day animals and those from the past, along with bones and different crucial organs like the brain, scientists can piece together the story of how these creatures changed and evolved over time.
This research underscores a vital lesson for the field of biology: unraveling the mysteries of animal evolution goes beyond the analysis of bone remains. To comprehend the transformation of creatures like snakes over time, scientists must consider other components of their bodies, including soft tissues and internal organs. This is particularly crucial when studying animals from eras when their bones might not have been well-preserved.
Original article
Macrì, S., Aalto, I.M., Allemand, R., and Di-Poï, N. Reconstructing the origin and early evolution of the snake brain. Science Advances, DOI: 10.1126/sciadv.adi6888 | Biology |
A rare case of mad cow disease, also known as bovine spongiform encephalopathy (BSE), has been detected at a slaughter plant in South Carolina but poses no threat to humans or other cattle. It is only the seventh confirmed case of the extremely deadly disease ever recorded in the U.S.
Officials from the U.S. Department of Agriculture (USDA) announced the discovery in a statement released May 19. A 5-year-old beef cow belonging to a herd from Tennessee tested positive for BSE after being deemed unfit for slaughter and undergoing routine testing.
"This animal never entered slaughter channels and at no time presented a risk to the food supply or to human health in the United States," USDA representatives wrote in the statement. An investigation into the exact cause of the infection is ongoing, but it is likely an isolated case, they added.
BSE is a progressive neurological disorder of cattle caused by proteins called prions; prions are found on the surface of cells, but in diseases like mad cow, these proteins fold abnormally and can cause other, healthy prions to do the same. In BSE, the prions affect proteins in the brain and central nervous system, causing a range of symptoms, including behavioral changes, coordination problems, weight loss, decreased milk production and eventually, death, according to the USDA.
There are two forms of BSE: classical BSE, which develops when a cow ingests infected material, such as meat or bone meal, made from an infected cow in their feed; and atypical BSE, which develops spontaneously in older cattle. The recently diagnosed cow had atypical BSE, which poses less of a concern for animal welfare officials.
There are two forms of BSE: classical BSE, which develops when a cow ingests infected material, such as meat or bone meal, made from an infected cow in their feed; and atypical BSE, which develops spontaneously in older cattle. The recently diagnosed cow had atypical BSE, which poses less of a concern for animal welfare officials.
Atypical vs. classical BSE
Both classical and atypical BSE are caused by prions, but each of the two forms has a unique prion structure and is triggered in different ways.
Classical BSE was first discovered in 1986 in the U.K.. The BSE outbreak peaked there in January 1993, when cases spiked to around 1,000 a week, according to the Centers for Disease Control and Prevention.
Scientists eventually discovered that the prions were being transmitted through the cows' feed, which contained infected brain and spinal tissues left over from the butchering of the animals. In 1997, the U.S. Food and Drug Administration (FDA) banned the use of use of ruminant — a group of hoofed, herbivorous grazing mammals that includes cattle, bison, goats, sheep and deer — protein in feed for other ruminants, and it later prohibited the use of certain high-risk cattle tissues in feed for all animals, according to the USDA.
Atypical BSE appears to sometimes form spontaneously in cattle that are normally older than 8 years, which makes the disease's emergence in a 5-year-old cow unusual. It is currently unclear what triggers atypical BSE.
It can take three to six years for the symptoms of either BSE form to appear after infection, and there is currently no cure or vaccine for the disease, according to USDA.
Can humans get mad cow disease?
Humans cannot get BSE directly, but they can develop a similar and equally deadly type of prion disease known as Creutzfeldt-Jakob disease (vCJD) by eating food products made from infected cattle. vCJD causes symptoms similar to BSE and also results in death. However, it is extremely rare. As of 2019, only 232 people worldwide have ever been diagnosed with vCJD, according to the FDA.
In an unusual case, a lab technician in France died in June 2019 from vCJD after accidentally injecting herself with BSE prions through her protective equipment as she was studying the disease in 2010.
The World Organisation for Animal Health recognizes the U.S. as having negligible risk for BSE, and this new case will not change that, USDA representatives wrote.
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Harry is a U.K.-based staff writer at Live Science. He studied Marine Biology at the University of Exeter (Penryn campus) and after graduating started his own blog site "Marine Madness," which he continues to run with other ocean enthusiasts. He is also interested in evolution, climate change, robots, space exploration, environmental conservation and anything that's been fossilized. When not at work he can be found watching sci-fi films, playing old Pokemon games or running (probably slower than he'd like). | Biology |
New sound navigation technology enables the blind to navigate
A new study by researchers at Reichman University's Brain Cognition and Technology Institute directed by Prof. Amir Amedi has shown that visual navigation areas in the brain can be activated using sound. By traversing mazes using sound information instead of visual information after training, visual navigation areas were activated.
This finding has numerous exciting implications, among them the findings chip away at the Nobel Prize winning theory of critical periods and provide new avenues for cognitive training to potentially detect and prevent Alzheimer's disease.
The team conducted a series of studies over the past years that challenge conventional beliefs about the human brain's functioning; claiming that the brain is divided by tasks, rather than the commonly accepted division by senses (seeing area, hearing area, etc...). These studies utilized Sensory Substitution Devices (SSDs), which are remarkable tools that transfer sensory information from one sense through another sense.
For example, SSDs can help visually impaired individuals "see" by converting visual information into sounds. Following training, individuals can identify shapes, object locations, words, letters, and even faces when represented through sound. Training on SSDs has been shown to be effective on people even in their 40's—60's+, calling to question the idea that there are critical periods for development of senses.
The classic theory of critical periods suggests that the senses can only be developed early in life, during childhood, through exposure to sights, sounds, and so on. And if they do not develop during this period, they cannot be used later in life. The fact that SSDs can be used for effective training well into adulthood, suggests that the theory of critical periods needs to be revised.
Taking this to the extreme, this body of research has shown that the brain can be reprogrammed through this training so that visual areas in the brain can be activated even in people with zero visual experience.
These non-invasive devices, SSDs, offer researchers unique opportunities to observe how different brain regions respond when relevant information comes from another sense. Using functional magnetic resonance imaging (fmri), the researchers in this new study examined the impact of using SSDs on visual retinotopically organized areas of the brain, in this case specifically Area V6, which is responsible for visual navigation and motion perception.
The results of this study indicate that through short training with the EyeCane, an SSD that conveys spatial information about the visual surroundings through sounds, even those who are congenitally blind can develop selective activation in Area V6.
The study further supports the idea that, despite years or a lifetime of blindness, the brain has the potential to process visual tasks and properties if the right technologies and training are employed. Additionally, the study found that the area contains motor neurons responsible for egocentric navigation.
Importantly, the findings from this study may have implications for improving detection and prevention of Alzheimer's disease. Spatial deficits are a common early symptom of Alzheimer's disease and navigation and spatial cognition rely on V6 among other brain regions. The fact that V6 can develop its selectivity for navigation in the absence of visual experience, as seen in the congenitally blind participants using the EyeCane SSD, suggests that there may be ways to train and enhance navigation abilities in individuals at risk for Alzheimer's disease, such as older adults or those with mild cognitive impairment.
Furthermore, by better understanding the neural mechanisms underlying development and functioning of spatial navigation, we may be able to identify early biomarkers and targets for interventions aimed at preventing or slowing the progression of Alzheimer's disease.
The work is published in the journal Current Biology.
More information: Elena Aggius-Vella et al, Activation of human visual area V6 during egocentric navigation with and without visual experience, Current Biology (2023). DOI: 10.1016/j.cub.2023.02.025 | Biology |
by Deborah Pirchner, Frontiers science writer
Forests are excellent at absorbing and storing carbon and can play a role in meeting global net zero targets. As more countries commit to forest creation, but mainly plant single species forests, an international team of researchers has examined how carbon stocks in mixed forests and monocultures compare. They found that mixed forests store more carbon, and that out of the forests assessed those with four species had the highest carbon stocks relative to monocultures.
To slow the effects of climate change, conserve biodiversity, and meet the sustainable development goals, replanting trees is vital. Restored forests store carbon within the forest’s soil, shrubs, and trees. Mixed forests are especially effective at carbon storage, as different species with complementary traits can increase overall carbon storage. Compared to single-species forests, mixed forests are also more resilient to pests, diseases, and climatic disturbances, which increases their long-term carbon storage potential. The delivery of other ecosystem services is also greater in mixed species forests, and they support higher levels of biodiversity.
Although the benefits of diverse forest systems are well known, many countries’ restoration commitments are focused on establishing monoculture plantations. Given this practice, an international team of scientists has compared carbon stocks in mixed planted forests to carbon stocks in commercial and best-performing monocultures, as well as the average of monocultures.
“Diverse planted forests store more carbon than monocultures – upwards of 70%,” said Dr Emily Warner, a postdoctoral researcher in ecology and biodiversity science at the Department of Biology, University of Oxford, and first author of the study published in Frontiers in Forests and Global Change. “We also found the greatest increase in carbon storage relative to monocultures in four-species mixtures.”
Species richness increases carbon storage potential
The researchers analyzed studies published since 1975 that directly compared carbon storage in mixed and single-species forests, and combined this with previously unpublished data from a global network of tree diversity experiments. “We wanted to pull together and assess the existing evidence to determine whether forest diversification provides carbon storage benefits,” Warner explained.
The mixed planted forests assessed in the study ranged in species richness from two to six species. In the dataset the scientists worked with, four-species mixtures were the most effective carbon sinks. One such mix was made up from different broadleaf trees which can be found across Europe. Mixes with two species also had greater aboveground carbon stocks than monocultures and stored up to 35% more carbon. Forests made up of six species, however, showed no clear advantage to monocultures. Accordingly, the researchers were able to show that diversification of forests enhances carbon storage. Altogether, aboveground carbon stocks in mixed forests were 70% higher than in the average monoculture. The researchers also found that mixed forests had 77% higher carbon stocks than commercial monocultures, made up of species bred to be particularly high yielding.
Forests for the future
“As momentum for tree planting grows, our study highlights that mixed species plantations would increase carbon storage alongside other benefits of diversifying planted forests,” said Dr Susan Cook-Patton, a senior forest restoration scientist at The Nature Conservancy and collaborator on the study. The results are particularly relevant to forest managers, showing that there is a productivity incentive for diversifying new planted forests, the researchers pointed out.
While showing the increased potential of mixed forests to store more carbon, the researchers cautioned that their study is not without limitations, including the overall limited availability of studies addressing mixed vs monoculture forests, particularly studies from older forests and with higher levels of tree diversity.
“This study demonstrates the potential of diversification of planted forests, and also the need for long-term experimental data to explore the mechanisms behind our results,” Warner said. “There is an urgent need to explore further how the carbon storage benefits of diversification change depending on factors such as location, species used and forest age.”
REPUBLISHING GUIDELINES: Open access and sharing research is part of Frontiers’ mission. Unless otherwise noted, you can republish articles posted in the Frontiers news site — as long as you include a link back to the original research. Selling the articles is not allowed. | Biology |
Standing on the marina, Rob Skelly peers into the darkness of the river where bright speckles of algae drift in the water. A neon green invader. “It’s starting to build,” he says. “Tomorrow, you’ll find that there’s clumps like that all over the river—and then the day after that there’ll be more and more.”
Until this summer, Skelly had never seen algae wax and wane like this in the River Bann, a major waterway in Northern Ireland. The owner of the Cranagh Activity Centre set up his thriving water sports business 27 years ago, and it has been in this location since 2015. The algae has killed it. Following news reports of toxin-producing blue-green algae in lakes and rivers around Northern Ireland, people began canceling their bookings for water-skiing lessons and similar activities in droves.
Skelly doesn’t blame them. “How can I put customers into that?” he says, looking at the mottled water below us. The season ruined, Skelly has decided to close his business for good. “You know, it’s heartbreaking.”
Blue-green algae is coming to a river or lake near you, almost without doubt. The scourge of toxic blooms is becoming increasingly problematic worldwide, in part due to the climate crisis. Despite the name, blue-green algae aren’t actually algae, but a group of photosynthesizing bacteria called cyanobacteria. Under the right conditions, they can suddenly proliferate across huge expanses of water, leaving characteristic grayish-blue marks at the edges of lakes or rivers. Often, a highly unpleasant, rich, drain-like smell pervades in affected areas.
These microbes sometimes produce huge quantities of toxins—cyanotoxins—which can cause diarrhea, vomiting, breathing difficulties, and occasionally even death in humans. Outbreaks have been associated with pet and livestock fatalities. People in the United States living near lakes where cyanobacteria regularly bloom have a higher risk of liver cancer, and some research suggests that cyanotoxins might even cause motor neurone disease, though further investigations are warranted to prove that particular connection. Research suggests that cyanotoxins can likely be aerosolized and breathed in when water is kicked up during recreational activities or fishing.
Genetic analysis hints that cyanobacteria have been around for roughly 3 billion years. While the dumping of sewage and nutrient runoff from farms have long been known to swell the bacteria’s ranks in bodies of water, the cyanobacteria seem to be really flourishing now as global temperatures and atmospheric levels of CO2 rise.
“That, I think, is the really compelling evidence for the link to climate change—we’re seeing these increases in places where there hasn’t been a really substantial increase in urbanization or fertilizer application,” says Hans Paerl at the University of North Carolina-Chapel Hill’s Institute of Marine Sciences. “It is a global problem.”
Cyanobacteria are proving to be a menace practically everywhere—from Florida to Africa and China, to name a few examples. In China’s Lake Taihu, the blooms are so bad that authorities have battled for years to physically remove the sludge with special machines that chew it up using hundreds of tiny teeth.
This year in Northern Ireland, some of the most serious blooms have occurred in Lough Neagh, the largest body of fresh water by surface area in the UK and Ireland. Some locals have described algal blooms on the lough as the worst they have seen in their lifetimes, and there have been reports of multiple dog deaths possibly caused by cyanotoxins. From Lough Neagh, water flows into the River Bann and heads north toward the town of Coleraine, where Rob Skelly’s water sports business was located until recently. Finally, the Bann enters the sea on the north coast of Northern Ireland. Warnings about blue-green algae were put up on beaches there earlier this summer.
WIRED showed Paerl pictures of a blueish residue above the waterline at a jetty very near to Lough Neagh. “It’s an indication of very high amounts of material,” he says.
Around 40 percent of all Northern Ireland’s drinking water is sourced from Lough Neagh. NI Water, the public body responsible for drinking water, says it uses methods known to remove cyanotoxins. Chlorination alone is not enough, notes Paerl. In 2007, a blue-green algal bloom at Lake Taihu in China was so severe that 2 million people were forced to go without drinking water for at least a week.
A spokeswoman for NI Water says that drinking water is treated using granular activated carbon, a kind of filtration that removes certain chemicals, including cyanotoxins. Tests for one particular cyanotoxin, microcystin-LR, in drinking water post-treatment have consistently shown extremely low levels throughout 2023, well below World Health Organization guidelines, she adds.
However, NI Water does not test for cyanotoxins in the source water. “To the best of my knowledge, no one has yet tested for toxins either in water or fish,” says Matt Service at Northern Ireland’s Agri-Food and Biosciences Institute. Some local scientists are concerned that our understanding of how abundant these toxins are in places like Lough Neagh remains very murky.
“I was interested in whether I could get some funding to specifically study the toxicology of the blue-green algae,” says Neil Reid, a senior lecturer in conservation biology at Queen’s University Belfast. He has collected multiple samples of surface water but hasn’t yet been able to secure the funding needed to conduct research on them.
Reid points out that quite a lot of the visible sludge could be a harmless species of algae and not the dreaded cyanobacteria. It would help local people understand the risk when fishing on the lough, for example, if they knew more about its toxicity, he suggests. But, for now, the samples will remain frozen in a laboratory freezer.
Besides nutrients entering lakes and rivers, which can spur the proliferation of algae and cyanobacteria, there are other factors that can trigger major blooms. Northern Ireland just had its wettest July on record—potentially accelerating the runoff of nutrients into bodies of water including Lough Neagh, says Reid. The lough is also 1° Celsius warmer today than it was just 30 years ago. That could benefit cyanobacteria over competing species, including algae, says Don Anderson, a senior scientist in the biology department at Woods Hole Oceanographic Institution in Massachusetts.
“When it gets too hot, other species don’t grow, or grow slowly,” he explains. “Cyanobacteria are extraordinarily flexible in terms of their tolerance.”
Then there’s the zebra mussels. These invasive mollusks have been resident in Lough Neagh since at least 2005. Here, as in other lakes in Europe and the United States, they appear to have consumed large quantities of algae, clarifying the water in the process. That might sound good, but the problem, Reid explains, is that this then allows more light into the lake, potentially giving the cyanobacteria a chance to thrive while their competitors get gobbled up by the mussels.
“I think it’s a very reasonable hypothesis,” says Robin Rohwer at the University of Texas at Austin, who has studied the prevalence of cyanotoxins in Lake Mendota in Wisconsin. Data collected across two decades suggests that, following zebra mussel invasion, the “toxic season” on the lake during the summer lengthened dramatically—lasting more than 50 days longer, on average. There are plenty of mysteries, though. Rohwer says she didn’t detect a boom in the cyanobacteria itself, just an increase in the volume of toxins present in the lake. What’s driving that remains unclear.
Rohwer adds that, as someone who enjoys sailing on the lake herself, she avoids boating whenever algae buildup is visible. In unpublished results, she says she has found that toxin levels out in the middle of the lake aren’t usually a serious concern—though she has detected “extremely toxic” scum washed up at the shoreline.
There’s little that humans can do to stymie blue-green algal blooms, says Paerl. And Rohwer notes that it is practically impossible to eradicate zebra mussels once they have become established. The only tactic available, really, is reducing nutrient runoff into lakes and rivers, for example by lowering fertilizer use on farms and building buffer zones or artificial wetlands around the edges of large bodies of water to try to soak up the nutrients. Paerl says such efforts have been reasonably successful in North Carolina, for example.
For Rob Skelly, the damage, sadly, is already done. He says he has spent recent months chasing public bodies over the cyanobacteria problem. “Nobody will take responsibility,” he alleges, adding that the sudden closure of his business feels like the end of an era. Many former customers have been in touch, he says, to express their regret at what has happened.
“I have loved every day of my working life because I’ve had the river. It’s just been part of my DNA,” adds Skelly. “I never thought it would be the river that would come back and bite me.”
This story originally appeared on wired.com. | Biology |
With the school year underway around the U.S., parents and caregivers are once again faced with the age-old struggle of wrangling groggy kids out of bed in the morning. For parents of preteens and teenagers, it can be particularly challenging. Sometimes this gets chalked up to laziness in teens. But the main reason why a healthy person is unable to naturally wake up without an alarm is that they are not getting the sleep their brain and body need. That’s because studies show that adolescents need more than nine hours of daily sleep to be physically and mentally healthy. But the likelihood that you know a teenager who gets enough sleep is rather slim. In the U.S., less than 30% of high school students – or those in grades 9 through 12 – sleep the recommended amount, according to the Centers for Disease Control and Prevention. Among middle schoolers in grades 6-8, nearly 60% do not get enough sleep at night. Yet my laboratory’s research suggests that a much higher percentage of teens are getting too little sleep. I am a professor of biology and have been studying sleep and circadian rhythms for more than 30 years. For the past seven years, my laboratory at the University of Washington has been doing research on sleep in Seattle-area teenagers. Our research has found that, just as in other areas of the U.S., high schoolers in Seattle are not getting the amount of sleep they need. Our study objectively measured sleep in 182 high school sophomores and seniors and found only two that slept at least nine hours at night during school days. Our studies and those of others indicate that three important factors lie behind this lack-of-sleep epidemic: a physiological regulation of sleep that leads to a delayed sleep timing in teens and that is not aligned with early school start times, a lack of morning exposure to daylight and excessive exposure to bright electric light and screens late in the evening. Teen sleep biology The time people go to bed, fall asleep and wake up is governed by two main factors in the brain. The first is a so-called “wakefulness tracker,” a physiological timer that increases our need to sleep the longer we stay awake. This is in part the consequence of the accumulation of chemical signals released by neurons, such as adenosine. Adenosine accumulates in the brain when we are awake, leading to increased sleepiness as the day wears on. If, for instance, a person wakes up at 7 a.m., these chemical signals will accumulate throughout the day until the levels are high enough that the person will fall asleep, typically in the late evening. The second factor that drives the sleep/wake cycle is a 24-hour biological clock that tells our brain what times of the day we should be awake and what times we should be sleeping. This biological clock is located in an area of the brain called the hypothalamus. The clock is composed of neurons that coordinate the brain areas regulating sleep and wakefulness to a 24-hour sleep/wake cycle. These two regulators operate with relative independence from each other. But under typical conditions, they are coordinated so that a person with access to electric-powered light would fall asleep in the late evening – between about 10 p.m. to 11 p.m., and wake up in the early morning, around 6 a.m. to 7 a.m. So why do teenagers often want to go to bed later and wake up later than their parents? It turns out that during adolescence, both the wakefulness tracker and the biological clock conspire to delay the timing of sleep. First, adolescents can be awake until later hours before their wakefulness tracker makes them feel sleepy enough to fall sleep. Second, the biological clock of teenagers is delayed because in some cases it appears to run at a slower pace, and because it responds differently to light cues that reset the clock daily. This combination leads to a sleep cycle that operates a couple of hours later than in an older adult – if an older adult feels the signals to fall asleep around 10 p.m. or 11 p.m., this won’t happen until midnight or later in a teenager. Sufficient sleep is key to teen health, but many things prevent adolescents from getting enough of it. How school start times contribute To help find more hours of sleep for teens, one measure that some school districts around the country have taken is to delay the school start time for middle schools and high schools. The American Academy of Pediatrics recommends that schools for this age group should not start before 8:30 a.m.. Yet the majority of high schools in the U.S start at 8 a.m. or earlier. Based on the recommendation of sleep experts, the Seattle school district, beginning with the 2016-2017 school year, delayed middle school and high school start times by nearly an hour, from 7:50 a.m. to 8:45 a.m. In a study our team conducted after the district enacted the plan, we found that students gained 34 minutes of daily sleep – a huge gain by sleep medicine standards. In addition, student attendance and punctuality improved, and median grades went up by 4.5%. Despite an abundance of research evidence and the advice from virtually all sleep experts in the country, most school districts are still stuck with school start times that promote chronic sleep deprivation in teenagers. The early school starts are further aggravated by daylight saving time – when clocks are set one hour ahead in the springtime. This time shift – one that could become permanent in the U.S. in 2023 – exposes teenagers to artificially dark mornings, which exacerbates their naturally delayed sleep timing. Teaching healthy sleep habits to teens School start times aside, kids also need to learn the importance of healthy habits that promote sufficient sleep. Getting bright daylight exposure, particularly during the morning, pushes our biological clock to an earlier time. This, in turn, will promote an earlier bedtime and a natural early morning wake time. In contrast, light in the evening – including the light emitted by screens – is highly stimulating to the brain. It inhibits the production of natural signals such as melatonin, a hormone that is produced by the brain’s pineal gland as the night arrives and in response to darkness. But when these cues are inhibited by artificial light in the evening, our biological clocks are delayed, promoting a later bedtime and a later morning wake time. And thus the cycle of having to roust a sleepy, yawning teenager from bed for school begins again. Yet few schools teach the importance of good daily routines and sleep timing, and parents and teens also do not fully appreciate their importance. Chronic sleep deprivation disrupts every physiological process in the body and has been consistently linked to disease, including depression and anxiety, obesity and addictive behavior. Conversely, sufficient sleep not only helps to reduce physical ailments and improve mental health, but it has also been shown to be fundamental for optimal physical and mental performance. | Biology |
image: Integrated average morphed cell showing 17 select structures view more Credit: Allen Institute for Cell Science By Rachel Tompa, Ph.D. / Allen Institute Seattle, WA—Working with hundreds of thousands of high-resolution images, the team at the Allen Institute for Cell Science, a division of the Allen Institute, put numbers on the internal organization of human cells — a biological concept that has to date proven exceptionally difficult to quantify. Through that work, the scientists also captured details about the rich variation in cell shape even among genetically identical cells grown under identical conditions. The team described their work in a paper published in the journal Nature today. “The way cells are organized tells us something about their behavior and identity,” said Susanne Rafelski, Ph.D., Deputy Director of the Allen Institute for Cell Science, who led the study along with Senior Scientist Matheus Viana, Ph.D. “What’s been missing from the field, as we all try to understand how cells change in health and disease, is a rigorous way to deal with this kind of organization. We haven’t yet tapped into that information.” This study provides a roadmap for biologists to understand organization of different kinds of cells in a measurable, quantitative way, Rafelski said. It also reveals some key organizational principles of the cells the Allen Institute team studies, which are known as human induced pluripotent stem cells. Understanding how cells organize themselves under healthy conditions — and the full range of variability contained within “normal” — can help scientists better understand what goes wrong in disease. The image dataset, genetically engineered stem cells, and code that went into this study are all publicly available for other scientists in the community to use. “Part of what makes cell biology seem intractable is the fact that every cell looks different, even when they are the same type of cell. This study from the Allen Institute shows that this same variability that has long plagued the field is, in fact, an opportunity to study the rules by which a cell is put together,” said Wallace Marshall, Ph.D., Professor of Biochemistry and Biophysics at the University of California, San Francisco, and a member of the Allen Institute for Cell Science’s Scientific Advisory Board. “This approach is generalizable to virtually any cell, and I expect that many others will adopt the same methodology.” Computing the pear-ness of our cells In a body of work launched more than seven years ago, the Allen Institute team first built a collection of stem cells genetically engineered to light up different internal structures under a fluorescent microscope. With cell lines in hand that label 25 individual structures, the scientists then captured high-resolution, 3D images of more than 200,000 different cells. All this to ask one seemingly straightforward question: How do our cells organize their interiors? Getting to the answer, it turned out, is really complex. Imagine setting up your office with hundreds of different pieces of furniture, all of which need to be readily accessed, and many of which need to move freely or interact depending on their task. Now imagine your office is a sac of liquid surrounded by a thin membrane, and many of those hundreds of pieces of furniture are even smaller bags of liquid. Talk about an interior design nightmare. The scientists wanted to know: How do all those tiny cellular structures arrange themselves compared to each other? Is “structure A” always in the same place, or is it random? The team ran into a challenge comparing the same structure between two different cells. Even though the cells under study were genetically identical and reared in the same laboratory environment, their shapes varied substantially. The scientists realized that it would be impossible to compare the position of structure A in two different cells if one cell was short and blobby and the other was long and pear-shaped. So they put numbers on those stubby blobs and elongated pears. Using computational analyses, the team developed what they call a “shape space” that objectively describes each stem cell’s external shape. That shape space includes eight different dimensions of shape variation, things like height, volume, elongation, and the aptly described “pear-ness” and “bean-ness.” The scientists could then compare apples to apples (or beans to beans), looking at organization of cellular structures inside all similarly shaped cells. “We know that in biology, shape and function are interrelated, and understanding cell shape is important to understand how the cells function,” Viana said. “We’ve come up with a framework that allows us to measure a cell’s shape, and the moment you do that you can find cells that are similar shapes, and for those cells you can then look inside and see how everything is arranged.” Strict organization When they looked at the position of the 25 highlighted structures, comparing those structures in groups of cells with similar shapes, they found that all the cells set up shop in remarkably similar ways. Despite the massive variations in cell shape, their internal organization was strikingly consistent. If you’re looking at how thousands of white-collar workers arrange their furniture in a high-rise office building, it’s as if every worker put their desk smack in the middle of their office and their filing cabinet precisely in the far-left corner, no matter the size or shape of the office. Now say you found one office with a filing cabinet thrown on the floor and papers strewn everywhere — that might tell you something about the state of that particular office and its occupant. The same goes for cells. Finding deviations from the normal state of affairs could give scientists important information about how cells change when they transition from stationary to mobile, are getting ready to divide, or about what goes wrong at the microscopic level in disease. The researchers looked at two variations in their dataset — cells at the edges of colonies of cells, and cells that were undergoing division to create new daughter cells, a process known as mitosis. In these two states, the scientists were able to find changes in internal organization correlating to the cells’ different environments or activities. “This study brings together everything we’ve been doing at the Allen Institute for Cell Science since the institute was launched,” said Ru Gunawardane, Ph.D., Executive Director of the Allen Institute for Cell Science. “We built all of this from scratch, including the metrics to measure and compare different aspects of how cells are organized. What I’m truly excited about is how we and others in the community can now build on this and ask questions about cell biology that we could never ask before.” Rachel Tompa is Senior Editor at the Allen Institute. She covers news from all scientific divisions at the Institute. Get in touch at [email protected]. Method of Research Data/statistical analysis Subject of Research Cells Article Title Integrated intracellular organization and its variations in human iPS cells Article Publication Date 4-Jan-2023 Disclaimer: AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert system. | Biology |
Image caption, The Winchcombe meteorite broke off an asteroid between Mars and JupiterA meteorite that crashed on the Gloucestershire town of Winchcombe last year contained water that was a near-perfect match for that on Earth.This bolsters the idea rocks from space brought key chemical components, including water, to the planet early in its history, billions of years ago.The meteorite is regarded as the most important recovered in the UK.Scientists publishing their first detailed analysis say it has yielded fascinating insights.More than 500g (1lb) of blackened debris was picked up from people's gardens and driveways and local fields, after a giant fireball lit up the night sky.The crumbly remains were carefully catalogued at London's Natural History Museum (NHM) and then loaned to teams across Europe to investigate.Water accounted for up to 11% of the meteorite's weight - and it contained a very similar ratio of hydrogen atoms to the water on Earth.Some scientists say the young Earth was so hot it would have driven off much of its volatile content, including water.For the Earth to have so much today - 70% of its surface is covered by ocean - suggests there must have been a later addition.Some say this could have come from a bombardment of icy comets - but their chemistry is not a great match.Carbonaceous chondrites, however - meteorites such as the Winchcombe one - most certainly are.And the fact it was recovered less than 12 hours after crashing means it had absorbed very little earthly water, or indeed any contaminants."All other meteorites have been compromised in some way by the terrestrial environment," co-first author Dr Ashley King, from the NHM, told BBC News."But Winchcombe is different because of the speed with which it was picked up."This means when we measure it, we know the composition we're looking at takes us all the way back to the composition at the beginning of the Solar System, 4.6 billion years ago."Bar fetching rock samples back from an asteroid with a spacecraft, we could not have a more pristine specimen."Precise trajectoryScientists examining the meteorite's carbon- and nitrogen-bearing organic compounds, including its amino acids, had a similarly clean picture.This is the type of chemistry that could have been a feedstock for biology to begin on the early Earth.The new analysis also confirms the meteorite's origin. Camera footage of the fireball has allowed researchers to work out a very precise trajectory. Calculating backwards, this indicates the meteorite came from the outer asteroid belt between Mars and Jupiter.Image source, NHMImage caption, Winchcombe material recently sold at auction for more than 120 times the value of its weight in goldFurther investigations reveal it was knocked off the top few metres of a parent asteroid, presumably in some collision.It then took only 200,000 to 300,000 years to arrive on Earth, the number of particular atoms, such as neon, created in the meteorite material through the constant irradiation from high-speed space particles, or cosmic rays, reveals."0.2-0.3 million years sounds like quite a long time - but from a geological perspective, it's actually very quick," Dr Helena Bates, from the NHM, said."Carbonaceous chondrites have to get here quickly or they won't survive, because they're so crumbly, so friable, they'll just break apart."'More secrets'The scientists first analysis, in this week's edition of the Science Advances journal, is just an overview of Winchcombe's properties.A dozen more papers on specialist topics are due to come out shortly in an issue of the Meteoritics & Planetary Science journal.And even they will not be the last word."Researchers will continue to work on this specimen for years to come, unlocking more secrets into the origins of our Solar System," co-first author Dr Luke Daly, from the University of Glasgow, said. | Biology |
Percy cored two samples from a rock called "Wildcat Ridge," which is about three feet (one meter) wide, and on July 20 abraded some of its surface so it could be analyzed with an instrument called SHERLOC that uses ultraviolet light.
NASA's Perseverance Mars rover has detected its highest concentrations yet of organic molecules, in a potential signal of ancient microbes that scientists are eager to confirm when the rock samples are eventually brought to Earth. While organic matter has been found on the Red Planet before, the new discovery is seen as especially promising because it came from an area where sediment and salts were deposited into a lake—conditions where life could have arisen.
"It is very fair to say that these are going to be, these already are, the most valuable rock samples that have ever been collected," David Shuster, a Perseverance return sample scientist, told reporters during a briefing.
Organic molecules—compounds made primarily of carbon that usually include hydrogen and oxygen, but also at times other elements—are not always created by biological processes.
Further analysis and conclusions will have to wait for the Mars Sample Return mission—a collaboration between NASA and the European Space Agency (ESA) to bring back the rocks that is set for 2033.
Nicknamed Percy, the rover landed on Mars' Jezero Crater in February 2021, tasked with caching samples that may contain signs of ancient life, as well as characterizing the planet's geology and past climate.
The delta it is exploring formed 3.5 billion years ago. The rover is currently there investigating sedimentary rocks, which came about from particles of various sizes settling in the then watery environment.
Percy cored two samples from a rock called "Wildcat Ridge," which is about three feet (one meter) wide, and on July 20 abraded some of its surface so it could be analyzed with an instrument called SHERLOC that uses ultraviolet light.
The results showed a class of organic molecules called aromatics, which play a key role in biochemistry.
"This is a treasure hunt for potential signs of life on another planet," NASA astrobiologist Sunanda Sharma said. "Organic matter is a clue and we're getting stronger and stronger clues...I personally find these results so moving because it feels like we're in the right place, with the right tools, at a very pivotal moment."
There have been other tantalizing clues about the possibility of life on Mars before, including repeated detections of methane by Perseverance's predecessor, Curiosity.
While methane is a digestive byproduct of microbes here on Earth, it can also be generated by geothermal reactions where no biology is at play. © 2022 AFP | Biology |
Long nails are a major trend these days, seen on the hands of superstars like Cardi B and Billie Eilish. But a biologist warns this new trend may come with health hazards when considering what may be growing underneath.Jeffrey Kaplan, a biology professor at American University, told USA TODAY that the area under the fingernail in the crevice is where most of the bacteria live."The longer the nail, the more surface area there is for microorganisms to adhere," he said. "Studies have found 32 different bacteria and 28 different fungi underneath fingernails."Kaplan said it doesn't matter if you have long artificial nails, long natural nails, gel nails, acrylic nails or nail polish, because there is an increased probability of carrying microorganisms which makes it more difficult to decontaminate with handwashing or scrubbing.Studies find MRSA, staph underneathOne study found MRSA, an antibiotic-resistant bacteria that causes serious infections in hospitalized patients, underneath half of the fingernail samples collected, according to Kaplan.A judge checks on the contestants' nails during a nail art creative design contest at the China 2011 Hair and Beauty exhibition in Beijing, China.Also, some of the bacteria under nails can be found on the skin like staphylococcus which can lead to an infection."You can transmit fingernail bacteria to your system by scratching, nail-biting, nose-picking and finger-sucking," Kaplan said.He said the worst thing that could happen from the bacteria and fungi is a nail infection, which would not be life-threatening, but could leave your fingernails disfigured.Infant deaths linked to long fingernailsThat is why most, if not all healthcare workers, are required to wear short nails due to being at risk for transmitting disease, according to Kaplan..Two nurses at an Oklahoma City hospital may have contributed to the deaths of 16 babies in 1997 and 1998 because of bacteria found underneath their long nails, The New York Times reported.What's everyone talking about?: Sign up for our trending newsletter to get the latest news of the dayEpidemiologists found a link between the deaths of the infants in the neonatal unit and the bacteria under the nails but did not prove it was the definite cause."When surgeons scrub for surgery and then they test their hands, there's always bacteria under the fingernail and you can't get rid of it," Kaplan said.Long nails trend on social mediaKayla Newman, a nail tech based in North Carolina, told USA TODAY that none of her clientele has had infections or "nasty nails" in her eight years of service."Generally people who have long nails know how to maneuver with them and keep them clean," she said. "If you're spending upwards of $60 to get your nails done and you don't keep them clean, that doesn't make sense."'I call it a spiritual CPR': Mobile hair and beauty service provides makeovers for the soul in Skid RowThank God It’s Natural: 30 Black-owned beauty brands you may not have heard of yetNewman has seen the trend for long nails grow over the last couple of years, and social media platforms like Instagram and TikTok showcase artistic designs on nails that can be over 2 inches long.She said the most common complaint she gets from clients who have long nails are broken nails, especially if they are new to the trend.Newman suggests for people with long nails to regularly make appointments with their nail tech because the strength of nails can shift when they grow out."Nails are an awesome luxury to have," she said. "I encourage people to get them done because when you look at your hands and see them nice and done whether they are long or short, it makes you feel amazing."Two-time Olympic champion Gail Devers of the U.S. sports her long green finger nails at the indoor track and field meeting in Erfurt, eastern Germany, Feb. 5, 1997. Devers finished third in the 60m sprint.Follow reporter Asha Gilbert @Coastalasha. Email: [email protected] article originally appeared on USA TODAY: Are long nails health hazards? Experts weigh in on bacteria, fungi | Biology |
Researchers from the University of Technology Sydney have developed a new device that can detect and analyse cancer cells from blood samples, enabling doctors to avoid invasive biopsy surgeries, and to monitor treatment progress.
Cancer is a leading cause of illness and death in Australia, with more than 150,000 Australians diagnosed every year. Those with suspected cancer, particularly in organs such as the liver, colon or kidney, often require surgery for a definitive diagnosis.
Professor Majid Warkiani from the UTS School of Biomedical Engineering said getting a biopsy can cause discomfort to patients, as well as an increased risk of complications due to surgery and higher costs, but an accurate cancer diagnosis is vital to effective treatment.
"Managing cancer through the assessment of tumour cells in blood samples is far less invasive than taking tissue biopsies. It allows doctors to do repeat tests and monitor a patient's response to treatment," he said.
The Static Droplet Microfluidic device is able to rapidly detect circulating tumour cells that have broken away from a primary tumour and entered the bloodstream.
The device uses a unique metabolic signature of cancer to differentiate tumour cells from normal blood cells.
The study, Rapid metabolomic screening of cancer cells via high-throughput static droplet microfluidics, has just been published in the peer-reviewed scientific journal, Biosensors and Bioelectronics.
"In the 1920s, Otto Warburg discovered that cancer cells consume a lot of glucose and so produce more lactate. Our device monitors single cells for increased lactate using pH sensitive fluorescent dyes that detect acidification around cells," said Professor Warkiani.
"A single tumour cell can exist among billions of blood cells in just one millilitre of blood, making it very difficult to find. The new detection technology has 38,400 chambers capable of isolating and classifying the number of metabolically active tumour cells," he said.
Once the tumour cells are identified with the device, they can undergo genetic and molecular analysis, which can aid in the diagnosis and classification of the cancer and inform personalised treatment plans.
Circulating tumour cells are also precursors of metastasis -- where cancer migrates to distant organs -- which is the cause of 90% of cancer-associated deaths. Studying these cells may provide insights into the biology of cancer metastasis, which can inform the development of new treatments.
Existing liquid biopsy technologies are time-consuming, expensive and rely on skilled operators, limiting their application in clinical settings.
This new technology is designed for integration into research and clinical labs without relying on high-end equipment and trained operators. This will enable doctors to diagnose and monitor cancer patients in a practical and cost-effective manner.
The UTS research team has filed a provisional patent for the Static Droplet Microfluidic device and has plans to commercialise the product.
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In 30 or 40 years, we'll have microscopic machines traveling through our bodies, repairing damaged cells and organs, effectively wiping out diseases. The nanotechnology will also be used to back up our memories and personalities.In an interview with Computerworld, author and futurist Ray Kurzweil said that anyone alive come 2040 or 2050 could be close to immortal. The quickening advance of nanotechnology means that the human condition will shift into more of a collaboration of man and machine, as nanobots flow through human blood streams and eventually even replace biological blood, he added.That may sound like something out of a sci-fi movie, but Kurzweil, a member of the Inventor's Hall of Fame and a recipient of the National Medal of Technology, says that research well underway today is leading to a time when a combination of nanotechnology and biotechnology will wipe out cancer, Alzheimer's disease, obesity and diabetes. It'll also be a time when humans will augment their natural cognitive powers and add years to their lives, Kurzweil said."It's radical life extension," Kurzweil said. "The full realization of nanobots will basically eliminate biological disease and aging. I think we'll see widespread use in 20 years of [nanotech] devices that perform certain functions for us. In 30 or 40 years, we will overcome disease and aging. The nanobots will scout out organs and cells that need repairs and simply fix them. It will lead to profound extensions of our health and longevity."Of course, people will still be struck by lightning or hit by a bus, but much more trauma will be repairable. If nanobots swim in, or even replace, biological blood, then wounds could be healed almost instantly. Limbs could be regrown. Backed up memories and personalities could be accessed after a head trauma.Today, researchers at MIT already are using nanoparticles to deliver killer genes that battle late-stage cancer. The university reported just last month the nano-based treatment killed ovarian cancer, which is considered to be one of the most deadly cancers, in mice.And earlier this year, scientists at the University of London reported using nanotechnology to blast cancer cells in mice with "tumor busting" genes, giving new hope to patients with inoperable tumors. So far, tests have shown that the new technique leaves healthy cells undamaged.With this kind of work going on now, Kurzweil says that by 2024 we'll be adding a year to our life expectancy with every year that passes. "The sense of time will be running in and not running out," he added. "Within 15 years, we will reverse this loss of remaining life expectancy. We will be adding more time than is going by."And in 35 to 40 years, we basically will be immortal, according to the man who wrote The Age of Spiritual Machines and The Singularity is Near: When Humans Transcend Biology. Kurzweil also maintains that adding microscopic machines to our bodies won't make us any less human than we are today or were 500 years ago."The definition of human is that we are the species that goes beyond our limitations and changes who we are," he said. "If that wasn't the case, you and I wouldn't be around because at one point life expectancy was 23. We've extended ourselves in many ways. This is an extension of who we are. Ever since we picked up a stick to reach a higher branch, we've extended who we are through tools. It's the nature of human beings to change who we are."But that doesn't mean there aren't parts of this future that don't worry him. With nanotechnology so advanced that it can travel through our bodies and affect great change on them, come dangers as well as benefits.The nanobots, he explained, will be self-replicating and engineers will have to harness and contain that replication. "You could have some self-replicating nanobot that could create copies of itself... and ultimately, within 90 replications, it could devour the body it's in or all humans if it becomes a non-biological plague," said Kurzweil. "Technology is not a utopia. It's a double-edged sword and always has been since we first had fire." | Biology |
Scientists from Stanford University and the University of Texas MD Anderson Cancer Center have discovered a class of molecules that use endogenous proteins to modulate genetic pathways involved in cell death. These molecules, which are called transcriptional/epigenetic chemical inducers of proximity (TCIPs), use local transcription factors or epigenetic regulators to restart the expression of genes responsible for instigating apoptosis in cancer cells. Full details of the study are described in a Nature paper titled “Rewiring cancer drivers to activated apoptosis” published this week.
“The coexistence of cell death pathways with driver mutations suggest that the cancer driver could be rewired to activate cell death using chemical inducers of proximity (CIPs),” the researchers wrote in the paper. Previous studies involving these molecules have rewired genes in signal transduction pathways and in protein localization and transcription pathways.
“To rewire transcriptional circuits within a genetically unmodified cell or organism, we developed small molecules that the recruitment of cancer-driving translational or epigenetic regulators to the regulatory regions of target therapeutic genes,” the study authors said. “[B]y making use of the intrinsic driving pathways of the cancer cell and rewiring them to activate pathways of cell death, we have introduced an approach to cancer chemotherapy that is analogous to a dominant gain-of-function mutation in genetics.”
The study focused on cells from a diffuse large B cell lymphoma, a type of non-Hodgkin lymphoma where the body produces abnormally sized B cells, and a transcription factor called B-cell lymphoma 6 (BCL6). The team generated a small library of TCIPs for testing on B-cell lymphoma cells lines alongside other types of cancer. The TCIPs combined small molecules that bind to and inhibit BCL6, with molecules that bind protein domains of B-cell transcription activators like BRD4. The linked molecules and proteins formed a complex that targets and activates some of the pathways that lead to cells’ death.
The research team generated a small library of TCIPs and tested them against various cancer cell lines. One TCIP, labeled TCIP1, selectively killed B cell lymphoma cell lines including some that were resistant to chemotherapy. The researchers tested TCIP1’s potency on a larger panel of 906 cancer cell lines culled from various lineages. The results showed that TCIP1 had the strongest effect on cancer cells that originated from hematopoietic and lymphoid tissues and had high levels of BCL6. It was less effective, however, in cell lines without BCL6. Further analysis showed that TCIP1 targets multiple death pathways including popular ones like TNF signaling and the p53 pathway.
A bonus of the treatment is that it remains robust even at low concentrations. “TCIPs produce their effect by activating cell death signaling and rewiring only a fraction of the cancer driver molecules per cell to drive the phenotype,” the scientists noted in the paper. “A gain-of-function mechanism would also explain the far more robust cell killing seen with substantially lower concentrations of TCIP1” compared to other small-molecule inhibitors of BCL6.
Although this study focused on cancers specifically, TCIPs are versatile and can be used to activate gene expression in a broader range of contexts. For example, they could be used to modulate gene expression in organisms used in synthetic biology projects. Importantly, these complexes are better suited for therapies than their predecessors, according to the study authors. Earlier CIP studies used genetically modified transcription factors in their complexes, which reduced their potential for use in therapeutic applications. In contrast TCIP’s use native proteins, and that opens several possible therapeutic applications. For example, scientists could design TCIPs for use in human immunotherapies or to induce apoptosis in aging cells. | Biology |
Fast-Aging Mice Live Longer When Oxygen Is Restricted
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Massachusetts General Hospital scientists have, for the first time, shown that oxygen restriction increases lifespan in a mouse model of aging. The research is published in PLOS Biology.
Restricted oxygen delays aging processes in cell cultures and other lab models
Aging is a significant risk factor for common diseases including neurodegeneration, diabetes and cancer. The field of aging and longevity research has accelerated over the last decade, with several biological hallmarks of aging identified. Equipped with this knowledge of the molecular underpinnings of aging, science continues its pursuit of interventions that can prolong a healthy lifespan by targeting such processes, with some drugs entering clinical trials.
As with any clinical research, interventions targeting the aging process are first tested for their safety and efficacy in laboratory models before progressing to human studies. Restricted oxygen intake – also known as continuous hypoxia – has been reported to delay cellular senescence in common aging models such as nematodes, yeast and fruit flies. Based on this data, Dr. Robert Rogers and colleagues at Massachusetts General Hospital chose to explore the potential of continuous hypoxia for slowing mammalian aging. | Biology |
Stanford study shows how modifying enzymes’ electric fields boosts their speed
A seemingly subtle swap of metals—substituting a zinc ion with a cobalt ion—and a mutation ramps up the overall electric field strength at the active site of an enzyme, Stanford scientists find. The result is a predictably modified enzyme that works an astonishing 50 times faster than its unmodified analog.
Stanford researchers have demonstrated a way to dramatically speed up the reaction rate of an enzyme, a finding that could pave the way to designing ultra-fast synthetic enzymes for a range of industrial and medical uses.
Honed over billions of years of evolution, biological enzymes are marvels of chemistry. These specialized proteins serve as catalysts for accelerating chemical reactions essential to life as well as processes used in the food, pharmaceutical, and cosmetic industries.
Ever since enzymes' discovery nearly two centuries ago, scientists have sought ways to make them even faster. Most fabricated enzymes, though, have failed to match the lofty efficiency standards of nature-made varieties. And even where some successes have been realized through directed evolution, a protein engineering method that mirrors nature's trial-and-error approach, these successes so far have been by chance, not because of a deeper understanding of how enzymes work or could be modified to work more swiftly.
Now, in a new study, researchers at Stanford’s School of Humanities and Sciences and SLAC National Accelerator Laboratory have debuted a modified enzyme that works an astonishing 50 times faster than its unmodified analog. The findings derive from pioneering research at the university regarding electric fields generated at "active sites," the pocketlike places where revved up chemical reactions occur. Based on this concept, the researchers tweaked the chemistry of the active site, boosting its electric field strength and specificity to deliver the zippy results.
"We have improved a natural enzyme's activity through an understanding of how changing atoms at the active site can intentionally enhance electric fields," said Chu Zheng, co-lead author with Zhe Ji of the study published Aug. 10 in the journal Nature Chemistry.
Zheng conducted the work as a graduate student in the lab of Steven G. Boxer, the Camille Dreyfus Professor of Chemistry in H&S. Zheng is now a postdoctoral scholar in the lab of Peter Kim, the Virginia and D.K. Ludwig Professor in Biochemistry. Ji, a former Stanford postdoctoral scholar in Boxer’s lab, is now an assistant professor at Peking University.
"With this study, we have succeeded in making an enzyme that works better—significantly better, in fact—than a natural enzyme and in a rational, predictable way," said Boxer, the chair of the Department of Chemistry and senior author of the study. "Our study presents a new paradigm for designing biological enzymes and should be readily applicable to designing non-biological catalysts as well."
Revamping an enzyme
Ten years ago, the Boxer Lab began developing methods for probing the electric fields produced by the highly organized 3D atomic structures of enzymes' active sites and connecting these fields with the rates of the reactions catalyzed by the enzyme. Lab studies since have borne out how the electrostatic interactions driven by these fields contribute heavily to the bespoke environments in active sites, where specific substrate molecules fleetingly bind, react, and transform into new molecules.
While examining such activity in an enzyme called horse liver alcohol dehydrogenase, Zheng and colleagues made a serendipitous discovery. The researchers noticed that the active site produced a stronger electric field when swapping out an amino acid, serine, for a similar amino acid called threonine. The hydrogen atoms in these amino acids form hydrogen bonds—often an essential interaction in enzyme catalysis.
Zheng, an expert in the chemistry of metals, delved further into tweaking other active site ingredients. In many enzymes, zinc (Zn) ions play a pivotal role in catalysis, forming a coordination complex (a central atom or ion surrounded by bound molecules or ions) within the active site. To wring out greater performance, Zheng and Ji tried replacing the zinc ion in the horse enzyme's active site with atoms of other metals.
As it turned out, subbing in cobalt (Co) for Zn looked promising in ramping up the overall electric field strength. Both elements in this coordination complex context appear in a catalytic ion state as Zn2+ and Co2+, meaning they have a net charge of +2. To incorporate this alternative metal, the researchers developed a method to replace the native Zn2+ with Co2+, but swapping metals in the enzyme could alter its overall structure and, as a consequence, its function.
To verify that the arrangement and bonding of atoms in their newly honed enzyme was unaltered, the Boxer Lab team enlisted the assistance of Irimpan Mathews, a lead scientist at SLAC. Mathews measured the 3D structure of each modified enzyme using X-ray crystallography and confirmed that the modification left the overall structure unaffected.
The researchers then measured the modified electric fields in the modified active sites via vibrational Stark effect spectroscopy, a method pioneered in the Boxer Lab. This technique measures the vibrational frequencies in molecules based on the wavelength of infrared light absorbed by their chemical bonds. Shifts in these vibrational frequencies reveal information about the electric fields present. The researchers also created computer models to investigate their theory that the alt-enzyme would have enhanced performance.
Proof-of-principle enzyme enhancement
With the adjusted enzyme thus prepped and the electric field measured, the researchers put it through its paces and measured its speed. Reassuringly, just as predicted in the researchers' computer models, the modified enzyme performed about 50 times faster than its natural counterpart.
To build on these proof-of-principle results, the researchers plan to continue devising enhanced enzymes and characterizing their electrostatic interactions.
"We have shown that hydrogen bonds and metal coordination, two entirely distinct yet essential forces in enzyme catalysis, can be unified via electric fields, a fundamental physical quantity," Zheng said.
"And because we're dealing with physical quantities, we can add or subtract them to achieve desired electric field strengths and then predict the resulting effect on the rate,” Ji said. “That's a very high level of control over enzyme performance."
"The approaches we demonstrated in this study could prove very effective in custom tailoring more powerful catalysts in the future," Boxer added. "We hope this study provides a basis for more rational design of better catalysts."
Acknowledgements
This work was funded by the National Institutes of Health. Use of the Stanford Synchrotron Radiation Lightsource, SLAC National Accelerator Laboratory, was funded by the U.S. Department of Energy, Office of Science, Office of Basic Energy Sciences. The SSRL Structural Molecular Biology Program was funded by the DOE Office of Biological and Environmental Research and by the National Institutes of Health, National Institute of General Medical Sciences | Biology |
New research links early Europeans' cultural and genetic development over several thousand years
A new DNA study has nuanced the picture of how different groups intermingled during the European Stone Age, but also how certain groups of people were actually isolated. The study was carried out by researchers at Uppsala University working with an international team of researchers, who produced new genetic data from 56 Central and Eastern European individuals from the Stone Age. The results have been published in the journal Communications Biology.
"Conducting studies like this one requires a broad interdisciplinary discussion. In this study, this discussion has been exceptionally fruitful," says Tiina Mattila, population geneticist at Uppsala University and the study's lead author.
Over the past 15 years, DNA research has pieced together a picture of the history of the European Stone Age. Before agriculture spread to Europe, there were different groups of hunter-gatherers in different parts of Eurasia, who also intermingled with each other. This study shows that the intermingling of these hunter-gatherer genetic lines was strongly linked to geography.
Several previous DNA studies of Europe's pre-history have also shown that the spread of agriculture was strongly linked to the gene flow from Anatolia. That group was very different—genetically and culturally—from the European hunter-gatherers. But agriculture spread in different ways in different geographical areas, and this led to ethnic groups intermingling in different ways in different parts of Europe.
"These differences in the intermingling of genetic lines and cultures can tell us about the power relations between different groups," says Tiina Mattila.The new study also looked at close relatives.
"Common graves are often assumed to be family graves, but in our study this was not always the case. This shows that even during the Stone Age other social factors also played a role in burial practices," says Helena Malmström, archaeogeneticist at Uppsala University.
A more comprehensive picture of the genetic history of Stone Age Europeans has emerged in recent years, and this new study adds further detail to this puzzle.
"We can show that some parts of Europe—such as the area around the Dnipro River delta—were inhabited by isolated groups of hunter-gatherers for many thousands of years, even though many other parts of Europe changed their way of life when new groups arrived who produced food by tilling the soil," says Mattias Jakobsson, professor of genetics at Uppsala University.
More information: Genetic continuity, isolation, and gene flow in Stone Age Central and Eastern Europe, Communications Biology (2023). DOI: 10.1038/s42003-023-05131-3
Journal information: Communications Biology
Provided by Uppsala University | Biology |
Spiny mice found to have bone-plated tails
Mammals are a bit odd when it comes to bones. Rather than the bony plates and scales of crocodiles, turtles, lizards, dinosaurs and fish, mammals long ago traded in their ancestral suit of armor for a layer of insulating hair.
Armadillos, with their protective and flexible shell of imbricated bone, are considered the only living exception. But a new study, published in the journal iScience, unexpectedly shows that African spiny mice produce the same structures beneath the skin of their tails, which until now had gone largely undetected.
The discovery was made during routine CT scanning of museum specimens for the openVertebrate program, an initiative to provide 3D models of vertebrate organisms for researchers, educators and artists.
"I was scanning a mouse specimen from the Yale Peabody Museum, and the tails looked abnormally dark," said co-author Edward Stanley, director of the Florida Museum of Natural History's digital imaging laboratory.
He initially assumed the discoloration was caused by an imperfection introduced during the specimen's preservation. But when he analyzed the X-rays several days later, Stanley observed an unmistakable feature he was intimately familiar with.
"My entire Ph.D. was focused on osteoderm development in lizards. Once the specimen scans had been processed, the tail was very clearly covered in osteoderms."
Spiny mice osteoderms have been observed at least once before and were noted by German biologist Jochen Niethammer, who compared their architecture to medieval stonework in an article published in 1975. Niethammer correctly interpreted the plates as being a type of bone but never followed up on his initial observations, and the group was largely overlooked for several decades—until scientists discovered another, seemingly unrelated peculiarity of spiny mice.
A study from 2012 demonstrated spiny mice can completely regenerate injured tissue without scarring, an ability common in reptiles and invertebrates but previously unknown in mammals. Their skin is also particularly fragile, tearing at roughly one-fourth the amount of force required to injure the skin of a common mouse. But spiny mice can heal twice as fast as their relatives.
Researchers hoping to find a model for human tissue regeneration have begun mapping the genetic pathways that give spiny mice their extraordinary powers of healing. One such researcher, Malcolm Maden, just so happened to have a lab in the building across from Stanley's office.
"Spiny mice can regenerate skin, muscle, nerves, spinal cord and perhaps even cardiac tissue, so we maintain a colony of these rare creatures for research," said Maden, a biology professor at the University of Florida and lead author on the study.
Maden and his colleagues analyzed the development of spiny mice osteoderms, confirming they were in fact similar to those of armadillos but had most likely evolved independently. Osteoderms are also distinct from the scales of pangolins or the quills of hedgehogs and porcupines, which are composed of keratin, the same tissue that makes up hair, skin and nails.
There are four genera of spiny mice, which all belong to the subfamily Deomyinae. However, aside from similarities in their DNA and potentially the shape of their teeth, scientists have been unable to find a single feature shared among species of this group that distinguishes them from other rodents.
Stanley, suspecting their differences might only be skin deep, scanned additional museum specimens from all four genera. In each, he found spiny mice tails were covered in the same sheath of bone. The closest relatives of Deomyinae—gerbils—lacked osteoderms, meaning the trait had likely evolved just once, in the ancestor of erstwhile disparate spiny mice.
The ubiquity of osteoderms in the group indicate they serve an important protective function. Just what that function might be wasn't immediately apparent, however, due to yet another peculiar attribute of spiny mice: Their tails are uncharacteristically detachable. Tail loss is so common in some spiny mouse species that nearly half the individuals of a given population have been shown to lack them in the wild.
"This was a real head-scratcher," Stanley said. "Spiny mice are famously able to deglove their tails, meaning the outer layer of skin comes off, leaving behind the muscle and bone. Individuals will often chew off the remainder of the tail when this happens."
Despite their powers of regeneration, tail shedding is a trick that spiny mice can only perform once. Unlike some lizards, they can't regrow their tails, and not every part of the tail separates easily.
To find out why rodents that seem ambivalent about keeping their tails would go through the trouble of covering them in armor, the authors turned to a group of similarly odd fish-tale geckos from Madagascar. Most geckos lack osteoderms, but as their name implies, fish-tale geckos are covered in thin, overlapping plates, and just like spiny mice, they have incredibly fragile skin that sheds at the slightest provocation.
According to Stanley, the osteoderms in fish-tale geckos and spiny mice possibly function like a type of escape mechanism.
"If a predator bites down on the tail, the armor might keep the teeth from sinking into the tissue beneath, which doesn't detach," he said. The outer skin and its complement of bone plating pull away from the tail when attacked, affording the mouse a quick escape.
More information: Malcolm Maden, Osteoderms in a mammal the spiny mouse Acomys and the independent evolution of dermal armor, iScience (2023). DOI: 10.1016/j.isci.2023.106779. www.cell.com/iscience/fulltext … 2589-0042(23)00856-8
Journal information: iScience
Provided by Florida Museum of Natural History | Biology |
Dr. Anthony Fauci said the quiet part out loud last month — or more precisely, wrote it — when he and two National Institute of Allergy and Infectious Diseases colleagues co-authored an article published by the prestigious Cell Host & Microbe.
In the article, the former director of NIAID and his colleagues declared that certain respiratory viruses such as Influenza A and SARS-CoV-2, among others, “have not to date been effectively controlled by licensed or experimental vaccines.”
According to the authors, past “attempts to elicit solid protection against mucosal respiratory viruses and to control the deadly outbreaks and pandemics they cause” have been “unsuccessful.”
Regarding influenza vaccines, they wrote, it has been known for decades that “the rates of effectiveness of our best approved influenza vaccines would be inadequate for licensure for most other vaccine-preventable diseases.”
More specifically, they noted, the effectiveness of influenza vaccines “against clinically apparent infection” tends to range from 14% to 60% and be short-lived. They also highlighted that influenza vaccine formulations “are frequently not precisely matched to circulating virus strains.”
SARS-CoV-2 vaccines, they went on to state, exhibit “deficiencies” that are “reminiscent of influenza vaccines.”
“The vaccines for these two very different viruses,” the authors explained, “have common characteristics: they elicit incomplete and short-lived protection against evolving virus variants that escape population immunity.”
The reasons for this, they elaborated, are that the kinds of respiratory viruses against which vaccines tend to be most effective are those that have long incubation periods, spread systemically throughout a person’s body after replicating mucosally, and ultimately result in long-term, if not lifelong, immunity once cleared due to interactions with multiple components of a person’s immune system.
Measles, mumps, and rubella, the authors pointed out, are examples of diseases caused by respiratory viruses that share these features, which is why they can effectively be controlled with vaccines.
Conversely, they explained, influenza viruses and SAR-CoV-2 are non-systemic respiratory viruses with short incubation periods and largely replicate locally in mucosal tissue, thus limiting the extent to which they interact with their host’s immune system.
Coupled with the tendency of these viruses to mutate frequently, long-term immunity through natural infection is not attained, they wrote. Moreover, they acknowledged this makes developing vaccines, which is already a long and difficult process, even more difficult, and contributes to the available vaccines for these viruses being “suboptimal.”
Hence, the trio called for the development of vaccines for these viruses that are better than “suboptimal” prior to discussing possible approaches for achieving this goal.
Similar claims regarding the effectiveness of the COVID-19 vaccines have been made by numerous other officials, scientists, and doctors in recent months, as well as over the course of the pandemic.
In an opinion piece for the New England Journal of Medicine, Dr. Paul Offit , a member of the Food and Drug Administration’s Vaccines and Related Biological Products Advisory Committee, wrote that the immunity induced by the bivalent COVID boosters is short-lived and expressed support for ending policies that attempt to prevent all infections.
Earlier this month, several leading critics of COVID policy, collectively known as the Norfolk Group , enumerated multiple shortcomings of the COVID vaccines, along with harms inflicted by policies based on erroneous assumptions that the vaccines prevent infection and transmission.
Yet, for those hoping that America’s top suboptimal infectious disease bureaucrat and his NIAID colleagues would themselves call for changes in COVID vaccine policy, the wait will have to continue. Fauci and company, despite counting these vaccines among other “suboptimal” injections and “unsuccessful attempts” to stop infections and control pandemics, simultaneously claim victory, assuring that the jabs “saved innumerable lives and helped to achieve early partial pandemic control.”
Daniel Nuccio is a Ph.D. student in biology and a regular contributor to the College Fix and the Brownstone Institute. | Biology |
Keanu Reeves - the molecule
New active ingredient from bacteria could protect plants
| by Charlotte Fuchs
Bacteria of the genus Pseudomonas produce a strong antimicrobial natural product, as researchers at the Leibniz Institute for Natural Product Research and Infection Biology (Leibniz-HKI) have discovered. They proved that the substance is effective against both plant fungal diseases and human-pathogenic fungi. The study was published in the Journal of the American Chemical Society.
The newly discovered natural product group of keanumycins in bacteria works effectively against the plant pest Botrytis cinerea, which triggers grey mould rot and causes immense harvest losses every year. But the active ingredient also inhibits fungi that are dangerous to humans, such as Candida albicans. According to previous studies, it is harmless to plant and human cells.
Keanumycins could therefore be an environmentally friendly alternative to chemical pesticides, but they could also offer an alternative in the fight against resistant fungi. "We have a crisis in anti-infectives," explains Sebastian Götze, first author of the study and postdoc at Leibniz-HKI. "Many human-pathogenic fungi are now resistant to antimycotics - partly because they are used in large quantities in agricultural fields."
Deadly like Keanu Reeves
The fact that the researchers have now found a new active ingredient in bacteria of the genus Pseudomonas is no coincidence. "We have been working with pseudomonads for some time and know that many of these bacterial species are very toxic to amoebae, which feed on bacteria," says study leader Pierre Stallforth. He is the head of the department of Paleobiotechnology at Leibniz-HKI and professor of Bioorganic Chemistry and Paleobiotechnology at Friedrich Schiller University in Jena. It appears that several toxins are responsible for the deadly effect of the bacteria, of which only one was known so far. In the genome of the bacteria, the researchers have now found biosynthesis genes for the newly discovered natural products, the keanumycins A, B and C. This group of natural products belongs to the nonribosomal lipopeptides with soap-like properties.
Together with colleagues at the Bio Pilot Plant of the Leibniz-HKI, the researchers succeeded in isolating one of the keanumycins and conducting further tests. "The lipopeptides kill so efficiently that we named them after Keanu Reeves because he, too, is extremely deadly in his roles," Götze explains with a wink.
The researchers suspected that keanumycins could also kill fungi, as these resemble amoebas in certain characteristics. This assumption was confirmed together with the Research Centre for Horticultural Crops at the University of Applied Sciences Erfurt. There, Keanumycin was shownto be effective against grey mould rot on hydrangea leaves. In this case, culture fluid that no longer contained bacterial cells was sufficient to significantly inhibit the growth of the fungus.
"Theoretically, the keanumycin-containing supernatant from Pseudomonas cultures could be used directly for plants," says Götze. Further testing will be carried out together with the colleagues in Erfurt. Keanumycin is biodegradable, so no permanent residues should form in the soil. This means that the natural product has the potential to become an environmentally friendly alternative to chemical pesticides.
Fungal diseases such as Botrytis cinerea, which causes grey mould rot, cause immense harvest losses in fruit and vegetable cultivation every year. More than 200 different types of fruit and vegetables are affected, especially strawberries and unripe grapes.
Possible applications in humans
"In addition, we tested the isolated substance against various fungi that infect humans. We found that it strongly inhibits the pathogenic fungus Candida albicans, among others," says Götze.
Instead of plants, Keanumycin could therefore possibly also be used in humans. According to the tests conducted so far, the natural product is not highly toxic for human cells and is already effective against fungi in very low concentrations. This makes it a good candidate for the pharmaceutical development of new antimycotics. These are also urgently needed, as there are very few drugs against fungal infections on the market.
The work was supported by the Werner Siemens Foundation, the Leibniz Association and the German Research Foundation (Deutsche Forschungsgemeinschaft, DFG) as part of the Balance of the Microverse Cluster of Excellence, and funded by the Dr. Illing Foundation.
Original publication
Götze S, Vij R, Burow K, Thome N, Urbat L, Schlosser N, Pflanze S, Müller R, Hänsch VG, Schlabach K, Fazlikhani L, Walther G, Dahse HM, Regestein L, Brunke S, Hube B, Hertweck C, Franken P, Stallforth P (2023). Ecological niche-inspired genome mining leads to the discovery of crop-protecting nonribosomal lipopeptides featuring a transient amino acid building block. J Am Chem Soc, doi: 10.1021/jacs.2c11107
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Credit: Bia Octavia on Unsplash. A new study from the University of Sheffield has identified a protein that supports milk production after a pause in breastfeeding. The research is published in PLOS Biology. A fail-safe mechanism for breastmilk production If an infant has been breastfed, once they progress to solid foods a molecular process commences in the breast tissue. Ultimately, the production of breastmilk winds down, and milk-producing mechanisms are dismantled via cellular suicide, removing the redundant tissue. However, if the infant resumes suckling, this process can be reversed, “kickstarting” breast milk production once again. But how does this occur?Want more breaking news?Subscribe to Technology Networks’ daily newsletter, delivering breaking science news straight to your inbox every day.Subscribe for FREEThat’s the focus of a new study from the University of Sheffield, led by Dr. Nasreen Akhtar, lecturer in Developmental Cell Biology in the Department of Oncology and Metabolism. “Despite the massive wave of cell death that occurs in the first phase of the end of lactation, if suckling resumes the breast can reverse the process and re-lactate. This is a fail-safe built-in mechanism to prevent the breast from drying up too quickly,” Akhtar says.Rac1 a key player for “kickstarting” breast milk production Akhtar and colleagues utilized mammary glands from mice for their research. This laboratory model is as a suitable choice, the researchers state, due to the structural similarity between mouse and human mammary glands. In mammary epithelial cells (MECS), the researchers found that the presence of a protein called Rac1 causes autophagy – a “cannibalistic” process whereby cells eat their own constituents in an effort to survive.Some half-dead, half-alive cells experiencing autophagy can be “brought back to life”, enabling milk production once again when the infant suckles on the breast. However, this process can only occur if Rac1 is present. “We have discovered that Rac1 acts as a nexus, controlling both the rate and balance of cell death and progenitor cell division in involution. Without Rac1, cell turnover accelerates with consequences on mammary gland remodelling in the irreversible phase,” the authors write.Pathways and proteins for the study of breast cancer The ability of breast tissue to recommence milk production is important for the survival of mammals, Akhtar emphasizes: “If a nursing mammal was separated from her pups for longer than expected whilst foraging, she would still be able feed once reunited.”“Remarkably some mammals have a really long reversible phase; for example, the cape fur seal, which goes on long offshore foraging trips for up to 28 days can still re-lactate once suckling resumes ashore,” she adds.In humans, the risk of breast cancer progression is higher in the years following a pregnancy. One proposed mechanism for this increased risk is the altered activity of breast cells during the remodeling processes that occur post-weaning. “The discovery here could expose potential pathways and proteins that cancer cells exploit to survive and grow,” Akhtar concludes.This article is a rework of a press release issued by the University of Sheffield. Material has been edited for length and content.Reference: Mironov A, Fisher M, Narayanan P, et al. Rac1 controls cell turnover and reversibility of the involution process in postpartum mammary glands. PLOS Biology. 2023;21(1):e3001583. doi: 10.1371/journal.pbio.3001583. | Biology |
A new paper in Annals of Botany, published by Oxford University Press, indicates that watching nature documentaries makes people more interested in plants, potentially provoking an involvement in botany and ecology.
Some 40% of plant species are under threat of extinction. Plants that are not directly useful to humans are particularly vulnerable. People often do not recognize how important many plants are due to a cognitive bias sometimes called “plant blindness” or “plant awareness disparity.” While humans are generally concerned with endangered animals, threats to plants are harder to recognize and address. In the United States, for example, plants receive less than 4% of federal funding for endangered species, despite comprising 57% of the endangered species list.
Researchers here noted that in the past several natural history productions, including Planet Earth II, Blue Planet II, Seven Worlds, and One Planet, made viewers much more aware of the animals on the shows. While scientists cannot draw a clear link between such TV shows and conservation efforts, nature documentaries provide a direct way to reach mass audiences and engage them.
Here, the researchers investigated whether nature documentaries can promote plant awareness, which may ultimately increase audience engagement with plant conservation programs. They focused on Green Planet, a 2022 BBC documentary narrated by Sir David Attenborough. The show, watched by nearly 5 million people in the United Kingdom, featured a diversity of plant species, highlighting vegetation from tropical rainforests, aquatic environments, seasonal lands, deserts, and urban spaces. The program also addressed environmental concerns directly, examining the dangers of invasive monocultures and deforestation.
The researchers measured whether Green Planet drove interest in the plants by exploring people’s online behavior around the time of the broadcast. First, they noted the species that appeared on the show and the time each one appeared on-screen. Then they extracted Google Trends and Wikipedia page hits for those same species before and after the episodes of the documentary aired.
The researchers here found a substantial effect of Green Planet on viewers’ awareness and interest in the portrayed plant species. Some 28.1% of search terms representing plants mentioned in the BBC documentary had peak popularity in the UK, measured using Google Trends, the week after the broadcast of the relevant episode. Wikipedia data showed this as well. Almost a third (31.3%) of the Wikipedia pages related to plants mentioned in Green Planet showed increased visits the week after the broadcast. The investigators also note that people were more likely to do online searches for plants that enjoyed more screen time on Green Planet.
“I think that increasing public awareness of plants is essential and fascinating," said the paper’s lead author, Joanna Kacprzyk. “In this study, we show that nature documentaries can increase plant awareness among the audience. Our results also suggest that the viewers found certain plant species particularly captivating. These plants could be used for promoting plant conservation efforts and counteracting the alarming loss of plant biodiversity.“
The paper, “Making a greener planet: nature documentaries promote plant awareness,” is available (at midnight on February 16th) at: https://academic.oup.com/aob/article-lookup/doi/10.1093/aob/mcac149.
Direct correspondence to:
Joanna Kacprzyk
School of Biology and Environmental Sciences
University College Dublin
Dublin 4, IRELAND
[email protected] | Biology |
Researchers enhance the function of natural proteins using 'protein Legos'
Johns Hopkins engineers have helped develop and characterize an artificial protein that triggers the same response in the human body as its natural counterpart—a breakthrough that not only has the potential to facilitate the design of drugs to accelerate healing but also sheds light on the mechanisms behind various diseases.
The team's research was published in Nature Chemical Biology.
"It's protein Legos, essentially," said team leader Jamie Spangler, an assistant professor of chemical and biomolecular engineering and biomedical engineering. "We know what the different pieces look like, and we put them together in an arrangement that is predicted to look like the protein we're trying to mimic. As far as the body is concerned, this newly created protein is as genuine as the one that occurs in nature."
The synthetic protein, called Neo-4, mimics the function of the natural protein interleukin-4 (IL-4), a crucial player in immune system regulation. White blood cells release IL-4 in response to a range of immune triggers, from allergic inflammation to muscle injuries. IL-4 can then attach to various receptors on cells throughout the body. However, when IL-4 is directly injected as a drug, it can bind to unintended cells, causing unwanted side effects.
"If you give someone IL-4 it just acts on everything," said Zachary Bernstein, team member and Ph.D. candidate in biomedical engineering. "But that makes it difficult for therapeutic use. Neo-4 is more specific and only activates immunologically relevant cells."
Neo-4 attaches to a narrower range of cells than IL-4, a characteristic that the researchers say could make it a promising candidate for future drug development. For instance, a torn anterior cruciate ligament (ACL) is a common season-ending sports injury. Cytokines like Neo-4 have the potential to speed up the healing of torn ACLs and other damaged ligaments and muscles.
"These are computationally designed proteins that behave like proteins in nature but have better properties," Spangler said. "That means we can build these robust, hyper-stable proteins to do whatever we want. The hope is that we can use this mimetic to deliver IL-4 in a way that is safer and more robust than the natural cytokine, which could help with its therapeutic advancement."
Huilin Yang, graduate of the doctoral program in chemical and biomolecular engineering and current postdoctoral fellow at ETH Zurich, contributed to this research.
More information: Huilin Yang et al, Design of cell-type-specific hyperstable IL-4 mimetics via modular de novo scaffolds, Nature Chemical Biology (2023). DOI: 10.1038/s41589-023-01313-6
Journal information: Nature Chemical Biology
Provided by Johns Hopkins University | Biology |
Inequality not inevitable among mammals, study shows
Because literature and film so often depict nature as inherently unfair, people assume that animals live in a "dog-eat-dog world." Inequality might seem like an inevitable fact of life, but a new analysis of data for 66 species of mammals reveals enormous flexibility of their social systems and many routes toward inequality.
Among mammals, including humans, competition for food and mates tends to increase inequality. But there is also sharing, cooperation, conflict resolution and aversion to inequity. These factors promote more equal societies.
A paper published in Philosophical Transactions of the Royal Society B: Biological Sciences shows that mammalian societies run the gamut from egalitarian to hierarchical. But while scientists have extensively studied the evolution of hierarchy, the paper's authors say, they have a poor understanding of how fairness evolves. In fact, mammals rely upon a suite of mechanisms to balance the costs and benefits of equality for group living, and evolution does not necessarily favor hierarchy.
"The evolution of fairness has played as big a role in the evolution of mammal species ... but it has been understudied," said senior author Michael Alfaro, professor of ecology and evolutionary biology at UCLA. "Our study is part of a larger effort to understand peacekeeping and conflict across mammalian societies and perhaps lend insight into human inequality."
Across mammals, hierarchy evolves through intergenerational transfer of resources, skills or tools that enhance individuals' ability to survive and raise more young than others.
"This can take the form of metabolic, nutritional and social advantages passed on to offspring by high-ranking mothers who experience less stress, through direct inheritance of resources, such as hunting territories or fruit trees; from dominant parents; or from coalitions and alliances between related individuals," said the study's co-author Barbara Natterson-Horowitz, a UCLA professor of ecology and evolutionary biology.
Parents with special skills—such as tool use or an innovative hunting technique—can pass these on to their young to give them an advantage over others.
One or more of these factors are present in most mammal species, and the resulting hierarchies can be shallow and shifting over time, or steep and persisting for generations. Hierarchies among humans' closest relatives, chimpanzees and gorillas, for example, fall somewhere in the middle. These apes have distinct dominance hierarchies that can persist for more than one generation, but other factors work against the resulting inequalities to destabilize and transform the hierarchy.
"Factors that work to promote fairness among mammals include food sharing and adoptions, revolutionary coalitions, conflict resolution, and an aversion to inequality," said former UCLA postdoctoral fellow and first author Jennifer Smith, now at the University of Wisconsin-Eau Claire.
Some mammals share food with relatives who are unable to find their own food, or to strengthen social ties. For example, vampire bats share blood meals with relatives who are weak from hunger, while chimpanzees share meat from a successful hunt with the entire group. Some animals, such as elephants and lions, adopt orphaned young and raise them as their own. These practices mitigate the unequal distribution of resources within a hierarchy and promote social relationships based on sharing, not dominance.
Lower-ranking individuals in numerous species also form coalitions to challenge dominant individuals, often making social dynamics operate more fairly, such as when female lions join forces to prevent infanticide by males. Coalitions can also overthrow the dominant individual altogether. After these and other conflicts, individuals make up with each other and might solve future conflicts more peacefully.
In addition, many species have an innate sense of fairness, or aversion to inequality. They notice when one individual has obtained or been given something of greater value and are willing to hold out for the better item. Capuchin monkeys, for example, will refuse to perform a behavior for a cucumber reward if they see others being given grapes.
In the overall picture painted by the research, evolution favors flexible social dynamics that help individuals from diverse species across the Tree of Life thrive under variable conditions. Dynamics that promote fairness and equality are central to the evolution of social behavior, and hierarchy and inequality are not inevitable.
"Where there is inequality in nature, biological mechanisms countering inequality will emerge," Natterson-Horowitz said.
More information: Jennifer E. Smith et al, Mechanisms of equality and inequality in mammalian societies, Philosophical Transactions of the Royal Society B: Biological Sciences (2023). DOI: 10.1098/rstb.2022.0307
Journal information: Philosophical Transactions of the Royal Society B
Provided by University of California, Los Angeles | Biology |
Evolution of the largest of the large dinosaurs
Sauropods—including iconic long-necked dinosaurs like Brachiosaurus and Apatosaurus—were the largest animals ever to walk the earth. No other dinosaur or land mammal even comes close. Now, a new Adelphi University study provides insights into how these super giants achieved their record-breaking sizes over time.
"It was previously thought that sauropods evolved their exceptional sizes independently a few times in their evolutionary history, but through a new analysis, we now know that this number is much higher, with around three dozen instances over the course of 100 million years around the globe," said paleontologist Michael D'Emic, assistant professor of biology at Adelphi University in New York and author of the study, "The Evolution of Maximum Body Size in Sauropod Dinosaurs," in the May 8 edition of Current Biology.
To investigate sauropod body size evolution, D'Emic compiled measurements of the circumferences of hundreds of weight-bearing bones, correlated with the weight of the animal they belonged to. He then used a technique called ancestral state reconstruction to map the reconstructed body masses of nearly 200 sauropod species onto their evolutionary tree.
The results show that sauropods reached their exceptional sizes early in their evolution and that with each new sauropod family to evolve, one or more lineages independently reached superlative status.
"Before going extinct with the other dinosaurs (besides birds) at the end of the Cretaceous Period, sauropods evolved their unrivaled sizes a total of three dozen times," he explains. "These largest-of-the-largest sauropods were ecologically distinct, having differently shaped teeth and heads and differently proportioned bodies, indicating that they occupied the 'large bodied' niche somewhat differently from one another."
Microscopic study of their bones revealed that sauropods had different growth rates as well, suggesting that the record-setters were metabolically distinct. This mirrors the pattern in mammals, which evolved very large body sizes quickly in the wake of the dinosaur extinction, before plateauing in the gigantic-mammoth range.
D'Emic's findings contradict Cope's rule, the popular 19th-century theory that animals' size evolves over time. Instead, the new study sees animals achieving different body sizes depending on their ecological context and whatever niches happened to be available—which can appear random when looked at from a large scale.
"While other researchers have explained sauropods' immense size in general based on their unique combination of features, there is no one feature or set of features that characterize the sauropods that did surpass terrestrial mammal size from the ones that didn't," he says.
Untangling why certain lineages evolved their super-giant sizes while other ones didn't will be the next step in the research.
More information: Michael D'Emic, The Evolution of Maximum Terrestrial Body Mass in Sauropod Dinosaurs, Current Biology (2023). DOI: 10.1016/j.cub.2023.02.067. www.cell.com/current-biology/f … 0960-9822(23)00240-3
Journal information: Current Biology
Provided by Adelphi University | Biology |
Levels of a protein present in tumours could predict someone's chances of surviving lung cancer and provide a new treatment, according to a study.Patients with high levels of TLR2 in early-stage lung cancer were found to have increased survival rates compared with those with lower levels.
A drug compound that activates TLR2 was also tested on mice and managed to reduce tumour growth.Researchers say the findings could help identify the disease earlier and improve people's chances of beating the disease.The five-year survival rate for late-stage lung cancer is 6%, but 50% when detected earlier.
TLR2 is linked with senescence, whereby cells stop growing and secrete chemicals and other proteins which trigger warning signals and defences against cancer.Senescent cells show up in early-stage lung cancers but not late-stage, suggesting they prevent progression of the disease. More from Science & Tech Fertilisers confuse bumblebees, making them less likely to land on flowers, study suggests First known sentence written in ancient alphabet discovered - on a head lice comb Ten possible jobs of the future - and why Britain may struggle to fill them "I think these results are really exciting," said Dr Fraser Millar, a lecturer in respiratory medicine at the University of Edinburgh."Very little is known about the biology of early lung cancer and, by understanding this process more, we have identified a possible new treatment for this devastating disease." The study was a collaboration between the University of Edinburgh, University College London, University of Cantabria, the Spanish National Research Council and the Mayo Clinic in the US.It's published in the Cell Reports journal.The experts hope it could lead to research into using senescence and the associated chemicals as part of a screening programme to provide earlier diagnosis.However, they say clinical trials would be needed to confirm whether the drug that activated TLR2 in mice is also effective in humans. | Biology |
Using an artificial intelligence algorithm, researchers at MIT and McMaster University have identified a new antibiotic that can kill a type of bacteria that is responsible for many drug-resistant infections.
If developed for use in patients, the drug could help to combat Acinetobacter baumannii, a species of bacteria that is often found in hospitals and can lead to pneumonia, meningitis, and other serious infections. The microbe is also a leading cause of infections in wounded soldiers in Iraq and Afghanistan.
“Acinetobacter can survive on hospital doorknobs and equipment for long periods of time, and it can take up antibiotic resistance genes from its environment. It’s really common now to find A. baumannii isolates that are resistant to nearly every antibiotic,” says Jonathan Stokes, a former MIT postdoc who is now an assistant professor of biochemistry and biomedical sciences at McMaster University.
The researchers identified the new drug from a library of nearly 7,000 potential drug compounds using a machine-learning model that they trained to evaluate whether a chemical compound will inhibit the growth of A. baumannii.
“This finding further supports the premise that AI can significantly accelerate and expand our search for novel antibiotics,” says James Collins, the Termeer Professor of Medical Engineering and Science in MIT’s Institute for Medical Engineering and Science (IMES) and Department of Biological Engineering. “I’m excited that this work shows that we can use AI to help combat problematic pathogens such as A. baumannii.”
Collins and Stokes are the senior authors of the new study, which appears today in Nature Chemical Biology. The paper’s lead authors are McMaster University graduate students Gary Liu and Denise Catacutan and recent McMaster graduate Khushi Rathod.
Drug discovery
Over the past several decades, many pathogenic bacteria have become increasingly resistant to existing antibiotics, while very few new antibiotics have been developed.
Several years ago, Collins, Stokes, and MIT Professor Regina Barzilay (who is also an author on the new study), set out to combat this growing problem by using machine learning, a type of artificial intelligence that can learn to recognize patterns in vast amounts of data. Collins and Barzilay, who co-direct MIT’s Abdul Latif Jameel Clinic for Machine Learning in Health, hoped this approach could be used to identify new antibiotics whose chemical structures are different from any existing drugs.
In their initial demonstration, the researchers trained a machine-learning algorithm to identify chemical structures that could inhibit growth of E. coli. In a screen of more than 100 million compounds, that algorithm yielded a molecule that the researchers called halicin, after the fictional artificial intelligence system from “2001: A Space Odyssey.” This molecule, they showed, could kill not only E. coli but several other bacterial species that are resistant to treatment.
“After that paper, when we showed that these machine-learning approaches can work well for complex antibiotic discovery tasks, we turned our attention to what I perceive to be public enemy No. 1 for multidrug-resistant bacterial infections, which is Acinetobacter,” Stokes says.
To obtain training data for their computational model, the researchers first exposed A. baumannii grown in a lab dish to about 7,500 different chemical compounds to see which ones could inhibit growth of the microbe. Then they fed the structure of each molecule into the model. They also told the model whether each structure could inhibit bacterial growth or not. This allowed the algorithm to learn chemical features associated with growth inhibition.
Once the model was trained, the researchers used it to analyze a set of 6,680 compounds it had not seen before, which came from the Drug Repurposing Hub at the Broad Institute. This analysis, which took less than two hours, yielded a few hundred top hits. Of these, the researchers chose 240 to test experimentally in the lab, focusing on compounds with structures that were different from those of existing antibiotics or molecules from the training data.
Those tests yielded nine antibiotics, including one that was very potent. This compound, which was originally explored as a potential diabetes drug, turned out to be extremely effective at killing A. baumannii but had no effect on other species of bacteria including Pseudomonas aeruginosa, Staphylococcus aureus, and carbapenem-resistant Enterobacteriaceae.
This “narrow spectrum” killing ability is a desirable feature for antibiotics because it minimizes the risk of bacteria rapidly spreading resistance against the drug. Another advantage is that the drug would likely spare the beneficial bacteria that live in the human gut and help to suppress opportunistic infections such as Clostridium difficile.
“Antibiotics often have to be administered systemically, and the last thing you want to do is cause significant dysbiosis and open up these already sick patients to secondary infections,” Stokes says.
A novel mechanism
In studies in mice, the researchers showed that the drug, which they named abaucin, could treat wound infections caused by A. baumannii. They also showed, in lab tests, that it works against a variety of drug-resistant A. baumannii strains isolated from human patients.
Further experiments revealed that the drug kills cells by interfering with a process known as lipoprotein trafficking, which cells use to transport proteins from the interior of the cell to the cell envelope. Specifically, the drug appears to inhibit LolE, a protein involved in this process.
All Gram-negative bacteria express this enzyme, so the researchers were surprised to find that abaucin is so selective in targeting A. baumannii. They hypothesize that slight differences in how A. baumannii performs this task might account for the drug’s selectivity.
“We haven’t finalized the experimental data acquisition yet, but we think it’s because A. baumannii does lipoprotein trafficking a little bit differently than other Gram-negative species. We believe that’s why we’re getting this narrow spectrum activity,” Stokes says.
Stokes’ lab is now working with other researchers at McMaster to optimize the medicinal properties of the compound, in hopes of developing it for eventual use in patients.
The researchers also plan to use their modeling approach to identify potential antibiotics for other types of drug-resistant infections, including those caused by Staphylococcus aureus and Pseudomonas aeruginosa.
The research was funded by the David Braley Center for Antibiotic Discovery, the Weston Family Foundation, the Audacious Project, the C3.ai Digital Transformation Institute, the Abdul Latif Jameel Clinic for Machine Learning in Health, the DTRA Discovery of Medical Countermeasures Against New and Emerging Threats program, the DARPA Accelerated Molecular Discovery program, the Canadian Institutes of Health Research, Genome Canada, the Faculty of Health Sciences of McMaster University, the Boris Family, a Marshall Scholarship, and the Department of Energy Biological and Environmental Research program. | Biology |
Conservationists have released new photos of the only known living albino giant anteater on Earth, who is now believed to be at least 1 year old.
Researchers from the Anteaters and Highways Project (AHP), a multi-year assessment of anteater-vehicle collisions set up by Brazil's Wild Animal Conservation Institute (ICAS), first discovered the anteater in December 2022 on a ranch in Brazil's Mato Grosso do Sul state. They named the unique animal Alvin.
Alvin was spotted clinging to his typically colored mother's back, a behavior seen in all young giant anteaters (Myrmecophaga tridactyla) below 10 months old. The team captured the snowy juvenile and fitted him with a GPS vest to track his future movements, AHP representatives wrote in a statement supplied to Live Science.
On May 10, AHP posted new images of Alvin on Facebook. The white anteater is now 4.9 feet (1.5 meters) long and weighs 31 pounds (14 kilograms), which suggests he is over 1 year old and not far from being fully grown, AHP representatives wrote on Facebook. Alvin was also given his second GPS vest after outgrowing his first one.
Albinism is a genetic condition that prevents animals from producing melanin, the pigment that gives color to their skin, fur, feathers, scales and eyes. As a result, individuals with albinism appear completely white and have pink eyes. Their eyes and skin are very sensitive to light, which can cause impaired vision and make individuals more susceptible to sunburn. Albinism is a recessive trait, meaning that both parents must carry a copy of the gene.
The main threat to most albino animals is a higher risk of predation because their discoloration often makes them stand out from their environment. And this seems to be the case with giant anteaters.
In August 2021, AHP researchers found the corpse of another juvenile male albino giant anteater, the first of its kind ever discovered, in the same area as Alvin. The body showed signs of predation.
"When we got there, he was already dead, but we were able to collect genetic samples that were sent to the lab for analysis," Dr. Débora Yogui, a veterinarian with the AHP team, said in the statement. By comparing the DNA collected from the first albino with Alvin's DNA, the team will be able to tell if the animals are related, she added.
If Alvin and the deceased albino are not directly related, it could suggest that the species gene pool has been decreased by inbreeding, which would explain why this rare condition has started appearing, AHP representatives wrote.
The researchers suspect that inbreeding is likely due to the destruction of the animals' natural habitat by human deforestation. Giant anteaters are currently listed as Vulnerable on the International Union for Conservation of Nature (IUCN) Red List.
The team is also concerned that, even if Alvin survives future predation, he may be impacted by overexposure to sunlight. Anteaters try to spend the hottest hours of the day in the shade because the land-dwelling mammals are poorly suited to dealing with extreme heat. But deforestation has robbed anteaters of this much-needed shade, which poses a particular problem to Alvin because of his sensitive skin.
The AHP researchers will continue to track and monitor Alvin's progress as he gets older. But they also warned that they will not step in to save Alvin if he falls ill or is attacked by predators.
"Even though we know that it runs several risks, we cannot interfere in the life of this animal directly, because we would be influencing natural ecological processes," Nina Attias, a wildlife biologist with ICAS, said in the statement. "As conservationists, we know that this is not good for the species or the environment."
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Harry is a U.K.-based staff writer at Live Science. He studied Marine Biology at the University of Exeter (Penryn campus) and after graduating started his own blog site "Marine Madness," which he continues to run with other ocean enthusiasts. He is also interested in evolution, climate change, robots, space exploration, environmental conservation and anything that's been fossilized. When not at work he can be found watching sci-fi films, playing old Pokemon games or running (probably slower than he'd like). | Biology |
Artificial Sweetener Metabolite Breaks DNA
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Scientists at the North Carolina State University found that a chemical compound produced through the digestion of a common artificial sweetener causes damage to DNA. The research is published in the Journal of Toxicology and Environmental Health, Part B.
Growing research on adverse effects of artificial sweeteners
Warnings around the health impact of consuming sugar has led many people to replace it in their diets with low calorie artificial sweetener alternatives, also known as non-sugar sweeteners (NSSs). However, a growing number of studies in the scientific literature are suggesting that there may be a cost behind this seemingly “healthy” swap.
Recent research on artificial sweeteners
In May, the World Health Organization (WHO) published new guidance on the use of non-sugar sweeteners (NSS), in which it recommends they are not to be used to control body weight or reduce the risk of non-communicable diseases (NCD). A few days later, researchers from the Institute for Food Systems Biology at the Technical University of Munich published new data demonstrating that even an “average” NSS intake can affect immune cells in the blood. A 2022 study of >100,000 adults suggested that artificial sweeteners are associated with an increased risk of cancer.
A team of researchers led by Dr. Susan Schiffman, adjunct professor in the joint department of biomedical engineering at North Carolina State University and the University of North Carolina at Chapel Hill, published new data demonstrating that a chemical formed when we metabolize a commonly used sweetener – sucralose – is genotoxic.
What does genotoxic mean?
Agents that are genotoxic can directly or indirectly cause damage to DNA. This is achieved through the agent adversely affecting enzymes that are key to DNA replication processes.
Sucralose-6-acetate breaks DNA strands
Previous research by Schiffman and colleagues identified that, when sucralose is ingested in rats, several fat-soluble compounds are produced in the gut, including sucralose-6-acetate. The team were concerned, as compounds that easily dissolve in fat are more likely to “stick around” in the body. This contradicts the reported findings of studies that were presented to gain regulatory approvals for sucralose, which claimed that it was not broken down in the body.
The new study involved a series of in vitro experiments where human blood cells were exposed to sucralose-6-acetate to assess genotoxicity markers using a high-throughput screening tool and a micronucleus test. | Biology |
Hogfish are the chameleons of the Atlantic Ocean, seamlessly changing their skin color depending on their environment. As if those morphing skills weren't impressive enough, these reef dwellers can also "see" with their skin with the help of special light-sensing cells, even after they die, according to a study published Tuesday (Aug. 22) in the journal Nature Communications.
Lorian Schweikert, an assistant professor in the Department of Biology and Marine Biology at the University of North Carolina Wilmington as well as an avid angler, witnessed this color-shifting phenomenon firsthand during a fishing expedition in Florida, when she watched a hogfish (Lachnolaimus maximus) she caught change its skin color to match the patterned white deck of the boat.
"They appear to be watching their own color change," Schweikert, who is also the lead author of the study, said in a statement.
Hogfish are typically found in coral reefs and are master magicians; as protogynous hermaphrodites, they can switch their sex from female at birth to male as adults, according to the Georgia Aquarium.
Now Schweikert and her co-authors think they've discovered how this color-shifting magic works by identifying specialized light-sensing cells located beneath a layer of color-changing cells in the hogfish's skin. This system enables them to watch their skin change color and adjust it to match their surroundings, according to the study.
This finding comes on the heels of a 2018 study in which Schweikert and her colleagues identified light-detecting proteins in hogfish skin. Called SWS1 opsins, these proteins are particularly sensitive to blue light. (Interestingly, they're also found in human retinas.) By using a biochemical technique known as immunolabeling, that research team pinpointed the proteins' exact locations in hogfish skin samples.
In the new study, the researchers likened the fish's light-sensitive opsins to "internal Polaroid film," since it "captures changes in the light" that hogfish can filter through their cells, according to the statement.
"The animals can literally take a photo of their own skin from the inside," co-author Sönke Johnsen, a biology professor at Duke University, said in the statement. "In a way they can tell the animal what its skin looks like, since it can't really bend over to look."
However, researchers were quick to emphasize that hogfish can't actually see with their skin as they do with their eyes, because eyes do more than detect light; they also receive information from the brain to unveil images.
"Just to be clear, we're not arguing that hogfish skin functions like an eye," Schweikert said in the statement. "We don't have any evidence to suggest that's what's happening in their skin."
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Jennifer Nalewicki is a Salt Lake City-based journalist whose work has been featured in The New York Times, Smithsonian Magazine, Scientific American, Popular Mechanics and more. She covers several science topics from planet Earth to paleontology and archaeology to health and culture. Prior to freelancing, Jennifer held an Editor role at Time Inc. Jennifer has a bachelor's degree in Journalism from The University of Texas at Austin. | Biology |
Bumblebees are fuzzy, rotund, and indisputably adorable. They’re also secretly swole. The insects can cart around loads up to 80% of their body weight during foraging flights, and new research demonstrates that doing so probably isn’t easy.
The heavier a bumblebees’ pollen haul, the hotter a bee’s body temperature is likely to get, according to a study published Tuesday in the journal Biology Letters. As with most other animals, there’s a ceiling on how hot a bumbler can be before its body fails. Together with climate change, the thermal tax of lifting pollen could pose a threat to the important agricultural pollinators.
Though nectar is the staple bee food, if you’ve ever noticed that a bee seemed to be wearing tiny Cheetos as leg warmers, then you’ve seen a bee foraging for pollen. The buzzing insects collect the protein-rich flower powder in specially structured hind leg pollen baskets. Adult bees snack a little bit on the stuff, but mostly pollen goes to provisioning bee larvae so the next generation can grow up small and strong. It’s a critical component of any balanced bee diet, and bumblebees need to forage pollen to get all their required nutrients.
Yet filling up those pollen baskets and flying around with the cargo takes energy and creates heat (likely even more than nectar foraging does), as shown in the new research. Specifically, the scientists found that for every milligram of pollen carried, common eastern bumblebees (Bombus impatiens) get about 0.07 degrees Celsius hotter. On average, carrying pollen resulted in a 2 C increase in body temp across all of the 91 bees collected and analyzed.
The researchers also established a thermal maximum for B. impatiens. In laboratory tests, they determined that the bumblebees seem to overheat between 41.3 and 48.4 C. Worryingly, the scientists often collected pollen-foraging bees with body temperatures within or approaching that threshold range. In other words: Those 2 degrees could easily be the difference between comfortable and too warm. Plus, the temperature tax of carrying pollen might make a crucial difference in the amount of foraging a bumblebee is able to perform on hot days.
The findings were a big surprise to study co-author Elsa Youngsteadt, an entomologist at North Carolina State University. Initially, when an undergraduate researcher in her lab (and her eventual co-author) Malia Naumchik suggested that bee pollen loads could be big enough to impact body temperature, Youngsteadt was skeptical. “I was like, ‘I’m not sure that we’d be able to pick up that signal,’” she told Gizmodo in a phone call. But Youngsteadt opted to support Naumchik, now a biology master’s student at Montana State University, in pursuing the idea, and the resulting data proved her first impulse incorrect. “I was floored by how clear of a signal it was,” the entomologist said.
To come to their conclusions, Naumchik and Youngsteadt trapped individual bumblebees that were actively foraging pollen. Immediately upon capture, each bee got stuffed into a tube-like contraption called a “bee squeezer” and had its temperature taken with a thin probe. From there, the researchers euthanized the bees, collected the pollen loads, and weighed the pollen and bee bodies separately.
As a baseline, the researchers didn’t want to just collect ambient temperature data but rather a more bee-specific data point. So, they stuck a dead bee on a temperature probe to keep continual tabs on a relevant thermal reading. “It’s perfectly controlled for the objectives of the study,” John Hranitz, a biologist at Bloomsburg University in Pennsylvania who was not involved in the new research, told Gizmodo in a phone call. “The study is well done and very complete.”
People often think of bees as cold-blooded animals whose temperatures are influenced solely by the environment, both Naumchik and Youngsteadt said. But actually, the complex insects are thought to control their body temperature in a few different ways. For instance, bees can rest in the shade or spit up nectar in order to get evaporative cooling going. Bee temp is a product of behavior and many of other variables.
The new data supports that pollen weight is one of those factors. A couple of past lab-based studies had already suggested that nectar foraging could make bees warmer and boost their metabolic rates. This research extends that knowledge to pollen and shows that the trend holds true even in the wild.
To compensate for the hot and heavy burden that pollen poses, the bees are likely making adjustments when it’s warm outside. “They’re making trade-offs,” said Hranitz. For individual bees, carrying pollen isn’t “a death sentence or anything,” Naumchik said. “Our study isn’t saying that all bees are going to die... they have a lot of ways to adapt, and they probably will adapt.”
Maybe bees carry less pollen or work more slowly on steamy afternoons. Maybe bumblers will spend more time selecting flowers in the shade and avoid available food in the sun as the climate warms. Maybe, when it’s too hot, the bumblebees will simply opt to stay in their nests. Such shifts probably won’t cause immediate and obvious harm to individuals. Ultimately, though, those theoretical alterations are bound to impact the hive. Less pollen means less food for larvae and potentially fewer bees next year.
Bumblebee populations and ranges are already in decline. It’s a problem for the insects and also for the future of the plants they pollinate and human agriculture. Tomatoes, cucumbers, squash, and more are all often the product of a bumblebee’s efforts.
Previous research suggests that direct impacts of rising temperatures, more frequent extreme weather, habitat destruction, and pesticide use all play a role in bumblebee losses. But the interplay of climate change and pollen foraging could be yet another part of the explanation. “It’s one of several potential stressors that bumblebees are facing,” said Naumchik. “This might be just one piece of the puzzle.” Bumblebees may be super strong, yet everything—even an insect power lifter—has its limits. | Biology |
Marine scientists found a previously unknown octopus nursery in a discovery that could help lead to greater protection for the surrounding area off the Costa Rican coast.
“The discovery of a new active octopus nursery over 2,800 meters beneath the sea surface in Costa Rican waters proves there is still so much to learn about our Ocean,” Dr. Jyotika Virmani, an executive director at the Schmidt Ocean Institute, said in a statement from the nonprofit published Wednesday. The international team of scientists made their ocean expedition on the institute’s research vessel, the Falkor (too).
Brooding octopus mothers on an unnamed outcrop off the coast of Costa Rica.
On the voyage, scientists explored the Dorado Outcrop, a rock formation where in 2013, octopus mothers were spotted gathering together to brood their eggs ― the first time scientists had ever seen that happen. But at the time, researchers weren’t sure if the nursery was viable. Deep-sea octopuses prefer cold temperatures, but the outcrop is next to a hydrothermal vent that causes warmer waters than the surrounding area, Gizmodo reported.
On the newest mission, scientists confirmed that the Dorado Outcrop was an “active nursery” and witnessed baby octopuses hatch. On top of that, they discovered another totally new nursery in the same general area. Those two nurseries, plus another one off the coast of Monterey, California, brings the total number of known octopus nurseries up to three.
Only three deep-sea octopus nurseries are known to humans.
“I was bouncing off the walls,” Dr. Rachel Lauer, a geoscience professor at Canada’s University of Calgary, said in a video about the expedition’s discoveries.
The octopuses found in the nurseries near Costa Rica belong to the genus Muusoctopus ― small to medium deep-sea octopuses that don’t have ink sacs. The scientists suspect the octopuses they saw are “potentially a new species” of Muusoctopus, the Schmidt Ocean Institute news release said, though this has not been confirmed.
The octopus that researchers believe may be a newly discovered species.
The research could be used to determine whether the seamounts in the area of the nurseries should be granted protection from human activities. Currently, there are no protections in place.
“For the majority of people, the ocean is just another body of water,” Dr. Jorge Cortés Núñez, a biology professor at the Universidad de Costa Rica, said in the video, translated from Spanish by Schmidt Ocean Institute. “They can’t imagine what’s there. The seafloor is 3 kilometers below us, and what we are seeing is a whole other world down there.” | Biology |
September 07, 2022 03:03 PM Scientists may have just discovered one of the most hospitable planets to life to date. A team of researchers from the University of Birmingham recently announced the discovery of SPECULOOS-2c in the middle of the habitable zone of a star system that is home to moderate-enough temperatures to sustain liquid water. The researchers claim the planet is the second most hospitable planet discovered outside Earth's solar system. CHINA TESTS ROCKET ENGINE FOR MOON LANDING AS SPACE RACE HEATS UP "The habitable zone is a concept under which a planet with similar geological and atmospheric conditions as Earth would have a surface temperature allowing water to remain liquid for billions of years," said Amaury Triaud, a professor of exoplanetology at the University of Birmingham who participated in the research, per Phys.org. SPECULOOS-2c is not guaranteed to host alien life, but the researchers contend it is one of the best-suited planets for life out of the worlds they have studied so far. The planet is roughly 30% to 40% larger than the Earth and orbits its star in about 8.4 days, according to the outlet. Triaud and his fellow researchers estimate that SPECULOOS-2c is the second most hospitable planet to life outside of TRAPPIST-1, a planet Triaud and his colleagues discovered in 2016. SPECULOOS-2c is tidally locked with its star, meaning one side is always facing it. SPECULOOS-2c, also named LP 890-9c, was discovered near LP 890-9b and orbits a star known as SPECULOOS-2, according to the researchers. LP 890-9b, a planet that was previously identified by NASA's Transiting Exoplanet Survey Satellite, could also be hospitable to life, the researchers contended. However, they have taken a keen interest in SPECULOOS-2c specifically. CLICK HERE FOR MORE FROM THE WASHINGTON EXAMINER Not much else is known about SPECULOOS-2c, and Triaud is hoping that technology such as the James Webb Space Telescope could shed additional light on the composition of its atmosphere to assess whether it could host alien life. “It is important to detect as many temperate terrestrial worlds as possible to study the diversity of exoplanet climates and eventually to be in a position to measure how frequently biology has emerged in the cosmos,” Triaud continued. | Biology |
The reaction of narwhals to the loud noise from seismic air guns used in oil exploration involves a disruption of the normal physiological response to intense exercise as the animals try to escape the noise. The overall effect is a large increase in the energetic cost of diving while a paradoxically reduced heart rate alters the circulation of blood and oxygen.
“They’re swimming as hard as they can to get away, and yet their heart rate is not increasing—we think because of a fear response. This affects how much blood and oxygen can circulate, and that’s going to be problematic,” said Terrie Williams, a professor of ecology and evolutionary biology at UC Santa Cruz who led the new study.
Published July 8 in the Journal of Functional Ecology, the study provides the first look at the impact of seismic noise on the physiological responses of a deep-diving cetacean. According to Williams, the combination of extremely low heart rates, increased heart rate variability, and high-intensity exercise during deep dives presents a significant physiological challenge for narwhals, especially if the disruptions are prolonged as would be likely during extended oil exploration activities.
Narwhals live year-round in high Arctic waters where sea ice has helped isolate them from disturbance by humans for millions of years. But declines in polar sea ice are making the region more accessible to shipping, natural resource exploration, and other human activities.
In a previous study, Williams and her coauthors showed that narwhals released after entanglement in nets set by indigenous hunters showed a similar physiological response, with extremely low heart rates during intense exercise in a series of escape dives. The difference between a capture event and noise, Williams said, is the potential duration of the disturbance.
“When they escape from the nets, their heart rate comes back up to a more normal rate within three or four dives, but with the seismic ship moving through and the sound bouncing around, the escape response occurred over a longer period,” she said.
The researchers recorded not only extremely low heart rates during noise exposure, but also increased variability, with heart rates switching rapidly between extremely low rates associated with fear and fast rates associated with intense exercise. Reduced heart rate, or bradycardia, is a normal part of the mammalian dive response, but during normal dives the heart rate still increases with exercise. In addition, narwhals and other deep-diving marine mammals usually save energy by gliding rather than actively swimming as they descend to depth.
During noise exposure, the narwhals performed 80% less gliding during diving descents, their swimming strokes exceeded 40 strokes per minute, their heart rates dropped below 10 beats per minute, and their breathing at the surface was 1.5 times faster. Overall, this unusual reaction is very costly in terms of energy consumption, Williams said.
“Not only is the reaction costly in terms of the energy needed for diving, the escape time will also take away from time spent foraging for food and other normal behaviors,” she said.
The studies were conducted in Scoresby Sound on the east coast of Greenland, where coauthor Mads Peter Heide-Jørgensen, a research professor at the Greenland Institute of Natural Resources, has been studying the East Greenland narwhal population for more than a decade.
Williams's group at UC Santa Cruz developed instruments that enable researchers to monitor the exercise physiology of marine mammals during dives. The instruments were attached to narwhals with suction cups and fell off after one to three days, floating to the surface where they could be recovered by the scientists.
Over the past two decades, noise from human activities such as military sonar has been linked to mass strandings of deep-diving cetaceans, mostly beaked whales. These deep-diving species are extremely difficult to study, and it was only through a partnership with indigenous hunters that Williams and Heide-Jørgensen’s teams were able to attach monitoring devices to narwhals.
“Most of the potential impacts on the animals take place underwater, so it’s really difficult to study,” Williams said. “We are fortunate to have this technology to show what’s happening at depth where these animals live in order to understand how their biology may be disrupted.”
In addition to Williams and Heide-Jørgensen, the coauthors of the paper include Susan Blackwell at Greeneridge Sciences, Outi Tervo and Eva Garde at the Greenland Institute of Natural Resources, Mikkel-Holger Sinding at University of Copenhagen, and Beau Richter at UC Santa Cruz. This work was supported by the U.S. Office of Naval Research, Greenland Institute of Natural Resources, the Environmental Agency for Mineral Resource Activities of the Government of Greenland, the Danish Ministry of Environment, and the Carlsberg Foundation. | Biology |
Researchers have discovered a previously unknown mechanism by which bacteria share their genetic material through virus parasites. The insights could help scientists to better understand how bacteria rapidly adapt and evolve, and how they become more virulent and resistant to antibiotics.
n a study published today in Cell, one of the most prominent peer-reviewed scientific journals in the field of Biochemistry & Molecular Biology, scientists from the National University of Singapore (NUS) and Imperial College London have discovered a new way by which bacteria transmit their genes, enabling them to evolve much faster than previously understood. Led by Assistant Professor John Chen from the Department of Microbiology and Immunology and the Infectious Diseases Translational Research Programme at the NUS Yong Loo Lin School of Medicine (NUS Medicine), the insights could help scientists to better understand how pathogenic bacteria evolve and become increasingly virulent and resistant to antibiotics.
The ability to share genetic material is the major driver of microbial evolution because it can transform a benign bacterium into a deadly pathogen in an instant. Phages, the viruses of bacteria, can act as conduits that allow genes to transfer from one bacterium to another by a process known as genetic transduction. Currently, there are three known mechanisms of transduction: generalised, specialised, and lateral. Lateral transduction was also discovered by the same groups of researchers in 2018, and it is at least one thousand times more efficient than the next most powerful mechanism, generalised transduction.
The new process is termed lateral cotransduction, and the architects behind this new frequency and speed in bacterial evolution are the Staphylococcus aureus pathogenicity islands (SaPIs), which are selfish DNA elements that exploit and parasitise phages and are commonly found integrated into the chromosomes of S. aureus isolates. S. aureus is a type of bacteria that can cause Staph infections in humans and animals. While it primarily manifests as skin infections, it can become life-threatening if it spreads to the bloodstream and infects organs, bones, or joints.
Professor José R. Penadés from the Department of Infectious Diseases, and Director for the Centre for Bacterial Resistance Biology at Imperial College London, said, "This breakthrough sheds light on a novel pathway through which bacteria evolve. Given the alarming surge of antibiotic-resistant superbugs, comprehending the mechanisms driving bacterial evolution becomes increasingly critical."
This newly discovered process, lateral cotransduction, rivals lateral transduction in terms of efficiency but surpasses the latter in versatility and complexity. While lateral transduction is only known to occur when dormant phages within bacterial genomes become reactivated and initiate reproduction in the lytic cycle, lateral cotransduction can occur during the reactivation process and the infection of new bacterial cells.
Additionally, unlike phages that sacrifice their genes to transmit bacterial host DNA, SaPIs can transfer themselves completely intact with bacterial DNA through lateral cotransduction. This remarkable capability enables them to perpetually repeat the process, making them significantly more potent and efficient in transmitting bacterial genes.
Asst Prof Chen said, "Through the study, we have demonstrated that bacteria can evolve much faster than we understood. While genetic transduction has always been the exclusive domain of phages, in an unexpected twist of irony, our research has shown that parasites of the most prolific parasites on the planet (the phages) are probably the most powerful and efficient transducing agents currently known."
The rise of superbugs has called for new ways to treat antibiotic-resistant strains. One such method that has gained traction in recent years is phage therapy, which involves the use of phages to eliminate harmful bacteria in infections and diseases. However, instead of just fighting bacteria, some therapeutic phages could turn out to be the unwitting accomplices of SaPIs or other related elements capable of lateral cotransduction.
According to Prof Penadés, "This process likely occurs in various other bacterial species as well. This groundbreaking finding marks a paradigm shift in our understanding of bacterial evolution and will immensely influence the ways we combat antibiotic resistance."
"They (phages) could be used to destroy bacteria in the short term but end up spreading harmful genes to other cells in the long term, which could prove to be disastrous. With this new way of understanding the evolutionary mechanisms of disease-causing organisms, it is important for therapeutic phages to be carefully vetted before they are used for therapy," said Asst Prof Chen.
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Polyrhachis femorata (Hymenoptera: Formicidae) habitat and colony defensive immobility strategySophie Petit A B * , Peter A. Hammond B , Brian Heterick C and John J. Weyland B
A University of South Australia, UniSA STEM, Mawson Lakes, SA 5095, Australia.
B Kangaroo Island Research Station, Dudley West, Penneshaw, SA 5222, Australia.
C Department of Terrestrial Zoology, Western Australian Museum, Welshpool, WA 6106, Australia.
Handling Editor: Paul Cooper
Australian Journal of Zoology 70(4) 126-131 https://doi.org/10.1071/ZO22042
Submitted: 22 November 2022 Accepted: 6 March 2023 Published: 28 April 2023
© 2022 The Author(s) (or their employer(s)). Published by CSIRO Publishing. This is an open access article distributed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND)
Abstract
Many animal species ‘play dead’ or feign death (in some cases called tonic immobility) as a defence strategy against predators, including some ants, although triggers and durations are poorly understood. We repeatedly observed such death-feigning behaviour in Polyrhachis femorata ants that occupied pygmy-possum nest boxes deployed on Kangaroo Island following the 2019–2020 bushfires that burnt half of the island. Most of the 759 bat and pygmy-possum boxes (901 cavities) were on burnt ground. In 3312 box cavity checks on 13 diverse properties during monitoring visits, 28 of 40 P. femorata records (first for South Australia) occurred in unburnt Critically Endangered Narrow-Leaf Mallee Woodland community, seven in adjacent mallee community containing narrow-leaf mallee, three in cup gum unburnt habitat, and two in one box on burnt ground. Fire may have affected the abundance and re-establishment of the species. Polyrhachis femorata engages in a surprising defensive immobility strategy in boxes, since it is not only undertaken by individuals facing a potential predator, but also by entire colonies. The death-feigning behaviours were complemented by plugging box entrances. Nest boxes may be used to study this mysterious behaviour in this poorly known species, although frequent observation could lead to nest abandonment by the ant.
Keywords: ant defence, bushfire, catalepsy, Eucalyptus cneorifolia, playing dead, thanatosis, tonic immobility, tree cavity, tree hollow.
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Review “Being You is an engaging and accessible tour through the field’s boldest theories, most creative experiments and most surprising findings. You could give the book to a smart teenager and get them asking questions that they will be thinking about for the rest of their lives.”—Current Biology“Whenever I hear that someone has found a new theory of consciousness, I start to lose my own… So when the latest would-be Einstein announces yet another theory, my eyes start to glaze over in anticipation of drivel and disappointment. Neuroscientist Anil Seth’s Being You is the exception that proves the rule. If you only read one book about consciousness, it must be his… An impressive work that handles complex issues with exceptional insight and beautiful clarity.”—Julian Baggini, Wall Street Journal“[Seth] tells us about the Japanese roboticist who builds ‘Geminoids’—robots as similar to human beings as possible, including one resembling himself, which delivered a 45-minute lecture to a large audience of students. It is a brilliant book…”—Claire Tomalin, New York Times Book Review"Exhilarating... a vast-ranging, phenomenal achievement that will undoubtedly become a seminal text." —The Guardian“Seth makes a convincing case that perception masquerades as conscious reality… Fluent and accessible.”—Financial Times “Drawing on philosophy, biology, cognitive science, neuroscience and artificial intelligence, he argues that our brains are prediction machines that constantly invent our world and then correct our mistakes, so that our sense of self derives from our body.”—Nature “Imaginative and compelling…”—Scientific American“A fantastic exposition to a family of revolutionary ideas gaining increasing support both from neuroscience and artificial-intelligence research. It is a much-rewarding read, both for people familiar with the central questions of consciousness and the interested newcomer.”—World Literature Review“Exhilarating, informed, passionate and provocative in equal measure—as much a groundbreaking work of philosophy as of science. It’s a book that lingers with you, while at the same time forcing you to rethink exactly who and what “you” are."—Research Professional News“In lucid, engaging prose Seth deftly navigates long-standing philosophical debates over the nature of consciousness… awe-inspiring.”—New Statesman“An accessible, unfailingly interesting look inside the workings of the human brain, celebrating its beguiling nature.”—Kirkus“[Seth’s] extraordinary debut sets out his exhilarating new theory about how we experience the world.”—The Bookseller (Editor's Choice)“[Anil Seth] takes on the prodigious task of defining consciousness and explaining its origins in this intense survey.”—Publishers Weekly“One of the most authoritative voices in a central question of neuroscience: what is consciousness? His new book is a page-turner and a mind-blower. If you've ever wondered how billions of neurons chattering in the dark equate to your experience, start here... Beautifully written, crystal clear, deeply insightful.”—David Eagleman, neuroscientist at Stanford University, author of Livewired and Incognito“A brilliant beast of a book. A wide ranging synthesis pulling together disparate stands—from philosophy, science, literature, personal experience and speculation—this latter being the most exciting for me, despite some proposals being as yet unproven. Seth proposes to explain not just what and how we are, but probably provocative for some folks, why we are the way we are. Why do we have the feeling of continually being the same person? (When obviously I, at least, am not.) Why do we have this feeling of being self aware? What is it for? Hugely inspirational—I filled up 10 pages with exuberant notes. Keep a pencil handy.”—David Byrne, founding member of Talking Heads“There could hardly be a better guide to the theories—good and bad—currently swirling around the science of consciousness. Seth writes with grace and charm, gently demolishing bad ideas—such as panpsychism, and Integrated Information Theory—while building a case for his own very good idea that consciousness is a kind of controlled hallucination, the brain’s best guess at inventing the future.”—Nicholas Humphrey, neuropsychologist and author A History of the Mind and Soul Dust“Seth provokes us to think about thinking. And he offers what the interested reader always needs—a book which makes complex ideas readable, relatable, and gripping. If you want to understand his subject better—he’ll help you. And who wouldn’t want to better understand consciousness? In our lives, there is nothing weirder or more fundamental.”—Alex Garland, director of EX MACHINA“Being You offers us new cause for astonishment and wonder. Through expert science writing and engaging personal narrative, Anil gives us a new perspective on everything we perceive, down to space and time itself. Being You is a must read for anyone seeking a better understanding of the brain and how nature sculpts the human experience.” —Annaka Harris, author of Conscious“Reality is real, but how our brains construct a picture of reality—perceiving, integrating, predicting—is far from direct. It's a complicated, fascinating mess, which neuroscientists are just beginning to piece together. Anil Seth's Being You is a wonderfully accessible and comprehensive account of how our minds capture the world, and how that makes us who we are.”—Sean Carroll, author of Something Deeply Hidden“In this lucid and thought-provoking exploration of the nature of consciousness, Seth takes us closer than ever to making sense of our experience of being conscious selves. A must-read.” —Anil Ananthaswamy, award-winning journalist and author of Through Two Doors at Once and The Man Who Wasn’t There “A fascinating book. A joy to read. Anil Seth explores fundamental questions about consciousness and the self from the perspective of a philosophically-informed neuroscientist. Highly recommended.” —Nigel Warburton, author of A Little History of Philosophy and Philosophy “Insightful and profound. The nature of consciousness is still one of the hardest problems in science, but Anil Seth brings us closer than ever before to the answer. This a hugely important book.” —Jim Al-Khalili, author of The World According to Physics“What makes you, you? What explains your consciousness and sense of self? In this remarkable and ground-breaking work, Anil Seth offers a surprising answer, rooted in the new science of the predictive brain. Compulsory reading for anyone who wants to better understand their inner ‘beast machine.’” —Andy Clark, author of Surfing Uncertainty: Prediction, Action, and the Embodied Mind “Seth is uniquely placed to truly advance our understanding of one of humanity’s deepest riddles.” —Chris Anderson, Curator of TED “The treatment of consciousness on offer is eclectic and delivered with a particular kind of generosity: it is both generous to the reader, in its earnest (and successful) attempt to lay bare the essentials of different contributions. It is generous to these contributions per se: ranging from anaesthesia—the art of turning people into objects—from information theory to the Wizards of Odds (abductive Bayesian inference), from the Beholder's Share to the free energy principle—aptly defined as there are more ways of being mush than there are of being alive. It's dénouement is a millennial take on being A Beast Machine: a potent account of embodied sentience and selfhood. An account that is rendered irresistible by Anil Seth’s gentle and inclusive arguments.” —Karl Friston, University College London “Anil Seth is one of the world’s leading consciousness researchers—his take on the subject is unique and refreshing, and his talks and writing always exciting, accessible, and engaging. I look forward to his book-length account concerning experience and its place in nature.” —Christof Koch, Allen Brain Institute, author of Consciousness: Confessions of a Romantic Reductionist “Anil Seth thinks clearly and sharply on one of the hardest problems of science and philosophy, cuts through weeds with a scientist’s mind and a storyteller’s skill.” —Adam Rutherford, author of A Brief History of Everyone Who Ever Lived“Anil Seth was my most anticipated guest in 2021, and our conversation was one of the highlights of the year. If you can only read one book this year, it should be Being You.”—Ginger Campbell, MD, host of Brain Science, the world’s leading neuroscience podcast About the Author Anil Seth is a professor of cognitive and computational neuroscience at the University of Sussex, and co-director of the Sackler Centre for Consciousness Science. | Biology |
There’s a strong relationship between diet in early life and food preferences in adulthood, research with mice finds.
The study in Science Advances highlights the importance of early exposure to a variety of tastes and identifies the neural basis regulating preferences for favorite foods, providing important new information about the relationship between nutrition and brain function.
Previous investigations of human infants hinted at the effect of early taste experience on food preference later in life. However, no previous study examined the neural bases of this phenomenon. This study looks at the neural bases of taste preference and provides findings that could form a basis to understanding the neural processes involved in taste preference.
The biology of the gustatory system is similar across all mammals. By using a rodent model, researchers from the Renaissance School of Medicine at Stony Brook University exposed groups of mice to a variety of taste solutions for one week. They exposed groups as either weanlings (early exposure) or as adults (late exposure). After the one week experiencing a variety of tastes, they returned the groups to their regular diet, which contained balanced nutrients but was not rich in taste. For comparison, a control group of mice was raised only on the regular, blander diet.
“Our research is directed at assessing whether and how the gustatory experience and diet influence brain development. This study shows that the gustatory experience has fundamental effects on the brain. The next steps will be to determine how different diets such as a high fat, or a high sugar or high salt, may influence taste preferences and neural activity,” explains Arianna Maffei, senior author and professor in the department of neurobiology and behavior.
Food preferences
Maffei, lead author Hillary Schiff, and colleagues increased taste variety in the healthy diets of mice and found that the development of neural circuits and taste preference are influenced by all aspects of the gustatory experience: sensations in the mouth, smell, and gut-brain relations.
Several weeks after exposing the groups to the one-week taste variety, the investigators measured preference for a sweet solution compared to water. Mice who experienced taste variety early in life had a stronger preference for sweet tastes in adulthood compared to the control group. This change preference depended on a combination of taste, smell, and gut-to-brain signals, and was specific to early exposure taste. Mice exposed to taste variety as adults did not show different sweet preferences from their age-matched control group.
These results indicate that taste experience influences preference, but only if given within a restricted time window.
The gustatory cortex
The researchers also recorded the activity of neurons in the gustatory cortex of all the subjects. This part of the brain is involved in taste perception and decisions about ingesting or rejecting foods. The recorded activity showed that the shift in sweet preference was associated with differences in the activity of inhibitory neurons of adult mice.
This led to the question of whether manipulating these inhibitory neurons in adulthood can re-open the window of sensitivity to the taste experience.
To answer this question, the research team injected a substance into the gustatory cortex that breaks down perineuronal nets, which are webs of proteins that accumulate around inhibitory neurons early in life. Once established, these nets play a key role in limiting plasticity—the ability to change in response to stimuli at inhibitory synapses.
When adult mice without perineuronal nets in the gustatory cortex were exposed to the taste variety, they showed a similar change in sweet preference as the group exposed earlier in life. This manipulation “rejuvenated” inhibitory synapses in the gustatory cortex and restored plasticity in response to taste experience, which confirmed the importance of maturation and plasticity in inhibitory circuits for the development of taste preference in the experimental model.
“It was striking to discover how long-lasting the effects of early experience with taste were in the young groups,” says Schiff. “The presence of a ‘critical period’ of the life cycle for the development of taste preference was a unique and exciting discovery. The prevailing view from other studies prior to this finding was that taste does not have a defined window of heightened sensitivity to experience like other sensory systems such as vision, hearing, and touch.”
From mice to humans
The authors maintain that while they conducted the study in mice, the results inform scientists on the fundamental biological aspects of experiences with taste that extends beyond animal models and to humans.
“The development of taste preference requires a full gustatory experience,” adds Maffei. “This includes the detection of taste in the mouth, its association with smell, and the activation of gastrointestinal sensations. All these aspects influence the activity of brain circuits, promoting their healthy development.”
Regarding humans, Maffei points out that we often favor food from our childhood, highlighting important cultural aspects of our taste experience. Additionally, in the public health realm, several neurodevelopmental and neurodegenerative disorders are often associated with hyper- or hyposensitivity to gustatory stimuli, suggesting links between taste and brain function in health and disease.
“Expanding our knowledge of the developmental neural circuits for tastes—as studies like this do—will contribute to our understanding of food choices, eating disorders, and diseases associated with brain disorders,” emphasizes Maffei.
Schiff, Maffei, and collaborators conclude that their overall experimental results establish a fundamental link between the gustatory experience, sweet preference, inhibitory plasticity, circuit function, and the importance of early life nutrition in setting taste preferences.
The research had support from the National Institute on Deafness and Other Communication Disorders and from the National Institute of Neurological Disorders and Stroke at the National Institutes of Health.
Source: Stony Brook University | Biology |
Image: Shutterstock (Shutterstock)People’s cancers are apparently playing host to their very own fungi. A pair of studies this week have documented the unique neighborhoods of fungal species that can live inside our tumors. It’s possible that these microbes may even influence how cancers grow or manage to fend off certain treatments.OffEnglishDating back to the 19th century, scientists have known that bacteria and other microscopic organisms routinely live on or inside our bodies, usually without making us acutely sick. But it’s only in the past few decades that we’ve started to appreciate the importance of these microbial communities, or microbiomes, to our well-being and health. And it’s only more recently that we’ve begun to closely study the microbiomes found within cancers.Much of the early research into these cancer microbiomes has focused on bacteria. But while fungi are less abundant in the human body, they’re still thought to play a vital role in how microbiomes influence our health. These new papers, both published Thursday in the journal Cell, are some of the first to try creating a rough map of the fungal microbiome found within our cancers.One of these studies involved researchers from the University of California-San Diego School of Medicine as well as the Weizmann Institute of Science in Israel. Looking at more than 17,000 blood and tissue samples that were taken from cancer patients, they were able to find low amounts of fungi across 35 different types of cancer.“The existence of fungi in most human cancers is both a surprise and to be expected,” said study author Rob Knight, a researcher and professor at UC San Diego, in a statement from the university. “It is surprising because we don’t know how fungi could get into tumors throughout the body. But it is also expected because it fits the pattern of healthy microbiomes throughout the body, including the gut, mouth and skin, where bacteria and fungi interact as part of a complex community.”Across the different cancer types, the microbiomes had different mixes of fungal species, but there were some common trends noticed by Knight and his team. These fungi usually appeared to be intracellular, meaning that they live inside cancer cells. They also found evidence that the fungi and bacteria within these cancers commonly interact with each other, and often not in a competitive way. Perhaps more importantly, the team found associations between these fungal microbiomes and aspects of the cancer itself, such as its response to immunotherapy treatments.The other study was led by researchers from Duke and Cornell University. This team also found plenty of fungi nestled within human cancers, with some cancers being more likely to harbor certain fungi than others. In lung cancer tumors, for instance, Blastomyces fungi were more commonly found, while Candida fungi were more common in gastrointestinal cancers. The presence of Candida fungi in particular was also linked to a lower chance of survival for patients with these cancers.At this point, these findings only show a correlation between the fungal microbiome and cancer outcomes, not a direct cause-and-effect relationship. And while the microbiome, in general, is important to human health, we’re still very early in studying exactly how it affects us, much less how to repair a microbiome that’s become harmful. But this research will give scientists a clearer understanding of the complex biology of cancer, and perhaps someday, might allow them to create improved treatments against it.“The finding that fungi are commonly present in human tumors should drive us to better explore their potential effects and re-examine almost everything we know about cancer through a ‘microbiome lens,’” said co-author Ravid Straussman, a principal investigator at the Weizmann Institute of Science. | Biology |
US college-level biology textbooks miss the mark on offering solutions to the climate crisis, according to a new analysis of books over the last 50 years.Fewer than three pages in a typical 1,000-page biology textbook from recent decades address climate change, according to the new study, despite experts warning it is humankind’s biggest problem.While the coverage of the topic has expanded since the 1970s, and sentences focused on climate solutions peaked in the 1990s, that emphasis declined by 80% in recent decades.The average coverage of climate change in biology textbooks from the past decade was 67 sentences, a step up from 51 sentences in the 2000s.Researchers said that was not enough given the scale of the crisis.“Climate change is affecting life all over the globe,” said Jennifer Landin, author of the study and an associate professor of biology at North Carolina State University. “And we are not covering it to nearly the degree it needs to be.”The researchers analyzed a total of 57 US college biology textbooks published between 1970s to 2019 for the new study, published in the Public Library of Science journal, Plos One.In that span, the placements of material about solutions to the climate crisis migrated further back in the books, from the last 15% to the last 2.5% of the pages.“People tend to move through books from beginning to end,” Landin said, “and of course, everybody sort of runs out of time, so if you have something at the very end, the odds are that that’s going to be either covered quickly or not at all.”In their analysis of sentences that cover solutions, national or international responsibility came up over four times that of individual or local solutions. No textbook mentioned actions related to dietary choices, with only eight books addressing transportation as means to lower greenhouse emissions.“I was never really taught about climate change, maybe a day or two but nothing in depth,” said Rabiya Arif Ansari, co-author of the paper who started researching these textbooks in her second year of college. “A lot of my peers lacked information regarding climate change so I was very curious about how people are learning it.”One of the possible reasons for the downward shift in solutions coverage that the paper points to might be stemming from textbook authors. In the 1990s, there were many authors focused on science education and science communication, while in recent decades the field saw an increase in the number of authors who specialize in cellular or molecular biology. Another possible reason that the paper discusses is the societal backlash against not only acceptance and action on climate change, but also conservation issues overall.The researchers conclude that the proportion of biology textbooks that cover climate change solutions don’t reflect the severity of the problem. And such a trend is not unique to biology.A 2019 study of top 11 best-selling introductory sociology textbooks show a similar pattern of relegating pages on environmental issues and climate toward the end of the books.“What troubles me a lot is that sociology rarely talks about climate change,” says John Chung-En Liu, associate professor of sociology at National Taiwan University. “Which is very ironic because climate change is a problem of our society, especially social inequality, not to mention the justice dimension.”Liu points to the role of the publication industry, with college textbooks known for not keeping up to date with the changes. Most textbooks are updated only every three or four years, with the structure remaining more or less the same.“Very often textbooks are 10 years behind in terms of how the research has progressed,” Liu says.He hopes to see an increase in page space devoted to the climate crisis, and shifting of that content from the end of the book to the center. Landin notes that biology textbooks tend to go from small-scale to large-scale, with the environmental issues and ecology appearing only in the end.“I think that students learn best when we start from what they know and then expand into the unknown,” Landin says, proposing the reversal of the order from large-scale organisms to small-scale topics of cellular and molecular biology.Another issue is that traditional textbook use is declining, which Landin views as an opportunity to look at what comes next and what needs to be emphasized to better help students. | Biology |
Using topology, researchers advance understanding of how cells organize themselves
The fact that humans and other living organisms can develop and grow from a single cell relies on a process called embryonic development. For healthy tissue to form, cells in the embryo have to organize themselves in the right way in the right place at the right time. When this process doesn't go right, it can result in birth defects, impaired tissue regeneration or cancer. All of this makes understanding how different cell types organize into a complex tissue architecture one of the most fundamental questions in developmental biology.
While researchers are still some distance from fully understanding the process, a group of Brown University scientists has spent the past handful of years helping the field inch closer. Their secret? A branch of mathematics called topology.
The research team at Brown, made up of biomedical engineers and applied mathematicians, created a machine learning algorithm using computational topology that profiles shapes and spatial patterns in embryos to study how these cells organize themselves into tissue-like architectures. In a new study, they take that system to the next level, opening a path to studying how multiple types of cells assemble themselves.
The work is described in npj Systems Biology and Applications.
"In tissues, there may be differences in how one cell adheres to the same cell type, relative to how it adheres to a different cell type," said Ian Y. Wong, an associate professor in Brown's School of Engineering who helped develop the algorithm. "There's this interesting question of how these cells know exactly where to end up within a given tissue, which is often spatially compartmentalized into distinct regions."
For example, in an animal embryo, the outer layer of cells goes on to form skin, the middle layer forms muscle and bone, while the innermost layer forms the liver or lungs. Cells within each layer will preferentially adhere to each other, sorting apart from cells in other layers that go on to form other parts of the body.
In the 1970s, scientists discovered that cells within frog embryos could be gently separated apart and when they were mixed back together, they would spontaneously rearrange into their initial organization. This occurs because the cells have different affinities for each other, and as they assemble and cluster, certain topological patterns of linkages and loops are preserved.
"In the context of these spatial arrangements of tissues, you can learn a lot from what's there, but also from what's not there at the same time," said Dhananjay Bhaskar, a recent Brown Ph.D. graduate who led the work and is now a postdoctoral researcher at Yale University.
The Brown researchers showed in 2021 how their approach can profile the topological traits of one cell type that organizes into different spatial configurations and could make predictions on it.
The hiccup with the original system was that it is a slow and labor-intensive process. The algorithm painstakingly compared these topological features one by one against those in other sets of cell positions to determine how topologically different or similar they are. The process took several hours, and essentially, held the algorithm back from its full potential in understanding how cells assemble themselves, and from being able to easily and accurately compare what happens when conditions change—a key in breaking down what happens when things go wrong.
In the new study, the research team begins to address that limitation with what are called persistence images. These images are a standardized picture-like format for representing topological features, enabling rapid comparison across large datasets of cell positions.
They then used those images to train other algorithms to generate "digital fingerprints" that capture the key topological features of the data. This drives down the computation time from hours to seconds, enabling the researchers to compare thousands of simulations of cell organization by using the fingerprints to classify them into similar patterns without human input.
The researchers say the goal is to work backward and infer the rules that describe how different cell types arrange themselves based on the final pattern. For instance, if they tinker with how certain cells are more adhesive or less adhesive, the researchers can identify how and when dramatic alterations occur in tissue architecture.
The approach has the potential to be applied to understanding what happens when the developmental process goes off track and for laboratory experiments testing how different drugs can alter cell migration and adhesion.
"If you can see a certain pattern, we can use our algorithm to tell why that pattern emerges," Bhaskar said. "In a way, it's telling us the rules of the game when it comes to cells assembling themselves."
Other Brown authors include William Y. Zhang, who earned a bachelor's degree in computer science in 2022; Alexandria Volkening, who earned her Ph.D. from Brown in 2017 and is now an assistant professor of mathematics at Purdue; and Bjorn Sandstede, a Brown professor of applied mathematics.
More information: Dhananjay Bhaskar et al, Topological data analysis of spatial patterning in heterogeneous cell populations: clustering and sorting with varying cell-cell adhesion, npj Systems Biology and Applications (2023). DOI: 10.1038/s41540-023-00302-8
Provided by Brown University | Biology |
Programmable mechanically active adhesive makes muscles stretch and contract, preventing and enabling recovery from atrophyBy Benjamin Boettner
(BOSTON) — Muscles waste as a result of not being exercised enough, as happens quickly with a broken limb that has been immobilized in a cast, and more slowly in people reaching an advanced age. Muscle atrophy, how clinicians refer to the phenomenon, is also a debilitating symptom in patients suffering from neurological disorders, such as amyotrophic lateral sclerosis (ALS) and multiple sclerosis (MS), and can be a systemic response to various other diseases, including cancer and diabetes.
This image shows examples of MAGENTA prototypes fabricated with a “shape memory alloy” spring and an elastomer, and how their sizes compare to that of a one cent coin. Credit: Wyss Institute at Harvard University
Mechanotherapy, a form of therapy given by manual or mechanical means, is thought to have broad potential for tissue repair. The best-known example is massage, which applies compressive stimulation to muscles for their relaxation. However, it has been much less clear whether stretching and contracting muscles by external means can also be a treatment. So far, two major challenges have prevented such studies: limited mechanical systems capable of evenly generating stretching and contraction forces along the length of muscles, and inefficient delivery of these mechanical stimuli to the surface and into the deeper layers of muscle tissue.
Now, bioengineers at the Wyss Institute for Biologically Inspired Engineering at Harvard University and the Harvard John A. Paulson School of Engineering and Applied Sciences (SEAS) have developed a mechanically active adhesive named MAGENTA, which functions as a soft robotic device and solves this two-fold problem. In an animal model, MAGENTA successfully prevented and supported the recovery from muscle atrophy. The team’s findings are published in Nature Materials. With MAGENTA, we developed a new integrated multi-component system for the mechanostimulation of muscle that can be directly placed on muscle tissue to trigger key molecular pathways for growth […] We think that the device’s core design can be broadly adapted to various disease settings where atrophy is a major issue.Dave Mooney
“With MAGENTA, we developed a new integrated multi-component system for the mechanostimulation of muscle that can be directly placed on muscle tissue to trigger key molecular pathways for growth,” said senior author and Wyss Founding Core Faculty member David Mooney, Ph.D. “While the study provides first proof-of-concept that externally provided stretching and contraction movements can prevent atrophy in an animal model, we think that the device’s core design can be broadly adapted to various disease settings where atrophy is a major issue.” Mooney leads the Wyss Institute’s Immuno-Materials Platform, and is also the Robert P. Pinkas Family Professor of Bioengineering at SEAS.
An adhesive that can make muscles move
One of MAGENTA’s major components is an engineered spring made from nitinol, a type of metal known as “shape memory alloy” (SMA) that enables MAGENTA’s rapid actuation when heated to a certain temperature. The researchers actuated the spring by electrically wiring it to a microprocessor unit that allows the frequency and duration of the stretching and contraction cycles to be programmed. The other components of MAGENTA are an elastomer matrix that forms the body of the device and insulates the heated SMA, and a “tough adhesive” that enables the device to be firmly adhered to muscle tissue. In this way, the device is aligned with the natural axis of muscle movement, transmitting the mechanical force generated by SMA deep into the muscle. Mooney’s group is advancing MAGENTA, which stands for “mechanically active gel-elastomer-nitinol tissue adhesive,” as one of several Tough Gel Adhesives with functionalities tailored to various regenerative applications across multiple tissues.
This illustration explains the MAGENTA concept developed by Nam and Mooney. The view zooms from the device implanted in a future patient (left) into a muscle to which it adheres (top right), and where it does its work of extending and contracting the muscle along its length (bottom middle), all the way down to the multifunctional material’s composition and interface with muscle tissue (bottom right). Credit: Wyss Institute at Harvard University
After designing and assembling the MAGENTA device, the team tested its muscle deforming potential, first in isolated muscles ex vivo and then by implanting it on one of the major calf muscles of mice. The device did not induce any serious signs of tissue inflammation and damage, and exhibited a mechanical strain of about 15% on muscles, which matches their natural deformation during exercise.
Next, to evaluate its therapeutic efficacy, the researchers used an in vivo model of muscle atrophy by immobilizing a mouse’s hind limb in a tiny cast-like enclosure for up to two weeks after implanting the MAGENTA device on it. “While untreated muscles and muscles treated with the device but not stimulated significantly wasted away during this period, the actively stimulated muscles showed reduced muscle wasting,” said first-author and Wyss Technology Development Fellow Sungmin Nam, Ph.D. “Our approach could also promote the recovery of muscle mass that already had been lost over a three-week period of immobilization, and induce the activation of the major biochemical mechanotransduction pathways known to elicit protein synthesis and muscle growth.”
Facets of mechanotherapy
In a previous study, Mooney’s group in collaboration with Wyss Associate Faculty member Conor Walsh’s group found that regulated cyclical compression (as opposed to stretching and contraction) of acutely injured muscles, using a different soft robotic device, reduced inflammation and enabled the repair of muscle fibers. In their new study, Mooney’s team asked whether those compressive forces could also protect from muscle atrophy. However, when they directly compared muscle compression via the previous device to muscle stretching and contraction via the MAGENTA device, only the latter had clear therapeutic effects in the mouse atrophy model. “There is a good chance that distinct soft robotic approaches with their unique effects on muscle tissue could open up disease or injury-specific mechano-therapeutic avenues,” said Mooney.
The MAGENTA device with its tough hydrogel adhesive surface (shown on the left) was implanted on a mouse’s calf muscle that in the atrophy model then was immobilized for a longer period of time to induce muscle wasting. Actuating the device by turning the electricity on lets it contract, generating mechanical stimulation to the underlying muscle, whereas turning the electricity off allows the device and muscle to relax (top row on the right). The panels on the bottom right show where muscle tissue is displaced as a result of contraction and relaxation of MAGENTA with a color shift from blue to red indicating displaced areas in muscle tissue. Credit: Wyss Institute at Harvard University
To further expand the possibilities of MAGENTA, the team explored whether the SMA spring could also be actuated by laser light, which had not been shown before and would make the approach essentially wireless, broadening its therapeutic usefulness. Indeed, they demonstrated that an implanted MAGENTA device without any electric wires could function as a light-responsive actuator and deform muscle tissue when irradiated with laser light through the overlying skin layer. While laser actuation did not achieve the same frequencies as electrical actuation, and fat tissue seemed to absorb some laser light, the researchers think that the demonstrated light sensitivity and performance of the device could be further improved. “The general capabilities of MAGENTA and fact that its assembly can be easily scaled from millimeters to several centimeters could make it interesting as a central piece of future mechanotherapy not only to treat atrophy, but perhaps also to accelerate regeneration in the skin, heart, and other places that might benefit from this form of mechanotransduction,” said Nam.
“The growing realization that mechanotherapies can address critical unmet needs in regenerative medicine in ways that drug-based therapies simply cannot has stimulated a new area of research that connects robotic innovations with human physiology down to the level of the molecular pathways that are transducing different mechanical stimuli,” said Wyss Founding Director Donald Ingber, M.D., Ph.D. “This study by Dave Mooney and his group is a very elegant and forward-looking example of how this type of mechanotherapy could be used clinically in the future.” Ingber is also the Judah Folkman Professor of Vascular Biology at Harvard Medical School and Boston Children’s Hospital, and the Hansjörg Wyss Professor of Bioinspired Engineering at SEAS.
Other authors on the study are Bo Ri Seo, Alexander Najibi, and Stephanie McNamara from Mooney’s group at the Wyss Institute and SEAS. The study was funded by the National Institute of Dental and Craniofacial Research (award# R01DE013349), the Eunice Kennedy Shriver National Institute of Child Health and Human Development (award# P2CHD086843) and the National Science Foundation’s Materials Research Science and Engineering Center at Harvard University (award# DMR14-20570).
Nature Materials: Active tissue adhesive activates mechanosensors and prevents muscle atrophy | Biology |
By comparing the genetic blueprints of an array of animals, scientists are gaining new insights into our own species and all we share with other creatures.
One of the most striking revelations is that certain passages in the instructions for life have persisted across evolutionary time, representing a through line that binds all mammals – including us.
The findings come from the Zoonomia Project, an international effort that offers clues about human traits and diseases, animal abilities like hibernation and even the genetics behind a sled dog named Balto who helped save lives a century ago.
Researchers shared some of their discoveries in 11 papers published Thursday in the journal Science.
David O’Connor, who studies primate genetics at the University of Wisconsin-Madison, said the studies tackle deep questions.
“It’s just the wonder of biology, how we are so similar and dissimilar to all the things around us,” said O’Connor, who wasn’t involved in the research. “It’s the sort of thing that reminds me why it’s cool to be a biologist.”
The Zoonomia team, led by Elinor Karlsson and Kerstin Lindblad-Toh at the Broad Institute of MIT and Harvard, looked at 240 species of mammals, from bats to bison. They sequenced and compared their genomes — the instructions organisms need to develop and grow.
They found that certain regions of these genomes have stayed the same across all mammal species over millions of years of evolution.
One study found that at least 10% of the human genome is largely unchanged across species. Many of these regions occur outside the 1% of genes that give rise to proteins that control the activity of cells, the main purpose of DNA.
Researchers theorized that long-preserved regions probably serve a purpose and are likely what they call “regulatory elements" containing instructions about where, when and how much protein is produced. Scientists identified more than 3 million of these in the human genome, about half of which were previously unknown.
Scientists also focused on change within the animal kingdom. When they aligned genetic sequences for species and compared them with their ancestors, Karlsson said, they discovered that some species saw a lot of changes in relatively short periods of time. This showed how they were adapting to their environments.
“One of the really cool things about mammals is that at this point in time, they’ve basically adapted to survive in nearly every single ecosystem on Earth,” Karlsson said.
One group of scientists looked for genes that humans don’t have but other mammals do.
Instead of focusing on new genes that might create uniquely human traits, “we kind of flipped that on its head," said Steven Reilly, a genetics researcher at Yale University.
“Losing pieces of DNA can actually generate new features,” Reilly said.
For example, he said, a tiny DNA deletion between chimps and humans caused a cascade of changes in gene expression that may be one of the causes of prolonged brain development in humans.
Another study focused on the fitness of one well-known animal: Balto.
Scientists sequenced the genome of the sled dog, who led a team of dogs carrying a lifesaving diphtheria serum to Nome, Alaska, in 1925. His story was made into a 1995 animated feature film and a statue of the pup stands in New York’s Central Park.
By comparing Balto’s genes to those of other dogs, researchers found he was more genetically diverse than modern breeds and may have carried genetic variants that helped him survive harsh conditions. One of the authors, researcher Katherine Moon of the University of California, Santa Cruz, said Balto “gives us this guide through comparative genomics,” showing how genetics can shape individuals.
O’Connor said he expects Zoonomia to yield even more insights in the future.
“To have these tools and to have the sort of audacity to ask these big questions” helps scientists and others “learn more about life around us,” he said. | Biology |
Under normal conditions, the floating macroalgae Sargassum spp. provide habitat for hundreds of types of organisms. However, the Great Atlantic Sargassum Belt (GASB) that emerged in 2011 has since then caused unprecedented inundations of this brown seaweed on Caribbean coastlines, with harmful effects on ecosystems while posing challenges to regional economies and tourism, and concerns for respiratory and other human health issues.
Researchers looking into the question of what is the nutrient supply for the GASB say that they have now clearly identified that the nutrient content of Sargassum tissue could help determine the enrichment sources and potentially improve predictions and Sargassum management efforts.
"We show clearly for the first time that Sargassum in the GASB is enhanced in both nitrogen and phosphorus, indicative of a healthy and thriving population," according to the journal article "Nutrient and arsenic biogeochemistry of Sargassum in the western Atlantic," published in Nature Communications.
"Stable nitrogen isotope values point to riverine sources in some circumstances and are more equivocal in others. Distinguishing the various nutrient sources sustaining the GASB will require systematic snapshots of nutrient content and isotopic composition across its entire breadth," according to the paper. "Presumably, the closer one gets to the source, the higher the nitrogen and / or phosphorus content of Sargassum should be. In that sense, basin-wide patterns in nitrogen and phosphorus elemental composition could provide the fingerprinting necessary to unequivocally determine the sources."
The paper notes that a variety of nutrient sources for the GASB blooms have been suggested, including upwelling, vertical mixing, discharge from the Amazon and Congo rivers, and atmospheric deposition. Though, the paper states that the causes of the GASB and the mechanisms controlling its variability remain unknown.
The paper also indicates that the nutritional status of Sargassum in the GASB is enriched, with higher nitrogen and phosphorus content than are populations of Sargassum that reside in its Sargasso Sea habitat.
"In its traditional environment, Sargassum is a great ecological benefit. However, the proliferation of biomass in the tropical Atlantic has proven the old adage that too much of a good thing can be bad," said journal article lead author Dennis McGillicuddy, Jr., senior scientist in the Applied Ocean Physics and Engineering Department at the Woods Hole Oceanographic Institution (WHOI).
The finding that nitrogen and phosphorus are higher in the GASB than in the Sargasso Sea "is a smoking gun that the GASB inundations are nutrient-driven," said McGillicuddy. "A consequence of this finding is that it presents us potentially with the opportunity to use those nitrogen and phosphorus markers in Sargassum tissue to fingerprint the ultimate sources of these nutrients that are sustaining these seaweed blooms."
In addition, the paper notes that the presence of arsenic in Sargassum tissue -- which reflects phosphorus limitation -- significantly constrains the utilization of the seaweed biomass that washes ashore.
"As the Great Atlantic Sargassum Belt has grown over the last decade, the public has become increasingly aware of this phenomenon and its impact on coastal communities," said co-author Peter Morton, associate research scientist in the Department of Oceanography at Texas A&M University, College Station. "Our research shows that Sargassum could become enriched in arsenic, depending on the conditions in which it grows. Plans to remove or exploit this material when it washes ashore should consider the potential for Sargassum to contain high concentrations of arsenic, so we encourage affected communities to proceed with caution when exploring options to deal with seasonal inundations of Sargassum."
Due to the threats that the Sargassum inundations pose to the environment, economy, and human health, the paper recommends the need for expanded observational and modeling studies to understand the GASB's physical, biological, and chemical drivers. The paper notes that "the societal need for scientific understanding is urgent: improved seasonal to interannual predictions would offer tremendous value for proactive planning and response, while quantification of the underlying causes could inform potential management actions to mitigate the problem."
McGillicuddy first saw Sargassum when he was a child growing up in Florida and his grandfather took him fishing near the seaweed because that was the best place to fish. "It was an oasis in the oceanic desert," McGillicuddy said.
"Now, the system has changed in a fundamental way. We've got an oceanographic process out there that is creating this. As a scientist, and as a fisherman, I feel an urgent need to try to understand this situation, not only to help answer the interesting scientific questions around this problem, but do so in a way that we are able to understand the situation and eventually mitigate it in a way that would be of value to society," he said.
McGillicuddy and co-author Brian Lapointe also stressed the importance of the interdisciplinary and collaborative nature of this research, which encompasses a number of disciplines including biology, chemistry, and physics.
"This collaborative study illustrates the value of interdisciplinary research teams to understanding complex oceanographic phenomena in an era of rapid global change, in this case, the Great Atlantic Sargassum Belt that formed in 2011," said co-author Brian Lapointe, a research professor at Florida Atlantic University's Harbor Branch Oceanographic Institute, and one of the world's foremost authorities on Sargassum.
Funding for this research was provided by the National Science Foundation, the National Institute of Environmental Health Sciences through the Woods Hole Center for Oceans and Human Health, WHOI, the Isham Family Charitable Fund, the State of Florida, and NASA.
Sargassum samples of opportunity were collected on U.S. GO-SHIP lines A20 (Ryan Woosley, chief scientist; marine physical chemist at the Massachusetts Institute of Technology's Center for Global Change Science), and A22 (Viviane Menezes, chief scientist; physical oceanographer at WHOI), carried out on the R/V Thomas G. Thompson (voyages TN389 and TN390) with the support of the U.S. National Science Foundation and the National Oceanic and Atmospheric Administration. U.S. GO-SHIP (Global Ocean Ship-based Hydrographic Investigations Program) is a component of International GO-SHIP.
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450-Million-Year-Old Organism Rebuilt as a “Soft” Robot
Soft robotics is giving researchers more insight into how ancient animals lived.
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Scientists have breathed new life into a 450-million-year-old organism, using fossil records to build a robotic replica out of flexible electronics and soft materials.
The new soft robot, called the “Rhombot,” is based on an ancient marine organism known as the pleurocystitid. This robot, and others like it, could be used to better understand the biomechanical factors that drove evolution in the distant past, the researchers say.
The research is published in the Proceedings of the National Academy of Sciences.
The field of Paleobionics
The earliest fossil records for early modern humans date back roughly 300,000 years. But in the span of the Earth’s existence, this is a mere blink of an eye – only 0.007% of the planet’s history. While the study of the modern-day animal kingdom continues to shed new light on evolution and offers a source of inspiration to today’s engineers, this is also just a snapshot of all of the creatures that have existed throughout history.
To broaden our understanding of evolution, animal design and movement, some researchers are casting their eyes further back. In this new research, scientists from the Carnegie Mellon University (CMU) Department of Mechanical Engineering, alongside paleontologists from Poland’s Institute of Paleobiology and Spain’s Geological and Mining Institute, are introducing a new field of study – Paleobionics.
This field is aimed at using Softbotics – an approach to robotics that makes use of flexible electronics and soft materials – to study ancient lifeforms with the goal of understanding their biomechanics.
“Our goal is to use Softbotics to bring biological systems back to life, in the sense that we can mimic them to understand how they operated,” said Philip LeDuc, the William J. Brown Professor of Mechanical Engineering at CMU.
“Softbotics is another approach to inform science using soft materials to construct flexible robot limbs and appendages,” explained Carmel Majidi, lead study author and the Clarence H. Adamson Professor of Mechanical Engineering at CMU. “A lot of fundamental principles of biology and nature can only fully be explained if we look back at the evolutionary timeline of how animals evolved. We are building robot analogs to study how locomotion has changed.”
Recreating pleurocystitids
The pleurocystitid was a member of the echinoderm class of animals, like modern-day starfish and sea urchins, and is believed to be one of the first echinoderms capable of movement using its muscular stem. While there is no direct modern-day equivalent to this ancient echinoderm, pleurocystitids have become a species of interest to paleontologists due to the pivotal role that they played in echinoderm evolution.
In the new study, the research team used fossil evidence to guide the creation of a pleurocystitid-like robot, using a combination of 3D-printed elements and polymers to mimic the flexible columnar structure of the pleurocystitid’s moving tail-like appendage.
They demonstrated how the ancient pleurocystitids were likely able to move over the terrain on the bottom of the sea floor using their stem, making wide sweeping movements to push themselves forward. The researchers found that pleurocystitids could significantly boost their maximum speed by increasing their stem length, without needing to exert more energy.
“Researchers in the bio-inspired robotics community need to pick and choose important features worth adopting from organisms over time,” said Richard Desatnik, a PhD candidate in the LeDuc lab and co-first author of the paper.
“Essentially, we have to decide on good locomotion strategies to get our robots moving. For example, would a starfish robot really need to use 5 limbs for locomotion or can we find a better strategy?” added Zach Patterson, CMU alumnus and co-first author.
Following the successful development of this Rhombot, the research team now hopes to use similar methods to study other extinct organisms, such as the first organism able to travel from sea to land – something which couldn’t be studied using traditional robot hardware, but which researchers say could be possible with Softbotics.
“Bringing a new life to something that existed nearly 500 million years ago is exciting in and of itself, but what really excites us about this breakthrough is how much we will be able to learn from it,” said LeDuc. “We aren’t just looking at fossils in the ground, we are trying to better understand life through working with amazing paleontologists.”
Reference: Desatnik R, Patterson ZJ, Gorzelak P, Zamora S, LeDuc P, Majidi C. Soft robotics informs how an early echinoderm moved. Proc Natl Acad Sci USA. 2023;120(46):e2306580120. doi: 10.1073/pnas.2306580120
This article is a rework of a press release issued by Carnegie Mellon University. Material has been edited for length and content. | Biology |
Antibiotic-resistant bacteria get extra nutrients and thrive when the drugs kill 'good' bacteria in the gut.
This is according to new research led by Imperial College London scientists, which could lead to better patient risk assessment and 'microbiome therapeutics' treatments to help combat antibiotic-resistant bacteria.
Some antibiotics target specific bacteria, but some are 'broad spectrum', meaning they can kill a wide range of bacteria including both 'bad' pathogenic bacteria that cause infections and 'good' bacteria that live in our guts and help with digestion and other processes.
Carbapenems are broad-spectrum antibiotics that are strong but often used as a last resort, due to their negative impacts on beneficial bacteria. Some pathogenic bacteria in the class Enterobacteriaceae however are even resistant to carbapenems, including strains of E. coli. These pathogenic bacteria colonise the gut but can spread to other sites in the body, causing difficult-to-treat infections such as bloodstream infections or recurrent urinary tract infections.
Now, a new study shows how these resistant bacteria thrive after antibiotic use, allowing them to multiply in the gut, forming a 'reservoir' of disease-causing bacteria. The results are published in Nature Communications.
More nutrients, less impairment
To determine the effect of antibiotics, the team tested them on samples of human faeces in the lab, alongside experiments in mice and lab tests of carbapenem-resistant Enterobacteriaceae (CRE).
Bacteria in the gut, whether 'good' or 'bad', need nutrients to grow and reproduce. The experiments showed that when antibiotics killed beneficial bacteria, the pathogenic bacteria were able to take advantage of the extra nutrients available due to less competition.
The team also showed that killing beneficial bacteria reduced the level of metabolites -- waste products that inhibit pathogenic bacteria from growing further. This helped the pathogenic bacteria to thrive.
First author Alexander Yip, from the Centre for Bacterial Resistance Biology in the Department of Life Sciences at Imperial, said: "Understanding how antibiotics cause carbapenem-resistant Enterobacteriaceae to grow in the intestine means that we can develop new treatments to restrict their growth in the intestine, which will lead to a reduction in these antibiotic-resistant infections."
Microbiome therapeutics
The team are now working on ways to interfere with this process. First, they want to identify which beneficial bacteria can 'out-compete' pathogenic bacteria in the absence of antibiotics: which good bacteria are able to make better use of the same nutrients and produce metabolites that restrict pathogenic bacterial growth.
With this information they hope to create 'microbiome therapeutics'. Lead researcher Dr Julie McDonald, from the Department of Life Sciences at Imperial, explained: "When a patient is taking antibiotics we could give them inhibitory metabolites to restrict the growth of resistant bacteria. After a patient has stopped taking antibiotics we could give them a mixture of beneficial gut bacteria to help their gut microbiome recover, restore depletion of nutrients, and restore production of inhibitory metabolites.
"These microbiome therapeutics could reduce the risk of patients developing invasive antibiotic resistant infections, reduce the recurrence of invasive CRE infections in chronically colonised patients, and reduce the spread of CRE to susceptible patients."
In the short term, the researchers say their results could be used to help reduce the risk of patients harbouring reservoirs of CRE in their guts. For example, clinicians could avoid prescribing antibiotics that elevate certain nutrients and deplete certain metabolites. Doctors could also screen patient faecal samples for these nutrients and metabolites, to identify those at increased risk of CRE colonisation.
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Scientists have discovered thousands of planets that orbit far from our sun. Some of these planets are rocky and some are gas giants. As these planets orbit their parent stars, chemical reactions start that result in gases. Some of these gases are produced in a way similar to ozone in Earth’s atmosphere.
Using the Webb telescope, scientists have captured images of an atmosphere on WASP-39 b, a Saturn-sized exoplanet that orbits a star in the Virgo constellation. The planet is about as massive as Saturn and orbits the star at a distance of about the same distance as Mercury from the sun.
The Webb telescope’s instruments were able to detect the presence of water, carbon dioxide, sodium, and potassium in the atmosphere of WASP-39 b. These compounds were only present at very low levels. The presence of these chemicals indicates that the planet has formed far from the star. However, scientists are still investigating whether abiotic oxygen is present in the atmosphere. If so, the presence of these chemicals could signal active biology.
The Webb telescope’s instruments have been used to probe the atmospheres of smaller rocky planets. These instruments have also provided a comprehensive molecular profile of the skies of a distant world. | Biology |
Plastic-eating enzymes could help solve pollution problem
Two new enzymes can break down one of the most common single-use plastics, according to the study "Modulating biofilm can potentiate activity of novel plastic-degrading enzymes" by Brunel University London published in the journal npj Biofilms and Microbiomes.
The enzymes could be developed to dissolve plastic bottles faster than current recycling methods and create the raw material to make new ones.
Bacteria shows potential to help tackle the waste crisis, with scientists pinpointing several new species that encode enzymes that can degrade plastic. But these enzymes degrade plastic too slowly to be useful.
"These new findings are really exciting," said Dr. Ronan McCarthy. "Not only have we identified two new PET (Polyethylene terephthalate) degrading enzymes, but we found a way to improve their degradation abilities by modifying the bacteria as whole, rather than modifying each enzyme individually."
Biomedical scientists at Brunel are doing extensive research in synthetic biology to find ways to make these useful plastic degrading enzymes work harder.
Synthetic biology uses ideas from engineering to design new biological pathways, organisms and devices and to modify ones found in nature. In this new study, the researchers use the techniques to boost bacteria's abilities to grow in communities called biofilms.
Like people, bacteria don't often like living on their own. Bacteria living together in biofilm communities can share nutrients and communication signals and better withstand extreme temperatures and chemical hazards.
The team genetically engineered plastic-degrading bacteria to attach to waste plastic and form biofilms on it. This ramped up the concentration of the enzyme around the plastic, making it much more powerful and better at breaking it down. "This suggests that modulating biofilm formation may be an effective strategy to increase the efficiency of plastic degrading bacteria," said Dr. McCarthy. "Using biofilms to enhance plastic-degrading enzyme activity could potentially be applied to all plastic-degrading enzymes currently in development."
Biofilms form on many natural surfaces, such as soil, water and rocks. In health settings, bacterial infections such as MRSA can form biofilms that create a barrier to antibiotics and the immune system.
The team now plan to test the two new enzymes in a bioreactor. "We want to see if increasing biofilm formation improves the degradation of plastic in a more industrial-like setting," added researcher Dr. Sophie Howard. "We also aim to further harness synthetic biology to give even greater control over biofilm formation."
More information: Sophie A. Howard et al, Modulating biofilm can potentiate activity of novel plastic-degrading enzymes, npj Biofilms and Microbiomes (2023). DOI: 10.1038/s41522-023-00440-1
Journal information: npj Biofilms and Microbiomes
Provided by Brunel University | Biology |
Researchers from UNSW have uncovered how these tiny organisms can restore their movement in unfavourable conditions. Being able to swim is crucial to how bacteria survive and spread. Photo: Shutterstock. A new study led by UNSW Sydney scientists unveils how nature's oldest wheel, found within bacteria, can fix itself when times get tough.
The findings, published today in Science Advances, show how the flagellar—the ancient motor that powers the swimming ability of bacteria—can also help these tiny organisms adjust to conditions where their motility is impaired.
Bacteria are one of Earths’ oldest living organisms. They are tiny single-celled organisms found across every habitat, including the human body—where there are more bacterial cells than human cells.
Being able to swim is crucial to how bacteria survive and spread. But little is known about how the motors that drive their movement help the organisms adapt to hostile environments.
Read more: Local bacteria help native seeds take root in arid landscapes The researchers from the School of Biotechnology and Biomolecular Sciences are the first in the world to use CRISPR gene-editing technology to alter a flagellar motor. They used synthetic biology techniques to engineer a sodium motor onto the genome to create a sodium-driven swimming bacteria. They then tested and tracked the bacteria’s ability to adapt when the environment was starved of sodium.
Sodium is an ion, which means that it carries a charge. It is this charge that powers the flagellar motor via stators, or ion channels.
The team found that the stators were able to rapidly self-repair the flagellar motor and restore movement. These findings could lead to new advances across the biological and medical science fields.
“We showed that environmental changes can cause ion channels to react quickly,” said lead author of the paper Dr Pietro Ridone.
“So, the CRISPR edits also revert quickly, and the flagellar motor evolves and then regulates itself,” Dr Ridone said.
“The fact that we saw mutations directly on the stators right away is surprising, and also inspires a lot of our future research plans in this area.”
The power of molecular machinery
The human body contains around 10,000 different types of molecular machines, which power a range of biological functions from energy conversion to movement.
The technology of a bacterial motor far surpasses what humans can synthetically engineer at nanoscale. At a millionth the size of a grain of sand, it can assemble itself and rotates at up to five times the speed of a Formula 1 engine.
“The motor that powers bacterial swimming is a marvel of nanotechnology,” said Associate Professor Matthew Baker, a co-author of the paper. “It is the absolute poster child for ancient and very sophisticated molecular machinery.”
A/Prof. Baker said the study’s findings can help us better understand the origin of molecular motors in mechanistic detail—how they came together and how do they adapt.
“These ancient parts are a powerful system to study evolution in general, as well as the origins and evolution of motility.”
A/Prof. Baker says the findings will inform how synthetic biology can help create new molecular motors. The findings may also have applications in understanding antimicrobial resistance and the virulence of disease.
“By shedding more light on life’s ancient history, we are gaining knowledge to create tools that can help better our futures,” A/Prof. Baker said. “It can also lead us to insights on how bacteria might adapt under future climate change scenarios.” | Biology |
Not far from Didcot, once a halfway stop between London and Bristol on the Great Western Railway celebrated for Isambard Kingdom Brunel’s engineering, innovation has returned with a hi-tech factory manufacturing DNA and RNA sequencing machines. Oxford Nanopore, a spinout from Oxford University, produces devices used to identify viruses and spot variants in the genetic makeup of humans, animals and plants. Its sequencers have been used to track Covid-19 variants globally and are now being trialled on intensive care patients with respiratory infections at Guy’s and St Thomas’ hospitals in London, and in the fight against the 200 drug-resistant strains of tuberculosis, the second-biggest killer worldwide after Covid in 2020.“Our DNA is not static: from birth to the life cycle of a plant, or an animal or a human, it changes over time, due to lifestyle, environmental factors,” says Gordon Sanghera, Nanopore’s co-founder and chief executive. “We are entering the genomic era; genomics will be at the centre of everything.”Demand from academics, governments and businesses is growing. Sanghera plans to build another factory in the next few years – probably in the UK, although he won’t rule out Asia or the US. “The plan is to be a global tech player,” he says.Founded in 2005 by three scientists who met at Oxford University, the company grew out of research by Hagan Bayley, one of the trio, who is still a professor of chemical biology there. In traditional sequencing, DNA samples are chopped into smaller pieces and copied, which can introduce errors. Bayley researched how a tiny hole, or nanopore, in a protein can be used to identify the molecules in DNA that pass through it, in a process compared by Sanghera to “sucking spaghetti really fast”.Nanopore’s factory on the Harwell campus near Didcot was built within 12 months in 2018. This is where flow cells are made, a key component of the sequencers, which have to be replaced regularly, much like printer cartridges.Nanopore’s operations chief, Rhodri Davies, explains how they work: “A nanopore is inserted within a membrane and a current passes through it. On either side there is an ionic solution and a couple of electrodes. As DNA passes through the hole, it modulates that ion flow – a bit like turning a tap on or off. These different levels of current are signals and our smart electronics convert that into the alphabet of DNA.”On our tour of the factory, we see a large room with orange lighting similar to a darkroom where P-chips – product chips with a sensor, “the heart of the system” – are manufactured from wafers. In the room opposite, Nanopore staff are busy assembling flow cells using the P-chips. The firm intends to automate the assembly process soon. The sequencing machines are largely made in the UK, across the different Oxford sites.The technology can be widely used to track disease outbreaks, optimise crop growing and protect endangered species. For example, Lara Urban, a Humboldt research fellow at the University of Otago in New Zealand, uses a handheld Nanopore device in the jungle to support conservation of the critically endangered kākāpō parrot.Nanopore floated on the London Stock Exchange just over a year ago in one of the UK’s best-ever market debuts. The shares jumped 44%, valuing the firm at nearly £5bn, and turning Sanghera and the other founders into paper millionaires. The share price has since plummeted, similar to peers on Nasdaq including California rival Illumina, which dominates the global sequencing market. Nanopore shares are now worth 279p, compared with its listing price of 425p.Sanghera says this reflects the worsening economic climate, adding that if Nanopore had not issued limited anti-takeover shares to him and two other executives, allowing them to block hostile approaches, the company would be “a sitting duck” for a takeover.Many promising UK science and tech startups on the brink of commercialisation have been acquired by bigger overseas rivals over the years. Medisense, the glucose monitoring startup, another Oxford spinout where Sanghera started his business career, was sold to US firm Abbott in 1996, he recalls, while Illumina in 2007 snapped up Solexa, a Cambridge university spinout whose technology forms the basis of its sequencing instruments. “We’ve just got to stop this happening,” Sanghera says.Referring to the Covid jab developed by Oxford University and AstraZeneca, Sanghera adds: “[It] made us [Britain] think about how we need to do things ourselves.”The anti-takeover shares expire in two years, but if Nanopore carries on growing on the current trajectory, “we expect to be in a strong position”.Nanopore received a one-off sales boost of £52m from Covid test kits in the six months to 30 June, but also made £71m from its other devices, up more than a third from a year earlier. It expects to generate revenues of between £145m and £160m this year.The wider British life sciences sector is sluggish, however. Revenues from UK companies making life science products declined by £7.7bn in real terms, adjusted for inflation, between 2011 and 2020, according to government data.Sanghera served on the council of business leaders under Theresa May and Boris Johnson and says that there was a real will at a senior level in the government to make the UK a “life sciences superpower” and to try to create hi-tech jobs. “It’s just cascading that down to the tech companies that could do with some streamlining,” he says. | Biology |
CNN — Scientists have created mouse embryos in a dish, and it could one day help families hoping to get pregnant, according to a new study. After 10 years of research, scientists created a synthetic mouse embryo that began forming organs without a sperm or egg, according to the study published Thursday in the journal Nature. All it took was stem cells. Stem cells are unspecialized cells that can be manipulated into becoming mature cells with special functions. “Our mouse embryo model not only develops a brain, but also a beating heart, all the components that go on to make up the body,” said lead study author Magdalena Zernicka-Goetz, professor of mammalian development and stem cell biology at the University of Cambridge in the United Kingdom. “It’s just unbelievable that we’ve got this far. This has been the dream of our community for years, and a major focus of our work for a decade, and finally we’ve done it.” The paper is an exciting advance and tackles a challenge scientists face studying mammal embryos in utero, said Marianne Bronner, a professor of biology at the California Institute of Technology in Pasadena (Caltech). Bronner was not involved in the study. “These develop outside of the mother and therefore can be easily visualized through critical developmental stages that were previously difficult to access,” Bronner added. The researchers hope to move from mouse embryos to creating models of natural human pregnancies – many of which fail in the early stages, Zernicka-Goetz said. By watching the embryos in a lab instead of a uterus, scientists got a better view into the process to learn why some pregnancies might fail and how to prevent it, she added. For now, researchers have only been able to track about eight days of development in the mouse synthetic embryos, but the process is improving, and they are already learning a lot, said study author Gianluca Amadei, a postdoctoral researcher at the University of Cambridge. “It reveals the fundamental requirements that have to be fulfilled to make the right structure of the embryo with its organs,” Zernicka-Goetz said. Where it stands, the research doesn’t apply to humans and “there needs to be a high degree of improvement for this to be truly useful,” said Benoit Bruneau, the director of the Gladstone Institute of Cardiovascular Disease and a senior investigator at Gladstone Institutes. Bruneau was not involved in the study. But researchers see important uses for the future. The process can be used immediately to test new drugs, Zernicka-Goetz said. But in the longer term, as scientists move from mouse synthetic embryos to a human embryo model, it also could help build synthetic organs for people who need transplants, Zernicka-Goetz added. “I see this work as being the first example of work of this kind,” said study author David Glover, research professor of biology and biological engineering at Caltech. In utero, an embryo needs three types of stem cells to form: One becomes the body tissue, another the sac where the embryo develops, and the third the placenta connecting parent and fetus, according to the study. In Zernicka-Goetz’s lab, researchers isolated the three types of stem cells from embryos and cultured them in a container angled to bring the cells together and encourage crosstalk between them. Day by day, they were able to see the group of cells form into a more and more complex structure, she said. There are ethical and legal considerations to address before moving to human synthetic embryos, Zernicka-Goetz said. And with the difference in complexity between mouse and human embryos, it could be decades before researchers are able to do a similar process for human models, Bronner said. But in the meantime, the information learned from the mouse models could help “correct failing tissues and organs,” Zernicka-Goetz said. The early weeks after fertilization are made up of these three different stem cells communicating with one another chemically and mechanically so the embryo can grow properly, the study said. “So many pregnancies fail around this time, before most women (realize) they are pregnant,” said Zernicka-Goetz, who is also professor of biology and biological engineering at Caltech. “This period is the foundation for everything else that follows in pregnancy. If it goes wrong, the pregnancy will fail.” But by this stage, an embryo created through in vitro fertilization is already implanted in the parent, so scientists have limited visibility into the processes it is going through, Zernicka-Goetz said. They were able to develop foundations of a brain – a first for models such as these and a “holy grail for the field,” Glover said. “This period of human life is so mysterious, so to be able to see how it happens in a dish – to have access to these individual stem cells, to understand why so many pregnancies fail and how we might be able to prevent that from happening – is quite special,” Zernicka-Goetz said in a press release. “We looked at the dialogue that has to happen between the different types of stem cell at that time – we’ve shown how it occurs and how it can go wrong.” | Biology |
Molecular scale structure and kinetics of layer-by-layer peptide self-organization at atomically flat solid surfaces
In a study recently published in the journal ACS Nano, researchers from Kanazawa University, Kanazawa, Japan, collaborating with University of Washington, Seattle, U.S., used frequency modulated atomic force microscopy to reveal the molecular architecture of a genetically designed peptide and its self-organization that forms single-molecule thick crystals on atomically flat graphite surfaces, offering a potential platform for hybrid technologies such as bioelectronics, biosensors and protein arrays.
Just like a protein, a peptide also has a chain of natural amino acids, but it is much shorter, say 10-30 units, compared to those in proteins, which could be hundreds and thousands of units long. Along with DNA (genetic code), polysaccharides (sugars) and lipids (fats), proteins are the fourth major building blocks that make life viable. Proteins collect ions and transport them, carry out enzymatic functions, and constitute the major structures of the cells.
Proteins, therefore, are the key building blocks of organisms carrying out life's functions making it dynamic. For decades, scientists have been trying to understand how the sequence of amino acids in proteins are correlated to their molecular architecture so that one can predict their specific functions. The understanding of the protein's shape and function is crucial to discover the origin of diseases and designing of vaccines and drugs.
Proteins can also be useful for technological applications such as in tissue engineering and designing biosensors for diagnostics. So far, however, predicting protein's structure has been elusive, even by using the recently developed computational models such as Alpha-Fold, based on Google's deep learning algorithms. Using proteins, therefore, has still not been practical because of their enormous size and unpredictable functions.
Peptides, on the other hand, are smaller versions of proteins with similar roles, and therefore are more practical as their roles also rely on the amino acid sequences that lead to their folding patterns. Because of their smaller sizes and disordered molecular structures, for years, peptides have been considered to be not so useful because of having unpredictable functions.
The "floppy" structures of peptides, however, could be turned into an advantage if these small biomolecules could be engineered using an interdisciplinary approach, combining biology, engineering and predictive modeling. This is exactly what a team of scientists, led by Ayhan Yurtsever, Linhao Sun, Kaito Hirata, and Takeshi Fukuma at Kanazawa University and their colleagues, Mehmet Sarikaya, a materials scientist, and his team, at the University of Washington, have accomplished.
Combining the Seattle-Team's expertise in genetic engineering in designing peptides that have exclusive affinity to technological solids and Kanazawa-Team's expertise in molecular imaging under biologically benign conditions, the scientists have demonstrated self-organization of the peptides on a solid surface and visualized them at unprecedented molecular resolution, the knowledge is essential in designing hybrid biomolecular nanodevices for use in biology and technology alike.
The scientists accomplished this feat by combining their expertise in their respective fields. The peptides used were selected by an ingenious approach, called directed evolution, normally used for selecting cancer drugs for a specific tumor by molecular biologists. In this case, the molecule used, called graphite binding peptide, was genetically selected using graphite as the substrate, by a materials scientist.
Armed with the expertise gained in examining molecular architectures in aqueous solutions, the Kanazawa team demonstrated the way the peptide self-organizes on atomically flat graphite surface is in patterns, predicted by computational modeling of the peptides.
Knowing that the way the proteins carry out their function is through molecular recognition of their biological substrates (for example, DNA, proteins, enzymes, other biomolecules, or diseased cells), the scientists realized that the peptides predictably self-organize on graphite, a synthetic substrate, because of the same molecular recognition principle as in biology.
The origin of molecular recognition and its control via designing a new amino acid sequence is the holy grail in biology as, if the process can be controlled, then many kinds of drugs and vaccines can be designed based on the target (diseased) molecule or the substrate. Here, the target is a technological material, graphite, or it can also be graphene, its single atomic layer version, a highly significant technological material of the last two decades.
In this work, the Kanazawa-Seattle collaborative teams have discovered that the graphite binding peptide not only recognizes graphite atomic lattice but also forms its own molecular crystal thereby establishing a coherent, continuous, soft interface between the peptide and the solid.
"The capability of seamlessly bridging biology with functional solids at the molecular level is the critical first step towards creating biology-inspired technologies and is likely to lend itself in the design of biosensors, bioelectronics, and peptide-based biomolecular arrays, and even logic devices, all hybrid technologies of the future," the scientists say.
The teams are currently busy in expanding their discovery in addressing further questions, such as the effects of mutations, structured water around peptides, on other solid substrates, and physical experiments across the peptide-graphite interfaces towards establishing the firm scientific foundations for the development of the next generation biology-inspired technologies.
More information: Ayhan Yurtsever et al, Molecular Scale Structure and Kinetics of Layer-by-Layer Peptide Self-Organization at Atomically Flat Solid Surfaces, ACS Nano (2023). DOI: 10.1021/acsnano.2c10673
Journal information: ACS Nano
Provided by Kanazawa University | Biology |
If you think giant pandas had it bad, spare a thought for the tiny parasitic mites that live in the pores of the skin on our faces which may be destined for an evolutionary dead-end, according to a new analysis of their DNA.More than 90% of us host the 0.3mm long-mites in the oily folds on our faces, most living in the pores near our noses and eyelashes.
It is probably the closest relationship to another animal most of us never knew we had.The mite, Demodex follicularum, spends its entire lifetime living in our skin follicles. In the daytime they feed on our oily skin secretions, at night they leave the pore to find mates, and find new follicles in which to have sex and lay their eggs.If the thought makes you want to wash your face, forget it. You've been carrying the mites since you were born - they're passed from mother to baby during breast feeding - and live too deep in the pores to be washed out. And besides, we need them, says Dr Alejandra Perotti of the University of Reading, who co-authored the study. "We should love them because they're the only animals that live on our bodies our entire life and we should appreciate them because they clean our pores."
"Besides, they're cute," says Dr Perotti. More from Science & Tech COVID-19: Brits to have first access to vaccines and treatments when new science super-centre opens UK to become 'true space superpower' with first rocket launch Hundreds of websites knocked offline due to Cloudflare outage - with Outlook also down for some users Perhaps not everyone would agree. The mites have four pairs of stubby legs each with a pair of claws. Beyond that a long worm like body which, under the microscope, can sometimes be seen protruding from our hair follicles.But this latest study, published in the journal Molecular Biology and Evolution, has shown just how incredibly intimate their relationship with humans has become.The researchers analysed the genome of the mites and found it has the smallest number of functional genes of any arthropod (insects, arachnids and crustaceans).The animals have become so dependent on their human host that their genome is "eroding" -- stripped down to the bare minimum of genes needed to survive, the researchers conclude.They found that the gene which normally regulates waking and sleeping in arthropods has been lost. Instead, the organism detects changes in levels of the hormone melatonin in our skin secretions. It goes up when we sleep, telling Demodex to get up, and goes down when we wake up - their cue to head back down our oily pores for dinner.They've also lost the gene that protects their bodies from UV light - what's the point when you only come out at night? Even their body plan is minimalist - each leg is powered by just a single muscle cell.Their ecology becoming so closely synchronised with humans shows the species is on its way from being an external parasite to an internal symbiont - an organism entirely dependent on us for its existence.As their genetic diversity shrinks, and with it their ability to leave their host and find new mates, they are also at possible risk of eventually going extinct - either when humans do or as a result of some significant change to their environment.It was once believed Demodex were a cause of common skin conditions, but in healthy people the evidence is Demodex actually help prevent problems like acne by unblocking pores.But that's not the only reason we should care about them, says Dr Perotti:"We are living in a world where we should be protecting biodiversity -- and these are our very own animal." | Biology |
UNIVERSITY PARK, Pa. — Artemisinin-based combination therapies (ACTs) are the globally-accepted first-line treatments for malaria — a mosquito-borne disease caused by the Plasmodium falciparum parasite that annually kills around 600,000 people, mostly children. Yet resistance to ACTs by P. falciparum has emerged in recent years in Africa, threatening their effectiveness.
To slow this resistance and reduce treatment failures, an international research team led by Penn State investigated various drug policy interventions in Rwanda, where artemisinin resistance was first reported in 2020. Among other strategies, the team found that next-generation interventions such as triple ACTs (TACTs) — which combine an artemisinin derivative with two partner drugs or which use a sequential course of one ACT formulation, followed by a different ACT formulation — resulted in treatment failure counts that were at least 81% lower. Their results were published today (Sept. 21) in Nature Medicine.
“The malaria drug-resistance situation in Rwanda is urgent,” said Robert Zupko assistant research professor of biology, Penn State. “If we let things continue as is, artemisinin-resistant genotypes will begin to dominate by the end of this decade. Of the two dozen interventions we evaluated, we found that TACTs — a treatment yet to be approved to treat malaria but undergoing clinical evaluations — was projected to minimize both treatment failures and drug resistance.”
Dr. Aline Uwimana, head of case management at the Rwanda Biomedical Center and a senior author on the study, cautioned that waiting for optimal therapies may not be the best approach as resistance could soon be widespread.
“Of the available and approved approaches that we evaluated for this study, there were several options using multiple first-line therapies, or MFT, that we could begin to put into place next year,” Uwimama said. “This is likely the most feasible choice in the near term.”
Under an MFT strategy, multiple therapies are deployed at once and different patients get treated with different drugs.
According to Maciej Boni, professor of biology, Penn State, the current situation in Rwanda is a repeat or “three-peat” of past malaria drug failures. Since the 1940s, multiple antimalarial drugs have been deployed worldwide, but the eventual development of drug resistance in the malaria parasite forced the withdrawal of all of them. In the 1990s, new artemisinin drugs were trialed and found to be effective, and by 2005 they were recommended worldwide, he said. The following year, Rwanda adopted the ACT artemether-lumefantrine (AL) as its first-line therapy for malaria, but by 2020, a mutation, known as ‘pfkelch13 R561H’, was shown to have emerged over the previous decade; the R561H mutation is associated with delayed clearance of the parasite in the presence of AL.
“Studies indicate that the pfkelch13 R561H mutation is increasing, but there still may be a window of opportunity to delay its spread and avert high numbers of treatment failures,” Boni said. “The World Health Organization has recommended that the Rwandan National Malaria Control Program begin considering strategies for mitigating the spread of pfkelch13 R561H.”
To address this recommendation, Zupko and Boni worked with the Rwandan National Malaria Control Program and the Rwanda Biomedical Centre to develop plans for slowing down the spread of artemisinin resistance in Rwanda. Specifically, they examined a range of possible drug policy interventions and their ability to reduce long-term treatment failures. These included replacing AL as the first-line therapy with another artemisinin drug, introducing multiple drugs to be used in combination and lengthening the dosing schedule for AL from a three-day course of treatment to up to a five-day course of treatment. Additionally, the researchers evaluated sequential therapy approaches — in which one drug is given for a period of time followed by another — and triple artemisinin combination therapies.
The team modeled the impacts of these strategies on projected treatment failures and the frequency of the R561H mutation within the Plasmodium genome three, five and ten years into the future.
“We found that lengthening courses of treatment, deploying multiple drugs and implementing custom rotation strategies all provide a benefit when compared to the currently recommended three-day course of AL,” Zupko said.
Specifically, the researchers found that extending the use of AL from three to five days and using multiple drugs simultaneously are two strategies that may hold treatment failure rates at or near 10%.
In another study, which was published on July 29 in Nature Communications, the team looked more closely at triple artemisinin combination therapies (TACTs) in general African malaria settings. This work was done by two teams independently – the Penn State team and a University of Oxford modeling team led by associate professor Ricardo Aguas – to ensure that the results were not strongly influenced by the build and design of a single model.
“TACTs have been shown in clinical trials to be effective and well tolerated by patients, and the fact that early TACT adoption may delay the emergence and spread of antimalarial drug resistance is a modeling result of vital importance,” Boni said.
Zupko noted that the results of the research underscore what is already known from historical experience — drug resistance can spread rapidly once it is established.
“It is important to quickly implement an antimalarial policy that contains the spread of artemisinin resistance, including the immediate introduction of TACTs,” he said.
Other Penn State authors on the paper include Tran Dang Nguyen, assistant research professor of biology; Thu Nguyen-Anh Tran, graduate student in biology; and Kien Trung Tran, postdoctoral scholar in biology. Others from the Rwanda Biomedical Centre include J. Claude S. Ngabonziza, division manager; Michee Kabera, director of epidemiology; and Aline Uwimana, director of case management. Haojun Li, recent Penn State graduate and current Columbia University graduate student, also is an author.
The National Institutes of Health and Bill and Melinda Gates Foundation supported this research.
Journal
Nature Medicine | Biology |
Neanderthals and anatomically modern humans initially interbred 250,000 years ago, a date that is far earlier than previously thought, a new study suggests.
Until now, Neanderthals and anatomically modern humans (Homo sapiens) were believed to have first interbred earlier than 75,000 years ago, according to a 2016 genetic analysis in the journal Nature. However, a new analysis, published Oct. 13 in the journal Current Biology, has revealed that one group of Homo sapiens from Africa interbred with Neanderthals in Eurasia around 250,000 years ago.
This group of humans died out, but left a genetic footprint in the DNA of Neanderthals that descended from this interbreeding event — with 6% of the genome of a Neanderthal discovered in Croatia containing human DNA. Some sub-Saharan populations of anatomically modern humans also inherited Neanderthal DNA when groups of humans who had interbred with Neanderthals migrated back into Africa.
"The enhanced understanding derived from this research will enable us to annotate Neanderthal DNA in modern human genomes, as well as the reverse process, with greater accuracy," Michael Dannemann, an associate professor of evolutionary and population genomics at the University of Tartu in Estonia who was not involved in the research, told Live Science in an email.
This will help scientists predict how interbreeding events impacted the physical characteristics of both groups and improve our understanding of the migration patterns and interactions between modern humans and Neanderthals, he said.
In 2020, the idea that most modern human-Neanderthal interbreeding happened in Eurasia was contested by a study in the journal Cell that found Neanderthal DNA in human genomes in sub-Saharan Africa. However, the origin of this DNA was unknown and the analysis was limited to populations with mainly Niger-Congo-related ancestry.
In the new study, the authors compared the genome of the 122,000-year-old "Altai Neanderthal" from Croatia with those of 180 people from 12 modern sub-Saharan Africa populations. They then developed a statistical tool to uncover the origins of the Neanderthal DNA in the modern human genome.
The statistical analysis looked at genes shared by both humans and Neanderthals and tried to determine whether certain alleles, or genetic variants looked like they were of a Neanderthal origin but found their way into modern humans or vice versa, said Alexander Platt, study co-author and senior research scientist in the Department of Genetics at the University of Pennsylvania, told Live Science.
The authors found that all of the studied sub-Saharan genomes contained Neanderthal DNA, which mainly came from this 250,000-year-old human-Neanderthal interbreeding event. Some sub-Saharan populations also had Neanderthal DNA in up to 1.5% of their genomes, which was inherited from humans who had migrated back into Africa.
In addition, the authors found that most of the human DNA in the Neanderthal genome was in non-coding regions (meaning DNA that does not code for proteins) implying that human genes had been selected against during Neanderthal evolution. What's more, Neanderthal DNA was missing in the human genomes at the same place.
"That means that neither one [region of DNA] is particularly better than the other, they're just bad matches for the rest of the genome," Fernando Villanea, a population geneticist at the University of Colorado Boulder who was not involved in the research, told Live Science. "I think that was really cool, walking away from this idea of, oh, the Neanderthals are inferior in some way, to this idea that we're just two different species and we evolve for different things in our genomes," he said.
The authors hope the current findings will help answer other questions about human evolution.
"It'd be really cool to learn more about the genome of that population that existed 250,000 years ago," and compare it to the genomes of modern humans, Sarah Tishkoff, senior study author and professor in genetics and biology at the University of Pennsylvania, told Live Science. "Maybe that'll tell us something interesting about human evolutionary history or adaptation."
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Emily is a health news writer based in London, United Kingdom. She holds a bachelor's degree in biology from Durham University and a master's degree in clinical and therapeutic neuroscience from Oxford University. She has worked in science communication, medical writing and as a local news reporter while undertaking journalism training. In 2018, she was named one of MHP Communications' 30 journalists to watch under 30. ([email protected]) | Biology |
In a world full of bizarre animals, hairworms are some of the strangest: parasitic worms that manipulate the behavior of their hosts in what's sometimes called "mind control." A new study in the journal Current Biology reveals another strange trait shared by different hairworm species: they're missing about 30% of the genes that researchers expected them to have. What's more, the missing genes are responsible for the development of cilia, the hair-like structures present in at least some of the cells of every other animal known.
Hairworms are found all over the world, and they look like skinny strands of spaghetti, a couple inches long. Their simple bodies hint at their parasitic lifestyle -- they have no excretory, respiratory, or circulatory systems, and they spend almost their entire lives inside the bodies of other animals. "One of the coolest things, maybe the thing that they are most known for, is that they can affect the behavior of their hosts and make them do things that they wouldn't do otherwise," says Tauana Cunha, a postdoctoral researcher at Chicago's Field Museum and lead author of the study done in collaboration with Harvard University and the University of Copenhagen.
There are a few hundred species of freshwater hairworms. Their eggs hatch in water, and the hairworm larvae get eaten by tiny water-dwelling predators like mayfly larvae, which in turn get eaten by bigger, land-dwelling predators like crickets. After growing into adulthood inside of their new hosts' bodies, the hairworms manipulate the hosts' behavior, causing them to jump into water. There, the worms swim out of their hosts' butts and seek out mates, knotting themselves together, to begin the cycle anew. (There are also five species of hairworms that live in marine environments and parasitize water-dwelling creatures like lobsters, but it's not clear if those ones also have host manipulation capabilities -- there's no pressure for the worms to get back to the water, since the hosts already live there.)
As strange as hairworms' behavior is, Cunha's research interest in the animals has more to do with their DNA. "We set out to sequence their genomes, because nothing like them has ever been sequenced before at that level," she says of the study conducted with her co-authors Bruno de Medeiros, Arianna Lord, Martin Sørensen, and Gonzalo Giribet. "The goal was to produce those genomes and eventually use them to understand the evolutionary relationships between hairworms and other kinds of animals."
She and her colleagues took DNA samples from two hairworm species -- one freshwater and one saltwater -- and sequenced them. But when they compared the hairworms' genetic codes to those of other animals, they found something striking.
"What we found, which was very surprising, was that both hairworm genomes were missing about 30% of a set of genes that are expected to be present across basically all groups of animals," says Cunha.
Results like that often make scientists wonder if they've made a mistake. But there was a connection between the missing genes in the two worm species. "The large majority of the missing genes were exactly the same between the two species. This was just implausible by chance," says Cunha.
By looking at what functions these missing genes are responsible for in other animal groups, Cunha and colleagues showed that they give the instructions for producing cilia. "Cilia are organelles, small structures at the cellular level, that are basically present across all animals and even more broadly, in protists and some plants and fungi. So they're present across a large diversity of life on Earth," says Cunha. They're present in many of the cells in the human body: for instance, the tails of sperm cells are cilia, and cells in the retinas of our eyes have cilia too.
Previously, scientists had found that hairworms seemed to be missing cilia where they'd normally be found. Hairworm sperm, for example, do not have tails. But while no one had ever seen a ciliated cell from a hairworm, that wasn't considered definitive proof that they didn't have them. It's hard to prove something with negative evidence. "Without the genomes, this would require looking at all cells in all life stages in all species," says Bruno de Medeiros, Curator of Pollinating Insects at the Field Museum and co-author of the paper.
"Based on previous observations, it didn't seem like hairworms had any cilia, but we didn't really know for sure," says Cunha. "Now with the genomes, we saw that they actually lack the genes that produce cilia in other animals -- they don't have the machinery to make cilia in the first place."
What's more, the fact that both the freshwater and marine hairworm species had lost the genes for cilia indicates that this evolutionary change happened in the deep past to the two species' common ancestor. "It is likely that the loss happened early on in the evolution of the group, and they just have been carrying on like that," says Cunha.
The finding opens the door to several new questions. It's not clear how the lack of cilia have affected hairworms, or if the hairworms' parasitic behavior could be related to the missing cilia. "There are plenty of other parasitic organisms that aren't missing these specific genes, so we cannot say that the genes are missing because of their parasitic lifestyle," says Cunha. "But parasitic organisms in general are often missing lots of genes. It's hypothesized that because parasites are not using certain structures and instead rely on their hosts, they end up losing those structures."
Hairworms aren't the only parasites capable of "mind control" -- it's a behavior that's cropped up in protozoans like the organism responsible for toxoplasmosis, which reduces rodents' fear of cats, and in the fungus Ophiocordyceps, made famous by the video game and TV show The Last of Us, which manipulates ants into spreading the fungus's spores. While these organisms are only distantly related to hairworms, Cunha says that the new study could help scientists find common threads for how this behavior works. "By doing this comparative analysis across organisms in the future, we might be able to look for similarities. Or maybe these organisms evolved similar behaviors in completely different ways from each other," says Cunha.
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The COVID-19 pandemic seemed like a never-ending parade of SARS-CoV-2 variants, each equipped with new ways to evade the immune system, leaving the world bracing for what would come next.
But what if there were a way to make predictions about new viral variants before they actually emerge?
A new artificial intelligence tool named EVEscape, developed by researchers at Harvard Medical School and the University of Oxford, can do just that.
The tool has two elements: A model of evolutionary sequences that predicts changes that can occur to a virus, and detailed biological and structural information about the virus. Together, they allow EVEscape to make predictions about the variants most likely to occur as the virus evolves.
In a study published Wednesday in Nature, the researchers show that had it been deployed at the start of the COVID-19 pandemic, EVEscape would have predicted the most frequent mutations and identified the most concerning variants for SARS-CoV-2. The tool also made accurate predictions about other viruses, including HIV and influenza.
The researchers are now using EVEscape to look ahead at SARS-CoV-2 and predict future variants of concern; every two weeks, they release a ranking of new variants. Eventually, this information could help scientists develop more effective vaccines and therapies. The team is also broadening the work to include more viruses.
“We want to know if we can anticipate the variation in viruses and forecast new variants — because if we can, that’s going to be extremely important for designing vaccines and therapies,” said senior author Debora Marks, professor of systems biology in the Blavatnik Institute at HMS.
From EVE to EVEscape
The researchers first developed EVE, short for evolutionary model of variant effect, in a different context: gene mutations that cause human diseases. The core of EVE is a generative model that learns to predict the functionality of proteins based on large-scale evolutionary data across species.
“You can use these generative models to learn amazing things from evolutionary information — the data have hidden secrets that you can reveal,” Marks said.
As the COVID-19 pandemic hit and progressed, the world was caught off guard by SARS-CoV-2’s impressive ability to evolve. The virus kept morphing, changing its structure in ways subtle and substantial to slip past vaccines and therapies designed to defeat it.
“We underestimate the ability of things to mutate when they’re under pressure and have a large population in which to do so,” Marks said. “Viruses are flexible — it’s almost like they’ve evolved to evolve.”
Watching the pandemic unfold, Marks and her team saw an opportunity to help: They rebuilt EVE into a new tool called EVEscape for the purpose of predicting viral variants.
They took the generative model from EVE — which can predict mutations in viral proteins that won’t interfere with the virus’s function — and added biological and structural details about the virus, including information about regions most easily targeted by the immune system.
“We’re taking biological information about how the immune system works and layering it on our learnings from the broader evolutionary history of the virus,” explained co-lead author Nicole Thadani, a former research fellow in the Marks lab.
Such an approach, Marks emphasized, means that EVEscape has a flexible framework that can be easily adapted to any virus.
Turning back the clock
In the new study, the team turned the clock back to January 2020, just before the COVID-19 pandemic started. Then they asked EVEscape to predict what would happen with SARS-CoV-2.
“It’s as if you have a time machine. You go back to day one, and you say, I only have that data, what am I going to say is happening?” Marks said.
EVEscape predicted which SARS-CoV-2 mutations would occur during the pandemic with accuracy similar to this of experimental approaches that test the virus’ ability to bind to antibodies made by the immune system. EVEscape outperformed experimental approaches in predicting which of those mutations would be most prevalent. More importantly, EVEscape could make its predictions more quickly and efficiently than lab-based testing since it didn’t need to wait for relevant antibodies to arise in the population and become available for testing.
Additionally, EVEscape predicted which antibody-based therapies would lose their efficacy as the pandemic progressed and the virus developed mutations to escape these treatments.
The tool was also able to sift through the tens of thousands of new SARS-CoV-2 variants produced each week and identify the ones most likely to become problematic.
“By rapidly determining the threat level of new variants, we can help inform earlier public health decisions,” said co-lead author Sarah Gurev, a graduate student in the Marks lab from the Electrical Engineering and Computer Science program at MIT.
In a final step, the team demonstrated that EVEscape could be generalized to other common viruses, including HIV and influenza.
Designing mutation-proof vaccines and therapies
The team is now applying EVEscape to SARS-CoV-2 in real time, using all of the information available to make predictions about how it might evolve next.
The researchers publish a biweekly ranking of new SARS-CoV-2 variants on their website and share this information with entities such as the World Health Organization. The complete code for EVEscape is also freely available online.
They are also testing EVEscape on understudied viruses such as Lassa and Nipah, two pathogens of pandemic potential for which relatively little information exists.
Such less-studied viruses can have a huge impact on human health across the globe, the researchers noted.
Another important application of EVEscape would be to evaluate vaccines and therapies against current and future viral variants. The ability to do so can help scientists design treatments that are able to withstand the escape mechanisms a virus acquires.
“Historically, vaccine and therapeutic design has been retrospective, slow, and tied to the exact sequences known about a given virus,” Thadani said.
Noor Youssef, a research fellow in the Marks lab, added, “We want to figure out how we can actually design vaccines and therapies that are future-proof.”
Additional authors: Pascal Notin, Nathan Rollins, Daniel Ritter, Chris Sander, and Yarin Gal.
Disclosures: Marks is an adviser for Dyno Therapeutics, Octant, Jura Bio, Tectonic Therapeutic, and Genentech, and is a co-founder of Seismic Therapeutic. Sander is an adviser for CytoReason Ltd.
Funding for the research was provided by the National Institutes of Health (GM141007-01A1), the Coalition for Epidemic Preparedness Innovations, the Chan Zuckerberg Initiative, GSK, the UK Engineering and Physical Sciences Research Council, and the Alan Turing Institute.
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The content of a small box on his roof terrace in central London has taught ecologist Tim Blackburn more about the natural world than he ever thought possible. Every night, the light-mounted trap attracts winged creatures that perhaps don't get the best publicity — despite making up roughly a ninth of all known animal species on Earth.
Blackburn's new book, "The Jewel Box" (Weidenfeld & Nicolson, 2023) unveils the hidden world of moths, as well as the laws of nature that govern them and all the other creatures on this planet. Inspired by the diversity and beauty of the insects that fall into the eponymous "jewel box" at night, Blackburn, a professor of invasion biology at University College London in the U.K., reflects on 30 years of work as a scientist, taking readers on a journey around the wide web of life.
Shortly after the book's publication on June 8, Blackburn told Live Science about what five years of moth trapping have taught him.
Q: Thank you so much for joining me to talk about moths, Tim. Let's start with what first drew you to these insects, because in the introduction to "The Jewel Box," you write that your lifelong obsession is actually birds. What kindled your love for moths?
Blackburn: It was a bit of an accident, really. Ever since I was little, I've been into birds. My mother says before I could talk I would sit in the pram pointing at birds as they flew past. I got into moths partly because I was a bit nature-deprived and didn't really have time to go off looking for birds. Simultaneously, I started to run an undergraduate field course to a place in Scotland where they had a moth trap. It's basically just a box with a light on the top. Moths are attracted to the light and fall into the box. I was just so completely blown away that first morning when I went out to see what that moth trap had conjured out of thin air. The obsession started there.
I started to run a moth trap in London — and again, it conjured up all these incredible creatures out of nowhere. I just got completely hooked. The last five years, I've been obsessively running a moth trap wherever and whenever I can.
Q: It must have been magical to discover that there is such a diversity and abundance of moths in central London — many people wouldn't expect that. When you opened your trap for the first time, was there a moth that particularly struck you?
Blackburn: One that really sticks in the memory is a thing called a tree-lichen beauty [Cryphia algae], which is about the size of my thumbnail. It has a jade cloak, its thorax is often quite bright green, and the wings have this lovely mottled, lichen-like green camouflage. It's a really beautiful little moth that until about 30 years ago was really rare in the U.K. There were literally three records of this moth before 1990 in the U.K., and I had a dozen of them on my roof terrace that first morning.
Q: You've been running the moth trap on your roof terrace for quite some time now. As an ecologist with plenty of experience in the field, have you learned anything surprising in five years of moth trapping?
Blackburn: Every day is a school day. I was constantly surprised by things I was catching that I had no idea were there. There are so many alien moths in the environment — species from Asia, Australia, New Zealand and southern Europe — all occurring together in London, because people have moved them there by accident.
There can be big problems when we introduce a species from one part of the world to somewhere that it has no evolutionary history of association with. The box-tree moth [Cydalima perspectalis] is a classic alien species that we have in the U.K. It was introduced from East Asia and it chews people's box [Buxus sempervirens] hedges down. In the U.K. and through a lot of Europe, we also have natural box woodland and forests, and the moths are really hitting those very hard — killing a lot of trees.
Q: The book is obviously heavily inspired by your moth trap, but that's not all you focus on, and it's packed with stories and anecdotes. What was your aim in writing it?
Blackburn: What I really wanted to write about was how scientists try to understand the natural world, but in a way that was accessible to the general reader. The book really tries to explain the ecological rules of nature — how life organizes itself to produce the diversity of organisms that we see around us in nature… I always say it's not a book about moths, but it's a book illuminated by moths.
Q: Humans have transformed the natural world, and those ecological rules are shifting. What challenges do moths face in this changing environment?
Blackburn: Not only do we switch natural vegetation to crops, which takes away habitat from species, but we then spray those crops with pesticides to stop insects from eating them. Those pesticides spread across the environment, which has a big impact on insects and moths.
For moths, there's the additional issue of light pollution, because they're nocturnal. Having light in the environment 24 hours a day disrupts developmental processes and feeding. We're also seeing large-scale shifts in the distribution of species as they track changes in the climate. Species living in cooler environments or at higher elevations are getting squeezed out as we push temperatures beyond the limits that organisms can cope with.
Q: Do moths play an important ecological role?
Blackburn: Moths are fantastic pollinators, and we've only discovered this recently because we're not nocturnal. When the sun goes down, the pollinator shift changes and the moths take over from bees and hoverflies. Moths pollinate a wider range of species than bees, and they're more efficient pollinators.
Essentially, moths sit squarely in the middle of the web of life on Earth: They pollinate plants and consume plants, and they're consumed by birds, mammals, bats, spiders, parasitoid wasps — all sorts of things. When you think that 1 in 9 species of animal that we know is a moth, it's kind of remarkable. They really hold together our natural system.
Q: In the introduction to the book, you write that you are "obsessive" about identifying moths. Why is it so important to name species?
Blackburn: One of the stories I tell towards the end of the book is about a species of moth that was only described in 2017. I catch it on my terrace, and it's quite an unprepossessing little thing. But for years, people thought it was a thing called the peach twig borer [Anarsia lineatella] that is considered a pest, because it bores into fruit like peaches and apricots.
When some of these moths appeared in Denmark, in an area where they grow a lot of soft fruit, growers were really concerned and considering large-scale pesticide applications to try and stop this species in its tracks. It turns out that two species had been lumped together and the one that colonized Denmark actually feeds on maple rather than fruit trees. They were going to spray all these crops with pesticides to deal with a problem that wasn't a problem at all. If you don't know what you're dealing with, it can lead to fundamental mistakes in how you respond to species.
Q: What do you wish more people knew about moths?
Blackburn: People think that they're little brown things that hide away at night and aren't really that exciting. Some of them eat your cardigans and carpets, so that doesn't go down well. Because we don't see them, we don't realize this incredible diversity and how beautiful they are. When you start running a moth trap, there's these bright red creatures and bright greens and yellows, candy pink and gold. Some of them have the wingspan of a small bird. They are absolutely gorgeous, and that's where the title "The Jewel Box" comes from: They're these incredible insect jewels, and people should get to know them and love them.
"The Jewel Box" by Tim Blackburn is published by Weidenfeld & Nicolson and available to buy now.
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Sascha is a U.K.-based trainee staff writer at Live Science. She holds a bachelor’s degree in biology from the University of Southampton in England and a master’s degree in science communication from Imperial College London. Her work has appeared in The Guardian and the health website Zoe. Besides writing, she enjoys playing tennis, bread-making and browsing second-hand shops for hidden gems. | Biology |
The canola plant (Brassica napus) was developed in Canada during the 1970s using conventional selective breeding and hybrid propagation techniques (i.e., not by genetic modification) from turnip rapeseed, black mustard, and leaf mustard. Rapeseed is high in erucic acid, an unhealthy fatty acid that is associated with increased risk of breast cancer, but the canola plant was developed to minimize this component. Canola oil is made from the pressed seed of the canola plant. Canola oil is low in saturated fat and has a high monounsaturated fat content. It contains oleic acid, linoleic acid and alpha-linolenic acid (ALA). The oil's ALA content makes it a good source of non-marine omega-3 fatty acids compared to other vegetable oils. Canola oil is also a dietary source of CoQ10, vitamin E and vitamin K.
Canola oil has anti-inflammatory and antioxidant properties. In one study, consumption of canola oil was found to lower LDL-cholesterol and improve endothelial function in subjects with peripheral arterial occlusive disease, indicating that canola oil might provide cardiovascular protection. Canola oil was shown to prevent diabetic renal injury in diabetic rates in another study. Canola meal (which is left over from the seeds after the oil has been extracted) has been shown to reduce the tumor incidence and volume of both melanoma and colon cancer in mice.
However, a 2017 study reported that mice fed a diet supplemented with canola oil showed signs of memory impairment compared to mice on a regular mouse chow diet. Breast cancer-related effects of consuming canola oil Canola oil has been shown to inhibit growth and induce apoptosis in both estrogen positive (ER+) and estrogen negative (ER-) human breast cancer cells. Female mammary gland cancer-prone rats consuming canola oil during pregnancy have been found to produce offspring with lower tumor numbers, lower tumor volume and lower percentage of mice with tumors than the offspring of mothers on a diet with equivalent amounts of corn oil.
Several studies have found that higher omega-3/omega-6 fatty acid ratios are associated with reduced risk of breast cancer; using canola oil would tend to improve the ratio for most women. A 2008 San Francisco population study found that women cooking mainly with olive/canola oil have a lower risk of breast cancer than those cooking with vegetable/corn oil or hydrogenated fats. Additional comments Frying with canola oil (especially deep frying or wok frying) has been shown to release carcinogenic polycyclic aromatic hydrocarbons (PAHs) in the cooking oil smoke and fumes (this is true of soybean oil, corn oil, peanut oil, and sunflower oil as well). Breathing such fumes should be avoided since this has been associated with increased risk of lung cancer in several population studies.
Mayonnaise made with canola oil is preferable to that made with soybean oil or grape seed oil because of canola oil's more favorable fatty acid profile.
While the canola plant was developed using conventional methods, the majority of current canola production comes from genetically modified plants developed for their resistance to herbicides. Organic canola oil is available for those concerned about consuming genetically modified foods.
Possibly because of its connection with rapeseed oil, canola oil has been the subject of many alarming negative (and false) health-related claims, especially on the internet. As mentioned above, rapeseed oil is high in erucic acid (30 to 60 percent) and should be avoided (canola oil contains between 0.3 and 1.2 percent erucic acid, an acceptable amount). Rapeseed oil normally is not sold in U.S. supermarkets but it can be found as an ingredient in some processed foods such as commercial peanut butter. Be aware that in Europe, canola oil is referred to as rape oil or rapeseed oil but it is, in fact, canola oil.
Below are links to recent studies concerning this food and its components. For a more complete list of studies, please click on canola oil. Fatty Acid Composition and Oxidative Potential of Food Products Prepared Using Low Erucic Brassica Oils Cite Saklani S, Grover K, Choudhary M, Sandhu SK, Javed M. Fatty Acid Composition and Oxidative Potential of Food Products Prepared Using Low Erucic Brassica Oils.
Proceedings of the National Academy of Sciences, India Section B: Biological Sciences. Springer Science and Business Media LLC; 2022; 10.1007/s40011-022-01415-6 Fabricating the canola oil Nanoemulsion and assessing its anti-cancer effects on the mouse mammary gland tumor Cite neamati a, Yousefi Y, Homayouni-Tabrizi M, Pournaghshband N. Fabricating the canola oil Nanoemulsion and assessing its anti-cancer effects on the mouse mammary gland tumor.
Research Square Platform LLC; 2022; 10.21203/rs.3.rs-1570102/v1 Accumulation of Arachidonic Acid, Precursor of Pro-Inflammatory Eicosanoids, in Adipose Tissue of Obese Women: Association with Breast Cancer Aggressiveness Indicators Cite Ouldamer L, Jourdan M, Pinault M, Arbion F, Goupille C. Accumulation of Arachidonic Acid, Precursor of Pro-Inflammatory Eicosanoids, in Adipose Tissue of Obese Women: Association with Breast Cancer Aggressiveness Indicators.
Biomedicines. MDPI AG; 2022; 10:995 10.3390/biomedicines10050995 Omega-9 fatty acids: potential roles in inflammation and cancer management Cite Farag MA, Gad MZ. Omega-9 fatty acids: potential roles in inflammation and cancer management.
Journal of Genetic Engineering and Biotechnology. Springer Science and Business Media LLC; 2022; 20 10.1186/s43141-022-00329-0 Fatty acids and their lipid mediators in the induction of cellular apoptosis in cancer cells Cite Biswas P, Datta C, Rathi P, Bhattacharjee A. Fatty acids and their lipid mediators in the induction of cellular apoptosis in cancer cells.
Prostaglandins & Other Lipid Mediators. Elsevier BV; 2022;:106637 10.1016/j.prostaglandins.2022.106637 Futuristic food fortification with a balanced ratio of dietary ω-3/ω-6 omega fatty acids for the prevention of lifestyle diseases Cite Patel A, Desai SS, Mane VK, Enman J, Rova U, Christakopoulos P, et al. Futuristic food fortification with a balanced ratio of dietary ω-3/ω-6 omega fatty acids for the prevention of lifestyle diseases.
Trends in Food Science & Technology. Elsevier BV; 2022; 120:140-153 10.1016/j.tifs.2022.01.006 Effects of cooking factors on the formation of heterocyclic aromatic amines in fried beef patties Cite Fan H, Hu H, Li C, Xie J, Chen J, Zeng M, et al. Effects of cooking factors on the formation of heterocyclic aromatic amines in fried beef patties.
Journal of Food Processing and Preservation. Wiley; 2022; 10.1111/jfpp.16288 The Brassica Napus Extract (BNE)-Loaded PLGA Nanoparticles as an Early Necroptosis and Late Apoptosis Inducer in Human MCF-7 Breast Cancer Cells Cite Shabestarian H, Tabrizi MH, Es-haghi A, Khadem F. The Brassica Napus Extract (BNE)-Loaded PLGA Nanoparticles as an Early Necroptosis and Late Apoptosis Inducer in Human MCF-7 Breast Cancer Cells.
Nutrition and Cancer. Informa UK Limited; 2021;:1-10 10.1080/01635581.2021.2008986 Dietary intake and biomarkers of alpha linolenic acid and risk of all cause, cardiovascular, and cancer mortality: systematic review and dose-response meta-analysis of cohort studies Cite Naghshi S, Aune D, Beyene J, Mobarak S, Asadi M, Sadeghi O. Dietary intake and biomarkers of alpha linolenic acid and risk of all cause, cardiovascular, and cancer mortality: systematic review and dose-response meta-analysis of cohort studies.
BMJ. BMJ; 2021;:n2213 10.1136/bmj.n2213 Epigenetic Reprogramming Mediated by Maternal Diet Rich in Omega-3 Fatty Acids Protects From Breast Cancer Development in F1 Offspring Cite Abbas A, Witte T, Patterson WL, Fahrmann JF, Guo K, Hur J, et al. Epigenetic Reprogramming Mediated by Maternal Diet Rich in Omega-3 Fatty Acids Protects From Breast Cancer Development in F1 Offspring.
Frontiers in Cell and Developmental Biology. Frontiers Media SA; 2021; 9 10.3389/fcell.2021.682593 Antiproliferative Rapeseed Defatted Meal Protein and Their Hydrolysates on MCF-7 Breast Cancer Cells and Human Fibroblasts Cite Ferrero RL, Soto-Maldonado C, Weinstein-Oppenheimer C, Cabrera-Muñoz Z, Zúñiga-Hansen ME. Antiproliferative Rapeseed Defatted Meal Protein and Their Hydrolysates on MCF-7 Breast Cancer Cells and Human Fibroblasts.
Foods. MDPI AG; 2021; 10:309 10.3390/foods10020309 α-Linolenic acid inhibits the migration of human triple-negative breast cancer cells by attenuating Twist1 expression and suppressing Twist1-mediated epithelial-mesenchymal transition Cite Wang S, Sun H, Hsu Y, Liu S, Lii C, Tsai C, et al. α-Linolenic acid inhibits the migration of human triple-negative breast cancer cells by attenuating Twist1 expression and suppressing Twist1-mediated epithelial-mesenchymal transition.
Biochemical Pharmacology. Elsevier BV; 2020; 180:114152 10.1016/j.bcp.2020.114152 Cold-pressed rapeseed (Brassica napus) oil: Chemistry and functionality Cite Chew SC. Cold-pressed rapeseed (Brassica napus) oil: Chemistry and functionality.
Food Research International. Elsevier BV; 2020; 131:108997 10.1016/j.foodres.2020.108997 Oils’ Impact on Comprehensive Fatty Acid Analysis and Their Metabolites in Rats Cite Stawarska A, Jelińska M, Czaja J, Pacześniak E, Bobrowska-Korczak B. Oils’ Impact on Comprehensive Fatty Acid Analysis and Their Metabolites in Rats.
Nutrients. MDPI AG; 2020; 12:1232 10.3390/nu12051232 Effect of canola oil consumption on memory, synapse and neuropathology in the triple transgenic mouse model of Alzheimer’s disease Cite Lauretti E, Praticò D. Effect of canola oil consumption on memory, synapse and neuropathology in the triple transgenic mouse model of Alzheimer’s disease.
Scientific Reports. Springer Science and Business Media LLC; 2017; 7 10.1038/s41598-017-17373-3 O3 An in vitro study on the anti-cancer properties of rapeseed pomace extracts Cite Goua M, Barron G, Thoo Lin PK, Bermano G. O3 An in vitro study on the anti-cancer properties of rapeseed pomace extracts.
Biochemical Pharmacology. Elsevier BV; 2017; 139:111 10.1016/j.bcp.2017.06.068 Polyunsaturated fatty acid interactions and breast cancer incidence: a population-based case-control study on Long Island, New York Cite Khankari NK, Bradshaw PT, Steck SE, He K, Olshan AF, Shen J, et al. Polyunsaturated fatty acid interactions and breast cancer incidence: a population-based case-control study on Long Island, New York.
Annals of Epidemiology. Elsevier BV; 2015; 25:929-935 10.1016/j.annepidem.2015.09.003 Assessment of antiproliferative activity of pectic substances obtained by different extraction methods from rapeseed cake on cancer cell lines Cite Cobs-Rosas M, Concha-Olmos J, Weinstein-Oppenheimer C, Zúñiga-Hansen M. Assessment of antiproliferative activity of pectic substances obtained by different extraction methods from rapeseed cake on cancer cell lines.
Carbohydrate Polymers. Elsevier BV; 2015; 117:923-932 10.1016/j.carbpol.2014.10.027 Maternal Dietary Canola Oil Suppresses Growth of Mammary Carcinogenesis in Female Rat Offspring Cite Mabasa L, Cho K, Walters MW, Bae S, Park CS. Maternal Dietary Canola Oil Suppresses Growth of Mammary Carcinogenesis in Female Rat Offspring.
Nutrition and Cancer. Informa UK Limited; 2013; 65:695-701 10.1080/01635581.2013.789539 Canola Oil Inhibits Breast Cancer Cell Growth in Cultures and In Vivo and Acts Synergistically with Chemotherapeutic Drugs Cite Cho K, Mabasa L, Fowler AW, Walsh DM, Park CS. Canola Oil Inhibits Breast Cancer Cell Growth in Cultures and In Vivo and Acts Synergistically with Chemotherapeutic Drugs.
Lipids. Wiley; 2010; 45:777-784 10.1007/s11745-010-3462-8 | Biology |
Sign up for CNN’s Wonder Theory science newsletter. Explore the universe with news on fascinating discoveries, scientific advancements and more. CNN — In the largest DNA analysis of its kind, scientists have found evidence to suggest that historic plague pandemics, such as the Black Death, were not caused by newly evolved strains of bacteria but ones that could have emerged up to centuries before their outbreaks. The plague-causing bacterium Yersinia pestis is dated to have first emerged in humans about 5,000 years ago. Through animals and trade routes, Y. pestis spread globally over time on multiple occasions, according to a study published Thursday in the journal Communications Biology. It caused the first plague pandemic in the sixth to eighth centuries and the second one in the 14th to 19th centuries. The latter pandemic is thought to have started with the medieval Black Death outbreak, which is estimated to have killed more than half of Europe’s population. The bacterium also caused the third plague pandemic between the 19th and 20th centuries. By amassing 601 Y. pestis genome sequences, including modern and ancient strains, researchers from Canada and Australia were able to calculate the time when the bacterial strains likely emerged as a threat. They divided the different strains of the plague bacterium and analyzed each strain population individually. The strain responsible for the Black Death, which the study says is thought to have begun in 1346, was newly estimated to have diverged from an ancestral strain between 1214 and 1315 — up to 132 years earlier. The strain of Y. pestis associated with the first plague pandemic was previously recorded as first appearing during the Plague of Justinian, which began in 541. However, the researchers estimated that the strain was already present between 272 and 465 — up to almost 270 years before the outbreak. “It shows that each major plague pandemic has likely emerged many decades to centuries earlier than what the historical record suggests,” study coauthor and evolutionary geneticist Hendrik Poinar, director of McMaster University’s Ancient DNA Centre in Canada, told CNN via email Thursday. He added that the bacterium emerged, created small epidemics and then “for reasons we don’t quite understand,” such as famine or war, “it takes off.” The study authors estimated that individually assessed bacterial strains from the third plague pandemic diverged from an ancestral strain between 1806 and 1901, with highly localized plague cases beginning to appear in southern China between 1772 and 1880 and later diverging into various strains that spread globally out of Hong Kong between 1894 and 1901. The study also found evidence to support recent academic research suggesting that the third and second plague pandemics were not mutually exclusive events, but that the third was partly the continuation or tail end of the second. Despite the pandemics having their own diverse genetic lineages that evolved differently, the third descended directly from the 14th century strain that caused the second. Poinar called this finding significant because “it takes into account that most of the history of this bacterium has been a Eurocentric view, so while plague supposedly disappeared from Europe in the 18th (century), it continued to rage in the Ottoman Empire and throughout the Middle East and likely North Africa.” However, even with so many sequences of the plague bacterium, researchers were not able to determine the path of the global spread of the plague. A lot of the genetic samples come from Europe. For example, the emergence of the bacterium in Africa has led to 90% of all modern plague cases occurring on the continent, yet there are no ancient sequences from the region, which is represented by just 1.5% of all genome samples — making it difficult to date the appearance of Y. pestis in Africa. There is also far less surviving historical evidence from the second plague pandemic to help estimate its geographic origins compared with the third, with the earliest textual evidence of the pandemic in Europe coming from the Black Death in 1346, the study authors said. The researchers estimated that the second pandemic originated in Russia. A study published in the journal Nature in June used DNA analysis to find the plague bacterium in three individuals who are dated to have died in 1338 in what’s now Kyrgyzstan in Central Asia. It provided evidence that the Black Death came from a strain originating in the area near Lake Issyk-Kul in Kyrgyzstan in the early 14th century. The latest study concluded that more ancient DNA will be needed to refine current estimates on the early events of the second pandemic. Via email, Poinar described the strain from Kyrgyzstan as “really fascinating” but said that it “still doesn’t sit at the root. So I would guess we’re still looking for something a good 20-50 years earlier.” He and the other authors noted that the only way to estimate the evolution of the plague bacterium strains precisely “is with well dated sequences, such as those from skeletal remains at Lake Issyk-Kul.” | Biology |
The National Zoo in Washington welcomed an adorable baby gorilla on Saturday morning, and visitors may be able to catch a glimpse of the baby, who has not yet been named, as soon as Tuesday, according to Smithsonian's National Zoo and Conservation Biology Institute.
The infant is a western lowland gorilla, which is a critically endangered species.
Mom Calaya, 20, has been nursing the baby, the zoo said. Animal care staff say the infant has been clinging closely to its mother.
"We are overjoyed to welcome a new infant to our western lowland gorilla troop," Becky Malinsky, curator of primates, said. "Calaya is an experienced mother, and I have every confidence she will take excellent care of this baby, as she did with her first offspring, Moke. Since his birth in 2018, it's been wonderful seeing her nurturing and playful side come out. I encourage people to visit our gorilla family and be inspired to help save this critically endangered species in the wild."
Zoo staff are leaving the mom and baby alone to bond, so they have not yet been able to determine the baby's gender. The zoo also closed the Great Ape House until Tuesday to give the gorillas a quiet space to bond. While the exhibit is reopening, Calaya and the baby will have access to a private, off-exhibit area.
Calaya and 31-year-old Baraka bred in September of last year, according to the zoo. In October, zoo keepers used a common human pregnancy test to confirm that Calaya was pregnant. They were able to give her ultrasounds throughout the pregnancy to monitor fetal development.
Baby western lowland gorillas weigh around 4 pounds at birth, according to the zoo. They crawl and ride on their mothers' backs starting around three months.
The newborn, its parents and Moke also live with a 41-year-old female named Mandara and her 14-year-old daughter, Kibibi.
This is the first time in five years a western lowland gorilla has been born at the zoo.
Keepers said they're excited to see how 5-year-old Moke will interact with his new sibling.
Mom Calaya is described as being protective and cautious. Dad Baraka has a relaxed and playful personality. Zoo keepers said "he has been very tolerant of his 5-year-old son's antics."
Scientists estimate that in the past 20 to 25 years, the number of wild western lowland gorillas has decreased by 60% because of habitat loss, disease and poaching. The species is native to Africa and lives in the forests of Gabon, Central Africa Republic, Cameroon, Angola, Equatorial Guinea and Congo.
Western lowland gorillas are quiet, peaceful and nonaggressive, according to the zoo. Adult males weigh an average of 300 pounds and up to 500 pounds. They stand up to 6 feet tall. Adult females weigh from 150 to 200 pounds and stand up to 4.5 feet tall.
Gorillas live for 30 or 40 years in the wild. In human care, gorillas may live into their 50s, according to the zoo.
for more features. | Biology |
Fossil of Tiny Ancient Whale Discovered in Egypt
The 8-foot-long species lived in the oceans of Earth over 41 million years ago.
Since leaving land roughly 50 million years ago, whales have generally gotten bigger, evolving into some of the largest animals ever. But these quintessential ocean giants could also be quite small, as a new fossil unearthed from the Egyptian desert shows.
Paleontologists uncovered the 41-million-year-old bones of a whale that likely measured just over 8 feet long and weighed only about 400 lbs. The new species, called Tutcetus rayanensis (after the Egyptian pharaoh Tutankhamun) is the smallest known member of a group of ancient whales called basilosaurids, researchers report Thursday in Communications Biology.
The land-loving ancestors of modern whales were comparatively small, likely not much bigger than a tapir. But within a dozen million years or so, some ancient whales ballooned in size, including one species that may be the heaviest animal ever, potentially weighing 340 tons.
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T. rayanensis followed a different evolutionary path. Researchers don’t have a full skeleton, but based on the bones they’ve found —parts of the skull, jaw, teeth and atlas vertebra— it measures nearly half the size of the previously smallest basilosaurid. Its diminutive body could be an evolutionary holdover from its ancestors’ days on land, or it could have been a response to global warming, the researchers suggest.
Around 42 million years ago, parts of the deep ocean got about 3.6 F warmer over roughly 30,000 years. That warming, the researchers suggest, may have favored smaller bodies that can shed excess heat more easily. Animals tend to be larger in colder climates and smaller in warmer climates, and aquatic animals in particular seem to shrink in size when temperatures rise over evolutionary timescales.
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A Japanese researcher has told a major genetics conference that he has created eggs from the cells of male mice.
The research, still in its early stages, involved turning male XY sex chromosomes into female XX ones.
Prof Katsuhiko Hayashi from Osaka University is working on developing fertility treatments.
The development, which he has submitted for publication in the scientific journal Nature, raises the prospect of male couples having their own children.
Prof George Daley of Harvard Medical School, who is not involved in the research, said that there was still a long way to go before society was faced with such a decision.
''Hayashi's work is unpublished but fascinating. [Doing this on Humans] is harder than the mouse," he said. We still don't understand enough of the unique biology of human gametogenesis (the formation of reproductive cells) to reproduce Hayashi's provocative work in mice''.
Details were presented at the human gene-editing summit at the Crick Institute in London.
Prof Hayashi, a globally respected expert in the field, told delegates at the meeting that the work was at a very early stage. The eggs, he said were of low quality and the technique could not be used safely on humans at this stage.
But he told BBC News that he could see current problems overcome in ten years and he would like to see it available as a fertility treatment for both male and female and same sex couples if it is proven to be safe to use.
"If people want it and if society accepts such a technology then yes, I'm for it".
The technique involves first taking a skin cell from a male mouse and then turning it into a stem cell - a cell that can turn into other types of cell.
The cells are male and therefore have XY chromosomes. Prof Katsuhiko's team then delete the Y chromosome, duplicate the X chromosome and then stick the two X's together. This adjustment allows the stem cell to be programmed to become an egg.
The technique could be used to help infertile couples where women are not able to produce their own eggs. He stressed though that it was a long way off from being available as a fertility treatment.
"Even in mice there are many problems in the quality of the egg. So before we can think of it as a fertility treatment we have to overcome these problems, which could take a long long time," he said.
Prof Hayashi said he would not be in favour of it being used by a man to create a baby using his own sperm and artificially created eggs.
"Technically this is possible. I'm not so sure whether at this stage it is safe or acceptable for society".
Prof Amander Clark, a stem cell scientist from the University of Californa, Los Angeles said that the LBGTQ+ community should have a say in the use of the technology for reproduction.
"The LGBTQ+ community have unique needs when it comes to having a family. It may be possible in the future for same-sex reproduction based upon current research using laboratory models to develop the technology.
"However, today this technology is not available for human use, safety and efficacy has not been proven, and it is unclear how long the technology will take to get to the clinic. There is still much to learn about the human germ line and fundamental knowledge gaps serve as a barrier to translating this research to humans."
Cultural differences
Alta Charo, who is a Professor of law at the University of Wisconsin Maddison, said that different cultures would have "profoundly different views' on how best to consider the application of the technique should it ever become available.
In some societies a genetic contribution to one's children is considered absolutely essential and for them it's a question of 'is this a step to take?' for those who are not in a heterosexual arrangement.
"For other societies that's not as nearly as important and child adoption is perfectly acceptable, because for them families are more about the personal relationship and less about the biological connection."
Prof Haoyi Wang, of the Chinese Academy of Science believes that there is a very a long way to go before the technology could be considered for use in the clinic
"Scientists never say never, in principle it has been done in mice so of course it may be possible in humans but I can foresee a lot of challenges and I couldn't predict how many years that would be".
Follow Pallab on Twitter | Biology |
My friend Mike Bruford, who has died aged 59 after a protracted illness, dedicated his career to unravelling the genetic consequences of biodiversity loss and was a professor of conservation genetics at Cardiff University.
Respected by governments and researchers worldwide, Mike was determined and driven, and communicated science in a compelling manner. When asked, after a talk in 2022: “Can we afford to make all these changes to protect biodiversity?” his response was simple: “We cannot afford not to.”
Born in Cardiff to Colin, an engineering draughtsman, and Anne (nee Lerego), who worked for a car dealership, Mike attended St Cyres school, in Penarth, south Wales, where his first encounters with nature came as a boy sneaking out to camp on Sully Island. He also began to support Cardiff City FC, following them through thick and thin for the rest of his life.
During studies for a degree in biomolecular science at Portsmouth Polytechnic (now the University of Portsmouth), he met a fellow student, Claire Lawes, whom he married in 1990.
Mike’s PhD, for which he studied at Leicester University for three years from 1986, examined the subject of hypervariable markers in the chicken genome, and coincided with the rapidly advancing field of genetic fingerprinting. In 1990 he joined the Zoological Society of London’s conservation genetics group as a research associate, becoming group leader in 1994. From there he developed his international career and nurtured a love of African wildlife.
Mike moved to Cardiff University as a reader in conservation genetics in 1999 and I became his first appointment. In 2001 he became a professor in the university’s new school of biosciences, from where he established the International Union for Conservation of Nature’s Conservation Genetics Specialist Group, promoting the use of genetic data in the organisation’s policies.
He also worked on a range of conservation genetics projects with the Darwin Initiative, a UK government grants scheme that helps to protect biodiversity and the natural environment through locally based projects worldwide, and was instrumental in establishing FrozenArk, a “biobank” containing deep-frozen genetic material from endangered species. In 2019 he became Cardiff University’s first dean for environmental sustainability.
Over the years Mike received a number of awards, including the Zoological Society of London’s Scientific Medal (2003), the Royal Society’s Wolfson Research Merit award (2012-1016) and the Marsh award for Conservation Biology (2020). His research has been cited more than 30,000 times by others, and he was supervisor to more than 70 doctoral and postdoctoral researchers. He was a collegiate, inspirational mentor who was always warm and humorous.
He is survived by Claire, their children, Erin and Rhys, his parents and his sister, Wendy. | Biology |
Mosquitoes and other insects can carry human diseases such as dengue and Zika virus, but when those insects are infected with certain strains of the bacteria Wolbachia, this bacteria reduces levels of disease in their hosts. Humans currently take advantage of this to control harmful virus populations across the world.
New research led at UC Santa Cruz reveals how the bacteria strain Wolbachia pipientis also enhances the fertility of the insects it infects, an insight that could help scientists increase the populations of mosquitoes that do not carry human disease.
"With insect population replacement approaches, they keep all the mosquitos and just add Wolbachia so that fewer viruses are carried in those mosquitoes and transmitted to humans when they bite them -- and it's working really, really well," said Shelbi Russell, an assistant professor of biomolecular engineering at UCSC who led this research. "If there is some fertility benefit of Wolbachia that could evolve over time, then we could use that to select for higher rates of mosquitos that suppress our viral transmission."
These results were detailed in a new paper led by Russell, published today in the journal PLOS Biology. UCSC Professor of Molecular, Cell, and Developmental Biology William Sullivan is the paper's senior author.
Humans and Wolbachia
Different strains of Wolbachia bacteria naturally infect a number of different animals worldwide, such as mosquitos, butterflies, and fruit flies. Once they infect an insect, the bacteria are able to manipulate the reproduction and development of their host to increase their own population. Humans take advantage of this to control the population size of insects that carry diseases that threaten us.
Wolbachia have developed a mechanism to poison the sperm of infected males so that if the male mates with an uninfected female, most of the potential offspring die at the very first cell division, and the rest are lost soon after. Humans have taken advantage of this to kill off insect populations.
However, research shows that later down the line once they have killed off as many uninfected hosts as possible, Wolbachia switch their evolutionary strategy to increase population levels of infected hosts. Understanding how this happens is important for avoiding unexpected consequences of human efforts to control insect populations.
"We need to understand all of these factors and their evolutionary potential if we're going to be releasing bacteria into new ecosystems," Russell said. "They're evolving in real time, so we need to understand where these trajectories are going."
Beyond disease prevention, controlling insect populations and range via bacteria could be an effective mechanism for crop security in the face of the changing climate.
Understanding increased fertility
The new results show that Wolbachia pipientis, which is native to fruit flies, has evolved to increase the fertility, and therefore the population size, of its fruit fly host. Previous research has found that the Wolbachia pipientis achieves this by manipulating a protein in fruit flies called Meiotic-P26 that affects fertility, but how exactly this happens was unclear.
To investigate, Russell and her colleagues bred fruit flies with various defects affecting Mei-P26, which caused them to have reduced fertility. These defects occasionally occur naturally in the wild, but are hard to track in that setting. The researchers then examined what happened when they infected the flies with Wolbachia pipientis.
They found that Wolbachia infection restored the fruit fly's fertility, enabling them to produce even more offspring than uninfected flies. The researchers found that Wolbachia can essentially undo gene defects in their host that would otherwise cause the population to go extinct. The Wolbachia rescue their host population through several strategies, including restoring fruit fly stem cells and ensuring that egg cells properly develop.
In further experiments, the researchers also found that, beyond rescuing fruit flies with defects, the Wolbachia pipientis infection also enhances the health and fertility of fruit flies without defects, resulting in higher egg lay and hatch rates for those insects.
Wolbachia in the lab
Russell focuses on Wolbachia because it and its fruit fly hosts are relatively easy to keep alive and reproduce in the lab. Oftentimes when scientists study bacteria, their efforts are hindered because either the host, the bacteria, or both are difficult to keep alive in the lab setting -- even research into common bacteria important to humans such as Chlamydia are slowed by this problem. Wolbachia and their fruit fly hosts offer a rare opportunity to understand how bacteria can change the DNA and biological processes of their host.
"Through studying this system, I can learn a lot about how these weird bacteria work and how they integrate with host biology," Russell said. "Bacteria are able to hop into these eukaryotes and leverage some of those mechanisms that their ancestors didn't even contain the genes for. It's a really fascinating thing in general, and it's cool that we can leverage this for biological control applications."
Russell and her lab will continue to hone in on the specific changes that occur in the genomes and gene expression of host species, and look at the fertility benefits that Wolbachia may bring to their hosts in other insect populations.
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Millions of years ago, as dinosaur giants were stomping around on land, other giant reptiles were dominating the oceans — and some of them, like plesiosaurs and similar animals, grew extremely long, snake-like necks.
Now, scientists have discovered how some of these early marine reptiles evolved these lengthy necks rather quickly — by adding new vertebrae to their spines.
Researchers in China and the U.K. examined the fossil of a marine reptile called a pachypleurosaur from the early Triassic period (251.9 to 201.3 million years ago), which kicked off the start of the dinosaur era. This newly discovered species, which they named Chusaurus xiangensis, had a neck about half as long as its torso.
Initially, the researchers were not sure whether C. xiangensis was a pachypleurosaur because its neck seemed too short —some of its relatives from later in the Triassic period sported necks more than 80% the length of their torsos, the authors noted in the study, published on Aug. 31 in the journal BMC Ecology and Evolution. But despite its relatively short neck, the researchers determined that the fossil was indeed, a pachypleurosaur.
To find out how these animals developed super-long necks in super-quick time, the researchers compared fossils of eosauropterygians — the group that includes pachypleurosaurs and other ancient, long-necked marine reptiles — from different periods of the Triassic era.
They found that the ratio of the length of their torsos to necks went from about 40% to 90% within roughly 5 million years.
After that, their necks stopped growing longer quite as quickly. "They had presumably reached some kind of perfect neck length for their mode of life," Benjamin Moon, one of the paper's co-authors and a paleontologist at the University of Bristol in the U.K., said in a statement.
"We think, as small predators, they were probably mainly feeding on shrimps and small fish, so their ability to sneak up on a small shoal, and then hover in the water, darting their head after the fast-swimming prey was a great survival tool."
These early long-necked animals also had fewer vertebrae than some of their later relatives. "Chusaurus already had 17, whereas later pachypleurosaur had 25," Long Cheng, one of the study's co-authors and a paleontologist at the Wuhan Centre of China Geological Survey, said in the statement.
"Some Late Cretaceous plesiosaurs [100 million to 66 million years ago] such as Elasmosaurus even had 72, and its neck was five times the length of its trunk," Cheng added. "With so many vertebrae, these long necks must have been super-snakey and they presumably whipped the neck around to grab fishy prey while keeping the body steady."
This speedy evolution of long necks early in the Triassic period was likely due to the mass extinction — dubbed the Great Dying — that preceded it. "The end-Permian mass extinction had been the biggest mass extinction of all time and only one in twenty species survived," study co-author Michael Benton, also a paleontologist at the University of Bristol, said in the statement. "The Early Triassic was a time of recovery and marine reptiles evolved very fast at that time, most of them predators on the shrimps, fishes and other sea creatures.
"They had originated right after the extinction, so we know their rates of change were extremely rapid in the new world after the crisis."
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Ethan Freedman is a science and nature journalist based in New York City, reporting on climate, ecology, the future and the built environment. He went to Tufts University, where he majored in biology and environmental studies, and has a master's degree in science journalism from New York University. | Biology |
New study shows that the Bachman's warbler was a distinct species
The Bachman's warbler, a songbird that was last seen in North America nearly 40 years ago, was a distinct species and not a hybrid of its two living sister species, according a new study in which the full genomes of seven museum specimens of the bird were sequenced. Genome comparisons of Bachman's warbler with the golden-winged and blue-winged warblers also helped researchers identify a new candidate gene involved in feather pigmentation in the group. A paper describing the study, led by Penn State researchers, highlights the crucial role that museum collections can play in science and appears June 16, 2023 in the journal Current Biology.
"The Bachman's warbler is the only songbird known to have recently gone extinct in North America," said David Toews, assistant professor of biology in the Penn State Eberly College of Science and the leader of the research team. "It is one of three species in the genus Vermivora. Our lab studies the two living species of this genus, which are known to mate with each other producing hybrid offspring."
Golden-winged and blue-winged warblers produce a spectrum of hybrids, but two distinct types of hybrid offspring, each with a unique combination of the parent species' coloration, have been the focus of bird watchers and ornithologists. This is because these two hybrids were thought to be distinct species themselves, known as Brewster's warbler and Lawrence's warbler, until careful study of wild hybrids and, now, modern genetic analysis has confirmed their hybrid origins. The extinct Bachman's warbler resembles one of these hybrid offspring in coloration, so there was some question as to whether the Bachman's warbler was itself a distinct species or if it might also have been a hybrid.
The research team collected seven specimens of the Bachman's warbler from museum collections and extracted DNA from the birds' toepads. They then performed whole-genome sequencing to compare the Bachman's warbler genome to existing genomes for the two living species in the genus.
"It's never easy to get DNA for sequencing from museum specimens," said Andrew Wood, the first author of the paper, who was a research technologist in Toews' lab at the time of the research and is now a postdoctoral researcher at the University of Minnesota. "These birds were collected over a hundred years ago and were not preserved in any special way, but we were able to extract enough DNA to get genome sequences that are comparable to those from the living species."
The genomes of the golden-winged and blue-winged warblers are very similar to each other, except for a few regions that are involved in determining the coloration patterns of the bird's feathers. In comparison, the Bachman's warbler genome was very different, which indicated to the researchers that it was, in fact, a distinct species.
"We only have a small sample size for the Bachman's warbler genome, but one of the interesting findings we saw by comparing the seven specimens was that there were long 'runs of homozygosity,'" said Toews. "These are regions of the genome where the two copies of the genome—one inherited from each parent—are identical to each other and is an indication that the population may have been small and there was a lot of inbreeding. We see similar patterns in the living species, so understanding if this might have contributed to the extinction of Bachman's warbler could help us to better understand the health and conservation of the living population."
The researchers also compared the genomes of the three species to look for regions of the genome that may have evolved differently in each lineage. These differences can be indicators that a particular region of the genome evolved via natural selection for a particular trait or because of another evolutionary process. Having a third species' genome to compare allowed the researchers to identify a region that contained a new candidate gene involved in warbler pigmentation.
"We began this study because we were interested in learning about the history and biology of Bachman's warbler," said Woods. "But our results also highlighted how we can use extinct species to learn about their living relatives. We lose a lot of biological and evolutionary context through the process of extinction and being able to compare Bachman's warbler to the two living species allowed us to identify a gene that we might not have otherwise found. Context is crucial to understanding biology. Natural history collections allow us to place new observations into contexts that may have disappeared from the natural world. This fuels discovery, and makes museums powerful, and underappreciated, tools."
More information: Andrew W. Wood et al, Genomes of the extinct Bachman's warbler show high divergence and no evidence of admixture with other extant Vermivora warblers, Current Biology (2023). DOI: 10.1016/j.cub.2023.05.058
Journal information: Current Biology
Provided by Pennsylvania State University | Biology |
Introduction
Seven years ago, researchers showed that they could strip cells down to their barest fundamentals, creating a life form with the smallest genome that still allowed it to grow and divide in the lab. But in shedding half its genetic load, that “minimal” cell also lost some of the hardiness and adaptability that natural life evolved over billions of years. That left biologists wondering whether the reduction might have been a one-way trip: In pruning the cells down to their bare essentials, had they left the cells incapable of evolving because they could not survive a change in even one more gene?
Now we have proof that even one of the weakest, simplest self-replicating organisms on the planet can adapt. During just 300 days of evolution in the lab, the generational equivalent of 40,000 human years, measly minimal cells regained all the fitness they had sacrificed, a team at Indiana University recently reported in the journal Nature. The researchers found that the cells responded to selection pressures about as well as the tiny bacteria from which they were derived. A second research group at the University of California, San Diego came to a similar conclusion independently in work that has been accepted for publication.
“It turns out life, even such simple wimpy life as a minimal cell, is much more robust than we thought,” said Kate Adamala, a biochemist and assistant professor at the University of Minnesota who was not involved in either study. “You can throw rocks at it, and it’s still going to survive.” Even in a genome where every single gene serves a purpose, and a change would seemingly be detrimental, evolution molds organisms adaptively.
“It’s a stunning achievement,” said Roseanna Zia, a physicist at the University of Missouri whose research aims to build a physics-based model of a minimal cell and who was not involved in the study. The new work showed that even without any genome resources to spare, she said, the minimal cells could increase their fitness with random changes in essential genes.
Introduction
The new evolution experiments are starting to provide insights into how the smallest, simplest organisms might evolve — and how principles of evolution unite all forms of life, even genetic novelties developed in labs. “Increasingly, we are seeing evidence that this [minimal cell] is an organism that is not something bizarro and unlike the rest of life on Earth,” said John Glass, an author on the Nature study and the leader of the synthetic biology group at the J. Craig Venter Institute (JCVI) in California that first engineered the minimal cell.
What If We ‘Let It Loose’?
Just as 19th- and 20th-century physicists used hydrogen, the simplest of all the atoms, to make seminal discoveries about matter, synthetic biologists have been developing minimal cells to study the basic principles of life. That goal was realized in 2016 when Glass and his colleagues produced a minimal cell, JCVI-syn3.0. They modeled it after Mycoplasma mycoides, a goat-dwelling parasitic bacterium that already gets by with a very small genome. In 2010, the team had engineered JCVI-syn1.0, a synthetic version of the natural bacterial cell. Using it as a guide, they drew up a list of genes known to be essential, assembled them in a yeast cell and then transferred that new genome into a closely related bacterial cell that was emptied of its original DNA.
Two years later at a conference in New England, Jay Lennon, an evolutionary biologist at Indiana University Bloomington, listened to a talk from Clyde Hutchison, a professor emeritus at JCVI who had led the team engineering the minimal cell. Afterward, Lennon asked him, “What happens when you let this organism loose?” That is, what would happen to the minimal cells if they were subjected to natural selection pressures like bacteria in the wild?
For Lennon as an evolutionary biologist, the question was an obvious one. But after he and Hutchison both pondered it for a few minutes, it became apparent that the answer wasn’t.
The minimal cell “is a type of life — it’s an artificial type of life, but it’s still life,” Lennon said, because it fulfills the most basic definition of life as something able to reproduce and grow. It should therefore respond to evolutionary pressures just as gorillas, frogs, fungi and all other organisms do. But the overarching hypothesis was that the streamlined genome might “cripple the ability of this organism to adaptively evolve,” Lennon said.
No one had a clue what would really happen, however, because researchers have generally taken great care to keep minimal cells from evolving. When samples of the cells are distributed by JCVI to any of the roughly 70 labs that now work with them, they’re delivered pristine and frozen at minus 80 degrees Celsius. When you take them out, it’s like their first day on Earth, Lennon said: “These are brand new cells that had never seen a day of evolution.”
Shortly after their encounter, Hutchison put Lennon in touch with Glass, who shared samples of his team’s minimal cells with Lennon’s lab in Indiana. Then Lennon and Roy Moger-Reischer, his graduate student at the time, got to work.
Testing the Streamlined Cells
They began with an experiment aimed at measuring mutation rates in the minimal cells. They repeatedly transferred a sliver of the growing minimal cell population into petri dishes, which freed the cells to grow without constraining influences like competition. They found that the minimal cell mutated at a rate comparable to that of the engineered M. mycoides — which is the highest of any recorded bacterial mutation rate.
The mutations in the two organisms were fairly similar, but the researchers noticed that a natural mutational bias was exaggerated in the minimal cell. In the M. mycoides cells, a mutation was 30 times more likely to switch an A or a T in the genetic code for a G or a C than the other way around. In the minimal cell, it was 100 times more likely. The probable explanation is that some genes removed during the minimization process normally prevent that mutation.
In a second series of experiments, rather than bringing over a small group of cells, the researchers transferred dense populations of cells for 300 days and 2,000 generations. That allowed more competition and natural selection to occur, favoring beneficial mutations and the emergence of genetic variants that eventually ended up in all the cells.
Introduction
To measure the fitness of the cells, they calculated their maximum growth rate every 65 to 130 generations. The faster the cells grew, the more daughter cells they produced for the next generation. To compare the fitness of evolved and unevolved minimal cells, the researchers made them compete against the ancestral bacteria. They measured how abundant the cells were at the start of the experiment and after 24 hours.
They calculated that the original minimal cell had lost 53% of its relative fitness along with its nonessential genes. The minimization had “made the cell sick,” Lennon said. Yet by the end of the experiments, the minimal cells had evolved all that fitness back. They could go toe-to-toe against the ancestral bacteria.
“That blew my mind,” said Anthony Vecchiarelli, a microbiologist at the University of Michigan who was not involved in the study. “You would think that if you have only essential genes, now you’ve really limited the amount of evolution that … can go in the positive direction.”
Yet the power of natural selection was clear: It rapidly optimized fitness in even the simplest autonomous organism, which had little to no flexibility for mutation. When Lennon and Moger-Reischer adjusted for the relative fitness of the organisms, they found that the minimal cells evolved 39% faster than the synthetic M. mycoides bacteria from which they were derived.
The Fear-Greed Trade-Off
The study was an “incredibly thought-provoking” first step, Vecchiarelli said. It’s uncertain what would happen if the cells were to keep evolving: Would they gain back some of the genes or complexity that they lost in the minimization process? After all, the minimal cell itself is still a bit of a mystery. About 80 of the genes essential to its survival have no known function.
The findings also raise questions about which genes need to stay in the minimal cell for natural selection and evolution to proceed.
Since 2016, the JCVI team has added back some nonessential genes to help the minimal cell lines grow and divide more like natural cells. Before they did that, JCVI-syn3.0 was growing and dividing into weird shapes, a phenomenon that Glass and his team are investigating to see if their minimal cells divide the way primordial cells did.
The researchers found that most of the beneficial mutations favored by natural selection in their experiments were in essential genes. But one critical mutation was in a nonessential gene called ftsZ, which codes for a protein that regulates cell division. When it mutated in M. mycoides, the bacterium grew 80% larger. Curiously, the same mutation in the minimal cell didn’t increase its size. That shows how mutations can have different functions depending on the cellular context, Lennon said.
Introduction
In a complementary study, which has been accepted by iScience but not yet published, a group led by Bernhard Palsson at the University of California, San Diego reported similar results from experiments on a variant of the same minimal cell. They didn’t find an ftsZ mutation in their evolved minimal cells, but they did find similar mutations in other genes that govern cell division, emphasizing the point that there are multiple ways to achieve a biological outcome, Palsson said.
They didn’t look at cell size, but they checked which genes were expressed before, during and after the episode of evolution. They observed a “fear-greed trade-off,” a tendency also seen in natural bacteria to evolve mutations in genes that will help it grow rather than mutations that would produce more DNA repair proteins to correct the errors.
Here you can see that “mutations tend to reflect the cellular processes that are needed to improve a function,” Palsson said.
Demonstrating that the minimal cell can evolve like cells with a more natural genome was important because it validated “how well it represents life in general,” Zia said. For many researchers, the entire point of a minimal cell is to serve as a critically useful guide to understanding more complex natural cells and the rules they follow.
Other studies are also beginning to probe how minimal cells respond to natural pressures. A group reported in iScience in 2021 that minimal cells can quickly evolve resistance to different antibiotics, just like bacteria.
Knowing which genes are more likely to mutate and lead to useful adaptations could someday help researchers design drugs that get better at what they do in the body over time. To build robust synthetic life forms that have very different abilities, evolutionary biologists and synthetic biologists must work together, “because no matter how much you engineer it, it’s still biology, and biology evolves,” Adamala said. | Biology |
Tiny waterfleas could play a pivotal role in removing persistent chemical pollutants from wastewater – making it safe to use in factories, farms and homes, a new study reveals.
Scientists and engineers have discovered a method to harness Daphnia to provide a scalable low-cost, low-carbon way of removing pharmaceuticals, pesticides, and industrial chemicals from wastewater. This approach avoids the toxic byproducts typically associated with current technologies.
The researchers have developed technology that allows them to retrofit populations of waterfleas into wastewater treatment plants. What makes their technology unique is the selection of strains based on their chemical tolerance which the researchers ‘resurrect’ from past environments.
The water flea's remarkable ability to remain dormant for centuries allows scientists to revive dormant populations that endured varying historical pollution pressures. Leveraging this trait, researchers sourced strains with diverse tolerances to chemical pollutants, incorporating them into the technology.Professor Luisa Orsini - University of Birmingham
Their findings are published in Science of the Total Environment and showcase an international team of researchers led by the University of Birmingham. They demonstrate the removal efficiency of four carefully selected strains of water flea on diclofenac (pharmaceutical), atrazine (pesticide), arsenic (heavy metal), and PFOS (industrial chemical).
Senior author Professor Luisa Orsini, from the University of Birmingham, commented: “Our profound understanding of water flea biology enabled us to pioneer a nature-inspired tertiary wastewater treatment technology. This refines municipal wastewater effluent and safeguards the ecological health of our rivers.
“The water flea's remarkable ability to remain dormant for centuries allows scientists to revive dormant populations that endured varying historical pollution pressures. Leveraging this trait, researchers sourced strains with diverse tolerances to chemical pollutants, incorporating them into the technology.”
Rapid urbanisation, population growth, unsustainable food production and climate change have put unprecedented pressure on water resources, culminating in a global water crisis. The sustainable management and reuse of water resources is paramount for ensuring societal, economic, and environmental well-being.
Persistent chemical pollutants, originating from domestic and industrial processes, escape conventional wastewater treatment and prevent its safe reuse. When wastewater effluent is released into rivers, it eventually finds its way into reservoirs, irrigation systems, and aquifer recharges. These chemical pollutants then enter the human food chain and water supply, detrimentally impacting the health of approximately 92 million individuals annually.
Co-author Dr Mohamed Abdallah, from the University of Birmingham, commented: “Our technology could improve the quality of wastewater effluent - meeting current and upcoming regulatory requirements to produce reusable water suitable for irrigation, industrial applications, and household use. By preventing persistent chemicals from entering waterways, we can also prevent environmental pollution.”
Co-author Professor Karl Dearn, also from the School of Engineering, University of Birmingham, commented: “We introduced these remarkable water fleas into custom containment devices to refine effluent before its final release. Once in place, our technology largely maintains itself, attributed to the water fleas' clonal reproduction capability.”
Lead author and University of Birmingham PhD student Muhammad Abdullahi added: “This novel nature-inspired technology provides a potentially revolutionary process for sustainably removing persistent chemical pollutants from wastewater. By preventing these chemicals from being discharged, we can protect our environment and biodiversity.” | Biology |
Mixing theory and observation to envision a warmer world
Climate changes are conjuring a whirlwind ride that seems to present some creatures opportunities to thrive. Scientists scripting supercharged scenarios caution the difference between seasonal coping and long-term adaption is vast—and tricky to predict.
Michigan State University biologists have studied damselflies—which resemble dragonflies and are abundant as both predator and prey in wetlands—to understand what happens throughout their lifecycle from nymph to winged insect, along with what they eat when summers grow warmer and longer.
Their work in this week's Proceedings of the Royal Society B has a twist—combining seasons of observational and experimental work in the field and lab with input from a theoretical ecologist, a mathematician by training with supersized modeling creds.
The results: A more realistic look at what a hot summer can bring to a nearby pond, and new respect for the blinding speed global warming is bringing.
"We are seeing the pace of climate change is much more rapid than organisms have endured in their evolutionary experience," said co-author Phoebe Zarnetske, an associate professor of integrative biology
PI of the Spatial and Community Ecology (SpaCE) Lab and director, IBEEM. "That rapid pace is going to be even more of an issue with the increase in extreme events like heat waves."
The work in "Life-history responses to temperature and seasonality mediate ectotherm consumer–resource dynamics under climate warming" finds that inserting the right level of data gleaned from field experiences, specifically the effects of seasonal changes in temperature on consumer lifecycles, creates a more robust predator-prey simulation model.
The work differs from the findings of similar models with less biological realism that predicted warming trends would doom predators. They see Michigan damselflies surviving climate warming by shifting into a lifecycle similar to their southern relatives—squeaking out two lifecycles in a season rather than one.
The work developed from first author Laura Twardochleb's work as a Ph.D. student in Zarnetske's lab. She had spent time observing damselflies' one-year lifecycle in Michigan. They emerge as adults from ponds in the spring. They mate, reproduce and the juveniles grow over a year in the pond by eating zooplankton. They make good study subjects, she said, because they thrive both outside and in the laboratory.
Twardochleb, now with the California State Water Resources Control Board, was part of MSU's Ecology, Evolution, and Behavior Program and as a part of that took a class by Chris Klausmeier, MSU Foundation Professor of Plant Biology and Integrative Biology.
She saw that early models projecting how warming climates would affect ectothermic predators were significantly simpler than the nature she was observing. For one thing, the models didn't allow for the north's change of seasons. The models also weren't keeping track of a predator's size and growth rate and changes in their lifecycle with warming.
Meanwhile, Klausmeier, a theoretical ecologist, was recognizing the special sauce an experimentalist brings when creating mathematical models that take assumptions about how organisms behave, grow, birth, die.
"I can make up any model I want unconstrained by reality," Klausmeier said. "But that's a little dangerous because of course you want something related to the real world. When you join with an experimentalist you can bring not just the experimental results and parameters, but also bring the deep natural history and knowledge to the system to know the key variables and constraints."
The work, factoring in a warmer, but still seasonal climate shows how the damselflies can grow and breed more quickly. Creating a model that only allowed the virtual damselflies to live a one-year lifecycle in a warmer world, they burned out and died. Extinction was on the horizon.
But allow the bugs the option of bringing two generations into a season, and thriving was a possibility. "A lot of models said [predators] were going to starve," Twardochleb said. "That's what's exciting—that we can make models more realistic."
Twardochleb said the work is good groundwork to understand how other species will respond to a warmer world, particularly species like mosquitoes which are both nuisances and potentially carry diseases.
Zarnetske added that the continual challenge will be beyond the idea that different species will be adapting to a new world. Climate change is outpacing that kind of evolution in an unprecedented way. And the weather extremes—heat waves, droughts, floods—are a whole variable.
"That's our next step," Zarnetske said. "Unpredictability is hard."
More information: Life-history responses to temperature and seasonality mediate ectotherm consumer-resource dynamics under climate warming, Proceedings of the Royal Society B: Biological Sciences (2023). DOI: 10.1098/rspb.2022.2377. royalsocietypublishing.org/doi … .1098/rspb.2022.2377
Journal information: Proceedings of the Royal Society B
Provided by Michigan State University | Biology |
Many new diseases that affect us humans find their origin in viruses derived from the world of animals. This is probably also the case for the infamous SARS-CoV-2 virus, colloquially known as the coronavirus. Unfortunately, identifying which animal viruses are at high risk of jumping over to humans has proven very challenging and time-consuming. Scientists have determined that machine learning can be the key here. AI may help us stop the next pandemic before it even happens. Identifying possible zoonotic virusesAn infectious disease triggered by a virus or parasite that has jumped from an animal to a human is called a zoonotic disease or zoonosis. Recognizing zoonotic viruses before they arise forms a big issue because just a small percentage of the approximate 1.67 million animal viruses are actually capable of infecting humans.When researchers discover a new virus among animals, it is very difficult to quickly assess whether it has the potential to make the transition from animals to humans and therefore also to determine whether this virus merits the investment of further research. But a new study, published in the science journal PLOS Biology, may make the lives of researchers chasing zoonoses a little easier. In the study, scientists present a method based on the genome of a virus (often the only thing we know about newly discovered or poorly characterized viruses) to determine whether it is able to jump from animals to humans. Using machine learning to identify dangerous virusesThe science team initially gathered a dataset of 861 virus species from 36 different families in order to construct machine learning models utilizing viral genome sequences. They created machine learning algorithms that used patterns in viral genomes to calculate the likelihood of human infection. The best-performing algorithm was then used to look for trends in the projected zoonotic potential of other viral genomes from a variety of species.The team discovered that viral genomes may have generalizable features that are independent of virus taxonomic connections and may adapt the viruses for life in conditions it has yet to encounter (IE to infect humans).Eventually, they succeed in creating machine learning models suitable to distinguish potential zoonotic diseases using viral genomes. However, these models have shortcomings, as computer models are only a preparatory step of distinguishing zoonotic viruses. Viruses flagged by the models will need further lab testing before confirmation. Mainly because deciding to do additional research on a virus is an impactful decision tied to large investments. One cannot simply make a decision without careful deliberation.On top of that, although these models can help forecast whether a particular virus may be capable of infecting people, the capacity to infect is just a single part of broader 'zoonotic risk.' Other relevant factors are the virus's ability to transmit between humans, its virulence in humans, and the ecological circumstances at the time of human exposure. | Biology |
Researchers have spotted how specific proteins within the chromosomes of roundworms enable their offspring to produce specialized cells generations later, a startling finding that upends classical thinking that hereditary information for cell differentiation is mostly ingrained within DNA and other genetic factors.
The Johns Hopkins University team reports for the first time the mechanisms by which a protein known as histone H3 controls when and how worm embryos produce both highly specific cells and pluripotent cells, cells that can turn certain genes on and off to produce varying kinds of body tissue. The details are published today in Science Advances.
The new research could shed light on how mutations associated with these proteins influence various diseases. In children and young adults, for example, histone H3 is closely associated with various cancers.
"These mutations are highly prevalent in different cancers, so understanding their normal role in regulating cell fate and potentially differentiation of tissues may help us understand why some of them are more prevalent in certain diseases," said lead author Ryan J. Gleason, a postdoctoral fellow in biology at Johns Hopkins. "The histones that we're looking at are some of the most mutated proteins in cancer and other diseases."
Histones are the building blocks of chromatin, the structural support of chromosomes within a cell's nucleus. While histone H3 is particularly abundant in multicellular organisms such as plants and animals, unicellular organisms teem with a nearly identical variant of H3. That's why scientists think the difference in rations of H3 and its variant hold crucial clues in the mystery of why pluripotent cells are so versatile during early development.
The researchers revealed that as C. elegans roundworm embryos grew, increasing H3 levels in their systems restricted the potential or "plasticity" of their pluripotent cells. When the team changed the worm's genome to lower the amount of H3, they successfully prolonged the window of time for pluripotency that is normally lost in older embryos.
"As cells differentiate, you start to get a hundredfold histone H3 being expressed at that time period, which coincides with that lineage-specific regulation," Gleason said. "When you lower the amount of H3 during embryogenesis, we were able to change the normal path of development to adopt alternative paths of cell fate."
In pluripotent cells, histones help switch certain genes on and off to commit to specific cell types, be they neurons, muscles, or other tissue. Highly regulated by histones, genes act as a voice that tell cells how to develop. How quiet or loud a gene is determines a cell's fate.
The new findings come from the gene-editing technique CRISPR, which helped the team track the role the two histones played as the worm's offspring developed. CRISPR has made it much easier for scientists in the last decade to study the nuts and bolts of changing genetic material and spot what that does to animal, plant, and microbe traits, Gleason said.
Even though the C. elegans roundworm gives finer insights into how these pluripotent cells evolve, further research is needed to zero in on how histones might also underpin embryogenesis in humans and animals composed of hundreds of types of cells, said Xin Chen, a Johns Hopkins biology professor and co-investigator.
"Even though we are using this small worm to make these discoveries, really this finding should not be specific to one animal," Chen said. "It's hard to imagine the findings are only going to be applicable to one histone or one animal but, of course, more research needs to be done."
The team includes Yanrui Guo of Johns Hopkins, Christopher S. Semancik of Tufts University, Cindy Ow of University of California, San Francisco, and Gitanjali Lakshminarayanan of Dana-Farber Cancer Institute.
The research is supported by grants NIGMS/NIH F32GM119347, NICHD/NIH K99HD09605, NIGMS/NIH R35GM127075, and a Faculty Scholarship and Investigator program from Howard Hughes Medical Institute.
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IntroductionFor centuries, the construction of combs by social insects has been endorsed as an archetype of swarm intelligence and self-organization. Hypotheses regarding the behaviors that enable comb-building range from a top-down blueprint inherited by individuals1 to a bottom-up emergent organization arising from the actions of agents in a collective2 Despite their structural complexity, models exploring these behaviors, which lead to the construction of organized comb cells3, construction of parallel combs4 or controlled distribution of brood or honey5 in beehives, have traditionally relied on detailed physical measurements and the direct observation of combs with the naked-eye6,7, which represents an incredibly labor-intensive and time-consuming process. To address these research bottlenecks, in this study, we introduce a computational toolset for investigating the morphology of comb built by the domestic honey bee, Apis mellifera. These methods provide novel means to characterize the process of comb building, thus furthering our understanding of the behaviors and health of a colony. To observe these social changes, we relate comb architecture to building behaviors to understand the mediations between bees and their environment.Typically, A. mellifera comb is constructed from a series of hexagonal cells with edge lengths ranging from ca. 2.25 to 2.75 mm8, edge thicknesses of ca. 0.75 mm9, and average depths ranging from ca. 10–11 mm10. This cell size is governed by the body size of worker bees, which have an average radius of ca. 4 mm11. Comb cells are built at an average angle of 13 degrees from an interface where the basal sides of two cells meet, and while it has been proposed that this angle helps better retain honey within the cell interiors, recent evidence suggest that it may also provide additional structural reinforcement for the growing comb12. Honey bees build parallel sheets of cells in this fashion, with an average center-to-center spacing of ca. 7 to 10 mm13. Comb cells may be filled with either honey to form honeycomb or larvae to form brood comb, and the quantity of comb within a hive is thus directly proportional to the hive’s need to produce young and store food. To illustrate these specific features, Fig. 1 provides a series of progressively magnified views of a feral hive. Consisting of a series of approximately parallel lobes (Fig. 1a), the combs are constructed upon an underlying substrate. Within a planar array (Fig. 1b) of predominantly uniform hexagonal unit cells (Fig. 1c), we can define the following geometric features (Fig. 1c): (1) the cell width, (2) the unit-cell vertices (the corners of a cell where three edges meet), and (3) the cell orientation (the vector that can be drawn continuously from the highest to the lowest vertex of a cell); and from a sectioned view of the comb (Fig. 1d), (4) the cell depth, and (5) the inclination angle of each cell.Fig. 1: General characteristics of A. mellifera comb.a A photograph of comb being constructed by a feral bee colony in Southern California demonstrates the typical parallel lobes of comb observed in A. mellifera hives (image courtesy of Super Bee Rescue, Santa Barbara, California). b A digital reconstruction of a section of feral comb, and (c), an isolated section of comb cells from the digital reconstruction in (b), outlining the characteristics of cells including vertex locations, the measurement of cell width, and cell orientation (which has been reported to be perpendicular to substrate orientation). d A 90-degree rotation of (c) outlines the interface where the basal side of cells meet, the angle of cell tilt is measured in reference to the normal of the comb’s dominant plane, and cell depth is measured along this vector.Full size imageThese parallel sheets and packed hexagonal cells are reported to approach their theoretical maximum packing density, while still allowing for efficient bee navigation within the hive, a phenomenon described by Darchen’s rule of parallelism14. However, deviation from this pattern can be observed under specific circumstances. For example, feral honey bee comb frequently contains roughly parallel (yet non-vertical) regions that follow the contours of the structures on which they are built. This effect has also been observed under experimental conditions, where parallel comb construction could be interrupted by obstructing the targeted build direction of the hive with a smooth sheet of glass, and the subsequent redirection of comb building to form a curved sheet8. Since these cell-level deviations inherently lead to the creation of structures that are sub-optimal for the storage of larvae and honey, they present an opportunity to better understand the ways in which hives may adapt comb architecture in response to environmental stimuli. To help address these questions, here we introduce a reproducible experimental research platform for the controlled generation of geometrically complex (non-parallel) comb architectures through the manual rotation of hives during the comb-building process.While historically, measuring the geometric characteristics of honey bee comb was performed by hand, more recent efforts have employed machine-learning methods to automate the identification of cell types in photographs of combs15, or micro-computed tomography (µCT) data to characterize three-dimensional (3D) material distributions within individual cells16. While these small-scale measurements have provided some intriguing insights into cell structural diversity and their stages of formation, the use of high-resolution volumetric data sets to study the geometric features of A. mellifera combs at the whole-hive scale has remained largely unexplored. We propose that such large-scale 3D data sets could thus provide a valuable resource for investigating multi-scale aspects of comb architecture, and when combined with computational geometry methods, enable the automated high-throughput characterization and quantification of features, which have previously been studied only through manual approaches, to provide insights into the comb construction process.In the following sections, we present a three-part framework for developing toolsets and achieving rapid digital characterization of comb architecture. First, we use micro-computed X-ray tomography (micro-CT) for the generation of fully interactive 3D comb models, providing a baseline for the investigation of comb properties, including geometry and material density, as well as their spatial variations within the hive. Second, we introduce toolsets and methods adapted from computational geometry for the shape interrogation of natural combs. Lastly, we use these tools in combination to elucidate rules that govern comb-building behaviors and, ultimately, the hive’s final structure. Through these methods, we enable the validation of previously proposed models and observe new behavioral changes manifested in the relations between geometric expressions and comb construction.ResultsIn order to examine the efficacy of the developed computational analysis tools, it was desirable to obtain a honey bee comb with complex architectures. In the present study, data were obtained from A. mellifera hives that were cultivated in Cambridge, Massachusetts between February and October 2020. Once the colonies established a stable population, experimental environments, each consisting of an acrylic cube measuring either 15 cm × 15 cm × 15 cm or 27 cm × 27 cm × 27 cm, were incorporated into their existing commercially available Langstroth hives (Fig. 2a). By rotating these environments in sequences described in the Methods section, perturbations in comb-building behavior were induced that resulted in the creation of hives with highly curved combs protruding in many different directions (Fig. 2b–f).Fig. 2: Hive experimental setup and data digitization workflow.a In our experimental approach, combs were constructed by A. mellifera colonies inside experimental acrylic cubes that were integrated into standard Langstroth hives. Periodic rotations applied to the acrylic cubes during hive construction induced changes in the hive’s build direction, resulting in combs with atypical protrusions and highly curved geometries. b After the comb construction process was complete, the acrylic cubes were removed from the hives and scanned using a commercial micro-CT imaging system. c For each cube, 2000 16-bit z slices at a resolution of 2000 × 2000 pixels were generated. d The slices were reassembled into a volumetric data set and stored as OpenVDB files for further analysis. e Photographs (upper) and digital reconstructions (lower) produced by the described workflow are shown for Hive 1. f Photographs showing two additional replicate experimental cubes (Hive 2 and Hive 3) produced and digitized with this workflow.Full size imageData representations for geometric analysisWhile the volumetric data obtained from micro-CT scans of our experimental hives were originally stored as OpenVDB files, we utilized three different representations to perform our geometric analysis to make use of their respective advantages. To begin, we assumed that the comb was a solid \(S\). The first representation was a volumetric representation of the data set composed of a set of voxels \(V={\left\{{v}_{i}\right\}}_{0\le i < {2000}^{3}}\) with positions \(p({v}_{i})\in {R}^{3}\) within a regular grid. Voxel values \(0\le i({v}_{i})\le 1\) represented the normalized density values of the respective materials at their spatial voxel positions. However, for methods that do not examine differences in material density, it can be advantageous to treat the volume as though its density were constant, which was used for calculating a signed distance field (SDF)17, as described below. Here, the comb shape was represented by a signed distance function \({d}_{S}\left({v}_{i}\right)={{{\rm{sign}}}}({v}_{i}){{\inf }}_{x\in \partial S}\Vert x-p({v}_{i})\Vert\), where \({{{\rm{sign}}}}\left({v}_{i}\right)=\left\{-1{if}{v}_{i}\in S,1{if}{v}_{i}\in S\right\}\) was evaluated at each voxel (a value of −1 denotes a point inside the volume, while a value of 1 denotes one that is outside). The third representation is the discretization of \(\partial S\) as a triangle mesh representing the boundary of our comb solid \(S\). In this case, a triangle mesh represents a collection of vertices \(W=\{{w}_{j}\}\), edges \(E=\{{e}_{k}\},{e}_{k}\in W\times W\), and triangles \(T=\{{t}_{q}\},{t}_{q}\in E\times E\times E\) with associated attributes, such as position. In the following section, we introduce a set of computational geometry tools that were used to analyze our different honeycomb architectures (Fig. 3).Fig. 3: Primary computational geometry tools used to analyze comb architectures.a To compute a Gaussian curvature estimation across a digital comb topography, at every point of the comb structure, a radius (r = 15 mm) corresponding to the size of an A. mellifera worker was used to sample neighboring positions to which a quadratic surface was fitted. The quadratic form was then used to compute the curvature analytically. b To plot a geodesic distance from a source point, the geodesic distance was computed on the surface of the shown comb structure, and 1-cm periods were plotted to show equidistant propagation from the selected point. c Different harmonic bases of the Laplace operator are shown with color values denoting the per-vertex amplitudes. Together with the eigenvalues of the Laplace operator, these are commonly employed as shape descriptors. d Morphological operations of dilation and closing were used in combination with combinatorial operators, such as subtraction and intersection, to extract cells and tunnels from comb architectures. e Normalized attenuation contrast values from X-ray data were used to discriminate different materials within the combs; i.e., bee-deposited wax, manually applied wax foundation, and 3D-printed polymer or acrylic support structures. f Thus, substructures of different density ranges could be selectively filtered for and visualized in the digital environment. A. mellifera constructed combs are displayed yellow, 3D-printed parts are shown in magenta (density = 1.19 g/cm³), and steel rods are displayed in cyan.Full size imageDevelopment of a Gaussian curvature toolSince the comb’s curvature may indicate a deviation from typical parallel construction behavior, the calculation of curvature was a primary goal of these analyses. For example, Gaussian curvature indicates when a structure is doubly curved, or curved in multiple directions at a specific location, while mean curvature is a signed (positive or negative) value that indicates curvature in two principal directions perpendicular to the surface normal. The Gaussian curvature \(K={\kappa }_{1}{\kappa }_{2}\) is the square of the geometric mean of the principal curvatures \({\kappa }_{1}\) and \({\kappa }_{2}\), and mean curvature \(H=\frac{{\kappa }_{1}+{\kappa }_{2}}{2}\) is the arithmetic mean of \({\kappa }_{1}\) and \({\kappa }_{2}\). These principal curvatures describe the maximum \({\kappa }_{1}\) and minimum \({\kappa }_{2}\) curvature at every point on \(\partial S\). In our analysis, curvature was used to assess the local deviation from typically parallel and planar comb building. Intuitively, a local positive Gaussian curvature corresponds to a local paraboloid surface, whereas a negative Gaussian curvature corresponds to a local hyperboloid surface. We estimated curvatures through the local quadratic surface fitting, and at every point of \(\partial S\), we sampled the local neighborhood in a 15-mm radius, relating the sampling region to the average size of an A. mellifera individual. Since the hive interior is dark, worker bees constructing comb are only able to assess hive geometry based on tactile signals from their immediate surroundings, and so sampling at a region of this size provides an assessment of curvature at the level that can be sensed by individual bees during comb construction. From this local sampling of the comb structure, we constructed a quadratic form \(f\left(x,y\right)=a{x}^{2}+b{y}^{2}+{cxy}+{dx}+{ey}\), with which both the Gaussian and mean curvatures can be estimated analytically by computing the eigenvalues of the shape operator18. The estimated values were then locally averaged, an example of which is shown in Fig. 3a.Development of a geodesic distance measuring toolTo understand comb architecture from the perspective of a honey bee, it is important to consider that bee movement within a hive’s interior is limited to travel across the comb surface and the walls of the container, since the confined space and lack of light limits bees from flying within the hive. To provide a sense of distance as it would be experienced by a bee traversing the comb surface, geodesic distance is a useful parameter to consider since it describes the shortest distance from a point in the domain, on \(\partial S\) or within \(S\), to any other point in the domain, on \(\partial S\) or within \(S\), respectively, and can be defined through the solution of the eikonal equation \(\left|\nabla u(x)\right|=\frac{1}{s(x)}\) [Eq. 1]. Several algorithms have been developed to compute these distances, including the heat and fast marching methods19. Distance computations can be weighted by a metric \(s(x)\), which is a field over the surface or solid that can be used to model the difficulty of traveling through a specific region. In the present study, the volume’s density value was used as the weight metric \(s(x)\) so as to obtain the distance along the object’s surface. Given the geodesic distance field from a source to every point in the domain, the gradient of this field can be used to construct the shortest paths within the domain (Fig. 3b).Development of Laplacian and frequency analysis toolsTo understand comb architecture at a scale larger than an individual bee, frequency analysis can be used as a tool to isolate and segment individual lobes or sections of comb. Such segmentation can be accomplished through the analysis of the Laplace operator eigenvalues. The Laplace operator \(\triangle \) is a linear operator that can be applied to the Cartesian xyz position of a point in a mesh representation of the object in order to evaluate the attribute’s local deviation from its mean value, and is commonly employed for investigating diffusion flow, geodesic computations, and interpolation20. Since the Laplace operator is linear and positive semidefinite, its eigenvectors comprise an orthogonal basis, which is the manifold harmonic basis for the attributes on our domain. The projection of an attribute to this basis results in a spectral representation that is often used in its frequency manipulation. Basic functions of this basis are shown in Fig. 3c, with color values denoting the per-vertex amplitudes.Development of morphological and Boolean operation toolsTo accomplish tasks such as quantifying the number of cells or analyzing their tilt, it can be useful to combine operations that isolate the negative space within the analyzed volume. Morphological operators comprise those that modify the volume’s density values by expansion or erosion, while Boolean operators consist of those that combine two inputs. Given a ball \(B=\left\{{b|d}(b,({{\mathrm{0,0}}}))\,\le r\right\}\) of radius \(r\) with a distance function \(d\), the morphological operators of dilation can be defined as \(V\oplus B=\{{v|}{{{\rm{sign}}}}\,\left(v\right)* d(v)\le r\}\) [Eq. 2] and erosion as \(V\ominus B=\{{v|}{{{\rm{sign}}}}\,\left(v\right)* d(v)\le -r\}\) [Eq. 3]. The composition of these operators yields morphological closing \((V\oplus B)\ominus B\) and opening \((V\ominus B)\oplus B\) operations, which can in turn be combined to yield algorithms for closing volumetric objects21. We used morphological operators on the SDF representation to extract geometrical features, such as the cells and tunnels of the hives22. By pairing morphological operators with Boolean operators, such as subtraction or intersection of volumes, we were able to extract these features from our combs, as shown in Fig. 3d.Development of a density discrimination toolWe also explored the use of variability in attenuation contrast values from micro-CT scans to characterize material distributions within the comb (Fig. 3e). Due to the elemental similarity of organic materials that are incorporated into the growing hive, variability in attenuation contrast is assumed to correlate to physical density (which can vary as a function of water or lipid content or intrinsic porosity). For example, new beeswax has a translucent-white color and a typical density23 of 0.958–0.970 g/cm3. Honey bees also produce propolis, at a measured density of 1.16 g/cm3, through the combination of saliva, wax, and plant-produced resins24. In addition to the potential identification of site-specific material deposition during hive construction, the attenuation contrast values from the micro-CT scans can also be used to separate comb from manually applied foundational wax and support structures of various materials, as shown in Fig. 3f. Since our micro-CT scans were taken from experiments in which A. mellifera constructed combs (yellow) on 3D-printed parts (magenta, density = 1.19 g/cm³) held by steel rods (cyan), material discrimination allowed analysis of constructed combs independent of other structures in the experimental setup.Application of the developed toolsWe used the computational geometry tools described in the previous sections to analyze comb architectures, validate common assumptions about comb construction, and make connections between bee behavior and comb geometry. The approaches presented for characterizing comb volumetric data sets include (1) curvature-based analysis to analyze the distortion and deformation of cell geometries, (2) geodesic distance analysis to examine build direction, and (3) algorithms for isolating and viewing the comb interface and cell tilt (see Fig. 1d).Wild combs are typically constructed as double-sided sheets of tessellated hexagonal cells. Comb construction is often guided by the rule of parallelism, first hypothesized by Darchen14, who observed that while bees may start to build clusters at different attachment sites, they modify their construction to keep a reasonably equal and parallel space between adjacent combs. Further, it has been previously proposed that cavity-nesting honey bees, such as A. mellifera, tend to establish a build direction in line with the force of gravity10. The combination of the unit-cell geometry and their parallel sheet construction has been previously proposed to represent optimal building material use to maximize honey and brood storage space25. In our current study, rotating the hives during the building process and providing variations in substrate geometry produced perturbations to the bees’ building environment that resulted in parallelism being disrupted and bees adjusting combs through torsion and irregular cell-building behavior. These perturbations induced curvature into the comb similar to that reported by Huber in studies where glass sheets were used to obstruct the intended direction of comb building8.Regarding cell shape, Fig. 4a–c demonstrates the use of computational geometry tools to identify an association between irregular cells and negative comb curvature. Here, we used the curvature estimation method, as introduced in the Methods section, approximating a quadratic surface the size of a bee at every point over the surface, to evaluate principal curvatures. Regions of irregular comb building (Fig. 4a), potentially resulting from the geometric accumulation of locally deformed cells, can be correlated to negative principal curvatures of \({\kappa }_{1}\) and \({\kappa }_{2}\), while regular comb building is related to zero or positive curvatures. Figure 4b shows high principal curvature values in violet and low values in yellow. Curvature fields were computed for two comb structures (Hives 2 and 3). In Fig. 4c, we show curvature histograms of the comb architectures and randomly sampled regions of cells for each range of curvature, exhibiting a relation between a high negative curvature and more irregular comb building.Fig. 4: Digitally driven observations of cell regularity and build direction.a Visually identified examples of regular (upper) and irregular (lower) cells within a comb digital reconstruction. b The relationship between comb curvature and irregular cell construction is analyzed for the comb architectures of two experimental cubes (Hives 2 and 3). Using the established Gaussian curvature tool, the combs are color-coded according to their principal curvature \({\kappa }_{1}\), distinguishing high curvatures (violet) and low curvatures (yellow). Curvature histograms of \({\kappa }_{1}\) are shown for each of the hives, displaying the distribution of curvature across the combs, and their corresponding color-coded images illustrate the extent of local cell distortion. c Comb build direction is compared to the gradient of the distance field from the initial underlying substrate. For the Hive 2 comb, the geodesic distance field is color-coded (red to blue) by increasing distance from the initial underlying substrate (top-right), and its gradient is shown as a vector field (bottom-right). Three sample regions of interest were selected for further analysis. d For each sample region, visualized (left), the gradients of the geodesic field over the region are displayed (middle), and the average of these gradients is calculated (right). The resulting vector corresponds to the bees’ build direction, as identified by Pratt’s method using one vertex of each cell oriented such that it points toward the substrate.Full size imageIn regard to cell orientation, it has been shown previously that cell orientation typically depends on substrate orientation6, and cells are built from a substrate with one vertex of each cell oriented such that it points toward the substrate. We validated and generalized this relationship by examining whether cell orientation is aligned with the gradient of the weighted geodesic distance from the substrate. In the process shown in Fig. 4d, we computed the density-weighted geodesic distances in our micro-CT scan data from the acrylic cross substrate using the geodesic distance measuring tool. Subsequently, we evaluated the gradient of this field using finite differencing. To determine local cell orientation, we compared the average of the gradient field for a region to the regional comb geometry from the micro-CT scan data, as shown in Fig. 4e. From these analyses, we observed that the average of the gradient of the weighted geodesic distance from the substrate aligns with Pratt’s analysis of the bees’ build direction, as determined by the cells’ vertex orientation.The comb interface (Fig. 1d) can be described as the zone where the basal region of comb cells come together, or where the base of each mirrored cell sheet contacts one another in a free-hanging lobe (Fig. 1a). In the parallel comb, this interface serves as the median plane along which rows of cells are tessellated. However, in a highly curved comb, observing this interface in isolation is nontrivial. In Fig. 5a, b, the segmentation of combs was demonstrated using the previously introduced Laplace operator described in Fig. 2c. Segmentation was based on approximately planar regions of comb using the smallest nonzero eigenvector of the Laplace operator, the Fiedler vector26. Typically, such segmentation is applied to structures with more clearly segmented architecture. For example, Fiedler vector segmentation of the human body isolates the appendages, torso, and head. We found that in the case of such atypical comb architectures, Fiedler segmentation was capable of isolating lobes of comb which are approximately planar.Fig. 5: Development of global descriptors of comb and building processes.a Curve skeletons and cross-sections are shown, dividing the combs at their medial plane. These cross-sections bisect cells along with the interface so that their depth, thickness, and pitch can be measured at any point. b Comb regions that share similar principal directionalities are shown. c By combining established knowledge of A. mellifera building behavior and computational analysis of structure, we demonstrate that the gravitational direction at the time of construction can be reconstructed for a selected region of comb. d For the selected comb region, morphological and combinatorial operators were used to extract individual cells, by subtracting the section itself from the closure of the section and then separating each cell by iterative opening operations. Once the internal volumes of individual cells were obtained, we computed an orthonormal basis for each cell using principal component analysis. For this comb selection, the principal axis of the orthonormal frame was almost orthogonal to the medial plane of the section and was projected onto the medial plane to reveal the upward tilt that bees typically build opposing the sensed direction of gravity.Full size imageFrom the Fiedler segmentation, isocontours were constructed and the centroid of each contour was linked using Prim’s algorithm27 to construct a curve skeleton28. This curve skeleton provides a minimum-spanning tree that connects each region of the Fiedler segmentation. The cross-sections of the volumetric data-oriented to the curve skeleton’s tangent indicate that the comb’s interface falls in line with the curve skeleton’s normal. These cross-sections bisect cells along with the interface so that cell depth, thickness, and pitch can be measured at any point. In some cases, the selected plane bisects more than one of the comb’s segmented regions. In this case, volumetric data from the segmented region corresponding to that point’s isocontour displayed a perpendicular view of the comb’s interface, but data from the other regions may not.Fiedler segmentation was also used to isolate comb regions that share similar principal directionalities. Comb segments with eigenvector values within a small range were selected from the volumetric data of the hive. The first two principal components of the isolated voxels were derived to provide a plane that represents the section’s orientation. The first component was found to align generally with the comb’s build direction within freeform protrusions. In hives with a greater variance in comb curvature, finer segmentation may be needed to isolate regions containing similar build directions. These results demonstrate that the Fiedler vector may be a useful tool for isolating approximately planar regions of comb and for reliably examining the comb interface in the highly curved comb.By combining established knowledge of A. mellifera building behavior and computational analyses of the resulting structures, we have demonstrated that the cell orientation and therefore the build order can be reconstructed from micro-CT scan data using our morphological operators. While honey-holding cells built by bees exhibit an upward tilt from a median plane toward gravity29, in examples such as the perturbed comb shown in Fig. 5c, or in the analysis of wild combs that have incurred large-scale structural damage at some point in their history, we can see that determining this direction is nontrivial. To determine the direction of gravity for a comb section in such cases, in Fig. 5d, we computed the combinatorial difference between the closure with a 10-mm radius and the section itself. We then iteratively applied a morphological opening operation to the resulting SDF until none of the cells were connected to any other cell. For the resulting cell volume, we computed a principal frame using principal component analysis. The z axis of this orthogonal basis aligns with the principal cell orientation and points away from the median plane, whereas the y- and x axes are almost orthogonal to it. The projection of the z-axis onto the median plane reveals the tilt of individual cells and, thus, the direction of gravity.DiscussionAs an application of the described results, we demonstrate how behaviors such as the order of comb building and the deposition of specific materials can be inferred. We propose that these methods will be most impactful when applied to honey bee behavioral studies validated by empirical measurements, and Figs. 6 and 7 illustrate how these methods may be used to examine specific behaviors within a hive.Fig. 6: Simulation of comb construction predicated from geometric measurements.An example prediction of a comb’s construction and morphological evolution over time, using geometric data gathered by determining (a) the medial axis, (b) the geodesic field from the substrate, and (c) the gravity vector of each cell. For a given digital comb, we moved back along the direction of gravity and the build direction until a branch in the medial axis was detected. At this branch, we reevaluated the gravity direction and build direction and moved back until another branch was reached, and so on. From these measurements, we can generate a construction timeline (d), where the process was run in the reverse direction, showing the morphological changes of the combs over time, guided by the combination of gravity, substrate, and the bees’ own agency. For each timepoint, the next constructed comb section is depicted with reduced opacity.Full size imageFig. 7: Attenuation contrast-based filtering and identification of specific material distributions.a Density analysis of a scanned comb (Hive F, Fig. S2) was applied to measure specific materials within a comb built on a 3D-printed substrate. The measured density values from the micro-CT scan data can be extrapolated to physical density measurements by identifying materials with measured densities within the scan. b Once real densities have been mapped, an isolated region of the hive where the broken comb was repaired by the colony was isolated and examined, suggesting that a higher-density wax was allocated to the fractured region and the comb’s interface. c This method was used to examine distributions of low- and high-density wax throughout the hive as well as to measure the volume of honey in capped cells.Full size imageFigure 6 shows how we reconstructed the comb build behavior and morphological evolution from the medial axis, the geodesic field from the substrate, and the gravity vector of each cell. For a given comb, starting from the endpoints of our medial axis tree, we moved back a | Biology |
Animal studies indicate that a new COVID-19 vaccine developed at Rutgers may provide more durable protection against SARS-CoV-2 and its emerging variants than existing vaccines.
“We need a better vaccine, one that provides years of robust protection with fewer booster shots against a variety of SARS-CoV-2 strains. Our data suggest this vaccine candidate might be able to do that,” said Stephen Anderson, associate professor of Molecular Biology and Biochemistry in the School of Arts and Sciences, resident member of the Rutgers Center for Advanced Biotechnology and Medicine and senior author of the paper in Vaccines.
Existing COVID vaccines often provide some protection against serious disease and death. However, these vaccines typically elicit temporary bursts of protective antibodies that rapidly wane, even after booster doses, leaving most individuals vulnerable to potentially dangerous repeat infections.
This new vaccine, dubbed MT-001, might provide longer-lasting protection against many COVID-19 varieties. “Thankfully, the current vaccines saved many lives, but they’re still not optimal in some important respects,” said Anderson. “They may not durably prevent people from getting sick.”
Rutgers researchers developed MT-001 using technological approaches informed by an ambitious National Institutes of Health project that aimed to create an antibody for every protein in the human body.
Both Food and Drug Administration approved RNA vaccines (and most other vaccines approved worldwide) use the entire COVID-19 spike protein as the trigger for the immune response. The new MT-001 vaccine candidate uses a unique section of that spike protein as its immunogen. This brings several advantages.
First, the spike protein section in this immunogen encompasses most of the targets for protective antibodies, including regions that are likely to remain unchanged in (and thus remain effective against) future variants. The data suggest that MT-001 (or its updated booster version) may elicit “broadly neutralizing” antibodies that confer protection against SARS-CoV-2 strain variants currently circulating in the human population and future variants that have not yet appeared.
Second, MT-001 was designed to be relatively straightforward to manufacture and distribute without special low-temperature handling. This could make vaccines based on the MT-001 prototype readily accessible from stockpiles, even in places where cold-storage infrastructure is lacking, should a coronavirus pandemic flare up again.
“In theory, it’s possible that a booster shot of our variant-updated version of MT-001 could provide lifelong protection. The animal data indicate that it should, at the very least, provide protective antibody levels for at least a year or more, which is a vast improvement over today’s vaccines, particularly given that many people are clearly unwilling to get a booster every few months,” said Anderson. “Our goal is to enable people to put the fear of catching COVID behind them.”
Vaccine development and testing were funded in part by the Rutgers Center for COVID-19 Response and Pandemic Preparedness and the New Jersey Health Foundation. Key collaborators included Lisa Denzin and Derek Sant’Angelo of the Rutgers Child Health Institute of New Jersey at Robert Wood Johnson Medical School, Selvakumar Subbian of the Rutgers Public Health Research Institute at New Jersey Medical School and Elliot Campbell, a visiting scientist from Macrotope, Inc., a Rutgers spin-out company. | Biology |
The U.S. Food and Drug Administration on Thursday granted traditional approval to the Alzheimer's drug lecanemab, known by the brand name Leqembi, after an earlier this year.
"Today's action is the first verification that a drug targeting the underlying disease process of Alzheimer's disease has shown clinical benefit in this devastating disease," Teresa Buracchio, acting director of the Office of Neuroscience in the FDA's Center for Drug Evaluation and Research, said in a news release.
Leqembi, from drugmakers Eisai and Biogen, is the first medication that's been shown to slow the progression of Alzheimer's disease, including declines in memory and thinking, by targeting the disease's underlying biology.
"Today marks a breakthrough in the treatment of Alzheimer's disease, and we are proud to be at the forefront of ushering in a new era of advances for a disease that was previously considered untreatable," Biogen president and CEO Christopher A. Viehbacher said in a statement.
He said the company will be "working alongside Eisai with the goal of making [Leqembi] accessible to eligible patients as soon as possible."
The FDA's initial approval in January was based on one mid-stage study in 800 people with early signs of Alzheimer's who were still able to live independently or with minimal assistance. Eisai later published the results of a larger 1,800-patient study that the FDA assessed as part of the full approval process.
The larger study tracked patients' results on an 18-point scale measuring memory and other cognitive functions. Results showed a difference of less than half a point after 18 months, sparking debate over whether this qualifies as a meaningful improvement.
According to the latest news release, the decision was unanimous, with all committee members voting that the study results verified the drug's benefit. Buracchio noted in her statement: "This confirmatory study verified that it is a safe and effective treatment for patients with Alzheimer's disease."
"This drug is not a cure. It doesn't stop people from getting worse, but it does measurably slow the progression of the disease," Dr. Joy Snider, a neurologist at Washington University in St. Louis, told The Associated Press in January. "That might mean someone could have an extra six months to a year of being able to drive."
Snider said that Leqembi (pronounced "leh-KEM-bee") also comes with downsides, including the need for twice-a-month infusions and possible side effects like brain swelling. Other reported side effects are infusion-related reactions and headaches, according to the Alzheimer's Association.
Access is another issue, with the drug expected to be priced at about $26,500 for a typical year's worth of treatment, without insurance.
On Thursday, the head of the Centers for Medicare and Medicaid Services, Chiquita Brooks-Lasure, pledged to "cover this medication broadly while continuing to gather data that will help us understand how the drug works" — a decision that will make it more affordable for many. Brooks-Lasure called the FDA's approval "welcome news for the millions of people in this country and their families who are affected by this debilitating disease."
Her office had previously said it expected to extend coverage once full FDA approval was granted.
The FDA defines Alzheimer's disease as "an irreversible, progressive brain disorder affecting more than 6.5 million Americans that slowly destroys memory and thinking skills and, eventually, the ability to carry out simple tasks."
In a news release from the initial approval, the FDA called the medication "an important advancement in the ongoing fight to effectively treat Alzheimer's disease."
"Alzheimer's disease immeasurably incapacitates the lives of those who suffer from it and has devastating effects on their loved ones," Dr. Billy Dunn, former director of the Office of Neuroscience in the FDA's Center for Drug Evaluation and Research, said in the release. "This treatment option is the latest therapy to target and affect the underlying disease process of Alzheimer's, instead of only treating the symptoms of the disease."
The decision on Leqembi followsof a previous Alzheimer's drug, Aduhelm, which was also developed by Biogen and Eisai. Aduhelm in 2021 despite warnings from independent medical advisers that it had not been shown to be effective and carried significant risks. The FDA later to significantly limit the drug's use.
Alex Tin contributed reporting. The Associated Press also contributed to this report.
for more features. | Biology |
MainNeurons communicate and process information using action potentials or spikes in membrane potentials1. This spike generation and the properties of the neuron are defined by voltage-, ion- and neurotransmitter-dependent conductance of various ion channels in the cell membrane. On receiving an electrical input, the cumulative effect of ionic currents through these channels—primarily the sodium and potassium channels—perturbs the membrane voltage from its resting value, resulting in an action potential. Thus, to create a realistic electrical circuit analogue to the biological neuron, one should emulate the conductance of the sodium channel, which shows a fast activation and inactivation, and the potassium channel, which activates after a certain delay. Simple leaky integrate-and-fire model neurons, based on silicon2 or organic semiconductors3,4, do not incorporate such complex ion channel dynamics and hence can emulate only limited neural features. More biorealistic conductance-based neuron models4,5 can be realized using silicon-based complementary metal-oxide semiconductor circuits2,5, Mott-memristor-based negative differential resistance (NDR) devices6,7 and antiambipolar p–n heterojunction8 transistors. However, these artificial neurons are restricted to pure electrical modulation of neural features, do not explore the ion-/neurotransmitter-based modulation mechanisms of real biological neurons and generally operate at time scales and spike voltage swings drastically different from those found in biology. As a result, these circuits do not facilitate integration with biology or direct sensing/processing of biological, chemical or physical stimuli at the neuron and require coupling of additional sensing elements to act as event-based neuromorphic sensing/processing elements9. Organic electrochemical transistors (OECTs) based on mixed ion–electron conducting polymers are attractive in this context due to their sensing capabilities (biological, chemical and physical signals), biocompatibility, biorealistic switching speeds, low operating voltages and coupled ionic–electronic transport properties which are amenable to modulation by external (ion/molecule) dopants10,11. Recently, we observed that rigid conjugated polymers such as the ladder-type poly(benzimidazobenzophenanthroline) (BBL) exhibit a reduction in the electrical conductivity on high electrochemical doping (>0.8 electrons per monomer) due to the formation of multiply charged species with reduced mobility12.In this article, we utilize this ion-tunable antiambipolarity to emulate the activation and inactivation of sodium channels in biological neurons and hence realize a conductance-based organic electrochemical neuron (c-OECN). This c-OECN can spike at bioplausible frequencies (100 Hz), replicate most neural features and exhibit stochastic response in the presence of noise. Since the antiambipolar element is responsive to ions and biomolecules, we demonstrate that this neuron can be operated as an event-based sensor transducing such biochemical signals to actuate/stimulate the vagus nerve of a mouse, showing the potential for c-OECN-based closed-loop regulation of physiology.Antiambipolarity in BBL and its modulationWhen used as the channel material in OECTs, BBL exhibits a unique, stable and reversible Gaussian-shaped transfer curve (or antiambipolar behaviour) which is similar to voltage-controlled NDR but here instead realized in a three-terminal configuration (Fig. 1a–c and Supplementary Figs. 1–4). When implemented in a circuit, the two sides of this Gaussian current evolution can be analogous to the activated and inactivated states of the voltage-gated sodium channel in the Hodgkin–Huxley neuron model (HH model; Supplementary Note 1)13. Although such antiambipolar behaviour can also be observed in other n- and p-type polymers (Supplementary Figs. 5–7), only BBL with suitable electron affinity (4.15 eV (ref. 14)) and a rigid ladder-like structure composed of double-strand chains linked by condensed π-conjugated units can sustain such high doping levels without any conformational disorder15, enabling reversibility.Fig. 1: Antiambipolarity in BBL and its modulation.a, Structure of BBL. b, Structure of an OECT device. c, The antiambipolar behaviour in BBL resembles the activation and inactivation of sodium channels in a neuron. d–h, Modulation of the antiambipolar behaviour by electrical and chemical means, showing the effects of VDS dependence (d), different gate electrodes (e), ion concentration (f), ion type (g) and different amino acids/neurotransmitters (h). The OECT used in the comparison has a W/L = 40 µm/6 µm and 20-nm-thick BBL except for the higher-current NH4Cl device, which uses a wider channel (W/L = 400 µm/6 µm). A concentration of 100 mM is used for comparing various types of ions. Neurotransmitter and amino acid studies are carried out in 100 mM NaCl. The vertical dashed lines in d–h denote the gate voltage corresponding to the peak drain current (VP). The solid and dashed lines in h denote the forward and reverse scans.Source dataFull size imageThe OECT configuration provides improved control over the antiambipolar response compared with a conventional two-terminal NDR device. For example, applying a higher drain voltage (VDS) increases the peak current, causes a shift in the voltage of the peak current (VP) and results in a Gaussian distribution of a greater full-width at half maximum (Fig. 1d) due to variable doping levels at the drain and source electrodes. The VP and threshold voltage (VT) can also be shifted and controlled by using gate electrodes of appropriate work function (Fig. 1e) and by tuning the concentration of ions in the electrolyte (Fig. 1f). In addition, for a given concentration (100 mM), different ions shift the transfer curve by varying degrees, with Ca2+, Mg2+ and NH4+ showing lower VP than Na+ and K+ (Fig. 1g). Interestingly, various ammonium-based organic cations also lead to unique Gaussian behaviours (Supplementary Fig. 8), unlocking the possibility of chemical-specific responses. Hence it is possible to tune the antiambipolar response using different neurotransmitters and amino acids such as acetylcholine, dopamine, γ-butyric acid (GABA) and glutamine with different configurations of amine groups (Fig. 1h). Adding 3.3 mM acetylcholine to the 100 mM NaCl electrolyte of the OECT does not shift the VP, whereas the same concentration of dopamine, GABA or glutamine causes changes in VP and the channel’s conductance. We attributed this effect to hydrogen-bonding interactions of these molecules with BBL (Supplementary Note 1 and Supplementary Figs. 9–14).Conductance-based organic electrochemical neuronThe c-OECN circuit described here uses two OECTs—one Na+-based (Na-OECT) and another K+-based (K-OECT)—coupled to two voltage sources ENa (500 mV) and EK (∼12 to −72 mV) like the two ion channels and batteries in the HH model13,16 (Fig. 2a–d). ENa is applied to the drain of Na-OECT and EK to the source of K-OECT. The switching speed of these OECTs is in the range of 0.5–1 ms (ref. 17) (Supplementary Figs. 15 and 16), which is comparable to the time scales of sodium and potassium channel activation in biological neurons. The K-OECT channel has a thicker BBL film (50 nm compared with 20 nm for the Na-OECT) to allow higher currents through the potassium channel.Fig. 2: Conductance-based organic electrochemical neuron.a–c, Analogy between biological neurons (a) showing Na+ and K+ channels (b) and the c-OECN circuit with Na+- and K+-based OECTs (c) and their modulation with Ca2+ and neurotransmitters. Cmem is optional in the circuit and can be embedded in the intrinsic capacitance of the OECT. d, The Hodgkin–Huxley circuit of the neuron. e,f, Comparison of the squid axon action potential studied by Hodgkin and Huxley13 (e) and the c-OECN action potential (f). Cmem is the membrane capacitance, Vmem the membrane voltage, Iin the input current and Rdk the resistance which induces delay. EL (RL), EK (RK) and ENa (RNa) represent the leakage, potassium and sodium batteries (resistances) in the HH model. VK and μK are the threshold voltage and mobility of the K-OECT. VNa-s (μNa-s) and VNa-m (μNa-m) are the threshold voltage (mobility) on the low- and high-voltage sides of the antiambipolar transfer curve of Na-OECT representing the single and multiply charged species. INa and IK are the sodium and potassium currents. Part e: copyright 1952 Wiley. Adapted with permission from A.L. Hodgkin, A.F. Huxley, A quantitative description of membrane current and its application to conduction and excitation in nerve, Journal of Physiology, John Wiley and Sons.Source dataFull size imageA current Iin (in the range 0.5–6 μA) injected into this circuit is integrated by the capacitance Cmem causing the voltage Vmem to increase from its resting value of ∼175 mV. This simultaneously sweeps the voltage on the gate of Na-OECT from ∼1.2 V to ∼0.8 V using an n-type metal-oxide semiconductor-based inverting amplifier (Supplementary Fig. 17) to traverse the antiambipolar transfer curve through VP, producing a spike in current INa1. This current spike charges the capacitor even further, resulting in a rapid increase of Vmem to ∼0.34 V (depolarization). The K-OECT, which turns on after a delay enabled by its intrinsic gate capacitance and resistance Rdk, reaches its peak current after Na-OECT has crossed its maximum at VP. The capacitor is thus discharged through K-OECT, causing the Vmem to drop (repolarization) and traversing the Gaussian response to its initial state back through VP, causing a secondary spike INa2. The secondary spike in Na-OECT (not present in the squid axon action potential; Fig. 2e,f) is unnecessary for spike generation but is unavoidable, hence is entirely discharged by the K-OECT (due to the higher conductivity of K-OECT) not to cause any further voltage increase. Since the current of K-OECT is higher and persists longer, the voltage is brought below the resting value of 175 mV for a brief period (hyperpolarization). All these processes repeat cyclically if the input current remains constant, resulting in continuous action potential generation (tonic spiking). The c-OECN action potential thus shows typical features of a biological action potential, including depolarization, repolarization and hyperpolarization (Fig. 2f, Supplementary Figs. 18–25 and Supplementary Video 1). Supplementary Note 4 provides the circuit analysis of the c-OECN and the SPICE simulation and compares the circuit equations with the HH model. Note that VDS for Na-OECT is not constant because the voltage at the source side is Vmem, which continuously fluctuates. Hence, the effective VDS of Na-OECT is ENa – Vmem. Similarly, Vmem acts at the drain of the K-OECT, and thus its effective VDS is Vmem – Ek.Features of the c-OECNThe resemblance between the operation of the c-OECN and that of the biological neuron means that several neural features17 can be mimicked by modulating the threshold and currents of OECTs (Fig. 3 and Supplementary Table 1). In the standard configuration, the neuron exhibits tonic spiking, that is, excitability in the presence of a constant input while remaining quiescent otherwise. Tuning the capacitance Cmem and the resistance Rdk can tune the frequency of this spiking. The c-OECN spikes at a frequency of around 5 Hz with a Cmem = 1 μF and Rdk = 470 kΩ (Fig. 3a) and can be increased to reach 45 Hz or 80 Hz (Fig. 3b,c) by excluding external capacitance and then utilizing only the internal capacitance of the OECT. Furthermore, the n-type metal-oxide semiconductor-based inverting amplifier can be replaced with an OECT-based amplifier to achieve spiking at 100 Hz (Supplementary Figs. 26 and 27). Hence, biorealistic frequencies can be achieved with a neuron based on three OECTs. For ease of measurement of neural features with various pulsed inputs, we used the lower-frequency c-OECN (~5 Hz) by employing Cmem = 1 μF. The peak power (energy) consumption of the circuit spiking at 80 Hz is around 60 μW (175 nJ per spike). Supplementary Note 5 discusses strategies to lower energy consumption.Fig. 3: Experimental demonstration of various neural features using c-OECN and their functions in biology.a–p, Tonic spiking (a), higher-frequency tonic spiking by modulating Rdk and Cmem (45 Hz, b; 80 Hz, c), latency (d), integration (e), refractoriness (f), resonance (g), threshold variability (h), rebound spike (i), accommodation (j), class 3 spiking—phasic bursting and spiking (k), class 1 spiking (l), class 2 spiking (m), stochastic spiking with noisy input (n), calcium-based modulation from class 1 to class 3 spiking (o) and modulation of spiking using the amino acid glutamine (p). The x axis of all the graphs represents time. Vmem and Iin are the membrane voltage and input current. The parameters used to enable these behaviours are listed in Supplementary Table 1.Source dataFull size imageMost neural features such as tonic spiking, latency, subthreshold oscillations, integration, refractoriness, resonance, threshold variability, rebound spiking, accommodation, phasic spiking, phasic bursting, and class 1 and class 2 excitability can be demonstrated using this circuit (Fig. 3d–m). Each of these has a specific function or serves as a mathematical operator in a neuron (Supplementary Note 6). Switching from class 1 (input-strength-dependent excitability) to class 2 (spiking only at high current inputs with a high frequency) and class 3 spiking (spiking/bursting only at the beginning of input) can be enabled by simple tuning of the threshold of the K-OECT (by changing Ek) to modify the relative timing of it turning on. For example, for the c-OECN demonstrated here, an Ek of −50 mV results in a class 1 spiking neuron, while causing K-OECT to turn on earlier by changing Ek to −65 mV changes the behaviour to class 2 spiking, and increasing it to a more negative value of −70 mV (−72 mV) results in phasic bursting (phasic spiking) which is class 3 behaviour. Incorporating additional channels in the circuit similar to the Ca2+ modulated channels in biological neurons18 may enable other missing features achievable by biological neurons such as tonic bursting, mixed-mode spiking, spike frequency adaptation, bistability and inhibition-induced spiking17.The c-OECN can also exhibit input-noise-dependent stochasticity or spike skipping, like the biological neurons19. The class 2 neuron shown in Fig. 3n does not spike at an input current of 2 μA. However, when very low noise is superimposed on this input, keeping the average current the same, it starts spiking at a particular frequency—increasing the input noise results in random skipping of spikes while keeping this base frequency constant. A similar mechanism is observed in biological neurons, for example, in mammalian cold thermoreceptors19 where temperature-induced noise causes stochasticity in spiking and is used to extend the range of encodable stimuli. Such stochastic spiking can also enable probabilistic neural sampling and finds application in spike-based Bayesian learning and inference20.Modulation using (bio)chemical signals and biointegrationThe unique feature of the c-OECN compared to other conductance-based circuit realizations of neurons is that it can be controlled using secondary ions such as Ca2+ and neurotransmitters as they can affect the VP and the maximum current of the Gaussian transfer curve. In biological neurons, Ca2+ plays crucial roles in regulating neural activity by modifying the opening and closing of sodium and potassium channels, stimulating the release of neurotransmitters leading to synaptic plasticity, and even regulating metabolism and cell growth21. Inspired by this, we tried to modulate the potassium channel of the c-OECN using external Ca2+ ions. Incorporating Ca2+ ions into the electrolyte of the K-OECT shifts its threshold VK towards lower values. This is equivalent to VK modulation by altering EK as described above and hence creates the same effect, that is, a shift from class 1 spiking to phasic bursting and finally phasic spiking on a slow increase of Ca2+ concentration (Fig. 3o). Such a transition is similar to the case in biological neurons, where the generation of phasic firing is known to be Ca2+ ion concentration dependent22. In addition to ions, biological neurons are also affected by the presence of neurotransmitters and amino acids. For example, GABA is an inhibitory neurotransmitter in the brain23 and inhibits the generation of action potentials by increasing chloride or potassium ion conductance and hyperpolarizing the membrane. Here we coupled GABA to the Na-OECT, and since GABA reduces the maximum current of the Na-OECT and shifts its VP towards lower values, the sodium current spike induced depolarization, and hence spiking is instantly inhibited in the c-OECN, thus enabling neurotransmitter-induced modulation of spiking similar to biology (Supplementary Fig. 41). Similarly, the c-OECN can be controlled by the amino acid glutamine such that it stops spiking above biologically relevant concentrations of around 1 mM (ref. 24) (Fig. 3p).To further illustrate the possibility of using c-OECNs in sensing, biointegration and nerve activation, we demonstrate event-based sensing of Na+ and glutamine (Fig. 4a–f) at the neuron combined with stimulation of the right cervical vagus nerve of a mouse to control its heart rate. Vagus nerve stimulation (VNS) is used as a therapeutic intervention for treating depression, controlling epileptic seizures and in clinical trials for treating chronic inflammatory diseases such as rheumatoid arthritis and inflammatory bowel disease25,26. Experimental animal models (commonly genetic mouse models) are often used to study the physiological effects and mechanisms of VNS and to estimate its therapeutic potential. Here we coupled the c-OECN with a mouse’s right cervical vagus nerve, which innervates the sinoatrial node where the pacemaker cells for heart rate are located, using a cuff electrode27 (Supplementary Fig. 43), and monitored the heart rate. We observed a 4.5% reduction in heart rate in response to an increased Na+ concentration sensed at the Na-OECT, consistent with electrical activation of the right cervical vagus nerve (Fig. 4g–k). As discussed previously, the NaCl concentration can substantially shift the VP of the Gaussian transfer curve (Fig. 1f) of the Na-OECT to modulate the spiking of the c-OECN, thus enabling event-based ion sensing at the neuron without external sensors (Fig. 4a–d). Sensing Na+ has high clinical significance in detecting diseases such as cystic fibrosis, where the sweat Na+ and Cl− concentrations can increase to high levels (>60 mM) compared with baseline (<30 mM)28. The c-OECN can be made to spike only at a high NaCl concentration (>25 mM) relevant to this condition (by choosing appropriate values of VK, VNa and inverter threshold) and resulting in an actuation; here, for example, the VNS-based control of heart rate. The sensing capability of the c-OECN is not limited to ions. It can also be made to spike only at either a low (<900 μM) or high (>1,800 μM) glutamine concentration in the biologically relevant range and combined with stimulation of the vagus nerve. The demonstration of sensor-triggered vagus nerve activation does not imply that a new therapeutic means is developed in this study but shows the potential for future c-OECN-based closed-loop regulation of physiology. Considering the key role the vagus nerve plays in regulating homeostasis, including immune-system and metabolic control29, VNS triggered by event-based internal sensing has interesting potential therapeutic applications, for example, in improving the regulation of cytokine release or glucose levels to treat autoimmune or metabolic diseases. This notion may be extended to sensor-based regulation of other aspects of normal physiology and pathological conditions through peripheral nerve activation, such as VNS and voltage-triggered drug delivery.Fig. 4: Modulation using (bio)chemical signals and biointegration.a–d, Modulation of spiking of c-OECN based on NaCl concentrations of 12.5 mM (a), 25 mM (b), 50 mM (c) and 100 mM (d). e,f, A neuron optimized to spike at low glutamine concentrations (<900 μM) (e) and at high glutamine concentrations (>1,800 μM) (f). g, The c-OECN circuit showing sensing of Na+ ions at the Na-OECT and integration with the vagus nerve using an OECT-based amplifier and cuff electrodes. h,i, The amplifier output at a low NaCl concentration of 25 mM (h) and the corresponding heart rate variation (i). j,k, The amplifier output at a high NaCl concentration of 100 mM (j) and the corresponding heart rate variation (k). The black horizontal dashed line in k represents the baseline heart rate. The purpose of this demonstration is to show the potential of c-OECN to sense biochemical signals and interface with nerves and does not imply that new therapeutic means are developed.Source dataFull size imageIn conclusion, we demonstrated a biorealistic OECN based on highly tunable, stable and reversible antiambipolar behaviour in BBL-based OECTs. Two OECTs modulated by Na+ and K+ ions resemble the voltage-gated ion channels in biological neurons, enabling various neural features and facile sensing and integration with the vagus nerve of a mouse. A comparison of the c-OECN with other neuron technologies is provided in Supplementary Table 2. The intrinsic capacitance of the OECTs and the biorealistic switching speeds circumvent the need for additional capacitors required in silicon-based circuits to spike at biologically plausible frequencies for interaction with real-world events and biological neurons30. Alternative implementations using Mott-memristors that can exhibit similar features are inherently faster than biology (ns to μs) and are associated with unfavourable temperature increases on operation, making them unsuitable for biointegration. In addition, using single-polymer material to achieve Gaussian behaviour similar to NDR averts complex fabrication strategies and helps achieve lower device dimensions compared with the heterojunction approach in 2D materials or p–n junction polymers. The ion-, amino acid- and neurotransmitter-based modulation in this c-OECN is unprecedented and may be extendable to other biomolecules that can interact with BBL. Although the sensing of molecules is done externally in the current study, it demonstrates the capability of tuning the c-OECN to respond to a specific concentration of biochemical signal by simple modulation of voltages in the circuit to enable event-based sensing. Similar stable ladder-like conjugated polymers functionalized to interact with specific biomolecules are a possible way forward to realize intelligent closed-loop event-based internal sensing and feedback neuromorphic biomedical systems and future brain–machine interfaces.MethodsMaterialsPoly(3,4-ethylenedioxythiophene) polystyrene sulfonate (PEDOT:PSS, Clevios PH1000) was purchased from Heraeus Holding. Naphthalenetetracarboxylic dianhydride (NDA), 1,2,4,5-tetraaminobenzene tetrahydrochloride (TABH), poly(phosphoric acid) (PPA), methanesulfonic acid (MSA), chloroform, 1,2-dichlorobenzene, ethylene glycol, (3-glycidyloxypropyl)trimethoxysilane and 4-dodecylbenzenesulfonic acid were purchased from Sigma-Aldrich. BBL (η = 6.3 dl g−1 in MSA at 30 °C, Mw = 35 kDa) was made by polycondensation of NDA and TABH in PPA at elevated temperatures17,31.Thin-film castingBBL was dissolved in MSA at 100 °C for 12 h, followed by cooling to room temperature to obtain the BBL–MSA solution. This solution was spin-coated (1,000 r.p.m., 60 s, acceleration 1,000 r.p.m. s−1) on OECT substrates. The residual MSA in the films was removed by immersing them in deionized water, followed by drying in nitrogen flow. PEDOT:PSS, ethylene glycol, (3-glycidyloxypropyl)trimethoxysilane and 4-dodecylbenzenesulfonic acid were mixed in the volume ratio of 100:5:1:0.1 and sonicated for 10 min. This solution was spin-coated (2,000 r.p.m., acceleration 2,000 r.p.m. s−1, 60 s) on OECT substrates and annealed at 120 °C for 1 min for crosslinking PEDOT:PSS.OECT fabrication and testingOECTs were fabricated according to a previous protocol17,32. Four-inch glass wafers were cleaned with acetone, deionized water and isopropyl alcohol and then dried using nitrogen. Electrodes (5 nm chromium and 50 nm gold) were thermally evaporated and then patterned by photolithography. A layer of parylene carbon (PaC, 1 µm) was then deposited in the presence of 3-(trimethoxysilyl)propyl methacrylate (A-174 Silane) (to increase adhesion). This forms an insulating layer to prevent unwanted capacitive effects at the electrode–electrolyte interface. After that, an antiadhesive layer of industrial surfactant (2% Micro-90) was spin-coated, and a sacrificial 2-µm-thick layer of PaC was deposited. A 5-µm-thick AZ10XT520CP positive photoresist was then spin-coated on this layer. This protects the PaC layers from the following plasma reactive ion etching (RIE) step (150 W, 500 sccm O2, 100 sccm CF4, 380 s). Another photolithographic patterning was performed to define the contact pads and the OECT channel, and the AZ developer was applied to the photoresist. A plasma RIE was carried out to remove the organic materials (photoresist and PaC), exposing the OECT channel area and the contact pads. The remaining surface remained covered with layers of PaC. This was followed by patterning the OECT channel to obtain a width/length (W/L) = 40 µm/6 µm or 80 µm/6 µm (for Na-OECTs), and 400 µm/6 µm (for K-OECTs). A 20-nm-thick (Na-OECT) or 50-nm-thick (K-OECT) film was obtained by spin-coating the BBL–MSA solution described previously. The sacrificial parylene layer was then peeled off to remove the unwanted BBL film outside the electrode area. This leaves separated pieces of semiconductor film confined to the wells, connecting the OECT source/drain electrodes. Ag/AgCl paste was drop-cast on the substrate to form a 1-μm-thick, 9 mm2 square gate electrode. OECTs based on PEDOT:PSS, P(g42T-T) and p(g7NC10N) were also made using the same procedure. The electrolyte for all the OECT measurements was 0.1 M NaCl aqueous solution unless otherwise specified. The OECTs were characterized using a Keithley 4200A-SCS.SPICE simulationThe SPICE models of K-OECT and Na-OECT were created in B2 SPICE (EMAG Technologies). These models simulate the spiking features of c-OECNs. The details of the simulation are presented in Supplementary Note 4.Cuff electrode fabrication and interfacing with the vagus nerveTo interface with the mouse’s vagus nerve, a flexible array of electrodes was fabricated based on a previous protocol33. Eight stimulation electrodes (450 µm × 200 µm in dimensions) in a 2 × 4 arrangement were included in the array. The substrate and insulation layers consisted of flexible PaC which allow the device to conformally wrap around the nerve, and thus to serve as a cuff-electrode-style interface. The first stage of the microfabrication process consisted of a cleaning procedure for glass microscope slides using ultrasonication in a dilute Hellmanex soap solution (2 vol% in deionized water), then in acetone, followed by isopropanol. A flexible PaC layer (2 µm) was then deposited using chemical vapour deposition (Diener Electronic) on the glass carrier substrates. Photolithographic patterning of metal interconnects (80 nm gold and 5 nm titanium adhesion layer) was carried out through a lift-off process using the negative photoresist AZ nLof 2070 and a MA6 Suss mask aligner with an i-line filter. These metal patterns provide the electrode contact surfaces and an electrical connection between the electrodes and the back-end contact pads. Following lift-off, a 2 min oxygen plasma process at a power of 50 W was performed before the deposition of an insulating PaC layer (1.5 µm) on the metal electrode lines (with A-174 adhesion enhancer in the deposition chamber). An AZ 10XT photoresist etch mask was patterned, and RIE was performed (O2/CF4 gases, 150 W) to define the shape of the probes. Acetone and isopropanol rinses were used to remove the photoresist etch mask. Next, a dilute soap antiadhesion layer (2.5 vol% in deionized water) was spin-coated at 1,000 r.p.m. on the sample surface. A thick sacrificial PaC layer (2 μm) was then deposited and the above RIE etch process was used to define the surface of the electrode and back-end contact openings. A conductive polymer electrode coating was spin-coated onto the substrates, consisting of a PEDOT:PSS-based dispersion, 5 wt% ethylene glycol, 0.1 wt% dodecyl benzene sulfonic acid and 1 wt% of (3-glycidyloxypropyl)trimethoxysilane. A soft bake was carried out at 100 °C for 60 s, followed by peel-off of the sacrificial PaC layer. Finally, a 45 min annealing process at 140 °C was used to crosslink the conducting polymer film, and the individual arrays were removed from the glass substrates using deionized water to assist the process.To provide electrical connection to the arrays, custom adaptors were created using zero-insertion-force clips (ZIF-Clip) mounted on printed circuit boards. Back-end wiring provided the possibility for connection to an Intan 16-channel head stage of an Intan RHS 128 channel stimulation/recording controller (Intan Technologies) with software that helps verify good contact and electrochemical impedance values. When interfacing the c-OECN and the right vagus nerve, four neighbouring electrodes were shorted together and connected to the output of the c-OECN.C57BL/6J male mice, 10–12 weeks of age, purchased from Charles River Laboratories, were used in experiments investigating the interface with the vagus nerve. Mice were housed under a 12 h light/dark cycle with adequate access to food and water. The approval for this experimental protocol was provided by the regional Stockholm Animal Research Ethics Committee (Stockholm, Sweden). The surgery used to isolate the vagus nerve has been described previously34. In brief, mice were anaesthetized with isoflurane and an equal mixture of air and oxygen. They were then placed in the supine position, and a ventral midline cervical incision was made to expose subcutaneous tissues and the mandibular salivary glands. After separation using blunt dissection, proper exposure revealed the right neurovascular bundle containing the cervical vagus nerve and carotid artery. The vagus nerve was dissected from the vasculature and isolated before immobilizing with a suture to facilitate electrode placement.Reporting summaryFurther information on research design is available in the Nature Portfolio Reporting Summary linked to this article. Data availabilityThe authors declare that the main data supporting the findings of this study are available within the paper and its Supplementary Information files. Source data are provided with this paper.ReferencesPurves, D. et al. (eds). Neuroscience 3rd edn. (Sinauer Associates Inc., 2004).Indiveri, G. et al. Neuromorphic silicon neuron circuits. Front. 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To begin to understand the link between the gut and the brain, all you have to do is look at the English language, according to Irish neurologist John Cryan.
“We use phrases like gut feelings, gut instincts, we have butterflies in our tummies when we’re nervous,” Cryan told Euronews Next. “So perhaps there’s an underlying biology to these phrases.”
The most basic connection we can observe every day revolves around eating, Cryan explained. When we’re hungry, our stomach sends a message to our brain to tell us to eat. It also tells us when we’re full and need to stop.
Cryan has been studying this gut/brain axis for decades, most recently at University of Cork in Ireland, where he leads the department of anatomy and neuroscience.
In recent years, he says a new variable has entered the equation: the microbiome. Scientists have discovered that the trillions of benevolent bacteria and viruses living in our intestines can have a huge impact on our brain and behaviour.
And feeding your microbes foods that they like can help reduce stress and even alleviate symptoms of anxiety and depression.
“We're beginning to really understand that these microbes that we have within our gut are really important for most aspects of our physiology,” Cryan said. “But what my lab has been interested in is how they're also playing a role in shaping our brain and our behaviour.”
How important is our microbiome?
The easiest way to know if something is important or not in the body is to take it out and see what happens, Cryan says.
So that’s what his lab at University of Cork did – they conducted a study on mice, raising them in a germ-free environment to see how this affected their behaviour. These germ-free mice were then given the option to spend time with other mice or to spend time alone in a chamber.
“Mice are quite social like humans, so they normally gravitate towards a social environment, but if they didn’t have microbes in their guts, they didn’t,” Cryan said.
Across the animal kingdom, from honeybees to baboons, the same patterns were observed – if you changed the microbiome, social structures and behaviour also changed.
In humans, the growing evidence that microbes can change behaviour has huge implications on a wide variety of mental disorders and conditions.
“Social behaviour is at the heart of a variety of disorders, like autism,” Cryan said. “We’re also studying it in the context of social anxiety disorder. It’s very much important for schizophrenia. And all of these are now implicating the microbiome in their overall pathophysiology.”
What throws our microbiome out of whack?
Our gut microbiome is sensitive, and it can be thrown off by a number of different things, like the environment, stress, antibiotics, and diet, Cryan said.
“Many aspects of our Western diet, the increase in processed food, sweeteners, emulsifiers, etc. have been shown to negatively impact the composition of the microbiome,” he said. “Diversity is really important in all aspects of life, and diversity is really important for our microbiomes.”
As humans evolved and moved away from our hunter-gatherer origins, our diets became less diverse, as did our microbiomes. New disorders of inflammation started showing up in Western populations, like irritable bowel syndrome (IBS) and multiple sclerosis (MS), both of which affect the brain.
Some of the microbes our ancestors had in their guts have gone completely extinct, Cryan said.
“We’re beginning to grapple with this as a society,” Cryan said. “How do we realign the microbiome that our ancestors had and how do we have the diets that are going to be good in fostering an appropriate microbiome?”
Can eating differently improve your mental health?
Cryan and his colleagues in Cork began to wonder - if diet can negatively affect the microbiome and brain, then maybe changing what we eat could enrich our microbiome and have a positive effect on mental health.
He and colleague Ted Dinan, a psychiatry professor at Cork, had come up with the term psychobiotics to describe any interventions that target the microbiome and have positive effects on mental health.
These include specific species of bacteria called probiotics, supplements that support good bacteria called prebiotics and the chemicals produced by the bacteria called postbiotics.
But Cryan and his team set out to prove that a psychobiotic diet could also exist.
“We brought people in and we either gave them some normal dietary advice or we got them to change their diet completely to this psychobiotic diet, really ramping up the fibre and fermented foods,” he said. “What we found was that there was a reduction in their feelings of stress, in their overall mood-related readouts and their sleep also improved.”
What foods can improve your mental health?
When it comes to feeding your microbiome, the worst thing you can eat is processed food, Cryan says.
“Work predominantly from Australia has shown that really highly processed food in particular has a negative effect on our mental health,” he said. “Diets that are really extreme in any way have also been shown to be quite negative on our mental health.”
There are four main things in our diets that have been found to improve mental health – Omega-3 fatty acids, polyphenols, fibre and fermented foods.
Omega-3 fatty acids are found in fish and flaxseeds; while polyphenols give plant-based food colour and are found in berries, olives and soy beans. Fibre-rich foods include lentils, avocados and broccoli. Fermented foods include kimchi, yoghurt and miso.
More studies are still being done to get a better idea of how diet and mental health are related, but Cryan says the findings are encouraging, because they suggest there are simple steps everyone can take to reduce stress.
“It’s not about creating an expensive product that’s only available in health food stores,” he said. “It’s about really telling people that you can change your fibre intake reasonably cheaply, you can change your fermented foods. This can be done without a huge expense and therefore we’re hoping that this could be implemented as a preventative mechanism to help people who have busy, stressful lives deal with the stress.” | Biology |
image: It might be hard to believe, but this is a picture of a memory. In this image, the blue dots are positive memory cells, and the red dots are negative memory cells. Memories exist in the brain as networks of cells called engrams, and are stored and processed all over the brain. The memories shown here are located in the hippocampus of a mouse. view more Credit: Photo by Stephanie Grella. You may not realize it, but each time you recall a memory—like your first time riding a bike or walking into your high school prom—your brain changes the memory ever so slightly. It’s almost like adding an Instagram filter, with details being filled in and information being updated or lost with each recall. “We’re inadvertently applying filters to our past experiences,” says Steve Ramirez (CAS’10), a Boston University neuroscientist. Even though a filtered memory is different from the original, you can tell what that basic picture is for the most part, he says. “Memory is less of a video recording of the past, and more reconstructive,” says Ramirez, a BU College of Arts & Sciences assistant professor of psychological and brain sciences. The malleable nature of memory is both a blessing and curse: it’s bad if we remember false details, but it’s good that our brains have the natural ability to mold and update memories to make them less potent, especially if it is something scary or traumatic. So, what if it’s possible to use the malleable nature of our memories to our advantage, as a way to cure mental health disorders like depression and post-traumatic stress disorder (PTSD)? That is exactly what Ramirez and his research team are working to do. And after years of studying memory in mice, they’ve found not only where the brain stores positive and negative memories, but also how to turn the volume down on negative memories by artificially stimulating other, happier ones. “Our million-dollar idea is, what if a solution for some of these mental disorders already exists in the brain? And what if memory is one way of getting there?” Ramirez says. In two new papers, he and his team demonstrate the power of our emotional memories and how our experiences—and the way we process them—leave actual physical footprints on the brain. Mapping Positive and Negative Memories One of the most important steps toward using memory to treat memory-related disorders is understanding where positive and negative memories exist in the brain, and how to distinguish between the two. Memories are stored in all different areas across the brain, and the individual memories themselves exist as networks of cells called engrams. Ramirez’s lab is particularly interested in the networks of memories located in the brain’s hippocampus, a cashew-shaped structure that stores sensory and emotional information important for forming and retrieving memories. In a new paper published in Nature Communications Biology, Ramirez, lead author Monika Shpokayte (MED’26), and a team of BU neuroscientists map out the key molecular and genetic differences between positive and negative memories, finding that the two are actually strikingly distinct on multiple levels. It turns out that emotional memories, like a positive or negative memory, are physically distinct from other types of brain cells—and distinct from each other. “That’s pretty wild, because it suggests that these positive and negative memories have their own separate real estate in the brain,” says Ramirez, who’s also a member of BU’s Center for Systems Neuroscience. The study authors found that positive and negative memory cells are different from each other in almost every way—they are mostly stored in different regions of the hippocampus, they communicate to other cells using different types of pathways, and the molecular machinery in both types of cells seems to be distinct. “So, there’s [potentially] a molecular basis for differentiating between positive and negative memories in the brain,” Ramirez says. “We now have a bunch of markers that we know differentiate positive from negative in the hippocampus.” Seeing and labeling positive and negative memories is only possible with the use of an advanced neuroscience tool, called optogenetics. This is a way to trick brain cell receptors to respond to light—researchers shine a harmless laser light into the brain to turn on cells that have been given a receptor that responds to light. They can also color code positive and negative memories by inserting a fluorescent protein that is stimulated by light, so that positive memory cell networks glow green, for example, and negative cell networks glow red or blue. Rewiring Bad Memories Before the researchers label a memory in a mouse, they first have to make the memory. To do this, they expose the rodents to a universally good or unpleasant experience—a positive experience could be nibbling on some tasty cheese or socializing with other mice; a negative experience could be receiving a mild but surprising electrical shock to the feet. Once a new memory is formed, the scientists can find the network of cells that hold on to that experience, and have them glow a certain color. Once they can see the memory, researchers can use laser light to artificially activate those memory cells—and, as Ramirez’s team has also discovered, rewrite the negative memories. In a paper published in Nature Communications, they found that artificial activation of a positive experience permanently rewrote a negative experience, dialing the emotional intensity of the bad memory down. The researchers had the mice recall a negative experience, and during the fear memory recall, they artificially reactivated a group of positive memory cells. The competing positive memory, according to the paper, updated the fear memory, reducing the fear response at the time and long after the memory was activated. The study builds on previous work from Ramirez’s lab that found it’s possible to artificially manipulate past memories. Activating a positive memory was the most powerful way to update a negative memory, but the team also found it’s not the only way. Instead of targeting just positive memory cells, they also tried activating a neutral memory—some standard, boring experience for an animal—and then tried activating the whole hippocampus, finding that both were effective. “If you stimulate a lot of cells not necessarily tied to any type of memory, that can cause enough interference to disrupt the fear memory,” says Stephanie Grella, lead author and a former postdoctoral fellow in the Ramirez Lab who recently started the Memory & Neuromodulatory Mechanisms Lab at Loyola University. Even though artificially activating memories is not possible to do in humans, the findings could still translate to clinical settings, Grella says. “Because you can ask the person, ‘Can you remember something negative, can you remember something positive?’” she says—questions you can’t ask a mouse. She suggests that it could be possible to override the impacts of a negative memory, one that has affected a person’s mental state, by having a person recall the bad memory, and correctly timing a vivid recall of a positive one in a therapeutic setting. “We know that memories are malleable,” Grella says. “One of the things that we found in this paper was that the timing of the stimulation was really critical.” The Quest for Game Changers For other more intensive types of treatment for severe depression and PTSD, Grella suggests that it could eventually be possible to stimulate large swaths of the hippocampus with tools like transcranial magnetic stimulation or deep brain stimulation—an invasive procedure—to help people overcome these memory-related disorders. Ramirez points out that more and more neuroscientists have started to embrace experimental treatments involving psychedelics and illicit drugs. For example, a 2021 study found that controlled doses of MDMA helped relieve some severe PTSD symptoms. “The theme here is using some aspects of reward and positivity to rewrite the negative components of our past,” Ramirez says. “It’s analogous to what we’re doing in rodents, except in humans—we artificially activated positive memories in rodents, and, in humans, what they did was give them small doses of MDMA to see if that could be enough to rewrite some of the traumatic components of that experience.” These types of experiments point to the importance of continuing to explore the clinical and beneficial methods of memory manipulation, but it’s important to note that these experiments were done under close medical supervision and shouldn’t be attempted at home. For now, Ramirez is excited to see how this work can further push the boundaries in neuroscience, and hopes to see researchers experiment with even more out-of-the-box ideas that can transform medicine in the future: “We want game changers, right? We want things that are going to be way more effective than the currently available treatment options.” Journal Communications Biology Method of Research Experimental study Subject of Research Animals Article Title Hippocampal cells segregate positive and negative engrams Article Publication Date 26-Sep-2022 Disclaimer: AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert system. | Biology |
Anna-Lisa Paul had tried for years to get her hands on some real samples of lunar soil collected by Apollo-era astronauts. After she’d refined her research proposal multiple times, NASA finally granted her request in 2021, allowing her team to try growing tiny plants in moon dirt that had been lifeless for billions of years.Her efforts paid off: Although the plants clearly struggled in the harsh, foreign material, they nonetheless managed to sprout. Paul’s team published their findings in a new study in the journal Communications Biology on Tuesday, arguing that their experiment shows that lunar astronauts could do their own greenhouse farming in a couple decades, making them able to provide some of their own sustenance.“After two days, we were amazed that every single seed germinated. It was extraordinary and a little breathtaking,” says Paul, a space biologist and geneticist at the University of Florida. “We were watching the very first seeds ever in the history of humanity—in the history of the solar system—growing in lunar material.” (The researchers aren’t affiliated with NASA, but the agency helped fund their work.)The lunar soil, called regolith, that astronauts scooped up in the 1960s and ’70s is extremely challenging to work with. The sand grains are dry, sharp, abrasive, and extremely fine, they have minerals and ions that Earth plants have never encountered before, and they have no organics whatsoever, because no plants have ever grown, and then died and decomposed, on the moon. To make it resemble earthly soil, the experimenters needed to add some nutrients and water. (Water is also hard to come by on the moon, although it exists.)Paul and her team made the most of their limited supply of authentic regolith. For each sample, they had about a gram, or a small spoonful, of material collected from Apollo 11—the first human landing on the moon, at the Sea of Tranquility—and the Apollo 12 and 17 missions, which landed west and north of there. For comparison, they also planted seeds in similar amounts of simulated lunar soil made from volcanic ash, which on Earth would be a poor choice for gardening. They had previously conducted numerous experiments with such simulated material, called JSC-1A (named after NASA’s Johnson Space Center), which allowed them to precisely fine-tune their diluted nutrient solution—sort of a liquid fertilizer.For the experimental apparatus, they planted the seeds in a plate with 48 wells, like a small ice cube tray. But they only filled a few of the wells: three with the moon dirt plus nutrient solution, and four with the JSC-1A plus nutrient solution. They repeated the same setup on three other plates, too, to gain better statistics. Then they moved the plates in their individual watering trays to ventilated terrarium boxes under growth lights. The boxes limited airflow, but they weren’t totally sterile; instead, they simulated what an open lab environment might be like in a crewed lunar habitat.Photograph: Tyler JonesThe little plants, known as thale cress (Arabidopsis thaliana), are in the same family as watercress and broccoli, which makes them a good model for vegetable crops. And, for the researchers, they have the advantage of growing quickly. When the seedlings first cropped up in both the lunar soil and control samples, they were still drawing nutrients from reserves stored in the seeds themselves. But after a week or so, differences emerged. “The seedlings in the lunar samples started to grow more slowly, and some of them started to show serious stress responses. Their roots were more bent and kinked and not as healthy-looking. It was difficult for them,” Paul says. Some of the plants seemed to adapt, while others looked increasingly sickly, with their leaves becoming gnarled and pigmented.Compared to their counterparts that grew in volcanic ash, all the plants in the moon soil took longer to develop broad leaves, were smaller, and some were severely stunted. Of the plants potted in regolith, the ones grown in the samples from the Apollo 12 and 17 missions fared the best.Paul and her team then ran genetic tests on all the plants to figure out which metabolic tools the plants used to adapt to their environment. They found that even the healthier-looking seedlings had gene activity—genes that had been turned off or on—indicating stress. This activity is comparable to that of plants surrounded by soil with too many metals or salts, Paul says. “They were working hard to make themselves healthy, if you will.”Still, the researchers have an optimistic outlook for the future of lunar gardening, especially since any plants grown in actual regolith would improve the soil for next generations. “I’m on the positive side of things. The fact that some of the plants showed stress, and some failed growing, doesn’t worry me at all. We here on Earth are getting very experienced about how to grow plants in increasingly salty and dry environments. I have no doubt that we’ll learn how to grow plants in lunar soil,” says Robert Ferl, Paul’s colleague and a study coauthor.Photograph: Tyler JonesNASA performed a few experiments following the 1960s and ’70s moon landing missions that brought back lunar material, but those were nothing like what Paul and Ferl attempted. “A small amount of regolith material was placed in contact with the plants, and the data showed there were no major negative effects,” says Sharmila Bhattacharya, NASA’s chief scientist of astrobionics. But Paul and Ferl’s new research is more ambitious. “This is a unique experiment, to actually grow those plants in the regolith, of course with supplementary material. This is the first time, and it’s why we’re quite excited,” Bhattacharya says.Today, NASA doesn’t have much regolith left to share with scientists, but they’ve been gradually handing it out for high-priority research. The agency recently opened up one of the last samples collected, in 1972, to study the regolith in the Apollo 17 landing area. The new Artemis program, Apollo’s successor, is now ramping up, and since astronauts will be returning to the moon in a few years, the agency anticipates many more samples to come.Learning how to grow food off-planet will likely be important, since every gram transported to space takes up room on a craft and adds to its costs and fuel requirements. Plus, in a remote, isolated environment like a space station or lunar habitat, a little greenery could go a long way for the mental health of the crew as well, even if it’s not providing a ton of food. “Having the touch and feel of plants can have psychological benefits,” Bhattacharya says.For these reasons, astronauts and researchers have already begun testing different ways to grow food on the International Space Station. Paul and Ferl’s research could be an important step forward toward space farming. “This is an impressive study for two reasons. They’re using the actual Apollo samples, and they’re applying modern biology tools,” says Kevin Cannon, a geologist and space resources researcher at the Colorado School of Mines, who was not involved in the paper. But it’s possible that other options for growing plants and vegetables without using dirt, like hydroponics, aeroponics, or growing cells in a reactor, might be more efficient for ISS or lunar missions, Cannon says.On the other hand, travel to Mars will require long trips and extended visits. And since the planet’s so far away, it will be even more difficult to ship food supplies, which might make it a better place to try growing crops on a larger scale, he says. Researchers have already started growing plants, including thale cress, in simulated Martian soil, and they could get a shot at experimenting with the real thing when NASA returns samples from the Perseverance Mars rover mission. If it works, a Mark Watney-like botanist-astronaut could one day grow potatoes on the Red Planet—but not until someone works out ways to help Earth plants thrive, instead of just survive, in space regolith.Still, for Paul and her colleagues, space agriculture, or at least space gardening, will be in our future. “Here we are introducing a portion of the moon to biology, and it works. To me, that is so symbolic. When we leave Earth, we will take plants with us,” she says. | Biology |
Rising global temperatures are making it harder for birds to know when it's spring and time to breed according to a new study published in Proceedings of the National Academy of Sciences.
A large collaboration led by scientists at UCLA and Michigan State University has found that birds produce fewer young if they start breeding too early or late in the season. With climate change resulting in earlier springlike weather, the researchers report, birds have been unable to keep pace.
And, the authors write, the mismatch between the start of spring and birds' readiness to reproduce is likely to become worse as the world warms, which could have large-scale consequences that would be catastrophic for many bird populations. Birds' breeding seasons begin whenever the first green plants and flowers appear, which is happening earlier and earlier as the climate warms.
"By the end of the 21st century, spring is likely to arrive about 25 days earlier, with birds breeding only about 6.75 days earlier," said the study's first author, Casey Youngflesh, who led the research as a postdoctoral researcher at UCLA and is now a postdoctoral fellow at Michigan State. "Our results suggest that breeding productivity may decrease about 12% for the average songbird species."
The authors stress that conservation strategies should address bird species' responses to climate-driven shifts.
Determining if the earlier springs will pose problems for migratory birds has been a major goal of biologists for decades.
"For nearly 30 years, scientists have hypothesized that animals could become mismatched from plants as springs begin earlier," said Morgan Tingley, a UCLA associate professor of ecology and evolutionary biology and the study's senior author. "While there have been a few very good case studies of this phenomenon, it has remained a major mystery whether advancing springs will pose a general problem for the majority of species."
When it comes to raising their young, timing matters for birds. If they breed too early or too late, harsh weather could harm their eggs or newborns. But timing relative to food sources matters too: If birds are looking for food before or after its natural availability, they might not have the resources to keep their young alive.
"Critically, we found evidence for impacts on bird reproduction of both the absolute and the relative timing of birds," Tingley said.
Using data from a large-scale collaborative bird banding program run by the Institute for Bird Populations, the researchers calculated the timing of breeding and the number of young produced for 41 migratory and resident bird species at 179 sites near forested areas throughout North America between 2001 and 2018.
Then, the authors used satellite imaging to determine when vegetation emerged around each site. They found that each species had an optimal time to breed, and that the number of young produced decreased when spring arrived very early, or when breeding occurred early or late relative to when plants emerged.
While the majority of birds were adversely affected by variations in the start of spring, several species -- the northern cardinal, Bewick's wren and wrentit among them -- countered the trend, demonstrating improved breeding productivity when spring began earlier. Those species are mostly non-migratory species that can respond more quickly to the emergence of spring plants that signal the start of the breeding season.
By breeding earlier and without the time constraints imposed by migration, the study noted, non-migratory species may also be able to reproduce more than once per season.
But those species were the exceptions to the rule. Even most non-migratory species couldn't keep up with earlier spring arrivals. Overall, for every four days earlier that leaves appeared on trees, species bred only about one day earlier.
For migratory species, that discrepancy means that the time between when they arrive at their breeding sites and breeding itself is likely to get shorter as springlike conditions begin earlier. Birds need time to establish territories and prepare physiologically for egg-laying and rearing their young, so that change could cause even greater disturbances to reproduction.
"North America has lost nearly a third of its bird populations since the 1970s," Tingley said. "While our study demonstrates that the worst impacts of timing mismatch likely won't occur for several decades yet, we need to focus now on concrete strategies to boost bird populations before climate change takes its toll."
The study received primary funding from the National Science Foundation and was supported by researchers from the University of Florida; Pennsylvania State University; University of North Carolina, Chapel Hill; and the Institute for Bird Populations.
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For the second time in five years, scientists are warning about declining human sperm counts. (I wrote about this issue in “Declining sperm counts: Nature’s answer to overpopulation?” early last year.)
Besides confirming the results of an important 2017 study, the authors now note an acceleration in the decline of sperm counts. In other words, whatever is causing that decline is getting worse. The rate of decline has doubled since 2000.
It’s important to remember that when the fertility rate declines below replacement—currently 2.1 births per woman in so-called developed countries—populations shrink. This may not be a bad thing at first since overpopulation and overconsumption are huge barriers to building sustainable societies. But there comes a point when if fertility rates don’t level off and then rise to replacement, extinction become a possibility.
That is apparently where we are heading as a global society. A phenomenon as complex as fertility cannot be explained by one or even a few factors. There is, for example, what is called the “demographic transition,” a theory which posits that the size of households declines as societies industrialize. This could result from many factors such as the empowerment of women (to control their own fertility); improvements in public health and nutrition that reduce mortality among infants and children (making parents less likely to have many children because some are likely to die); the rising cost of raising and educating children; and cultural factors that lead parents to want to have more time for themselves. But some scientists have been pointing to other factors associated with industrialization, namely, the widespread dispersion of toxic chemicals in the environment that can adversely affect fertility; the increasing use of pharmaceuticals; the ubiquitous presence of plastics in the environment and human bodies; smoking; poor diet; and obesity (which itself may be a product of endocrine disruption caused by environmental toxins).
The shocking conclusion of the 2017 study was that if the rate of decline in sperm counts observed then continued, those counts would reach zero by 2045. This latest study concludes that we as a society may be moving even more quickly toward that destination.
Given the monumental increases in world population since the beginning of the industrial revolution, it is hard to imagine a collapse in human population that might be almost as swift. And, yet that is what population biology and this latest sperm count study suggests. If the suspects listed above are major reasons for the decline, it’s hard to see how the monied interests behind them would allow much to be done.
Photo: Human sperm stained for semen quality testing. By Bobjgalindo – Own work, CC BY-SA 4.0, https://commons.wikimedia.org/w/index.php?curid=5654847 | Biology |
Metastatic breast cancer has no cure and has proven stubbornly resistant to one of the most innovative and promising new cancer treatments: immunotherapy.
Now, researchers at Washington University School of Medicine in St. Louis have identified a way to treat the area surrounding breast tumors that have spread to bone so that such tumors become vulnerable to attack by the body’s immune system. When the researchers boosted the activity of certain immune cells, called T cells and macrophages, these immune cells worked together to clear metastatic breast tumors that had spread to the bones of mice, and continued to eliminate tumor cells that eventually returned.
The study is published March 8 in Cancer Discovery, a journal of the American Association for Cancer Research.
Macrophages are myeloid immune cells that attack cancer cells through the body’s innate immune response to general threats, such as tumors or viruses. Such macrophages further activate T cells by showing the T cells what they should be looking for, thereby harnessing the adaptive immune response as well. In this case, these macrophages present T cells with bits of recognizable tumor — called tumor antigens — from dead cancer cells, and the antigens direct the killing activities of T cells.
“After breast cancer has spread to other parts of the body, it becomes extraordinarily difficult to treat; current therapies can only try to slow it down,” said senior author Sheila A. Stewart, PhD, the Gerty Cori Professor of Cell Biology & Physiology. “About 70% of patients with metastatic breast cancer have tumors that have spread to their bones. Our study suggests we may be able to use two treatments — one to sensitize the myeloid tumor microenvironment to immunotherapy, and one to activate T cells — to target these bone metastases in a way that eliminates the tumor, prevents the cancer from returning and protects against bone loss in the process.”
Stewart, also a research member of Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine, and her colleagues found that blocking a molecule called p38MAPK reprograms the tumor microenvironment to become more vulnerable to attack by the immune system, including by immune cells and signaling molecules called anti-tumor cytokines. While a p38MAPK inhibitor alone reduced tumor size, it didn’t eliminate the tumor entirely. So, the researchers investigated whether adding another therapy that activates T cells and boosts their ability to find and destroy the tumor cells could be more effective at eliminating the metastatic cancer cells.
Common immunotherapies — called immune checkpoint inhibitors — are often described as “taking the brakes off” immune T cells, ushering them into battle against cancer. In this case, Stewart described the new approach as “hitting the gas” on T cells, supercharging them to be more effective against the cancer.
The researchers investigated two models of human metastatic breast cancer in mice and found that the metastatic tumors were eliminated in mice that received a p38MAPK inhibitor and an immune therapy called an OX40 agonist, which binds and activates T cells. All these mice were still alive and tumor-free at least 80 days after treatment. Among mice receiving either of the two treatments alone, only about half of them were still alive 60 days after treatment.
“If we targeted the microenvironment to make it more sensitive to T cells and simultaneously hit the gas on the T cells, all of the mice were cleared of the metastatic tumors,” Stewart said. “If we came back after two weeks and challenged the mice again with the same tumor cells, their immune systems could clear those cells as well. It appears that their immune systems developed long-term memory and knew to attack those returning cancer cells. The mice look like they’re basically vaccinated against the cancer.”
Three different OX40 agonists are being investigated in phase 2 clinical trials for cancer, including breast cancer. And p38MAPK inhibitors have been investigated in a number of inflammatory disorders, including rheumatoid arthritis and chronic obstructive pulmonary disease.
“We are hopeful that our study will interest companies that make these drugs, so that we can work toward developing a clinical trial that could investigate this strategy in patients with metastatic breast cancer,” Stewart said. | Biology |
Algae. It’s what’s for dinner. This variation on the iconic US advertising slogan from the beef industry may sound funny, but it’s no joke that the current agriculture system is a major source of greenhouse gas emissions and environmental pollution. In turn, the climate crisis and ecosystem degradation threaten long-term food security for billions of people around the world. Researchers at the University of California, San Diego (UCSD), believe algae could be a new kind of superfood thanks to its high protein and nutrition content. They make their case in a paper recently published in the journal Frontiers in Nutrition that examines the current scientific literature on microalgae, a catch-all term for the thousands of microscopic algal species and other photosynthetic organisms like cyanobacteria found in various aquatic environments. A more efficient food source The review highlights the current technologies for commercially developing and growing microalgae, as well as the scientific and economic challenges to scaling production. While long studied as a source of biofuel thanks to their high lipid or fat content, algae are also attracting interest from researchers because of their potential to be a more efficient food source. “Many of us have known the potential of algae for food for years, and have been working on it as a food source, but now, with climate change, deforestation, and a population of eight billion people, most everyone realizes that the world simply has to become more efficient in protein production,” said co-author Dr Stephen Mayfield, a professor of biology at UCSD and director of the California Center for Algae Biotechnology. For instance, a 2014 study cited in the current paper by Mayfield and his team found that algae can produce 167 times more useful biomass than corn annually while using the same amount of land. Other models predict that existing algae strains could potentially replace 25% of European protein consumption and 50% of the total vegetable oil consumption when grown on available land that is not currently used for traditional crops. “The biggest advantage is the protein production per acre,” Mayfield noted. “Algae simply dwarf the current gold standard of soybean by at least 10 times, maybe 20 times, more production per acre.” In addition, some algal species can be grown in brackish or salty water – and, in at least one case, wastewater from a dairy operation – meaning freshwater can be reserved for other needs. Nutritionally, many algal species are rich in vitamins, minerals and especially macronutrients essential to the human diet, such as amino acids and omega-3 fatty acids. Creating the best algal strain for humans Challenges still remain, starting with finding or developing algal strains that check all of the boxes: high biomass yields, high protein content, full nutrition profile, and the most efficient growing conditions in terms of land use, water requirements, and nutrient inputs. In the paper, the UCSD authors describe the various scientific tools available to produce the most desirable traits for a commercially viable algal product. For example, one previously published experiment described enhancing astaxanthin, an antioxidant pigment that has been shown to have various health benefits, through targeted genetic mutations. Another mutagenic experiment was able to increase both biomass yield and protein content for a different algal strain, particularly when grown in a simple, low-cost sweet sorghum juice. Mayfield said the most likely approaches for commercial development of a superior algal crop would involve a combination of traditional breeding with molecular engineering. “This is the way modern crops are being developed, so this is the way algae will be developed,” he said. “They are both plants – one terrestrial and one aquatic.” Nutrition and yield aren’t the only considerations. Some tweaking of color, taste, and decreasing that characteristic fishy smell may be needed to convert some consumers. Other experiments have already demonstrated the ability to modify these organoleptic traits while boosting protein content in new strains of algae. The need to feed a growing population Indeed, the biggest challenge for commercial development, Mayfield added, isn’t necessarily scientific, technical or aesthetic. It’s the ability to scale production globally. “You just can’t know all the challenges of going to world scale, until you do,” he said, “But the world has done this [with] smartphones, computers, photovoltaic panels, and electric cars – all of these had challenges, and we overcame them to take these ‘new’ technologies to world scale, so we know we can do it with algae.” Mayfield said the need for alternative food systems has never been more urgent, as the human population swells, pushing resources and systems to the breaking point. “The only way to avoid a really bleak future is to start transitioning now to a much more sustainable future, and algae as food is one of those transitions that we need to make,” he said. Journal Frontiers in Nutrition Method of Research Literature review Subject of Research Not applicable Article Title Developing Algae as a Sustainable Food Source Article Publication Date 19-Jan-2023 COI Statement The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: S.P.M. is a founder of, and holds an equity position in, Algenesis Inc. Disclaimer: AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert system. | Biology |
Stanford-led study reveals a fifth of California’s Sierra Nevada conifer forests are stranded in habitats that have grown too warm for them
The researchers created maps showing where warmer weather has left trees in conditions that don’t suit them, making them more prone to being replaced by other species. The findings could help inform long-term wildfire and ecosystem management in these “zombie forests.”
Like an old man suddenly aware the world has moved on without him, the conifer tree native to lower elevations of California’s Sierra Nevada mountain range finds itself in an unrecognizable climate. A new Stanford-led study reveals that about a fifth of all Sierra Nevada conifer forests – emblems of Western wilderness – are a “mismatch” for their regions’ warming weather. The paper, published Feb. 28 in PNAS Nexus, highlights how such “zombie forests” are temporarily cheating death, likely to be replaced with tree species better adapted to the climate after one of California’s increasingly frequent catastrophic wildfires.
Go to the web site to view the video.
“Forest and fire managers need to know where their limited resources can have the most impact,” said study lead author Avery Hill, a graduate student in biology at Stanford’s School of Humanities & Sciences at the time of the research. “This study provides a strong foundation for understanding where forest transitions are likely to occur, and how that will affect future ecosystem processes like wildfire regimes.” Hill led a related study this past November showing how wildfires have accelerated the shifting of Western trees’ ranges.
Understanding and managing zombie forests
Sierra Nevada conifers, such as ponderosa pine, sugar pine, and Douglas fir are among Earth’s tallest and most massive living things. They have stood watch as temperatures around them warmed by an average of a little over 1 degree Celsius or 2 degrees Fahrenheit since the 1930s. Meanwhile, recent years have seen a giant wave of new human residents drawn to the lower elevations of the Sierra Nevada by spectacular scenery, relaxed lifestyles, and relative affordability. The combination of hotter weather, more construction, and a history of fire suppression have fueled increasingly destructive wildfires, making the names of communities like Paradise and Caldor synonymous with Mother Nature’s fury.
Hill and his co-authors started by combing through vegetation data going back 90 years, when the vast majority of human-caused warming had yet to occur. Fed this information, a computer model designed by the researchers showed that the mean elevation of conifers has shifted 34 meters or almost 112 feet upslope since the 1930s, while the temperatures most suitable for conifers have outclimbed the trees, shifting 182 meters or nearly 600 feet upslope on average. In other words, the speed of change has outpaced the ability of many conifers to adapt or shift their range, making them highly vulnerable to replacement, especially after stand-clearing wildfires.
The study estimates that about 20% of all Sierra Nevada conifers are mismatched with the climate around them. Most of those mismatched trees are found below an elevation of 2,356 meters or 7,730 feet. The prognosis: even if global heat-trapping pollution decreases to the low end of scientific projections, the number of Sierra Nevada conifers no longer suited to the climate will double within the next 77 years.
“Given the large number of people who live in these ecosystems and the wide range of ecosystem services they confer, we should be looking seriously at options for protecting and enhancing the features that are most important,” said study co-author Chris Field, the Perry L. McCarty Director of the Stanford Woods Institute for the Environment within the Stanford Doerr School of Sustainability.
The study’s first-of-its-kind maps paint a picture of rapidly changing landscapes that will require more adaptive wildfire management that eschews suppression and resistance to change for the opportunity to direct forest transitions for the benefit of ecosystems and nearby communities. Similarly, conservation and post-fire reforestation efforts will need to consider how to ensure forests are in equilibrium with future conditions, according to the researchers. Should a burned forest be replanted with species new to the area? Should habitats that are predicted to go out of equilibrium with an area’s climate be burned proactively to reduce the risk of catastrophic blazes and corresponding vegetation conversion?
“Our maps force some critical – and difficult – conversations about how to manage impending ecological transitions,” said Hill. “These conversations can lead to better outcomes for ecosystems and people.”
Field is also the Melvin and Joan Lane Professor for Interdisciplinary Environmental Studies, a professor of Earth system science and biology, and a senior fellow at the Precourt Institute for Energy. Hill is a postdoctoral researcher at the California Academy of Sciences. Study co-authors also include Connor Nolan, a postdoctoral scholar in biology at the Stanford Woods Institute for the Environment; Kyle Hemes, a research affiliate at the Stanford Woods Institute for the Environment; and Trevor Cambron, an undergraduate student in the Earth Systems Program at the Stanford Doerr School of Sustainability.
The research was funded by the Gordon and Betty Moore Foundation.
To read all stories about Stanford science, subscribe to the biweekly Stanford Science Digest. | Biology |
In a pioneering study, researchers from Harvard Medical School, University of Maine, and MIT have introduced a chemical method for reversing cellular aging. This revolutionary approach offers a potential alternative to gene therapy for age reversal. The findings could transform treatments for age-related diseases, enhance regenerative medicine, and potentially lead to whole-body rejuvenation.
Groundbreaking Discovery in Aging Reversal
In a monumental study, a team of researchers has revealed a novel approach to combating aging and age-related diseases. This work, undertaken by scientists at Harvard Medical School, introduces the first chemical method to rejuvenate cells, bringing them to a more youthful state. Prior to this, only powerful gene therapy could achieve this feat.
On July 12, 2023, researchers from Harvard Medical School, the University of Maine, and the Massachusetts Institute of Technology (MIT) published a fresh research paper in Aging. The paper, titled, “Chemically induced reprogramming to reverse cellular aging,” extends upon a previously groundbreaking discovery. The researchers are Jae-Hyun Yang, Christopher A. Petty, Thomas Dixon-McDougall, Maria Vina Lopez, Alexander Tyshkovskiy, Sun Maybury-Lewis, Xiao Tian, Nabilah Ibrahim, Zhili Chen, Patrick T. Griffin, Matthew Arnold, Jien Li, Oswaldo A. Martinez, Alexander Behn, Ryan Rogers-Hammond, Suzanne Angeli, Vadim N. Gladyshev, and David A. Sinclair.
Exploring the Methodology
This discovery builds on the finding that the expression of specific genes, known as Yamanaka factors, can transform adult cells into induced pluripotent stem cells (iPSCs). This breakthrough, which earned a Nobel Prize, prompted scientists to question if cellular aging could be reversed without pushing cells to become too young and potentially cancerous.
In this recent study, the scientists probed for molecules that could, in tandem, revert cellular aging and refresh human cells. They designed advanced cell-based assays to differentiate between young and old, as well as senescent cells. The team employed transcription-based aging clocks and a real-time nucleocytoplasmic protein compartmentalization (NCC) assay. In a significant development, they identified six chemical combinations that could return NCC and genome-wide transcript profiles to youthful states, reversing transcriptomic age in less than a week.
Relevance and Potential Applications
The Harvard team has previously shown the possibility of reversing cellular aging without causing unregulated cell growth. This was done by inserting specific Yamanaka genes into cells using a viral vector. Studies on various tissues and organs like the optic nerve, brain, kidney, and muscle have yielded encouraging results, including improved vision and extended lifespan in mice. Additionally, recent reports have documented improved vision in monkeys.
These findings have profound implications, paving the way for regenerative medicine and potentially full-body rejuvenation. By establishing a chemical alternative to gene therapy for age reversal, this research could potentially transform the treatment of aging, injuries, and age-related diseases. The approach also suggests the possibility of lower development costs and shorter timelines. Following successful results in reversing blindness in monkeys in April 2023, plans for human clinical trials using the lab’s age reversal gene therapy are currently underway.
Views from the Research Team
“Until recently, the best we could do was slow aging. New discoveries suggest we can now reverse it,” said David A. Sinclair, A.O., Ph.D., Professor in the Department of Genetics and co-Director of the Paul F. Glenn Center for Biology of Aging Research at Harvard Medical School and lead scientist on the project. “This process has previously required gene therapy, limiting its widespread use.”
The team at Harvard envisions a future where age-related diseases can be effectively treated, injuries can be repaired more efficiently, and the dream of whole-body rejuvenation becomes a reality. “This new discovery offers the potential to reverse aging with a single pill, with applications ranging from improving eyesight to effectively treating numerous age-related diseases,” Sinclair said.
Reference: “Chemically induced reprogramming to reverse cellular aging” by Jae-Hyun Yang, Christopher A. Petty, Thomas Dixon-McDougall, Maria Vina Lopez, Alexander Tyshkovskiy, Sun Maybury-Lewis, Xiao Tian, Nabilah Ibrahim, Zhili Chen, Patrick T. Griffin, Matthew Arnold, Jien Li, Oswaldo A. Martinez, Alexander Behn, Ryan Rogers-Hammond, Suzanne Angeli, Vadim N. Gladyshev and David A. Sinclair, 12 July 2023, Aging-US.
DOI: 10.18632/aging.204896 | Biology |
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