text:
Do muscles still hold glycogen reserves if there is no carbohydrate input
Afaik skeletal muscles take glucose from the blood to store it localy as glycogen, to be used in the case of intensive exercise.
Does this still happen

if the calorie input is exclusively made up of fats and proteins?
while fasting / starving?

I know that muscles can run on fatty acids and ketone bodies.
And that the liver can create glucose by gluconeogenesis.
But is this "backup"-glucose still used to refill the glycogen stores in the skeletal muscles in those two respective cases? (while resting)
If not, how would the performance of exercises like sprinting, that normally make use of those stores, be affected?

Most of it isn't but a little bit is.
When your body has very little glucose and a lot of fat(Which can be the case if an overweight or obese person goes on a low carb diet) the ketones and fatty acids and glucose produced by the liver are used almost exclusively to keep the body alive although a little is synthesized into glycogen.
Specifically when you don't eat anything gluconeogenesis alone supplies enough for 1 day. Then the fat metabolism accelerates because gluconeogenesis is not enough. This is when you get into a state of ketosis(this can also happen in bodybuilders since increased muscle = increased fat metabolism). This ketosis causes fast weight loss from not just water like a lot of other diets but also from fat. This fat then eventually depletes and it metabolizes protein exclusively(during all this time it does metabolise some protein). However that can't continue forever even if the amino acids get reused over and over again because some are used to produce ATP. Thus you eventually would die from starvation with obese people surviving longer than underweight people.
Anyway as far as exercise assuming that you start off obese, getting your body into a state of ketosis makes your performance even better than on just glucose alone after a while of adjusting to fat metabolism since 1 molecule of palmatic acid(16 carbon fatty acid) produces 106 ATP compared to 32 ATP for 1 glucose molecule so your muscles can go longer without being exhausted. Theoretically someone who is 50 pounds overweight could exercise 24/7 for several days if he/she is in a state of ketosis.
Here is a reference to the low glycogen and increased muscle performance:
http://www.bodybuilding.com/fun/glen12.htm
As to why it is 106 ATP it is because each NADH produces 2.5 ATP and each FADH2 produces 1.5 ATP and because of the activation step using 2 ATP just like how NADH transport from cytoplasm to mitochondria takes 2 ATP, 1 per NADH in glycolysis.

interesting, can you add some references? I'm not convinced you can draw any conclusions about muscle performance from the molar ATP yield of fatty acids vs. glucose, those are two very different substrates ... Also, for the original question, is there some data showing that muscle does not synthesize glycogen when on low carb diets? I imagine low insulin would have this effect, but I'm not aware of a study.

Well I looked at some websites and I was wrong about no glycogen being synthesized when the body is in a state of ketosis but there is a very low level of glycogen that is synthesized because of the low insulin. This low insulin also makes the fat be the primary metabolite since insulin causes there to be more fat in adipose tissue.


text:
Genetic Relationship Matrix
The classical definition of the Genetic Matrix
G = ZZ'/2p(1-p)
where Z = M - P
where P = 2(p-0.5)
I don't have a background in biology but understand Maths and Computer Science very well. I am trying to wrap my head around
1) Why do we define P the way we do?
2) Why do we subtract  P from M
3) How to interpret a negative entry in G?
4) Does the j,k element of G give me the genetic distance between j and k individuals?

Welcome to Biology.SE. What is P? what is M? What is this genetic matrix suppose to represent? Is it a matrix of genetic variance and covariance for $n$ traits? Can you link to where you found those things?

Sure, here it is. http://nce.ads.uga.edu/wiki/lib/exe/fetch.php?media=uga_3_relationship.pdf

Any clarifications you could provide would be much appreciated.

source: Stack Exchange

license: Creative Commons - Attribution Share-Alike - https://creativecommons.org/licenses/by-sa/3.0/

sort: votes


text:
Which sequence assemblers I can use to compare different paradigms?
I'm a high school student whose interested in bioinformatics. Therefore I chose a project which I study Sequence Assembly. My main goal is to compare different paradigms (Greedy, OLC, De Bruijn).
I have done my initial research but I don't know which assembler to use for comparing paradigms. Most of them are designed for real world usage, where there are many different factors to consider, but in my case the problem is more like a Computer Science problem: Reconstructing an array of symbols from it's fragments.
If there is no hope, I will try to implement them myself but I want to avoid that since it will very likely to be error-prone and slower than real world implementations.
Thanks!

Well, if I understand correctly, you would need at least three assemblers, one for each of the "paradigms" you wish to evaluate. Do you have a dataset of DNA reads to use as input? What exactly do you hope to determine? Off the top of my head people usually want to minimize the length of time that it takes and maximize the accuracy. Additional variables include the number of compute cores and amount of RAM required. Of course the estimated dollar cost may also be germane. There are very likely several review articles out there that have already made side-by-side comparisons like this.

Velvet is a De Bruijn graph based assembler, the original Staden package usues the OLC method as far as I know, an I think you can write a greedy one for yourself, as I don't know any software that uses that approach.

an article on comparison of OLC and De Bruijn assemblers: http://bfg.oxfordjournals.org/content/11/1/25.full

http://www.sciencedirect.com/science/article/pii/S0888754310000492 this paper may also help. It reviews different algorithms.

@mdperry: Yes, you understand correctly. I initially thought using Human Genome at gutenberg and creating random sequences, then I will cut them into reads. I hope to measure the lengths of the contigs and calculate their distance to initial sequence. Also I want to measure implementations resource (time, processing power, memory) usage. At the end, I want to repeat these tests as coverage and count of repetitive sequences changes.

@poka.nandor: Thanks for the information and the links! I'm currently reading them.

all_licenses: Creative Commons - Attribution Share-Alike - https://creativecommons.org/licenses/by-sa/3.0/


text:
What does it mean when a protein has a different excitation spectra than wildtype, but the same emission spectra?
We have a GFP mutant that displays a different excitation spectra with emission at 510nm than the WT. However, their emission profiles with excitation at 490nm are the same, and we do not observe the same trend.
We're confused as to what might be happening.

@AliceD What you said about emission/excitation is wrong. It is actually the opposite, the excitation is always shorter than the emission as shorter wavelengths are more energetic. The question is therefore valid in this regard. I think he is referring to an experiment they have done rather than a paper. Yet more informations would be indeed quite helpful for providing an answer. For example can you post the actual spectra? Also can you please provide the ranges you used for emission/excitation wavelengths in both experiments?

@cagliari2005 - yep noticed it, and removed comment. Thanks

emission spectra should not depend on excitation wavelength. Only scales.

@aandreev What? The emission spectrum totally depends on the fixed excitation wavelength... And vice-versa for a fixed emission wavelength.

in most practical applications shape of emission does not depend on excitation wavelength. (in range where $\lambda_{em}>\lambda_{ex}$) see here: http://www.olympusconfocal.com/theory/fluoroexciteemit.html

Hi, OP here, thank you guys so much for the help. It turns out there was a calibration error, and when we recollected the data, the symmetry in peak height was observed for both Wt and our mutant. Much appreciated either way!

Let me start from short description of fluorescence (since we talk about it here).
Fluorescence is one of the processes through which excited molecule can relax, lose its excessive energy. That is, quantum interaction between atoms in molecule (organic dye or complex GFP) create permitted energy levels. There is "ground state" $S_0$, for example, and excited state $S_1$. You "pump" your molecule with excitation light from $S_0$ to $S_1$. All this can be nicely illustrated as absorption in Jablonski diagram (look at a for now):

via http://micro.magnet.fsu.edu/
"Loss of energy" here is some process via which molecule returns to ground state. In case of GFP energy is released as an emission photon. Nature of fluorophores is that they tend to return to ground state as the state of less energy, and almost all systems tends to go to state with lesser energy.
Now, to your question. Why GFP can has different excitation profile but same emission? Notice, how in (a) molecule get pumped to highest state, then relaxes a bit to lowest of $S_1$ states and then go all the way to $S_0$? That initial relaxation is thermal relaxation. Some energy is lost, essentially, to water molecules around GFP. That is why emission is always "more red", i.e. has lower energy than excitation. Initial relaxation is why your GFP spectra also broad. There are many levels GFP can emit from, as well as be excited to. In crystals of GFP transitions will be very narrow, because much less of excitation energy will go not into fluorescence.
So, my point is following. Nobody prevents one from engineering a mutant molecule of GFP that could be pumped to some even higher level $S_2$, which then relaxes to $S_1$ via non-irradiative process (e.g. gives energy to water, but not into fluorescence!). Only requirement is that for mutant direct pathway from $S_0$ to $S_1$ would be forbidden (see b and c).
Another point is that whether your spectra are different in shape or only intensity. Different shape of spectra means there are differences in those levels and transitions.


text:
How do signalling molecules find their receptors at large distances?
I have been baffled with this question approx. for a dozen of years for now.
There is a default "lock & key" mechanism of action assumed for the interaction between a signalling molecule and its receptor, but while applying a bit of combinatorics and biophysics to it I find the following inconsistencies.
Suppose a long-lasting neuropeptide is circulating in a CSF or blood macrocirculation. Or suppose a norepinephrine or other neurohormones are released by hypothalamic and pituitary cells into the macrocirculation for sympathetic or parasympathetic signalling. Accroding to the logic of "lock & key" mechanism, in order for a "key" signalling molecule to activate its "lock" receptor an active site of this molecule - the molecule partition which directly reacts with the receptor as it is generally not the whole molecule which reacts with the receptor - should come in direct contact with the relevant active site of its in-membrane receptor. So by such combinatorial logic, if there are thousands of receptors on outer membranes of cells in CSF or vessel endotelium along the way of which this "key"-molecule is travelling, this molecule should try to "lock into" every such potential "lock" receptor in order to "check" if this is the right "lock". In other words, while travelling across long distances such "key" signalling molecules should not just float in CSF or blood vessels as is generally depicted, but slide across all outer cell membranes in CSF or across vascular endotelium in blood or lymph circulation in order to "check" every potential "lock" receptor for finding their relevant receptors for eventual activation. It is definitely not the case, but it the result of applying combinatorial "lock&key" logic.
Somehow it seems (for myself, at least) that it is just assumed that a "key" molecule released at distances which are millions> of times larger than the molecule size should just "lock" for granted into its appropiate receptors throughout the organism. But suppose a "key" molecule travels in CSF or interstitial fluid in the vicinity of its appropriate membrane "lock" receptor, but with the molecule's reaction (active) site pointed away from its receptor or at an angle. Should the "key" molecule not then react with its "lock" receptor?? Is there a minimum effective reaction distance established between a "key" molecule and its "lock" receptor in order to effectively activate the receptor?
The latter argument holds true also for small distance 20-40 nm synapses with molecules released in it whose size would be minimum 1000 times smaller than the synapse size. Should a neurotransmitter molecule not react with its receptor in a synapse if the molecule's active site would be pointed 180 degrees away from the receptor's active site?

Yes, any individual ligand may have the wrong orientation to interact effectively with an individual receptor, but so what?  There are typically thousands of each type of receptor on a single cell1 and there will be many molecules of a given ligand present as well.
For your synapse example, I suggest looking up:

How many neurotransmitter molecules will be present in a synapse
How many receptors will present in a synapse
How many of those receptors need to be bound to get a signal

I think that will help you make sense of this phenomenon and I encourage you to post a detailed answer to your own question!
You might also want to look into molecular dynamics simulations ...
1: Milo, R., & Phillips, R. (2015). Cell biology by the numbers. Garland Science.

The ligand orientation is a subquestion and synapse is a short-distanced space. The main question is related to ligands at long distances, flowing in cardio-vascular, lymphatic systems and between cells, as well as ligands for extrasynaptic receptors.

license: Creative Commons - Attribution Share-Alike - https://creativecommons.org/licenses/by-sa/4.0/


text:
What is a regulable promoter? And how does one regulate it?
I'm reading a patent where they (in S. cerevisae YNP5 strain):

downregulate the ERG9 gene by replacing the native ERG9 promoter with
  the regulable MET3 promoter

What's a regulable promoter and how does one regulate it? Must one add something to the broth to down-regulate the expression?
I don't see anything special in the culture medium.

I believe MET3 is repressed by methionine. The repression procedure (amount, concentration, delivery method, etc.) varies depending on the experiment.

Regulatable promoter means that the expression of the gene downstream of this promoter can be either induced or repressed. Met3 is an example of such regulatable promoters and it is regulated by the addition of methionine to the media. In yeast, Met3 gene encodes for ATP sulphurylase, an enzyme in the methionine biosynthetic pathway. Upon the addition of methionine, the gene driven by Met3 promoter is repressed, as its expression level is reversely correlated with the concentration of methionine added to the media (Figure from this paper):

It would be great if you can also briefly explain what the other "non-inducible" i.e. constitutive promoter is. That will clarify the difference.


text:
Why log pathogen reduction for pasteurization validation and not absolute counts?
I notice that most guidelines for heat treatment processes such as pasteurization or sterilization use a "x-log pathogen reduction" target for validating the success of such processes. e.g. For pasteurization typically the US-FDA mentions 5-log pathogen reduction.
For sterilization I often see a 9-log pathogen reduction target.
My question is: both of these are relative / ratio targets. From a product point of view wouldn't some sort of absolute target on the amount of pathogens (count) make sense?
i.e. If I have a feed which is "unclean" (has a high pathogen count) wouldn't it be easier to demonstrate a certain log reduction? Isn't this metric penalizing "clean" feeds in a sense?

I suspect it has something to do with a given counting method varying in efficiency between implementations. You may not know if a given counter reports 1 in 10 pathogen cells or 1 in 1000 pathogen cells, but that fraction shouldn't vary much over multiple counts and so count ratios should be comparable from machine to machine.

Why log pathogen reduction for pasteurization validation and not absolute counts? From a product point of view wouldn't some sort of absolute target on the amount of pathogens (count) make sense?

Because pasteurization is a manufacturing processes, not a product, it makes sense to define this process in terms of what it achieves. Namely, reducing pathogens. There may be a number of different ways to accomplish this task, and such a process may be used on a number of different products or batches of product with varying pathogen loads. A definition like this helps by providing an objective benchmark for manufacturers as well as inspectors, and often provide criteria for the specific types of organisms which should be reduced in by these processes.

If I have a feed which is "unclean" (has a high pathogen count) wouldn't it be easier to demonstrate a certain log reduction? Isn't this metric penalizing "clean" feeds in a sense?

Using a validated process during manufacturing does not excuse a producer from performing additional testing on finished products when such quality standards are in place. It essentially adds and additional layer of protection to help improve product safety. Absolute counts are often used in quality standards for finished products, in addition to pasteurization process requirements. For example, quality standards for milk, as laid out in the Pasteurized Milk Ordinance (PMO), define the numbers of total bacteria, coliform bacteria, and somatic cells (per milliliter) which may be present in "Grade A" pasteurized milk. But, these methods don't require the organisms present to be specifically identified. So, theoretically a product could contain a relatively high concentration of a single pathogen, but still meet the quality standard based on absolute counts alone. Since certain pathogens of public health concern can be found in unpasteurized milk, it remains important to use a well defined pasteurization process in addition to meeting absolute count standards.

all_licenses: Creative Commons - Attribution Share-Alike - https://creativecommons.org/licenses/by-sa/4.0/


text:
Ways to fight black mold
Is it possible to introduce a microorganism to a colony of black mold that will kill off the black mold entirely and permanently? Is there a common microorganism that likes to eat them and is harmless to us?
In other words, I ask if there's a way to get rid of the mold biologically, maybe a different mold that at least won't stink?
Alternatively, will getting a UV lamp to shine in the opening once in a while be an optimal solution?
I also read that copper sulfate is a popular fungicide with plantations, will it kill and prevent the mold from coming back? Could this ruin the AC with corrosion or be harmful to people if it will be airborne?
I ask this because I have black mold in my AC and I can't take it apart and disinfect it.
PS: it's probably Aspergillus, they're black and make these white structures like in this picture:

I assume by "AC" you mean air conditioner.  What type of unit is it (car, home...?)  Why can't you take it apart to clean it?

Yes it's an air conditioner, it's a home unit. first of all, it's has a copper pipe and power cable that's connecting to the outside unit that I don't know how to disconnect properly so I could take it down. Secondly, it's built such that the fan part is really inside so taking it out means that I'll have to take out a lot of other parts fist. I don't know how to do it and I'm too afraid of breaking it in the process. @augurar

Frankly, I would suggest spraying it with some old fashioned water and vinegar. Creating an acidic environment is a pretty good mold treatment in the home. You should be able to tell if it's working- the color will fade as the mold dies. (Just unplug it first!)

@chauxvive I'm afraid this will stink more than the mold...

Bleach, borax and vinegar are good methods for fighting black mold. Don't work with bleach in the ventilation or mix it with anything! If you go w/ vinegar, you can mix salt into your solution for added effect. Borax is toxic if swallowed, as well, so vinegar is the safest option, and the smell will dissipate.

Well won't salt make it corrosive? I can order copper sulfate instead, it's pretty cheap. @Kendall

Uhh, well you're right, if it's something like stainless steel both salt and bleach would have some corrosive properties. Just be careful with the copper sulfate, too, especially in ventilation because that stuff isn't very good to get on your or in you, either. I'm not 100% in the know about cons for copper sulfate, though!

interesting question, but yet without the expected answer. The new gene editing tools might bring some hope. But until that, the most rational and effective way seems to involve Chlorine Dioxide gas (which kills -deactivates- the spores). But it's far from easy to deal with since the gas has to be produced when needed as a high concentration of the gas makes it explosive.

I write this as an answer instead of a comment because I don't have the reputation to do otherwise (frustrating!) even to edit my answer-which-is-now-a-comment
A weak vinegar solution (maybe 1:1 ratio water and vinegar) will solve your problem and will not stink up your home. Vinegar smell evaporates very quickly and are great for areas you can't reach easily to clean by hand. I promise your AC won't smell like egg salad.
Here's the first mold-cleaning with vinegar article I could find, there are plenty more where that came from

Alright, I'll give it a try.


text:
What is the germ layer origin of human lung fibroblasts?
What is the germ layer origin of human lung-derived fibroblasts?

All normal fibroblasts are mesenchymal in origin, including lung fibroblasts. In certain situations, usually injury related, epithelial cells can undergo an epithelial to mesenchymal transition (EMT).

Even dermal fibroblasts?

Yes, all fibroblasts with the exception I listed in my answer.

The table at http://genome-mirror.duhs.duke.edu/ENCODE/cellTypes.html lists many commercially available cell lines. The four lung fibroblast lines, including adult and fetal, are listed as endodermal in origin.


text:
Do only large birds float?
So, I've noticed a pattern in water fowl (here meaning birds who can take off and land on water, who float in the intervening time) tend to be larger birds.
The smallest I know of are gulls.
Are there any smaller water fowl? Anything the size of a partridge? Or a wren?
If it is only large birds, why is this?

baby swans/ducks/geese?

Many ducks are about the size of a partridge.  And indeed, about the (body) size of gulls, though gulls seem to have a longer wingspan.

There are many seabirds smaller than partridges. The smallest seabird (according to the National Trust of Scotland) is the European Storm Petrel, which weighs in at an average of 28g. That's not quite as small as the European Wren (6 - 10 g), but it definitely counts as 'small', nonetheless.
Being seabirds which spend their life at sea except during breeding, storm petrels float well.
Below is a European Storm Petrel weighing in at less than 35 grams in Fig. 1.

Great answer and hope you appreciate the edit. Feel free to remove as it clashes somewhat with your average weight of the bird.

I'm OK with the picture staying in, but I would make a couple of clarifications. Judging from the fluffy down on the underside, that's an unfledged young bird taken from the burrow. As such, that particular individual may not yet be waterproof. Also, it is common for tube-nosed seabird parents to feed their young until they weigh more than the adults just before fledging (Miskelly et al (2009) Biological Conservation 142(10):1965-1980). This way, they have some fat reserves while they learn to forage.

The Cotton Pigmy Goose for example is about 26 cm long and weight about 160grams (smaller than a grey partridge) can take off and land on water. Have a look at this video for example.
As @WYSIWYG said, any young of "water fowl" species are small and are still "water fowls".
I would also bet that if you put a dead hummingbird on standing water, it would float! It obviously wouldn't be able to take off though.

Perhaps the hummingbird would float, but could it then take flight? ;)


text:
Question regarding aposematism
Are all aposematic insects chemically defended? Can there be insects that mimic chemically defended insects that are also aposematic?
Any ideas?

I think you're talking about Batesian mimickry. For example, hoverfly species without stings mimic wasp species (with bright black and yellow striped patterns) which do have them. And there are several examples in the butterfly world. Males of the species Danaus chrysippus are inedible due to their consumption of plants containing toxic chemicals. They are also aposematic. Females of that species, as well as butterflies of other species, mimic D. chrysippus males. Can you let me know if this is the sort of thing you're asking about, so I can turn this into an answer if so?

@Astrid_Redfern The question asks "are all aposematic insects chemically defended"? The way I see this is: "Is part of the definition of aposematism, that the insect that has this attribute is chemically defended?" I want to be sure about the answer, but the main thing that confuses me is this: "Can an edible insect that mimics an inedible model with bright colors or some aposematic-like attribute be defined to be aposematic?"

I think the answer to the question would be "no, an aposematic insect must be chemically defended, if it is not, and it is a mimic, then it exhibits batesian mimicry, not aposematism.

@Astrid_Redfern what do you think?


text:
identifying OTU interactions / hubs
I would like to know how can i run a network analysis for identifying major OTUs hubs. I wish to build a network of co-occurring OTUs found in different soils samples.
I've started going through the VEGAN R package but i'm not sure it's what i'm looking for.
any recommendations network analysis packages ?
thank you!

Can you better define "major OTU hubs"?  Are you attempting to build a network of co-occurring OTUs and observe groupings?  Please revise your question.

can you tell us what your starting data look like? raw reads? count tables?

I am going to assume you have a count table that you are starting with. Every tool you decide to use is going to have its own respective instructions so let me get you pointed in a direction to find one that works for you.
I wrote a simple R package for my lab awhile back but there are much better ways to put together Co-occurrence networks (in no particular order):

SparCC
CoNet
MENA
Spiec-Easi
MDiNE

Now speaking specifically about "hubs", "connectors", and other keystone organisms, I would recommend reading more about what they are and how they were developed. Again, I have a brief summary here but the original "hub" came from a paper on bee pollination networks


text:
Can microorganisms (e.g. bacteria) be damaged or killed by 253,7 nm light?
The question arose in a hospital, where I saw these flyers advertising lamps that emit such light. It was claimed that they can clean the air of microorganisms up to an arbitrary degree.
Does anyone know if that is a thing? (If it is, doesn't it also kill the beneficent types of microorganisms?)
Online I found quite a bit on the matter, but only from other distributors of similar installations.

This is UV-C radiation and light of this wavelength (which is emitted by low pressure mecury lamps) can indeed be used for disinfection purposes. The nucleic acids (DNA and RNA) has an absorption maximum for UVC radiation at 265nm, causing DNA/RNA damage. The radiation of the mercury lamps is only a little below, making them still quite effective (see the image from here):

This is used in "Ultraviolett germicidal irradiation" for example in water disinfection systems or also for workplaces. The problem with this irradiation is that it causes severe sunburns (and very fast) and also causes plastic materials to decompose (like leaving them in sunlight but much faster). Since I know the precautions for using such devices at workplaces, I wouldn't consider them safe for home use.
The other problem is that you need a pretty clean area for the radiation to be effective. We have to clean our work benches for doing cell culture work entirely so that no shadows are cast in which the UV radiation wouldn't be working since the area is shielded. Imagine this for your home. Additionally I think the fear for germs at home is massively overrated and that there is not need for theses devices at home.

Wow, thank you very much for this fast and concise answer! I wasn't thinking about using it at home^^, just wondering if it was a scam.

@Grantwalzer I wouldn't call it scam, but mostly these are useless for the home use. And most user would probably buy it for this purpose.


text:
Macrophages and what they consume
Do macrophages in the dermis consume any foreign invader to the body, or simply pathogens and cellular debris?  For example, would macrophages consume vitamins or medications injected into the dermal layer of the skin?  Thank you

Macrophages take up pathogens to present them to other specific immune cells. The things they take up via phagocytosis have specific markers on them called PAMPs (Pathogen Associated Molecular Patterns). Hence they won't phagocytose locally injected substances (until and unless it has a PAMP like region).

This is utmost interesting to me (so long ago you answered) in the framework of Corona crisis and the newly introduced RNA-vaccines. These come in "Nano Lipids". Would you say they are being uptaken by phagocyt.? ( their antigens must be presented by APC for vaccination to be effective). Infering from your answer: Nano lipd particels wouldn't be "deliberately" engulfed and taken up (I like your answer as it alludes to some relationship between receptor uptake and presentation) - nanos would be uptaken through diffusion - not different from any other cell that is no APC?

Macrophages and dendritic cells generally recognize large foreign complexes. They often do this through the recognition of pathogen or damage-associated molecular patterns (PAMPs or DAMPs). Otherwise, cell-mediated pathways involve cyto/chemokines which direct macrophages and the like in the region. We also have to consider, does the compound in question belong in the region, or is it insoluble amongst the tissue? In these cases, the compounds are also degraded/engulfed. So how does the body go about recognizing small, soluble foreign molecules?
These are called haptens. If these small molecules can bind to a larger carrier complex in your body, so that it now looks like there's something foreign, regardless if the initial carrier complex was foreign or not, this may present cause for immunologic reponse (as in the mechanism of urushiol, the toxin in poison ivy). There are certain T-cells, like NKT and γδ T cells, which can "see" these antigens despite their lacking a type I or II MHC presentation.
The short answer is it depends on what the injected drug does once it begins interacting with your physiology. Vitamins, on the other hand, are regularly uptaken by cells for metabolism, and I wouldn't imagine macrophages engulfing exogenous vitamins outside of it's needs on their own.
Source: Cellular and Molecular Immunology, 8th ED.

"... or is it insoluble amongst the tissue..." Would you say, current covid vaccine "nano lipid particles" are insoluble in that sense? By any chance, are your familiar with "lipid particles"? And, please correct: I do think, with "lipids", that they "they turn the other cheek", that they have a non-polar coating, outside. I have heard, by the way, that lipids may become polarized, attracting proteins, in the blood.


text:
Trying to understand the big picture behind DNA sequencing, alignment and searching
I'm about to start a bioinformatics research project but I haven't any biological background.
I know my project is in regards to a performance analysis of DNA sequencing and searching "weapons" like Hadoop, Apache Spark and Apache Flink - so I've spent the last couple of days trying to put together the "DNA picture" before I get started with the programming stuff.
My understanding of the situation is that:

Next-generation sequencing (NGS) techniques are used to efficiently provide reads of DNA (conversions from real, physical DNA to something that can be read and analysed), however today's most practical methods provide reads that are short and in disorder.
Reads tell us which nucleotides, labeled one of ACGT, occur in sequence. Different nucleotides or values to take their place may exist, like N or X. Reads could range from 50 to 1000s of nucleotides in length depending on the method of sequencing.
You can find historical raw read data in various places online, including the Sequence Read Archive (SRA). The same website contains lots of other DNA/bio related information. Reads are commonly stored in .fasta files which follow a simple and practical standard. A single file could contain a very small or very large read or sequence.
Reads are then provided to DNA alignment programs like bowtie which will place them back in the correct order. The algorithms could use a template sequence to align them, or run "de novo" (without a template). The result of these alignments have also been indexed online however for the purpose of my studies I'll probably be aligning them myself.
Once aligned (or maybe during alignment), nucleotide differences from a template sequence can be programmatically found or searched for, with crossbow for instance. Note that many other tasks can too be performed - not only this search. If a particular substitution occurs in more than 1% of a what I think is called a "genome's" population, then it is called a Single-nucleotide Polymorphism (SNP or snip). Most SNPs have two alleles, or two different recorded nucleotides (like either G or C), but more than two is possible.
SNPs can be studied and mapped to various conditions or characteristics. A particular nucleotide could be responsible for part of one's emotional tendencies, reaction to particular medicines, or maybe anything, so a particular SNP could make a big difference.

What am I missing/what did I get wrong?

Did you find an exemplary/representative application that highlight usage of Spark or Flink (Hadoop MapReduce is dying AFAIK)?

@Phil It appears as though Flink has yet to gain significant traction, but Spark is well on its way. This is observable as a rough trend in table 1 of my draft literature review (https://bilalakil.github.io/mphil/assets/literature-review.pdf) - there you can also see that Hadoop isn't quite dying yet. Again, that's a very rough form of measurement, however it should be fairly indicative of trend. I've yet to describe such a explary/representative use of Spark thus far.

Here's a quick summary of a few mis-hits in your otherwise good analysis:
Not many bioinformatics applications use Hadoop, Apache Spark or Apache Flink. In fact, I have never heard of the Apache Spark and Flink tools, and I've seen only 2 people use Hadoop to process alignment files.

Reads are not "converted" real, physical DNA. They are representations of the signals from the molecules making up the DNA, as read by sequencing machines.
A,T,C,G are molecules making up DNA. N refers to "any of A,T,C,G", which translates to either unknown or ambiguous.
Reads are stored in FASTQ files. Sequences are stored in FASTA files. Reads include sequence as well as quality information, so, FASTA+QUAL=FASTQ
Re-ordering is a crude but approximate way to think about it. Remember, this process involves overlaps while reordering seldom does. Overlaps are crucial to the process of assembly/alignment. You are correct about the alignment to reference sequence and de novo assembly parts.
This is correct, though statistical models are applied to account for differences that are not necessarily significant variants (such as for sequencing errors)
Yes, variants, which include SNPs, can be correlated to differences in phenotype (traits). Emotional tendencies is something a bit too advanced, think of something more basic like diabetes or eye color.

The picture you have here is of a regular NGS analysis pipeline. This involves alignment/assembly, variant calling and biological analysis with relevant hypotheses. The assembly/alignment is the most computationally expensive part, and we use either HPC clusters or scalable cloud services such as AWS to get this done.
You should definitely talk to a biologist that has some computational experience to gain insight into the reason behind our analyses. Once you understand the motivations, your contribution will be more relevant and helpful to the community.

Mind my naivety, but if A, G, C and T are molecules, then what's a nucleotide?

@BilalAkil Nucleotides are a type of molecule. A, G, C, and T are both molecules and nucleotides

A nucleotide is a phosphate, pentose sugar, and a nitrogenous base in the most general sense. The A/C/G/T are derived from the type of nitrogenous base affixed to the sugar-phosphate.

@BilalAkil I wished to avoid as much biology as possible, hence the term "molecule". a nucleotide is a biological molecule with a sugar (ribose/deoxyribose) and a nitrogenous base (adenosine, guanosine, cytosine, thymidine) attached to it with a phosphate bond. The first part determines if the nucleotide is a part of DNA or RNA, and the second determines the base. DNA is a macromolecule, a super large molecule build from smaller constituent molecules :)

RAM's answer is very good, I'll just add on the computational side, short reads are error prone.  That's important to account for when aligning or assembling.  The reads themselves can just be inaccurate, which we detect by having multiple reads overlapping by a lot; we assume that stray discrepancies seen in only a single read at a position are errors.  Also, if a reference genome is not quite close enough to the sample, reads might be misaligned.
The genomes of many organisms also have repetitive elements which can make it hard to correctly align reads, and hard to make an accurate reference genome.
And note that there can be many more discrepancies other than single nucleotide substitutions, though anything more involved can be challenging to detect with short read data alone.  And most traits that are actually interesting to study are polygenic, so it's not exactly easy to say that one difference in DNA causes a detectable difference in phenotype.

Thank you. I did not wish to delve deep into the complexities we face. Pathogenic Single Nucleotide Variants in single-gene diseases are the easiest example of mutations with a phenotypical effect, aren't they? Note to OP: 1. Pathogenic, 2. single nucleotide, 3. single-gene 4. diseases, 5.phenotypical effect are the points of variability, each with at least 4 other entities that can take their place - the combinatorics give you the possible categories. Imagine the research when most of what we do it try and assign these categories to thousands of variants!


text:
Are These Oyster Crabs?
I found these crabs at the end of September, 2018. My family was vacationing on the coast of Lopez Island in the Pacific Ocean off of Washington State. I have been trying to figure out what they are ever since.
I found two crabs, one that was orange and black, and another crab that was off-white and black. They are both about an inch and a half across and an inch from front to back. I did some research and the closest match I could find are oyster crabs, which are found inside oysters on the East Coast of North America (I found my information on oyster crabs here).
However, I found these inside clams on the West Coast. Also, the pictures of oyster crabs I can find online (figure 1) do not look like my oyster crabs. I was wondering if anyone can identify these crabs. Sorry about the picture quality and thanks in advance!

[Figure 1: A picture of an oyster crab that I found online. There are not very many pictures of oyster crabs online, and they all look similar to this one.]

[Figure 2: The back of the two supposed oyster crabs I found. They are not fighting, I just put them close together for the picture.]

[Figure 3: The front of the off-white supposed oyster crab. In the picture, you can see its tiny eyes and small mouth, along with the claws.]

[Figure 4: The front of the orange supposed oyster crab. In the picture, you can see its tiny eyes, small mouth, and claws.]

[Figure 5: The back of the orange supposed oyster crab.]

[Figure 6: The back of the off-white supposed oyster crab.]

[Figure 7: The undersides of the two supposed oyster crabs. As you can see, they both have eight legs and two claws, making them crabs and part of the crustacean family.]

What you have found are pea crabs, which have a fascinating life history of parasitism. https://www.whitestoneoysters.com/blogs/an-oyster-life/what-the-shuck-is-a-pea-crab

Thanks for answering this question! We appreciate when new users with expert knowledge begin answering questions! Please update your post, however, to include more information about why your ID is correct. Given the propensity for external links to go defunct, we ask that your answer here can adequately stand on its own in explaining both the correct answer and your rationale. Support as a link is fine (and citing/linking sources is preferred/required), but please capture some of the relevant detail from your external source in your post itself. Thanks!


text:
Can an injection of unipotent stem cells cause teratoma?
I understand that injecting pluripotent stem cells causes formation of teratomas.
Does injecting unipotent stem cells also cause teratoma?
If it does not form teratoma, is the injection of unipotent stem cells a safer way to heal/regenerate the tissue that was damaged?

As I understand it they are less harmful because unipotent stem cells differentiate into only one specific cell type and form a single lineage, whereas pluripotent stem cells can develop into all three germ layers, which can result into teratoma, but an injection of unipotent hESC can also form malignant tumors (which teratoma can as well -> A "benign" grade 0 (mature) teratoma nonetheless has a risk of malignancy. Recurrence with malignant endodermal sinus tumor has been reported in cases of formerly benign mature teratoma, even in fetiform teratoma). Just my understanding - hence the comment

"Can an injection of unipotent stem cells cause teratoma?" No, because they form a single lineage and therefore can't lead to teratoma or so called dermoid cyst/twin cyst. "..is the injection of unipotent stem cells a safer way to heal/regenerate the tissue that was damaged?" remains to be answered by someone with more knowledge and sources of scientific research regarding this topic..

Sir/Mdm, what does hESC stand for?

Human Embryonic Stem Cells - often abreviated as HESC or hESC


text:
Do phagocytes need antibodies to be able to engulf pathogens (to function)?
I recently saw a question about monoclonal antibodies, that are specific to a certain virus, being split (into their constant and variable regions via an enzyme), and the question asked whether some statements were false or true.
One of the statements said that the virus could be engulfed by phagocytes if any were present. The statement turned out to be false and I'm not completely sure why. Is it because phagocytes need fully intact antibodies to function so that they can attach to them via receptors specific to the constant region of the antibodies consequently becoming attached to the virus and so being able to engulf it?
I thought that phagocytes could work on their own and that antibodies just made their job easier. Is that assumption correct?

Phagocytes don't necessarily need antibodies to recognize intruders, i.e. by presence of non-self sugars. Additionally, phagocytes can aid amplification of effective anti-bodies by presenting degraded pathogens to the adaptive immune-system. I found this concise summary of the innate immune system, that I would strongly recommend to read!
Now to your more specific question: Detection of viruses. You have to consider, that viruses are highly optimized to evade the innate immune system:
Viruses can happily replicate and mutate without proof-reading without negative consequences and with relatively low conceptual constraints, as they are so simple, compared to cells. This is why the innate immune-system is prone to miss viruses (at least those, that are optimized for a certain species). Imagine how big of a genome you would need to cover all possible viral substances by at least 1 innate gene! Read about hyper-mutation to understand the role of antibodies to detect even these highly evasive viruses.


text:
Manual Primer Design for a gene on the reverse strand
My question might sound very naive and stupid but I am hopeless now. I read so many websites and pages but could not figure out this PCR primer design thing completely.
Some genes are on the reverse strand of the DNA as we can see on the certain databases. Like this:

Source: http://www.wormbase.org/species/c_elegans/gene/WBGene00019616#0de1-9g4356caf-3
So when I click and get the sequence data of that gene, it also says it's on (-) strand. My most potentially silly question is: Do I just copy paste that sequence and try to find my primers manually or do I need to get a reverse complement of that sequence to make it (+) strand so I can design my primers? This minus, plus stand and reverse complement thing confuses me a lot! And I also do not get why do we get the reverse complement of the reverse primer sequence once we design it.
Thanks for the help in advance!

Not a stupid question at all. I was just as confused by this as a beginner in molecular biology. You get the hang of it after a while. :)
I find it much more difficult to design primers from just one strand, especially the minus strand, so I always try to get both to work with. If you don't feel like doing that, just one strand is sufficient (plus or minus), but I would recommend at least getting the reverse complement in your case because plus strands are much easier to work with.
For a quick example, let's say I have a ten bp sequence I want to design primers for and this is my plus sequence:
5' ATAACTTCGT 3'
Now let's say I want a three bp primer. So the forward primer would simply be 5' ATA 3', that's easy. The reverse primer, if I just take it from there without flipping it, would be 5' CGT 3'. But if I put that into my PCR reaction, it will not do anything because DNA binds to it's complement strand, meaning that primer would only bind to 3' ACG 5', or 5' GCA 3'. So instead, I'm going to want 3' ACG 5' because it will bind to its compliment, the 5' CGT 3' part of my sequence. (Technical issue here, suppliers usually only give the option to write in 5' to 3', which makes sense, but you must remember to flip your reverse primer before giving it to them because it will be in 3' to 5' originally. In this case, I would ask for 5' GCA 3'.)
This is easier to visualize if I have both the plus and minus strand though, which would look like this:
5' ATAACTTCGT 3'
3' TATTGAAGCA 5'
If you have both strands like the example above, you can find both the forward and reverse primer without much difficulty.
I could give a more comprehensive answer of how this all works out during DNA replication that would involve illustrations, allegories, and maybe a few mildly humorous jokes, but I would hate to bore you unnecessarily, so let me know if you understand now or if you need more. ;)
Edit: Exactly (to your third comment I mean)! Remember, DNA is always read and replicated 5' to 3', so the forward primer will bind to the minus strand and be replicated 5' to 3', so will extend the sequence to the right. The reverse primer is the opposite, 3' to 5', so it will extend the plus strand to the left. After both of those happen, you will end up with two full strands. As promised, here is an illustration:

Now, to your question about Primer-BLAST. You do not have to enter a plus strand, but the tool is assuming that you are entering the plus strand, so you will get the right primers, it will just call them the wrong names (i.e. with the example above, it would give you 5' GCA 3' as your forward primer and 5' ATA 3' as your reverse). The forward and reverse primers are treated exactly the same, so this wouldn't throw off your PCR, but it would be incorrect nonetheless. To avoid confusion, I suggest utilizing a tool to reverse-compliment your minus sequence into plus before running it. It's rather easy to get the reverse compliment of any sequence; here is a good tool for that.
I hope this helps. :)

Thank you very much for the answer with a positive attitude. :) It indeed helped me to establish some concepts in my head. If you feel like elaborating your answer and have time for it, feel free to do so, I would read it with pleasure :)
However, some confusion continues. When we design a forward primer, it is to bind to + strand, and reverse binds to the - strand, no? So if I am correct, wouldn't the fwd primer: 5'-TAT so it binds to 5'-ATA? And rev: 5'CGT so it binds to 5'-ACG on - strand? Or am I completely wrong now?

And another thing: If I decide to use primer-BLAST to design primers, do I still need to reverse complement the sequence or it does not matter anymore it is + or - strand as the program will calculate the possible primers?

Oh no, ok now I got it. Fwd primer extends the - strand and rev is the other way around. So what you say definitely makes sense now. But my BLAST question is still on :)

Thank you very much :) Finally I can design some primers! Have a great day.

My pleasure. :) Good luck!


text:
How did the Spanish Flu disappear?
In 1918 through 1920, an Influenza pandemic colloquially named the "Spanish Flu", ravaged the world. It infected about half a billion people, and killed as many as 50 million people. But my question is - how did the 1918 flu virus disappear in 1920?
One can hardly believe that after infecting half a billion people, the virus was contained in any sense of the word. Why didn't the more than one billion uninfected people get infected? Why didn't we see some small epidemics continue to circulate the globe infecting the yet-uninfected as well as newly born people for many years - potentially until today?

What research have you done on the epidemiology of flu virus infections, before posting here? The Spanish flu was no different in that respect from the Asian Flu of the 50s, or last year’s flu strain. (Some would say that epidemiology is off-topic here, as it is some distance from biological mechanisms, but if you ask questions here you need to demonstrate that you have researched them first. )

I tried to see if there was any similar question on this site, and found none. I tried to Google a bit and didn't find any answer. I thought that even if an answer could be found on the Web, it wasn't obvious (at least to me) how, and it would be useful to have an answer here, on this site, for posterity. If "epidemiology is off-topic here", were is it not offtopic? Please note that I wasn't asking why the Spanish Flu is no longer a pandemic. I was asking why it went completely extinct. Is there something in the flu virus which makes it a particularly bad surviver compared to other viruses?

Another clarification: I know there is no reason why the Spanish Flu had to remain particularly common. It could remain one of hundreds different viruses going around - flus, "common colds" and so on, and reach a few people here and there. But the particular 1918 strain was very visible - it killed a large percentage of people infected. If this virus was still extant, wouldn't we see small deadly flu epidemics in various places over the last 100 years? What in the flu virus or the circumstances allowed that not to happen?

It's didn't disappear.  It's still around today, over 100 years later.  The 1918 influenza virus is the parent virus for all the human seasonal influenza viruses that are around today, as well as for most of the swine influenza viruses out there.
In fact, the presently circulating H1N1 viruses in humans are close enough to the 1918 virus that they probably immunize against each other (Seasonal trivalent inactivated influenza vaccine protects against 1918 Spanish influenza virus infection in ferrets.).
What did happen is that the 1918 virus mutated, becoming less virulent in the process, within a year or so of entering the human population. Why? Presumably because, after infecting virtually the entire human population in its first year, there was so much population immunity that it needed to mutate a little in order to continue to infect. That is, after all, what flu viruses do.
But it continued to circulate for decades, as a very similar H1N1 virus. Also, it almost immediately infected pigs and became endemic in the swine population, only to resurface  after 90 years to cause the 2009 influenza pandemic.

In 2009, persons who had lived through the first decades of the 1918 pandemic H1N1 era, especially those born before about 1950, were substantially protected from the 2009 pandemic virus by having acquired immunity to the antigenically similar H1 or N1 of the 1918 virus, or both, or to the descendant seasonal H1N1 viruses that circulated over subsequent decades. This is because the 2009 H1 gene was a 1918 viral progeny that had survived for more than 90 years, with minimal antigenic drift, in a domestic pig “time capsule.”

—The Mother of All Pandemics Is 100 Years Old (and Going Strong)! (Am J Public Health. 2018 November; 108(11): 1449–1454)
In 1957 and 1968, the H1N1 virus reassorted with avian viruses to generate first H2N2 and then H3N2 viruses (the great-grandchildren of the H3N2 pandemic still circulate today). But most of the internal genes in those reassortants remained the 1918 versions.
So the 1918 flu never went away. It’s still killing hundreds of thousands of people every year. It’s just that everyone has got used to it, and thinks it’s fine and normal to have hundreds of millions of influenza cases every year.

Thanks for the detailed and informative response! The reason why I'm still puzzled by all of this is that the 1918 strain was distinctive in that it killed a very large percentage of young, otherwise-healthy, of infected individuals. Somehow we're not seeing this phenomenon any more.  Even if the original strain mutated to create 100 different strains, if the original strain was still around as well, wouldn't we have seen small local epidemics of it from time to time killing large percentages of the healthy adults in certain towns, etc.?

We don't know in detail why the 1918 flu was so virulent; we do know that the surface protein hemagglutinin (HA) was a significant part of it, and we know that the HA of flu viruses changes very rapidly in response to population immunity pressure. The presumption is that virulence depended on a very narrow and precise sequence, that changed as a result of adaptation to human immunity - probably because virulence per se was not an adaptive  trait but was simply a side effect of other factors.

nice answer! Another related question: Before 1918, there were other influenza viruses circulating? The 1918 influenza was of a zoonotic origin? Where did it came from?

1918 was an avian influenza, perhaps passed through swine before infecting humans. Many strains of influenza circulated before 1918, but we don’t know much about them because we don’t have samples. There were many pandemics, presumably zoonotic, most probably avian origin but perhaps also equine

Check out the below link where I have put a graph on why it killed more young people. I have also linked there a PNAS article if you're curious. https://biology.stackexchange.com/questions/95652/when-someone-gets-infected-with-the-influenza-and-gains-some-immunity-is-that/95667#95667

worth noting that the war created nearly the perfect conditions to favor more virulent strains, since no matter how quickly it spread new solders were cycled in to feed it. eliminating at least one condition that normally disfavors virulence, running out of hosts too quickly.

Although the accepted answer is good and very possibly correct, I was never fully convinced by it. It describes a situation where less than a third of the world's population was infected, and yet for some reason the virus had to mutate to escape immunity to continue spreading, while the original violent strain died off. This would only make sense if the flu's R was so low that at 30% population infected, we reached herd immunity. I don't think this is plausible - unless the flu was grossly under diagnosed.
I recently read a different theory which I found more convincing:
The alternative theory posits that the flu virus often mutates in a way that does not evade immunity. In other words, being infected with one mutant protects you from the another. Now, consider that the violent virus (that appeared in the second wave of 1918) further mutated and a less violent mutant appeared.  It is likely that the new mutant will have a higher R than the original. This may happen both because of a-priori reasons (namely, a less violent strain would lead more people to go out and spread it) and for a-posteriori reasons (namely, we only noticed a new strain when it has an higher R than the original).
Now we have a less violent mutant with a higher R than the original violent strain. The less violent version would spread faster than the violent one, until more people are inected with the less violent one than the violent one.
Remember that we assume that catching any one of the two strains immunizes you to both, so both strains R number begin to go down, until the old strain's R is below 1 while the new one is above R. At this point the old strain goes extinct, while the new strain continues to spread for a while longer. Moreover, as the new virus is less scary, people relax all their prevention measures (masks, social isolation, etc.) so its R increases even more, allowing it to infect even more people before reaching herd immunity.

Re: " It is likely that the new mutant will have a higher R than the original." Isn't this just the same as the original answer? "there was so much population immunity that it needed to mutate a little in order to continue to infect." - that is, it had a higher R. Remember, some of the human population already had resistance to the 1918 strain, whether because of prior exposure to a similar strain, or because of some gene polymorphism.

The original answer posits that the new mutant has a R higher than the original's because the new mutant strain escaped immunity that the population had to the original strain. My question about this is why, under that assumption, they couldn't both serotypes continue to spread if you could get infected with both. So my new answer is that maybe you couldn't get infected with both - there was no immunity escape - getting the mild strain protected you from the violent strain (and vice versa), which can explain why today we see only the milder strain.

I think you are perhaps assuming that the "other" 2/3 of the population lacked immunity to the original strain. The working hypothesis seems to be that in fact they DID have some immunity already, whether because of past exposure to related strains or because of the versions of genes in their immune systems, and so the original strain petered out. My understanding is that in recent times we have not observed any individual strains persisting for more than a year or two, so I am not sure why the original Spanish Flu strain would behave any differently.

This review may be of interest: "The evolution of seasonal influenza viruses"  https://www.nature.com/articles/nrmicro.2017.118.pdf

@Armand "they DID have some immunity already ... because of past exposure to related strains" - that's an interesting reversal of the theory I mentioned. So it's not that the mild strain evolved after the violent strain, but perhaps the opposite - the mild strain evolved first, infected most people on earth until 1918 but nobody really cared because it was a mild flu, and when in the second wave of 1918 it mutated and became violent (but still with the same antigens), it could only infect about a third of the population before herd immunity was reached and the violent strain died out.

@Armand but then the question becomes - why didn't the violent strain do what all other strains do since - mutate their antigens to evade prior immunity. The theory I mentioned might solve this question - if the violent strain was first replaced by a less violent strain with the same antigens - and only then did the antigenic drift occur.

Sorry, I guess I'm not being clear.  Flu has been around for thousands of years, it mutates all the time, both on its own and by incorporating segments from e.g. animal viruses. I think you're overthinking this, focusing on one or two strains and ignoring the rest at a short moment in time and not considering the past exposure history of the population. Check out the reference I mentioned above.

Currently COVID-19 Omicron variant and its subvariants, each subsequent one with lower virulence, but higher transmissiblity, seem to provide real-time evidence in support of the "crowding out" theory. Note however, that the increase in transmissibility is not the only viral strain "success factor" here, because it is hard to distinguish from growing immune evasion causing re-infections.

Right, the COVID-19 pandemic is a good test-case for "my" (I didn't invent it...) theory: Before 2020, nobody had any prior immunity to COVID. Because of quarantines etc, and vaccines, when Omicron arrived, only 50% (say) had any prior (even partial) immunity. But Omicron had higher R and people who got Omicron had partial immunity for the previous strains - so the previous strains all died out.


text:
Should fat calories' numerical values be increased to better reflect the new scientific findings?
According to a study discussed on this website, people lose more weight on a calorie restricted fat reduced diet than on a similar calorie restricted carb reduced diet.

Is this study a fair dinkum, non-bogus study?
If so, shouldn't fat calories' numerical values be increased to better reflect the new scientific findings?
And if so, how should this be done?

Because the calories of food are not estimated with a dice but with a calorimeter.

@Chris. That is the present way of doing it. In light of new scientific evidences, isn't it time for an overhaul of the method? Or are you saying that this study is false?

I am not saying the study is false, but a certain amount of food has a measurable amount of calories. This will not change because a social construct demands changing it.

I’m voting to close this question because it is about the articulation of dietary advice, rather than a problem in biology.

@David. A calorie is “the amount of heat needed to raise the temperature of 1 kilogram of water from 0 to 1 degree Celsius”. There seems to be contention between chemistry and biology here. Maybe it is time to distinguish between dietary calories and calories in general.

That single definition is fine as heat is a form of energy. The digestion of food involves oxidation of molecules but the energy released by this is not only in the form of heat but also chemical energy that can be used to build new large molecules including, but not exclusively, fat, or mechanical energy to do muscle work. The new molecules synthesised will depend to some extent on the constitution of the food — what small units it is broken down to. So although calorific value may be a general indicator of whether a foodstuff will make you put on weight it cannot be an exact measure.

It should be pointed out that the study doesn't conclude that "people lose more weight on a calorie restricted fat reduced diet than on a similar calorie restricted carb reduced diet." More like, some people in study lost more weight. But a study sample size of 19 without a non-intervention control group isn't nearly enough evidence to make inferences about the human population as a whole.

@MikeyC It is also an extremely short study of what is supposed to be a long-term effect (to be of any practical relevance).

Calories is a unit of energy, which cannot be changed. The efficiency of using the energy coming in different forms is however different. The original article in which the study was reported points out that indeed the matter at stake is the balance between the fat consumed and the fat burned:

The most sensitive method for detecting the rate of body fat change requires calculating daily fat balance as the difference between fat intake and net fat oxidation (i.e., fat oxidation minus de novo lipogenesis) measured by indirect calorimetry while residing in a metabolic chamber. At the end of the diet periods, our study had a minimum detectable difference in daily fat balance of 220 kcal/day (or 23 g/day) and the cumulative fat loss had a minimum detectable difference of 110 g. The observed differences in fat balance and cumulative body fat loss between RC and RF diets were substantially larger than these values and were statistically significant. While the fat balance method does not determine the anatomical location of lost fat, decreased adipose tissue triglyceride likely makes up the majority. Any additional loss of ectopic fat from liver or skeletal muscle would likely be even more beneficial.

What makes me personally skeptical is comparing the fat intake with net fat oxidation, since the former does not really replace the latter. It is better to say that carbohydrates are used more efficiently, i.e., they satisfy energetic needs of the organism better than the fatty foods, and hence the energy shortage that needs to be replenished at the expense of burning the fat stocked in the body is lower, and the weight loss os lower.
This could be modeled by the simplest energy balance equation:
$$
\frac{d M(t)}{dt} = \alpha E - \beta M^{3/4},
$$
where $M(t)$ is the body mass measured in the energy units, $E$ is the energy intake (in calories), $\alpha$ is the efficiency of energy extraction, and the last term describes the energy expenditure due to metabolism, according to the Kleiber's law.
The equilibrium solution of this equation is
$$
M=\left(\frac{\alpha E}{\beta}\right)^{\frac{4}{3}}
$$
Now, if we assume that $\alpha_{fat} < \alpha_{carb}$, the fatty foods should result in lower body mass, provided the same energy intake $E$.
In principle, one could label foods by the effective caloric content relative to that of pure fat, that is by value $\alpha_{food}E/\alpha_{fat}$.
Remark:

since the argument in the comments is about the meaning of calories, let me also point out that calories defined as "the amount of heat needed to raise the temperature of 1 kilogram of water from 0 to 1 degree Celsius" are actually kilo-calories - a rather common misuse of this word.
I also agree with the comments pointing out the shortcomings of the study in question: the small sample size and its short duration.


text:
How can one relate in vitro studies of caffeine (dose expressed as concentration) to dietary intake of caffeine (dose in mass)?
Having difficulty making the data in the below charts to apply to daily life. What is the right interpretation and implementation? How are the “in vitro” results of the below charts relevant to levels that cells would experience "in vivo" after the consumption of caffeinated beverages?

Link to the medical research article which the two above charts were taken from

Good - hope you get some useful answers. I could add that in the lab I work in, we often do in vitro experiments with cells or tissue in a dish, and it's a normal part of our daily business to ask questions exactly like this - it's a great question, though can also be difficult to answer sometimes. The science that figures out answers to these types of questions is called "pharmacology", by the way.

You're asking how skin growth rate is affected in vivo "confluent fibroblasts" by caffeine and it looks like that without the factors and matrix growth environment, that the caffeine metabolically stimulates the fibroblasts away from confluence in graph 1.

In the mentioned study, they tried to support the evidence from earlier studies in which caffeine consumption was associated with skin aging and slow wound healing:

Our research confirms our earlier observations that caffeine may have
  an adverse effect on the wound healing process, as well as on the
  aging process, of the human skin.

...and by "earlier observations" they mean another in vitro study.
In the study, they used 1, 2 and 5 mM caffeine solutions. 1 cup (~250 mL) of brewed tea can contain 95-165 mg caffeine (source), which makes it 2-3.4 mM, so much like the solutions used in the study. When you drink 1 cup of coffee (let's say, 2 mM caffeine solution), the caffeine, which is water- and lipid-soluble (StatPearls), will be dissolved in the body water and fat, which can together make ~50 kg in a 70 kg person. So, you would need to drink ~200 cups of coffee (~20 g caffeine) in ~2 hours (caffeine half-life is ~5 hours - source) to achieve 2 mM caffeine solution in the skin cells.
I haven't found any actual human clinical trial in which caffeine consumption would be associated with adverse effects on the skin. In a recent review: Coffee consumption and health: umbrella review of meta-analyses of multiple health outcomes (BMJ, 2017), they don't even mention skin or wound healing and regular drinking of 3-4 cups of coffee per day was not associated with an increased risk of various health conditions (except in pregnancy).

Since caffeine is water soluble, wouldn't you have to consume (approximately) 194 mg per liter of water to reach that concentration in skin?  That is above the LD50 for caffeine.

I edited the bold paragraph about the amounts. The concentrations of caffeine solutions used in the study and in coffee seem to be about the same, but when you drink a cup of coffee, caffeine would be dissolved in the whole body and would not be so concentrated in the skin cells any more. I think you would need unrealistic amounts of coffee to reach such concentrations.

The LD50 of caffeine is 150-200 mg per kilogram of body weight. So, the lethal dose for a 70 kg man would need to be at least 10 grams of caffeine (~100 cups of coffee) consumed in a short time.

Ah yes, weight not volume, so the 2 molar solution is about the LD50.

How can one relate in vitro studies of caffeine (dose expressed as concentration) to dietary intake of caffeine (dose in mass)?
Caffeine rapidly diffuses throughout the body's water, both intra and extracellular.
Therefore, since the caffeine will be relatively evenly distributed, you can calculate the amount of caffeine needed to reach a given molar concentration within any particular cell by knowing the total water in a person and the molar mass of caffeine (194.19 g/mol ).  A 72 kg person has about 40 liters of water in their body.
Combining those numbers, reaching 1mM requires 7.7676 grams of caffeine.  Reaching 5mM requires 38.838 grams.
How are the “in vitro” results of the below charts relevant to levels that cells would experience "in vivo" after the consumption of caffeinated beverages?
Wikipedia puts the LD50 of caffeine at 150-200 mg/kg, or 10.8-14.4g for our hypothetical 72kg man.  These numbers are likely very approximate as there isn't going to be a lot of well controlled clinical data on caffeine toxicity in humans, but someone reaching those concentrations stands a good chance of dying from caffeine poisoning.
For that reason I don't think these results are relevant to normal caffeine consumption.  I interpreted the high concentrations used in that study as a deliberate attempt to induce cell injury, not as a means to simulate normal caffeine consumption.


text:
Does the composition of a meal play a big, or small, role in food's thermogenic effect on the body?
Reading in: "Diet and Health: Implications for Reducing Chronic Disease Risk /  Calories: Total Macronutrient Intake, Energy Expenditure, and Net Energy Stores" [NCBI Resources]:

"The thermogenic effect of a meal usually amounts to approximately 10% of the caloric value of the ingested food, and is higher for carbohydrates and protein than for fats".

Does that mean that the thermogenic effect of a meal fluctuates between 9% and 11%, depending on it's composition? If so, the thermogenic impact on the body by a meal's composition would be quite small in comparison with the impact of a meal's calorie content. Or, does food's composition play a bigger role than that? Looking for information from reputable sources.
Calories: Total Macronutrient Intake, Energy Expenditure, and Net Energy Stores

"It only takes 2.5 calories to convert 100 calories of fatty acids into body fat. It takes 23 calories (10 times as much energy) to convert 100 calories of protein or glucose into body fat." (Sweet Poison: David Gillespie)

According to Diet Induced Thermogenesis (Nutrition & Metabolism, 2004), the percent of calories converted to heat depends on a nutrient:

Proteins: 15-30%
Alcohol: 10-30%
Carbohydrates: 5-10%
Fats: 1-3%
A mixed meal: ~10% (this is an estimated average)

The thermic effect of nutrients is not a fixed value and can vary greatly within a person and from person to person:

Reported intra-individual variability in DIT, determined with
  ventilated-hood systems, is 6 to 30% [7,8]. Reported within-subject
  variability in DIT, determined with a respiration chamber, is 43 to
  48%.


text:
BWA-MEM single strand or doublestrand alignment
In whole genome secondary analysis does BWA-MEM use a double stranded fasta reference or are reads aligned to only one, single stranded fasta reference?

BWA-mem (like most aligners), takes a normal single-stranded fasta file (I've never seen one with both strands listed) and aligns to both strand.

This means that BWA-MEM takes into consideration the complementary strand of each single stranded read prior to alignment?

Yes, all normal aligners do this.


text:
Constant or variable number of chiasmata during recombination?
During recombination, is the number of chiasmata consistent for each gamete and are the chiasmata regions consistent within a single organism?

Welcome to Biology.SE. What do you mean by [..] are the chiasmata regions consistent within a single organism?? Do you mean "Are there regions of high recombination rate and other regions of low recombination rate?"?

Maybe I should rephrase the question, how many recombination events occur in a single germ cell? Is recombination really random or is recombination deterministic? If not, what influences randomness in recombination. Does the cell nucleus secrete some enzyme the randomly glues homologous chromosomes at random sites?

There is a large amount of variation in the distribution and number of chiasmata or crossing overs (COs). The total number of chiasmata per cell can vary within the same organism.
Where chiasmata occur along the chromosome is also not consistent cell to cell. Hotspots are 1-2kb regions that experience elevated recombination compared to neighboring genomic regions. A way to think of the distribution of COs is that ~80% of recombination happens in hotspots which comprise ~10% of the genome.
Recombination depends on the chromatin context, so chiasmata are rare near the centromere and positive interference results in chiasmata being spaced out along the chromosome. A good prediction of total chiasmata number per cell is at least 1 per chromosome. Some researchers argue that one CO per chromosome arm is more accurate.
Below is a link to a good article that expands on some of the ways recombination varies in humans.
http://www.nature.com/nrg/journal/v8/n1/abs/nrg1947.html

Thanks!!! Your answer along with the article turned out to be very helpful!!!


text:
Why does cold kill humans but not bacteria?
Bacteria can continue like nothing happened after being exposed to low temperatures why doesn't this happen to humans as well? Why can't our metabolic machinery continue as normal?

I think a better question would be something along the lines of "Do human cell lines tolerate cold temperatures?" The question as is is quite trivial - we are multicellular organs that rely on systemic functional integrity, whereas generally bacteria are single-cellular organisms. It's comparing apples and oranges at the minute. I think there is an interesting question in there, but major edits would be required.

@James Why would this be a homework question?

Let's look at what happens when a single cell within a cell wall freezes. We end up with a little drop of ice, within which are encased all the cellular structures. Thaw this ice, and all is well - provided neither freezing nor thawing happen too rapidly.
Now take what happens in a human being.
First, the blood in the extremities gets colder, and cools the interior somewhat. But we have mechanisms to conserve heat in the core, at least for a little while. This doesn't help the extremities much. If the blood freezes there, we get frostbite - the tissues die for lack of blood supply. Fingers and toes and the end of the nose, and other extremities, are compromised.
Now let the core temperature drop. Below a certain temperature, conduction in the heart slows and eventually stops. This is fatal.
There are many other effects, all of them related to the relative vulnerability of different tissues to cold. Freezing is generally bad for animal cells, which will rupture because of the mechanical effects of the expansion of water as it forms ice. Frozen body fluids can't do their jobs. Frozen nerves can't conduct impulses, so muscles won't contract once their temperature drops below the shivering point. And so on.

But why can't our cells resume normal activity after being frozen? Once that blood reaches the cells again why can't it function normally? What structures in our body or cells prohibits this from happening?

I edited to make clear that ice formation will rupture the cells. If the heart has stopped, the body dies. And when the formerly frozen body thaws, the cells do function normally by decaying, which is normal function for dead cells.


text:
What would happen if there were no more spiders?
In an office conversation about arachnophobia, one colleague declared "they're hoorrible and they should all be killed". He doesn't like spiders.
I've heard of the scenario where bees die out quite a lot, sounds like that would be pretty catastrophic.
So what would happen if suddenly there were no more spiders?

Spiders are extremely important predators, both in "natural" ecosystems and in agriculture. They therefore function as biocontrol agents, and without them we would suffer larger crop damage from pest insects (or would require much higher levels of pesticide use). Loosing them from all natural ecosystems would also cause enormous effects, due to cascading effects through the foodwebs. The effects would differ between different ecosystems though (with the largest effects probably in forests and grasslands, see links 3 and 4 below), and nobody can really overview or predict the full implications.

A new study reveals some stunning estimates about just how much the world’s spiders eat annually: between 400 and 800 million tons of insects, springtails, and other invertebrates. In the process, these eight-legged carnivores play an important role to keep countless insect pests, especially in forests and grassland areas, in check.

(from third link below)
For more, see e.g.:

Rusch & Bommarco. 2016. Agricultural landscape simplification reduces natural pest control: A quantitative synthesis. Agriculture, Ecosystems & Environment
Öberg & Ekbom. 2006. Recolonisation and distribution of spiders and carabids in cereal fields after spring sowing. Annals of applied biology. DOI: 10.1016/j.agee.2016.01.039
Spiders eat astronomical numbers of Insects (popular overview of paper below)
Nyffeler, M. & Birkhofer, K. (2017). An estimated 400-800 million tons of prey are annually killed by the global spider community. The Science of Nature


text:
Why do we turn darker in the sun?
I tried the all powerful google to answer this question - but I am not getting the answer I seek. I know we turn darker because the skin produces melanin. The question remains - why darker?
I am a physicist and it would make sense to me that the bodies response would want us to turn whiter- since a higher albedo would reflect more UV radiation. It seems that evolution took the way of absorbing more and more UV radiation by this melanin and then converting it to heat. Which begs the question as well - do black people get hotter than white people given the temperature is constant? Although this a side point to my original question.
What sparked this question was the use of thousand of black balls being dumped into LA's water reservoir in the hopes to reduce evaporation. Again... BLACK balls. This makes no sense to me - why the heck not use white balls to reflect more sunlight?

http://biology.stackexchange.com/questions/35713/what-is-happening-when-we-get-a-tan

Well if you used white it would reflect most all of the solar energy back at the water and what happens to molecules when the get a bump from a photon?

Interesting question. I don't know the answer, but I am guessing that either no suitable white pigment has evolved, or maybe it's too costly to produce compared to the benefits over black. The extra heat absorbed radiates away quickly in most situations anyway, and even when it doesn't, sunburns are hardly life threatening.

For the concern of the black balls, I googled black balls California and the first link gave me an explanation. Note, btw that the question for the black balls is off-topic here (but this is not your main question in your post)and would be on-topic on Physics.SE.


text:
Why are there so many species of bats?
I read that roughly 20% of all species of mammals are bats. Is there a good explanation for why bats have diversified so much compared to other mammals? Is it because bats' ability to fly allows them to fill niches that are completely out of reach (pun intended) of other mammals? If so, how is this reconciled with the coexistence of bat populations and bird populations?

Indeed, good question. There's tiny bats, large bats, and so many different species of them! A clue can be found in the observation that each bat species is almost always restricted to a small geographical region. With this in mind, it has been shown that an animal lineage's ability to diversify quickly in new environments depends largely on its diet. Bats have an incredible variety of dietary sources. Plant nectar, insects (there's so many different kinds of insects...), blood-feeding, and more! So, as you can imagine, bat species are restricted because they have specialized diets and because they are very good at taking up new diets over evolutionary time. Unfortunately for them, it restricts them to a geographical location much of the time. Geographical restriction is always a good starting point for speciation events, and there have been many in the bat clade. But why bats, specifically, you might ask? Well - it is argued (below) that it is due to the characteristics of their skulls, rather than their wings.
Dumont, E. R., Dávalos, L. M., Goldberg, A., Santana, S. E., Rex, K., & Voigt, C. C. (2012). Morphological innovation, diversification and invasion of a new adaptive zone. Proc. R. Soc. B, 279(1734), 1797-1805.


text:
How is the Allee effect modeled in the presence of a highly variable carrying capacity?
Consider a rather standard model of population dynamics in the presence of a strong Allee effect:
$$ \frac{du}{dt}=u\left(1-\frac{u}{K}\right)\left(\frac{u}{A}-1\right),$$
where $u(t)$ is population, $K>0$ is carrying capacity, and $A>0$ is the Allee threshold---the population below which the species, for one reason or another, cannot survive (for example, a social species which relies on being in large groups for survival).
Now suppose that the carrying capacity is also changing in time: $K=K(t)$. Let us suppose that it is varying in a given, predetermined way due to, e.g., climate change. If $K(t)$ remains larger than $A$ for all $t$, then this model remains acceptable to study population dynamics. But if eventually, $K(t)<A$, then for $K(t)<u<A$, we actually have $\frac{du}{dt}>0$, despite $u$ being both above the carrying capacity and below the Allee threshold. Obviously, this model for population dynamics is no longer relevant in this regime.
It seems that a solution to this problem would be to use the model
$$\frac{du}{dt}=\begin{cases} u\left(1-\frac{u}{K}\right)\left(\frac{u}{A}-1\right) & K>A\\  F(u;K,A) & K\leq A,\end{cases}$$
where $F(0)=0$ and $F(u;K,A)<0$ for all $u>0$ whenever $K<A$ is chosen so that the right hand side of the above ODE is smooth or at least continuous in $K$. My questions are:

Has this been studied in the math biology literature?
If so, is a solution similar to mine proposed?
If so, what is the function $F$ that is used?

this maybe of interest https://iopscience.iop.org/article/10.1088/1757-899X/332/1/012051/pdf

@RoniSaiba That is interesting, thanks.


text:
Is it still true that C. elegans has no known natural viruses?
I read in a 2009 review that

While mammals and C. elegans each have a single Dicer that makes both miRNAs and siRNAs, Drosophila has two Dicers: Dcr-1 makes miRNAs, whereas Dcr-2 is specialized for siRNA production. The fly RNAi pathway defends against viral infection, and Dicer specialization may reduce competition between pre-miRNAs and viral dsRNAs for Dicer. Alternatively, Dcr-2 and Ago2 specialization might reflect the evolutionary pressure on the siRNA pathway to counter rapidly evolving viral strategies to escape RNAi. In fact, dcr-2 and ago2 are among the most rapidly evolving Drosophila genes. C. elegans may achieve similar specialization with a single Dicer by using the double-stranded RNA-binding protein, RDE-4, as the gatekeeper for entry into the RNAi pathway. However, no natural virus infection has been documented in C. elegans. In contrast, mammals may not use the RNAi pathway to respond to viral infection, having evolved an elaborate, protein-based immune system.

Is it still true that no know natural virus infects C. elegans? And is this [thought to be] due to the effectiveness of its viRNA (virus-derived small interfering RNAs) immunity/defense mechanism?

It has a natural virus, an Orsay virus.
https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1000586
is the paper of the discovery. found by searching "virus infecting C elegans"

Indeed even has wiki page https://en.wikipedia.org/wiki/Orsay_virus

Also the RNAi suppressors of the Orsay virus have been studied already. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3648182/ And it seems to have a novel fusion protein https://www.sciencedirect.com/science/article/pii/S004268221300679X

And it seems to have an egress protein https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6026750/


text:
What is the difference among these compounds?
I'll preface this question by making clear that I'm not not well versed in biology.
Anyway, within the context of biocides/antimicrobial products using them as active substances, what is the difference among these three quaternary ammonium compounds:
benzyl-C12-16-alkyldimethyl, chlorides (CAS number - 68424-85-1)
benzyl-C8-18-alkyldimethyl, chlorides (CAS number - 63449-41-2)
dimethyloctadecyl[3-(trimethoxysilyl)propyl]ammonium chloride (CAS number - 27668-52-6)
How does one's antimicrobial properties differ from the other? And which is more hazardous? And which is least hazardous?

At a glance, they all seem potentially hazardous. The relative risk from using them will vary more with how and where they are used, in what forms, who's using them, how are disposed of, etc. It would be helpful if you included some context for their intended use in your question.

As you point out, these are all quaternary ammonium compounds that are likely to work in a similar way (membrane disruption) and are very broad spectrum. Any differences in efficacy against a given pathogen would need to be established by empirical testing on that particular organism, as these kind of things are highly idiosyncratic--it's not like an enzyme inhibitor where you can ask whether the organism has the relevant enzyme or not. The first two are even not pure compounds, they're mixtures whose precise composition is not known a priori.
As for hazards, these kind of quaternary ammonium compounds are frequently used in topical disinfectants for use on human skin, and even in low concentration in things like eye drops that go in the eye. Obviously as with anything, the dose makes the poison, and a concentration you would use to scrub your bathroom sink is not safe to put on a mucous membrane on your body.


text:
What is this sea shell?
Found in Belgrade, possibly carried back from the Mediterranean or Aegean coast.

It is not /Bolma rugosa/, but in fact /Angaria delphinus/, from the Indo-Pacific.
Listing on gastropods.com

Welcome to Biology.SE! You are more likely to get a positive response to your answer if you explain why your identification is correct. Specifically, please [edit] your answer to add discussion of key features that led you to this conclusion and supporting references or at least validated images. (Answers must also be self-sufficient, not just links.) Without this your answer is indistinguishable from opinion and instead should be a comment on another answer. ——— Please take the [tour] and then consult the help pages for additional advice on [Answer] effectively on this site. Thank you!

This ID seems accurate. The species varies a lot and it's often like the one from the OP.