Geranylgeranylation

Geranylgeranylation is a form of prenylation, which is a post-translational modification of proteins that involves the attachment of one or two 20-carbon lipophilic geranylgeranyl isoprene units from geranylgeranyl diphosphate to one or two cysteine residue(s) at the C-terminus of specific proteins. Prenylation (including geranylgeranylation) is thought to function, at least in part, as a membrane anchor for proteins.
The process of geranylgeranylation can be catalyzed by either geranylgeranyl transferase I (GGTase I) or Rab GGTase (also GGTase II). GGTase I catalyzes the addition of one geranylgeranyl group onto the C-terminal consensus sequence CAAL (somewhat similar to farnesyltransferase reactions), where C=cysteine, A=any aliphatic amino acid, and L=leucine. Rab GGTase adds a total of two geranylgeranyl groups onto two cysteine residues at the C-terminal consensus sequence CXC or XXCC. The source of the geranylgeranyl group is geranylgeranyl diphosphate, which is synthesized by GGPS1 within the isoprenoid biosynthetic pathway.
An example of this can be seen in the lipid anchoring of the Rho GTPase family of signaling molecules and the gamma subunit of heterotrimeric G proteins.


Enteroglucagon

Enteroglucagon is a peptide hormone derived from preproglucagon. It is a gastrointestinal hormone, secreted from mucosal cells primarily of the colon and terminal ileum. It consists of 37 amino acids. Enteroglucagon is released when fats and glucose are present in the small intestine; which decrease the motility to allow sufficient time for these nutrients to be absorbed.
= Discovery =
In 1948, Sutherland and De Duve identified a gastrointestinal glucagon-like material in gastric mucosa, the term "enteroglucagon" was used to describe this material that shared a similar immunoreactivity with glucagon. A half-century later, Brubaker and Drucker studied proglucagon gene expression, they discovered the function of enteroglucagon is related to the growth of intestinal epithelium.
= Function =
Enteroglucagon is a proglucagon-derived peptide or enteroendocrine cells derived peptide in the small intestine. Preproglucagon undergoes post translational modification to release glucagon-like peptides (GLP-1 and GLP-2) and other molecules derived from L-cells of intestine. GLP-1 is derived from a class of intestinal hormones called incretin and the molecule exists in two forms GLP-1(7-37) and GLP-1(7-36) amide. GLP-1 form of incretin starts circulating in response to a high blood glucose level. Incretin effect is a negative feedback loop between glucose and insulin level, it promotes insulin release from beta cells of pancreas islet and suppresses glucagon when the glucose level is high. In vertebrate mammals, GLP-2 sequences are highly conversed in the intestine. The molecule functions as apart of adaptive response, such that contributes intestinal growth, proliferation effect, intestinal dilation (increases the mucosal blood flow) and reduces the chance of apoptosis.
= Clinical Significance =
GLP-1 is effective at reducing blood glucose levels. GLP-1 analogs have a significant therapeutic effect and high efficacy on diabetes treatments and hypoglycemia prevention. Proliferation effect and trophic effect on the small intestine, GLP-2 is used as a therapy to support patients with short-bowel syndrome and other underlying intestinal conditions.


L-methionine (R)-S-oxide reductase

In enzymology, a L-methionine (R)-S-oxide reductase () is an enzyme that catalyzes the chemical reaction
The 3 substrates of this enzyme are L-methionine, thioredoxin disulfide, and H2O, whereas its two products are L-methionine (R)-S-oxide and thioredoxin.
This enzyme belongs to the family of oxidoreductases, specifically those acting on a sulfur group of donors with a disulfide as acceptor. The systematic name of this enzyme class is L-methionine:thioredoxin-disulfide S-oxidoreductase [L-methionine (R)-S-oxide-forming]. Other names in common use include fRMsr, FRMsr, free met-R-(o) reductase, and free-methionine (R)-S-oxide reductase. This enzyme participates in methionine metabolism.


Rhynchocyon

Rhynchocyon is a genus of elephant shrew (or sengi) in the family Macroscelididae. Members of this genus are known colloquially as the checkered elephant shrews or giant sengis.
It contains the following five species:
Ecology.
The giant sengis are endemic to Africa, and usually live in lowland montane and dense forests, often "avoiding" edges of forest patches. They eat primarily insects such as beetles, termites, ants, and centipedes, using their proboscises to dig them from the soil and its tongue to lick them up. Their facial morphology limits their diets to tiny invertebrates, and unlike other members of Macroscelidea, do not supplement their diet with foods such as nuts or small fruits.
They typically build ground level nests for shelter requiring dry leaf litter. The primary structure of a nest for "R. udzungwensis", for example, consists of the excavation of a cup-like indentation in the soil, layered with leaves, and the covered with looser leaves as a roof covering. They usually construct their nests at the base of trees. They also use hollowed, fallen trees or trunks to retreat in shelter.
They are typically active in the day (diurnal), spending their nights sheltered. Other Macroscelidea species are known to bask in the sun as a method of thermoregulation to save energy. Giant sengis do not bask—and it is most likely due to their adaptation to shaded canopy forest environments.
Sengis live in monogamous pairs, defending hectare-sized territories. Pairs spend little time together except when the female is in estrous. Mating occurs quickly and offspring grow quickly with minimal parental investment—none of which of is paternal.
Each species exhibits distinct and varying coat patterns and colors. Species and subspecies found in denser forests exhibit darker coloration and patterns while open woodland species exhibit lighter, chequers. The darker species "R. petersi", "R. chrysopygus", and "R. udzungwensis" still contain vestigial chequers, but are masked by the blended dark fur between them. This makes coat patterns an unreliable indicator of species delineation. The species are described as follows:
Taxonomy, distribution, and speciation.
The genus' taxonomic status has been difficult to determine due to the very close similarities between populations. Up to ten species have been recognized, but over time they have been regrouped into four species. Recently, "R. cirnei", the species with the most subspecies, has had "R. c. stuhlmanni" separated into its own species based on updated molecular data.
"R. chrysopyguus", "R. cirnei", and "R. petersi" are allopatrically distributed; with the more recently discovered "R. udzungwensis" and subspecies "R. cirnei reichardi" exhibiting parapatric distributions. Some introgression (hybridization) has taken place between "R. udzungwensis" and "R. cirnei reichardi" as detected by mtDNA.
Estimated of population size and density vary and can be difficult to determine. However, measurements of the species populations has been undertaken. "R. chrysopyguus", in protected areas, is about 150 individuals per square kilometer (about 20,000 individuals); "R. petersi" is between 19-80 individuals per square kilometer; "R. udzungwensis" has an estimated 15,000-24,000 individuals. "R. udzungwensis" has a tiny distribution compared to the other species but resides in a protected forest.
External links.
Sengis.org is an overview website concerning all the sengi species maintained by researcher Galen B Rathbun of the university of the California Academy of Sciences. It hosts images, videos, bibliographies, among other topics about the order Macroscelididae.


Cotadutide

Cotadutide is an experimental drug for the treatment of type 2 diabetes mellitus. It lowers blood glucose levels by mimicking the human hormones glucagon-like peptide 1 and glucagon, which play a role in blood sugar regulation. The drug is a peptide that is injected under the skin.
Cotadutide is in Phase II clinical trials .


Geogale


Arnold J. Levine

Arnold J. Levine (born 1939), is an American Molecular biologist. He was awarded the 1998 Louisa Gross Horwitz Prize for Biology or Biochemistry and was the first recipient of the Albany Medical Center Prize in Medicine and Biomedical Research in 2001 for his discovery of the tumor suppressor protein p53.
He is currently Professor of Systems Biology at the Institute for Advanced Study in Princeton, New Jersey.
Career.
Levine received his Ph.D. from the University of Pennsylvania in 1966.
Levine discovered, with several colleagues, the p53 tumor suppressor gene in 1979, a protein involved in cell cycle regulation, and one of the most frequently mutated genes in human cancer, in work done as a professor in the biochemistry department at Princeton University. In 1979 Levine moved to become Chairman of the Department of Microbiology at Stony Brook School of Medicine before moving back to Princeton in 1984.
In 1998 Levine became the Robert and Harriet Heilbrunn Professor of Cancer Biology and President of Rockefeller University. In 2002, Levine resigned the presidency following allegations that he had an inappropriate sexual encounter with a female graduate student, while both were intoxicated. According to the woman involved, the encounter was consensual and blown out of proportion.
In 2002 he was appointed professor at The Cancer Institute of New Jersey in New Brunswick, New Jersey, then a part of the Robert Wood Johnson Medical School. Simultaneous to this appointment, in 2003, Levine became a visiting professor, then professor, in the newly created Simons Center for Systems Biology at the Institute for Advanced Study (IAS) in Princeton, New Jersey, where he has remained since.
In 2017, Levine, with collaborators Benjamin Greenbaum, and Marta Luksza, developed the first mathematical model for predicting patient response to immunotherapy. Their recent work extends to studying immune resistance mechanisms and patterns of evolution.
Award and honors.
In addition to the Louisa Gross Horwitz Prize (Columbia University) (1998) and the inaugural Albany Medical Center Prize in 2001, Levine has received numerous awards and honors. He was elected a Member of the U.S. National Academy of Sciences in 1991, and a Member of the Institute of Medicine in 1995. He won the Ciba-Drew Award in 1995. The importance of p53 in cancer biology led to a number of cancer-related awards, including the Bristol-Myers Squibb Award for Distinguished Achievement in Cancer Research (1994), the Charles S. Mott Prize from the General Motors Cancer Research Foundation (1999), the Keio Medical Science Prize (2000), the Memorial Sloan-Kettering Cancer Center's Medal for Outstanding Contributions to Biomedical Research (2000), the Albany Medical Center Prize in Medicine and Biomedical Research (2001), the Dart/NYU Biotechnology Achievement Award in Basic Biotechnology (2008); the American Association for Cancer Research's Kirk A. Landon–AACR Prize for Basic Cancer Research (2008), the American Cancer Society's Medal of Honor (2009), and the Lars Onsager Medal (2012).


Henry M. Fales

Henry M. Fales (February 12, 1927, New York, NY – October 28, 2010, Silver Spring, MD) was an American organic chemist and mass spectrometrist. He authored and co-authored over 350 scientific publications on natural substances and biochemistry and was one of the pioneers in bioanalytical mass spectrometry.
Academic career.
Fales obtained his PhD from Rutgers University. He worked at the National Heart, Lung, and Blood Institute of the National Institutes of Health in Bethesda, Maryland, since 1954, first as Chief of the Laboratory of Biophysical Chemistry and later as Chief of the Laboratory of Applied Mass Spectrometry.
Under his direction, the Laboratory of Chemistry in NHLBI became a world-renowned center for structural chemistry during the 1960s, integrating nmr, x-ray crystallography and mass spectrometry. Fales and coworkers also began a reference library of molecular weights which was incorporated into the Merck Index.
He served on the editorial boards for the Journal of Mass Spectrometry, the Journal of the American Society for Mass Spectrometry, Analytical Chemistry and Bioanalytical Chemistry. He served on the advisory panel on Chemistry of the National Science Foundation. H. M. Fales held several functions in the Board of Directors of the American Society for Mass Spectrometry including President.
Awards.
Fales received several awards including Chromatographer of the Year of the Washington Chromatography Discussion Group (1973), DHEW Superior Service Awards (1973, 1986), the Hillebrand Prize from the Chemical Society of Washington in 1977, and a Professional Service Award of Alpha Chi Sigma, Washington, D.C. (1988). His bibliography up to the year 2005 was published in the Journal of Biomacromolecular Mass Spectrometry.


Isocitric acid

Isocitric acid is a structural isomer of citric acid. Salts and esters of isocitric acid are known as isocitrates. The isocitrate anion is a substrate of the citric acid cycle. Isocitrate is formed from citrate with the help of the enzyme aconitase, and is acted upon by isocitrate dehydrogenase.
Isocitric acid is commonly used as a marker to detect the authenticity and quality of fruit products, most often citrus juices. In authentic orange juice, for example, the ratio of citric acid to D-isocitric acid is usually less than 130. An isocitric acid value higher than this may be indicative of fruit juice adulteration.


Dot blot

A dot blot (or slot blot) is a technique in molecular biology used to detect proteins. It represents a simplification of the western blot method, with the exception that the proteins to be detected are not first separated by electrophoresis. Instead, the sample is applied directly on a membrane in a single spot, and the blotting procedure is performed.
The technique offers significant savings in time, as chromatography or gel electrophoresis, and the complex blotting procedures for the gel are not required. However, it offers no information on the size of the target protein.
Uses.
Performing a dot blot is similar in idea to performing a western blot, with the advantage of faster speed and lower cost.
Dot blots are also performed to screen the binding capabilities of an antibody.
Methods.
A general dot blot protocol involves spotting 1–2 microliters of a samples onto a nitrocellulose or PVDF membrane and letting it air dry. Samples can be in the form of tissue culture supernatants, blood serum, cell extracts, or other preparations.
The membrane is incubated in blocking buffer to prevent non-specific binding. It is then incubated with a primary antibody followed by a detection antibody or a primary antibody conjugated to a detection molecule (commonly HRP or alkaline phosphatase). After antibody binding, the membrane is incubated with a chemiluminescent substrate and imaged.
Apparatus.
Dot blot is conventionally performed on a piece of nitrocellulose membrane or PVDF membrane. After the protein samples are spotted onto the membrane, the membrane is placed in a plastic container and sequentially incubated in blocking buffer, antibody solutions, or rinsing buffer on shaker. Finally, for chemiluminescence imaging, the piece of membrane need to be wrapped in a transparent plastic film filled with enzyme substrate.
Vacuum-assisted dot blot apparatus has been used to facilitate the rinsing and incubating process by using vacuum to extract the solution from underneath the membrane, which is assembled in between several layers of plates to ensure good seal between sample wells, hold waste solution, and deliver suction force. For chemiluminescence signal detection, apparatus need to be disassembled and the membrane need to be taken out and wrapped in a transparent plastic film.


Methylenetetrahydromethanopterin dehydrogenase

In enzymology, a methylenetetrahydromethanopterin dehydrogenase () is an enzyme that catalyzes the chemical reaction
Thus, the two substrates of this enzyme are 5,10-methylenetetrahydromethanopterin and coenzyme F420, whereas its two products are 5,10-methenyltetrahydromethanopterin and reduced coenzyme F420.
This enzyme belongs to the family of oxidoreductases, specifically those acting on the CH-NH group of donors with other acceptors. The systematic name of this enzyme class is 5,10-methylenetetrahydromethanopterin:coenzyme-F420 oxidoreductase. Other names in common use include N5,N10-methylenetetrahydromethanopterin dehydrogenase, and 5,10-methylenetetrahydromethanopterin dehydrogenase. This enzyme participates in folate biosynthesis.
Structural studies.
As of late 2007, 4 structures have been solved for this class of enzymes, with PDB accession codes , , , and .


Intercept Pharmaceuticals

Intercept Pharmaceuticals, Inc. is an American biopharmaceutical company incorporated in 2002, focusing on the development of novel synthetic bile acid analogs to treat chronic liver diseases, such as primary biliary cirrhosis (PBC) now called primary biliary cholangitis, non-alcoholic fatty liver disease (or non-alcoholic steatohepatitis, NASH), cirrhosis, portal hypertension, primary sclerosing cholangitis and also the intestinal disorder, bile acid diarrhea.
Products.
The company's lead product is obeticholic acid, OCA, also known as 6-ethyl-chenodeoxycholic acid or INT-747, marketed as Ocaliva. OCA is a potent first-in-class farnesoid X receptor (FXR) agonist. As of March 2017, Ocaliva is approved in the US and the EU for use in primary biliary cholangitis. It is in phase III studies for non-alcoholic steatohepatitis (NASH) and phase II studies for primary sclerosing cholangitis.
Other products in the development pipeline include INT-767, a dual FXR/TGR5 agonist, and INT-777, a TGR5 agonist.
On June 29, 2020, the company released a statement announcing that FDA had rejected its lead product obeticholic acid, OCA, because FDA officials had determined that "the predicted benefit of the drug does not sufficiently outweigh the predicted risks".
Initial public offering and stock history.
Intercept trades on the NASDAQ exchange under the ticker symbol ICPT. The initial public offering of the stock on October 16, 2012 was at $15. A follow-on public offering at $33 took place on June 24, 2013.
On January 9, 2014, the stock skyrocketed from $72.39 to $275.49, or about 280%, after a planned interim analysis by the independent data safety monitoring board showed that Obeticholic acid met the main goal (improvement of liver histology) at the mid-stage in the FLINT trial in NASH, sponsored by NIDDK. The stock continued to climb to $497 over the next few days before falling back to around $317 on March 29, 2014, giving a market capitalization of around $6.2 billion.
In March 2014, the company released the results of the POISE study of Obeticholic acid in PBC, which showed the drug met the trial's primary endpoint of a reduction in serum alkaline phosphatase, a biomarker for the disease. These results were presented at an international liver meeting in April 2014.
As of 31 December 2014, the company has 136 employees.


Galactolysis

Galactolysis refers to the catabolism of galactose.
In the liver, galactose is converted through the Leloir pathway to glucose 6-phosphate in the following reactions:
 galacto- uridyl phosphogluco-
 kinase transferase mutase
 gal --------> gal 1 P ------------------> glc 1 P -----------> glc 6 P
 / v
 UDP-glc UDP-gal
 \___________/
 epimerase
Metabolic disorders.
There are 3 types of galactosemia or galactose deficiencies:


Tolamolol

Tolamolol is a beta adrenergic receptor antagonist.


Phosphopeptide

Phosphopeptides are modified self antigens which may induce an immune response.
Phosphorylation of serine and threonine residues is conserved during MHC class I and MHC class II antigen processing. Phosphopeptides are thus displayed on the surface of cells. As modified self antigens, they are potentially immunogenic when compared to unmodified self proteins as the immune cells (T-cells) which recognise them are possibly not subject to central tolerance mechanisms. This may contribute to the potential capability of phosophopeptides to serve as tumor antigens in the treatment of colorectal cancer.


Jeffrey Siewerdsen

Jeffrey Harold Siewerdsen (born 1969) is an American physicist and biomedical engineer who is a Professor of Biomedical Engineering, Computer Science, Radiology, and Neurosurgery at Johns Hopkins University. He is Co-Director of the Carnegie Center for Surgical Innovation at Johns Hopkins School of Medicine and is a member of the Malone Center for Engineering in Healthcare. He is among the original inventors of cone-beam CT-guided radiotherapy as well as weight-bearing cone-beam CT for musculoskeletal radiology and orthopedic surgery. His work also includes the early development of flat-panel detectors on mobile C-arms for intraoperative cone-beam CT in image-guided surgery. He developed early models for the signal and noise performance of flat-panel detectors and later extended such analysis to dual-energy imaging and 3D imaging performance in cone-beam CT. His core laboratory at Johns Hopkins University is the ISTAR Lab (Imaging for Surgery, Therapy, and Radiology) in the Department of Biomedical Engineering at the Johns Hopkins Hospital.
Biography and scientific work.
Jeffrey Siewerdsen did his undergraduate studies at the University of Minnesota in Minneapolis, MN, where he received his Bachelor of Arts degree in Physics and Astrophysics with a minor in Japanese in 1992. His undergraduate research experience included construction and testing of particle detectors for the Soudan 2 proton decay project.
Siewerdsen began graduate studies at the University of Michigan in Ann Arbor, MI, in 1992, working initially in high-energy physics (D0 experiment) under supervision of Professor Homer Neal and earning his Master of Science degree in Physics in 1994.
Siewerdsen's doctoral research involved early development of amorphous silicon Flat panel detector for medical x-ray imaging under the supervision of Professor Larry E. Antonuk. Siewerdsen's work focused on the development of early flat-panel detector systems for diagnostic radiography, fluoroscopy, and mammography as well as megavoltage portal imaging for guidance of radiation therapy. His doctoral dissertation established mathematical models for the signal-to-noise properties (specifically, the modulation transfer function, noise-power spectrum, and detective quantum efficiency) of flat-panel x-ray detectors. His Ph.D. thesis was awarded the Kent M. Terwilliger Prize for Best Doctoral Dissertation in Physics, 1998.
Siewerdsen conducted post-graduate research beginning in 1998 as a Research Scientist at William Beaumont Hospital in Royal Oak, MI, with Dr. David Jaffray and Dr. John Wong on the topic of cone beam computed tomography (CBCT) for image-guided radiation therapy (IGRT). The Beaumont team produced the first IGRT system for CBCT, beginning with laboratory studies to investigate image quality characteristics, and translating to clinical studies for guidance of prostate cancer therapy.
Siewerdsen joined the Ontario Cancer Institute and University of Toronto Department of Medical Biophysics as a Scientist and Assistant Professor, respectively, in 2002, and subsequently as Senior Scientist and Associate Professor in 2007. Research in his laboratory focused on image-guided surgery, new imaging methods such as dual-energy imaging, and image registration. His work involved the development of early systems for cone beam computed tomography (CBCT) with a flat-panel detector on mobile C-arms for image-guided surgery and translated the first such systems to clinical studies in image-guided Otolaryngology–Head and Neck Surgery with Dr. Jonathan Irish. He also collaborated closely with Dr. Kristy Brock on deformable image registration using the Demons algorithm and with Dr. Narinder Paul on development of dual-energy chest radiography systems for detection of early stage lung cancer. His research also extended cascaded systems models for x-ray imaging performance to describe 3D imaging performance in CBCT and helped to establish mathematical methods for imaging system optimization according to the imaging task. Siewerdsen joined Johns Hopkins Biomedical Engineering as an Associate Professor in 2009 and subsequently as a Professor in 2012, with cross-appointment in Computer Science, Radiology, and Neurosurgery. He founded the I-STAR Lab (Imaging for Surgery, Therapy, and Radiology) as a collaborative research endeavor bridging biomedical engineering with clinical collaborators at Johns Hopkins Hospital. In 2015, he established the Carnegie Center for Surgical Innovation in the Johns Hopkins School of Medicine. He is also a John C. Malone Professor in Computer Science and Member of the Malone Center for Engineering in Healthcare. Research in Siewerdsen's laboratory includes: mathematical modeling / imaging science of digital x-ray, dual-energy imaging, cone beam computed tomography (CBCT), and computed tomography (CT) systems; image-guided surgery; multi-modality medical image registration; new imaging systems for musculoskeletal radiology and orthopedic surgery; and clinical research collaborations in robot-assisted surgery and data science related to medical imaging.
Notable scientific contributions from Siewerdsen's work include:


Morphogen

A morphogen is a substance whose non-uniform distribution governs the pattern of tissue development in the process of morphogenesis or pattern formation, one of the core processes of developmental biology, establishing positions of the various specialized cell types within a tissue. More specifically, a morphogen is a signaling molecule that acts directly on cells to produce specific cellular responses depending on its local concentration.
Typically, morphogens are produced by source cells and diffuse through surrounding tissues in an embryo during early development, such that concentration gradients are set up. These gradients drive the process of differentiation of unspecialised stem cells into different cell types, ultimately forming all the tissues and organs of the body. The control of morphogenesis is a central element in evolutionary developmental biology (evo-devo).
History.
The term was coined by Alan Turing in the paper "The Chemical Basis of Morphogenesis", where he predicted a chemical mechanism for biological pattern formation, decades before the formation of such patterns was demonstrated.
The concept of the morphogen has a long history in developmental biology, dating back to the work of the pioneering "Drosophila" (fruit fly) geneticist, Thomas Hunt Morgan, in the early 20th century. Lewis Wolpert refined the morphogen concept in the 1960s with the French flag model, which described how a morphogen could subdivide a tissue into domains of different target gene expression (corresponding to the colours of the French flag). This model was championed by the leading "Drosophila" biologist, Peter Lawrence. Christiane Nüsslein-Volhard was the first to identify a morphogen, Bicoid, one of the transcription factors present in a gradient in the "Drosophila" syncitial embryo. She was awarded the 1995 Nobel Prize in Physiology and Medicine for her work explaining the morphogenic embryology of the common fruit fly. Groups led by Gary Struhl and Stephen Cohen then demonstrated that a secreted signalling protein, decapentaplegic (the "Drosophila" homologue of transforming growth factor beta), acted as a morphogen during the later stages of "Drosophila" development.
Mechanism.
During early development, morphogen gradients result in the differentiation of specific cell types in a distinct spatial order. The morphogen provides spatial information by forming a concentration gradient that subdivides a field of cells by inducing or maintaining the expression of different target genes at distinct concentration thresholds. Thus, cells far from the source of the morphogen will receive low levels of morphogen and express only low-threshold target genes. In contrast, cells close to the source of morphogen will receive high levels of morphogen and will express both low- and high-threshold target genes. Distinct cell types emerge as a consequence of the different combination of target gene expression. In this way, the field of cells is subdivided into different types according to their position relative to the source of the morphogen. This model is assumed to be a general mechanism by which cell type diversity can be generated in embryonic development in animals.
Some of the earliest and best-studied morphogens are transcription factors that diffuse within early "Drosophila melanogaster" (fruit fly) embryos. However, most morphogens are secreted proteins that signal between cells.
Genes and signals.
A morphogen spreads from a localized source and forms a concentration gradient across a developing tissue. In developmental biology, 'morphogen' is rigorously used to mean a signalling molecule that acts directly on cells (not through serial induction) to produce specific cellular responses that depend on morphogen concentration. This definition concerns the mechanism, not any specific chemical formula, so simple compounds such as retinoic acid (the active metabolite of retinol or vitamin A) may also act as morphogens. The model is not universally accepted due to specific issues with setting up a gradient in the tissue outlined in the French flag model and subsequent work showing that the morphogen gradient of the Drosophila embryo is more complex than the simple gradient model would indicate.
Examples.
Proposed mammalian morphogens include retinoic acid, sonic hedgehog (SHH), transforming growth factor beta (TGF-β)/bone morphogenic protein (BMP), and Wnt/beta-catenin. Morphogens in "Drosophila" include decapentaplegic and hedgehog.
During development, retinoic acid, a metabolite of vitamin A, is used to stimulate the growth of the posterior end of the organism. Retinoic acid binds to retinoic acid receptors that acts as transcription factors to regulate the expression of Hox genes. Exposure of embryos to exogenous retinoids especially in the first trimester results in birth defects.
TGF-β family members are involved in dorsoventral patterning and the formation of some organs. Binding to TGF-β to type II TGF beta receptors recruits type I receptors causing the latter to be transphosphorylated. The type I receptors activate Smad proteins that in turn act as transcription factors that regulate gene transcription.
Sonic hedgehog (SHH) are morphogens that are essential to early patterning in the developing embryo. SHH binds to the Patched receptor which in the absence of SHH inhibits the Smoothened receptor. Activated smoothened in turn causes Gli1, Gli2, and Gli3 to be translocated into the nucleus where they activate target genes such at PTCH1 and Engrailed.
Fruit fly.
"Drosophila melanogaster" has an unusual developmental system, in which the first thirteen cell divisions of the embryo occur within a syncytium prior to cellularization. Essentially the embryo remains a single cell with over 8000 nuclei evenly spaced near the membrane until the fourteenth cell division, when independent membranes furrow between the nuclei, separating them into independent cells. As a result, in fly embryos transcription factors such as Bicoid or Hunchback can act as morphogens because they can freely diffuse between nuclei to produce smooth gradients of concentration without relying on specialized intercellular signalling mechanisms. Although there is some evidence that homeobox transcription factors similar to these can pass directly through cell membranes, this mechanism is not believed to contribute greatly to morphogenesis in cellularized systems.
In most developmental systems, such as human embryos or later "Drosophila" development, syncytia occur only rarely (such as in skeletal muscle), and morphogens are generally secreted signalling proteins. These proteins bind to the extracellular domains of transmembrane receptor proteins, which use an elaborate process of signal transduction to communicate the level of morphogen to the nucleus. The nuclear targets of signal transduction pathways are usually transcription factors, whose activity is regulated in a manner that reflects the level of morphogen received at the cell surface. Thus, secreted morphogens act to generate gradients of transcription factor activity just like those that are generated in the syncitial "Drosophila" embryo.
Discrete target genes respond to different thresholds of morphogen activity. The expression of target genes is controlled by segments of DNA called 'enhancers' to which transcription factors bind directly. Once bound, the transcription factor then stimulates or inhibits the transcription of the gene and thus controls the level of expression of the gene product (usually a protein). 'Low-threshold' target genes require only low levels of morphogen activity to be regulated and feature enhancers that contain many high-affinity binding sites for the transcription factor. 'High-threshold' target genes have relatively fewer binding sites or low-affinity binding sites that require much greater levels of transcription factor activity to be regulated.
The general mechanism by which the morphogen model works, can explain the subdivision of tissues into patterns of distinct cell types, assuming it is possible to create and maintain a gradient. However, the morphogen model is often invoked for additional activities such as controlling the growth of the tissue or orienting the polarity of cells within it (for example, the hairs on your forearm point in one direction) which cannot be explained by model.
Eponyms.
The organizing role that morphogens play during animal development was acknowledged in the 2014 naming of a new beetle genus, "Morphogenia". The type species, "Morphogenia struhli", was named in honour of Gary Struhl, the US developmental biologist who was instrumental in demonstrating that the "decapentaplegic" and "wingless" genes encode proteins that function as morphogens during "Drosophila" development.


Catabolism

Catabolism () is the set of metabolic pathways that breaks down molecules into smaller units that are either oxidized to release energy or used in other anabolic reactions. Catabolism breaks down large molecules (such as polysaccharides, lipids, nucleic acids, and proteins) into smaller units (such as monosaccharides, fatty acids, nucleotides, and amino acids, respectively). Catabolism is the breaking-down aspect of metabolism, whereas anabolism is the building-up aspect.
Cells use the monomers released from breaking down polymers to either construct new polymer molecules or degrade the monomers further to simple waste products, releasing energy. Cellular wastes include lactic acid, acetic acid, carbon dioxide, ammonia, and urea. The creation of these wastes is usually an oxidation process involving a release of chemical free energy, some of which is lost as heat, but the rest of which is used to drive the synthesis of adenosine triphosphate (ATP). This molecule acts as a way for the cell to transfer the energy released by catabolism to the energy-requiring reactions that make up anabolism. (Catabolism is seen as destructive metabolism and anabolism as constructive metabolism). Catabolism, therefore, provides the chemical energy necessary for the maintenance and growth of cells. Examples of catabolic processes include glycolysis, the citric acid cycle, the breakdown of muscle protein in order to use amino acids as substrates for gluconeogenesis, the breakdown of fat in adipose tissue to fatty acids, and oxidative deamination of neurotransmitters by monoamine oxidase.
Catabolic hormones.
There are many signals that control catabolism. Most of the known signals are hormones and the molecules involved in metabolism itself. Endocrinologists have traditionally classified many of the hormones as anabolic or catabolic, depending on which part of metabolism they stimulate. The so-called classic catabolic hormones known since the early 20th century are cortisol, glucagon, and adrenaline (and other catecholamines). In recent decades, many more hormones with at least some catabolic effects have been discovered, including cytokines, orexin (also known as hypocretin), and melatonin.
Etymology.
The word "catabolism" is from New Latin, which got the roots from Greek: κάτω "kato", "downward" and βάλλειν "ballein", "to throw".


L-694247

L-694247 is a somewhat selective 5-HT1D agonist, with a 10-fold greater affinity for the 5-HT1B receptor, and 25-fold greater affinity for the 5-HT1A receptor. When L-694247 was injected intraventricularly in dehydrated rats, it inhibited water intake. Pre-treatment with a 5-HT1D antagonist abolished this effect. Administration of L-694,247 to normally hydrated rats had no effect on water intake.


Cardiovirus cis-acting replication element

This family represents a Cardiovirus cis-acting replication element (CRE) which is located within the region encoding the capsid protein VP2 and is required for viral replication.


New Zealand Public Party

The New Zealand Public Party was a political party in New Zealand led by Billy Te Kahika. It was founded in June 2020, and two months later became a component party of registered party Advance New Zealand in order to contest the . Advance received only 1.0% of the party vote and neither Advance nor Public won any electorate seats, so the Public Party did not win any representation in Parliament. The Public Party split from Advance shortly after the election acrimoniously, and Public's party secretary and director both resigned in January 2021.
The party was "conspiracy theory driven", opposing the United Nations, 5G technology, 1080 poison, fluoridation, and electromagnets. It spreads misinformation related to the COVID-19 pandemic and aims to repeal the COVID-19 Public Health Response Act 2020, the primary legal mechanism for fighting the COVID-19 pandemic in New Zealand.
In mid–February 2021, after briefly renaming it the New Zealand Freedom Party, Te Kahika announced that he was shutting down the party to focus on activism.
History.
Foundation.
Billy Te Kahika, son of guitarist and musician Billy TK, founded the party in June 2020. At the party's launch, Te Kahika said that the COVID-19 pandemic would enable globalist leaders to implement UN agendas that would totally control people's lives, and that billionaires had developed weaponised viruses and patented treatments for the viruses they had made, in order to enslave humanity. Despite an initial lack of coverage in mainstream media, the party collected a following on social media.
Alliance with Advance New Zealand.
After it missed the deadline for registration to contest the party vote in the 2020 general election, the Public Party attempted to form an electoral alliance with Vision NZ. Vision refused to provide Te Kahika the leadership position of a merged party and the plan fell apart. Talks with the New Zealand Outdoors Party were also unsuccessful. The party did not apply for a broadcasting allocation for the 2020 election.
On 26 July 2020 the party announced an electoral alliance with Advance New Zealand. Billy Te Kahika became co-leader of Advance and had the number one ranking on Advance's party's list. Advance New Zealand was registered on 6 August 2020, and so was eligible to contest the party vote.
The Public Party announced that it would run candidates for electorates under the Public Party name. Billy Te Kahika contested Te Tai Tokerau, and Jenny Brown was announced as a candidate for the East Coast electorate. Self-proclaimed psychic Jeanette Wilson announced her candidacy, but withdrew it the next day. As the Public Party was a component party of Advance New Zealand, then if the Public Party were to have won an electorate seat, this would have ensured Advance's entry to parliament.
In early August 2020, the New Zealand Outdoors Party's co-leader Sue Grey alleged that her party had been the target of a harassment campaign by supporters of the NZ Public Party after they had a rejected a takeover offer in April and refused to join an alliance with Advance New Zealand. Public Party leader Billy Te Kahika said that he found the behaviour "absolutely reprehensible" and asked his supporters not to abuse Grey, but also alleged that supporters of the Outdoors Party had been abusive towards his party.
On 16 August the Public Party was recognised as a component party of Advance New Zealand by the Electoral Commission.
2020 election campaign.
On 27 August the Public Party drew controversy after it posted a video on its Facebook page claiming that the New Zealand Government had passed a law allowing it to force citizens to get a COVID-19 vaccine. According to Agence France-Presse's Fact Check, key parts of MPs' speeches had been cut out and edited to distort what they were saying. The Advance Party's co-leader Jami-Lee Ross defended the video, claiming that the Labour-led coalition government had passed a law to forcibly vaccinate citizens. After refusing to remove the video, Ross was referred to the Parliamentary Privileges Committee by Speaker of the House Trevor Mallard, which concluded that the video was "deliberately misleading".
The anti-domestic violence charity White Ribbons ended Te Kahika's ambassadorship in August 2020, on the grounds that his recent remarks about COVID-19 and other issues undermined the trust's evidence-based approach. Te Kahika also alleged that he was the target of an international assassin.
On 8 September 2020 lawyers acting for the party threatened a former member with legal action for defamation over claims party director Michael Stace was a "CIA agent". On 9 September 2020 the Electoral Commission announced that it was investigating the Public Party's collection and use of party donations, following a complaint passed on by the Serious Fraud Office. On 10 September, the Electoral Commission suspended its investigation into the Public Party's collection and use of donations since it is not subject to the rules of the Electoral Act as an unregistered party. The party reportedly received $255,000 in undeclared donations.
A poll of Te Tai Tokerau, released on 8 October, reported Te Kahika had less than 1% of people in the electorate intended to vote for him.
At the election, the Advance Party received only 1.0% of the party vote, below the 5% threshold required to enter Parliament. Advance also failed to win any electorate seats. Te Kahika himself won only 1,349 electorate votes, coming fourth, and Jennie Brown received 832 votes and came fifth. As such, no members of the Public Party were elected.
Post-election.
After the election, Billy Te Kahika claimed the election had been rigged, and said he feared votes for Advance were not counted because voters added comments or smiley faces to their ballots. He also said he was "very worried" that 200,000 votes had been not been properly counted. He refused to accept the election result and said he planned a tally of Advance voters to prove the official process was corrupt. The Electoral Commission said that adding comments to a ballot would not invalidate it, and did not understand his reasoning for claim about the 200,000 lost votes. In a later post, he said that his figure of 200,000 was a mistake, but insisted that Advance NZ supporters' had written comments and drawn smiley faces on their voting forms, causing them to be disqualified.
On 26 October, Te Kahika severed ties with Advance NZ after its election failure, stating that he had decided not to continue with the party. Later that day, Te Kahika issued a statement clarifying that he was not severing relations with Advance NZ but was instead restoring its "autonomy." Te Kahika also vowed not to step down as party leader and reiterated his support for Advance NZ. By December 2020, the Public Party was no longer recorded as a component party of Advance, according to the Electoral Commission, and Te Kahika was no longer mentioned as a co-leader of Advance on that party's website.
According to a Stuff report by Matt Shand, Ross had brushed aside concerns by senior party officials about irregularities with Te Kahika's donations (or koha) on the grounds that he had little prospect of being re-elected without Te Kahika's party. Ross also reportedly threaten to resign if Te Kahika was removed over financial irregularities.
In November 2020, the Public Party received a letter from Advance New Zealand saying that policies on the Public Party website were copyrighted by Advance NZ and that the Public Party must stop using them, and that the Public Party must not use certain colours associated with Advance. Public Party director Michael Stace also said they had been locked out of a joint bank account and has asked police to investigate to recover funds (worth NZ$60,000), but Advance NZ's lawyer Graeme Edgeler stated that the bank account in question was always in Advance's name only and that it did not owe the Public Party any money. Stace alleged that Advance NZ had a mole within the Public Party who was leaking information about the Public Party's movements and activities to the other party's leadership. Edgeler proposed a settlement in which Advance NZ would pay the costs of an advertisement in the Christchurch-based "The Press" newspaper and an invoice from the East City Community Trust for election night party costs. However, he also warned that Advance NZ would file legal action against Te Kahika and the Public Party if the latter did not drop their allegations that Ross and Advance NZ had committed theft and misconduct.
On 2 January 2021, the party secretary Michelle Hood, and the director Michael Stace, resigned from the party, with Stace posting details of financial irregularities on the party website. Stace labelled the party "a cult", while Hood stated Te Kahika was "more interested in a rock and roll lifestyle than politics".
On 19 February, Te Kahika announced the dissolution of the NZ Public Party, which he had briefly renamed the Freedom Party. However, he vowed to continue his activist work via social media.


CD8.4

CD8.4 is a murine chimeric coreceptor. The extracellular and transmembrane part of the coreceptor is from wild-type CD8 coreceptor, whereas the intracellular domain from CD4 coreceptor. This model was created to examine role of coreceptor coupling to Lck (lymphocyte-specific protein tyrosine kinase) as the CD4 and CD8 coreceptors have an Lck-binding site in their intracellular domain. CD4 coreceptor has higher coupling to Lck in thymocytes than CD8 coreceptor. CD8.4 coreceptor has similar coupling to Lck as CD4 coreceptor, while the MHC I-binding site remains identical to wild-type CD8. This chimeric coreceptor therefore enables addressing influence of different coupling to Lck on TCR signaling.


RiAFP

RiAFP refers to an antifreeze protein (AFP) produced by the "Rhagium inquisitor" longhorned beetle. It is a type V antifreeze protein with a molecular weight of 12.8 kDa; this type of AFP is noted for its hyperactivity. "R. inquisitor" is a freeze-avoidant species, meaning that, due to its AFP, "R. inquisitor" prevents its body fluids from freezing altogether. This contrasts with freeze-tolerant species, whose AFPs simply depress levels of ice crystal formation in low temperatures. Whereas most insect antifreeze proteins contain cysteines at least every sixth residue, as well as varying numbers of 12- or 13-mer repeats of 8.3-12.5kDa, RiAFP is notable for containing only one disulfide bridge. This property of RiAFP makes it particularly attractive for recombinant expression and biotechnological applications.
AFPs.
AFPs work through an interaction with small ice crystals that is similar to an enzyme-ligand binding mechanism which inhibits recrystallization of ice. This explanation of the interruption of the ice crystal structure by the AFP has come to be known as the "adsorption-inhibition hypothesis".
According to this hypothesis, AFPs disrupt the thermodynamically favourable growth of an ice crystal via kinetic inhibition of contact between solid ice and liquid water. In this manner, the nucleation sites of the ice crystal lattice are blocked by the AFP, inhibiting the rapid growth of the crystal that could be fatal for the organism. In physical chemistry terms, the AFPs adsorbed onto the exposed ice crystal force the growth of the ice crystal in a convex fashion as the temperature drops, which elevates the ice vapour pressure at the nucleation sites. Ice vapour pressure continues to increase until it reaches equilibrium with the surrounding solution (water), at which point the growth of the ice crystal stops.
The aforementioned effect of AFPs on ice crystal nucleation is lost at the thermal hysteresis point. At a certain low temperature, the maximum convexity of the ice nucleation site is reached. Any further cooling will actually result in a "spreading" of the nucleation site away from this convex region, causing rapid, uncontrollable nucleation of the ice crystal. The temperature at which this phenomenon occurs is the thermal hysteresis point.<br>
The "adsorption-inhibition hypothesis" is further supported by the observation that antifreeze activity increases with increasing AFP concentration – the more AFPs adsorb onto the forming ice crystal, the more 'crowded' these proteins become, making ice crystal nucleation less favourable.
In the "R. inquisitor" beetle, AFPs are found in the haemolymph, a fluid that bathes all the cells of the beetle and fills a cavity called the haemocoel. The presence of AFPs in "R. inquisitor" allows the tissues and fluids within the beetle to withstand freezing up to -30 °C (the thermal hysteresis point for this AFP). This strategy provides an obvious survival benefit to these beetles, who are endemic to cold climates, such as Scandinavia, Siberia, and Alaska.
RiAFP Ice Binding.
The primary structure of RiAFP (the sequence may be found here) determined by Mass Spectroscopy, Edman degradation and by constructing a partial cDNA sequence and PCR have shown that a TxTxTxT internal repeat exists. Sequence logos constructed from the RiAFP internal repeats, have been particularly helpful in the determination of the consensus sequence of these repeats. The TxTxTxT domains are irregularly spaced within the protein and have been shown to be conserved from the TxT binding motif of other AFPs. The hydroxyl moiety of the T residues fits well, when spaced as they are in the internal repeats, with the hydroxyl moieties of externally facing water molecules in the forming ice lattice. This mimics the formation of the growth cone at a nucleation site in the absence of AFPs. Thus, the binding of RiAFP inhibits the growth of the crystal in the basal and prism planes of the ice.
RiAFP Predicted Structure.
The fact that the binding motif appears as a "triplet" of the conserved TxT repeat, as well as the observation that blastp queries have returned no viable matches, has led some researchers to suggest that RiAFP represents a new type of AFP – one that differs from the heavily studied "TmAFP" (from "T. molitor"), "DcAFP" (from "D. canadensis"), and "CfAFP" (from "C. fumiferana"). On the basis of these observations, it has been predicted that the need for insect AFPs came about after insect evolutionary divergence, much like the evolution of fish AFPs; thus, different AFPs most likely evolved in parallel from adaptations to cold (environmental) stress. As a result, homology modelling with "TmAFP", "DcAFP", or "CfAFP" would prove to be fruitless.
Secondary structure modelling algorithms have determined that the internal repeats are spaced sufficiently to tend towards β-strand configuration; no helical regions include the conserved repeats; and all turn regions are located at the ends of β-strand regions. These data suggest that RiAFP is a well-folded β-helical protein, having six β-strand regions consisting of 13-amino acids (including one TxTxTxT binding motif) per strand.
Primary crystallographic studies, have been published on a RiAFP crystal (which diffracted to 1.3Å resolution) in the trigonal space group P3121 (or P3221), with unit-cell parameters a = b = 46.46, c = 193.21Å.


Walker Bleakney

Walker Bleakney (February 8, 1901 – January 15, 1992) was an American physicist, one of inventors of mass spectrometers, and widely noted for his research in the fields of atomic physics, molecular physics, fluid dynamics,the ionization of gases, and blast waves. Bleakney was the chair of the department of physics at Princeton University.
He was the head of the Princeton Ballistic Project during World War II.
Career.
Bleakney graduated from Whitman College in 1924 with a BS degree. He received his Ph.D. from the University of Minnesota in 1930.
He then spent his entire career at Princeton University, first as a National Research Fellow, then as an instructor in 1932.
He then became an assistant professor in 1935 , an associate professor in 1938 and a full professor in 1944. Bleakney became the chair of the Department of Physics in 1960, and remained in that capacity until 1967.
Early in his career at Princeton, Bleaker was able to make a difference in nuclear physics. For example, he proved that heavy water contains traces of triple-weight hydrogen (1935). In a team with other Princeton physicists he produced Hydrogen 3 in 1934.


Alfred Bucherer

Alfred Heinrich Bucherer (* 9 July 1863 in Cologne; † 16 April 1927 in Bonn) was a German physicist, who is known for his experiments on relativistic mass. He also was the first who used the phrase "theory of relativity" for Einstein's theory of special relativity.
Education.
He studied from 1884 until 1899 at the University of Hannover, the Johns Hopkins University, the University of Strassburg, the University of Leipzig, and the University of Bonn. In Bonn he habilitated in 1899 and taught there until 1923.
In 1903 Bucherer published the first German-language book to be completely based on vector calculus.
Theory of relativity.
Like Henri Poincaré (1895, 1900), Bucherer (1903b) believed in the validity of the Principle of relativity, i.e. that all descriptions of electrodynamic effects should only contain the relative motion of bodies, not of the aether. However, he went a step further and even assumed the physical non-existence of the aether. Based on those ideas he developed a theory in 1906, which also included the assumption that the geometry of space is riemannian. But the theory was vaguely formulated and in 1908 Walther Ritz showed that Bucherer's theory leads to wrong conclusions with respect to electrodynamics. And contrary to Albert Einstein, he didn't connect his rejection of the aether with the relativity of space and time.
In 1904 he developed a theory of electrons in which the electrons contract in the line of motion and expand perpendicular to it. Independently of him Paul Langevin developed a very similar model in 1905. The Bucherer-Langevin model was an alternative to the electron models of:
All three models predicted an increase of the electron mass if their velocities are approaching the speed of light. The Bucherer-Langevin model was quickly abandoned, so some experimentalists tried to distinguish between Abraham's theory and the Lorentz-Einstein theory by experiment. This was done by Walter Kaufmann (1901–1905) who believed that his experiments confirmed Abraham's theory, and disproved the Lorentz-Einstein theory. But in 1908 Bucherer conducted some experiments as well, and obtained results which seem to confirm the Lorentz-Einstein theory and the principle of relativity. With exceptions like Adolf Bestelmeyer with whom Bucherer had a polemical dispute, Bucherer's experiments were regarded as decisive. But it was shown in 1938 that all those experiments of Kaufmann, Bucherer, Neumann etc. showed only a qualitative increase in mass, but were too imprecise to distinguish between the different models. This lasted until 1940, when similar experimental equipments were sufficiently accurate to confirm the Lorentz-Einstein formula, see Kaufmann–Bucherer–Neumann experiments and Tests of relativistic energy and momentum.
Bucherer (1906) was the first who used — during some critical remarks on Einstein's theory — the expression "Einsteinian relativity theory / theory of relativity" ("Einsteinsche Relativitätstheorie"). This was based on Max Planck's term "relative theory" for the Lorentz-Einstein theory. And in 1908 Bucherer himself rejected his own version of the relativity principle, and accepted the "Lorentz-Einstein theory".
Later (1923, 1924), Bucherer criticized general relativity in some papers. However, this criticism was rejected because Bucherer misinterpreted Einstein's equivalence hypothesis.


Morphant

An organism which has been treated with a morpholino antisense oligo to temporarily knock down expression of a targeted gene is called a morphant.
Background.
This term was coined by Prof. Steve Ekker to describe the zebrafish with which he was experimenting; by knocking down embryonic gene expression using Morpholinos, Prof. Ekker "phenocopied" known zebrafish mutations, that is, he raised embryos that had the same morphological phenotype as embryonic zebrafish with specific gene mutations. Prof. Ekker's papers and presentations describing morphant phenocopies of mutant phenotypes, in combination with Prof. Janet Heasman's earlier work with Morpholinos in Xenopus embryos, led to rapid adoption of Morpholino technology by the developmental biology community.


Ribose-5-phosphate adenylyltransferase

In enzymology, a ribose-5-phosphate adenylyltransferase () is an enzyme that catalyzes the chemical reaction
Thus, the two substrates of this enzyme are ADP and D-ribose 5-phosphate, whereas its two products are phosphate and ADP-ribose.
This enzyme belongs to the family of transferases, specifically those transferring phosphorus-containing nucleotide groups (nucleotidyltransferases). The systematic name of this enzyme class is ADP:D-ribose-5-phosphate adenylyltransferase. Other names in common use include ADP ribose phosphorylase, and adenosine diphosphoribose phosphorylase.


Sir William Dunn Professor of Biochemistry

The Sir William Dunn Professorship of Biochemistry is the senior professorship in biochemistry at the University of Cambridge. The position was established in 1914 by the trustees of the will of Sir William Dunn, banker, merchant and philanthropist.
The first holder of the chair was Frederick Gowland Hopkins, winner of the 1929 Nobel Prize in Medicine for his work on the discovery of vitamins.


Cytokinin dehydrogenase

In enzymology, a cytokinin dehydrogenase () is an enzyme that catalyzes the chemical reaction
The 3 substrates of this enzyme are cytokinin (here represented by "N"6-dimethylallyladenine), electron acceptor, and H2O, whereas its 3 products are adenine, 3-methylbut-2-enal (or other aldehyde in case of different substrate), and reduced acceptor.
This enzyme belongs to the family of oxidoreductases, specifically those acting on the CH-NH group of donors with other acceptors. The systematic name of this enzyme class is N"6-dimethylallyladenine:acceptor oxidoreductase. Other names in common use include N"6-dimethylallyladenine:(acceptor) oxidoreductase, 6-N-dimethylallyladenine:acceptor oxidoreductase, and cytokinin oxidase/dehydrogenase abbreviated as CKX.
Structural studies.
As of late 2007, 6 structures have been solved for this class of enzymes, with PDB accession codes , , , , , and .
As of March 2016, there have been 18 structures deposited to PDB. 16 of these were of enzymes from maize and two from Arabidopsis.


Peter Hermann Stillmark

Peter Hermann Stillmark (22 July 1860, Penza, Russia – 23 June 1923, Pärnu, Estonia) was a Baltic-German microbiologist.
In 1888 at the University in Dorpat, now Tartu in Estonia under prof. Rudolf Kobert's supervision Peter Hermann Stillmark (1860–1923) completed his doctoral thesis "Über Ricin, ein giftiges Ferment aus den Samen von Ricinus comm. L. und einigen anderen Euphorbiaceen", which is a description of the isolation of ricin, a poisonous protein component from castor beans. That event is internationally recognised as the birth of a new branch of science called lectinology.
Any of a group of proteins, derived from plants, that can bind to specific oligosaccharides on the surface of cells, causing the cells to clump together. Lectins can be used to identify mutant cells in cell cultures and to determine blood groups as they can cause the agglutination of red blood cells. Lectins are found in seeds of legumes and in other tissues, in which they are thought to act as a toxin.
Sources.
"This article incorporates language from Herrmann Stillmark, which is released under GFDL."


Pseudarthrobacter chlorophenolicus

Pseudarthrobacter chlorophenolicus, also known as Arthrobacter chlorophenolicus, is a species of bacteria capable of degrading high concentrations of 4-chlorophenol, hence its name. As such. It may be useful in bioremediation. Its type strain is DSM 12829T.
Before the year 2016, this bacterium species was said to be a species of Arthrobacter genus. The bacterium species is reclassified in 2016 to be a member of Pseudarthrobacter. Therefore it had a new name as "Pseudarthrobacter chlorophenolicus".


Urolithin

Urolithins are microflora human metabolites of dietary ellagic acid derivatives such as ellagitannins. They are produced in the human gut, and found in the urine in the form of urolithin B glucuronide after absorption of ellagitannins-containing food such as pomegranate, strawberries, red raspberries, walnuts or oak-aged red wine.
During intestinal metabolism by bacteria, ellagitannins and punicalagins are converted to urolithins, which have unknown biological activity "in vivo" in humans. Urolithins metabolites of pomegranate juice ellagitannins localize specifically in the prostate gland, colon, and intestinal tissues of mice.
Ellagitannins exhibit low bioavailability and are transformed in the gut to ellagic acid and its microbiota metabolites. Urolithins are found in plasma mostly as glucuronides at low concentrations.
Urolithins production is dependent on the gut microbiome enterotype. Individuals producing urolithins show a much higher abundance of the "Clostridium leptum" group of Firmicutes phylum than "Bacteroides" or "Prevotella".
Urolithin M7 has also been synthetized from 2-hydroxy-4-methoxybenzaldehyde using the inverse electron-demand Diels–Alder reaction.
Known molecules.
catabolic intermediates:


Giant otter shrew

The giant otter shrew ("Potamogale velox") is a semiaquatic, carnivorous afrotherian mammal. It is found in the main rainforest block of central Africa from Nigeria to Zambia, with a few isolated populations in Kenya and Uganda. It lives in streams, wetlands and slow flowing larger rivers. It is the only species in the genus "Potamogale". Otter shrews are most closely related to the tenrecs of Madagascar.
They are nocturnal carnivores that feed on aquatic animals. Despite its name, the giant otter shrew is not a true shrew (Soricidae). The common name refers to their resemblance to otters with their flat face, stiff whiskers, and muscular tails, and to their overall superficial similarity to true shrews.
Description.
The giant otter shrew is a mammal superficially similar to an otter in appearance.
It is characterized by a long, flat tail, which it uses for swimming by sideways undulation like a fish. It has a muzzle covered with bristles, and flat shielded nostrils. It has dense, soft hair, silky on the tail.
It has small eyes and external ears. Its fur consists of a dense undercoat and coarse guard hairs. It possesses counter-shading with dark brown on its back and whitish or yellowish under parts. The tail is covered with a short, silky coat of fur and is compressed laterally which allow it to swim by horizontal undulations as in fishes and crocodiles. Its legs are short and lack webbing so they are not used for swimming. The hind feet have a flap of skin along the inside that allows them to be held snugly against the body when swimming. There are also two syndactylous (2nd and 3rd toes are fused) toes on the hind feet, used for grooming. On land "P. velox" is plantigrade. Females have two mammae on the lower abdomen for feeding young.
The mass ranges from 300 to 950 g. Head and body length is 290–350 mm, and reaches 535–640 mm with tail.
Geographic range.
Giant otter shrews are native to central Africa, from the southern regions of Nigeria (central Rainforest Zone), and then eastward through Equatorial Guinea, Gabon, and the Central African Republic, Chad, the Republic of Congo, the Democratic Republic of the Congo, South Sudan to the northern regions of Angola and Zambia. There is a small population that lives between Uganda and Kenya and the preserved rainforest of Kakamega, Kenya.
Habitat.
This species prefers fresh water aquatic microhabitats in the rainforest. Preferred environments include fast flowing rivers, streams, swamps, coastal rivers, and during rainy season some may retreat to small forest pools (altitude range from 0–1,800m). River banks provide good habitats for breeding and nesting. These animals make burrows with an entrance below water level (like otters) and during the day find shelter there and then become active in the afternoon.
Behavior.
The giant otter shrew builds burrows among riverbank crevices. It chooses dry leaves with which to line its nest. This is also where breeding takes place. The burrows are frequently changed. When foraging, otter shrews take frequent grooming breaks. When traveling upstream the otter shrew travels on the bank and then swims downstream. The night foraging routine is regular and predictable, and covers up to 800 meters a night. "P. velox" regularly visits discrete piles of feces that are sheltered and probably used to mark boundaries of territory.
Giant otter shrews are solitary with one shrew occupying between 500–1,000 m of stream.
Food habits.
"P. velox" is a nocturnal predator, hunting primarily by touch and scent in and around calm pools. Each dive lasts only seconds. "P. velox" searches both within the pool and along the bank for prey using the sensitive vibrissae and odor and apparently not eyesight. It prefers areas that have cover to retreat to when it feels threatened. "P. velox" attacks prey using sharp bites, sometimes pinning the prey with its fore feet, and flipping crabs over to attack their weaker ventral surface. They usually avoid crabs larger than 7 cm across. The prey preference varies among individuals; some prefer crabs; others, frogs or fish. Frogs are eaten headfirst and fish are pulled apart into manageable bits. Prey is consumed on the bank. "P. velox" also eats insects, mollusks, and freshwater prawns.
In captivity it eats 15–20 crabs per night.
Lifespan.
Giant otter shrews fare very poorly in captivity. Captive specimens have been recorded to deteriorate in health very quickly, living only 1– 14 days.
Reproduction.
Giant otter shrews breed during the wet/rainy season. They give birth to one or two young per litter, once or twice a year. Males move long distances via water in search of mates and it is thought that males rut (or fight) during the wet season.
Conservation status.
Currently this species is listed as being of least concern by the IUCN because its declining rate is not significant enough to move to the next category. However it is on the decline. One of the major threats to this species is the soil erosion caused by deforestation especially in Cameroon. While they can tolerate seasonally cloudy streams, streams muddied from erosion and deforestation are little used. Some drown in fishing nets or fish traps, and members of this species have not survived well in captivity. There is ongoing research about the effects of human activity on them. It is also hunted extensively for its skin.


JUMPstart RNA motif

The JUMPstart RNA motif describes a conserved RNA-based secondary structure associated with JUMPstart elements. The 39-base-pair JUMPstart sequence describes a conserved element upstream of genes that participate in polysaccharide synthesis. The JUMPstart element has been shown to function as an RNA, and is present in the 5' untranslated regions of the genes it regulates.
JUMPstart sequences include an ops element, which is an acronym for "operon-polarity suppressor" and has the nucleotide consensus GGCGGUAG. The ops element acts in concert with the RfaH protein to improve transcription of genes downstream of the ops element, especially genes far away within long operons.


Membrane transport

In cellular biology, membrane transport refers to the collection of mechanisms that regulate the passage of solutes such as ions and small molecules through biological membranes, which are lipid bilayers that contain proteins embedded in them. The regulation of passage through the membrane is due to selective membrane permeability - a characteristic of biological membranes which allows them to separate substances of distinct chemical nature. In other words, they can be permeable to certain substances but not to others.
The movements of most solutes through the membrane are mediated by membrane transport proteins which are specialized to varying degrees in the transport of specific molecules. As the diversity and physiology of the distinct cells is highly related to their capacities to attract different external elements, it is postulated that there is a group of specific transport proteins for each cell type and for every specific physiological stage[1]. This differential expression is regulated through the differential transcription of the genes coding for these proteins and its translation, for instance, through genetic-molecular mechanisms, but also at the cell biology level: the production of these proteins can be activated by cellular signaling pathways, at the biochemical level, or even by being situated in cytoplasmic vesicles.
Background.
Thermodynamically the flow of substances from one compartment to another can occur in the direction of a concentration or electrochemical gradient or against it. If the exchange of substances occurs in the direction of the gradient, that is, in the direction of decreasing potential, there is no requirement for an input of energy from outside the system; if, however, the transport is against the gradient, it will require the input of energy, metabolic energy in this case.
For example, a classic chemical mechanism for separation that does not require the addition of external energy is dialysis. In this system a semipermeable membrane separates two solutions of different concentration of the same solute. If the membrane allows the passage of water but not the solute the water will move into the compartment with the greatest solute concentration in order to establish an equilibrium in which the energy of the system is at a minimum. This takes place because the water moves from a high solvent concentration to a low one (in terms of the solute, the opposite occurs) and because the water is moving along a gradient there is no need for an external input of energy.
The nature of biological membranes, especially that of its lipids, is amphiphilic, as they form bilayers that contain an internal hydrophobic layer and an external hydrophilic layer. This structure makes transport possible by simple or passive diffusion, which consists of the diffusion of substances through the membrane without expending metabolic energy and without the aid of transport proteins. If the transported substance has a net electrical charge, it will move not only in response to a concentration gradient, but also to an electrochemical gradient due to the membrane potential.
As few molecules are able to diffuse through a lipid membrane the majority of the transport processes involve transport proteins. These transmembrane proteins possess a large number of alpha helices immersed in the lipid matrix. In bacteria these proteins are present in the beta lamina form. This structure probably involves a conduit through hydrophilic protein environments that cause a disruption in the highly hydrophobic medium formed by the lipids.[1] These proteins can be involved in transport in a number of ways: they act as pumps driven by ATP, that is, by metabolic energy, or as channels of facilitated diffusion.
Thermodynamics.
A physiological process can only take place if it complies with basic thermodynamic principles. Membrane transport obeys physical laws that define its capabilities and therefore its biological utility.
A general principle of thermodynamics that governs the transfer of substances through membranes and other surfaces is that the exchange of free energy, Δ"G", for the transport of a mole of a substance of concentration C1 in a compartment to another compartment where it is present at C2 is:
When C2 is less than C1, Δ"G" is negative, and the process is thermodynamically favorable. As the energy is transferred from one compartment to another, except where other factors intervene, an equilibrium will be reached where C2=C1, and where Δ"G" = 0. However, there are three circumstances under which this equilibrium will not be reached, circumstances which are vital for the "in vivo" functioning of biological membranes:
Where F is Faraday's constant and Δ"P" the membrane potential in volts. If Δ"P" is negative and Z is positive, the contribution of the term "ZFΔP" to Δ"G" will be negative, that is, it will favor the transport of cations from the interior of the cell. So, if the potential difference is maintained, the equilibrium state Δ"G" = 0 will not correspond to an equimolar concentration of ions on both sides of the membrane.
Where Δ"Gb" corresponds to a favorable thermodynamic reaction, such as the hydrolysis of ATP, or the co-transport of a compound that is moved in the direction of its gradient.
Transport types.
Passive diffusion and active diffusion.
As mentioned above, passive diffusion is a spontaneous phenomenon that increases the entropy of a system and decreases the free energy. The transport process is influenced by the characteristics of the transport substance and the nature of the bilayer. The diffusion velocity of a pure phospholipid membrane will depend on:
Active and co-transport.
In active transport a solute is moved against a concentration or electrochemical gradient; in doing so the transport proteins involved consume metabolic energy, usually ATP. In primary active transport the hydrolysis of the energy provider (e.g. ATP) takes place directly in order to transport the solute in question, for instance, when the transport proteins are ATPase enzymes. Where the hydrolysis of the energy provider is indirect as is the case in secondary active transport, use is made of the energy stored in an electrochemical gradient. For example, in co-transport use is made of the gradients of certain solutes to transport a target compound against its gradient, causing the dissipation of the solute gradient. It may appear that, in this example, there is no energy use, but hydrolysis of the energy provider is required to establish the gradient of the solute transported along with the target compound. The gradient of the co-transported solute will be generated through the use of certain types of proteins called biochemical pumps.
The discovery of the existence of this type of transporter protein came from the study of the kinetics of cross-membrane molecule transport. For certain solutes it was noted that the transport velocity reached a plateau at a particular concentration above which there was no significant increase in uptake rate, indicating a log curve type response. This was interpreted as showing that transport was mediated by the formation of a substrate-transporter complex, which is conceptually the same as the enzyme-substrate complex of enzyme kinetics. Therefore, each transport protein has an affinity constant for a solute that is equal to the concentration of the solute when the transport velocity is half its maximum value. This is equivalent in the case of an enzyme to the Michaelis–Menten constant.
Some important features of active transport in addition to its ability to intervene even against a gradient, its kinetics and the use of ATP, are its high selectivity and ease of selective pharmacological inhibition
Secondary active transporter proteins.
Secondary active transporter proteins move two molecules at the same time: one against a gradient and the other with its gradient. They are distinguished according to the directionality of the two molecules:
Both can be referred to as co-transporters.
Pumps.
A pump is a protein that hydrolyses ATP to transport a particular solute through a membrane, and in doing so, generating an electrochemical gradient membrane potential. This gradient is of interest as an indicator of the state of the cell through parameters such as the Nernst potential. In terms of membrane transport the gradient is of interest as it contributes to decreased system entropy in the co-transport of substances against their gradient.
One of the most important pumps in animal cells is the sodium potassium pump, that operates through the following mechanism:
Membrane selectivity.
As the main characteristic of transport through a biological membrane is its selectivity and its subsequent behavior as a barrier for certain substances, the underlying physiology of the phenomenon has been studied extensively. Investigation into membrane selectivity have classically been divided into those relating to electrolytes and non-electrolytes.
Electrolyte selectivity.
The ionic channels define an internal diameter that permits the passage of small ions that is related to various characteristics of the ions that could potentially be transported. As the size of the ion is related to its chemical species, it could be assumed "a priori" that a channel whose pore diameter was sufficient to allow the passage of one ion would also allow the transfer of others of smaller size, however, this does not occur in the majority of cases. There are two characteristics alongside size that are important in the determination of the selectivity of the membrane pores: the facility for dehydration and the interaction of the ion with the internal charges of the pore.
In order for an ion to pass through a pore it must dissociate itself from the water molecules that cover it in successive layers of solvation. The tendency to dehydrate, or the facility to do this, is related to the size of the ion: larger ions can do it more easily that the smaller ions, so that a pore with weak polar centres will preferentially allow passage of larger ions over the smaller ones.
When the interior of the channel is composed of polar groups from the side chains of the component amino acids, the interaction of a dehydrated ion with these centres can be more important than the facility for dehydration in conferring the specificity of the channel. For example, a channel made up of histidines and arginines, with positively charged groups, will selectively repel ions of the same polarity, but will facilitate the passage of negatively charged ions. Also, in this case, the smallest ions will be able to interact more closely due to the spatial arrangement of the molecule (stericity), which greatly increases the charge-charge interactions and therefore exaggerates the effect.
Non-electrolyte selectivity.
Non-electrolytes, substances that generally are hydrophobic and lipophilic, usually pass through the membrane by dissolution in the lipid bilayer, and therefore, by passive diffusion. For those non-electrolytes whose transport through the membrane is mediated by a transport protein the ability to diffuse is, generally, dependent on the partition coefficient K.
Partially charged non-electrolytes, that are more or less polar, such as ethanol, methanol or urea, are able to pass through the membrane through aqueous channels immersed in the membrane. There is no effective regulation mechanism that limits this transport, which indicates an intrinsic vulnerability of the cells to the penetration of these molecules.
Creation of membrane transport proteins.
There are several databases which attempt to construct phylogenetic trees detailing the creation of transporter proteins. One such resource is the Transporter Classification database


Petrosaltator


Bacillus-plasmid RNA motif

The "Bacillus"-plasmid RNA motif is a predicted conserved RNA structure usually located in plasmids. It is known in species under the genera "Bacillus" and "Lactobacillus". In "Bacillus subtilis", it is found upstream of the hypothetical gene "ydcS", whose function is unknown.
The fact that the RNA structure is typically found in plasmids suggests that it might be involved in the regulation plasmid copy number by a "cis"-antisense mechanism in a manner similar to that of R1162-like plasmid antisense RNA. However, the "Bacillus"-plasmid RNA motif does not appear to be homologous to any such known RNA.


Nallin Farm Springhouse and Bank Barn

The Nallin Farm Springhouse and Bank Barn are closely associated with the Nallin Farm House on the grounds of Fort Detrick, Maryland, US. The barn is a good example of a fieldstone-built bank barn with a byre on the lower level and an earth ramp on the opposite side providing access to a haymow.
The simple stone springhouse is the source of -acre Nallin Pond. The barn and springhouse were built .
The Nallin Farm Springhouse and Bank Barn was listed on the National Register of Historic Places in 1977.


Mark Inghram

Mark Gordon Inghram (November 13, 1919 – September 29, 2003) was an American physicist. Inghram was a member of the National Academy of Sciences.
Life.
Inghram was born in Livingston, Montana. He did undergraduate work at Olivet College, receiving a B.A. in 1939. He worked in the Manhattan Project during World War II and at Argonne National Laboratories from 1945 to 1947. He received his Ph.D. from the University of Chicago in 1947. He began teaching at the University of Chicago as an instructor in 1947 and remained there until his retirement in 1985. He died at his home in Holland, Michigan in 2003.
Age of the earth.
Together with Clair Patterson and George Tilton, Inghram was one of the first scientists to combine measurements on meteorites and the Earth to find the age of the Earth. Over time, the decay of uranium to lead will change the isotopic makeup of terrestrial lead. Patterson, Tilton and Inghram assumed that iron meteorites, which contain lead but virtually no uranium, formed at the same time as the Earth. Assuming this to be true, the isotopic makeup of lead in iron meteorites should still be the same as that of the newly formed Earth, so the Earth can be dated by comparing the composition of lead in iron meteorites with that in new volcanic material on the Earth. Patterson, Tilton and Inghram did this and found that the Earth was approximately 4.5 billion years old.


Piberaline

Piberaline (EGYT-475; Trelibet) is a psychoactive drug and member of the piperazine chemical class which was developed in the 1980s. It has stimulant and antidepressant effects which are thought to be due largely to its active metabolite benzylpiperazine. It was researched to a limited extent in Hungary and Spain, but was not widely accepted and does not seem to be in current use, although a closely related drug befuraline with similar effects has been slightly more successful.


Noradrenergic and specific serotonergic antidepressant

Noradrenergic and specific serotonergic antidepressants (NaSSAs) are a class of psychiatric drugs used primarily as antidepressants. They act by antagonizing the α2-adrenergic receptor and certain serotonin receptors such as 5-HT2A and 5-HT2C, but also 5-HT3, 5-HT6, and/or 5-HT7 in some cases. By blocking α2-adrenergic autoreceptors and heteroreceptors, NaSSAs enhance adrenergic and serotonergic neurotransmission in the brain involved in mood regulation, notably 5-HT1A-mediated transmission. In addition, due to their blockade of certain serotonin receptors, serotonergic neurotransmission is not facilitated in unwanted areas, which prevents the incidence of many side effects often associated with selective serotonin reuptake inhibitor (SSRI) antidepressants; hence, in part, the "specific serotonergic" label of NaSSAs.
List of NaSSAs.
The NaSSAs include the following agents:
Notably, all of these compounds are analogues and are also classified as tetracyclic antidepressants (TeCAs) based on their chemical structures.
S32212, a structurally novel NaSSA with an improved selectivity profile (e.g., no antihistamine effects, etc.), was reported in 2012. It has completed preliminary preclinical research and may go on to undergo clinical trials.


GlmZ RNA

GlmZ (formally known as SraJ) is a small non-coding RNA (ncRNA). It is the functional product of a gene which is not translated into protein.
This ncRNA was discovered in the bacteria "Escherichia coli" during a large scale computational screen for transcription signals and genomic features of known small RNA-encoding genes. During this screen 14 novel ncRNA genes were identified, including SraB, SraC, SraD and SraG.
The expression of SraJ was experimentally confirmed by Northern blotting. This ncRNA is expressed in early logarithmic phase, but its level decreases into stationary phase. Northern blot analysis also indicated this RNA undergoes specific cleavage processing.
The GlmZ sRNA has been shown to positively control the synthesis of GlmS mRNA. GlmZ is regulated by a related sRNA called GlmY. GlmY functions as an anti-adaptor, it binds to RapZ (RNase adaptor protein for sRNA GlmZ), this binding prevents RapZ from binding to GlmZ and targeting it for cleavage by RNase E.


Adverum Biotechnologies

Adverum Biotechnologies, formerly known as Avalanche Biotechnologies, is a publicly traded (NASDAQ:ADVM) clinical stage gene therapy company located in Redwood City, California. The company is targeting unmet medical needs for serious ocular and rare diseases, including wet age-related macular degeneration (wet AMD) and diabetic macular edema (DME).
History.
Avalanche Biotechnologies was founded in 2006 by Tom Chalberg, Mark Blumenkranz, Mitchell Finer, and Steven Schwartz. Avalanche went public through an IPO in 2014, raising $102 million.
In 2015, co-founder Tom Chalberg stepped down as CEO following Phase IIa trial results that were labeled as "iffy".
In May 2016, Avalanche acquired Annapurna Therapeutics and changed its name to Adverum Biotechnologies. It also changed its ticker symbol on the Nasdaq exchange from AAVL to ADVM. In October 2016, former Annapurna Therapeutics CEO Amber Salzman became CEO of Adverum.
In May 2018, CEO Amber Salzman left Adverum, and Chief Medical Officer Athena Countouriotis resigned after less than one year in the job. Leone Patterson was named the new CEO of Adverum.
In September 2019, Adverum announced six month data from the first cohort of its phase I trial. The stock price dropped 50% due to investor concerns over deterioration of vision that these trial subjects suffered, as well as several reports of occular inflammation.
In June 2020, Laurent Fischer replaced Patterson as CEO of Adverum.


Urolithin A

Urolithin A is a metabolite compound resulting from the transformation of ellagitannins by the gut bacteria. It belongs to the class of organic compounds known as benzo-coumarins or dibenzo-α-pyrones. Its precursors – ellagic acids and ellagitannins – are ubiquitous in nature, including edible plants, such as pomegranates, strawberries, raspberries, and walnuts. Since the 2000s, urolithin A has been subject of preliminary studies regarding its possible biological effects.
Urolithin A is not known to be found in any food source. Its bioavailability mostly depends on individual microbiota composition, as only some bacteria are able to convert ellagitannins into urolithins.
Chemistry.
Urolithin A belongs to the class of organic compounds known as benzo-coumarins or dibenzo-α-pyrones. These are polycyclic aromatic compounds containing a 1-benzopyran moiety with a ketone group at the C2 carbon atom (1-benzopyran-2-one).
Biochemistry and metabolism.
Pomegranate fruits, walnuts or raspberries are sources of ellagitannins. Ellagitannins are hydrolyzed in the gut to release ellagic acid, which is further processed by the gut microflora into urolithins through the loss of one of its two lactones and by successive removal of hydroxyl groups.
While studies have shown that "Gordonibacter urolithinfaciens" and "Gordonibacter pamelaeae" play a role in the conversion of ellagic acids and ellagitannins into urolithin A, the microorganisms responsible for the complete transformation into the final urolithins are still unknown. The efficiency of the conversion of ellagitannins into urolithin A significantly varies in humans, and some individuals do not show any conversion.
When synthesized and absorbed in the intestines, urolithin A enters the systemic circulation where it becomes available to tissues throughout the body where it is further subjected to additional chemical transformations (including glucuronidation, methylation, sulfation, or a combination of them) within the enterocytes and hepatocytes. Urolithin A and its derivatives - urolithin A glucuronide and urolithin A sulfate being most abundant - release into the circulation, before being excreted in the urine.
Potential mechanism of action.
In laboratory studies, urolithin A was shown to induce mitophagy, which is a selective recycling of mitochondria by autophagy, a process that cleans defective mitochondria following damage or stress, and tends to become less efficient during aging. This effect has been observed in different animal species (mammalian cells, rodents and "C. elegans").
Safety.
"In vivo" studies did not determine any toxicity or specific adverse effects following dietary intake of urolithin A. Safety studies in elderly humans indicated urolithin A was well tolerated. In 2018, the US Food and Drug Administration listed urolithin A as a safe ingredient for food or dietary supplement products having content in the range of 250 mg to one gram per serving.
Dietary sources.
Urolithin A is not known to be found in any food. It forms as the result of transformation of ellagic acids and ellagitannins by the gut microflora in humans. Ellagic acid itself results from the hydrolysis of ellagitannins in the gut in the presence of water.
Sources of ellagitannins are: pomegranates, nuts, some berries (raspberries, strawberries, blackberries, cloudberries), tea, muscadine grapes, many tropical fruits, and oak-aged wines (table below).
The conversion of the ellagic acids into urolithin A depends on individual microflora composition and can vary significantly.
Research.
Laboratory research on the potential biological roles of urolithin A includes studies of lifespan and muscle function.


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Dipeptide

A dipeptide is an organic compound derived from two amino acids. The constituent amino acids can be the same or different. When different, two isomers of the dipeptide are possible, depending on the sequence. Several dipeptides are physiologically important, and some are both physiologically and commercially significant. A well known dipeptide is aspartame, an artificial sweetener.
Dipeptides are white solids. Many are far more water-soluble than the parent amino acids. For example, the dipeptide Ala-Gln has the solubility of 586 g/L more than 10x the solubility of Gln (35 g/L). Dipeptides also can exhibit different stabilities, e.g. with respect to hydrolysis. Gln does not withstand, sterilization procedures, whereas this dipeptide does. Because dipeptides are prone to hydrolysis, the high solubility is exploited in infusions, i.e. to provide nutrition.
Examples.
Commercial value.
About six dipeptides are of commercial interest.
Production.
Synthetic dipeptides.
Dipeptides are produced by coupling amino acids. The amino group on one amino acid is rendered non-nucleophilic (P in eq) and the carboxylic acid group in the second amino acid is deactivated as its methyl ester. The two modified amino acids are then combined in the presence of a coupling agent, which facilitates formation of the amide bond:
Subsequent to this coupling reaction, the amine protecting group P and the ester are converted to the free amine and carboxylic acid, respectively.
For many amino acids, the ancillary functional groups are protected. The condensation of the amine and the carboxylic acid to form the peptide bond generally employs coupling agents to activate the carboxylic acid.
The Bergmann azlactone peptide synthesis is a classic organic synthesis for the preparation of dipeptides.
Biosynthesis.
Dipeptides are produced from polypeptides by the action of the hydrolase enzyme dipeptidyl peptidase. Dietary proteins are digested to dipeptides and amino acids, and the dipeptides are absorbed more rapidly than the amino acids, because their uptake involves a separate mechanism. Dipeptides activate G-cells found in the stomach to secrete gastrin.
Diketopiperazines (cyclic dipeptides).
Diketopiperazines are a special class of dipeptides, which are cyclic. They form as side products in peptide synthesis. Many have been produced from non-canonical amino acids.


Prince Antasari

Prince Antasari (Jawi: ; 1797 – 11 October 1862), also known by his Indonesian name Pangeran Antasari, was a sultan of Banjar and is a National Hero of Indonesia. His son Prince Hijrah is one of The Navy leader.
Biography.
Antasari was born in 1797. He was son of Prince Mashud and grandson of Prince Amir. He was a prince from a line of the royal family whose power had been usurped in the 18th century.
Antasari was concerned about the coronation of Sultan Tamjid (or Tamjidillah), instead of Prince Hidayat (or Hidayatullah), as the replacement to Sultan Adam in Banjar in 1859; Tamjidillah's coronation was backed by the Dutch colonials, who were looking to sow unrest and discord to make their attempts to take over Borneo easier. As Antasari wanted to repel the Dutch, he cooperated with the leaders of Martapura, Kapuas, Pelaihari, Barito, and Kahayan. He was also aided by Hidayatullah and Demang Leman.
On 18 April 1859, the Banjarmasin War broke out between Antasari's alliance, which was able to field some 6,000 armed men, and the Dutch. The war took place mainly in South and Central Kalimantan. Antasari's forces attacked the Dutch in Gunung Jabuk and also the Dutch coal mines in Pengaron. Meanwhile, his allies attacked other Dutch posts. They also attacked Dutch ships, killing Lieutenants Van der Velde and Bangert when they sank the ship "Onrust" in December 1859. Antasari rejected Dutch attempts to negotiate an end to the war, in which they offered him wealth and power in exchange for his surrender.
In early August 1860, Antasari's forces were in Ringkau Katan. They were defeated in a battle on 9 August, after Dutch reinforcements had arrived from Amuntai. Hidayatullah was exiled to Java, but Antasari, together with Prince Miradipa and Tumenggung Mancanegara, defended Tundakan fort on 24 September 1861. He also defended a fort in Mount Tongka on 8 November 1861 with Gusti Umar and Tumenggung Surapati.
In October 1862, Antasari was planning a big attack. However, an outbreak of smallpox led to his death on 11 October 1862. He was buried in Banjarmasin; and several other resistance leaders, from different periods, were later buried there; the place was later named the Antasari Heroes' Cemetery. After Antasari's death, his son, Muhammad Seman, continued his struggle against the Dutch. The resistance ended with Seman's death in 1905.
His son pangeran Hijrah has 10 granddaughters with his daughters, and has 20 great granddaughters with his granddaughter.
Legacy.
Antasari was given the title 'Panembahan Amiruddin Khaliful Mukmin' on 14 March 1862 by his people, which made him a religious leader for his people. He was declared a National Hero of Indonesia in 1968 by President Suharto through presidential decree No. 06/TK/1968.
In the mid-1990s a documentary on Antasari's life was made. Antasari is featured on the obverse of the 2009 series 2,000 rupiah bill, which shows traditional Bornean dancers on the reverse.


Norton Zinder

Norton David Zinder (November 7, 1928 – February 3, 2012) was an American biologist famous for his discovery of genetic transduction. Zinder was born in New York City, received his Ph.D. from the University of Wisconsin–Madison, and became a member of the National Academy of Sciences in 1969. He led a lab at Rockefeller University until shortly before his death.
In 1966 he was awarded the NAS Award in Molecular Biology from the National Academy of Sciences.
Genetic transduction and RNA bacteriophage.
Working as a graduate student with Joshua Lederberg, Zinder discovered that a bacteriophage can carry genes from one bacterium to another. Initial experiments were carried out using "Salmonella". Zinder and Lederberg named this process of genetic exchange transduction.
Later, Zinder discovered the first bacteriophage that contained RNA as its genetic material. At that time, Harvey Lodish (now of the Massachusetts Institute of Technology and Whitehead Institute for Biomedical Research) worked in his lab.
Norton Zinder died in 2012 of pneumonia after a long illness.