Seminal RNase

Bovine seminal RNase (BS-RNase) is a member of the ribonuclease superfamily produced by the bovine seminal vesicles. This enzyme can not be differentiated from its members distinctly since there are more features that this enzyme shares with its family members than features that it possess alone. The research on the question of how new functions arrive in proteins in evolution led the scientists to find an uncommon consequence for a usual biological event called gene conversion in the case of the ribonuclease (RNase) protein family. The most well-known member of this family, RNase A (also called pancreatic RNase), is expressed in the pancreas of oxen. It serves to digest RNA in intestine, and evolved from bacteria fermenting in the stomach of the first ox. The homologous RNase, called seminal RNase, differs from RNase A by 23 amino acids and is expressed in seminal plasma in the concentration of 1-1.5 mg/ml, which constitutes more than 3% of the fluid protein content. Bovine seminal ribonuclease (BS-RNase) is a homologue of RNase A with specific antitumor activity.
Functional properties of bovine seminal RNase.
The physiological role of this enzyme is not yet found and thus it is still a mystery why the seminal fluid in bovine has such a higher concentration of this enzyme. In the evolutionary process, it has acquired new behaviors such as being a dimer with composite active sites binding firmly to anionic glycolipids, including bovine spermatozoa seminolipid, a fusogenic sulfated galactolipid possessing immunosuppressive and cytostatic activities whereas the ancestral RNase does not possess these behaviors. The homolog of RNase A, bovine seminal ribonuclease (BS-RNase), has a specific antitumor activity. In the immunoregulation of both male and female genital systems, the seminal plasma plays a prominent role in immunosuppression. The direct or indirect interference of the seminal plasma with the function of many types of immunocompetent cells including T cells, B cells, NK cells and macrophages has been shown. These effects of immunosuppression are not species-specific and are found to be in physiological concentrations that are normally seen in the urogenital tract of females. RNase secretion has not been detected in the seminal fluid of any other mammal.
Origin of seminal RNase gene.
The recruitment of established proteins after the gene duplication leads to play some new biomolecular functions. Among different models that exist, one model suggests that after the gene duplication, among the two copies of genes, one will be subjected to continuous evolution under ancestral dictated functional constraints whereas the duplicate meanwhile will not be restricted by a functional role and feels free to find protein “structure space”. In the end, it may come with encoded new behaviors that which are required for a new physiological function and thereby discourse the selective advantage. In any case, we may consider it as an ambiguous model since most duplicates have to become pseudogenes, which are considered as an inexpressible genetic information (referred to as “junk DNA”) in just a few million years. Because selective pressure can do nothing much with duplicated genes, they are prone to deleterious mutations that present their incapability to encode a protein useful for any function. This restricts to use a functionally unconstrained gene duplicate as a tool for investigating protein structure space of new behaviors that might discourse selectable physiological function. Then how would new functions arise in proteins? One of the possibilities is the resurrection of the pseudogenes due to some biological events like gene conversion. One such an example is the resurrection of the bovine seminal RNase gene.
From the laboratory reconstructions of ancient RNases, it is shown that each of these traits was absent in the most recent common ancestor of seminal and pancreatic RNase and a bit later arose in the seminal lineage after the divergence of the above two protein families. The RNase genes from all taxa in a true ruminant phylogenetic tree that was constructed by parsimony analysis were analyzed by the researchers, and they revealed that early after the gene duplication, pancreatic RNases and seminal RNases separated at about 35 million years ago (MYA). Several marker substitutions, including Pro 19, Cys 32 and Lys 62, have been introduced in seminal RNase genes which made them to be recognized as different from their pancreatic cousins. Based on this, the seminal RNase family includes the taxa called saiga, sheep, duiker, kudu and cape buffalo, while peccary has been excluded from it. Later on, from the sequence analyses, mass spectrophotometry and western blotting studies on taxa that comes under the seminal RNase gene family, it has been revealed that they are consistent with the model which assumes that immediately after duplication the seminal RNase gene gained a physiological function and this function has been continued throughout the divergent evolution (each copy of gene gets evolved independently) and later on it was lost in all other species including modern kudu and cape buffalo except in modern oxen. This would require, however, that this function was lost independently multiple times in different lineages.
After the divergence of Cape buffalo in the lineage leading to modern oxen, the seminal RNase gene was resurrected very recently. It is intriguing to ask whether the domestication of the ox is related to the emergence of seminal RNase as a functioning protein. In modern oxen, does the seminal RNase gene have a function? This is the question that arises now. To address this question we can take into consideration the non-silent to silent substitution ratio in these gene families. The average ratio of non-silent to silent substitutions is 2:1 for unexpressed seminal RNase sequences, which is consistent with the model that these seminal RNases are pseudogenes and is close to that expected for random substitution in a gene that serves with no selected function. On other hand, the average ratio is less than 1:1 in case of pancreatic RNases which exhibits consistency with the model that states that pancreatic RNases are functional where selective pressure constrains the amino acid replacements. However, when the expressed ox seminal RNase is compared with its nearest unexpressed homologs (homologous chromosomes) in buffalo and kudu, a most remarkable ratio of non-silent to silent substitutions, 4:1, is observed. Pseudogenes in order to perform a new function and to provide new selected properties they search protein “structure space” with rapidly introduced amino acid replacements and such pseudogenes are only expected to have the above-mentioned remarkable ratio of non-silent to silent substitutions. The resurrection of the seminal RNase gene is evidently associated with the introduction of Cys 31.
Then how was this pseudogene resurrected? It is not so clear to say and one can note that the similarity between the region of the kudu deletion and the sequence of the expressed seminal RNase pseudogene extends some 70 base pairs into the 3’ –untranslated region are 89% identical (with 62 of the 70 nucleotides). We can expect that in order to repair the damaged seminal RNase there might be the gene conversion event took place between it and the pancreatic gene to create a new physiological evolution. Gene conversion is of two types - interallelic and interlocus gene conversions. The resurrection of seminal RNase gene function is believed to be the unexpected consequence of the interlocus gene conversion event of seminal RNase pseudogene with its homologous functional gene. In these recombination events, the genetic information is transferred from a donor functional locus to that of an acceptor pseudogene which is non-functional. Thus the non-functional seminal RNase pseudogene has acquired some new physiological functions being in the state of dead for many million years. This might be the first example in the literature with for the resurrection of a pseudogene by gene conversion event and it would be interesting to further test this data with more sequencing data. Later on another evolutionary aspect has been proposed in case of seminal RNase showing that the seminal RNase has been left with two quaternary forms: one is to exhibit special biological actions and the other is just an RNA-degrading enzyme. Based on this proposal the evolution of seminal RNase into these two structures that coexists and are more versatile structurally and biologically can be considered as treated as an evolutionary progress.
Scientists from all over the world studied and recognized a plenty of pseudogenes. They have launched several projects which are worldwide to identify and study the potential roles of pseudogenes. ENCODE is one of such projects. Even though the pseudogenes accelerate the issues formolecular analysis, they are still regarded as genome fossils that provide a sound record of evolution since they offer a plethora of diverse information for molecular analysis. The worldwide researchers are building different ways to identify the pseudogenes by various scheme and criteria for computation such that they give a set of pseudogenes that are consistent. Sometimes, the resurrected pseudogenes have been identified as functional and they may also be altered back to be non-functional, which again can be reversed. Not all the pseudogenes in a genome should be considered as a “junk DNA”. The evidence for functional pseudogenes strengthens their significance, and they have also become a hotspot in research due to their significance and possible resurrection. To study the characteristics of this soundless fossil in human and other organisms, researchers are contributing their attempts. In the near future, the real evolutionary fates of the pseudogenes will be found with the embedded picture of genome annotation.


3,5-Dihydroxybenzoic acid

3,5-Dihydroxybenzoic acid (α-resorcylic acid) is a dihydroxybenzoic acid. It is a colorless solid.
Preparation and occurrence.
It is prepared by disulfonation of benzoic acid followed by hydrolysis of the disulfonate.
It is a metabolite of alkylresorcinols, first identified in human urine and can be quantified in urine and plasma, and may be an alternative, equivalent biomarker of whole grain wheat intake.


Rombach Place

The Rombach Place is a historic house in the city of Wilmington, Ohio, United States. Built in the first third of the nineteenth century, it was home to a family that produced two prominent national politicians. No longer used as a residence, the house is now a museum, and it has been named a historic site.
History.
Robert Wickersham built the Rombach Place in 1831. It was later home to the family of James W. Denver, a politician who achieved national prominence in the middle of the century.
James Denver was born in Winchester, Virginia in 1817, and at the age of thirty-nine he married the former Louise Rombach of Wilmington; to this union were born four children. Much of his youth was spent on a farm near Wilmington, but he later moved far to the west, serving as a U.S. Representative from California, a governor of the Kansas Territory (a new settlement in the far west of the territory, now part of Colorado, was named for him), as the Commissioner of Indian Affairs, and as a U.S. Army general during the Civil War. However, after the war, he returned to Wilmington for a time. In 1870, while he and his family were resident in the Rombach Place, their youngest son was born; named Matthew, he was later elected a U.S. Representative from Ohio.
Architecture.
Built in the Greek Revival style of architecture, the primary portion of the house is two stories tall and five bays wide. An entrance is located in the middle bay of the first floor, covered by a small portico with a pediment and four square columns. Smaller windows and prominent chimneys are located on the ends of the house, to which are attached one-bay, single-story sections. Built in the shape of the letter "T", the house is constructed of brick and covered with a shingled roof that rises to a pair of gables; the walls are covered with stucco, and a fence encircles the roofs of the single-story sections on the ends.
Preservation.
Today, the Rombach Place is no longer used as a residence: it is the home of the Clinton County Historical Society, which operates it as a museum, genealogy library, and conference center. The house was listed on the National Register of Historic Places in 1979, qualifying both because of its historically significant architecture and because of its place as the home of General James Denver. It was the city's third building to be listed on the National Register; the Doan House on the city's east side was listed on the same day, and College Hall on the Wilmington College campus preceded both buildings by six years.


William Fogerty

William Fogerty, FRIAI, FRIBA, AAI was an Irish architect active in mid-nineteenth-century Limerick, London, New York City and Dublin.
Born in Limerick, he studied in the early 1850s at Queen's College, Cork. He moved to Dublin in the early 1860s, to London and then New York in the early 1870s, and back to Dublin in 1875. His offices were at 23 Harcourt Street, Dublin. He died of smallpox at the age of forty-four in 1878. Architects in his family included his father, John Fogerty of Limerick, his brother Joseph Fogerty of London, and his son, John Frederick Fogerty of Dublin.


Borate buffered saline

Borate buffered saline (abbreviated BBS) is a buffer used in some biochemical techniques to maintain the pH within a relatively narrow range. Borate buffers have an alkaline buffering capacity in the 8–10 range.
Boric acid has a pKa of 9.14 at 25°C.
Applications.
BBS has many uses because it is isotonic and has a strong bactericidal effect. It can be used to dilute substances and has applications in coating procedures. Additives such as [Polysorbate 20] and milk powder can be used to add to BBS's functionality as a washing buffer or blocking buffer.
Contents.
The following is a sample recipe for BBS:
Adjust pH to pH 8.2
The simplest way to prepare a BBS solution is to use BBS tablets. They are formulated to give a ready to use borate buffered saline solution upon dissolution in 500 ml of deionized water.
Concentration of borate and NaCl as well as the pH can vary, and the resulting solution would still be referred to as "borate buffered saline".
Borate concentration (giving buffering capacity) can vary from 10 mM to 100 mM. As BBS is used to emulate physiological conditions (as in animal or human body), the pH value is slightly alkaline, ranging from 8.0–9.0.
NaCl gives the isotonic (mostly used 150 mM NaCl corresponds to physiological conditions: 0.9% NaCl) salt concentration.


Kadmon Corporation

Kadmon Corporation (originally "Kadmon Pharmaceuticals") is a biopharmaceutical company based in New York City. It also has operations in Warrendale, PA and Brighton, MA. The company was founded in 2009 by Samuel D. Waksal, founder and former CEO of ImClone Systems, now fully merged into Eli Lilly and Company. Waksal had served a federal prison sentence stemming from his fiduciary role as CEO in the 2001 ImClone stock trading case. When released in 2009 he was barred from serving as an officer for any publicly traded company but Kadmon was privately financed.
In September 2014, amid plans to take the company to an IPO Harlan W. Waksal, brother of Samuel Waksal, became President and Chief Executive Officer while Samuel Waksal remained on with the title Chief of Innovation, Science and Strategy. In early 2016 Sam Waksal left Kadmon and in June the company filed paperwork for its IPO. On July 27, 2016 the company's stock began trading on the NYSE under the symbol KDMN but switched to NASDAQ in October 2020.
As of 2019 Kadmon had ongoing clinical trials for KD025 in specific fibrotic and neurodegenerative diseases and tesevatinib to treat autosomal dominant polycystic kidney disease (PKD) and autosomal recessive PKD.
Product acquisitions.
During Waksal's leadership of ImClone the company was engaged in early stage research projects for 15 years before filing its first drug application. Kadmon however immediately began acquiring drugs further advanced - either already marketed in the US or in the later stages of clinical development. It acquired the Warrendale, PA-based company Three Rivers Pharmaceuticals and their Ribasphere and topotecan products. It also signed an agreement with Ontario, Canada-based Valeant Pharmaceuticals for their Hepatitis C drugs ribavirin and taribavirin (now KD024). Cancer drugs XL647 and XL844 were acquired from Exelixis. An inhibitor of several protein kinases, tesevatinib (XL647, KD019) entered Phase II clinical trial for certain indications of non-small cell lung cancer. and in polycystic kidney disease. XL844 is an inhibitor of protein kinases Chk1 and Chk2 and may increase the sensitivity of cancer cells to radiation therapy.
In an acquisition atypical for a biotechnology company, an 1800-year-old Chinese herbal formula was added to Kadmon's portfolio. PhytoCeutica's PHY906 (KD018) is a formula of four botanical products that had long been used for the treatment of gastrointestinal distress. Preclinical studies have shown it to enhance the therapeutic activity of several anticancer agents. In 2014 KD018 was in a Phase II trial in combination with irinotecan in metastatic colon cancer.
In 2011 the company acquired rights from Brighton, MA-based Nano Terra Inc. for their "Pharmacomer Technology" research platform and three drug candidates in clinical development. These compounds include SLx-2119 (KD025), an inhibitor to Rho kinase 2 (ROCK2) with possible potential in fibrotic disease and focal cerebral ischemia. SLx-4090 (KD026) is a triglyceride transfer protein (MTP) inhibitor being explored for metabolic disorders. SLx-2101 (KD027) is a phosphodiesterase 5 (PDE5) inhibitor, a class of drug used in the treatment of erectile dysfunction.
In 2012 the rights to salirasib ("KD032"), a Ras antagonist in development for cancer therapy, were acquired from Concordia Pharmaceuticals of Fort Lauderdale, FL. It also acquired the rights from Burlington, MA-based Dyax Corp. for DX-2400, a Matrix metalloproteinase-14 (MPP-14) targeted monoclonal antibody intended to inhibit tumor blood vessel formation and metastasis.
Products.
As of 2019 Kadmon produces several generic drugs approved by the Food and Drug Administration in the United States.


Clebopride

Clebopride is a dopamine antagonist drug with antiemetic and prokinetic properties used to treat functional gastrointestinal disorders. Chemically, it is a substituted benzamide, closely related to metoclopramide.
A small Spanish study found that more adverse reactions are reported with clebopride than with metoclopramide, particularly extrapyramidal symptoms.


Desulfovibrio arcticus

Desulfovibrio arcticus is a Gram-negative, psychrotolerant, sulfate-reducing and motile bacterium from the genus of Desulfovibrio with a single polar flagellum which has been isolated from water from permafrost from the Barents Sea.


Dimethylallyl pyrophosphate

Dimethylallyl pyrophosphate (DMAPP; or alternatively, dimethylallyl diphosphate (DMADP); also isoprenyl pyrophosphate) is an isoprenoid precursor. It is a product of both the mevalonate pathway and the MEP pathway of isoprenoid precursor biosynthesis. It is an isomer of isopentenyl pyrophosphate (IPP) and exists in virtually all life forms. The enzyme isopentenyl pyrophosphate isomerase catalyzes isomerization between DMAPP and IPP.
In the mevalonate pathway DMAPP is synthesised from mevalonic acid. In contrast, DMAPP is synthesised from HMBPP in the MEP pathway.
At present, it is believed that there is crossover between the two pathways in organisms
that use both pathways to create terpenes and terpenoids, such as in plants, and that DMAPP is the crossover product.


Twin-arginine translocation pathway

The twin-arginine translocation pathway (Tat pathway) is a protein export, or secretion pathway found in plants, bacteria, and archaea. In contrast to the Sec pathway which transports proteins in an unfolded manner, the Tat pathway serves to actively translocate folded proteins across a lipid membrane bilayer. In plants, the Tat translocase is located in the thylakoid membrane of the chloroplast, where it acts to export proteins into the thylakoid lumen. In bacteria, the Tat translocase is found in the cytoplasmic membrane and serves to export proteins to the cell envelope, or to the extracellular space. The existence of a Tat translocase in plant mitochondria is also proposed.
In the plant thylakoid membrane and in Gram-negative bacteria the Tat translocase is composed of three essential membrane proteins; TatA, TatB, and TatC. In the most widely studied Tat pathway, that of the Gram-negative bacterium "Escherichia coli", these three proteins are expressed from an operon with a fourth Tat protein, TatD, which is not required for Tat function. A fifth Tat protein TatE that is homologous to the TatA protein is present at a much lower level in the cell than TatA and is not believed to play any significant role in Tat function.
The Tat pathways of Gram-positive bacteria differ in that they do not have a TatB component. In these bacteria the Tat system is made up from a single TatA and TatC component, with the TatA protein being bifunctional and fulfilling the roles of both "E. coli" TatA and TatB.
The name of the Tat pathway relates to a highly conserved twin-arginine leader motif (S/TRRXFLK) which is found in the N terminal Signal peptide of the corresponding passenger proteins. The signal peptide is removed by a signal peptidase after release of the transported protein from the Tat complex. At least two TatC molecules co-exist within each Tat translocon.
In pathogens.
Not all bacteria carry the "tatABC" genes in their genome; however, of those that do, there seems to be no discrimination between pathogens and nonpathogens. Despite that fact, some pathogenic bacteria such as "Pseudomonas aeruginosa", "Legionella pneumophila", "Yersinia pseudotuberculosis", and rely on a functioning Tat pathway for full virulence in infection models. In addition, a number of exported virulence factors have been shown to rely on the Tat pathway. One such category of virulence factors are the phospholipase C enzymes, which have been shown to be Tat-exported in "Pseudomonas aeruginosa", and thought to be Tat-exported in "Mycobacterium tuberculosis".


Metazosin

Metazosin is an antihypertensive alpha-adrenergic antagonist.


Richard O. Spertzel

Richard Oscar Spertzel (9 February 1933 – 24 March 2016) was a veterinarian, microbiologist and expert in the area of biological warfare. He participated in germ warfare research at U.S. Army Medical Unit (USAMU), Fort Detrick, Frederick, Maryland. (USAMU is now known as the U.S. Army Medical Research Institute of Infectious Diseases, or USAMRIID). Spertzel held several positions USAMRIID including Deputy for Research, Deputy Commander, and Chief of the Animal Assessment Division. From 1994 to 1998 Spertzel served as the Senior Biologist for the United Nations Special Commission in Iraq. His Congressional testimonial about the WMD capabilities of Iraq helped to justify the subsequent US invasion of Iraq. After the invasion, Spertzel was a member of the Iraq Survey Group, which found that Iraq was not producing nor planning to produce WMD at the time of the invasion.
Education.
He was born on February 9, 1933, in Huntington Township, Adams County, Pennsylvania. In 1955, Spertzel earned a Bachelor of Arts in microbiology at the University of Pennsylvania. Sperzel did postgraduate work at the University of Pennsylvania School of Veterinary Medicine and in 1962 he was awarded a Master's Degree in radiation biology by the Graduate School of Medicine and Dentistry at the University of Rochester. His terminal degree was obtained in 1970, a Doctor of Philosophy in microbiology from the University of Notre Dame.
2003 Invasion of Iraq.
As part of the Congressional hearings prior to authorization of the invasion of Iraq, Spertzel provided testimony to the United States House Committee on Armed Services on September 10, 2002.
Testimony by Spertzel:
After the 2003 invasion of Iraq, the United States government concluded that Iraq did not have weapons of mass destruction during the period leading up to the 2003 invasion of Iraq after reviewing the Iraq Survey Group's final report on September 30, 2004. Claimed links of Iraq to terrorist groups like al Qaeda were never verified, and the National Commission on Terrorist Attacks Upon the United States concluded that there was no real evidence of such links. Much of the "intelligence" suggesting WMD in Iraq prior to the 2003 invasion was fabricated by groups like the Iraqi National Congress.


Kathryn Stowell

Kathryn Mary Stowell is a New Zealand academic. She is currently a full professor at the Massey University.
Academic career.
Stowell joined Massey University in 1976, after a 1990 PhD titled " 'Cloning and expression of the cDNA for human lactoferrin,' " she rose to full professor in 2015.
Stowell is best-known publicly for her work on
malignant hyperthermia (MH), a genetic disorder which causes a severe and potentially fatal hypermetabolic reaction in susceptible people when exposed to inhaled anaesthetics or the muscle relaxant suxamethonium. Malignant hyperthermia has an incidence of between 1:10,000 and 1:250,000 worldwide, but 1:200 at Palmerston North Hospital due to a large family in the area carrying the gene for many generations. Stowell's work has largely concentrated on identifying the genetic basis for MH susceptibility, and developing genetic testing to replace the invasive muscle biopsy test currently used.
In 2015, Stowell was made an Officer of the New Zealand Order of Merit (ONZM) for her services to biomedical science.


Jim Morrison (chemist)

James Douglas Morrison AO, FAA, FRSE, FRACI (1924–2013) was a Scottish born Australian physical chemist. Born and educated in Glasgow (BSc 1945, PhD 1948), he moved to Australia in 1949 to work with the CSIRO. There he switched from X-Ray crystallography to mass spectrometry as a research topic.
In 1967 he was appointed as the foundation chair of physical chemistry at La Trobe University, where he was a professor of chemistry until retiring in 1989.
He is known for his work in mass spectrometry and he is one of the inventors of the triple quadrupole mass spectrometer.


Massilia eurypsychrophila

Massilia eurypsychrophila is a Gram-negative, aerobic, rod-shaped and facultatively psychrophilic bacterium from the genus "Massilia" with a polar flagella which has been isolated from the ice core of the Muztagh Glacier in Xinjiang in China.


Abcam

Abcam is a producer, distributor and seller of protein research tools.
History.
The company was founded in 1998 by Jonathan Milner with co-founders professor Tony Kouzarides and David Cleevely, with the idea of making it easier for research scientists to buy antibodies across the web. Milner was a postdoctoral researcher studying the newly discovered breast cancer protein BRCA2 in Kouzarides' Cambridge University laboratory. The project had slowed because of problems finding quality antibody reagents that had honest and up-to-date information about their uses and limitations. This scenario provided the motivation to form an on-line service that would help themselves and researchers across the globe.
Since its inception in 1998, the company has diversified from carrying only antibodies. It supplies antibody related products such as immunoassays (e.g. SimpleStep ELISA Kits), peptides, proteins and protein detection products (e.g. immunohistochemistry (IHC) staining kits). Abcam also has a portfolio of non-antibody related products such as biochemicals, cellular assays, and epigenetics kits (e.g. FirePlex Multiplex miRNA Kits).
Abcam is listed on the London Stock Exchange and on Nasdaq.
Acquisitions.
In May 2011, Abcam announced the acquisition of MitoSciences, a privately held biotech company based in Eugene, Oregon (US). The company produced and distributed immunoassay platforms and high performance monoclonal antibodies. It was founded in 2004 with the mission of advancing mitochondrial research and developing products that support critical research in cancer, neurodegeneration, and metabolic disorders.
On 12 September 2011, Abcam completed the purchase of Ascent Scientific. Ascent Scientific was a company based in Bristol, United Kingdom that provided high-quality biochemical products that modulate the function of proteins for use in life science research. After outsourcing biochemical production, the Bristol site and manufacturing facilities were closed in 2017.
On 19 April 2012, Abcam completed the purchase of Epitomics. Epitomics was a privately held biotech company in Burlingame, California (US) and Hangzhou (China) that focused on the development, production, and distribution of rabbit monoclonal antibodies for biomedical research and diagnostic applications.
On 20 January 2015, Abcam announced the acquisition of Firefly BioWorks, a privately held company based in Cambridge, Massachusetts (US), for . Firefly developed a novel multiplex assay platform for the detection of biomarkers, based on a microfabrication technology developed by Daniel Pregibon and Patrick Doyle at Massachusetts Institute of Technology, and launched its first products for the multiplex detection of microRNA from RNA and crude biofluid. Firefly was rebranded to FirePlex in 2016.
On 11 November 2015, Abcam announced the acquisition of AxioMx. AxioMx, based in Branford, Connecticut (US), "provides a comprehensive custom recombinant antibody discovery and development services platform".
Abcam acquired Calico Biolabs in January 2019. A year later, on 6 January 2020, Abcam announces the successful acquisition of Expedeon’s Proteomics and Immunology business, which includes Innova and TGR Biosciences. On 4 March 2020, Abcam extend their assay and labelling capabilities by acquiring Marker Gene Technologies for an undisclosed amount. The acquisition of Marker Gene Technologies bring expertise in the areas of biology, organic synthesis and fluorescence chemistry. The team from MGT are experienced in the creation of detection tools that enable enhanced understanding of biological processes.


Human rhinovirus internal cis-acting regulatory element

Human rhinovirus internal cis-acting regulatory element (CRE) is
a CRE from the human rhinoviruses. The CRE is located within the genome segment encoding the capsid proteins so is found in a protein coding region. The element is essential for efficient viral replication and it has been suggested that the CRE is required for initiation of minus-strand RNA synthesis.


4-HO-DSBT

4-HO-DsBT (4-hydroxy-"N,N"-di-"sec"-butyltryptamine) is a tryptamine derivative which acts as a serotonin receptor agonist. It was first made by Alexander Shulgin and is mentioned in his book TiHKAL, but was never tested by him. However it has subsequently been tested "in vitro" and unlike the "n"-butyl and isobutyl isomers which are much weaker, the "s"-butyl derivative retains reasonable potency, with a similar 5-HT2A receptor affinity to MiPT but better selectivity over the 5-HT1A and 5-HT2B subtypes.


Pantetheine-phosphate adenylyltransferase

In enzymology, a pantetheine-phosphate adenylyltransferase () is an enzyme that catalyzes the chemical reaction
Thus, the two substrates of this enzyme are ATP and 4'-Phosphopantetheine, whereas its two products are diphosphate and 3'-dephospho-CoA.
This enzyme belongs to the family of transferases, specifically those transferring phosphorus-containing nucleotide groups (nucleotidyltransferases). The systematic name of this enzyme class is ATP:pantetheine-4'-phosphate adenylyltransferase. Other names in common use include dephospho-CoA pyrophosphorylase, pantetheine phosphate adenylyltransferase, dephospho-coenzyme A pyrophosphorylase, and 3'-dephospho-CoA pyrophosphorylase. This enzyme participates in pantothenate and coa biosynthesis.
Structural studies.
As of late 2007, 8 structures have been solved for this class of enzymes, with PDB accession codes , , , , , , , and .


4-Benzylpiperidine

4-Benzylpiperidine is a drug and research chemical used in scientific studies. It acts as a monoamine releasing agent with 20- to 48-fold selectivity for releasing dopamine versus serotonin. It is most efficacious as a releaser of norepinephrine, with an ec50 of 109/41.4/5246nM for DA/NE/5HT, respectively . It has a fast onset of action and a short duration. It also functions as a monoamine oxidase inhibitor (MAOI) with preference for MAO-A.
Synthesis.
4-Cyanopyridine can be reacted with toluene to give 4-benzylpyridine. Catalytic hydrogenation of the pyridine ring then completes the synthesis.


John Torrence Tate Sr.

John Torrence Tate Sr. (July 28, 1889 – May 27, 1950) was an American physicist noted for his editorship of "Physical Review" between 1926 and 1950. He is the father of mathematician John Torrence Tate Jr.
Biography.
Tate was born on 28 July 1889 in Lenox, Iowa. He attended the University of Nebraska, studying electrical engineering, earning a BS in 1910. He continued at the University of Nebraska, shifting his focus to physics and earning an MA in 1912. Like many American students interested in pursuing advanced degrees in physics, he departed for Germany to further his studies, earning a PhD under James Franck in 1914, with a dissertation on "The Heat of Vaporization of Metals." He returned to the University of Nebraska as a faculty member, where he stayed until 1916, when he was offered a post at the University of Minnesota. With the exception of brief sabbaticals to conduct war-related work, Tate remained at Minnesota for the following 34 years. Tate Laboratory of Physics at the University of Minnesota is named in his honor.
Editor of "Physical Review".
While a professor at the University of Minnesota, Tate presided over the growth of the "Physical Review" into a high impact journal. Physicist John H. Van Vleck, who was a colleague of Tate's at Minnesota from 1923 to 1928, recalled that in the early 20th century ""The Physical Review" was only so-so, especially in theory, and in 1922 I was greatly pleased that my doctor’s thesis was accepted for publication by the "Philosophical Magazine" in England . . . By 1930 or so, the relative standings of "The Physical Review" and Philosophical Magazine were interchanged." Alfred Nier and John Van Vleck credited the rapid growth of the journal's size and influence in the 1920s to Tate's sensitivity to the importance of the emerging quantum revolution, and in particular the rapidity with which he published papers relating to quantum phenomena.
Reviewing Einstein and Rosen.
On the 1st of June 1936 Tate, as the editor of the "Physical Review", received a submission from Albert Einstein and Nathan Rosen. Tate sent the submission to H.P. Robertson, who made an anonymous critical peer review (correctly) questioning the basic conclusion of the paper. On the 23rd of July, Tate returned the submission with the anonymous review. On the 27th of July, Einstein replied:


Vicki Wysocki

Vicki Wysocki is an American scientist. She is a professor at Ohio State University. She received a BS in Chemistry from Western Kentucky University in 1982 and her PhD in Chemistry at Purdue University in 1987. She was the president of the American Society for Mass Spectrometry for the period of 2016-2018 and has received the Field and Franklin Award in 2017.


Corey lactone 4-phenylbenzoate

Corey lactone 4-phenylbenzoate is a synthetic intermediate used in the manufacture of some prostaglandin derivatives. It has been used as a false name by some designer drug manufacturers as a label to sell substituted cathinone derivatives after the banning of mephedrone and related drugs in some jurisdictions - but there is no evidence to suggest that Corey lactone 4-phenylbenzoate has any stimulant effects in its own right.


5-Ethoxy-DMT

5-Ethoxy-DMT (5-ethoxy-"N","N"-dimethyltryptamine, 5-EtO-DMT, "O"-ethylbufotenine) is a tryptamine derivative which has been previously synthesized as a chemical intermediate, but has not been studied to determine its pharmacology.
The widespread recreational use of "N","N"-dialkylated 5-methoxytryptamine derivatives including 5-MeO-DMT, 5-MeO-MiPT and 5-MeO-DiPT has led to concern that the 5-ethoxy homologs of these drugs could emerge as novel designer drugs, and consequently 5-EtO-DMT and other derivatives including 5-EtO-DET, 5-EtO-DPT, 5-EtO-DiPT, 5-EtO-DALT, 5-EtO-MPT, 5-EtO-MiPT, 5-EtO-EiPT, 5-EtO-MET and 5-EtO-EPT have been synthesized as analytical standards in order to facilitate future research into these compounds.


Fluo-3

Fluo-3 is a fluorescence indicator of intracellular calcium (Ca2+). It is used to measure Ca2+ inside living cells in flow cytometry and confocal laser scanning microscopy using visible light excitation (compatible with argon laser sources operating at 488 nm). Fluo-3 is an essentially nonfluorescent compound, but upon binding of Ca2+ its fluorescence increases sharply with an emission maximum at 525 nm suitable for conventionally used detectors designed for fluorescein isothiocyanate (FITC) measurements. This large change in fluorescence coupled with a good yield of photons provides very high contrast which allowed the detection of microscopic Ca2+ release events inside cells called "Calcium sparks". Whereas the salts of fluo-3 are unable to penetrate cells, loading can be achieved using its acetoxymethyl (AM) ester derivative. Once inside the cell, unspecific esterases cleave the ester effectively trapping fluo-3.
As calcium is a key second messenger within cells, the specific properties of fluo-3 enable researchers to investigate the time-resolved dynamics of intracellular signal transduction in a diverse range of cells.


Arginylglycylaspartic acid

Arginylglycylaspartic acid (RGD) is the most common peptide motif responsible for cell adhesion to the extracellular matrix (ECM), found in species ranging from "Drosophila" to humans. Cell adhesion proteins called integrins recognize and bind to this sequence, which is found within many matrix proteins, including fibronectin, fibrinogen, vitronectin, osteopontin, and several other adhesive extracellular matrix proteins.
Discovery.
RGD was identified as the minimal recognition sequence within fibronectin required for cell attachment by Ruoslahti and Pierschbacher in the early 1980s. These foundational studies also identified of the cellular receptors that recognize the sequence; these receptors were later named integrins. The RGD motif is presented in a slightly different ways in different proteins, making it possible for the many RGD-binding integrins to selectively distinguish individual adhesion proteins.
Use in drug discovery.
Understanding of the molecular basis of binding to integrins has enabled the development of several drugs for cardiovascular disease and cancer, including eptifibatide, tirofiban, cilengitide, and the PET radiotracer fluciclatide.
Eptifibatide and tirofiban are anti-clotting drugs indicated to prevent thrombosis in acute ischemic coronary syndromes. They block activation of the integrin responsible for aggregation of platelets (αIIbβ3, also known as glycoprotein IIb/IIIa) in response to the blood glycoproteins fibrinogen and von Willebrand factor. Eptifibatide (marketed as Integrilin) is a cyclic (circular) seven amino acid peptide, whereas tirofiban is a small molecule designed to mimic the chemistry and binding affinity of the RGD sequence.
Cilengitide, a cyclic pentapeptide (RGDfV), is an investigational drug intended to block the growth of new blood vessels in tumors by interfering with the activation of integrin αVβ3. It has been evaluated for the treatment of glioblastoma, but, as is the case for other anti-angiogenic therapies, has not been shown to alter progression or improve survival either alone or in combination with standard treatments.
Fluciclatide, an 18F-labelled small peptide that binds to integrin αVβ3 and integrin αVβ5, is being tested as a tool to monitor treatment response of tumors to anti-angiogenic therapies.
CEND-1, also known as iRGD, is a cyclic peptide that homes to tumors via binding to Integrin alpha V receptors. However, it also binds and activates neuropilin-1, leading to a temporary opening of the tumor and an enhanced delivery of anti-cancer agents into the tumor tissue. It is currently being tested in clinical trials in solid tumor patients.
Use in bioengineering.
RGD-based peptides have found many applications in biological research and medical devices. Culture plates coated with peptides mimicking ECM proteins’ adhesion motifs, which restrict the differentiation of stem and progenitor cells, are on the market. RGD-coated implantable medical devices are under active study to enhance attachment of endothelial cells, which would help avoid the foreign body reaction. RGD is also a universally used tool in the construction of multifunctional “smart” materials, such as tumor-targeted nanoparticles.


Bio-Techne

Bio-Techne Corporation is a holding company for biotechnology and clinical diagnostic brands. It was founded in 1976 as Techne Corporation and changed its name to Bio-Techne in 2014. The company's brands include flagship R&D Systems (Research and Diagnostic Systems Inc.), Novus Biologicals, Tocris Bioscience, ProteinSimple, Exosome Diagnostics, BiosPacific, Cliniqa, Advanced Cell Diagnostics, RNA Medical, Bionostics, and Boston Biochem. The company's products are used in both clinical and research contexts. The company was co-founded as a "hematology controls developer" by Dr. Roger C. Lucas, who presently serves as its Chief Scientific Advisor.
Bio-Techne is listed on the NASDAQ under the ticker symbol TECH. Writing for Forbes from an investor's perspective, John Reese praised the management team saying it "...appears to be doing a solid job...", a sentiment echoed by Philip van Doorn, writing for Dow Jones MarketWatch. Interviewing investor Edward B. White for "The New York Times", Carole Gould noted that White thought the chief executive, Thomas Oland, was a "deeply committed scientist."
Beginning in 2013, the company's chief executive officer was Charles (Chuck) Kummeth, who had previously been employed by 3M and Thermo Fisher Scientific.
In an article by the Star Tribune, Joe Carlson wrote "Analysts like how Bio-Techne is growing, combining well-considered acquisition targets with the company's long-running reputation for producing top-quality raw proteins and antibodies for use in research."


MAEB RNA motif

The MAEB RNA motif (Metabolism-Associated Element in "Burkholderia" RNA motif) is a conserved stem-loop RNA structure present in many species in the genus Burkholderia. MAEB stem-loops typically occur in blocks of repeats, usually with 2–6 consecutive instances of MAEB stem-loops separated by a short and conserved linker sequence. As many as 12 consecutive MAEB stem-loops have been observed in a single block.
Most MAEB blocks are positioned in the presumed 5' UTR of downstream genes. Out of 141 blocks of consecutive MAEB stem-loops, 132 are positioned in a possible 5' UTR. Therefore, MAEB stem-loops are likely to correspond to a cis-regulatory element. It was observed that the genes apparently regulated by MAEB generally have a role in primary metabolism, i.e., the synthesis, catabolism or transport of small molecules; few MAEB-associated genes are involved in other functions, such as signal transduction, motility or replication. Thus, the motif is associated with a metabolic role, and indeed a weak association with the glycine cleavage system was observed.
Three hypotheses for the biological role of MAEB were considered. One is that the MAEB stem-loop is really a DNA-binding domain of a dimeric protein, and that the two subunits of this protein bind on opposite strands of the duplex DNA. However, two nucleotides at complementary positions on the 5' and 3' side of the stem are almost always purines. If the MAEB motif is really a short DNA-binding domain and its reverse complement, then the 3' part of the apparent RNA stem at this position should contain the complementary pyrimidine, and not also be a purine. Therefore, this hypothesis is unlikely to be true.
The second hypothesis considered is that MAEB is a repetitive DNA sequence. Although the repetitive nature of MAEB stem-loops supports this kind of a role, the association of MAEB with metabolic genes is inconsistent with known repetitive elements, which are typically the result of selfish replication or errors in replication. Rather the repetitive nature of MAEB stem-loops probably has a functional role for the cell.
The third hypothesis advanced is that MAEB stem-loops bind a protein, and the multiple occurrences of MAEB stem-loops within a single RNA molecule would allow the binding of more proteins per RNA molecule. Such an arrangement is similar to CsrB RNA, which contains roughly 18 hairpins, each of which binds one CsrA protein subunit. The true function of MAEB stem-loops remain unknown.


Gurken localisation signal

mRNA localization is a common mode of posttranscriptional regulation of gene expression that targets a protein to its site of function.
Proteins are highly dependent on cellular environments for stability and function, therefore, mRNA localization signals are crucial for maintaining protein function. The Gurken localisation signal is an RNA regulatory element conserved across many species of "Drosophila". The element consists of an RNA stem loop within the coding region of the messenger RNA that forms a signal for dynein-mediated Gurken mRNA transport to the dorsoanterior cap near the nucleus of the oocyte.
Mechanism of action.
During "Drosophila" oogenesis, signaling between the germline and the soma leads to the establishment of anterior-posterior polarity in the egg and the embryo. This process involves the interaction of gurken (grk), a TGFα-like protein, with torpedo (top), the "Drosophila" epidermal growth factor receptor (EGFR). Localization of gurken RNA defines cell morphology by regulating the distribution of the gurken protein. Gurken mRNA transcripts which are not localized to the dorsal-anterior of an oocyte become silenced via post-translational modifications. Post-translational modifications of gurken protein have been observed to determine the protein's localization and function. Polyadenylation of gurken transcripts occur throughout oogenesis; the length of the poly(A) tail determines the stage in oogenesis at which the gurken protein is adenylated. 30-50 gurken adenlyated residues are associated in initial oogenesis whilst 50-90 adenlyated residues are associated with late-stage oogenesis.
The major difference between the gurken localization signal and other localization signals is that gurken localization signals are distributed throughout coding regions, whereas the majority of the other localization signals are found in 3' untranslated regions.[9]. The gurken localization signal does not function properly if it is located in the 3' untranslated region.


Somali elephant shrew

The Somali elephant shrew or Somali sengi ("Galegeeska revoilii") is a species of elephant shrew in the family Macroscelididae.
Natural habitat.
Its natural habitat is arid and semiarid desert with rocky substrates and sparse shrubs. In some parts of Somalia, the Somali sengi and rufous sengi may be locally sympatric. It is found in the northern Horn of Africa; it was formerly thought to be exclusively endemic to Somalia, but a 2020 sighting also indicates they are found in Djibouti and potentially Ethiopia.
Classification.
It was formerly classified in the genus "Elephantulus", but a 2020 study found it to be the sister taxon of the clade containing the genera "Petrodromus" and "Petrosaltator"; due to this, it was reclassified in the monotypic genus "Galegeeska." The split with the "Petrodromus"-"Petrosaltator" clade is estimated to have occurred about 20.6 million years ago.
Disappearance and rediscovery.
The Somali sengi was among the 25 "most wanted lost" species that were the focus of Global Wildlife Conservation's “Search for Lost Species” initiative. On , 50 years after it was last seen and recorded, it was announced that a population had been found in Djibouti, the first documented since 1968.
Etymology.
"Galegeeska" translates to "weasel of the horn". In the Somali language, 'geeska' means corner or horn, as in the Horn of Africa. Galê in Ancient Greek means weasel, and has been used in other small mammal taxa. 'Gale' also honours one of the authors, Galen B. Rathbun (1944-2019) who searched for the Somali sengi and devoted several decades of research into sengi biology.


Sphingomonas psychrolutea

Sphingomonas psychrolutea is a Gram-negative, rod-shaped, aerobic and psychrotolerant bacteria from the genus of Sphingomonas which has been isolated from the Midui glacier in Tibet in China.


Walter Reed Biosystematics Unit

The Walter Reed Biosystematics Unit ("WRBU") is a US Army organization that conducts laboratory and field research on the systematics of medically important arthropods in support of epidemiological investigations and disease prevention and control strategies of importance to the military. Research is carried out worldwide, within geographic or faunistic restrictions of the material available and military requirements. Research efforts focus on the development of accurate and reliable means of identifying vectors of arbopathogens of humans.
The WRBU also performs arthropod collections management for the Department of Entomology, National Museum of Natural History mosquito collection and maintains a molecular entomology laboratory within the Smithsonian Institution Museum Support Center for joint use of WRBU and National Museum of Natural History (NMNH) personnel.
History.
Army entomologists began formal collaborations with Smithsonian Institution entomologists as early as 1961. The WRBU's unit lineage begins with the stand up of the Army Mosquito Project (AMP) in 1964. In 1966, the AMP's mission was refocused on the vectorborne disease threat facing troops deployed to southeast Asia for the Vietnam War and the unit was reorganized as the Southeast Asia Mosquito Project (SEAMP). After the war in southeast Asia wound down, SEAMP was reorganized in 1974 as the Medical Entomology Project (MEP) to encompass a broader long-term mission. In 1981, the MEP was reorganized as the Walter Reed Biosystematics Unit, and the unit has retained that identity through subsequent moves and restructurings. The name commemorates U.S. Army physician Major Walter Reed who in 1901 led the team that established that yellow fever is transmitted by mosquitoes.
The WRBU currently (2017) operates under the direction of the Department of Entomology, Walter Reed Army Institute of Research (WRAIR), with laboratories and offices in the Smithsonian Museum Support Center in Suitland, Maryland. Collaborative partners in addition to the WRAIR include the U. S. Army Medical Research and Materiel Command, the NMNH, and the Armed Forces Pest Management Board.
Specimen collection.
The WRBU assists in conserving the NMNH Mosquito Collection, the largest mosquito collection in the world, with over 1.5 million specimens. The WRBU maintains and secures specimens, handles transactions including loans of material, improves the collection, provides assistance to Department of Entomology personnel, Smithsonian Institution Research Associates, visiting scientists, and mosquito researchers in locating and examining specimens in the collection.


Listeria Hfq binding LhrC

Listeria LhrC ncRNA was identified by screening for RNA molecules which co-immunoprecipitated with the RNA chaperone Hfq. However, neither the stability nor the activity of LhrC seem to depend on the presence of Hfq. This RNA is transcribed from an intergenic region between the protein coding genes cysK, a putative cysteine synthase and sul, a putative dihydropteroate synthase. In Listeria monocytogenes four additional copies of lhrC have been identified in the genome, three of which are located in tandem repeat upstream of the originally characterised lhrC. This RNA molecule appears to be conserved amongst Listeria species but has not been identified in other bacterial species. It is involved in virulence. The direct mRNA targets of LhrC are the virulence adhesion LapB, and the oligo-peptide binding protein OppA. The 3 conserved UCCC motifs common to all copies of LhrC are involved in the mRNA binding and post-transcriptional repression of the target genes. Two other "Listerina monocytogenes" sRNAs Rli22 and Rli33 contain 2 UCCC motifs and use them to repress "oppA" mRNA expression.


Polyuridylation

Polyuridylation, also called oligouridylation, is the addition of several uridine nucleotides to the 3' end of an RNA. One group of RNAs that can be polyuridylated are histone mRNAs that lack a poly(A) tail. Polyuridylation of a histone mRNA promotes its degradation, involving the exosome. Other RNAs in "Arabidopsis" and mouse have been seen to be polyuridinylated after cleavage.


Polyamine oxidase

In enzymology, a polyamine oxidase () is an enzyme that catalyzes the chemical reaction
The 3 substrates of this enzyme are N1-acetylspermine, O2, and H2O, whereas its 3 products are N1-acetylspermidine, 3-aminopropanal, and H2O2.
This enzyme belongs to the family of oxidoreductases, specifically those acting on the CH-NH group of donors with oxygen as acceptor. The systematic name of this enzyme class is N1-acetylspermidine:oxygen oxidoreductase (deaminating). This enzyme is also called 1-N-acetylspermidine:oxygen oxidoreductase (deaminating). It has 2 cofactors: FAD, and Iron. A similar enzyme in plants catalyzes non-acetylated polyamines.
Structural studies.
As of late 2007, 9 structures have been solved for this class of enzymes, with PDB accession codes , , , , , , , , and .


Mycena pura

Mycena pura, commonly known as the lilac bonnet, is a species of mushroom in the family Mycenaceae. First called "Agaricus prunus" in 1794 by Christian Hendrik Persoon, it was assigned its current name in 1871 by German Paul Kummer. "Mycena pura" is known to bioaccumulate the element boron.
Bioactive compounds.
"Mycena pura" contains the chemical puraquinonic acid, a sesquiterpene. This compound induces mammalian cells (specifically, the cell line HL60) to differentiate into granulocyte- or macrophage-like cells. The fungus also contains the mycotoxin muscarine, and the antifungal metabolite strobilurin D, the latter previously found in "Cyphellopsis anomala". Despite the presence of these toxins, some guides list "M. pura" as edible.


Christopher J. Hernandez

Christopher J. Hernandez is an American engineer and scientist who currently serves as professor of mechanical and aerospace engineering and biomedical engineering at Cornell University and is also an adjunct scientist in the Research Division of the Hospital for Special Surgery.
Education.
Hernandez received his BS in Engineering Sciences at Harvard University in 1996. He went on to graduate from Stanford University with a MS and PhD in Mechanical Engineering in 1997 and 2001 respectively.
Career.
Hernandez worked at the Mount Sinai School of Medicine in New York and at UC Berkeley prior to joining the faculty at Case Western Reserve University. He joined the faculty at Cornell University in 2010.
He currently leads the Hernandez Research Group at Cornell University. Hernandez's "research in biomechanics examines the musculoskeletal system and microscopic organisms."
Honors and awards.
Some of Hernandez's honors have included:
Hernandez is a member of the American Society for Bone and Mineral Research and the Orthopaedic Research Society.
Personal life.
Hernandez was born in Fresno, California and is Mexican American.


Enzyme and Microbial Technology

Enzyme and Microbial Technology is a peer-reviewed scientific journal covering research on the basic and applied aspects of biotechnological processes involving the use of enzymes, microorganisms, and animal and plant cells.
Abstracting and indexing.
The journal is abstracted and indexed in:
According to the "Journal Citation Reports", the journal has a 2010 impact factor of 2.287.


Target peptide

A target peptide is a short (3-70 amino acids long) peptide chain that directs the transport of a protein to a specific region in the cell, including the nucleus, mitochondria, endoplasmic reticulum (ER), chloroplast, apoplast, peroxisome and plasma membrane. Some target peptides are cleaved from the protein by signal peptidases after the proteins are transported.
Types by protein destination.
Secretion.
Almost all proteins that are destined to the secretory pathway have a sequence consisting of 5-30 hydrophobic amino acids on the N-terminus, which is commonly referred to as the signal peptide, signal sequence or leader peptide. Signal peptides form alpha-helical structures. Proteins that contain such signals are destined for either extra-cellular secretion, the plasma membrane, the lumen or membrane of either the (ER), Golgi or endosomes. Certain membrane-bound proteins are targeted to the secretory pathway by their first transmembrane domain, which resembles a typical signal peptide.
In prokaryotes, signal peptides direct the newly synthesized protein to the SecYEG protein-conducting channel, which is present in the plasma membrane. A homologous system exists in eukaryotes, where the signal peptide directs the newly synthesized protein to the Sec61 channel, which shares structural and sequence homology with SecYEG, but is present in the endoplasmic reticulum. Both the SecYEG and Sec61 channels are commonly referred to as the translocon, and transit through this channel is known as translocation. While secreted proteins are threaded through the channel, transmembrane domains may diffuse across a lateral gate in the translocon to partition into the surrounding membrane.
ER-Retention Signal.
In eukaryotes, most of the newly synthesized secretory proteins are transported from the ER to the Golgi apparatus. If these proteins have a particular 4-amino-acid retention sequence for the ER's lumen, KDEL, on their C-terminus, they are retained in the ER's lumen or are routed back to the ER's lumen (in instances where they escape) via interaction with the KDEL receptor in the Golgi apparatus. If the signal is KKXX, the retention mechanism to the ER will be similar but the protein will be transmembranal.
Nucleus.
A "nuclear localization signal" (NLS) is a target peptide that directs proteins to the nucleus and is often a unit consisting of five basic, positively charged amino acids. The NLS normally is located anywhere on the peptide chain.
A "nuclear export signal" (NES) is a target peptide that directs proteins from the nucleus back to the cytosol. It often consists of several hydrophobic amino acids (often leucine) interspaced by 2-3 other amino acids.
Many proteins are known to constantly shuttle between the cytosol and nucleus and these contain both NESs and NLSs.
Nucleolus.
The nucleolus within the nucleus can be targeted with a sequence called a "nucleolar localization signal" (abbreviated NoLS or NOS).
Mitochondria and plastid.
The "mitochondrial targeting signal" also known as "presequence" is a 10-70 amino acid long peptide that directs a newly synthesized protein to the mitochondria. It is found at the N-terminus end consists of an alternating pattern of hydrophobic and positively charged amino acids to form what is called an amphipathic helix. Mitochondrial targeting signals can contain additional signals that subsequently target the protein to different regions of the mitochondria, such as the mitochondrial matrix or inner membrane. In plants, an N-terminal signal (or "transit peptide") targets to the plastid in a similar manner. Like most signal peptides, mitochondrial targeting signals and plastid specific transit peptides are cleaved once targeting is complete. Some plant proteins have an N-terminal transport signal that targets both organelles often referred to as "dual-targeted" transit peptide. Approximately 5% of total organelle proteins are predicted to be dual-targeted however the specific number could be higher considering the variable degree of accumulation of passenger proteins in both organelles. The targeting specificity of these transit peptides depends on many factors including net charge and affinity between transit peptides and organelle transport machinery.
Peroxisome.
There are two types of target peptides directing to peroxisome, which are called "peroxisomal targeting signals" (PTS). One is PTS1, which is made of three amino acids on the C-terminus. The other is PTS2, which is made of a 9-amino-acid sequence often present on the N-terminus of the protein.
Examples of target peptides.
The following content uses protein primary structure single-letter location. A "[n]" prefix indicates the N-terminus and a "[c]" suffix indicates the C-terminus; sequences lacking either are found in the middle of the protein.


Teleost leptins

Teleost leptins are a family of peptide hormones found in fish (teleostei) that are orthologs of the mammalian hormone leptin. The teleost and mammalian leptins appear to have similar functions, namely, regulation of energy intake and expenditure.
The leptin (LEP) hormone was long thought to be specific to mammals, but in recent years the gene ("lep") has been found in amphibia such as the tiger salamander ("Ambystoma tigrinum"), and the African clawed frog ("Xenopus laevi"). The discovery of "lep" in puffer fish ("Takifugu rubripes") demonstrates the ancient ancestry of this hormone.
Examples.
There are two closely related "lep" paralogues in Atlantic salmon ("Salmo salar"). A single "lep" gene has been documented for green-spotted pufferfish ("Tetraodon nigroviridis"), rainbow trout ("Oncorhynchus mykiss"), Arctic charr ("Salvelinus alpinus"), silver carp ("Hypophthalmichthys molitrix"), and grass carp ("Ctenopharyngodon idellus"). In other species there are reports of two closely related lep paralogues, including common carp ("Cyprinus carpio") and Atlantic salmon. More distantly related lep genes have been found in medaka ("Oryzias latipes") and zebrafish ("Danio rerio"). At least 2 leptin genes ("lepa" and "lepb") exist in the crown-clade (Fig. 1). Early findings have shown that "lepa" and "lepb" share low interspecies aa identity, and are argued to have arisen through whole genome duplication, which occurred early in the teleost lineage. The duplicity of genes has been described for Atlantic salmon, Japanese medaka, common carp and zebrafish. Both "lep" paralogues cluster with "lepa", and therefore suggest that at least one or more form ("lepb") may exist in this species, since it is tetraploid. However, previous attempts using genomic synteny have only found the putative genomic duplicates in medaka and zebrafish paralogue. Currently it remains unclear, whether "lepb" exists in other teleosts due to the degenerative nature of this paralogue.
Comparison with mammalian leptin.
The large differences among endothermic (warm-blooded) mammalian and ectothermic (cold-blooded) teleost leptins raised the question of whether the energy homeostatic functions of the teleost leptins are conserved. Initial phylogenetic analysis has revealed that amino acid conservation with other vertebrate Lep orthologues is low, with only 13.2% sequence identity between torafugu and human LEP. Subsequent investigations have confirmed the low amino acid identity of teleost "leps" compared to mammalian LEP.
Structure.
The three-dimensional homology modeling predicts strong conservation of the tertiary structure between Atlantic salmon and other teleost Leps compared to their mammalian orthologues (Fig. 2).
Both "lepa1" and "lepa2" have two characteristic cysteine residues which predict the formation of a disulfide bond in Lep, which is a pre-equisite for this 3D configuration and bioactivity of human LEP. The models suggest that the bonding of "lepa2" might be different from "lepa1". There are several differences between the 3D structures of "lepa1" and "lepa2"; e.g. α-helix 5 is considerable shorter in "lepa1" than "lepa2". Furthermore, α-helix 1 for "lepa2" appears to be split by a short-disordered region, and may therefore have a poorer affinity. However, considering that it is a predicted model based upon the structure mask of human LEP, the significance of these putative conformational adjustments remains to be tested.
The importance of the conserved tertiary structure of Lep is most likely explained by requirements for specific LepR-binding affinity and is constrained by the structure of the receptor-binding pocket. This might also explain some of the results from studies on teleost using heterologous mammalian Lep. E.g. treatment with the mammalian hormone caused an anorexic effect in goldfish ("Carassius auratus") and green sunfish ("Lepomis cyanellus"), but not in Coho salmon ("Oncorhynchus kisutch"), channel catfish ("Ictalurus punctatus") and green sunfish. These contradicting results have been explained by the relatively large differences in amino acid sequences observed between mammals and fish.
Rønnestad and colleagues recently detected five isoforms of the leptin receptor ("lepr") that have differences in 3'-end of the mRNA sequence. Of these, only the longest form conserved all functionally important domains (such as three fibronectin type III domains, the Ig C2-like domain, a pair of WSXWS motifs, two JAK2-binding motif boxes, and a STAT-binding domain), while the other four forms have only the intra-cellular region. The long form of mammalian LepR has a function for full signal transduction through the JAK/STAT pathways, whereas the shorter forms exhibit partial or no signaling capabilities. The biological importance of long form LepR via the JAK/STAT pathway in maintaining body weight and energy homeostasis has been demonstrated. Previous studies in teleosts have only identified a single "lepr". Rønnestad et al., is the first to report that plural LepR transcripts in any ectotherm species. When looking at the available motif for "lepr", the model suggests that it would bind easily to "lepa1" and not "lepa2" (Fig. 2). Furthermore, the relatively ubiquitous expression of "lepr" in salmon tissues supports diverse roles of "lep" in teleosts.
Tissue distribution.
The study on torafugu indicated that "lep" is mainly expressed in the liver in contrasts to the adipose secretion in mammals. However recent studies have shown that "lep" is expressed in several peripheral tissues, including intestine, kidney, ovary, muscle and adipose tissue. The multiplicity of "lep" genes and their low conservation in Teleostei. suggest that their physiological roles may be more divergent than reported for mammals.
The tissue expression pattern for the Atlantic salmon "lep" paralogues differs substantially (Fig.3) and hence indicates a possible difference in function. With the exception of the results presented here, and those for zebrafish and Japanese medaka. Few studies have investigated the broad tissue distribution of "lep" in teleost fishes. The more distantly related "lep" genes ("lepa" and "lepb") showed distinct differences in tissue distribution, as shown in e.g. medaka, where "lepa" is being expressed in liver and muscle, while "lepb" is more highly expressed in the brain and eye. However, these differences are also observed for more closely related "lep" paralogues, such as "lepa1" in Atlantic salmon, being more highly expressed in brain, liver and white muscle, while "lepa2" is mainly expressed in the stomach and midgut. (Fig. 3).
Effects of nutritional status.
The observations that long-term feed restriction does not significantly affect "lep" expression in Atlantic salmon has also been noted in other teleosts. However it is likely that prolonged feed restriction can influence several endocrine parameters to adapt to the nutritional condition. For example, in common carp, a rapid response in ob gene expression in hepatic tissue of common carp shortly after feeding, but no changes in expression in response to different long-term feeding regime was observed. These authors suggested that this effect could be explained by the fact that starved fish do not lose weight as rapidly as mammals, a consequence of being ectothermic and possessing a much lower standard metabolic rate, and therefore can withstand longer periods of starvation. A similar study on grass carp showed that chronic injection of species-specific Lep did not affect long-term food intake and body weight, while acute injection decreased food intake. Conversely, Murashita et al., (unpublished results) observed increased proopiomelanocortin a1("pomca1") levels following chronic injection of Lep in Atlantic salmon, which suggests that chronic exposure to elevated Lep levels can decrease food intake through the Pomc pathway in this species. Recent studies in Atlantic salmon did not observe any difference of feed restriction in circulating plasma levels, which contrasts recent results in rainbow trout and suggest that the relation between circulating lep levels and energy status differs from that in mammals. However, salmon RIA appears to allow interspecies assessment of plasma lep levels. This only confirms that more comprehensive studies are needed for conclusive data interpretation. Studies on rainbow trout also implicated Lep as an anorectic hormone as in mammals. Injection of rainbow trout with recombinant trout leptin ("rt-leptin") resulted in a significantly reduced appetite over two days that coincided with a decrease in hypothalamic mRNA expression of neuropeptide Y ("npy") and increase of "pomc" mRNAs, respectively. Whether these observations are due to species-specific differences in long-term leptin regulation of appetite or growth is not known, however, consensus data indicate that the effects of Lep on appetite regulation may be short-term in teleosts.
Short-term feed restriction.
Recent studies on short-term effects of a meal or the absence of a meal has revealed that "lepa1" expression specifically peaks in the peripheral tissues after 6 – 9 hr in the unfed fish. This suggests that the transcript specific response could be associated with the absence of food. Conversely, since the unfed fish had not received food for 33 hr (24 + 9 hr), the peaks could represent an unrelated effect. Each "lepa1" peak occurred during a phase of falling plasma Lep, and since this occurred in both fed and unfed fish, the temporal upregulation of "lepa1" does not in fact appear to be specifically related to the absence of food.
The earliest peak of "lepa1" occurred in the white muscle, which represents an important lipid reservoir in Atlantic salmon. Unlike pufferfish, which utilizes the liver as a major lipid repository, Atlantic salmon shows that despite a high visceral lipid content, hepatocytes contain few lipid droplets compared to other fish species, yet are an important site for leptin expression. Moen and colleagues reported that both "lepa1" and "lepa2" peaked at 9 hr in the liver of unfed fish. By contrast, however, studies in common carp demonstrated a peak in leptin-I("lepa1") and leptin–II ("lepa2") in liver at 3 and 6 hr post feeding respectively. The earlier expression response of leptins in common carp likely reflects the higher temperature under which the experiments were conducted, but contrasts the findings of upregulation of "lepa1" due to the absence of food. Similarly, in mice, a postprandial increase in hepatic leptin expression has also been reported. However, in grass carp, intraperitoneal injection of recombinant leptin only alters the appetite on the first day, and does not influence food intake during the ensuing 12 days. At present, the data for Atlantic salmon are therefore quite different and suggest that leptin expression in this species may have a complex lipostatic function.


Aminoshikimate pathway

The Aminoshikimate pathway is a biochemical pathway present in some plants, which has been studied by biologists, biochemists and especially those interested in manufacture of novel antibiotic drugs. The pathway is a novel variation of the shikimate pathway. The aminoshikimate pathway was first discovered and studied in the rifamycin B producer "Amycolatopsis mediterranei". Its end product, 3-amino-5-hydroxybenzoate, serves as an initiator for polyketide synthases in the biosynthesis of ansamycins.
Overview.
Floss and coworkers identified the gene cluster associated with the aminoshikimate pathway in "Amycolatopsis mediterranei". The enzyme-catalyzed condensation of 1-deoxy-1-imino--erythrose 4-phosphate with phosphoenolpyruvate to form 4-amino-3,4-dideoxy--arabino-heptulosonic acid 7-phosphate has been proposed to be the first committed step in the aminoshikimate pathway. Guo and Frost demonstrated that the unusual metabolite, 1-deoxy-1-imino--erythrose 4-phosphate, is derived from 3-amino-3-deoxy--fructose 6-phosphate. In addition, kanosamine biosynthesis has been directly implicated by Guo and Frost as the source of the aminoshikimate pathway's nitrogen atom.
Uses.
Aminoshikimate pathway has been assembled in "E. coli" to synthesize aminoshikimic acid, which is a promising starting material for the synthesis of antiinfluenza agent oseltamivir (brand name Tamiflu).


Roridomyces irritans

Roridomyces irritans is a species of fungus in the genus "Roridomyces", family Mycenaceae. Originally described from New Caledonia as "Mycena irritans" by Egon Horak in 1978, the species was transferred to "Roridomyces" in 1994. The fruit bodies are bioluminescent.


Daturaolone

Daturaolone is a triterpene found in "Datura" species such as "Datura stramonium" and "Datura innoxia".
History.
It was isolated for the first time from "Solanum arundo".
Research.
It has shown to exhibit dose-dependent anti-inflammatory results in in-vivo models of inflammation by inhibiting COX-1 as well as having potent α-glucosidase and β-secretase inhibitory activity however further studies are needed to better clarify its effect on humans.
It may have antipyretic, muscle relaxant properties and decrease gastrointestinal motility although it is only evaluated in animals.


Glycogenesis

Glycogenesis is the process of glycogen synthesis, in which glucose molecules are added to chains of glycogen for storage. This process is activated during rest periods following the Cori cycle, in the liver, and also activated by insulin in response to high glucose levels.
Control and regulations.
Glycogenesis responds to hormonal control.
One of the main forms of control is the varied phosphorylation of glycogen synthase and glycogen phosphorylase. This is regulated by enzymes under the control of hormonal activity, which is in turn regulated by many factors. As such, there are many different possible effectors when compared to allosteric systems of regulation.
Epinephrine (adrenaline).
Glycogen phosphorylase is activated by phosphorylation, whereas glycogen synthase is inhibited.
Glycogen phosphorylase is converted from its less active "b" form to an active "a" form by the enzyme phosphorylase kinase. This latter enzyme is itself activated by protein kinase A and deactivated by phosphoprotein phosphatase-1.
Protein kinase A itself is activated by the hormone adrenaline. Epinephrine binds to a receptor protein that activates adenylate cyclase. The latter enzyme causes the formation of cyclic AMP from ATP; two molecules of cyclic AMP bind to the regulatory subunit of protein kinase A, which activates it allowing the catalytic subunit of protein kinase A to dissociate from the assembly and to phosphorylate other proteins.
Returning to glycogen phosphorylase, the less active "b" form can itself be activated without the conformational change. 5'AMP acts as an allosteric activator, whereas ATP is an inhibitor, as already seen with phosphofructokinase control, helping to change the rate of flux in response to energy demand.
Epinephrine not only activates glycogen phosphorylase but also inhibits glycogen synthase. This amplifies the effect of activating glycogen phosphorylase. This inhibition is achieved by a similar mechanism, as protein kinase A acts to phosphorylate the enzyme, which lowers activity. This is known as co-ordinate reciprocal control. Refer to glycolysis for further information of the regulation of glycogenesis.
Calcium ions.
Calcium ions or cyclic AMP (cAMP) act as secondary messengers. This is an example of negative control. The calcium ions activate phosphorylase kinase. This activates glycogen phosphorylase and inhibits glycogen synthase.


Neurophysins

Neurophysins are carrier proteins which transport the hormones oxytocin and vasopressin to the posterior pituitary from the paraventricular and supraoptic nucleus of the hypothalamus, respectively. Inside the neurosecretory granules, the analogous neurophysin I and II form stabilizing complexes via covalent interactions. Stabilizing neurophysin-hormone complexes that are formed within neurosecretory granules located in the posterior pituitary gland aid in intra-axonal transport. During intra-axonal transport, the neurophysin's are believed to prevent the bound hormone from leaking into the cytoplasmic space and proteolytic digestion via enzymes. However, due to the low concentration of neurophysin in the blood, it is likely the protein-hormone complex dissociates, indicating the neurophysin does not aid in transporting the hormone through the circulatory system.
Neurophysins are also secreted out of the posterior pituitary hypothalamus, each carrying their respective associated passenger hormone. When the posterior pituitary hypothalamus secretes vasopressin and its neurophysin carrier, it also secretes a glycopeptide.
There are two types:
Biosynthesis of Neurophysins.
These proteins are synthesized in the cell bodies of the supraoptic and paraventricular regions of the hypothalamus.
The disulfide-rich neurophysin protein is suggested to be congruent with the synthesis of insulin in which a precursor molecule of higher molecular weight is proteolytically cleaved and forms disulfide linkages.
Although not enough data has been obtained, it is hypothesized that there is a common precursor molecule between neurophysin and the two hormones it stabilizes.
Structure.
Neurophysins are acidic proteins with a molecular weight of approximately 10,000 Da that are rich in cysteine, glycine, and proline residues . The protein is double domain with a polypeptide chain of 93-95 residues with 14 cysteine residues forming 7 disulfide bridges . Domain I contains a COOH terminal with a disulfide loop; domain II lacks this COOH terminal disulfide loop . Based on the resemblance of the disulfide loop present on vasopressin and oxytocin, it is suggested that the hormones form covalent linkages to this disulfide loop present on the COOH terminal of domain I.


Serotonin receptor antagonist

A serotonin antagonist, or serotonin receptor antagonist, is a drug used to inhibit the action at serotonin (5-HT) receptors.
Types.
5-HT2A antagonists.
Antagonists of the 5-HT2A receptor are sometimes used as atypical antipsychotics (contrast with typical antipsychotics, which are purely dopamine antagonists).
They include, but are not limited to:
5-HT3 antagonists.
Another subclass consists of drugs selectively acting at the 5-HT3 receptors, and thus are known as 5-HT3 antagonists. They are efficacious in treating chemotherapy-induced emesis and postoperative nausea and vomiting.
They include, but are not limited to:
Other 5-HT3 antagonists are used for the treatment of irritable bowel syndrome:
Also, the antidepressant mirtazapine acts as a 5-HT3 antagonist.
Non-selective 5-HT antagonists.
Please note, that although some non-selective serotonin antagonists may have a particular affinity for a specific 5-HT receptor (and thus may be listed below e.g., methysergide), they still may also possess a generalised non-selective action.
They include, but are not limited to:


Douglas Noll

Douglas C. Noll is an American bioengineer currently the Ann and Robert H. Lurie Professor at University of Michigan and is an Elected Fellow of the American Institute for Medical and Biological Engineering, International Society of Magnetic Resonance in Medicine and Biomedical Engineering Society. Prior to working at the University of Michigan he also worked at the University of Illinois, Carnegie Mellon University and University of Pittsburgh. He completed his studies at Stanford and Bucknell Universities where he obtained B.S., M.S., and eventually Ph.D. in electrical engineering.


Richard K. Wilson

Richard K. Wilson (born March 23, 1959) is a leading American molecular geneticist. He is the founding Executive Director of the Institute for Genomic Medicine at Nationwide Children’s Hospital and Professor of Pediatrics at the Ohio State University College of Medicine. He received his A.B. degree (Microbiology) from Miami University in Ohio in 1981, his Ph.D. (Chemistry) from the University of Oklahoma in 1986, and was a Research Fellow in the Division of Biology at the California Institute of Technology (1986-1990). In 1990, Dr. Wilson joined the faculty of Washington University School of Medicine where he co-founded the Genome Sequencing Center/McDonnell Genome Institute. At Washington University, Dr. Wilson was the Alan A. and Edith L. Wolff Distinguished Professor of Medicine, Professor of Genetics, Professor of Molecular Microbiology, and a member of the Senior Leadership Committee of the Siteman Cancer Center.
Dr. Wilson’s laboratories have been among the world’s leaders in genome analysis. His teams have sequenced and analyzed billions of bases of DNA from the genomes of bacteria, yeast, plants, invertebrates, vertebrates, primates and humans. Dr. Wilson and his colleagues at Washington University sequenced the first animal genome – that of the roundworm Caenorhabditis elegans – and contributed substantially to the sequencing and analysis of the human genome. Following the Human Genome Project, they also sequenced the genomes of the mouse, chimpanzee, orangutan, gorilla, rhesus macaque, platypus, the plants Arabidopsis thaliana and Zea mays (corn), as well as various invertebrates, insect vectors and microorganisms. His team was the first to sequence the genome of a cancer patient and discover genetic signatures relevant to the pathogenesis of the disease. Building upon these achievements, Dr. Wilson and his colleagues helped initiate and participated in several landmark genomics projects including The Cancer Genome Atlas, the Pediatric Cancer Genome Project, the Genome Reference Consortium, the Human Microbiome Project, and the Centers for Common Disease Genomics.
In 2008, Dr. Wilson was elected as a Fellow of the American Association for the Advancement of Science (2008). In 2011, he received the Distinguished Achievement Award from Miami University and the Distinguished Alumnus Award from the University of Oklahoma College of Arts and Sciences.
In 2016, Dr. Wilson and several colleagues moved to Nationwide Children’s Hospital and launched the Institute for Genomic Medicine. Their mission is to utilize cutting-edge genome sequencing and analysis technology to discover clues that will lead to more effective diagnosis and treatment of cancer and other human diseases in children and adults.


Androgen receptor

The androgen receptor (AR), also known as NR3C4 (nuclear receptor subfamily 3, group C, member 4), is a type of nuclear receptor that is activated by binding any of the androgenic hormones, including testosterone and dihydrotestosterone in the cytoplasm and then translocating into the nucleus. The androgen receptor is most closely related to the progesterone receptor, and progestins in higher dosages can block the androgen receptor.
The main function of the androgen receptor is as a DNA-binding transcription factor that regulates gene expression; however, the androgen receptor has other functions as well. Androgen-regulated genes are critical for the development and maintenance of the male sexual phenotype.
Function.
Effect on development.
In some cell types, testosterone interacts directly with androgen receptors, whereas, in others, testosterone is converted by 5-alpha-reductase to dihydrotestosterone, an even more potent agonist for androgen receptor activation. Testosterone appears to be the primary androgen receptor-activating hormone in the Wolffian duct, whereas dihydrotestosterone is the main androgenic hormone in the urogenital sinus, urogenital tubercle, and hair follicles. Testosterone is therefore responsible primarily for the development of male primary sexual characteristics, whilst dihydrotestosterone is responsible for secondary male characteristics.
Androgens cause slow maturation of the bones, but more of the potent maturation effect comes from the estrogen produced by aromatization of androgens. Steroid users of teen age may find that their growth had been stunted by androgen and/or estrogen excess. People with too little sex hormones can be short during puberty but end up taller as adults as in androgen insensitivity syndrome or estrogen insensitivity syndrome.
Knockout-mice studies have shown that the androgen receptor is essential for normal female fertility, being required for development and full functionality of the ovarian follicles and ovulation, working through both intra-ovarian and neuroendocrine mechanisms.
Maintenance of male skeletal integrity.
Via the androgen receptor, androgens play a key role in the maintenance of male skeletal integrity. The regulation of this integrity by androgen receptor (AR) signaling can be attributed to both osteoblasts and osteocytes.
Role in females.
The AR plays a role in regulating female sexual, somatic, and behavioral functions. Experimental data using AR knockout female mice, provides evidence that the promotion of cardiac growth, kidney hypertrophy, cortical bone growth and regulation of trabecular bone structure is a result of DNA-binding-dependent actions of the AR in females.
Moreover, the importance of understanding female androgen receptors lies in their role in several genetic disorders including androgen insensitivity syndrome (AIS). Complete (CAIS) and partial (PAIS) which are a result of mutations in the genes that code for AR. These mutations cause the inactivation of AR due to mutations conferring resistance to circulating testosterone, with more than 400 different AR mutations reported.
Mechanism of action.
Genomic.
The primary mechanism of action for androgen receptors is direct regulation of gene transcription. The binding of an androgen to the androgen receptor results in a conformational change in the receptor that, in turn, causes dissociation of heat shock proteins, transport from the cytosol into the cell nucleus, and dimerization. The androgen receptor dimer binds to a specific sequence of DNA known as a hormone response element. Androgen receptors interact with other proteins in the nucleus, resulting in up- or down-regulation of specific gene transcription. Up-regulation or activation of transcription results in increased synthesis of messenger RNA, which, in turn, is translated by ribosomes to produce specific proteins. One of the known target genes of androgen receptor activation is the insulin-like growth factor 1 receptor (IGF-1R). Thus, changes in levels of specific proteins in cells is one way that androgen receptors control cell behavior.
One function of androgen receptor that is independent of direct binding to its target DNA sequence is facilitated by recruitment via other DNA-binding proteins. One example is serum response factor, a protein that activates several genes that cause muscle growth.
Androgen receptor is modified by post-translational modification through acetylation, which directly promotes AR-mediated transactivation, apoptosis and contact-independent growth of prostate cancer cells. AR acetylation is induced by androgens and determines recruitment into chromatin. The AR acetylation site is a key target of NAD-dependent and TSA-dependent histone deacetylases and long non-coding RNA.
Non-genomic.
More recently, androgen receptors have been shown to have a second mode of action. As has been also found for other steroid hormone receptors such as estrogen receptors, androgen receptors can have actions that are independent of their interactions with DNA. Androgen receptors interact with certain signal transduction proteins in the cytoplasm. Androgen binding to cytoplasmic androgen receptors can cause rapid changes in cell function independent of changes in gene transcription, such as changes in ion transport. Regulation of signal transduction pathways by cytoplasmic androgen receptors can indirectly lead to changes in gene transcription, for example, by leading to phosphorylation of other transcription factors.
Genetics.
Gene.
In humans, the androgen receptor is encoded by the "AR" gene located on the X chromosome at Xq11–12.
Deficiencies.
The androgen insensitivity syndrome, formerly known as testicular feminization, is caused by a mutation in the androgen receptor gene on the X chromosome (locus: Xq11–Xq12). The androgen receptor seems to affect neuron physiology and is defective in Kennedy's disease. In addition, point mutations and trinucleotide repeat polymorphisms have been linked to a number of additional disorders.
CAG repeats.
The AR gene contains CAG repeats that affect receptor function, where fewer repeats leads to increased receptor sensitivity to circulating androgens and more repeats leads to decreased receptor sensitivity. Studies have shown that racial variation in CAG repeats exists, with African-Americans having fewer repeats than non-Hispanic white Americans. The racial trends in CAG repeats parallels the incidence and mortality of prostate cancer in these groups.
Structure.
Isoforms.
Two isoforms of the androgen receptor (A and B) have been identified:
Domains.
Like other nuclear receptors, the androgen receptor is modular in structure and is composed of the following functional domains labeled A through F:
Splice variants.
AR-V7 is an androgen receptor splice variant that can be detected in circulating tumor cells of metastatic prostate cancer patients and is predictive of resistance to some drugs.
Clinical significance.
High expression in androgen receptor has been linked to aggression and sex drive by affecting the HPA and HPG axis
Aberrant androgen receptor coregulator activity may contribute to the progression of prostate cancer.
As a drug target.
The AR is an important therapeutic target in prostate cancer. Thus many different antiandrogens have been developed, primarily targeting the ligand-binding domain of the protein. AR ligands can either be classified based on their structure (steroidal or nonsteroidal) or based on their ability to activate or inhibit transcription (agonists or antagonists). Inhibitors that target alternative functional domains (N-terminal domain, DNA-binding domain) of the protein are still under development.
Interactions.
Androgen receptor has been shown to interact with:


Nancy Allbritton

Nancy Allbritton is a Professor of Bioengineering and Frank & Julie Jungers Dean of the College of Engineering at the University of Washington. Until the end of October 2019, she was a Kenan Professor and Chair in the Joint Department of Biomedical Engineering at the University of North Carolina at Chapel Hill and North Carolina State University.
She is best known for her work in single-cell analysis. Using engineering methods, Allbritton creates tools for better understanding and manipulating living cells and tissues. Microengineered platforms, microfluidics, and novel biochemical assays enable scientists to study cell signaling and signal transduction at the single-cell level.
Education.
Allbritton studied at Johns Hopkins University for a M.D in medicine and at the Massachusetts Institute of Technology for a Ph.D in medical engineering in the 1980s.
Research interests.
Allbritton's interest in single-cell analysis have hinged on the use of capillary electrophoresis (CE) and microfabricated technologies. Through this work she has studied lipid signaling at the single-cell level, the isolation cytotoxic t-cells with specific properties, and the capture of colonic crypts. In the organ-on-a-chip field, Allbritton has focused on developing devices that effectively capture the environment of both the small and large intestine.


Fluorophore-assisted carbohydrate electrophoresis

Fluorophore assisted carbohydrate electrophoresis or FACE is a biochemical technology suited for detecting complex mixtures of high molecular weight N-glycans. A specialized form of this technique is the DSA-FACE, which is an acronym for DNA sequencer-assisted flurophore-assisted carbohydrate electrophoresis. DSA-FACE has higher resolution and sensitivity than classical FACE.


2C-B-BZP

4-Bromo-2,5-dimethoxy-1-benzylpiperazine (2C-B-BZP) is a psychoactive drug and research chemical of the piperazine chemical class which has been sold as a "designer drug". It produces stimulant effects similar to those of benzylpiperazine (BZP).
Chemistry.
2C-B-BZP contains a benzylpiperazine base as well as the ring-substitution pattern of the psychedelic phenethylamine 2C-B. 2C-B-BZP is not a phenethylamine itself and does not produce psychedelic effects, as the binding groups are in the wrong position to activate the 5-HT2A receptor, while the phenylpiperazine homologue 2C-B-PP substitutes for DOM in DOM-trained rats with around 1/10th the potency of DOM, but does not substitute for TFMPP.
Effects.
2C-B-BZP produces stimulant effects which last 3–6 hours. It is also said by several sources to increase the effects of other compounds when combined . Side effects include headaches and nausea, similar to those of other recreationally-used piperazine derivatives.
Legality.
2C-B-BZP is unscheduled and uncontrolled in the United States, but possession and sale of 2C-B-BZP could possibly be prosecuted under the Federal Analog Act because of its structural similarities to benzylpiperazine. 2C-B-BZP is illegal to possess, use or sell in Japan where it used to be sold in local smartshops.


Ptolemaiida

Ptolemaiida is a taxon of wolf-sized afrothere mammals that lived in northern and eastern Africa during the Paleogene. The oldest fossils are from the latest Eocene strata of the Jebel Qatrani Formation, near the Fayum oasis in Egypt. A tooth is known from an Oligocene-aged stratum in Angola, and Miocene specimens (of "Kelba") are known from Kenya and Uganda
The origin of the Ptolemaiida is obscure, and debated. The type species was originally thought to be a primate, but, later, when elongated skulls with long canines of "Ptolemaia" and "Qarunavus" were found, they were then thought to be hyaenodontids, or giant, carnivorous relatives of the pantolestids "Palaeosinopa", and of modern shrews The family Ptolemaiidae was elevated to order level in 1995, although some experts later placed the Ptolemaiidae within the pantolestids.
Recently, Ptolemaiida has been placed within Afrotheria on the basis of paleobiology, as the taxon was endemic to Africa, and because of some similarities in the anatomical features of the skull in common with aardvarks. It is currently unclear if they form a sister taxon to Tubulidentata or are a paraphyletic sequence leading to them. Regardless, their close relation may offer the possibility for true dental synapomorphies in Afroinsectiphilia.
As mentioned earlier, there has been much confusion about the origins and even identities of the ptolemaiidans. The first specimen, a set of isolated molar teeth, of the type species, "Ptolemaia lyonsi", was originally identified as being a primate, as they were flat and nearly identical to those of primates. Later, when the first skull was found, it was then thought to be a monstrous, wolf-sized shrew, as the skull had long canine fangs, and was very gracile. However, recently, there has been a reconsideration of the ptolemaiidan diet, and possible behavior, as wear on the teeth suggest that it crushed hard or abrasive food, and that the teeth had little or no shearing ability. Even so, some sources still refer to them as being gigantic, carnivorous shrews.


N6-methyl-lysine oxidase

In enzymology, a N6-methyl-lysine oxidase () is an enzyme that catalyzes the chemical reaction
The 3 substrates of this enzyme are N6-methyl-L-lysine, H2O, and O2, whereas its 3 products are L-lysine, formaldehyde, and H2O2.
This enzyme belongs to the family of oxidoreductases, specifically those acting on the CH-NH group of donors with oxygen as acceptor. The systematic name of this enzyme class is N6-methyl-L-lysine:oxygen oxidoreductase (demethylating). Other names in common use include epsilon-alkyl-L-lysine:oxygen oxidoreductase, N6-methyllysine oxidase, epsilon-N-methyllysine demethylase, epsilon-alkyllysinase, and 6-N-methyl-L-lysine:oxygen oxidoreductase (demethylating).