Sono-Seq

Sono-Seq (Sonication of Cross-linked Chromatin Sequencing) is a method in molecular biology used for determining the sequences of those DNA regions in the genome near regions of open chromatin of expressed genes. It is also known as "Input" in the Chip-Seq protocol, since it follows the same steps except it doesn't require immunoprecipitation.<ref name="doi10.1073/pnas.0905443106"></ref>


4-HO-pyr-T

4-HO-pyr-T (4-hydroxy-"N","N"-tetramethylenetryptamine) is a lesser-known psychedelic drug. It is the 4-hydroxyl analog of pyr-T. 4-HO-pyr-T was first synthesized by Alexander Shulgin. In his book "TiHKAL" ("Tryptamines I Have Known and Loved"), neither the dosage nor the duration are reported. 4-HO-pyr-T produces few to no effects. Very little data exists about the pharmacological properties, metabolism, and toxicity of 4-HO-pyr-T.


Rohit Pappu

Rohit Pappu is an Indian born computational and theoretical biophysicist. He is the Edwin H. Murty Professor of Engineering and the director of the Center for Biological Systems Engineering at Washington University in St. Louis.
Education and career.
Pappu did his undergraduate work in physics, mathematics, and electronics at the St. Joseph's College, Bangalore. He received an M.S. in solid state physics in 1992 and Ph.D. in biological physics in 1996, both at Tufts University where he worked theoretical aspects of protein folding. He spent two years as a postdoctoral fellow at Washington University in St. Louis with Jay Ponder and then from 1998 to 2001 he was a postdoctoral fellow with George Rose at Johns Hopkins University. He joined Washington University in St. Louis as an Assistant Professor in Biomedical Engineering in 2001, becoming Associate Professor in 2007 and Professor in 2011. He was inducted as the Edwin H. Murty Professor of Engineering in 2015.
Research.
Pappu uses theoretical, computational, and experimental approaches to study intrinsically disordered proteins in the context of normal cellular function and neurodegenerative diseases (notably Huntington's disease ). He has made major contributions to understanding the driving forces associated with protein aggregation, and how the linear amino acid sequence of a disordered proteins determines its conformational behaviour, with a particular focus on the role of polar and charged amino acids. With postdoctoral fellow Rahul Das, Pappu discovered that the patterning of charged residues has a major impact on the conformational ensemble of a disordered protein. More recently, his work has focussed on the polymer physics of biological phase transitions to understand the theoretical and molecular underpinnings that drive intracellular phase separation.
Pappu was named a fellow of the American Association for the Advancement of Science (AAAS) in 2013, and in 2016 was elected as a fellow of the American Institute for Medical and Biological Engineering (AIMBE) for "outstanding contributions to protein engineering and design and the molecular basis of neurodegeneration through advances in computational biology".


Heteroscorpine

Heteroscopine (HS-1) is the main component of the venom of "Heterometrus laoticus". It belongs to the Scorpine toxin family. It is a polypeptide consisting of a defensin-like component on its N-terminal end and a putative potassium channel blocking component on its C-terminal end. It has antimicrobial effect on some bacteria, but not on fungi.
Sources.
Heteroscorpine (HS-1) is a component of the venom of the Thai giant scorpion "Heterometrus laoticus". This species is a member of the scorpion family commonly known as giant forest scorpions, indigenous to large parts of South and South-East Asia.
Chemistry.
The gene coding for HS-1 consists of one intron flanked by two exons. HS-1 is a polypepide consisting of 95 amino acids. The HS-1 protein has a large resemblance to other toxins of the Scorpine family (which is a subgroup of the Beta-KTx toxin family). The polypepides of the Scorpine family possess two structural and functional domains: a N-terminal α-helix (which has a cytolytic and/or antimicrobial activity similar to that of insect defensins), and a C-terminal region with a CSαβ motif, which causes potassium channel-blocking activity. HS-1 is highly homologous in particular to the Scorpine toxin Panscorpine (from "Emperor scorpion") and Opiscorpine (from "Opistophthalmus carinatus"), with an 80% similarity in amino acid sequence. Opiscorpine and HS-1 are both classified as scorpine-like peptides.
Based on its sequence homology with other scorpine-like peptides, HS-1 is likely to be a voltage-gated potassium channel blocker.
HS-1 also has antimicrobial effects on some bacterial species, i.e. "Bacillus subtilis", "Klebsiella pneumoniae" and "Pseudomonas aeruginosa"; it has no inhibitory effects on fungi. The inhibitory effect on bacteria has no gram specificity. Scanning electron microscopy shows that HS-1 causes roughening and blebbing of bacterial cell surfaces. HS-1 contains three disulfide bridges followed by a typical Cys pattern, similar to that of invertebrate defensins. Thus, HS-1 is likely to act accordingly.
Toxicity.
Symptoms from envenomation in humans from the Heterometrus genera are reported to be of mild severity. Sting can cause redness, swelling, inflammation and pain for hours up to a few days. Injection of the purified toxin in crickets causes paralysis.


Alexander Gettler

Alexander Oscar Gettler (August 13, 1883 – August 4, 1968) was a toxicologist with the Office of Chief Medical Examiner of the City of New York (OCME) between 1918 and 1959, and the first forensic chemist to be employed in this capacity by a U.S. city. His work at OCME with Charles Norris, the chief medical examiner, created the foundation for modern medicolegal investigation in the U.S. and Gettler has been described by peers as "the father of forensic toxicology in America."
The Alexander O. Gettler Award is a prize established in his name by the American Academy of Forensic Sciences.
Early life and education.
Gettler was born Jewish in Galicia, Poland, a part of the Empire of Austria-Hungary in 1883. As Oscar Gettler, aged seven, he emigrated to the U.S. with his father, Joseph Gettler, and sister, Elise, on board the Red Star Line steamer, "Westernland", which arrived at the Port of New York on May 6, 1891; they settled in Brooklyn, where he was raised. He studied at the City College of New York and in 1912 received his PhD in Biochemistry from Columbia University. Prior to his employment with OCME he worked as a clinical chemist at the Bellevue Hospital in Manhattan and taught Biochemistry at the New York University School of Medicine. He married Alice Gorman in 1912.
Toxicology work.
Charles Norris established the Office of the Chief Medical Examiner (OCME) in 1918 and set up his first offices in the Pathology Building (the 'City Morgue') of Bellevue Hospital. While there he asked Gettler if he would be willing to conduct any chemical testing that might be required to which Gettler agreed. An OCME laboratory, where testing was carried out for the presence of the common poisons, was set up on the third floor of the City Morgue building on First Avenue and 29th Street.
Gettler often had to create new tests to isolate poisons. He regularly experimented by poisoning raw liver and attempting to isolate ever-smaller amounts of poison from it. These tests often involved mashing or liquifying tissue, followed by such tests as crystal formation, melting and boiling point analysis, color reactions, and titration. In 1935, Gettler was the first scientist to use a spectrometer in a criminal investigation in order to prove that the thallium that had poisoned the four children of Brooklyn bookkeeper Frederick Gross did not come from cocoa powder Gross had brought home from work. A previous chemical test had mistaken copper contamination from the box for thallium leading to Gross's arrest. The examiners eventually concluded that his wife had murdered the children before dying herself of encephalitis.
In addition to this, Gettler wrote numerous papers on isolating poisons such as benzene from human bodies. In 1933, Gettler was among the first to recognize a normal endogenous presence of carbon monoxide in the human body and was the first to suggest the human gut microbiome as a contributing source.
Gettler often had to work for low pay, due to severe budget cuts to the toxicology office.
Teaching.
In the 1920s, Gettler took the post of professor of chemistry at Washington Square College of New York University. At the same time he held a post at the New York University Graduate School. There, Gettler established a toxicology course in 1935. He retired from teaching in 1948, when he reached the mandatory retirement age.
Later life and death.
Gettler retired from the office of the medical examiner on January 1, 1959, when he was 75. He remained interested in toxicology until he died due to a terminal illness approximately ten years after retiring.


Small RNA sequencing

Small RNA sequencing (Small RNA-Seq) is a type of RNA sequencing based on the use of NGS technologies that allows to isolate and get information about noncoding RNA molecules in order to evaluate and discover new forms of small RNA and to predict their possible functions. By using this technique, it is possible to discriminate small RNAs from the larger RNA family to better understand their functions in the cell and in gene expression. Small RNA-Seq can analyze thousands of small RNA molecules with a high throughput and specificity. The greatest advantage of using RNA-seq is represented by the possibility of generating libraries of RNA fragments starting from the whole RNA content of a cell.
Introduction.
Small RNAs are noncoding RNA molecules between 20 and 200 nucleotide in length. The item "small RNA" is a rather arbitrary term, which is vaguely defined based on its length comparing with regular RNA such as messenger RNA (mRNA). Previously bacterial short regulatory RNAs have been referred to as small RNAs, but they are not related to eukaryotic small RNAs.
Small RNAs include several different classes of noncoding RNAs, depending on their sizes and functions: snRNA, snoRNA, scRNA, piRNA, miRNA,YRNA, tsRNA, rsRNA, and siRNA. Their functions go from RNAi (specific for endogenously expressed miRNA and exogenously derived siRNA), RNA processing and modification, gene silencing (i.g. X chromosome inactivation by Xist RNA), epigenetics modifications, protein stability and transport.
Small RNA sequencing.
Purification.
This step is very critical and important for any molecular-based technique since it ensures that the small RNA fragments found in the samples to be analyzed are characterized by a good level of purity and quality. There are different purification methods that can be used, based on the purposes of the experiment:
Once small RNAs have been isolated, it is important to quantify them and to evaluate the quality of the purification. There are two different methods to do this:
Library preparation and amplification.
Many of the NGS sequencing protocols rely on the production of a genomic library that contains thousands of fragments of the target nucleic acids that will then be sequenced by proper technologies. According to the sequencing methods to be used, libraries can be created differently (in the case of the Ion Torrent technology RNA fragments are directly attached to a magnetic bead through an adapter, while for Illumina sequencing, the RNA fragments are firstly ligated to the adapters and then attached to the surface of a plate): generally, universal adapters A and B (containing well known sequences comprehensive of Unique Molecular Identifiers that are used to quantify small RNAs in a sample and sample indexing that allows to discriminate between different RNA molecules deriving from different samples) are ligated to the 5' and 3' ends of the RNA fragments thanks to the activity of the T4 RNA ligase 2 truncated. After the adapters are ligated to both ends of the small RNAs, retrotranscription occurs producing complementary DNA molecules (cDNAs) which will be, eventually, amplified by different amplification techniques depending on the sequencing protocol that is being followed (Ion Torrent exploits the emulsion PCR, while Illumina requires a bridge PCR) in order to obtain up to billions of amplicons to be sequenced. Besides the regular PCR mix, masking oligonucleotides targeting 5.8s rRNA are added to increase sensitivity to small RNA targets and to improve the amplification results. Caution has to be used, as RNA samples are prone to degradation, and further improvement of this technique should be oriented towards the elimination of adapter dimers. Some specific RNA modifications (such as 5′ hydroxyl (5′-OH), 3′-phosphate (3′-P) and 2′,3′-cyclic phosphate (2′3′-cP)) can block the adapter ligation process, while some other RNA modifications ( such as m1A, m3C, m1G and m22G) can interfere with reverse transcription process. Small RNA bearing one or more of these modifications are often inefficiently and incompletely converted into cDNAs, leading to challenges with their detection and quantitation by deep sequencing, which can be overcome by enzyme (such as PNK and AlkB) pre-treatment.
Sequencing.
Depending on the purpose of the analysis, RNA-seq can be performed using different approaches:
Data analysis and storage.
The final step regards analysis of data and storage: after obtaining the sequencing reads, UMI and index sequences are automatically removed from the reads and their quality is analyzed by PHRED (software able to evaluate the quality of the sequencing process); reads can then be mapped or aligned to a reference genome in order to extract information about their similarity: reads having the same length, sequence and UMI are considered as equal and are removed from the hit list. Indeed, the number of different UMIs for a given small RNA sequence reflects its copy number.
The small RNAs are finally quantified by assigning molecules to transcript annotations from different databases (Mirbase, GtRNAdb and Gencode).
Applications.
Small RNA sequencing can be useful for:


Henry Lingen

Sir Henry Lingen (23 October 1612 – 22 January 1662), Lord of Sutton, Lingen and Stoke Edith, was a Royalist military commander in Herefordshire during the English Civil War, and later a member of parliament. He was the son of Edward Lingen and Blanche Bodenham. He fathered 2 sons, Henry and William and 7 daughters, Elizabeth, Joan, Blanch, Mary (Dobbyns), Cecilia, Frances (Unett), and Alice (Herring). Both sons died without issue but the daughters left considerable posterity.
Ancestry.
The Lingen family had long been settled in that county and are recorded in early documents including Doomsday Book. The manor of Lingen was settled on Turstan de Lingen and his wife Agnes, heiress and daughter of Alfred of Marlborough, Baron of Ewyas with his extensive Doomsday landholding. Turstan's and Agnes's descendants included Isolde de Lingen who married Brian Harley, ancestor or the Harley Earls of Oxford and Dukes of Portland and Queen Elizabeth the Queen Mother. Another descendant and sister of Isolde was Isabella de Lingen, Lady Pembruggue of Tong Castle, founderess of the Chantry Church and buried at Tong, ancestor of the Ludlows of Stokesay Castle, Vernons of Hadden Hall and the Manners, Dukes of Rutland. Another descendant was Sir John Lingen of Lingen d 1506, who fought at the Battle of Mortimer's Cross which elevated Edward IV as king and the family's arms were amended with the three white roses of York. Sir John married Elisabeth de Burgh (d. 1522) who was a co-heiress of Sir John de Burgh and thus descended from the native Welsh Princes of Powys and Llewellyn the Great, Prince of Wales. Elisabeth also shared common descent with the Royal House of Tudor with a grandmother being a sister of Margaret ferch Thomas who married Fychan Tudor and was grandmother of Henry VII, and another of these sisters Ellen ferch Thomas being the mother of Owain Glyndŵr "Prince of Wales". Both Elisabeth and Sir John are buried in Aymestrey church near Lingen with in the chancel. Their descendants included Sir Henry Lingen, Sir Ralph Robert Wheeler Lingen the 1st Baron Lingen of Lingen, the Lingen's of Stoke Edith, Andrew Lingen-Stallard Esq, a former Council member of Royal College of Midwives and the present senior line of the Burton-Lingen's of Longner Hall near Shrewsbury, in which any co rights of the former Principality of Powys now rest.
Early career.
He was High Sheriff of Herefordshire in 1638, and made much money from collecting taxes and rent.
The English Civil War.
During the Civil War he was again appointed High Sheriff of the county in 1643 and commanded Goodrich Castle, defending it against the Parliamentarians until July 1646 when Colonel John Birch finally broke the defences using the famous cannon Roaring Meg.
His house of Freen's Court at Sutton was besieged until Prince Rupert of the Rhine was called to the rescue. Lingen was knighted by Charles I on his visit to Hereford in 1645. He himself in turn besieged Brampton Bryan Castle, home of his distant kinsman Robert Harley (1579-1656) (quite a common occurrence during the Civil War), the Harley family were later holders of the title Earl of Oxford and Earl Mortimer. This siege was defended by Lady Brilliana Harley but to no avail. In 1646 he defended Goodrich Castle but the castle's defences were breached and he was allowed to leave and the castle slighted. He attempted to rally the citizens of Hereford to rebel against the parliamentary forces with out success. A portrait of Sir Henry and his wife is in the Old House in Butcher Row in the centre of the city of Hereford.
Aftermath of war.
After the Civil War, Sir Henry retired to Stoke Edith "The Fairer House of the Lingens" near Hereford but was fined heavily by Parliament of the sum of six thousand pounds for supporting the former King. Later, his heirs sold Stoke Edith, his principal estate to the Foley family in 1670, it becoming the principal house of Paul Foley, later Speaker of the House of Commons, who rebuilt the house from 1695.
Marriage.
Sir Henry married Alice Pye of the Mynnd. (Both were later interred in the Church at Stoke Edith but during remodelling of the Church their monuments were lost). With the Restoration he became a member of parliament for Herefordshire but died of smallpox in Gloucester on his way back from a sitting in London in 1662.
Posterity.
His male heirs died with no issue. Other family lines exist, including heirs of his daughters. Other Lingen lines exist which descend from Sir John Lingen and Elisabeth de Burgh are represented by the Burton-Lingens of Longner Hall in Shropshire who are now the senior branch of the family, Ralph Lingen, 1st Baron Lingen (a title now extinct), Permanent Secretary to the Treasury d 1905 and buried in Brompton cemetery in London. Also, Andrew Lingen-Stallard (born 1962) MSc, RM, RN FRSA, Consultant Midwife for The London Ambulance Service, elected member of council of the Royal College of Midwives (2003–2007) and former midwifery advisor, Nursing and Midwifery Council (NMC 2006–2008).
Legacy.
The Herefordshire folk song "Sir Harry's Fancy" was based upon his Civil War days and sung by his troops after his surrender of Goodrich Castle.


Traffic (journal)

Traffic is a monthly, peer-reviewed, scientific journal, which was established in 2000, and is published by Wiley-Blackwell. The online version is at the Wiley Online Library. This journal is co-edited by Sharon Tooze (Crick Institute), Michael S. Marks (University of Pennsylvania), Trina A. Schroer (Johns Hopkins University), and Robert G. Parton (University of Queensland). The journal covers all aspects of signal transduction (intracellular transport) in health and disease, for both mammalian and non-mammalian biological systems.
History.
The journal was established by Frances Brodsky, Mark Marsh, Sandra Schmid, and Thomas Kreis. Kreis died in a plane crash before the first issue was published.
Abstracting and indexing.
This journal is abstracted and indexed in:
According to the "Journal Citation Reports", the journal has a 2017 impact factor of 4.400.


Nitrite oxidoreductase

Nitrite oxidoreductase (NOR or NXR) is an enzyme involved in nitrification. It is the last step in the process of aerobic ammonia oxidation, which is carried out by two groups of nitrifying bacteria: ammonia oxidizers such as "Nitrosospira", "Nitrosomonas" and "Nitrosococcus" convert ammonia to nitrite, while nitrite oxidizers such as "Nitrobacter" and "Nitrospira" oxidize nitrite to nitrate.
The enzyme is bound to the inner cytoplasmic surface of the bacterial membrane and contains multiple subunits, iron-sulfur centers and a molybdenum cofactor. The enzyme is relatively abundant, making up 10-30% of the total protein in these bacteria and forms densely packed structures on the membrane surface.


CCA tRNA nucleotidyltransferase

CCA tRNA nucleotidyltransferase (, "CCA-adding enzyme", "tRNA adenylyltransferase", "tRNA CCA-pyrophosphorylase", "tRNA-nucleotidyltransferase", "transfer-RNA nucleotidyltransferase", "transfer ribonucleic acid nucleotidyl transferase", "CTP(ATP):tRNA nucleotidyltransferase", "transfer ribonucleate adenylyltransferase", "transfer ribonucleate adenyltransferase", "transfer RNA adenylyltransferase", "transfer ribonucleate nucleotidyltransferase", "ATP (CTP):tRNA nucleotidyltransferase", "ribonucleic cytidylic cytidylic adenylic pyrophosphorylase", "transfer ribonucleic adenylyl (cytidylyl) transferase", "transfer ribonucleic-terminal trinucleotide nucleotidyltransferase", "transfer ribonucleate cytidylyltransferase", "ribonucleic cytidylyltransferase", "-C-C-A pyrophosphorylase", "ATP(CTP)-tRNA nucleotidyltransferase", "tRNA adenylyl(cytidylyl)transferase", "CTP:tRNA cytidylyltransferase") is an enzyme with systematic name "CTP,CTP,ATP:tRNA cytidylyl,cytidylyl,adenylyltransferase". This enzyme catalyses the following chemical reaction
The acylation of all tRNAs with an amino acid occurs at the terminal ribose of a 3' CCA sequence.


Operation May Day

Operation May Day was a series of entomological warfare (EW) tests conducted by the U.S. military in Savannah, Georgia in 1956.
Operation.
Operation May Day involved a series of EW tests from April to November 1956. The tests were designed to reveal information about the dispersal of yellow fever mosquitoes in an urban area. The mosquitoes were released from ground level in Savannah, Georgia and then recovered using traps baited with dry ice. The operation was detailed in a partially declassified U.S. Army report in 1981.


Suzanne Walker

Suzanne Walker is a professor of Microbiology and Molecular Genetics at Harvard University. Her research focuses on mechanisms of antibiotics and antibiotic resistance. She was elected to the National Academy of Sciences in 2020.
Career.
Walker earned a B.A. in English literature from the University of Chicago in 1983 and a PhD in organic chemistry from Princeton University in 1992. In 1995, Walker joined the faculty at Princeton University as an adjunct professor in chemistry, reaching the rank of full professor in 2003. She was the first woman to become a full professor of chemistry at Princeton. In 2004, Walker joined the faculty at the Harvard Medical School.
She was elected as a fellow of the National Academy of Sciences in 2020 and to the American Academy of Microbiology in 2019. She is also a recipient of the American Chemical Society's Arthur C. Cope Scholar Award and the Alfred P. Sloan Foundation Fellowship.


Flux (metabolism)

Flux, or metabolic flux is the rate of turnover of molecules through a metabolic pathway. Flux is regulated by the enzymes involved in a pathway. Within cells, regulation of flux is vital for all metabolic pathways to regulate the pathway's activity under different conditions. Flux is therefore of great interest in metabolic network modelling, where it is analysed via flux balance analysis.
In this manner, flux is the movement of matter through metabolic networks that are connected by metabolites and cofactors, and is therefore a way of describing the activity of the metabolic network as a whole using a single characteristic.
Metabolic Flux.
It is easiest to describe the flux of metabolites through a pathway by considering the reaction steps individually. The flux of the metabolites through each reaction (J) is the rate of the forward reaction (Vf), less that of the reverse reaction (Vr):
formula_1
At equilibrium, there is no flux. Furthermore, it is observed that throughout a steady state pathway, the flux is usually determined by the rate determining step of the reaction.
Control of metabolic flux.
Control of flux through a metabolic pathway requires that
Metabolic networks.
Cellular metabolism is represented by a large number of metabolic reactions involving the conversion of the carbon source (usually glucose) into the building blocks needed for macromolecular biosynthesis. These reactions form metabolic networks within cells. These networks can then themselves be used to study metabolism within cells.
To allow these networks to interact, a tight connection between them is necessary. This connection is provided by usage of common cofactors such as ATP, ADP, NADH and NADPH. In addition to this, sharing of some metabolites between the different networks further tightens the connections between the different networks.
Control of metabolic networks.
Existing metabolic networks control the movement of molecules through their enzymatic steps by regulating enzymes that catalyze irreversible reactions. The movement of molecules through reversible steps is generally unregulated by enzymes, but rather regulated by the concentration of products and reactants. Irreversible reactions at regulated steps of a pathway have a negative free energy change, thereby promoting spontaneous reactions in one direction only. Reversible reactions have no or very small free energy change. As a result, the movement of molecules through a metabolic network is governed by simple chemical equilibria (at reversible steps), with specific key enzymes that are subject to regulation (at irreversible steps). This enzymatic regulation may be indirect, in the case of an enzyme being regulated by some cell signalling mechanism (like phosphorylation), or it may be direct, as in the case of allosteric regulation, where metabolites from a different portion of a metabolic network bind directly to and affect the catalytic function of other enzymes in order to maintain homeostasis.
Fluxes and genotype.
Metabolic fluxes are a function of gene expression, translation, post translational protein modifications and protein-metabolite interactions.
Fluxes and phenotype.
The function of the central carbon metabolism (metabolism of glucose) has been fine-tuned to exactly meet the needs of the building blocks and Gibbs free energy in conjunction with cell growth. There is therefore tight regulation of the fluxes through the central carbon metabolism.
The flux in a reaction can be defined based on one of three things
Considering the above, the metabolic fluxes can be described as the ultimate representation of the cellular phenotype when expressed under certain conditions.
Roles of metabolic flux in cells.
Regulation of mammalian cell growth.
Research has shown that cells undergoing rapid growth have shown changes in their metabolism. These changes are observed with regards to glucose metabolism. The changes in metabolism occur because the rate of metabolism controls various signal transduction pathways that coordinate the activation of transcription factors as well as determining cell-cycle progress.
Growing cells require synthesis of new nucleotides, membranes and protein components. These materials can be obtained from carbon metabolism (e.g. glucose metabolism) or from peripheral metabolism. The enhanced flux observed in abnormally growing cells is brought about by high glucose uptake.
Cancer.
Metabolic flux and more specifically how metabolism is affected due to changes in the various pathways has grown in importance since it was observed that tumour cells exhibit enhanced glucose metabolism compared to normal cells. Through studying these changes, it is possible to better understand the mechanisms of cell growth and where possible develop treatments to counter the effects of enhanced metabolism.
Measuring fluxes.
There are several ways of measuring fluxes, however all of these are indirect. Due to this, these methods make one key assumption which is that all fluxes into a given intracellular metabolite pool balance all the fluxes out of the pool.
This assumption means that for a given metabolic network the balances around each metabolite impose a number of constraints on the system.
The techniques currently used mainly revolve around the use of either Nuclear magnetic resonance (NMR) or gas chromatography-mass spectrometry (GC-MS).
In order to avoid the complexity of data analysis, a simpler method of estimating flux ratios has recently been developed which is based on cofeeding unlabelled and uniformly 13C labelled glucose. The metabolic intermediate patterns are then analysed using NMR spectroscopy.
This method can also be used to determine the metabolic network topologies.


Small nucleolar RNA U3

U3 snoRNA is a non-coding RNA found predominantly in the nucleolus.
U3 has C/D box motifs that technically make it a member of the box C/D class of snoRNAs; however, unlike other C/D box snoRNAs, it has not been shown to direct 2'-"O"-methylation of other RNAs.
Rather, U3 is thought to guide site-specific cleavage of ribosomal RNA (rRNA) during pre-rRNA processing.
The box C/D element is a subset of the six short sequence elements found in all U3 snoRNAs, namely boxes A, A', B, C, C', and D. The U3 snoRNA secondary structure is characterized by a small 5' domain (with boxes A and A'), and a larger 3' domain (with boxes B, C, C', and D), the two domains being linked by a single-stranded hinge. Boxes B and C form the B/C motif, which appears to be exclusive to U3 snoRNAs, and boxes C' and D form the C'/D motif. The latter is functionally similar to the C/D motifs found in other snoRNAs. The 5' domain and the hinge region act as a pre-rRNA-binding domain. The 3' domain has conserved protein-binding sites. Both the box B/C and box C'/D motifs are sufficient for nuclear retention of U3 snoRNA. The box C'/D motif is also necessary for nucleolar localization, stability and hyper-methylation of U3 snoRNA. Both box B/C and C'/D motifs are involved in specific protein interactions and are necessary for the rRNA processing functions of U3 snoRNA.
Species-specific secondary structure models.
"S. cerevisiae" secondary structure determined by chemical mapping of U3A RNA in a purified snoRNP is available. A human structure model has also been proposed. Like yeast and human, protozoan protist Entamoeba histolytica : a primitive eukaryote adopted the same conserved secondary structure of U3 snoRNA. Four consensus structures specific to metazoa, fungi, plants and basal eukaryotes have been proposed.


Amphibolic

The term amphibolic () is used to describe a biochemical pathway that involves both catabolism and anabolism. Catabolism is a degradative phase of metabolism in which large molecules are converted into smaller and simpler molecules, which involves two types of reactions. First, hydrolysis reactions, in which catabolism is the breaking apart of molecules into smaller molecules to release energy. Examples of catabolic reactions are digestion and cellular respiration, where sugars and fats are broken down for energy. Breaking down a protein into amino acids, or a triglyceride into fatty acids, or a disaccharide into monosaccharides are all hydrolysis or catabolic reactions. Second, oxidation reactions involve the removal of hydrogens and electrons from an organic molecule. Anabolism is the biosynthesis phase of metabolism in which smaller simple precursors are converted to large and complex molecules of the cell. Anabolism has two classes of reactions. The first are dehydration synthesis reactions; these involve the joining of smaller molecules together to form larger, more complex molecules. These include the formation of carbohydrates, proteins, lipids and nucleic acids. The second are reduction reactions, in which hydrogens and electrons are added to a molecule. Whenever that is done, molecules gain energy.
The term amphibolic was proposed by B. Davis in 1961 to emphasise the dual metabolic role of such pathways. These pathways are considered to be central metabolic pathways which provide, from catabolic sequences, the intermediates which form the substrate of the metabolic processes.
Reactions exist as amphibolic pathway.
All the reactions associated with synthesis of biomolecule converge into the following pathway, viz., glycolysis, the Krebs cycle and the electron transport chain, exist as an amphibolic pathway, meaning that they can function anabolically as well as catabolically.
Other important amphibolic pathways are the Embden-Meyerhof pathway, the pentose phosphate pathway and the Entner–Doudoroff pathway.
Embden-Meyerhoff.
The Embeden–Meyerhof pathway and the Krebs cycle are the centre of metabolism in nearly all bacteria and eukaryotes. They provide not only energy but also precursors for biosynthesis of macromolecules that make up living systems.
Citric acid cycle.
The citric acid cycle (Krebs cycle) is a good example of an amphibolic pathway because it functions in both the degradative (carbohydrate, protein, and fatty acid) and biosynthetic processes. The citric acid cycle occurs on the cytosol of bacteria and within the mitochondria of eukaryotic cells. It provides electrons to the electron transport chain which is used to drive the production of ATP in oxidative phosphorylation. Intermediates in the citric acid cycle, such as oxaloacetate, are used to synthesize macromolecule constituents such as amino acids, e.g. glutamate and aspartate.
The first reaction of the cycle, in which oxaloacetate (a four-carbon compound) condenses with acetate (a two-carbon compound) to form citrate (a six-carbon compound) is typically anabolic. The next few reactions, which are intramolecular rearrangements, produce isocitrate. The following two reactions, namely the conversion of D-isocitrate to α-Ketoglutarate followed by its conversion to succinyl-CoA, are typically catabolic. Carbon dioxide is lost in each step and succinate (a four-carbon compound) is produced.
There is an interesting and critical difference in the coenzymes used in catabolic and anabolic pathways; in catabolism NAD+ serves as an oxidizing agent when it is reduced to NADH. Whereas in anabolism the coenzyme NADPH serves as the reducing agent and is converted to its oxidized form NADP+.
Citric acid cycle has two modes that play two roles, the first being energy production produced by the oxidative mode, as the acetyl group of acetyl-coA is fully oxidized to CO2. This produces most of the ATP in the metabolism of aerobic heterotrophic metabolism, as this energy conversion in the membrane structure (cytoplasmic membrane in bacteria and mitochondria in eukaryotes) by oxidative phosphorylation by moving electron from donor (NADH and FADH2) to the acceptor O2. Every cycle give 3 NADH, 1 FADH2, CO2 and GTP. The second role is biosynthetic, as citric acid cycle regenerate oxaloacetate when cycle intermediates are removed for biosynthesis.
Pentose phosphate pathway.
The pentose phosphate pathway gets its name because it involves several intermediates that are phosphorylated five-carbon sugars (pentoses). This pathway provides monomers for many metabolic pathways by transforming glucose into the four-carbon sugar erythrose and the five-carbon sugar ribose; these are important monomers in many metabolic pathways. Many of the reactants in this pathway are similar to those in glycolysis, and both occur in cytosol. The ribose-5-phosphate can be transported into the nucleic acid metabolism, producing the basis of DNA and RNA monomers, the nucleotides. In meristematic cells, large amounts of DNA must be produced during the S-phase of a short cell cycle; this pathway is an extremely important part of the metabolism of these cells. In these cells, the pentose phosphate pathway is active and shifted in favor of ribose production.
Entner-Doudoroff pathway.
The Entner-Doudoroff pathway is a glycolytic pathway that is considered the second pathway used for carbohydrates used by certain microbes. In this process, glucose-6-phosphate is oxidized through 6-phosphogluconate to pyruvate and glyceraldehyde 3-phosphate, with the concomitant reduction of NADP. By conventional glyceraldehyde-3-phosphate oxidation to pyruvate, one NAD is reduced and a net one ATP is formed. In that pathway, for every glucose molecule there is an "investment" of one ATP molecule and a yield of two ATP and two pyruvate molecules and one NADH. The difference between the glycolytic used by humans and this pathway is that the latter requires one ATP to yield two ATP and two pyruvates as a net of only one NADPH produced and one ATP result (from substrate-level phosphorylation), and the former requires two ATP molecules to yield four ATP and two pyruvate molecules per glucose as a net of two ATP molecules.
Regulation.
The cell determines whether the amphibolic pathway will function as an anabolic or catabolic pathway by enzyme–mediated regulation at a transcriptional and post-transcriptional level. As many reactions in amphibolic pathways are freely reversible or can be bypassed, irreversible steps that facilitate their dual function are necessary. The pathway uses a different enzyme for each direction for the irreversible step in the pathway, allowing independent regulation of catabolism and anabolism. Due their inherent duality, amphibolic pathways represent the regulation modes of both anabolic by its negative feedback end product and catabolic by feedback by energy indicator sequences.


Lynne Quarmby

Lynne Quarmby is a Canadian scientist, activist, and politician. She is a professor and Chair of the Department of Molecular Biology and Biochemistry at Simon Fraser University in Burnaby, British Columbia. She was a candidate for the Green Party of Canada in Burnaby North—Seymour in the 2015 federal election, and is the Green Party of Canada's Science Policy Critic.
Research and education.
Quarmby completed a BSc in Marine Biology and a MSc in Biological Oceanography at the University of British Columbia before moving to the University of Connecticut to complete her PhD in Biochemistry. She worked as a postdoctoral fellow in the lab of Nobel laureate Alfred Gilman at the University of Texas Southwestern Medical Center in Austin, TX, then in the lab of Criss Hartzell at Emory University in Atlanta, GA, where she also held her first faculty position. She moved her lab to Simon Fraser University in 2000.
Quarmby's research has been aimed at understanding the signals and mechanisms of deflagellation, the process by which cells shed their cilia into the environment. Cilia are found on most eukaryotic cells and on most cells in the human body, and defects in a cell's ability to form or maintain its cilia can cause diseases known as ciliopathies, that may include symptoms such as cystic kidney disease, blindness, and obesity. Through her research using the single-celled ciliated green alga Chlamydomonas reinhardtii as a model organism, Quarmby identified members of the NIMA-related family of serine/threonine kinases that function in deflagellation as well as in the assembly and maintenance of cilia. Her group went on to show that NEK8 localizes to cilia, and that mutations in NEK8 interfere with its ciliary localization and cause a severe juvenile cystic kidney disease known as nephronophthisis, underscoring the important link between cilia and cystic kidney disease.
Quarmby's work has been funded by the Natural Sciences and Engineering Research Council of Canada (NSERC), the Canadian Institutes for Health Research (CIHR), and the Kidney Foundation of Canada (KFoC). In 2011 NSERC recognized Quarmby's research program by awarding her a Discovery Accelerator Supplement, a funding program reserved for researchers who show strong potential to become international leaders within their field.
Quarmby is known for outstanding undergraduate teaching, and received a SFU Teaching Excellence Award in 2011.
Quarmby was the co-recipient of the 2015 Nora and Ted Sterling Prize in Support of Controversy.
Personal life.
Quarmby lives in Burnaby, British Columbia. She is a painter, and her science-inspired art has been featured in the magazine "The Scientist". Her adult son, Jacob Sheehy, lives in Toronto Ontario, where he runs a company called PressureNET.
Advocacy and politics.
In May 2010, Quarmby wrote an op-ed in the Ottawa Citizen on gender equality in Canadian science and technology, after the Canada Excellence Research Chairs program did not select any women scientists for the nineteen awards it handed out. This prompted the Vancouver Sun to name her one of 100 BC "Women of Influence" in 2010. She has been an active member of the American Society for Cell Biology's Women in Cell Biology Committee throughout her career.
Quarmby has maintained a blog called "The Crux" on which she has written on the process of science and the state of science funding in Canada, with guest posts on a variety of science and climate issues. Her work has been featured on the literary blog "Numero Cinq".
More recently, Quarmby has been an advocate for action on climate change. In May 2012, she joined the group Voters Taking Action on Climate Change (VTACC) in an anti-coal protest in which they blockaded a coal train carrying coal from Wyoming to Deltaport for export overseas. Thirteen protesters, including Quarmby, were arrested for trespassing under the Railway Safety Act. She was a featured speaker at the People's Climate March in Vancouver, BC.
In November 2014, while Quarmby was involved in the protests of the Trans Mountain Oil Pipeline, she was arrested for civil contempt. The charges were dismissed after it was discovered that she and other protestors had not actually crossed the line prohibited by the court because of a mix-up about GPS coordinates used in the relevant court order.
In December 2014, Quarmby announced that she would be seeking the Green Party of Canada nomination in Burnaby North—Seymour for the upcoming federal election. She was confirmed as the candidate in January 2015, and placed fourth, with five percent of the vote.


Epic Systems

Epic Systems Corporation, or Epic, is a privately held healthcare software company. According to the company, hospitals that use its software held medical records of 54% of patients in the United States and 2.5% of patients worldwide in 2015.
History.
Epic was founded in 1979 by Judith R. Faulkner with a $70,000 investment (). Originally headquartered in Madison, Wisconsin, Epic moved its headquarters to a large campus in the suburb of Verona, Wisconsin in 2005, where it employs 10,000 people as of 2019. The campus has themed areas/buildings, such as a castle-like structure, a "fantasy-land" that appears to be inspired by J.K. Rowling's "Harry Potter", and a dining facility designed to mimic a train station.
As of 2015, the company was in the fifth phase of campus expansion with five new buildings each planned to be around 100,000 square feet. The company also has offices in Bristol, UK; 's-Hertogenbosch, Netherlands; Dubai, United Arab Emirates; Dhahran, Saudi Arabia; Helsinki, Finland; Melbourne, Australia; Singapore; Trondheim, Norway; and Søborg, Denmark.
Product and market.
Epic primarily develops, manufactures, licenses, supports, and sells a proprietary electronic medical record software application, known in whole as 'Epic' or an Epic EMR. The company's healthcare software is centered on its Chronicles database management system. Epic's applications support functions related to patient care, including registration and scheduling; clinical systems for doctors, nurses, emergency personnel, and other care providers; systems for lab technologists, pharmacists, and radiologists; and billing systems for insurers.
Epic also offers cloud hosting for customers that do not wish to maintain their own servers; and short-term optimization and implementation consultants through their wholly-owned subsidiary Boost Services.
The company's competitors include Cerner, MEDITECH, Allscripts, athenahealth, and units of IBM, McKesson, and Siemens.
The majority of U.S. News & World Report's top-ranked hospitals and medical schools use Epic. In 2003, Kaiser Permanente began using Epic for its electronic records system. Among many others, Epic provides electronic record systems for Cedars-Sinai Medical Center in Los Angeles, the Cleveland Clinic, Johns Hopkins Hospital, UC Davis Medical Center in Sacramento, and all Mayo Clinic campuses. Partners HealthCare began adopting Epic in 2015 in a project initially reported to cost $1.2 billion, which critics decried and which is greater than the cost of any of its buildings. By 2018, the total expenses for the project were $1.6 billion, with payments for the software itself amounting to less than $100 million and the majority of the costs caused by lost patient revenues, tech support and other implementation work.
Criticisms and controversies.
Data sharing.
Care Everywhere is Epic's health information exchange software, which comes with its EHR system. A 2014 article in "The New York Times" interviews two doctors who say that their Epic systems won't allow them to share data with users of competitors' software in a way that will satisfy the Meaningful Use requirements of the HITECH Act. At first, Epic charged a fee to send data to some non-Epic systems. Epic says the yearly cost for an average-sized hospital is around $5,000 a year. However, after Congressional hearings, Epic and other major software vendors announced that they would suspend per-transaction sharing fees. Epic customers must still pay for one-time costs of linking Epic to each individual non-Epic system with which they wish to exchange data; in contrast, Epic's competitors have formed the CommonWell Health Alliance which set a common Interoperability Software standard for electronic health records. A 2014 report by the RAND Corporation described Epic as a "closed" platform that made it "challenging and costly for hospitals" to interconnect with the clinical or billing software of other companies. The report also cited other research showing that Epic's implementation in the Kaiser Permanente system led to efficiency losses.
In September 2017, Epic announced Share Everywhere, which allows patients to authorize any provider who has internet access to view their record in Epic and to send progress notes back. Share Everywhere was named Healthcare Dive's "Health IT Development of the Year" in 2017.
UK experience.
An Epic electronic health record system costing £200 million was installed at Cambridge University Hospitals NHS Foundation Trust in October 2014, the first installation of an Epic system in the UK.
After 2.1 million records were transferred to it, it developed serious problems and the system became unstable. Ambulances were diverted to other hospitals for five hours and hospital consultants noted issues with blood transfusion and pathology services. Other problems included delays to emergency care and appointments, and problems with discharge letters, clinical letters and pathology test results. Chief information officer, Afzal Chaudhry, said "well over 90% of implementation proceeded successfully".
In July 2015, the BBC reported that the hospital's finances were being investigated. In September 2015, both the CEO and CFO of the hospital resigned. Problems with the clinical-records system, which were said to have compromised the "ability to report, highlight and take action on data" and to prescribe medication properly, were held to be contributory factors in the organization's sudden failure. In February 2016, digitalhealth.net reported that Clare Marx, president of the Royal College of Surgeons of England and member of the NHS National Information Board, found that at the time of implementation, "staff, patients and management rapidly and catastrophically lost confidence in the system. That took months and a huge amount of effort to rebuild."
Danish experience.
In 2016, Danish health authorities spent 2.8 billion DKK on the implementation of Epic in 18 hospitals in a region with 2.8 million residents. On May 20, Epic went live in the first hospital. Doctors and nurses reported chaos in the hospital and complained of severe under preparation and training. Epic and its Danish partners insisted that normal testing and training were carried out.
Since some elements of the Epic system were not properly translated from English to Danish, physicians resorted to Google Translate. As one example, when inputting information about a patient's condition, physicians were given the option to report between the left and the "correct" leg, not the left and right legs. As of 2019, Epic had still not been fully integrated with Denmark's national medical record system, which is meant to be accessed every time a patient is seen. Danish anesthesiologist and computer architect Gert Galster worked to adapt the system. According to Galster, these Epic systems were designed specifically to fit the U.S. health care system, and could not be disentangled for use in Denmark.
An audit of the implementation that voiced concerns was published in June 2018. At the end of 2018, 62% of physicians expressed they were not satisfied with the system and 71 physicians signed a petition calling for the system to be removed.
COVID-19 response.
In 2020, the novel coronavirus pandemic spread in the United States. Epic Systems faced considerable criticism for their initial plan to have their 10,000 employees return to work on-campus. Employees expressed concern about returning to the office, with the first group being required to return as early as August 10 while the pandemic continued to spread. This plan was abandoned, and as of December 2020, employees were still able to work from home. The plan had come about despite a Dane County public health order requiring remote work "to the greatest extent possible." Criticism revolved in particular around the fact that employees were being ordered back to preserve the company "culture," despite CEO Judy Faulkner's admission that work was getting done remotely. According to The Capital Times, who interviewed 26 Epic employees about the plan, "13 [employees] said they have knowledge of managers being demoted for expressing concern about the company’s plans to bring its nearly 10,000 workers back" to on-campus work, and all requested anonymity for fear of employer retribution.
In a survey of Epic employees, 89% of employees expressed dissatisfaction with how Epic was handling the pandemic.
Fundings.
In 2013, Epic funded $30 million to the Dane County Regional Airport for a project on expansion of available parking space.


5,6-MDO-DMT

5,6-MDO-DMT, or 5,6-methylenedioxy-"N","N"-dimethyltryptamine, is a lesser-known psychedelic drug. It is the 5,6-methylenedioxy analog of DMT. 5,6-MDO-DMT was first synthesized by Alexander Shulgin. In his book "TiHKAL" ("Tryptamines I Have Known and Loved"), 5,6-MDO-DMT produces no noticeable psychoactive effects, although it was only tested up to a dose of 5 mg. Very little data exists about the pharmacological properties, metabolism, and toxicity of 5,6-MDO-DMT.


N-Formylmethionine-leucyl-phenylalanine

N"-Formylmethionyl-leucyl-phenylalanine (fMLF, fMLP or N"-formyl-met-leu-phe) is an "N"-formylated tripeptide and sometimes simply referred to as chemotactic peptide is a potent polymorphonuclear leukocyte (PMN) chemotactic factor and is also a macrophage activator.
fMLF is the prototypical representative of the "N"-formylated oligopeptide family of chemotactic factors. These oligopeptides are known to be, or mimic the actions of, the "N"-formyl oligopeptides that are (a) released by tissue bacteria, (b) attract and activate circulating blood leukocytes by binding to specific G protein coupled receptors on these cells, and (c) thereby direct the inflammatory response to sites of bacterial invasion. fMLF is involved in the innate immunity mechanism for host defense against pathogens.
fMLF led to the first discovery of a leukocyte receptor for a chemotactic factor, defined three different types of fMLF receptors that have complementary and/or opposing effects on inflammatory responses as well as many other activities, and helped define the stimulus-response coupling mechanisms by which diverse chemotactic factors and their G protein coupled receptors induce cellular function.
Discovery.
In 1887, Élie Metchnikoff observed that leukocytes isolated from the blood of various animals were attracted towards certain bacteria. This attraction was soon proposed to be due to soluble elements released by the bacteria (see Harris for a review of this area up to 1953). Peter Ward, Elmer Becker, Henry Showell, and colleagues showed that these elements were made by a variety of growing gram positive bacteria and gram negative bacteria and were of low molecular weight, i.e. below 3600 Dalton (unit)s. Further studies by Schiffmann and colleges found that cultures of growing Escherichia coli released oligopeptides of between 150 and 1500 daltons that appeared to have a free Carboxylic acid group but not a free Amine group.
Given these clues and knowledge that bacteria transcribe (see Transcription (genetics)) proteins starting with "N"-formylmethionine whereas eukaryotic cells mostly initiate protein synthesis with non-formylated methionine, Schiffmann, Corcoran, and Wahl theorized and then showed that "N"-formyl-methionine and a series "N"-formyl-methionyl dipeptides and tripeptides stimulated the chemotaxis of neutrophils isolated from rabbit peritoneal exudates as well as of macrophages isolated from guinea pig peritoneal exudates. In further studies of various "N"-formylated oligopeptides, fMLF proved the most potent in stimulating rabbit neutrophil chemotaxis. fMLF and a sampling of other, less potent, "N"-formyl oligopeptides were then found to stimulate a wide array of rabbit neutrophil functions such as: the transient auto-aggregation of these cells in suspension and equally transient fall in circulating neutrophils when injected into rabbit veins (these responses result from an increase in neutrophil adhesiveness to each other and/or vascular endothelium); the release (see degranulation) of intracellular granule-bound enzymes and other antimicrobial cytotoxic molecules; and the production and release of cytotoxic reactive oxygen species such as Superoxide and hydrogen peroxide. All of these responses are part of the innate immune systems initial line of defense against bacterial invasions.
Follow-up studies found that the genes of mitochondria and chloroplasts organelles of Eukaryote cells, including those of humans, which, unlike nuclear genes, code for "N"-formyl-methionine proteins, release "N"-formyl-methionyl containing peptides with chemotactic activities that exactly mimic those of fMLF chemotaxis These organelle-derived formylated peptides are true analogs of fMLF that operate through fMLF receptors to recruit circulating blood leukocytes to and thereby initiate inflammation responses at sites of cell damage and tissue destruction not caused by bacteria. fMLF and other "N"-formylated oligopeptides were found to be similarly active in human neutrophils. The high degree of structural specificity of a broad series of formylated peptides in stimulating these neutrophil responses, the specific binding of "N"-formylated oligopeptides to neutrophils with affinities that paralleled their stimulating potencies, the ability of "t"-carbobenzoxy-phenylalanyl-methionine to bind to but not stimulate neutrophils and thereby to block the neutrophil binding and stimulating activity of N-formylated oligopeptides, and the ability of the formylated oligopeptides to desensitize (i.e. render unresponsive) neutrophil functional responses to themselves but have no or a lesser ability to desensitize to a range of other chemotactic stimuli provided strong suggestive evidence that the formylated peptides acted on cells through a common, dedicated receptor system that differed from other chemotactic factor receptors.
Receptors.
The studies cited above lead to the eventual cloning of the human Formyl peptide receptor 1, a G protein coupled receptor that binds fMLF and other formylated oligopeptides to mediate their stimulatory actions on human and rabbit neutrophils. Subsequently, Formyl peptide receptor 2 and Formyl peptide receptor 3 were also cloned based on the similarities in their amino acid sequence to that of formyl peptide receptor 1. Formyl peptide receptors 2 and 3 have very different abilities to bind and respond to formylated oligopeptides including fMLF compared to formyl peptide receptor 1 and compared to each other and have very different functions than those of formyl peptide receptor 1.


Yizhi Jane Tao

Yizhi Jane Tao, Ph.D., is a Chinese biochemist, structural biologist, and Professor of Biochemistry and Cell Biology at Rice University in Houston, Texas. Professor Tao led a team of researchers to be the first to map the structure of the influenza A virus nucleoprotein to an atomic level, a feat which circulated widely in the popular press. She was named among the top ten most influential Chinese of 2006 by a consortium of China's leading media outlets including Phoenix Satellite Television, China News Service, Asia Newsweek, and World Journal.
Education.
Born in China, Yizhi Jane Tao received a B.Sc. degree in biology from Peking University in Beijing, China, in 1992. She later moved to West Lafayette, Indiana, where she received her Ph.D. in biological science while studying under the German-American biophysicist Michael Rossmann. She completed a postdoctoral fellowship under Stephen C. Harrison at Harvard University in 2002. Upon completing her postdoctoral studies, Tao joined the faculty of Rice University, where she has made important contributions to the study of influenza, hepatitis, and birnaviruses.


Constitutive androstane receptor

The constitutive androstane receptor (CAR) also known as nuclear receptor subfamily 1, group I, member 3 is a protein that in humans is encoded by the "NR1I3" gene. CAR is a member of the nuclear receptor superfamily and along with pregnane X receptor (PXR) functions as a sensor of and xenobiotic substances. In response, expression of proteins responsible for the metabolism and excretion of these substances is upregulated. Hence, CAR and PXR play a major role in the detoxification of foreign substances such as drugs.
Androstenol and several isomers of androstanol, androstanes, are endogenous antagonists of the CAR, and despite acting as antagonists, were the basis for the naming of this receptor. More recently, dehydroepiandrosterone (DHEA), also an androstane, has been found to be an endogenous agonist of the CAR.
Function.
CAR is a member of the nuclear receptor superfamily, and is a key regulator of xenobiotic and metabolism. Unlike most nuclear receptors, this transcriptional regulator is constitutively active in the absence of ligand and is regulated by both agonists and inverse agonists. Ligand binding results in translocation of CAR from the cytosol into the nucleus, where the protein can bind to specific DNA sites, called response elements. Binding occurs both as a monomer and together with the retinoid X receptor (RXR) resulting in activation or repression of target gene transcription. CAR-regulated genes are involved in drug metabolism and bilirubin clearance. Examples for CAR-regulated genes are members of the CYP2B, CYP2C, and CYP3A subfamilies, sulfotransferases, and glutathione-S-transferases. Ligands binding to CAR include bilirubin, a variety of foreign compounds, steroid hormones, and prescription drugs.
Activation mechanism.
Phosphorylated CAR forms a multiprotein complex with the heat shock protein 90 (hsp90) and the cytoplasmic CAR retention protein (CCRP) which keep CAR in the cytosol thereby inactivating it. CAR can be activated in two ways: by direct binding of a ligand (e.g. TCPOBOP) or indirect regulation by phenobarbital (PB), a common seizure medication, facilitating the dephosphorylation of CAR through protein phosphatase 2 (PP2A) (Fig. 1).
Both lead to the release of CAR from the multiprotein complex and its translocation into the nucleus. Here, CAR forms a heterodimer with retinoid X receptor (RXR) and interacts with the phenobarbital-responsive enhancer module (PBREM), a distal enhancer activating transcription of CAR target genes.
The consensus sequence of PBREM, containing direct repeat-4 motifs, was found to be conserved in mouse, rat and human 'Cyp2b' genes.
Direct activation.
1,4-bis[2-(3,5-dichloropyridyloxy)]benzene (TCPOBOP) is thought to bind directly to mouse CAR, thus inducing its translocation into the nucleus. TCPOBOP does not bind to human CAR and hence has no effect on it. Human CAR can be activated by CITCO (6-(4-chlorophenyl)imidazo(2,1-b)(1,3)thiazole-5-carbaldehyde O-(3,4-dichlorobenzyl)oxime).
Indirect activation.
Phenobarbital (PB), a widely used anticonvulsant, is used as a model ligand for indirect CAR activation. PB activates CAR, by inducing the dephosphorylation of CAR through PP2A. How PP2A is activated remains unclear, but several different mechanisms have been proposed. The recruitment of PP2A has been shown to be mediated by the multiprotein complex. As PB is involved in the activation of AMP-activated protein kinase, it has been suggested that AMPK activates PP2A.
Alternatively, PP2A might be activated through another pathway including the epidermal growth factor receptor (EGFR) and the receptor for activated C kinase 1 (RACK1). In the absence of PB, the epidermal growth factor (EGF) binds to EGFR, thereby activating the steroid receptor coactivator-1 (Src1), which in turn phosphorylates RACK1. Upon PB-exposure, PB binds competitively to EGFR and thus leads to inactivation of Src1. This results in a dephosphorylation of RACK1, which can subsequently stimulate PP2A to activate CAR.
External links.


NAD(P)+ transhydrogenase (Re/Si-specific)

In enzymology, a NAD(P)+ transhydrogenase ("Re"/"Si"-specific () is an enzyme that catalyzes the chemical reaction
Thus, the two substrates of this enzyme are NADPH and NAD+, whereas its two products are NADP+ and NADH.
This enzyme belongs to the family of oxidoreductases, specifically those acting on NADH or NADPH with NAD+ or NADP+ as acceptor. This enzyme participates in nicotinate and nicotinamide metabolism.
Nomenclature.
The systematic name of this enzyme class is NADPH:NAD+ oxidoreductase ("Re"/"Si"-specific). Other names in common use include pyridine nucleotide transhydrogenase, transhydrogenase, NAD(P)+ transhydrogenase, nicotinamide adenine dinucleotide (phosphate) transhydrogenase, NAD+ transhydrogenase, NADH transhydrogenase, nicotinamide nucleotide transhydrogenase, NADPH-NAD+ transhydrogenase, pyridine nucleotide transferase, NADPH-NAD+ oxidoreductase, NADH-NADP+-transhydrogenase, NADPH:NAD+ transhydrogenase, H+-Thase, energy-linked transhydrogenase, and NAD(P)+ transhydrogenase (AB-specific).


Small conditional RNA

A small conditional RNA (scRNA) is a small RNA molecule or complex (typically less than approximately 100 nt) engineered to interact and change conformation conditionally in response to cognate molecular inputs so as to perform signal transduction in vitro, in situ, or in vivo.
In the absence of cognate input molecules, scRNAs are engineered to coexist metastably or stably without interacting. Detection of the cognate inputs initiates downstream conformational changes of one or more scRNAs leading to generation of the desired output signal. The output signal may be intended to read out the state of endogenous biological circuitry (e.g., mapping gene expression for biological research or medical diagnosis), or to regulate the state of endogenous biological circuitry (e.g., perturbing gene expression for biological research or medical treatment). scRNA sequences can be programmed to recognize different inputs or to activate different outputs, achieving even single-nucleotide sequence selectivity. scRNA signal transduction exploits principles from the emerging disciplines of dynamic RNA nanotechnology, molecular programming, and synthetic biology.
Examples of scRNA signal transduction.
Fluorophore-labeled scRNAs have been engineered to transduce between detection of mRNA targets and generation of bright fluorescent amplification polymers in situ (Figure 1). In this context, scRNA signal transduction enables multiplexed mapping of mRNA expression within intact vertebrate embryos (Figure 2).
scRNAs have been engineered to perform shape and sequence transduction to conditionally produce a Dicer substrate targeting 'silencing target' mRNA Y upon detection of an independent 'detection target' mRNA X, with subsequent Dicer processing yielding a small interfering RNA (siRNA) targeting mRNA Y for destruction (Figure 3). In this context, scRNA signal transduction provides a step towards implementing conditional RNA interference (Figure 4).
Design elements.
scRNAs can be engineered to exploit diverse design elements:


2,3-Dihydroxycinnamic acid

2,3-Dihydroxycinnamic acid is a hydroxycinnamic acid. It is an isomer of caffeic acid.
It is a metabolite found in human urine.


5-MAPDB

5-MAPDB (1-(2,3-dihydrobenzofuran-5-yl)-N-methylpropan-2-amine) is a chemical compound which acts as an entactogenic drug. It is structurally related to drugs like 5-APDB and 5-MAPB, which have similar effects to MDMA and have been used as recreational drugs. 5-MAPDB has been studied to determine its pharmacological activity, and was found to be a relatively selective serotonin releaser, though with weaker actions as a releaser of other monoamines and 5-HT2 receptor family agonist, similar to older compounds such as 5-APDB.
Legality.
5-MAPDB was banned in the UK in June 2013 as a temporary class drug along with 9 other related compounds, despite having never been sold as a street drug itself. This was due to concerns that it would have similar effects to drugs such as 5-APB that had been widely sold already, and 5-MAPDB might therefore be likely to become used recreationally also, if it were not banned preemptively.


Mixed-function oxidase

Mixed-function oxidase is the name of a family of oxidase enzymes that catalyze a reaction in which each of the two atoms of oxygen in O2 is used for a different function in the reaction.
Oxidase is a general name for enzymes that catalyze oxidations in which molecular oxygen is the electron acceptor but oxygen atoms do not appear in the oxidized product. Often, oxygen is reduced to either water (cytochrome oxidase of the mitochondrial electron transfer chain) or hydrogen peroxide (dehydrogenation of fatty acyl-CoA in peroxisomes). Most of the oxidases are flavoproteins.
The name "mixed-function oxidase" indicates that the enzyme oxidizes two different substrate simultaneously. Desaturation of fatty acyl-CoA in vertebrates is an example of the mixed-function oxidase reaction. In the process, saturated fatty acyl-CoA and NADPH are oxidized by molecular oxygen (O2) to produce monounsaturated fatty acyl-CoA, NADP+ and 2 molecules of water.
Reaction.
The mixed-function oxidase reaction proceeds as follows:
AH + BH2 + O2 --> AOH + B + H2O (H2O as catalyst.)
Medical significance.
High levels of mixed-function oxidase activity has been studied for their activation effects in human colon carcinoma cell lines, to study the susceptibility to certain cancers. The research has been successful in mice but remains inconclusive in humans.


Multifunctional peptide

A multifunctional peptide is a peptide which occurs when two genes band together. This process gives new properties to the polypeptide.


Pierre Monsan

Pierre Monsan (born June 25, 1948, in Prades, Pyrénées-Orientales, France) is a French biochemist and entrepreneur. He is currently Professor emeritus at the Institut national des sciences appliquées de Toulouse (INSA Toulouse, affiliated to the University of Toulouse) and the founding director of the pre-industrial demonstrator "Toulouse White Biotechnology" (TWB).
Monsan's scientific interests include biocatalysis, biochemical and enzyme engineering. Beyond his academic work, Monsan is co-inventor on numerous patents and co-founded several industrial biotechnology companies.
Education and career.
Monsan was educated at INSA Toulouse and the University of Toulouse where he graduated with an engineer degree ("Ingénieur diplômé)" in Biological Chemistry in 1969. He was then awarded his Doctor-Engineer Degree in 1971 and his PhD degree in 1977 from INSA Toulouse for research on enzyme immobilization. He served as lecturer in the Department of Biochemical Engineering at INSA Toulouse from 1969 and was later promoted to Assistant Professor (1973) and then Professor (1981).
In 1984, Monsan took a leave from Academia and co-founded BioEurope, a startup company specialized in industrial biocatalysis. There he served as CSO from 1984 to 1989, CEO from 1989 to 1993 and CSO again from 1993 to 1999 after the acquisition of the company by the Solabia Group. In 1993, Monsan returned to INSA Toulouse to lead a research group focusing on the discovery, characterisation and molecular engineering of enzymes, including glucansucrases and lipases. He was also appointed Professor at Ecole des Mines-ParisTech in 1993. From 1999 to 2003 he served as head of Department of Biochemical Engineering at INSA Toulouse. In 2012, he founded the pre-industrial demonstrator “Toulouse White Biotechnology” (TWB) with a €20M grant within the framework of the "Investing for the Future" national program (also called the "grand emprunt").
Monsan is presently Professor emeritus at INSA Toulouse and the founding director of TWB.
Scientific work.
Research by Monsan and his collaborators has focused on biocatalysis, biochemical engineering and enzyme engineering, published in over 230 articles. His fundamental includes investigation of structure-activity relationships of enzymes, (particularly glycoside hydrolases and lipases), and enzyme discovery by functional metagenomics. His more applied research involves biocatalysis in non-conventional (anhydrous) media for the synthesis of chemicals ("e.g.", chiral resolution to obtain enantiopure compounds), protein engineering (e.g. modification of substrate specificity, enantioselectivity, or thermostability), methods for enzyme immobilization, and bioreactor design and development.
Technology transfer and entrepreneurship.
Monsan has been heavily involved in technology transfer throughout his career and is co-inventor of over 60 patents. He has developed several industrial biocatalytic processes for the production of polysaccharides, oligosaccharides and amino acid derivatives. Companies he has co-founded include BioEurope (1984; biocatalytic synthesis of reagents for the food, pharma and nutrition industries; now owned by the Solabia group), Biotrade (1996; waste water treatment) and Genibio (1998, food additives). He is and has been member of the scientific advisory board of several companies, including Danisco Venture, ,
or Deinove.
In 2012, Monsan founded the pre-industrial demonstrator Toulouse White Biotechnology (TWB), an original institute dedicated to technology transfer through a consortium of public and industrial partners. TWB promotes industrial biotechnology and biobased economy through collaborative public/private research and development projects ("e.g.", THANAPLAST project in partnership with Carbios) and the creation of startups such as EnobraQ (development of yeasts able to metabolize CO2) or Pili (production of bacterial ink).


Ectopic expression

Ectopic is a word used with a prefix, ecto, meaning “out of place.” Ectopic expression is an abnormal gene expression in a cell type, tissue type, or developmental stage in which the gene is not usually expressed. The term ectopic expression is predominately used in studies using metazoans, especially in "Drosophila melanogaster" for research purposes.
How is it used.
Although ectopic expression can be caused by a natural condition, it is uncommonly seen in nature because it is a product of defects in gene regulation. In fact, ectopic expression is more commonly used for research purposes. Artificially induced gene expression helps to determine the function of a gene of interest. Common techniques such as overexpressing or misexpressing the genes by "UAS-Gal4" system in "D. melanogaster" are used. In model organisms, such techniques are used to perform genetic screens to identify a function of the gene involved in specific cellular or developmental processes.
Ectopic expression using these techniques is a useful tool because phenotypes induced in a tissue or cell type where are not normally expressed are easily distinguishable compared to a tissue or cell type where the gene is normally expressed. By the comparison with its basal expression, the function of a gene of interest can be identified.
Although the understanding of ectopic expressions deals with endogenous genes in an organism, it can be expended to a similar concept like transgenesis, which an exogenous gene is introduced to a cell or tissue type in which the gene is not usually expressed. Practices of ectopic expression in biological science is not only limited to identifying a function of the gene in a known cell or tissue type but also implemented to discover unknown or additional functions of the gene by ectopic expression.
Research examples.
Paired box protein.
Paired box protein Pax-6 in humans is a transcription factor, which is a main regulatory gene of eye and brain development. Ectopic expression of "Drosophila" homolog "eyeless" ("ey") has been used to identify roles of Pax-6 in humans. Using tissue specific "UAS-Gal4" system, "ey" can be induced on the legs, wings, halters and antennae of the transgenic flies to demonstrate that functions of "ey".
Olfactory receptor genes.
Olfactory receptor gene (OR) is normally expressed in human and mouse olfactory tissue with a main function as odorant receptor for the detection of odorants. Individuals with a defect in this gene have disorders of taste and smell. It has been reported that ORs is also expressed on sperms and testis with special emphasis in a manner of ectopic expression. In a study, researchers identified ectopic expression of OR genes in non-olfactory tissues in the mouse model by measuring transcript levels. Here they found relatively low OR gene expression compared to the olfactory tissue, which result indicates that the OR gene in other tissue have no extra function, but they suggest that there is a possibility that small OR subsets can have functional roles in different tissue.
Synovial Sarcoma X chromosome breakpoint-2.
Synovial Sarcoma X chromosome breakpoint-2 (SSX2) proteins are known to localize in nucleus and work as a transcriptional repressor. In addition, expression of SSX2 is frequently observed in melanoma, but the role of the gene has not been evaluated. Thus, researchers have used the principle of ectopic expression to express SSX2 to different cell lines including cancer model cells. They found important phenotypes of ectopic SSX2 expression that is involved in tumorigenesis: 1) immediate induction of genomic instability, 2) long-term support of tumor cell growth.


Tejal A. Desai

Tejal Ashwin Desai (born June 3, 1972) is the Ernest L. Prien Professor and Chair of the Department of Bioengineering and Therapeutic Sciences at University of California, San Francisco and head of the Therapeutic Micro and Nanotechnology Laboratory. She was formerly an associate professor at Boston University (2002–06) and an assistant professor at University of Illinois at Chicago (1998–2001). She is a researcher in the area of therapeutic micro and nanotechnology and has authored and edited at least one book on the subject and another on biomaterials.
Desai attended Brown University, where she received a Sc. B. in biomedical engineering in 1994. In 1998 she graduated with a Ph.D. from the joint UCSF/UC Berkeley Bioengineering department, advised by Mauro Ferrari.
She was elected a fellow of the American Institute for Medical and Biological Engineering in 2012.


GRIN2B

Glutamate [NMDA] receptor subunit epsilon-2, also known as "N"-methyl D-aspartate receptor subtype 2B (NMDAR2B or NR2B), is a protein that in humans is encoded by the "GRIN2B" gene.
NMDA receptors.
"N"-methyl-D-aspartate (NMDA) receptors are a class of ionotropic glutamate receptors. The NMDA receptor channel has been shown to be involved in long-term potentiation, an activity-dependent increase in the efficiency of synaptic transmission thought to underlie certain kinds of memory and learning. NMDA receptor channels are heterotetramers composed of two molecules of the key receptor subunit NMDAR1 (GRIN1) and two drawn from one or more of the four NMDAR2 subunits: NMDAR2A (GRIN2A), NMDAR2B (GRIN2B), NMDAR2C (GRIN2C), and NMDAR2D (GRIN2D). The NR2 subunit acts as the agonist binding site for glutamate, one of the predominant excitatory neurotransmitter receptors in the mammalian brain.
Function.
NR2B has been associated with age- and visual-experience-dependent plasticity in the neocortex of rats, where an increased NR2B/NR2A ratio correlates directly with the stronger excitatory LTP in young animals. This is thought to contribute to experience-dependent refinement of developing cortical circuits.
Both mice and rats that were engineered to over-express GRIN2B in their brains have increased mental ability. The "Doogie" mouse had double the learning ability on one measure of learning.
Interactions.
GRIN2B has been shown to interact with:


HgcF RNA

The HgcF RNA gene is a non-coding RNA identified computationally and experimentally verified in AT-rich hyperthermophiles. The genes were named hgcA through hgcG ("high GC"). It was later identified as Pab35 H/ACA snoRNA with rRNA targets.


Leslie Collier

Leslie Harold Collier (9 February 1921 – 14 March 2011) was a scientist responsible for developing a freeze-drying method to produce a more heat stable smallpox vaccine in the late 1940s.
 Collier added a key component, peptone, a soluble protein, to the process. This protected the virus, enabling the production of a heat-stable vaccine in powdered form. Previously, smallpox vaccines would become ineffective after 1–2 days at ambient temperature.
The development of his vaccine production method played a large role in enabling the World Health Organization to initiate its global smallpox eradication campaign in 1967.
Publications.
Collier was a co-editor of the eighth edition and editor-in-chief of the five-volume ninth edition of the "microbiologist’s bible", Topley and Wilson's "Principles of Bacteriology and Immunity" (now Topley and Wilson's "Microbiology and Microbial Infections"), which won the Society of Authors' 1998 award in the advanced edited book category.<br>He was also joint editor of "Developments in Antiviral Chemotherapy" (1980).He was a co-author of "Human Virology" (1993).


Plaque hybridization

Plaque hybridization is a technique used in Molecular biology for the identification of recombinant phages.
The procedure can also be used for the detection of differentially represented repetitive DNA.
The technique (similar to colony hybridization) involves hybridizing isolated phage DNA to a label probe for the gene of study. This is followed by autoradiography to detect the position of the label.
The plaque hybridization procedure has some advantages over colony hybridization due to the smaller and well defined area of the filter to which the DNA binds.


Hfq binding sRNA

An Hfq binding sRNA is an sRNA that binds the bacterial RNA binding protein called Hfq. A number of bacterial small RNAs which have been shown to bind to Hfq have been characterised (see list).
Many of these RNAs share a similar structure composed of three stem-loops. Several studies have expanded this list, and experimentally validated a total of 64 Hfq binding sRNA in "Salmonella Typhimurium". A transcriptome wide study on Hfq binding sites in "Salmonella" mapped 126 Hfq binding sites within sRNAs. Genomic SELEX has been used to show that Hfq binding RNAs are enriched in the sequence motif 5′-AAYAAYAA-3′. Genome-wide study identified 40 candidate Hfq-dependent sRNAs in plant pathogen "Erwinia amylovora." 12 of them were confirmed by Northern blot.


Avecia

Avecia, a part of Nitto Denko Inc., is a private biotechnology company focused on the development and manufacture of novel medicines using biotechnology techniques. Avecia operates as a contract manufacturing organization (CMO), specializing in oligonucleotide production.
Avecia has two US FDA-audited facilities, one near Boston, MA, and the second in Cincinnati, OH. The combined capacity of these two sites allows Avecia to handle oligonucleotide programs from the pre-clinical through commercial stages. In 2016 Avecia acquired the assets of Irvine Pharmaceutical Services and Avrio Biopharmaceuticals.
It was named as one of the top companies in Oligonucleotide Synthesis industry in January 2019.


3-Oxoacyl-CoA

3-Oxoacyl-CoA is a group of coenzymes involved in the metabolism of fatty acids.


Lysine dehydrogenase

In enzymology, a lysine dehydrogenase () is an enzyme that catalyzes the chemical reaction
Thus, the two substrates of this enzyme are L-lysine and NAD+, whereas its 4 products are 1,2-didehydropiperidine-2-carboxylate, NH3, NADH, and H+.
This enzyme belongs to the family of oxidoreductases, specifically those acting on the CH-NH2 group of donors with NAD+ or NADP+ as acceptor. The systematic name of this enzyme class is L-lysine:NAD+ oxidoreductase (deaminating, cyclizing).


Lihong V. Wang

Lihong V. Wang () is the Bren Professor of Medical Engineering and Electrical Engineering at the Andrew and Peggy Cherng Department of Medical Engineering at California Institute of Technology and was formerly the Gene K. Beare Distinguished Professorship of Biomedical Engineering at Washington University in St. Louis. Wang is renowned for his contributions to the field of Photoacoustic imaging technologies and inventing the world's fastest camera with more than 10 trillion frames per second. Wang was elected as the member of National Academy of Engineering (NAE) in 2018.
Education.
Wang received B.S. and M.S. degrees in optics engineering from Huazhong University of Science & Technology respectively in 1984 and 1987.
Wang earned a PhD from Rice University in Houston, Texas.
Career.
Wang's laboratory was the first to report functional photoacoustic tomography, 3D photoacoustic microscopy (PAM), photoacoustic endoscopy, photoacoustic reporter gene imaging, the photoacoustic Doppler effect, the universal photoacoustic reconstruction algorithm, microwave-induced thermoacoustic tomography, ultrasound-modulated optical tomography, time-reversed ultrasonically encoded (TRUE) optical focusing, nonlinear photoacoustic wavefront shaping (PAWS), compressed ultrafast photography (10 trillion frames/s), Mueller-matrix optical coherence tomography, and optical coherence computed tomography. Wang was the recipient of several award, including NIH's FIRST, NSF's CAREER, NIH Director's Pioneer, and NIH Director's Transformative Research awards. Wang also received the OSA C.E.K. Mees Medal "for seminal contributions to photoacoustic tomography and Monte Carlo modeling of photon transport in biological tissues and for leadership in the international biophotonics community". Prof. Wang has been conferred upon by an honorary doctorate degree by Lund University located in Sweden for his contributions towards the field of Biomedical Imaging.
Wang has received more than 37 research grants as principal investigator with an estimated cumulative budget of more than $47M. Wang has published more than 470 peer-reviewed journal articles including Nature, Science, and PNAS. His book "Biomedical Optics: Principles and Imaging" was one of the first in the field, and received the Joseph W. Goodman Book Writing Award. Wang was the editor-in-chief of the Journal of Biomedical Optics from 2010-2017.
In 2018, Wang was elected as the member of National Academy of Engineering(NAE) for "inventions in photoacoustic microscopy enabling functional, metabolic, and molecular imaging in vivo".


5-MeO-pyr-T

5-MeO-pyr-T (5-methoxy-"N","N"-tetramethylenetryptamine) is a lesser-known psychedelic drug. It is the 5-methoxy analog of pyr-T. 5-MeO-pyr-T was first synthesized by Hunt & Brimblecombe, who credited S. Mitzal for characterization of chemical properties. Later human tests were reported by Alexander Shulgin, in his book "TiHKAL". An oral dosage of 0.5 to 2 mg, and an inhaled dosage of 2–3 mg are reported. 5-MeO-pyr-T causes varying reactions, such as amnesia, tinnitus, vomiting, and a 5-MeO-DMT-like rushing sensation. At the highest dosage reported in TiHKAL, the subject describes awakening from an apparent fugue state during which they were wandering the streets, with complete amnesia upon awakening.
Pharmacology.
Testing was performed on rats using this compound while characterizing various agonists of the 5-HT7 receptor. It is an agonist with a Ki value of 630.96nM.
Very little other data exists about the pharmacological properties, metabolism, and toxicity of 5-MeO-pyr-T.


Aribas

The ARIBAS, New Vallabh Vidhyanagar, Gujarat, India is an Institute of Science offering mainly master's degree programmes. The Institute was established in 2005. It is affiliated with Sardar Patel University.
It is the first institute to offer the Integrated Biotechnology course in the state of Gujarat.
The major courses run at ARIBAS are MSc Biotechnology, MSc Integrated Biotechnology (5½ Years after 12th grade), MSc Microbiology, MSc Genetics and MSc Pharmaceutical Chemistry.
The institute also offers PhD and bachelor's degrees in Biochemistry, Botany, Biotechnology, Genetics, Pharmaceutical Chemistry and Physics, among others.


Mycena pseudostylobates

Mycena pseudostylobates is a species of agaric fungus in the family Mycenaceae. It is bioluminescent.


L-myc internal ribosome entry site (IRES)

The L-myc internal ribosome entry site (IRES) is an RNA element present in the 5' UTR of the mRNA of L-myc that allows cap-independent translation. L-myc undergoes translation via the internal ribosome entry site and bypasses the typical eukaryotic cap-dependent translation pathway [1]. The myc family of genes when expressed are known to be involved in the control of cell growth, differentiation and apoptosis.


NADH dehydrogenase (quinone)

In enzymology, a NADH dehydrogenase (quinone) () is an enzyme that catalyzes the chemical reaction
The 3 substrates of this enzyme are NADH, H+, and a quinone (electron acceptor), whereas its two products are NAD+ and a quinol (reduced acceptor).
This enzyme belongs to the family of oxidoreductases, specifically those acting on NADH or NADPH with other acceptors. The systematic name of this enzyme class is NADH:(quinone-acceptor) oxidoreductase. Other names in common use include reduced nicotinamide adenine dinucleotide (quinone) dehydrogenase, NADH-quinone oxidoreductase, NADH ubiquinone oxidoreductase, DPNH-menadione reductase, D-diaphorase, and NADH2 dehydrogenase (quinone), and mitochondrial (mt) complex I. This enzyme participates in oxidative phosphorylation. Several compounds are known to inhibit this enzyme, including AMP, and 2,4-dinitrophenol. NADH dehydrogenase is involved in the first step of the electron transport chain of oxidative phosphorylation (OXPHOS). Any change in the electron transport component caused by a mutation might effect the normal electron flow. This might be leading "an increase of bifurcation and generation of superoxidase radicals and increase oxidative stress in various types of cancer cells."
In the electron transport chain NADH is mainly used to create a concentration gradient of hydrogen in order to make ATP. Since After NADH is oxidized a hydrogen is pumped out and NAD+ will be a product.
Structural studies.
Several structures are available of this enzyme, which is part of the respiratory chain. It is a multi-subunit enzyme in which this activity is located in the hydrophilic domain. The subunits of the membrane-embedded domain are responsible for proton translocation.


Codexis

Codexis, Inc. is a protein engineering company that produces enzymes for pharmaceutical, food and medical applications.
The company is based in Redwood City, CA and was incorporated in 2002. It went public in April 2010 on NASDAQ.
Codexis won the Presidential Green Chemistry Challenge Award from the U.S. Environmental Protection Agency (EPA) in 2006 for its work on a building block of Lipitor and a second time with Merck in 2010 for its work on the active ingredient in Januvia.


Dinapsoline

Dinapsoline is a drug developed for the treatment of Parkinson's disease, that acts as a selective full agonist at the dopamine D1 receptor.


Robert Malkin

Robert A. Malkin is an engineer specializing in medical instrumentation for the developing world.
At Duke, Malkin is a professor of the practice of Biomedical Engineering, professor of the practice of global health, and an affiliate of the Duke Initiative for Science & Society.
He is best known for his work concerning medical equipment design for the developing world, for which he was named among "Today's Engineering Heroes" by IEEE in 2015.
Pratt Pouch.
Among his work, the best-known technology is the "Pratt Pouch," a ketchup packet-like envelope containing antiretroviral drugs. The pouch is credited with saving thousands of lives in South America and Africa.
Named for Duke's Pratt School of Engineering, the pouch was developed by Malkin in collaboration with Duke undergraduate engineering students. In 2012, the World Health Organization placed the pouch on its Top 10 Most Innovative Health Technologies list.
Organizations Founded.
Malkin founded Engineering World Health, a nonprofit which delivers technical expertise and medical equipment to the developing world. He also founded The Global Public Service Academies an organization that places high school students in developing world clinics and hospitals.
Working at Duke, Malkin helped launch several efforts for making and distributing medical devices for the developing world including a bili light company called PhotoGenesis Medical and a colposcope project at Family Health Ministries.
Early Years and Education.
Born in Cleveland, Ohio, Malkin earned a master's and a PhD in electrical engineering from Duke University and two bachelor's from The University of Michigan.
Malkin is a fellow of the American Institute for Medical and Biological Engineering and an expert advisor to WHO committees on health care technology.


John Dix Fisher

John Dix Fisher (March 27, 1797 – March 3, 1850) was a physician and founder of Perkins Institution for the Blind in Boston, Massachusetts.
He was born in Needham, Massachusetts, the youngest of the six sons of Aaron and Lucy (Stedman) Fisher. The Fisher family was descended from Anthony Fisher, one of the signers of the Dedham Covenant in 1636. All six sons were self-made men who became successful merchants, traders and professional men in Dedham and Boston, Massachusetts.
With the support of his older brothers, John Dix Fisher entered Brown University, graduating in 1820. After receiving his M.D. degree in 1825 from what was then called Massachusetts Medical College of Harvard University, he immediately accompanied his brother, the artist Alvan Fisher, on a trip to Europe. In Paris, he pursued his professional studies with such eminent physicians of the period as René Laennec, inventor of the stethoscope; Gabriel Andral, distinguished pathologist; and Alfred Velpeau, renowned for his knowledge of surgical anatomy. In medical school, Dr. Fisher had studied with Dr. James Jackson, Harvard's first professor of clinical medicine and one of the "fathers" of Massachusetts General Hospital. Dr. Jackson had touched on the difficulties of distinguishing smallpox from other eruptive diseases and the need for a series of colored pictures which would illustrate the progress of the disease. Dr. Fisher undertook such a project while in Paris and wrote "Description of the Distinct, Confluent, and Inoculated Small Pox, Varioloid Disease, Cow Pox, and Chicken Pox" (1829) which included thirteen colored plates. The paintings from which the plates were made were executed under Dr. Fisher's direction by a French artist working at the bedside of the patients during 1825 and 1826 when smallpox was an epidemic in Paris.
Dr. Fisher also observed the methods of instructing the blind that were being practiced in Paris. He visited the world's first school for blind children, L'Institution Nationale des Jeunes Aveugles, founded by Valentin Haüy in 1784. He was impressed with the manner in which students were taught to read from raised-type books, to write, and to learn mathematics, geography, languages, music and manual arts. Inspired, he returned to Boston and spent the next three years persuading family and friends who had both the means and the conscience to help fund an American version of the Paris school. The Massachusetts legislature eventually signed an act incorporating the New England Asylum for the Blind on March 2, 1829, and soon after provided $6,000 of funding. The trustees searched for two years for a superintendent for the new school until, in 1831, Dr. Fisher recruited his friend, Dr. Samuel Gridley Howe. The two men had studied together at Brown University and at Harvard Medical School. Dr. Howe opened the school in the summer of 1832 using an approach that gave students both the ability to think and the skills to support themselves with the goal of turning out independent, productive, well-educated members of society. Dr. Fisher continued as the school's doctor and vice president. The school's name was eventually changed to Perkins School for the Blind and is now located in Watertown, Massachusetts.
Dr. Fisher was a pioneer for medical reform in Boston. He is credited with introducing the stethoscope into the United States and was an early advocate for the practice of mediate auscultation—listening to the body through a stethoscope—using the techniques that he had learned during his studies in Paris with Laënnec. In July 1832, while using auscultation to examine a child affected with chronic hydrocephalus, he discovered what was called "cephalic bellows-sound" or "cerebral murmur", a phenomenon related to cerebral circulation which was thought to be a physical symptom of diseases of the brain. His findings were circulated in medical journals throughout the world. However, the phenomenon was dismissed in 1880 as being without pathological significance. He was among those present in the Ether Dome at Massachusetts General Hospital when ether was first used in public for a surgical operation, described by many as the most significant event in American medical history. He was one of the first to use ether during childbirth. Although Antoine Jean Desormeaux, a French surgeon, first introduced the endoscope to a patient and is considered the "Father of Endoscopy", Dr. Fisher had several years earlier described an endoscope initially to inspect the vagina, but later modified it to examine the bladder and urethra. As one of a group of young American doctors influenced by the teachings of another French physician, Pierre Louis, Dr. Fisher was an advocate of the "numerical method" in the United States, where the emphasis on the collection of observable, detailed data and their statistical analysis became a guideline for medical research and the foundation for epidemiology. He was present along with William Cogswell, Richard Fletcher, Oliver Peabody and Lemuel Shattuck at a meeting held on November 17, 1839, in which the American Statistical Association (ASA) was formed. These men were graduates of Brown, Dartmouth, and Harvard and were trained in law, medicine, theology, literature and education. The constitution of the Society set out as its aims: "...to collect, preserve, and diffuse statistical information in the different departments of human knowledge." It was particularly instrumental in improving public health and encouraging advances in preventive medicine. He was also a member of the Massachusetts Medical Society which, in concert with the ASA in 1842, led the effort to establish the first statewide system to collect and publish vital statistics in the United States. In 1846, Dr. Fisher was elected attending physician at Massachusetts General Hospital, a position he held until his death on March 3, 1850, at his home in Hayward Place, Boston. On March 17, 1850, the hospital's Board of Trustees expressed its deep regret for "...the loss of an officer who, to high scientific attainments, united amiable and unassuming manners and the greatest kindness of heart; one who has uniformly discharged in a most zealous, faithful, and acceptable manner his duties toward this institution." A white marble monument in his memory stands in Mount Auburn Cemetery, Cambridge, Massachusetts.
Trivia.
According to an extract from "Flashes of Light from the Spirit-Land" compiled by Allen Putnam and published in 1872 by William White & Co., Boston, Mrs. J. H Conant was an American medium who, through the generosity of Luther Colby, editor of "The Banner of Light", (a weekly subtitled "An Exponent of the Spiritual Philosophy of the Nineteenth Century," which had the largest circulation of any spiritualist paper in the world) gave, for the last 17 years of her life, free public séances in Boston. Her trance messages, characterized by the impersonation of the departed, were published weekly in "The Banner". Mrs. Conant was known in spiritualist circles as both an inspirational speaker and a platform healer. For her medical diagnosis, the medium relied on the spirit of Dr. John Dix Fisher, a famous old Boston physician.


Quinazosin

Quinazosin is an antihypertensive adrenoreceptor antagonist.