Generalised compound

A generalized compound is a mixture of chemical compounds of constant composition, despite possible changes in the total amount. The concept is used in the Dynamic Energy Budget theory, where biomass is partitioned into a limited set of generalised compounds, which contain a high percentage of organic compounds. The amount of generalized compound can be quantified in terms of weight, but more conveniently in terms of C-moles. The concept of strong homeostasis has an intimate relationship with that of generalised compound.


Antibodies from lymphocyte secretions

The antibodies from lymphocyte secretions (ALS) assay is an immunological assay to detect active diseases like tuberculosis, cholera, typhoid etc. Recently, ALS assay nods the scientific community as it is rapidly used for diagnosis of Tuberculosis. The principle is based on the secretion of antibody from "in vivo" activated plasma B cells found in blood circulation for a short period of time in response to TB-antigens during active TB infection rather than latent TB infection.
Procedure of ALS assay.
PBMCs were separated from blood on Ficoll-Paque by differential centrifugation and were suspended in 24-well tissue culture plates culture medium. Different dilutions of PBMCs were incubated at 37 °C with 5% CO2. Culture supernatants were collected at 24, 48, 72, and 96 h after incubation and the supernatants were test against BCG or PPD by ELISA. The ELISA titer indicate the positive or negative result.
Advantages of ALS Assay in TB diagnosis.
The diagnosis of TB is most complicated. The routine diagnosis for TB patient is sputum culture based. But culture need 6-8week with 10-20% false positive results. A rapid serological test for diagnosis, follow-up of disease activity, and response to therapy would be useful to clinicians. The purified protein derivative (PPD) skin test (Mantoux test) is an important tool for diagnosis of latent TB infection and disease in the developed world, but it has low predictive value in Bacillus Calmette-Guérin (BCG)–vaccinated individuals, as well as in individuals living in areas where TB is endemic. The low predictive value is a result of cross-reactivity with BCG and atypical mycobacteria, as well as false negative reactions in malnourished children. BCG has been used as an antigen in EIAs in in vitro studies to determine disease activity, but its use was suspended because of difficulties in interpretation, problems differentiating between active or past disease, and low sensitivity and specificity. The antibodies from lymphocyte secretion (ALS) assay was earlier used to detect specific antibody response after oral vaccination with a killed cholera vaccine in healthy adults without any requirement for in vitro antigen stimulation.
The main advantages are:
Pitfalls.
This method cannot be applied if Mantoux test (tuberculin skin test) has been done within the last 40 days, because it can hamper the results of the ALS test. This test is used as a complementary test to other tests, e.g. chest X-ray, ESR, CRP, history of contact with active TB case, failure with conventional antibiotic treatment etc.; anti-TB therapy is not provided if only ALS test is positive. The reason is that this method is potentially an early biomarker of active infection. However, if a subject does not show any physical symptoms, the doctors cannot prescribe anti-TB treatment.


Cliotide

Cliotides are a group of related peptides that have been isolated from the heat-stable fraction of "Clitoria ternatea" (Cliotides) extracts. Cliotides belong to a larger classification of peptides, the cyclotides.
Preliminary studies show that cliotides display a variety of biochemical properties which have attracted scientific interest in the possibility of developing antimicrobial and anti-cancer agents from them.
Cliotides display "in vitro" antimicrobial activity against "E. coli", "K. pneumoniae", and "P. aeruginosa" and cytotoxicity against HeLa cells.
Cliotides also possess immunostimulating activity. At a concentration of 1 μM, cationic cliotides are capable of augmenting the secretion of various cytokines and chemokines in human monocytes at both resting and LPS-stimulated states. Chemokines such as RANTES, MIP-1β, MIP-1α, IP-10, IL-8 and TNF-α were among the most upregulated with up to 129-fold increase in secretion level.
Different cyclotides have protein sequences which engender different biophysical and functional properties, to be expressed in different organs. For example, cyclotides from aerial organs possess tighter binding activity to insect-like membranes, whereas cyclotides from roots and seed, two organs that contact soil, have relatively higher effectiveness against juveniles of the model nematode "Caenorhabditis elegans". The isolated Cter M cyclotide that is highly expressed in aerial organs was shown to effectively slow the growth and kill moth larvae.
The enzyme responsible for the biosynthesis and backbone cyclization of cliotides has recently been isolated. It was named butelase 1 in accordance to its local name in Malaysia and Singapore ("bunga telang" ligase). Butelase 1 is the fastest peptide ligase known capable of catalyzing peptide cyclization at an extraordinary efficiency.


George Pearson (doctor)

George Pearson, MD, FRS (1751–1828) was a British physician, chemist and early advocate of Jenner's cowpox vaccination.
Davies Gilbert, who was then President of the Royal Society, began his 1829 memoir (written anonymously) of Dr. Pearson thus:
He continued:
Pearson studied in Edinburgh, took his MD in 1771 and went to study for a year at St. Thomas's Hospital. He settled in Doncaster in 1777. In his six years there he became a close friend of John Philip Kemble and analysed the water at Buxton, about which he produced a two-volume work.
In 1783 he moved to London, to Leicester Square, and was admitted a Licentiate of the Royal College of Physicians on 25 June 1784. He began to lecture. He was elected (chief) Physician of St George's Hospital on 23 February 1787, and was there for the next forty years. He was elected a Fellow of the Royal Society on 23 June 1791. (He served on the Society's Council in 1802 and in 1827, in which year he gave the Bakerian Lecture, "Researches to discover the Faculties of Pulmonary Absorption with respect to Charcoal").
Davies went on:
On Sunday 9 November 1828 he died at his home in George Street (9 St. George Street), Hanover Square, in Davies' words: 'in consequence of a fall down stairs'.
He left two daughters; one, Frances Priscilla, married John Dodson, DCL (and formerly M. P.), and the other, Mary-Anne, was, once again as Davies put it in 1828, single.
Pearson and the Royal Society.
His first application to the Royal Society had been rejected on ballot 15 June 1786, when his neighbour and St. George's colleague John Hunter (surgeon) had been his lead proposer.
For his second attempt in 1791 Pearson's proposers were George Baker; William Heberden; Robert Hallifax (Royal physician); William Seward; John Gunning; Andrew Kippis; Thomas Bowdler; James Keir; Maxwell Garthshore; James Carmichael Smyth; Bp. Landaff; George Staunton; John Paradise; William Young; John Ash; Tiberius Cavallo; William Watson; Dr. (?) Gray; John Gillies.
Pearson and Smallpox Vaccination.
Pearson was a very early advocate of smallpox vaccination and supporter of Edward Jenner and published his early observations within months of the publication of Jenner's "Inquiry". Early in 1799 he helped to set up the Original Vaccine Pock Institute in London and started to distribute vaccine, some samples of which were contaminated with smallpox virus. This caused a rift with Jenner who thought his own work was being overshadowed. In turn, Pearson became envious of Jenner's growing reputation. When Jenner petitioned Parliament for a financial reward in 1802, Pearson published a detailed account of his own contribution, together with evidence that Jenner did not "discover" vaccination, bringing attention to farmer Benjamin Jesty and others who he maintained had prior claims. When Jenner sought a further Parliamentary grant in 1805, Pearson brought Jesty to London to visit the Original Vaccine Pock Institute to further his claim, with no success. By this time, although there was opposition to vaccination as such, Jenner's role in its introduction was firmly established and Pearson played little further part. However, his role in the introduction of smallpox vaccine was examined in detail much later when controversy arose over the origin of vaccinia virus, the active constituent of smallpox vaccine.
No. 52 Leicester Square.
For 20 years, between the ages of 34 and 54, from 1785–1805, Dr. Pearson lived at 52 Leicester Square.
His predecessors there included Sir Paul Rycaut, the traveller, diplomat, and historian of Turkey, 1679-c. 1684; Justice Robert Perryman or Perrismore, 1704–11; Jacques Christophe Le Blon (Le Blond), painter, engraver and printer, 1734–5; Sir William Wolseley, of Wolseley, Staffordshire, fifth baronet, 1757– 1768; Vice-Admiral John Campbell, 1774–82. The house was demolished in the 1840s making way for New Coventry Street.
Pearson of Tyers Hill.
As a result of his marriage to (probably his cousin) Frances Pearson, co-heir and daughter of Nathaniel Pearson (mayor of Doncaster, 1763) by his heiress (married 1743) wife Priscilla Rayney (died 1751), of Tyers Hill, George Pearson became involved with Tyers Hill a small estate near Ardsley, Darfield, Barnsley.
Priscilla Rayney, a first cousin, four times removed, of the first of the Rayney baronets, was daughter and co-heir of Alderman (mayor of Doncaster 1725) Thomas Rayney (d.1731?) by (married 1715) Frances daughter of Alderman John Fayram (Doncaster mayor, 1658).
Thomas Rayney was son of Henry Rayney (1614–1682) by (married 1650) Priscilla (1625–1682) daughter of William Wordsworth (c1590-1666), of Falthwaite, Silkstone, Penistone (who left three closes in Barnsley to Priscilla) by Helen Crosland. Henry Rayney was son of John Rayney of Tyers Hill by Anne, daughter of William Wentworth (1580–1635) of South Kirkby, S. Yorks.
John Rayney's grandfather, Henry Rayney of Ferrymoor, had bought Tyers Hill from John Byron in 1569. The nearby Monk Bretton priory was dissolved on 30 November 1538.
Into the mid-twentieth century the heirs of Pearson and Rayneys were leasing Meltonfield and Parkgate seams of coal under Tyershill Farm and land at Cudworth, Darfield and Royston, (probably including the land at Ferry Moor (Ferrymoor) just west of Grimethorpe), to the Mitchell's Main Colliery Company Limited.
George Pearson's wife was a third cousin once removed of William Wordsworth. Between 1775–1799 George Pearson's father, the apothecary, who owned Mosborough Hall, Sheffield, and his mother was Deborah daughter of George Smith by Mary, daughter of John Burnley of Moorgate, Rotherham, a butcher. George Smith is associated with property in Wortley; Tankersley; and Mortomley and High Green, Ecclesfield.
On Pearson's death the Tyers Hill property was inherited by Sir John Dodson, who had married Frances-Priscilla, Pearson's eldest daughter, on 24 December 1822, thus according to John Bateman, who derived his information from statistics published in 1873, John Dodson's son John George Dodson (Lord Monk Bretton) had 181 acres of farmland in the West Riding of Yorkshire, with a rental income worth 300 guineas per annum.
The arms of Pearson of Tyers Hill:
Shield: "azure between two palets wavy ermine three suns or".
Crest: "out of a cloud, a sun".
Wife's nephew.
On 10 July 1798 Bower was appointed a Lieutenant in the Fifth West Yorkshire Militia, and then on 1 April 1808 he was promoted to Captain in the Doncaster Volunteer Infantry.


Digene

Digene Corporation was a molecular diagnostics company with company headquarters in Gaithersburg, Maryland, U.S. Floyd Taub, M.D, founded the company in 1984 and it was incorporated in 1985. In 1988, the first diagnostic test for human papillomavirus gained FDA approval; the test was ViraPap, developed by Life Technologies, which had been formed by the merger of GIBCO and Bethesda Research Laboratories in 1983. Clinical uptake was slow, and Life sold the test and associated intellectual property to Digene in 1990. It became Digene's most important product line.
In 2007, Qiagen bought the company for US$1.6 billion.


Scatchard equation

The Scatchard equation is an equation used in molecular biology to calculate the affinity and number of binding sites of a receptor for a ligand. It is named after the American chemist George Scatchard.
Equation.
Throughout this article, ["RL"] denotes the concentration of a receptor-ligand complex, ["R"] the concentration of free receptor, and ["L"] the concentration of free ligand (so that the total concentration of the receptor and ligand are ["R"]+["RL"] and ["L"]+["RL"], respectively). Let "n" be the number of binding sites for ligand on each receptor molecule, and let represent the average number of ligands bound to a receptor. Let "Kd" denote the dissociation constant between the ligand and receptor. The Scatchard equation is given by
By plotting /["L"] versus , the Scatchard plot shows that the slope equals to -1/"Kd" while the x-intercept equals the number of ligand binding sites "n".
Derivation.
"n"=1 Ligand.
When each receptor has a single ligand binding site, the system is described by
with an on-rate ("k"on) and off-rate ("k"off) related to the dissociation constant through "Kd"="k"off/"k"on. When the system equilibrates,
so that the average number of ligands bound to each receptor is given by
which is the Scatchard equation for "n"=1.
"n"=2 Ligands.
When each receptor has two ligand binding sites, the system is governed by
At equilibrium, the average number of ligands bound to each receptor is given by
which is equivalent to the Scatchard equation.
General Case of "n" Ligands.
For a receptor with "n" binding sites that independently bind to the ligand, each binding site will have an average occupancy of ["L"]/("Kd" + ["L"]). Hence, by considering all "n" binding sites, there will
ligands bound to each receptor on average, from which the Scatchard equation follows.
Problems with the method.
The Scatchard method is less used nowadays because of the availability of computer programs that directly fit parameters to binding data. Mathematically, the Scatchard equation is related to Eadie-Hofstee method, which is used to infer kinetic properties from enzyme reaction data. Many modern methods for measuring binding such as surface plasmon resonance and isothermal titration calorimetry provide additional binding parameters that are globally fit by computer-based iterative methods.


Bacterial secretion system

Bacterial secretion systems are protein complexes present on the cell membranes of bacteria for secretion of substances. Specifically, they are the cellular devices used by pathogenic bacteria to secrete their virulence factors (mainly of proteins) to invade the host cells. They can be classified into different types based on their specific structure, composition and activity. Generally, proteins can be secreted through two different processes. One process is a one-step mechanism in which proteins from the cytoplasm of bacteria are transported and delivered directly through the cell membrane into the host cell. Another involves a two-step activity in which the proteins are first transported out of the inner cell membrane, then deposited in the periplasm, and finally through the outer cell membrane into the host cell.
These major differences can be distinguished between Gram-negative (diderm) and Gram-positive bacteria (monoderm). But the classification is by no means clear and complete. There are at least eight types specific to Gram-negative bacteria, four to Gram-positive bacteria, while two are common to both. In addition, there is appreciable difference between diderm bacteria with lipopolysaccharide on the outer membrane (diderm-LPS) and those with mycolic acid (diderm-mycolate).
Export pathways.
The export pathway is responsible for crossing the inner cell membrane in diderms, and the only cell membrane in monoderms.
Sec system.
The general secretion (Sec) involves secretion of unfolded proteins that first remain inside the cells. In Gram-negative bacteria, the secreted protein is sent to either the inner membrane or the periplasm. But in Gram-positive bacteria, the protein can stay in the cell or is mostly transported out of the bacteria using other secretion systems. Among Gram-negative bacteria, "Vibrio cholerae", "Klebsiella pneumoniae", and "Yersinia enterocolitica" use the Sec system. "Staphylococcus aureus" and "Listeria monocytogenes" are Gram-positive bacteria that use the Sec system.
The Sec system utilises two different pathways for secretion: the SecA and signal recognition particle (SRP) pathways. SecA is an ATPase motor protein and has many related proteins including SecD, SecE, SecF, SegG, SecM, and SecY. SRP is a ribonucleoprotein (protein-RNA complex) that recognizes and targets specific proteins to the endoplasmic reticulum in eukaryotes and to the cell membrane in prokaryotes. The two pathways require different molecular chaperones and ultimately use a protein-transporting channel SecYEG for transporting the proteins across the inner cell membrane. In the SecA pathway, SecB acts as a chaperone, helping protein transport to the periplasm after complete synthesis of the peptide chains. Whereas in the SRP pathway, YidC is the chaperone, and transport proteins to the cell membrane while they are still undergoing peptide synthesis.
SecA or post-translational pathway.
Proteins are synthesised in ribosomes by a process of serially adding amino acids, called translation. In SecA pathway, a chaperone trigger factor (TF) first bind to the exposed N-terminal signal sequence of the peptide chain. As elongation of peptide chain continues, TF is replaced by SecB. SecB specifically maintains the peptide in an unfolded state, and aids in the binding of SecA. The complex can then bind to SecYEG, by which SecA is activated by binding with ATP. Driven by ATP energy, SecA pushes the protein through the secYEG channel. SecD/F complex also helps in the pulling of the protein from the other side of the cell membrane.
SRP pathway.
In this pathway, SRP competes with TF and binds to the N-terminal signal sequence. Proteins from inner membrane stops the process of chain elongation. The SRP then binds to a membrane receptor, FtsY. The peptide chain-SRP-FtsY complex is then transported to SecY, where peptide elongation resumes.
Tat system.
The twin arginine translocation (Tat) system is similar to Sec in the process of protein secretion, however, it sends proteins only in their folded (tertiary) state. It is used by all types of bacteria, as well as archaea, and chloroplasts and mitochondria of plants. In bacteria, the Tat system exports proteins from the cytoplasm across the inner cell membrane; whereas in chloroplasts, it is present in the thylakoid membrane where it aids the import of proteins from the stroma. Tat proteins are highly variable in different bacteria and are classified into three major types, namely TatA, TatB, and TatC. For example, while there are only two functional Tat proteins in "Bacillus subtilis", there can be over a hundred in "Streptomyces coelicolor". Signal peptides that can recognise the Tat proteins are characterised by a consensus motif Ser/Thr-Arg-Arg-X-Phe-Leu-Lys (where X can be any polar amino acid). It is the two successive arginines from which the name twin arginine translocation came from. Replacement of any of the arginine leads to slow down or failure of secretion.
Wss/Esx pathway.
The Wss/Esx (ESAT-6 system) pathway is sometimes called a type VII secretion system (T7SS) despite being an export pathway. It is present in Gram-positive bacteria (as WSS) and Mycobacteria (as Esx in all diderm-mycolates) such as "M. tuberculosis", "M. bovis", "Streptomyces coelicolor" and "S. aureus". It is also called T7b system in "Bacillus subtilis" and "S. aureus". It is composed of two basic components: a membrane-bound hexameric ATPase that is member of the FtsK/SpoIIIE protein family, and any one of the EsxA/EsxB-related protein such as EsaA, EsaD, EsxB, EsxD, as well as Ess system (EssA, EssB, and EsxC found in "S. aureus"). EsxA and EsxB belong to a superfamily of WXG100 proteins that form dimeric helical hairpins.
In "S. aureus", T7SS secretes a large toxin called EsaD, which is a member of nuclease enzymes. EsaD is made harmless (detoxified) during its biosynthesis with the help of its counterpart antitoxin EsaG. The EsaD-EsaG complex then binds with EsaE. The EsaE portion binds to EssC, which is an enzyme ATPase of the T7SS complex. During secretion, EsaG is left in the cytoplasm, and only EsaD and EsaE are secreted together. But in some strains of "S. aureus", EsaD is not produced, but two copies of EsaG-like proteins are formed instead. This might explain the occurrence of T7SS in non-pathogenic species such as "B. subtilis" and "S. coelicolor".
Secretion systems.
The secretion systems are responsible for crossing the outer cell membrane or both membranes in diderms. The current nomenclature applies to diderm-LPS only, as nothing is known about what diderm-mycolate bacteria use to cross their outer membrane.
Type I.
Type I secretion system (T1SS or TOSS) is found in Gram-negative bacteria. It depends on chaperone activity using Hly and Tol proteins. The system activates as a signal sequence HlyA binds HlyB on the cell membrane. This signal sequence is an ABC transporter. The HlyAB complex activates HlyD which uncoils and moves to the outer cell membrane. The terminal signal is recognised by TolC in the inner membrane. The HlyA is secreted out of the outer membrane through a tunnel-like protein channel.
T1SS transports various molecules including ions, carbohydrates, drugs, proteins. The secreted molecules vary in size from the small "Escherichia coli" peptide colicin V, which is 10 kDa, to the "Pseudomonas fluorescens" cell adhesion protein LapA, which is 520 kDa. Among the most well known molecules are RTX toxins and lipase enzymes.
Type II.
Type II (T2SS) secretion system depends on the Sec or Tat system for initial secretion inside the bacterial cell. From the periplasm, proteins are secreted out of the outer membrane secretins. Secretins are multimeric (12–14 subunits) complex of pore-forming proteins. Secretin is supported by 10–15 other inner and outer membrane proteins to constitute the complete secretion apparatus.
Type III.
Type III secretion system (T3SS or TTSS) is structurally similar and related to the basal body of bacterial flagella. Seen in some of the most virulent Gram-negative bacteria such as "Salmonella", "Shigella", "Yersinia", "Vibrio", it is used to inject toxic proteins into eukaryotic cells. The structure of T3SS is often described as an injectisome or needle/syringe-like apparatus. Discovered in "Yersinia pestis", it was found that T3SS can inject toxins directly from the bacterial cytoplasm into the cytoplasm of its host's cells.
Type IV.
Type IV secretion system (T4SS or TFSS) is related to bacterial conjugation system, by which different bacteria can exchange their DNAs. The participating bacteria can be of the same or different Gram-negative bacterial species. It can transport single proteins, as well as protein-protein and DNA-protein complexes. Secretion is transferred directly from the recipient cell through the cell membranes. "Agrobacterium tumefaciens", from which it was originally discovered, uses this system to send the T-DNA portion of the Ti plasmid into plant cells, in which a crown gall (tumor) is produced as a result. "Helicobacter pylori" uses it for delivering CagA into gastric epithelial cells, to induce gastric cancer. "Bordetella pertussis", the causative bacterium of whooping cough, secretes its pertussis toxin partly through T4SS. "Legionella pneumophila" that causes legionellosis (Legionnaires' disease) has a T4SS called icm/dot (intracellular multiplication/defect in organelle trafficking genes) that transport many bacterial proteins into its eukaryotic host. More recently, it has been shown that the phytopathogen "Xanthomonas citri" utilizes its T4SS to secrete effectors that are lethal to other bacterial species, thus placing this system as a major fitness determinant of interspecies bacterial competition. The prototypic Type IVA secretion system is the VirB complex of "Agrobacterium tumefaciens".
Type V.
Type V secretion systems (T5SS) are different from other secretion systems in that they secrete themselves and only involves the outer cell membrane. For secreted protein to pass through the inner cell membrane, T5SS depends on Sec system. They have a β-barrel domain, which inserts into the outer cell membrane and forms a channel that can transport secreted protein along with it. For this activity, they are also called the autotransporter systems. When the secreted proteins are exposed outside, the autotransporters are cut off (cleaved), releasing the protein from the β-barrel domain. An example of autotransporter is the Trimeric Autotransporter Adhesins.
Type VI.
Type VI secretion systems (T6SS) were discovered by the team of John Mekalanos at the Harvard Medical School in 2006 from "Vibrio cholerae" and "Pseudomonas aeruginosa". They were recognised when mutations in the "Vibrio Cholerae" "Hcp" and "VrgG" genes caused diminished virulence and pathogenicity. In addition to their classic role as the pathogenicity factor, T6SS are also involved in defense against simple eukaryotic predators and in inter-bacteria interactions. The gene for T6SS form a gene cluster that consists of more than 15 genes. "Hcp" and "VgrG" genes are the most universal genes. Structural similarity of T6SS with the tail spike of the T4 phage suggest that the process of infection is similar to that of the phage.
Type VII.
The T7SS of diderm-LPS bacteria is the chaperone-usher pathway (CUP).
Type VIII.
The T8SS of diderm-LPS bacteria is the extracellular nucleation-precipitation (ENP) pathway.
Type IX.
Type IX secretion systems (T9SS) are found regularly in the Fibrobacteres-Chlorobi-Bacteroidetes lineage of bacteria, where member species include an outer membrane. The system is involved variably in one type of gliding motility, in the proper targeting of certain virulence factors to the cell surface, and the degradation of complex of biopolymers. T9SS has also been known as Por (porphyrin accumulation on the cell surface) secretion, after the oral pathogen Porphyromonas gingivalis. At least sixteen structural components of the system have been described, including PorU, a protein-sorting transpeptidase that removes the C-terminal sorting signal from cargo proteins and mediates their attachment instead to lipopolysaccharide.


TDBzcholine

TDBzcholine is a diazirine analog of acetylcholine that can be used to label the nicotinic acetylcholine receptor.
Mechanism of action.
TDBzcholine is able to bind to the nicotinic acetylcholine receptor. Once TDBzcholine is bound to the receptor, TDBzcholine can be activated by exposing the sample to UV light. This led to formation of a highly reactive carbene radical that can react with amino acid residues in the receptor and become covalently bound to the receptor.


Hazel Sanders

Hazel Mary Sanders (16 July 1926 – 29 December 1995) was an English cricketer who played as a right-handed batter. She appeared in 12 Test matches for England between 1949 and 1958. She played domestic cricket for Surrey.
Sanders made her debut on England's first post-war tour of Australia and New Zealand in early 1949, reaching 54, her highest Test score, in a victory over New Zealand at Auckland. She scored another half-century, against Australia, at Scarborough in 1951.
Off the field, Sanders was a biochemist, who worked on lipids at the Courtauld Institute of Biochemistry at Middlesex Hospital. She published scientific papers on Lipids and Lipid Metabolism, describing a modification of an existing scientific process using column chromatography to separate and identify lipids from human brain cell matter, allowing phosphatidylserine to be isolated more simply and quickly.


Delta-sleep-inducing peptide

Delta-sleep-inducing peptide, abbreviated DSIP, is a neuropeptide that when infused into the mesodiencephalic ventricle of recipient rabbits induces spindle and delta EEG activity and reduced motor activities.
Its aminoacid sequence is Trp-Ala-Gly-Gly-Asp-Ala-Ser-Gly-Glu. However, the gene is unknown, raising serious questions regarding the actual existence of this peptide in nature.
Discovery.
Delta-sleep-inducing peptide was first discovered in 1974 by the Swiss Schoenenberger-Monnier group who isolated it from the cerebral venous blood of rabbits in an induced state of sleep. It was primarily believed to be involved in sleep regulation due to its apparent ability to induce slow-wave sleep in rabbits, but studies on the subject have been contradictory.
DSIP-like material has been found in human breast milk.
Structure and interactions.
DSIP is an amphiphilic peptide of molecular weight 850 daltons with the amino acid motif:N-Trp-Ala-Gly-Gly-Asp-Ala-Ser-Gly-Glu-C
It has been found in both free and bound forms in the hypothalamus, limbic system and pituitary as well as various peripheral organs, tissues and body fluids. In the pituitary it co-localises with many peptide and non-peptide mediators such as corticotropin-like intermediate peptide (CLIP), adrenocorticotrophic hormone (ACTH), melanocyte-stimulating hormone (MSH), thyroid-stimulating hormone (TSH) and melanin concentrating hormone (MCH). It is abundant in the gut secretory cells and in the pancreas where it co-localises with glucagon.
In the brain its action may be mediated by NMDA receptors. In another study delta-sleep-inducing peptide stimulated acetyltransferase activity through α1 receptors in rats. It is unknown where DSIP is synthesized.
"In vitro" it has been found to have a low molecular stability with a half life of only 15 minutes due to the action of a specific aminopeptidase-like enzyme. It has been suggested that in the body it complexes with carrier proteins to prevent degradation, or exists as a component of a large precursor molecule, but as yet no structure or gene has been found for this precursor.
Evidence supports the current belief that it is regulated by glucocorticoids.
Gimble "et al." suggest that DSIP interacts with components of the MAPK cascade and is homologous to glucocorticoid-induced leucine zipper (GILZ). GILZ can be induced by Dexamethasone. It prevents Raf-1 activation, which inhibits phosphorylation and activation of ERK.
Function.
Many roles for DSIP have been suggested following research carried out using peptide analogues with a greater molecular stability and through measuring DSIP-like immunological (DSIP-LI) response by injecting DSIP antiserum and antibodies.
Roles in disease and medicine.
Safety and possible side-effects of long-term DSIP use haven't been established in clinical research studies.


Hepatitis B virus PRE alpha

The Hepatitis B virus PRE stem-loop alpha (HBV PRE SL alpha) is an RNA structure that is shown to play a role in nuclear export of HBV mRNAs.
HBV PREalpha consists of a 30 nt stem-loop, with a 5 nt apical loop. The conserved stem-loop was predicted within the HBV PRE sequence and confirmed by mutagenesis.
The exact role of this structure in nuclear export has not yet been determined.


N-acylneuraminate cytidylyltransferase

In enzymology, a N-acylneuraminate cytidylyltransferase () is an enzyme that catalyzes the chemical reaction
Thus, the two substrates of this enzyme are CTP and N-acylneuraminate, whereas its two products are diphosphate and CMP-N-acylneuraminate.
This enzyme belongs to the family of transferases, specifically those transferring phosphorus-containing nucleotide groups (nucleotidyltransferases). The systematic name of this enzyme class is CTP:N-acylneuraminate cytidylyltransferase. Other names in common use include CMP-sialate pyrophosphorylase, CMP-sialate synthase, cytidine 5'-monophosphosialic acid synthetase, CMP-Neu5Ac synthetase, CMP-NeuAc synthetase, acylneuraminate cytidyltransferase, CMP-N-acetylneuraminate synthetase, CMP-N-acetylneuraminate synthase, CMP-N-acetylneuraminic acid synthase, CMP-NANA synthetase, CMP-sialate synthetase, CMP-sialic synthetase, cytidine 5'-monophospho-N-acetylneuraminic acid synthetase, cytidine 5-monophosphate N-acetylneuraminic acid synthetase, cytidine monophosphosialic acid synthetase, cytidine monophosphoacetylneuraminic synthetase, cytidine monophosphosialate pyrophosphorylase, cytidine monophosphosialate synthetase, and acetylneuraminate cytidylyltransferase. This enzyme participates in aminosugars metabolism.
Structural studies.
As of late 2007, three structures have been solved for this class of enzymes, with PDB accession codes , , and .


Simon Cherry

Simon R. Cherry is a biomedical engineer, currently a Distinguished Professor at University of California, Davis, and a published author.
In 2016, Cherry was elected as a member to the National Academy of Engineering for "development of nuclear emission imaging and magnetic resonance technologies for medical science".


Hydroxylamine reductase

In enzymology, a hydroxylamine reductase () is an enzyme that catalyzes the chemical reaction
The 3 substrates of this enzyme are NH3, H2O, and acceptor, whereas its two products are hydroxylamine and reduced acceptor.
This enzyme belongs to the family of oxidoreductases, specifically those acting on other nitrogenous compounds as donors with other acceptors. The systematic name of this enzyme class is ammonia:acceptor oxidoreductase. Other names in common use include hydroxylamine (acceptor) reductase, and ammonia:(acceptor) oxidoreductase. This enzyme participates in nitrogen metabolism. It has 2 cofactors: FAD, and Flavoprotein.


Buphedrone

Buphedrone, also known as α-methylamino-butyrophenone (MABP), is a stimulant of the phenethylamine and cathinone chemical classes that was first synthesized in 1928. It is legal in most countries as a research chemical, as long as it is not intended for human consumption.
Chemistry.
Buphedrone is a beta-ketone and is related to the naturally occurring compounds, cathinone and cathine. It is also related to methamphetamine, differing by the β-ketone substituent (at the beta carbon) and an ethyl group replacing the methyl group at the carbon alpha to the amine.
One other name for Buphedrone is : Phenylacetoethyl-methylamine
Buphedrone as free base is very unstable; the ketone is readily reduced to a hydroxyl group, thus forming the corresponding alcohol. Structurally, this occurs when the C=O bond at the Rβ-position is converted into a C-OH bond. Because of this, it is sold as various salts, with a hydrochloride being most common.
Effects.
Buphedrone increases spontaneous rodent locomotor activity, potentiates the release of dopamine from dopaminergic nerve terminals in the brain, and causes appetite suppression. It also causes a possibly dangerous effect of decreasing subjective feeling of thirst. The effects of buphedrone have also been compared to methamphetamine, with more euphoria and less physical stimulation. Most commonly reported effects include:
Depending on the route of administration, the duration varies from approximately 2.5 (IV) to 6 hours (orally) and may be followed by unpleasant symptoms associated with withdrawal, which may include:
Legal Status.
As of October 2015 Buphedrone is a controlled substance in China.
Buphedrone is an Anlage II controlled drug in Germany.


Arbutamine

Arbutamine is a cardiac stimulant. It stimulates β adrenergic receptors.


Stem Cells (journal)

Stem Cells is a peer-review scientific journal of cell biology. It was established as The International Journal of Cell Cloning in 1983, acquiring its current title in 1993.
The journal is published by AlphaMed Press, and is currently edited by Jan Nolta (University of California). "Stem Cells" currently has an impact factor of 5.587, ranking it 4th out of 24 journals in the category "Cell & Tissue Engineering".
Abstracting and indexing.
The journal is abstracted and indexed in the following bibliographic databases:


Cahill cycle

The Cahill cycle, also known as the alanine cycle or glucose-alanine cycle, is the series of reactions in which amino groups and carbons from muscle are transported to the liver. It is quite similar to the Cori cycle in the cycling of nutrients between skeletal muscle and the liver. When muscles degrade amino acids for energy needs, the resulting nitrogen is transaminated to pyruvate to form alanine. This is performed by the enzyme alanine transaminase (ALT), which converts L-glutamate and pyruvate into α-ketoglutarate and L-alanine. The resulting L-alanine is shuttled to the liver where the nitrogen enters the urea cycle and the pyruvate is used to make glucose.
The Cahill cycle is less productive than the Cori cycle, which uses lactate, since a byproduct of energy production from alanine is production of urea. Removal of the urea is energy-dependent, requiring four "high-energy" phosphate bonds (3 ATP hydrolyzed to 2 ADP and one AMP), thus the net ATP produced is less than that found in the Cori cycle. However, unlike in the Cori cycle, NADH is conserved because lactate is not formed. This allows for it to be oxidized via the electron transport chain.
Studies have demonstrated a clinical relevance of the Cahill cycle in the development of new treatments for liver associated diseases and cancers.
Reactions.
Because skeletal muscle is unable to utilize the urea cycle to safely dispose of ammonium ions generated in the breakdown of branch chain amino acids, it must get rid of it in a different way. To do so, the ammonium is combined with free α-ketoglutarate via a transamination reaction in the cell, yielding glutamate and α-keto acid. Alanine aminotransaminase (ALT), also known as Glutamic-pyruvic transaminase (GPT), then coverts glutamate back into α-ketoglutarate, this time transferring the ammonium to pyruvate resulting from glycolysis, forming free alanine. The alanine amino acid acts as a shuttle - it leaves the cell, entering the blood stream and traveling to hepatocytes in the liver, where essentially this entire process is reversed. Alanine undergoes a transamination reaction with free α-ketoglutarate to yield glutamate, which is then deaminated to form pyruvate and, ultimately, free ammonium ion. Hepatocytes are capable of metabolizing the toxic ammonium by the urea cycle, thus disposing of it safely. Having rid the muscle cells of the ammonium ion successfully, the cycle then provides the energy-deprived skeletal muscle cells with glucose. Pyruvate formed from the deamination of glutamate in the hepatocytes undergoes gluconeogenesis to form glucose, which can then enter the bloodstream and be shuttled to the skeletal muscle tissue, thus providing it with the energy source it needs.
Function.
The Cahill cycle ultimately serves as a method of ridding the muscle tissue of the toxic ammonium ion, as well as indirectly providing glucose to energy-deprived muscle tissue. Under long periods of fasting, skeletal muscle can be degraded for use as an energy source to supplement the glucose being produced from the breakdown of glycogen. The breakdown of branch chain amino acids yields a carbon skeleton utilized for energy purposes, as well as free ammonium ions. However, its presence and physiological significance in non-mammalian land vertebrates is unclear. For example although some fish use alanine as a nitrogen carrier, the cycle is unlikely to take place due to a slower glucose turnover rate and lower release of alanine from exercising muscle tissue.
The alanine cycle also serves other purposes, such as the recycling of carbon skeletons in skeletal muscle and the liver, and participation in the transport of ammonium to the liver and conversion into urea.
Studies have demonstrated that the glucose-alanine cycle may play a direct role in regulation of hepatic (liver) mitochondrial oxidation, particularly during periods of extended fasting. Hepatic mitochondrial oxidation is a key process in the metabolism of glucose and fatty acids, involving the Citric Acid Cycle and oxidative phosphorylation, for the generation of ATP. Understanding the factors that influence hepatic mitochondrial oxidation are of great interest due to its function in mediating diseases such as Non-Alcoholic Fatty Liver Disease (NAFLD), Non-Alcoholic steatohepatitis (NASH), and Type 2 Diabetes. A current active area of research is attempting to exploit the regulatory role of hepatic mitochondrial oxidation for the purpose of developing both targeted and non targeted therapeutics for such diseases. The glucose-alanine cycle may be one of these key factors. A study performed on both rodents and humans showed that decreased alanine turnover during a 60 hour period of fasting did correlate with a notable reduction in hepatic mitochondrial oxidation, as compared to subjects who underwent a 12 hour overnight fast. The rate of oxidative activity was quantified primarily by monitoring rates of Citrate Synthase flux (VCS ), a critical enzyme in the process of mitochondrial oxidation. To confirm whether or not the glucose-alanine cycle has a causal relationship with the observed effect, a secondary group of patients, also subjected to the same fasting conditions, were subsequently injected with a dose of L-alanine. Post-infusion, the 60 hour fasted patients showed a marked increase in hepatic mitochondrial oxidation, confirming the relationship.
The glucose-alanine cycle may also be of significant clinical relevance in oncological (cancer) pathogenesis. A recent study explored the role of the glucose-alanine cycle in the metabolic reprogramming of Hepatocellular Carcinoma (HCC). HCC is the most common form of liver cancer and the third most common cause of cancer-related deaths worldwide. The search for alternative treatment options remains a lucrative area of research as current available therapeutics (surgery, radiotherapy, chemotherapy) generally have severe side effects and/or low success rates with HCC. One common characteristic of many novel alternative and/or supplementary treatments is the targeting of cellular metabolism of cancer cells, due to their general hyper-metabolic state which favors rapid growth and proliferation. In conjunction with consuming glucose at a much more rapid rate than healthy cells, cancers cells heavily rely on amino acid metabolism to satisfy their avid nutritional needs. The researchers involved in this study speculated exogenous alanine, processed via the glucose-alanine cycle, to be one of the alternative energy sources for HCC cells in a nutrient deficient environment and that this dependency can be harnessed for targeted therapy. To demonstrate this experimentally, HCC cells were cultured in vitro in a nutrient poor media and then supplied with alanine. The alanine supplication was enough to promote HCC cell growth under those conditions- a phenomena called metabolic reprogramming. Next, they performed a series of over expression and loss of function experiments and determined that specifically Glutamic Pyruvate Transaminase 1 (GPT1) is the GPT isomer primarily involved in alanine turnover in HCC cells, consistent with previous findings that GPT1 tends to be found in the liver. They proceeded by treating the metabolically reprogrammed HCC cells with Berberine, a naturally occurring inhibitor of GPT1; the observed affect was to curb ATP production and subsequently the growth of the alanine-supplied cancer cells. Their study demonstrated that components of the glucose-alanine cycle, particularly GPT1, may be a good choice as a target for alternative HCC therapies and that Berberine, as a plant- derived selective GPT1 inhibitor, has potential for use in one of these novel medicines. The concept of alanine as an alternative fuel for cancer cells was similarly demonstrated in other studies performed on pancreatic cancer cells.


Colistin

Colistin, also known as polymyxin E, is an antibiotic medication used as a last-resort treatment for multidrug-resistant Gram negative infections including pneumonia. These may involve bacteria such as "Pseudomonas aeruginosa", "Klebsiella pneumoniae", or "Acinetobacter". It comes in a form which can be injected into a vein or into a muscle, or inhaled, known as colistimethate sodium and one which is applied to the skin or taken by mouth, known as colistin sulfate. Resistance to colistin began to appear as of 2015.
Common side effects of the injectable form include kidney problems and neurological problems. Other serious side effects may include anaphylaxis, muscle weakness, and "Clostridium difficile"-associated diarrhea. The inhaled form may result in constriction of the bronchioles. It is unclear if use during pregnancy is safe for the fetus. Colistin is in the polymyxin class of medications. It works by breaking down the cytoplasmic membrane which generally results in bacterial cell death.
Colistin was discovered in 1947 and colistimethate sodium was approved for medical use in the United States in 1970. It is on the World Health Organization's List of Essential Medicines. The World Health Organization classifies colistin as critically important for human medicine. It is available as a generic medication. It is derived from bacteria of the genus "Paenibacillus".
Medical uses.
Antibacterial spectrum.
Colistin has been effective in treating infections caused by "Pseudomonas, Escherichia", and "Klebsiella" species. The following represents MIC susceptibility data for a few medically significant microorganisms:
For example, colistin in combination with other drugs are used to attack "P. aeruginosa" biofilm infection in lungs of CF patients. Biofilms have a low oxygen environment below the surface where bacteria are metabolically inactive and colistin is highly effective in this environment. However, "P. aeruginosa" reside in the top layers of the biofilm, where they remain metabolically active. This is because surviving tolerant cells migrate to the top of the biofilm via pili motility and form new aggregates via quorum sensing.
Administration and dosage.
Forms.
Two forms of colistin are available commercially: colistin sulfate and colistimethate sodium (colistin methanesulfonate sodium, colistin sulfomethate sodium). Colistin sulfate is cationic; colistimethate sodium is anionic. Colistin sulfate is stable, but colistimethate sodium is readily hydrolysed to a variety of methanesulfonated derivatives. Colistin sulfate and colistimethate sodium are eliminated from the body by different routes. With respect to "Pseudomonas aeruginosa", colistimethate is the inactive prodrug of colistin. The two drugs are not interchangeable .
Dosage.
Colistin sulfate and colistimethate sodium may both be given intravenously, but the dosing is complicated. The very different labeling of the parenteral products of colistin methanesulfonate in different parts of the world was first revealed by Li et al. Colistimethate sodium manufactured by Xellia (Colomycin injection) is prescribed in international units, but colistimethate sodium manufactured by Parkdale Pharmaceuticals (Coly-Mycin M Parenteral) is prescribed in milligrams of colistin base:
Because colistin was introduced into clinical practice over 50 years ago, it was never subject to the regulations that modern drugs are subject to, and therefore there is no standardised dosing of colistin and no detailed trials on pharmacology or pharmacokinetics: The optimal dosing of colistin for most infections is therefore unknown. Colomycin has a recommended intravenous dose of 1 to 2 million units three times daily for patients weighing 60 kg or more with normal renal function. Coly-Mycin has a recommended dose of 2.5 to 5 mg/kg colistin base a day, which is equivalent to 6 to 12 mg/kg colistimethate sodium per day. For a 60 kg man, therefore, the recommended dose for Colomycin is 240 to 480 mg of colistimethate sodium, yet the recommended dose for Coly-Mycin is 360 to 720 mg of colistimethate sodium. Likewise, the recommended "maximum" dose for each preparation is different (480 mg for Colomycin and 720 mg for Coly-Mycin). Each country has different generic preparations of colistin, and the recommended dose depends on the manufacturer. This complete absence of any regulation or standardisation of dose makes intravenous colistin dosing difficult for any physician.
Colistin has been used in combination with rifampicin, and evidence of "in-vitro" synergy exists, and the combination has been used successfully in patients. There is also in-vitro evidence of synergy for colistimethate sodium used in combination with other antipseudomonal antibiotics.
Colistimethate sodium aerosol (Promixin; Colomycin Injection) is used to treat pulmonary infections, especially in cystic fibrosis. In the UK, the recommended adult dose is 1–2 million units (80–160 mg) nebulised colistimethate twice daily. Nebulized colistin has also been used to decrease severe exacerbations in patients with chronic obstructive pulmonary disease and infection with "Pseudomonas aeruginosa".
Resistance.
Resistance to colistin is rare, but has been described. The first colistin-resistance gene in a plasmid which can be transferred between bacterial strains was found in 2011 in China and became publicly known in November 2015. The presence of this plasmid-borne "mcr-1" gene was confirmed starting December 2015 in South-East Asia, several European countries and the United States. It is produced by certain strains of the bacteria "Paenibacillus polymyxa".
, no agreement exists about how to look for colistin resistance. The uses a cut-off of 2 mg/l, whereas the British Society for Antimicrobial Chemotherapy sets a cutoff of 4 mg/l or less as sensitive, and 8 mg/l or more as resistant. No standards for measuring colistin sensitivity are given in the US.
The plasmid-borne "mcr-1" gene has been found to confer resistance to colistin. The first colistin-resistance gene in a plasmid which can be transferred between bacterial strains was found in 2011 and became publicly known in November 2015. This plasmid-borne "mcr-1" gene has since been isolated in China, Europe and the United States.
India reported the first detailed colistin-resistance study which mapped 13 colistin-resistant cases recorded over 18 months. It concluded that pan-drug resistant infections, particularly those in the blood stream, have a higher mortality. Multiple other cases were reported from other Indian hospitals. Although resistance to polymyxins is generally less than 10%, it is more frequent in the Mediterranean and South-East Asia (Korea and Singapore), where colistin resistance rates are continually increasing. Colistin-resistant "E. coli" was identified in the United States in May 2016.
Use of colistin to treat "Acinetobacter baumannii" infections has led to the development of resistant bacterial strains. which have also developed resistance to antimicrobial compounds LL-37 and lysozyme, produced by the human immune system.
It's worth noting that not all resistance to colisin and some other antibiotics is due to the presence of resistance genes. Heteroresistance, the phenomenon wherein apparently genetically identical microbes exhibit a range of resistance to an antibiotic, has been observed in some species of "Enterobacter" since at least 2016 and in some strains of "Klebsiella pneumoniae" in 2017–2018. In some cases this phenomenon has significant clinical consequences.
Adverse reactions.
The main toxicities described with intravenous treatment are nephrotoxicity (damage to the kidneys) and neurotoxicity (damage to the nerves), but this may reflect the very high doses given, which are much higher than the doses currently recommended by any manufacturer and for which no adjustment was made for renal disease. Neuro- and nephrotoxic effects appear to be transient and subside on discontinuation of therapy or reduction in dose.
At a dose of 160 mg colistimethate IV every eight hours, very little nephrotoxicity is seen. Indeed, colistin appears to have less toxicity than the aminoglycosides that subsequently replaced it, and it has been used for extended periods up to six months with no ill effects. The colistin-induced nephrotoxicity is particularly favoured in patients with hypoalbuminemia.
The main toxicity described with aerosolised treatment is bronchospasm, which can be treated or prevented with the use of beta2-agonists such as salbutamol or following a desensitisation protocol.
Mechanism of action.
Colistin is a polycationic peptide and has both hydrophilic and lipophilic moieties. These cationic regions interact with the bacterial outer membrane, by displacing magnesium and calcium bacterial counter ions in the lipopolysaccharide. Hydrophobic/hydrophilic regions interact with the cytoplasmic membrane just like a detergent, solubilizing the membrane in an aqueous environment. This effect is bactericidal even in an isosmolar environment.
Pharmacokinetics.
No clinically useful absorption of colistin occurs in the gastrointestinal tract. For systemic infection, colistin must, therefore, be given by injection.
Colistimethate is eliminated by the kidneys, but colistin is supposed to be eliminated by non-renal mechanism(s) that are as of yet not characterised.
History.
Colistin was first isolated in Japan in 1949, from a flask of fermenting "Bacillus" "polymyxa" var. "colistinus" by the Japanese scientist Koyama and became available for clinical use in 1959.
Colistimethate sodium, a less toxic prodrug, became available for injection in 1959. In the 1980s, polymyxin use was widely discontinued because of nephro- and neurotoxicity. As multi-drug resistant bacteria became more prevalent in the 1990s, colistin started to get a second look as an emergency solution, in spite of toxic effects.
Biosynthesis.
The biosynthesis of colistin requires the use of three amino acids threonine, leucine, and 2,4-diaminobutryic acid. It is important to synthesis the linear form of colistin before cycliziation. Elongation of non ribosomal peptide biosynthesis begins by a loading module and then the addition of each subsequent amino acid. The subsequent amino acids are added with the help of an adenylation domain (A), a peptidyl carrier protein domain (PCP), an epimerization domain (E), and a condensation domain (C). Cyclization is accomplished by utilizing a thioesterase. The first step is to have a loading domain, 6-methyl-heptanoic acid, associate with the A and PCP domains. Now with a C, A, and PCP domain that is associated with 2,4-diaminobutryic acid. This continues with each amino acid until the linear peptide chain is completed. The last module will have a thioesterase to complete the cyclization and form the product colistin.


Desulfofrigus oceanense

Desulfofrigus oceanense is a bacterium. It is a psychrophilic Gram-negative and sulfate-reducing bacteria with type strain Asv26T.


Diisopropyltryptamine

Diisopropyltryptamine (; also known as "N,N"-diisopropyltryptamine or DiPT) is a psychedelic hallucinogenic drug of the tryptamine family that has a unique effect. While the majority of hallucinogens affect the visual sense, DiPT is primarily aural.
Hallucinogenic properties.
DiPT's effects are primarily aural. At lower doses, Alexander Shulgin reported effects similar to a flanging or a phase shift. At medium and higher dosages, the effect of DiPT is typically a radical shift downward in perceived pitch. This shift tends to be nonlinear, in that the shift downwards varies in relation to the initial pitch. This can produce bizarre sounds and render music disharmonious. There has been an experiment involving subjects with perfect pitch, the goal of which was to determine whether the pitch difference is truly distortive or linear, the results of which indicated that there is no clear relationship between perceived pitch and actual pitch. Aside from these, the most prevalent non-auditory effect is inner ear pressure (which has been painful in some instances, for example when combined with MDMA).
Chemistry.
DiPT is a derivative of tryptamine formed by substituting isopropyl groups for the two hydrogen atoms attached to the non-aromatic nitrogen atom in the tryptamine molecule.
Legal status.
United Kingdom.
As is the case with many PiHKAL and TiHKAL drugs, it is Class A in the UK, making it illegal to possess or use.
United States.
DiPT is not scheduled at the federal level in the United States, but it could be considered an analog of 5-MeO-DiPT, in which case purchase, sale, or possession could be prosecuted under the Federal Analog Act. Some of the people arrested in Operation Web Tryp were selling DiPT.
Florida.
"DiPT (N,N-Diisopropyltryptamine)" is a Schedule I controlled substance in the state of Florida making it illegal to buy, sell, or possess in Florida.
Sweden.
Sweden's public health agency suggested classifying DiPT as a hazardous substance, on May 15, 2019.


3-Methoxy-4-hydroxyphenylglycol

3-Methoxy-4-hydroxyphenylglycol (MHPG, MOPEG) is a metabolite of norepinephrine degradation. In the brain, it is the principal norepinephrine metabolite. It is released into the blood and cerebrospinal fluid, and a blood sample of it may therefore be an indication of recent sympathetic nervous system activity.
Low levels of MHPG in the blood and cerebrospinal fluid are associated with anorexia nervosa and pathological gambling, indicating that norepinephrine may play a role in these behaviors.


Luisa Ottolini

Luisa Ottolini (born July 10, 1954, in Tortona, province of Alessandria, Italy) is an Italian physicist.
Biography.
In 1978, Luisa Ottolini graduated in Physics at the University of Pavia. From 1982 to 1986, she was the Head of the Structuristic Section at the Istituto Sperimentale dei Metalli Leggeri (I.S.M.L.) in Novara. In 1987, she activated the Strategic Project of the National Research Council of Italy (CNR) "An Ion Microprobe for Advanced Researches in the Earth Sciences" with the installation at the “Centro di Studio per la Cristallografia Strutturale” in Pavia of the first, and so far, the only one National Laboratory of Secondary Ion Mass Spectrometry (SIMS) in the Earth Sciences. Since that time she has been the Head of the SIMS Lab. Starting from 1989, she activated the National SIMS service for University and CNR Institutions offering the Earth Science Committee (05), following more than 90 research projects. In 2002-2005 she coordinated a research Unit in Pavia, sponsored by the European Framework Project EUROMELT (European Community’s Human Potential Programme, contract HPRN-CT-2002-00211). Since December 19, 2005, she has been the Head of CNR-Institute of Geosciences and Geo-resources (IGG)-Section of Pavia.
She co-authored more than 150 international ISI publications, of which 5 in "Nature"; more than 200 Abstracts at International and National Meetings, 35 monographs and inner reports.
Main scientific interests.
Her research activities mainly concerned the use of SIMS for the quantitative measurement of low-concentration constituents, of light (Lithium, Beryllium and Boron) and volatile elements (Hydrogen, Fluorine, Chlorine, Carbon) in geological samples, with particular reference to the investigation of the physical/chemical processes underlying the production of secondary ions, aiming at overcoming the limitations of the technique (interferences and non-linear effects, “matrix effects”); the development, set up and optimization of SIMS procedures for trace elements, light and volatile elements, and ultra-trace elements in the frame of petrologic, geochemical and crystal-chemical studies, with particular reference to the investigation of melt inclusions, silicate minerals, artificial glasses, chemically-complex silicate and non-silicate matrixes, experimental charges.


Chloroflexi (phylum)

The Chloroflexi or Chlorobacteria are a phylum of bacteria containing isolates with a diversity of phenotypes, including members that are aerobic thermophiles, which use oxygen and grow well in high temperatures; anoxygenic phototrophs, which use light for photosynthesis (green non-sulfur bacteria); and anaerobic halorespirers, which uses halogenated organics (such as the toxic chlorinated ethenes and polychlorinated biphenyls) as electron acceptors.
Most bacteria, in terms of diversity, are diderms and stain gram-negative, notable exceptions being "Firmicutes" (low G+C gram-positives), "Actinobacteria" (high-G+C gram-positives) and the "Deinococcus–Thermus" group (gram-positive diderms with thick peptidoglycan). In contrast, the members of the phylum Chloroflexi are monoderms, but stain mostly gram-negative.
History.
The taxon name was created in the 2001 edition of Volume 1 of Bergey's Manual of Systematic Bacteriology and is the Latin plural of the name "Chloroflexus", the name of the type genus of the phylum, a common practice.
In 1987, Carl Woese, regarded as the forerunner of the molecular phylogeny revolution, divided Eubacteria into 11 divisions based on 16S ribosomal RNA (SSU) sequences and grouped the genera "Chloroflexus", "Herpetosiphon" and "Thermomicrobium" into the "green non-sulfur bacteria and relatives", which was temporarily renamed as "Chloroflexi" in Volume One of Bergey's Manual of Systematic Bacteriology.
Chloroflexi being a deep branching phylum (see Bacterial phyla), it was considered in Volume One of Bergey's Manual of Systematic Bacteriology to include a single class with the same name, the class Chloroflexi. Since 2001, however, new classes have been created thanks to newly discovered species, and the phylum Chloroflexi is now divided as follows:
"Dehalococcoidetes" is a placeholder name given by Hugenholtz & Stackebrandt, 2004, after "Dehalococcoides ethenogenes" a species partially described in 1997.<ref name="doi10.1126/science.276.5318.1568"></ref> The first species fully described was "Dehalogenimonas lykanthroporepellens", by Moe et al. 2009, but in the description of that species the class was not made official nor were families or orders laid out as the two species share only 90% 16S ribosomal RNA identity, meaning that they could fall in different families or even orders.
Recent phylogenetic analysis of the Chloroflexi has found very weak support for the grouping together of the different classes currently part of the phylum. The six classes that make up the phylum did not consistently form a well-supported clade in phylogenetic trees based on concatenated sequences for large datasets of proteins, and no conserved signature indels were identified that were uniquely shared by the entire phylum. However, the classes Chloroflexi and Thermomicrobia were found to group together consistently by both the usual phylogenetic means and the identification of shared conserved signature indels in the 50S ribosomal protein L19 and the enzyme UDP-glucose 4-epimerase. It has been suggested that the phylum Chloroflexi "sensu stricto" should comprise only the classes Chloroflexi and Thermomicrobia, and the other four classes ("Dehalococcoidetes," Anaerolineae, Caldilineae and Ktedonobacteria) may represent one or more independent phyla branching in the neighborhood of the Chloroflexi.
Phylogeny.
The currently accepted taxonomy is based on the List of Prokaryotic names with Standing in Nomenclature (LPSN) and National Center for Biotechnology Information (NCBI). The phylogeny is based on 16S rRNA-based LTP release 132 by The All-Species Living Tree Project
Notes:
♠ Strains found at the National Center for Biotechnology Information (NCBI) but not listed in the List of Prokaryotic names with Standing in Nomenclature (LSPN).
♪ Prokaryotes where no pure (axenic) cultures are isolated or available; i.e., they are not cultivated or cannot be sustained in culture for more than a few serial passages.
Taxonomy.
Genus ""Candidatus" Chlorothrix"
Class Thermoflexia
Class Dehalococcoidia ["Dehalococcoidetes" ]
Class Anaerolineae
Class Ardenticatenia
Class Caldilineae
Class Ktedonobacteria ["Ktedobacteria" (sic) ]
Class Thermomicrobia
Class Chloroflexia
Etymology.
The name "Chloroflexi" is a Neolatin nominative case masculine plural of "Chloroflexus", which is the name of the first genus described. The noun is a combination of the Greek adjective "chloros, -a, on (χλωρός, -ά, -όν)", meaning "greenish-yellow," and the Latin masculine passive perfect participle "flexus" (of "flecto"), meaning "bent." The etymology is unrelated to chlorine, an element that was discovered in 1810 by Sir Humphry Davy and named after its pale green colour. Another phylum with the same root is "Chlorobi", whereas "Cyanobacteria" has the root "cyanos" ("κύανος"), meaning "blue-green."
Unlike some other phyla, there is no theme root in the name of genera of Chloroflexi, and in fact many genera beginning with "Chloro-" or ending in "-chloris" are either cyanobacteria or chlorobi.


Calcium imaging

Calcium imaging is a microscopy technique to optically measure the calcium (Ca2+) status of an isolated cell, tissue or medium. Calcium imaging takes advantage of calcium indicators, fluorescent molecules that respond to the binding of Ca2+ ions by changing their fluorescence properties. Two main classes of calcium indicators exist: chemical indicators and genetically encoded calcium indicators (GECI). This technique has allowed studies of calcium signalling in a wide variety of cell types. In neurons, electrical activity is always accompanied by an influx of Ca2+ ions. Thus, calcium imaging can be used to monitor the electrical activity in hundreds of neurons in cell culture or in living animals, which has made it possible to dissect the function of neuronal circuits.
Chemical indicators.
Chemical indicators are small molecules that can chelate calcium ions. All these molecules are based on an EGTA homologue called BAPTA, with high selectivity for calcium (Ca2+) ions versus magnesium (Mg2+) ions.
This group of indicators includes fura-2, indo-1, fluo-3, fluo-4, Calcium Green-1.
These dyes are often used with the chelator carboxyl groups masked as acetoxymethyl esters, in order to render the molecule lipophilic and to allow easy entrance into the cell. Once this form of the indicator is in the cell, cellular esterases will free the carboxyl groups and the indicator will be able to bind calcium. The free acid form of the dyes (i.e. without the acetoxymethyl ester modification) can also be directly injected into cells via a microelectrode or micropipette which removes uncertainties as to the cellular compartment holding the dye (the acetoxymethyl ester can also enter the endoplasmic reticulum and mitochondria). Binding of a Ca2+ ion to a fluorescent indicator molecule leads to either an increase in quantum yield of fluorescence or emission/excitation wavelength shift. Individual chemical Ca2+ fluorescent indicators are utilized for cytosolic calcium measurements in a wide variety of cellular preparations. The first real time (video rate) Ca2+ imaging was carried out in 1986 in cardiac cells using intensified video cameras. Later development of the technique using laser scanning confocal microscopes revealed sub-cellular Ca2+ signals in the form of Ca2+ sparks and Ca2+ blips. Relative responses from a combination of chemical Ca2+ fluorescent indicators were also used to quantify calcium transients in intracellular organelles such as mitochondria.
Calcium imaging, also referred to as calcium mapping, is also used to perform research on myocardial tissue. Calcium mapping is a ubiquitous technique used on whole, isolated hearts such as mouse, rat, and rabbit species.
Genetically encoded calcium indicators.
Genetically encodable calcium indicators (GECIs) are powerful tools useful for in vivo imaging of cellular, developmental, and physiological process. GECIs do not need to be loaded into cells; instead the genes encoding for these proteins can be easily transfected to cell lines. It is also possible to create transgenic animals expressing the dye in all cells or selectively in certain cellular subtypes. GECIs have been used in the studies of neuron, T-cell, cardiomyocyte, etc. Broadly speaking, GECIs can be divided into classes in which calcium detection is based on fluorescence or luminescence; however, both of these inevitably rely on fluorescent proteins as reporters, including green fluorescent protein GFP and its variants (eGFP, YFP, CFP).
Of the fluorescent variants, calcium indicator systems can be further divided into single fluorescent protein (FP) systems, and paired fluorescent protein systems. Camgaroos were one of the first developed variants involving a single protein system. Camgaroos take advantage of calmodulin (CaM), a calcium binding protein. In these structures, CaM is inserted in the middle of yellow fluorescent protein (YFP) at Y145. Previous mutagenesis studies revealed that mutations at this position conferred pH stability while maintaining fluorescent properties, making Y145 an insertion point of interest. Additionally, the N and C termini of YFP are linked by a peptide linker (GGTGGS). When CaM binds to Ca2+, the effective pKa is lowered, allowing for chromophore deprotonation. This results in increased fluorescence upon calcium binding in an intensiometric fashion. Such detection is in contrast with ratiometric systems, in which there is a change in the absorbance/emission spectra as a result of Ca2+ binding. A later developed single-FP system, dubbed G-CaMP, also invokes circularly permuted GFP. One of the termini is fused with CaM, and the other termini is fused with M13 (the calmodulin binding domain of myosin light kinase). The protein is designed such that the termini are close in space, allowing for Ca2+ binding to cause conformational changes and chromophore modulation, allowing for increased fluorescence. G-CaMP and its refined variants have nanomolar values for binding affinity. A final single protein variant is the CatchER, which is generally considered to be a lower affinity indicator. Its calcium binding pocket is quite negative; binding of the cation helps to shield the large concentration of negative charge and allows for recovered fluorescence.
In contrast to these systems are paired fluorescent protein systems, which include the prototypical Cameleons. Cameleons consist of two different fluorescent proteins, CaM, M13, and a glycylglycine linker. In the absence of Ca2+, only the donor blue-shifted fluorescent protein will be fluorescent. However, a conformational change caused by calcium binding repositions the red-shifted fluorescent protein, allowing for FRET (Forster resonance energy transfer) to take place. Cameleon indicators produce a ratiometric signal (ie. the measured FRET efficiency depends on the calcium concentration). Original variants of chameleons were originally more sensitive to Ca2+ and were acid quenched. Such shortcomings were abrogated by Q69K and V68L mutations. Both of these residues were close to the buried anionic chromophore and these mutations probably hinder protonation, conferring greater pH resistance.
Of growing importance in calcium detection are near-IR (NIR) GECIs, which may open up avenues for multiplexing different indicator systems and allowing deeper tissue penetration. NIRs rely on biliverdin-binding fluorescent proteins, which are largely derived from bacterial phytochromes. NIR systems are similar to inGCverse pericams in that both experience a decrease in fluorescence upon Ca2+ binding. RCaMPs and RGECOs are functional at 700+ nm, but are quite dim and experience high scattering. A Cameleon analog involving NIR FRET has been successfully constructed as well.
A special class of GECIs are designed to form a permanent fluorescent tag in active neurons. They are based on the photoswitchable protein Eos which turns from green to red through photocatalyzed (with violet light) backbone cleavage. Combined with the CaM, violet light photoconverts only neurons that have elevated calcium levels. SynTagMA is a synapse-targeted version of CaMPARI2.
While fluorescent systems are widely used, bioluminescent Ca2+ reporters may also hold potential because of their ability to abrogate autofluorescence, photobleaching [no excitation wavelength is needed], biological degradation and toxicity, in addition to higher signal-to-noise ratios. Such systems may rely on aequorin and the luciferin coelenterazine. Ca2+ binding causes a conformational change that facilitates coelenterazine oxidation. The resultant photoproduct emits blue light as it returns to the ground state. Colocalization of aequorin with GFP facilitates BRET/CRET (Bioluminescence or Chemiluminescence Resonance Energy Transfer), resulting in a 19 - 65 brightness increase. Such structures can be used to probe millimolar to nanomolar calcium concentrations. A similar system invokes obelin and its luciferin coelenteramide, which may possess faster calcium response time and Mg2+ insensitivity than its aqueorin counterpart. Such systems can also leverage the self-assembly of luciferase components. In a system dubbed “nano-lantern,” the luciferase RLuc8 is split and placed on different ends of CaM. Calcium binding brings the RLuc8 components in close proximity, reforming luciferase, and allowing it to transfer to an acceptor fluorescent protein.
To minimize damage to the visualized cells, two-photon microscopy is often invoked to detect the fluorescence from the reporters. The use of near-IR wavelengths and minimization of axial spread of the point function allows for nanometer resolution and deep penetration into the tissue. The dynamic range is often determined from such measurements. For non-ratiometric indicators (typically single protein indicators), it is the ratio of the fluorescence intensities obtained under Ca2+ saturated and depleted conditions, respectively. However, for ratiometric indicators, the dynamic range is the ratio of the maximum FRET efficiency ratio (calcium saturated) to the minimum FRET efficiency ratio (calcium depleted). Yet another common quantity used to measure signals produced by calcium concentration fluxes is the signal-to-baseline ratio (SBR), which is simply the ratio of the change in fluorescence (F - F0) over the baseline fluorescence. This can be related to the SNR (signal to noise ratio) by multiplying the SBR by the square root of the number of counted photons.
A special class of genetically encoded calcium indicators are designed to form a permanent fluorescent tag in active neurons. They are based on the photoswitchable protein mEos which turns from green to red when illuminated with violet light. Combined with the calcium sensor calmodulin, violet light photoconverts only neurons that have elevated calcium levels. SynTagMA is a synapse-targeted version of CaMPARI2.
Usage.
Regardless of the type of indicator used the imaging procedure is generally very similar. Cells loaded with an indicator, or expressing it in the case of a GECI, can be viewed using a fluorescence microscope and captured by a Scientific CMOS (sCMOS) camera or CCD camera. Confocal and two-photon microscopes provide optical sectioning ability so that calcium signals can be resolved in microdomains such as dendritic spines or synaptic boutons, even in thick samples such as mammalian brains. Images are analyzed by measuring fluorescence intensity changes for a single wavelength or two wavelengths expressed as a ratio (ratiometric indicators). If necessary, the derived fluorescence intensities and ratios may be plotted against calibrated values for known Ca2+ levels to measure absolute Ca2+ concentrations. Light field microscopy methods extend functional readout of neural activity capabilities in 3D volumes.


Methanosarcina sRNAs

sRNA162, sRNA154, sRNA41 are small non-coding RNA (sRNA) identified together with 248 other sRNA candidates by RNA sequencing in methanogenic archaeon "Methanosarcina mazei" Gö1. These sRNAs were further characterised. It was shown that sRNA162 can interact with both, a "cis-" and a "trans"-encoded mRNAs using two distinct domains. The sRNA overlaps the 5′UTR of the MM2442 mRNA and acts as a cis-encoded antisense RNA, and it also regulates MM2441 expression as a trans-encoded sRNA. It exhibits a regulatory role in the metabolic switch between methanol and trimethylamine as carbon and energy source. sRNA154, exclusively expressed under nitrogen deficiency, has a central regulatory role in nitrogen metabolism affecting nitrogenase and glutamine synthetase by masking the ribosome binding site or positively affecting transcript stability. sRNA41, highly expressed during nitrogen sufficiency, is capable to bind several ribosome binding sites independently within a polycistronic mRNA. It was proposed to inhibits translation initiation of all ACDS (acetyl-CoA decarbonylase/synthase complex) genes in N-dependent manner.
See also.
Bacterial sRNA involved in nitrogen metabolism: NsiR4
Other archaeal sRNAs:


Pribnow box

The Pribnow box (also known as the Pribnow-Schaller box) is a sequence of "TATAAT" of six nucleotides (thymine, adenine, thymine, etc.) that is an essential part of a promoter site on DNA for transcription to occur in bacteria. It is an idealized or consensus sequence—that is, it shows the most frequently occurring base at each position in many promoters analyzed; individual promoters often vary from the consensus at one or more positions. It is also commonly called the -10 sequence, because it is centered roughly ten base pairs upstream from the site of initiation of transcription.
The Pribnow box has a function similar to the TATA box that occurs in promoters in eukaryotes and archaea: it is recognized and bound by a subunit of RNA polymerase during initiation of transcription. This region of the DNA is also the first place where base pairs separate during prokaryotic transcription to allow access to the template strand. The AT-richness is important to allow this separation, since adenine and thymine are easier to break apart (not only due to fewer hydrogen bonds, but also due to weaker base stacking effects).
It is named after David Pribnow and Heinz Schaller.


3,5-Dihydroxyphenylpropionoic acid

3,5-Dihydroxyphenylpropionoic acid is a metabolite of alkylresorcinols, first identified in human urine and can be quantified in urine and plasma, and may be an alternative, equivalent biomarker of whole grain wheat intake.


Hormone response element

A hormone response element (HRE) is a short sequence of DNA within the promoter of a gene, that is able to bind to a specific hormone receptor complex and therefore regulate transcription. The sequence is most commonly a pair of inverted repeats separated by three nucleotides, which also indicates that the receptor binds as a dimer. Specifically, HRE responds to steroid hormones, as the activated steroid receptor is the transcription factor binding HRE. This regulates the transcription of genes signalled by the steroid hormone.
A gene may have many different response elements, allowing complex control to be exerted over the level and rate of transcription.
HRE are used in transgenic animal cells as inducers of gene expression.
Examples of HREs include estrogen response elements (EREs) and androgen response elements (AREs).


Metaproscaline

Metaproscaline, or 3,4-dimethoxy-5-propoxyphenethylamine, is a lesser-known psychedelic drug. It is an analog of proscaline. Metaproscaline was first synthesized by Alexander Shulgin. In his book "PiHKAL (Phenethylamines i Have Known And Loved)", the dosage and the duration are unknown. Metaproscaline produces few to no effects. Very little data exists about the pharmacological properties, metabolism, and toxicity of metaproscaline.


3-Carboxy-cis,cis-muconic acid

3-Carboxy-"cis","cis"-muconic acid is a metabolite of the catechin degradation by "Bradyrhizobium japonicum".
The enzyme 3-carboxy-"cis","cis"-muconate cycloisomerase uses 2-carboxy-2,5-dihydro-5-oxofuran-2-acetate to produce 3-carboxy-"cis","cis"-muconate.
The enzyme carboxy-"cis","cis"-muconate cyclase uses 3-carboxy-2,5-dihydro-5-oxofuran-2-acetate to produce 3-carboxy-"cis","cis"-muconate.
The enzyme protocatechuate 3,4-dioxygenase uses 3,4-dihydroxybenzoate and O2 to produce 3-carboxy-"cis","cis"-muconate.


Setifer


GRIN2C

Glutamate [NMDA] receptor subunit epsilon-3 is a protein that in humans is encoded by the "GRIN2C" gene.
Function.
N-methyl-D-aspartate (NMDA) receptors are a class of ionotropic glutamate receptors. NMDA 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 heteromers composed of the key receptor subunit NMDAR1 (GRIN1) and 1 or more of the 4 NMDAR2 subunits: NMDAR2A (GRIN2A), NMDAR2B (GRIN2B), NMDAR2C (GRIN2C), and NMDAR2D (GRIN2D).
Interactions.
GRIN2C has been shown to interact with DLG4 and DLG3.


Carpindolol

Carpindolol is a beta blocker.


Porphobilinogen

Porphobilinogen (PBG) is an organic compound that occurs in living organisms as an intermediate in the biosynthesis of porphyrins, which include critical substances like hemoglobin and chlorophyll.
The structure of the molecule can be described as molecule of pyrrole with sidechains substituted for hydrogen atoms at positions 2, 3 and 4 in the ring (1 being the nitrogen atom); respectively, an aminomethyl group , an acetic acid (carboxymethyl) group , and a propionic acid (carboxyethyl) group .
Biosynthesis.
In the first step of the porphyrin biosynthesis pathway, porphobilinogen is generated from aminolevulinate (ALA) by the enzyme ALA dehydratase.
Metabolism.
In the typical porphyrin biosynthesis pathway, four molecules of porphobilinogen are concatenated by carbons 2 and 5 of the pyrrole ring (adjacent to the nitrogen atom) into hydroxymethyl bilane by the enzyme porphobilinogen deaminase, also known as hydroxymethylbilane synthase.
Pathologies.
Acute intermittent porphyria causes an increase in urinary porphobilinogen.


Peter Twumasi

Peter Twumasi (born May 25, 1974) is a Ghanaian biochemist, author and professor at the Kwame Nkrumah University Of Science and Technology. He is currently the Director General of the National Sports Authority of Ghana.
He was the Head of Department of Biochemistry and Biotechnology, College of Science at KNUST.
Education.
Peter had his undergraduate studies at the Kwame Nkrumah University of Science and Technology where obtained a bachelors degree in biochemistry. He continued to pursue a masters and doctor of philosophy degree at Wageningen University and Research Centre in the Netherlands. Whilst in Wageningen University and Research, he developed an Apoptotic Model in Zinnia Plant Cell Culture System, which is today considered the best model for apoptotic and programmed cell death studies worldwide in animals and plants alike.
Career.
In 2007, he started his career path as a lecturer in the Kwame Nkrumah University of Science and Technology.He taught biochemistry in the university. In his years as a lecturer, he served as a Senior Lecturer, Research Fellow and Visiting Lecturer, Head of the Department of Biochemistry and Biotechnology at KNUST from 2017 to 2019.> He was appointed as the Director General of National Sports Authority by the president of Ghana in 2018.
Peter is a CV Raman Research Fellow in India; and as part of this he spent three (3) months at the Amity University in Uttar Pradesh, India, as visiting Lecturer/Researcher. His research focuses in areas of biochemistry, molecular biology, biotechnology, microbiology, health and environment, and sports have resulted in over 60 publications. He has successfully supervised several hundreds of undergraduate and postgraduate (masters and PhD) theses, with some outcomes published in scientific journals. He has written five books and tens of articles in dailies on science and society. His recent memoir entitled “Rising from the Farmhouse” was launched in 2019 by the Vice President of Ghana, Dr Mahamudu Bawumia.
He initiated the Laboratory and Office Equipment Transfer Initiative (LOETI) Programme which attracted molecular, biotechnology and food science equipment worth GHS 593,544.00 for the Biochemistry and Food Science Laboratories in 2009. Among the assorted advanced laboratory equipment included PCR machines, DNA sequences, centrifuges, rotary shakers, UV Spectrophotometers, DNA scanners, micropipettes, laminar flowhoods and chambers, etc. This significant contribution initiated advanced DNA and molecular research and teaching in the Department of Biochemistry and Biotechnology and other adjoining Departments at KNUST. Today KNUST prides itself to be among global leaders in making contributions to globally new frontiers in molecular genetic and DNA research.
He is a member of the American Society for Microbiology (ASM), American Society of Plant Biologists (ASPB), Alumni Association for Graduates and Professionals of Wageningen University and Research.He was the Kumasi Branch President for the Ghana Science Association from 2011-2015 during which he initiated the famous GSA Kumasi Branch “One-day Research Seminar and Poster Presentations” which had its 8th Edition held in April 2019 in Kumasi. He has always been an active Member of GSA, supported the Branch activities in divers ways (including funding) and chaired a number of conference/poster sessions and press releases at both local and national meetings or conferences of GSA.


Regenerative Medicine (journal)

Regenerative Medicine is a peer-reviewed medical journal covering stem cell research and regenerative medicine. It was established in 2006 and is published by Future Medicine. The editor-in-chief is Chris Mason (University College London).
"Regenerative Medicine" has an online sister community site called RegMedNet.RegMedNet is a free-to-join website that publishes news on regenerative medicine and cell therapy research, policy and business, editorials from leaders in the field and free educational webinars.
Abstracting and indexing.
The journal is abstracted and indexed in Biological Abstracts, BIOSIS Previews, Biotechnology Citation Index, Chemical Abstracts, EMBASE/Excerpta Medica, EMCare, Index Medicus/MEDLINE/PubMed, Science Citation Index Expanded, and Scopus. According to the "Journal Citation Reports", the journal has a 2016 impact factor of 2.868, ranking it 15th out of 21 journals in the category "Cell & Tissue Engineering" and 23rd out of 77 journals in the category "Engineering, Biomedical".


Overflow metabolism

Overflow metabolism refers to the seemingly wasteful strategy in which cells incompletely oxidize their growth substrate (e.g. glucose) instead of using the respiratory pathway, even in the presence of oxygen. As a result of employing this metabolic strategy, cells excrete (or "overflow") metabolites like lactate, acetate and ethanol. Incomplete oxidation of growth substrates yields less energy (e.g. ATP) than complete oxidation through respiration, and yet overflow metabolism - known as the Warburg effect in the context of cancer - occurs ubiquitously among fast-growing cells, including bacteria, fungi and mammalian cells.
Based on experimental studies of acetate overflow in Escherichia coli, recent research has offered a general explanation for the association of overflow metabolism with fast growth. According to this theory, the enzymes required for respiration are more costly than those required for partial oxidation of glucose. That is, if the cell were to produce enough of these enzymes to support fast growth with respiratory metabolism, it would consume much more energy, carbon and nitrogen (per unit time) than supporting fast growth with an incompletely oxidative metabolism (e.g. fermentation). Given that cells have limited energy resources and fixed physical volume for proteins, there is thought to be a trade-off between efficient energy capture through central metabolism (i.e. respiration) and fast growth achieved through high central-metabolic fluxes (e.g. through fermentation as in yeast).
As an alternative explanation, it was suggested that cells could be limited by the rate with which they can dissipate Gibbs energy to the environment. Using combined thermodynamic and stoichiometric metabolic models in flux balance analyses with (i) growth maximization as objective function and (ii) an identified limit in the cellular Gibbs energy dissipation rate, correct predictions of physiological parameters, intracellular metabolic fluxes and metabolite concentrations were achieved.


Methanobactin

Methanobactin (mb) is a class of copper-binding and reducing chromophoric peptides initially identified in the methanotroph "Methylococcus capsulatus" Bath - and later in "Methylosinus trichosporium" OB3b - during the isolation of the membrane-associated or particulate methane monooxygenase (pMMO). It is thought to be secreted to the extracellular media to recruit copper, a critical component of methane monooxygenase, the first enzyme in the series that catalyzes the oxidation of methane into methanol. Methanobactin functions as a chalkophore, similar to iron siderophores, by binding to Cu(II) or Cu(I) then shuttling the copper into the cell. Methanobactin has an extremely high affinity for binding and Cu(I) with a "K"d of approximately 1020 M−1 at pH 8.
Additionally, methanobactin can reduce Cu(II), which is toxic to cells, to Cu(I), the form used in pMMO. Moreover, different species of methanobactin are hypothesized to be ubiquitous within the biosphere, especially in light of the discovery of molecules produced by other type II methanotrophs that similarly bind and reduce copper (II) to copper (I).
Strains of Methanobactin.
OB3b.
Methanobactin OB3b is a commonly studied methanobactin. It has a molecular weight of 1154Da when metal free. OB3b is composed of 9 amino acid residues with two oxazolone rings, which take part in binding to copper ions. The oxazalone rings are susceptible to cleavage under low pH conditions, which releases any metal ion bound to the rings. Copper is bound and reduced at a tetradentate binding site composed of 2 oxazolone rings and 2 modified enethiol groups. In particular, the origin and function of these oxazolone rings in methanobactin OB3b has been the subject of research, since these domains appear unique.
Recently, it has been suggested that mb OB3b is derived from a small, ribsomally-produced peptide precursor with the sequence of L-C-G-S-C-Y-P-C-S-C-M. Functional mbOB3b is composed of (isobutyl group)-(Oxazolone ring A)-G-S-C-Y-(Oxazolone ring B)-S-M. (Note that some specimens of mBOB3b are found without the C-terminal methionine and appear fully functional.)
It has been argued that the chromophoric rings of this particular species of methanobactin enable mbOB3b to bind and reduce other metals. For example, mbOB3b can reduce Ag(I) to Ag(0), Au(III) to Au(0), Cr(VI) to Cr(III), and Hg(II) to Hg(I); it is also able to bind Co(II), Zn (II), Mn(II), Pb(II), and U(IV). Because of this, it is possible that methanobactin may have several medical and environmental applications as a metal chelator and reducing agent.
The mechanism of metal reduction is currently undetermined. It has been shown that the tetradentate binding configuration of copper(I) in mbOB3b necessitates the ligation of a water molecule to the copper ion as a ligand. This has been used to argue that water is the source of electrons for reducing the bound metal ion. Others have suggested that the disulfide bridge in methanobactin's structure is the source of the electron, though XPS has shown that this bond is still intact in copper-bound methanobactin. The source of this reducing electron remains elusive at the moment.
SB2.
Methanobactin SB2 is produced by "Methylocystis" bacteria. SB2 is much smaller than OB3b with a molecular weight of 851Da when metal free. SB2 contains one imidazole ring and one oxazalone ring as well as a sulfate group that are thought to partake in binding copper.


Austin L. Wahrhaftig

Austin Levy Wahrhaftig (May 5, 1917 – November 11, 1997) was an American chemist and mass spectrometrist known for his development of the quasi-equilibrium theory of fragmentation of molecular ions. The Wahrhaftig diagram that illustrates the relationship between internal energy and unimolecular ion decomposition is named after him.
Early life and education.
Wahrhaftig was born in Sacramento, California where he attended grade school, high school, and two years at Sacramento Junior College. He attended the University of California, Berkeley where he did undergraduate research with Joel Hildebrand and received an A.B. in chemistry in 1938.
He went to graduate school at the California Institute of Technology where he worked under Richard M. Badger and Verner Schomaker . He received his Ph.D. in 1941. He was a research fellow at Caltech from 1941 to 1945.
He then worked at the Wright Air Development Center in Pasadena, California, and as a University Fellow at the Ohio State University with Herrick L. Johnston.
Academic career.
Wahrhaftig joined the faculty at the Chemistry Department at the University of Utah in 1947 where he rose through the ranks and spent the rest of his career. He retired to become an emeritus professor in 1987.


Leone N. Farrell

Leone Norwood Farrell (1904 – 1986) was a Canadian biochemist and microbiologist who identified microbial strains of industrial importance and developed innovative techniques for the manufacture of vaccines and antibiotics. Her inventions enabled the mass production of the polio vaccine.
Early life and education.
Farrell was born in Monkland, Ontario in 1904 and moved to Toronto as a child. She attended Parkdale Collegiate Institute, earning academic prizes in English and history and a science scholarship. She completed her MA on the chemistry of fermentation in 1929 at the University of Toronto. She obtained a PhD in biochemistry from the University of Toronto in 1933, which was rare for women at the time.
Research.
Farrell studied yeasts found in honey at the National Research Council of Canada and worked at the London School of Hygiene and Tropical Medicine following her PhD. She was recruited to Toronto's Connaught Research Laboratories in 1934. At Connaught, she worked on a team focused on developing toxoid vaccines for staphylococcus. Upon turning her attention to the pertussis vaccine, she developed a method of rocking bacterial cultures to stimulate growth of the bacteria and increase yield.
She began studying dysentery toxin in 1941 for use as a vaccine due to the wartime rise in infections. In 1943, Connaught undertook a research program to increase penicillin production for the war effort and Farrell identified a strain of penicillium that allowed increased yield of antibiotic. Following the war, she continued her efforts to improve penicillin production.
In 1953, she and her team undertook the challenging task of producing live virus for the polio vaccine in bulk quantities. After months of experimentation, she adapted her rocking method (now termed the Toronto Method) to greatly increase the yield of live virus. The live polio virus was then shipped to the United States to be killed for use in Jonas Salk's field trials, as the Toronto team was the only one that could produce the virus in large enough quantities. When Salk travelled to Toronto to meet the team, Farrell was not allowed to attend the reception because it was held in a room reserved for men only.
A prototype of Farrell's "rocking bottle" equipment was later included in an exhibition at the Smithsonian Institute about polio.
Farrell continued to lead her team, making improvements to the vaccine and its use, as well as developing a method of increasing the production of penicillin. She conducted research and wrote scientific papers about diseases and vaccines, and retired in 1969. Her colleagues describe her as "a very serious person" possessed of "knowledge and mental fertility"; "She was a classic researcher and disciplined in her work to the extent that she knew you laid out a plan and followed it carefully for things to get done."
Personal life.
Farrell was remembered as 'very much a lady' by her colleagues and as "a thoroughly charming and pleasant person" by her family. She never married, and lived by herself. Near the end of her life she suffered from dementia; she died in hospital in the presence of family in 1986.


Tees Renewable Energy Plant

Tees Renewable Energy Plant is a proposed biomass fueled power station situated on the River Tees at Teesport in Redcar and Cleveland, North East England. The plant will operate alongside other renewable energy units and industrial processes operating in the Northeast of England Process Industry Cluster (NEPIC)
Development.
The station would burn of woodpellets per year, sustainably sourced and primarily imported from Europe and America. This would generate 299 megawatts of electricity, enough to power 600,000 homes. If constructed the plant would be one of the largest dedicated wood pellet biomass power station in the United Kingdom, and one of the largest ever biomass-fueled power stations in the world. It is expected to save 1.2 million tonnes of carbon dioxide per year, accounting for 5.5% of the UK's renewables target.
Redcar and Cleveland borough council approved the scheme in November 2008, before the government gave their consent in July 2009. The station is expected to cost £650 million to construct, employing 600 people during its three-year construction period. The station is planned to be opened for commercial operation in 2020.
MGT sold the plant to Macquarie Group and Danish pension fund PKA in 2016, and construction started, with expected completion in 2020.


Acetoacetyl-CoA

Acetoacetyl CoA is the precursor of HMG-CoA in the mevalonate pathway, which is essential for cholesterol biosynthesis. It also takes a similar role in the ketone bodies synthesis (ketogenesis) pathway of the liver. In the ketone bodies digestion pathway (in the tissue), it is no longer associated with having HMG-CoA as a product or as a reactant.
It is created from acetyl-CoA, a thioester, which reacts with the enolate of a second molecule of acetyl-CoA in a Claisen condensation reaction, and it is acted upon by HMG-CoA synthase to form HMG-CoA. During the metabolism of leucine, this last reaction is reversed. Some individuals may experience Acetoacetyl-CoA deficiency. This deficiency is classified as a disorder ketone body and isoleucine metabolism that can be inherited.
References.
See also:


Bamboo mosaic virus satellite RNA cis-regulatory element

The bamboo mosaic virus satellite RNA cis-regulatory element is an RNA element found in the 5' UTR of the genome of the bamboo mosaic virus. This element is thought to be essential for efficient RNA replication.