Klaus H. Hofmann

Klaus H. Hofmann (February 21, 1911 – December 25, 1995) was an American biological chemist and medical researcher.
The New York Times called Hofmann an "expert on synthesis of body compounds". His career was highlighted by synthesis of a prototype birth control pill, isolation and structural characterization of biotin (vitamin H), determination of the lysine specificity of the pancreatic protease trypsin (an attribute that made it the enzyme of first choice in protein sequence determinations), the first chemical synthesis of a fully biologically-active portion of the peptide hormone (adrenocorticotopic hormone - ACTH), and structure-function studies on ribonuclease (RNase).
Early life and entry to science.
Hofmann was born in Germany but when his father died, his mother returned with her one-year-old son to her family home in Switzerland. The family was business oriented but Klaus was determined to pursue a career in science. He studied steroid chemistry at the Federal Institute of Technology in Zürich (ETH) in the laboratories of Leopold Ružička. Here he developed a friendship with another faculty member, Tadeus Reichstein from whom he learned laboratory technique. For his postdoctoral experience he traveled to the United States to work with Max Bergmann on peptides, an entirely new field for him. From there he migrated across the street to the laboratory of Vincent du Vigneaud where he was introduced to a new vitamin, Biotin.
The war years.
What was meant to be a short stay in the US turned into a much longer one as a result of World War II. Switzerland, ringed by hostile forces, advised Hofmann, an officer in the Swiss militia, not to return for the course of the war. He spent the war years working as a guest at Ciba Pharmaceutical Company in New Jersey. From there he moved to the University of Pittsburgh at a time when the institution was trying to build a research reputation.
A scientific home in Pittsburgh.
In a few short years, the Dean of the School of Medicine, himself a professor of Biochemistry, invited Hofmann to become Chairman of the Department.
From the moment he took the position of Chairman of Biochemistry, it became clear that although he would always be a son of Switzerland, the United States offered him career opportunities he could never hope for in a small country like Switzerland. The US was to become his permanent home. The burgeoning field of peptide chemistry became his scientific focus and, in his own words, he fell in love with a molecule that was known to stimulate the adrenal cortex to produce the very steroids that had so fascinated him in Reichstein's laboratory. That molecule, not yet isolated, was ACTH and the love affair was lifelong. Despite detours into other areas, he kept returning to ACTH. In the last years before his death, he was developing methods to isolate the ACTH receptor.
Areas of scientific accomplishments.
Steroid Chemistry.
As a PhD student in the laboratories of future Nobel Laureates, Leopold Ruzicka and Tadeus Reichstein in Zürich, Hofmann synthesized a number of compounds related to terpenes, the hypothetical building block of steroids. One of these was a dehydroandrosterone derivative, a prototype for the birth control pill. Unfortunately the biological basis for reproduction was not known for many years subsequent to this and therefore the importance of this compound was not recognized.
Trypsin.
While working in the laboratory of Max Bergmann at Rockefeller Institute, now Rockefeller University, Hofmann synthesized analogs of the amino acid lysine and proved that the enzyme trypsin cleaves linkages involving the carboxyl group of that amino acid.
Biotin.
Subsequently, with Vincent du Vigneaud, he used the newly developed technique of chromatography that he had learned while a student in Zürich, to isolate and then crystallize biotin. This work began a theme that continued throughout his career of determining the importance of sulfur in biologically active structures. He applied this to peptides as well.
Peptide synthesis/ACTH.
The first chemical synthesis of an active peptide hormone, the nine amino acid cyclic peptide, oxytocin, was achieved in 1954 by du Vigneaud for which he was awarded the Nobel Prize. At the same time, the isolation and structure determination of the anterior pituitary hormone, ACTH, was being pursued in three laboratories. The peptide was eventually determined to be 39 amino acids in length, however enzymatic and mild acid cleavage suggested that a structure comprising only the first 24 amino acids had full biological activity. It was apparent from the outset that ACTH contained the amino acid Arginine and thus methods had to be developed for the incorporation of this basic amino acid into peptides. Hofmann and his group set about this task. Their efforts led to the synthesis of the melanocyte stimulating hormone, β-MSH, which corresponds to the first 13 amino acids of ACTH and to the synthesis of a fully active ACTH peptide corresponding to the amino acid sequence of the first 23 amino acids.
In the course of the peptide synthetic work on ACTH, a novel chain cleavage was observed at an acyl-proline linkage while removing protecting groups using metallic sodium in liquid ammonia. This unexpected reaction has subsequently proved useful in special analytical cases.
RNaseA.
In 1959, Fred Richards discovered that a proteolytic enzyme, Subtilisin, had the ability to cleave the enzyme Ribonuclease A into two components, a peptide corresponding to the first 20 amino acids of the enzyme (S-Peptide) and the remainder of the protein (S-Protein). When separated from one another, each piece was inactive but when they were simply mixed together, full enzymatic activity was restored. Hofmann speculated that this system might be a model for the way peptide hormones interact with their receptors. Structure-function studies with ACTH were complicated by the necessity to assess activity in the whole animal. The S-Peptide:S-Protein system afforded a simple system with none of the biological complications inherent in testing ACTH analogs.
To study which amino acids might be important in establishing the binding between peptide hormones and their receptors, Hofmann and his group began a systematic evaluation of the contributions each amino acid in the S-Peptide molecule made to the binding with S-Protein. The ability of synthetic analogs of S-Peptide to activate S-Protein correlated well with those of synthetic ACTH analogs to elicit hormonal activity: 1) only a portion of the S-Peptide chain was essential for re-establishing full activity with the S-Protein; 2) methionine was not important; 3) substituting one particular amino acid in the peptide not only destroyed the activity of the peptide but created an antagonist as well.
Once it was established that peptide hormone receptors resided on the plasma membrane of cells, direct studies of the activity of ACTH derivatives that had so long eluded researchers finally became a reality. Hofmann and his colleagues isolated plasma membranes from beef adrenals and were able to conduct structure-activity studies with synthetic analogs of ACTH. Importantly they found that substituting Phenylalanine for theTryptophan residue in position 9 produced a peptide that bound to the ACTH receptor without activating it, i.e. and ACTH antagonist.
Return to Biotin receptor isolation.
Hofmann came full circle to his early work on biotin when he attached this vitamin to insulin. He spent a sabbatical leave in Aachen in Helmut Zahn's laboratory to learn techniques for modifying insulin). Using this information, he was able to chemically attach biotin to one of the three Lys residues of the insulin chains, thus producing an insulin that would bind to columns of avidin-Sepharose. The biotinyl-insulin receptor complex could then be displaced by biotin. With this tool, Hofmann and his coworkers successfully isolated a fully active insulin receptor. His final work was directed toward isolation of the ACTH receptor using the same approach used on the insulin receptor but by this time his health was in decline.
Distinctions.
Hofmann was the founder and the director of Protein Research Laboratory at the School of Medicine at University of Pittsburgh, a member of the National Academy of Sciences, Professor Emeritus of Experimental Medicine and Biochemistry at the University of Pittsburgh School of Medicine, and a member of American Association for the Advancement of Science.
Awards and distinctions.
Hoffman was a member of
Hoffman was recognized with the following awards:


Boulet Asphyxiant

The Boulet Asphyxiant was a rumoured Russian chemical weapon during the Crimean War. The rumour was first found in the French newspaper "Atlas" before spreading to English-language publications.
According to the rumour, the Asphyxiant was developed by a French chemical researcher, M. Fortier, in 1839. He approached the Minister of Marine, who refused to accept the design, noting "the great number of means for the destruction of human life already existing", and the proposal ended there. The same proposal was made again in 1842, this time by a M. Champion, and again rejected, ending the matter until Champion "repaired his broken fortunes in Russia".
Fortier's Asphyxiant was then allegedly discovered during the Crimean War after the Battle of Sinop; those Turkish sailors who escaped reported that the Russians were using Greek fire. This was treated as humour until a French engineer examined the destroyed ships and found that the weapons used against them were new and unknown, sending fragments to his commander, who served with an officer who had been on the Council of the Marine when Fortier made his initial proposal. The Asphyxiant, according to the rumour, was a liquid fire that exploded under the water's surface, producing a gas that suffocated anyone on the surface. The rumour was countered by allegations amongst British forces that they had invented a secret device of their own, MacIntosh's Portable Buoyant Wave Repressor, which suppressed waves.


Parasympatholytic

A parasympatholytic agent is a substance or activity that reduces the activity of the parasympathetic nervous system. (The parasympathetic nervous system is often colloquially described as the "Feed and Breed" or "Rest and Digest" portion of the autonomic nervous system. The parasympathetic nervous system becomes strongly engaged during or after a meal and during times when the body is at rest.)
The term parasympatholytic typically refers to the effect of a drug, although some poisons act to block the parasympathetic nervous system as well. Most drugs with parasympatholytic properties are anticholinergics.
"Parasympatholytic" and sympathomimetic agents have similar but not identical effects. For example, both cause mydriasis, but parasympatholytics reduce accommodation (cycloplegia), whereas sympathomimetics do not.
Clinical significance.
Parasympatholytic drugs are sometimes used to treat slow heart rhythms (bradycardias or bradydysrhythmias) caused by myocardial infarctions or other pathologies, as well as to treat conditions that cause bronchioles in the lung to constrict, such as asthma. By blocking the parasympathetic nervous system, parasympatholytic drugs can increase heart rate in patients with bradycardic heart rhythms, and open up airways and reduce mucous production in patients suffering from asthma.


Charles Holland (actor)

Charles Holland (12 March 1733 – 7 December 1769) was an English actor, born in Chiswick, the son of a baker.
Life.
Holland made his first appearance on the stage in the title role of Oroonoko at Drury Lane in 1755, John Palmer, Richard Yates and Susanna Cibber being in the cast. He played under David Garrick, and was the original Florizel in the latter's adaptation of Shakespeare's "The Winter's Tale".
Holland died from smallpox at the age of 36. He did not marry. He was engaged to the actress Jane Pope, but she broke off the engagement when she found him boating at Richmond with the actress Sophia Baddeley. He was known for having affairs; the one with Mrs K. Earle led her husband, William Earle, to prosecute Holland successfully.
Garrick thought highly of him, and wrote a eulogistic epitaph for his monument in St Nicholas Church, Chiswick. His nephew, Charles Holland (1768–1849) was also an actor, who played with Sarah Siddons and Edmund Kean.


Bouvardin

Bouvardin is a bicyclic hexapeptide isolated from "Bouvardia ternifolia". Its chemical formula is C40H48N6O10. It is derived from the amino acid sequence Ala-Ala-Tyr-Ala-Tyr-Tyr. It has demonstrated certain anti-cancerous activities by inhibiting protein synthesis through inhibition of 80S ribosomes (eukaryotic ribosomes).
The synthetic derivative of bouvardin SVC112 suppresses cancer stem cells and inhibits growth in head and neck squamous cell carcinoma.


NRON

NRON also known as ncRNA repressor of the nuclear factor of activated T cells is a non-coding RNA involved in repressing NFAT. The function of this ncRNA was identified by a large-scale screen of 512 non-coding RNAs discovered in earlier EST sequencing projects.
Each of the RNAs that were conserved between human and mouse were knocked down using shRNAs. The resulting cell-lines were screened for changes in activity of NFAT.


Beta-3 adrenergic antagonist

A Beta-3 adrenergic antagonist (β3-adrenoceptor antagonist) is an adrenergic antagonist which blocks the Beta-3 adrenergic receptors of cells, with either high specificity (an antagonist which is selective for β3 adrenoceptors) like L-748,328, L-748,337 and SR 59,230A or non-specifically (an antagonist for β3 and for β1 or β2 adrenoceptors) like the non-selective betablocker Carvedilol.


LPAR2

Lysophosphatidic acid receptor 2 also known as LPA2 is a protein that in humans is encoded by the "LPAR2" gene. LPA2 is a G protein-coupled receptor that binds the lipid signaling molecule lysophosphatidic acid (LPA).
Function.
This gene encodes a member of family I of the G protein-coupled receptors, as well as the EDG family of proteins. This protein functions as a lysophosphatidic acid (LPA) receptor and contributes to Ca2+ mobilization, a critical cellular response to LPA in cells, through association with Gi and Gq proteins.
Interactions.
LPAR2 has been shown to interact with TRIP6.


FEBS Open Bio

FEBS Open Bio is a monthly peer-reviewed open access scientific journal covering research and education in molecular and cellular life sciences. It was established in 2011 and is published by John Wiley & Sons on behalf of the Federation of European Biochemical Societies (FEBS). According to the journal, papers are not to be excluded on the basis of lack of perceived importance.
Articles originally submitted to other FEBS journals ("FEBS Letters", "The FEBS Journal", and "Molecular Oncology") can be transferred to this journal with their original reviewer reports, without the need to resubmit or reformat the manuscript.
Abstracting and indexing.
The journal is abstracted and indexed in:
According to the "Journal Citation Reports", the journal has a 2015 impact factor of 2.101, ranking it 197th out of 289 journals in the category "Biochemistry & Molecular Biology".


Francis Russell, 4th Earl of Bedford

Francis Russell, 4th Earl of Bedford PC (1587 – 9 May 1641) was an English nobleman and politician. He built the square of Covent Garden, with the piazza and church of St. Paul's, employing Inigo Jones as his architect. He is also known for his pioneering project to drain The Fens of Cambridgeshire.
Early life.
He was the only son of William Russell, 1st Baron Russell of Thornhaugh and his wife Elizabeth Long, to which barony he succeeded in August 1613. For a short time previously he had been Member of Parliament for the borough of Lyme Regis. In 1623 he was made Lord Lieutenant of Devon and on 3 May 1627 became Earl of Bedford on the death of his cousin Edward Russell, 3rd Earl of Bedford.
In 1621 Russell was one of the thirty-three peers who petitioned James I on the prejudice caused to the English peerage by the lavish grant of Irish and Scottish titles of nobility. In 1628, during the debates on the "Petition of Right", he supported the demands of the House of Commons, and was a member of the committee which reported against the king's right to imprison. In May he was sent down to Devon, ostensibly to assist in refitting the fleet returned from Rochelle, but according to report, on account of his opposition in the House of Lords. Bedford was one of the three peers implicated in the circulation of Sir Robert Dudley's "Proposition for His Majesty s Service" (the others being William Seymour, Earl of Hertford and John Holles, 1st Earl of Clare), was arrested on 5 November 1629, and was brought before the Star-chamber. The prosecution, however, was dropped when the real nature of the paper was discovered, and Bedford was quickly released.
Politician of the parliamentary crisis.
The Short Parliament meeting in April 1640 found the earl as one of the King Charles I leading opponents. He was greatly trusted by John Pym and Oliver St John, and is mentioned by Clarendon as among the "great contrivers and designers" in the House of Lords. In July 1640 he was among the peers who wrote to the Scottish leaders refusing to invite a Scottish army into England, but promising to stand by the Scots in all legal and honourable ways. His signature was afterwards forged by Thomas, Viscount Savile, in order to encourage the Scots to invade England. In the following September he was among those peers who urged Charles to call a parliament, to make peace with the Scots, and to dismiss his obnoxious ministers; and was one of the English commissioners appointed to conclude the Treaty of Ripon.
When the Long Parliament met in November 1640, Bedford was generally regarded as the leader of the parliamentarians. In February 1641 he was made a privy councillor, and during the course of some negotiations was promised the office of Lord High Treasurer. He was essentially a moderate man, and seemed anxious to settle the question of the royal revenue in a satisfactory manner. He did not wish to alter the government of the church, was on good terms with Archbishop Laud, and, although convinced of the guilt of Strafford, was anxious to save his life. In the midst of the parliamentary struggle Bedford died of smallpox on 9 May 1641.
Clarendon described him as "a wise man, and of too great and plentiful a fortune to wish the subversion of the government," and again referring to his death, said that "many who knew him well thought his death not unseasonable as well to his fame as his fortune, and that it rescued him as well from some possible guilt as from those visible misfortunes which men of all conditions have since undergone."
Estate development.
In about 1631 with architect Inigo Jones he built the square of Covent Garden, with the piazza and church of St. Paul's. He was threatened with a Star-chamber suit for contravening the proclamation against new buildings, but the matter seems to have been resolved by compromise.
Bedford was the head of those who undertook to drain the great level of The Fens of Cambridgeshire, which were renamed the "Bedford Level" in his honour. He and the other undertakers were to receive ninety-five thousand acres of land, of which twelve thousand were to be set apart for the king, and the profits of forty thousand were to serve as a security for keeping up the drainage works. He spent a large sum of money over this work, and received 43,000 acres (174 km²) of land; but the project involved him in great difficulties. By 1637 he had spent £100,000 on the undertaking but after various jealousies and difficulties the king took the work into his own hands in 1638, making a further grant of land to the Earl. The work was not declared finished till March 1653, twelve years after Bedford's death.
The 4th Earl is buried in the 'Bedford Chapel' at St. Michael's Church, Chenies.
Children.
Bedford married Catherine Brydges (d. 1657), daughter of Giles Brydges, 3rd Baron Chandos. They had eight children:


Biological membrane

A biological membrane, biomembrane or cell membrane is a selectively permeable membrane that separates cell from the external environment or creates intracellular compartments. Biological membranes, in the form of eukaryotic cell membranes, consist of a phospholipid bilayer with embedded, integral and peripheral proteins used in communication and transportation of chemicals and ions. The bulk of lipid in a cell membrane provides a fluid matrix for proteins to rotate and laterally diffuse for physiological functioning. Proteins are adapted to high membrane fluidity environment of lipid bilayer with the presence of an annular lipid shell, consisting of lipid molecules bound tightly to surface of integral membrane proteins. The cell membranes are different from the isolating tissues formed by layers of cells, such as mucous membranes, basement membranes, and serous membranes.
Composition.
Asymmetry.
The lipid bilayer consists of two layers- an outer leaflet and an inner leaflet. The components of bilayers are distributed unequally between the two surfaces to create asymmetry between the outer and inner surfaces. This asymmetric organization is important for cell functions such as cell signaling. The asymmetry of the biological membrane reflects the different functions of the two leaflets of the membrane. As seen in the fluid membrane model of the phospholipid bilayer, the outer leaflet and inner leaflet of the membrane are asymmetrical in their composition. Certain proteins and lipids rest only on one surface of the membrane and not the other.
• Both the plasma membrane and internal membranes have cytosolic and exoplasmic faces
• This orientation is maintained during membrane trafficking – proteins, lipids, glycoconjugates facing the lumen of the ER and Golgi get expressed on the extracellular side of the plasma membrane. In eucaryotic cells, new phospholipids are manufactured by enzymes bound to the part of the endoplasmic reticulum membrane that faces the cytosol. These enzymes, which use free fatty acids as substrates, deposit all newly made phospholipids into the cytosolic half of the bilayer. To enable the membrane as a whole to grow evenly, half of the new phospholipid molecules then have to be transferred to the opposite monolayer. This transfer is catalyzed by enzymes called flippases. In the plasma membrane, flippases transfer specific phospholipids selectively, so that different types become concentrated in each monolayer.
Using selective flippases is not the only way to produce asymmetry in lipid bilayers, however. In particular, a different mechanism operates for glycolipids—the lipids that show the most striking and consistent asymmetric distribution in animal cells.
Lipids.
The biological membrane is made up of lipids with hydrophobic tails and hydrophilic heads. The hydrophobic tails are hydrocarbon tails whose length and saturation is important in characterizing the cell. Lipid rafts occur when lipid species and proteins aggregate in domains in the membrane. These help organize membrane components into localized areas that are involved in specific processes, such as signal transduction.
Red blood cells, or erythrocytes, have a unique lipid composition. The bilayer of red blood cells is composed of cholesterol and phospholipids in equal proportions by weight. Erythrocyte membrane plays a crucial role in blood clotting. In the bilayer of red blood cells is phosphatidylserine. This is usually in the cytoplasmic side of the membrane. However, it is flipped to the outer membrane to be used during blood clotting.
Proteins.
Phospholipid bilayers contain different proteins. These membrane proteins have various functions and characteristics and catalyze different chemical reactions. Integral proteins span the membranes with different domains on either side. Integral proteins hold strong association with the lipid bilayer and cannot easily become detached. They will dissociate only with chemical treatment that breaks the membrane. Peripheral proteins are unlike integral proteins in that they hold weak interactions with the surface of the bilayer and can easily become dissociated from the membrane. Peripheral proteins are located on only one face of a membrane and create membrane asymmetry.
Oligosaccharides.
Oligosaccharides are sugar containing polymers. In the membrane, they can be covalently bound to lipids to form glycolipids or covalently bound to proteins to form glycoproteins. Membranes contain sugar-containing lipid molecules known as glycolipids. In the bilayer, the sugar groups of glycolipids are exposed at the cell surface, where they can form hydrogen bonds. Glycolipids provide the most extreme example of asymmetry in the lipid bilayer. Glycolipids perform a vast number of functions in the biological membrane that are mainly communicative, including cell recognition and cell-cell adhesion. Glycoproteins are integral proteins. They play an important role in the immune response and protection.
Formation.
The phospholipid bilayer is formed due to the aggregation of membrane lipids in aqueous solutions. Aggregation is caused by the hydrophobic effect, where hydrophobic ends come into contact with each other and are sequestered away from water. This arrangement maximises hydrogen bonding between hydrophilic heads and water while minimising unfavorable contact between hydrophobic tails and water. The increase in available hydrogen bonding increases the entropy of the system, creating a spontaneous process.
Function.
Biological molecules are amphiphilic or amphipathic, i.e. are simultaneously hydrophobic and hydrophilic. The phospholipid bilayer contains charged hydrophilic headgroups, which interact with polar water. The layers also contain hydrophobic tails, which meet with the hydrophobic tails of the complementary layer. The hydrophobic tails are usually fatty acids that differ in lengths. The interactions of lipids, especially the hydrophobic tails, determine the lipid bilayer physical properties such as fluidity.
Membranes in cells typically define enclosed spaces or compartments in which cells may maintain a chemical or biochemical environment that differs from the outside. For example, the membrane around peroxisomes shields the rest of the cell from peroxides, chemicals that can be toxic to the cell, and the cell membrane separates a cell from its surrounding medium. Peroxisomes are one form of vacuole found in the cell that contain by-products of chemical reactions within the cell. Most organelles are defined by such membranes, and are called "membrane-bound" organelles.
Selective permeability.
Probably the most important feature of a biomembrane is that it is a selectively permeable structure. This means that the size, charge, and other chemical properties of the atoms and molecules attempting to cross it will determine whether they succeed in doing so. Selective permeability is essential for effective separation of a cell or organelle from its surroundings. Biological membranes also have certain mechanical or elastic properties that allow them to change shape and move as required.
Generally, small hydrophobic molecules can readily cross phospholipid bilayers by simple diffusion.
Particles that are required for cellular function but are unable to diffuse freely across a membrane enter through a membrane transport protein or are taken in by means of endocytosis, where the membrane allows for a vacuole to join onto it and push its contents into the cell. Many types of specialized plasma membranes can separate cell from external environment: apical, basolateral, presynaptic and postsynaptic ones, membranes of flagella, cilia, microvillus, filopodia and lamellipodia, the sarcolemma of muscle cells, as well as specialized myelin and dendritic spine membranes of neurons. Plasma membranes can also form different types of "supramembrane" structures such as caveolae, postsynaptic density, podosome, invadopodium, desmosome, hemidesmosome, focal adhesion, and cell junctions. These types of membranes differ in lipid and protein composition.
Distinct types of membranes also create intracellular organelles: endosome; smooth and rough endoplasmic reticulum; sarcoplasmic reticulum; Golgi apparatus; lysosome; mitochondrion (inner and outer membranes); nucleus (inner and outer membranes); peroxisome; vacuole; cytoplasmic granules; cell vesicles (phagosome, autophagosome, clathrin-coated vesicles, COPI-coated and COPII-coated vesicles) and secretory vesicles (including synaptosome, acrosomes, melanosomes, and chromaffin granules).
Different types of biological membranes have diverse lipid and protein compositions. The content of membranes defines their physical and biological properties. Some components of membranes play a key role in medicine, such as the efflux pumps that pump drugs out of a cell.
Fluidity.
The hydrophobic core of the phospholipid bilayer is constantly in motion because of rotations around the bonds of lipid tails. Hydrophobic tails of a bilayer bend and lock together. However, because of hydrogen bonding with water, the hydrophilic head groups exhibit less movement as their rotation and mobility are constrained. This results in increasing viscosity of the lipid bilayer closer to the hydrophilic heads.
Below a transition temperature, a lipid bilayer loses fluidity when the highly mobile lipids exhibits less movement becoming a gel-like solid. The transition temperature depends on such components of the lipid bilayer as the hydrocarbon chain length and the saturation of its fatty acids. Temperature-dependence fluidity constitutes an important physiological attribute for bacteria and cold-blooded organisms. These organisms maintain a constant fluidity by modifying membrane lipid fatty acid composition in accordance with differing temperatures.
In animal cells, membrane fluidity is modulated by the inclusion of the sterol cholesterol. This molecule is present in especially large amounts in the plasma membrane, where it constitutes approximately 20% of the lipids in the membrane by weight. Because cholesterol molecules are short and rigid, they fill the spaces between neighboring phospholipid molecules left by the kinks in their unsaturated hydrocarbon tails. In this way, cholesterol tends to stiffen the bilayer, making it more rigid and less permeable.
For all cells, membrane fluidity is important for many reasons. It enables membrane proteins to diffuse rapidly in the plane of the bilayer and to interact with one another, as is crucial, for example, in cell signaling. It permits membrane lipids and proteins to diffuse from sites where they are inserted into the bilayer after their synthesis to other regions of the cell. It allows membranes to fuse with one another and mix their molecules, and it ensures that membrane molecules are distributed evenly between daughter cells when a cell divides. If biological membranes were not fluid, it is hard to imagine how cells could live, grow, and reproduce.


Somali golden mole

The Somali golden mole ("Calcochloris tytonis") is a golden mole endemic to Somalia. In 1964, Dr. Alberto Simonetta of the University of Florence discovered the mole's jaw and ear bone fragments in a barn owl pellet in Giohar, Somalia.


Rabinder Buttar

Dr Rabinder Buttar is the founder, CEO & Chair Person of a clinical research organisation.
Academia.
Dr Buttar holds a BSc in Biochemistry from the University of Glasgow and a PhD in Immunology from the University of Strathclyde. as well as a certificate in Management from Reading, and received an honorary doctorate from the University of the West of Scotland. She served for four years on the board of the Institute of Clinical Research UK (ICR), is an Honorary Fellow of ICR, a Fellow of the Royal Society of Medicine, a Fellow of the Royal Society of Medicine and, in 2014, she became a Fellow of the Royal Society of Edinburgh.
Awards.
In 2009, Dr Rabinder Buttar was named the Institute of Directors, 'Director of the Year' for Glasgow & West of Scotland, and in 2010, she received the Ernst & Young Scottish Entrepreneur of the Year award


Marinomonas arctica

Marinomonas arctica is a Gram-negative, psychrotolerant and motile bacterium from the genus of "Marinomonas" which has been isolated from sea-ice from the Canadian Basin from the Arctic Ocean.


Charles E. Warren

Charles E. Warren (September 17, 1962 – July 30, 2005) was an assistant professor of biochemistry and molecular biology at the University of New Hampshire.
Early life and education.
Warren was born on September 17, 1962, in Guildford, UK. He was son of Joan (Staples) Warren and the late Charles Peter Warren. He was educated at Oxford University, where he received his PhD in 1989 under the tutelage of Raymond Dwek, an eminent early leader in glycobiology. His thesis was entitled "Glycosylation in Mice and Rats".
Research.
After graduation he helped establish the first commercially focused effort in glycotechnology: Oxford Glycosystems, Ltd. He subsequently moved to Toronto, Canada, to broaden his interest in glycosyltransferase and spent his postdoctoral time with Dr. Harry Schachter at the Hospital for Sick Children in Toronto, and two years later across the street with Dr. Jim Dennis at the Lunenfeld-Tanenbaum Research Institute. Charles Warren moved to the University of New Hampshire in 2002 as an assistant professor in the Department of Biochemistry and Molecular Biology.
He conducted research on the structure-function relationships of glycosylation. These specific efforts focused on evolution, animal development and human diseases. He used C. elegans as his model organism.
Awards.
After only three years at the University of New Hampshire, he was nominated for a named professorship, the "Class of 1944 Award". This university-wide award recognizes outstanding faculty members.
Death.
Charles Warren died prematurely on July 30, 2005, in a paragliding accident.
Warren Workshops.
Since 2006, Warren Workshops are held every second years in Warren's memory. The initial purpose of the Warren Workshop series on Glycoconjugate Analysis was to bring together concerned analysts in the field to discuss the various methodologies in use with the aim to share and appraise protocols for carbohydrate sequencing. Discussion among the experts in the discipline would hopefully lead to establishing a working framework and course of action to bring unanimity to the goals and requirements of glycoconjugate structural analysis. The growing need, aspirations of automation and high throughput analysis, made open discussion among experts very timely and important.
WW-I, July 6–9, 2006, UNH Glycomics Center, Durham, NH, USA; Organiser: Vern Reinhold
WW-II, July 9–12, 2008, UNH Glycomics Center, Durham, NH, USA; Organiser: Vern Reinhold
WW-III, August 27–30, 2010, Hindasgarden Conference Center, Hindås, Sweden; Organiser: Niclas G. Karlsson
WW-IV, August 8–11, 2012, CCRC, Athens, Georgia USA; Organisers: Mike Tiemeyer and Lance Wells
WW-V, August 6–9, 2014, University of Galway, Ireland; Organisers: Rob Woods and Pauline Rudd
WW-VI, August 24–26, 2016, Sapporo University, Japan; Organisers: Kiyoko Aoki-Kinoshita and Hisashi Narimatsu
WW-VII, August 15–18, 2018, Boston University, Massachusetts, USA; Organisers: Joseph Zaia and Catherine Costello


Helen Burt

Helen M. Burt is a British-Canadian pharmaceutical scientist who is the Angiotech Professor of Drug Delivery at the University of British Columbia. She serves as Associate Vice President of Research and Innovation at UBC. Her research considers novel therapeutics based on nanotechnology, including drug delivery systems for the treatment of bladder cancer and coronary artery disease.
Early life and education.
Burt is from Manchester in the United Kingdom. During a high school trip to a local hospital, she was first introduced to pharmacy. Burt was an undergraduate student at the University of Bath, where she specialised in pharmacy. She moved to Canada to complete her graduate research as a doctoral student at the University of British Columbia, where she studied anisotropy and defects on dissolution of crystals.
Research and career.
Burt joined the faculty at the University of British Columbia. Her research involves the use of nanotechnology for drug delivery. She has demonstrated that systems can provide targeted relief to different parts of the body, and release specific amounts of drug and controlled rates. In particular, Burt has studied nanocrystalline cellulose, a molecular substrate that has large surfaces areas and negative surface charges. Nanocrystalline cellulose can withstand binding of high quantities of drugs, and contain hydroxyl groups that can be used for surface modification. The hydroxyl groups can be used to selective load and release treatments, including ant-infective agents in wound dressings.
Burt worked alongside Sitka Biopharma on STK-01, a polymer nanoparticle based drug-delivery system that can be used to treat bladder cancer. The drug, which delivers targeted chemotherapy (Docetaxel) to non-muscle invasive bladder cancer, entered clinical trials in 2017.
Burt co-founded the Centre for Drug Research and Development in 2004. The centre later became adMare BioInnovations, which allows biomedical scientists to translate their research into industry. In 2011, Burt was made Associate Vice President of Research and Innovation.


Xbox Live Vision

Xbox Live Vision is a webcam accessory that was developed as an accessory for the Xbox 360 video game console. It was announced at E3 2006 and was released in North America on September 19, 2006, Europe and Asia on October 2, 2006, and Japan on November 2, 2006.
In 2010, Xbox Live Vision was succeeded by Kinect, a new camera accessory that also incorporates a motion tracking system and adds voice recognition functionality to the console.
Overview.
The camera can be used for video chat, personalized gamer pictures, in-game video chat, and still pictures. The camera features 640 × 480 video at 30 fps and is capable of taking still images at 1.3 megapixels. It allows for video chat and picture messages (requires Xbox Live Gold) with video effects along with in-game compatibility. Certain games allow a digital zoom of 2x or 4x while video chatting.
It also features three camera effects, in which the currently captured video image is overlaid on the dashboard background. The three effects are 'watery', 'edgy', and 'dotty'. The camera uses a standard USB 2.0 connection and is also Windows (XP and newer) and Mac OS X (v10.4.9 and newer) compatible.
The Xbox Live Vision Camera was announced at E3 2006 and released in North America on September 19, 2006, following a 1-month pre-launch period in which Toys "R" Us stores in New York City and Los Angeles sold them to build up hype. It was released in Europe and Asia on October 6, 2006, and November 2, 2006 in Japan.
Compatibility with other platforms.
Windows.
Using its USB 2.0 connection, the Vision Camera is compatible with Windows XP Service Pack 2 (32-bit only), Windows Vista (32-bit and 64-bit), and Windows 7 (32-bit and 64-bit, although 64-bit is not confirmed by Microsoft). Because the Vision Camera lacks audio input, a microphone must also be connected to the computer for voice chat and audio recording. Drivers are not included with the Vision Camera but can be downloaded automatically by Windows when prompted. One restriction of the Vision cam when used on the Windows is that it will not natively record videos, only take pictures. Additional software may be used to alleviate this problem.
Mac OS X.
Mac OS X 10.4.9 added support for the USB "video class" group of peripherals, which includes the Vision Camera. The Vision Camera works in iChat, Photo Booth, Facetime for Mac, and other applications that use QuickTime for video display, such as Skype. A USB 2.0 connection is also mandatory. The camera continued to work from 10.5 to 10.7, but soon after that support was removed.
PlayStation 3.
PlayStation 3 system software (firmware) version 1.54 added support for "video class" USB devices, allowing use of the Vision camera, as well as webcams and other similar devices.
Linux.
Linux The Vision Camera works with native support, tested with v 4.19.66-v7+ on a Raspberry Pi with resolutions upto 960x720.
Compatible games.
In-game video support
Controller functionality
Face mapping support (Digimask)
Other


E-6837

E-6837 is an orally active, 5-HT6 agonist developed in an attempt to create an anti-obesity medication. In cell lines expressing rat 5-HT6 receptors, it acted as a partial agonist (on presumed silent receptors), while it acted as a full agonist on human 5-HT6 receptors (which are constitutively active). Oral administration of E-6837 reduced food intake, but only transiently. In rats, twice daily administration of E-6837 over the course of 4 weeks resulted in a 15.7% reduction in body weight, compared to 11% reduction for sibutramine. This weight loss remained significant for E-6837 after a 43-day withdrawal period, whereas the weight difference was non-significant for sibutramine (i.e., sibutramine had a rebound effect while E-6837 did not), and this weight loss was found to be due to a loss of fat mass. The reduction in fat mass in E-6837 treated animals was associated with a 50% decrease in plasma leptin levels, and also reduced glucose and insulin levels in plasma after a glucose tolerance test. This indicates that weight loss from E-6837 is associated with improved insulin sensitivity, and thus, better glycemic control.
One proposed mechanism of action is that E-6837 acts on neurons in the hypothalamus, which has shown significant levels of 5-HT6 receptor mRNA. The hypothalamus is one key structure involved in regulating food intake.


RBL cells

RBL (Rat Basophilic Leukemia cells) are cancerous basophil cells that are well suited for the study of allergies.
Uses.
RBL cells are used in allergy studies due to the strong response of the cells to IgE and its FcεRI receptor. They are used in place of mast cells due to a higher stability in tissue culture. RBL cells can also be humanized, aiding in the specificity of allergy studies to human patients.
Infections.
Mycoplasma bacterial infections greatly affects the cell mediator release for biological assays, therefore regular Mycoplasma tests need to be performed since the bacteria colonizes the cell surface and cannot be visualized through a light microscope.


AxoGen

AxoGen is a developer of surgical solutions, including human tissue grafts, based in Alachua, Florida. Axogen products are designed to remedy peripheral nerve damage. In 2013 the company raised $18 million in its initial public offering (IPO). AxoGen uses a cell graft technology AVANCE to mimic a human nerve. The company also creates nerve connectors and soft tissue membranes. The company reports sensory and movement recovery in 87 percent of patients with peripheral nerve injuries. AxoGen is part of the Sid Martin Biotechnology Incubator.
As of 2019, AxoGen was the only commercially available allograft approved by the Food and Drug Administration (FDA) for clinical use.


Desulfovibrio ferrireducens

Desulfovibrio ferrireducens is a psychrotolerant bacterium from the genus of Desulfovibrio which has been isolated from permanently cold sediments from Fjord in Svalbard.


ACADSB

ACADSB is a human gene that encodes short/branched chain specific acyl-CoA dehydrogenase (SBCAD), an enzyme in the acyl CoA dehydrogenase family.
It can cause short/branched-chain acyl-CoA dehydrogenase deficiency.
Structure.
The human ACADSB gene is located on chromosome 10; its exact localization has been identified as 10q25-q26. The open reading frame (ORF) encodes a precursor protein that contains 431 amino acids; post-translational processing results in a mature protein with 399 amino acids. The cDNA is significantly similar to the cDNA of other members of the acyl-CoA dehydrogenase family; its structure is closest to that of short chain acyl-CoA dehydrogenase. The structure of the catalytic pocket has also been studied; position 104 at the bottom of the substrate-binding pocket has been identified as important in determining the length of the primary carbon chain that can be accommodated. Altering residues at positions 105 and 177 have been demonstrated to affect the rate of the dehydrogenation reactions.
Function.
Short/branched chain acyl-CoA dehydrogenase (ACADSB) is a member of the acyl-CoA dehydrogenase family of enzymes that catalyze the dehydrogenation of acyl-CoA derivatives in the metabolism of fatty acids or branch chained amino acids. Substrate specificity is the primary characteristic used to define members of this gene family. The ACADSB gene product has the greatest activity towards the short branched chain acyl-CoA derivative, (S)-2-methylbutyryl-CoA, but also reacts significantly with other 2-methyl branched chain substrates and with short straight chain acyl-CoAs. The encoded protein is also involved in L-leucine catabolism.
Clinical significance.
Mutations in the ACADSB gene have been associated with 2-Methylbutyryl-CoA dehydrogenase deficiency (SBCADD, also known as MBD) deficiency, an autosomal recessive metabolic disorder of impaired isoleucine degradation. Many mutations across the gene's 10 exons have been identified, with the mutations causing exon skipping and other transcriptional and translational errors. The disorder may be detected by MS/MS-based routine newborn screening due to the heightened presence of 2-methylbutyrylcarnitine in tissue samples. The disorder may also be identified using urinary organic acid analysis, by detecting the presence of 2-methylbutyryl glycinuria. While many individuals with a mutation in this gene may be asymptomatic, some patients have been reported to have symptoms in early infancy. Infants may experience apneic episodes, generalized muscle atrophy, hypotonia, lethargy, seizures, and delayed motor development. Patients may also experience metabolic symptoms such as hypothermia and hypoglycemia. Finally, genetic polymorphisms of the ACADSB gene may also be involved in the development of hypertension in the Japanese population.


2F-Viminol

2F-Viminol is a pyrrole derived opioid analgesic drug, which was originally developed by a team at the drug company Zambon in the 1960s. It is around twice as potent as the parent compound viminol, though unlike viminol, 2F-viminol has never passed clinical trials or been approved for medical use. 2F-Viminol has been sold as a designer drug, first being identified in Sweden in 2019. It is one of a number of structurally atypical opioid agonists to have appeared on the designer drug grey-market since broad controls over fentanyl analogues were introduced in China in 2015. It was made illegal in Sweden in August 2019 and in Latvia in November 2019.


Ferritin light chain

Ferritin light chain is a protein that in humans is encoded by the "FTL" gene. Ferritin is the major protein responsible for storing intracellular iron in prokaryotes and eukaryotes. It is a heteropolymer consisting of 24 subunits, heavy and light ferritin chains. This gene has multiple pseudogenes.
It is abnormally expressed in fetuses of both IVF and ICSI, which may contribute to the increase risk of birth defects in these assisted reproductive technologies.
Function.
Iron is extremely important in the development of neurons, transport through iron-sulfur clusters, the electron transport chain, and synthesis and breakdown of neurotransmitters. The function of the FTL is to act as both an iron reservoir and to remove excess iron from the body. Since iron plays a role in electron transfer, there is potential for the generation of free, highly toxic radicals which makes the role of the FTL as an iron detoxifier very significant. The rates of iron uptake and release may be affected by changes to the components of the ferritin light chains and heavy chains. Although the ferritin light chain unlike the ferritin heavy chain has no ferroxidase activity, the light chain may be responsible for the electron transfer across the ferritin protein cage.
Clinical significance.
Oxidative stress caused by iron radicals generated in the ETC and an increase in iron levels caused by defects in the FTL gene has been known to be a cause of the onset of neurodegenerative diseases and hyperferritinemia-cataract syndrome.
Mutations of the FTL gene cause the rare adult-onset basal ganglia disease also known as neuroferritinopathy. These mutations are specifically in exon four of the FTL gene. There are two distinct toxic mechanisms that lead to neuroferritinopathy and these are abnormalities in iron metabolism and the creation of free iron radicals, resulting in oxidative stress and cell death.
Interactions.
Ferritin light chain has been shown to interact with FTH1. An oxygen molecule acts as the terminal electron acceptor during the oxidation of iron in aerobic metabolism. A study conducted with different apoferritins with distinct compositions of heavy and light subunits revealed that both subunits have key roles in the electron transport chain. Neither subunit on its own has the ability to reduce cytochrome c and thus the first step, the oxidation of Fe2+ to Fe3+, can be carried out by the heavy chain and the light chains are responsible for the transfer of electrons.
FTL is regulated by iron and with an increase in iron, there is both an increase in the FTL expression and PEN-2 levels, which results in increased γ- secretase activity. In relation to this, the downregulation of FTL expression leads to a decrease in the protein levels of PEN-2.


Robert R. Squires

Robert Reed Squires (January 11, 1953 – September 30, 1998) was an American chemist known for his work in gas phase ion chemistry and flowing afterglow mass spectrometry.
Early life and education.
Squires was born in Northern California and grew up in Los Angeles. He received an A.A. degree at El Camino College in 1973 and then returned to Northern California where he received a B.A. at California State University, Chico. He then went on to Yale University where he worked in the laboratory of Kenneth B. Wiberg on the thermochemistry of organic compounds. He received his M.Phil. degree in 1977 and a Ph.D. in 1980. He took a postdoctoral position with Charles DePuy and Veronica Bierbaum at the University of Colorado, Boulder where he studied the reactions of gas-phase ions using the flowing afterglow technique.
Academic career.
Squires took a position as an assistant professor at Purdue University in 1981 where he constructed two unique mass spectrometers: a flowing afterglow triple quadrupole mass spectrometer and a flowing afterglow selected ion flow tube triple quadrupole mass spectrometer. In 1986, he was promoted to Associate Professor and in 1990 to Professor.
Awards.
Among his awards were an Alfred P. Sloan Foundation Fellowship in 1987, the American Chemical Society Nobel Laureate Signature Award for Graduate Education in Chemistry (with Susan Graul) in 1991, and the American Society for Mass Spectrometry Biemann Medal in 1998. The Purdue University Department of Chemistry Robert R. Squires Scholarship was established in his honor.


Applera

Applera Corporation of Norwalk, Connecticut, at #874 on the 2007 Fortune 1000 list, was one of the largest international biotechnology companies based in the United States. It was the successor company to what was the Life Sciences Division of Perkin-Elmer Corporation. Applera was not publicly traded, but instead it consisted of two major groups which are publicly traded tracking stocks in the proteomics industrial sector. These two groups were the S&P 500 listed Applera Corp-Applied Biosystems Group of Foster City, California, and Applera Corp-Celera Genomics Group of Rockville, Maryland. In 2006, the company spun off the Celera Genomics group and changed its name from Applera to Applied Biosystems.
As the former Perkin-Elmer, Applera had a history dating back to 1931. But more precisely, its history dates from 1999, when Perkin-Elmer effectively split in half, and sold off its more traditional half of the business to EG&G Inc. As part of the deal, it also sold the Perkin-Elmer name, because that most properly associated with that traditional line of products, and EG&G then became the new PerkinElmer. At that point the remaining Connecticut Life Sciences company issued its two tracking stocks, and also changed its own name to PE Corporation. The Applied Biosystems group had earlier already been renamed PE Biosystems, and it retained that name in the first incarnation of its tracking stock. In 2000, the Applied Biosystems name was restored to the group, with the new stock ticker symbol ABI, and PE Corporation became Applera, a combination of its two components' names, Appl(iedCel)era.
Board of directors.
The Applera Corporation Directors oversaw the parent corporation along with the operations of both tracking stock groups, and consequently they had the responsibility of fairly balancing the interests of both groups of investors in each stock.
History.
The original Perkin-Elmer, and then its successor PE Corporation and Applera Corporation have been headquartered in Norwalk, Connecticut. The company address is at 50 Danbury Rd.
In the early 1990s, Perkin-Elmer, which had been a maker of diverse electronic instruments and analytical and optical equipment, established strong ties with groups closely involved with the business of decoding the human genome. By the late 1990s, Perkin-Elmer's Life Sciences division had become centrally involved in highly publicized intense competition against the public consortium that was also working on the massive task. Consequently, Perkin-Elmer's people and companies became among the most famous players of the decade in biotechnology and in that segment of the technology bubble. In the process, Perkin-Elmer divided and transformed itself into Applera, a company entirely focused in life sciences.
Beginning in 1990, the U.S. government approved financing to support the Human Genome Project (HGP). James D. Watson, who founded the public consortium, forecast that the project could be completed in 15 years from its 1990 starting date, at a cost of US$3 billion. The HGP was a public consortium of eight university centers funded through the U.S. Department of Energy, the National Institutes of Health and the Wellcome Trust of London. The government-backed project targeted completion of human DNA mapping by the year 2005.
In 1993, Perkin-Elmer acquired a key equipment maker, Applied Biosystems, Inc., and that stock's symbol ABIO ceased trading on the NASDAQ exchange, as it became a division of Perkin-Elmer. Michael W. Hunkapiller, Ph.D., who had been Applied Biosystem's chairman, president and CEO since 1983, became a senior vice president of Perkin-Elmer, and president of the Applied and PE Biosystems Divisions.
In 1994, Perkin-Elmer reported net revenues of over $1 billion, of which Life Sciences accounted for 42% of the business. The company has 5,954 employees. The new competitive genomics industry had formed for the development of new pharmaceuticals, based on the work of the Human Genome Project. The Applied Biosystems Division made thermal cyclers and automated sequencers for these new genomics companies.
In 1995, Perkin-Elmer sold its 30,000th thermal cycler. To meet Human Genome Project goals, Perkin-Elmer developed mapping kits with markers every 10 million bases along each chromosome. Also that year, DNA fingerprinting using polymerase chain reaction (PCR) became accepted in court as reliable forensic evidence. In 1993, Perkin-Elmer had become the world's leading manufacturer of instruments and reagents for (PCR). It marketed PCR reagents kits in alliance with Hoffman-La Roche Inc.
In 1996, Perkin-Elmer acquired Tropix, Inc., a chemiluminescence company, for its life sciences division.
PE Applied Biosystems Division.
Also In 1996, Tony L. White from Baxter International Inc. became president and chief executive officer of Perkin-Elmer and reorganized it into two separate operating divisions, Analytical Instruments and PE Applied Biosystems. The PE Applied Biosystems division accounted for half of Perkin-Elmer's total revenue, with net revenues up by 26%.
In 1997, Perkin-Elmer revenues reached almost US$1.3 billion, of which PE Applied Biosystems was US$653 million. Acquisitions included GenScope, Inc., and Linkage Genetics, Inc., which combined with Zoogen to form PE AgGen, focused on genetic analysis services for plant and animal breeding. Partnerships were begun with Hyseq, Inc., on the new DNA chip technology, and also with Tecan U.S., Inc., on combinatorial chemistry automation systems, and also with Molecular Informatics, Inc. on genetic data management and analysis automated systems.
In 1998, Perkin-Elmer acquired PerSeptive Biosystems (formerly ), a leader in the bio-instrumentation field where it made biomolecule purification systems for protein analysis. Noubar Afeyan, Ph.D., had been the founder, chairman, and CEO of PerSeptive, and after the acquisition he became a senior vice president and chief business officer of Perkin-Elmer. He had earlier founded and co-built several successful life science and technology startup companies through the 1990s, after earning his Ph.D. in biochemical engineering from the Massachusetts Institute of Technology in 1987.
PE Biosystems Division.
In 1998, Perkin-Elmer formed the PE Biosystems division, by consolidating Applied Biosystems, PerSeptive Biosystems, Tropix and PE Informatics. Informatics was formed from the Perkin-Elmer combination of two other acquisitions, Molecular Informatics and Nelson Analytical Systems, with existing units of Perkin-Elmer.
By 1998, Perkin-Elmer had a presence on the World Wide Web at http://www.perkin-elmer.com.
While planning the next new generation of machines, PE Biosystems' president, Michael W. Hunkapiller, calculated that it would be possible for their own private industry to decode the human genome before the academic consortium could complete it. The company would decode all of the 3.5 billion chemical letters in the human DNA by 2001, at a cost of only US$200 million, about 1/10 of the consortium projected cost of US$3 billion. However, it would mean starting from scratch, eight years already into the consortium's program. It was a bold prediction, given that the consortium target date set by Watson back in 1990 had been the forward year of 2005, only seven years away, and with the consortium already half the way to the completion target date by then.
Also, it meant that Hunkapiller's idea would require competing against his own customers, to all of whom Applied Biosystems sold its sequencing machines and their chemical reagents. However, he calculated that it would also mean doubling the market for that equipment.
Hunkapiller brought in J. Craig Venter to direct the project. Tony L. White, president of the Perkin-Elmer Corporation backed Hunkapiller on the venture. Perkin-Elmer's interest was driven largely by its monopoly, through the equipment of Applied Biosystems, of the market for automated DNA sequencing machines. Venter boldly declared to the media that he would complete the genome decoding by 2001. That bold pronouncement prompted the academic consortium to accelerate their own deadline by a couple years, to 2003.
In May 1998, the company's newly formed unit to accomplish the task, Celera Genomics Group, in Rockville, Maryland, was created to become the definitive source of genomic and related medical information with the goal of sequencing the human genome by the year 2001. Celera became the primary commercial competitor to the government-funded effort of the Human Genome Project. Venter became president and chief scientific officer of Celera.
At the time, Venter operated his own independent lab, The Institute for Genomic Research (TIGR), which had developed a "random shotgun" approach to DNA decoding, making it the most prolific genome lab in the world.
At year end 1998, the PE Biosystems Group's sales reached US$940 million. Its chief new genomics instrument was the ABI PRISM 3700 DNA Analyzer, which it had developed in conjunction with Hitachi, Ltd. The new machine, an electrophoresis-based genetic analysis system, cost US$300,000 each, but was a major leap beyond its predecessor, the 377, and was fully automated, allowing genetic decoding to run around the clock with little supervision. According to Venter, the machine was so revolutionary that it could decode in a single day the same amount of genetic material that most DNA labs could produce in a year.
The partnership sold hundreds of the 3700 analyzers to Celera, and also to others worldwide. The public consortium also bought one of the Applied Biosytems 3700 sequencers, and had plans to buy 200 more. The machine proved to be so fast that by late March 1999 the consortium announced that it had revised its timeline, and would release by the Spring of 2000 a "first draft sequence" for 80% of the human genome.
PE Corporation.
On March 19, 1999, Perkin-Elmer Corporation, as a New York corporation, filed SEC Form S-4/A, to enter a reincorporation merger with a subsidiary of PE Corporation of Delaware. Shareholders of the New York corporation stock (NYSE:PKN) would receive shares in two new stocks instead.
On April 27, 1999, the shareholders of Perkin-Elmer Corporation approved the reorganization of Perkin-Elmer into a pure-play life science company, resulting in the name change to PE Corporation and the de-listing of the PKN stock. Each share of the Perkin-Elmer New York (PKN) was to be exchanged for one share and for of a share respectively of the two new common share tracking stocks for the two component Life Sciences groups, PE Biosystems Group (NYSE:PEB) and Celera Genomics Group (NYSE:CRA). (PKN now)
On April 28, 1999, the two replacement tracking stocks for the new PE Corporation were issued to shareholders. The Pacific Stock Exchange began trading PE Corporation options for the two new stocks that day. Michael W. Hunkapiller remained as senior vice president of PE Corporation, and as president of PE Biosystems. Afeyan initiated and oversaw the creation of the tracking stock for Celera Genomics Group. Then later in 1999 Afeyan left, to co-found Flagship Ventures, an early-stage entrepreneurial venture capital firm. J. Craig Venter remained as senior vice president of PE Corporation and also president of Celera Genomics Group. Tony L. White remained as PE Corporation's chairman, president and chief executive officer.
Other officers who remained in PE Corporation included William B. Sawch, as senior vice president, general counsel and secretary.
On May 6, 1999, the reorganization was made effective, as the Perkin-Elmer Corporation was merged into a temporarily created subsidiary of PE Corporation, a new Delaware corporation. The recapitalization of the company resulted in issuance of the two new classes of common stock, called PE Corporation-PE Biosystems Group Common Stock and PE Corporation-Celera Genomics Group Common Stock. On that date, trading began in both new stocks on the New York Stock Exchange, to great excitement.
On May 28, 1999, as part of the recapitalization and reorganization, the company completed the sale of its traditional business unit, the Analytical Instruments Division to EG&G Inc., along with the Perkin-Elmer name, for US$425 million. EG&G was based in Wellesley, Massachusetts, and made products for diverse industries including automotive, medical, aerospace and photography. On July 14, 1999, that new analytical instruments maker PerkinElmer cut 350 jobs, or 12%, in its cost reduction reorganization.
On June 17, 1999, the board of PE Corporation announced a two-for-one split of PE Biosystems Group Common Stock.
At year end 1999, after the major divestment that year of the former Analytical Instruments Division, the new PE Corporation assets totalled over US$1.5 billion, split between the two Life Sciences groups. Of that, PE Biosystems Group, with 3,500 employees had net revenues of over US$1.2 billion.
By June 2000, the genomics segment of the technology bubble was peaking. Celera Genomics (CRA) and PE Biosystems (PEB) were among five genetics pioneers leading at that time, along with Incyte Genomics (), Human Genome Sciences (), and Millennium Pharmaceuticals (). All five of those stocks by then had exceeded a price above $100 a share in the market, before ultimately crashing back down.
Applera.
On November 28, 2000, PE Corporation filed SEC Form 8-K to report its announcement of the change of its name to Applera Corporation. At the same time, PE Biosystems Group changed its name to Applied Biosystems Group, and changed its ticker symbol from PEB to ABI. Both name changes became effective November 30, 2000. Also that date, the parent corporation web site address changed from https://web.archive.org/web/20070929001200/http://www.pecorporation.com/ to https://web.archive.org/web/20070822133148/http://www.applera.com:80/
The combined Applera then had 5,000 employees. PE/Applied Biosystems Group's net revenues rose to almost US$1.4 billion. Celera that year made milestone headlines when it announced that it had completed the sequencing and first assembly of the two largest genomes in history, that of the fruit fly, and of the human.
In 2001, the Applied Biosystems division of Applera reached revenues of US$1.6 billion, and developed a new workstation instrument specifically for the new field of proteomics, which had become Celera's new core business focus, as it shifted away from gene discovery. The instrument analyzed 1,000 protein samples per hour.
In January 2002, J. Craig Venter was pushed out of Celera, when it was decided that the group would make pharmaceuticals instead. Venter lacked experience in pharmaceutical development.
On April 22, 2002, the Celera Genomics Group announced its decision to abandon what had been its core business since its 1998 inception, and to shift the role of marketing data from its genetic database over to its sister company, the Applied Biosystems Group. Celera would instead develop pharmaceutical drugs. Applera CEO Tony L. White had noted earlier that the database business would distract from pharmaceutical development.
Applied Biosystems was a better fit for the database, because Applied already had the huge sales force in place for the marketing of its instruments. Plans were to expand those sales and those of the database into an electronic commerce system.
The database itself, Celera Discovery System (CDS), would remain with Celera, because of shareholder approval complications. Celera would retain responsibility for its maintenance and support to existing customers, and would receive royalties from Applied Biosystems. The database revenues were expected to reach US$100 million for the June fiscal year end, which would be its first profitable year. But it had always faced the problem that its public competitor, the consortium project, provides free data from its own database.
In 2002, Applied Biosystems Group again posted revenues of US$1.6 billion for the year.
In 2004, the long-term Applied Biosystems president, Mike Hunkapiller, retired and Cathy Burzik, who had joined the Group in 2003, replaced him as president of Applied Biosystems Group.


Prenylcysteine oxidase

In enzymology, a prenylcysteine oxidase () is an enzyme that catalyzes the chemical reaction
The 3 substrates of this enzyme are "S"-prenyl--cysteine, O2, and H2O, whereas its 3 products are prenal, -cysteine, and H2O2.
This enzyme belongs to the family of oxidoreductases, specifically those acting on a sulfur group of donors with oxygen as acceptor. The systematic name of this enzyme class is S-prenyl-L-cysteine:oxygen oxidoreductase. This enzyme is also called prenylcysteine lyase.


Hepatitis B virus PRE beta

The Hepatitis B virus PRE stem-loop beta (HBV PRE SL-beta) is an RNA structure that is shown to play a role in nuclear export of HBV mRNAs.
The minimal HBV PREbeta structure consists of a 23 nt stem-loop, with a 9 nt apical loop. The conserved stem-loop was predicted within the HBV PRE sequence and confirmed by mutagenesis.


Jeffrey Brent

Jeffrey A. Brent is a medical toxicologist who is a distinguished clinical professor of medicine and emergency medicine at the University of Colorado, School of Medicine. In addition, he is a professor at the Department of Environmental and Occupational Health at the Colorado School of Public Health. He is also the past president of the American Academy of Clinical Toxicology, was editor in chief of the journal Toxicological Reviews, and was a member of the board of directors of the American College of Medical Toxicology. Previously, most of Brent's research focused on the use of fomepizole as a treatment for both methanol and ethylene glycol poisoning, and he led a trial of this drug which resulted in the FDA approving it in December 1997. Currently, Dr. Brent serves as Director of the Toxicology Investigators Consortium, an NIH and FDA supported multi center research and surveillance group. Brent is also a senior editor of "Critical Care Toxicology: Diagnosis and Management of the Critically Poisoned Patient," originally published in 2005, and now in its second edition, which was published in 2017.
Education.
In 1970, Brent graduated from Hunter College with a Bachelor of Arts in chemistry, as well as a masters' degree in molecular biology. He completed his PhD in biochemistry at Mount Sinai School of Medicine and earned his MD from State University of New York at Buffalo's school of medicine. He also completed a fellowship at Denver Health Medical Center, a residency at Emory University and an internship at Beth Israel Deaconess Medical Center.
Career.
He was initially appointed to the University of Colorado in 1987 as an instructor, and then was promoted to assistant professor, then associate, then full, and finally to distinguished professor. He has authored more than 200 peer-reviewed publications. He was the chair of the toxicology section of the American College of Emergency Physicians from 1991 to 1993. Brent has published many scientific studies, primarily in the area of medical toxicology.
Brent was one of the U.S. government's experts in the autism omnibus hearing, in which he testified in support of the scientific consensus that thimerosal-containing vaccines do not cause autism, and specifically criticized a study by Holmes et al. which the plaintiffs had cited to argue that TCVs were dangerous to a specific subpopulation who were not as good at excreting mercury in hair. He also argued that chelation therapy is of no use as a treatment for autism, and that the signs and symptoms of autism are very different from those of ethylmercury poisoning.
Testimony.
In the so-called autism omnibus trial, Brent testified on behalf of the government, i.e. that thimerosal does not cause autism. In particular, he criticized the concept of hypersensitivity to thimerosal as a concept that had been invoked as a way to bypass real science. He also testified that, with regard to the levels of mercury in the urine of Jordan King and William Mead, who had been chelated, that "You always expect to see levels in the urine bump post-chelation." He also criticized the plaintiff's use of Doctor's Data Laboratories as relying on urine mercury levels rather than the gold standard, blood mercury levels. Brent has also voiced opposition to the use of chelation therapy as an autism treatment both in the omnibus trial, where he testified that "there was absolutely no reason to chelate them [the children who served as the test cases] for any mercury-related reason," and in peer-reviewed journals.


Osmotic stress technique

The osmotic stress technique is a method for measuring the effect of water on biological molecules, particularly enzymes. Just as the properties of molecules can depend on the presence of salts, pH, and temperature, they can depend significantly on the amount of water present. In the osmotic stress technique, flexible neutral polymers such as polyethylene glycol and dextran are added to the solution containing the molecule of interest, replacing a significant part of the water. The amount of water replaced is characterized by the chemical activity of water.


Nangibotide

Nangibotide is an inhibitor of TREM-1, a receptor found on certain white blood cells. Activation of TREM-1 stimulates inflammation. Nangibotide is therefore being investigated as a treatment for the overwhelming inflammation typically seen in severe sepsis.
Chemistry.
Nangibotide is a 12-amino-acid polypeptide derived from TLT-1.
Mode of action.
TREM-1 is a receptor found on neutrophils, macrophages and monocytes, key elements of the immune system. Activation of TREM-1 results in expression of NF-κB, which promotes systemic inflammation. Nangibotide inhibits TREM-1, thereby preventing the inflammatory activation. Absence of TREM-1 results in vastly reduced inflammation without impairing the ability to fight infection.
Animal models.
LR17, a mouse equivalent of nangibotide, improves survival in mouse models of severe sepsis. In a pig model of sepsis, LR12 - another animal equivalent of nangibotide - resulted in significantly improved haemodynamics and less organ failure. In monkeys, LR12 also reduced the inflammatory and hypotensive effects of sepsis.
Human studies.
Nangibotide has demonstrated safety in Phase 1 (healthy volunteers) and Phase 2 (sick patients with septic shock) studies. The ASTONISH trial will examine clinical efficacy in 450 patients with septic shock.


Thyroid hormone receptor

The thyroid hormone receptor (TR) is a type of nuclear receptor that is activated by binding thyroid hormone. TRs act as transcription factors, ultimately affecting the regulation of gene transcription and translation. These receptors also have non-genomic effects that lead to second messenger activation, and corresponding cellular response.
Structure.
There are four domains that are present in all TRs. Two of these, the DNA-binding (DBD) and hinge domains, are involved in the ability of the receptor to bind hormone response elements( HREs). TRs also have a ligand binding domain (LBD) that allows them to bind to thyroid hormone with high affinity. The fourth domain is a transactivation domain which allows the receptor to bind other transcription factors.
Function.
Thyroid hormone receptors play critical roles in the regulation of metabolism, heart rate, and development of organisms.
These receptors are typically associated with retinoic acid receptors (RXR), forming heterodimers. In its inactivated form, the TR inhibits gene transcription by binding corepressors. This adds an additional level of regulation to an already tightly regulated process. When activated, these receptors become associated with other activators and initiate gene transcription. TRs are also involved in cell viability, and are believed to have other non-genomic affects that are currently being investigated.
Mechanism of action.
Thyroid hormone is transported into the cell through a transporter. Once inside of the cell, the hormone can have genomic or non-genomic effects. The genomic signaling pathway directly influences gene transcription and translation, while the non-genomic pathway involves more rapid, cellular changes, some of which also regulate gene expression through more indirect signaling.
Genomic signaling pathway.
Thyroid hormone receptors regulate gene expression by binding to hormone response elements (HREs) in DNA either as monomers, heterodimers with other nuclear receptors, or homodimers. Dimerizing with different nuclear receptors leads to the regulation of different genes. THR commonly interacts with the retinoid X receptor (RXR), a nuclear retinoic acid receptor. TR/RXR heterodimers are the most transcriptionally active form of TR.
Retinoic acid receptors.
Retinoic acid receptors are located in the nucleus and commonly form complexes with steroid hormone receptors in order to regulate the production of essential gene products. Retinoic acid receptors bind corepressors in the absence of their ligand, retinoic acid, which is formed from the metabolism of vitamin A. Retinoid X receptors are activated by binding to 9-"cis"-retinoic acid, a specific isomer of retinoic acid. Other retinoic acid receptors are less specific, allowing them to bind isomers of retinoic acid with similar affinities.
Once RXRs bind ligand, they undergo conformational changes that reduce their affinity for corepressors—allowing them to attract coactivators to the transcription site. Once all of the necessary cofactors are present, the presence of a DNA binding domain permits the binding of response elements, initiating gene transcription. Due to their role in gene regulation, studies have shown that these receptors are necessary for growth and development.
Regulation of TRE gene products.
In the absence of hormone, TR forms a complex with corepressor proteins such as nuclear receptor co-repressor 1 (N-CoR) and 2 (N-CoR2). While these cofactors are present, TR binds HREs in a transcriptionally inactive state. This inhibition of gene transcription allows for tight regulation of gene products. Binding of thyroid hormone results in a conformational change in helix 12 of the TR transactivation domain, which displaces the corepressors from the receptor/DNA complex. Coactivator proteins are recruited, forming a DNA/TR/coactivator complex. One coactivator recruited to the site is nuclear receptor co-activator 1 (NCoA-1). RNA polymerase is recruited to the site and transcribes downstream DNA into messenger RNA (mRNA). The mRNA generated is then translated into the corresponding proteins. The protein products from this process drive the changes in cell function observed in the presence of thyroid hormone.
Non-genomic signaling pathway.
Non-genomic effects are faster than genomic effects because they do not require transcription and translation—two very precise and time-consuming processes. Initially most scientists presumed that non-genomic effects were mediated by non-nuclear receptors, but now there is growing evidence for non-genomic effects mediated in the cytoplasm by the traditional nuclear receptors. For example,TR-α1 (a specific isoform of TR) has been linked to cell viability, which is hypothesized to involve a rise in cGMP concentration (through an unknown mechanism) and the corresponding activation of protein kinase G.
Other non-genomic effects that have been observed include the regulation of mitochondrial metabolism, stimulation of glucose uptake, altering cytoskeleton organization, regulating ion pump concentrations at the membrane, and the regulation of osteogenesis. Unfortunately, no specific molecular mechanisms have been provided for these nongenomic signaling pathways, so testing the relative importance of genomic and nongenomic signaling by the nuclear receptors using specific mutations that selectively eliminate one action or the other was not carried out. In contrast, more recently, a specific molecular mechanism for TR-β signaling through the PI3 kinase has been identified, which allowed scientists to obtain direct genetic evidence for the involvement of TR-β signaling through the PI3 kinase in brain development and metabolism, two of the primary physiological effects of thyroid hormone action.
Isoforms.
There are two main classes of the thyroid hormone receptor, alpha and beta. The localization of these subtypes, summarized in Table 1, is largely dependent upon post-transcriptional splicing. Genes on chromosomes 3 and 17 are transcribed and translated into c-erbA gene products. Splicing of these gene products leads to the production of different isoforms. There are three TR-α receptor splice variants encoded by the "THRA" (thyroid hormone receptor alpha) gene and three TR-β isoform splice variants encoded by the "THRB" (thyroid hormone receptor beta) gene. Of these variants, thyroxine is only able to bind to four of them: TR-α1,TR-β1,TR-β2, and TR-β3.
Disease linkage.
Certain mutations in the thyroid hormone receptor are associated with thyroid hormone resistance. The clinical diagnosis of thyroid hormone resistance syndrome (THRS) depends on the location of the resistance, which can be localized to the pituitary gland, peripheral tissues, or both. Patients who present with resistance in both tissue types are diagnosed with global resistance to thyroid hormone. Mutations to both TR genes have been observed clinically, however, THRB gene mutations are much more common.
THRB gene mutation.
TR-βresistance an autosomal dominant disease. This means only one copy of the mutated gene on chromosome 3 needs to be inherited in order for an individual to present with this condition. THRB mutation directly affects the regulation of the hypothalamic-pituitary-thyroid (HPT) axis. In a healthy individual, the TR-β2 expressed in the pituitary gland plays a major role in regulating thyroid-stimulating hormone (TSH) levels through negative feedback. TSH stimulates the thyroid to secrete thyroid hormone. Once secreted, thyroid hormone acts on these receptors and inhibits transcription of "Tshb". This feedback inhibition stops further TSH production, inhibiting thyroid hormone secretion downstream. When the THRB gene is mutated, the receptors on the pituitary can no longer bind thyroid hormone. Due to this, TSH production and secretion is not regulated to the same degree and the thyroid continues to be stimulated. The elimination of the negative feedback loop results in the heightened levels of thyroid hormone presented by patients with this condition.
THRA gene mutation.
The THRA gene is located on chromosome 17. Not as much information is known about mutations to this gene because it is far less common than mutations to THRB. Unlike THRB mutations, THRA mutations do not disrupt the HPT axis. This can make TR-α resistance more difficult to diagnose because patients do not typically present with elevations in thyroid hormone concentration. Due to the high TR-α1 expression in the heart, the cardiovascular system is highly affected by this condition. Additionally, thyroid hormone plays an important role in bone development. Thus, patients with this condition have consistently presented with short stature.
Symptoms.
Symptoms of thyroid hormone resistance syndrome can be similar to those seen in hypothyroidism. Hypothyroidism is a disease in which the thyroid does not produce enough thyroid hormone. Patients with this condition have also presented with symptoms similar to hyperthyroidism. In contrast to hypothyroidism, hyperthyroidismis a disease in which the thyroid produces too much thyroid hormone. Due to the large array of potential symptoms, this condition can be misleading and is often difficult for medical professionals to diagnose.
Common symptoms of TR mutation include:
Changes to the menstrual cycle
Treatment.
Treating patients with hypothyroidism caused by the absence of functional TRs is difficult. Treatments prescribed to patients with thyroid hormone resistance largely depend on the symptoms they present and the type of resistance they have.
For those whose conditions mimic hypothyroidism, prescribing normal thyroid hormone doses may not remedy the symptoms they are experiencing. In order for a ligand to have an effect, it must be able to bind to a receptor. Individuals with a THRB or THRA mutation have less receptors that are able to bind ligand, and a corresponding drop in tissue responsiveness to thyroid hormone. For this reason, physicians may prescribe higher doses of the hormone to increase the probability that the ligand will reach a TR that is functional.
Prescribing thyroid hormone in any dose to patients presenting with symptoms mimicking hyperthyroidism does not improve the condition. For these individuals, beta-blockers can be prescribed to treat the increased sympathetic activation they experience. Beta-blockers are competitive inhibitors of adrenaline, the post-ganglionic neurotransmitter released by cells of the sympathetic nervous system. By blocking the ability of receptors to bind adrenaline, beta-blockers have been observed to alleviate symptoms of anxiety, increased blood pressure, and irregular heartbeat, amongst others. Anti-anxiety medications can also be prescribed to individuals with this conditions to treat symptoms of anxiety.


LGR4

Leucine-rich repeat-containing G-protein coupled receptor 4 is a protein that in humans is encoded by the "LGR4" gene. LGR4 is known to have a role in the development of the male reproductive tract, eyelids, hair and bone.
Mutations in this gene have been associated to osteoporosis (doi:10.1038/nature12124).


LPAR3

Lysophosphatidic acid receptor 3 also known as LPA3 is a protein that in humans is encoded by the "LPAR3" gene. LPA3 is a G protein-coupled receptor that binds the lipid signaling molecule lysophosphatidic acid (LPA).
Function.
This gene encodes a member of the G protein-coupled receptor family, as well as the EDG family of proteins. This protein functions as a cellular receptor for lysophosphatidic acid and mediates lysophosphatidic acid-evoked calcium mobilization. This receptor couples predominantly to G(q/11) alpha proteins.


Flopropione

Flopropione (Compacsul, Cospanon, Ecapron, Pellegal, Argobyl, Floveton, Saritron, Spamorin, Labrodax, Tryalon, Mirulevatin, Padeskin, Profenon) is a spasmolytic or antispasmodic agent. It acts as a COMT inhibitor.
It is synthetized from phloroglucinol in a Hoesch reaction.


Propylnorapomorphine

N-n-Propylnorapomorphine (NPA) is an aporphine derivative dopamine agonist closely related to apomorphine. In rodents it has been shown to produce hyperactivity, stereotypy, hypothermia, antinociception, and penile erection, among other effects. Notably, its effects on locomotion are biphasic, with low doses producing inhibition and catalepsy and high doses resulting in enhancement of activity. This is likely due to preferential activation of D2/D3 autoreceptors versus postsynaptic receptors, the latter of which overcomes the former to increase postsynaptic dopaminergic signaling only with high doses.


Adil Shamoo

Adil E. Shamoo (born August 1, 1941) is an Assyrian biochemist with an interest in biomedical ethics and foreign policy. He is currently a professor at the Department of Biochemistry and Molecular Biology at the University of Maryland.
Professional.
In 1998, he founded the journal "Accountability in Research", and has served as its editor-in-chief since its inception. He is on the editorial boards of several other journals, including the "Drug Information Journal". From 2000 to 2002, he served on the advisory committee for National Human Research Protections. Although he has an extensive list of publications in the fields of biochemistry and microbiology, he is currently busied by his work as an analyst for Foreign Policy In Focus, a project of the Institute for Policy Studies, a think tank, to which he has been contributing since 2005. Shamoo has also authored and co-authored many op-eds on U.S. foreign policy that have been published in newspapers across the country.
Shamoo is also currently occupied with his work in the field of ethics. Since 1991, he has taught a graduate course at the University of Maryland entitled "Responsible Conduct of Research". In 1995, he co-founded the human rights organization, Citizens for Responsible Care and Research (CIRCARE). In 2003, he chaired a Special Issue GlaxoSmithKline Pharmaceuticals' Ethics Advisory Group. Shamoo was then appointed to the Armed Forces Epidemiological Board (AFEB) of the United States Department of Defense as ethics consultant (2003–2004). Because he served as chairman on nine international conferences in ethics in research and human research protection, he was asked to testify before a congressional committee and the National Bioethics Advisory Commission. Since 2006, he has served on the Defense Health Board. And from 2006 to 2007,Shamoo was a member of the new Maryland Governor's Higher Education Transition Working Group. He was an invited participant and presenter in the 2007 New Year Renaissance Weekend.
Shamoo has held visiting professorships at the Institute for Political Studies in Paris, France and at East Carolina University.
Shamoo has been cited and/or appeared frequently in local and national media both print and television. He has published numerous articles and books.
Personal.
Shamoo currently resides in Columbia, MD with his wife and occasional co-author, Bonnie Bricker; his daughter, and stepdaughter. He has two sons and another stepdaughter who also all reside in the Washington Metropolitan Area.
Early life and education.
Shamoo was born and raised in Baghdad, Iraq. He is an ethnic Assyrian. He attended the University of Baghdad and graduated with a degree in physics in 1962. In 1966, he earned a Master's of Science in physics from the University of Louisville. Four years later, in 1970, he finished his Ph.D. in the program in Biology at the City University of New York.


Sandra Pizzarello

Sandra Pizzarello, D.Bi.Sc. is a Venetian biochemist known for her co-discovery of amino acid enantiomeric excess in carbonaceous chondrite meteorites. Her research interests concern the characterization of meteoritic organic compounds in elucidating the evolution of planetary homochirality. Pizzarello is a project collaborator and co-investigator for the NASA Astrobiology Institute (NAI), the president of the International Society for the Study of the Origin of Life, and an emerita professor at Arizona State University (ASU).
Early life and education.
Sandra Pizzarello was born in Venice, Italy in 1933. In 1955, she graduated "summa cum laude" from the University of Padua earning her Doctor of Biological Sciences degree under her adviser Professor Roncato. Pizzarello went on to work as a research associate developing tranquilizers for Farmitalia Research Laboratories in the Department of Neuropharmacology. Over the course of several years, Pizzarello transitioned from research to raising a family. Following a career opportunity for her husband, an aeronautical engineer and computer scientist, she moved her family to Phoenix, Arizona in 1970.
Once Pizzarello's youngest of four children finished primary school, her focus returned to her career after a decade away from scientific research. She audited a graduate biochemistry seminar course at ASU where she met Professor John Cronin, future co-discoverer of amino acid enantiomeric excess in meteorites. Due to her outstanding performance in the course, she was offered a job to work with Cronin at the university as a research professor in analyzing the recently recovered Murchison meteorite.
Research.
Sandra Pizzarello's research over the last forty years has involved the analysis of organic compounds in several carbonaceous chondrites, particularly molecular, chiral, and isotopic characterization of amino acids. Because the formation of these organic-rich meteorites pre-date the origin of life, they had been under investigation as potential sites of primal organic compounds which could shed light on abiogenesis, specifically the origin of biological homochirality. Such studies, however, had been inconclusive until 1997 when Cronin and Pizzarello detected 7-9% L-enantiomeric excesses of three abiological amino acids while analyzing the Murchison meteorite.
Given Earth's history of meteoric impacts and the observation that meteors contain an excess of the biologically relevant L-stereoisomer of certain amino acids, Pizzarello studied the effect of meteoritic amino acids in enantiomeric excess on the formation of other biological molecules. In one study, Pizzarello found that nonracemic solutions of abiological isovaline and proteinogenic alanine can direct the condensation of glycolaldehyde to produce nonracemic solutions of threose and erythrose via an aldol reaction concluding that amino acids can act as asymmetric catalysts in carbohydrate synthesis. These findings support the origin of life hypothesis that homochirality originated prior to life and from extraterrestrial origins. However, Pizzarello's theoretical inquiries into cosmochemical evolution remain debated based on suspect analytical evidence of meteoritic enantiomeric excesses.