Heparan sulfate (HS) is a linear polysaccharide found in all animal tissues.[1] It occurs as a proteoglycan (HSPG, i.e. Heparan Sulfate ProteoGlycan) in which two or three HS chains are attached in close proximity to cell surface or extracellular matrix proteins.[2][3] It is in this form that HS binds to a variety of protein ligands, including Wnt,[4][5] and regulates a wide range of biological activities, including developmental processes, angiogenesis, blood coagulation, abolishing detachment activity by GrB (Granzyme B),[6] and tumour metastasis. HS has also been shown to serve as cellular receptor for a number of viruses, including the respiratory syncytial virus.[7] One study suggests that cellular heparan sulfate has a role in SARS-CoV-2 Infection, particularly when the virus attaches with ACE2.[8]
The major cell membrane HSPGs are the transmembrane syndecans and the glycosylphosphatidylinositol (GPI) anchored glypicans.[9][10] Other minor forms of membrane HSPG include betaglycan[11] and the V-3 isoform of CD44 present on keratinocytes and activated monocytes.[12]
In the extracellular matrix, especially basement membranes, the multi-domain perlecan, agrin and collagen XVIII core proteins are the main HS-bearing species.
Heparan sulfate is a member of the glycosaminoglycan family of carbohydrates and is very closely related in structure to heparin. Heparin, commonly known as an anticoagulant, is a highly sulfated form of HS which, in contrast to HS, is mainly found in mast cell secretory granules.[13] Both consist of a variably sulfated repeating disaccharide unit. The main disaccharide units that occur in heparan sulfate and heparin are shown below.
The most common disaccharide unit within heparan sulfate is composed of a glucuronic acid (GlcA) linked to N-acetylglucosamine (GlcNAc), typically making up around 50% of the total disaccharide units. Compare this to heparin, where IdoA(2S)-GlcNS(6S) makes up 85% of heparins from beef lung and about 75% of those from porcine intestinal mucosa. Problems arise when defining hybrid GAGs that contain both 'heparin-like' and 'HS-like' structures. It has been suggested that a GAG should qualify as heparin only if its content of N-sulfate groups largely exceeds that of N-acetyl groups and the concentration of O-sulfate groups exceeds those of N-sulfate.[14]
Not shown below are the rare disaccharides containing a 3-O-sulfated glucosamine (GlcNS(3S,6S) or a free amine group (GlcNH3+). Under physiological conditions the ester and amide sulfate groups are deprotonated and attract positively charged counterions to form a salt. It is in this form that HS is thought to exist at the cell surface.
Abbreviations[edit]
- GlcA = β-D-glucuronic acid
- IdoA = α-L-iduronic acid
- IdoA(2S) = 2-O-sulfo-α-L-iduronic acid
- GlcNAc = 2-deoxy-2-acetamido-α-D-glucopyranosyl
- GlcNS = 2-deoxy-2-sulfamido-α-D-glucopyranosyl
- GlcNS(6S) = 2-deoxy-2-sulfamido-α-D-glucopyranosyl-6-O-sulfate
The cell surface receptor binding region of Interferon-γ overlaps with the HS binding region, near the protein's C-terminal. Binding of HS blocks the receptor binding site and as a result, protein-HS complexes are inactive.[41]
WNTGlypican-3 (GPC3) interacts with both Wnt and Frizzled to form a complex and triggers downstream signaling.[4][10] It has been experimentally established that Wnt recognizes a heparan sulfate modif on GPC3, which contains IdoA2S and GlcNS6S, and that the 3-O-sulfation in GlcNS6S3S enhances the binding of Wnt to the glypican.[5]
The HS-binding properties of a number of other proteins are also being studied:
Heparan sulfate analogues are thought to display identical properties as heparan sulfate with exception of being stable in a proteolytic environment like a wound.[42][43] Because heparan sulfate is broken down in chronic wounds by heparanase, the analogues only bind sites where natural heparan sulfate is absent and cannot be broken down by any known heparanases and glycanases.[citation needed] Also the function of the heparan sulfate analogues is the same as heparan sulfate, protecting a variety of protein ligands such as growth factors and cytokines. By holding them in place, the tissue can then use the different protein ligands for proliferation.
https://en.wikipedia.org/wiki/Heparan_sulfate
| Unsulfated, extracellular | |
|---|---|
| Sulfated, extracellular | |
| Sulfated, intracellular | |
| Synthetic | |
respiratory syncytial virus.[7]
Heparan sulfate proteoglycans (HSPGs) are glycoproteins, with the common characteristic of containing one or more covalently attached heparan sulfate (HS) chains, a type of glycosaminoglycan (GAG) (Esko et al. 2009). Cells elaborate a relatively small set of HSPGs (∼17) that fall into three groups according to their location: membrane HSPGs, such as syndecans and glycosylphosphatidylinositol-anchored proteoglycans (glypicans), the secreted extracellular matrix HSPGs (agrin, perlecan, type XVIII collagen), and the secretory vesicle proteoglycan, serglycin (Table 1). Much of the early work in the field concentrated on composition (size, chain number, and structure of the HS chains), biosynthesis, and binding properties of the chains. In 1985, the first somatic cell mutants altered in HSPG expression were identified (Esko et al. 1985), which allowed functional studies in the context of a cell culture model (Zhang et al. 2006). A decade later, the first HSPG mutants in a model organism (Drosophila melanogaster) were identified (Rogalski et al. 1993; Nakato et al. 1995; Häcker et al. 1997; Bellaiche et al. 1998; Lin et al. 1999), which was followed by identification of mutants in nematodes, tree frogs, zebrafish, and mice (Tables 2 and and3).3). HS is evolutionarily ancient and its composition has remained relatively constant from Hydra to humans (Yamada et al. 2007; Lawrence et al. 2008).
Heparan Sulfate Proteoglycans
Parahepadnavirus
Metavirus is a genus of viruses in the family Metaviridae.[1] They are retrotransposons that invade a eukaryotic host genome and may only replicate once the virus has infected the host.[2] These genetic elements exist to infect and replicate in their host genome and are derived from ancestral elements unrelated from their host. Metavirus may use several different hosts for transmission, and has been found to be transmissible through ovule and pollen of some plants.[3]
Metavirus contains five families of the Ty3/Gypsy element with either one or two open-reading frames; these families are mdg1, mdg3, blastopia, 412, and micropia.[4] Each of the five families contains either one or two open-reading frames, gag3 and/or pol3.[5] There is evidence to support that amino acid deprivation in the elements host genome has frequently caused a frameshift towards the Ty3 element.[6] Metavirus corresponds with the Ogre/Tat gene lineage.[7]
https://en.wikipedia.org/wiki/Metavirus
Pseudoviridae is a family of viruses,[1] which includes three genera.[2]
Viruses of the family are actually LTR retrotransposons of the Ty1-copia family. They replicate via structures called virus-like particles (VLPs). VLPs are not infectious like normal virions, but they nevertheless make up an essential part of the pseudoviral lifecycle.[2]
https://en.wikipedia.org/wiki/Pseudoviridae
Sirevirus
Hemivirus
Prosimiispumavirus
Spumaretrovirinae, commonly called spumaviruses (spuma, Latin for "foam") or foamyviruses, is a subfamily of the Retroviridae family.[2] Spumaviruses are exogenous viruses that have specific morphology with prominent surface spikes. The virions contain significant amounts of double-stranded full-length DNA, and assembly is rather unusual in these viruses. Spumaviruses are unlike most enveloped viruses in that the envelope membrane is acquired by budding through the endoplasmic reticulum instead of the cytoplasmic membrane. Some spumaviruses, including the equine foamy virus (EFV), bud from the cytoplasmic membrane.
Some examples of these viruses are simian foamy virus and the human foamy virus.
While spumaviruses will form characteristic large vacuoles in their host cells while in vitro, there is no disease association in vivo.[3]
https://en.wikipedia.org/wiki/Spumaretrovirinae
Vaccinivirus
Caprine arthritis encephalitis virus (CAEV) is a retrovirus which infects goats and cross-reacts immunologicallywith HIV,[1] due to being from the same family of viruses.[2] CAEV cannot be transmitted to humans, including through the consumption of milk from an infected goat.[3] There is no evidence that CAEV can cure HIV in humans.[2][4]
CAEV is commonly transferred within the goat species by ingestion of colostrum or milk from an infected goat, and to a less extent, cross species CAEV transfer by sheep is possible.[3][5]
https://en.wikipedia.org/wiki/Caprine_arthritis_encephalitis_virus
Hepadnaviridae[a] is a family of viruses.[2] Humans, apes, and birds serve as natural hosts. There are currently 18 species in this family, divided among 5 genera.[3] Its best-known member is hepatitis B virus. Diseases associated with this family include: liver infections, such as hepatitis, hepatocellular carcinomas (chronic infections), and cirrhosis.[3][4] It is the sole family in the order Blubervirales.
https://en.wikipedia.org/wiki/Hepadnaviridae
https://gold.jgi.doe.gov/organism?id=Go0333346
Gold Grid | 0000
Respiratory Syncytial Virus Infection
John W. Schweitzer; Nathaniel A. Justice.
Last Update: August 1, 2021.
Continuing Education Activity
The human respiratory syncytial virus (RSV) is one of the most common viruses to infect children worldwide and increasingly is recognized as an important pathogen in adults, especially the elderly. The most common clinical scenario encountered in RSV infection is an upper respiratory infection, but RSV commonly presents in young children as bronchiolitis, a lower respiratory tract illness with small airway obstruction, and can rarely progress to pneumonia, respiratory failure, apnea, and death. This activity reviews the pathophysiology of respiratory syncytial virus infection and highlights the role of the interprofessional team in its management.
https://www.ncbi.nlm.nih.gov/books/NBK459215/
SIV, Simian, Polio SIV AIDS HIV
08-10-2021-2358 - Polio Modified Live Live Vaccine - SIV Cont (Animal derived vaccine only permissible)
The oral polio vaccine (OPV) AIDS hypothesis states that the AIDS pandemic originated from live polio vaccines prepared in chimpanzee tissue cultures, accidentally contaminated with SIV virus and then administered to up to one million Africans between 1957 and 1960 in experimental mass vaccination campaigns.
https://en.wikipedia.org/wiki/Oral_polio_vaccine_AIDS_hypothesis
Sunday, August 15, 2021
08-15-2021-0333 - Viral Lentivirus and Prion Disease Compatible by Incubation Time Comparison/Indication/Similarity/Synergy/etc..
This hypothesis postulates that an as of yet undiscovered infectious viral agent is the cause of the disease. Evidence for this hypothesis is as follows:
Incubation time is comparable to a lentivirus
Strain variation of different isolates of PrPSc[28]
An increasing titre of PrPSc as the disease progresses suggests a replicating agent.
https://en.wikipedia.org/wiki/Transmissible_spongiform_encephalopathy#Genetics
Sunday, August 15, 2021
08-15-2021-0333 - Viral Lentivirus and Prion Disease Compatible by Incubation Time Comparison/Indication/Similarity/Synergy/etc..
This hypothesis postulates that an as of yet undiscovered infectious viral agent is the cause of the disease. Evidence for this hypothesis is as follows:
Incubation time is comparable to a lentivirus
Strain variation of different isolates of PrPSc[28]
An increasing titre of PrPSc as the disease progresses suggests a replicating agent.
https://en.wikipedia.org/wiki/Transmissible_spongiform_encephalopathy#Genetics
Poliovirus, the causative agent of polio (also known as poliomyelitis), is a serotype of the species Enterovirus C, in the family of Picornaviridae.[1]
Poliovirus is composed of an RNA genome and a protein capsid. The genome is a single-stranded positive-sense RNA (+ssRNA) genome that is about 7500 nucleotides long.[2] The viral particle is about 30 nm in diameter with icosahedral symmetry. Because of its short genome and its simple composition—only RNA and a nonenvelopedicosahedral protein coat that encapsulates it, poliovirus is widely regarded as the simplest significant virus.[3]
Poliovirus was first isolated in 1909 by Karl Landsteiner and Erwin Popper.[4] The structure of the virus was first elucidated in 1958 using x-ray diffraction by a team at Birkbeck College led by Rosalind Franklin,[5][6] showing the polio virus to have icosahedral symmetry.[7]
In 1981, the poliovirus genome was published by two different teams of researchers: by Vincent Racaniello and David Baltimore at MIT[8] and by Naomi Kitamura and Eckard Wimmer at Stony Brook University.[9]
The three-dimensional structure of poliovirus was determined in 1985 by James Hogle at Scripps Research Institute using X-ray crystallography.[10]
Poliovirus is one of the most well-characterized viruses, and has become a useful model system for understanding the biology of RNA viruses.
Poliovirus is structurally similar to other human enteroviruses (coxsackieviruses, echoviruses, and rhinoviruses), which also use immunoglobulin-like molecules to recognize and enter host cells.[13] Phylogenetic analysis of the RNA and protein sequences of poliovirus suggests that it may have evolved from a C-cluster Coxsackie A virus ancestor, that arose through a mutation within the capsid.[39] The distinct speciation of poliovirus probably occurred as a result of a change in cellular receptor specificity from intercellular adhesion molecule-1 (ICAM-1), used by C-cluster Coxsackie A viruses, to CD155; leading to a change in pathogenicity, and allowing the virus to infect nervous tissue.
The mutation rate in the virus is relatively high even for an RNA virus with a synonymous substitution rate of 1.0 x 10−2 substitutions/site/year and non synonymous substitution rate of 3.0 x 10−4 substitutions/site/year.[40] Base distribution within the genome is not random with adenosine being less common than expected at the 5' end and higher at the 3' end.[41] Codon use is not random with codons ending in adenosine being favoured and those ending in cytosine or guanine being avoided. Codon use differs between the three genotypes and appears to be driven by mutation rather than selection.[42]
The three serotypes of poliovirus, PV-1, PV-2, and PV-3, each have a slightly different capsid protein. Capsid proteins define cellular receptor specificity and virus antigenicity. PV-1 is the most common form encountered in nature, but all three forms are extremely infectious.[4] As of March 2020, wild PV-1 is highly localized to regions in Pakistan and Afghanistan. Wild PV-2 was declared eradicated in September 2015 after last being detected in 1999,[43] whilst wild PV-3 was declared eradicated in 2019 after last being detected in 2012.[44]
Specific strains of each serotype are used to prepare vaccines against polio. Inactive polio vaccine is prepared by formalin inactivation of three wild, virulent reference strains, Mahoney or Brunenders (PV-1), MEF-1/Lansing (PV-2), and Saukett/Leon (PV-3). Oral polio vaccine contains live attenuated (weakened) strains of the three serotypes of poliovirus. Passaging the virus strains in monkey kidney epithelial cells introduces mutations in the viral IRES, and hinders (or attenuates) the ability of the virus to infect nervous tissue.[34]
Polioviruses were formerly classified as a distinct species belonging to the genus Enterovirus in the family Picornaviridae. In 2008, the Poliovirus species was eliminated and the three serotypes were assigned to the species Human enterovirus C (later renamed Enterovirus C), in the genus Enterovirus in the family Picornaviridae. The type species of the genus Enterovirus was changed from Poliovirus to (Human) Enterovirus C.[45]
The primary determinant of infection for any virus is its ability to enter a cell and produce additional infectious particles. The presence of CD155 is thought to define the animals and tissues that can be infected by poliovirus. CD155 is found (outside of laboratories) only on the cells of humans, higher primates, and Old World monkeys. Poliovirus is, however, strictly a human pathogen, and does not naturally infect any other species (although chimpanzees and Old World monkeys can be experimentally infected).[46]
The CD155 gene appears to have been subject to positive selection.[47] The protein has several domains of which domain D1 contains the polio virus binding site. Within this domain, 37 amino acids are responsible for binding the virus.
Poliovirus is an enterovirus. Infection occurs via the fecal–oral route, meaning that one ingests the virus and viral replication occurs in the alimentary tract.[48] Virus is shed in the feces of infected individuals. In 95% of cases only a primary, transient presence of viremia (virus in the bloodstream) occurs, and the poliovirus infection is asymptomatic. In about 5% of cases, the virus spreads and replicates in other sites such as brown fat, reticuloendothelial tissue, and muscle. The sustained viral replication causes secondary viremia and leads to the development of minor symptoms such as fever, headache, and sore throat.[49] Paralytic poliomyelitis occurs in less than 1% of poliovirus infections. Paralytic disease occurs when the virus enters the central nervous system (CNS) and replicates in motor neurons within the spinal cord, brain stem, or motor cortex, resulting in the selective destruction of motor neurons leading to temporary or permanent paralysis. This is a very rare event in babies, who still have anti-poliovirus antibodies acquired from their mothers.[50] In rare cases, paralytic poliomyelitis leads to respiratory arrest and death. In cases of paralytic disease, muscle pain and spasms are frequently observed prior to onset of weakness and paralysis. Paralysis typically persists from days to weeks prior to recovery.[51]
n many respects, the neurological phase of infection is thought to be an accidental diversion of the normal gastrointestinal infection.[17] The mechanisms by which poliovirus enters the CNS are poorly understood. Three nonmutually exclusive hypotheses have been suggested to explain its entry. All theories require primary viremia. The first hypothesis predicts that virions pass directly from the blood into the central nervous system by crossing the blood–brain barrier independent of CD155.[52] A second hypothesis suggests that the virions are transported from peripheral tissues that have been bathed in the viremic blood, for example muscle tissue, to the spinal cord through nerve pathways via retrograde axonal transport.[53][54][55] A third hypothesis is that the virus is imported into the CNS via infected monocytes or macrophages.[11]
https://en.wikipedia.org/wiki/Poliovirus
Enterovirus C is a species of enterovirus. Its best known subtype is poliovirus, the cause of poliomyelitis.[1] There are three serotypes of poliovirus, PV1, PV2, and PV3. Other subtypes of Enterovirus C include EV-C95, EV-C96, EV-C99, EV-C102, EV-C104, EV-C105, EV-C109, EV-C116, EV-C117, and EV-C118. Some non-polio types of Enterovirus C have been associated with the polio-like condition AFP (acute flaccid paralysis), including 2 isolates of EV-C95 from Chad.[2]
https://en.wikipedia.org/wiki/Enterovirus_C
Picornaviruses are a group of related nonenveloped RNA viruses which infect vertebrates including mammals and birds. They are viruses that represent a large family of small, positive-sense, single-stranded RNA viruses with a 30-nm icosahedral capsid. The viruses in this family can cause a range of diseases including the common cold, poliomyelitis, meningitis, hepatitis, and paralysis.[2][3][4][5]
Picornaviruses constitute the family Picornaviridae, order Picornavirales, and realm Riboviria. There are 158 species in this family, assigned to 68 genera. Notable examples are genera Enterovirus (including Rhinovirus and Poliovirus), Aphthovirus, Cardiovirus, and Hepatovirus.[1][6]
https://en.wikipedia.org/wiki/Picornavirus
In immunology, the mononuclear phagocyte system or mononuclear phagocytic system (MPS) also known as the reticuloendothelial system or macrophage system is a part of the immune system that consists of the phagocytic cells[1] located in reticular connective tissue. The cells are primarily monocytes and macrophages, and they accumulate in lymph nodes and the spleen. The Kupffer cells of the liver and tissue histiocytes are also part of the MPS. The mononuclear phagocyte system and the monocyte macrophage system refer to two different entities, often mistakenly understood as one.[citation needed]
"Reticuloendothelial system" is an older term for the mononuclear phagocyte system, but it is used less commonly now, as it is understood that most endothelial cells are not macrophages.[2]
The mononuclear phagocyte system is also a somewhat dated concept trying to combine a broad range of cells, and should be used with caution.[3]
https://en.wikipedia.org/wiki/Mononuclear_phagocyte_system
https://en.wikipedia.org/wiki/Poliovirus
Progressive multifocal leukoencephalopathy
Progressive multifocal leukoencephalopathy (PML) is a rare and often fatal viral disease characterized by progressive damage (-pathy) or inflammation of the white matter (leuko-) of the brain(-encephalo-) at multiple locations (multifocal). It is caused by the JC virus, which is normally present and kept under control by the immune system. The JC virus is harmless except in cases of weakened immune systems. In general, PML has a mortality rate of 30–50% in the first few months, and those who survive can be left with varying degrees of neurological disabilities.
PML occurs almost exclusively in patients with severe immune deficiency, most commonly among patients with acquired immune deficiency syndrome (AIDS), but people on chronic immunosuppressivemedications including chemotherapy are also at increased risk of PML, such as patients with transplants, Hodgkin's lymphoma, multiple sclerosis, psoriasis, and other autoimmune diseases.
https://en.wikipedia.org/wiki/Progressive_multifocal_leukoencephalopathy
White matter fibromatosis/fibrosarcoma, cartiledge, connective tissue - inflammation, keloid scarring, biofilm, plaque, tartar, calculus, mineralization, caviation, liquefication. lipo, polysa, prot, mixtures (phospholip), acid base salt etc., etc..
White Tissues - cancer, myelin sheath, fibromatosis, fibrosarcoma, fibroid, keloid, scar, white matter brain, syncytia, connective tissue, cartiledge, bone, joint cav, tubular proteins, protein, precipitate, bacteria shell, biofilm, channels, macrophage, leukocyte, sclera, etc.
https://en.wikipedia.org/wiki/Myelin
https://en.wikipedia.org/wiki/Egg_white
Blubervirales, Hepadnaviridae, Buboules, Globulins
granulovirus, bacillus, black lead fungee, mucormycosis, etc..
sewer and water and food treatments, methroxetrate insecticides pesticides industrial chemicals run off nuclear chemicals (USA water treatments) anti-neoplasics sterilytics abortinants growth-impeditors insect-chemicals disease run off etc..
Human polyomavirus 2, commonly referred to as the JC virus or John Cunningham virus, is a type of human polyomavirus (formerly known as papovavirus).[3] It was identified by electron microscopy in 1965 by ZuRhein and Chou,[4] and by Silverman and Rubinstein, and later isolated in culture and named using the two initials of a patient, John Cunningham, with progressive multifocal leukoencephalopathy (PML).[5] The virus causes PML and other diseases only in cases of immunodeficiency, as in AIDS or during treatment with immunosuppressive drugs (e.g. in organ transplant patients).[6] (poliomyelitis and steve silvers span-eur-lat-middleeast-etc.)
https://en.wikipedia.org/wiki/Human_polyomavirus_2
Rabies is a viral disease that causes inflammation of the brain in humans and other mammals.[1] Early symptoms can include fever and tingling at the site of exposure.[1] These symptoms are followed by one or more of the following symptoms: nausea, vomiting, violent movements, uncontrolled excitement, fear of water, an inability to move parts of the body, confusion, and loss of consciousness.[1][5][6][7] Once symptoms appear, the result is nearly always death.[1] The time period between contracting the disease and the start of symptoms is usually one to three months but can vary from less than one week to more than one year.[1] The time depends on the distance the virus must travel along peripheral nerves to reach the central nervous system.[8] (RAbles)
https://en.wikipedia.org/wiki/Rabies
https://en.wikipedia.org/wiki/Neglected_tropical_diseases
08-23-2021-1127 - Simian foamy virus SFV Cancer - SFV causes cells to fuse with each other to form syncytia, whereby the cell becomes multi-nucleated and many vacuoles form, giving it a "foamy" appearance. Tropism Molecular Clock Substitution Rate Rates 1.16 COII COll cospeciation evolved at a very low rate substitutions per site per year 30 million years vertebrate RNA virus etc.
https://nikiyaantonbettey.blogspot.com/2021/08/08-23-2021-1127-simian-foamy-virus.html
08-23-2021-1048 - BIOLOGICAL TISSUES - animals Connective Epithelial Muscular Nervous
Methotrexate (MTX), formerly known as amethopterin, is a chemotherapy agent and immune-system suppressant.[4] It is used to treat cancer, autoimmune diseases, and ectopic pregnancy and for medical abortions.[4] Types of cancers it is used for include breast cancer, leukemia, lung cancer, lymphoma, gestational trophoblastic disease, and osteosarcoma.[4] Types of autoimmune diseases it is used for include psoriasis, rheumatoid arthritis, and Crohn's disease.[4] It can be given by mouth or by injection.[4]
Common side effects include nausea, feeling tired, fever, increased risk of infection, low white blood cell counts, and breakdown of the skin inside the mouth.[4] Other side effects may include liver disease, lung disease, lymphoma, and severe skin rashes.[4] People on long-term treatment should be regularly checked for side effects.[4] It is not safe during breastfeeding.[4] In those with kidney problems, lower doses may be needed.[4] It acts by blocking the body's use of folic acid.[4]
Methotrexate was first made in 1947 and initially was used to treat cancer, as it was less toxic than the then current treatments.[7] In 1956 it provided the first cures of a metastatic cancer.[8] It is on the World Health Organization's List of Essential Medicines, the safest and most effective medicines needed in a health system.[9] Methotrexate is available as a generic medication.[4] In 2018, it was the 123rd most commonly prescribed medication in the United States, with more than 5 million prescriptions.[10][11]
The physical stress of beating egg whites can create a foam. Two types of physical stress are caused by beating them with a whisk.
The first of which occurs as the whisk drags the liquid through itself, creating a force that unfolds the protein molecules. This process is called denaturation.
The second stress comes from the mixing of air into the whites, which causes the proteins to come out of their natural state. These denatured proteins gather together where the air and water meet and create multiple bonds with the other unraveled proteins, and thus become a foam, holding the incorporated air in place, because the proteins consist of amino acids; some are hydrophilic (attracted to water) and some are hydrophobic (repelled by water). This process is called coagulation.[6][3]
When beating egg whites, they are classified in three stages according to the peaks they form when the beater is lifted: soft, firm, and stiff peaks. Overbeaten eggs take on a dry appearance, and eventually collapse. Egg whites do not beat up correctly if they are exposed to any form of fat, such as cooking oils or the fats contained in egg yolk.
Copper bowls have been used in France since the 18th century to stabilize egg foams. The copper in the bowl assists in creating a tighter bond in reactive sulfur items such as egg whites. The bond created is so tight that the sulfurs are prevented from reacting with any other material. A silver-plated bowl has the same result as the copper bowl, as will a pinch of powdered copper supplement from a health store used in a glass bowl. Drawbacks of the copper bowl include the expense of the bowl itself, and that the bowls are difficult to keep clean. Copper contamination from the bowl is minimal, as a cup of foam contains a tenth of a human's normal daily intake level.[3][7]
https://en.wikipedia.org/wiki/Egg_white
Note. Prion disease, defective interfering particle, etc.
Defective interfering particles (DIPs), also known as defective interfering viruses, are spontaneously generated virus mutants in which a critical portion of the particle's genome has been lost due to defective replication or non-homologous recombination.[2][3] The mechanism of their formation is presumed to be as a result of template-switching during replication of the viral genome, although non-replicative mechanisms involving direct ligation of genomic RNA fragments have also been proposed.[4][5] DIPs are derived from and associated with their parent virus, and particles are classed as DIPs if they are rendered non-infectious due to at least one essential gene of the virus being lost or severely damaged as a result of the defection.[6] A DIP can usually still penetrate host cells, but requires another fully functional virus particle (the 'helper' virus) to co-infecta cell with it, in order to provide the lost factors.[7][8]
DIPs were first observed as early as the 1950s by Von Magnus and Schlesinger, both working with influenza viruses.[9] However, the formalization of DIPs terminology was in 1970 by Huang and Baltimore when they noticed the presence of ‘stumpy’ particles of vesicular stomatitis virus in electron micrographs.[10] DIPs can occur within nearly every class of both DNA and RNA viruses both in clinical and laboratory settings including poliovirus, SARS coronavirus, measles, alphaviruses, respiratory syncytial virus and influenza virus.[11][12][13][14][15][16][17][18]
https://en.wikipedia.org/wiki/Defective_interfering_particle
Full length plasminogen comprises seven domains. In addition to a C-terminal chymotrypsin-like serine protease domain, plasminogen contains an N-terminal Pan Apple domain (PAp) together with five Kringle domains (KR1-5). The Pan-Apple domain contains important determinants for maintaining plasminogen in the closed form, and the kringle domains are responsible for binding to lysine residues present in receptors and substrates.
Plasmin deficiency may lead to thrombosis, as the clots are not adequately degraded. Plasminogen deficiency in mice leads to defective liver repair,[11]defective wound healing, reproductive abnormalities.[citation needed]
In humans, a rare disorder called plasminogen deficiency type I (Online Mendelian Inheritance in Man (OMIM): 217090) is caused by mutations of the PLG gene and is often manifested by ligneous conjunctivitis.
https://en.wikipedia.org/wiki/Plasmin
Sadir R, Forest E, Lortat-Jacob H (May 1998). "The heparan sulfate binding sequence of interferon-gamma increased the on rate of the interferon-gamma-interferon-gamma receptor complex formation". The Journal of Biological Chemistry. 273 (18): 10919–25. doi:10.1074/jbc.273.18.10919. PMID 9556569.
- Silbert JE (November 1967). "Biosynthesis of heparin. 3. Formation of a sulfated glycosaminoglycan with a microsomal preparation from mast cell tumors". The Journal of Biological Chemistry. 242 (21): 5146–52. PMID 4228675.
As an HS chain polymerises, it undergoes a series of modification reactions carried out by four classes of sulfotransferases and an epimerase. The availability of the sulfate donor PAPS is crucial to the activity of the sulfotransferases.[19][20]
 | |
| Names | |
|---|---|
| Preferred IUPAC name [(2R,3S,4R,5R)-5-(6-Amino-9H-purin-9-yl)-4-hydroxy-3-(phosphonooxy)oxolan-2-yl]methyl hydrogen (sulfooxy)phosphonate |
APS and PAPS are intermediates in the reduction of sulfate to sulfite, an exothermic conversion that is carried out by sulfate-reducing bacteria. In these organisms, sulfate serves as an electron acceptor, akin to the use of O2 as an electron acceptor by aerobic organisms. Sulfate is not reduced directly but must be activated by the formation of APS or PAPS. These carriers of activated sulfate are produced by reaction with ATP. The first reaction is catalysed by ATP sulfurylase:
- SO42− + ATP → APS + PPi
The conversion of APS to PAPS is catalysed by APS kinase:
- APS + ATP → PAPS + ADP
Reduction of APS leads to sulfite, which is further reduced to hydrogen sulfide, which is excreted. This process is called dissimilatory sulfate reduction. Reduction of PAPS, a more elaborated sulfate ester, leads also to hydrogen sulfide. But in this case, the product is used in biosynthesis, e.g. for the production of cysteine. The latter process is called assimilatory sulfate reduction because the sulfate sulfur is assimilated.[4]
Other names
3′-Phosphoadenylyl sulfate
Phosphoadenosine phosphosulfate
3′-Phospho-5′-adenylyl sulfate
References[edit]
- ^ Negishi M; Pedersen LG; Petrotchenko E; et al. (2001). "Structure and function of sulfotransferases". Arch. Biochem. Biophys. 390 (2): 149–57. doi:10.1006/abbi.2001.2368. PMID 11396917.
- ^ Xu, Zhen-Hua; Otterness, Diane M.; Freimuth, Robert R.; Carlini, Edward J.; Wood, Thomas C.; Mitchell, Steve; Moon, Eunpyo; Kim, Ung-Jin; Xu, Jing-Ping; Siciliano, Michael J.; Weinshilboum, Richard M. (February 2000). "Human 3′-Phosphoadenosine 5′-Phosphosulfate Synthetase 1 (PAPSS1) and PAPSS2: Gene Cloning, Characterization and Chromosomal Localization". Biochemical and Biophysical Research Communications. 268 (2): 437–444. doi:10.1006/bbrc.2000.2123. PMID 10679223.
- ^ Venkatachalam, K. V. (2003). "Human 3′-phosphoadenosine 5′-phosphosulfate (PAPS) synthase: Biochemistry, molecular biology and genetic deficiency". IUBMB Life. 55 (1): 1–11. doi:10.1080/1521654031000072148. PMID 12716056. S2CID 37733913.
- ^ M. T. Madigan, J. M. Martinko, J. Parker “Brock Biology of Microorganisms” Prentice Hall, 1997. ISBN 0-13-520875-0.
In enzymology, a sulfate adenylyltransferase (EC 2.7.7.4) is an enzyme that catalyzes the chemical reaction
- ATP + sulfate pyrophosphate + adenylyl sulfate
Thus, the two substrates of this enzyme are ATP and sulfate, whereas its two products are pyrophosphateand adenylyl sulfate.
This enzyme belongs to the family of transferases, specifically those transferring phosphorus-containing nucleotide groups (nucleotidyltransferases). The systematic name of this enzyme class is ATP:sulfate adenylyltransferase. Other names in common use include adenosine-5'-triphosphate sulfurylase, adenosinetriphosphate sulfurylase, adenylylsulfate pyrophosphorylase, ATP sulfurylase, ATP-sulfurylase, and sulfurylase. This enzyme participates in 3 metabolic pathways: purine metabolism, selenoamino acid metabolism, and sulfur metabolism.
Some sulfate adenylyltransferases are part of a bifunctional polypeptide chain associated with adenosyl phosphosulfate (APS) kinase. Both enzymes are required for PAPS (phosphoadenosine-phosphosulfate) synthesis from inorganic sulfate.[1][2]
Sulfate-reducing microorganisms (SRM) or sulfate-reducing prokaryotes (SRP) are a group composed of sulfate-reducing bacteria (SRB) and sulfate-reducing archaea (SRA), both of which can perform anaerobic respiration utilizing sulfate (SO42–) as terminal electron acceptor, reducing it to hydrogen sulfide (H2S).[1][2]Therefore, these sulfidogenic microorganisms "breathe" sulfate rather than molecular oxygen (O2), which is the terminal electron acceptor reduced to water (H2O) in aerobic respiration.
Most sulfate-reducing microorganisms can also reduce some other oxidized inorganic sulfur compounds, such as sulfite (SO32–), dithionite (S2O42–), thiosulfate (S2O32–), trithionate (S3O62–), tetrathionate (S4O62−), elemental sulfur (S8), and polysulfides (Sn2−). Depending on the context, "sulfate-reducing microorganisms" can be used in a broader sense (including all species that can reduce any of these sulfur compounds) or in a narrower sense (including only species that reduce sulfate, and excluding strict thiosulfate and sulfur reducers, for example).
Sulfate-reducing microorganisms can be traced back to 3.5 billion years ago and are considered to be among the oldest forms of microbes, having contributed to the sulfur cycle soon after life emerged on Earth.[3]
Many organisms reduce small amounts of sulfates in order to synthesize sulfur-containing cell components; this is known as assimilatory sulfate reduction. By contrast, the sulfate-reducing microorganisms considered here reduce sulfate in large amounts to obtain energy and expel the resulting sulfide as waste; this is known as dissimilatory sulfate reduction.[4] They use sulfate as the terminal electron acceptor of their electron transport chain.[5] Most of them are anaerobes; however, there are examples of sulfate-reducing microorganisms that are tolerant of oxygen, and some of them can even perform aerobic respiration.[6] No growth is observed when oxygen is used as the electron acceptor.[7] In addition, there are sulfate-reducing microorganisms that can also reduce other electron acceptors, such as fumarate, nitrate (NO3−), nitrite (NO2−), ferric iron [Fe(III)], and dimethyl sulfoxide (DMSO).[1][8]
In terms of electron donor, this group contains both organotrophs and lithotrophs. The organotrophs oxidize organic compounds, such as carbohydrates, organic acids (e.g., formate, lactate, acetate, propionate, and butyrate), alcohols (methanol and ethanol), aliphatic hydrocarbons (including methane), and aromatic hydrocarbons (benzene, toluene, ethylbenzene, and xylene).[9] The lithotrophs oxidize molecular hydrogen (H2), for which they compete with methanogens and acetogens in anaerobic conditions.[9] Some sulfate-reducing microorganisms can directly utilize metallic iron [Fe(0)] (zerovalent iron, or ZVI) as electron donor, oxidizing it to ferrous iron [Fe(II)].[10]
https://en.wikipedia.org/wiki/Sulfate-reducing_microorganism
In chemistry, pyrophosphates are phosphorus oxyanions that contain two phosphorus atoms in a P-O-P linkage. A number of pyrophosphate salts exist, such as disodium pyrophosphate (Na2H2P2O7) and tetrasodium pyrophosphate (Na4P2O7), among others. Often pyrophosphates are called diphosphates. The parent pyrophosphates are derived from partial or complete neutralization of pyrophosphoric acid. The pyrophosphate bond is also sometimes referred to as a phosphoanhydride bond, a naming convention which emphasizes the loss of water that occurs when two phosphates form a new P-O-P bond, and which mirrors the nomenclature for anhydrides of carboxylic acids. Pyrophosphates are found in ATP and other nucleotide triphosphates, which are very important in biochemistry.
Pyrophosphates are prepared by heating phosphates, hence the name pyro-phosphate (from the Ancient Greek: πῦρ, πυρός, romanized: pyr, pyros, lit. 'fire'[1]). More precisely, they are generated by heating phosphoric acids to the extent that a condensation reaction occurs.
Pyrophosphates are generally white or colorless. The alkali metal salts are water-soluble.[2] They are good complexing agents for metal ions (such as calcium and many transition metals) and have many uses in industrial chemistry. Pyrophosphate is the first member of an entire series of polyphosphates.[3]
The term pyrophosphate is also the name of esters formed by the condensation of a phosphorylated biological compound with inorganic phosphate, as for dimethylallyl pyrophosphate. This bond is also referred to as a high-energy phosphate bond.
https://en.wikipedia.org/wiki/Pyrophosphate
Sulfur Oxene - chainey worm
phosphate
Pyrophosphate
The anion P
2O4−
7 is abbreviated PPi, standing for inorganic pyrophosphate. It is formed by the hydrolysis of ATP into AMP in cells.
- ATP → AMP + PPi
For example, when a nucleotide is incorporated into a growing DNA or RNA strand by a polymerase, pyrophosphate (PPi) is released. Pyrophosphorolysis is the reverse of the polymerization reaction in which pyrophosphate reacts with the 3′-nucleosidemonophosphate (NMP or dNMP), which is removed from the oligonucleotide to release the corresponding triphosphate (dNTP from DNA, or NTP from RNA).
The pyrophosphate anion has the structure P
2O4−
7, and is an acid anhydride of phosphate. It is unstable in aqueous solution and hydrolyzes into inorganic phosphate:
- P
2O4−
7 + H2O → 2 HPO2−
4
or in biologists' shorthand notation:
- PPi + H2O → 2 Pi + 2 H+
In the absence of enzymic catalysis, hydrolysis reactions of simple polyphosphates such as pyrophosphate, linear triphosphate, ADP, and ATP normally proceed extremely slowly in all but highly acidic media.[4]
(The reverse of this reaction is a method of preparing pyrophosphates by heating phosphates.)
This hydrolysis to inorganic phosphate effectively renders the cleavage of ATP to AMP and PPi irreversible, and biochemical reactions coupled to this hydrolysis are irreversible as well.
PPi occurs in synovial fluid, blood plasma, and urine at levels sufficient to block calcification and may be a natural inhibitor of hydroxyapatite formation in extracellular fluid (ECF).[5] Cells may channel intracellular PPi into ECF.[6] ANK is a nonenzymatic plasma-membrane PPi channel that supports extracellular PPi levels.[6] Defective function of the membrane PPi channel ANK is associated with low extracellular PPi and elevated intracellular PPi.[5]Ectonucleotide pyrophosphatase/phosphodiesterase (ENPP) may function to raise extracellular PPi.[6]
From the standpoint of high energy phosphate accounting, the hydrolysis of ATP to AMP and PPi requires two high-energy phosphates, as to reconstitute AMP into ATP requires two phosphorylation reactions.
- AMP + ATP → 2 ADP
- 2 ADP + 2 Pi → 2 ATP
The plasma concentration of inorganic pyrophosphate has a reference range of 0.58–3.78 µM (95% prediction interval).[7]
https://en.wikipedia.org/wiki/Pyrophosphate
- Bailly, Anatole. "Greek-french dictionary online". www.tabularium.be. Retrieved March 12, 2019.
- ^ C.Michael Hogan. 2011. Phosphate. Encyclopedia of Earth. Topic ed. Andy Jorgensen. Ed.-in-Chief C.J.Cleveland. National Council for Science and the Environment. Washington DC
- ^ Greenwood, Norman N.; Earnshaw, Alan (1997). Chemistry of the Elements (2nd ed.). Butterworth-Heinemann. ISBN 978-0-08-037941-8.
- ^ Van Wazer JR, Griffith EJ, McCullough JF (Jan 1955). "Structure and Properties of the Condensed Phosphates. VII. Hydrolytic Degradation of Pyro- and Tripolyphosphate". J. Am. Chem. Soc. 77 (2): 287–291. doi:10.1021/ja01607a011.
- ^ a b Ho AM, Johnson MD, Kingsley DM (Jul 2000). "Role of the mouse ank gene in control of tissue calcification and arthritis". Science. 289 (5477): 265–70. Bibcode:2000Sci...289..265H. doi:10.1126/science.289.5477.265. PMID 10894769.
- Bandurski RS, Wilson LG, Squires CL (1956). "The mechanism of "active sulfate" formation". J. Am. Chem. Soc. 78 (24): 6408–6409. doi:10.1021/ja01605a028.
- Hilz H; Lipmann F (1955). "The enzymatic activation of sulfate". Proc. Natl. Acad. Sci. USA. 41 (11): 880–890. Bibcode:1955PNAS...41..880H. doi:10.1073/pnas.41.11.880. PMC 534298. PMID 16589765.
The role of heparan sulphate in inflammation
Nature Reviews Immunology 6, 633–643 (2006)
Key Points
Leukocyte extravasation into inflammatory sites is a multistep process involving cell adhesion, transendothelial migration and entry into tissues.
Heparan sulphate proteoglycans (HSPGs) are distributed throughout the blood-vessel wall and are now known to participate in every stage of leukocyte extravasation.
The multifunctional role of HSPGs in inflammation is mainly due to their heparan sulphate chains, which are negatively charged polysaccharides with enormous sequence diversity. This allows HSPGs to interact with a vast array of ligands.
Owing to their structural diversity, heparan sulphates can do the following: function as lymphocyte (L)-selectin ligands and mediate initial adhesion of leukocytes to the inflamed endothelium; bind chemokines and establish chemokine gradients within the vessel wall; transport chemokines across the vessel wall through a process known as transcytosis; and provide a reservoir of growth factors and cytokines within the subendothelial basement membrane, which are released by the heparan-sulphate-degrading enzyme heparanase during inflammatory responses.
HSPGs in the subendothelial basement membrane can also act as a barrier to leukocyte extravasation, with heparanase having an important role in degrading this barrier.
Heparan-sulphate mimetics that block some of these HSPG-dependent processes have considerable potential as anti-inflammatory drugs.
Abstract
The polysaccharide heparan sulphate is ubiquitously expressed as a proteoglycan in extracellular matrices and on cell surfaces. Heparan sulphate has marked sequence diversity that allows it to specifically interact with many proteins. This Review focuses on the multiple roles of heparan sulphate in inflammatory responses and, in particular, on its participation in almost every stage of leukocyte transmigration through the blood-vessel wall. Heparan sulphate is involved in the initial adhesion of leukocytes to the inflamed endothelium, the subsequent chemokine-mediated transmigration through the vessel wall and the establishment of both acute and chronic inflammatory reactions.