Plasmin is an important enzyme present in blood that degrades many blood plasma proteins, including fibrin clots. The degradation of fibrin is termed fibrinolysis. In humans, the plasmin protein is encoded by the PLG gene. Plasmin is a serine protease. Apart from fibrinolysis, plasmin proteolyses proteins in various other systems: It activates collagenases, some mediators of the complement system, weakens the wall of the Graafian follicle, leading to ovulation, it cleaves fibrin, thrombospondin and von Willebrand factor. Plasmin, like trypsin, belongs to the family of serine proteases. Plasmin is released. Two major glycoforms of plasminogen are present in humans - type I plasminogen contains two glycosylation moieties, whereas type II plasminogen contains only a single O-linked sugar. Type II plasminogen is preferentially recruited to the cell surface over the type I glycoform. Conversely, type I plasminogen appears more recruited to blood clots. In circulation, plasminogen adopts a activation resistant conformation.
Upon binding to clots, or to the cell surface, plasminogen adopts an open form that can be converted into active plasmin by a variety of enzymes, including tissue plasminogen activator, urokinase plasminogen activator and factor XII. Fibrin is a cofactor for plasminogen activation by tissue plasminogen activator. Urokinase plasminogen activator receptor is a cofactor for plasminogen activation by urokinase plasminogen activator; the conversion of plasminogen to plasmin involves the cleavage of the peptide bond between Arg-561 and Val-562. Plasmin cleavage produces angiostatin. 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 together with five Kringle domains; the Pan-Apple domain contains important determinants for maintaining plasminogen in the closed form, the kringle domains are responsible for binding to lysine residues present in receptors and substrates. The X-ray crystal structure of closed plasminogen reveals that the PAp and SP domains maintain the closed conformation through interactions made throughout the kringle array.
Chloride ions further bridge the PAp / KR4 and SP / KR2 interfaces, explaining the physiological role of serum chloride in stabilizing the closed conformer. The structural studies reveal that differences in glycosylation alter the position of KR3; these data help explain the functional differences between the type I and type II plasminogen glycoforms. In closed plasminogen, access to the activation bond targeted for cleavage by tPA and uPA is blocked through the position of the KR3/KR4 linker sequence and the O-linked sugar on T346; the position of KR3 may hinder access to the activation loop. The Inter-domain interactions block all kringle ligand-binding sites apart from that of KR-1, suggesting that the latter domain governs pro-enzyme recruitment to targets. Analysis of an intermediate plasminogen structure suggests that plasminogen conformational change to the open form is initiated through KR-5 transiently peeling away from the PAp domain; these movements expose the KR5 lysine-binding site to potential binding partners, suggest a requirement for spatially distinct lysine residues in eliciting plasminogen recruitment and conformational change respectively.
Plasmin is inactivated by proteins such as α2-antiplasmin. The mechanism of plasmin inactivation involves the cleavage of an α2-macroglobulin at the bait region by plasmin; this initiates a conformational change such that the α2-macroglobulin collapses about the plasmin. In the resulting α2-macroglobulin-plasmin complex, the active site of plasmin is sterically shielded, thus decreasing the plasmin's access to protein substrates. Two additional events occur as a consequence of bait region cleavage, namely a h-cysteinyl-g-glutamyl thiol ester of the α2-macroglobulin becomes reactive and a major conformational change exposes a conserved COOH-terminal receptor binding domain; the exposure of this receptor binding domain allows the α2-macroglobulin protease complex to bind to clearance receptors and be removed from circulation. Plasmin deficiency may lead to thrombosis. Plasminogen deficiency in mice leads to defective liver repair, defective wound healing, reproductive abnormalities. In humans, a rare disorder called plasminogen deficiency type I is caused by mutations of the PLG gene and is manifested by ligneous conjunctivitis.
Plasmin has been shown to interact with Thrombospondin 1, Alpha 2-antiplasmin and IGFBP3. Moreover, plasmin induces the generation of bradykinin in mice and humans through high molecular weight kininogen cleavage; the MEROPS online database for peptidases and their inhibitors: S01.233 Plasmin at the US National Library of Medicine Medical Subject Headings This article incorporates text from the United States National Library of Medicine, in the public domain
Ceratopsia or Ceratopia is a group of herbivorous, beaked dinosaurs that thrived in what are now North America and Asia, during the Cretaceous Period, although ancestral forms lived earlier, in the Jurassic. The earliest known ceratopsian, Yinlong downsi, lived between 155.7 million years ago. The last ceratopsian species, Triceratops prorsus, became extinct during the Cretaceous–Paleogene extinction event, 66 million years ago. Early members of the ceratopsian group, such as Psittacosaurus, were small bipedal animals. Members, including ceratopsids like Centrosaurus and Triceratops, became large quadrupeds and developed elaborate facial horns and frills extending over the neck. While these frills might have served to protect the vulnerable neck from predators, they may have been used for display, the attachment of large neck and chewing muscles or some combination of the above. Ceratopsians ranged in size from 23 kilograms to over 9 meters and 9,100 kg. Triceratops is by far the best-known ceratopsian to the general public.
It is traditional for ceratopsian genus names to end in "-ceratops", although this is not always the case. One of the first named genera was Ceratops itself, which lent its name to the group, although it is considered a nomen dubium today as its fossil remains have no distinguishing characteristics that are not found in other ceratopsians. Ceratopsians are recognized by features of the skull. On the tip of a ceratopsian upper jaw is the rostral bone, an edentulous ossification, unique to ceratopsians. Othniel Charles Marsh recognized and named this bone, which acts as a mirror image of the predentary bone on the lower jaw; this ossification evolved to morphologically aid the mastication of plant matter. Along with the predentary bone, which forms the tip of the lower jaw in all ornithischians, the rostral forms a superficially parrot-like beak; the jugal bones below the eye are prominent, flaring out sideways to make the skull appear somewhat triangular when viewed from above. This triangular appearance is accentuated in ceratopsians by the rearwards extension of the parietal and squamosal bones of the skull roof, to form the neck frill.
The epoccipital is a distinctive bone found lining the frills of ceratopsians. The name is a misnomer. Epoccipitals begin as separate bones that fuse during the animal's growth to either the squamosal or parietal bones that make up the base of the frill; these bones were ornamental instead of functional, may have helped differentiate species. Epoccipitals were present in all known ceratopsids with the possible exception of Zuniceratops, they appear to have been broadly different between short-frilled ceratopsids and long-frilled ceratopsids, being elliptical with constricted bases in the former group, triangular with wide bases in the latter group. Within these broad definitions, different species would have somewhat different numbers. In centrosaurines like Centrosaurus and Styracosaurus, these bones become long and spike- or hook-like. A well-known example is the coarse sawtooth fringe of broad triangular epoccipitals on the frill of Triceratops; when regarding the ossification's morphogenetic traits, it can be described as dermal.
The term epoccipital was coined by famous paleontologist Othniel Charles Marsh in 1889. The first ceratopsian remains known to science were discovered during the U. S. Geological and Geographical Survey of the Territories led by the American geologist F. V. Hayden. Teeth discovered during an 1855 expedition to Montana were first assigned to hadrosaurids and included within the genus Trachodon, it was not until the early 20th century. During another of Hayden's expeditions in 1872, Fielding Bradford Meek found several giant bones protruding from a hillside in southwestern Wyoming, he alerted paleontologist Edward Drinker Cope. Cope recognized the remains as a dinosaur, but noted that though the fossil lacked a skull, it was different from any type of dinosaur known, he named the new species Agathaumas sylvestris, meaning "marvellous forest-dweller". Soon after, Cope named two more dinosaurs that would come to be recognized as ceratopsids: Polyonax and Monoclonius. Monoclonius was notable for the number of disassociated remains found, including the first evidence of ceratopsid horns and frills.
Several Monoclonius fossils were found by Cope, assisted by Charles Hazelius Sternberg, in summer 1876 near the Judith River in Chouteau County, Montana. Since the ceratopsians had not been recognised yet as a distinctive group, Cope was uncertain about much of the fossil material, not recognizing the nasal horn core, nor the brow horns, as part of a fossil horn; the frill bone was interpreted as a part of the breastbone. In 1888 and 1889, Othniel Charles Marsh described the first well preserved horned dinosaurs and Triceratops. In 1890 Marsh classified them together in the order Ceratopsia; this prompted Cope to reexamine his own specimens and to realize that Triceratops and Agathaumas all represented a single group of similar dinosaurs, which he named Agathaumidae in 1891. Cope redescribed Monoclonius as a horned dinosaur, with a large nasal horn and two smaller horns over the eyes, a large frill. Ceratopsia was coined by Othniel Charles Marsh in 1890 to include dinosaurs possessing certain characteristic features, including horns, a rostral bone, teeth with two roots, fused neck vertebrae, a forward-oriented pubis.
Camarasaurus was a genus of quadrupedal, herbivorous dinosaurs. It was the most common of the giant sauropods to be found in North America, its fossil remains have been found in the Morrison Formation of Colorado and Utah, dating to the Late Jurassic epoch, between 155 and 145 million years ago. Camarasaurus presented a distinctive cranial profile of a blunt snout and an arched skull, remarkably square, it travelled in herds, or at least in family groups. The name means "chambered lizard", referring to the hollow chambers in its vertebrae. Camarasaurus is among the most common and well-preserved sauropod dinosaurs; the maximum size of the most common species, C. lentus, was about 15 meters in length. The largest species, C. supremus, reached a maximum length of 23 meters and maximum estimated weight of 47 tonnes. The arched skull of Camarasaurus was remarkably square and the blunt snout had many fenestrae, though it was sturdy and is recovered in good condition by paleontologists; the 19 centimeter long teeth were arranged evenly along the jaw.
The strength of the teeth indicates that Camarasaurus ate coarser plant material than the slender-toothed diplodocids. Each front limb bore five toes, with the inner toe having a large sharpened claw. Like most sauropods, the front limbs were shorter than the hind legs, but the high position of the shoulders meant there was little slope in the back. Serving the purpose of weight-saving, as seen in other sauropods, many of the vertebrae were hollowed out, or pneumatic; this feature was little understood at the time Camarasaurus was discovered, but its structure was the inspiration for the creature's name, meaning "chambered lizard". The neck and counterbalancing tail were shorter than usual for a sauropod of this size. Camarasaurus, like certain other sauropods, had an enlargement of the spinal cord near the hips. Palaeontologists believed this to be a second brain necessary to co-ordinate such a huge creature. Indeed, while it would have been an area of intensive nervous system—probably reflex, or automatic—activity, it was not, however, a brain.
Camarasaurus grandis had a more robust radius than fellow sauropod Venenosaurus. A specimen of Camarasaurus called SMA 0002 from Wyoming’s Howe-Stephens Quarry, referred to as "E. T.", shows evidence of soft tissue. Along the jaw line, ossified remains of what appear to have been the animal's gums have been recovered, indicating that Camarasaurus had deep-set teeth covered by gums, with only the tips of the crowns protruding; the teeth were upon death, pushed further out from their sockets as the gums retracted dried, tightened through decay. The examinations of the specimen indicate that the teeth were covered by tough outer scales and a beak of some variety, though this is not known for certain; the first record of Camarasaurus comes from 1877, when a few scattered vertebrae were located in Colorado, by Oramel W. Lucas. Pursuing his long-running and acrimonious competition with Othniel Charles Marsh, the paleontologist Edward Drinker Cope paid for the bones and, moving named them in the same year.
For his part, Marsh named some of his sauropod findings Morosaurus grandis, but most paleontologists today consider them to be a species of Camarasaurus. Such naming conflicts were common between the two rival dinosaur hunters, the most famous being Brontosaurus and Apatosaurus, it was not until 1925. Because, however, it was the skeleton from a young Camarasaurus, many illustrations from the time show the dinosaur to be much smaller than it is now known to be; the type species of Camarasaurus is Cope's original species, C. supremus, named in 1877. Other species since discovered include C. grandis in 1877, C. lentus in 1889, C. lewisi in 1988. C. supremus, as its name suggests, is the largest known species of Camarasaurus and one of the most massive sauropods known from the late Jurassic Morrison Formation. Except for its huge size, it was nearly indistinguishable from C. lentus. C. supremus was not typical of the genus as a whole, is known only from the latest, uppermost parts of the formation.
Both C. grandis and C. lentus were smaller as well as occurring in the earlier stages of the Morrison. Stratigraphic evidence suggests that chronological sequence aligned with the physical differences between the three species. C. grandis occurred in the lowest rock layers of the Morrison. C. lentus appeared co-existing with C. grandis for several million years due to different ecological niches as suggested by differences in the spinal anatomy of the two species. At a stage, C. grandis disappeared from the rock record, leaving only C. lentus. C. lentus too disappeared. This immediate succession of species, as well as the close similarity between the two, suggests that C. supremus may have evolved directly from C. lentus, representing a larger, later-surviving population of animals. Camarasaurus lewisi species
Flushing is to become markedly red in the face and other areas of the skin, from various physiological conditions. Flushing is distinguished, despite a close physiological relation between them, from blushing, milder restricted to the face, cheeks or ears, assumed to reflect emotional stress, such as embarrassment, anger, or romantic stimulation. Flushing is a cardinal symptom of carcinoid syndrome—the syndrome that results from hormones being secreted into systemic circulation. Abrupt cessation of physical exertion abdominal cutaneous nerve entrapment syndrome in patients who have had abdominal surgery alcohol flush reaction antiestrogens such as tamoxifen atropine poisoning body contact with warm or hot water butorphanol reaction with some narcotic analgesics caffeine consumption carbon monoxide poisoning carcinoid tumor chronic obstructive pulmonary disease emphysema cluster headache attack or headache compression of the nerve by the sixth thoracic vertebrae coughing severe coughing fits Cushing's syndrome dehydration dysautonomia emotions: anger, embarrassment fever Kratom fibromyalgia high doses of non flush free niacin histamines homocystinuria Horner's syndrome hot flush hyperglycaemia hyperstimulation of the parasympathetic nervous system the vagus nerve hyperthyroidism inflammation iron poisoning Jarisch-Herxheimer reaction keratosis pilaris rubra faceii Limerence mastocytosis medullary thyroid cancer mixing an antibiotic with alcohol pheochromocytoma polycythemia vera powerful vasodilators, such as dihydropyridine calcium channel blockers rosacea severe pain sexual arousal orgasm sexual intercourse sneezing some recreational drugs, such as alcohol, heroin and amphetamines spicy foods sunburn tachycardia vinpocetine Allergies Commonly referred to as the sex flush, vasocongestion of the skin can occur during all four phases of the human sexual response cycle.
Studies show that the sex flush occurs in 50–75% of females and 25% of males, yet not consistently. The sex flush tends to occur more under warmer conditions and may not appear at all under lower temperatures. During the female sex flush, pinkish spots develop under the breasts spread to the breasts, face, soles of the feet, over the entire body. Vasocongestion is responsible for the darkening of the clitoris and the walls of the vagina during sexual arousal. During the male sex flush, the coloration of the skin develops less than in the female, but starts with the epigastrium, spreads across the chest continues to the neck, forehead and sometimes, shoulders and forearms; the sex flush disappears soon after reaching orgasm, but in other cases it may take up to two hours or so, sometimes intense sweating occurs simultaneously. Cholinergic urticaria Erythema Pallor Rash
Leidyosuchus is an extinct genus of alligatoroid from the Late Cretaceous of Alberta. It was named in 1907 by Lawrence Lambe, the type species is L. canadensis. It is known from a number of specimens from the middle Campanian age Dinosaur Park Formation, it was a medium-sized alligatorid, with a maximum skull length greater than 40 centimeters. A number of species had been assigned to this genus over the years, including: L. acutidentatus, from the Paleocene of Saskatchewan. However, in 1997 Chris Brochu reevaluated the genus and reassigned most of the species, transferring L. acutidentatus, L. formidabilis, L. sternbergii, L. wilsoni to the new genus Borealosuchus, L. multidentatus to the new genus Listrognathosuchus, proposing L. gilmorei as a synonym of L. canadensis, finding L. riggsi to be too fragmentary to be determinable
Inflammation is part of the complex biological response of body tissues to harmful stimuli, such as pathogens, damaged cells, or irritants, is a protective response involving immune cells, blood vessels, molecular mediators. The function of inflammation is to eliminate the initial cause of cell injury, clear out necrotic cells and tissues damaged from the original insult and the inflammatory process, initiate tissue repair; the five classical signs of inflammation are heat, redness and loss of function. Inflammation is a generic response, therefore it is considered as a mechanism of innate immunity, as compared to adaptive immunity, specific for each pathogen. Too little inflammation could lead to progressive tissue destruction by the harmful stimulus and compromise the survival of the organism. In contrast, chronic inflammation may lead to a host of diseases, such as hay fever, atherosclerosis, rheumatoid arthritis, cancer. Inflammation is therefore closely regulated by the body. Inflammation can be classified as either chronic.
Acute inflammation is the initial response of the body to harmful stimuli and is achieved by the increased movement of plasma and leukocytes from the blood into the injured tissues. A series of biochemical events propagates and matures the inflammatory response, involving the local vascular system, the immune system, various cells within the injured tissue. Prolonged inflammation, known as chronic inflammation, leads to a progressive shift in the type of cells present at the site of inflammation, such as mononuclear cells, is characterized by simultaneous destruction and healing of the tissue from the inflammatory process. Inflammation is not a synonym for infection. Infection describes the interaction between the action of microbial invasion and the reaction of the body's inflammatory response—the two components are considered together when discussing an infection, the word is used to imply a microbial invasive cause for the observed inflammatory reaction. Inflammation on the other hand describes purely the body's immunovascular response, whatever the cause may be.
But because of how the two are correlated, words ending in the suffix -itis are sometimes informally described as referring to infection. For example, the word urethritis means only "urethral inflammation", but clinical health care providers discuss urethritis as a urethral infection because urethral microbial invasion is the most common cause of urethritis, it is useful to differentiate inflammation and infection because there are typical situations in pathology and medical diagnosis where inflammation is not driven by microbial invasion – for example, trauma and autoimmune diseases including type III hypersensitivity. Conversely, there is pathology where microbial invasion does not cause the classic inflammatory response – for example, parasitosis or eosinophilia. Acute inflammation is a short-term process appearing within a few minutes or hours and begins to cease upon the removal of the injurious stimulus, it involves a coordinated and systemic mobilization response locally of various immune and neurological mediators of acute inflammation.
In a normal healthy response, it becomes activated, clears the pathogen and begins a repair process and ceases. It is characterized by five cardinal signs:An acronym that may be used to remember the key symptoms is "PRISH", for pain, immobility and heat; the traditional names for signs of inflammation come from Latin: Dolor Calor Rubor Tumor Functio laesa The first four were described by Celsus, while loss of function was added by Galen. However, the addition of this fifth sign has been ascribed to Thomas Sydenham and Virchow. Redness and heat are due to increased blood flow at body core temperature to the inflamed site. Loss of function has multiple causes. Acute inflammation of the lung does not cause pain unless the inflammation involves the parietal pleura, which does have pain-sensitive nerve endings; the process of acute inflammation is initiated by resident immune cells present in the involved tissue resident macrophages, dendritic cells, Kupffer cells and mast cells. These cells possess surface receptors known as pattern recognition receptors, which recognize two subclasses of molecules: pathogen-associated molecular patterns and damage-associated molecular patterns.
PAMPs are compounds that are associated with various pathogens, but which are distinguishable from host molecules. DAMPs are compounds that are associated with host-related cell damage. At the onset of an infection, burn, or other injuries, these cells undergo activation and release inflammatory mediators responsible for the clinical signs of inflammation. Vasodilation and its resulting increased blood flow causes increased heat. Increased permeability of the blood vessels results in an exudation of plasma proteins and fluid into the tissue, which manifests itself as swelling; some of the released mediators such as bradykinin increase the sensitivity to pain. The mediator molecules alter the blood vessels to
Granule (cell biology)
In cell biology, a granule is a small particle. It can be any structure visible by light microscopy; the term is most used to describe a secretory vesicle. A group of leukocytes called granulocytes contain granules and play an important role in the immune system; the granules of certain cells, such as natural killer cells, contain components which can lead to the lysis of neighboring cells. The granules of leukocytes are classified as specific granules. Leukocyte granules are released in response to immunological stimuli during a process known as degranulation; the granules of platelets are alpha granules. In 1957, André and Rouiller first coined the term "nuage".. Its amorphous and fibrous structure occurred in drawings as early as in 1933. Today, the nuage is accepted to represent a characteristic, electrondense germ plasm organelle encapsulating the cytoplasmic face of the nuclear envelope of the cells destined to the germline fate; the same granular material is known under various synonyms: dense bodies, mitochondrial clouds, yolk nuclei, Balbiani bodies, perinuclear P granules in Caenorhabditis elegans, germinal granules in Xenopus laevis, chromatoid bodies in mouse, polar granules in Drosophila.
Molecularly, the nuage is a interwoven network of differentially localized RNA-binding proteins, which in turn localize specific mRNA species for differential storage, asymmetric segregation, differential splicing and/or translational control. The germline granules appear to be ancestral and universally conserved in the germlines of all metazoan phyla. Many germline granule components are part of the piRNA pathway and function to repress transposable elements. A specific type of granule found in the pancreas is an insulin granule. Insulin is a hormone that helps to regulate the amount of glucose in the blood from getting too high, hyperglycemia, or too low, hypoglycemia. Insulin granules are secretory granules, which can release their contents from the cell into the bloodstream; the beta cells in the pancreas are responsible for the storage of insulin and release of it at appropriate times. The beta cells control the release, use unusual mechanisms to do so. Immature insulin granules function as a sorting chamber during the maturation process listed below.
Insulin and other insoluble granule components are kept within the granules. Other soluble proteins and granule parts bud off from the immature granule in a clathrin-coated transport vesicle; the process of proteolysis, removes the unwanted parts from the secretory granule resulting in mature granules. Insulin granules mature in three steps: the lumen of the granule undergoes acidification, due to the acidic properties of a secretory granule; the endoproteases PC1/3 and PC2 aid in this transformation from proinsulin to insulin. Granules are one of the non-living cell organelle of plant cell, it serves as small container of starch in plant cell. In photosynthesis, plants use light energy to produce glucose from carbon dioxide; the glucose is stored in the form of starch granules, in plastids such as chloroplasts and amyloplasts. Toward the end of the growing season, starch accumulates in twigs of trees near the buds. Fruit, seeds and tubers store starch to prepare for the next growing season. Chromaffin granule Kurloff cell