Hyaluronic acid called hyaluronan, is an anionic, nonsulfated glycosaminoglycan distributed throughout connective and neural tissues. It is unique among glycosaminoglycans in that it is nonsulfated, forms in the plasma membrane instead of the Golgi apparatus, can be large: human synovial HA averages about 7 million Da per molecule, or about twenty thousand disaccharide monomers, while other sources mention 3–4 million Da. One of the chief components of the extracellular matrix, contributes to cell proliferation and migration, may be involved in the progression of some malignant tumors; the average 70 kg person has 15 grams of hyaluronan in the body, one-third of, turned over every day. Hyaluronic acid is a component of the group A streptococcal extracellular capsule, is believed to play a role in virulence; until the late 1970s, hyaluronic acid was described as a "goo" molecule, a ubiquitous carbohydrate polymer, part of the extracellular matrix. For example, hyaluronic acid is a major component of the synovial fluid, was found to increase the viscosity of the fluid.
Along with lubricin, it is one of the fluid's main lubricating components. Hyaluronic acid is an important component of articular cartilage, where it is present as a coat around each cell; when aggrecan monomers bind to hyaluronan in the presence of HAPLN1, large negatively charged aggregates form. These aggregates are responsible for the resilience of cartilage; the molecular weight of hyaluronan in cartilage decreases with age. A lubricating role of hyaluronan in muscular connective tissues to enhance the sliding between adjacent tissue layers has been suggested. A particular type of fibroblasts, embedded in dense fascial tissues, has been proposed as being cells specialized for the biosynthesis of the hyaluronan-rich matrix, their related activity could be involved in regulating the sliding ability between adjacent muscular connective tissues. Hyaluronic acid is a major component of skin, where it is involved in tissue repair; when skin is exposed to excessive UVB rays, it becomes inflamed and the cells in the dermis stop producing as much hyaluronan, increase the rate of its degradation.
Hyaluronan degradation products accumulate in the skin after UV exposure. While it is abundant in extracellular matrices, hyaluronan contributes to tissue hydrodynamics and proliferation of cells, participates in a number of cell surface receptor interactions, notably those including its primary receptors, CD44 and RHAMM. Upregulation of CD44 itself is accepted as a marker of cell activation in lymphocytes. Hyaluronan's contribution to tumor growth may be due to its interaction with CD44. Receptor CD44 participates in cell adhesion interactions required by tumor cells. Although hyaluronan binds to receptor CD44, there is evidence hyaluronan degradation products transduce their inflammatory signal through toll-like receptor 2, TLR4, or both TLR2 and TLR4 in macrophages and dendritic cells. TLR and hyaluronan play a role in innate immunity. There are limitations including the in vivo loss of this compound limiting the duration of effect. In some cancers, hyaluronic acid levels correlate well with poor prognosis.
Hyaluronic acid is, thus used as a tumor marker for prostate and breast cancer. It may be used to monitor the progression of the disease; as shown in Figure 1, the various types of molecules that interact with hyaluronan can contribute to many of the stages of cancer metastasis, i.e. further the spread of cancer. Hyaluronic acid synthases play roles in all stages of cancer metastasis. By producing anti-adhesive HA, HAS can allow tumor cells to release from the primary tumor mass, if HA associates with receptors such as CD44, the activation of Rho GTPases can promote epithelial–mesenchymal transition of the cancer cells. During the processes of intravasation or extravasation, the interaction of HAS produced HA with receptors such as CD44 or RHAMM promote the cell changes that allow for the cancer cells to infiltrate the vascular or lymphatic systems. While traveling in these systems, HA produced by HAS protects the cancer cell from physical damage. In the formation of a metastatic lesion, HAS produces HA to allow the cancer cell to interact with native cells at the secondary site and to produce a tumor for itself.
HA fragments promote angiogenesis, hyaluronidases produce these fragments. Hypoxia increases production of HA and activity of hyaluronidases; the hyaluronic acid receptors, CD44 and RHAMM, are most studied in terms of their roles in cancer metastasis. Increased clinical CD44 expression has been positively correlated to metastasis in a number of tumor types. In terms of mechanics, CD44 affects adhesion of cancer cells to each other and to endothelial cells, rearranges the cytoskeleton through the Rho GTPases, increases the activity of ECM degrading enzymes. Increased RHAMM expression has been clinically correlated with cancer metastasis. In terms of mechanics, RHAMM promotes cancer cell motility through a number of pathways including focal adhesion kinase, MAP kinase, pp60, the downstream targets of Rho kinase. RHAMM can cooperate with CD44 to promote angiogenesis toward the metastatic lesion. Hyaluronic acid is a main component of the extracellular matrix, has a key role in tissue regeneration, inflammation response, angiogenesis, which are phases of skin wound repair.
As of 2016, reviews assessing its effect to promote wo
In cell biology, an organelle is a specialized subunit within a cell that has a specific function. Organelles are either separately enclosed within their own lipid bilayers or are spatially distinct functional units without a surrounding lipid bilayer; the name organelle comes from the idea that these structures are parts of cells, as organs are to the body, hence organelle, the suffix -elle being a diminutive. Organelles are identified by microscopy, can be purified by cell fractionation. There are many types of organelles in eukaryotic cells. While prokaryotes do not possess organelles per se, some do contain protein-based bacterial microcompartments, which are thought to act as primitive organelles. In biology organs are defined as confined functional units within an organism; the analogy of bodily organs to microscopic cellular substructures is obvious, as from early works, authors of respective textbooks elaborate on the distinction between the two. In the 1830s, Félix Dujardin refuted Ehrenberg theory which said that microorganisms have the same organs of multicellular animals, only minor.
Credited as the first to use a diminutive of organ for cellular structures was German zoologist Karl August Möbius, who used the term organula. In a footnote, published as a correction in the next issue of the journal, he justified his suggestion to call organs of unicellular organisms "organella" since they are only differently formed parts of one cell, in contrast to multicellular organs of multicellular organisms. While most cell biologists consider the term organelle to be synonymous with cell compartment, a space bound by one or two lipid bilayers, some cell biologists choose to limit the term to include only those cell compartments that contain deoxyribonucleic acid, having originated from autonomous microscopic organisms acquired via endosymbiosis. Under this definition, there would only be two broad classes of organelles: mitochondria plastids. Other organelles are suggested to have endosymbiotic origins, but do not contain their own DNA. A second, less restrictive definition of organelles is.
However by using this definition, some parts of the cell that have been shown to be distinct functional units do not qualify as organelles. Therefore, the use of organelle to refer to non-membrane bound structures such as ribosomes is common and accepted; this has led many texts to delineate between non-membrane bound organelles. The non-membrane bound organelles called large biomolecular complexes, are large assemblies of macromolecules that carry out particular and specialized functions, but they lack membrane boundaries. Many of these are referred to as "proteinaceous organelles" as there many structure is made of proteins; such cell structures include: large RNA and protein complexes: ribosome, vault large protein complexes: proteasome, DNA polymerase III holoenzyme, RNA polymerase II holoenzyme, symmetric viral capsids, complex of GroEL and GroES. Eukaryotic cells are structurally complex, by definition are organized, in part, by interior compartments that are themselves enclosed by lipid membranes that resemble the outermost cell membrane.
The larger organelles, such as the nucleus and vacuoles, are visible with the light microscope. They were among the first biological discoveries made after the invention of the microscope. Not all eukaryotic cells have each of the organelles listed below. Exceptional organisms have cells that do not include some organelles that might otherwise be considered universal to eukaryotes. There are occasional exceptions to the number of membranes surrounding organelles, listed in the tables below. In addition, the number of individual organelles of each type found in a given cell varies depending upon the function of that cell. Mitochondria and plastids, including chloroplasts, have double membranes and their own DNA. According to the endosymbiotic theory, they are believed to have originated from incompletely consumed or invading prokaryotic organisms. Other related structures: cytosol endomembrane system nucleosome microtubule cell membrane Prokaryotes are not as structurally complex as eukaryotes, were once thought not to have any internal structures enclosed by lipid membranes.
In the past, they were viewed as having little internal organization, but details are emerging about prokaryotic internal structures. An early false turn was the idea developed in the 1970s that bacteria might contain membrane folds termed mesosomes, but these were shown to be artifacts produced by the chemicals used to prepare the cells for electron microscopy. However, more recent research has revealed that at least some prokaryotes have microcompartments such as carboxysomes; these subcellular compartments are enclosed by a shell of proteins. More striking is the description of membrane-b
Carina of trachea
In anatomy, the carina is a ridge of cartilage in the trachea that occurs between the division of the two main bronchi. This occurs at the lower end of the trachea; this ridge lies to the left of the midline, runs antero-posteriorly. Foreign bodies that fall down the trachea are more to enter the right bronchus; the mucous membrane of the carina is the most sensitive area of the trachea and larynx for triggering a cough reflex. Widening and distortion of the carina is a serious sign because it indicates carcinoma of the lymph nodes around the region where the trachea divides. Tracheobronchial injury, an injury to the airways, occurs within 2.5 cm of the carina 60% of the time. Atlas image: lung_carina at the University of Michigan Health System - "Cast of trachea and bronchi, anterior view" "Trachea and carina — tomogram, coronal plane" at SUNY Downstate Medical Center Carina tracheae entry in the public domain NCI Dictionary of Cancer Terms This article incorporates public domain material from the U.
S. National Cancer Institute document "Dictionary of Cancer Terms"
Chondrogenesis is the process by which cartilage is developed. In embryogenesis, the skeletal system is derived from the mesoderm germ layer. Chondrification is the process by which cartilage is formed from condensed mesenchyme tissue, which differentiates into chondrocytes and begins secreting the molecules that form the extracellular matrix. Early in fetal development, the greater part of the skeleton is cartilaginous; this temporary cartilage is replaced by bone, a process that ends at puberty. In contrast, the cartilage in the joints remains unossified during the whole of life and is, permanent. Adult hyaline articular cartilage is progressively mineralized at the junction between cartilage and bone, it is termed articular calcified cartilage. A mineralization front advances through the base of the hyaline articular cartilage at a rate dependent on cartilage load and shear stress. Intermittent variations in the rate of advance and mineral deposition density of the mineralizing front, lead to multiple "tidemarks" in the articular calcified cartilage.
Adult articular calcified cartilage is penetrated by vascular buds, new bone produced in the vascular space in a process similar to endochondral ossification at the physis. A cement line demarcates articular calcified cartilage from subchondral bones. Once damaged, cartilage has limited repair capabilities; because chondrocytes are bound in lacunae, they cannot migrate to damaged areas. Because hyaline cartilage does not have a blood supply, the deposition of new matrix is slow. Damaged hyaline cartilage is replaced by fibrocartilage scar tissue. Over the last years and scientists have elaborated a series of cartilage repair procedures that help to postpone the need for joint replacement. In a 1994 trial, Swedish doctors repaired damaged knee joints by implanting cells cultured from the patient's own cartilage. In 1999 US chemists created an artificial liquid cartilage for use in repairing torn tissue; the cartilage is injected into a wound or damaged joint and will harden with exposure to ultraviolet light.
Researchers say their lubricating layers of "molecular brushes" can outperform nature under the highest pressures encountered within joints, with important implications for joint replacement surgery. Each 60-nanometre-long brush filament has a polymer backbone from which small molecular groups stick out; those synthetic groups are similar to the lipids found in cell membranes. "In a watery environment, each of these molecular groups attracts up to 25 water molecules through electrostatic forces, so the filament as a whole develops a slick watery sheath. These sheathes ensure that the brushes are lubricated as they rub past each other when pressed together to mimic the pressures at bone joints."Known as double-network hydrogels, the incredible strength of these new materials was a happy surprise when first discovered by researchers at Hokkaido in 2003. Most conventionally prepared hydrogels - materials that are 80 to 90 percent water held in a polymer network - break apart like a gelatin; the Japanese team serendipitously discovered that the addition of a second polymer to the gel made them so tough that they rivaled cartilage - tissue which can withstand the abuse of hundreds of pounds of pressure.
Bone morphogenetic proteins are growth factors released during embryonic development to induce condensation and determination of cells, during chondrogenesis. Noggin, a developmental protein, inhibits chondrogenesis by preventing condensation and differentiation of mesenchymal cells; the molecule sonic hedgehog modifies the activation of the L-Sox5, Sox6, Sox9 and Nkx3.2. Sox9 and Nkx3.2 induce each other in a positive feedback loop where Nkx3.2 inactivates a Sox9 inhibitor. This loop is supported by BMP expression; the expression of Sox9 induces the expression of BMP, which causes chondrocytes to proliferate and differentiate. L-Sox5 and Sox6 share this common role with Sox9. L-Sox5 and Sox6 are thought to induce the activation of the Col2a1 and the Col11a2 genes, to repress the expression of Cbfa1, a marker for late stage Chondrocytes. L-Sox5 is thought to be involved in embryonic chondrogenesis, while Sox6 is thought to be involved in post-natal chondrogenesis; the molecule Indian hedgehog is expressed by prehypertrophic chondrocytes.
Ihh stimulates chondrocyte proliferation and regulates chondrocyte maturation by maintaining the expression of PTHrP. PTHrP acts as a patterning molecule, determining the position in which the chondrocytes initiate differentiation; the SLC26A2 is a sulfate transporter. Defects result in several forms of osteochondrodysplasia
A micrograph or photomicrograph is a photograph or digital image taken through a microscope or similar device to show a magnified image of an object. This is opposed to a macrograph or photomacrograph, an image, taken on a microscope but is only magnified less than 10 times. Micrography is the art of using microscopes to make photographs. A micrograph contains extensive details of microstructure. A wealth of information can be obtained from a simple micrograph like behavior of the material under different conditions, the phases found in the system, failure analysis, grain size estimation, elemental analysis and so on. Micrographs are used in all fields of microscopy. A light micrograph or photomicrograph is a micrograph prepared using an optical microscope, a process referred to as photomicroscopy. At a basic level, photomicroscopy may be performed by connecting a camera to a microscope, thereby enabling the user to take photographs at reasonably high magnification. Scientific use began in England in 1850 by Prof Richard Hill Norris FRSE for his studies of blood cells.
Roman Vishniac was a pioneer in the field of photomicroscopy, specializing in the photography of living creatures in full motion. He made major developments in light-interruption photography and color photomicroscopy. Photomicrographs may be obtained using a USB microscope attached directly to a home computer or laptop. An electron micrograph is a micrograph prepared using an electron microscope. Micrographs have micron bars, or magnification ratios, or both. Magnification is a ratio between the size of an object on its real size. Magnification can be a misleading parameter as it depends on the final size of a printed picture and therefore varies with picture size. A scale bar, or micron bar, is a line of known length displayed on a picture; the bar can be used for measurements on a picture. When the picture is resized the bar is resized making it possible to recalculate the magnification. Ideally, all pictures destined for publication/presentation should be supplied with a scale bar. All but one of the micrographs presented on this page do not have a micron bar.
The microscope has been used for scientific discovery. It has been linked to the arts since its invention in the 17th century. Early adopters of the microscope, such as Robert Hooke and Antonie van Leeuwenhoek, were excellent illustrators. After the invention of photography in the 1820s the microscope was combined with the camera to take pictures instead of relying on an artistic rendering. Since the early 1970s individuals have been using the microscope as an artistic instrument. Websites and traveling art exhibits such as the Nikon Small World and Olympus Bioscapes have featured a range of images for the sole purpose of artistic enjoyment; some collaborative groups, such as the Paper Project have incorporated microscopic imagery into tactile art pieces as well as 3D immersive rooms and dance performances. Close-up Digital microscope Macro photography Microphotograph Microscopy USB microscope Make a Micrograph – This presentation by the research department of Children's Hospital Boston shows how researchers create a three-color micrograph.
Shots with a Microscope – a basic, comprehensive guide to photomicrography Scientific photomicrographs – free scientific quality photomicrographs by Doc. RNDr. Josef Reischig, CSc. Micrographs of 18 natural fibres by the International Year of Natural Fibres 2009 Seeing Beyond the Human Eye Video produced by Off Book - Solomon C. Fuller bio Charles Krebs Microscopic Images Dennis Kunkel Microscopy Andrew Paul Leonard, APL Microscopic Cell Centered Database - Montage Nikon Small World Olympus Bioscapes Other examples
White fibrocartilage consists of a mixture of white fibrous tissue and cartilaginous tissue in various proportions. It owes its inflexibility and toughness to the former of these constituents, its elasticity to the latter, it is the only type of cartilage that contains type I collagen in addition to the normal type II. Fibrocartilage is found in the soft tissue-to-bone attachments,pubic symphysis, the anulus fibrosus of intervertebral discs, the triangular fibrocartilage and the TMJ. During labor, relaxin loosens the pubic symphysis to aid in delivery, but this can lead to joint problems. If hyaline cartilage is torn all the way down to the bone, the blood supply from inside the bone is sometimes enough to start some healing inside the lesion. In cases like this, the body will form a scar in the area using a special type of cartilage called fibrocartilage. Fibrocartilage is a tough and fibrous material that helps fill in the torn part of the cartilage. Degeneration of fibrocartilage is seen in degenerative disc disease.
Cartilage This article incorporates text in the public domain from page 281 of the 20th edition of Gray's Anatomy Histology image: 03201loa – Histology Learning System at Boston University
Glycosaminoglycans or mucopolysaccharides are long unbranched polysaccharides consisting of a repeating disaccharide unit. The repeating unit consists of an amino sugar along with a uronic galactose. Glycosaminoglycans are polar and attract water, they are therefore useful to the body as a shock absorber. Mucopolysaccharidoses are a group of metabolic disorders in which abnormal accumulations of glycosaminoglycans occur because of enzyme deficiencies. Glycosaminoglycans have high degrees of heterogeneity with regards to molecular mass, disaccharide construction, sulfation due to the fact that GAG synthesis, unlike proteins or nucleic acids, is not template driven, dynamically modulated by processing enzymes. Based on core disaccharide structures, GAGs are classified into four groups. Heparin/heparan sulfate and chondroitin sulfate/dermatan sulfate are synthesized in the Golgi apparatus, where protein cores made in the rough endoplasmic reticulum are posttranslationally modified with O-linked glycosylations by glycosyltransferases forming proteoglycans.
Keratan sulfate may modify core proteins through N-linked glycosylation or O-linked glycosylation of the proteoglycan. The fourth class of GAG, hyaluronic acid, is not synthesized by the Golgi, but rather by integral membrane synthases which secrete the dynamically elongated disaccharide chain. HSGAG and CSGAG modified proteoglycans first begin with a consensus Ser-Gly/Ala-X-Gly motif in the core protein. Construction of a tetrasaccharide linker that consists of -GlcAβ1–3Galβ1–3Galβ1–4Xylβ1-O--, where xylosyltransferase, β4-galactosyl transferase,β3-galactosyl transferase, β3-GlcA transferase transfer the four monosaccharides, begins synthesis of the GAG modified protein; the first modification of the tetrasaccharide linker determines whether the HSGAGs or CSGAGs will be added. Addition of a GlcNAc promotes the addition of HSGAGs while addition of GalNAc to the tetrasaccharide linker promotes CSGAG development. GlcNAcT-I transfers GlcNAc to the tetrasaccahride linker, distinct from glycosyltransferase GlcNAcT-II, the enzyme, utilized to build HSGAGs.
EXTL2 and EXTL3, two genes in the EXT tumor suppressor family, have been shown to have GlcNAcT-I activity. Conversely, GalNAc is transferred to the linker by the enzyme GalNAcT to initiate synthesis of CSGAGs, an enzyme which may or may not have distinct activity compared to the GalNAc transferase activity of chondroitin synthase. With regard to HSGAGs, a multimeric enzyme encoded by EXT1 and EXT2 of the EXT family of genes, transfers both GlcNAc and GlcA for HSGAG chain elongation. While elongating, the HSGAG is dynamically modified, first by N-deacetylase, N-sulfotransferase, a bifunctional enzyme that cleaves the N-acetyl group from GlcNAc and subsequently sulfates the N-position. Next, C-5 uronyl epimerase coverts d-GlcA to l-IdoA followed by 2-O sulfation of the uronic acid sugar by 2-O sulfotransferase; the 6-O and 3-O positions of GlcNAc moities are sulfated by 6-O and 3-O sulfotransferases. Chondroitin sulfate and dermatan sulfate, which comprise CSGAGs, are differentiated from each other by the presence of GlcA and IdoA epimers respectively.
Similar to the production of HSGAGs, C-5 uronyl epimerase converts d-GlcA to l-IdoA to synthesize dermatan sulfate. Three sulfation events of the CSGAG chains occur: 4-O and/or 6-O sulfation of GalNAc and 2-O sulfation of uronic acid. Four isoforms of the 4-O GalNAc sulfotransferases and three isoforms of the GalNAc 6-O sulfotransferases are responsible for the sulfation of GalNAc. Unlike HSGAGs and CSGAGs, the third class of GAGs, those belonging to keratan sulfate types, are driven towards biosynthesis through particular protein sequence motifs. For example, in the cornea and cartilage, the keratan sulfate domain of aggrecan consists of a series of tandemly repeated hexapeptides with a consensus sequence of EPFPS. Additionally, for three other keratan sulfated proteoglycans, lumican and mimecan, the consensus sequence NX along with protein secondary structure was determined to be involved in N-linked oligosaccharide extension with keratan sulfate. Keratan sulfate elongation begins at the nonreducing ends of three linkage oligosaccharides, which define the three classes of keratan sulfate.
Keratan sulfate. Keratan sulfate II and keratan sulfate III are O-linked, with KSII linkages identical to that of mucin core structure, KSIII linked to a 2-O mannose. Elongation of the keratan sulfate polymer occurs through the glycosyltransferase addition of Gal and GlcNAc. Galactose addition occurs through the β-1,4-galactosyltransferase enzyme while the enzymes responsible for β-3-Nacetylglucosamine have not been identified. Sulfation of the polymer occurs at the 6-position of both sugar residues; the enzyme KS-Gal6ST transfers sulfate groups to galactose while N-acetylglucosaminyl-6-sulfotransferase transfers sulfate groups to terminal GlcNAc in keratan sulfate. The fourth class of GAG, hyaluronan, is not sulfated and is synthesized by three transmembrane synthase proteins HAS1, HAS2, HAS3. HA, a linear polysaccharide, is composed of repeating disaccharide units of →4)GlcAβGlcNAcβ(1→ and has a high molecular mass, ranging from 105 to 107 Da; each HAS enzyme is capable of transglycosylation when supplied with UDP-G