Cell adhesion is the process by which cells interact and attach to neighbouring cells through specialised molecules of the cell surface. This process can occur either through direct contact between cell surfaces or indirect interaction, where cells attach to surrounding extracellular matrix, a gel-like structure containing molecules released by cells into spaces between them. Cells adhesion occurs from the interactions between cell-adhesion molecules, transmembrane proteins located on the cell surface. Cell adhesion link cells in different ways and can be involved in signal transduction for cells to detect and respond to changes in the surroundings. Other cellular processes regulated by cell adhesion include cell migration and tissue development in multicellular organisms. Alterations in cell adhesion can disrupt important cellular processes and lead to a variety of diseases, including cancer and arthritis. Cell adhesion is essential for infectious organisms, such as bacteria or viruses, to cause diseases.
CAMs are classified into four major families: integrins, immunoglobulin superfamily and selectins. Each of these adhesion molecules recognizes different ligands. Cadherins and immunoglobulins are homophilic CAMs, as they directly bind to the same type of CAMs on another cell, while integrins and selectins are heterophilic CAMs that bind to different types of CAMs. Defects in cell adhesion are attributable to defects in expression of CAMs. In multicellular organisms, bindings between CAMs allow cells to adhere to one another and creates structures called cell junctions. According to their functions, the cell junctions can be classified as: Anchoring junctions, which maintain cells together and strengthens contact between cells. Occluding junctions, which seal gaps between cells through cell–cell contact, making an impermeable barrier for diffusion Channel-forming junctions, which links cytoplasm of adjacent cells allowing transport of molecules to occur between cells Signal-relaying junctions, which can be synapses in the nervous systemAlternatively, cell junctions can be categorised into two main types according to what interacts with the cell: cell–cell junctions mediated by cadherins, cell–matrix junctions mediated by integrins.
Cell–cell junctions can occur in different forms. In anchoring junctions between cells such as adherens junctions and desmosomes, the main CAMs present are the cadherins; this family of CAMs are membrane proteins that mediate cell–cell adhesion through its extracellular domains and require extracellular Ca2+ ions to function correctly. Cadherins forms homophilic attachment between themselves, which results in cells of a similar type sticking together and can lead to selective cell adhesion, allowing vertebrate cells to assemble into organised tissues. Cadherins are essential for cell–cell adhesion and cell signalling in multicellular animals and can be separated into two types: classical cadherins and non-classical cadherins. Adherens junctions function to maintain shape of tissues and hold cells together. In adherens junctions, classical cadherins between neighbouring cells interact through their extracellular domains. Classical cadherins share a conserved calcium-sensitive region in their extracellular domains.
When this region comes into contact with Ca2+ ions, extracellular domains of cadherins change from the inactive flexible conformation to a more rigid conformation to undergo homophilic binding. Intracellular domains of classical cadherins are highly conserved as they bind to proteins called catenins forming catenin-cadherin complexes, which links classical cadherins to actin filaments; this association with actin filaments is essential for adherens junctions to stabilises cell–cell adhesion. Interactions with actin filaments can promote clustering of cadherins, involved in assembly of adherens junctions, as cadherin clusters promotes actin filaments polymerisation which in turn assembles adherens junctions by binding to cadherin–catenin complexes forming at the junction. Desmosomes are structurally similar to adherens junctions but composed of different components. Instead of classical cadherins, non-classical cadherins such as desmogleins and desmocollins act as adhesion molecules and they are linked to intermediate filaments instead of actin filaments.
No catenin is present in desmosomes as intracellular domains of desmosomal cadherins interact with desmosomal plaque proteins, which form the thick cytoplasmic plaques in desmosomes and link cadherins to intermediate filaments. Desmosomes provides strength and resistance to mechanical stress by unloading forces onto the flexible but resilient intermediate filaments, something that cannot occur with the rigid actin filaments; this makes desmosomes important in tissues that encounter high levels of mechanical stress, such as heart muscle and epithelia, explains why it appears in these types of tissues. Tight junctions are present in epithelial and endothelial tissues, where they seal gaps and regulate paracellular transport of solutes and extracellular fluids in these tissues that function as barriers. Tight junction is formed by transmembrane proteins, including claudins and tricellulins, that bind to each other on adjacent membranes in a homophilic manner. Similar to anchoring junctions, intracellular domains of these tight junction proteins are bound with scaffold proteins that keep these proteins in clusters and link them to actin filaments in order to maintain structure of the tight junction.
Claudins, essential for formation of tight junctions, form paracellular pores which allow selective passage of specific ions across tight junctions making the barrier selectively p
Merriam-Webster, Inc. is an American company that publishes reference books and is known for its dictionaries. In 1828, George and Charles Merriam founded the company as G & C Merriam Co. in Springfield, Massachusetts. In 1843, after Noah Webster died, the company bought the rights to An American Dictionary of the English Language from Webster's estate. All Merriam-Webster dictionaries trace their lineage to this source. In 1964, Encyclopædia Britannica, Inc. acquired Inc. as a subsidiary. The company adopted its current name in 1982. In 1806, Webster published A Compendious Dictionary of the English Language. In 1807 Webster started two decades of intensive work to expand his publication into a comprehensive dictionary, An American Dictionary of the English Language. To help him trace the etymology of words, Webster learned 26 languages. Webster hoped to standardize American speech, since Americans in different parts of the country used somewhat different vocabularies and spelled and used words differently.
Webster completed his dictionary during his year abroad in 1825 in Paris, at the University of Cambridge. His 1820s book contained 70,000 words, of which about 12,000 had never appeared in a dictionary before; as a spelling reformer, Webster believed that English spelling rules were unnecessarily complex, so his dictionary introduced American English spellings, replacing colour with color, waggon with wagon, centre with center. He added American words, including skunk and squash, that did not appear in British dictionaries. At the age of 70 in 1828, Webster published his dictionary. However, in 1840, he published the second edition in two volumes with much greater success. In 1843, after Webster's death, George Merriam and Charles Merriam secured publishing and revision rights to the 1840 edition of the dictionary, they published a revision in 1847, which did not change any of the main text but added new sections, a second update with illustrations in 1859. In 1864, Merriam published a expanded edition, the first version to change Webster's text overhauling his work yet retaining many of his definitions and the title "An American Dictionary".
This began a series of revisions. In 1884 it contained 118,000 words, "3000 more than any other English dictionary". With the edition of 1890, the dictionary was retitled Webster's International; the vocabulary was vastly expanded in Webster's New International editions of 1909 and 1934, totaling over half a million words, with the 1934 edition retrospectively called Webster's Second International or "The Second Edition" of the New International. The Collegiate Dictionary was introduced in 1898 and the series is now in its eleventh edition. Following the publication of Webster's International in 1890, two Collegiate editions were issued as abridgments of each of their Unabridged editions. With the ninth edition, the Collegiate adopted changes which distinguish it as a separate entity rather than an abridgment of the Third New International; some proper names were returned including names of Knights of the Round Table. The most notable change was the inclusion of the date of the first known citation of each word, to document its entry into the English language.
The eleventh edition includes more than 225,000 definitions, more than 165,000 entries. A CD-ROM of the text is sometimes included; this dictionary is preferred as a source "for general matters of spelling" by the influential The Chicago Manual of Style, followed by many book publishers and magazines in the United States. The Chicago Manual states. Merriam overhauled the dictionary again with the 1961 Webster's Third New International under the direction of Philip B. Gove, making changes that sparked public controversy. Many of these changes were in formatting, omitting needless punctuation, or avoiding complete sentences when a phrase was sufficient. Others, more controversial, signaled a shift from linguistic prescriptivism and towards describing American English as it was used at that time. Since the 1940s, the company has added many specialized dictionaries, language aides, other references to its repertoire; the G. & C. Merriam Company lost its right to exclusive use of the name "Webster" after a series of lawsuits placed that name in public domain.
Its name was changed to "Merriam-Webster, Incorporated", with the publication of Webster's Ninth New Collegiate Dictionary in 1983. Previous publications had used "A Merriam-Webster Dictionary" as a subtitle for many years and will be found on older editions; the company has been a subsidiary of Encyclopædia Britannica, Inc. since 1964. In 1996, Merriam-Webster launched its first website, which provided free access to an online dictionary and thesaurus. Merriam-Webster has published dictionaries of synonyms, English usage, biography, proper names, medical terms, sports terms, Spanish/English, numerous others. Non-dictionary publications include Collegiate Thesaurus, Secretarial Handbook, Manual for Writers and Editors, Collegiate Encyclopedia, Encyclopedia of Literature, Encyclopedia of World Religions. On February 16, 2007, Merriam-Webster announced the launch of a mobile dictionary and thesaurus service developed with mobile search-and-information provider AskMeNow. Consumers use the service to access definitions and synonyms via text message.
Services include Merr
New Latin was a revival in the use of Latin in original and scientific works between c. 1375 and c. 1900. Modern scholarly and technical nomenclature, such as in zoological and botanical taxonomy and international scientific vocabulary, draws extensively from New Latin vocabulary. In such use, New Latin is viewed as still existing and subject to new word formation; as a language for full expression in prose or poetry, however, it is distinguished from its successor, Contemporary Latin. Classicists use the term "Neo-Latin" to describe the Latin that developed in Renaissance Italy as a result of renewed interest in classical civilization in the 14th and 15th centuries. Neo-Latin describes the use of the Latin language for any purpose, scientific or literary and after the Renaissance; the beginning of the period cannot be identified. The end of the New Latin period is indeterminate, but Latin as a regular vehicle of communicating ideas became rare after the first few decades of the 19th century, by 1900 it survived in international scientific vocabulary and taxonomy.
The term "New Latin" came into widespread use towards the end of the 1890s among linguists and scientists. New Latin was, at least in its early days, an international language used throughout Catholic and Protestant Europe, as well as in the colonies of the major European powers; this area consisted including Central Europe and Scandinavia. Russia's acquisition of Kiev in the 17th century introduced the study of Latin to Russia; the use of Latin in Orthodox eastern Europe did not reach high levels due to their strong cultural links to the cultural heritage of Ancient Greece and Byzantium, as well as Greek and Old Church Slavonic languages. Though Latin and New Latin are considered extinct, large parts of their vocabulary have seeped into English and several Germanic languages. In the case of English, about 60% of the lexicon can trace its origin to Latin, thus many English speakers can recognize New Latin terms with relative ease as cognates are quite common. New Latin was inaugurated by the triumph of the humanist reform of Latin education, led by such writers as Erasmus and Colet.
Medieval Latin had been the practical working language of the Roman Catholic Church, taught throughout Europe to aspiring clerics and refined in the medieval universities. It was a flexible language, full of neologisms and composed without reference to the grammar or style of classical authors; the humanist reformers sought both to purify Latin grammar and style, to make Latin applicable to concerns beyond the ecclesiastical, creating a body of Latin literature outside the bounds of the Church. Attempts at reforming Latin use occurred sporadically throughout the period, becoming most successful in the mid-to-late 19th century; the Protestant Reformation, though it removed Latin from the liturgies of the churches of Northern Europe, may have advanced the cause of the new secular Latin. The period during and after the Reformation, coinciding with the growth of printed literature, saw the growth of an immense body of New Latin literature, on all kinds of secular as well as religious subjects; the heyday of New Latin was its first two centuries, when in the continuation of the Medieval Latin tradition, it served as the lingua franca of science, to some degree diplomacy in Europe.
Classic works such as Newton's Principia Mathematica were written in the language. Throughout this period, Latin was a universal school subject, indeed, the pre-eminent subject for elementary education in most of Europe and other places of the world that shared its culture. All universities required Latin proficiency to obtain admittance as a student. Latin was an official language of Poland—recognised and used between the 9th and 18th centuries used in foreign relations and popular as a second language among some of the nobility. Through most of the 17th century, Latin was supreme as an international language of diplomatic correspondence, used in negotiations between nations and the writing of treaties, e.g. the peace treaties of Osnabrück and Münster. As an auxiliary language to the local vernaculars, New Latin appeared in a wide variety of documents, legal, diplomatic and scientific. While a text written in English, French, or Spanish at this time might be understood by a significant cross section of the learned, only a Latin text could be certain of finding someone to interpret it anywhere between Lisbon and Helsinki.
As late as the 1720s, Latin was still used conversationally, was serviceable as an international auxiliary language between people of different countries who had no other language in common. For instance, the Hanoverian king George I of Great Britain, who had no command of spoken English, communicated in Latin with his Prime Minister Robert Walpole, who knew neither German nor French. By about 1700, the growing movement for the use of national languages had reached academia, an example of the transition is Newton's writing career, which began in New Latin and ended in Eng
Oxford University Press
Oxford University Press is the largest university press in the world, the second oldest after Cambridge University Press. It is a department of the University of Oxford and is governed by a group of 15 academics appointed by the vice-chancellor known as the delegates of the press, they are headed by the secretary to the delegates, who serves as OUP's chief executive and as its major representative on other university bodies. Oxford University has used a similar system to oversee OUP since the 17th century; the Press is located on opposite Somerville College, in the suburb Jericho. The Oxford University Press Museum is located on Oxford. Visits are led by a member of the archive staff. Displays include a 19th-century printing press, the OUP buildings, the printing and history of the Oxford Almanack, Alice in Wonderland and the Oxford English Dictionary; the university became involved in the print trade around 1480, grew into a major printer of Bibles, prayer books, scholarly works. OUP took on the project that became the Oxford English Dictionary in the late 19th century, expanded to meet the ever-rising costs of the work.
As a result, the last hundred years has seen Oxford publish children's books, school text books, journals, the World's Classics series, a range of English language teaching texts. Moves into international markets led to OUP opening its own offices outside the United Kingdom, beginning with New York City in 1896. With the advent of computer technology and harsh trading conditions, the Press's printing house at Oxford was closed in 1989, its former paper mill at Wolvercote was demolished in 2004. By contracting out its printing and binding operations, the modern OUP publishes some 6,000 new titles around the world each year; the first printer associated with Oxford University was Theoderic Rood. A business associate of William Caxton, Rood seems to have brought his own wooden printing press to Oxford from Cologne as a speculative venture, to have worked in the city between around 1480 and 1483; the first book printed in Oxford, in 1478, an edition of Rufinus's Expositio in symbolum apostolorum, was printed by another, printer.
Famously, this was mis-dated in Roman numerals as "1468", thus pre-dating Caxton. Rood's printing included John Ankywyll's Compendium totius grammaticae, which set new standards for teaching of Latin grammar. After Rood, printing connected with the university remained sporadic for over half a century. Records or surviving work are few, Oxford did not put its printing on a firm footing until the 1580s. In response to constraints on printing outside London imposed by the Crown and the Stationers' Company, Oxford petitioned Elizabeth I of England for the formal right to operate a press at the university; the chancellor, Robert Dudley, 1st Earl of Leicester, pleaded Oxford's case. Some royal assent was obtained, since the printer Joseph Barnes began work, a decree of Star Chamber noted the legal existence of a press at "the universitie of Oxforde" in 1586. Oxford's chancellor, Archbishop William Laud, consolidated the legal status of the university's printing in the 1630s. Laud envisaged a unified press of world repute.
Oxford would establish it on university property, govern its operations, employ its staff, determine its printed work, benefit from its proceeds. To that end, he petitioned Charles I for rights that would enable Oxford to compete with the Stationers' Company and the King's Printer, obtained a succession of royal grants to aid it; these were brought together in Oxford's "Great Charter" in 1636, which gave the university the right to print "all manner of books". Laud obtained the "privilege" from the Crown of printing the King James or Authorized Version of Scripture at Oxford; this "privilege" created substantial returns in the next 250 years, although it was held in abeyance. The Stationers' Company was alarmed by the threat to its trade and lost little time in establishing a "Covenant of Forbearance" with Oxford. Under this, the Stationers paid an annual rent for the university not to exercise its full printing rights – money Oxford used to purchase new printing equipment for smaller purposes.
Laud made progress with internal organization of the Press. Besides establishing the system of Delegates, he created the wide-ranging supervisory post of "Architypographus": an academic who would have responsibility for every function of the business, from print shop management to proofreading; the post was more an ideal than a workable reality, but it survived in the loosely structured Press until the 18th century. In practice, Oxford's Warehouse-Keeper dealt with sales and the hiring and firing of print shop staff. Laud's plans, hit terrible obstacles, both personal and political. Falling foul of political intrigue, he was executed in 1645, by which time the English Civil War had broken out. Oxford became a Royalist stronghold during the conflict, many printers in the city concentrated on producing political pamphlets or sermons; some outstanding mathematical and Orientalist works emerged at this time—notably, texts edited by Edward Pococke, the Regius Professor of Hebrew—but no university press on Laud's model was possible before the Restoration of the Monarchy in 1660.
It was established by the vice-chancellor, John Fell, Dean of Christ Church, Bishop of Oxford, Secretary to the Delegates. Fell regarded Laud as a martyr, was determined to honour his vision of the Press. Using the provisions of the Great Charter, Fell persuaded Oxford to refuse any further payments from the Stationers and drew
The gastrointestinal wall surrounding the lumen of the gastrointestinal tract is made up of four layers of specialised tissue – from the lumen outwards: Mucosa Submucosa Muscular layer Serosa / Adventitia -- these last two tissue types differ in form and function according to the part of the gastrointestinal tract they belong to The epithelium, the most exposed part of the mucosa, is a glandular epithelium with many goblet cells. Goblet cells secrete mucus, which lubricates the passage of food along and protects the intestinal wall from digestive enzymes. In the small intestine, villi are folds of the mucosa that increase the surface area of the intestine; the villi contain a lacteal, a vessel connected to the lymph system that aids in the removal of lipids and tissue fluids. Microvilli are present on the epithelium of a villus and further increase the surface area over which absorption can take place. Numerous intestinal glands as pocket-like invaginations are present in the underlying tissue.
In the large intestines, villi are absent and a flat surface with thousands of glands is observed. Underlying the epithelium is the lamina propria, which contains myofibroblasts, blood vessels and several different immune cells, the muscularis mucosa, a layer of smooth muscle that aids in the action of continued peristalsis and catastalsis along the gut; the submucosa contains nerves including the submucous plexus, blood vessels and elastic fibres with collagen, that stretches with increased capacity but maintains the shape of the intestine. Surrounding this is the muscular layer, which comprises both longitudinal and circular smooth muscle that helps with continued peristalsis and the movement of digested material out of and along the gut. In between the two layers of muscle lies the myenteric plexus. Lastly, there is the serosa/adventitia, made up of loose connective tissue and coated in mucus so as to prevent any friction damage from the intestine rubbing against other tissue. Holding all this in place are the mesenteries which suspend the intestine in the abdominal cavity and stop it being disturbed when a person is physically active.
The gastrointestinal tract has a form of general histology with some differences that reflect the specialization in functional anatomy. The mucosa is the innermost layer of the gastrointestinal tract, it surrounds the lumen of the tract, comes into direct contact with digested food. The mucosa itself is made up of three layers: The epithelium is the innermost layer, it is where most digestive and secretory processes occur. Lamina propria is a layer of connective tissue within the mucosa. Unusually cellular compared to most connective tissue Muscularis mucosae is a thin layer of smooth muscle; the mucosae are specialized in each organ of the gastrointestinal tract to deal with the different conditions. The most variation is seen in the epithelium: In the oesophagus and external anal canal the epithelium is stratified and non-keratinising, for protective purposes. In the stomach, the epithelium is simple columnar, is organised into gastric pits and glands to deal with secretion. In the small intestine, epithelium is simple columnar and specialised for absorption.
The epithelium is arranged into villi, creating a brush border and increasing the area for absorption. Each cell has microvilli, it is organised into plicae circulares and villi, the enterocytes have microvilli. This creates a brush border which increases the surface area for absorption; the epithelium is simple columnar with microvilli. In the ileum there are Peyer's patches in the lamina propria. Brunner's glands are found in the duodenum but not in other parts of the small intestine. In the colon, epithelium is simple columnar and without villi. Goblet cells, which secrete mucous, are present; the appendix has a mucosa resembling the colon but is infiltrated with lymphocytes. Transition between the different types of epithelium occurs at the junction between the oesophagus and stomach; the submucosa consists of a dense and irregular layer of connective tissue with blood vessels and nerves branching into the mucosa and muscular layer. It contains the submucous plexus, enteric nervous plexus, situated on the inner surface of the muscular layer.
The muscular layer consists of two layers of the inner and outer layer. The muscle of the inner layer is arranged in circular rings around the tract, whereas the muscle of the outer layer is arranged longitudinally; the stomach has an inner oblique muscular layer. Between the two muscle layers are the myenteric or Auerbach's plexus; this controls peristalsis. Activity is initiated by the pacemaker cells; the gut has intrinsic peristaltic activity due to its self-contained enteric nervous system. The rate can of course be modulated by the rest of the autonomic nervous system; the layers are not longitudinal or circular, rather the layers of muscle are helical with different pitches. The inner circular is helical with a steep pitch and the outer longitudinal is helical with a much shallower pitch; the coordinated contractions of these layers is called peristalsis and propels the food through the tract. Food in the GI tract is called a bolus from the mouth down to the stomach. After the stomach, the food is digested and semi-liquid, is referred to as chyme.
In the large intestine the remaining semi-solid substanc
Desmoplakin is a protein in humans, encoded by the DSP gene. Desmoplakin is a critical component of desmosome structures in cardiac muscle and epidermal cells, which function to maintain the structural integrity at adjacent cell contacts. In cardiac muscle, desmoplakin is localized to intercalated discs which mechanically couple cardiac cells to function in a coordinated syncytial structure. Mutations in desmoplakin have been shown to play a role in dilated cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy, striate palmoplantar keratoderma, Carvajal syndrome and paraneoplastic pemphigus. Desmoplakin exists as two predominant isoforms; these isoforms are identical except for the shorter rod domain in DPII. DPI is the predominant isoform expressed in cardiac muscle; the DSP gene is located on chromosome 6p24.3, containing 24 exons and spanning 45 kDa of genomic DNA. Desmoplakin is a large desmosomal plaque protein that homodimerizes and adopts a dumbbell-shaped conformation; the N-terminal globular head domain of desmoplakin is composed of a series of alpha helical bundles, is required for both the localization to the desmosome and interaction with the N-terminal region of plakophilin 1 and plakoglobin as well as desmocollin and desmoglein.
This is further sub divided into a region called the "Plakin domain" made up of six spectrin repeat domains separated by SH3 domain. A crystal structure of part of the plakin domain has been resolved, while the entire plakin domain has been elucidated using small angle X-ray scattering which revealed a non-linear structure, an unexpected result considering spectrin repeats are observed in linear orientations; the C-terminal region of desmoplakin is composed of three plakin repeat domains, termed A, B and C, which are essential for coalignment and binding of intermediate filaments. Located at the most distal C-terminus of desmoplakin is a region rich in glycine–serine–arginine. In the mid-region of desmoplakin, a coiled-coil rod domain is responsible for homodimerization. Desmosomes are intercellular junctions that link adjacent cells. Desmoplakin is an obligate component of functional desmosomes that anchors intermediate filaments to desmosomal plaques. In cardiomyocytes, desmoplakin forms desmosomal plaques with the intermediate filament desmin, whereas in endothelial cells cytokeratin type intermediate filaments are recruited, vimentin in arachnoid and follicular dendritic cell types.
Both types of intermediate filaments attach in a lateral fashion to desmoplakin to form the plaque. In cardiac muscle, desmoplakin is localized to desmosomes in intercalated discs. Desmoplakin isoform DPI is expressed and is thought to play a role in both the assembly and stabilization of desmosomes. In mice overexpressing a C-terminal mutated desmoplakin protein, desmoplakin binding to desmin is disrupted in cardiac muscle and hearts display abnormal intercalated disc formation and structure. Much has been learned regarding desmoplakin function from mutations in patients with arrhythmogenic right ventricular cardiomyopathy, where mutations in specific binding domains alter desmoplakin binding to plakoglobin or desmin and result in cell death and dysfunction. Mutations in this gene are the cause of several cardiomyopathies, including dilated cardiomyopathy and arrhythmogenic right ventricular cardiomyopathy. Mutations in DSP have been associated with striate palmoplantar keratoderma. Carvajal syndrome results from an autosomal recessive mutation of a frameshift in DSP that results in a combination of above conditions, including dilated cardiomyopathy and woolly hair.
Patients with Carvajal syndrome suffer from heart failure in teenage years. A case of compound heterozygosity for two DSP nonsense mutations resulting in lethal acantholytic epidermolysis bullosa has been reported. Autoantibodies to DSP are a hallmark of the autoimmune disease paraneoplastic pemphigus. Decreased desmoplakin expression has been found in patients with oropharyngeal cancer and breast cancer, which may alter cell-cell adhesion properties and propagate metastasis. Desmoplakin has been shown to interact with: List of target antigens in pemphigus List of conditions caused by problems with junctional proteins GeneReviews/NCBI/NIH/UW entry on Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy, Autosomal Dominant OMIM entries on Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy, Autosomal Dominant Desmoplakins at the US National Library of Medicine Medical Subject Headings
Cardiac muscle is one of three types of vertebrate muscles, with the other two being skeletal and smooth muscles. It is an striated muscle that constitutes the main tissue of the walls of the heart; the myocardium forms a thick middle layer between the outer layer of the heart wall and the inner layer, with blood supplied via the coronary circulation. It is composed of individual heart muscle cells joined together by intercalated discs, encased by collagen fibres and other substances that form the extracellular matrix. Cardiac muscle contracts in a similar manner to skeletal muscle, although with some important differences. An electrical stimulation in the form of an action potential triggers the release of calcium from the cell's internal calcium store, the sarcoplasmic reticulum; the rise in calcium causes the cell's myofilaments to slide past each other in a process called excitation contraction coupling. Diseases of heart muscle are of major importance; these include conditions caused by a restricted blood supply to the muscle including angina pectoris and myocardial infarction, other heart muscle disease known as cardiomyopathies.
Cardiac muscle tissue or myocardium forms the bulk of the heart. The heart wall is a three layered structure with a thick layer of myocardium sandwiched between the inner endocardium and the outer epicardium; the inner endocardium lines the cardiac chambers, covers the cardiac valves, joins with the endothelium that lines the blood vessels that connect to the heart. On the outer aspect of the myocardium is the epicardium which forms part of the pericardium, the sack that surrounds and lubricates the heart. Within the myocardium there cardiomyocytes; the sheets of muscle that wrap around the left ventricle closest to the endocardium are oriented perpendicularly to those closest to the epicardium. When these sheets contract in a coordinated manner they allow the ventricle to squeeze in several direction – longitudinally and with a twisting motion to squeeze the maximum amount of blood out of the heart with each heartbeat. Contracting heart muscle uses a lot of energy, therefore requires a constant flow of blood to provide oxygen and nutrients.
Blood is brought to the myocardium by the coronary arteries. These lie on the outer or epicardial surface of the heart. Blood is drained away by the coronary veins into the right atrium; when looked at microscopically, cardiac muscle can be likened to the wall of a house. Most of the wall is taken up by bricks, which in cardiac muscle are individual cardiac muscle cells or cardiomyocytes; the mortar which surrounds the bricks is known as the extracellular matrix, produced by supporting cells known as fibroblasts. In the same way that the walls of a house contain electrical wires and plumbing, cardiac muscle contains specialised cells for conducting electrical signals and blood vessels to bring nutrients to the muscle cells and take away waste products. Cardiac muscle cells or cardiomyocytes are the contracting cells; each cardiomyocyte needs to contract in coordination with its neighbouring cells to efficiently pump blood from the heart, if this coordination breaks down – despite individual cells contracting – the heart may not pump at all, such as may occur during abnormal heart rhythms such as ventricular fibrillation.
Viewed through a microscope, cardiac muscle cells are rectangular, measuring 100–150μm by 30–40μm. Individual cardiac muscle cells are joined together at their ends by intercalated disks to form long fibres; each cell contains myofibrils, specialised protein fibres that slide past each other. These are organised into the fundamental contractile units of muscle cells; the regular organisation of myofibrils into sarcomeres gives cardiac muscle cells a striped or striated appearance when looked at through a microscope, similar to skeletal muscle. These striations are caused by lighter I bands composed of a protein called actin, darker A bands composed of myosin. Cardiomyocytes contain T-tubules, pouches of membrane that run from the surface to the cell's interior which help to which improve the efficiency of contraction; the majority of these cells contain only one nucleus, unlike skeletal muscle cells which contain many nuclei. Cardiac muscle cells contain many mitochondria which provide the energy needed for the cell in the form of adenosine triphosphate, making them resistant to fatigue.
T-tubules are microscopic tubes. They are continuous with the cell membrane, are composed of the same phospholipid bilayer, are open at the cell surface to the extracellular fluid that surrounds the cell. T-tubules in cardiac muscle are fewer in number. In the centre of the cell they join together, running into and along the cell as a transverse-axial network. Inside the cell they lie close to the sarcoplasmic reticulum. Here, a single tubule pairs with part of the sarcoplasmic reticulum called a terminal cisterna in a combination known as a diad; the functions of T-tubules include transmitting electrical impulses known as action potentials from the cell surface to the cell's core, helping to regulate the concentration of cal