The cerebral cortex known as the cerebral mantle, is the outer layer of neural tissue of the cerebrum of the brain, in humans and other mammals. It is separated into two cortices, by the longitudinal fissure that divides the cerebrum into the left and right cerebral hemispheres; the two hemispheres are joined beneath the cortex by the corpus callosum. The cerebral cortex is the largest site of neural integration in the central nervous system, it plays a key role in memory, perception, thought and consciousness. In most mammals, apart from small mammals that have small brains, the cerebral cortex is folded, providing a greater surface area in the confined volume of the cranium. Apart from minimising brain and cranial volume cortical folding is crucial for the wiring of the brain and its functional organisation. In mammals with a small brain there is no folding and the cortex is smooth. A fold or ridge in the cortex is termed a gyrus and a groove is termed a sulcus; these surface convolutions appear during fetal development and continue to mature after birth through the process of gyrification.
In the human brain the majority of the cerebral cortex is not visible from the outside, but buried in the sulci, the insular cortex is hidden. The major sulci and gyri mark the divisions of the cerebrum into the lobes of the brain. There are between 16 billion neurons in the cerebral cortex; these are organised into cortical columns and minicolumns of neurons that make up the layers of the cortex. Most of the cerebral cortex consists of the six-layered neocortex. Cortical areas have specific functions; the cerebral cortex is the outer covering of the surfaces of the cerebral hemispheres and is folded into peaks called gyri, grooves called sulci. In the human brain it is between two and three or four millimetres thick, makes up 40 per cent of the brain's mass. There are between 14 and 16 billion neurons in the cortex, these are organized in cortical columns, minicolumns of the layers of the cortex. About two thirds of the cortical surface is buried in the sulci and the insular cortex is hidden; the cortex is thickest over thinnest at the bottom of a sulcus.
The cerebral cortex is folded in a way that allows a large surface area of neural tissue to fit within the confines of the neurocranium. When unfolded in the human, each hemispheric cortex has a total surface area of about 1.3 square feet. The folding is inward away from the surface of the brain, is present on the medial surface of each hemisphere within the longitudinal fissure. Most mammals have a cerebral cortex, convoluted with the peaks known as gyri and the troughs or grooves known as sulci; some small mammals including some small rodents have smooth cerebral surfaces without gyrification. The larger sulci and gyri mark the divisions of the cortex of the cerebrum into the lobes of the brain. There are four main lobes: the frontal lobe, parietal lobe, temporal lobe, occipital lobe; the insular cortex is included as the insular lobe. The limbic lobe is a rim of cortex on the medial side of each hemisphere and is often included. There are three lobules of the brain described: the paracentral lobule, the superior parietal lobule, the inferior parietal lobule.
For species of mammals, larger brains tend to have thicker cortices. The smallest mammals, such as shrews, have a neocortical thickness of about 0.5 mm. There is an logarithmic relationship between brain weight and cortical thickness. Magnetic resonance imaging of the brain makes it possible to get a measure for the thickness of the human cerebral cortex and relate it to other measures; the thickness of different cortical areas varies but in general, sensory cortex is thinner than motor cortex. One study has found some positive association between the cortical intelligence. Another study has found that the somatosensory cortex is thicker in migraine sufferers, though it is not known if this is the result of migraine attacks or the cause of them. A study using a larger patient population reports no change in the cortical thickness in migraine sufferers. A genetic disorder of the cerebral cortex, whereby decreased folding in certain areas results in a microgyrus, where there are four layers instead of six, is in some instances seen to be related to dyslexia.
The six cortical layers of the neocortex each contain a characteristic distribution of different neurons and their connections with other cortical and subcortical regions. There are direct connections between different cortical areas and indirect connections via the thalamus. One of the clearest examples of cortical layering is the line of Gennari in the primary visual cortex; this is a band of whiter tissue that can be observed with the naked eye in the fundus of the calcarine sulcus of the occipital lobe. The line of Gennari is composed of axons bringing visual information from the thalamus into layer IV of the visual cortex. Staining cross-sections of the cortex to reveal the position of neuronal cell bodies and the intracortical axon tracts allowed neuroanatomists in the early 20th century to produce a detailed description of the laminar structure of the cortex in different species. After the work of Korbinian Brodmann the neurons of the cerebral cortex are grouped into six main layers, from the outer pial surface to the inner white matter.
Layer I is the molecular layer, contains few scattered neurons, including GABAergic rosehip neurons. Layer I consists of extensions of apical dendritic tufts of pyramidal neurons and horiz
Leucism is a condition in which there is partial loss of pigmentation in an animal resulting in white, pale, or patchy coloration of the skin, feathers, scales or cuticle, but not the eyes. It is spelled leukism. Unlike albinism, it is caused by a reduction in multiple types of pigment, not just melanin. Leucism is a general term for the phenotype resulting from defects in pigment cell differentiation and/or migration from the neural crest to skin, hair, or feathers during development; this results in either the entire surface or patches of body surface having a lack of cells capable of making pigment. Since all pigment cell-types differentiate from the same multipotent precursor cell-type, leucism can cause the reduction in all types of pigment; this is in contrast to albinism, for which leucism is mistaken. Albinism results in the reduction of melanin production only, though the melanocyte is still present, thus in species that have other pigment cell-types, for example xanthophores, albinos are not white, but instead display a pale yellow colour.
More common than a complete absence of pigment cells is localized or incomplete hypopigmentation, resulting in irregular patches of white on an animal that otherwise has normal colouring and patterning. This partial leucism is known as a "pied" or "piebald" effect; this is notable in horses, cats, the urban crow and the ball python but is found in many other species. A further difference between albinism and leucism is in eye colour. Due to the lack of melanin production in both the retinal pigmented epithelium and iris, those affected by albinism have red eyes due to the underlying blood vessels showing through. In contrast, most leucistic animals have coloured eyes; this is because the melanocytes of the RPE are not derived from the neural crest, instead an outpouching of the neural tube generates the optic cup which, in turn, forms the retina. As these cells are from an independent developmental origin, they are unaffected by the genetic cause of leucism. Genes that, when mutated, can cause leucism include, c-kit, mitf and EDNRB.
The terms leucistic and leucism are derived from medical terminology. The stem leuc- is the Latin variant of leuk- from the Greek leukos meaning "white". Leucism has been noted in a number of animal species, including: Kermode bear White buffalo White lion Seneca white deer Leucistic giraffes in Kenya White stag White tiger White peafowl Moby Dick White stag Kimba the White Lion
Deoxyribonucleic acid is a molecule composed of two chains that coil around each other to form a double helix carrying the genetic instructions used in the growth, development and reproduction of all known organisms and many viruses. DNA and ribonucleic acid are nucleic acids; the two DNA strands are known as polynucleotides as they are composed of simpler monomeric units called nucleotides. Each nucleotide is composed of one of four nitrogen-containing nucleobases, a sugar called deoxyribose, a phosphate group; the nucleotides are joined to one another in a chain by covalent bonds between the sugar of one nucleotide and the phosphate of the next, resulting in an alternating sugar-phosphate backbone. The nitrogenous bases of the two separate polynucleotide strands are bound together, according to base pairing rules, with hydrogen bonds to make double-stranded DNA; the complementary nitrogenous bases are divided into two groups and purines. In DNA, the pyrimidines are cytosine. Both strands of double-stranded DNA store the same biological information.
This information is replicated as and when the two strands separate. A large part of DNA is non-coding, meaning that these sections do not serve as patterns for protein sequences; the two strands of DNA are thus antiparallel. Attached to each sugar is one of four types of nucleobases, it is the sequence of these four nucleobases along the backbone. RNA strands are created using DNA strands as a template in a process called transcription. Under the genetic code, these RNA strands specify the sequence of amino acids within proteins in a process called translation. Within eukaryotic cells, DNA is organized into long structures called chromosomes. Before typical cell division, these chromosomes are duplicated in the process of DNA replication, providing a complete set of chromosomes for each daughter cell. Eukaryotic organisms store most of their DNA inside the cell nucleus as nuclear DNA, some in the mitochondria as mitochondrial DNA, or in chloroplasts as chloroplast DNA. In contrast, prokaryotes store their DNA only in circular chromosomes.
Within eukaryotic chromosomes, chromatin proteins, such as histones and organize DNA. These compacting structures guide the interactions between DNA and other proteins, helping control which parts of the DNA are transcribed. DNA was first isolated by Friedrich Miescher in 1869, its molecular structure was first identified by Francis Crick and James Watson at the Cavendish Laboratory within the University of Cambridge in 1953, whose model-building efforts were guided by X-ray diffraction data acquired by Raymond Gosling, a post-graduate student of Rosalind Franklin. DNA is used by researchers as a molecular tool to explore physical laws and theories, such as the ergodic theorem and the theory of elasticity; the unique material properties of DNA have made it an attractive molecule for material scientists and engineers interested in micro- and nano-fabrication. Among notable advances in this field are DNA origami and DNA-based hybrid materials. DNA is a long polymer made from repeating units called nucleotides.
The structure of DNA is dynamic along its length, being capable of coiling into tight loops and other shapes. In all species it is composed of two helical chains, bound to each other by hydrogen bonds. Both chains are coiled around the same axis, have the same pitch of 34 angstroms; the pair of chains has a radius of 10 angstroms. According to another study, when measured in a different solution, the DNA chain measured 22 to 26 angstroms wide, one nucleotide unit measured 3.3 Å long. Although each individual nucleotide is small, a DNA polymer can be large and contain hundreds of millions, such as in chromosome 1. Chromosome 1 is the largest human chromosome with 220 million base pairs, would be 85 mm long if straightened. DNA does not exist as a single strand, but instead as a pair of strands that are held together; these two long strands coil in the shape of a double helix. The nucleotide contains both a segment of the backbone of a nucleobase. A nucleobase linked to a sugar is called a nucleoside, a base linked to a sugar and to one or more phosphate groups is called a nucleotide.
A biopolymer comprising multiple linked nucleotides is called a polynucleotide. The backbone of the DNA strand is made from alternating sugar residues; the sugar in DNA is 2-deoxyribose, a pentose sugar. The sugars are joined together by phosphate groups that form phosphodiester bonds between the third and fifth carbon atoms of adjacent sugar rings; these are known as the 3′-end, 5′-end carbons, the prime symbol being used to distinguish these carbon atoms from those of the base to which the deoxyribose forms a glycosidic bond. When imagining DNA, each phosphoryl is considered to "belong" to the nucleotide whose 5′ carbon forms a bond therewith. Any DNA strand therefore has one end at which there is a phosphoryl attached to the 5′ carbon of a ribose and another end a
National Institutes of Health
The National Institutes of Health is the primary agency of the United States government responsible for biomedical and public health research. It was founded in the late 1870s and is now part of the United States Department of Health and Human Services; the majority of NIH facilities are located in Maryland. The NIH conducts its own scientific research through its Intramural Research Program and provides major biomedical research funding to non-NIH research facilities through its Extramural Research Program; as of 2013, the IRP had 1,200 principal investigators and more than 4,000 postdoctoral fellows in basic and clinical research, being the largest biomedical research institution in the world, while, as of 2003, the extramural arm provided 28% of biomedical research funding spent annually in the U. S. or about US$26.4 billion. The NIH comprises 27 separate institutes and centers of different biomedical disciplines and is responsible for many scientific accomplishments, including the discovery of fluoride to prevent tooth decay, the use of lithium to manage bipolar disorder, the creation of vaccines against hepatitis, Haemophilus influenzae, human papillomavirus.
NIH's roots extend back to the Marine Hospital Service in the late 1790s that provided medical relief to sick and disabled men in the U. S. Navy. By 1870, a network of marine hospitals had developed and was placed under the charge of a medical officer within the Bureau of the Treasury Department. In the late 1870s, Congress allocated funds to investigate the causes of epidemics like cholera and yellow fever, it created the National Board of Health, making medical research an official government initiative. In 1887, a laboratory for the study of bacteria, the Hygienic Laboratory, was established at the Marine Hospital in New York. In the early 1900s, Congress began appropriating funds for the Marine Hospital Service. By 1922, this organization changed its name to Public Health Services and established a Special Cancer Investigations laboratory at Harvard Medical School; this marked the beginning of a partnership with universities. In 1930, the Hygienic Laboratory was re-designated as the National Institute of Health by the Ransdell Act, was given $750,000 to construct two NIH buildings.
Over the next few decades, Congress would increase funding tremendously to the NIH, various institutes and centers within the NIH were created for specific research programs. In 1944, the Public Health Service Act was approved, the National Cancer Institute became a division of NIH. In 1948, the name changed from National Institute of Health to National Institutes of Health. In the 1960s, virologist and cancer researcher Chester M. Southam injected HeLa cancer cells into patients at the Jewish Chronic Disease Hospital; when three doctors resigned after refusing to inject patients without their consent, the experiment gained considerable media attention. The NIH was a major source of funding for Southam's research and had required all research involving human subjects to obtain their consent prior to any experimentation. Upon investigating all of their grantee institutions, the NIH discovered that the majority of them did not protect the rights of human subjects. From on, the NIH has required all grantee institutions to approve any research proposals involving human experimentation with review boards.
In 1967, the Division of Regional Medical Programs was created to administer grants for research for heart disease and strokes. That same year, the NIH director lobbied the White House for increased federal funding in order to increase research and the speed with which health benefits could be brought to the people. An advisory committee was formed to oversee further development of the NIH and its research programs. By 1971 cancer research was in full force and President Nixon signed the National Cancer Act, initiating a National Cancer Program, President's Cancer Panel, National Cancer Advisory Board, 15 new research and demonstration centers. Funding for the NIH has been a source of contention in Congress, serving as a proxy for the political currents of the time. In 1992, the NIH encompassed nearly 1 percent of the federal government's operating budget and controlled more than 50 percent of all funding for health research, 85 percent of all funding for health studies in universities. While government funding for research in other disciplines has been increasing at a rate similar to inflation since the 1970s, research funding for the NIH nearly tripled through the 1990s and early 2000s, but has remained stagnant since then.
By the 1990s, the NIH committee focus had shifted to DNA research, launched the Human Genome Project. The NIH Office of the Director is the central office responsible for setting policy for NIH, for planning and coordinating the programs and activities of all NIH components; the NIH Director plays an active role in shaping outlook. The Director is responsible for providing leadership to the Institutes and Centers by identifying needs and opportunities in efforts involving multiple Institutes. Within this Office is the Division of Program Coordination and Strategic Initiatives with 12 divisions including: Office of AIDS Research Office of Research on Women's Health Office of Disease Prevention Sexual and Gender Minority Research Office Tribal Heath Research Office Office of Program Evaluation and PerformancePrevious directors: Joseph J. Kinyoun, served August 1887 – April 30, 1899 Milton J. Rosenau, served May 1, 1899 – September 30, 1909 John F. Anderson, served October 1, 1909 – November 19, 1915 George W. McCoy, served November 20, 1915 – January 31, 1937 Lewis R. Thompson, served February 1, 1937 – January 31, 1942 R
Blaschko's lines called the lines of Blaschko, named after Alfred Blaschko, are lines of normal cell development in the skin. These lines are invisible under normal conditions, they become apparent when some diseases of the skin or mucosa manifest themselves according to these patterns. They follow a "V" shape over the back, "S" shaped whirls over the chest and sides, wavy shapes on the head; the lines are believed to trace the migration of embryonic cells. The stripes are a type of genetic mosaicism, they do not correspond to nervous, muscular, or lymphatic systems. The lines can be observed in other animals such as dogs. German dermatologist Alfred Blaschko is credited with the first demonstration of these lines in 1901; the skin lesions. They include genetic and acquired conditions. Examples include: Pigmentary disorders Naevus achromicus Epidermal Naevus Nevus sebaceous Inflammatory Linear Verrucous Epidermal Nevus X-linked genetic skin disorder Incontinentia pigmenti CHILD syndrome XLPDR syndrome Acquired inflammatory skin rashes Lichen striatus lichen planus lupus erythematosus Chimerism Kraissl's lines Langer's lines List of cutaneous conditions "Blaschko's lines".
Www.pcds.org.uk. Humans Have Stripes Picture of the Blaschko's lines Illustrations of the various patterns of cutaneous mosaicism Understanding Genetics - ask a geneticist Description of Blaschko's lines
Amelanism is a pigmentation abnormality characterized by the lack of pigments called melanins associated with a genetic loss of tyrosinase function. Amelanism can affect fish, reptiles and mammals including humans; the appearance of an amelanistic animal depends on the remaining non-melanin pigments. The opposite of amelanism is a higher percentage of melanin. A similar condition, albinism, is a hereditary condition characterised in animals by the absence of pigment in the eyes, hair, feathers or cuticle; this results in an all white animal with pink or red eyes. Melanin is a compound found in plants and protists, is derived from the amino acid tyrosine. Melanin is a photoprotectant. Vertebrates have melanin in feathers, or scales, they have two layers of pigmented tissue in the eye: the stroma, at the front of the iris, the iris pigment epithelium, a thin but critical layer of pigmented cells at the back of the iris. Melanin is present in the inner ear, is important for the early development of the auditory system.
Melanin is found in parts of the brain and adrenal gland. Melanins are produced in organelles called melanosomes; the production of melanins is called melanogenesis. Melanosomes are found in specialized pigment cells called melanocytes, but may be engulfed by other cells, which are called melanophages. Hair acquires pigment from melanocytes in the root bulb, which deposit melanosomes into the growing hair structure. A critical step in the production of melanins is the catalysis of tyrosine by an enzyme called tyrosinase, producing dopaquinone. Dopaquinone may become phaeomelanin. Eumelanin, meaning true black, is a dense compound that absorbs most wavelengths of light, appears black or brown as a result. Phaeomelanin, meaning rufous-black, is characterized by the presence of sulfur-containing cysteine, it appears reddish to yellowish as a result. Melanosomes containing eumelanin are eumelanosomes, while those containing phaeomelanin are phaeomelanosomes. Melanocyte-stimulating hormone binds to the Melanocortin 1 receptor and commits melanocytes to the production of eumelanin.
In the absence of this signal, melanocytes produce phaeomelanin. Another chemical, Agouti signalling peptide, can attach itself to MC1R and interfere with MSH/MC1R signalling. In many mammals, variation in the level of ASP switches melanocytes between eumelanin and phaeomelanin production, resulting in coloured patterns. Melanocytes, the parallel melanophores found in fishes and reptiles, are derived from a strip of tissue in the embryo called the neural crest. Stem cells in the neural crest give rise to the cells of the autonomic nervous system, supportive elements of the skeleton such as chondrocytes, cells of the endocrine system, melanocytes; this strip of tissue is found along the dorsal midline of the embryo, multipotent cells migrate down along the sides of the embryo, or through germ layers, to their ultimate destinations. Melanocyte stem. Conditions associated with abnormalities in the migration of melanoblasts are known collectively as piebaldism. Pigment cells of the iris pigment epithelium have a separate embryological origin.
Piebaldism and amelanism are distinct conditions. The only pigments that mammals produce are melanins. For a mammal to be unable to chemically manufacture melanin renders it pigmentless; this condition is more called albinism. Amelanistic mammals have white hair, pink skin, eyes that have a pink, red, or violet appearance. Reddish eyes are due to the lack of pigment in the iris pigment epithelium; when the stroma is unpigmented but the iris pigment epithelium is not, mammalian eyes appear blue. Melanin in the pigment epithelium is critical for visual contrast. Loss of melanogenesis function is linked to the gene. Certain alleles of this gene, TYR, at the Color locus, cause oculocutaneous albinism type 1 in humans and the familiar red-eyed albino conditions in mice and other mammals. Other vertebrates, such as fishes, amphibians and birds, produce a variety of non-melanin pigments. Disruption of melanin production does not affect the production of these pigments. Non-melanin pigments in other vertebrates are produced by cells called chromatophores.
Within this categorization, xanthophores are cells that contain yellowish pteridines, while erythrophores contain orangish carotenoids. Some species possess iridophores or leucophores, which do not contain true pigments, but light-reflective structures that give iridescence. An uncommon type of chromatophore, the cyanophore, produces a vivid blue pigment. Amelanism in fishes, amphibians and birds has the same genetic etiology as in mammals: loss of tyrosinase function. However, due to the presence of other pigments, other amelanistic vertebrates are white and red-eyed like amelanistic mammals. Melanocytes depend on the Melanocortin 1 receptor to signal the production of eumelanin. Loss of melanocortin 1 receptor function or high activity of the MC1R-antagonist, Agouti signalling peptide, can cause the widespread absence of eumelanin. Loss of MC1R function, a recessive trait, has been observed in many species. In humans, various mutations of the MC1R gene result in red hair, blond hair, fair skin, susceptibility to sundamaged skin and melanoma.
Aeumelanic hair coats, associated with mutations of the MC1R gene, have been identified in mice, cattle and horses. These coat colors are called "yellow" in dogs, "red" in cattle and chestnut in horses; the loss of eumelan
Zygosity is the degree of similarity of the alleles for a trait in an organism. Most eukaryotes have two matching sets of chromosomes. Diploid organisms have the same loci on each of their two sets of homologous chromosomes except that the sequences at these loci may differ between the two chromosomes in a matching pair and that a few chromosomes may be mismatched as part of a chromosomal sex-determination system. If both alleles of a diploid organism are the same, the organism is homozygous at that locus. If they are different, the organism is heterozygous at that locus. If one allele is missing, it is hemizygous; the DNA sequence of a gene varies from one individual to another. Those variations are called alleles. While some genes have only one allele because there is low variation, others have only one allele because deviation from that allele can be harmful or fatal, but most genes have two or more alleles. The frequency of different alleles varies throughout the population; some genes may have two alleles with equal distribution.
For other genes, one allele may be common, another allele may be rare. Sometimes, one allele is a disease-causing variation. Sometimes, the different variations in the alleles make no difference at all in the function of the organism. In diploid organisms, one allele is inherited from one from the female parent. Zygosity is a description of whether those two alleles have different DNA sequences. In some cases the term "zygosity" is used in the context of a single chromosome; the words homozygous and hemizygous are used to describe the genotype of a diploid organism at a single locus on the DNA. Homozygous describes a genotype consisting of two identical alleles at a given locus, heterozygous describes a genotype consisting of two different alleles at a locus, hemizygous describes a genotype consisting of only a single copy of a particular gene in an otherwise diploid organism, nullizygous refers to an otherwise-diploid organism in which both copies of the gene are missing. A cell is said to be homozygous for a particular gene when identical alleles of the gene are present on both homologous chromosomes.
The cell or organism in question is called a homozygote. True breeding organisms are always homozygous for the traits. An individual, homozygous-dominant for a particular trait carries two copies of the allele that codes for the dominant trait; this allele called the "dominant allele", is represented by a capital letter. When an organism is homozygous-dominant for a particular trait, the genotype is represented by a doubling of the symbol for that trait, such as "PP". An individual, homozygous-recessive for a particular trait carries two copies of the allele that codes for the recessive trait; this allele called the "recessive allele", is represented by the lowercase form of the letter used for the corresponding dominant trait. The genotype of an organism, homozygous-recessive for a particular trait is represented by a doubling of the appropriate letter, such as "pp". A diploid organism is heterozygous at a gene locus when its cells contain two different alleles of a gene; the cell or organism is called a heterozygote for the allele in question, therefore, heterozygosity refers to a specific genotype.
Heterozygous genotypes are represented by a capital letter and a lowercase letter, such as "Rr" or "Ss". Alternatively, a heterozygote for gene "R" is assumed to be "Rr"; the capital letter is written first. If the trait in question is determined by simple dominance, a heterozygote will express only the trait coded by the dominant allele, the trait coded by the recessive allele will not be present. In more complex dominance schemes the results of heterozygosity can be more complex. A heterozygous genotype can have a higher relative fitness than either the homozygous dominant or homozygous recessive genotype - this is called a heterozygote advantage. A chromosome in a diploid organism is hemizygous; the cell or organism is called a hemizygote. Hemizygosity is observed when one copy of a gene is deleted, or, in the heterogametic sex, when a gene is located on a sex chromosome. Hemizygosity must not be confused with haploinsufficiency, which describes a mechanism for producing a phenotype. For organisms in which the male is heterogametic, such as humans all X-linked genes are hemizygous in males with normal chromosomes, because they have only one X chromosome and few of the same genes are on the Y chromosome.
Transgenic mice generated through exogenous DNA microinjection of an embryo's pronucleus are considered to be hemizygous, because the introduced allele is expected to be incorporated into only one copy of any locus. A transgenic individual can be bred to homozygosity and maintained as an inbred line to reduce the need to confirm the genotype of each individual. In cultured mammalian cells, such as the Chinese hamster ovary cell line, a number of genetic loci are present in a functional hemizygous state, due to mutations or deletions in the other alleles. A nullizygous organism carries two mutant alleles for the same gene; the mutant alleles are both complete loss-of-function or'null' alleles, so homozygous null and n