are specialized cells in the skin which produce melanin
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Melanocytes are melanin-producing neural crest-derived cells located in the bottom layer (the stratum basale) of the skin's epidermis, the middle layer of the eye (the uvea), the inner ear, vaginal epithelium, meninges, bones, and heart. Melanin is a dark pigment primarily responsible for skin color. Once synthesized, melanin is contained in special organelles called melanosomes which can be transported to nearby keratinocytes to induce pigmentation. Thus darker skin tones have more melanosomes present than lighter skin tones. Functionally, melanin serves as protection against UV radiation. Melanocytes also have a role in the immune system. Function Through a process called melanogenesis, melanocytes produce melanin, which is a pigment found in the skin, eyes, hair, nasal cavity, and inner ear. This melanogenesis leads to a long-lasting pigmentation, which is in contrast to the pigmentation that originates from oxidation of already-existing melanin. There are both basal and activated levels of melanogenesis; in general, lighter-skinned people have low basal levels of melanogenesis. Exposure to UV-B radiation causes increased melanogenesis. The purpose of melanogenesis is to protect the hypodermis, the layer under the skin, from damage by UV radiation. The color of the melanin is black, allowing it to absorb a majority of the UV light and block it from passing through the epidermis. Since the action spectrum of sunburn and melanogenesis are virtually identical, they are assumed to be induced by the same mechanism. The agreement of the action spectrum with the absorption spectrum of DNA points towards the formation of cyclobutane pyrimidine dimers (CPDs) - direct DNA damage. Typically, between 1000 and 2000 melanocytes are found per square millimeter of skin or approximately 5% to 10% of the cells in the basal layer of epidermis. Although their size can vary, melanocytes are typically 7 μm in length. Both lightly and darkly pigmented skin contain similar numbers of melanocytes, with difference in skin color due to differences the packing of eumelanin into the melanosomes of keratinocytes: those in dark-toned skin are "packaged into peri-nuclear distributed, ellipsoid" melanosomes while those light-tone skin are "assembled into clustered small, circular melanosomes". There are also differences in the quantity and relative amounts of eumelanin and pheomelanin. Pigmentation including tanning is under hormonal control, including the MSH and ACTH peptides that are produced from the precursor proopiomelanocortin. Vitiligo is a skin disease where people lack melanin in certain areas in the skin. People with oculocutaneous albinism typically have a very low level of melanin production. Albinism is often but not always related to the TYR gene coding the tyrosinase enzyme. Tyrosinase is required for melanocytes to produce melanin from the amino acid tyrosine. Albinism may be caused by a number of other genes as well, like OCA2, SLC45A2, TYRP1, and HPS1 to name some. In all, already 17 types of oculocutaneous albinism have been recognized. Each gene is related to different protein having a role in pigment production. People with Chédiak–Higashi syndrome have a buildup of melanin granules due to abnormal function of microtubules. Role in the immune system
Melanocyte
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Amelanism (also known as amelanosis) is a pigmentation abnormality characterized by the lack of pigments called melanins, commonly associated with a genetic loss of tyrosinase function. Amelanism can affect fish, amphibians, reptiles, birds, and mammals including humans. The appearance of an amelanistic animal depends on the remaining non-melanin pigments. The opposite of amelanism is melanism, a higher percentage of melanin. A similar condition, albinism, is a hereditary condition characterised in animals by the absence of pigment in the eyes, skin, hair, scales, feathers or cuticle. This results in an all white animal, usually with pink or red eyes. Melanins and melanin production Melanin is a compound found in plants, animals, and protists, and is derived from the amino acid tyrosine. Melanin is a photoprotectant, absorbing the DNA-damaging ultraviolet radiation of the sun. Vertebrates have melanin in their skin and hair, feathers, or scales. They also have two layers of pigmented tissue in the eye: the stroma, at the front of the iris, and the iris pigment epithelium, a thin but critical layer of pigmented cells at the back of the iris. Melanin is also present in the inner ear, and is important for the early development of the auditory system. Melanin is also 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 also be engulfed by other cells, which are then 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 eumelanin, or phaeomelanin. Eumelanin, meaning true black, is a dense compound that absorbs most wavelengths of light, and appears black or brown as a result. Phaeomelanin, meaning rufous-black, is characterized by the presence of sulfur-containing cysteine, and it appears reddish to yellowish as a result. Melanosomes containing eumelanin are eumelanosomes, while those containing phaeomelanin are phaeomelanosomes. Melanocyte-stimulating hormone (MSH) binds to the Melanocortin 1 receptor (MC1R) and commits melanocytes to the production of eumelanin. In the absence of this signal, melanocytes produce phaeomelanin. Another chemical, Agouti signalling peptide (ASP), 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, and the parallel melanophores found in fishes, amphibians, 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, and melanocytes. This strip of tissue is found along the dorsal midline of the embryo, and multipotent cells migrate down along the sides of the embryo, or through germ layers, to their ultimate destinations. Melanocyte stem cells are called
Amelanism
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P protein, also known as melanocyte-specific transporter protein or pink-eyed dilution protein homolog, is a protein that in humans is encoded by the oculocutaneous albinism II (OCA2) gene. The P protein is believed to be an integral membrane protein involved in small molecule transport, specifically of tyrosine—a precursor of melanin. Certain mutations in OCA2 result in type 2 oculocutaneous albinism. OCA2 encodes the human homologue of the mouse p (pink-eyed dilution) gene. The human OCA2 gene is located on the long arm (q) of chromosome 15, specifically from base pair 28,000,020 to base pair 28,344,457 on chromosome 15. Function OCA2 provides instructions for making the protein called P protein which is located in melanocytes which are specialized cells that produce melanin, and in the cells of the retinal pigment epithelium. Melanin is responsible for giving color to the skin, hair, and eyes. Moreover, melanin is found in the light-sensitive tissue of the retina of the eye which plays a role in normal vision. The exact function of protein P is unknown, but it has been found that it is essential for the normal coloring of skin, eyes, and hair; and likely involved in melanin production. This gene seems to be the main determinant of eye color depending on the amount of melanin production in the iris stroma (large amounts giving rise to brown eyes; little to no melanin giving rise to blue eyes). This gene is mutated in Astyanax mexicanus, a Mexican fish which is characterized by a chronic Albinism in cave's individuals. It exists as a deletion in Pachón and Molino's caves fish that produces the albinism. Clinical significance Mutations in the OCA2 gene cause a disruption in the normal production of melanin; therefore, causing vision problems and reductions in hair, skin, and eye color. Oculocutaneous albinism caused by mutations in the OCA2 gene is called oculocutaneous albinism type 2. The prevalence of OCA type 2 is estimated at 1/38,000-1/40,000 in most populations throughout the world, with a higher prevalence in the African population of 1/3,900–1/1,500. Other diseases associated with the deletion of the OCA2 gene are Angelman syndrome (light-colored hair and fair skin) and Prader–Willi syndrome (unusually light-colored hair and fair skin). With both these syndromes, the deletion often occurs in individuals with either syndrome. A mutation in the HERC2 gene adjacent to OCA2, affecting OCA2's expression in the human iris, is found common to nearly all people with blue eyes. It has been hypothesized that all blue-eyed humans share a single common ancestor with whom the mutation originated. The His615Arg allele of OCA2 is involved in the light skin tone and the derived allele is restricted to East Asia with high frequencies, with highest frequencies in Eastern East Asia (49-63%), midrange frequencies in Southeast Asia, and the lowest frequencies in Western China and some Eastern European populations. References Further reading External links GeneReviews/NCBI/NIH/UW entry on Oculocutaneous Albinism Type 2 Genes on human chromosome 15 Eye color Proteins
P protein
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Smoker's melanosis is seen with the naked eye as a brown to black pigmentation of the oral tissue i.e. the gums, cheeks or palate as well as in larynx. It is most often seen in the lower labial gingiva of tobacco users. Most easily it is found in Caucasians, due to their lack of a genetically caused melanin pigmentation. The brown to black colour is melanin. In skin, melanin prevents harmful UV-light from reaching deeper, sensible parts of the tissue. If UV-light penetrates deeply, some of the toxic substances caused by UV-light damage to cells are bound to melanin in the epithelial cells and travel with the ageing cells to the skin surface, where they are expelled from the tissue surface. In this way the melanocytes and keratinocytes together protect the tissue, with melanin serving as a toxic defence and cleaning agent. In the oral mucosa, where the ageing epithelial cells move faster to the surface compared to skin, a similar defence-mechanism seems to be present, cleaning the mucosa from different toxic chemicals penetrating the epithelium. Besides chemicals in tobacco also antimalaria-drugs cause an oral pigmentation. Smoker's melanosis is like the genetic melanin pigmentations, a defence-system in action. The microscope shows smoker's melanosis to be characterized by a melanin hyperpigmentation of the lower part of the oral epithelium, similar to sun-tanned skin. The hyperpigmentation consists of melanin granules which have the shape and colour of "coffea beans". They are produced by the dendritic, octopus-like melanocytes, seen between the epithelial cells situated closest to the epithelium/connective tissue border. In tobacco-users the melanocytes are stimulated to produce melanin granules and to distribute them out to the surrounding epithelial cells for further transport to the mucosal surface, like the mechanism in melanin-pigmented skin. Small amounts of melanin-like granules together with other electron-dense particles can also be seen within large melanosome complexes in the underlying connective tissue. If the granules derive from the epithelium, a phenomenon known as melanin incontinence, is not known. In Caucasians these granules are not expected to influence on the clinically observed degree of smoker's melanosis. Causes Smoking or the use of nicotine-containing drugs is the cause to Smoker's melanosis,. Also tar-components (benzopyrenes) are known to stimulate melanocytes to melanin production, and other unknown toxic agents in tobacco may also be the cause. These chemical agents have a polycyclic, chain-like structure. Environmental tobacco smoke from parents is causing smoker's melanosis in their children Swedish snuff causes a small elevation of oral melanin pigmented individuals from 3.0% to 4.7%. Nicotine tablets have shown to stimulate to melanin pigmentation of the oral mucosa. Treatment and prognosis Lesions usually disappear between 3 months to 3 years for those who stop smoking. Smoker's melanosis is a benign, normal physiological reaction, and does not develop into cancer. If it does not disappear, however, a biopsy can verify the diagnosis. If smoker's melanosis is destroyed by excessive smoking, as in the hard palate of reverse smokers, who smoke with the glowing part of the cigarette inside
Smoker's melanosis
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Sun tanning or tanning is the process whereby skin color is darkened or tanned. It is most often a result of exposure to ultraviolet (UV) radiation from sunlight or from artificial sources, such as a tanning lamp found in indoor tanning beds. People who deliberately tan their skin by exposure to the sun engage in a passive recreational activity of sun bathing. Some people use chemical products that can produce a tanning effect without exposure to ultraviolet radiation, known as sunless tanning. Impact on skin health Moderate exposure Moderate exposure to direct sunlight contributes to the production of melanin and vitamin D by the body. Excessive exposure Excessive exposure to ultraviolet rays has negative health effects, including sunburn. Some people tan or sunburn more easily than others. This may be the result of different skin types and natural skin color, and these may be a result of genetics. The term "tanning" has a cultural origin, arising from the color tan. Its origin lies in the Western culture of Europe when it became fashionable for young women to seek a less pale complexion (see Cultural history below). Long-term Excessive exposure may in the long-term increase the risk of skin cancer, as well as depressed immune system function and accelerated aging of the skin. Tanning process Melanin is a natural pigment produced by cells called melanocytes in a process called melanogenesis. Melanocytes produce two types of melanin: pheomelanin (red) and eumelanin (very dark brown). Melanin protects the body by absorbing ultraviolet radiation. Excessive UV radiation causes sunburn along with other direct and indirect DNA damage to the skin, and the body naturally combats and seeks to repair the damage and protect the skin by creating and releasing further melanin into the skin's cells. With the production of the melanin, the skin color darkens. The tanning process can be triggered by natural sunlight or by artificial UV radiation, which can be delivered in frequencies of UVA, UVB, or a combination of both. The intensity is commonly measured by the UV Index. There are two different mechanisms involved in the production of a tan by UV exposure: Firstly, UVA radiation creates oxidative stress, which in turn oxidizes existing melanin and leads to rapid darkening of the melanin. UVA may also cause melanin to be redistributed (released from melanocytes where it is already stored), but its total quantity is unchanged. Skin darkening from UVA exposure does not lead to significantly increased production of melanin or protection against sunburn. In the second process, triggered primarily by UVB, there is an increase in production of melanin (melanogenesis), which is the body's reaction to direct DNA photodamage (formation of pyrimidine dimers) from UV radiation. Melanogenesis leads to delayed tanning, and typically becomes visible two or three days after exposure. The tan that is created by increased melanogenesis typically lasts for a few weeks or months, much longer than the tan that is caused by oxidation of existing melanin, and is also actually protective against UV skin damage and
Sun tanning
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The melanocortin 1 receptor (MC1R), also known as melanocyte-stimulating hormone receptor (MSHR), melanin-activating peptide receptor, or melanotropin receptor, is a G protein–coupled receptor that binds to a class of pituitary peptide hormones known as the melanocortins, which include adrenocorticotropic hormone (ACTH) and the different forms of melanocyte-stimulating hormone (MSH). It is coupled to Gαs and upregulates levels of cAMP by activating adenylyl cyclase in cells expressing this receptor. It is normally expressed in skin and melanocytes, and to a lesser degree in periaqueductal gray matter, astrocytes and leukocytes. In skin cancer, MC1R is highly expressed in melanomas but not carcinomas. MC1R is one of the key proteins involved in regulating mammalian skin color and hair color. It is located on the plasma membrane of specialized cells known as melanocytes, which produce the pigment melanin through the process of melanogenesis. It controls the type of melanin being produced, and its activation causes the melanocyte to switch from generating the yellow-red phaeomelanin by default to the brown-black eumelanin in replacement. In humans, a number of loss-of-function mutations of MC1R have been described, with redheads often having multiple individual loss-of-function mutations, but as of 2001, activating mutations that increase eumelanin synthesis have not been described. MC1R has also been reported to be involved in cancer (independent of skin coloration), developmental processes, and susceptibility to infections and pain. Functions Coloration in mammals The MC1R protein lies within the cell membrane, and is signalled by melanocyte-stimulating hormone (MSH) released by the pituitary gland. When activated by one of the variants of MSH, typically α-MSH, MC1R initiates a complex signaling cascade that leads to the production of eumelanin. In contrast, the receptor can also be antagonized by agouti signalling peptide (ASIP), which reverts the cell back to producing the yellow or red phaeomelanin. The yellow and black agouti banding pattern observed on most mammalian hair is caused by the pulsative nature of ASIP signalling through MC1R. Exceptions include particoloured bay horses, which have reddish bodies, and black legs, mane, and tail, where ASIP signaling is limited to regions instead of pulsating. Human hair, which is neither banded nor particoloured, is thought to be regulated by α-MSH signaling through MC1R exclusively. The prevalence of red hair in humans varies considerably worldwide. In the United States, about 25% of the human population carries the mutated melanocortin 1 receptor that causes red hair. With one in four people as carriers, the chance of two people having a child with red hair is about 2% (one in 64). People with freckles and no red hair have an 85% chance of carrying the MC1R gene that is connected to red hair. People with no freckles and no red hair have an 18% chance of carrying the MC1R gene linked to red hair. Eight genes have been identified in humans that control whether the MC1R gene is turned on and the person has red hair. Coloration in birds MC1R is responsible for melanic polymorphisms in at least three unrelated species: the bananaquit,
Melanocortin 1 receptor
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alpha-Arbutin, or α-arbutin, is a glycosylated hydroquinone, and an anomer of the naturally occurring arbutin. α-Arbutin is used in the cosmetic and pharmaceutical industries for its skin lightening effects, treatment of hyperpigmentation, and as a safer alternative to hydroquinone. Properties and synthesis α-Arbutin is a synthetic substance that can be produced by enzymatic glycosylation of hydroquinone in the presence of α-amylase and dextrin. In one example, this has been done in recombinant Escherichia coli, using amylase of Bacillus subtilis and sucrose phosphorylase of Leuconostoc mesenteroides. Structurally it is the α-anomer of arbutin (β-arbutin), and like the β-form it is an enzyme inhibitor of human tyrosinase. Uses α-Arbutin is used in the cosmetic and pharmaceutical industries for its skin lightening effects, treatment of hyperpigmentation, and as a possibly safer alternative to hydroquinone. It may also possess antioxidant properties, which can protect the skin from free radical damage. It is used in products aimed at fading solar lentigo, freckles, melasma, and other forms of hyperpigmentation where excess melanin is a concern, providing a more even skin complexion. For this purpose, concentrations of up to 2% α-arbutin are found in face creams and serums and 0.5% in body creams. α-Arbutin showed a significant reduction in melanin synthesis in cultured human melanoma cells and a three-dimensional human skin model, with melanin synthesis reduced to 40% of the control, indicating its potency as a skin lightening agent without affecting cell viability. Mechanism of action α-Arbutin's mechanism of action as a skin lightening agent is primarily through the competitive enzymatic inhibition of tyrosinase, leading to a decrease in melanin production without affecting the mRNA gene expression of tyrosinase. It is more potent an inhibitor of tyrosinase than arbutin. α-Arbutin directly inhibits the enzymatic activity of tyrosinase, which is essential for melanin synthesis. Tyrosinase catalyzes the first two steps in melanin production: the hydroxylation of tyrosine to -DOPA and the oxidation of -DOPA to dopaquinone. By inhibiting tyrosinase, α-arbutin reduces the formation of melanin in melanocytes. α-Arbutin does not affect the gene expression of tyrosinase mRNA. This means that while α-arbutin inhibits the activity of the tyrosinase enzyme, it does not decrease the enzyme's production at the genetic level. This reduction in melanin leads to lighter skin tones and can help in the treatment of hyperpigmentation disorders. The efficacy of α-arbutin in reducing melanin synthesis was demonstrated in cultured human melanoma cells and a three-dimensional human skin model, where it effectively reduced melanin synthesis. Safety and regulation α-Arbutin is generally considered safe for topical application in cosmetic products. However, its usage concentrations in the European Union (EU) are restricted by the European Commission Scientific Committee on Consumer Safety to 2% in facial creams and 0.5% in body lotions. References Phenol glucosides Cosmetics chemicals Enzyme inhibitors
Alpha-Arbutin
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Oculocutaneous albinism type I or type 1A is an autosomal recessive skin disease. This subtype of oculocutaneous albinism is caused when the gene for tyrosinase (symbol TYR or OCA1) does not function properly. The location of OCA1 may be written as "11q1.4–q2.1", meaning it is on chromosome 11, long arm, somewhere in the range of band 1, sub-band 4, and band 2, sub-band 1. Since the disorder is autosomal recessive, genetic counseling can be used to determine if both parents are heterozygous for the condition when considering having children. If both parents are heterozygous, their child has a 25% chance of inheriting both recessive copies of OCA1 and having the skin disease. This symptoms in this disease include absence of pigmentation, due to a mutation that affects melanin levels in the eyes, hair, and skin. This rare disease is found in 1 out of 20,000 people around the world, being much more prevalent in Caucasians. There is no known cure for this disease as of present, but there are various ways to manage this disease, including safety around the sun and regular checks for other skin diseases such as skin cancer. Signs and symptoms OCA is characterized by the absence of pigmentation caused by the mutation that effects the production of tyrosinase that causes partial or total absence of melanin in the hair, skin, and eyes. Reduction in melanin production specifically in the peripheral retina during embryonic development can trigger other symptoms such as abnormal nerve fiber projection that causes defects in neuronal migration that interrupts visual pathways and creates reduced visual acuity in the range of 20/60 to 20/400. This vision acuity is dependent upon the amount of pigmentation in the eye. Acuity is usually better in individuals with greater amounts of pigment. Aside from decreased pigment in the iris and retina, optic changes include decreased visual acuity, misrouting of the optic nerves at the chiasm, and nystagmus. OCA1 is one of the more extreme types of albinism where the iris is translucent and the eye appears pink or red in ambient light and have white skin with slight to no pigmentation when other types may have residual pigmentation. OCA1 is caused by mutations in the TYR gene, where there is a complete lack of tyrosinase activity. Genetics The tyrosinase (TYR) gene is located on chromosome 11q14. This protein coding gene produces tyrosinase, an enzyme which catalyzes a total of three steps in the conversion of tyrosine to the end product, melanin. This enzyme and conversion process takes place within melanocytes, which are specialized cells for melanin production. Melanin is a large group of molecules that give skin, eyes, and hair their respective colors. It is also partially responsible for vision, as it protects the light sensitive portion of the eye, the retina, through absorbing light. OCA Type 1A is an autosomal recessive condition, meaning there is a homozygous or compound heterozygous mutation related to the TYR gene. There are many different types of albinism, differing due to the
Oculocutaneous albinism type I
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Pigmentation disorders are disturbances of human skin color. There may be a loss or reduction, which may be related to loss of melanocytes or the inability of melanocytes to produce melanin or transport melanosomes correctly. Most pigmentation disorders involve the underproduction or overproduction of melanin. Causes Skin pigmentation is a frequent disorder that has a number of potential causes. Genetics, sun exposure, and some drugs are the three main factors that contribute to skin pigmentation. The most frequent cause of low melanin concentration (hypopigmentation) is prior skin trauma, which includes skin lesions including blisters, burns, infections, exposure to chemicals, and other wounds. The skin will appear paler than the surrounding skin surface once an injury has healed. Different areas of the skin may become hypopigmented as a result of other genetic illnesses. Hypopigmentation can be caused by hereditary conditions such as vitiligo, melasma, pityriasis versicolor, pityriasis alba, albinism, and fungal infections. Hyperpigmentation results from an increase in melanin synthesis, which is mostly brought on by sun exposure, dermatological disorders, hormones, aging, genetic factors, skin injuries or inflammation, and acne. Sun exposure is the most common cause of hyperpigmentation since it greatly increases the synthesis of melanin. Mechanism Genetics is one of the most common causes of skin color. The number of melanocytes that each person will have may be predicted by genetics. Skin cells called melanocytes are responsible for producing melanin. Melanosomes, which are organelles containing melanin, must be transported and increased during hyperpigmentation and tanning, while they shrink during hypopigmentation. Skin pigmentation is frequently caused by sun exposure. To protect itself against UV radiation from the sun, the body makes more melanin. As a result, the skin may become more pigmented to protect it from the sun's rays. The pigmentation of the skin may also be lightened by certain drugs. Antibiotics are one type of medications that can increase the synthesis of melanin, which darkens skin. Skin pigmentation may also become more intense when certain drugs, such birth control pills, are taken concurrently. References Further reading External links DermNet Johns Hopkins Medicine
Pigmentation disorder
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Freckles are clusters of concentrated melaninized cells which are most easily visible on people with a fair complexion. Freckles do not have an increased number of the melanin-producing cells, or melanocytes, but instead have melanocytes that overproduce melanin granules (melanosomes) changing the coloration of the outer skin cells (keratinocytes). As such, freckles are different from lentigines and moles, which are caused by accumulation of melanocytes in a small area. Freckles can appear on all types of skin tones. Of the six Fitzpatrick skin types, they are most common on skin tones 1 and 2, which usually belong to North Europeans. However, it can also be found on people all over the world. In England a historical term for freckles is summer-voys, sometimes spelt summervoise, which may be related to the German "summersprosse". Biology The formation of freckles is caused by exposure to sunlight. The exposure to UV-B radiation activates melanocytes to increase melanin production, which can cause freckles to become darker and more visible. This means that one who has never developed freckles may develop them suddenly following extended exposure to sunlight. Freckles are predominantly found on the face, although they may appear on any skin exposed to the sun, such as arms or shoulders. Heavily distributed concentrations of melanin may cause freckles to multiply and cover an entire area of skin, such as the face. Freckles are rare on infants, and more commonly found on children before puberty. Upon exposure to the sun, freckles will reappear if they have been altered with creams or lasers and not protected from the sun, but do fade with age in some cases. Freckles are not a skin disorder, but people with freckles generally have a lower concentration of photo-protective melanin, and are therefore more susceptible to the harmful effects of UV radiation. It is suggested that people whose skin tends to freckle should avoid overexposure to sun and use sunscreen. Genetics The presence of freckles is related to rare alleles of the MC1R gene, though it does not differentiate whether an individual will have freckles if they have one or even two copies of this gene. Also, individuals with no copies of the MC1R do sometimes display freckles. Even so, individuals with a high number of freckling sites have one or more of variants of the MC1R gene. Of the variants of the MC1R gene Arg151Cys, Arg160Trp, and Asp294His are the most common in the freckled subjects. The MC1R gene is also associated with red hair more strongly than with freckles. Most red-haired individuals have two variants of the MC1R gene and almost all have one. The variants that cause red hair are the same that cause freckling. Freckling can also be found in areas, such as Japan, where red hair is not seen. These individuals have the variant Val92Met which is also found in Europeans, although it has minimal effects on their pigmentation. The R162Q allele has a disputed involvement in freckling. The variants of the MC1R gene that are linked
Freckle
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Gum depigmentation, also known as gum bleaching, is a procedure used in cosmetic dentistry to lighten or remove black spots or patches on the gums consisting of melanin. Melanin in skin is very common in inhabitants in many parts of the world due to genetic factors. Melanin pigmentation in skin, oral mucosa, inner ear and other organs is a detoxification mechanism. Some toxic agents bind to melanin and will move out of the tissue with the ageing cells and are expelled to the tissue surfaces. Also in the gums and oral mucosa a visible pigmentation is most often caused by genetic factors, but also by tobacco smoking or in a few cases by long-term use of certain medications. If stopping smoking or change of medication do not solve the problem with a disfigurating melanin pigmentation, a surgical operation may be performed. The procedure itself can involve laser ablation techniques. Laser gum depigmentation Melanocytes are cells which reside in the basal layer of the gingival epithelium. These cells produce melanin, which are pigments that cause light or dark brown spots in gums and oral mucosa. The most common cause is genetic factors or tobacco smoking, Smoker's melanosis. If the melanin pigmentation is found in a person smoking cigarettes, the most effective way to get rid of the pigmentation is to stop smoking. Most of the patients are free from the melanin pigmentation after 3 months. A dental laser can target and ablate the melanocytes, thus reducing the production of melanin in the gingival tissue. Following laser depigmentation, the gingiva heals by secondary intention. This results in a lighter and more uniform color of the gums. A study found that (Er,Cr:YSGG) laser was effective and there were no signs of re-pigmentation after a 6-month follow up period. See also Tooth whitening References Dentistry procedures Periodontology
Gum depigmentation
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Snakeskin may either refer to the skin of a live snake, the shed skin of a snake after molting, or to a type of leather that is made from the hide of a dead snake. Snakeskin and scales can have varying patterns and color formations, providing protection via camouflage from predators. The colors and iridescence in these scales are largely determined by the types and amount of chromatophores located in the dermis of the snake skin. The snake's skin and scales are also an important feature to their locomotion, providing protection and minimizing friction when gliding over surfaces. Skin of a living snake In a living snake, its skin often deals with various forms of abrasion. To combat rough substrates, snakes have formed specialized and multilayered organizational epidermal structures to provide a safe and efficient sliding locomotion when maneuvering over rough surfaces. Display Pattern formation Snakes can be ornately patterned. They can be striped, banded, solid, green, blue, yellow, red, black, orange, brown, spotted, or have a unique pattern all their own. These color schemes can serve many functions, including camouflage, heat absorption or reflection, or may play other, less understood roles. Melanin cells in the skin often overlap and form complex patterns and sheets that are highly recognizable. Sometimes the soft integument of a snake is colored differently than their hard scales. This is often utilized as a method of predator determent. Color and iridescence Coloration of snakes is largely due to pigment cells and their distribution. Some scales have lightly colored centers, which arise from regions with a reduced cuticle. A thinner cuticle indicates that some sensory organ is present. Scales in general are numerous and coat the epidermis, and come in all shapes and colors. They are helpful in identification of snake species. Chromatophores in the dermis yield coloration when light shines through the corneal layer of the epidermis. There are many kinds of chromatophores. Melanophores yield brown pigmentation, and when paired with guanophores, yield grey. When paired with guanophores and lipophores, yellow results. When guanophores and allophores are added to melanophores, red pigment results. Carotenoids also help produce orange and red colors. Dark snakes (dark brown or black in color) appear as such due to melanocytes that are active in the epidermis. When melanin is absent, albino individuals result. Snakes do not possess blue or green pigments, instead these arise from guanophores, which are also called iridocytes. Iridocytes reside in the dermis, and are responsible for the iridescent appearance of many dark-colored snakes. Males and females may show varied coloration, as might hatchlings and adults of the same species. Structures and function Snakeskin, or integument, is more than just patterns and scales. Scales and patterning are features of snakeskin, and they are derived from a soft and complex integument. These scale patterns are unique to species, and the scales themselves help in locomoting by providing a friction buffer between the snake and the ground Organization Reptiles, including snakes, possess extensive keratinization of the epidermis in the
Snakeskin
969598
A melanosome is an organelle found in animal cells and is the site for synthesis, storage and transport of melanin, the most common light-absorbing pigment found in the animal kingdom. Melanosomes are responsible for color and photoprotection in animal cells and tissues. Melanosomes are synthesised in the skin in melanocyte cells, as well as the eye in choroidal melanocytes and retinal pigment epithelial (RPE) cells. In lower vertebrates, they are found in melanophores or chromatophores. Structure Melanosomes are relatively large organelles, measuring up to 500 nm in diameter. They are bound by a bilipid membrane and are, in general, rounded, sausage-like, or cigar-like in shape. The shape is constant for a given species and cell type. They have a characteristic ultrastructure on electron microscopy, which varies according to the maturity of the melanosome, and for research purposes a numeric staging system is sometimes used. Synthesis of melanin Melanosomes are dependent for their pigment on certain enzymes, especially tyrosinase, that synthesise the large polymers of melanin within the cell. Before it generates sufficient pigment to be seen on light microscopy it is known as a pre-melanosome. Dysfunction or absence of the melanin-synthesising enzymes (in conditions such as Chédiak–Higashi syndrome) leads to various patterns of albinism. Pseudopodia and tanning In some melanocytes, the melanosomes remain static within the cell. In others the cell can extend its surface lengthwise as temporary projections known as pseudopodia, which carry melanosomes away from the center of the cell, thereby increasing the cell's effectiveness in absorbing light. The pseudopodial process (aka the tanning process) happens slowly in dermal melanocytes in response to ultraviolet light and to production of new melanosomes and increased donation of melanosomes to adjacent keratinocytes, which are typical skin surface cells. Donation occurs when some keratinocytes engulf the end of the melanocyte pseudopodia, which contain many melanosomes. Cytoplasmic dynein will carry the vesicles containing the melanin to the center of the cell, which causes melanosomes to sequester the keratinocyte's nucleus, providing optimal protection from UV rays. These changes are responsible for tanning of human skin after exposure to UV light or sunlight. In animals In many species of fish, amphibians, crustaceans, and reptiles, melanosomes can be highly mobile within the cell in response to hormonal (or sometimes neural) control, which leads to visible changes in colour that are used for behavioural signaling or photoprotection. Melanosomes found in certain fish species contain pigments that control the color of the fish's scales. Molecular motors, when signaled, will either carry melanosomes containing pigments out to the periphery of the cell, or concentrate them at the center. The motor protein dynein is responsible for concentrating the melanosomes toward the center of the cell, or the "minus end" of microtubules. Conversely, the protein kinesin is responsible for dispersing the melanosomes to the periphery of the cell, and are plus end directed motors. Because the plus ends of microtubules are oriented towards the periphery, kinesin will carry melanosomes to the periphery. Dispersing melanosomes to the periphery causes the cell to
Melanosome
1419101
Pars intermedia is the boundary between the anterior and posterior lobes of the pituitary. It contains colloid-filled cysts and two types of cells - basophils and chromophobes. The cysts are the remainder of Rathke's pouch. As technically part of the anterior pituitary, it separates the posterior pituitary and pars distalis. It is composed of large, pale cells that encompass the aforementioned colloid-filled follicles. In human fetal life, this area produces melanocyte stimulating hormone or MSH which causes the release of melanin pigment in skin melanocytes (pigment cells). However, the pars intermedia is normally either very small or entirely absent in adulthood. In lower vertebrates (fish, amphibians), MSH from the pars intermedia is responsible for darkening of the skin, often in response to changes in background color. This color change is due to MSH stimulating the dispersion of melanin pigment in dermal (skin) melanophore cells. References External links Endocrine system Human head and neck
Pars intermedia
7330969
Microphthalmia-associated transcription factor also known as class E basic helix-loop-helix protein 32 or bHLHe32 is a protein that in humans is encoded by the MITF gene. MITF is a basic helix-loop-helix leucine zipper transcription factor involved in lineage-specific pathway regulation of many types of cells including melanocytes, osteoclasts, and mast cells. The term "lineage-specific", since it relates to MITF, means genes or traits that are only found in a certain cell type. Therefore, MITF may be involved in the rewiring of signaling cascades that are specifically required for the survival and physiological function of their normal cell precursors. MITF, together with transcription factor EB (TFEB), TFE3 and TFEC, belong to a subfamily of related bHLHZip proteins, termed the MiT-TFE family of transcription factors. The factors are able to form stable DNA-binding homo- and heterodimers. The gene that encodes for MITF resides at the mi locus in mice, and its protumorogenic targets include factors involved in cell death, DNA replication, repair, mitosis, microRNA production, membrane trafficking, mitochondrial metabolism, and much more. Mutation of this gene results in deafness, bone loss, small eyes, and poorly pigmented eyes and skin. In human subjects, because it is known that MITF controls the expression of various genes that are essential for normal melanin synthesis in melanocytes, mutations of MITF can lead to diseases such as melanoma, Waardenburg syndrome, and Tietz syndrome. Its function is conserved across vertebrates, including in fishes such as zebrafish and Xiphophorus. An understanding of MITF is necessary to understand how certain lineage-specific cancers and other diseases progress. In addition, current and future research can lead to potential avenues to target this transcription factor mechanism for cancer prevention. Clinical significance Mutations As mentioned above, changes in MITF can result in serious health conditions. For example, mutations of MITF have been implicated in both Waardenburg syndrome and Tietz syndrome. Waardenburg syndrome is a rare genetic disorder. Its symptoms include deafness, minor defects, and abnormalities in pigmentation. Mutations in the MITF gene have been found in certain patients with Waardenburg syndrome, type II. Mutations that change the amino acid sequence of that result in an abnormally small MITF are found. These mutations disrupt dimer formation, and as a result cause insufficient development of melanocytes. The shortage of melanocytes causes some of the characteristic features of Waardenburg syndrome. Tietz syndrome, first described in 1923, is a congenital disorder often characterized by deafness and leucism. Tietz is caused by a mutation in the MITF gene. The mutation in MITF deletes or changes a single amino acid base pair specifically in the base motif region of the MITF protein. The new MITF protein is unable to bind to DNA and melanocyte development and subsequently melanin production is altered. A reduced number of melanocytes can lead to hearing loss, and decreased melanin production can account for the light skin and hair color that make Tietz syndrome so noticeable. Melanoma Melanocytes are commonly known as cells that are responsible for producing the pigment melanin which gives coloration to the
Microphthalmia-associated transcription factor
13871016
Greying of hair, also known as greying, canities, or achromotrichia, is the progressive loss of pigmentation in the hair, eventually turning the hair grey or white which typically occurs naturally as people age. Terminology Greying of hair is the partial or complete process of a hair becoming grey or white. It is also known as canities or achromotrichia. The word "canities" is derived from the Latin word cānitiēs for "gray hair, old age". Overview Changes in hair color typically occur naturally as people age, eventually turning the hair grey and then white. This normally begins in the early to mid-twenties in men and late twenties in women. More than 60 percent of Americans have some grey hair by age 40. The age at which greying begins seems almost entirely due to genetics. Sometimes people are born with grey hair because they inherit the trait. The order in which greying happens is usually: nose hair, hair on the head, beard, body hair, eyebrows. Greying is a gradual process; according to a study by L'Oreal, overall, of those between 45 and 65 years old, 74% had some grey hair, covering an average of 27% of their head, and approximately 1 in 10 people had no grey hairs even after the age of 60. Causes Grey or white hair is not caused by a true grey or white pigment, but is due to a lack of pigmentation and melanin. The clear hairs appear as grey or white because of the way light is reflected from the hairs. The change in hair color occurs when melanin ceases to be produced in the hair root and new hairs grow in without pigment. The stem cells at the base of hair follicles produce melanocytes, the cells that produce and store pigment in hair and skin. The death of the melanocyte stem cells causes the onset of greying. It remains unclear why the stem cells of one hair follicle may fail to activate well over a decade before those in adjacent follicles less than a millimeter apart. In non-balding individuals, hair may grow faster once it turns grey. Unlike in the skin where pigment production is continuous, melanogenesis in the hair is closely associated with stages of the hair cycle. Hair is actively pigmented in the anagen phase and is "turned off" during the catagen phase, and absent during telogen. Thus, a single hair cannot be white on the root side, and colored on the terminal side. Several genes appear to be responsible for the process of greying. Bcl2 and Bcl-w were the first two discovered, then in 2016, the IRF4 (interferon regulatory factor 4) gene was announced after a study of 6,000 people living in five Latin American countries. However, it found that environmental factors controlled about 70% of cases of hair greying. In some cases, grey hair may be caused by thyroid deficiencies, Waardenburg syndrome or a vitamin B12 deficiency. At some point in the human life cycle, cells that are located in the base
Greying of hair
65847
Vitiligo () is a chronic autoimmune disorder that causes patches of skin to lose pigment or color. The cause of vitiligo is unknown, but it may be related to immune system changes, genetic factors, stress, or sun exposure. Treatment options include topical medications, light therapy, surgery and cosmetics. Signs and symptoms The only sign of vitiligo is the presence of pale patchy areas of depigmented skin which tend to occur on the extremities. Some people may experience itching before a new patch appears. The patches are initially small, but often grow and change shape. When skin lesions occur, they are most prominent on the face, hands and wrists. The loss of skin pigmentation is particularly noticeable around body orifices, such as the mouth, eyes, nostrils, genitalia and umbilicus. Some lesions have increased skin pigment around the edges. Those affected by vitiligo who are stigmatized for their condition may experience depression and similar mood disorders. Causes Although multiple hypotheses have been suggested as potential triggers that cause vitiligo, studies strongly imply that changes in the immune system are responsible for the condition. Vitiligo has been proposed to be a multifactorial disease with genetic susceptibility and environmental factors both thought to play a role. It is hypothesized that damaging environmental factors can disrupt redox reactions necessary for protein folding, so skin cells may initiate the unfolded protein response which releases cytokines, thus mounting an immune response The National Institutes of Health states that some believe that sunburns can cause or exacerbate the condition, but this idea is not well-supported by good evidence. Immune Melanin is the pigment that gives skin its color; it is produced by skin cells called melanocytes. Variations in genes that are part of the immune system or part of melanocytes have both been associated with vitiligo. It is also thought to be caused by the immune system attacking and destroying the melanocytes of the skin. A genome wide association study found approximately 36 independent susceptibility loci for generalized vitiligo. The TYR gene encodes the protein tyrosinase, which is not a component of the immune system, but is an enzyme of the melanocyte that catalyzes melanin biosynthesis, and a major autoantigen in generalized vitiligo. Autoimmune associations Vitiligo is sometimes associated with autoimmune and inflammatory diseases such as Hashimoto's thyroiditis, scleroderma, rheumatoid arthritis, type 1 diabetes mellitus, psoriasis, Addison's disease, pernicious anemia, alopecia areata, systemic lupus erythematosus, and celiac disease. Among the inflammatory products of NLRP1 are caspase 1 and caspase 7, which activate the inflammatory cytokine interleukin-1β. Interleukin-1β and interleukin-18 are expressed at high levels in people with vitiligo. In one of the mutations, the amino acid leucine in the NALP1 protein was replaced by histidine (Leu155 → His). The original protein and sequence is highly conserved in evolution, and is found in humans, chimpanzee, rhesus monkey, and the bush baby. Addison's disease (typically an autoimmune destruction of the adrenal glands) may also be seen in individuals with vitiligo. Diagnosis An ultraviolet light can be used in the early
Vitiligo
14755368
Melanocyte protein PMEL also known as premelanosome protein (PMEL), silver locus protein homolog (SILV) or Glycoprotein 100 (gp100), is a protein that in humans is encoded by the PMEL gene. Its gene product may be referred to as PMEL, silver, ME20, gp100 or Pmel17. Structure and function PMEL is a 100 kDa, 661 amino acids long type I transmembrane glycoprotein that is expressed primarily in melanosomes, which are the melanin-producing organelles in melanocytes of pigment cells of the skin and eye, and in most malignant melanomas. This protein is involved in melanosome maturation, including melanogenesis, melanosome biogenesis, and melanin polymerization (Eisenberg) . The transmembrane form of PMEL is modified in the secretory pathway by elaboration of N-linked oligosaccharides and addition and modification of O-linked oligosaccharides. It is then targeted to precursors of the pigment organelle, the melanosome, where it is proteolytically processed to several small fragments. Some of these fragments form non-pathological amyloid that assemble into sheets and form the striated pattern that underlies melanosomal ultrastructure. PMEL cleavage is mediated by several proteases including a proprotein convertase of the furin family, a "sheddase" that might include members of the a disintegrin and metalloproteinase (ADAM) family, and additional proteases in melanosomes or their precursors. After the amyloidogenic region is cleaved, the small remaining integral membrane fragment is digested by γ-secretase. The expression of the PMEL gene is regulated by the microphthalmia-associated transcription factor (MITF). Function in cancer and cancer treatment The gp100 protein is a melanoma antigen i.e. a tumor-associated antigen. Short fragments of it have been used to develop the gp100 cancer vaccine which is or contains gp100:209-217(210M). Hydrophilic recombinant gp100 protein (HR-gp100) has been topically applied on human intact skin in vitro, and used as a vaccine in a mouse model. It was demonstrated that HR-gp100 permeates into human skin, and is processed and presented by human dendritic cells. In the mouse model, an HR-gp100-based vaccine triggered antigen-specific T cell responses, as shown by proliferation assays, ELISA and intracellular staining for IFN-γ. The gp100 protein contains differentiation antigens., and has been widely studied to be used as a target for melanoma immunotherapy. Different sequences of the GP100 peptide could be used for immunization against tumors. According to a case study, modifications of GP100, such as GP100-209 and GP100-208, have shown a greater number of antigen-specific CTL's (cytotoxic T lymphocytes), which can target and kill cancer cells (Eisenberg). References Further reading External links Oncology
PMEL (gene)
536557
The melanocyte-stimulating hormones, known collectively as MSH, also known as melanotropins or intermedins, are a family of peptide hormones and neuropeptides consisting of α-melanocyte-stimulating hormone (α-MSH), β-melanocyte-stimulating hormone (β-MSH), and γ-melanocyte-stimulating hormone (γ-MSH) that are produced by cells in the pars intermedia of the anterior lobe of the pituitary gland. Synthetic analogues of α-MSH, such as afamelanotide (melanotan I; Scenesse), melanotan II, and bremelanotide (PT-141), have been developed and researched. Biosynthesis The various forms of MSH are generated from different cleavages of the proopiomelanocortin protein, which also yields other important neuropeptides like adrenocorticotropic hormone. Melanocytes in skin make and secrete MSH in response to ultraviolet light, where it increases synthesis of melanin. Some neurons in arcuate nucleus of the hypothalamus make and secrete α-MSH in response to leptin; α-MSH is also made and secreted in the anterior lobe of the pituitary gland. Function Acting through melanocortin 1 receptor, α-MSH stimulates the production and release of melanin (a process referred to as melanogenesis) by melanocytes in skin and hair. Acting in the hypothalamus, α-MSH suppresses appetite. α-MSH secreted in the hypothalamus also contributes to sexual arousal. In amphibians In some animals (such as the claw-toed frog Xenopus laevis) production of MSH is increased when the animal is in a dark location. This causes pigment to be dispersed in pigment cells in the toad's skin, making it become darker, and harder for predators to spot. The pigment cells are called melanophores and therefore, in amphibians, the hormone is often called melanophore-stimulating hormone. In humans An increase in MSH will cause darker skin in humans too. MSH increases in humans during pregnancy. This, along with increased estrogens, causes increased pigmentation in pregnant women. Cushing's disease due to excess adrenocorticotropic hormone (ACTH) may also result in hyperpigmentation, such as acanthosis nigricans in the axilla. Most people with primary Addison's disease have darkening (hyperpigmentation) of the skin, including areas not exposed to the sun; characteristic sites are skin creases (e.g. of the hands), nipple, and the inside of the cheek (buccal mucosa), new scars become hyperpigmented, whereas older ones do not darken. This occurs because MSH and ACTH share the same precursor molecule, proopiomelanocortin (POMC). Different levels of MSH are not the major cause of variation in skin colour. However, in many red-headed people, and other people who do not tan well, there are variations in their hormone receptors, causing them to not respond to MSH in the blood. Structure of MSH The different forms of MSH belong to a group called the melanocortins. This group includes ACTH, α-MSH, β-MSH, and γ-MSH; these peptides are all cleavage products of a large precursor peptide called proopiomelanocortin (POMC). α-MSH is the most important melanocortin for pigmentation. The different forms of MSH have the following amino acid sequences: Synthetic MSH Synthetic analogues of α-MSH have been developed for human use. Two of the better known are afamelanotide (melanotan I) in testing by Clinuvel Pharmaceuticals and bremelanotide by Palatin Technologies. Others include modimelanotide and setmelanotide. Afamelanotide (brand name Scenesse)
Melanocyte-stimulating hormone
716631
Melanoma is the most dangerous type of skin cancer; it develops from the melanin-producing cells known as melanocytes. It typically occurs in the skin, but may rarely occur in the mouth, intestines, or eye (uveal melanoma). In women, melanomas most commonly occur on the legs; while in men, on the back. Melanoma is frequently referred to as malignant melanoma. However, the medical community stresses that there is no such thing as a 'benign melanoma' and recommends that the term 'malignant melanoma' should be avoided as redundant. About 25% of melanomas develop from moles. Changes in a mole that can indicate melanoma include increaseespecially rapid increasein size, irregular edges, change in color, itchiness, or skin breakdown. The primary cause of melanoma is ultraviolet light (UV) exposure in those with low levels of the skin pigment melanin. The UV light may be from the sun or other sources, such as tanning devices. Those with many moles, a history of affected family members, and poor immune function are at greater risk. A number of rare genetic conditions, such as xeroderma pigmentosum, also increase the risk. Diagnosis is by biopsy and analysis of any skin lesion that has signs of being potentially cancerous. Avoiding UV light and using sunscreen in UV-bright sun conditions may prevent melanoma. Treatment typically is removal by surgery of the melanoma and the potentially affected adjacent tissue bordering the melanoma. In those with slightly larger cancers, nearby lymph nodes may be tested for spread (metastasis). Most people are cured if metastasis has not occurred. For those in whom melanoma has spread, immunotherapy, biologic therapy, radiation therapy, or chemotherapy may improve survival. With treatment, the five-year survival rates in the United States are 99% among those with localized disease, 65% when the disease has spread to lymph nodes, and 25% among those with distant spread. The likelihood that melanoma will reoccur or spread depends on its thickness, how fast the cells are dividing, and whether or not the overlying skin has broken down. Melanoma is the most dangerous type of skin cancer. Globally, in 2012, it newly occurred in 232,000 people. In 2015, 3.1 million people had active disease, which resulted in 59,800 deaths. Australia and New Zealand have the highest rates of melanoma in the world. High rates also occur in Northern Europe and North America, while it is less common in Asia, Africa, and Latin America. In the United States, melanoma occurs about 1.6 times more often in men than women. Melanoma has become more common since the 1960s in areas mostly populated by people of European descent. Signs and symptoms Early signs of melanoma are changes to the shape or color of existing moles or, in the case of nodular melanoma, the appearance of a new lump anywhere on the skin. At later stages, the mole may itch, ulcerate, or bleed. Early signs of melanoma are summarized by the mnemonic "ABCDEEFG": Asymmetry Borders (irregular with edges and corners) Colour (variegated) Diameter (greater than , about the size of
Melanoma
2136925
The lips are a horizontal pair of soft appendages attached to the jaws and are the most visible part of the mouth of many animals, including humans. Vertebrate lips are soft, movable and serve to facilitate the ingestion of food (e.g. suckling and gulping) and the articulation of sound and speech. Human lips are also a somatosensory organ, and can be an erogenous zone when used in kissing and other acts of intimacy. Structure The upper and lower lips are referred to as the labium superius oris and labium inferius oris, respectively. The juncture where the lips meet the surrounding skin of the mouth area is the vermilion border, and the typically reddish area within the borders is called the vermilion zone. The vermilion border of the upper lip is known as the Cupid's bow. The fleshy protuberance located in the center of the upper lip is a tubercle known by various terms including the procheilon (also spelled prochilon), the "tuberculum labii superioris", and the "labial tubercle". The vertical groove extending from the procheilon to the nasal septum is called the philtrum. The skin of the lip, with three to five cellular layers, is very thin compared to typical face skin, which has up to 16 layers. With light skin color, the lip skin contains fewer melanocytes (cells which produce melanin pigment, which give skin its color). Because of this, the blood vessels appear through the skin of the lips, which leads to their notable red coloring. With darker skin color this effect is less prominent, as in this case the skin of the lips contains more melanin and thus is visually darker. The skin of the lip forms the border between the exterior skin of the face, and the interior mucous membrane of the inside of the mouth. The lip skin is not hairy and does not have sweat glands. Therefore, it does not have the usual protection layer of sweat and body oils which keep the skin smooth, inhibit pathogens, and regulate warmth. For these reasons, the lips dry out faster and become chapped more easily. The lower lip is formed from the mandibular prominence, a branch of the first pharyngeal arch. The lower lip covers the anterior body of the mandible. It is lowered by the depressor labii inferioris muscle and the orbicularis oris borders it inferiorly. The upper lip covers the anterior surface of the body of the maxilla. Its upper half is of usual skin color and has a depression at its center, directly under the nasal septum, called the philtrum, which is Latin for "lower nose", while its lower half is a markedly different, red-colored skin tone more similar to the color of the inside of the mouth, and the term vermillion refers to the colored portion of either the upper or lower lip. It is raised by the levator labii superioris and is connected to the lower lip by the thin lining of the lip itself. Thinning of the vermilion of the upper
Lip
1396651
Melasma (also known as chloasma faciei, or the mask of pregnancy when present in pregnant women) is a tan or dark skin discoloration. Melasma is thought to be caused by sun exposure, genetic predisposition, hormone changes, and skin irritation. Although it can affect anyone, it is particularly common in women, especially pregnant women and those who are taking oral or patch contraceptives or hormone replacement therapy medications. Signs and symptoms The symptoms of melasma are dark, irregular, well-demarcated, hyperpigmented macules to patches. These patches often develop gradually over time. Melasma does not cause any other symptoms beyond the cosmetic discoloration. Patches can vary in size from 0.5 cm to larger than 10 cm depending on the person. Its location can be categorized as centrofacial, malar, or mandibular. The most common is centrofacial, in which patches appear on the cheeks, nose, upper lip, forehead, and chin. The mandibular category accounts for patches on the bilateral rami, while the malar location accounts for patches only on the nose and cheeks. Cause The exact cause of melasma is unknown. Melasma is thought to be the stimulation of melanocytes (cells in the dermal layer, which transfer the pigment melanin to the keratinocytes of skin) when the skin is exposed to ultraviolet light from the sun. Small amounts of sun exposure can make melasma return to the skin after it has faded, which is why people with melasma often get it again and again, particularly in the summer. Pregnant women often get melasma, or chloasma, known as the mask of pregnancy. Birth-control pills and hormone replacement therapy also can trigger melasma. The discoloration usually disappears spontaneously over a period of several months after giving birth or stopping the oral contraceptives or hormone treatment. Genetic predisposition is also a major factor in determining whether someone will develop melasma. People with the Fitzpatrick skin type III or greater from African, Asian, or Hispanic descent are at a much higher risk than others. In addition, women with a light brown skin type who are living in regions with intense sun exposure are particularly susceptible to developing this condition. The incidence of melasma also increases in patients with thyroid disease. It is thought that the overproduction of melanocyte-stimulating hormone brought on by stress can cause outbreaks of this condition. Other rare causes of melasma include allergic reaction to medications and cosmetics. Addison's disease Melasma suprarenale (Latin: "above the kidneys") is a symptom of Addison's disease, particularly when caused by pressure or minor injury to the skin, as discovered by FJJ Schmidt of Rotterdam in 1859. Diagnosis Types The two different kinds of melasma are epidermal and dermal. Epidermal melasma results from melanin pigment that is elevated in the suprabasal layers of the epidermis. Dermal melasma occurs when the dermal macrophages have an elevated melanin level. Melasma is usually diagnosed visually or with assistance of a Wood's lamp (340–400 nm wavelength). Under Wood's lamp, excess melanin in the epidermis can be distinguished from that of the dermis. This is done
Melasma
50524
A melanocytic nevus (also known as nevocytic nevus, nevus-cell nevus and commonly as a mole) is usually a noncancerous condition of pigment-producing skin cells. It is a type of melanocytic tumor that contains nevus cells. Some sources equate the term mole with "melanocytic nevus", but there are also sources that equate the term mole with any nevus form. The majority of moles appear during the first two decades of a person's life, with about one in every 100 babies being born with moles. Acquired moles are a form of benign neoplasm, while congenital moles, or congenital nevi, are considered a minor malformation or hamartoma and may be at a higher risk for melanoma. A mole can be either subdermal (under the skin) or a pigmented growth on the skin, formed mostly of a type of cell known as a melanocyte. The high concentration of the body's pigmenting agent, melanin, is responsible for their dark color. Moles are a member of the family of skin lesions known as nevi, occurring commonly in humans. Signs and symptoms According to the American Academy of Dermatology, the most common types of moles are skin tags, raised moles and flat moles. Benign moles are usually brown, tan, pink or black (especially on dark-colored skin). They are circular or oval and are usually small (commonly between 1–3 mm), though some can be larger than the size of a typical pencil eraser (>5 mm). Some moles produce dark, coarse hair. Common mole hair removal procedures include plucking, cosmetic waxing, electrolysis, threading and cauterization. Aging Moles tend to appear during early childhood and during the first 30 years of life. They may change slowly, becoming raised, changing color or gradually fading. Most people have between 30 and 40 moles, but some have as many as 600. The number of moles a person has was found to have a correlation with telomere length. However, the relation between telomeres and aging remains uncertain. Complications The American Academy of Dermatology says that the vast majority of moles are benign. Data on the chances of transformation from melanocytic nevus to melanoma is controversial, but it appears that about 10% of malignant melanomas have a precursor lesion, of which about 10% are melanocytic nevi. Therefore, it appears that malignant melanoma quite seldom (1% of cases) has a melanocytic nevus as a precursor. Cause The cause is not clearly understood, but is thought to be caused by a defect in embryologic development. This is in the first twelve weeks of pregnancy. The defect is thought to cause a proliferation of melanocytes. This means melanocytes, the cells in the body in charge of normal skin color, are being produced at an extremely fast rate, thus causing the melanocytes to form in clusters instead of spreading out, causing abnormal skin pigmentation in some areas of the body. Genetics Genes can have an influence on a person's moles. Dysplastic nevus syndrome is a largely hereditary condition which causes a person to have a large quantity of moles
Melanocytic nevus
14755789
Tyrosinase-related protein 1, also known as TYRP1, is an intermembrane enzyme which in humans is encoded by the TYRP1 gene. Function Tyrp1 is a melanocyte-specific gene product involved in melanin synthesis within melanosomes. Most Tyrp1 possess 5,6-dihydroxyindole-2-carboxylic acid (melanogenic intermediate) oxidase activity. The catalytic function of Tyrp1 in human melanocytes is less clear. Tyrp1 is involved in stabilizing of tyrosinase protein and modulating its catalytic activity. Tyrp1 is also involved in maintenance of melanosome structure and affects melanocyte proliferation and melanocyte cell death. Melanocytes are derived from the neural crest and migrate into the overlying epidermal ectoderm of a developing organism which forms skin and hair. Therefore, Tyrp1 influences the expression of melanin notably in the skin and hair of an organism. The Tyrp1 gene also has a non-coding function which indirectly promotes melanoma tumor cell proliferation, especially when highly expressed in a cell. Tyrp1 mRNA interacts with miR-16 and affects its ability to repress genes involved in melanoma cell production. Clinical significance Mutations in the mouse Tyrp1 gene are associated with brown pelage and in the human TYRP1 gene with oculocutaneous albinism type 3 (OCA3). An allele of TYRP1 common in Solomon Islanders results in blond hair. Although the phenotype is similar to Northern European blond hair, this allele is not found in Europeans. More recent study, Ju et al. 2020 found TYRP1 allele was selected in European population. Norton et al. 2016 study found TYRP1 is not associated with blond hair color in Melanesians as many populations in Oceania did not carry TYRP1 alleles but still displayed blondism, study indicates that additional unknown alleles contribute to the blondism phenotype in Melanesians. Alterations of the Tyrp1 gene is responsible for some of the differing phenotypes of skin and coat appearance in various animals. In Dalmatians, black versus "liver" spot color is due to genetic variation of the TYRP1 gene. A particular deletion in the Tyrp1 gene of domestic Chinese-Tibetan swine results in a "brown coloration" of the swine's skin and hair as opposed to the wild-type "black" phenotype. In Oujiang-color carp, mutations of the Tyrp1 gene influenced the expression of "grey" or "brown" phenotypic color of scales. Elevated levels of Tyrp1 gene expression is also associated with unfavorable patient outcome of those affected by melanoma. The role of Tyrp1 in melanoma progression was determined by comparing "knockout" cell lines which have inactive Tyrp1 to cells with normal and highly expressed Tyrp1. Such studies provide insight to possible clinical usage and treatment of melanoma via regulation of Tyrp1 expression in cells. Regulation The expression of TYRP1 is regulated by the microphthalmia-associated transcription factor (MITF). Interactions TYRP1 has been shown to interact with GIPC1. See also Dopachrome tautomerase (DCT; also known as TYRP2) References Further reading External links
TYRP1
21035041
Melanonychia is a black or brown pigmentation of a nail, and may be present as a normal finding on many digits in Afro-Caribbeans, as a result of trauma, systemic disease, or medications, or as a postinflammatory event from such localized events as lichen planus or fixed drug eruption. There are two types, longitudinal and transverse melanonychia. Signs and symptoms Melanonychia is defined by a darkening of the nail plate that is brown to black; the pigment in question is typically melanin. It can affect one or more fingernails as well as toenails. Causes Melanocytic activation and melanocyte proliferation are the two primary processes of melanonychia. Increased melanin production from a typical number of activated melanocytes in the nail matrix is referred to as melanocytotic activation. Increased melanin pigment results from a greater quantity of melanocytes within the nail matrix, which is known as melanocyte proliferation. Both pregnancy and racial melanonychia are physiological causes of longitudinal melanonychia. People with dark skin tones, including African Americans, Asians, Hispanics, and people from the Middle East, often exhibit harmless longitudinal pigmented stripes. It is important to investigate the possibility of onychotillomania, nail-biting, frictional trauma, and even carpal tunnel syndrome if melanonychia is linked to anomalies of the nail plate or the periungual tissues. A common cause of symmetric melanonychia that affects the great toe, the lateral and external portion of the fourth or fifth toenail, is recurrent trauma from overriding toes or poorly fitting shoes. Skin disorders such onychomycosis, paronychia, psoriasis, lichen planus, amyloidosis, and chronic radiodermatitis can cause inflammation, which can activate melanocytes and result in the formation of a light-brown band. Melanonychia frequently develops after the inflammatory process has resolved. Nonmelanocytic tumors such as subungual linear keratosis, verruca vulgaris, subungual fibrous histiocytoma, basal cell carcinoma, myxoid pseudocyst, Bowen's disease, and onychomatricoma have also been shown to induce melanocytic activation, which leads to longitudinal melanonychia. Systemic-related melenonychia sometimes presents as numerous bands including the fingernails and toenails. Interestingly, cutaneous and mucosal pigmentation are frequently seen in conjunction with melanonychia linked to nutritional problems, AIDS, and Addison's disease. Alcaptonuria, hemosiderosis, hyperbilirubinemia, and porphyria have all been linked to melanonychia. Medication (particularly chemotherapy drugs), phototherapy, radiation exposure from X-rays, and electron beam therapy are examples of iatrogenic causes of melanocytic activation. Melanonychia linked with syndromes, such as Peutz-Jeghers, Touraine, and Laugier-Hunziker, usually affects numerous digits and is accompanied by mucosal pigmented macules including the lips and oral cavity. The most frequent cause of brown-black coloration on nails is hematomas. It can be chronic (repeated, tiny trauma) or acute (after a single large trauma). Both dematiaceous and nondematiaceous fungi can induce fungal melanonychia; the most prevalent ones are Trichophyton rubrum and Scytalidium dimidiatum, followed by Alternaria and Exophiala. Mechanism While melanocytes are found in the nail bed and matrix, most of them are dormant or quiescent. Melanocyte activation in response to trauma, infection, or inflammation starts the manufacture of melanin. Then, melanin-rich melanosomes are transported by dendrites to the developing matrix cells. The nail plate becomes
Melanonychia
4505284
Griscelli syndrome is a rare autosomal recessive disorder characterized by albinism (hypopigmentation) with immunodeficiency, that usually causes death by early childhood. Researchers have developed three different classifications of the form of disorder, characterised by different signs and symptoms. Type 1 Griscelli Syndrome is assosciated with severe brain function issues along with distinctive discolouring of the hair and skin. Type 2 Griscelli Syndrome have immune system abnormalities in addition to hypopigmentation of skin and hair. Finally, Type 3 is seen as those only affected by hypopigmentation of the skin and hair. This type is not associated with immune deficiencies or neurological abnormalities. Signs and symptoms Griscelli syndrome is defined by the characteristic hypopigmentation, with frequent pyogenic infection, enlargement of the liver and spleen, a low blood neutrophil level, low blood platelet level, and immunodeficiency. Very often there is also impaired natural killer cell activity, absent delayed-type hypersensitivity and a poor cell proliferation response to antigenic challenge. This may be caused by the loss of three different genes, each of which has different additional effects, resulting in three types of syndrome. Its inheritance is autosomal recessive. Examination of the hair in this syndrome may be useful. Under light microscopy, these hairs exhibit bigger and irregular melanin granules, distributed mainly near the medulla. Under polarized light microscopy, the hairs appear monotonously white. There are three main types of Grescelli syndrome: type 1, type 2, and type 3. Regardless of type, people with Griscelli syndrome have hypopigmented skin and light, silvery-gray hair. People with Griscelli syndrome type 1 have severe problems concerning brain function, typically characterized as delayed development, intellectual disability, seizures, hypotonia, and eye and vision abnormalities. People with Griscelli syndrome type 2 have immune system abnormalities and are susceptible to recurrent infections; they develop hemophagocytic lymphohistiocytosis, which may damage organs and body tissues. People with Griscelli syndrome type 3 only have the baseline light skin and hair coloring abnormalities. Pathophysiology In melanocytes, melanosomes (vesicles containing the pigment melanin) are transported on microtubules. They are then bound by Rab27A which recruits Slac2-a and myosin Va. This complex then transfers the melanosomes from the microtubules to actin filaments. This transfer is necessary for the transport of melanosomes from the perinuclear area to the cell periphery. The loss of any one of these proteins interrupts melanosome transport and results in the hypopigmentation. However, these three proteins do not work together in other cells and RAB27A effectors may be 'mix and match.' For example, the knockout of Rab27 causes the hypopigmentation but also immunodeficiency due to deficiencies in cytotoxic killing activity in cytotoxic T cells (something that also depends on vesicle transport). While, the knockout of myosin Va does not cause immunodeficiency, but it does cause neural defects. Though some neural problems (i.e. brain damage) can be seen in Rab27A deficient children, this is thought to be a secondary effect of the immune problems, and not directly due to the lack of Rab27A. Munc13-4 has also drawn attention based on its involvement in causing bleeding manifestations
Griscelli syndrome
2404069
Leucism () is a wide variety of conditions that result in partial loss of pigmentation in an animal—causing white, pale, or patchy coloration of the skin, hair, feathers, scales, or cuticles, but not the eyes. It is occasionally spelled leukism. Some genetic conditions that result in a "leucistic" appearance include piebaldism, Waardenburg syndrome, vitiligo, Chédiak–Higashi syndrome, flavism, isabellinism, xanthochromism, axanthism, amelanism, and melanophilin mutations. Pale patches of skin, feathers, or fur (often referred to as "depigmentation") can also result from injury. Details Leucism is often used to describe the phenotype that results 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 (if all pigment cells fail to develop) or patches of body surface (if only a subset are defective) having a lack of cells that can make 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 often mistaken. Albinism results in the reduction of melanin production only, though the melanocyte (or melanophore) is still present. Thus in species that have other pigment cell-types, for example xanthophores, albinos are not entirely white, but instead display a pale yellow color. 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 coloring and patterning. This partial leucism is known as a "pied" or "piebald" effect; and the ratio of white to normal-colured skin can vary considerably not only between generations, but between different offspring from the same parents, and even between members of the same litter. This is notable in horses, cows, cats, dogs, the urban crow and the ball python but is also found in many other species. Due to the lack of melanin production in both the retinal pigmented epithelium (RPE) and iris, those affected by albinism sometimes have pink pupil due to the underlying blood vessels showing through. However, this is not always the case and many albino animals do not have pink pupils. The common belief that all albinos have pink pupils results in many albinos being incorrectly labeled as 'leucistic'. The neural crest disorders that cause leucism do not result in pink pupils and therefore most leucistic animals have normally colored eyes. This is because the melanocytes of the RPE do not derive from the neural crest. Instead, an out-pouching of the neural tube generates the optic cup that, in turn, forms the retina. As these cells are from an independent developmental origin, they are typically unaffected by the genetic cause of leucism. Notable examples Platypus (Ornithorhynchus anatinus) – in 2021, a leucistic example was found in the Gwydir River, near Armidale, New South Wales, Australia. Genetics Genes that, when mutated, can cause leucism include c-kit, mitf and EDNRB. Etymology The terms leucistic and leucism are derived from the stem leuc-
Leucism
5070047
Piebaldism refers to the absence of mature melanin-forming cells (melanocytes) in certain areas of the skin and hair. It is a rare autosomal dominant disorder of melanocyte development. Common characteristics include a congenital white forelock, scattered normal pigmented and hypopigmented macules and a triangular shaped depigmented patch on the forehead. There is nevertheless great variation in the degree and pattern of presentation, even within affected families. In some cases, piebaldism occurs together with severe developmental problems, as in Waardenburg syndrome and Hirschsprung's disease. Piebaldism has been documented to occur in all races, and is found in nearly every species of mammal. The condition is very common in mice, rabbits, dogs, sheep, deer, cattle and horses—where selective breeding has increased the incidence of the mutation—but occurs among chimpanzees and other primates only as rarely as among humans. Piebaldism is unrelated to conditions such as vitiligo or poliosis. Although "partial albinism" is a synonym for piebaldism, it is a fundamentally different condition from true albinism. The vision problems associated with albinism are not usually present as eye pigmentation is normal. Piebaldism differs from albinism in that the affected cells maintain the ability to produce pigment but have that specific function turned off. In albinism the cells lack the ability to produce pigment altogether. Human piebaldism has been observed to be associated with a very wide range and varying degrees of endocrine disorders, and is occasionally found together with heterochromia of the irises, congenital deafness, or incomplete gastrointestinal tract development, possibly all with the common cause of premature cutting off of human fetal growth hormone during gestation. Piebaldism is a kind of neurocristopathy, involving defects of various neural crest cell lineages that include melanocytes, but also involving many other tissues derived from the neural crest. Oncogenic factors, including mistranscription, are hypothesized to be related to the degree of phenotypic variation among affected individuals. Genetics Piebaldism is an autosomal dominant hereditary condition, which tends to produce high rates of inheritance and long chains of generational transmission. All who inherit the gene have at some time in life evidence of piebald hypopigmentation of the hair or skin, most likely both. Piebaldism may be associated with the genes KIT or SNAI2. Diagnosis Usually diagnosed at birth with the appearance of patches of white skin on the arms, legs, stomach, forehead, and a white lock of hair. History Early photographers took many photographs of African people with piebaldism as a form of entertainment and exoticism, and George Catlin is believed to have painted several portraits of Native Americans of the Mandan tribe who were affected by piebaldism. Historically, persons with extensive piebaldism have experienced abuse of the sort still suffered in the present by albinos, especially in Africa. This has ranged from display of unclothed African piebalds in "freak" shows and postcards of the early 20th century to the forcing of piebalds (as in the case of albinos) to work long hours exposed to the sun (producing high rates of lethal skin cancers), to the use of
Piebaldism
22290971
Photoaging or photoageing (also known as "dermatoheliosis") is a term used for the characteristic changes to skin induced by chronic UVA and UVB exposure. Tretinoin is the best studied retinoid in the treatment of photoaging. The deterioration of biological functions and ability to manage metabolic stress is one of the major consequences of the aging process. Aging is a complex, progressive process that leads to functional and aesthetic changes in the skin. This process can result from both intrinsic (i.e., genetically determined) as well as extrinsic processes (i.e., environmental factors). Photoaging is attributed to continuous, long-term exposure to ultraviolet (UV) radiation of approximately 300–400 nm, either natural or synthetic, on an intrinsically aged skin. Effects of UV light Molecular and genetic changes UVB rays are a primary mutagen that can only penetrate through the epidermal (outermost) layer of the skin, resulting in DNA mutations. These mutations arise due to chemical changes, the formation of cyclobutane pyrimidine dimers and photoproducts formed between adjacent pyrimidine bases. These mutations may be clinically related to specific signs of photoaging such as wrinkling, increasing in elastin and collagen damage. The epidermal layer does not contain any blood vessels or nerve endings but melanocytes and basal cells are embedded in this layer. Upon exposure to UVB rays, melanocytes will produce melanin, a pigment that gives the skin its color tone. However, UVB will cause the formation of freckles and dark spots, both of which are symptoms of photoaging. With constant exposure to UVB rays, signs of photoaging might appear and precancerous lesions or skin cancer may develop. UVA rays are able to penetrate deeper into the skin as compared to UVB rays. Hence, in addition to the epidermal layer, the dermal layer will also be damaged. The dermis is the second major layer of the skin and it comprises collagen, elastin, and extrafibrillar matrix which provides structural support to the skin. However, with constant UVA exposure, the size of the dermis layer will be reduced, thereby causing the epidermis to start drooping off the body. Due to the presence of blood vessels in the dermis, UVA rays can lead to dilated or broken blood vessels which are most commonly visible on the nose and cheeks. UVA can also damage DNA indirectly through the generation of reactive oxygen species (ROS), which include superoxide anion, peroxide and singlet oxygen. These ROS damage cellular DNA as well as lipids and proteins. Pigmentation UV exposure can also lead to inflammation and vasodilation which is clinically manifested as sunburn. UV radiation activates the transcription factor, NF-κB, which is the first step in inflammation. NF-κB activation results in the increase of proinflammatory cytokines, for example: interleukin 1 (IL-1), IL-6 vascular endothelial growth factor, and tumor necrosis factor (TNF-α). This then attracts neutrophils which lead to an increase in oxidative damage through the generation of free radicals. Additionally, UV radiation would cause the down-regulation of an angiogenesis inhibitor, thrombospondin-1, and the up-regulation of an angiogenesis activator which is platelet-derived endothelial cell growth factor,
Photoaging
18593371
Self-domestication is a scientific hypothesis that suggests that, similar to domesticated animals, there has been a process of artificial selection among members of the human species conducted by humans themselves. In this way, during the process of hominization, a preference for individuals with collaborative and social behaviors would have been shown to optimize the benefit of the entire group: docility, language, and emotional intelligence would have been enhanced during this process of artificial selection. The hypothesis is raised that this is what differentiated Homo sapiens from Homo neanderthalensis and Homo erectus. Origin and status of the hypothesis In general, domesticated animals possess common characteristics that differentiate them from their non-domesticated counterparts (for example, in the case of Canis familiaris compared to their relatives, Canis lupus, among many other cases): they tend to be more docile and playful, exhibit less aggressive behavior, and show marked neoteny, often resulting in a smaller body, a slightly smaller brain and skull, as well as shorter teeth and snout. One of the first to scientifically observe that humans present similar traits was the naturalist, anthropologist, and physician Johann Friedrich Blumenbach around 1800. The author of the thesis "De generis humani varietate nativa" ('On the natural variations in the human lineage') consequently proposed the hypothesis that humans could have been domesticated. A few years later, Charles Darwin addressed the topic using the theory of evolution, which already considered the process of artificial selection in animals. Unable to explain the concept of human domestication from an exclusively scientific perspective (the question of who domesticated humans could only be answered in religious or theistic terms), he eventually dismissed the hypothesis. However, the studies of Dimitri Beliayev in the 20th century were important for the proposal: research on the silver fox demonstrated that in the process of animal domestication, simultaneous changes occurred in behavior (lower levels of adrenaline were observed) and in coat color (alterations in pigmentation): adrenaline could share a biochemical pathway with melanin, a pathway that would be altered during the process of artificial selection. In 2014, scientists Adam Wilkins (from Humboldt University, Berlin), Richard Wrangham (from Harvard University, Massachusetts), and Tecumseh Fitch (from the University of Vienna) proposed that the common origin of these changes lay in neural crest cells, exclusive stem cells of vertebrates that migrate to different parts of the body during the embryonic phase, giving rise to the adrenal glands (responsible for managing the fear and stress response through adrenaline production), melanocytes (responsible for producing skin or coat melanin), and jaws simultaneously. The deficit of these cells would explain the common characteristics of all domesticated animals: tameness, cranial and mandibular reduction, and alterations in pigmentation. Of the three members of the research team, it was primatologist Richard Wrangham who translated these results to humans, asserting that humans have "domesticated" themselves through a process of self-selection (a proposal he would elaborate in "The Goodness Paradox: The Strange Relationship Between Virtue and Violence in Human Evolution"). In July 2019, a team from the Institute of
Self-domestication
13530724
Transient receptor potential cation channel subfamily M member 1 is a protein that in humans is encoded by the TRPM1 gene. Function The protein encoded by this gene is a member of the transient receptor potential (TRP) family of non-selective cation channels. It is expressed in the retina, in a subset of bipolar cells termed ON bipolar cells. These cells form synapses with either rods or cones, collecting signals from them. In the dark, the signal arrives in the form of the neurotransmitter glutamate, which is detected by a G protein-coupled receptor (GPCR) signal transduction cascade. Detection of glutamate by the GPCR Metabotropic glutamate receptor 6 results in closing of the TRPM1 channel. At the onset of light, glutamate release is halted and mGluR6 is deactivated; this results in opening of the TRPM1 channel, influx of sodium and calcium, and depolarization of the bipolar cell. In addition to the retina, TRPM1 is also expressed in melanocytes, which are melanin-producing cells in the skin. The expression of TRPM1 is inversely correlated with melanoma aggressiveness, suggesting that it might suppress melanoma metastasis. However, subsequent work showed that a microRNA located in an intron of the TRPM1 gene, rather than the TRPM1 protein itself, is responsible for the tumor suppressor function. The expression of both TRPM1 and the microRNA are regulated by the Microphthalmia-associated transcription factor. Clinical significance Mutations in TRPM1 are associated with congenital stationary night blindness in humans and coat spotting patterns in Appaloosa horses. See also TRPM References External links Ion channels
TRPM1
60116985
Rhododendrol (RD) also called 4-[(3R)-3-hydroxybutyl]phenol (systemic name), is an organic compound with the formula C10H14O2. It is a naturally occurring ingredient present in many plants, such as the Rhododendron. The phenolic compound was first developed in 2010 as a tyrosinase inhibitor for skin-lightening cosmetics. In 2013, after rhododendrol reportedly caused skin depigmentation in consumers using RD-containing skin-brightening cosmetics, the cosmetics were withdrawn from the market. The skin condition, caused by RD, is called RD-induced leukoderma. Rhododendrol exerts melanocyte cytotoxicity via a tyrosinase-dependent mechanism. It has been shown to impair the normal proliferation of melanocytes through reactive oxygen species-dependent activation of GADD45. It is now well established that rhododendrol is a potent tyrosinase inhibitor. Structure and synthesis Structure Rhododendrol occurs as the glucoside rhododendrin in leaves of the Rhododendron (Ericacae), and it naturally occurs as a phenolic compound in plants such as Acer nikoense , Betula platyphylla, and the Chinese red birch Betula Alba. The compound can be obtained from alkylation of phenols (C6H5OH). The molecule has a para-substituted structure, and one chiral center. Also, the compound has a natural charge. Biosynthesis There are several ways to synthesise rhododendrol. First, the synthesis can be achieved in six steps from benzaldehyde. The key reactions in this method include aldol condensation and trichloroacetimidate glycosylation. The compound can also be prepared by reducing raspberry ketone (4-(4-hydroxyphenyl)-2- butanone) with Raney nickel in EtOH. In addition, Rhododendrol can be synthesised from p-coumaric acid. This pathway involves reduction of the aliphatic double bond present in p-coumaric acid. Mechanisms of action The mechanism of action of rhododendrol has been investigated in multiple studies which revealed that RD competes with tyrosine for hydroxylation by tyrosinase and interferes with melanin synthesis. First, RD is catalysed by tyrosinase to produce toxic metabolites as RD-cyclic catechol. These reactive metabolites cause damage to the melanocytes. There is still uncertainty, however, how the metabolites result in melanocyte damage. A previous report reported that the melanocyte toxicity of rhododendrol is caused by the production of cytotoxic reactive oxygen species (ROS). However, another study stated that there was no ROS detected in the rhododendrol-treated melanocytes, but a tyrosinase-dependent accumulation of endoplasmic reticulum stress and activation of the apoptotic pathway. Even though there is still no full agreement on the exact mechanism of action, it is suggested that the mechanism of RD-induced leukoderma closely resembles the mechanism displayed in the figure below (Suggested mechanism of Rhododendrol.png). In some individuals, a T-cell response is observed. The melanocyte cell lysates may sensitise T-cells, and the immunised cytotoxic T-lymphocytes (specific to Melan A, which is a melanocytic differentiation marker) may enhance the RD-induced leukoderma or evoke vitiligo-like lesions on the non-applied skin. Metabolism Rhododendrol is metabolised via tyrosinase-catalysed oxidation. Therefore, the enzyme tyrosinase is necessary for the oxidation of rhododendrol. Tyrosinase regularly plays an essential role in the production of melanocytes called the melanogenesis. After oxidation of rhododendrol by the tyrosinase enzyme, several kinds of phenols and catechols are formed. These phenols and catechols together form ortho-quinones (o-quinones). Presence of
Rhododendrol
39201589
Anolis grahami, commonly known as the Jamaican turquoise anole and Graham's anole, is a species of lizard in the family Dactyloidae. The species is native to the island of Jamaica, and has also been introduced to the territory of Bermuda. It is one of many different species of anole lizards found in Jamaica. There are two recognized subspecies. Etymology The specific name of this species, grahami, was assigned to it in honor of James Duncan Graham, who founded the Corps of Topographical Engineers in the United States Army. Description The upper body of Anolis grahami is usually a rich emerald or aquamarine while its trunk and legs are a bright deep blue. It has a bright orange dewlap. The first half of the tail is a deep blue, while the lower half is brilliant violet. Its underside is usually a light blue gray. Occasionally, especially in females and younger individuals, these colors may be somewhat muted, though still quite gaudy. Fully grown males can be exceptionally colorful; occasionally a pure turquoise blue lizard may be observed. Mature male Anolis grahami can grow to a total length of 16 centimetres (6.3 in) and a snout–vent length (SVL) of 8 cm (3.1 in); females are smaller than males. During confrontations over territory or when threatened males may raise a small dorsal crest atop their heads. Colorization These lizards have a special ability to camouflage and change color when necessary. Under the anole's skin are pigment cells called chromatophores responsible for its usual coloration. Underneath these pigment cells are specialized pigment cells called melanocytes which contain the pigment melanin, in response to changes in the lizards hormones these cells can expand and mask the ordinary pigment cells, resulting in a change to a darker coloration, thus the anole is capable of changing its hue from bright blue, to varying shades of brown or almost completely black when stressed, often the end of the tail, and sometimes the trunk, remains colored during a color change. These lizards also have the ability to change the color of only one half of their bodies. Taxonomy Two subspecies are recognized as being valid, including the nominotypical subspecies. Anolis grahami aquarum – Portland Parish and St. Thomas Parish, Jamaica Anolis grahami grahami - Most of northern, western, southern and central Jamaica The order of the Anolis grahami is Squamata, which is a category that refers to scaled reptiles. Squamata is the most common order of reptile, and it includes species of snakes, lizards, and amphisbaenians. Species that are part of this order can be found all across the world, on every continent except Antarctica. Due to the wide variety of habitats and conditions that they live in, other lizard species in this order display significantly different adaptations and traits from the Anolis grahami. Structure The Anolis grahami have a developed, movable hinge in their skull called the quadratojugal hinge, which is a defining trait of the order Squamata. Members of this order have developed a specific jaw structure
Anolis grahami
7320592
Indoor tanning lotions accelerate the tanning process, by promoting the production of melanin. Increasing blood flow to the skin is a proposed mechanism, which may in turn stimulate production of melanin by melanocytes. Historically, indoor tanning lotions have contained no sunscreen and offer no protection from the sun. However, many tanning lotions currently contain sunscreen. Unlike sunless tanning lotions, these are designed for use with an ultraviolet source such as a tanning bed or booth. Ingredients Some of the active ingredients found in common tanning lotions include melanin and L-Tyrosine. Other commonly found ingredients include tea oil, copper (in many different chemical compounds), green tea extract and many other natural oils. Indoor tanning lotions are usually designed to only use ingredients that will not cause damage or build up on acrylic surfaces. This is because all tanning beds use 100% acrylic in their protective shields. This is one reason people should not use outdoor tanning lotion in a tanning bed, as some common ingredients such as mineral oil (common ingredient in cosmetics, including some baby oil brands) will damage the surface of the acrylics. Tingle is a standard description for indoor tanning lotions that contain ingredients that increase blood flow at the skin level, or cause a "tingling" sensation. Bronzers Some lotions have a bronzing effect to them. There are three different types of bronzers; cosmetic, natural and DHA. DHA (dihydroxyacetone) is a higher level of bronzer that stays on the skin for about 4–5 days depending on how much one exfoliates. Natural bronzers that are made from plant extracts, and stay on the skin for about 3–4 days, also exist. Cosmetic bronzers stain the skin the most, they stay on the skin for about 1–3 days and can be easily washed off in the shower. These bronzers work with the skin to provide a darker cosmetic color. They take approximately 4–6 hours to develop full color. Having a base tan before using a bronzer produces a more natural looking color. Natural bronzers use natural ingredients, such as caramel, riboflavin, etc. These ingredients provide a slight instant boost of color, but will wash off in the shower. Higher quality natural bronzer lotions will have certain organic ingredients/natural or exotic extracts that aid in the process of tanning (melanin production/oxidization). Moisturizing One of the primary purposes for using indoor tanning lotions is to moisturize the skin. This is because tanning (indoors or out) can dehydrate the skin so additional moisturization is needed to compensate and leave the skin looking smooth and healthy. One of the most popular moisturizing elements in tanning lotions is hempseed oil, although other oils are also common. The primary moisturizing ingredients in tanning lotions are essentially the same as in regular hand lotions, although they tend to have less alcohol in them. Outdoor use Most indoor tanning lotions do not offer protection from the sun (have no SPF) and are not intended for outdoor use. However, many tanning lotions now contain SPF. See also Indoor tanning References
Indoor tanning lotion
4616860
Gastrodermis (From Ancient Greek: , , "stomach"; , , "skin") is the inner layer of cells that serves as a lining membrane of the gastrovascular cavity in Cnidarians. It is distinct from the outer epidermis and the inner dermis and is primarily associated with the ventral side of Cnidarians. It is composed of specialized cells responsible for several vital physiological processes. The term is also used for the analogous inner epithelial layer of Ctenophores. Functions The gastrodermis has a role in many biological functions, including respiration, pigmentation, and digestion. The gastrodermis provides a large surface area for gas exchange to occur, via cutaneous respiration, which involves the exchange of oxygen and carbon dioxide through the skin. The gastrodermis contains specialised cells called chromatophores, which are responsible for producing and controlling pigmentation. These cells contain pigments such as melanin that help in coloration and camouflage. In Coelenterates, the gastrodermis contains mucous secreting cells and gland cells, that secrete digestive enzymes to assist in digestion. The gastrodermis is among the sites where early signals of heat stress are expressed in corals. References Cnidarian anatomy
Gastrodermis
6021465
Biological pigments, also known simply as pigments or biochromes, are substances produced by living organisms that have a color resulting from selective color absorption. Biological pigments include plant pigments and flower pigments. Many biological structures, such as skin, eyes, feathers, fur and hair contain pigments such as melanin in specialized cells called chromatophores. In some species, pigments accrue over very long periods during an individual's lifespan. Pigment color differs from structural color in that it is the same for all viewing angles, whereas structural color is the result of selective reflection or iridescence, usually because of multilayer structures. For example, butterfly wings typically contain structural color, although many butterflies have cells that contain pigment as well. Biological pigments See conjugated systems for electron bond chemistry that causes these molecules to have pigment. Heme/porphyrin-based: chlorophyll, bilirubin, hemocyanin, hemoglobin, myoglobin Light-emitting: luciferin Carotenoids: Hematochromes (algal pigments, mixes of carotenoids and their derivates) Carotenes: alpha and beta carotene, lycopene, rhodopsin Xanthophylls: canthaxanthin, zeaxanthin, lutein Proteinaceous: phytochrome, phycobiliproteins Psittacofulvins: a class of red and yellow pigments unique to parrots Turacin and Turacoverdin: red and green pigments found in turacos and related species Anthoxanthins: white color of some plants Other: melanin, urochrome, flavonoids Pigments in plants The primary function of pigments in plants is photosynthesis, which uses the green pigment chlorophyll and several colorful pigments that absorb as much light energy as possible. Pigments are also known to play a role in pollination where pigment accumulation or loss can lead to floral color change, signaling to pollinators which flowers are rewarding and contain more pollen and nectar. Plant pigments include many molecules, such as porphyrins, carotenoids, anthocyanins and betalains. All biological pigments selectively absorb certain wavelengths of light while reflecting others. The principal pigments responsible are: Chlorophyll is the primary pigment in plants; it is a chlorin that absorbs blue and red wavelengths of light while reflecting a majority of green. It is the presence and relative abundance of chlorophyll that gives plants their green color. All land plants and green algae possess two forms of this pigment: chlorophyll a and chlorophyll b. Kelps, diatoms, and other photosynthetic heterokonts contain chlorophyll c instead of b, while red algae possess only chlorophyll a. All chlorophylls serve as the primary means plants use to intercept light in order to fuel photosynthesis. Carotenoids are red, orange, or yellow tetraterpenoids. During the process of photosynthesis, they have functions in light-harvesting (as accessory pigments), in photoprotection (energy dissipation via non-photochemical quenching as well as singlet oxygen scavenging for prevention of photooxidative damage), and also serve as protein structural elements. In higher plants, they also serve as precursors to the plant hormone abscisic acid. Betalains are red or yellow pigments. Like anthocyanins they are water-soluble, but unlike anthocyanins they are synthesized from tyrosine. This class of pigments is found only in the Caryophyllales (including cactus and amaranth), and never co-occur in plants with anthocyanins. Betalains are responsible for the deep red color of beets. Anthocyanins (literally "flower blue") are water-soluble flavonoid
Biological pigment
1192959
Dermatofibrosarcoma protuberans (DFSP) is a rare locally aggressive malignant cutaneous soft-tissue sarcoma. DFSP develops in the connective tissue cells in the middle layer of the skin (dermis). Estimates of the overall occurrence of DFSP in the United States are 0.8 to 4.5 cases per million persons per year. In the United States, DFSP accounts for between 1 and 6 percent of all soft-tissue sarcomas and 18 percent of all cutaneous soft-tissue sarcomas. In the Surveillance, Epidemiology and End Results (SEER) tumor registry from 1992 through 2004, DFSP was second only to Kaposi sarcoma. Presentation Dermatofibrosarcoma protuberans begins as a minor firm area of skin most commonly about to 1 to 5 cm in diameter. It can resemble a bruise, birthmark, or pimple. It is a slow-growing tumor and is usually found on the torso but can occur anywhere on the body. About 90% of DFSPs are low-grade sarcomas. About 10% are mixed, containing a high-grade sarcomatous component (DFSP-FS); therefore, they are considered to be intermediate-grade sarcomas. DFSPs rarely lead to a metastasis (fewer than 5% metastasize), but DFSPs can recur locally. DFSPs most often arise in patients who are in their thirties but this may be due to diagnostic delay. Location Commonly located on the chest and shoulders, the following is the site distribution of DFPS as was observed in Surveillance, Epidemiology, and End Results (SEER) database between 2000 and 2010. Trunk/torso – 42% Lower extremity – 21% Upper extremity – 21% Head and neck – 13% Genitals – 1% Variants The World Health Organization in 2020 classified the fibro sarcomatous DFSP (DFSP-FS) variant (also termed dermatofibrosarcoma protuberans, fibro sarcomatous) of the dermatofibrosarcoma protuberans as a specific form of the intermediate (rarely metastasizing) fibroblastic and myofibroblastic tumors and other variants of this disorder as a specific form of the intermediate (locally aggressive) fibroblastic and myofibroblastic tumors. Bednar tumors Bednar, or pigmented DFSP, is distinguished by the dispersal of melanin-rich dendritic cells of the skin. It represents 1–5 percent of all DFSP occurring in people rich in melanin pigments. Bednar is characterized by a dermal spindle cell proliferation like DFSP but distinguished by the additional presence of melanocytic dendritic cells. It occurs at the same rate as DFSP on fairer skin and should be considered to have the same chances of metastasis. Myxoid DFSP Myxoid DFSP has areas of myxoid degeneration in the stroma. Giant cell fibroblastoma Giant cell fibroblastoma contains giant cells, and is also known as juvenile DFSP. Giant cell fibroblastomas are skin and soft-tissue tumors that usually arise in childhood. They are sometimes seen in association with dermatofibrosarcoma protuberans (DFSP, hybrid lesions) or may transform or recur as DFSP. Atrophic DFSP Atrophic DFSP resemble other benign lesions such as morphea, idiopathic atrophoderma, atrophic scar, anetoderma or lipoatrophy. It behaves like classic DFSP. It commonly favours young to middle-aged adults. It has a slow infiltrative growth and a high rate of local recurrence if not completely excised. Sclerosing DFSP Sclerosing DFSP is a variant in which the cellularity is
Dermatofibrosarcoma protuberans
5982854
Melanosis coli, also pseudomelanosis coli, is a disorder of pigmentation of the wall of the colon, often identified at the time of colonoscopy. It is benign and may have no significant correlation with disease. The brown pigment is lipofuscin in macrophages, not melanin. It is most commonly associated with the use of certain laxatives. Cause The most common cause of melanosis coli is the extended use of laxatives, and commonly anthraquinone containing laxatives such as senna, aloe vera, and other plant glycosides. The anthranoid laxatives pass through the gastrointestinal tract unabsorbed until they reach the large intestine, where they are changed into their active forms. The resulting active compounds cause damage to the cells in the lining of the intestine and leads to apoptosis (a form of cell death). The damaged (apoptotic) cells appear as darkly pigmented bodies that may be taken up by scavenger cells known as macrophages. When enough cells have been damaged, the characteristic pigmentation of the bowel wall develops. The condition can develop after just a few months of laxative use. However, other causes are identified, including an increase in colonic epithelial apoptosis. Endoscopically, the mucosa may show a brownish discoloration in a moiré pattern. Histologic appearance On biopsy, melanosis coli shows characteristic pigment-laden macrophages within the mucosa on PAS staining. The histologic differential diagnosis of mucosal pigmentation is: lipofuscin (melanosis coli), hemosiderin-laden macrophages, and melanin (rare). Prognosis No adverse effects or consequences of melanosis coli have been identified. Relation to true melanoses The condition is unrelated to true melanoses, such as Peutz–Jeghers syndrome and smoker's melanosis. Peutz–Jeghers syndrome causes pigmentation of the skin and mucous surfaces with melanin, and polyps in the digestive tract. Non-colonic pseudomelanoses Pseudomelanoses of other parts of the gastrointestinal tract have also been reported, and are of unclear relevance. Patients with colostomies can have melanosis involving the stoma, which is also of no significance. References External links Gastrointestinal tract disorders
Melanosis coli
15737471
Indirect DNA damage occurs when a UV-photon is absorbed in the human skin by a chromophore that does not have the ability to convert the energy into harmless heat very quickly. Molecules that do not have this ability have a long-lived excited state. This long lifetime leads to a high probability for reactions with other molecules—so-called bimolecular reactions. Melanin and DNA have extremely short excited state lifetimes in the range of a few femtoseconds (10−15s). The excited state lifetime of compounds used in sunscreens such as menthyl anthranilate, avobenzone or padimate O is 1,000 to 1,000,000 times longer than that of melanin, and therefore they may cause damage to living cells that come in contact with them. The molecule that originally absorbs the UV-photon is called a "chromophore". Bimolecular reactions can occur either between the excited chromophore and DNA or between the excited chromophore and another species, to produce free radicals and reactive oxygen species. These reactive chemical species can reach DNA by diffusion and the bimolecular reaction damages the DNA (oxidative stress). It is important to note that, unlike direct DNA damage which causes sunburn, indirect DNA damage does not result in any warning signal or pain in the human body. The bimolecular reactions that cause the indirect DNA damage are illustrated in the figure: 1O2 is reactive harmful singlet oxygen: Location of the damage Unlike direct DNA damage, which occurs in areas directly exposed to UV-B light, reactive chemical species can travel through the body and affect other areas—possibly even inner organs. The traveling nature of the indirect DNA damage can be seen in the fact that the malignant melanoma can occur in places that are not directly illuminated by the sun—in contrast to basal-cell carcinoma and squamous cell carcinoma, which appear only on directly illuminated locations on the body. See also Free radical damage to DNA Photoprotection Sunscreen References Photochemistry Skin conditions resulting from physical factors Sun tanning
Indirect DNA damage
298541
Intense pulsed light (IPL) is a technology used by cosmetic and medical practitioners to perform various skin treatments for aesthetic and therapeutic purposes, including hair removal, photorejuvenation (e.g. the treatment of skin pigmentation, sun damage, and thread veins) as well as to alleviate dermatologic diseases such as acne. IPL is increasingly used in optometry and ophthalmology as well, to treat evaporative dry eye disease due to meibomian gland dysfunction. The technology uses a high-powered, hand-held, computer-controlled flashgun to deliver an intense, visible, broad-spectrum pulse of light, generally in the visible spectral range of 400 to 1200 nm. Various cutoff filters are commonly used to selectively filter out shorter wavelengths, especially potentially damaging ultraviolet light. The resulting light has a spectral range that targets specific structures and chromophores (e.g. melanin in hair, or oxyhemoglobin in blood vessels) that are heated to destruction and reabsorbed by the body. IPL shares some similarities with laser treatments, in that they both use light to heat and destroy their targets. But unlike lasers that use a single wavelength (color) of light which typically matches only one chromophore and hence only treats one condition, IPL uses a broad spectrum that when used with interchangeable filters, allowing it to be used against several conditions. This can be achieved when the IPL technician selects the appropriate filter that matches a specific chromophore. Description Intense pulsed light is the use of intense pulses of non-coherent light over a range of wavelengths from 500 nm to 1200 nm. Xenon flashlamps produce high output bursts of broad spectrum. Cooling is used to protect the skin in contact with the device. Regulations governing IPL vary by jurisdiction. A distinction is sometimes made between beauty-grade and medical-grade machines, mainly to get around regulations. The first FDA approval of IPL was for telangiectasias in 1995. Use quickly spread to a variety of medical and cosmetic settings. Treatment is generally safe and effective, but complications can occur, such as hyperpigmentation. The polychromatic light can reach multiple chromophores in human skin: mainly hemoglobin, water, and melanin. This results in selective photothermolysis of blood vessels, pigmented cells, or hair follicles. Hair removal IPL can reduce hair growth, most effectively in darker, coarser hair. IPL is distinct from laser hair removal which uses coherent monochromatic laser light. Protocol Broad-spectrum light is applied to the surface of the skin, targeting melanin. This light travels through the skin until it strikes the hair shafts or hair follicle. The follicle is usually where the highest concentration of melanin is located. As the light is absorbed, the bulb and most of the hair shaft are heated, destroying the hair-producing papilla. It is also claimed that heat conversion occurs directly in the darker capillaries that bring blood to the follicle. At any one time, not all hair follicles are 'active', and only active hair follicles can be affected by the treatment. 'Inactive' hair follicles can be treated as they become 'active' over time. For IPL treatments, an average of 8–10 treatments, 4–6 weeks
Intense pulsed light
19851554
The cortex of the hair shaft is located between the hair cuticle and medulla and is the thickest hair layer. It contains most of the hair's pigment, giving the hair its color. The major pigment in the cortex is melanin, which is also found in skin. The distribution of this pigment varies from animal to animal and person to person. In humans, the melanin is primarily denser nearer the cuticle whereas in animals, melanin is primarily denser nearer the medulla. See also List of distinct cell types in the adult human body References Hair anatomy
Cortex (hair)
63772134
Fish coloration, a subset of animal coloration, is extremely diverse. Fish across all taxa vary greatly in their coloration through special mechanisms, mainly pigment cells called chromatophores. Fish can have any colors of the visual spectrum on their skin, evolutionarily derived for many reasons. There are three factors to coloration, brightness (intensity of light), hue (mixtures of wavelengths), and saturation (the purity of wavelengths). Fish coloration has three proposed functions: thermoregulation, intraspecific communication, and interspecific communication. Fishes' diverse coloration is possibly derivative of the fact that "fish most likely see colors very differently than humans". Mechanisms Fish coloration is produced through specialized cells called chromatophores. The dermal chromatophore is a basic color unit in amphibians, reptiles, and fish which has three cell layers: "the xanthophore (contains carotenoid and pteridine pigments), the iridophore (reflects color structurally), and the melanophore (contains melanin)". The pigments in the chromatophores are generally classified into two groups: melanin (makes browns, grays, and blacks), and carotenoids (makes reds, oranges, and yellows). Xanthophores, iridophores, and melanophores "originate from neural crest‐derived stem cells associated with the dorsal root ganglia of the peripheral nervous system". Specific mechanisms by color Black: produced by melanin granules dispersing inside the melanophore Gray and brown: produced by melanin granules concentrating inside the melanophore White: appears from light reflected by crystals of guanine in iridophores and leucophores Red, orange, yellow: produced by carotenoids that come from fish's diet Green, blue, violet: (generally) structural colors produced by the reflection and refraction of light by the skin and scale layers An example of a family of fish that is widely known for their highly varied and bright coloration are the Labridae (wrasses) and Scaridae (parrotfish). These fishes are known to possess all of the above pigments in different ratios depending on where they live in relation to the coral reef environment. Different wavelengths, and thus different colors, travel differently and therefore appear differently depending on the depth of the water and the things on which they are reflecting. Evolutionary function Signalling One way that fish coloration can be categorized is into "static" or "dynamic" coloration/displays. Static coloration often serves as an "identification badge" for information such as species, reproductive condition, sex, or age. An example of a type of static coloration that conveys clear information to predators of different species is aposematic coloration. An example of aposematic coloration is in the lionfish (Pterois sp.). Dynamic displays consist of either changes of color or "rapid exposure of colored, previously hidden structures" such as colored fins that can be erected at will, colored mouth opening and closing, or flaring gills with bright coloration on the gill margins. For example, grunts have a bright red lining on their mouth that they can show by opening it in a head-to-head encounter. Another common example is the betta fish, or Siamese fighting fish, that will flare its gills as an aggressive behavior. These gills have brightly colored margins that contrast the rest of the body. Camouflage Some fish are famous for their
Fish coloration
997576
The alpine salamander (Salamandra atra) is a black salamander that can be found in the French Alps, and through the mountainous range in Europe. It is a member of the genus Salamandra. Their species name, atra, may be derived from the Latin ater, meaning dull black. The salamanders' coloration has evolved over time, as some species are completely monochrome black and others have yellow spotting and marks. Their life expectancy is at least 10 years. There are four subspecies of the alpine salamander, with varied distribution and physical coloration. Unlike other salamanders, whose larvae are developed in water, the alpine salamander and its subspecies are a fully terrestrial species in life and gestation. They give birth to live young. Alpine salamanders produce toxic compounds from their skin. These compounds may protect them from both predator and microbial threats. Description Alpine salamanders are often small in size, and dark brown or black. Members of the subspecies are not wholly black or brown monochrome, but rather have mosaic or spotted patterns. Members of the subspecies Salamandra atra aurorae have bright splotches on its dorsal side and head. The color is often bright yellow, but can range to shades of white or even gray. Distribution of the pigment is dependent on the distribution of certain cells, so may be smooth and even or patchy. Female S. atra tend to be larger than the males, and can grow up to 151 millimeters, or around 5.9 inches. Males will grow to around 144 millimeters, or 5.6 inches: both measurements include the tail. Males have swollen, visible cloacae, and are more slender than females. The salamanders have parotid glands posterior and lateral to their eyes, giving them an elongated head shape. They tend to have between 11 and 13 costal grooves along the sides of their bodies, and a double row of dorsal glands runs down their backs on either side of their spines, down to the tips of their tails. Coloration Most alpine salamanders that are either completely black (melanistic) or predominantly black have the dark pigment as a baseline, but the evolution behind this dark coloring has a winding history. Scientists have studied the hypothesis of if the salamanders start completely black, or if they evolved like that over time. DNA-evidence traced through maternal lineages suggest the latter: that salamanders evolved their black coloration over time. Biological pigmentation is determined by presentation of specific color-producing cells, called chromatophores, which absorb and/or reflect light in a particular way to then appear as a color. In S. atra, there are different cells present or activated, which yield different colors: melanophores contribute to the dark coloration by producing the dark pigment melanin, while xanthophores produce a yellow pigment, and iridophores are simply light-reflecting. The fully-black phenotype seen in S. a. atra results from the salamanders' melanophores in the dermis and epidermis, producing melanin alone. Xanthophore-iridophore complexes are responsible for production of yellow spotting, which appears bright. In species without yellow patches, it appears that they do not
Alpine salamander
5723938
beta-Arbutin, also known as β-arbutin or by its International Nomenclature of Cosmetic Ingredients (INCI) name, arbutin, is a glycosylated derivative of hydroquinone. β-Arbutin is naturally present in the leaves and bark of a variety of plants, notably the bearberry plant, Arctostaphylos uva-ursi. Utilized as a biosynthetic active ingredient in topical treatments for skin lightening, β-arbutin is aimed at addressing hyperpigmentation issues. Its mechanism of action involves inhibiting the activity of tyrosinase, an essential enzyme for melanin synthesis in the human skin, thereby leading to a reduction in hyperpigmentation. It is important to distinguish β-arbutin from its structurally similar stereoisomer, α-arbutin, which exhibits similar effects in clinical applications. Properties Arbutin is a compound where a glucose molecule, specifically -glucose, is chemically bound to hydroquinone. In aqueous solutions, glucose can exist in one of three stereoisomeric forms: α, β, or γ, with the β-anomer being the predominant form. The standard known form of arbutin, β-Arbutin, has a molecular formula of C12H16O7 and a molecular weight of 272.25g/mol. Its stereoisomers, α-arbutin and γ-arbutin, share the same molecular formula and weight but are distinct in their atoms' spatial arrangement. β-Arbutin is soluble in water, presenting typically as a white powder that remains stable under standard storage conditions. It exhibits stability in both ethanol and water and demonstrates resistance to light exposure. When dissolved in water, β-arbutin may undergo hydrolysis, converting to hydroquinone, which can subsequently oxidize to benzoquinone. Occurrence and preparation The compound is naturally occurring and can be extracted from several plant species. Traditionally extracted from the bearberry plant (Arctostaphylos uva-ursi), it also occurs in high levels in plants in the families of Ericaceae and Saxifragaceae. Others include the pear (Pyrus spp.), and certain species of wheat. It is also found in very small quantities in Viburnum opulus, Bergenia crassifolia and Schisandra chinensis. Synthetically, it can also be prepared from the reaction of acetobromoglucose and hydroquinone in the presence of an alkali. Uses The main application of β-arbutin is in the cosmetic industry, where it is incorporated into various skin care products, including creams, serums and lotions, aimed at lightening skin tone and correcting hyperpigmentation. Its efficacy and safety profile make it a sought-after ingredient for products targeting solar lentigo, freckles, melasma, and other forms of hyperpigmentation. Herbal medicine For centuries, β-arbutin has been used in phytotherapy, or herbal medicine. Extracted from the leaves of bearberry plants, it is used as a mixture with other herbal drugs as a treatment for urinary tract infections. Mechanism of action Regulation of melanin synthesis β-Arbutin acts as an enzyme inhibitor of cellular tyrosinase by inactivating it. Tyrosinase is an enzyme needed in melanin synthesis in the melanin producing cell of the skin, the melanocyte. By reducing the activity of tyrosinase, β-arbutin reduces the synthesis of melanin, leading to a lighter skin tone and the diminished appearance of hyperpigmentation. It is not as potent an inhibitor of tyrosinase as α-arbutin. It has also been shown act as a substrate for tyrosinase. Tyrosinase catalyses the hydroxylation of tyrosine,
Arbutin
2638550
An appressorium is a specialized cell typical of many fungal plant pathogens that is used to infect host plants. It is a flattened, hyphal "pressing" organ, from which a minute infection peg grows and enters the host, using turgor pressure capable of punching through even Mylar. Following spore attachment and germination on the host surface, the emerging germ tube perceives physical cues such as surface hardness and hydrophobicity, as well as chemical signals including wax monomers that trigger appressorium formation. Appressorium formation begins when the tip of the germ tube ceases polar growth, hooks, and begins to swell. The contents of the spore are then mobilized into the developing appressorium, a septum develops at the neck of the appressorium, and the germ tube and spore collapse and die. As the appressorium matures, it becomes firmly attached to the plant surface and a dense layer of melanin is laid down in the appressorium wall, except across a pore at the plant interface. Turgor pressure increases inside the appressorium and a penetration hypha emerges at the pore, which is driven through the plant cuticle into the underlying epidermal cells. The osmotic pressure exerted by the appressorium can reach up to 8 MPa, which allows it to puncture the plant cuticle. This pressure is achievable due to a melanin-pigmented cell wall which is impermeable to compounds larger than water molecules, so the highly-concentrated ions cannot escape from it. Formation The attachment of a fungal spore on the surface of the host plant is the first critical step of infection. Once the spore is hydrated, an adhesive mucilage is released from its tip. During germination, mucilaginous substances continue to be extruded at the tips of the germ tube, which are essential for germ tube attachment and appressorium formation. Spore adhesion and appressorium formation is inhibited by hydrolytic enzymes such as α-mannosidase, α-glucosidase, and protease, suggesting that the adhesive materials are composed of glycoproteins. Germination is also inhibited at high spore concentrations, which might be due to a lipophilic self inhibitor. Self inhibition can be overcome by hydrophobic wax from rice leaf. In response to surface signals, the germ tube tip undergoes a cell differentiation process to form a specialized infection structure, the appressorium. Frank B. (1883), in 'Ueber einige neue und weniger bekannte Pflanzenkrankheiten', coined the name "appressorium" for the adhesion body formed by the bean pathogen Gloeosporium lindemuthianum on the host surface. Appressorium development involves a number of steps: nuclear division, first septum formation, germling emergence, tip swelling and second septum formation. Mitosis first occurs soon after surface attachment, and a nucleus from the second round of mitosis during tip swelling migrates into the hooked cell before septum formation. A mature appressorium normally contains a single nucleus. The outside plasma membrane of the mature appressorium is covered by a melanin layer except at the region in contact with the substratum, where the penetration peg, a specialized hypha that penetrates the tissue surface, develops. Cellular glycerol concentration sharply increases during spore germination, but it
Appressorium
56317749
"Melanin Magic", alternatively "Melanin Magic (Pretty Brown)", is a song by American rapper Remy Ma featuring American singer Chris Brown. It was written by the artists alongside Keirston Lewis, Ricky Kinchen, Stokley Williams, Atia "INK" Boggs, Jeffrey Allen, Lawrence Waddell, and producer Dallas Austin. The song was released via Reminisce Records on January 19, 2018. The song was nominated for the BET Her Award at the BET Awards 2018. Background and release The collaboration was first revealed by Ma during her appearance on Total Request Live in November 2017. "The next single is with Chris Brown," she said. "'Melanin Magic', aka 'Pretty Brown', It's amazing." On January 16, 2018, Ma shared a snippet of the song on social media. The song samples Mint Condition's "Breakin' My Heart (Pretty Brown Eyes)", and was announced with a cover art contest, which allowed fans to vote on three different options. Ma explained in a video on Instagram that this song was meant to empower. "I just wanted to make something to let people know that you're beautiful, you're pretty," she said. "You can be brown skin, dark skin, light skinned. None of that is what makes you pretty or beautiful. It's what's inside." Commercial performance Commercially, Melanin Magic peaked at #17 on Billboard Mainstream R&B/Hip-Hop chart, #24 on Billboard Rhythmic chart, #18 on Billboard Rap Airplay chart, #29 on Billboard R&B/Hip-Hop Airplay chart and was the #1 most added song on Urban Radio. Critical reception C. Vernon Coleman II of XXL opined that Ma "puts a new spin on an old classic", writing that "Austin chops the R&B track into something more suitable to spit over, and Rem takes the opportunity to talk a little greasy". Eric Skelton of Complex thinks that the song shows Ma's "catchier, more radio-friendly side". Jasmine Grant of VH1 described the song as "a ladies anthem and '90s tribute all wrapped into one", and wrote that Brown is "the perfect selection for the catchy hook". Will Lavin of Joe felt that Ma and Brown "have created an ode to the regality of brown skin". Mike Nied of Idolator deemed the song "a retro romance with an empowering message for women" which "has a bit more crossover appeal" over the album's lead single "Wake Me Up", calling it "another promising release" from Ma. James Dinh of iHeartRadio regarded the song as "a romantic ode to loving your own body". Credits and personnel Credits adapted from Tidal. Remy Ma – songwriting Chris Brown – songwriting Keirston Lewis – songwriting Ricky Kinchen – songwriting Stokley Williams – songwriting Atia Boggs – songwriting Jeffrey Allen – songwriting Dallas Austin – songwriting, production Lawrence Waddell – songwriting Matthew Testa – mix engineering Colin Leonard – master engineering Alexander "Smitty Beatz" Smith – record engineering Charts References External links 2018 songs 2018 singles Remy Ma songs Chris Brown songs Songs written by Remy Ma Songs written by Chris Brown Songs written by Dallas Austin Song recordings produced by Dallas Austin
Melanin Magic
2909
Albinism is a congenital condition characterized in humans by the partial or complete absence of pigment in the skin, hair and eyes. Albinism is associated with a number of vision defects, such as photophobia, nystagmus, and amblyopia. Lack of skin pigmentation makes for more susceptibility to sunburn and skin cancers. In rare cases such as Chédiak–Higashi syndrome, albinism may be associated with deficiencies in the transportation of melanin granules. This also affects essential granules present in immune cells, leading to increased susceptibility to infection. Albinism results from inheritance of recessive gene alleles and is known to affect all vertebrates, including humans. It is due to absence or defect of tyrosinase, a copper-containing enzyme involved in the production of melanin. Unlike humans, other animals have multiple pigments and for these, albinism is considered to be a hereditary condition characterised by the absence of melanin in particular, in the eyes, skin, hair, scales, feathers or cuticle. While an organism with complete absence of melanin is called an albino, an organism with only a diminished amount of melanin is described as leucistic or albinoid. The term is from the Latin albus, "white". Signs and symptoms There are two principal types of albinism: oculocutaneous, affecting the eyes, skin and hair, and ocular affecting the eyes only. There are different types of oculocutaneous albinism depending on which gene has undergone mutation. With some there is no pigment at all. The other end of the spectrum of albinism is "a form of albinism called rufous oculocutaneous albinism, which usually affects dark-skinned people". According to the National Organization for Albinism and Hypopigmentation, "With ocular albinism, the color of the iris of the eye may vary from blue to green or even brown, and sometimes darkens with age. However, when an optometrist or ophthalmologist examines the eye by shining a light from the side of the eye, the light shines back through the iris since very little pigment is present." Because individuals with albinism have skin that entirely lacks the dark pigment melanin, which helps protect the skin from the sun's ultraviolet radiation, their skin can burn more easily from overexposure. The human eye normally produces enough pigment to color the iris blue, green or brown and lend opacity to the eye. In photographs, those with albinism are more likely to demonstrate "red eye", due to the red of the retina being visible through the iris. Lack of pigment in the eyes also results in problems with vision, both related and unrelated to photosensitivity. Those with albinism are generally as healthy as the rest of the population (but see related disorders below), with growth and development occurring as normal, and albinism by itself does not cause mortality, although the lack of pigment blocking ultraviolet radiation increases the risk of melanomas (skin cancers) and other problems. Visual problems Development of the optical system is highly dependent on the presence of melanin. For this reason, the reduction or absence of this pigment in people with albinism may lead to: Misrouting
Albinism in humans
14400759
Amelanotic melanoma is a type of skin cancer in which the cells do not make any melanin. They can be pink, red, purple or of normal skin color, and are therefore difficult to diagnose correctly. They can occur anywhere on the body, just as a typical melanoma can. Often, amelanotic melanomas are mistaken for benign lesions, including dermatitis, benign neoplastic processes, or a different malignancy such as basal-cell carcinoma or squamous-cell carcinoma. A poor prognosis is associated with amelanotic lesions, partially due to the difficulty in achieving a diagnosis; however, metastatic amelanotic melanoma has a worse prognosis than other subtypes. Survival after diagnosis of amelanotic melanoma was found in a 2014 seven-year study of 3,000 patients to be poorer than for pigmented melanoma, which was attributed to the more advanced stage at diagnosis due probably to difficulty of diagnosis. The study also suggested that amelanotic melanomas might grow faster than pigmented melanomas. Signs and symptoms Three primary clinical forms of amelanotic melanoma have been proposed skin-colored dermal plaque with no epidermal alterations, papulonodular form, and erythematous macule along with epidermal changes on skin exposed to the sun. 58% of cases of amelanotic melanoma are of the papulonodular form, which can mimic pyogenic granuloma or hemangioma and present as an ulcerated nodule or vascular lesion. 'ABCD' criteria (Asymmetry, Border irregularity, Color variegation, Diameter>6 mm) are rarely seen in non-papulonodular forms of amelanotic melanomas, which can present as erythematous macules or patches, scaly eczema-like, or skin-colored dermal plaques. Though not around truly amelanotic melanomas, a faint flush or periphery of the pigment is frequently seen surrounding amelanotic lesions. The appearance of amelanotic melanomas can vary; they can be skin-colored, pink, red, or erythematous, with red amelanotic melanomas making up almost 70% of all amelanotic melanomas without melanin. Causes Risk factors Patients with amelanotic melanoma are typically diagnosed later in life—after age 50, in comparison to those with pigmented melanoma. However, amelanotic melanoma accounts for about 70% of childhood cases. The relationship between amelanotic melanoma and sex is debatable; varying research indicates that the condition is more common in men, women, or neither sex. The potential preference for women may stem from the fact that they self-report suspicious skin conditions more frequently than men, while the potential predominance of men may be related to the fact that men expose themselves to more chronic outdoor sun exposure than women. The majority of patients with amelanotic melanomas are white, and those with oculocutaneous albinism or type I skin and red hair are more likely to have them. According to a population-based study, the likelihood of developing amelanotic melanoma is also increased by freckles, a sun-sensitive phenotype, the absence of nevi on the back, and a history of the disease in the past. Mechanism Amelanotic melanoma's underlying mechanism is still unknown. Previous research categorized amelanotic melanoma as either poorly differentiated or dedifferentiated. Tyrosinase and microphthalmia-associated transcription factor (MITF) expression, however, allow amelanotic melanoma cells to retain their melanocytic lineage and melanin-forming capacity, just like their pigmented
Amelanotic melanoma
617004
Laser hair removal is the process of hair removal by means of exposure to pulses of laser light that destroy the hair follicle. It had been performed experimentally for about twenty years before becoming commercially available in 1995–1996. One of the first published articles describing laser hair removal was authored by the group at Massachusetts General Hospital in 1998. Laser hair removal is widely practiced in clinics, and even in homes using devices designed and priced for consumer self-treatment. Many reviews of laser hair removal methods, safety, and efficacy have been published in the dermatology literature. R. Rox Anderson and Melanie Grossman discovered that it was possible to selectively target a specific chromophore with a laser to partially damage basal stem cells inside the hair follicles. This method proved to be successful, and was first applied in 1996. In 1997, the United States Food and Drug Administration approved this tactic of hair removal. As this technology continued to be researched, laser hair removal became more effective and efficient; thus, it is now a common method in removing hair for long periods of time. Procedure The primary principle behind laser hair removal is selective photothermolysis (SPTL), the matching of a specific wavelength of light and pulse duration to obtain optimal effect on a targeted tissue with minimal effect on surrounding tissue. Lasers can cause localized damage by selectively heating dark target matter, melanin, thereby heating up the basal stem cells in the follicle which causes hair growth, the hair follicle, while not directly heating the rest of the skin. Light is absorbed by dark objects but reflected by light objects and water, so laser energy can be absorbed by dark material in the hair or skin, with much more speed and intensity than just the skin without any dark adult hair or melanin. Melanin is considered the primary chromophore for all hair removal lasers currently on the market. Melanin occurs naturally in the skin and gives skin and hair their color. There are two types of melanin in hair. Eumelanin gives hair brown or black color, while pheomelanin gives hair blonde or red color. Because of the selective absorption of photons of laser light, only hair with color such as black, brown, or reddish-brown hair or dirty blonde can be removed. White hair, light blonde and strawberry blonde hair does not respond well. Laser works best with dark coarse hair. Light skin and dark hair are an ideal combination, being most effective and producing the best results, but lasers such as the Nd:YAG laser are able to target black hair in patients with dark skin with some success. Hair removal lasers have been in use since 1997 and have been approved for "permanent hair reduction" in the United States by the Food and Drug Administration (FDA). Under the FDA's definition, "permanent" hair reduction is the long-term, stable reduction in the number of hairs regrowing after a treatment regime. Many patients experience complete regrowth of hair on their treated areas in the
Laser hair removal
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Membrane-associated transporter protein (MATP), also known as solute carrier family 45 member 2 (SLC45A2) or melanoma antigen AIM1, is a protein that in humans is encoded by the SLC45A2 gene. Function SLC45A2 is a transporter protein that mediates melanin synthesis. It may regulate the pH of the melanosome, affecting tyrosinase activity. SLC45A2 is also a melanocyte differentiation antigen that is expressed in a high percentage of melanoma cell lines. A similar sequence gene in medaka fish, 'B,' encodes a transporter that mediates melanin synthesis. Mutations in this gene are a cause of oculocutaneous albinism type 4. Alternative splicing results in multiple transcript variants encoding different isoforms. Protein expression is localized to the melanosome, and analysis of the by knockdown of RNA expression leads to altered melanosome pH potentially altering tyrosinase function by affecting copper binding. In melanocytic cell types, the SLC45A2 gene is regulated by microphthalmia-associated transcription factor. SLC45A2 has been found to play a role in pigmentation in several species. In humans, it has been identified as a factor in the light skin of Europeans and as an ancestry-informative marker (AIM) for distinguishing Sri Lankan from European ancestry. Mutations in the gene have also been identified as the cause of human Type IV oculocutaneous albinism. SLC45A2 is the so-called cream gene responsible in horses for buckskin, palomino and cremello coloration, while a mutation in this gene underlies the white tiger variant. In dogs a mutation to this gene causes white fur, pink skin, and blue eyes. SLC45A2 was identified as a melanoma tumor-associated antigen with high tumor specificity and reduced potential for autoimmune toxicity, and is currently in clinical development as a target for T-cell based immunotherapy. See also Solute carrier family References Further reading External links GeneReviews/NCBI/NIH/UW entry on Oculocutaneous Albinism Type 4 Solute carrier family
Membrane-associated transporter protein