Homosexual behavior in animals is sexual behavior among non-human species that is interpreted as homosexual or bisexual. This may include same-sex sexual activity, courtship, affection, pair bonding, and parenting among same-sex animal pairs.[1][2][3][4] Research indicates that various forms of this are found in every major geographic region and every major animal group. The sexual behavior of non-human animals takes many different forms, even within the same species, though homosexual behavior is best known from social species.

Scientists perceive homosexual behavior in animals to different degrees. The motivations for and implications of these behaviors have yet to be fully understood, since most species have yet to be fully studied.[5] According to Bruce Bagemihl, the animal kingdom engages in homosexual behavior "with much greater sexual diversity including homosexual, bisexual and nonreproductive sex than the scientific community and society at large have previously been willing to accept."[6] Bagemihl adds, however, that this is "necessarily an account of human interpretations of these phenomena".[7] Simon LeVay introduced caveat that "[a]lthough homosexual behavior is very common in the animal world, it seems to be very uncommon that individual animals have a long-lasting predisposition to engage in such behavior to the exclusion of heterosexual activities. Thus, a homosexual orientation, if one can speak of such thing in animals, seems to be a rarity."[8] One species in which exclusive homosexual orientation occurs, however, is that of domesticated sheep (Ovis aries).[9][10] "About 10% of rams (males), refuse to mate with ewes (females) but do readily mate with other rams."[10]

According to Bagemihl (1999), same-sex behavior (comprising courtship, sexual, pair-bonding, and parental activities) has been documented in over 450 species of animals worldwide.[11]

The term homosexual was coined by Karl-Maria Kertbeny in 1868 to describe same-sex sexual attraction and sexual behavior in humans.[12] Its use in animal studies has been controversial for two main reasons: animal sexuality and motivating factors have been and remain poorly understood, and the term has strong cultural implications in western society that are irrelevant for species other than humans.[13] Thus homosexual behavior has been given a number of terms over the years. According to Bruce Bagemihl, when describing animals, the term homosexual is preferred over gay, lesbian, and other terms currently in use, as these are seen as even more bound to human homosexuality.[14]

Bailey et al. says: "Homosexual: in animals, this has been used to refer to same-sex behavior that is not sexual in character (e.g. homosexual tandem running in termites), same-sex courtship or copulatory behavior occurring over a short period of time (e.g. homosexual mounting in cockroaches and rams) or long-term pair bonds between same-sex partners that might involve any combination of courting, copulating, parenting and affectional behaviors (e.g. homosexual pair bonds in gulls). In humans, the term is used to describe individual sexual behaviors as well as long-term relationships, but in some usages connotes a gay or lesbian social identity. Scientific writing would benefit from reserving this anthropomorphic term for humans and not using it to describe behavior in other animals, because of its deeply rooted context in human society".[15]

Animal preference and motivation is always inferred from behavior. In wild animals, researchers will as a rule not be able to map the entire life of an individual, and must infer from frequency of single observations of behavior. The correct usage of the term homosexual is that an animal exhibits homosexual behavior or even same-sex sexual behavior; however, this article conforms to the usage by modern research,[14][16][17][18][pageneeded][19]applying the term homosexuality to all sexual behavior (copulation, genital stimulation, mating games and sexual display behavior) between animals of the same sex. In most instances, it is presumed that the homosexual behavior is but part of the animal's overall sexual behavioral repertoire, making the animal "bisexual" rather than "homosexual" as the terms are commonly understood in humans.[18][pageneeded], but cases of homosexual preference and exclusive homosexual pairs are known.[20]

The observation of homosexual behavior in animals can be seen as both an argument for and against the acceptance of homosexuality in humans, and has been used especially against the claim that it is a peccatum contra naturam ("sin against nature"). For instance, homosexuality in animals was cited by the American Psychiatric Association and other groups in their amici curiae brief to the United States Supreme Court in Lawrence v. Texas, which ultimately struck down the sodomy laws of 14 states.[21][22]

A majority of the research available concerning homosexual behavior in animals lacks specification between animals that exclusively exhibit same-sex tendencies and those that participate in heterosexual and homosexual mating activities interchangeably. This lack of distinction has led to differing opinions and conflicting interpretations of collected data amongst scientists and researchers. For instance, Bruce Bagemihl, author of the book Biological Exuberence: Animal Homosexuality and Natural Diversity, emphasizes that there are no anatomical or endocrinological differences between exclusively homosexual and exclusively heterosexual animal pairs.[23][pageneeded] However, if the definition of "homosexual behavior" is made to include animals that participate in both same-sex and opposite-sex mating activities, hormonal differences have been documented among key sex hormones, such as testosterone and estradiol, when compared to those who participate solely in heterosexual mating.[24]

Many of the animals used in laboratory-based studies of homosexuality do not appear to spontaneously exhibit these tendencies often in the wild. Such behavior is often elicited and exaggerated by the researcher during experimentation through the destruction of a portion of brain tissue, or by exposing the animal to high levels of steroid hormones prenatally.[25][pageneeded] Information gathered from these studies is limited when applied to spontaneously occurring same-sex behavior in animals outside of the laboratory.[25]

Homosexual behaviour in animals has been discussed since classical antiquity. The earliest written mention of animal homosexuality appears to date back to 2,300 years ago, when Aristotle (384322 BC) described copulation between pigeons, partridges and quails of the same sex.[26] The Hieroglyphics of Horapollo, written in the 4th century AD by the Egyptian writer Horapollo, mentions "hermaphroditism" in hyenas and homosexuality in partridges.[26] The first review of animal homosexuality was written by the zoologist Ferdinand Karsch-Haack in 1900.[26]

Until recent times, the presence of same-sex sexual behavior was not "officially" observed on a large scale, possibly due to observer bias caused by social attitudes to same-sex sexual behavior,[27] innocent confusion, lack of interest, distaste, scientists fearing loss of their grants or even from a fear of "being ridiculed by their colleagues".[28][29] Georgetown University biologist Janet Mann states "Scientists who study the topic are often accused of trying to forward an agenda, and their work can come under greater scrutiny than that of their colleagues who study other topics."[30] They also noted "Not every sexual act has a reproductive function ... that's true of humans and non-humans."[30] It appears to be widespread amongst social birds and mammals, particularly the sea mammals and the primates. The true extent of homosexuality in animals is not known. While studies have demonstrated homosexual behavior in a number of species, Petter Bckman, the scientific advisor of the exhibition Against Nature? in 2007, speculated that the true extent of the phenomenon may be much larger than was then recognized:

No species has been found in which homosexual behaviour has not been shown to exist, with the exception of species that never have sex at all, such as sea urchins and aphis. Moreover, a part of the animal kingdom is hermaphroditic, truly bisexual. For them, homosexuality is not an issue.[28]

An example of overlooking homosexual behavior is noted by Bagemihl describing mating giraffes where nine out of ten pairings occur between males:

Every male that sniffed a female was reported as sex, while anal intercourse with orgasm between males was only "revolving around" dominance, competition or greetings.[31]

Some researchers believe this behavior to have its origin in male social organization and social dominance, similar to the dominance traits shown in prison sexuality. Others, particularly Bagemihl, Joan Roughgarden, Thierry Lod[32] and Paul Vasey suggest the social function of sex (both homosexual and heterosexual) is not necessarily connected to dominance, but serves to strengthen alliances and social ties within a flock. Others have argued that social organization theory is inadequate because it cannot account for some homosexual behaviors, for example, penguin species where male individuals mate for life and refuse to pair with females when given the chance.[33][34] While reports on many such mating scenarios are still only anecdotal, a growing body of scientific work confirms that permanent homosexuality occurs not only in species with permanent pair bonds,[19] but also in non-monogamous species like sheep.

One report on sheep cited below states:

Approximately 8% of rams exhibit sexual preferences [that is, even when given a choice] for male partners (male-oriented rams) in contrast to most rams, which prefer female partners (female-oriented rams). We identified a cell group within the medial preoptic area/anterior hypothalamus of age-matched adult sheep that was significantly larger in adult rams than in ewes...[35]

In fact, apparent homosexual individuals are known from all of the traditional domestic species, from sheep, cattle and horses to cats, dogs and budgerigars.[36][pageneeded]

A definite physiological explanation or reason for homosexual activity in animal species has not been agreed upon by researchers in the field. Numerous scholars are of the opinion that varying levels (either higher or lower) of the sex hormones in the animal,[37] in addition to the size of the animal's gonads,[24] play a direct role in the sexual behavior and preference exhibited by that animal. Others firmly argue no evidence to support these claims exists when comparing animals of a specific species exhibiting homosexual behavior exclusively and those that do not. Ultimately, empirical support from comprehensive endocrinological studies exist for both interpretations.[37][38] Researchers found no evidence of differences in the measurements of the gonads, or the levels of the sex hormones of exclusively homosexual western gulls and ring-billed gulls.[39] However, when analyzing these differences in bisexual rams, males were found to have lower levels of testosterone and estradiol in their blood, as well as smaller gonads than their heterosexual counterpart.[citation needed]

Additional studies pertaining to hormone involvement in homosexual behavior indicate that when administering treatments of testosterone and estradiol to female heterosexual animals, the elevated hormone levels increase the likelihood of homosexual behavior. Additionally, boosting the levels of sex hormones during an animal's pregnancy appears to increase the likelihood of it birthing a homosexual offspring.[37]

Researchers found that disabling the fucose mutarotase (FucM) gene in laboratory mice which influences the levels of estrogen to which the brain is exposed caused the female mice to behave as if they were male as they grew up. "The mutant female mouse underwent a slightly altered developmental programme in the brain to resemble the male brain in terms of sexual preference" said Professor Chankyu Park of the Korea Advanced Institute of Science and Technology in Daejon, South Korea, who led the research. His most recent findings have been published in the BMC Genetics journal on July 7, 2010.[40][41] Another study found that by manipulating a gene in fruit flies (Drosophila), homosexual behavior appeared to have been induced. However, in addition to homosexual behavior, several abnormal behaviors were also exhibited apparently due to this mutation.[42]

In March 2011, research showed that serotonin is involved in the mechanism of sexual orientation of mice.[43][44] A study conducted on fruit flies found that inhibiting the dopamine neurotransmitter inhibited lab-induced homosexual behavior.[45]

An estimated one-quarter of all black swans pairings are of males. They steal nests, or form temporary threesomes with females to obtain eggs, driving away the female after she lays the eggs. The males spent time in each other's society, guarded the common territory, performed greeting ceremonies before each other, and (in the reproductive period) pre-marital rituals, and if one of the birds tried to sit on the other, an intense fight began.[1][2] More of their cygnets survive to adulthood than those of different-sex pairs, possibly due to their superior ability to defend large portions of land. The same reasoning has been applied to male flamingo pairs raising chicks.[46][47]

Female albatross, on the north-western tip of the island of Oahu, Hawaii, form pairs for co-growing offspring. On the observed island, the number of females considerably exceeds the number of males (59% N=102/172), so 31% of females, after mating with males, create partnerships for hatching and feeding chicks. Compared to male-female couples female partnerships have a lower hatching rate (41% vs 87%) and lower overall reproductive success (31% vs. 67%).[48]

Research has shown that the environmental pollutant methylmercury can increase the prevalence of homosexual behavior in male American white ibis. The study involved exposing chicks in varying dosages to the chemical and measuring the degree of homosexual behavior in adulthood. The results discovered was that as the dosage was increased the likelihood of homosexual behavior also increased. The endocrine blocking feature of mercury has been suggested as a possible cause of sexual disruption in other bird species.[49][50]

Mallards form male-female pairs only until the female lays eggs, at which time the male leaves the female. Mallards have rates of male-male sexual activity that are unusually high for birds, in some cases, as high as 19% of all pairs in a population.[36][pageneeded] Kees Moeliker of the Natural History Museum Rotterdam has observed one male mallard engage in homosexual necrophilia.[51]

Penguins have been observed to engage in homosexual behaviour since at least as early as 1911. George Murray Levick, who documented this behaviour in Adlie penguins at Cape Adare, described it as "depraved". The report was considered too shocking for public release at the time, and was suppressed. The only copies that were made available privately to researchers were translated into Greek, to prevent this knowledge becoming more widely known. The report was unearthed only a century later, and published in Polar Record in June 2012.[52]

In early February 2004 the New York Times reported that Roy and Silo, a male pair of chinstrap penguins in the Central Park Zoo in New York City had successfully hatched and fostered a female chick from a fertile egg they had been given to incubate.[21] Other penguins in New York zoos have also been reported to have formed same-sex pairs.[53][54]

In Odense Zoo in Denmark, a pair of male king penguins adopted an egg that had been abandoned by a female, proceeding to incubate it and raise the chick.[55][56]Zoos in Japan and Germany have also documented homosexual male penguin couples.[33][34] The couples have been shown to build nests together and use a stone as a substitute for an egg. Researchers at Rikkyo University in Tokyo found 20 homosexual pairs at 16 major aquariums and zoos in Japan.

The Bremerhaven Zoo in Germany attempted to encourage reproduction of endangered Humboldt penguins by importing females from Sweden and separating three male pairs, but this was unsuccessful. The zoo's director said that the relationships were "too strong" between the homosexual pairs.[57] German gay groups protested at this attempt to break up the male-male pairs[58] but the zoo's director was reported as saying "We don't know whether the three male pairs are really homosexual or whether they have just bonded because of a shortage of females ... nobody here wants to forcibly separate homosexual couples."[59]

A pair of male Magellanic penguins who had shared a burrow for six years at the San Francisco Zoo and raised a surrogate chick, split when the male of a pair in the next burrow died and the female sought a new mate.[60]

Buddy and Pedro, a pair of male African penguins, were separated by the Toronto Zoo to mate with female penguins.[61][62] Buddy has since paired off with a female.[62]

Suki and Chupchikoni are two female African penguins that pair bonded at the Ramat Gan Safari in Israel. Chupchikoni was assumed to be male until her blood was tested.[63]

In 2014 Jumbs and Hurricane, two Humboldt penguins at Wingham Wildlife Park became the center of international media attention as two male penguins who had pair bonded a number of years earlier and then successfully hatched and reared an egg given to them as surrogate parents after the mother abandoned it halfway through incubation.[64]

In 1998 two male griffon vultures named Dashik and Yehuda, at the Jerusalem Biblical Zoo, engaged in "open and energetic sex" and built a nest. The keepers provided the couple with an artificial egg, which the two parents took turns incubating; and 45 days later, the zoo replaced the egg with a baby vulture. The two male vultures raised the chick together.[65] A few years later, however, Yehuda became interested in a female vulture that was brought into the aviary. Dashik became depressed, and was eventually moved to the zoological research garden at Tel Aviv University where he too set up a nest with a female vulture.[66]

Two male vultures at the Allwetter Zoo in Muenster built a nest together, although they were picked on and their nest materials were often stolen by other vultures. They were eventually separated to try to promote breeding by placing one of them with female vultures, despite the protests of German homosexual groups.[67]

Both male and female pigeons sometimes exhibit homosexual behavior. In addition to sexual behavior, same-sex pigeon pairs will build nests, and hens will lay (infertile) eggs and attempt to incubate them.[citation needed]

The Amazon river dolphin or boto has been reported to form up in bands of 35 individuals engaging in sexual activity. The groups usually comprise young males and sometimes one or two females. Sex is often performed in non-reproductive ways, using snout, flippers and genital rubbing, without regard to gender.[68] In captivity, they have been observed to sometimes perform homosexual and heterosexual penetration of the blowhole, a hole homologous with the nostril of other mammals, making this the only known example of nasal sex in the animal kingdom.[68][69] The males will sometimes also perform sex with males from the tucuxi species, a type of small porpoise.[68]

Courtship, mounting, and full anal penetration between bulls has been noted to occur among American bison. The Mandan nation Okipa festival concludes with a ceremonial enactment of this behavior, to "ensure the return of the buffalo in the coming season".[70] Also, mounting of one female by another (known as "bulling") is extremely common among cattle. The behaviour is hormone driven and synchronizes with the emergence of estrus (heat), particularly in the presence of a bull.

More than 20 species of bat have been documented to engage in homosexual behavior.[26][71] Bat species that have been observed engaging in homosexual behavior in the wild include:[26]

Bat species that have been observed engaging in homosexual behavior in captivity include the Comoro flying fox (Pteropus livingstonii), the Rodrigues flying fox (Pteropus rodricensis) and the common vampire bat (Desmodus rotundus).[26]

Homosexual behavior in bats has been categorized into 6 groups: mutual homosexual grooming and licking, homosexual masturbation, homosexual play, homosexual mounting, coercive sex, and cross-species homosexual sex.[26][71]

In the wild, the grey-headed flying fox (Pteropus poliocephalus) engages in allogrooming wherein one partner licks and gently bites the chest and wing membrane of the other partner. Both sexes display this form of mutual homosexual grooming and it is more common in males. Males often have erect penises while they are mutually grooming each other. Like opposite-sex grooming partners, same-sex grooming partners continuously utter a pre-copulation call, which is described as a "pulsed grating call," while engaged in this activity.[26][71]

In wild Bonin flying foxes (Pteropus pselaphon), males perform fellatio or 'male-male genital licking' on other males. Malemale genital licking events occur repeatedly several times in the same pair, and reciprocal genital licking also occurs. The male-male genital licking in these bats is considered a sexual behavior. Allogrooming in Bonin flying foxes has never been observed, hence the male-male genital licking in this species does not seem to be a by-product of allogrooming, but rather a behavior of directly licking the male genital area, independent of allogrooming.[71] In captivity, same-sex genital licking has been observed among males of the Comoro flying fox (Pteropus livingstonii) as well as among males of the common vampire bat (Desmodus rotundus).[26][71]

In wild Indian flying foxes (Pteropus giganteus), males often mount one another, with erections and thrusting, while play-wrestling.[26] Males of the long-fingered bat (Myotis capaccinii) have been observed in the same position of male-female mounting, with one gripping the back of the others fur. A similar behavior was also observed in the common bent-wing bat (Miniopterus schreibersii).[26]

In wild little brown bats (Myotis lucifugus), males often mount other males (and females) during late autumn and winter, when many of the mounted individuals are torpid.[26] 35% of matings during this period are homosexual.[72] These coercive copulations usually include ejaculation and the mounted bat often makes a typical copulation call consisting of a long squawk.[26] Similarly, in hibernacula of the common noctule (Nyctalus noctula), active males were observed to wake up from lethargy on a warm day and engage in mating with lethargic males and (active or lethargic) females. The lethargic males, like females, called out loudly and presented their buccal glands with opened mouth during copulation.[26]

Vesey-Fitzgerald (1949) observed homosexual behaviours in all 12 British bat species known at the time: Homosexuality is common in the spring in all species, and, since the males are in full possession of their powers, I suspect throughout the summer...I have even seen homosexuality between Natterer's and Daubenton's bats (Myotis nattereri and M. daubentonii)."[26]

Dolphins of several species engage in homosexual acts, though it is best studied in the bottlenose dolphins.[36][pageneeded] Sexual encounters between females take the shape of "beak-genital propulsion", where one female inserts her beak in the genital opening of the other while swimming gently forward.[73] Between males, homosexual behaviour includes rubbing of genitals against each other, which sometimes leads to the males swimming belly to belly, inserting the penis in the others genital slit and sometimes anus.[74]

Janet Mann, Georgetown University professor of biology and psychology, argues that the strong personal behavior among male dolphin calves is about bond formation and benefits the species in an evolutionary context.[75] She cites studies showing that these dolphins later in life as adults are in a sense bisexual, and the male bonds forged earlier in life work together for protection as well as locating females to reproduce with. Confrontations between flocks of bottlenose dolphins and the related species Atlantic spotted dolphin will sometimes lead to cross-species homosexual behaviour between the males rather than combat.[76]

African and Asian males will engage in same-sex bonding and mounting. Such encounters are often associated with affectionate interactions, such as kissing, trunk intertwining, and placing trunks in each other's mouths. Male elephants, who often live apart from the general herd, often form "companionships", consisting of an older individual and one or sometimes two younger males with sexual behavior being an important part of the social dynamic. Unlike heterosexual relations, which are always of a fleeting nature, the relationships between males may last for years. The encounters are analogous to heterosexual bouts, one male often extending his trunk along the other's back and pushing forward with his tusks to signify his intention to mount. Same-sex relations are common and frequent in both sexes, with Asiatic elephants in captivity devoting roughly 45% of sexual encounters to same-sex activity.[77]

Male giraffes have been observed to engage in remarkably high frequencies of homosexual behavior. After aggressive "necking", it is common for two male giraffes to caress and court each other, leading up to mounting and climax. Such interactions between males have been found to be more frequent than heterosexual coupling.[78] In one study, up to 94% of observed mounting incidents took place between two males. The proportion of same sex activities varied between 30 and 75%, and at any given time one in twenty males were engaged in non-combative necking behavior with another male. Only 1% of same-sex mounting incidents occurred between females.[79]

Olympic marmot (left) and Hoary marmot (right).

Homosexual behavior is quite common in wild marmots.[80] In Olympic marmots (Marmota olympus) and Hoary Marmots (Marmota caligata), females often mount other females as well as engage in other affectionate and sexual behaviors with females of the same species.[80] They display a high frequency of these behaviors especially when they are in heat.[80][81] A homosexual encounter often begins with a greeting interaction in which one female nuzzles her nose on the other females cheek or mouth, or both females touch noses or mouths. Additionally, a female may gently chew on the ear or neck of her partner, who responds by raising her tail. The first female may sniff the other's genital region or nuzzle that region with her mouth. She may then proceed to mount the other female, during which the mounting female gently grasps the mounted female's dorsal neck fur in her jaws while thrusting. The mounted female arches her back and holds her tail to one side to facilitate their sexual interaction.[80][82]

Both male and female lions have been seen to interact homosexually.[83][84] Male lions pair-bond for a number of days and initiate homosexual activity with affectionate nuzzling and caressing, leading to mounting and thrusting. About 8% of mountings have been observed to occur with other males. Pairings between females are held to be fairly common in captivity but have not been observed in the wild.

European polecats Mustela putorius were found to engage homosexually with non-sibling animals. Exclusive homosexuality with mounting and anal penetration in this solitary species serves no apparent adaptive function.[85][pageneeded]

Bonobos, which have a matriarchal society, unusual among apes, are a fully bisexual speciesboth males and females engage in heterosexual and homosexual behavior, being noted for femalefemale homosexuality in particular, including[86] between juveniles and adults. Roughly 60% of all bonobo sexual activity occurs between two or more females. While the homosexual bonding system in bonobos represents the highest frequency of homosexuality known in any primate species, homosexuality has been reported for all great apes (a group which includes humans), as well as a number of other primate species.[87][88][89][pageneeded][90][86][91][92][93][94]

Dutch primatologist Frans de Waal on observing and filming bonobos noted that there were two reasons to believe sexual activity is the bonobo's answer to avoiding conflict. Anything that arouses the interest of more than one bonobo at a time, not just food, tends to result in sexual contact. If two bonobos approach a cardboard box thrown into their enclosure, they will briefly mount each other before playing with the box. Such situations lead to squabbles in most other species. But bonobos are quite tolerant, perhaps because they use sex to divert attention and to defuse tension.

Bonobo sex often occurs in aggressive contexts totally unrelated to food. A jealous male might chase another away from a female, after which the two males reunite and engage in scrotal rubbing. Or after a female hits a juvenile, the latter's mother may lunge at the aggressor, an action that is immediately followed by genital rubbing between the two adults.[95]

With the Japanese macaque, also known as the "snow monkey", same-sex relations are frequent, though rates vary between troops. Females will form "consortships" characterized by affectionate social and sexual activities. In some troops up to one quarter of the females form such bonds, which vary in duration from a few days to a few weeks. Often, strong and lasting friendships result from such pairings. Males also have same-sex relations, typically with multiple partners of the same age. Affectionate and playful activities are associated with such relations.[96]

Homosexual behavior forms part of the natural repertoire of sexual or sociosexual behavior of orangutans. Male homosexual behavior occurs both in the wild and in captivity, and it occurs in both adolescent and mature individuals. Homosexual behavior in orangutans is not an artifact of captivity or contact with humans.[97]

Among monkeys[clarification needed], Lionel Tiger and Robin Fox conducted a study on how Depo-Provera contraceptives lead to decreased male attraction to females.[98]

Ovis aries has attracted much attention due to the fact that around 810% of rams have an exclusive homosexual orientation.[9][99][100][101][102] Furthermore, around 1822% of rams are bisexual.[100]

An October 2003 study by Dr. Charles E. Roselli et al. (Oregon Health and Science University) states that homosexuality in male sheep (found in 8% of rams) is associated with a region in the rams' brains which the authors call the "ovine Sexually Dimorphic Nucleus" (oSDN) which is half the size of the corresponding region in heterosexual male sheep.[35] Scientists found that, "The oSDN in rams that preferred females was significantly larger and contained more neurons than in male-oriented rams and ewes. In addition, the oSDN of the female-oriented rams expressed higher levels of aromatase, a substance that converts testosterone to estradiol, a form of estrogen which is believed to facilitate typical male sexual behaviors. Aromatase expression was no different between male-oriented rams and ewes."

"The dense cluster of neurons that comprise the oSDN express cytochrome P450 aromatase. Aromatase mRNA levels in the oSDN were significantly greater in female-oriented rams than in ewes, whereas male-oriented rams exhibited intermediate levels of expression." These results suggest that "... naturally occurring variations in sexual partner preferences may be related to differences in brain anatomy and its capacity for estrogen synthesis."[35] As noted before, given the potential unagressiveness of the male population in question, the differing aromatase levels may also have been evidence of aggression levels, not sexuality. It should also be noted that the results of this study have not been confirmed by other studies.

The Merck Manual of Veterinary Medicine appears to consider homosexuality among sheep as a routine occurrence and an issue to be dealt with as a problem of animal husbandry.[103]

Homosexual courtship and sexual activity routinely occur among rams of wild sheep species, such as Bighorn sheep (Ovis canadensis), Thinhorn sheep (Ovis dalli), mouflons and urials (Ovis orientalis).[104] Usually a higher ranking older male courts a younger male using a sequence of stylized movements. To initiate homosexual courtship, a courting male approaches the other male with his head and neck lowered and extended far forward in what is called the 'low-stretch' posture. He may combine this with the 'twist,' in which the courting male sharply rotates his head and points his muzzle toward the other male, often while flicking his tongue and making grumbling sounds. The courting male also often performs a 'foreleg kick,' in which he snaps his front leg up against the other males belly or between his hind legs. He also occasionally sniffs and nuzzles the other males genital area and may perform the flehmen response. Thinhorn rams additionally lick the penis of the male they are courting. In response, the male being courted may rub his cheeks and forehead on the courting males face, nibble and lick him, rub his horns on the courting males neck, chest, or shoulders, and develop an erection. Males of another wild sheep species, the Asiatic Mouflons, perform similar courtship behaviors towards fellow males.[104]

Sexual activity between wild males typically involves mounting and anal intercourse. In Thinhorn sheep, genital licking also occurs. During mounting, the larger male usually mounts the smaller male by rearing up on his hind legs and placing his front legs on his partners flanks. The mounting male usually has an erect penis and accomplishes full anal penetration while performing pelvic thrusts that may lead to ejaculation. The mounted male arches his back to facilitate the copulation. Homosexual courtship and sexual activity can also take place in groups composed of three to ten wild rams clustered together in a circle. These non-aggressive groups are called 'huddles' and involve rams rubbing, licking, nuzzling, horning, and mounting each other. Female Mountain sheep also engage in occasional courtship activities with one another and in sexual activities such as licking each others genitals and mounting.[104]

The family structure of the spotted hyena is matriarchal, and dominance relationships with strong sexual elements are routinely observed between related females. Due largely to the female spotted hyena's unique urogenital system, which looks more like a penis rather than a vagina, early naturalists thought hyenas were hermaphroditic males who commonly practiced homosexuality.[105][not in citation given] Early writings such as Ovid's Metamorphoses and the Physiologus suggested that the hyena continually changed its sex and nature from male to female and back again. In Paedagogus, Clement of Alexandria noted that the hyena (along with the hare) was "quite obsessed with sexual intercourse". Many Europeans associated the hyena with sexual deformity, prostitution, deviant sexual behavior, and even witchcraft.

The reality behind the confusing reports is the sexually aggressive behavior between the females, including mounting between females. Research has shown that "in contrast to most other female mammals, female Crocuta are male-like in appearance, larger than males, and substantially more aggressive,"[106] and they have "been masculinized without being defeminized".[105][not in citation given]

Study of this unique genitalia and aggressive behavior in the female hyena has led to the understanding that more aggressive females are better able to compete for resources, including food and mating partners.[105][107] Research has shown that "elevated levels of testosterone in utero"[108] contribute to extra aggressiveness; both males and females mount members of both the same and opposite sex,[108][109] who in turn are possibly acting more submissive because of lower levels of testosterone in utero.[106]

Parthenogenesis. Several species of whiptail lizard (especially in the genus Aspidoscelis) consist only of females that have the ability to reproduce through parthenogenesis.[110] Females engage in sexual behavior to stimulate ovulation, with their behavior following their hormonal cycles; during low levels of estrogen, these (female) lizards engage in "masculine" sexual roles. Those animals with currently high estrogen levels assume "feminine" sexual roles. Some parthenogenetic lizards that perform the courtship ritual have greater fertility than those kept in isolation due to an increase in hormones triggered by the sexual behaviors. So, even though asexual whiptail lizards populations lack males, sexual stimuli still increase reproductive success. From an evolutionary standpoint, these females are passing their full genetic code to all of their offspring (rather than the 50% of genes that would be passed in sexual reproduction). Certain species of gecko also reproduce by parthenogenesis.[111]

"True" homosexuality in lizards. Some species of sexually reproducing geckos have been found to display homosexual behavior, e.g the day geckos Phelsuma laticauda and Phelsuma cepediana.[112]

Jonathan, the world's oldest tortoise (an Aldabra giant tortoise), had been mating with another tortoise named Frederica since 1991. In 2017, it was discovered that Frederica was actually probably male all along, and was renamed Frederic.[113]

There is evidence of same-sex sexual behavior in at least 110 species of insects and arachnids.[114] Scharf et al. says: "Males are more frequently involved in same-sex sexual (SSS) behavior in the laboratory than in the field, and isolation, high density, and exposure to female pheromones increase its prevalence. SSS behavior is often shorter than the equivalent heterosexual behavior. Most cases can be explained via mistaken identification by the active (courting/mounting) male. Passive males often resist courting/mating attempts".[114]

Scharf et al. continues: "SSS behavior has been reported in most insect orders, and Bagemihl (1999) provides a list of ~100 species of insects demonstrating such behavior. Yet, this list lacks detailed descriptions, and a more comprehensive summary of its prevalence in invertebrates, as well as ethology, causes, implications, and evolution of this behavior, remains lacking".[114]

Male homosexuality has been inferred in several species of dragonflies (the order Odonata). The cloacal pinchers of male damselflies and dragonflies inflict characteristic head damage to females during sex. A survey of 11 species of damsel and dragonflies[115][116] has revealed such mating damages in 20 to 80% of the males too, indicating a fairly high occurrence of sexual coupling between males.

Male Drosophila melanogaster flies bearing two copies of a mutant allele in the fruitless gene court and attempt to mate exclusively with other males.[20] The genetic basis of animal homosexuality has been studied in the fly Drosophila melanogaster.[117] Here, multiple genes have been identified that can cause homosexual courtship and mating.[118] These genes are thought to control behavior through pheromones as well as altering the structure of the animal's brains.[119][120] These studies have also investigated the influence of environment on the likelihood of flies displaying homosexual behavior.[121][122]

Male bed bugs (Cimex lectularius) are sexually attracted to any newly fed individual and this results in homosexual mounting. This occurs in heterosexual mounting by the traumatic insemination in which the male pierces the female abdomen with his needle-like penis. In homosexual mating this risks abdominal injuries as males lack the female counteradaptive spermalege structure. Males produce alarm pheromones to reduce such homosexual mating.

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Homosexual behavior in animals - Wikipedia

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The old rats appeared newly invigorated after receiving their injections. As hoped, the cardiac stem cells improved heart function yet also provided additional benefits. The rats' fur fur, shaved for surgery, grew back more quickly than expected, and their chromosomal telomeres, which commonly shrink with age, lengthened.

The old rats receiving the cardiac stem cells also had increased stamina overall, exercising more than before the infusion.

"It's extremely exciting," said Dr. Eduardo Marbn, primary investigator on the research and director of the Cedars-Sinai Heart Institute. Witnessing "the systemic rejuvenating effects," he said, "it's kind of like an unexpected fountain of youth."

"We've been studying new forms of cell therapy for the heart for some 12 years now," Marbn said.

Some of this research has focused on cardiosphere-derived cells.

"They're progenitor cells from the heart itself," Marbn said. Progenitor cells are generated from stem cells and share some, but not all, of the same properties. For instance, they can differentiate into more than one kind of cell like stem cells, but unlike stem cells, progenitor cells cannot divide and reproduce indefinitely.

Since heart failure with preserved ejection fraction is similar to aging, Marbn decided to experiment on old rats, ones that suffered from a type of heart problem "that's very typical of what we find in older human beings: The heart's stiff, and it doesn't relax right, and it causes fluid to back up some," Marbn explained.

He and his team injected cardiosphere-derived cells from newborn rats into the hearts of 22-month-old rats -- that's elderly for a rat. Similar old rats received a placebo injection of saline solution. Then, Marbn and his team compared both groups to young rats that were 4 months old. After a month, they compared the rats again.

Even though the cells were injected into the heart, their effects were noticeable throughout the body, Marbn said

"The animals could exercise further than they could before by about 20%, and one of the most striking things, especially for me (because I'm kind of losing my hair) the animals ... regrew their fur a lot better after they'd gotten cells" compared with the placebo rats, Marbn said.

The rats that received cardiosphere-derived cells also experienced improved heart function and showed longer heart cell telomeres.

Why did it work?

The working hypothesis is that the cells secrete exosomes, tiny vesicles that "contain a lot of nucleic acids, things like RNA, that can change patterns of the way the tissue responds to injury and the way genes are expressed in the tissue," Marbn said.

It is the exosomes that act on the heart and make it better as well as mediating long-distance effects on exercise capacity and hair regrowth, he explained.

Looking to the future, Marbn said he's begun to explore delivering the cardiac stem cells intravenously in a simple infusion -- instead of injecting them directly into the heart, which would be a complex procedure for a human patient -- and seeing whether the same beneficial effects occur.

Dr. Gary Gerstenblith, a professor of medicine in the cardiology division of Johns Hopkins Medicine, said the new study is "very comprehensive."

"Striking benefits are demonstrated not only from a cardiac perspective but across multiple organ systems," said Gerstenblith, who did not contribute to the new research. "The results suggest that stem cell therapies should be studied as an additional therapeutic option in the treatment of cardiac and other diseases common in the elderly."

Todd Herron, director of the University of Michigan Frankel Cardiovascular Center's Cardiovascular Regeneration Core Laboratory, said Marbn, with his previous work with cardiac stem cells, has "led the field in this area."

"The novelty of this bit of work is, they started to look at more precise molecular mechanisms to explain the phenomenon they've seen in the past," said Herron, who played no role in the new research.

One strength of the approach here is that the researchers have taken cells "from the organ that they want to rejuvenate, so that makes it likely that the cells stay there in that tissue," Herron said.

He believes that more extensive study, beginning with larger animals and including long-term followup, is needed before this technique could be used in humans.

"We need to make sure there's no harm being done," Herron said, adding that extending the lifetime and improving quality of life amounts to "a tradeoff between the potential risk and the potential good that can be done."

Capicor hasn't announced any plans to do studies in aging, but the possibility exists.

After all, the cells have been proven "completely safe" in "over 100 human patients," so it would be possible to fast-track them into the clinic, Marbn explained: "I can't tell you that there are any plans to do that, but it could easily be done from a safety viewpoint."

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Cardiac stem cells rejuvenate rats' aging hearts ... - CNN

Recommendation and review posted by Jack Burke

1. Cellular Dynamics International, Owned by FujiFilm Holdings

Founded in 2004 and listed on NASDAQ in July 2013, Cellular Dynamics International (CDI) is headquartered in Madison, Wisconsin. The company is known for its extremely robust patent portfolio containing more than 900 patents.

According to the company, CDI is the worlds largest producer of fully functional human cells derived from induced pluripotent stem (iPS) cells.[1] Their trademarked, iCell Cardiomyocytes, derived from iPSCs, are human cardiac cells used to aid drug discovery, improve the predictability of a drugs worth, and screen for toxicity. In addition, CDI provides: iCell Endothelial Cells for use in vascular-targeted drug discovery and tissue regeneration, iCell Hepatocytes, and iCell Neurons for pre-clinical drug discovery, toxicity testing, disease prediction, and cellular research.[2]

Induced pluripotent stem cells were first produced in 2006 from mouse cells and in 2007 from human cells, by Shinya Yamanaka at Kyoto University,[3] who also won the Nobel Prize in Medicine or Physiology for his work on iPSCs.[4] Yamanaka has ties to Cellular Dynamics International as a member of the scientific advisory board of iPS Academia Japan. IPS Academia Japan was originally established to manage the patents and technology of Yamanakas work, and is now the distributor of several of Cellular Dynamics products, including iCell Neurons, iCell Cardiomyocytes, and iCell Endothelial Cells.[5]

Importantly, in 2010 Cellular Dynamics became the first foreign company to be granted rights to use Yamanakas iPSC patent portfolio. Not only has CDI licensed rights to Yamanakas patents, but it also has a license to use Otsu, Japan-based Takara Bios RetroNectin product, which it uses as a tool to produce its iCell and MyCell products.[6]

Furthermore, in February 2015, Cellular Dynamics International announced it would be manufacturing cGMP HLA Superdonor stem cell lines that will support cellular therapy applications through genetic matching.[8] Currently, CDI has two HLA super donor cell lines that provide a partial HLA match to approximately 19% of the population within the U.S., and it aims to expand its master stem cell bank by collecting more donor cell lines that will cover 95% of the U.S. population.[9] The HLA super donor cell lines were manufactured using blood samples and used to produce pluripotent iPSC lines, giving the cells the capacity to differentiate into nearly any cell within the human body.

On March 30, 2015, Fujifilm Holdings Corporation announced that it was acquiring CDI for $307 million, allowing CDI to continue to run its operations in Madison, Wisconsin, and Novato, California as a consolidated subsidiary of Fujifilm.[14] A key benefit of the merger is that CDIs technology platform enables the production of high-quality fully functioning iPSCs (and other human cells) on an industrial scale, while Fujifilm has developed highly-biocompatible recombinant peptides that can be shaped into a variety of forms for use as a cellular scaffold in regenerative medicine when used in conjunction with CDIs products.[15]

Additionally, Fujifilm has been strengthening its presence in the regenerative medicine field over the past several years, including a recent A$4M equity stake in Cynata Therapeutics and an acquisition of Japan Tissue Engineering Co. Ltd. in December 2014. Most commonly called J-TEC, Japan Tissue Engineering Co. Ltd. successfully launched the first two regenerative medicine products in the country of Japan. According to Kaz Hirao, CEO of CDI, It is very important for CDI to get into the area of therapeutic products, and we can accelerate this by aligning it with strategic and technical resources present within J-TEC.

Kaz Hirao also states, For our Therapeutic businesses, we will aim to file investigational new drugs (INDs) with the U.S. FDA for the off-the-shelf iPSC-derived allogeneic therapeutic products. Currently, we are focusing on retinal diseases, heart disorders, Parkinsons disease, and cancers. For those four indicated areas, we would like to file several INDs within the next five years.

Finally, in September 2015, CDI again strengthened its iPS cell therapy capacity by setting up a new venture, Opsis Therapeutics. Opsis is focused on discovering and developing novel medicines to treat retinal diseases and is a partnership with Dr. David Gamm, the pioneer of iPS cell-derived retinal differentiation and transplantation.

In summary, several key events indicate CDIs commitment to developing iPS cell therapeutics, including:

Australian stem cell company Cynata Therapeutics (ASX:CYP) is taking a unique approach by creating allogeneic iPSC derived mesenchyal stem cell (MSCs) on a commercial scale. Cynatas Cymerus technology utilizes iPSCs provided by Cellular Dynamics International, a Fujifilm company, as the starting material for generating mesenchymoangioblasts (MCAs), and subsequently, for manufacturing clinical-grade MSCs. According to Cynatas Executive Chairman Stewart Washer who was interviewed by The Life Sciences Report, The Cymerus technology gets around the loss of potency with the unlimited iPS cellor induced pluripotent stem cellwhich is basically immortal.

On January 19, 2017, Fujifilm took an A$3.97 million (10%) strategic equity stake in Cynata, positioning the parties to collaborate on the further development and commercialization of Cynatas lead Cymerus therapeutic MSC product CYP-001 for graft-versus-host disease (GvHD). (CYP-001 is the product designation unique to the GVHD indication). The Fujifilm partnership also includes potential future upfront and milestone payments in excess of A$60 million and double-digit royalties on CYP-001 product net sales for Cynata Therapeutics, as well as a strategic relationship for the potential future manufacture of CYP-001 and certain rights to other Cynata technology.

One of the key inventors of Cynatas technology is Igor Slukvin, MD, Ph.D., Scientific Founder of Cellular Dynamics International (CDI) and Cynata Therapeutics. Dr. Slukvin has released more than 70 publications about stem cell topics, including the landmark article in Cell describing the now patented Cymerus technique. Dr. Slukvins co-inventor is Dr. James Thomson, the first person to isolate an embryonic stem cell (ESC) and one of the first people to create a human induced pluripotent stem cell (hiPSC). Dr. James Thompson was the Founder of CDI in 2004.

There are three strategic connections between Cellular Dynamics International (CDI) and Cynata Therapeutics, which include:

Recently, Cynata received advice from the UK Medicines and Healthcare products Regulatory Agency (MHRA) that its Phase I clinical trial application has been approved, titled An Open-Label Phase 1 Study to Investigate the Safety and Efficacy of CYP-001 for the Treatment of Adults With Steroid-Resistant Acute Graft Versus Host Disease. It will be the worlds first clinical trial involving a therapeutic product derived from allogeneic (unrelated to the patient) induced pluripotent stem cells (iPSCs).

Participants for Cynatas upcoming Phase I clinical trial will be adults who have undergone an allogeneic haematopoietic stem cell transplant (HSCT) to treat a hematological disorder and subsequently been diagnosed with steroid-resistant Grade II-IV GvHD. The primary objective of the trial is to assess safety and tolerability, while the secondary objective is to evaluate the efficacy of two infusions of CYP-001 in adults with steroid-resistant GvHD.

Using Professor Yamanakas Nobel Prize-winning achievement of ethically uncontentious iPSCs and CDIs high-quality iPSCs as source material, Cynata has achieved two world firsts:

Cynata has also released promising pre-clinical data in Asthma, Myocardial Infarction (Heart Attack), and Critical Limb Ischemia.

There are four key advantages of Cynatas proprietary Cymerus MSC manufacturing platform. Because the proprietary Cymerus technology allows nearly unlimited production of MSCs from a single iPSC donor, there is batch-to-batch uniformity. Utilizing a consistent starting material allows for a standardized cell manufacturing process and a consistent cell therapy product. Unlike other companies involved with MSC manufacturing, Cynata does not require a constant stream of new donors in order to source fresh stem cells for its cell manufacturing process, nor does it require the massive expansion of MSCs necessitated by reliance on freshly isolated donations.

Finally, Cynata has achieved a cost-savings advantage through its unique approach to MSC manufacturing. Its proprietary Cymerus technology addresses a critical shortcoming in existing methods of production of MSCs for therapeutic use, which is the ability to achieve economic manufacture at commercial scale.

On June 22, 2016, RIKEN announced that it is resuming its retinal induced pluripotent stem cell (iPSC) study in partnership with Kyoto University.

2013 was the first time in which clinical research involving transplant of iPSCs into humans was initiated, led by Masayo Takahashi of the RIKEN Center for Developmental Biology (CDB) in Kobe, Japan. Dr. Takahashi and her team were investigating the safety of iPSC-derived cell sheets in patients with wet-type age-related macular degeneration. Although the trial was initiated in 2013 and production of iPSCs from patients began at that time, it was not until August of 2014 that the first patient, a Japanese woman, was implanted with retinal tissue generated using iPSCs derived from her own skin cells.

A team of three eye specialists, led by Yasuo Kurimoto of the Kobe City Medical Center General Hospital, implanted a 1.3 by 3.0mm sheet of iPSC-derived retinal pigment epithelium cells into the patients retina.[196] Unfortunately, the study was suspended in 2015 due to safety concerns. As the lab prepared to treat the second trial participant, Yamanakas team identified two small genetic changes in the patients iPSCs and the retinal pigment epithelium (RPE) cells derived from them. Therefore, it is major news that the RIKEN Institute will now be resuming the worlds first clinical study involving the use of iPSC-derived cells in humans.

According to the Japan Times, this attempt at the clinical study will involve allogeneic rather than autologous iPSC-derived cells for purposes of cost and time efficiency. Specifically, the researchers will be developing retinal tissues from iPS cells supplied by Kyoto Universitys Center for iPS Cell Research and Application, an institution headed by Nobel prize winner Shinya Yamanaka. To learn about this announcement, view this article from Asahi Shimbun, a Tokyo- based newspaper.

In November 2015 Astellas Pharma announced it was acquiring Ocata Therapeutics for $379M. Ocata Therapeutics is a biotechnology company that specializes in the development of cellular therapies, using both adult and human embryonic stem cells to develop patient-specific therapies. The companys main laboratory and GMP facility are in Marlborough, Massachusetts, and its corporate offices are in Santa Monica, California.

When a number of private companies began to explore the possibility of using artificially re-manufactured iPSCs for therapeutic purposes, one such company that was ready to capitalize on the breakthrough technology was Ocata Therapeutics, at the time called Advanced Cell Technology. In 2010, the company announced that it had discovered several problematic issues while conducting experiments for the purpose of applying for U.S. Food and Drug Administration approval to use iPSCs in therapeutic applications. Concerns such as premature cell death, mutation into cancer cells, and low proliferation rates were some of the problems that surfaced. [17]

As a result, the company shifted its induced pluripotent stem cell approach to producing iPS cell-derived human platelets, as one of the benefits of a platelet-based product is that platelets do not contain nuclei, and therefore, cannot divide or carry genetic information. While the companys Induced Pluripotent Stem Cell-Derived Human Platelet Program received a great deal of media coverage in late 2012, including being awarded the December 2012 honor of being named one of the 10 Ideas that Will Shape the Year by New Scientist Magazine,[178]. Unfortunately, the company did not succeed in moving the concept through to clinical testing in 2013.

Nonetheless, Astellas is clearly continuing to develop Ocatas pluripotent stem cell technologies involving embryonic stem cells (ESCs) and induced pluripotent stem cells (iPS cells). In a November 2015 presentation by Astellas President and CEO, Yoshihiko Hatanaka, he indicated that the company will aim to develop an Ophthalmic Disease Cell Therapy Franchise based around its embryonic stem cell (ESC) and induced pluripotent stem cell (iPS cell) technology. [19]

What other companies are developing iPSC derived therapeutics and products? Share your thoughts in the comments below.

BioInformant is the first and only market research firm to specialize in the stem cell industry. BioInformant research has been cited by major news outlets that include the Wall Street Journal, Nature Biotechnology, Xconomy, and Vogue Magazine. Serving Fortune 500 leaders that include GE Healthcare, Pfizer, and Goldman Sachs. BioInformant is your global leader in stem cell industry data.

Footnotes[1] CellularDynamics.com (2014). About CDI. Available at: http://www.cellulardynamics.com/about/index.html. Web. 1 Apr. 2015.[2] Ibid.[3] Takahashi K, Yamanaka S (August 2006). Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 126 (4): 66376.[4] 2012 Nobel Prize in Physiology or Medicine Press Release. Nobelprize.org. Nobel Media AB 2013. Web. 7 Feb 2014. Available at: http://www.nobelprize.org/nobel_prizes/medicine/laureates/2012/press.html. Web. 1 Apr. 2015.[5] Striklin, D (Jan 13, 2014). Three Companies Banking on Regenerative Medicine. Wall Street Cheat Sheet. Retrieved Feb 1, 2014 from, http://wallstcheatsheet.com/stocks/3-companies-banking-on-regenerative-medicine.html/?a=viewall.%5B6%5D Striklin, D (2014). Three Companies Banking on Regenerative Medicine. Wall Street Cheat Sheet [Online]. Available at: http://wallstcheatsheet.com/stocks/3-companies-banking-on-regenerative-medicine.html/?a=viewall. Web. 1 Apr. 2015.[7] Cellular Dynamics International (July 30, 2013). Cellular Dynamics International Announces Closing of Initial Public Offering [Press Release]. Retrieved from http://www.cellulardynamics.com/news/pr/2013_07_30.html.%5B8%5D Investors.cellulardynamics.com,. Cellular Dynamics Manufactures Cgmp HLA Superdonor Stem Cell Lines To Enable Cell Therapy With Genetic Matching (NASDAQ:ICEL). N.p., 2015. Web. 7 Mar. 2015.[9] Ibid.[10] Cellulardynamics.com,. Cellular Dynamics | Mycell Products. N.p., 2015. Web. 7 Mar. 2015.[11]Sirenko, O. et al. Multiparameter In Vitro Assessment Of Compound Effects On Cardiomyocyte Physiology Using Ipsc Cells.Journal of Biomolecular Screening 18.1 (2012): 39-53. Web. 7 Mar. 2015.[12] Sciencedirect.com,. Prevention Of -Amyloid Induced Toxicity In Human Ips Cell-Derived Neurons By Inhibition Of Cyclin-Dependent Kinases And Associated Cell Cycle Events. N.p., 2015. Web. 7 Mar. 2015.[13] Sciencedirect.com,. HER2-Targeted Liposomal Doxorubicin Displays Enhanced Anti-Tumorigenic Effects Without Associated Cardiotoxicity. N.p., 2015. Web. 7 Mar. 2015.[14] Cellular Dynamics International, Inc. Fujifilm Holdings To Acquire Cellular Dynamics International, Inc.. GlobeNewswire News Room. N.p., 2015. Web. 7 Apr. 2015.[15] Ibid.[16] Cyranoski, David. Japanese Woman Is First Recipient Of Next-Generation Stem Cells. Nature (2014): n. pag. Web. 6 Mar. 2015.[17] Advanced Cell Technologies (Feb 11, 2011). Advanced Cell and Colleagues Report Therapeutic Cells Derived From iPS Cells Display Early Aging [Press Release]. Available at: http://www.advancedcell.com/news-and-media/press-releases/advanced-cell-and-colleagues-report-therapeutic-cells-derived-from-ips-cells-display-early-aging/.%5B18%5D Advanced Cell Technology (Dec 20, 2012). New Scientist Magazine Selects ACTs Induced Pluripotent Stem (iPS) Cell-Derived Human Platelet Program As One of 10 Ideas That Will Shape The Year [Press Release]. Available at: http://articles.latimes.com/2009/mar/06/science/sci-stemcell6. Web. 9 Apr. 2015.[19] Astellas Pharma (2015). Acquisition of Ocata Therapeutics New Step Forward in Ophthalmology with Cell Therapy Approach. Available at: https://www.astellas.com/en/corporate/news/pdf/151110_2_Eg.pdf. Web. 29 Jan. 2017.

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Market Players Developing iPS Cell Therapies - BioInformant

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Stem cell facts

What are stem cells?

Stem cells are cells that have the potential to develop into many different or specialized cell types. Stem cells can be thought of as primitive, "unspecialized" cells that are able to divide and become specialized cells of the body such as liver cells, muscle cells, blood cells, and other cells with specific functions. Stem cells are referred to as "undifferentiated" cells because they have not yet committed to a developmental path that will form a specific tissue or organ. The process of changing into a specific cell type is known as differentiation. In some areas of the body, stem cells divide regularly to renew and repair the existing tissue. The bone marrow and gastrointestinal tract are examples of areas in which stem cells function to renew and repair tissue.

The best and most readily understood example of a stem cell in humans is that of the fertilized egg, or zygote. A zygote is a single cell that is formed by the union of a sperm and ovum. The sperm and the ovum each carry half of the genetic material required to form a new individual. Once that single cell or zygote starts dividing, it is known as an embryo. One cell becomes two, two become four, four become eight, eight become sixteen, and so on, doubling rapidly until it ultimately grows into an entire sophisticated organism composed of many different kinds of specialized cells. That organism, a person, is an immensely complicated structure consisting of many, many, billions of cells with functions as diverse as those of your eyes, your heart, your immune system, the color of your skin, your brain, etc. All of the specialized cells that make up these body systems are descendants of the original zygote, a stem cell with the potential to ultimately develop into all kinds of body cells. The cells of a zygote are totipotent, meaning that they have the capacity to develop into any type of cell in the body.

The process by which stem cells commit to become differentiated, or specialized, cells is complex and involves the regulation of gene expression. Research is ongoing to further understand the molecular events and controls necessary for stem cells to become specialized cell types.

Stem Cells:One of the human body's master cells, with the ability to grow into any one of the body's more than 200 cell types.

All stem cells are unspecialized (undifferentiated) cells that are characteristically of the same family type (lineage). They retain the ability to divide throughout life and give rise to cells that can become highly specialized and take the place of cells that die or are lost.

Stem cells contribute to the body's ability to renew and repair its tissues. Unlike mature cells, which are permanently committed to their fate, stem cells can both renew themselves as well as create new cells of whatever tissue they belong to (and other tissues).

Why are stem cells important?

Stem cells represent an exciting area in medicine because of their potential to regenerate and repair damaged tissue. Some current therapies, such as bone marrow transplantation, already make use of stem cells and their potential for regeneration of damaged tissues. Other therapies that are under investigation involve transplanting stem cells into a damaged body part and directing them to grow and differentiate into healthy tissue.

Embryonic stem cells

During the early stages of embryonic development the cells remain relatively undifferentiated (immature) and appear to possess the ability to become, or differentiate, into almost any tissue within the body. For example, cells taken from one section of an embryo that might have become part of the eye can be transferred into another section of the embryo and could develop into blood, muscle, nerve, or liver cells.

Cells in the early embryonic stage are totipotent (see above) and can differentiate to become any type of body cell. After about seven days, the zygote forms a structure known as a blastocyst, which contains a mass of cells that eventually become the fetus, as well as trophoblastic tissue that eventually becomes the placenta. If cells are taken from the blastocyst at this stage, they are known as pluripotent, meaning that they have the capacity to become many different types of human cells. Cells at this stage are often referred to as blastocyst embryonic stem cells. When any type of embryonic stem cells is grown in culture in the laboratory, they can divide and grow indefinitely. These cells are then known as embryonic stem cell lines.

Fetal stem cells

The embryo is referred to as a fetus after the eighth week of development. The fetus contains stem cells that are pluripotent and eventually develop into the different body tissues in the fetus.

Adult stem cells

Adult stem cells are present in all humans in small numbers. The adult stem cell is one of the class of cells that we have been able to manipulate quite effectively in the bone marrow transplant arena over the past 30 years. These are stem cells that are largely tissue-specific in their location. Rather than typically giving rise to all of the cells of the body, these cells are capable of giving rise only to a few types of cells that develop into a specific tissue or organ. They are therefore known as multipotent stem cells. Adult stem cells are sometimes referred to as somatic stem cells.

The best characterized example of an adult stem cell is the blood stem cell (the hematopoietic stem cell). When we refer to a bone marrow transplant, a stem cell transplant, or a blood transplant, the cell being transplanted is the hematopoietic stem cell, or blood stem cell. This cell is a very rare cell that is found primarily within the bone marrow of the adult.

One of the exciting discoveries of the last years has been the overturning of a long-held scientific belief that an adult stem cell was a completely committed stem cell. It was previously believed that a hematopoietic, or blood-forming stem cell, could only create other blood cells and could never become another type of stem cell. There is now evidence that some of these apparently committed adult stem cells are able to change direction to become a stem cell in a different organ. For example, there are some models of bone marrow transplantation in rats with damaged livers in which the liver partially re-grows with cells that are derived from transplanted bone marrow. Similar studies can be done showing that many different cell types can be derived from each other. It appears that heart cells can be grown from bone marrow stem cells, that bone marrow cells can be grown from stem cells derived from muscle, and that brain stem cells can turn into many types of cells.

Peripheral blood stem cells

Most blood stem cells are present in the bone marrow, but a few are present in the bloodstream. This means that these so-called peripheral blood stem cells (PBSCs) can be isolated from a drawn blood sample. The blood stem cell is capable of giving rise to a very large number of very different cells that make up the blood and immune system, including red blood cells, platelets, granulocytes, and lymphocytes.

All of these very different cells with very different functions are derived from a common, ancestral, committed blood-forming (hematopoietic), stem cell.

Umbilical cord stem cells

Blood from the umbilical cord contains some stem cells that are genetically identical to the newborn. Like adult stem cells, these are multipotent stem cells that are able to differentiate into certain, but not all, cell types. For this reason, umbilical cord blood is often banked, or stored, for possible future use should the individual require stem cell therapy.

Induced pluripotent stem cells

Induced pluripotent stem cells (iPSCs) were first created from human cells in 2007. These are adult cells that have been genetically converted to an embryonic stem celllike state. In animal studies, iPSCs have been shown to possess characteristics of pluripotent stem cells. Human iPSCs can differentiate and become multiple different fetal cell types. iPSCs are valuable aids in the study of disease development and drug treatment, and they may have future uses in transplantation medicine. Further research is needed regarding the development and use of these cells.

Why is there controversy surrounding the use of stem cells?

Embryonic stem cells and embryonic stem cell lines have received much public attention concerning the ethics of their use or non-use. Clearly, there is hope that a large number of treatment advances could occur as a result of growing and differentiating these embryonic stem cells in the laboratory. It is equally clear that each embryonic stem cell line has been derived from a human embryo created through in-vitro fertilization (IVF) or through cloning technologies, with all the attendant ethical, religious, and philosophical problems, depending upon one's perspective.

What are some stem cell therapies that are currently available?

Routine use of stem cells in therapy has been limited to blood-forming stem cells (hematopoietic stem cells) derived from bone marrow, peripheral blood, or umbilical cord blood. Bone marrow transplantation is the most familiar form of stem cell therapy and the only instance of stem cell therapy in common use. It is used to treat cancers of the blood cells (leukemias) and other disorders of the blood and bone marrow.

In bone marrow transplantation, the patient's existing white blood cells and bone marrow are destroyed using chemotherapy and radiation therapy. Then, a sample of bone marrow (containing stem cells) from a healthy, immunologically matched donor is injected into the patient. The transplanted stem cells populate the recipient's bone marrow and begin producing new, healthy blood cells.

Umbilical cord blood stem cells and peripheral blood stem cells can also be used instead of bone marrow samples to repopulate the bone marrow in the process of bone marrow transplantation.

In 2009, the California-based company Geron received clearance from the U. S. Food and Drug Administration (FDA) to begin the first human clinical trial of cells derived from human embryonic stem cells in the treatment of patients with acute spinal cord injury.

What are experimental treatments using stem cells and possible future directions for stem cell therapy?

Stem cell therapy is an exciting and active field of biomedical research. Scientists and physicians are investigating the use of stem cells in therapies to treat a wide variety of diseases and injuries. For a stem cell therapy to be successful, a number of factors must be considered. The appropriate type of stem cell must be chosen, and the stem cells must be matched to the recipient so that they are not destroyed by the recipient's immune system. It is also critical to develop a system for effective delivery of the stem cells to the desired location in the body. Finally, devising methods to "switch on" and control the differentiation of stem cells and ensure that they develop into the desired tissue type is critical for the success of any stem cell therapy.

Researchers are currently examining the use of stem cells to regenerate damaged or diseased tissue in many conditions, including those listed below.

References

REFERENCE:

"Stem Cell Information." National Institutes of Health.

Originally posted here:
Stem Cells - MedicineNet

Recommendation and review posted by Rebecca Evans

After three bitter years and tens of millions of dollars in legal fees, the epic battle over who owns one of the most common methods for editing the DNA in any living thing is finally drawing to a close. On Monday, the US Court of Appeals for the Federal Circuit issued a decisive ruling on the rights to Crispr-Cas9 gene editingawarding crucial intellectual property spoils to scientists at the Broad Institute of Cambridge, Massachusetts.

The fight for Crispr-Cas9which divided the research community and triggered an uncomfortable discussion about science for personal profit versus public goodhas dramatically shaped how biology research turns into real-world products. But its long-term legacy is not what happened in the courtroom, but what took place in the labs: A wealth of innovation that is now threatening to make Cas9 obsolete.

This latest legal decision, which upholds a 2017 ruling by the US Patent and Trademark Office, was an expected one, given how rarely such rulings are overturned. And it more or less seals defeat for researchers at the University of California Berkeley, who also have claims to invention of the world-remaking technology.

The Broad celebrated the win while calling for a cease-fire, saying it was time to work together to ensure wide, open access to this transformative technology. UCs general counsel, Charles F. Robinson, struck a less conciliatory note, saying in a statement that the university was evaluating further litigation options. Those could include a rehearing from the same court or appeal to the Supreme Court.

But legal experts say the chances of either happening are vanishingly slim. It is very possible that there is no path forward for Berkeley in regards to broad patents covering Crispr-Cas9 at this point , says Jacob Sherkow a scholar of patent law at New York Law School who has closely followed the case. In addition to the Broad Institutes claims, UC-Berkeley also has to contend with another foundational patent for Crispr-Cas9 gene editing filed before anyone else in March 2012, by Virginijus iknys, a Lithuanian scientist who shares the prestigious Kavli Prize with Berkeleys Jennifer Doudna and The University of Viennas Emmanuelle Charpentier for their early work on Crispr. The USPTO has since granted his patent. UC didnt know about it at the time of its own filing because of an 18-month secrecy statute surrounding new applications. If this was a choose-your-own-adventure book, they just turned all the wrong pages, says Sherkow.

The University of California isnt the only loser here; the companies that already placed bets on it being the patent victor must now tread a difficult though not impassable IP landscape. That includes Intellia and Crispr Therapeuticscompanies cofounded by Doudna and Charpentier respectivelywhich are both developing Crispr treatments for human disease. The two firms released a joint statement Monday afternoon underscoring their faith in the strength and scope of UCs foundational IP. A spokesperson for Intellia also said in an email that the Federal Circuit decision will not impact the companys freedom to operate going forward.

For all the ferocity that fueled the fight from its outset, Mondays decision was met with muted interest from inside the halls of science to the crowded trading floors of Wall Street. Thats because a lot has changed since the first gene editing pioneers filed the original Crispr-Cas9 patents. In 2012, Cas9 was the entire Crispr universe. That little enzyme powered all the promise of Crispr gene editing, and the stakes for owning it couldnt have been higher. Scientists didnt yet know that biology would prove to be more creative than patent lawyers. They still had no notion of the vast constellations of constructs and enzymes that could be engineered, evolved in a lab, or harvested from the wild to replace Cas9.

Since then though, the fast-moving field of Crispr biology has yielded more than just alternative pairs of molecular scissors. Researchers have updated the Crispr system to manipulate the code of life in myriad novel waysfrom swapping out individual DNA letters to temporarily flipping genes on and off to detecting dangerous infections. And theyve unearthed dozens of Crispr enzymes of still unknown functions that might one day solve problems scientists havent even thought of yet.

The rush of discoveries and inventions has led to a full-blown patent race, says Sherkow, with anyone who found any new variation racing to file IP protections. The irony is that as the universe of Crispr expands, owning a part of it becomes less and less valuable. Twenty years from now, when the umpteenth drug gets approved using Crispr and some nuclease named Cas132013, people are going to look back on this patent battle and think, what a godawful waste of money, says Sherkow.

He expects that the field will eventually reach a point where the value of each new Crispr patent is so low that researchers dont bother going through all the paperwork and spending the thousands of dollars necessary to file an application. Already, biotechnologists are beginning to learn this lesson in adjacent fields; a land grab for patents is not the only way to go.

The Biobricks Foundation is a nonprofit dedicated to supporting the development of an open-source biotechnology commons. In 2015, it created a legal framework for scientists to put their discoveries in the public domain, safeguarding them from being patented elsewhere, and ensuring that anyone can access them. So far, the organization has begun to stockpile gene sequences for useful tools like fluorescent proteins. Linda Kahl, Biobricks senior counsel and a director there, says theyre still waiting for a group to design an open-source Crispr system. Thats a gauntlet thats in front of researchers, she says. With the ashes of the patent fight still glowing, it might be too soon to expect anyone to give a Crispr tool away for free just yet. But it probably wont take long.

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Stem cell, an undifferentiated cell that can divide to produce some offspring cells that continue as stem cells and some cells that are destined to differentiate (become specialized). Stem cells are an ongoing source of the differentiated cells that make up the tissues and organs of animals and plants. There is great interest in stem cells because they have potential in the development of therapies for replacing defective or damaged cells resulting from a variety of disorders and injuries, such as Parkinson disease, heart disease, and diabetes. There are two major types of stem cells: embryonic stem cells and adult stem cells, which are also called tissue stem cells.

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cardiovascular disease: Cardiac stem cells

Cardiac stem cells, which have the ability to differentiate (specialize) into mature heart cells and therefore could be used to repair damaged or diseased heart tissue, have garnered significant interest in the development of treatments for heart disease and cardiac defects. Cardiac stem

Embryonic stem cells (often referred to as ES cells) are stem cells that are derived from the inner cell mass of a mammalian embryo at a very early stage of development, when it is composed of a hollow sphere of dividing cells (a blastocyst). Embryonic stem cells from human embryos and from embryos of certain other mammalian species can be grown in tissue culture.

The most-studied embryonic stem cells are mouse embryonic stem cells, which were first reported in 1981. This type of stem cell can be cultured indefinitely in the presence of leukemia inhibitory factor (LIF), a glycoprotein cytokine. If cultured mouse embryonic stem cells are injected into an early mouse embryo at the blastocyst stage, they will become integrated into the embryo and produce cells that differentiate into most or all of the tissue types that subsequently develop. This ability to repopulate mouse embryos is the key defining feature of embryonic stem cells, and because of it they are considered to be pluripotentthat is, able to give rise to any cell type of the adult organism. If the embryonic stem cells are kept in culture in the absence of LIF, they will differentiate into embryoid bodies, which somewhat resemble early mouse embryos at the egg-cylinder stage, with embryonic stem cells inside an outer layer of endoderm. If embryonic stem cells are grafted into an adult mouse, they will develop into a type of tumour called a teratoma, which contains a variety of differentiated tissue types.

Mouse embryonic stem cells are widely used to create genetically modified mice. This is done by introducing new genes into embryonic stem cells in tissue culture, selecting the particular genetic variant that is desired, and then inserting the genetically modified cells into mouse embryos. The resulting chimeric mice are composed partly of host cells and partly of the donor embryonic stem cells. As long as some of the chimeric mice have germ cells (sperm or eggs) that have been derived from the embryonic stem cells, it is possible to breed a line of mice that have the same genetic constitution as the embryonic stem cells and therefore incorporate the genetic modification that was made in vitro. This method has been used to produce thousands of new genetic lines of mice. In many such genetic lines, individual genes have been ablated in order to study their biological function; in others, genes have been introduced that have the same mutations that are found in various human genetic diseases. These mouse models for human disease are used in research to investigate both the pathology of the disease and new methods for therapy.

Extensive experience with mouse embryonic stem cells made it possible for scientists to grow human embryonic stem cells from early human embryos, and the first human stem cell line was created in 1998. Human embryonic stem cells are in many respects similar to mouse embryonic stem cells, but they do not require LIF for their maintenance. The human embryonic stem cells form a wide variety of differentiated tissues in vitro, and they form teratomas when grafted into immunosuppressed mice. It is not known whether the cells can colonize all the tissues of a human embryo, but it is presumed from their other properties that they are indeed pluripotent cells, and they therefore are regarded as a possible source of differentiated cells for cell therapythe replacement of a patients defective cell type with healthy cells. Large quantities of cells, such as dopamine-secreting neurons for the treatment of Parkinson disease and insulin-secreting pancreatic beta cells for the treatment of diabetes, could be produced from embryonic stem cells for cell transplantation. Cells for this purpose have previously been obtainable only from sources in very limited supply, such as the pancreatic beta cells obtained from the cadavers of human organ donors.

The use of human embryonic stem cells evokes ethical concerns, because the blastocyst-stage embryos are destroyed in the process of obtaining the stem cells. The embryos from which stem cells have been obtained are produced through in vitro fertilization, and people who consider preimplantation human embryos to be human beings generally believe that such work is morally wrong. Others accept it because they regard the blastocysts to be simply balls of cells, and human cells used in laboratories have not previously been accorded any special moral or legal status. Moreover, it is known that none of the cells of the inner cell mass are exclusively destined to become part of the embryo itselfall of the cells contribute some or all of their cell offspring to the placenta, which also has not been accorded any special legal status. The divergence of views on this issue is illustrated by the fact that the use of human embryonic stem cells is allowed in some countries and prohibited in others.

In 2009 the U.S. Food and Drug Administration approved the first clinical trial designed to test a human embryonic stem cell-based therapy, but the trial was halted in late 2011 because of a lack of funding and a change in lead American biotech company Gerons business directives. The therapy to be tested was known as GRNOPC1, which consisted of progenitor cells (partially differentiated cells) that, once inside the body, matured into neural cells known as oligodendrocytes. The oligodendrocyte progenitors of GRNOPC1 were derived from human embryonic stem cells. The therapy was designed for the restoration of nerve function in persons suffering from acute spinal cord injury.

Embryonic germ (EG) cells, derived from primordial germ cells found in the gonadal ridge of a late embryo, have many of the properties of embryonic stem cells. The primordial germ cells in an embryo develop into stem cells that in an adult generate the reproductive gametes (sperm or eggs). In mice and humans it is possible to grow embryonic germ cells in tissue culture with the appropriate growth factorsnamely, LIF and another cytokine called fibroblast growth factor.

Some tissues in the adult body, such as the epidermis of the skin, the lining of the small intestine, and bone marrow, undergo continuous cellular turnover. They contain stem cells, which persist indefinitely, and a much larger number of transit amplifying cells, which arise from the stem cells and divide a finite number of times until they become differentiated. The stem cells exist in niches formed by other cells, which secrete substances that keep the stem cells alive and active. Some types of tissue, such as liver tissue, show minimal cell division or undergo cell division only when injured. In such tissues there is probably no special stem-cell population, and any cell can participate in tissue regeneration when required.

The epidermis of the skin contains layers of cells called keratinocytes. Only the basal layer, next to the dermis, contains cells that divide. A number of these cells are stem cells, but the majority are transit amplifying cells. The keratinocytes slowly move outward through the epidermis as they mature, and they eventually die and are sloughed off at the surface of the skin. The epithelium of the small intestine forms projections called villi, which are interspersed with small pits called crypts. The dividing cells are located in the crypts, with the stem cells lying near the base of each crypt. Cells are continuously produced in the crypts, migrate onto the villi, and are eventually shed into the lumen of the intestine. As they migrate, they differentiate into the cell types characteristic of the intestinal epithelium.

Bone marrow contains cells called hematopoietic stem cells, which generate all the cell types of the blood and the immune system. Hematopoietic stem cells are also found in small numbers in peripheral blood and in larger numbers in umbilical cord blood. In bone marrow, hematopoietic stem cells are anchored to osteoblasts of the trabecular bone and to blood vessels. They generate progeny that can become lymphocytes, granulocytes, red blood cells, and certain other cell types, depending on the balance of growth factors in their immediate environment.

Work with experimental animals has shown that transplants of hematopoietic stem cells can occasionally colonize other tissues, with the transplanted cells becoming neurons, muscle cells, or epithelia. The degree to which transplanted hematopoietic stem cells are able to colonize other tissues is exceedingly small. Despite this, the use of hematopoietic stem cell transplants is being explored for conditions such as heart disease or autoimmune disorders. It is an especially attractive option for those opposed to the use of embryonic stem cells.

Bone marrow transplants (also known as bone marrow grafts) represent a type of stem cell therapy that is in common use. They are used to allow cancer patients to survive otherwise lethal doses of radiation therapy or chemotherapy that destroy the stem cells in bone marrow. For this procedure, the patients own marrow is harvested before the cancer treatment and is then reinfused into the body after treatment. The hematopoietic stem cells of the transplant colonize the damaged marrow and eventually repopulate the blood and the immune system with functional cells. Bone marrow transplants are also often carried out between individuals (allograft). In this case the grafted marrow has some beneficial antitumour effect. Risks associated with bone marrow allografts include rejection of the graft by the patients immune system and reaction of immune cells of the graft against the patients tissues (graft-versus-host disease).

Bone marrow is a source for mesenchymal stem cells (sometimes called marrow stromal cells, or MSCs), which are precursors to non-hematopoietic stem cells that have the potential to differentiate into several different types of cells, including cells that form bone, muscle, and connective tissue. In cell cultures, bone-marrow-derived mesenchymal stem cells demonstrate pluripotency when exposed to substances that influence cell differentiation. Harnessing these pluripotent properties has become highly valuable in the generation of transplantable tissues and organs. In 2008 scientists used mesenchymal stem cells to bioengineer a section of trachea that was transplanted into a woman whose upper airway had been severely damaged by tuberculosis. The stem cells were derived from the womans bone marrow, cultured in a laboratory, and used for tissue engineering. In the engineering process, a donor trachea was stripped of its interior and exterior cell linings, leaving behind a trachea scaffold of connective tissue. The stem cells derived from the recipient were then used to recolonize the interior of the scaffold, and normal epithelial cells, also isolated from the recipient, were used to recolonize the exterior of the trachea. The use of the recipients own cells to populate the trachea scaffold prevented immune rejection and eliminated the need for immunosuppression therapy. The transplant, which was successful, was the first of its kind.

Research has shown that there are also stem cells in the brain. In mammals very few new neurons are formed after birth, but some neurons in the olfactory bulbs and in the hippocampus are continually being formed. These neurons arise from neural stem cells, which can be cultured in vitro in the form of neurospheressmall cell clusters that contain stem cells and some of their progeny. This type of stem cell is being studied for use in cell therapy to treat Parkinson disease and other forms of neurodegeneration or traumatic damage to the central nervous system.

Following experiments in animals, including those used to create Dolly the sheep, there has been much discussion about the use of somatic cell nuclear transfer (SCNT) to create pluripotent human cells. In SCNT the nucleus of a somatic cell (a fully differentiated cell, excluding germ cells), which contains the majority of the cells DNA (deoxyribonucleic acid), is removed and transferred into an unfertilized egg cell that has had its own nuclear DNA removed. The egg cell is grown in culture until it reaches the blastocyst stage. The inner cell mass is then removed from the egg, and the cells are grown in culture to form an embryonic stem cell line (generations of cells originating from the same group of parent cells). These cells can then be stimulated to differentiate into various types of cells needed for transplantation. Since these cells would be genetically identical to the original donor, they could be used to treat the donor with no problems of immune rejection. Scientists generated human embryonic stem cells successfully from SCNT human embryos for the first time in 2013.

While promising, the generation and use of SCNT-derived embryonic stem cells is controversial for several reasons. One is that SCNT can require more than a dozen eggs before one egg successfully produces embryonic stem cells. Human eggs are in short supply, and there are many legal and ethical problems associated with egg donation. There are also unknown risks involved with transplanting SCNT-derived stem cells into humans, because the mechanism by which the unfertilized egg is able to reprogram the nuclear DNA of a differentiated cell is not entirely understood. In addition, SCNT is commonly used to produce clones of animals (such as Dolly). Although the cloning of humans is currently illegal throughout the world, the egg cell that contains nuclear DNA from an adult cell could in theory be implanted into a womans uterus and come to term as an actual cloned human. Thus, there exists strong opposition among some groups to the use of SCNT to generate human embryonic stem cells.

Due to the ethical and moral issues surrounding the use of embryonic stem cells, scientists have searched for ways to reprogram adult somatic cells. Studies of cell fusion, in which differentiated adult somatic cells grown in culture with embryonic stem cells fuse with the stem cells and acquire embryonic stem-cell-like properties, led to the idea that specific genes could reprogram differentiated adult cells. An advantage of cell fusion is that it relies on existing embryonic stem cells instead of eggs. However, fused cells stimulate an immune response when transplanted into humans, which leads to transplant rejection. As a result, research has become increasingly focused on the genes and proteins capable of reprogramming adult cells to a pluripotent state. In order to make adult cells pluripotent without fusing them to embryonic stem cells, regulatory genes that induce pluripotency must be introduced into the nuclei of adult cells. To do this, adult cells are grown in cell culture, and specific combinations of regulatory genes are inserted into retroviruses (viruses that convert RNA [ribonucleic acid] into DNA), which are then introduced to the culture medium. The retroviruses transport the RNA of the regulatory genes into the nuclei of the adult cells, where the genes are then incorporated into the DNA of the cells. About 1 out of every 10,000 cells acquires embryonic stem cell properties. Although the mechanism is still uncertain, it is clear that some of the genes confer embryonic stem cell properties by means of the regulation of numerous other genes. Adult cells that become reprogrammed in this way are known as induced pluripotent stem cells (iPS).

Similar to embryonic stem cells, induced pluripotent stem cells can be stimulated to differentiate into select types of cells that could in principle be used for disease-specific treatments. In addition, the generation of induced pluripotent stem cells from the adult cells of patients affected by genetic diseases can be used to model the diseases in the laboratory. For example, in 2008 researchers isolated skin cells from a child with an inherited neurological disease called spinal muscular atrophy and then reprogrammed these cells into induced pluripotent stem cells. The reprogrammed cells retained the disease genotype of the adult cells and were stimulated to differentiate into motor neurons that displayed functional insufficiencies associated with spinal muscular atrophy. By recapitulating the disease in the laboratory, scientists were able to study closely the cellular changes that occurred as the disease progressed. Such models promise not only to improve scientists understanding of genetic diseases but also to facilitate the development of new therapeutic strategies tailored to each type of genetic disease.

In 2009 scientists successfully generated retinal cells of the human eye by reprogramming adult skin cells. This advance enabled detailed investigation of the embryonic development of retinal cells and opened avenues for the generation of novel therapies for eye diseases. The production of retinal cells from reprogrammed skin cells may be particularly useful in the treatment of retinitis pigmentosa, which is characterized by the progressive degeneration of the retina, eventually leading to night blindness and other complications of vision. Although retinal cells also have been produced from human embryonic stem cells, induced pluripotency represents a less controversial approach. Scientists have also explored the possibility of combining induced pluripotent stem cell technology with gene therapy, which would be of value particularly for patients with genetic disease who would benefit from autologous transplantation.

Researchers have also been able to generate cardiac stem cells for the treatment of certain forms of heart disease through the process of dedifferentiation, in which mature heart cells are stimulated to revert to stem cells. The first attempt at the transplantation of autologous cardiac stem cells was performed in 2009, when doctors isolated heart tissue from a patient, cultured the tissue in a laboratory, stimulated cell dedifferentiation, and then reinfused the cardiac stem cells directly into the patients heart. A similar study involving 14 patients who underwent cardiac bypass surgery followed by cardiac stem cell transplantation was reported in 2011. More than three months after stem cell transplantation, the patients experienced a slight but detectable improvement in heart function.

Patient-specific induced pluripotent stem cells and dedifferentiated cells are highly valuable in terms of their therapeutic applications because they are unlikely to be rejected by the immune system. However, before induced pluripotent stem cells can be used to treat human diseases, researchers must find a way to introduce the active reprogramming genes without using retroviruses, which can cause diseases such as leukemia in humans. A possible alternative to the use of retroviruses to transport regulatory genes into the nuclei of adult cells is the use of plasmids, which are less tumourigenic than viruses.

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The coveted prize was awarded to a Scottish veterinarian, two scientists who championed an overlooked protein and a pioneering researcher who helped advance the careers of other women.

The Lasker Awards, which are among the nations most prestigious prizes in medicine, were awarded on Tuesday to a Scottish veterinarian who developed the drug propofol, two scientists who discovered the hidden influence of genetic packing material called histones and a researcher who in addition to doing groundbreaking work in RNA biology, paved the way for a new generation of female scientists.

The awards are given by the Albert and Mary Lasker Foundation and carry a prize of $250,000 for each of three categories. They are sometimes called the American Nobels because 87 of the Lasker recipients have gone on to win the Nobel Prize.

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He developed the drug propofol, now a widely used anesthetic that has transformed surgery.

Dr. Glen, the recipient of the Lasker-DeBakey Clinical Medical Research Award, is only the second veterinarian to win a Lasker in 73 years, according to the foundation.

A pharmaceutical career was an unlikely path for Dr. Glen, but the fact that he was interested in anesthesia was no surprise: for years, he had taught the subject to students at Glasgow Universitys veterinary school. I was anesthetizing dogs, cats, horses whatever animals came around, Dr. Glen said in an interview. Once he used anesthesia on a pelican to fix its beak.

When he arrived in the 1970s at ICI Pharmaceuticals, later acquired by AstraZeneca, Dr. Glen had turned his attention to humans and was on the hunt for a replacement for thiopentone, a widely used anesthetic that quickly put patients to sleep but often made them groggy afterward.

In lab tests on mice, he and his colleagues discovered that one of the companys existing compounds, propofol, seemed to work as well as thiopentone but wore off quickly, without the hangover effect of the earlier drug. Propofol was approved in 1986 in the United Kingdom and in the United States three years later.

The drug, known as the milk of amnesia because of its milky consistency, has since been used by hundreds of millions of patients and is credited with leading to the rapid expansion of outpatient surgery because patients recover so quickly.

In 2009, propofols reputation took a hit after Michael Jacksons personal physician, Dr. Conrad Murray, administered a lethal dose of the drug to the singer. Dr. Murray was convicted in 2011 on charges of involuntary manslaughter, and Dr. Glen said he followed the trial closely.

It was never intended to be used in that way, Dr. Glen said. But of the drugs broader success, he said, Im delighted that it has become so widely used.

She became a champion of women in her field and trained nearly 200 future scientists.

Dr. Steitz, the recipient of the Lasker-Koshland Award for Special Achievement in Medical Science, said winning the award is particularly significant because it signals how far she has come since her days as an undergraduate lab technician in the early 1960s.

When I started out being excited by science but seeing that there werent any women scientists I thought I had no prospects whatsoever, she said in an interview. The one thing that I really wanted was to have the respect of my peers for the scientific contributions I made, and for my participation in the scientific community.

More than four decades later, Dr. Steitz has her own lab at Yale University and her work has led to several breakthroughs in the understanding of RNA, a type of molecule that carries out many tasks in the cell, such as helping to read the information in our genes.

One of her biggest discoveries was particles made up of RNA molecules and proteins, known as small nuclear ribonucleoproteins, or snRNPs for short. Theyre scattered throughout cells and among other things, they help cut messenger RNA into pieces, some of which get pasted back together. This process, called splicing, is essential to the process of making proteins from genes. This discovery led to an entire new field of research in cell biology.

She was an author of a 2007 National Academy of Sciences report that recommended specific steps for maximizing the potential of women in academic science and engineering. Since then, she gives talks about how to encourage more women in science and is also being recognized for her work as a mentor. She has trained almost 200 students and postdoctoral fellows, according to the Lasker foundation.

Of the 360 papers that have come from her laboratory, 60 do not include her name, a gesture of generosity that reflects her belief that students and postdoctoral fellows who work completely independently should be allowed to publish on their own, according to the Lasker foundations citation.

In an interview, Dr. Steitz downplayed this detail. She said in her early days running her own lab, she frequently left her name off papers because she was following in the scientific tradition she had learned as a young researcher.

As for her role as an activist, I sort of feel a little embarrassed by that, because there are so many women that have done so much more, she said. What she has done, she said is to be a good citizen and try to help women and other underrepresented people to fulfill their potential.

They took a new look at a protein once considered the packing material of DNA.

From opposite ends of the country, Dr. Allis, whose lab is at The Rockefeller University in New York, and Dr. Grunstein, at the University of California, Los Angeles, pioneered work that elevated the importance of histones, proteins in the chromosomes that previously had gone overlooked. They are the recipients of the Albert Lasker Basic Medical Research Award.

DNA molecules are so long that, if they were stretched from end to end, one strand would reach six feet. Histones are the proteins that coil and cram these strands into a microscopic cell and they were long seen as little more than DNA spools, part of the basic machinery of the cell.

I went into the field thinking, everyones working on gene activity, I want to work on packing material, Dr. Grunstein said in a video produced by the Lasker foundation. I didnt want to go the direction everyone else was going in.

What Dr. Grunstein and Dr. Allis discovered is that, in fact, histones play a crucial role in turning genes on and off, which allows each cell to do its assigned task. The two worked separately, Dr. Grunstein focusing on genetics, and Dr. Allis on biochemical processes.

While their award is for basic science, the practical implications for their discoveries are profound. Mistakes in setting this up seem to be very clearly causing cancer, Dr. Allis said in the video.

Drug developers used the evolving understanding of histones to come up with new treatments, including to treat cancer, such as Zolinza, sold by Merck. More are in the pipeline.

Its spawned really a whole new area of potential therapies in humans, and thats pretty rewarding, Dr. Allis said.

More coverage of the Lasker Awards

Katie Thomas covers the business of health care, with a focus on the drug industry. She started at The Times in 2008 as a sports reporter. @katie_thomas

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Lasker Awards Given for Work in Genetics, Anesthesia and ...

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Cardiac stem cell research has a turbulent history. Studies revealing the presence of regenerative progenitors in adult rodents hearts formed the basis of numerous clinical trials, but several experiments have cast doubt on these cells ability to produce new tissue. Some scientists are now lauding the results of a report published in April in Circulation as undeniable evidence against the idea that resident stem cells can give rise to new cardiomyocytes.

The concept of [many] clinical trials arose from the basic science in labs of a few individuals more than 15 years ago, and that basic science is whats now being called into question, says Jeffery Molkentin, a cardiovascular biologist at Cincinnati Childrens Hospital who penned an editorial about the latest work.

The first evidence supporting the notion of cardiac stem cells in adults emerged in the early 2000s, when researchers reported that cells derived from bone marrow or adult heart expressing the protein c-kit could give rise to new muscle tissue when injected into damaged myocardium in rodents. These studies caused some controversy right from the start, Molkentin says. The main reason that this struck a raw nerve with people is because we already know that heart, in human patients, doesnt regenerate itself after an infarct.

Early skepticism arose in 2004, when two separate groups of researchers published back-to-back papers refuting the claims that bone marrowderived c-kit cells could regenerate damaged heart tissue. Still, the concept of endogenous cardiac stem cells remained a mainstream idea until Molkentin and his colleagues published a study in 2014 reporting that c-kit cells in the adult mouse heart almost never produced new cardiomyocytes, says Bin Zhou, a cell biologist at the Chinese Academy of Sciences and a coauthor of the new study.

Although Molkentins findings were replicated shortly afterwards by two independent groups (including Zhous), some researchers held fast to the idea that cardiac progenitors could regenerate injured heart tissue. Earlier this year, a team of researchersincluding Bernardo Nadal-Ginard and Daniele Torella of Magna Graecia University in Italy and several other scientists who conducted the early work on c-kit cellspublished a paper reporting the flaws in the cell lineage tracing technique employed by Molkentin, Zhou, and their colleagues. For example, they noted that the method, which involved tagging c-kitexpressing cells and their progeny with a fluorescent marker, compromised the gene required to express the c-kit protein, impairing the progenitors regenerative abilities.

In the new Circulationstudy, Zhou and his colleagues used a different approach to examine endogenous stem cell populations in mice. Instead of tagging c-kit cells, the team applied a technique that would fluorescently label nonmyocytes and newly generated muscle cells a different color from existing myocytes. This method allowed the researchers to investigate all proposed stem cell populations, rather than specifically addressing c-kit cells. We wanted to ask the broader question of whether there are any stem cells in the adult heart, Zhou says.

These experiments revealed that, while nonmyocytes generate cardiomyocytes in mouse embryos, they do not give rise to new muscle cells in adult rodents hearts. The results also address the concerns raised about c-kit lineage tracing, Zhou tells The Scientist. We think our system can conclude that nonmyocytes cannot become myocytes in adults in homeostasis and after injury.

Torella says that hes not convinced by Zhous evidence. The main issue, he explains, is that the researchers did not explicitly test whether cardiac stem cells were indeed labeled as nonmyocytes to ensure that they were not inadvertently tagging them as myocytes instead.

Molkentin disagrees with this critique, stating that the only way the system would label a myocyte progenitor as a myocyte is if it was no longer a true stem cell, but instead an immature myocyte. Zhous group uses an exhausting and very rigorous genetic approach, he adds. My opinion is that we need to go back to the bench and conduct additional research to truly understand the mechanisms at play to better inform how we design the next generation of clinical trials.

Other scientists note that stem cells may not need to become new myocytes to help repair the injured heart. According to Phillip Yang, a cardiologist at Stanford University who did not take part in the work, many scientists now agree that stem cells are not regenerating damaged cardiomyocytes. Instead, he explains, a growing body of research now supports an alternative theory, which posits that progenitor cells secrete small molecules called paracrine factors that help repair injured heart cells. (Yang is involved in several stem cell clinical trials).

When you inject these stem cells, its pretty incontrovertible that they help heart function in a mouse injury model, Yang says. But the truth is, most of these cells are dead upon arrival [to the site of injury]. So the question is: Why is heart function still improving if these cells are dying?

Y. Li et al., Genetic lineage tracing of nonmyocyte population by dual recombinases, Circulation, 138:793-805, 2018.

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Adult Cardiac Stem Cells Don't Exist: Study | The ...

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BERcellFLEX24

COLLEGE STATION, Texas (PRWEB) September 05, 2018

Following up on the launch of the iCON Turnkey Facility Platform for a mAb manufacturing facility late last year, IPS-Integrated Project Services, LLC and G-CON Manufacturing have successfully designed and delivered the first BERcellFLEX PODs for the manufacturing of autologous cell therapies. The iCON solution provides a pre-fabricated modular cleanroom infrastructure for the drug manufacturers requirements for both clinical and commercial manufacture of critical therapies. Following the iCON model, IPS provided the engineering design while G-CON built, tested and delivered the BERcellFLEX CAR-T processing suites in both twelve (12) foot and twenty-four (24) foot wide POD configurations.

This is an exciting time for our companies as the iCON platform is being adopted by clients who recognize that new innovative approaches are needed to meet the growing demand for cell and gene therapy manufacturing said Dennis Powers, Vice President of Business Development and Sales Engineering at G-CON Manufacturing Inc. We believe that the iCON platform approach with its faster and more predictable project schedules for new facility construction are essential for supplying life changing therapies to the patients that need them.

The gene therapy industry needs standardized solutions to meet its speed to market requirements, said Tom J. Piombino, Vice President & Process Architect at IPS. In addition to our larger 2K mAb facility platform that we rolled out earlier this year, the BERcellFLEX12 and 24 represent a line of gene/cell therapy products that operating companies can buy today, ready-to-order, in either an open or closed-processing format with little to no engineering time we start fabricating almost immediately after URS alignment. Multiple cellFLEX units can be installed to scale up/out from Phase 1 Clinical production to Commercial Manufacturing and serve the needs of thousands of CAR-T patients per year. Being able to meet this critical need is consistent with our vision; were thrilled to be able to offer this modular solution to help our clients get therapies to their patients.

About iCONThe iCON platform, the collaborative efforts of IPS and G-CON Manufacturing, Inc., is redefining facility project execution for the biopharma industry where there is a growing need for more rapidly deployable and flexible manufacturing capability. iCON has launched turnkey designs for monoclonal antibody facilities and autologous cell therapies, and is developing platforms for cell and gene therapies, vaccines, OSD, and aseptic filling. An iCON solution can be deployed for:

About G-CONG-CON Manufacturing designs, produces and installs prefabricated cleanroom PODs. G-CONs cleanroom POD portfolio encompasses a variety of different dimensions and purposes, from laboratory environments to personalized medicine and production process platforms. The POD cleanroom units are unique from traditional cleanroom structures due to the ease of scalability, mobility and the ability to repurpose the PODs once the production process reaches the end of its lifecycle. For more information, please visit the Company's website at http://www.gconbio.com.

About IPSIPS is a global leader in developing innovative facility and bioprocess solutions for the biotechnology and pharmaceutical industries. Through operational expertise and industry-leading knowledge, skill and passion, IPS provides consulting, architecture, engineering, construction management, and compliance services that allow clients to create and manufacture life-impacting products around the world. Headquartered in Blue Bell, PA-USA, IPS is one of the largest multi-national companies servicing the life sciences industry with over 1,100 professionals in the US, Canada, Brazil, UK, Ireland, Switzerland, Singapore, China, and India. Visit our website at http://www.ipsdb.com.

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Recommendation and review posted by Jack Burke

One of the biggest and most important science stories of the past few years will probably also be one of the biggest science stories of the next few years. So this is as good a time as any to get acquainted with the powerful new gene editing technology known as CRISPR.

If you havent heard of CRISPR yet, the short explanation goes like this: In the past six years, scientists have figured out how to exploit a quirk in the immune systems of bacteria to edit genes in other organisms plants, mice, even humans. With CRISPR, they can now make these edits quickly and cheaply, in days rather than weeks or months. (The technology is often known as CRISPR/Cas9, but well stick with CRISPR, pronounced crisper.)

Let that sink in. Were talking about a powerful new tool to control which genes get expressed in plants, animals, and even humans; the ability to delete undesirable traits and, potentially, add desirable traits with more precision than ever before.

In 2017 alone, researchers reported in Nature that theyd successfully used CRISPR in human embryos to fix a mutation that causes a terrible heart muscle disorder called hypertrophic cardiomyopathy. (Other researchers have since called some of the conclusions into question.) Another team used it to reduce the severity of genetic deafness in mice, suggesting it could one day be used to treat the same type of hearing loss in people.

Meanwhile, researchers at the Broad Institute of MIT and Harvard launched a coordinated blitz with two big studies that move CRISPR in that safer and more precise direction. A paper published in Science describes an entirely new CRISPR-based gene editing tool that targets RNA, DNAs sister, allowing for transient changes to genetic material. In Nature, scientists published on a more refined type of CRISPR gene editing that can alter a single bit of DNA without cutting it increasing the tools precision and efficiency.

And these are just a few of the astounding things researchers have recently shown CRISPR can do. Weve already learned that it can help us create mushrooms that dont brown easily and edit bone marrow cells in mice to treat sickle-cell anemia. Down the road, CRISPR might help us develop drought-tolerant crops and create powerful new antibiotics. CRISPR could one day even allow us to wipe out entire populations of malaria-spreading mosquitoes or resurrect once-extinct species like the passenger pigeon.

But there are real limits to what CRISPR can do, at least right now. Scientists have recently learned that the approach to gene editing can inadvertently wipe out and rearrange large swaths of DNA in ways that may imperil human health. That follows recent studies showing that CRISPR-edited cells can inadvertently trigger cancer.

As scientists work to overcome these limitations, much of the hype around CRISPR has focused on whether we might engineer humans with specific genetic traits (like heightened intelligence). But in some ways, thats a sideshow. Designer babies are still far off, and there are enormous obstacles to making those sorts of complex genetic modifications. The stuff thats closer at hand from new therapies to fighting malaria is whats most exciting. So heres a basic guide to what CRISPR is and what it can do.

If we want to understand CRISPR, we should go back to 1987, when Japanese scientists studying E. coli first came across some unusual repeating sequences in the bacterias DNA. The biological significance of these sequences, they wrote, is unknown. Over time, other researchers found similar clusters in the DNA of other bacteria (and archaea). They gave these sequences a name: Clustered Regularly Interspaced Short Palindromic Repeats or CRISPR.

Yet these CRISPR sequences were mostly a mystery until 2007, when food scientists studying the Streptococcus bacteria used to make yogurt showed how these odd clusters actually served a vital function: Theyre part of the bacterias immune system.

See, bacteria are under constant assault from viruses and produce enzymes to fight off viral infections. Whenever the bacterias enzymes manage to kill off an invading virus, other little enzymes will come along, scoop up the remains of the viruss genetic code, cut it into little bits, and then store it in those CRISPR spaces.

Now comes the clever part: The bacteria use the genetic information stored in these CRISPR spaces to fend off future attacks. When a new infection occurs, the bacteria produce special attack enzymes, known as Cas9, that carry around those stored bits of viral genetic code like a mug shot. When these Cas9 enzymes come across a virus, they see if the viruss RNA matches whats in the mug shot. If theres a match, the Cas9 enzyme starts chopping up the viruss DNA to neutralize the threat. It looks a little like this:

So thats what CRISPR/Cas9 does. For a while, these discoveries werent of much interest to anyone except microbiologists until a series of further breakthroughs occurred.

In 2011, Jennifer Doudna of the University of California Berkeley and Emmanuelle Charpentier of Ume University in Sweden were puzzling over how the CRISPR/Cas9 system actually worked. How did the Cas9 enzyme match the RNA in the mug shots with that in the viruses? How did the enzymes know when to start chopping?

The scientists soon discovered they could fool the Cas9 protein by feeding it artificial RNA a fake mug shot. When they did that, the enzyme would search for anything with that same code, not just viruses, and start chopping. In a landmark 2012 paper, Doudna, Charpentier, and Martin Jinek showed they could use this CRISPR/Cas9 system to cut up any genome at any place they wanted.

While the technique had only been demonstrated on molecules in test tubes at that point, the implications were breathtaking.

Further advances followed. Feng Zhang, a scientist at the Broad Institute in Boston, co-authored a paper in Science in February 2013 showing that CRISPR/Cas9 could be used to edit the genomes of cultured mouse cells or human cells. In the same issue of Science, Harvards George Church and his team showed how a different CRISPR technique could be used to edit human cells.

Since then, researchers have found that CRISPR/Cas9 is ridiculously versatile. Not only can scientists use CRISPR to silence genes by snipping them out, they can also harness repair enzymes to substitute desired genes into the hole left by the snippers (though this latter technique is trickier to pull off). So, for instance, scientists could tell the Cas9 enzyme to snip out a gene that causes Huntingtons disease and insert a good gene to replace it.

Gene editing itself isnt new. Various techniques to knock out genes have been around for years. What makes CRISPR so revolutionary is that its incredibly precise: The Cas9 enzyme mostly goes wherever you tell it to. And its incredibly cheap and easy: In the past, it might have cost thousands of dollars and weeks or months of fiddling to alter a gene. Now it might cost just $75 and only take a few hours. And this technique has worked on every organism its been tried on.

This has become one of the hottest fields around. In 2011, there were fewer than 100 published papers on CRISPR. In 2017, there were more than 14,000 and counting, with new refinements to CRISPR, new techniques for manipulating genes, improvements in precision, and more. This has become such a fast-moving field that I even have trouble keeping up now, says Doudna. Were getting to the point where the efficiencies of gene editing are at levels that are clearly going to be useful therapeutically as well as a vast number of other applications.

Theres been an intense legal battle over who exactly should get credit for this CRISPR technology was Doudnas 2012 paper the breakthrough, or was Zhangs 2013 paper the key advance? Ultimately, a court ruled in February that the patent should go to Zhang and the Broad Institute, Harvard, and MIT. In the July, the University of California and others on Doudnas side said they were launching an appeal of the decision. But the important thing is that CRISPR has arrived.

So many things. Paul Knoepfler, an associate professor at UC Davis School of Medicine, told Vox that CRISPR makes him feel like a kid in a candy store.

At the most basic level, CRISPR can make it much easier for researchers to figure out what different genes in different organisms actually do by, for instance, knocking out individual genes and seeing which traits are affected. This is important: While weve had a complete map of the human genome since 2003, we dont really know what function all those genes serve. CRISPR can help speed up genome screening, and genetics research could advance massively as a result.

Researchers have also discovered there are numerous CRISPRs. So CRISPR is actually a pretty broad term. Its like the term fruit it describes a whole category, said the Broads Zhang. When people talk about CRISPR, they are usually referring to the CRISPR/Cas9 system weve been talking about here. But in recent years, researchers like Zhang have found other types of CRISPR proteins that also work as gene editors. Cas13, for example, can edit DNAs sister, RNA. Cas9 and Cas13 are like apples and bananas, Zhang added.

The real fun and, potentially, the real risks could come from using CRISPRs to edit various plants and animals. A recent paper in Nature Biotechnology by Rodolphe Barrangou and Doudna listed a flurry of potential future applications:

1) Edit crops to be more nutritious: Crop scientists are already looking to use CRISPR to edit the genes of various crops to make them tastier or more nutritious or better survivors of heat and stress. They could potentially use CRISPR to snip out the allergens in peanuts. Korean researchers are looking to see if CRISPR could help bananas survive a deadly fungal disease. Some scientists have shown that CRISPR can create hornless dairy cows a huge advance for animal welfare.

Recently, major companies like Monsanto and DuPont have begun licensing CRISPR technology, hoping to develop valuable new crop varieties. While this technique wont entirely replace traditional GMO techniques, which can transplant genes from one organism to another, CRISPR is a versatile new tool that can help identify genes associated with desired crop traits much more quickly. It could also allow scientists to insert desired traits into crops more precisely than traditional breeding, which is a much messier way of swapping in genes.

With genome editing, we can absolutely do things we couldnt do before, says Pamela Ronald, a plant geneticist at the University of California Davis. That said, she cautions that its only one of many tools for crop modification out there and successfully breeding new varieties could still take years of testing.

Its also possible that these new tools could attract controversy. Foods that have had a few genes knocked out via CRISPR are currently regulated more lightly than traditional GMOs. Policymakers in Washington, DC, are currently debating whether it might make sense to rethink regulations here. This piece for Ensia by Maywa Montenegro delves into some of the debates CRISPR raises in agriculture.

2) New tools to stop genetic diseases: As the new Nature paper shows, scientists are now using CRISPR/Cas9 to edit the human genome and try to knock out genetic diseases like hypertrophic cardiomyopathy. Theyre also looking at using it on mutations that cause Huntingtons disease or cystic fibrosis, and are talking about trying it on the BRCA-1 and 2 mutations linked to breast and ovarian cancers. Scientists have even shown that CRISPR can knock HIV infections out of T cells.

So far, however, scientists have only tested this on cells in the lab. There are still a few hurdles to overcome before anyone starts clinical trials on actual humans. For example, the Cas9 enzymes can occasionally misfire and edit DNA in unexpected places, which in human cells might lead to cancer or even create new diseases. As geneticist Allan Bradley, of Englands Wellcome Sanger Institute, told STAT, CRISPRs ability to wreak havoc on DNA has been seriously underestimated.

And while there have also been major advances in improving CRISPR precision and reducing these off-target effects, scientists are urging caution on human testing. Theres also plenty of work to be done on actually delivering the editing molecules to particular cells a major challenge going forward.

3) Powerful new antibiotics and antivirals: One of the most frightening public health facts around is that we are running low on effective antibiotics as bacteria evolve resistance to them. Currently, its difficult and costly to develop fresh antibiotics for deadly infections. But CRISPR/Cas9 systems could, in theory, be developed to eradicate certain bacteria more precisely than ever (though, again, figuring out delivery mechanisms will be a challenge). Other researchers are working on CRISPR systems that target viruses such as HIV and herpes.

4) Gene drives that could alter entire species: Scientists have also demonstrated that CRISPR could be used, in theory, to modify not just a single organism but an entire species. Its an unnerving concept called gene drive.

It works like this: Normally, whenever an organism like a fruit fly mates, theres a 50-50 chance that it will pass on any given gene to its offspring. But using CRISPR, scientists can alter these odds so that theres a nearly 100 percent chance that a particular gene gets passed on. Using this gene drive, scientists could ensure that an altered gene propagates throughout an entire population in short order:

By harnessing this technique, scientists could, say, genetically modify mosquitoes to only produce male offspring and then use a gene drive to push that trait through an entire population. Over time, the population would go extinct. Or you could just add a gene making them resistant to the malaria parasite, preventing its transmission to humans, Voxs Dylan Matthews explains in his story on CRISPR gene drives for malaria.

Suffice to say, there are also hurdles to overcome before this technology is rolled out en masse and not necessarily the ones youd expect. The problem of malaria gene drives is rapidly becoming a problem of politics and governance more than it is a problem of biology, Matthews writes. Regulators will need to figure out how to handle this technology, and ethicists will need to grapple with knotty questions about its fairness.

5) Creating designer babies: This is the one that gets the most attention. Its not entirely far-fetched to think we might one day use CRISPR to edit the human genome to eliminate disease, or to select for athleticism or superior intelligence.

That said, scientists arent even close to being able to do this. Were not even close to the point where scientists could safely make the complex changes needed to, for instance, improve intelligence, in part because it involves so many genes. So dont go dreaming of Gattaca just yet.

I think the reality is we dont understand enough yet about the human genome, how genes interact, which genes give rise to certain traits, in most cases, to enable editing for enhancement today, Doudna said in 2015. Still, she added: Thatll change over time.

Given all the fraught issues associated with gene editing, many scientists are advocating a slow approach here. They are also trying to keep the conversation about this technology open and transparent, build public trust, and avoid some of the mistakes that were made with GMOs.

In February 2017, a report from the National Academy of Sciences said that clinical trials could be greenlit in the future for serious conditions under stringent oversight. But it also made clear that genome editing for enhancement should not be allowed at this time.

Society still needs to grapple with all the ethical considerations at play here. For example, if we edited a germline, future generations wouldnt be able to opt out. Genetic changes might be difficult to undo. Even this stance has worried some researchers, like Francis Collins of the National Institutes of Health, who has said the US government will not fund any genomic editing of human embryos.

In the meantime, researchers in the US who can drum up their own funding, along with others in the UK, Sweden, and China, are moving forward with their own experiments.

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CRISPR, one of the biggest science stories of the decade ...

Recommendation and review posted by sam

In the movie Rampage, the character played by Dwayne Johnson uses a genetic engineering technology called CRISPR to transform a gorilla into a flying dragon-monster with gigantic teeth. Although this is science fiction, not to mention impossible, the movie captures the recent interest and fascination with one of the newest scientific technologies.

CRISPR which stands for clustered regularly interspaced short palindromic repeats was originally seen as part of a bacterial defense system that evolved to destroy foreign DNA that entered a bacterium. But this system is also capable of editing DNA and now geneticists have honed the technology to alter DNA sequences that we specify.

This has generated enormous excitement and great expectations about the possibility of using CRISPR to alter genetic sequences to improve our health, to treat diseases, to improve the quality and quantity of our food supplies, and to tackle environmental pollution.

Using genome editing to treat human diseases is very tantalizing. Correcting inherited genetic defects that cause human disease just as one edits a sentence is the obvious application. This strategy has been successful in tests on animals.

But a few recent scientific papers suggest that CRISPR is not without its problems. The research reveals that CRISPR can damage DNA located far from the target DNA we are trying to correct. As a cancer biologist at the University of Pittsburgh School of Medicine, I use CRISPR in my lab to study human cancers and develop ways to kill cancer cells.

Although the new findings appear significant, I dont think that these revelations rule out using the technology in a clinical setting; rather, they suggest we take additional cautionary measures as we implement these strategies.

Treating human diseases

In the United States and Europe, clinical trials have been planned for several human diseases. Most notably, a gene-editing Phase I/II trial is planned in Europe for beta-thalassemia, a hereditary blood disorder that causes anemia that requires lifelong blood transfusions. This year, a CRISPR trial for sickle cell anemia, another inherited blood disorder caused by a mutation that deforms the red blood cells, is planned in the United States.

For both of these trials, the gene editing is done ex vivo meaning outside the patients body. Hematopoietic blood cells the stem cells that generate red blood cells are taken from the patient and edited in the lab. The cells are then reintroduced into the same patients after the mutations have been corrected. The expectation is that by correcting the stem cells, the cells they produce will be normal, curing the disease.

The ex vivo approach has also been used in China to test treatments against an array of human cancers. There, researchers take immune cells called T cells from cancer patients and use CRISPR to stop these cells from producing a protein called PD-1 (program cell death-1). Normally, PD-1 prevents T cells from attacking ones own tissues. However, cancer cells exploit this protective mechanism to evade the bodys defense system. Removing PD-1 allows T cells to attack cancer cells vigorously. The initial results from clinical trials using gene-edited T cells appear mixed.

In my lab, we have recently been focusing on chromosome rearrangement, a genetic defect where a segment of chromosome skips and joins distant parts of the same or a different chromosome. A scrambled chromosome is a defining characteristic of most cancers. The most famous example of such an alteration is the Philadelphia Chromosome in which Chromosome 9 is connected to Chromosome 22 which causes acute myeloid leukemia.

My team has used CRISPR in animal models to insert a suicide gene to specifically target liver and prostate cancer cells that harbor such rearrangements. Since these chromosome rearrangements occur only in cancer cells but not normal cells, we can target the cancer without collateral damage to healthy cells.

CRISPR concerns

Despite all the excitement surrounding CRISPR editing, researchers have urged caution about moving too fast. Two recent studies have raised concerns that CRISPR may not be as effective as previously thought, and in some cases it may produce unwanted side effects.

The first study showed that when the Cas9 protein part of the CRISPR system that snips the DNA before correcting the mutation cuts the DNA of stem cells, it causes them to become stressed and stops them from being edited. While some cells can recover after their DNA has been corrected, other cells could die.

The second study showed that a protein called p53, which is well known for guarding against tumors, is activated by cellular stress. The protein then inhibits CRISPR from editing. Since CRISPR activity causes stress, the editing process may be thwarted before it even accomplishes its task.

Another study over the past year has revealed an additional potential issue with using CRISPR in humans. Because CRISPR is a bacterial protein, a significant portion of the human population may have been exposed to it during common bacterial infections. In these cases, the immune systems of these people may have developed immune defense against the protein, which means a persons body could attack the CRISPR machinery, just as it would attack an invading bacterium or virus, preventing the cell from the benefits of CRISPR-based therapy.

Additionally, like most technologies, not all editing is accurate. Occasionally, CRISPR targets the wrong sites in the DNA and makes changes that researchers fear could cause disease. A recent study showed that CRISPR caused large chunks of the chromosome to rearrange near the site of genome editing in mouse embryonic stem cells, although this effect isnt always observed in the other cell systems. Most published results indicate that off-target rates range from 1 to 5 percent. Even if the off-target rate is relatively low, we dont yet understand the long-term consequences.

Dangers have been hyped

The studies referenced above have led to a glut of media reports about the potential negative effect of CRISPR, many citing potential cancer risk. More often than not, these involve a far-fetched extrapolation of actual results. As far as I am aware, no animals treated with the CRISPR-Cas9 system have been shown to develop cancers.

Studies have shown CRISPR-based genome editing works more efficiently in cancer cells than normal cells. Indeed, the resistance of normal cells to CRISPR editing actually makes it more appealing for cancer treatment since there would be less potential collateral damage to normal tissues, a conclusion that is supported by research in our lab.

Looking forward, it is obvious that the technology has great potential to treat human diseases. The recent studies have revealed new aspects of how CRISPR works that may have implications for the ways in which these therapies are developed. However, the long-term effect of genome editing can only be assessed after CRISPR has been used widely to treat human diseases.

health-science@washpost.com

Luo is a professor of pathology at the University of Pittsburgh. This article was originally published on theconversation.com.

Read more

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CRISPR safety calls for cautious approach - washingtonpost.com

Recommendation and review posted by simmons

A stallion is a male horse that has not been gelded (castrated).Stallions follow the conformation and phenotype of their breed, but within that standard, the presence of hormones such as testosterone may give stallions a thicker, "cresty" neck, as well as a somewhat more muscular physique as compared to female horses, known as mares, and castrated males, called geldings.

Temperament varies widely based on genetics, and training, but because of their instincts as herd animals, they may be prone to aggressive behavior, particularly toward other stallions, and thus require careful management by knowledgeable handlers. However, with proper training and management, stallions are effective equine athletes at the highest levels of many disciplines, including horse racing, horse shows, and international Olympic competition.

The term "stallion" dates from the era of Henry VII, who passed a number of laws relating to the breeding and export of horses in an attempt to improve the British stock, under which it was forbidden to allow uncastrated male horses to be turned out in fields or on the commons; they had to be "kept within bounds and tied in stalls." (The term "stallion" for an uncastrated male horse dates from this time; stallion = stalled one.)[1] "Stallion" is also used to refer to males of other equids, including zebras and donkeys.

Contrary to popular myths, many stallions do not live with a harem of mares. Nor, in natural settings, do they fight each other to the death in competition for mares. Being social animals, stallions who are not able to find or win a harem of mares usually band together in stallions-only "bachelor" groups which are composed of stallions of all ages. Even with a band of mares, the stallion is not the leader of a herd but defends and protects the herd from predators and other stallions. The leadership role in a herd is held by a mare, known colloquially as the "lead mare" or "boss mare." The mare determines the movement of the herd as it travels to obtain food, water, and shelter. She also determines the route the herd takes when fleeing from danger. When the herd is in motion, the dominant stallion herds the straggling members closer to the group and acts as a "rear guard" between the herd and a potential source of danger. When the herd is at rest, all members share the responsibility of keeping watch for danger. The stallion is usually on the edge of the group, to defend the herd if needed.

There is usually one dominant mature stallion for every mixed-sex herd of horses. The dominant stallion in the herd will tolerate both sexes of horses while young, but once they become sexually mature, often as yearlings or two-year-olds, the stallion will drive both colts and fillies from the herd. Colts may present competition for the stallion, but studies suggest that driving off young horses of both sexes may also be an instinctive behavior that minimizes the risk of inbreeding within the herd, as most young are the offspring of the dominant stallion in the group. In some cases, a single younger mature male may be tolerated on the fringes of the herd. One theory is that this young male is considered a potential successor, as in time the younger stallion will eventually drive out the older herd stallion.

Fillies usually soon join a different band with a dominant stallion different from the one that sired them. Colts or young stallions without mares of their own usually form small, all-male, "bachelor bands" in the wild. Living in a group gives these stallions the social and protective benefits of living in a herd. A bachelor herd may also contain older stallions who have lost their herd in a challenge.[2]

Other stallions may directly challenge a herd stallion, or may simply attempt to "steal" mares and form a new, smaller herd. In either case, if the two stallions meet, there rarely is a true fight; more often there will be bluffing behavior and the weaker horse will back off. Even if a fight for dominance occurs, rarely do opponents hurt each other in the wild because the weaker combatant has a chance to flee. Fights between stallions in captivity may result in serious injuries; fences and other forms of confinement make it more difficult for the losing animal to safely escape. In the wild, feral stallions have been known to steal or mate with domesticated mares.

The stallion's reproductive system is responsible for his sexual behavior and secondary sex characteristics (such as a large crest).The external genitalia comprise:

The internal genitalia comprise the accessory sex glands, which include the vesicular glands, the prostate gland and the bulbourethral glands. These contribute fluid to the semen at ejaculation, but are not strictly necessary for fertility.[3][9]

Domesticated stallions are trained and managed in a variety of ways, depending on the region of the world, the owner's philosophy, and the individual stallion's temperament. In all cases, however, stallions have an inborn tendency to attempt to dominate both other horses and human handlers, and will be affected to some degree by proximity to other horses, especially mares in heat. They must be trained to behave with respect toward humans at all times or else their natural aggressiveness, particularly a tendency to bite, may pose a danger of serious injury.[2]

For this reason, regardless of management style, stallions must be treated as individuals and should only be handled by people who are experienced with horses and thus recognize and correct inappropriate behavior before it becomes a danger.[10] While some breeds are of a more gentle temperament than others, and individual stallions may be well-behaved enough to even be handled by inexperienced people for short periods of time, common sense must always be used. Even the most gentle stallion has natural instincts that may overcome human training. As a general rule, children should not handle stallions, particularly in a breeding environment.

Management of stallions usually follows one of the following models: confinement or "isolation" management, where the stallion is kept alone, or in management systems variously called "natural", "herd", or "pasture" management where the stallion is allowed to be with other horses. In the "harem" model, the stallion is allowed to run loose with mares akin to that of a feral or semi-feral herd. In the"bachelor herd" model, stallions are kept in a male-only group of stallions, or, in some cases, with stallions and geldings. Sometime stallions may periodically be managed in multiple systems, depending on the season of the year.

The advantage of natural types of management is that the stallion is allowed to behave "like a horse" and may exhibit fewer stable vices. In a harem model, the mares may "cycle" or achieve estrus more readily. Proponents of natural management also assert that mares are more likely to "settle" (become pregnant) in a natural herd setting. Some stallion managers keep a stallion with a mare herd year-round, others will only turn a stallion out with mares during the breeding season.[11]

In some places, young domesticated stallions are allowed to live separately in a "bachelor herd" while growing up, kept out of sight, sound or smell of mares. A Swiss study demonstrated that even mature breeding stallions kept well away from other horses could live peacefully together in a herd setting if proper precautions were taken while the initial herd hierarchy was established.[12]

As an example, in the New Forest, England, breeding stallions run out on the open Forest for about two to three months each year with the mares and youngstock. On being taken off the Forest, many of them stay together in bachelor herds for most of the rest of the year.[13][14][15] New Forest stallions, when not in their breeding work, take part on the annual round-ups, working alongside mares and geldings, and compete successfully in many disciplines.[16][17]

There are drawbacks to natural management, however. One is that the breeding date, and hence foaling date, of any given mare will be uncertain. Another problem is the risk of injury to the stallion or mare in the process of natural breeding, or the risk of injury while a hierarchy is established within an all-male herd. Some stallions become very anxious or temperamental in a herd setting and may lose considerable weight, sometimes to the point of a health risk. Some may become highly protective of their mares and thus more aggressive and dangerous to handle. There is also a greater risk that the stallion may escape from a pasture or be stolen. Stallions may break down fences between adjoining fields to fight another stallion or mate with the "wrong" herd of mares, thus putting the pedigree of ensuing foals in question.[18]

The other general method of managing stallions is to confine them individually, sometimes in a small pen or corral with a tall fence, other times in a stable, or, in certain places, in a small field (or paddock) with a strong fence. The advantages to individual confinement include less of a risk of injury to the stallion or to other horses, controlled periods for breeding mares, greater certainty of what mares are bred when, less risk of escape or theft, and ease of access by humans. Some stallions are of such a temperament, or develop vicious behavior due to improper socialization or poor handling, that they must be confined and cannot be kept in a natural setting, either because they behave in a dangerous manner toward other horses, or because they are dangerous to humans when loose.

The drawbacks to confinement vary with the details of the actual method used, but stallions kept out of a herd setting require a careful balance of nutrition and exercise for optimal health and fertility. Lack of exercise can be a serious concern; stallions without sufficient exercise may not only become fat, which may reduce both health and fertility, but also may become aggressive or develop stable vices due to pent-up energy. Some stallions within sight or sound of other horses may become aggressive or noisy, calling or challenging other horses. This sometimes is addressed by keeping stallions in complete isolation from other animals.

However, complete isolation has significant drawbacks; stallions may develop additional behavior problems with aggression due to frustration and pent-up energy. As a general rule, a stallion that has been isolated from the time of weaning or sexual maturity will have a more difficult time adapting to a herd environment than one allowed to live close to other animals. However, as horses are instinctively social creatures, even stallions are believed to benefit from being allowed social interaction with other horses, though proper management and cautions are needed.[12]

Some managers attempt to compromise between the two methods by providing stallions daily turnout by themselves in a field where they can see, smell, and hear other horses. They may be stabled in a barn where there are bars or a grille between stalls where they can look out and see other animals. In some cases, a stallion may be kept with or next to a gelding or a nonhorse companion animal such as a goat, a gelded donkey, a cat, or other creature.

Properly trained stallions can live and work close to mares and to one another. Examples include the Lipizzan stallions of the Spanish Riding School in Vienna, Austria, where the entire group of stallions live part-time in a bachelor herd as young colts, then are stabled, train, perform, and travel worldwide as adults with few if any management problems. However, even stallions who are unfamiliar with each other can work safely in reasonable proximity if properly trained; the vast majority of Thoroughbred horses on the racetrack are stallions, as are many equine athletes in other forms of competition. Stallions are often shown together in the same ring at horse shows, particularly in halter classes where their conformation is evaluated. In horse show performance competition, stallions and mares often compete in the same arena with one another, particularly in Western and English "pleasure"-type classes where horses are worked as a group. Overall, stallions can be trained to keep focused on work and maybe brilliant performers if properly handled.[19]

A breeding stallion is more apt to present challenging behavior to a human handler than one who has not bred mares, and stallions may be more difficult to handle in spring and summer, during the breeding season, than during the fall and winter. However, some stallions are used for both equestrian uses and for breeding at the same general time of year. Though compromises may need to be made in expectations for both athletic performance and fertility rate, well-trained stallions with good temperaments can be taught that breeding behavior is only allowed in a certain area, or with certain cues, equipment, or with a particular handler.[20][21] However, some stallions lack the temperament to focus on work if also breeding mares in the same general time period, and therefore are taken out of competition either temporarily or permanently to be used for breeding. When permitted by a breed registry, use of artificial insemination is another technique that may reduce behavior problems in stallions.

Attitudes toward stallions vary between different parts of the world. In some parts of the world, the practice of gelding is not widespread and stallions are common. In other places, most males are gelded and only a few stallions are kept as breeding stock.Horse breeders who produce purebred bloodstock often recommend that no more than the top 10 percent of all males be allowed to reproduce, to continually improve a given breed of horse.

People sometimes have inaccurate beliefs about stallions, both positive and negative. Some beliefs are that stallions are always mean and vicious or uncontrollable, other beliefs are that misbehaving stallions should be allowed to misbehave because they are being "natural", "spirited" or "noble." In some cases, fed by movies and fictional depictions of horses in literature, some people believe a stallion can bond to a single human individual to the exclusion of all others. However, like many other misconceptions, there is only partial truth to these beliefs. Some, though not all stallions can be vicious or hard to handle, occasionally due to genetics, but usually due to improper training. Others are very well-trained and have excellent manners. Misbehaving stallions may look pretty or be exhibiting instinctive behavior, but it can still become dangerous if not corrected. Some stallions do behave better for some people than others, but that can be true of some mares and geldings, as well.

In some parts of Asia and the Middle East, the riding of stallions is widespread, especially among male riders. The gelding of stallions is unusual, viewed culturally as either unnecessary or unnatural. In areas where gelding is not widely practised, stallions are still not needed in numbers as great as mares, and so many will be culled, either sold for horsemeat or simply sold to traders who will take them outside the area. Of those that remain, many will not be used for breeding purposes.

In Europe, Australia, and the Americas, keeping stallions is less common, primarily confined to purebred animals that are usually trained and placed into competition to test their quality as future breeding stock. The majority of stallions are gelded at an early age and then trained for use as everyday working or riding animals.

If a stallion is not to be used for breeding, gelding the male horse will allow it to live full-time in a herd with both males and females, reduce aggressive or disruptive behavior, and allow the horse to be around other animals without being seriously distracted.[22] If a horse is not to be used for breeding, it can be gelded prior to reaching sexual maturity. A horse gelded young may grow taller[22] and behave better if this is done.[23] Older stallions that are sterile or otherwise no longer used for breeding may also be gelded and will exhibit calmer behavior, even if previously used for breeding. However, they are more likely to continue stallion-like behaviors than horses gelded at a younger age, especially if they have been used as a breeding stallion. Modern surgical techniques allow castration to be performed on a horse of almost any age with relatively few risks.[24]

In most cases, particularly in modern industrialized cultures, a male horse that is not of sufficient quality to be used for breeding will have a happier life without having to deal with the instinctive, hormone-driven behaviors that come with being left intact. Geldings are safer to handle and present fewer management problems.[23] They are also more widely accepted. Many boarding stables will refuse clients with stallions or charge considerably more money to keep them. Some types of equestrian activity, such as events involving children, or clubs that sponsor purely recreational events such as trail riding, may not permit stallions to participate.[citation needed]

However, just as some pet owners may have conflicting emotions about neutering a male dog or cat, some stallion owners may be unsure about gelding a stallion. One branch of the animal rights community maintains that castration is mutilation and damaging to the animal's psyche.[25]

A ridgling or "rig" is a cryptorchid, a stallion which has one or both testicles undescended. If both testicles are not descended, the horse may appear to be a gelding, but will still behave like a stallion. A gelding that displays stallion-like behaviors is sometimes called a "false rig".[26] In many cases, ridglings are infertile, or have fertility levels that are significantly reduced. The condition is most easily corrected by gelding the horse. A more complex and costly surgical procedure can sometimes correct the condition and restore the animal's fertility, though it is only cost-effective for a horse that has very high potential as a breeding stallion. This surgery generally removes the non-descended testicle, leaving the descended testicle, and creating a horse known as a monorchid stallion. Keeping cryptorchids or surgically-created monorchids as breeding stallions is controversial, as the condition is at least partially genetic and some handlers claim that cryptorchids tend to have greater levels of behavioral problems than normal stallions.[27][28]

Term for a male horse that has not been castrated

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Recommendation and review posted by sam

Embryonic stem cells (ES cells or ESCs) are pluripotent stem cells derived from the inner cell mass of a blastocyst, an early-stage pre-implantation embryo.[1][2] Human embryos reach the blastocyst stage 45 days post fertilization, at which time they consist of 50150 cells. Isolating the embryoblast, or inner cell mass (ICM) results in destruction of the blastocyst, a process which raises ethical issues, including whether or not embryos at the pre-implantation stage should have the same moral considerations as embryos in the post-implantation stage of development.[3][4] Researchers are currently focusing heavily on the therapeutic potential of embryonic stem cells, with clinical use being the goal for many labs. These cells are being studied to be used as clinical therapies, models of genetic disorders, and cellular/DNA repair. However, adverse effects in the research and clinical processes have also been reported.

Embryonic stem cells (ESCs), derived from the blastocyst stage of early mammalian embryos, are distinguished by their ability to differentiate into any cell type and by their ability to propagate. It is these traits that makes them valuable in the scientific/medical fields. ESC are also described as having a normal karyotype, maintaining high telomerase activity, and exhibiting remarkable long-term proliferative potential.[5]

Embryonic stem cells of the inner cell mass are pluripotent, meaning they are able to differentiate to generate primitive ectoderm, which ultimately differentiates during gastrulation into all derivatives of the three primary germ layers: ectoderm, endoderm, and mesoderm. These include each of the more than 220 cell types in the adult human body. Pluripotency distinguishes embryonic stem cells from adult stem cells, which are multipotent and can only produce a limited number of cell types.

Under defined conditions, embryonic stem cells are capable of propagating indefinitely in an undifferentiated state. Conditions must either prevent the cells from clumping, or maintain an environment that supports an unspecialized state.[2] While being able to remain undifferentiated, ESCs also have the capacity, when provided with the appropriate signals, to differentiate (presumably via the initial formation of precursor cells) into nearly all mature cell phenotypes.[6]

Due to their plasticity and potentially unlimited capacity for self-renewal, embryonic stem cell therapies have been proposed for regenerative medicine and tissue replacement after injury or disease. Pluripotent stem cells have shown potential in treating a number of varying conditions, including but not limited to: spinal cord injuries, age related macular degeneration, diabetes, neurodegenerative disorders (such as Parkinson's disease), AIDS, etc.[7] In addition to their potential in regenerative medicine, embryonic stem cells provide an alternative source of tissue/organs which serves as a possible solution to the donor shortage dilemma. Not only that, but tissue/organs derived from ESCs can be made immunocompatible with the recipient. Aside from these uses, embryonic stem cells can also serve as tools for the investigation of early human development, study of genetic disease and as in vitro systems for toxicology testing.[5]

According to a 2002 article in PNAS, "Human embryonic stem cells have the potential to differentiate into various cell types, and, thus, may be useful as a source of cells for transplantation or tissue engineering."[8]

However, embryonic stem cells are not limited to cell/tissue engineering.

Current research focuses on differentiating ESCs into a variety of cell types for eventual use as cell replacement therapies (CRTs). Some of the cell types that have or are currently being developed include cardiomyocytes (CM), neurons, hepatocytes, bone marrow cells, islet cells and endothelial cells.[9] However, the derivation of such cell types from ESCs is not without obstacles, therefore current research is focused on overcoming these barriers. For example, studies are underway to differentiate ESCs in to tissue specific CMs and to eradicate their immature properties that distinguish them from adult CMs.[10]

Besides becoming an important alternative to organ transplants, ESCs are also being used in field of toxicology and as cellular screens to uncover new chemical entities (NCEs) that can be developed as small molecule drugs. Studies have shown that cardiomyocytes derived from ESCs are validated in vitro models to test drug responses and predict toxicity profiles.[9] ES derived cardiomyocytes have been shown to respond to pharmacological stimuli and hence can be used to assess cardiotoxicity like Torsades de Pointes.[17]

ESC-derived hepatocytes are also useful models that could be used in the preclinical stages of drug discovery. However, the development of hepatocytes from ESCs has proven to be challenging and this hinders the ability to test drug metabolism. Therefore, current research is focusing on establishing fully functional ESC-derived hepatocytes with stable phase I and II enzyme activity.[18]

Several new studies have started to address the concept of modeling genetic disorders with embryonic stem cells. Either by genetically manipulating the cells, or more recently, by deriving diseased cell lines identified by prenatal genetic diagnosis (PGD), modeling genetic disorders is something that has been accomplished with stem cells. This approach may very well prove invaluable at studying disorders such as Fragile-X syndrome, Cystic fibrosis, and other genetic maladies that have no reliable model system.

Yury Verlinsky, a Russian-American medical researcher who specialized in embryo and cellular genetics (genetic cytology), developed prenatal diagnosis testing methods to determine genetic and chromosomal disorders a month and a half earlier than standard amniocentesis. The techniques are now used by many pregnant women and prospective parents, especially couples who have a history of genetic abnormalities or where the woman is over the age of 35 (when the risk of genetically related disorders is higher). In addition, by allowing parents to select an embryo without genetic disorders, they have the potential of saving the lives of siblings that already had similar disorders and diseases using cells from the disease free offspring.[19]

Differentiated somatic cells and ES cells use different strategies for dealing with DNA damage. For instance, human foreskin fibroblasts, one type of somatic cell, use non-homologous end joining (NHEJ), an error prone DNA repair process, as the primary pathway for repairing double-strand breaks (DSBs) during all cell cycle stages.[20] Because of its error-prone nature, NHEJ tends to produce mutations in a cells clonal descendants.

ES cells use a different strategy to deal with DSBs.[21] Because ES cells give rise to all of the cell types of an organism including the cells of the germ line, mutations arising in ES cells due to faulty DNA repair are a more serious problem than in differentiated somatic cells. Consequently, robust mechanisms are needed in ES cells to repair DNA damages accurately, and if repair fails, to remove those cells with un-repaired DNA damages. Thus, mouse ES cells predominantly use high fidelity homologous recombinational repair (HRR) to repair DSBs.[21] This type of repair depends on the interaction of the two sister chromosomes formed during S phase and present together during the G2 phase of the cell cycle. HRR can accurately repair DSBs in one sister chromosome by using intact information from the other sister chromosome. Cells in the G1 phase of the cell cycle (i.e. after metaphase/cell division but prior the next round of replication) have only one copy of each chromosome (i.e. sister chromosomes arent present). Mouse ES cells lack a G1 checkpoint and do not undergo cell cycle arrest upon acquiring DNA damage.[22] Rather they undergo programmed cell death (apoptosis) in response to DNA damage.[23] Apoptosis can be used as a fail-safe strategy to remove cells with un-repaired DNA damages in order to avoid mutation and progression to cancer.[24] Consistent with this strategy, mouse ES stem cells have a mutation frequency about 100-fold lower than that of isogenic mouse somatic cells.[25]

On January 23, 2009, Phase I clinical trials for transplantation of oligodendrocytes (a cell type of the brain and spinal cord) derived from human ES cells into spinal cord-injured individuals received approval from the U.S. Food and Drug Administration (FDA), marking it the world's first human ES cell human trial.[26] The study leading to this scientific advancement was conducted by Hans Keirstead and colleagues at the University of California, Irvine and supported by Geron Corporation of Menlo Park, CA, founded by Michael D. West, PhD. A previous experiment had shown an improvement in locomotor recovery in spinal cord-injured rats after a 7-day delayed transplantation of human ES cells that had been pushed into an oligodendrocytic lineage.[27] The phase I clinical study was designed to enroll about eight to ten paraplegics who have had their injuries no longer than two weeks before the trial begins, since the cells must be injected before scar tissue is able to form. The researchers emphasized that the injections were not expected to fully cure the patients and restore all mobility. Based on the results of the rodent trials, researchers speculated that restoration of myelin sheathes and an increase in mobility might occur. This first trial was primarily designed to test the safety of these procedures and if everything went well, it was hoped that it would lead to future studies that involve people with more severe disabilities.[28] The trial was put on hold in August 2009 due to FDA concerns regarding a small number of microscopic cysts found in several treated rat models but the hold was lifted on July 30, 2010.[29]

In October 2010 researchers enrolled and administered ESTs to the first patient at Shepherd Center in Atlanta.[30] The makers of the stem cell therapy, Geron Corporation, estimated that it would take several months for the stem cells to replicate and for the GRNOPC1 therapy to be evaluated for success or failure.

In November 2011 Geron announced it was halting the trial and dropping out of stem cell research for financial reasons, but would continue to monitor existing patients, and was attempting to find a partner that could continue their research.[31] In 2013 BioTime (AMEX:BTX), led by CEO Dr. Michael D. West, acquired all of Geron's stem cell assets, with the stated intention of restarting Geron's embryonic stem cell-based clinical trial for spinal cord injury research.[32]

BioTime company Asterias Biotherapeutics (NYSE MKT: AST) was granted a $14.3 million Strategic Partnership Award by the California Institute for Regenerative Medicine (CIRM) to re-initiate the worlds first embryonic stem cell-based human clinical trial, for spinal cord injury. Supported by California public funds, CIRM is the largest funder of stem cell-related research and development in the world.[33]

The award provides funding for Asterias to reinitiate clinical development of AST-OPC1 in subjects with spinal cord injury and to expand clinical testing of escalating doses in the target population intended for future pivotal trials.[33]

AST-OPC1 is a population of cells derived from human embryonic stem cells (hESCs) that contains oligodendrocyte progenitor cells (OPCs). OPCs and their mature derivatives called oligodendrocytes provide critical functional support for nerve cells in the spinal cord and brain. Asterias recently presented the results from phase 1 clinical trial testing of a low dose of AST-OPC1 in patients with neurologically-complete thoracic spinal cord injury. The results showed that AST-OPC1 was successfully delivered to the injured spinal cord site. Patients followed 23 years after AST-OPC1 administration showed no evidence of serious adverse events associated with the cells in detailed follow-up assessments including frequent neurological exams and MRIs. Immune monitoring of subjects through one year post-transplantation showed no evidence of antibody-based or cellular immune responses to AST-OPC1. In four of the five subjects, serial MRI scans performed throughout the 23 year follow-up period indicate that reduced spinal cord cavitation may have occurred and that AST-OPC1 may have had some positive effects in reducing spinal cord tissue deterioration. There was no unexpected neurological degeneration or improvement in the five subjects in the trial as evaluated by the International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI) exam.[33]

The Strategic Partnership III grant from CIRM will provide funding to Asterias to support the next clinical trial of AST-OPC1 in subjects with spinal cord injury, and for Asterias product development efforts to refine and scale manufacturing methods to support later-stage trials and eventually commercialization. CIRM funding will be conditional on FDA approval for the trial, completion of a definitive agreement between Asterias and CIRM, and Asterias continued progress toward the achievement of certain pre-defined project milestones.[33]

The major concern with the possible transplantation of ESC into patients as therapies is their ability to form tumors including teratoma.[34] Safety issues prompted the FDA to place a hold on the first ESC clinical trial, however no tumors were observed.

The main strategy to enhance the safety of ESC for potential clinical use is to differentiate the ESC into specific cell types (e.g. neurons, muscle, liver cells) that have reduced or eliminated ability to cause tumors. Following differentiation, the cells are subjected to sorting by flow cytometry for further purification. ESC are predicted to be inherently safer than IPS cells created with genetically-integrating viral vectors because they are not genetically modified with genes such as c-Myc that are linked to cancer. Nonetheless, ESC express very high levels of the iPS inducing genes and these genes including Myc are essential for ESC self-renewal and pluripotency,[35] and potential strategies to improve safety by eliminating c-Myc expression are unlikely to preserve the cells' "stemness". However, N-myc and L-myc have been identified to induce iPS cells instead of c-myc with similar efficiency.[36]More recent protocols to induce pluripotency bypass these problems completely by using non-integrating RNA viral vectors such as sendai virus or mRNA transfection.

Due to the nature of embryonic stem cell research, there is a lot of controversial opinions on the topic. Since harvesting embryonic stem cells necessitates destroying the embryo from which those cells are obtained, the moral status of the embryo comes into question. Scientists argue that the 5-day old mass of cells is too young to achieve personhood or that the embryo, if donated from an IVF clinic (which is where labs typically acquire embryos from), would otherwise go to medical waste anyway. Opponents of ESC research counter that any embryo has the potential to become a human, therefore destroying it is murder and the embryo must be protected under the same ethical view as a developed human being.[37]

In vitro fertilization generates multiple embryos. The surplus of embryos is not clinically used or is unsuitable for implantation into the patient, and therefore may be donated by the donor with consent. Human embryonic stem cells can be derived from these donated embryos or additionally they can also be extracted from cloned embryos using a cell from a patient and a donated egg.[49] The inner cell mass (cells of interest), from the blastocyst stage of the embryo, is separated from the trophectoderm, the cells that would differentiate into extra-embryonic tissue. Immunosurgery, the process in which antibodies are bound to the trophectoderm and removed by another solution, and mechanical dissection are performed to achieve separation. The resulting inner cell mass cells are plated onto cells that will supply support. The inner cell mass cells attach and expand further to form a human embryonic cell line, which are undifferentiated. These cells are fed daily and are enzymatically or mechanically separated every four to seven days. For differentiation to occur, the human embryonic stem cell line is removed from the supporting cells to form embryoid bodies, is co-cultured with a serum containing necessary signals, or is grafted in a three-dimensional scaffold to result.[50]

Embryonic stem cells are derived from the inner cell mass of the early embryo, which are harvested from the donor mother animal. Martin Evans and Matthew Kaufman reported a technique that delays embryo implantation, allowing the inner cell mass to increase. This process includes removing the donor mother's ovaries and dosing her with progesterone, changing the hormone environment, which causes the embryos to remain free in the uterus. After 46 days of this intrauterine culture, the embryos are harvested and grown in in vitro culture until the inner cell mass forms egg cylinder-like structures, which are dissociated into single cells, and plated on fibroblasts treated with mitomycin-c (to prevent fibroblast mitosis). Clonal cell lines are created by growing up a single cell. Evans and Kaufman showed that the cells grown out from these cultures could form teratomas and embryoid bodies, and differentiate in vitro, all of which indicating that the cells are pluripotent.[41]

Gail Martin derived and cultured her ES cells differently. She removed the embryos from the donor mother at approximately 76 hours after copulation and cultured them overnight in a medium containing serum. The following day, she removed the inner cell mass from the late blastocyst using microsurgery. The extracted inner cell mass was cultured on fibroblasts treated with mitomycin-c in a medium containing serum and conditioned by ES cells. After approximately one week, colonies of cells grew out. These cells grew in culture and demonstrated pluripotent characteristics, as demonstrated by the ability to form teratomas, differentiate in vitro, and form embryoid bodies. Martin referred to these cells as ES cells.[42]

It is now known that the feeder cells provide leukemia inhibitory factor (LIF) and serum provides bone morphogenetic proteins (BMPs) that are necessary to prevent ES cells from differentiating.[51][52] These factors are extremely important for the efficiency of deriving ES cells. Furthermore, it has been demonstrated that different mouse strains have different efficiencies for isolating ES cells.[53] Current uses for mouse ES cells include the generation of transgenic mice, including knockout mice. For human treatment, there is a need for patient specific pluripotent cells. Generation of human ES cells is more difficult and faces ethical issues. So, in addition to human ES cell research, many groups are focused on the generation of induced pluripotent stem cells (iPS cells).[54]

On August 23, 2006, the online edition of Nature scientific journal published a letter by Dr. Robert Lanza (medical director of Advanced Cell Technology in Worcester, MA) stating that his team had found a way to extract embryonic stem cells without destroying the actual embryo.[55] This technical achievement would potentially enable scientists to work with new lines of embryonic stem cells derived using public funding in the USA, where federal funding was at the time limited to research using embryonic stem cell lines derived prior to August 2001. In March, 2009, the limitation was lifted.[56]

The iPSC technology was pioneered by Shinya Yamanakas lab in Kyoto, Japan, who showed in 2006 that the introduction of four specific genes encoding transcription factors could convert adult cells into pluripotent stem cells.[57] He was awarded the 2012 Nobel Prize along with Sir John Gurdon "for the discovery that mature cells can be reprogrammed to become pluripotent." [58]

In 2007 it was shown that pluripotent stem cells highly similar to embryonic stem cells can be generated by the delivery of three genes (Oct4, Sox2, and Klf4) to differentiated cells.[59] The delivery of these genes "reprograms" differentiated cells into pluripotent stem cells, allowing for the generation of pluripotent stem cells without the embryo. Because ethical concerns regarding embryonic stem cells typically are about their derivation from terminated embryos, it is believed that reprogramming to these "induced pluripotent stem cells" (iPS cells) may be less controversial. Both human and mouse cells can be reprogrammed by this methodology, generating both human pluripotent stem cells and mouse pluripotent stem cells without an embryo.[60]

This may enable the generation of patient specific ES cell lines that could potentially be used for cell replacement therapies. In addition, this will allow the generation of ES cell lines from patients with a variety of genetic diseases and will provide invaluable models to study those diseases.

However, as a first indication that the induced pluripotent stem cell (iPS) cell technology can in rapid succession lead to new cures, it was used by a research team headed by Rudolf Jaenisch of the Whitehead Institute for Biomedical Research in Cambridge, Massachusetts, to cure mice of sickle cell anemia, as reported by Science journal's online edition on December 6, 2007.[61][62]

On January 16, 2008, a California-based company, Stemagen, announced that they had created the first mature cloned human embryos from single skin cells taken from adults. These embryos can be harvested for patient matching embryonic stem cells.[63]

The online edition of Nature Medicine published a study on January 24, 2005, which stated that the human embryonic stem cells available for federally funded research are contaminated with non-human molecules from the culture medium used to grow the cells.[64] It is a common technique to use mouse cells and other animal cells to maintain the pluripotency of actively dividing stem cells. The problem was discovered when non-human sialic acid in the growth medium was found to compromise the potential uses of the embryonic stem cells in humans, according to scientists at the University of California, San Diego.[65]

However, a study published in the online edition of Lancet Medical Journal on March 8, 2005 detailed information about a new stem cell line that was derived from human embryos under completely cell- and serum-free conditions. After more than 6 months of undifferentiated proliferation, these cells demonstrated the potential to form derivatives of all three embryonic germ layers both in vitro and in teratomas. These properties were also successfully maintained (for more than 30 passages) with the established stem cell lines.[66]

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Embryonic stem cell - Wikipedia

Recommendation and review posted by simmons

-A curious adult from CaliforniaAugust 6, 2004What a fun question! This sort of thing has been bothering me too lately. The usual statistic is that all people are 99.9% the same. But is that true for men and women?And what about our similarity to other animals? We are really only about 80% the same as a mouse at the genetic level so men and women are clearly more similar to each other than to mice. But what about chimpanzees? If people really are 98.7% the same as a chimpanzee, are male chimpanzees closer genetically to men than men are to women? As you know, men have an X and a Y chromosome and women have two X chromosomes. So besides the usual 0.1% (or 3.2 million base pair) difference between people, men and women differ by the presence of the Y chromosome.The Y chromosome is a tiny thing; it is about 59 million base pairs long and has only 78 genes. If we look at base pairs, the difference between men and women would be 59 million divided by 3.2 billion or about 1.8%. This translates to men and women being 98.2% the same.Men and women are actually a bit more similar as the Y chromosome has about 5% of its DNA sequences in common with the X chromosome. This would change the number to 98.4% the same.If the 98.7% number for chimp-human similarity is right, then by this measure, men and women are less alike than are female chimps and women. (More recent data suggests that chimps may be 95% instead of 98.7% the same, but this is still up in the air.) Now if we look at the gene level instead of at the base pair level, men and women become much more similar. If we assume 30,000 total genes, then men and women are about 99.7% the same instead of 98.4%. (I haven't been able to find a good number for how many genes chimpanzees and humans share.)So is the bottom line that men and male chimps have more in common than men and women? Of course not. If we take a closer look, we see some of the dangers of looking at raw percentages instead of individual changes.Another way to think about this is the 55 million or so differences between men and women are all concentrated on one chromosome and 78 genes. For chimps, the 42-150 million differences are spread out all over the chromosomes over many, many more genes.In other words, while the quantity of changes may be the same, the quality is different. Even though we share most of our genes with a chimpanzee, lots of the chimp's genes have changed in ways not seen in people. These changes make a chimp a chimp and a human a human.Some of the products of these changed genes in a chimp now do different things, or do things differently, do them in different places, do them more strongly or weakly, or even do nothing at all. It only takes a single DNA change to make a gene stop working and there are millions and millions of differences between you and a chimp. What all of this means is that in essence, chimps have many more "different" genes than the 78 different ones between men and women even though the % difference at the DNA level may be comparable. So, even if it may not seem like it sometimes, your brother has more in common with you than with a chimp.

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Understanding Genetics - genetics.thetech.org

Recommendation and review posted by Jack Burke

In this video Paul Andersen explains how the CRISPR/Cas immune system was identified in bacteria and how the CRISPR/Cas9 system was developed to edit genomes.

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All of the images are licensed under creative commons and public domain licensing:Adenosine. (2009). English: Artistic rendering of a T4 bacteriophage. The colours grey and orange do not signify anything, they are just used to illustrate structure. Created for Wikipedia. Retrieved from https://commons.wikimedia.org/wiki/Fi...E. coli Bacteria. (n.d.). Retrieved February 17, 2016, from https://www.flickr.com/photos/niaid/1...Fioretti, B. F. Hallbauer &. (2015). English: Director, Max Planck Institute for Infection Biology, Department of Regulation in Infection Biology. Visiting professor The Laboratory for Molecular Infection Medicine Sweden MIMS; http://www.mpiib-berlin.mpg.de/resear.... Retrieved from https://commons.wikimedia.org/wiki/Fi...Foresman, P. S. ([object HTMLTableCellElement]). English: Line art drawing of a chimera. Retrieved from https://commons.wikimedia.org/wiki/Fi...Magladem96. (2014). English: Picture of DNA Base Flipping. Retrieved from https://commons.wikimedia.org/wiki/Fi...project, C. wiki. (2014). English: Crystal Structure of Cas9 bound to DNA based on the Anders et al 2014 Nature paper. Rendition was performed using UCSFs chimera software. Retrieved from https://commons.wikimedia.org/wiki/Fi...Providers, P. C. (1979). English: Photomicrograph of Streptococcus pyogenes bacteria, 900x Mag. A pus specimen, viewed using Pappenheims stain. Last century, infections by S. pyogenes claimed many lives especially since the organism was the most important cause of puerperal fever and scarlet fever. Streptococci. Retrieved from https://commons.wikimedia.org/wiki/Fi...RRZEicons. (2010). English: zipper, open, close. Retrieved from https://commons.wikimedia.org/wiki/Fi...UC Berkeley. (n.d.). Gene editing with CRISPR-Cas9. Retrieved from https://www.youtube.com/watch?v=avM1Y...

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What is CRISPR? - YouTube

Recommendation and review posted by Jack Burke

Genetic testing can have implications for management of the cancer patients, including: surgical treatment, chemotherapy choices, prognosis and risk for additional cancers. It is therefore important to assess the risk of a hereditary syndrome at diagnosis, at decision points along the cancer treatment trajectory and again when entering survivorship or surveillance. An exhaustive list of implications of all cancer predisposition syndromes or germline alterations is beyond the scope of this toolkit; however we will provide some of the more common implications of identification of germline mutations in patients with cancer.

Genetic testing of a cancer assesses somatic genetic changes that may guide therapeutic choices (e.g., EGFR mutations for treatment of lung cancer). Some tumor (somatic) genetic testting will include mutations potentially inherited (germline) as well as those acquired in the tumor (somatic). Other genetic tests of the tumor will "subtract out" germline mutations by comparing mutations in the tumor to those found in sample of normal tissue or blood. It is important to understand which approach the genetic test you are reviewing has used. This toolkit does not address tumor somatic mutations. Germline genetic testing, usually performed on a blood sample, evaluates inherited genetic changes that increase the risk of certain cancers in an individual.

Benefits of Germline Genetic TestingGenetic testing can help identify cancers for which an individual is at increased risk. This increased risk can often be managed by increased surveillance, consideration of preventive medication or prophylactic surgery. In addition, identification of a familial germline mutation in a cancer susceptibility gene can alert family members who would also undergo genetic testing to clarify their own risk of cancer. Finally, identifying certain germline mutations may guide local and systemic treatment of a cancer (e.g., colectomy for a patient with colorectal cancer and Lynch syndrome; PARP inhibitor for a patient withovarian cancerwith aBRCA1/2mutation; avoidance of therapeutic radiation in a patient with breast cancerwith inheritedTP53mutation).

Germline mutations and second cancer risk: Second primary cancers occur in approximately 16% of all patients with cancer. Those individuals with strong family histories and/or pathogenic germline mutations in cancer-causing genes are at highest risk of second primary cancers. Genetic testing during survivorship or surveillance can identify those at greatest risk and action (more intense screening or preventive surgery) can be taken.

The guidelines below represent a selection of publicly available resources on genetic testing for specified cancer syndromes; this list is not exhaustive due to restrictions of member-only content. **Inclusion of third-party guidelines and recommendations should not be interpreted as formal endorsement by ASCO.**

Breast and Ovarian Cancer

Colorectal Cancer

Other Topics

Counseling

Heredity Diffuse Gastric Cancer

Medullary Thyroid Cancer

von Hippel-Lindau Syndrome

Comments or Questions?Please contact us atPrevention@asco.org

The ideas and opinions expressed here do not necessarily reflect the opinions of the American Society of Clinical Oncology (ASCO). The mention of any product, service, or therapy herein should not be construed as an endorsement of the products mentioned. The information herein should not be relied on as being complete or accurate, nor should it be considered as inclusive of all proper treatments or methods of care or as a statement of the standard of care. The information is not continually updated and may not reflect the most recent evidence. The information addresses only the topics specifically identified therein and is not applicable to other interventions, diseases, or stages of diseases. This information does not mandate any particular course of medical care. Furthermore, the information is not intended to substitute for the independent professional judgment of the treating provider, because the information does not account for individual variation among patients. Use of the information is voluntary. ASCO provides this information on an as-is basis and makes no warranty, express or implied, regarding the information. ASCO specifically disclaims any warranties of merchantability or fitness for a particular use or purpose. Links to third party websites are provided for your convenience, and ASCO does not endorse and is not responsible for any content, advertising or other material available from such sites. ASCO assumes no responsibility for any injury or damage to persons or property arising out of or related to any use of this information or for any errors or omissions.

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Recommendation and review posted by Jack Burke

Scientists in the US may be out in front developing the next generation of Crispr-based genetic tools, but its China thats pushing those techniques toward human therapies the fastest. Chinese researchers were the first to Crispr monkeys, and non-viable embryos, and to stick Crisprd cells into a real live human. And now, a team of scientists in China have used a cutting-edge Crispr technique, known as base editing, to repair a disease-causing mutation in viable human embryos.

Published last week in the journal Molecular Therapy, and reported first by Stat, the study represents significant progress over previous attempts to remodel the DNA of human embryos. Thats in part because the editing worked so well, and in part because that editing took place in embryos created by a standard in-vitro fertilization technique.

So-called germline editing, the contentious technology that can permanently change the code in every cell in the human body, has been gaining acceptance in the last few years as research has pushed forward, illuminating the possibilities of Crispr. Immediately following those first reports of embryonic gene-editing in China in 2015, an international summit convened by the US National Academy of Sciences concluded that actually trying to produce a human pregnancy from such modified germlines was irresponsible, given ongoing safety concerns and lack of societal consensus. Two years later, a report from the NAS and the National Academy of Medicine stated that clinical trials for editing out heritable diseases could be permitted in the future, but only for serious conditions under stringent oversight.

Attitudes may be slowly changing: Last month, the United Kingdoms Nuffield Council on Bioethics went so far as to say that heritable genome editing could be ethically acceptable in some circumstances. A Pew Research Council study released at the end of July found that 72 percent of Americans think changing an unborn babys DNA to treat a serious disease would be an appropriate use of gene-editing technology.

In the study published in Molecular Therapy, the Chinese scientists corrected a mutation that causes Marfan syndrome, an incurable connective tissue disorder that affects about 1 in 5,000 people. A single letter mistake in the gene for FBN1, which codes for the fibrillin protein, can cause a ripple effect of problemsfrom loose joints to weak vision to life-threatening tears in the hearts walls. Starting with healthy eggs and sperm donated by a Marfan syndrome patient, the team of researchers from Shanghai Tech University and Guangzhou Medical University used an IVF technique to make viable human embryos. Then they injected the embryos with a Crispr construct known as a base editor, which swaps out a single DNA nucleotide for anotherin this case, removing a C and replacing it with a T.1 They kept the embryos alive for another two days in the lab, long enough to run tests to see how well the editing worked.

Sequencing revealed that all 18 embryos had been edited, with 16 of the embryos bearing only the corrected version of the FBN1 gene. In two of the embryos, additional unwanted edits had also taken place. Previously, the most successful demonstration of gene editing in the human germline was the correction of a mutation that causes a hereditary heart condition in 42 out of 58 embryos. That study, which was published last year, used standard Crispr cut-and-paste technology.

Its a nice demonstration of the use of base editors to correct a well-known point mutation that causes a human genetic disease in a setting that may become therapeutically relevant, says David Liu, whose lab at Harvard developed the base editor used to correct the Marfan mutation, though he was not involved in the study.

Rather than breaking the double-stranded DNA molecule and allowing the cell to repair itself with a healthy gene template, these newer versions of Crispr change just a single letter. If Crispr is a pair of molecular scissors, Lius base editors are more like a pencil with a squeaky new eraser. While the hope is that such precise gene-writing implements wont cause the kind of sloppy chaos that Crispr 1.0 is capable of, Liu says its too early to make any general statements about their relative risks as a therapeutic. Despite more than 50 publications using base editors from laboratories around the world, the entire field of base editing is only about two years old, and additional studies are needed to assess as many possible consequences of base editing as can be reasonably detected.

Some of those studies are being conducted at Beam Therapeutics, the startup that Liu co-founded earlier this year with fellow Crispr pioneer Feng Zhang. Beams first license agreement with Harvard covers Lius C base editor, which makes programmable G-to-A or C-to-T edits, like the one used to correct the Marfan mutation. The second is the A base editor, which can do T-to-C as well as A-to-G edits. But dont expect Beam to be erasing genetic diseases from the germline any time soon. The company is focused on using base editing to treat serious diseases in children and adults only, not on embryo editing, says CEO John Evans. More consideration would be needed before society is ready to consider embryo editing, and we look forward to participating in the discussion.

In the meantime, Beam will be just one of many US companies looking at an increasingly streamlined path for genetic medicines. In July, FDA Commissioner Scott Gottlieb announced a new regulatory framework for gene therapies to treat rare diseases. The agency issued a suite of six guidance documents updating the approval process. And on August 17, the FDA along with the National Institutes of Health proposed changes in the way the agencies together assess the safety of gene-therapy human trials.

Specifically, the proposals will eliminate review by the NIHs Recombinant DNA Advisory Committee, which was established in 1974 to advise on emerging genetic technologies. In a New England Journal of Medicine editorial describing the changes, Gottlieb and NIH Director Francis Collins wrote it was their view that there is no longer sufficient evidence to claim that the risks of gene therapy are entirely unique and unpredictableor that the field still requires special oversight that falls outside our existing framework for ensuring safety. A more streamlined approval process may help the US move faster in the long-run, though probably not enough to catch Chinas head start. But when it comes to gene editing's most controversial applications, theres nothing wrong with being slow.

1Correction appended 8-27-2018, 10:45 EDT. The researchers changed a cytosine to a thymine, not an adenine to guanine, as previously stated.

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With Embryo Base Editing, China Gets Another Crispr First

Recommendation and review posted by Rebecca Evans

Welcome to the Antiviral Gene Therapy Research Unit (AGTRU) of the University of the Witwatersrand and South African Medical Research Council (SAMRC)

Investigation by the AGTRU team is focused on countering viral infections that cause serious health problems in South Africa. The long term objectives of AGTRU are to

Discovery of the RNA interference (RNAi) pathway and advances in the engineering of sequence-specific nucleases have provided the means for powerful and specific disabling of genes. These advances led to considerable enthusiasm for use of gene therapy to counter viral infections, such as are caused by persistence of hepatitis B virus (HBV) and human immunodeficiency virus type 1 (HIV-1). The focus of the AGTRU has been on optimising use of RNAi activators and transcription activator-like effector nucleases (TALENs) to inhibit viral proliferation. Development of suitable vectors for delivery of antiviral sequences to infected cells is also an active field of investigation within the unit.

Research activities are generously supported by South African and International funding agencies. South African and international partnerships have been established, and these are an important contributor to the groups resource base.

The unit currently has approximately 20 members and these include molecular biologists, clinicians and postgraduate students. There are four tenured university appointees in the unit and the director is Professor Patrick Arbuthnot. AGTRU is equipped as a modern molecular biology research laboratory and has expertise in a range of techniques. These are advanced methods of nucleic acid manipulation, gene transfer to mammalian cells, use of lipoplex and recombinant viral vectors. AGTRU is set up to investigate efficacy of antiviral compounds in vivo in murine (e.g. HBV transgenic mice) and cell culture models of viral replication.

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Antiviral Gene Therapy Research Unit - Wits University

Recommendation and review posted by Jack Burke

Alternative names for hypopituitarism

Hypopit; pituitary insufficiency; partial hypopituitarism; panhypopituitarism (pan referring to all pituitary hormones being affected); anterior hypopituitarism

Hypopituitarism is failure of the pituitary gland to produce one, some, or all of the hormones it normally produces. The pituitary gland has two parts, the anterior pituitary and the posterior pituitary, and hormone production can be affected in both parts.

Below are listed some of the causes of hypopituitarism:

The signs and symptoms of hypopituitarism depend on which of the pituitary gland hormones are involved, to what extent and for how long. It also depends on whether the hormone deficiencies began as a child or later in adult life. Symptoms can be slow at the start and vague.It is worth understanding the normal function and effects of these hormones in order to understand the signs and symptoms of hypopituitarism. (See the article on pituitary gland.) There may also be additional symptoms due to the underlying cause of the hypopituitarism, such as the effects of pressure from a tumour.

Symptoms can include:

Hypopituitarism is rare. At any given time, between 300 and 455 people in a million may have hypopituitarism. A number of endocrinologists believe that hypopituitarism is quite common after brain injuries. If this belief is confirmed, then hypopituitarism may be significantly more common than previously believed.

Most cases of hypopituitarism are not inherited.However, there are some very rare genetic abnormalities than can cause hypopituitarism.

Blood tests are required to check the level of the hormones, which are either produced by the pituitary gland itself, or by peripheral endocrine glands controlled by the pituitary gland. These blood tests may be one-off samples or the patient may require more detailed testing on a day-unit. These are called dynamic tests and they measure hormone levels before and after stimulation to see if the normal pituitary gland is working properly.They usually last between1 to 4 hours.

If it is suspected that there is a lack of anti-diuretic hormone, the doctor may organise a water deprivation test. The patient will be deprived of water for a period of eight hours under very close supervision with regular blood and urine tests.The test may be extended to a 24 hour period if needed, which means an overnight stay in hospital.

Other tests may also be organised to try and identify the underlying cause of the hypopituitarism. These could include blood tests, scans such as computerised tomography (CT) or magnetic resonance imaging (MRI) scans, and tests for vision.

Hypopituitarism is treated by replacing the deficient hormones. Treatment will be tailored to the individual depending on which hormones they are deficient in:

Since the treatment of hypopituitarism only involves replacing hormones that the body should be making but is unable to, there should be no side-effects if the appropriate amounts of hormones are replaced.Patients will be monitored to ensure they are receiving the correct amount of replacement hormones. Some side-effects can occur from hormone replacement if the amount replaced is higher than the individuals body requirements.If the patient has any concerns, they should discuss them with their doctor.

People with long-term hypopituitarism will need to take daily medication and will require regular checks with an endocrinologist at an outpatients clinic.

People with hypopituitarism may have an impaired quality of life.Hypopituitarism is associated with an increased risk of heart disease and strokes as a result of the physical changes that occur in body fat, cholesterol and circulation. Healthy living, a balanced diet and exercise to prevent becoming overweight are essential to reduce this risk.

People with hypopituitarism also have a higher risk of developing osteoporosis or brittle bones and, therefore, have a higher risk of developing fractures from minor injuries. A diet that is rich in calcium and vitamin D along with moderate amounts of weight-bearing exercise and training are helpful in decreasing this risk.

Appropriate pituitary hormone replacement therapy can reduce all these risks.

Last reviewed: Jan 2015

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Hypopituitarism | You and Your Hormones from the Society for ...

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Panhypopituitarism: Practice Essentials, Pathophysiology ...

Recommendation and review posted by simmons

What is hypopituitarism?

Hypopituitarism happens when your pituitary gland is not active enough. As a result the gland does not make enough pituitary hormones.

The pituitary is a small gland at the base of your brain. It is one of several glands that make hormones. Hormones are chemicals that send information and instructions from one set of cells to another. The pituitary gland makes many types of hormones. These hormones affect many things, including bone and tissue growth, your thyroid gland, and sexual development and reproduction.

Causes can directly affect the pituitary gland. Or they can indirectly affect the glandthrough changes inthe hypothalamus. This is a part of the brain that is just above the pituitary gland.

Direct causes include:

Indirect causes include:

Symptoms are different for each person. They may happen over time or right away. They depend on which hormones the pituitary gland is not making enough of. These hormone deficiencies, and the symptoms they cause, include:

These symptoms may look like other health problems. Always see your healthcare provider for a diagnosis.

Your healthcare provider will ask about your medical history. You will also need an exam. Other tests you may need include:

Your healthcare provider will figure out the best treatment for you based on:

Treatment depends on what is causing the condition. The treatment goal is to have the pituitary gland work as it should. Treatment may include:

Tell your healthcare provider if your symptoms get worse or you have new symptoms.

Tips to help you get the most from a visit to your healthcare provider:

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Hypopituitarism | Lifespan

Recommendation and review posted by simmons

There was a very sad example of this in the last decade.There's a wonderful drug, and a class of drugs actually,but the particular drug was Vioxx, andfor people who were suffering from severe arthritis pain,the drug was an absolute lifesaver,but unfortunately, for another subset of those people,they suffered pretty severe heart side effects,and for a subset of those people, the side effects wereso severe, the cardiac side effects, that they were fatal.But imagine a different scenario,where we could have had an array, a genetically diverse array,of cardiac cells, and we could have actually testedthat drug, Vioxx, in petri dishes, and figured out,well, okay, people with this genetic type are going to havecardiac side effects, people with these genetic subgroupsor genetic shoes sizes, about 25,000 of them,are not going to have any problems.The people for whom it was a lifesavercould have still taken their medicine.The people for whom it was a disaster, or fatal,would never have been given it, andyou can imagine a very different outcome for the company,who had to withdraw the drug.

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Susan Solomon: The promise of research with stem cells ...

Recommendation and review posted by sam

What is pre-implantation genetic testing (PGT)?

Pre-implantation Genetic Testing (PGT) is a sophisticated scientific technique which can be used to test embryos for either a specific known genetic condition or chromosome abnormality.

This enables only chromosomally normal embryos or those unaffected by a specific disorder to be selected for transfer during an IVF cycle, maximising the chance of a healthy baby.

Up to 70% of embryos created, either via natural conception or IVF dont survive the first 3 months of pregnancy and many dont achieve implantation because of those two reasons.

IVFAustralia offers an internationally recognised pre-implantation genetics program, managed by Australias leading pre-implantation genetics laboratory Virtus Diagnostics.

You may wish to consider pre-implantation genetic testing if you are concerned about any of the following issues:

In pre-implantation genetic testing, the woman goes through a standard IVF cycle. While the embryos are developing in the IVF laboratory, a few cells are removed from each embryo and tested in one of two ways.

The technique of Next Generation Sequencing tests all 24 chromosomes in an embryo to enable the selection and transfer of only chromosomally healthy embryos.

Read more about PGT with Next Generation Sequencing >

Karyomapping is used if you or your partner are known to be carriers of a serious single gene disorder.

Karyomapping can identify which embryos are NOT affected by the disorder preventing the condition from being passed on to the next generation.

Read more about PGT with Karyomapping >

Our genetic material, or DNA, is tightly coiled into structures called chromosomes. Every cell in an embryo should have 46 chromosomes, arranged in 23 pairs.An extra or missing chromosome means the embryo is abnormal. This is called aneuploidy and includes conditions such as Down syndrome, where there is an extra chromosome number 21.

These chromosome abnormalities or aneuploidies can affect up to 70% of early human embryos, and most cause the embryo to stopping developing resulting in failure to become pregnant or miscarriage.

We are able to test for a wide range of single gene disorders, including:

A chromosomal translocation is a condition where a piece, or pieces, of one chromosome are attached to a different chromosome.

Up to 2% of people with reproductive problems are found to have a balanced translocation.

A balanced translocation is where there is a chromosomal rearrangement but overall there is the correct amount of genetic material present so that the person himself or herself is completely healthy.

However, in this situation, some of their eggs or sperm will end up with the wrong amount of genetic material, leading to the embryo having an unbalanced translocation. i.e the embryo has the wrong amount of genetic material.

Embryos with an unbalanced translocation, usually miscarry, or are born with severe abnormalities.

If either partner carries a balanced translocation, we can use PGT with Next Generation Sequencing to test each embryo for the presence of an unbalanced translocation.

This enables the selection and transfer of only chromosomally normal embryos, maximising the chance of a successful pregnancy and a healthy baby.

Some genetic conditions affect one gender, for example haemophilia and muscular dystrophy. When it is not possible to detect the exact genetic error that causes the disease, PGT can be used to determine the gender of embryos, so only embryos of the required gender and with the correct number of chromosomes will be transferred.

Gender selection is prohibited for family balancing and can only be used for medical reasons.

Not as far as we know. Current research shows that the likelihood of a biopsied embryo implanting is exactly the same as a non-biopsied embryo. Despite the removal of a few cells from the embryo, there have been no reports of any health problems as a result of embryo biopsy in children conceived after PGT.

An IVF cycle with PGT has three components of cost:

PGT with Karyomapping for single gene disorders costs $1,640 for the preliminary evaluation plus $700 per embryo biopsied with a maximum cost of $2460 for 6 or more embryos from a single IVF cycle.

PGT with Next Generation Sequencingcosts $700 per embryo biopsied with a maximum cost of $3995 for up to 10 embryos.

There is no Medicare rebate associated with PGT. However your final costs may vary depending on your individual circumstances.

If you have any questions about the cost of pre-implantation genetic testing with IVF Australia please phone 18000 111 483 or email us.

Read more about the cost of IVF >

Pre-implantation genetic testing (previously referred amongst the community as PGD or pre-implantation genetic diagnosis) has helped many couples conceive healthy babies, many after long periods of infertility or with serious genetic diseases in the family.

We have a genetic team dedicated to helping patients who are at risk of inherited conditions and can provide you with information about these risks, and support you with any decisions you make.

If you know or suspect you have a genetic or chromosomal abnormality please come to a free fertility seminar or book an appointment with a fertility specialist.

Appointments are available within the next couple of weeks and will cost approximately $150 for a couple after the Medicare rebate.

Find out more about the costs of Pre-implantation Genetic Testing...Learn about Next Generation Sequencing...Find out more about Karyomapping...Find out more about Non-Invasive Prenatal Testing...Contact us for more information on PGT...

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Pre-implantation Genetic Testing | IVF Australia

Recommendation and review posted by Bethany Smith

Stem cell therapy can be described as a means or process by which stem cells are used for the prevention, treatment or the cure of diseases. Stem cells are a special kind of cells that have features other types of cells dont have. As an illustration, stem cells are capable of proliferation. This implies that they can develop into any type of cell, and grow to start performing the functions of the tissue. In addition, they can regenerate. This means they can multiply themselves. This is most important when a new tissue has to be formed. Also, they modulate immune reactions. This has made them useful for the treatment of autoimmune diseases, especially those that affect the musculoskeletal system such as rheumatoid arthritis, systemic lupus erythematosus and so on. Stem cells can be derrived from different sources. They can be extracted from the body, and in some specific parts of the body. This includes the blood, bone marrow, umbilical cord in newborns, adipose tissue, and from embryos. There are 2 main types of stem cell transplant. These are autologous stem cell transplant, and allogeneic stem cell transplant. The autologous stem cell transplant means that stem cells are extracted from the patient, processed, and then transplanted back to the patient, for therapeutic purposes. On the other hand, allogeneic stem cell transplant means the transplant of stem cells or from another individual, known as the donor, to another person, or recipient. Some treatments must be given to the receiver to prevent any cases of rejections, and other complications. The autologous is usually the most preferred type of transplant because of its almost zero side effects. Below are some of the stem cell treatments. Our goal is to provide education, research and an opportunity to connect with Stem Cell Doctors, as well as provide stem cell reviews

Adipose Stem Cell TreatmentsAdipose stem cell treatment is one of the most commonly used. This is because large quantities of stem cells can be derrived from them. According to statistics, the number of stem cells in adipose tissue are usually hundreds of times higher than what can be obtained from other sources, such as the bone marrow stem cells. Adipose stem cells have taken the center stage in the world of stem cell therapy. Apart from the ease that comes with the harvesting of these cells from the adipose tissue, they also have some special features, that separates them from other types of cells. Adipose stem cells are capable of regulating and modulating the immune system. This includes immune suppression, which is important for the treatment of autoimmune diseases. In addition, adipose stem cells can differentiate to form other types of cells. Some of them include the bone forming cells, cardiomyocytes, and cells of the nervous system.

This process can be divided into four parts. These are

Stem cell joint injection is fast becoming the new treatment of joint diseases. Stem cells derived from bone marrow, adipose and mesenchymal stem cells are the most commonly used. The stem cells are injected into the joints, and they proceed to repair and replace the damaged tissues. The cells also modulate the inflammatory process going on. Overall, stem cell joint injections significantly reduce the recovery time of patients and also eliminates pain and risks associated with surgery. Examples of diseases where this treatment is used include osteoarthritis, rheumatoid arthritis, and so on. Researchers and physicians have rated this procedure to be the future of joint therapy.

Losing a tooth as a kid isnt news because youd eventually grow them back, but losing one as an adult isnt a pleasant experience. Youd have to go through the pains of getting a replacement from your dentist. Apart from the cost of these procedures, the pain and number of days youd have to stay at home nursing the pain is also a problem. Nevertheless, there are great teeth replacement therapies available for all kinds of dental problems. Although there are already good dental treatment methods, stem cell therapy might soon become the future of dental procedures. Currently, a lot of research is being done on how stem cells can be used to develop teeth naturally, especially in patients with dental problems. The aim of the project is to develop a method whereby peoples stem cells are used in regenerating their own teeth and within the shortest time possible. Some of the benefits of the stem cell tooth would be:

The quality of life of those that underwent serious procedures, especially those that had an allogeneic hematopoietic stem cell transplantation done was studied. It was discovered that this set of people had to cope with some psychological problems, even years after the procedure. In addition, allogeneic stem cell transplantation often comes with some side effects. However, this a small price to pay, considering that the adverse effects are not usually life-threatening. Also theses types of procedures are used for severe disorders or even terminal diseases. On the other hand, autologous stem cell transplantation bears the minimum to no side effects. Patients do have a great quality of life, both in the short term and in the long term.

This is one of the many uses of stem cells. The stem cell gun is a device that is used in treating people with wounds or burns. This is done by simply triggering it, and it sprays stem cells on the affected part. This kind of treatment is crucial for victims of a severe burn. Usually, people affected by severe burns would have to endure excruciating pain. The process of recovery is usually long, which might vary from weeks to months, depending on the severity of the burn. Even after treatment, most patients are left with scars forever. However, the stem cell gun eliminates these problems, the skin can be grown back in just a matter of days. The new skin also grows evenly and blends perfectly with the other part of the body. This process is also without the scars that are usually associated with the traditional burns therapy. The stem cell gun is without any side effects.

There is one company that focuses on the production of stem cell supplements. These stem cells are usually natural ingredients that increase the development of stem cells, and also keeps them healthy. The purpose of the stem cell supplements is to help reduce the aging process and make people look younger. These supplements work by replacing the dead or repairing the damaged tissues of the body. There have been a lot of testimonials to the efficacy of these supplements.

It is the goal of researchers to make stem cell therapy a good alternative for the millions of patients suffering from cardiac-related diseases. According to some experiments carried out in animals, stem cells were injected into the ones affected by heart diseases. A large percentage of them showed great improvement, even within just a few weeks. However, when the trial was carried out in humans, some stem cells went ahead to develop into heart muscles, but overall, the heart function was generally improved. The reason for the improvement has been attributed to the formation of new vessels in the heart. The topic that has generated a lot of arguments have been what type of cells should be used in the treatment of heart disorders. Stem cells extracted from the bone marrow, embryo have been in use, although bone marrow stem cells are the most commonly used. Stem cells extracted from bone marrow can differentiate into cardiac cells, while studies have shown that other stem cells cannot do the same. Even though the stem cell therapy has a lot of potential in the future, more research and studies have to be done to make that a reality.

The use of stem cells for the treatment of hair loss has increased significantly. This can be attributed to the discovery of stem cells in bone marrow, adipose cells, umbilical cord, and so on. Stem cells are extracted from the patient, through any of the sources listed above. Adipose tissue stem cells are usually the most convenient in this scenario, as they do not require any special extraction procedure. Adipose tissue is harvested from the abdominal area. The stem cells are then isolated from the other cells through a process known as centrifugation. The stem cells are then activated and are now ready for use. The isolated stem cells are then introduced into the scalp, under local anesthesia. The entire process takes about three hours. Patients are free to go home, after the procedure. Patients would begin to see improvements in just a few months, however, this depends largely on the patients ability to heal. Every patient has a different outcome.

Human umbilical stem cells are cells extracted from the umbilical cord of a healthy baby, shortly after birth. Umbilical cord tissue is abundant in stem cells, and the stem cells can differentiate into many types of cells such as red blood cells, white blood cells, and platelets. They are also capable of differentiating into non-blood cells such as muscle cells, cartilage cells and so on. These cells are usually preferred because its' extraction is minimally non invasive. It also is nearly painless. It also has zero risks of rejecting, as it does not require any form of matching or typing.Human umbilical stem cell injections are used for the treatment of spinal cord injuries. A trial was done on twenty-five patients that had late-stage spinal cord injuries. They were placed on human umbilical stem cell therapy, while another set of 25 patients were simultaneously placed on the usual rehabilitation therapy. The two groups were studied for the next twelve months. The results of the trial showed that those people placed on stem cell therapy by administering the human umbilical cell tissue injections had a significant recovery, as compared to the other group that underwent the traditional rehabilitation therapy. It was concluded that human umbilical tissue injections applied close to the injured part gives the best outcomes.

Stem cell therapy has been used for the treatment of many types diseases. This ranges from terminal illnesses such as cancer, joint diseases such as arthritis, and also autoimmune diseases. Stem cell therapy is often a better alternative to most traditional therapy today. This is because stem cell procedure is minimally invasive when compared to chemotherapy and so on. It harnesses the bodys own ability to heal. The stem cells are extracted from other parts of the body and then transplanted to other parts of the body, where they would repair and maintain the tissues. They also perform the function of modulating the immune system, which makes them important for the treatment of autoimmune diseases. Below are some of the diseases that stem cell therapies have been used successfully:

A stem cell bank can be described as a facility where stem cells are stored for future purposes. These are mostly amniotic stem cells, which are derived from the amnion fluid. Umbilical cord stem cells are also equally important as it is rich in stem cells and can be used for the treatment of many diseases. Examples of these diseases include cancer, blood disorders, autoimmune diseases, musculoskeletal diseases and so on. According to statistics, umbilical stem cells can be used for the treatment of over eighty diseases. Storing your stem cells should be seen as an investment in your health for future sake. Parents do have the option of either throwing away their babys umbilical cord or donating it to stem cell banks.

The adipose tissue contains a lot of stem cells, that has the ability to transform into other cells such as muscle, cartilage, neural cells. They are also important for the treatment of some cardiovascular diseases. This is what makes it important for people to want to store their stem cells. The future health benefit is huge. The only way adults can store their stem cells in sufficient amounts is to extract the stem cells from their fat tissues. This process is usually painless and fast. Although, the extraction might have to be done between 3 to 5 times before the needed quantity is gotten. People that missed the opportunity to store their stem cells, using their cord cells, can now store it using their own adipose tissues. This can be used at any point in time.

Side effects often accompany every kind of treatment. However, this depends largely on the individual. While patients might present with side effects, some other people wouldnt. Whether a patient will present with adverse effects, depends on the following factors;

Some of the common side effects of stem cell transplant are;

Stem cell treatment has been largely successful so far, however, more studies and research needs to be done. Stem cell therapy could be the future.

Stem cells are unique cells that have some special features such as self-regeneration, tissue repair, and modulation of the immune system. These are the features that are employed in the treatment of diseases.

Our doctors are certified by iSTEMCELL but operate as part of a medical group or as independent business owners and as such are free to charge what the feel to be the right fit for their practice and clients. We have seen Stem Cell Treatment costs range from $3500 upwards of $30,000 depending on the condition and protocol required for intended results. Find the Best Stem Cell Doctor Near me If you are interested in saving money, try our STEM CELL COUPON!

Travel Medcations are becoming very popular around the globe for several reasons but not for what one might think. It is not about traveling to Mexico to save money, but to get procedures or protocols that are not yet available in your home country. Many procedures are started in your home country, then the tissue is set to the tissue lab where it is then grown in a process to maximize live cells, then sent to a hospital in Mexico designed to treat or provide different therapies for different conditions. If you're ready to take a medical vacation call 972-800-6670 for our"WHITE GLOVE" service.

Chen, C. and Hou, J. (2016). Mesenchymal stem cell-based therapy in kidney transplantation. Stem Cell Research & Therapy, 7(1).

Donnelly, A., Johar, S., OBrien, T. and Tuan, R. (2010). Welcome to Stem Cell Research & Therapy. Stem Cell Research & Therapy, 1(1), p.1.

Groothuis, S. (2015). Changes in Stem Cell Research. Stem Cell Research, 14(1), p.130.

Rao, M. (2012). Stem cells and regenerative medicine. Stem Cell Research & Therapy, 3(4), p.27.

Vunjak-Novakovic, G. (2013). Physical influences on stem cells. Stem Cell Research & Therapy, 4(6), p.153.

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Stem Cell Therapy and Stem Cell Injection Provider Finder ...

Recommendation and review posted by Bethany Smith

Cas9 and Cpf1 can be reprogrammed to different sites or multiple sites using multiple gRNAs. The availability of the different engineered variants of Cas9 and Cpf1 allows for different types of cuts for genome editing, which include the following:

Cut & Revise and Cut & Remove typically result in disruption of a problematic gene or elimination of a mutation. These approaches leverage the cell's natural DNA repair mechanisms known as non-homologous end joining, or NHEJ, to complete the edit.

When a cell repairs a DNA cut by NHEJ, it leaves small insertions and deletions at the cut site, collectively referred to as indels. NHEJ can be used to either cut and revise the targeted gene or to cut and remove a segment of DNA. In the ''cut and revise'' process, a single cut is made. In the ''cut and remove'' process, two cuts are made, which results in the removal of the intervening segment of DNA. This approach could be used to delete either a small or a large segment of DNA depending on the type of repair desired.

The second mechanism our Cut & Replace approach leverages a different DNA repair mechanism known as homology directed repair, or HDR. In this approach, a DNA template is also provided, one that is similar to the DNA that has been cut. The cell can use the template to construct reparative DNA, resulting in the replacement of a defective genetic sequence with the correct one.

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CRISPR | Genome Editing, DNA Repair

Recommendation and review posted by simmons