Page 11234..1020..»

Home – Revive IV Therapy

Your body is trying to tell you it needs hydration. Drinking plenty of water is a good start, but absorption through the digestive tract takes time. IV hydration is the fastest & most effective method of introducing fluid, nutrients & health supplements throughout your entire body. With board-certified physicians, clinical science professionals & a staff of experts in nutrition and supplements,Revive Hydration IV treatments are a safe, fast and easy way to revive, replenish and rejuvenate your body and mind.

See the original post:
Home - Revive IV Therapy

Recommendation and review posted by Bethany Smith

Genes and Gene Therapy: MedlinePlus

Genes are the building blocks of inheritance. Passed from parent to child, they contain instructions for making proteins. If genes don't produce the right proteins or don't produce them correctly, a child can have a genetic disorder.. Gene therapy is an experimental technique that uses genes to treat or prevent disease.

Read the original post:
Genes and Gene Therapy: MedlinePlus

Recommendation and review posted by Bethany Smith

Female Genetic Contributions to Sperm Competition in …

Abstract

In many species, sperm can remain viable in the reproductive tract of a female well beyond the typical interval to remating. This creates an opportunity for sperm from different males to compete for oocyte fertilization inside the female's reproductive tract. In Drosophila melanogaster, sperm characteristics and seminal fluid content affect male success in sperm competition. On the other hand, although genome-wide association studies (GWAS) have demonstrated that female genotype plays a role in sperm competition outcome as well, the biochemical, sensory and physiological processes by which females detect and selectively use sperm from different males remain elusive. Here, we functionally tested 26 candidate genes implicated via a GWAS for their contribution to the female's role in sperm competition, measured as changes in the relative success of the first male to mate (P1). Of these 26 candidates, we identified eight genes that affect P1 when knocked down in females, and showed that five of them do so when knocked down in the female nervous system. In particular, Rim knockdown in sensory pickpocket (ppk)+ neurons lowered P1, confirming previously published results, and a novel candidate, caup, lowered P1 when knocked down in octopaminergic Tdc2+ neurons. These results demonstrate that specific neurons in the female's nervous system play a functional role in sperm competition and expand our understanding of the genetic, neuronal and mechanistic basis of female responses to multiple matings. We propose that these neurons in females are used to sense and integrate signals from courtship or ejaculates, to modulate sperm competition outcome accordingly.

Read more:
Female Genetic Contributions to Sperm Competition in ...

Recommendation and review posted by Bethany Smith

Success in Cryonics – osiriscryonics.com

Despite the fact that no human placed in a cryonic suspension has yet been revived, some living organisms can be, and have been, brought back from a dead or near-dead state.

Many biological specimens, including whole insects, many types of human tissue including brain tissue, and human embryos have been cryogenically preserved, stored at liquid nitrogen temperature where all decay ceases, and revived. Cooling living cells to cryogenic temperatures slows metabolic process almost to a stop, making sure the cell doesn't use anymore energy, receive chemical signals, or to carry out any living processes. This would allow a cell to stay in its current state for any amount of time needed, until it is heated to normal functioning temperatures, where the body would continue its processes of life with freezing being a pause on life. This leads scientists to believe that the same can be done with whole human bodies, and that any minimal harm can be reversed with future advancements in medicine.

Neurosurgeons often cool patients bodies so they can operate on aneurysms without damaging or rupturing the nearby blood vessels. Human embryos that are frozen in fertility clinics, defrosted and implanted in a mothers uterus grow into perfectly normal human beings. This method isnt new or groundbreaking- successful cryopreservation of human embryos was first reported in 1983 by Trounson and Mohr with multicellular embryos that had been slow-cooled using dimethyl sulphoxide (DMSO).

Even though a mammal has not been fully frozen at cryogenic temperatures and revived, similar tests have been done on monkeys and dogs. The animals had their blood removed and the cryoprotectant inserted. The animals were then cooled to temperatures under 0 degrees Celsius and fully revived.

Some frogs and other amphibians have a protein manufactured by their cells that act as a natural antifreeze which can protect them if theyre frozen completely solid.

And just in Feb. of 2016, there was a cryonics breakthrough when for the first time, scientists vitrified a rabbits brain and, after warming it back up, showed that it was in near perfect condition. Problems with the brain are the main reason why people are skeptical about cryonics, yet the rabbit's brain retained all memory and learning ability. This was the first time a cryopreservation was provably able to protect everything associated with learning and memory.

Cryogenically preserved rabbit brain

Originally posted here:
Success in Cryonics - osiriscryonics.com

Recommendation and review posted by Bethany Smith

Explainer: How CRISPR works | Science News for Students

(more about Power Words)

applicationA particular use or function of something.

base (in genetics) A shortened version of the term nucleobase. These bases are building blocks of DNA and RNA molecules.

biologyThe study of living things. The scientists who study them are known as biologists.

Cas9An enzyme that geneticists are now using to help edit genes. It can cut through DNA, allowing it to fix broken genes, splice in new ones or disable certain genes. Cas9 is shepherded to the place it is supposed to make cuts by CRISPRs, a type of genetic guides. The Cas9 enzyme came from bacteria. When viruses invade a bacterium, this enzyme can chop up the germs DNA, making it harmless.

cellThe smallest structural and functional unit of an organism. Typically too small to see with the naked eye, it consists of watery fluid surrounded by a membrane or wall. Animals are made of anywhere from thousands to trillions of cells, depending on their size. Some organisms, such as yeasts, molds, bacteria and some algae, are composed of only one cell.

chemicalA substance formed from two or more atoms that unite (become bonded together) in a fixed proportion and structure. For example, water is a chemical made of two hydrogen atoms bonded to one oxygen atom. Its chemical symbol is H2O.

CRISPRAn abbreviation pronounced crisper for the term clustered regularly interspaced short palindromic repeats. These are pieces of RNA, an information-carrying molecule. They are copied from the genetic material of viruses that infect bacteria. When a bacterium encounters a virus that it was previously exposed to, it produces an RNA copy of the CRISPR that contains that virus genetic information. The RNA then guides an enzyme, called Cas9, to cut up the virus and make it harmless. Scientists are now building their own versions of CRISPR RNAs. These lab-made RNAs guide the enzyme to cut specific genes in other organisms. Scientists use them, like a genetic scissors, to edit or alter specific genes so that they can then study how the gene works, repair damage to broken genes, insert new genes or disable harmful ones.

developmental(in biology) An adjective that refers to the changes an organism undergoes from conception through adulthood. Those changes often involve chemistry, size and sometimes even shape.

DNA(short for deoxyribonucleic acid) A long, double-stranded and spiral-shaped molecule inside most living cells that carries genetic instructions. It is built on a backbone of phosphorus, oxygen, and carbon atoms. In all living things, from plants and animals to microbes, these instructions tell cells which molecules to make.

engineeringThe field of research that uses math and science to solve practical problems.

fieldAn area of study, as in: Her field of research was biology. Also a term to describe a real-world environment in which some research is conducted, such as at sea, in a forest, on a mountaintop or on a city street. It is the opposite of an artificial setting, such as a research laboratory.

fluorescentCapable of absorbing and reemitting light. That reemitted light is known as a fluorescence.

gene(adj. genetic) A segment of DNA that codes, or holds instructions, for producing a protein. Offspring inherit genes from their parents. Genes influence how an organism looks and behaves.

genomeThe complete set of genes or genetic material in a cell or an organism. The study of this genetic inheritance housed within cells is known as genomics.

muscleA type of tissue used to produce movement by contracting its cells, known as muscle fibers. Muscle is rich in a protein, which is why predatory species seek prey containing lots of this tissue.

mutation(v. mutate) Some change that occurs to a gene in an organisms DNA. Some mutations occur naturally. Others can be triggered by outside factors, such as pollution, radiation, medicines or something in the diet. A gene with this change is referred to as a mutant.

nucleusPlural is nuclei. (in biology) A dense structure present in many cells. Typically a single rounded structure encased within a membrane, the nucleus contains the genetic information.

organ(in biology) Various parts of an organism that perform one or more particular functions. For instance, an ovary is an organ that makes eggs, the brain is an organ that interprets nerve signals and a plants roots are organs that take in nutrients and moisture.

palindrome (adj. palindromic) A word, a name or a phrase that has the same ordering of letters when read forwards or backwards. For instance, dad and mom are both palindromes.

proteinCompoundmade from one or more long chains of amino acids. Proteins are an essential part of all living organisms. They form the basis of living cells, muscle and tissues; they also do the work inside of cells. The hemoglobin in blood and the antibodies that attempt to fight infections are among the better-known, stand-alone proteins. Medicines frequently work by latching onto proteins.

RNAA molecule that helps read the genetic information contained in DNA. A cells molecular machinery reads DNA to create RNA, and then reads RNA to create proteins.

tag(in biology) To attach some rugged band or package of instruments onto an animal. Sometimes the tag is used to give each individual a unique identification number. Once attached to the leg, ear or other part of the body of a critter, it can effectively become the animals name. In some instances, a tag can collect information from the environment around the animal as well. This helps scientists understand both the environment and the animals role within it.

Read the original:
Explainer: How CRISPR works | Science News for Students

Recommendation and review posted by Bethany Smith

Are Calico Cats Always Female? – thesprucepets.com

Many people are surprised to hear that the vast majority of calico cats are female. Why is this? Can a calico cat to ever be male? Learn more about the genetics of coat color in felines.

A calico cat is not a breed of cat, it is a color pattern. To be called "calico," three colors must be present: black, white, and orange. Variations of these colors include gray, cream, and ginger. A true calico cat has large blocks of these three colors. Other names for calico cats include tortoiseshell or "torties," brindle, or tricolor cats.

Calico cats areusually female. And, this is due in large part togenetics.Coat color is a complex process that is the result of dominant and non-dominate genes interacting within the X chromosomes. Since coat color is a sex-linked trait, it is one of the cat's physical traits that vary based on gender.

Female animals have two X chromosomes (XX), while males have one X chromosome and one Y chromosome (XY). The genetic coding for having black or orange color in thecoat is found in the X chromosome. The color display is either orange or black.The coding for white is a completely separate gene.

In femalemammals, one of the X chromosomes is randomly deactivated,called X-inactivation,in each cell.For calico cats, the random mix of color genes that are activated or deactivated gives the blotchy orange and black color display.

Since females have two X chromosomes, they are able to have two different colors (orange or black, depending what X was deactivated) and white; creating the three-color calico mix.

Since males have only one X chromosome, they only have one black or orange gene and can only display orange or black (plus or minus white, controlled by another gene).

Calico cats are not always female. Male calico cats do exist and typically have a chromosomal aberration of two X chromosomes and one Y chromosome (XXY). Cats with this chromosomal configuration are usually sterile,which means that they are not able to breed. This syndrome is similar to a condition in humans called Klinefelter's syndrome, or XXY syndrome.

On October 1, 2001, the calico cat became the official cat of the state of Maryland in the United States.Calico cats are believed to bringgood luckin the folklore of many cultures.Japanese sailors often had a calicoship's catto protect against misfortune at sea.

Cat genetics is responsible for producing many different varieties of cats and coat types. Common types include the bicolor or tuxedo cat (mostly black with a white chest), striped or marbled tabby cats, and solid color cats.

White cats, true albino cats, are quite rare. Much more common is the appearance of white coat color that is caused by a lack ofmelanocytes, or pigmentation cells, in the skin.White cats with one or two blue eyes have a particularly high likelihood of being deaf.

Continued here:
Are Calico Cats Always Female? - thesprucepets.com

Recommendation and review posted by Bethany Smith

RNA targeting with CRISPRCas13 | Nature

Fire, A. et al. Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans. Nature 391, 806811 (1998)

Elbashir, S. M. et al. Duplexes of 21-nucleotide RNAs mediate RNA interference in cultured mammalian cells. Nature 411, 494498 (2001)

Root, D. E., Hacohen, N., Hahn, W. C., Lander, E. S. & Sabatini, D. M. Genome-scale loss-of-function screening with a lentiviral RNAi library. Nat. Methods 3, 715719 (2006)

Jackson, A. L. et al. Expression profiling reveals off-target gene regulation by RNAi. Nat. Biotechnol. 21, 635637 (2003)

Tyagi, S. Imaging intracellular RNA distribution and dynamics in living cells. Nat. Methods 6, 331338 (2009)

Shmakov, S. et al. Diversity and evolution of class 2 CRISPRCas systems. Nat. Rev. Microbiol. 15, 169182 (2017)

Shmakov, S. et al. Discovery and functional characterization of diverse class 2 CRISPRCas systems. Mol. Cell 60, 385397 (2015)

Abudayyeh, O. O. et al. C2c2 is a single-component programmable RNA-guided RNA-targeting CRISPR effector. Science 353, aaf5573 (2016)

Gootenberg, J. S. et al. Nucleic acid detection with CRISPRCas13a/C2c2. Science 356, 438442 (2017)

Dahlman, J. E. et al. Orthogonal gene knockout and activation with a catalytically active Cas9 nuclease. Nat. Biotechnol. 33, 11591161 (2015)

Hutchinson, J. N. et al. A screen for nuclear transcripts identifies two linked noncoding RNAs associated with SC35 splicing domains. BMC Genomics 8, 39 (2007)

East-Seletsky, A. et al. Two distinct RNase activities of CRISPRC2c2 enable guide-RNA processing and RNA detection. Nature 538, 270273 (2016)

Zetsche, B. et al. Multiplex gene editing by CRISPRCpf1 using a single crRNA array. Nat. Biotechnol. 35, 3134 (2017)

Subramanian, A. et al. Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. Proc. Natl Acad. Sci. USA 102, 1554515550 (2005)

Rath, S. et al. Human RNase L tunes gene expression by selectively destabilizing the microRNA-regulated transcriptome. Proc. Natl Acad. Sci. USA 112, 1591615921 (2015)

Gross, G. G. et al. Recombinant probes for visualizing endogenous synaptic proteins in living neurons. Neuron 78, 971985 (2013)

Unsworth, H., Raguz, S., Edwards, H. J., Higgins, C. F. & Yage, E. mRNA escape from stress granule sequestration is dictated by localization to the endoplasmic reticulum. FASEB J. 24, 33703380 (2010)

Nelles, D. A. et al. Programmable RNA tracking in live cells with CRISPR/Cas9. Cell 165, 488496 (2016)

Tourrire, H. et al. The RasGAP-associated endoribonuclease G3BP assembles stress granules. J. Cell Biol. 160, 823831 (2003).

Tafer, H. et al. The impact of target site accessibility on the design of effective siRNAs. Nat. Biotechnol. 26, 578583 (2008)

Mann, D. G. et al. Gateway-compatible vectors for high-throughput gene functional analysis in switchgrass (Panicum virgatum L.) and other monocot species. Plant Biotechnol. J. 10, 226236 (2012)

Zhang, Y. et al. A highly efficient rice green tissue protoplast system for transient gene expression and studying light/chloroplast-related processes. Plant Methods 7, 30 (2011)

Joung, J. et al. Genome-scale CRISPRCas9 knockout and transcriptional activation screening. Nat. Protocols 12, 828863 (2017)

Jain, M., Nijhawan, A., Tyagi, A. K. & Khurana, J. P. Validation of housekeeping genes as internal control for studying gene expression in rice by quantitative real-time PCR. Biochem. Biophys. Res. Commun. 345, 646651 (2006)

Bernhart, S. H., Hofacker, I. L. & Stadler, P. F. Local RNA base pairing probabilities in large sequences. Bioinformatics 22, 614615 (2006)

Li, B. & Dewey, C. N. RSEM: accurate transcript quantification from RNA-Seq data with or without a reference genome. BMC Bioinformatics 12, 323 (2011)

Schindelin, J. et al. Fiji: an open-source platform for biological-image analysis. Nat. Methods 9, 676682 (2012)

Read more:
RNA targeting with CRISPRCas13 | Nature

Recommendation and review posted by Bethany Smith

CRISPR Timeline | Broad Institute

Discovery of CRISPR and its function 1993 - 2005 Francisco Mojica, University of Alicante, Spain

Francisco Mojica was the first researcher to characterize what is now called a CRISPR locus, reported in 1993. He worked on them throughout the 1990s, and in 2000, he recognized that what had been reported as disparate repeat sequences actually shared a common set of features, now known to be hallmarks of CRISPR sequences (he coined the term CRISPR through correspondence with Ruud Jansen, who first used the term in print in 2002). In 2005 he reported that these sequences matched snippets from the genomes of bacteriophage (Mojica et al., 2005). This finding led him to hypothesize, correctly, that CRISPR is an adaptive immune system. Another group, working independently, published similar findings around this same time (Pourcel et al., 2005)

Discovery of Cas9 and PAMMay, 2005 Alexander Bolotin, French National Institute for Agricultural Research (INRA)

Bolotin was studying the bacteria Streptococcus thermophilus, which had just been sequenced, revealing an unusual CRISPR locus (Bolotin et al., 2005). Although the CRISPR array was similar to previously reported systems, it lacked some of the known cas genes and instead contained novel cas genes, including one encoding a large protein they predicted to have nuclease activity, which is now known as Cas9. Furthermore, they noted that the spacers, which have homology to viral genes, all share a common sequence at one end. This sequence, the protospacer adjacent motif (PAM), is required for target recognition.

Hypothetical scheme of adaptive immunityMarch, 2006 Eugene Koonin, US National Center for Biotechnology Information, NIH

Koonin was studying clusters of orthologous groups of proteins by computational analysis and proposed a hypothetical scheme for CRISPR cascades as bacterial immune system based on inserts homologous to phage DNA in the natural spacer array, abandoning previous hypothesis that the Cas proteins might comprise a novel DNA repair system.(Makarova et al., 2006)

Experimental demonstration of adaptive immunityMarch, 2007 Philippe Horvath, Danisco France SAS

S. thermophilus is widely used in the dairy industry to make yogurt and cheese, and scientists at Danisco wanted to explore how it responds to phage attack, a common problem in industrial yogurt making. Horvath and colleagues showed experimentally that CRISPR systems are indeed an adaptive immune system: they integrate new phage DNA into the CRISPR array, which allows them to fight off the next wave of attacking phage (Barrangou et al., 2007). Furthermore, they showed that Cas9 is likely the only protein required for interference, the process by which the CRISPR system inactivates invading phage, details of which were not yet known.

Spacer sequences are transcribed into guide RNAsAugust, 2008 John van der Oost, University of Wageningen, Netherlands

Scientists soon began to fill in some of the details on exactly how CRISPR-Cas systems interfere with invading phage. The first piece of critical information came from John van der Oost and colleagues who showed that in E-scherichia coli, spacer sequences, which are derived from phage, are transcribed into small RNAs, termed CRISPR RNAs (crRNAs), that guide Cas proteins to the target DNA (Brouns et al., 2008).

CRISPR acts on DNA targets December, 2008 Luciano Marraffini and Erik Sontheimer, Northwestern University, Illinois

The next key piece in understanding the mechanism of interference came from Marraffini and Sontheimer, who elegantly demonstrated that the target molecule is DNA, not RNA (Marraffini and Sontheimer, 2008). This was somewhat surprising, as many people had considered CRISPR to be a parallel to eukaryotic RNAi silencing mechanisms, which target RNA. Marraffini and Sontheimer explicitly noted in their paper that this system could be a powerful tool if it could be transferred to non-bacterial systems. (It should be noted, however, that a different type of CRISPR system can target RNA (Hale et al., 2009)).

Cas9 cleaves target DNADecember, 2010 Sylvain Moineau, University of Laval, Quebec City, Canada

Moineau and colleagues demonstrated that CRISPR-Cas9 creates double-stranded breaks in target DNA at precise positions, 3 nucleotides upstream of the PAM (Garneau et al., 2010). They also confirmed that Cas9 is the only protein required for cleavage in the CRISPR-Cas9 system. This is a distinguishing feature of Type II CRISPR systems, in which interference is mediated by a single large protein (here Cas9) in conjunction with crRNAs.

Discovery of tracrRNA for Cas9 systemMarch, 2011 Emmanuelle Charpentier, Umea University, Sweden and University of Vienna, Austria

The final piece to the puzzle in the mechanism of natural CRISPR-Cas9-guided interference came from the group of Emmanuelle Charpentier. They performed small RNA sequencing on Streptococcus pyogenes, which has a Cas9-containing CRISPR-Cas system. They discovered that in addition to the crRNA, a second small RNA exists, which they called trans-activating CRISPR RNA (tracrRNA) (Deltcheva et al., 2011). They showed that tracrRNA forms a duplex with crRNA, and that it is this duplex that guides Cas9 to its targets.

CRISPR systems can function heterologously in other species July, 2011 Virginijus Siksnys, Vilnius University, Lithuania

Siksnys and colleagues cloned the entire CRISPR-Cas locus from S. thermophilus (a Type II system) and expressed it in E. coli (which does not contain a Type II system), where they demonstrated that it was capable of providing plasmid resistance (Sapranauskas et al., 2011). This suggested that CRISPR systems are self-contained units and verified that all of the required components of the Type II system were known.

Biochemical characterization of Cas9-mediated cleavageSeptember, 2012 Virginijus Siksnys, Vilnius University, Lithuania

Taking advantage of their heterologous system, Siksnys and his team purified Cas9 in complex with crRNA from the E. coli strain engineered to carry the S. thermophilus CRISPR locus and undertook a series of biochemical experiments to mechanistically characterize Cas9s mode of action (Gasiunas et al., 2012).They verified the cleavage site and the requirement for the PAM, and using point mutations, they showed that the RuvC domain cleaves the non-complementary strand while the HNH domain cleaves the complementary site. They also noted that the crRNA could be trimmed down to a 20-nt stretch sufficient for efficient cleavage. Most impressively, they showed that they could reprogram Cas9 to target a site of their choosing by changing the sequence of the crRNA.

June, 2012 Charpentier and Jennifer Doudna, University of California, Berkeley

Similar findings as those in Gasiunas et al. were reported at almost the same time by Emmanuelle Charpentier in collaboration with Jennifer Doudna at the University of California, Berkeley (Jinek et al., 2012). Charpentier and Doudna also reported that the crRNA and the tracrRNA could be fused together to create a single, synthetic guide, further simplifying the system. (Although published in June 2012, this paper was submitted after Gasiunas et al.)

CRISPR-Cas9 harnessed for genome editingJanuary, 2013 Feng Zhang, Broad Institute of MIT and Harvard, McGovern Institute for Brain Research at MIT, Massachusetts

Zhang, who had previously worked on other genome editing systems such as TALENs, was first to successfully adapt CRISPR-Cas9 for genome editing in eukaryotic cells (Cong et al., 2013). Zhang and his team engineered two different Cas9 orthologs (from S. thermophilus and S. pyogenes) and demonstrated targeted genome cleavage in human and mouse cells. They also showed that the system (i) could be programmed to target multiple genomic loci, and (ii) could drive homology-directed repair. Researchers from George Churchs lab at Harvard University reported similar findings in the same issue of Science (Mali et al., 2013).

Citations

Barrangou, R., Fremaux, C., Deveau, H., Richards, M., Boyaval, P., Moineau, S., Romero, D.A., and Horvath, P. (2007). CRISPR provides acquired resistance against viruses in prokaryotes. Science 315, 17091712.

Bolotin, A., Quinquis, B., Sorokin, A.,and Ehrlich, S.D. (2005). Clustered regularly interspaced short palindrome repeats (CRISPRs) have spacers of extrachromosomal origin. Microbiology 151, 25512561.

Brouns, S.J., Jore, M.M., Lundgren, M., Westra, E.R., Slijkhuis, R.J., Snijders, A.P., Dickman, M.J., Makarova, K.S., Koonin, E.V., van der Oost, J. (2008) Small CRISPR RNAs guide antiviral defense in prokaryotes. Science 321, 960-964.

Cong, L., Ran, F.A., Cox, D., Lin, S., Barretto, R., Habib, N., Hsu, P.D., Wu, X., Jiang, W., Marraffini, L.A., et al. (2013). Multiplex genome engineering using CRISPR/Cas systems. Science 339, 819823.

Deltcheva, E., Chylinski, K., Sharma, C.M., Gonzales, K., Chao, Y., Pirzada, Z.A., Eckert, M.R., Vogel, J., and Charpentier, E. (2011). CRISPR RNA maturation by trans-encoded small RNA and host factor RNase III. Nature 471, 602607.

Gasiunas, G., Barrangou, R., Horvath, P., and Siksnys, V. (2012). Cas9crRNA ribonucleoprotein complex mediates specific DNA cleavage for adaptive immunity in bacteria. Pnas 109, E2579E2586.

Hale, C.R., Zhao, P., Olson, S., Duff, M.O., Graveley, B.R., Wells, L., Terns, R.M., and Terns, M.P. (2009). RNA-Guided RNA Cleavage by a CRISPR RNA-Cas Protein Complex. Cell 139, 945956.

Jinek, M., Chylinski, K., Fonfara, I., Hauer, M., Doudna, J.A., and Charpentier, E. (2012). A programmable dual-RNA-guided DNA endonuclease in adaptive bacterial immunity. Science 337, 816821.

Makarova, K.S., Grishin, N.V., Shabalina, S.A., Wolf, Y.I., Koonin, E.V. (2006). A putative RNA-interference-based immune system in prokaryotes: computational analysis of the predicted enzymatic machinery, functional analogies with eukaryotic RNAi, and hypothetical mechanisms of action. Biology Direct 2006, 1:7.

Mali, P., Yang, L., Esvelt, K.M., Aach, J., Guell, M., DiCarlo, J.E., Norville, J.E., and Church, G.M. (2013). RNA-guided human genome engineering via Cas9. Science 339, 823826.

Marraffini, L.A., and Sontheimer, E.J. (2008). CRISPR interference limits horizontal gene transfer in staphylococci by targeting DNA. Science 322, 18431845.

Mojica, F.J.M., D ez-Villase or, C.S., Garc a-Mart nez, J.S., and Soria, E. (2005). Intervening Sequences of Regularly Spaced Prokaryotic Repeats Derive from Foreign Genetic Elements. J Mol Evol 60, 174182.

Pourcel, C., Salvignol, G., and Vergnaud, G. (2005). CRISPR elements in Yersinia pestis acquire new repeats by preferential uptake of bacteriophage DNA, and provide additional tools for evolutionary studies. Microbiology 151, 653663.

Sapranauskas, R., Gasiunas, G., Fremaux, C., Barrangou, R., Horvath, P., and Siksnys, V. (2011). The Streptococcus thermophilus CRISPR/Cas system provides immunity in Escherichia coli. Nucl. Acids Res. 39, gkr606gkr9282.

Read the original:
CRISPR Timeline | Broad Institute

Recommendation and review posted by Bethany Smith

Gene Therapy – Sickle Cell Anemia News

Gene therapy is an experimental technique that aims to treat genetic diseases by altering a disease-causing gene or introducing a healthy copy of a mutated gene to the body. The U.S. Food and Drug Administrationapprovedthe first gene therapy for an inherited disease a genetic form of blindness in December 2017.

Sickle cell anemia is caused by a mutation in the HBB gene which provides the instructions to make part of hemoglobin, the protein in red blood cells that carries oxygen.

Researchers are working on two different strategies to treat sickle cell anemia with gene therapy. Both of these strategies involve genetically altering the patients own hematopoietic stem cells. These are cells in the bone marrow that divide and specialize to produce different types of blood cells, including the red blood cells.

One strategy is to remove some of the patients hematopoietic stem cells, replace the mutated HBB gene in these cells with a healthy copy of the gene, and then transplant those cells back into the patient. The healthy copy of the gene is delivered to the cells using a modified, harmless virus. These genetically corrected cells will then hopefully repopulate the bone marrow and produce healthy, rather than sickled, red blood cells.

The other strategy is to genetically alter another gene in the patients hematopoietic stem cells so they boost production of fetal hemoglobin a form of hemoglobin produced by babies from about seven months before birth to about six months after birth. This type of hemoglobin represses sickling of cells in patients with sickle cell anemia, but most people only produce a tiny amount of it after infancy. Researchers aim to increase production of fetal hemoglobin in stem cells by using a highly specific enzyme to cut the cells DNA in the section containing one of the genes that suppress production of fetal hemoglobin. When the cell repairs its DNA, the gene no longer works and more fetal hemoglobin is produced.

Gene therapy offers an advantage over bone marrow transplant, in that complications associated with a bone marrow donation now the only cure for the disease such as finding the right match are not a concern.

Twelve clinical trials studying gene therapy to treat sickle cell anemia are now ongoing. Nine of the 12 are currently recruiting participants.

Four trials (NCT02186418, NCT03282656, NCT02247843, NCT02140554) are testing the efficacy and safety of gene therapy to replace the mutated HBB gene with a healthy HBB gene. These Phase 2 trials are recruiting both children and adults in the United States and Jamaica.

Three trials (NCT02193191, NCT02989701, NCT03226691) are investigating the use ofMozobil (plerixafor) in patients with sickle cell anemia to increase the production of stem cells to be used for gene therapy. This medication is already approved to treat certain types of cancer. All three are recruiting U.S. participants.

One trial (NCT00669305) is recruiting sickle cell anemia patients in Tennessee to donate bone marrow to be used in laboratory research to develop gene therapy techniques.

The final study(NCT00012545) is examining the best way to collect, process and store umbilical cord blood from babies with and without sickle cell anemia. Cord blood contains abundant stem cells that could be used in developing gene therapy for sickle cell anemia. This trial is open to pregnant women in Maryland both those who risk having an infant with sickle cell anemia, and those who do not.

One clinical trial (NCT02151526) conducted in France is still active but no longer recruiting participants. It is investigating the efficacy of gene therapy in seven patients. For the trial, a gene producing a therapeutic hemoglobin that functions similarly to fetal hemoglobin is introduced into the patients stem cells. A case studyfrom one of the seven was published in March 2017; it showed that the approach was safe and could be an effective treatment option for sickle cell anemia.

***

Sickle Cell Anemia News is strictly a news and information website about the disease. It does not provide medical advice, diagnosis or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website.

Original post:
Gene Therapy - Sickle Cell Anemia News

Recommendation and review posted by Bethany Smith

Bone Marrow & Blood Stem Cell Transplant | IU Health

What are Bone Marrow and Stem Cells?

Bone marrow is a sponge-like tissue found inside bones. Within bone marrow, stem cells grow and develop into the three main types of blood cells:

Stem cells also grow many other cell types of the immune system.

At IU Health, we offer many types of bone marrow transplant, including:

For this type of transplant, we use your own stem cells. We collect the stem cells and then place them back into your body.

We use this method to treat blood-related cancers like multiple myeloma, non-Hodgkin lymphomas and Hodgkin disease, as well as certain germ-cell cancers.

CAR T-cell therapy is an emerging form of cancer immunotherapy. This therapy involves supercharging a patients T cells, a subtype of white blood cell, to recognize and attack cancer cells.

IU Health is the first healthcare system in Indiana to offer CAR T-cell therapy to treat non-Hodgkin lymphoma and Acute Lymphoblastic Leukemia (ALL).

For this type of transplant, the stem cells of another person are used. The donor can be a relative or a nonrelative whose blood cells are a close match.

The stem cells can come from peripheral (circulating) blood, bone marrow or umbilical cord blood (the blood in the cord connecting a fetus to a placenta).

This method is used to treat blood-related cancers like leukemias and some lymphomas or multiple myeloma. It is also used to treat bone marrow failure disorders like myelodysplastic syndrome (MDS) and aplastic anemia.

If you have an acute leukemia or lymphoma, IU Health Medical Center conducts haploidentical (half-matched) stem cell transplantation. This procedure also greatly expands the potential donor pool, making more patients eligible for the transplant.

Read more from the original source:
Bone Marrow & Blood Stem Cell Transplant | IU Health

Recommendation and review posted by Bethany Smith

Learn How to Donate Bone Marrow | Be The Match

Join Be The Match Registry

The first step to being someone's cure is to join Be The Match Registry. If you are between the ages of 18-44, committed to donating to any patient in need, and meet the health guidelines, there are two ways to join.

Join in-person at a donor registry drive in your community.Be The One to Save a Life

Find a donor registry drive

Or join online today:

Join online

If you are between the ages of 18 and 44 patients especially need you. Research shows that cells from younger donors lead to more successful transplants. Doctors request donors in the 18-44 age group 86% of the time.

At donor registry drives, we focus on adding registry members most likely to donate. If you are between the ages of 45 and 60 and want to join the registry, you're welcome to join online with a $100 tax-deductible payment to cover the cost to join.

There are many other ways you can be the cure for patients with blood cancers.

Check outFAQs about donationor call us at 1 (800) MARROW2 for more information about bone marrow donation.

Read the original:
Learn How to Donate Bone Marrow | Be The Match

Recommendation and review posted by Bethany Smith

Selecting Male Genetics for Cannabis Plants – School of …

https://vimeo.com/336372742Get Exclusive Videos- http://SchoolOfHardNugs.com/Get Seeds- http://seedsherenow.com Get 10% off use coupon code- SOHN10Visit our store- https://shop.schoolofhardnugs.com/Instagram- https://www.instagram.com/school_of_hard_nugs/Facebook- https://www.facebook.com/SchoolOfHardNugs/

This is the place to be if you are looking to grow your own Marijuana! We will cover everything you need to know in order to grow your own weed at home, set up a home grow, learn about cannabis genetics, make hash and edibles. We will be dropping tips and tricks that will help you increase your yields so be sure to subscribe for more!

All content provided on this Channel is for EDUCATIONAL AND ENTERTAINMENT purposes only. The employees, agents, producer, and affiliates of this Channel make no representations as to the accuracy, completeness, fitness or legality of any information on this Channel or in ANY of its Videos or Links.

The School of Hard Nugs is based in Colorado, USA. Recreational and medical marijuana use, cultivation, and manufacture are legal under the laws of the State of Colorado; however, the Content of the Videos and the Channel itself is for ENTERTAINMENT AND EDUCATIONAL PURPOSES ONLY. THE POSSESSION, USE, CULTIVATION AND DISTRIBUTION OF ANY AMOUNT OF MARIJUANA, INCLUDING SEEDS, IS ILLEGAL UNDER U.S. FEDERAL LAW, AS WELL AS MANYSTATE LAWS. THE SCHOOL OF HARD NUGS DOES NOT ADVOCATE OR ENDORSE THE CONTRAVENTION OF THE LAW.

The School of Hard Nugs features content about marijuana, marijuana cultivation, marijuana products manufacture, marijuana consumption, hemp, and other cannabis-related subject matter, including but not limited to: drug laws, drug tests, the recreationaluse of marijuana, and the medical uses of marijuana. The School of Hard Nugs features pictures and videos of marijuana cultivation, marijuana products manufacture, marijuana consumption, hemp, and other cannabis-related subject matter as legal under ColoradoLaw (all together the Content). The School of Hard Nugs does not sell or distribute marijuana or any marijuana products.

Your use of any information or materials on this website is entirely at your own risk, for which School of Hard Nugs shall not be liable. By entering this website you expressly agree to indemnify and hold harmless the School of Hard Nugs and any person, entity, associate, or party affiliated with the School of Hard Nugs from any and all loss, liability or damages incurred as a result of your use of this site. Although the information on this Website is accessible worldwide, if you are not a resident of a state or country where medical or recreational marijuana is legal, by entering this site, you agree that you will not use the content or information for any illegal purpose.

The Content on this Channel is provided ON AN AS IS BASIS, AND THE SCHOOL OF HARD NUGS EXPRESSLY DISCLAIMS ANY AND ALL WARRANTIES, EXPRESS OR IMPLIED, WITHOUT LIMITATION, WITH RESPECT TO THE CONTENT AND IN NO EVENT SHALL THE SCHOOL OF HARD NUGS BE LIABLE FOR ANY DIRECT, INDIRECT, INCIDENTAL, PUNITIVE, OR CONSEQUENTIAL DAMAGES OF ANY KIND WHATSOEVER WITH RESPECT TO THE CONTENT.

Through this website you may be able to link to other websites which are not under the control of or affiliated with The School of Hard Nugs. We have no control over the nature, content and availability of those sites. The inclusion of any links does not imply arecommendation or endorsement of any products or views and content expressed within the links.

All content at The School of Hard Nugs is for EDUCATIONAL AND ENTERTAINMENT purposes ONLY. This website is for mature audiences only. WE STRONGLY ENCOURAGE VIEWERS UNDER 21 YEARS OF AGE TO EXIT THIS SITE IMMEDIATELY. BY ACCESSING THIS WEBSITE, YOU AGREE TO THE TERMS AND CONDITIONS ABOVE.

Written by Justin Sardi

More here:
Selecting Male Genetics for Cannabis Plants - School of ...

Recommendation and review posted by Bethany Smith

Nine Things To Know About Stem Cell Treatments A Closer …

It can be hard to tell the difference between doctors conducting responsible clinical trials and clinics selling unproven treatments. One common differentiator is the way a treatment is marketed. Most specialized doctors receive patient referrals, while clinics selling stem cell treatments tend to market directly to patients, often through persuasive language on the Internet, Facebook and in newspaper advertisements.

Clinics peddling unproven stem cell treatments frequently overstate the benefits of their offerings and use patient testimonials to support their claims. These testimonials can be intentionally or unintentionally misleading. For example, a person may feel better immediately after receiving a treatment, but the perceived or actual improvement may be due to other factors, such as an intense belief that the treatment will work, auxiliary treatments accompanying the main treatment, healthy lifestyle changes adapted in conjunction with the treatment and natural fluctuations in the disease or condition. These factors are complex and difficult to measure objectively outside the boundaries of carefully designed clinical trials. Learn more about why we need to perform clinical trials here.

Beware of clinics that use persuasive language, including patient testimonials, on the Internet, Facebook and newspapers, to market their treatments, instead of science-based evidence.

Visit link:
Nine Things To Know About Stem Cell Treatments A Closer ...

Recommendation and review posted by Bethany Smith

Ultrasound: Sonogram – American Pregnancy Association

An ultrasound exam is a procedure that uses high-frequency soundwaves to scan a womans abdomen and pelvic cavity, creating a picture(sonogram) of the baby and placenta. Although the terms ultrasoundand sonogram are technically different, they are used interchangeablyand reference the same exam.

There are basically seven different ultrasound exams, but the basic process is the same.

The different types of procedures include:

Transvaginal Scans Specially designed probe transducersare used inside the vagina to generate sonogram images. Most oftenused during the early stages of pregnancy.

Standard Ultrasound Traditional ultrasound examwhich uses a transducer over the abdomen to generate 2-D images ofthe developing fetus.

Advanced Ultrasound This exam is similar to thestandard ultrasound, but the exam targets a suspected problem anduses more sophisticated equipment.

Doppler Ultrasound This imaging procedure measuresslight changes in the frequency of the ultrasound waves as they bounceoff moving objects, such as blood cells.

3-D Ultrasound Uses specially designed probes andsoftware to generate 3-D images of the developing fetus.

4-D or Dynamic 3-D Ultrasound Uses specially designedscanners to look at the face and movements of the baby prior to delivery.

Fetal Echocardiography Uses ultrasound waves toassess the babys heart anatomy and function. This is used to helpassess suspected congenital heart defects.

The traditional ultrasound procedure involves placing gel on yourabdomen to work as a conductor for the sound waves. Your healthcareprovider uses a transducer to produce sound waves into the uterus.The sound waves bounce off bones and tissue returning back to thetransducer to generate black and white images of the fetus.

Ultrasounds may be performed at any point during pregnancy, and theresults are seen immediately on a monitor during the procedure. Transvaginalscans may be used early in pregnancy to diagnose potential ectopicor molar pregnancies.

There is not a recommended number of ultrasounds that should be performedduring routine prenatal care. Because ultrasound should only be usedwhen medically indicated, many healthy pregnancies will not require an ultrasound. The average number of ultrasounds varies with each healthcareprovider.

Additional ultrasounds might be ordered separately if yourhealthcare provider suspects a complication or problem related toyour pregnancy.

Ultrasounds are diagnostic procedures that detect or aid in the detectionof abnormalities and conditions related to pregnancy. Ultrasoundsare usually combined with other tests, such as tripletests, amniocentesis,or chorionic villus sampling,to validate a diagnosis.

An ultrasound exam may be performedthroughout pregnancy for the following medically-necessary reasons:

First Trimester:

Second Trimester:

Third Trimester:

The ultrasound is a noninvasive procedure which, when used properly,has not demonstrated fetal harm. The long-term effects of repeatedultrasound exposures on the fetus are not fully known. It is recommendedthat ultrasound only be used if medically indicated.

No, itdoes not mean there is a problem. The heartbeat may not be detectedfor reasons that include: tipped uterus, larger abdomen, or inaccuratedating with last menstrual period. Heartbeats are best detected withtransvaginal ultrasounds early in pregnancy.

Concern typically developsif there is no fetal heart activity in an embryo with a crown-rumplength greater than 5mm. If you receive an ultrasound exam after week6, your healthcare provider will begin to be concerned, if there isno gestational sac.

Your healthcare provider will use hormone levels in yourblood, the date of your last menstrual period and, in some cases,results from an ultrasound to generate an estimated gestational age.However, variations in each womans cycle and each pregnancy may hinderthe accuracy of the gestational age calculation.

If your healthcareprovider uses an ultrasound to get an estimated delivery date to basethe timing of your prenatal care, the original estimated gestationalage will not be changed.

If there are any questions regarding gestational age, placenta location,or possible complications then more ultrasounds may be scheduled.Because ultrasound should only be used when medically indicated, manyhealthy pregnancies will not require an ultrasound. The average numberof ultrasounds varies with each healthcare provider.

Your healthcare provider willuse hormone levels in your blood, the date of your last menstrualperiod and, in some cases, results from an ultrasound to generatean expected date of conception. However, many differences in eachwomans cycle may hinder the accuracy of the conception date calculation.

The viability of sperm varies as well, which means intercoursethree to five days prior to ovulation may result in conception. Ultrasounddating of conception is not reliable for determining paternity becausethe ultrasound can be off by at least 5-7 days in early pregnancy.

Youmay have an ultrasound between 18 to 20 weeks to evaluate dates, amultiples pregnancy, placenta location or complications. It may alsobe possible to determine the gender of your baby during this ultrasound.Several factors, such as the stage of pregnancy and position of the fetus,will influence the accuracy of the gender prediction.

To be 100% sureyou will have an anxious wait until the birth!

Ultrasoundsare only necessary if there is a medical concern. As noted above,ultrasounds enable your healthcare provider to evaluate the babyswell being as well as diagnose potential problems. For women withan uncomplicated pregnancy, an ultrasound is not a necessary partof prenatal care.

Last updated: November 3, 2017 at 14:29 pm

Compiled using information from the following sources:

1. Williams Obstetrics Twenty-Second Ed. Cunningham,F. Gary, et al, Ch. 16.

2. American Institute of Ultrasound in Medicine

https://www.aium.org

View post:
Ultrasound: Sonogram - American Pregnancy Association

Recommendation and review posted by Bethany Smith

Hyperparathyroidism – Symptoms and causes – Mayo Clinic

Overview

Hyperparathyroidism is an excess of parathyroid hormone in the bloodstream due to overactivity of one or more of the body's four parathyroid glands. These glands are about the size of a grain of rice and are located in your neck.

The parathyroid glands produce parathyroid hormone, which helps maintain an appropriate balance of calcium in the bloodstream and in tissues that depend on calcium for proper functioning.

Two types of hyperparathyroidism exist. In primary hyperparathyroidism, an enlargement of one or more of the parathyroid glands causes overproduction of the hormone, resulting in high levels of calcium in the blood (hypercalcemia), which can cause a variety of health problems. Surgery is the most common treatment for primary hyperparathyroidism.

Secondary hyperparathyroidism occurs as a result of another disease that initially causes low levels of calcium in the body and over time, increased parathyroid hormone levels occur.

Hyperparathyroidism is often diagnosed before signs or symptoms of the disorder are apparent. When symptoms do occur, they're the result of damage or dysfunction in other organs or tissues due to high calcium levels circulating in the blood and urine or too little calcium in bones.

Symptoms may be so mild and nonspecific that they don't seem at all related to parathyroid function, or they may be severe. The range of signs and symptoms include:

See your doctor if you have any signs or symptoms of hyperparathyroidism. These symptoms could be caused by any number of disorders, including some with serious complications. It's important to get a prompt, accurate diagnosis and appropriate treatment.

Hyperparathyroidism is caused by factors that increase the production of parathyroid hormone.

The parathyroid glands maintain proper levels of both calcium and phosphorus in your body by turning the secretion of parathyroid hormone (PTH) off or on, much like a thermostat controls a heating system to maintain a constant air temperature. Vitamin D also is involved in regulating the amount of calcium in your blood.

Normally, this balancing act works well. When calcium levels in your blood fall too low, your parathyroid glands secrete enough PTH to restore the balance. PTH raises calcium levels by releasing calcium from your bones and increasing the amount of calcium absorbed from your small intestine.

When blood-calcium levels are too high, the parathyroid glands produce less PTH. But sometimes one or more of these glands produce too much hormone, leading to abnormally high levels of calcium (hypercalcemia) and low levels of phosphorus in your blood.

The mineral calcium is best known for its role in keeping your teeth and bones healthy. But calcium has other functions. It aids in the transmission of signals in nerve cells, and it's involved in muscle contraction. Phosphorus, another mineral, works in conjunction with calcium in these areas.

The disorder can generally be divided into two types based on the cause. Hyperparathyroidism may occur because of a problem with the parathyroid glands themselves (primary hyperparathyroidism) or because of another disease that affects the glands' function (secondary hyperparathyroidism).

Primary hyperparathyroidism occurs because of some problem with one or more of the four parathyroid glands:

Primary hyperparathyroidism usually occurs randomly, but some people inherit a gene that causes the disorder.

Secondary hyperparathyroidism is the result of another condition that lowers calcium levels. Therefore, your parathyroid glands overwork to compensate for the loss of calcium. Factors that may contribute to secondary hyperparathyroidism include:

Severe vitamin D deficiency. Vitamin D helps maintain appropriate levels of calcium in the blood, and it helps your digestive system absorb calcium from your food.

Your body produces vitamin D when your skin is exposed to sunlight, and you consume some vitamin D in food. If you don't get enough vitamin D, then calcium levels may drop.

You may be at an increased risk of primary hyperparathyroidism if you:

Complications of hyperparathyroidism are primarily related to the long-term effect of too little calcium in your bones and too much calcium circulating in your bloodstream. Common complications include:

Here is the original post:
Hyperparathyroidism - Symptoms and causes - Mayo Clinic

Recommendation and review posted by Bethany Smith

melatonin | Description, Hormone, & Effects | Britannica.com

Melatonin, hormone secreted by the pineal gland, a tiny endocrine gland situated at the centre of the brain. Melatonin was first isolated in 1958 by American physician Aaron B. Lerner and his colleagues at Yale University School of Medicine. They gave the substance its name on the basis of its ability to lighten skin colour in frogs by reversing the skin-darkening effects of melanocyte-stimulating hormone. Melatonin, a derivative of the amino acid tryptophan, is produced in humans, other mammals, birds, reptiles, and amphibians.

In humans, melatonin plays an important role in the regulation of sleep cycles (i.e., circadian rhythm). Its production is influenced by the detection of light and dark by the retina of the eye. For example, the production of melatonin is inhibited when the retina detects light and is stimulated in the absence of light. Special photoreceptor cells in the retina send signals about light status to the suprachiasmatic nucleus (SCN) in the hypothalamus of the brain. These signals are then transmitted to the pineal gland. Melatonin generation by the pineal gland, which peaks during the nighttime hours, induces physiological changes that promote sleep, such as decreased body temperature and respiration rate. During the day, melatonin levels are low because large amounts of light are detected by the retina. Light inhibition of melatonin production is central to stimulating wakefulness in the morning and to maintaining alertness throughout the day.

Melatonin receptors are found in the SCN and the pituitary gland of the brain, as well as in the ovaries, blood vessels, and intestinal tract. There is a high concentration of receptors in the SCN because this is where melatonin mediates the majority of its affects on circadian rhythm. The binding of melatonin to its receptors on the pituitary gland and the ovaries appears to play a role in regulating the release of reproductive hormones in females. For example, the timing, length, and frequency of menstrual cycles in women are influenced by melatonin. In addition, in certain mammals (other than humans), such as horses and sheep, melatonin acts as a breeding and mating cue, since it is produced in greater amounts in response to the longer nights of winter and less so during summer. Animals who time their mating or breeding to coincide with favourable seasons (such as spring) may depend on melatonin production as a kind of biological clock that regulates their reproductive cycles on the basis of the length of the solar day.

Melatonin has antiaging properties. For example, it acts as an antioxidant, neutralizing harmful oxidative radicals, and it is capable of activating certain antioxidant enzymes. Melatonin production gradually declines with age, and its loss is associated with several age-related diseases. Melatonin also plays a role in modulating certain functions of the immune system.

Synthetic melatonin is available in pill form and can be used to treat insomnia and other sleep disorders, to adjust sleep schedules following jet lag or other major disruptions, and to help blind people establish night and day cycles. Melatonin supplements may also help lower blood pressure and aid in withdrawal from benzodiazepines, though further research is needed.

Read more:
melatonin | Description, Hormone, & Effects | Britannica.com

Recommendation and review posted by Bethany Smith

Androgen insensitivity syndrome – Wikipedia

Androgen insensitivity syndrome (AIS) is an intersex condition that results in the partial or complete inability of the cell to respond to androgens.[1][2][3] The unresponsiveness of the cell to the presence of androgenic hormones can impair or prevent the masculinization of male genitalia in the developing fetus, as well as the development of male secondary sexual characteristics at puberty, but does not significantly impair female genital or sexual development.[3][4] As such, the insensitivity to androgens is clinically significant only when it occurs in genetic males (i.e. individuals with a Y-chromosome, or more specifically, an SRY gene).[1] Clinical phenotypes in these individuals range from a normal male habitus with mild spermatogenic defect or reduced secondary terminal hair, to a full female habitus, despite the presence of a Y-chromosome.[1][5][6][7][8][9]

AIS is divided into three categories that are differentiated by the degree of genital masculinization: complete androgen insensitivity syndrome (CAIS) is indicated when the external genitalia are that of a normal female; mild androgen insensitivity syndrome (MAIS) is indicated when the external genitalia are that of a normal male, and partial androgen insensitivity syndrome (PAIS) is indicated when the external genitalia are partially, but not fully, masculinized.[1][2][5][6][7][10][11][12][13] Androgen insensitivity syndrome is the largest single entity that leads to 46,XY undermasculinized genitalia.[14]

Management of AIS is currently limited to symptomatic management; no method is currently available to correct the malfunctioning androgen receptor proteins produced by AR gene mutations. Areas of management include sex assignment, genitoplasty, gonadectomy in relation to tumor risk, hormone replacement therapy, genetic counseling, and psychological counseling.

The human androgen receptor (AR) is a protein encoded by a gene located on the proximal long arm of the X chromosome (locus Xq11-Xq12).[15] The protein coding region consists of approximately 2,757 nucleotides (919 codons) spanning eight exons, designated 1-8 or A-H.[1][3] Introns vary in size between 0.7 and 26 kb.[3] Like other nuclear receptors, the AR protein consists of several functional domains: the transactivation domain (also called the transcription-regulation domain or the amino / NH2-terminal domain), the DNA-binding domain, the hinge region, and the steroid-binding domain (also called the carboxyl-terminal ligand-binding domain).[1][2][3][13] The transactivation domain is encoded by exon 1, and makes up more than half of the AR protein.[3] Exons 2 and 3 encode the DNA-binding domain, while the 5' portion of exon 4 encodes the hinge region.[3] The remainder of exons 4 through 8 encodes the ligand binding domain.[3]

The AR gene contains two polymorphic trinucleotide microsatellites in exon 1.[2] The first microsatellite (nearest the 5' end) contains 8 [16] to 60 [17][18] repetitions of the glutamine codon "CAG" and is thus known as the polyglutamine tract.[3] The second microsatellite contains 4 [19] to 31 [20] repetitions of the glycine codon "GGC" and is known as the polyglycine tract.[21] The average number of repetitions varies by ethnicity, with Caucasians exhibiting an average of 21 CAG repeats, and Blacks 18.[22] In men, disease states are associated with extremes in polyglutamine tract length; prostate cancer,[23] hepatocellular carcinoma,[24] and intellectual disability [16] are associated with too few repetitions, while spinal and bulbar muscular atrophy (SBMA) is associated with a CAG repetition length of 40 or more.[25] Some studies indicate that the length of the polyglutamine tract is inversely correlated with transcriptional activity in the AR protein, and that longer polyglutamine tracts may be associated with male infertility [26][27][28] and undermasculinized genitalia in men.[29] However, other studies have indicated no such correlation exists.[30][31][32][33][34][35] A comprehensive meta-analysis of the subject published in 2007 supports the existence of the correlation, and concluded these discrepancies could be resolved when sample size and study design are taken into account.[11] Some studies suggest longer polyglycine tract lengths are also associated with genital masculinization defects in men.[36][37] Other studies find no such association.[38]

As of 2010, over 400 AR mutations have been reported in the AR mutation database, and the number continues to grow.[2] Inheritance is typically maternal and follows an X-linked recessive pattern;[1][39] individuals with a 46,XY karyotype always express the mutant gene since they have only one X chromosome, whereas 46,XX carriers are minimally affected. About 30% of the time, the AR mutation is a spontaneous result, and is not inherited.[10] Such de novo mutations are the result of a germ cell mutation or germ cell mosaicism in the gonads of one of the parents, or a mutation in the fertilized egg itself.[40] In one study,[41] three of eight de novo mutations occurred in the postzygotic stage, leading to the estimate that up to one-third of de novo mutations result in somatic mosaicism.[1] Not every mutation of the AR gene results in androgen insensitivity; one particular mutation occurs in 8 to 14% of genetic males,[42][43][44][45] and is thought to adversely affect only a small number of individuals when other genetic factors are present.[46]

Some individuals with CAIS or PAIS do not have any AR mutations despite clinical, hormonal, and histological features sufficient to warrant an AIS diagnosis; up to 5% of women with CAIS do not have an AR mutation,[2] as well as between 27[6][47] and 72%[48] of individuals with PAIS.

In one patient, the underlying cause for presumptive PAIS was a mutant steroidogenic factor-1 (SF-1) protein.[49] In another patient, CAIS was the result of a deficit in the transmission of a transactivating signal from the N-terminal region of the normal androgen receptor to the basal transcription machinery of the cell.[50] A coactivator protein interacting with the activation function 1 (AF-1) transactivation domain of the androgen receptor may have been deficient in this patient.[50] The signal disruption could not be corrected by supplementation with any coactivators known at the time, nor was the absent coactivator protein characterized, which left some in the field unconvinced that a mutant coactivator would explain the mechanism of androgen resistance in CAIS or PAIS patients with a normal AR gene.[1]

Depending on the mutation, a person with a 46,XY karyotype and AIS can have either a male (MAIS) or female (CAIS) phenotype,[51] or may have genitalia that are only partially masculinized (PAIS).[52] The gonads are testes regardless of phenotype due to the influence of the Y chromosome.[53][54] A 46,XY female, thus, does not have ovaries or a uterus,[55] and can neither contribute an egg towards conception nor gestate a child.

Several case studies of fertile 46,XY males with AIS have been published,[4][56][57][58][59] although this group is thought to be a minority.[13] Additionally, some infertile males with MAIS have been able to conceive children after increasing their sperm count through the use of supplementary testosterone.[1][60] A genetic male conceived by a man with AIS would not receive his father's X chromosome, thus would neither inherit nor carry the gene for the syndrome. A genetic female conceived in such a way would receive her father's X chromosome, thus would become a carrier.

Genetic females (46,XX karyotype) have two X chromosomes, thus have two AR genes. A mutation in one (but not both) results in a minimally affected, fertile, female carrier. Some carriers have been noted to have slightly reduced body hair, delayed puberty, and/or tall stature, presumably due to skewed X-inactivation.[3][4] A female carrier will pass the affected AR gene to her children 50% of the time. If the affected child is a genetic female, she, too, will be a carrier. An affected 46,XY child will have AIS.

A genetic female with mutations in both AR genes could theoretically result from the union of a fertile man with AIS and a female carrier of the gene, or from de novo mutation. However, given the scarcity of fertile AIS men and low incidence of AR mutation, the chances of this occurrence are small. The phenotype of such an individual is a matter of speculation; as of 2010, no such documented case has been published.

Individuals with partial AIS, unlike those with the complete or mild forms, present at birth with ambiguous genitalia, and the decision to raise the child as male or female is often not obvious.[1][40][61] Unfortunately, little information regarding phenotype can be gleaned from precise knowledge of the AR mutation itself; the same AR mutation may cause significant variation in the degree of masculinization in different individuals, even among members of the same family.[1][39][52][62][63][64][65][66][67][68] Exactly what causes this variation is not entirely understood, although factors contributing to it could include the lengths of the polyglutamine and polyglycine tracts,[69] sensitivity to and variations in the intrauterine endocrine milieu,[52] the effect of coregulatory proteins active in Sertoli cells,[21][70] somatic mosaicism,[1] expression of the 5RD2 gene in genital skin fibroblasts,[62] reduced AR transcription and translation from factors other than mutations in the AR coding region,[71] an unidentified coactivator protein,[50] enzyme deficiencies such as 21-hydroxylase deficiency,[4] or other genetic variations such as a mutant steroidogenic factor-1 protein.[49] The degree of variation, however, does not appear to be constant across all AR mutations, and is much more extreme in some.[1][4][46][52] Missense mutations that result in a single amino acid substitution are known to produce the most phenotypic diversity.[2]

The effects that androgens have on the human body (virilization, masculinization, anabolism, etc.) are not brought about by androgens themselves, but rather are the result of androgens bound to androgen receptors; the androgen receptor mediates the effects of androgens in the human body.[73] Likewise, under normal circumstances, the androgen receptor itself is inactive in the cell until androgen binding occurs.[3]

The following series of steps illustrates how androgens and the androgen receptor work together to produce androgenic effects:[1][2][3][13][18][74][75]

In this way, androgens bound to androgen receptors regulate the expression of target genes, thus produce androgenic effects.

Theoretically, certain mutant androgen receptors can function without androgens; in vitro studies have demonstrated that a mutant androgen receptor protein can induce transcription in the absence of androgen if its steroid binding domain is deleted.[76][77] Conversely, the steroid-binding domain may act to repress the AR transactivation domain, perhaps due to the AR's unliganded conformation.[3]

Human embryos develop similarly for the first six weeks, regardless of genetic sex (46,XX or 46,XY karyotype); the only way to tell the difference between 46,XX or 46,XY embryos during this time period is to look for Barr bodies or a Y chromosome.[79] The gonads begin as bulges of tissue called the genital ridges at the back of the abdominal cavity, near the midline. By the fifth week, the genital ridges differentiate into an outer cortex and an inner medulla, and are called indifferent gonads.[79] By the sixth week, the indifferent gonads begin to differentiate according to genetic sex. If the karyotype is 46,XY, testes develop due to the influence of the Y chromosomes SRY gene.[53][54] This process does not require the presence of androgen, nor a functional androgen receptor.[53][54]

Until around the seventh week of development, the embryo has indifferent sex accessory ducts, which consist of two pairs of ducts: the Mllerian ducts and the Wolffian ducts.[79] Sertoli cells within the testes secrete anti-Mllerian hormone around this time to suppress the development of the Mllerian ducts, and cause their degeneration.[79] Without this anti-Mllerian hormone, the Mllerian ducts develop into the female internal genitalia (uterus, cervix, fallopian tubes, and upper vaginal barrel).[79] Unlike the Mllerian ducts, the Wolffian ducts will not continue to develop by default.[80] In the presence of testosterone and functional androgen receptors, the Wolffian ducts develop into the epididymides, vasa deferentia, and seminal vesicles.[79] If the testes fail to secrete testosterone, or the androgen receptors do not function properly, the Wolffian ducts degenerate.[81]

Masculinization of the male external genitalia (the penis, penile urethra, and scrotum), as well as the prostate, are dependent on the androgen dihydrotestosterone.[82][83][84][85] Testosterone is converted into dihydrotestosterone by the 5-alpha reductase enzyme.[86] If this enzyme is absent or deficient, then dihydrotestosterone is not created, and the external male genitalia do not develop properly.[82][83][84][85][86] As is the case with the internal male genitalia, a functional androgen receptor is needed for dihydrotestosterone to regulate the transcription of target genes involved in development.[73]

Mutations in the androgen receptor gene can cause problems with any of the steps involved in androgenization, from the synthesis of the androgen receptor protein itself, through the transcriptional ability of the dimerized, androgen-AR complex.[3] AIS can result if even one of these steps is significantly disrupted, as each step is required for androgens to activate the AR successfully and regulate gene expression.[3] Exactly which steps a particular mutation will impair can be predicted, to some extent, by identifying the area of the AR in which the mutation resides. This predictive ability is primarily retrospective in origin; the different functional domains of the AR gene have been elucidated by analyzing the effects of specific mutations in different regions of the AR.[3] For example, mutations in the steroid binding domain have been known to affect androgen binding affinity or retention, mutations in the hinge region have been known to affect nuclear translocation, mutations in the DNA-binding domain have been known to affect dimerization and binding to target DNA, and mutations in the transactivation domain have been known to affect target gene transcription regulation.[3][80] Unfortunately, even when the affected functional domain is known, predicting the phenotypical consequences of a particular mutation (see Correlation of genotype and phenotype) is difficult.

Some mutations can adversely impact more than one functional domain. For example, a mutation in one functional domain can have deleterious effects on another by altering the way in which the domains interact.[80] A single mutation can affect all downstream functional domains if a premature stop codon or framing error results; such a mutation can result in a completely unusable (or unsynthesizable) androgen receptor protein.[3] The steroid binding domain is particularly vulnerable to the effects of a premature stop codon or framing error, since it occurs at the end of the gene, and its information is thus more likely to be truncated or misinterpreted than other functional domains.[3]

Other, more complex relationships have been observed as a consequence of mutated AR; some mutations associated with male phenotypes have been linked to male breast cancer, prostate cancer, or in the case of spinal and bulbar muscular atrophy, disease of the central nervous system.[9][23][87][88][89] The form of breast cancer seen in some men with PAIS is caused by a mutation in the AR's DNA-binding domain.[87][89] This mutation is thought to cause a disturbance of the AR's target gene interaction that allows it to act at certain additional targets, possibly in conjunction with the estrogen receptor protein, to cause cancerous growth.[3] The pathogenesis of spinal and bulbar muscular atrophy (SBMA) demonstrates that even the mutant AR protein itself can result in pathology. The trinucleotide repeat expansion of the polyglutamine tract of the AR gene that is associated with SBMA results in the synthesis of a misfolded AR protein that the cell fails to proteolyze and disperse properly.[90] These misfolded AR proteins form aggregates in the cell cytoplasm and nucleus.[90] Over the course of 30 to 50 years, these aggregates accumulate and have a cytotoxic effect, eventually resulting in the neurodegenerative symptoms associated with SBMA.[90]

The phenotypes that result from the insensitivity to androgens are not unique to AIS, thus the diagnosis of AIS requires thorough exclusion of other causes.[14][64] Clinical findings indicative of AIS include the presence of a short vagina [91] or undermasculinized genitalia,[1][63][82] partial or complete regression of Mllerian structures,[92] bilateral nondysplastic testes,[93] and impaired spermatogenesis and/or virilization.[1][5][6][9] Laboratory findings include a 46,XY karyotype[2] and normal or elevated postpubertal testosterone, luteinizing hormone, and estradiol levels.[2][14] The androgen binding activity of genital skin fibroblasts is typically diminished,[3][94] although exceptions have been reported.[95] Conversion of testosterone to dihydrotestosterone may be impaired.[3] The diagnosis of AIS is confirmed if androgen receptor gene sequencing reveals a mutation, although not all individuals with AIS (particularly PAIS) will have an AR mutation (see Other Causes).[2][6][47][48]

Each of the three types of AIS (complete, partial, and mild) has a different list of differential diagnoses to consider.[1] Depending on the form of AIS suspected, the list of differentials can include:[53][54][96][97][98]

AIS is broken down into three classes based on phenotype: complete androgen insensitivity syndrome (CAIS), partial androgen insensitivity syndrome (PAIS), and mild androgen insensitivity syndrome (MAIS).[1][2][5][6][7][10][11][12][13] A supplemental system of phenotypic grading that uses seven classes instead of the traditional three was proposed by pediatric endocrinologist Charmian A. Quigley et al. in 1995.[3] The first six grades of the scale, grades 1 through 6, are differentiated by the degree of genital masculinization; grade 1 is indicated when the external genitalia is fully masculinized, grade 6 is indicated when the external genitalia is fully feminized, and grades 2 through 5 quantify four degrees of decreasingly masculinized genitalia that lie in the interim.[3] Grade 7 is indistinguishable from grade 6 until puberty, and is thereafter differentiated by the presence of secondary terminal hair; grade 6 is indicated when secondary terminal hair is present, whereas grade 7 is indicated when it is absent.[3] The Quigley scale can be used in conjunction with the traditional three classes of AIS to provide additional information regarding the degree of genital masculinization, and is particularly useful when the diagnosis is PAIS.[2][99]

Management of AIS is currently limited to symptomatic management; no method is currently available to correct the malfunctioning androgen receptor proteins produced by AR gene mutations. Areas of management include sex assignment, genitoplasty, gonadectomy in relation to tumor risk, hormone replacement therapy, genetic counseling, and psychological counseling.

Estimates for the incidence of androgen insensitivity syndrome are based on a relatively small population size, thus are known to be imprecise.[1] CAIS is estimated to occur in one of every 20,400 46,XY births.[100] A nationwide survey in the Netherlands based on patients with genetic confirmation of the diagnosis estimates that the minimal incidence of CAIS is one in 99,000.[62] The incidence of PAIS is estimated to be one in 130,000.[101] Due to its subtle presentation, MAIS is not typically investigated except in the case of male infertility,[82] thus its true prevalence is unknown.[2]

Preimplantation genetic diagnosis (PGD or PIGD) refers to genetic profiling of embryos prior to implantation (as a form of embryo profiling), and sometimes even of oocytes prior to fertilization. When used to screen for a specific genetic sequence, its main advantage is that it avoids selective pregnancy termination, as the method makes it highly likely that a selected embryo will be free of the condition under consideration.

In the UK, AIS appears on a list of serious genetic diseases that may be screened for via PGD.[102] Some ethicists, clinicians, and intersex advocates have argued that screening embryos to specifically exclude intersex traits are based on social and cultural norms as opposed to medical necessity.[103][104][105][106][107]

Recorded descriptions of the effects of AIS date back hundreds of years, although significant understanding of its underlying histopathology did not occur until the 1950s.[1] The taxonomy and nomenclature associated with androgen insensitivity went through a significant evolution that paralleled this understanding.

The first descriptions of the effects of AIS appeared in the medical literature as individual case reports or as part of a comprehensive description of intersex physicalities. In 1839, Scottish obstetrician Sir James Young Simpson published one such description[117] in an exhaustive study of intersexuality that has been credited with advancing the medical community's understanding of the subject.[118] Simpson's system of taxonomy, however, was far from the first; taxonomies or descriptions for the classification of intersexuality were developed by Italian physician and physicist Fortun Affaitati in 1549,[119][120] French surgeon Ambroise Par in 1573,[118][121] French physician and sexology pioneer Nicolas Venette in 1687 (under the pseudonym Vnitien Salocini),[122][123] and French zoologist Isidore Geoffroy Saint-Hilaire in 1832.[124] All five of these authors used the colloquial term "hermaphrodite" as the foundation of their taxonomies, although Simpson himself questioned the propriety of the word in his publication.[117] Use of the word "hermaphrodite" in the medical literature has persisted to this day,[125][126] although its propriety is still in question. An alternative system of nomenclature has been recently suggested,[127] but the subject of exactly which word or words should be used in its place still one of much debate.[97][128][129][130][131]

"Pseudohermaphroditism" has, until very recently,[127] been the term used in the medical literature to describe the condition of an individual whose gonads and karyotype do not match the external genitalia in the gender binary sense. For example, 46,XY individuals who have a female phenotype, but also have testes instead of ovaries a group that includes all individuals with CAIS, as well as some individuals with PAIS are classified as having "male pseudohermaphroditism", while individuals with both an ovary and a testis (or at least one ovotestis) are classified as having "true hermaphroditism".[126][127] Use of the word in the medical literature antedates the discovery of the chromosome, thus its definition has not always taken karyotype into account when determining an individual's sex. Previous definitions of "pseudohermaphroditism" relied on perceived inconsistencies between the internal and external organs; the "true" sex of an individual was determined by the internal organs, and the external organs determined the "perceived" sex of an individual.[117][124]

German-Swiss pathologist Edwin Klebs is sometimes noted for using the word "pseudohermaphroditism" in his taxonomy of intersexuality in 1876,[133] although the word is clearly not his invention as is sometimes reported; the history of the word "pseudohermaphrodite" and the corresponding desire to separate "true" hermaphrodites from "false", "spurious", or "pseudo" hermaphrodites, dates back to at least 1709, when Dutch anatomist Frederik Ruysch used it in a publication describing a subject with testes and a mostly female phenotype.[132] "Pseudohermaphrodite" also appeared in the Acta Eruditorum later that same year, in a review of Ruysch's work.[134] Also some evidence indicates the word was already being used by the German and French medical community long before Klebs used it; German physiologist Johannes Peter Mller equated "pseudohermaphroditism" with a subclass of hermaphroditism from Saint-Hilaire's taxonomy in a publication dated 1834,[135] and by the 1840s "pseudohermaphroditism" was appearing in several French and German publications, including dictionaries.[136][137][138][139]

In 1953, American gynecologist John Morris provided the first full description of what he called "testicular feminization syndrome" based on 82 cases compiled from the medical literature, including two of his own patients.[1][3][140] The term "testicular feminization" was coined to reflect Morris' observation that the testicles in these patients produced a hormone that had a feminizing effect on the body, a phenomenon now understood to be due to the inaction of androgens, and subsequent aromatization of testosterone into estrogen.[1] A few years before Morris published his landmark paper, Lawson Wilkins had shown through experiment that unresponsiveness of the target cell to the action of androgenic hormones was a cause of "male pseudohermaphroditism".[64][108] Wilkins' work, which clearly demonstrated the lack of a therapeutic effect when 46,XY women were treated with androgens, caused a gradual shift in nomenclature from "testicular feminization" to "androgen resistance".[82]

A distinct name has been given to many of the various presentations of AIS, such as Reifenstein syndrome (1947),[141] Goldberg-Maxwell syndrome (1948),[142] Morris' syndrome (1953),[140] Gilbert-Dreyfus syndrome (1957),[143] Lub's syndrome (1959),[144] "incomplete testicular feminization" (1963),[145] Rosewater syndrome (1965),[146] and Aiman's syndrome (1979).[147] Since it was not understood that these different presentations were all caused by the same set of mutations in the androgen receptor gene, a unique name was given to each new combination of symptoms, resulting in a complicated stratification of seemingly disparate disorders.[64][148]

Over the last 60 years, as reports of strikingly different phenotypes were reported to occur even among members of the same family, and as steady progress was made towards the understanding of the underlying molecular pathogenesis of AIS, these disorders were found to be different phenotypic expressions of one syndrome caused by molecular defects in the androgen receptor gene.[1][13][64][148]

AIS is now the accepted terminology for the syndromes resulting from unresponsiveness of the target cell to the action of androgenic hormones.[1] CAIS encompasses the phenotypes previously described by "testicular feminization", Morris' syndrome, and Goldberg-Maxwell syndrome;[1][149] PAIS includes Reifenstein syndrome, Gilbert-Dreyfus syndrome, Lub's syndrome, "incomplete testicular feminization", and Rosewater syndrome;[148][150][151] and MAIS includes Aiman's syndrome.[152]

The more virilized phenotypes of AIS have sometimes been described as "undervirilized male syndrome", "infertile male syndrome", "undervirilized fertile male syndrome", etc., before evidence was reported that these conditions were caused by mutations in the AR gene.[58] These diagnoses were used to describe a variety of mild defects in virilization; as a result, the phenotypes of some men who have been diagnosed as such are better described by PAIS (e.g. micropenis, hypospadias, and undescended testes), while others are better described by MAIS (e.g. isolated male infertility or gynecomastia).[1][58][59][151][153][154]

In the film Orchids, My Intersex Adventure, Phoebe Hart and her sister Bonnie Hart, both women with CAIS, documented their exploration of AIS and other intersex issues.[155]

Recording artist Dalea is a Hispanic-American Activist who is public about her CAIS. She has given interviews about her condition[156][157] and founded "Girl Comet, a non-profit diversity awareness and inspiration initiative.[158]

In 2017, fashion model Hanne Gaby Odiele disclosed that she was born with the intersex trait androgen insensitivity syndrome. As a child, she underwent medical procedures relating to her condition,[159] which she said took place without her or her parents' informed consent.[160] She was told about her intersex condition weeks before beginning her modelling career.[160]

In the 1991 Japanese horror novel Ring, by Koji Suzuki (later adapted into Japanese, Korean, and American films), the central antagonist Sadako has this syndrome.

In season 2, episode 13 ("Skin Deep") of the TV series House, the main patient's cancerous testicle is mistaken for an ovary due to the patient's undiscovered CAIS.

In season 2 of the MTV series Faking It, a character has CAIS. The character, Lauren Cooper, played by Bailey De Young, was the first intersex series regular on American television.[161][162]

In season 8, episode 11 ("Delko for the Defense") of the TV series CSI: Miami, the primary suspect has AIS which gets him off a rape charge.

In series 8, episode 5 of Call the Midwife, a woman discovers that she has AIS. She attends a cervical smear and brings up that she has never had a period, and is concerned about having children as she is about to be married. She is then diagnosed with "testicular feminisation syndrome", the old term for AIS. [163]

View post:
Androgen insensitivity syndrome - Wikipedia

Recommendation and review posted by Bethany Smith

New Jersey Hormone Therapy Centers – Growth Hormone

Doctor Certified Testosterone Replacement Therapy, HGH and Hormone Optimization Treatments in New Jersey: New Brunswick, East Brunswick, Camden, andCranberry. We have locations in Jersey City, Newark, Atlantic City, Hoboken, Morristown, Alpine and Elizabeth. Also in Hackensack, Trenton, Parsippany, Secaucus, and in North Bergen.New Jersey Testosterone Replacement Therapy, HGH and HRT TherapyHormone Replacement and Testosterone Therapy Doctors in New Jersey

You can age optimally with medically supervised interventional wellness programs such as:

-- Are you feeling as strong and vital as you did in your 20s or 30s? -- Do you have the energy you once had? -- The body? -- The sex life? -- Would you like to look and feel that way again?

You can with testosterone replacement, HGH therapy, and Hormone Optimization.

Hormones are a key part of the way your body functions. They are the chemical messengers secreted by the many glands of the endocrine system, and carried by the blood stream that stimulate and regulate most body processes.

Hormones are responsible for:

As you age all hormone levels decline, but the loss of testosterone and human growth hormone (HGH), have the greatest impact on your vitality, health, and sexual wellness.

The decline of testosterone that begins after you reach your peak testosterone levels in your 20s, in particular, effects your ability to perform in, and out of the bedroom!

Low testosterone in men, also referred to as Low-T, causes a number of symptoms we commonly attribute to aging. These include: thinning hair, weight gain, fatigue, loss of muscle tone, depression, and sexual wellness issues.

Bioidentical Hormone Therapy for men, and HGH Therapy can help with these symptoms and put you back on your path to peak performance at any age.

Hormone replacement therapy, or HRT, as the name implies, is all about renewing vitality by giving you back what age takes away.

Biologically speaking, hormones stimulate, facilitate, or regulate almost all of your bodily functions. Your body naturally produces and replaces hormones as needed. However, its ability to do so is not unlimited. As we age, our ability to produce hormones decreases. In particular are the hormones associated with sexual function and youthful vitality.

Dr. Richard Gaines, who supervises all of our New Jersey Testosterone Replacement Clinics, is a pioneer in the use of Bioidentical Testosterone Replacement Therapy for men. Dr. Gaines was one of the first physicians in New Jersey to recognize the condition of andropause also known as male menopause and how testosterone replacement can be used to treat it. In fact, he literally wrote the book, on optimal aging.

In very general terms, the symptoms of a hormone deficiency affect three areas: mental health, physical health and sexual health. In many cases you may be experiencing all or some of these symptoms, and you may be deficient in more than one hormone.

Typical symptoms of less-then-optimal hormone levels include:

At New Jersey Hormone Therapy Centers we have helped hundreds of men just like you overcome the issues of decreased hormone with the best quality service and most competitive pricing on doctor certified Hormone Replacement (HRT) Therapy including Bioidentical Hormone Replacement (BHRT) for men, Testosterone replacement, and HGH replacement.

Contact us today to find our Hormone Lab Testing facilities throughout New Jersey and to see if any of our anti-aging and hormone optimization programs using Testosterone, HGH, Sermorelin, Thyroid replacement, and/or PRP for sexual wellness are right for you. If you live in Newark, New Brunswick, Princeton, or around the City of Trenton, we have a hormone optimization specialist that is in your area.

At New Jersey HealthGains hormone replacement centers we are pioneers and experts in testosterone, hormone optimization, PRP, Platelet Rich Plasma, and HGH replacement therapy.

We customize your anti-aging and hormone optimization plans to your particular needs and lifestyle.Your testosterone, HGH (IGF-1) levels and otherhormone levels will be thoroughly tested for any imbalances or deficiencies. Low Testosterone, Low-T, andropause, male menopause as well as Human Growth Hormone Deficiency are legitimate medical health conditions that require proper diagnosis and treatment.

The Hormone Optimization medical specialists at New Jersey Optimal Aging Centers are certified professionals. Not all physicians or general practitioners have equal training or understanding of bio-identical hormone therapy (BHRT), or our expertise in diagnosing and developing treatment plans for men with low testosterone and/or HGH deficiencies. At our Testosterone Replacement and HGH Optimization centers our doctors have the knowledge and the know-how to help you age well through hormone optimization.

New Jersey Hormone Therapy Centers has testosterone replacement and optimal aging clinics throughout New Jersey, including: Trenton, Newark, Camden, Jersey City, Hampton, Alpine, Secaucus, and Elizabeth. Found us inFort Lee or Cherry Hill. We have locations inAtlantic City, North Bergen Hackensack, Parsippany, Arlington, and Hoboken.

Testosterone and male enhancement, male enhancement and testosterone, testosterone and penis size, penis size and testosterone, Erectile dysfunction, erectile dysfunction cures, issues of erectile dysfunction, HGH, HRT therapy, hormone therapy for men, hormone replacement therapy, testosterone optimization, testosterone levels, HCG, HGH Diet, low testosterone, low testosterone symptoms, LowT, Low-T, low-T, penis enlargement, Priapus shot, andropause, male menopause, hormones for men, increase libido medically, medical treatments for Low-T, doctors who treat erectile dysfunction, Physicians specializing in Testosterone, medical treatments for testosterone, testosterones doctors, who fixes low testosterone, testosterone help, help with Low-T, medical male enhancement.

Common New Jersey Testosterone Searches: New Jersey Hormone Optimization, Testosterone Treatment NJ, penis enlargement in Trenton, California Male Clinic, Anti-aging in New Jersey, male enhancement California, Testosterone Therapies New Jersey, testosterone and penis size NJ, penis size and testosterone NJ, Erectile Dysfunction Clinic California, Mens Testosterone Clinic New Jersey, erectile dysfunction cures NJ, HGH in New Brunswick, HRT therapy Ft. Lee, hormone therapy Hoboken, Hormones for men NJ, East Brunswick, hormone replacement therapy, California testosterone optimization, testosterone levels, HCG, HGH Diet Providers New Jersey, low testosterone California, testosterone symptoms NJ, Low-T treatment New Jersey, California Low-T, penis enlargement New Jersey, Jersey Shore Priapus shot, hormones NJ, male hormones NJ.

When it comes to the production of testosterone, most men hit their peak around the age of 17. By the time you reach 80,your testosterone level will likely be about half of what it was when you were atyour peak. For some men, the decrease in production has little effect. But for many men, as you hit your 50s, 60s and older, you may actually start to feel the impact of the reduced level, experiencing low testosterone or Low-T.

Symptoms of Low-T include reduction of libido or sex drive, a feeling of reduced virility or vitality, changes in mood, erectile dysfunction, decreased energy, reduced muscle and bone mass, and memory issues.

If you are a man over 40, and you are experiencing any of these, you may have low testosterone. However, the only way to truly determine if you have an imbalance of one or more hormones related to your vitality, is with proper diagnosis and analysis.

All of our hormone optimization programs are overseen by Dr. Richard Gaines, a world-renowned leader in the field of hormone replacement therapy for men.

Call HealthGains (800) 325-1325 to find out if testosterone replacement, HGH treatments, or any of our other Hormone Optimization, or Hormone Replacement Therapies are right for you.

Continue reading here:
New Jersey Hormone Therapy Centers - Growth Hormone

Recommendation and review posted by Bethany Smith

What is cryonics? – Cryogenics Human & Pet Freezing for …

Cryonics is an effort to save lives by using temperatures so cold that a person beyond help by today's medicine might be preserved for decades or centuries until a future medical technology can restore that person to full health. Cryonics is a second chance at life. It is the reasoned belief in the advancement of future medicinal technologies being able to cure things we cant today.

Many biological specimens, including whole insects, many types of human tissue including brain tissue, and human embryos have been cryogenically preserved, stored at liquid nitrogen temperature where all decay ceases, and revived. This leads scientists to believe that the same can be done with whole human bodies, and that any minimal harm can be reversed with future advancements in medicine.

Neurosurgeons often cool patients bodies so they can operate on aneurysms without damaging or rupturing the nearby blood vessels. Human embryos that are frozen in fertility clinics, defrosted, and implanted in a mothers uterus grow into perfectly normal human beings. This method isnt new or groundbreaking- successful cryopreservation of human embryos was first reported in 1983 by Trounson and Mohr with multicellular embryos that had been slow-cooled using dimethyl sulphoxide (DMSO).

And just in Feb. of 2016, there was a cryonics breakthrough when for the first time, scientists vitrified a rabbits brain and, after warming it back up, showed that it was in near perfect condition. This was the first time a cryopreservation was provably able to protect everything associated with learning and memory.

Read more:
What is cryonics? - Cryogenics Human & Pet Freezing for ...

Recommendation and review posted by Bethany Smith

Embryo stem cells created from skin cells Scope of …

These are 4-cell stage mouse embryos.

Researchers have found a way to transform skin cells into the three major stem cell types that comprise early-stage embryos. The work (in mouse cells) has significant implications for modeling embryonic disease and placental dysfunctions, as well as paving the way to create whole embryos from skin cells.

Researchers at the Hebrew University of Jerusalem (HU) have found a way to transform skin cells into the three major stem cell types that comprise early-stage embryos. The work (in mouse cells) has significant implications for modelling embryonic disease and placental dysfunctions, as well as paving the way to create whole embryos from skin cells.

As published in Cell Stem Cell, Dr. Yossi Buganim of HUs Department of Developmental Biology and Cancer Research and his team discovered a set of genes capable of transforming murine skin cells into all three of the cell types that comprise the early embryo: the embryo itself, the placenta and the extra-embryonic tissues, such as the umbilical cord. In the future, it may be possible to create entire human embryos out of human skin cells, without the need for sperm or eggs. This discovery also has vast implications for modelling embryonic defects and shedding light on placental dysfunctions, as well as solving certain infertility problems by creating human embryos in a petri dish.

Back in 2006, Japanese researchers discovered the capacity of skin cells to be reprogrammed into early embryonic cells that can generate an entire fetus, by expressing four central embryonic genes. These reprogrammed skin cells, termed Induced Plutipotent Stem Cells (iPSCs), are similar to cells that develop in the early days after fertilization and are essentially identical to their natural counterparts. These cells can develop into all fetal cell types, but not into extra-embryonic tissues, such as the placenta.

Now, the Hebrew University research team, headed by Dr. Yossi Buganim, Dr. Oren Ram from the HUs Institute of Life Science and Professor Tommy Kaplan from HUs School of Computer Science and Engineering, as well as doctoral students Hani Benchetrit and Mohammad Jaber, found a new combination of five genes that, when inserted into skin cells, reprogram the cells into each of three early embryonic cell types iPS cells which create fetuses, placental stem cells, and stem cells that develop into other extra-embryonic tissues, such as the umbilical cord. These transformations take about one month.

The HU team used new technology to scrutinize the molecular forces that govern cell fate decisions for skin cell reprogramming and the natural process of embryonic development. For example, the researchers discovered that the gene Eomes pushes the cell towards placental stem cell identity and placental development, while the Esrrb gene orchestrates fetus stem cells development through the temporary acquisition of an extrae-mbryonic stem cell identity.

To uncover the molecular mechanisms that are activated during the formation of these various cell types, the researchers analyzed changes to the genome structure and function inside the cells when the five genes are introduced into the cell. They discovered that during the first stage, skin cells lose their cellular identity and then slowly acquire a new identity of one of the three early embryonic cell types, and that this process is governed by the levels of two of the five genes.

Recently, attempts have been made to develop an entire mouse embryo without using sperm or egg cells. These attempts used the three early cell types isolated directly from a live, developing embryo. However, HUs study is the first attempt to create all three main cell lineages at once from skin cells. Further, these findings mean there may be no need to sacrifice a live embryo to create a test tube embryo.

Like Loading...

Related

Read the original post:
Embryo stem cells created from skin cells Scope of ...

Recommendation and review posted by Bethany Smith

Could skin-related stem cells help in treating …

UMSOM Researchers Discovered that Pigment-Producing Stem Cells Can Help Regenerate Vital Part of Nervous System

Neurodegenerative diseases like multiple sclerosis (MS) affect millions of people worldwide and occur when parts of the nervous system lose function over time. Researchers at the University of Maryland School of Medicine (UMSOM) have discovered that a type of skin-related stem cell could be used to help regenerate myelin sheaths, a vital part of the nervous system linked to neurodegenerative disorders.

The discovery into these types of stem cells is significant because they could offer a simpler and less invasive alternative to using embryonic stem cells. This early stage research showed that by using these skin-related stem cells, researchers were able to restore myelin sheath formation in mice.

This research enhances the possibility of identifying human skin stem cells that can be isolated, expanded, and used therapeutically. In the future, we plan to continue our research in this area by determining whether these cells can enhance functional recovery from neuronal injury, saidThomas J. Hornyak, MD, PhD, Associate Professor and Chairman of theDepartment of Dermatology, and Principal Investigator in this research. In the future, we plan to continue our research in this area by determining whether these cells can enhance functional recovery from neuronal injury.

Using a mouse model, Dr. Hornyaks team of researchers discovered a way to identify a specific version of a cell known as a melanocyte stem cell. These are the precursor cells to the cells in skin and hair follicles that make a pigment know as melanin, which determines the color of skin and hair. These melanocyte stem cells have the ability to continue to divide without limit, which is a trait that is not shared by other cells in the body. Additionally, the researchers discovered that these stem cells can make different types of cells depending on the type of signals they receive. This research was published inPLoS Genetics.

Importantly, unlike the embryonic stem cell, which must be harvested from an embryo, melanocyte stem cells can be harvested in a minimally-invasive manner from skin.

Dr. Hornyaks research team found a new way to not only identify the right kind of melanocyte stem cells, but also the potential applications for those suffering from neurodegenerative disorders. By using a protein marker that is only found on these specialized cells, Dr. Hornyaks research group was able to isolate this rare population of stem cells from the majority of the cells that make up skin. Additionally, they found that there exist two different types of melanocyte stem cells, which helped in determining the type of cells they could create.

Using this knowledge, the UMSOM researchers determined that under the right conditions, these melanocyte stem cells could function as cells that produce myelin, the major component of a structure known as the myelin sheath, which protects neurons and is vital to the function of our nervous system. Some neurodegenerative diseases, like multiple sclerosis, are caused by the loss of these myelin-producing, or glial, cells which ultimately lead to irregular function of the neurons and ultimately a failure of our nervous system to function correctly.

Dr. Hornyak and members of his laboratory grew melanocyte stem cells with neurons isolated from mice that could not make myelin. They discovered that these stem cells behaved like a glial cell under these conditions. These cells ultimately formed a myelin sheath around the neurons that resembled structures of a healthy nerve cell. When they took this experiment to a larger scale, in the actual mouse, the researchers found that mice treated with these melanocyte stem cells had myelin sheath structures in the brain as opposed to untreated mice who lacked these structures.

This research holds promise for treating serious neurodegenerative diseases that impact millions of people each year. Our researchers at the University of Maryland School of Medicine have discovered what could be a critical and non-invasive way to use stem cells as a therapy for these diseases,said UMSOM Dean,E. Albert Reece, MD, PhD, MBA, Executive Vice President for Medical Affairs, UM Baltimore, and the John Z. and Akiko K. Bowers Distinguished Professor.

Learn more: UMSOM Researchers Discover Certain Skin-Related Stem Cells Could Help in Treating Neurogenerative Diseases

viaGoogle News

via Bing News

Like Loading...

Read the original here:
Could skin-related stem cells help in treating ...

Recommendation and review posted by Bethany Smith

Embryo stem cells created from skin cells | SciSeek

Researchers at the Hebrew University of Jerusalem (HU) have found a way to transform skin cells into the three major stem cell types that comprise early-stage embryos. The work (in mouse cells) has significant implications for modelling embryonic disease and placental dysfunctions, as well as paving the way to create whole embryos from skin cells.

As published in Cell Stem Cell, Dr. Yossi Buganim of HUs Department of Developmental Biology and Cancer Research and his team discovered a set of genes capable of transforming murine skin cells into all three of the cell types that comprise the early embryo: the embryo itself, the placenta and the extra-embryonic tissues, such as the umbilical cord. In the future, it may be possible to create entire human embryos out of human skin cells, without the need for sperm or eggs. This discovery also has vast implications for modelling embryonic defects and shedding light on placental dysfunctions, as well as solving certain infertility problems by creating human embryos in a petri dish.

Back in 2006, Japanese researchers discovered the capacity of skin cells to be reprogrammed into early embryonic cells that can generate an entire fetus, by expressing four central embryonic genes. These reprogrammed skin cells, termed Induced Plutipotent Stem Cells (iPSCs), are similar to cells that develop in the early days after fertilization and are essentially identical to their natural counterparts. These cells can develop into all fetal cell types, but not into extra-embryonic tissues, such as the placenta.

Now, the Hebrew University research team, headed by Dr. Yossi Buganim, Dr. Oren Ram from the HUs Institute of Life Science and Professor Tommy Kaplan from HUs School of Computer Science and Engineering, as well as doctoral students Hani Benchetrit and Mohammad Jaber, found a new combination of five genes that, when inserted into skin cells, reprogram the cells into each of three early embryonic cell types iPS cells which create fetuses, placental stem cells, and stem cells that develop into other extra-embryonic tissues, such as the umbilical cord. These transformations take about one month.

The HU team used new technology to scrutinize the molecular forces that govern cell fate decisions for skin cell reprogramming and the natural process of embryonic development. For example, the researchers discovered that the gene Eomes pushes the cell towards placental stem cell identity and placental development, while the Esrrb gene orchestrates fetus stem cells development through the temporary acquisition of an extrae-mbryonic stem cell identity.

To uncover the molecular mechanisms that are activated during the formation of these various cell types, the researchers analyzed changes to the genome structure and function inside the cells when the five genes are introduced into the cell. They discovered that during the first stage, skin cells lose their cellular identity and then slowly acquire a new identity of one of the three early embryonic cell types, and that this process is governed by the levels of two of the five genes.

Recently, attempts have been made to develop an entire mouse embryo without using sperm or egg cells. These attempts used the three early cell types isolated directly from a live, developing embryo. However, HUs study is the first attempt to create all three main cell lineages at once from skin cells. Further, these findings mean there may be no need to sacrifice a live embryo to create a test tube embryo.

Story Source:

Materials provided by The Hebrew University of Jerusalem. Note: Content may be edited for style and length.

Read this article:
Embryo stem cells created from skin cells | SciSeek

Recommendation and review posted by Bethany Smith

‘Extraordinary’ tale: Stem cells heal a young boy’s lethal …

The complications of the little boys genetic skin disease grew as he did. Tiny blisters had covered his back as a newborn. Then came the chronic skin wounds that extended from his buttocks down to his legs.

By June 2015, at age 7, the boy had lost nearly two-thirds of his skin due to an infection related to the genetic disorder junctional epidermolysis bullosa, which causes the skin to become extremely fragile. Theres no cure for the disease, and it is often fatal for kids. At the burn unit at Childrens Hospital in Bochum, Germany, doctors offered him constant morphine and bandaged much of his body, but nothing not even his fathers offer to donate his skin worked to heal his wounds.

We were absolutely sure we could do nothing for this kid, Dr. Tobias Rothoeft, a pediatrician with Childrens Hospital in Bochum, which is affiliated with Ruhr University. [We thought] that he would die.

advertisement

As a last-ditch effort, the boys father asked if there were any available experimental treatments. The German doctors reached out to Dr. Michele De Luca, an Italian stem cell expert who heads the Center for Regenerative Medicine at the University of Modena and Reggio Emilia, to see if a transplant of genetically modified skin cells might be possible. De Luca knew the odds were against them such a transplant had only been performed twice in the past, and never on such a large portion of the body. But he said yes.

The doctors were ultimately able to reconstruct fully functional skin for 80 percent of the boys body by grafting on genetically modified cells taken from the boys healthy skin. The researchers say the results of this single-person clinical trial, published on Wednesday in Nature, show that transgenic stem cells can regenerate an entire tissue. De Luca told reporters the procedure not only offers hope to the 500,000 epidermolysis bullosa patients worldwide but also could offer a blueprint for using genetically modified stem cells to treat a variety of other diseases.

To cultivate replacement skin, the medical team took a biopsy the size of a matchbook from the boys healthy skin and sent it to De Lucas team in Italy. There, researchers cloned the skin cells and genetically modified them to have a healthy version of the gene LAMB3, responsible for making the protein laminin-332. They grew the corrected cultures into sheets, which they sent back to Germany. Then, over a series of three operations between October 2015 and January 2016, the surgical team attached the sheets on different parts of the boys body.

The gene-repaired skin took, and spread. Within just a month the wounds were islands within intact skin. The boy was sent home from the hospital in February 2016, and over the next 21 months, researchers said his skin healed normally. Unlike burn patients whose skin grafts arent created from genetically modified cells the boy wont need ointment for his skin and can regrow his hair.

And unlike simple grafts of skin from one body part to another, we had the opportunity to reproduce as much as those cells as we want, said plastic surgeon Dr. Tobias Hirsch, one of the studys authors. You can have double the whole body surface or even more. Thats a fantastic option for a surgeon to treat this child.

Dr. John Wagner, the director of the University of Minnesota Masonic Childrens Hospitals blood and marrow transplant program, told STAT the findings have extraordinary potential because, until now, the only stem cell transplants proven to work in humans was of hematopoietic stem cells those in blood and bone marrow.

Theyve proven that a stem cell is engraftable, Wagner said. In humans, what we have to demonstrate is that a parent cell is able to reproduce or self-renew, and differentiate into certain cell populations for that particular organ. This is the first indication that theres another stem cell population [beyond hematopoietic stem cells] thats able to do that.

The researchers said the aggressive treatment outlined in the study necessary in the case of the 7-year-old patient could eventually help other patients in less critical condition. One possibility, they noted in the paper, was to bank skin samples from infants with JEB before they develop symptoms. These could then be used to treat skin lesions as they develop rather than after they become life-threatening.

The treatment might be more effective in children, whose stem cells have higher renewal potential and who have less total skin to replace, than in adults, Mariaceleste Aragona and Cdric Blanpain, stem cell researchers with the Free University of Brussels, wrote in an accompanying commentary for Nature.

But De Luca said more research must be conducted to see if the methods could be applied beyond this specific genetic disease. His group is currently running a pair of clinical trials in Austria using genetically modified skin stem cells to treat another 12 patients with two different kinds of epidermolysis bullosa, including JEB.

For the 7-year-old boy, life has become more normal now that it ever was before, the researchers said. Hes off pain meds. While he has some small blisters in areas that didnt receive a transplant, they havent stopped him from going to school, playing soccer, or behaving like a healthy child.

The kid is doing quite well. If he gets bruises like small kids [do], they just heal as normal skin heals, Rothoeft said. Hes quite healthy.

See the rest here:
'Extraordinary' tale: Stem cells heal a young boy's lethal ...

Recommendation and review posted by Bethany Smith

Hebrew University researchers create embryo stem cells …

Researchers at the Hebrew University of Jerusalem say they have found a way to transform skin cells into the three major stem cell types that comprise early-stage embryos.

The discovery could pave the way to creating entire human embryos out of human skin cells, without the need for sperm or eggs, the researchers say. And it could also have vast implications for modeling embryonic defects and shedding light on placental dysfunctions, as well as solving certain infertility problems by creating human embryos in a petri dish, a Hebrew University statement said.

You could say we are close to generating a synthetic embryo, which is a really crazy thing, said Dr. Yossi Buganim of the universitys Department of Developmental Biology and Cancer Research, who led the study that was published in Cell Stem Cell.

Get The Start-Up Israel's Daily Start-Up by email and never miss our top storiesFree Sign Up

This discovery could allow researchers in future to generate embryos from sterile men and women, using only their skin cells, and generate a real embryo in a dish and implant the embryo in the mother, Buganim said in a phone interview.

Researchers at the Hebrew Hebrew University of Jerusalem say they have found a way to transform skin cells into the three major stem cell types that comprise early-stage embryos; the image shows 4-cell stage mouse embryos (Kirill Makedonski)

Buganim and his team discovered a set of five genes capable of transforming murine skin cells into all three of the cell types that make up the early embryo: the fetus itself, the placenta and the extra-embryonic tissues, such as the umbilical cord.

In 2006, Japanese researchers Kazutoshi Takahashi and Shinya Yamanaka discovered the capacity of skin cells to be reprogrammed into early embryonic cells that can generate an entire fetus through the use of four central embryonic genes. These genes reprogrammed the skin cells into induced pluripotent stem cells (iPSCs), which are similar to cells that develop in the early days after fertilization and are essentially identical to their natural counterparts. These cells can develop into all fetal cell types, but not into extra-embryonic tissues, such as the placenta.

The Japanese researchers discovered that the four central embryonic genes can be used to rejuvenate the skin cells to function like embryonic stem cells, explained Buganim.

After fertilization of the egg, the cell divides into 64, creating a bowl of cells that make up the three crucial parts of an embryo the epiblast, the inner cell mass which gives rise to the fetus itself; the primitive endoderm that is responsible for the umbilical cord; and a third part, the trophectoderm, that is responsible for creating the placenta.

What the Japanese managed to do, Buganim said, was to transform the skin cells into fetus stem cells. But that is not enough to create an entire embryo, he said, because the other parts are also needed those that develop the umbilical cord and the placenta.

Dr. Yossi Buganim of The Hebrew Universitys Department of Developmental Biology and Cancer Research (Shai Herman)

The breakthrough of the Hebrew University team, Buganim said, was creating with five genes all of the three essential compartments that make up the embryonic and extra-embryonic features necessary for the creation of an in-vitro embryo. The work was done with mice, and the team is now starting to apply the same research to human embryos, he added.

The researchers used five genes that are completely different from those used by the Japanese researchers, Buganim noted. The genes the Israeli researchers used are those that play a role in the early development of the embryo. They specify and direct what each cell will develop into, whether the umbilical cord, the placenta or the fetus itself.

The team used new technology to study the molecular forces that dictate how each of the cells develop. For example, the researchers discovered that the gene Eomes pushes the cell toward placental stem cell identity and placental development, while Esrrb orchestrates the development of fetus stem cells, attaining first, but just temporarily, an extra-embryonic stem cell identity.

It was our idea to use those genes, Buganim said.

The researchers then combined these five genes in such a way that, when inserted into skin cells, they managed to reprogram the cells into each of three early embryonic cell types in the same petri dish.

The discovery will enable researchers to better understand and address embryonic malfunctions and diseases such as placental insufficiencies or miscarriages, he said. This could enable researchers to use a dish to model the embryonic cells and identify early markers for risk.

The challenges ahead, however, are still huge, said Buganim. An embryo is a three dimensional structure. We need to learn how to put this all together to generate a real embryo. We need to identify the ratios of placental stem cells, umbilical cord cells and iPS cells, which create the fetuses, and in what scaffold to place them, he said.

These cells know how to stick together, Buganim said. I need to give them the proper environment and the proper ratio to organize themselves into a real embryo.

The study was done by Buganim together with Dr. Oren Ram from Hebrew Universitys Institute of Life Science and Professor Tommy Kaplan from the universitys School of Computer Science and Engineering, as well as doctoral students Hani Benchetrit and Mohammad Jaber.

Visit link:
Hebrew University researchers create embryo stem cells ...

Recommendation and review posted by Bethany Smith

Hebrew U Researchers Created Embryo Stem Cells from Skin …

Photo Credit: Hebrew U

A new, groundbreaking study by the Hebrew University of Jerusalem (HU) found a way to transform skin cells into the three major stem cell types that comprise early-stage embryos. This work has significant implications for modelling embryonic disease and placental dysfunctions, as well as paving the way to create whole embryos from skin cells.

As published in Cell Stem Cell, Dr. Yossi Buganim of HUs Department of Developmental Biology and Cancer Research and his team discovered a set of genes capable of transforming murine skin cells into all three of the cell types that comprise the early embryo: the embryo itself, the placenta and the extraembryonic tissues, such as the umbilical cord. In the future, it may be possible to create entire human embryos out of human skin cells, without the need for sperm or eggs. This discovery also has vast implications for modelling embryonic defects and shedding light on placental dysfunctions, as well as solving certain infertility problems by creating human embryos in a petri dish.

Back in 2006, Japanese researchers discovered the capacity of skin cells to be reprogrammed into early embryonic cells that can generate an entire fetus, by expressing four central embryonic genes. These reprogrammed skin cells, termed Induced Plutipotent Stem Cells (iPSCs), are similar to cells that develop in the early days after fertilization and are essentially identical to their natural counterparts. These cells can develop into all fetal cell types, but not into extra-embryonic tissues, such as the placenta.

Now, the Hebrew University research team, headed by Dr. Yossi Buganim, Dr. Oren Ram from the HUs Institute of Life Science and Professor Tommy Kaplan from HUs School of Computer Science and Engineering, as well as doctoral students Hani Benchetrit and Mohammad Jaber, found a new combination of five genes that, when inserted into skin cells, reprogram the cells into each of three early embryonic cell typesiPS cells which create fetuses, placental stem cells, and stem cells that develop into other extraembryonic tissues, such as the umbilical cord. These transformations take about one month.

The HU team used new technology to scrutinize the molecular forces that govern cell fate decisions for skin cell reprogramming and the natural process of embryonic development. For example, the researchers discovered that the gene Eomes pushes the cell towards placental stem cell identity and placental development, while the Esrrb gene orchestrates fetus stem cells development through the temporary acquisition of an extraembryonic stem cell identity.

To uncover the molecular mechanisms that are activated during the formation of these various cell types, the researchers analyzed changes to the genome structure and function inside the cells when the five genes are introduced into the cell. They discovered that during the first stage, skin cells lose their cellular identity and then slowly acquire a new identity of one of the three early embryonic cell types, and that this process is governed by the levels of two of the five genes.

Recently, attempts have been made to develop an entire mouse embryo without using sperm or egg cells. These attempts used the three early cell types isolated directly from a live, developing embryo. However, HUs study is the first attempt to create all three main cell lineages at once from skin cells. Further, these findings mean there may be no need to sacrifice a live embryo to create a test tube embryo.

Visit link:
Hebrew U Researchers Created Embryo Stem Cells from Skin ...

Recommendation and review posted by Bethany Smith


Archives