Tuesday, December 4, 2018

Genes tied to dementia identified; may lead to new therapies

Sunday, December 2, 2018

‘HIV self-screening test has potential to become major game-changer in country’

China suspends scientist who tweaked human gene

China suspends scientist who tweaked human gene

Mid-Day

Wednesday, November 28, 2018

Scientists regrow hair

Scientists regrow hair on wounded skin

Chunav Manch Rajasthan 2018

Scientists regrow hair on wounded skin

The findings by researchers at the New York University (NYU) School of Medicine in the US better explain why hair does not normally grow on wounded skin.  

Reported by: PTI, New York [ Published on: November 28, 2018 15:32 IST ]
Representational Image
Researchers have regrown hair strands on damaged skin by stirring crosstalk among skin cells that form the roots of hair.
The findings by researchers at the New York University (NYU) School of Medicine in the US better explain why hair does not normally grow on wounded skin.
The study, published in the journal Nature Communications, may help in the search for better drugs to restore hair growth.
It examined the effect of distinct signalling pathways in damaged skin of laboratory mice.
Experiments focused on cells called fibroblasts that secrete collagen, the structural protein most responsible for maintaining the shape and strength of skin and hair.
Researchers activated the sonic hedgehog signalling pathway used by cells to communicate with each other.
The pathway is known to be very active during the early stages of human growth in the womb, when hair follicles are formed, but is otherwise stalled in wounded skin in healthy adults.
Researchers said this possibly explains why hair follicles fail to grow in skin replaced after injury or surgery.
"Our results show that stimulating fibroblasts through the sonic hedgehog pathway can trigger hair growth not previously seen in wound healing," said Mayumi Ito, an associate professor at NYU.
Regrowing hair on damaged skin is an unmet need in medicine, Ito said, because of the disfigurement suffered by thousands from trauma, burns, and other injuries.
However, her more immediate goal, she said, is to signal mature skin to revert back to its embryonic state so that it can grow new hair follicles, not just on wounded skin, but also on people who have gone bald from ageing.
Ito said scientists have until now assumed that, as part of the healing process, scarring and collagen buildup in damaged skin were behind its inability to regrow hair.
"Now we know that it's a signalling issue in cells that are very active as we develop in the womb, but less so in mature skin cells as we age," she said.
Key among the study's findings was that no signs of hair growth were observed in untreated skin, but were observed in treated skin, offering evidence that sonic hedgehog signalling was behind the hair growth, researchers said.
To bypass the risk of tumours reported in other experiments that turned on the sonic hedgehog pathway, the team turned on only fibroblasts located just beneath the skin's surface where hair follicle roots (dermal papillae) first appear.
Researchers also zeroed in on fibroblasts because the cells are known to help direct some of the biological processes involved in healing.
Hair regrowth was observed within four weeks after skin wounding in all treated mice, with hair root and shaft structures starting to appear after nine weeks.

Hedgehog Signaling Interactive Pathway

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Pathway Description:

The evolutionarily conserved Hedgehog (Hh) pathway is essential for normal embryonic development and plays critical roles in adult tissue maintenance, renewal and regeneration. Secreted Hh proteins act in a concentration- and time-dependent manner to initiate a series of cellular responses that range from survival and proliferation to cell fate specification and differentiation.
Proper levels of Hh signaling require the regulated production, processing, secretion and trafficking of Hh ligands– in mammals this includes Sonic (Shh), Indian (Ihh) and Desert (Dhh). All Hh ligands are synthesized as precursor proteins that undergo autocatalytic cleavage and concomitant cholesterol modification at the carboxy terminus and palmitoylation at the amino terminus, resulting in a secreted, dually-lipidated protein. Hh ligands are released from the cell surface through the combined actions of Dispatched and Scube2, and subsequently trafficked over multiple cells through interactions with the cell surface proteins LRP2 and the Glypican family of heparan sulfate proteoglycans (GPC1-6).
Hh proteins initiate signaling through binding to the canonical receptor Patched (PTCH1) and to the co-receptors GAS1, CDON and BOC. Hh binding to PTCH1 results in derepression of the GPCR-like protein Smoothened (SMO) that results in SMO accumulation in cilia and phosphorylation of its cytoplasmic tail. SMO mediates downstream signal transduction that includes dissociation of GLI proteins (the transcriptional effectors of the Hh pathway) from kinesin-family protein, Kif7, and the key intracellular Hh pathway regulator SUFU.
GLI proteins also traffic through cilia and in the absence of Hh signaling are sequestered by SUFU and Kif7, allowing for GLI phosphorylation by PKA, GSK3β and CK1, and subsequent processing into transcriptional repressors (through cleavage of the carboxy-terminus) or targeting for degradation (mediated by the E3 ubiquitin ligase β-TrCP). In response to activation of Hh signaling, GLI proteins are differentially phopshorylated and processed into transcriptional activators that induce expression of Hh target genes, many of which are components of the pathway (e.g. PTCH1 and GLI1). Feedback mechanisms include the induction of Hh pathway antagonists (PTCH1, PTCH2 and Hhip1) that interfere with Hh ligand function, and GLI protein degradation mediated by the E3 ubiquitin ligase adaptor protein, SPOP.
In addition to vital roles during normal embryonic development and adult tissue homeostasis, aberrant Hh signaling is responsible for the initiation of a growing number of cancers including, classically, basal cell carcinoma, edulloblastoma, and rhabdomyosarcoma; more recently overactive Hh signaling has been implicated in pancreatic, lung, prostate, ovarian, and breast cancer. Thus, understanding the mechanisms that control Hh pathway activity will inform the development of novel therapeutics to treat a growing number of Hh-driven pathologies.

Tuesday, November 27, 2018

Herpes Test: What You Should Know

Herpes Test: What You Should Know

Genital herpes is a common sexually transmitted disease. It’s caused by two different viruses called herpes simplex type 1 (HSV-1) and herpes simplex type 2 (HSV-2
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You get genital herpes by having sex -- vaginal, oral, or anal -- with someone who already has it.
Thinking you have genital herpes naturally can bring up strong emotions. Talk to your doctor about getting tested. It could help you to learn more about the disease and talk honestly with your sexual partner. You might want to join a support group, too.

Do I Need to Get Tested?

Many people with herpes don’t have any symptoms. If symptoms do show up, you might first feel tingling or burning near your genitals.
You might then get blisters around your genitals, anus, thighs, or buttocks. When the blisters break, they leave sores that can take a few weeks to heal. They usually won’t leave any scars.
To check for herpes, your doctor usually does a physical exam and then likely orders one of these tests:
  • Viral culture
  • Polymerase chain reaction (PCR) test
  • Blood test
If you get a “positive” result from the viral culture or PCR tests, it likely means you have herpes. .
A “negative” viral culture or PCR result could mean you don’t have genital herpes. But in some cases, a person could still have genital herpes and a negative result. That's likely due to other factors related to how much virus there is in the sores.
You don’t need to do anything to prepare for these tests. They don’t take long, but how soon you get your results depends on the type of test and the lab that does it.

Viral Culture

For this test, your doctor scrapes or swabs one of your sores to take a sample. A lab then checks the sample for the herpes virus. It can take up to 7 days to get your results.
This test is best used within 48 hours of when you first see symptoms. After that time, the level of herpes virus starts to drop. That means there’s a higher chance the test could say you don’t have herpes when you really do.

Polymerase Chain Reaction (PCR) Test

As with the viral culture, your doctor swabs or scrapes a sample from one of your sores. A lab gets the sample and looks for genes from the herpes virus. PCR test results usually come back to you within 24 hours.
You’re more likely to get this test if you have symptoms but it’s been longer than 48 hours since they showed up. In this case, you can rely on the results from this test more than the viral culture.

Blood Test

A small amount of blood is sent to a lab that then checks it for herpes “antibodies.” Those are something your body makes to fight the virus.
Continue Reading Below
You might get a blood test if you think you have been exposed but you don’t have any symptoms.
Labs may use different types of blood tests. With some you can get results the same day, but others may take up to 3 weeks.

Next Steps

There’s no cure for genital herpes, but it can be treated.
If you do have it, your doctor can help you manage it. There are drugs that can shorten or prevent outbreaks, ease symptoms, and lower the chances your sex partners will get it.

Sunday, November 25, 2018

First Gene-Edited Babies Claimed in China

2 hours ago - A Chinese researcher claims that he helped make the world's first genetically edited babies — twin girls whose DNA he said he altered with a ...
 
 




  • HONG KONG — A Chinese researcher claims that he helped make the world's first genetically edited babies — twin girls born this month whose DNA he said he altered with a powerful new tool capable of rewriting the very blueprint of life.
    If true, it would be a profound leap of science and ethics.
    A U.S. scientist said he took part in the work in China, but this kind of gene editing is banned in the United States because the DNA changes can pass to future generations and it risks harming other genes.
    Many mainstream scientists think it's too unsafe to try, and some denounced the Chinese report as human experimentation.
    The researcher, He Jiankui of Shenzhen, said he altered embryos for seven couples during fertility treatments, with one pregnancy resulting thus far. He said his goal was not to cure or prevent an inherited disease, but to try to bestow a trait that few people naturally have — an ability to resist possible future infection with HIV, the AIDS virus.
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    He said the parents involved declined to be identified or interviewed, and he would not say where they live or where the work was done.
    There is no independent confirmation of He's claim, and it has not been published in a journal, where it would be vetted by other experts. He revealed it Monday in Hong Kong to one of the organizers of an international conference on gene editing that is set to begin Tuesday, and earlier in exclusive interviews with The Associated Press.
    "I feel a strong responsibility that it's not just to make a first, but also make it an example," He told the AP. "Society will decide what to do next" in terms of allowing or forbidding such science.
    Some scientists were astounded to hear of the claim and strongly condemned it.
    It's "unconscionable ... an experiment on human beings that is not morally or ethically defensible," said Dr. Kiran Musunuru, a University of Pennsylvania gene editing expert and editor of a genetics journal.
    "This is far too premature," said Dr. Eric Topol, who heads the Scripps Research Translational Institute in California. "We're dealing with the operating instructions of a human being. It's a big deal."
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    However, one famed geneticist, Harvard University's George Church, defended attempting gene editing for HIV, which he called "a major and growing public health threat."
    "I think this is justifiable," Church said of that goal.
    In recent years scientists have discovered a relatively easy way to edit genes, the strands of DNA that govern the body. The tool, called CRISPR-cas9, makes it possible to operate on DNA to supply a needed gene or disable one that's causing problems.
    It's only recently been tried in adults to treat deadly diseases, and the changes are confined to that person. Editing sperm, eggs or embryos is different — the changes can be inherited. In the U.S., it's not allowed except for lab research. China outlaws human cloning but not specifically gene editing.
    He Jiankui (HEH JEE'-an-qway), who goes by "JK," studied at Rice and Stanford universities in the U.S. before returning to his homeland to open a lab at Southern University of Science and Technology of China in Shenzhen, where he also has two genetics companies.
    The U.S. scientist who worked with him on this project after He returned to China was physics and bioengineering professor Michael Deem, who was his adviser at Rice in Houston. Deem also holds what he called "a small stake" in — and is on the scientific advisory boards of — He's two companies.
    The Chinese researcher said he practiced editing mice, monkey and human embryos in the lab for several years and has applied for patents on his methods.
    He said he chose embryo gene editing for HIV because these infections are a big problem in China. He sought to disable a gene called CCR5 that forms a protein doorway that allows HIV, the virus that causes AIDS, to enter a cell.
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    All of the men in the project had HIV and all of the women did not, but the gene editing was not aimed at preventing the small risk of transmission, He said. The fathers had their infections deeply suppressed by standard HIV medicines and there are simple ways to keep them from infecting offspring that do not involve altering genes.
    Instead, the appeal was to offer couples affected by HIV a chance to have a child that might be protected from a similar fate.
    He recruited couples through a Beijing-based AIDS advocacy group called Baihualin. Its leader, known by the pseudonym "Bai Hua," told the AP that it's not uncommon for people with HIV to lose jobs or have trouble getting medical care if their infections are revealed.
    Here is how He described the work:
    The gene editing occurred during IVF, or lab dish fertilization. First, sperm was "washed" to separate it from semen, the fluid where HIV can lurk. A single sperm was placed into a single egg to create an embryo. Then the gene editing tool was added.
    When the embryos were 3 to 5 days old, a few cells were removed and checked for editing. Couples could choose whether to use edited or unedited embryos for pregnancy attempts. In all, 16 of 22 embryos were edited, and 11 embryos were used in six implant attempts before the twin pregnancy was achieved, He said.
    Tests suggest that one twin had both copies of the intended gene altered and the other twin had just one altered, with no evidence of harm to other genes, He said. People with one copy of the gene can still get HIV, although some very limited research suggests their health might decline more slowly once they do.
    Several scientists reviewed materials that He provided to the AP and said tests so far are insufficient to say the editing worked or to rule out harm.
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    They also noted evidence that the editing was incomplete and that at least one twin appears to be a patchwork of cells with various changes.
    "It's almost like not editing at all" if only some of certain cells were altered, because HIV infection can still occur, Church said.
    Church and Musunuru questioned the decision to allow one of the embryos to be used in a pregnancy attempt, because the Chinese researchers said they knew in advance that both copies of the intended gene had not been altered.
    "In that child, there really was almost nothing to be gained in terms of protection against HIV and yet you're exposing that child to all the unknown safety risks," Musunuru said.
    The use of that embryo suggests that the researchers' "main emphasis was on testing editing rather than avoiding this disease," Church said.
    Even if editing worked perfectly, people without normal CCR5 genes face higher risks of getting certain other viruses, such as West Nile, and of dying from the flu. Since there are many ways to prevent HIV infection and it's very treatable if it occurs, those other medical risks are a concern, Musunuru said.
    There also are questions about the way He said he proceeded. He gave official notice of his work long after he said he started it — on Nov. 8, on a Chinese registry of clinical trials.
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    It's unclear whether participants fully understood the purpose and potential risks and benefits. For example, consent forms called the project an "AIDS vaccine development" program.
    The Rice scientist, Deem, said he was present in China when potential participants gave their consent and that he "absolutely" thinks they were able to understand the risks.
    Deem said he worked with He on vaccine research at Rice and considers the gene editing similar to a vaccine.
    "That might be a layman's way of describing it," he said.
    Both men are physics experts with no experience running human clinical trials.
    The Chinese scientist, He, said he personally made the goals clear and told participants that embryo gene editing has never been tried before and carries risks. He said he also would provide insurance coverage for any children conceived through the project and plans medical follow-up until the children are 18 and longer if they agree once they're adults.
    Further pregnancy attempts are on hold until the safety of this one is analyzed and experts in the field weigh in, but participants were not told in advance that they might not have a chance to try what they signed up for once a "first" was achieved, He acknowledged. Free fertility treatment was part of the deal they were offered.
    He sought and received approval for his project from Shenzhen Harmonicare Women's and Children's Hospital, which is not one of the four hospitals that He said provided embryos for his research or the pregnancy attempts.
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    Some staff at some of the other hospitals were kept in the dark about the nature of the research, which He and Deem said was done to keep some participants' HIV infection from being disclosed.
    "We think this is ethical," said Lin Zhitong, a Harmonicare administrator who heads the ethics panel.
    Any medical staff who handled samples that might contain HIV were aware, He said. An embryologist in He's lab, Qin Jinzhou, confirmed to the AP that he did sperm washing and injected the gene editing tool in some of the pregnancy attempts.
    The study participants are not ethicists, He said, but "are as much authorities on what is correct and what is wrong because it's their life on the line."
    "I believe this is going to help the families and their children," He said. If it causes unwanted side effects or harm, "I would feel the same pain as they do and it's going to be my own responsibility."
    ___
    AP Science Writer Christina Larson, AP videographer Emily Wang and AP translator Fu Ting contributed to this report from Beijing and Shenzhen, China.

    Friday, November 23, 2018

    Now, a way to diagnose ovarian cancer early Australian scientists develop a blood test that can

    Down To Earth Magazine

    New blood test can detect ovarian cancer in its early stages

    Medical News Today