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HIV Exploits a Human Cytokine in Semen to Promote Its Own Transmission
A new report suggests that the concentration of one human cytokine, interleukin 7 (IL-7), in the semen of HIV-1-infected men may be a key determinant of the efficiency of HIV-1 transmission to an uninfected female partner. In their study published February 7 in the Open Access journal PLOS Pathogens, a research group from the Eunice Kennedy-Shriver National Institute of Child Health and Human Development (NICHD) led by Leonid Margolis report that the increased IL-7 concentration in semen facilitates HIV transmission to cervical tissue ex vivo.
Semen is a complex biological fluid containing not only spermatozoa but also cytokines, a group of extracellular proteins that modulate immune responses. As a result of HIV infection, the concentrations of various cytokines in semen is profoundly modified, in particular the concentration of interleukin 7 (IL-7) is greatly increased. Despite this evidence of strikingly elevated IL-7 levels in seminal plasma, there was limited knowledge about any effects this cytokine might have on HIV-1 sexual transmission.
To investigate the question about the effects of this increased IL-17 on HIV-1 sexual transmission, Andrea Introini and colleagues from the Margolis lab developed a system of explants of cervico-vaginal tissue that can be maintained outside of the body in culture for up to two weeks while preserving the cytoarchitecture of the tissue. In this system, HIV transmission can be simulated and studied under controlled laboratory conditions. When researchers added IL-7 in concentrations comparable to that found in the semen of HIV-1 infected men, HIV was transmitted more efficiently and replicated to a higher level than without IL-7. Normally, HIV-1-infected cells quickly die as the result of apoptosis, a programmed death triggered by HIV infection. IL-7 inhibits apoptosis of infected cells, allowing them to produce more virus and thus increasing the chances of the incoming virus to disseminate through the tissue. Also, IL-7 stimulates T cell proliferation, thereby also providing to HIV even more potential targets to infect.
The authors speculate that IL-7, together with other cytokines, may determine sexual transmission rates of HIV-1 and that changes in the seminal cytokine load may explain differences in HIV transmission from different individuals. However, whether the effect of IL-7 that has been demonstrated ex vivo occurs also for sexual partners in vivo, is a subject for future research. If this increase does occur in vivo, then it should be investigated whether HIV-1 infected individuals that have been treated systemically with IL-7 in order to increase their T cell counts may have also resulted in the unintended increase of their seminal IL-7 levels. Finally, this study suggests that seminal cytokines may become new targets for HIV-preventive strategies.
Tiny Human Liver Built from a Cocktail of Cells
Tiny human livers grown from stem cells get to work when they are transplanted into mice, cranking out proteins and breaking down drugs that mice normally can't, say scientists in Japan who created the working organs.
The human "liver buds" grew blood vessels and produced proteins such as albumin that are specific to humans.
The researchers further confirmed the livers were working by showing that transplanting a liver into a mouse whose liver was lethally damaged allowed the animal to live longer then expected.
"It's a human liver, functioning in a mouse," said study researcher Takanori Takebe, a stem-cell biologist at Yokohama City University in Japan. He and his colleagues detailed their work in an article published today (July 3) in the journal Nature.
In humans, liver buds form during embryonic development, and are the precursors to the fully formed organ. In their experiments, the researchers grew the buds in dishes, from a cocktail of three cell types including stem cells that were programmed to become liver cells.
“We basically mimicked the early processes of liver bud forming,” Takebe said.
It took two days for the cells in the dish to self-organize into a three-dimensional liver bud. The key reason for the success of this technique was using stem cells together with cells from the umbilical cord and bone marrow, the researchers said. Such cells are involved in the formation of an organ during development.
Putting stem cells together with other cell types has been tried before, the researchers said. However, in previous efforts, the cell mixture was put onto scaffolds that formed the shape of an organ, and the experiments didn't work because the cells failed to attach to the scaffold properly.
Takebe said he was surprised when he saw the liver buds growing in some of the plates. He showed the results to his colleagues, and some of them thought there was some kind of contamination in the petri dish, he said.
This is the first time stem cells have been combined with other elements in a way that lets them move about freely and grow into a three-dimensional structure, the researchers said.
There are a number of challenges to face before such liver buds could be transplanted in humans. The most important next step, Takebe said, is to make a large number of liver buds in vitro, perhaps tens of thousands. “We have to develop an automated culture system able to mass produce liver buds. This takes five to six years,” he said.
Currently, there’s a shortage of donor livers for treating end-stage liver failure. While about 6,000 liver transplants are done every year in the United States, there are more than 16,000 Americans on the waiting list for a liver transplant, according to the American Liver Foundation.
Takebe said it's possible the technique could one day be used with other organs that have a similar course of development, and require complex vascularization, such as the pancreas, lungs and kidneys.
“Now we are trying to apply a self-organizing approach into the pancreas formation, and so far got good results,” he said.
If the liver buds were to one day be tried in humans, it's likely the first patients would be newborns or children with liver damage who otherwise would die without a treatment, the researchers said.
Once in the body, the buds could grow and serve as a permanent replacement, or a temporary graft while a patient's damaged liver recovers.
Scientists "produced" human liver
Japanese scientists succeeded for the first time to "grow" in the laboratory miniature human liver from stem cells, according to the journal Nature, quoted by the BBC.
Researchers from the University of Yokohama have been using reprogrammed stem cells that become the hepatocytes (liver cells).
Scientists transplanted into mice tiny body began to grow and shows no signs of performance.
However biologists warn that the method will have to be further developed, so that the artificial organ can be used to treat patients. Researchers believe that the work of these miniature livers could replace only 30% of the body of the patient, says New York Times.
The liver, however, is known for its high regenerative capacity and therefore the sick who need a new organ is often implanted a small part of it taken from a living donor. This gives hope that the discovery of Japanese scientists could solve the problem of the shortage of organs for transplantation in the future.
Stem-cell transplants may purge HIV
Two men with HIV may have been cured after they received stem-cell transplants to treat the blood cancer lymphoma, their doctors announced today at the International AIDS Society Conference in Kuala Lumpur.
One of the men received stem-cell transplants to replace his blood-cell-producing bone marrow about three years ago, and the other five years ago. Their regimens were similar to one used on Timothy Ray Brown, the 'Berlin patient' who has been living HIV-free for six years and is the only adult to have been declared cured of HIV. Last July, doctors announced that the two men — the ‘Boston patients’ — appeared to be living without detectable levels of HIV in their blood, but they were still taking antiretroviral medications at that time.
Timothy Henrich, an HIV specialist at Brigham and Women’s Hospital in Boston, Massachusetts, who helped to treat the men, says that they have now stopped their antiretroviral treatments with no ill effects. One has been off medication for 15 weeks and the other for seven. Neither has any trace of HIV DNA or RNA in his blood, Henrich says.
If the men stay healthy, they would be the third and fourth patients ever to be cured of HIV, after Brown and a baby in Mississippi who received antiretroviral therapy soon after birth.
But Henrich and Daniel Kuritzkes, a colleague at Brigham who also worked with the men, caution that it is still too early know whether or not the Boston patients have been cured. For that, doctors will need to follow the men closely for at least a year, because the virus may be hiding out in 'reservoirs' — parts of the men’s bodies, such as their brain or gut, that can harbour the virus for decades.
“We’re being very careful not to say that these patients are cured,” Kuritzkes says. “But the findings to date are very encouraging.”
HIV researcher Steven Deeks of the University of California, San Francisco, says that doctors might need to wait at least two years before declaring that a cure has been achieved. “Any evidence that we might be able to cure HIV infection remains a major advance,” Deeks says. But, he adds, “there have been cases of patients who took many weeks off therapy before the virus took off”.
Exciting news
Still, researchers and doctors are excited about the news, especially because the Boston patients’ treatment differed from the Berlin patient’s regimen in one key way. Brown was given stem cells that were predisposed to resist HIV infection, because the donor happened to have a mutated version of a key protein — CCR5 — that is needed for HIV to infect cells. So Brown’s transplant was akin to gene therapy with HIV-resistant cells.
But the Boston patients received stem cells without the protective mutation. The transplanted cells must therefore have been protected from infection by the antiretroviral drugs taken during cancer treatment. Their doctors think that an immune response called graft-versus-host disease — a post-transplant reaction in which donated cells kill off a patient’s own cells — may have then wiped out the patients’ HIV reservoirs, potentially curing the men.
Transplant specialist Christine Durand of Johns Hopkins University School of Medicine in Baltimore, Maryland, says that the case of the Boston patients may show that current antiretroviral drugs are powerful enough, on their own, to protect the transplanted cells. “If cure has been achieved in the Boston patients, then it was the antiretroviral therapy, not gene therapy, that protected the donor cells,” she says.
The finding is very important for people with HIV who also need blood-cell transplants, but the treatment is unlikely to be used more generally because the risks from transplants are high. Durand says that Johns Hopkins is now revising its transplant procedures to keep people with both cancer and HIV on antiretroviral drugs during the transplant regimen.
Separately, the International Maternal Pediatric Adolescent AIDS Clinical Trials (IMPAACT) Group, based in Silver Spring, Maryland, is trying to replicate the Berlin patient’s cure by giving CCR5-mutated HIV-resistant blood from umbilical cords to children and adults with HIV and cancer.
Everyone with HIV could benefit from this work, researchers say, because it could yield valuable information about how to eliminate the HIV reservoir.
“We are still a long way off from a viable cure option for most patients,” Durand says. “But every step counts, and these cases can teach us important lessons.”
Japanese scientists cloned a mouse from blood drop
Scientists in Japan cloned a mouse from a drop of blood. Moving blood cells taken from the tail of the mouse donor were used to create the clone, said researchers from the center Ricken Bioresources. Some time ago the same scientists have created nearly 600 exact genetic copies of a mouse.
Mice were cloned from different sources of donor cells, including white blood cells of the lymph nodes, bone marrow and liver. Japanese researchers studied whether the moving blood cells can be used for cloning. Their goal was to find an easy source of donor cells for cloning valuable scientifically types of laboratory mice.
Scientists led by Atsuo Ogura of Bioresources Rikes center in Tsukuba, blood taken from the tail of a mouse donor, isolated white blood cells and used kernel cloning experiments using the same technique as for the cloning of Dolly the sheep in Edinburgh.
The process, known as somatic cell nuclear transfer involving transfer of the nucleus from a cell in the adult body as blood cells or skin unfertilized egg, which was removed the nucleus. Scientists, whose research was published in the journal Biology of Reproduction, said that it shows for the first time that mice can be cloned using the nucleus of peripheral blood cells.
"These cells can be used to clone immediately after isolation, without requiring euthanasia of donor" complemented researchers.
New Way to Induce Programmed Cell Death, or Apoptosis
Researchers from the Hebrew University of Jerusalem and the Weizmann Institute of Science have developed a technique to cause apoptosis, or programmed cell death, that could lead to new approaches to treating cancer.
Apoptosis is an essential defense mechanism against the spread of abnormal cells such as cancer. It is a complex process that occurs through networks of proteins that interact with each other. Cancer cells usually avoid this process due to mutations in the genes that encode the relevant proteins. The result is that the cancer cells survive and take over while healthy cells die.
The research, by graduate student Chen Hener-Katz at the Hebrew University, involved collaboration between Prof. Assaf Friedler of the Hebrew University's Institute of Chemistry and Prof. Atan Gross of the Weizmann Institute's Department of Biological Regulation. It was published in the Journal of Biological Chemistry under the title ''Molecular Basis of the Interaction between Proapoptotic Truncated BID (tBID) Protein and Mitochondrial Carrier Homologue 2 (MTCH2) Protein.''
The study examined the interaction between two important proteins involved in cell death: mitochondrial carrier homologue 2 (MTCH2), which was discovered in the lab of Prof. Gross, and truncated BID (tBID), which are both involved in the apoptotic process. The researchers found the regions in the two proteins that are responsible for binding to each other, a critical step in initiating apoptosis. Following their discovery, the researchers developed short synthetic protein fragments, or peptides, that mimicked the areas on the proteins that bind to each other, and by doing so inhibited this binding. In lab experiments conducted on cell cultures, this resulted in the death of cancer cells of human origin.
''These protein segments could be the basis of future anti-cancer therapies in cases where the mechanism of natural cell death is not working properly,'' said Prof. Friedler. ''We have just begun to uncover the hidden potential in the interaction between these proteins. This is an important potential target for the development of anticancer drugs that will stimulate apoptosis by interfering with its regulation. ''
Prof. Friedler is the head of the school of chemistry at the Hebrew University. His major research interests are using peptides to study protein-protein interactions in health and disease, and developing peptides as drug leads that modulate these interactions, specifically in relation to HIV and cancer. Prof. Friedler won the prestigious starting grant from the ERC (European Research Council) as well as the outstanding young scientist prize by the Israeli Chemical Society. His research was supported by a grant from the Israel Ministry of Health and by a starting grant from the European Research Council.
Probiotics increasing levels of vitamin D
No need to overdo it with sunbathing to get some much needed vitamin D. According to a new study, the intake of probiotic supplements significantly improved levels of the vitamin in the body by 25%.
This is the first ever evidence that probiotics play an important role in maintaining and strengthening the bones.
Previous studies have established the effect of a specific probiotic strain Lactobacillus reuteri NCIMB 30242, which has a beneficial effect in reducing cholesterol levels, but its effect on the absorption of fat-soluble vitamins, vitamin D is unknown.
Researchers examine health data of a group of middle-aged volunteers who took probiotics for nine weeks.
They analyze the vitamin D levels by monitoring the levels of 25-hydroxyvitamin D in the blood.
The results show that taking probiotics has significantly increased the levels of the vitamin.
This is an important finding since mass is deficient in vitamin D, the researchers explain. Vitamin D deficiency is associated with osteoporosis and rickets in children. Lack of vitamin restricted absorption of calcium from the bones.
Naked mole rats kept secret to cancer treatment
The body of naked mole rat has a unique capacity - develop cancer. A team of scientists led by Professor Vera Gorbunova Faculty of Biology, University of Rochester, New York, managed to find a substance which prevents rodents from the development of cancer cells, according livescience.com. It is called hyaluronan and it locked the secret to treating one of the most feared diseases in humans, is convinced Professor Gorbounova.
Naked mole rat is widespread in East Africa, especially in southern Ethiopia, Somalia and Kenya. Live underground settlements of 70-80 individuals as their societies are headed by the Queen and her male "courtiers", a number between one and three, which alone can fertilize it. Everyone else is kind of staff which, as for example in some bee species are subject to the "division of labor"
Weird looking animals are known for their longevity - they are about ten times longer than other rodents.
Substance hyaluronan serves to sticky cells and tissues. It also has a role in controlling the growth of some types of cells, says Prof. Andrew Seluanov, co-author of the study.
The researchers looked at tissue from mole nude rats. Then found that rodents synthesize a unique form of hyaluronan known as HMW-HA.
When removed this substance from the body of naked mole rats, they develop cancers. This convinced the scientists that it is HMW-HA protects bare naked mole rats in the development of cancer.
People also produce hyaluronan, but in much smaller quantities, said Prof Vera Gorbunova. In the future, the researchers plan to determine whether HMW-HA can effectively protect human cancer cells.
Silver and antibiotics - star duo
Antibiotic resistance - the ability of pathogens to evolve and overcome the antibiotic preparations is about to collide with an unexpected ending. New research allows the silver to deter frighteningly rapid adaptation of microorganisms to the drugs, which the discovery of penicillin has increase exponentially. Currently, data on resistance to accumulate and it proved to be amplified, while the amount of new antibiotics in development or on the market falls.
There are thousands of written information about the healing power of silver. Today there are many homeopathic preparations containing precious metals. According to proponents of homeopathy silver enhances immunity and heals the body. These therapies, however, are unpredictable and sometimes have an effect sometimes - not. What is certain and confirmed, however we offer James Collins, a researcher from the University "Boston" Massachusetts.
His team has discovered how the metal in the form of dissolved ions, damaging bacteria. It makes them more membrane permeable and disrupts intracellular harmony of balance, leading to over-production of highly reactive and toxic oxygen compounds. When using silver solution in relatively small quantities as a supplement to the antibiotic, the scientific team found that the antibiotic kills from 10 to 1,000 times more bacteria. More permeable membranes allow more antibiotics to invade rogue cells, exacerbating the drug repeatedly.
Development of a pill is still in its infancy, as it should be considered the optimal amount of silver - enough to help, not harm. Even in moderate doses, it causes argyria - a disease in which the skin becomes permanent blue color. At higher doses, toxic effects are much more dangerous - mainly damage the cardiovascular system.
Scientists hope to understand the mechanism by which silver affects the cell walls and create a synthetic compound that perform the same functions, without incurring the side effects of the metal.
Genetically Modified Tobacco Plants Produce Antibodies to Treat Rabies
Smoking tobacco might be bad for your health, but a genetically altered version of the plant might provide a relatively inexpensive cure for the deadly rabies virus. In a new research report appearing in The FASEB Journal, scientists produced a monoclonal antibody in transgenic tobacco plants that was shown to neutralize the rabies virus. This new antibody works by preventing the virus from attaching to nerve endings around the bite site and keeps the virus from traveling to the brain.
"Rabies continues to kill many thousands of people throughout the developing world every year and can also affect international travelers," said Leonard Both, M.Sc., a researcher involved in the work from the Hotung Molecular Immunology Unit at St. George's, University of London, in the United Kingdom. "An untreated rabies infection is nearly 100 percent fatal and is usually seen as a death sentence. Producing an inexpensive antibody in transgenic plants opens the prospect of adequate rabies prevention for low-income families in developing countries."
To make this advance, Both and colleagues "humanized" the sequences for the antibody so people could tolerate it. Then, the antibody was produced using transgenic tobacco plants as an inexpensive production platform. The antibody was purified from the plant leaves and characterized with regards to its protein and sugar composition. The antibody was also shown to be active in neutralizing a broad panel of rabies viruses, and the exact antibody docking site on the viral envelope was identified using certain chimeric rabies viruses.
"Although treatable by antibodies if caught in time, rabies is bad news," said Gerald Weissmann, M.D., Editor-in-Chief of The FASEB Journal. "This is especially true for people in the developing world where manufacturing costs lead to treatment shortages. Being able to grow safe, humanized antibodies in genetically modified tobacco should reduce costs to make treatments more accessible, and save more lives."