Health Meaning

Why obesity increases the risk of developing cancer? A new study suggests that the wrong mix of intestinal bacteria may be to blame. The researchers report that the obese mice carry the modified insect intestinal communities, which produce acid damaging DNA which leave mice more susceptible to liver cancer. The results suggest that bacteria help the development of the drive cancer and may eventually help scientists better predict and prevent disease.

Obesity increases the chances of becoming a victim of some types of cancer, including colorectal and liver tumors, but scientists have not been able to identify the mechanism behind this link. They suspected that our gut microbiota, the complex community of trillions of microbes living in our intestines, play a role. After all, the markers of the intestine have been linked to other diseases, including inflammatory bowel disease, allergies, and even heart disease, and are known to vary between thin and obese individuals.

Eiji Hara molecular biologist from the Institute of Cancer at the Japanese Foundation for Cancer Research in Tokyo and colleagues set out to connect the dots between cancer and intestinal microbes by studying the development of cancer in obese and lean mice. They started with two groups of mice: Lean mice that grew up on a normal diet and mice that ate a diet heavy in fat until they were obese. To encourage rodents to develop cancer- "Mice do not smoke or drink alcohol, so they are quite without cancer," Hara said they exposed the animals to a chemical carcinogen shortly after birth.

The mice showed the same link to obesity cancer observed in humans and other animals. Only 5% of lean mice exposed to the carcinogen developed cancer later in life, while all obese mice did. When the researchers repeated the experiment using high mouse to be obese even on a normal diet, they also saw an increased incidence of cancer, suggesting that obesity itself, and not "the animal diet increased their risk of cancer.

obese mice were prone to liver cancer, their tumors showed high concentrations of molecules called pro-inflammatory cytokines which trigger inflammation. the obese mice also had higher levels of deoxycholic acid (DCA), a by-product remaining after certain intestinal microbes break bile acids produced by the liver. DCA damages DNA and has been associated with certain cancers in humans.

to trace the origins of these two signs, the presence of inflammatory cytokines and promoting higher levels of DCA-the researchers scrutinized the entrails of animals. They found that obese mice received a different mix of bacteria. So-called gram-positive bacterial strains, in particular, seemed to thrive in luscious mouse. When Hara and colleagues treated mice with vancomycin, an antibiotic that targets Gram-positive bacteria, the animals showed a reduction in cancer incidence and levels of DCA. Furthermore, by directly reducing the DCA levels of animals (more stimulating the secretion of bile acid or slow distribution of bile acids) also reduces the risk of cancer, and giving them extra DCA increased their risk, reports online today in team Nature .

Together, the results suggest that obesity causes a domino effect causing cancer in which DCA is key, says Hara. Changes gut microbiota, stimulating populations of gut microbes that produce more than DCA. Then, the excess of DCA causes DNA damage and inflammation in the liver, which in turn leads to liver cancer.

"I am very surprised by the process," said Hara. "We did not expect that changes in the gut microbiota could cause increased risk of cancer."

"I think this study is very exciting, "said Peter Turnbaugh, a Harvard University microbiologist who was not involved in the work. "It was a mystery for a while why obesity leads to a higher risk of cancer. They convincingly that the microbial community is involved. "

Turnbaugh notes that more research is needed to show that a similar mechanism is at work in humans. But if it is, the results could pave the way for better methods of prediction and prevention of cancer. Changes DCA levels, for example, could allow doctors to assess the risk of cancer and to take measures for prevention, he said.

"If it is true that the production of this acid leads to cancer, there may be ways to inhibit production by manipulating microbial communities of diet or fine tuning people," says Turnbaugh. "But there is certainly much more to learn first."

In a setback vaccine against cancer, the pharmaceutical giant GlaxoSmithKline (GSK) announced yesterday that it had immunotherapy was tested in a trial phase III flopped. The company holds hope, however, that some patients with a certain genetic signature will always be helped, and the trial continues.

The treatment "did not prolong disease-free survival significantly compared with placebo ..." in volunteers with melanoma, the London-based company, said bluntly in a statement Press. Called MAGE-A3, the vaccine targets the same name proteins that are expressed on tumor cells in a subset of patients. It is supposed to stimulate the immune system to destroy the cells.

The likely problem with MAGE-A3 is one that a myriad of other vaccines against cancer has not been able to overcome, said Steven Rosenberg, a immunotherapist and head of the branch of surgery the National cancer Institute in Bethesda, Maryland: He could not prevent immune reactions that hinder the vaccine's ability to mount a successful attack on tumors. "I thought there was a very small chance that MAGE vaccine would have an impact," Rosenberg said, "because no vaccine as it was effective."

GSK scientists -A it with others, have tried hard to predict exactly who could respond to immune therapies such as MAGE-A3 and other treatments against cancer in general. in July, the company's researchers and academic collaborators published an article in the Journal of Clinical Oncology identification of 84 gene "signature" that seemed to correlate with the way people with metastatic melanoma responded to therapy. Now, said the spokesman for GSK Melinda Stubbee, the company will test some variation of this signature I in the ongoing melanoma trial, which includes 1345 people. a data safety monitoring board is to allow the study to continue while it tested.

GSK also has an essay on Cancer III lung in phase with MAGE-A3 and plans to present these results next year. In a presentation to analysts and investors in late July, CEO of GSK Andrew Witty, described MAGE-A3 as he continued "high-risk, but potentially high rewards". "I'm not naive, I am completely open to the possibility that these programs fail. "

a genetic variant that increases the risk of testicular cancer may be favored by evolution because it helps protect people with fair skin against the harmful ultraviolet rays of the sun, according to a new study. The finding could explain the white men are more sensitive than black men with this type of cancer. It may also explain why testicular cancer is so easily treatable.

Gareth Bond, a molecular biologist at the Ludwig Institute for Cancer Research in Oxford, UK, and his colleagues hit on the unexpected compromise in the study of hereditary genes that influence cancer risk. They were particularly interested in a gene called p53, which is mutated in more than half of all cancers. The protein produced by this gene is a key defense for the action cell on a wide range of other genes to protect against many kinds of stress, including DNA damage and oxygen deprivation. It also protects against cancer, saying severely damaged cells to commit suicide. Mutations in p53, or other genes with which it acts, prevent the order being received, and damaged cells continue to reproduce, forming tumors.

Because cancers involving p53 are so common, Bond and his colleagues suspected that inherited mutations in the gene, or genes it activates, could affect cancer risk. But these inherited mutations are hard to find because they are usually eliminated during evolution, he said. In fact, we do not know why they should persist at all.

In the new study, Bond and his colleagues were looking in the p53 target genes for mutations who had managed to hang on. First, they pored through genetic dredges previously published, looking for DNA changes in which a single building block or nucleotide is substituted for another. These variants, called single nucleotide polymorphisms (SNPs, "shears" pronounced) is the way in which changes in traits such as hair and eye color, as well as many diseases are often passed on to future generations.

The researchers first verified the published databases for SNPs in the human genome that are known to be associated with a cancer-about 60,000 possibilities. To see if any of these lay in genetic sequences where acts of p53 protein, the researchers used data from several lines of healthy and cancerous cells subjected to various p53-activated treatments. This tour led to 86 SNPs linked to cancer and as "living" in regions where p53 tie. Finally, research, today announced online in Cell reduced to a SNP in a DNA sequence strongly bound p53 . The sequence is a switch to a protein known kit ligand (KITLG); Previous studies have linked three SNPs in this region with testicular cancer.

So why has this mutation causing cancer stuck around? An analysis of the evolution showed the SNP had become more common, not less, humans have migrated north of Africa: It is found in 80% of white Europeans, but in only 24% people of African descent. Probably not coincidentally, testicular cancer is four to five times more common in white men than in black men.

One way apparently deleterious mutation can become common over time in a group of people is if it also has an advantage that outweighs the bad, says co-author Douglas Bell, biologist molecular to the National Institute of environmental health sciences in Research Triangle Park, North Carolina. The advantage, the researchers suggest, is that in normal circumstances, protects KITLG pale skin against sun damage. Previous research, some of them by members of the current team, showed that KITLG triggers the production of pigment-producing cells called melanocytes in response to UV light. But work has not connected the dots between p53, the target DNA sequence, enabling KITLG, and production of melanocytes.

In the new study, the Bond team exposed mice and normal mice missing p53 to UV radiation. Normal mice produced more than four times that melanocytes made the p53 mice "knockout". In normal mice, the UV treatment doubled the amount of KITLG product, while p53 KO could not produce any. The results clearly show that active KITLG UV damage to trigger the production of melanocytes, and that the process depends on p53, the authors say. The study covered the variant increases the degree to which its active p53 target gene to stimulate the production of cells. But it also raises the risk that malignant testicular cells-cells, in this case could be produced inappropriately.

"Of all the SNPs associated with cancer, this is the only indicated in response to p53," said Guillermina Lozano, a geneticist at the University of Texas MD Anderson Cancer Center in Houston who was not affiliated in the study. She adds that although the individual components of this pathway by stimulating cells were known, this study is the first to connect the whole process.

the authors say that the study could also explain high cure testicular cancer rates almost 100% if the disease has not spread, and up to 0%, although it has. (the cyclist Lance Armstrong has been cured even after the cancer had spread his brain.) most of chemotherapy work by damaging the DNA of cancer cells divide rapidly, trying to wake p53 to give the command to commit suicide. When they do not work, it is often because the cancer has found a way to paralyze p53. testicular cancer, however, is an unintended consequence of the ability of p53 to stimulate, not call off the production cells. Because the protein is already working well in this context, its stop-capacity growth in other, more frequent unwanted cells can also be easier to exploit, the researchers suggest.

"As early humans migrated north on Africa, loss of pigmentation of the skin allowed them to retain more vitamin D in the dimly lit ground. But those who were better able to repair UV damage had an advantage, "says Bell.

The increased risk of testicular cancer may have been an evolutionary compromise acceptable because the disease only affects men and occurs usually after they have had a chance to reproduce. Bond added: "For our ancestors, protection against sun damage is essential to survival. For example, poor combustion may violate the protective barrier of the skin against infection, and our ancestors were no antibiotics. "

jet lag, shift work, and even evenings watching your tablet or smartphone can be taken from you 're sick. Indeed, the body's internal clock is set to two periods of light and darkness to 12 hours, and when this rate is broken, so that the immune system. One reason may be that the genes that define the body clock are intimately related to certain immune cells, according to a new study.

The discovery "was a happy accident," says Lora Hooper, an immunologist at the University of Texas Southwestern Medical Center in Dallas. She and her colleagues studied NFIL3, a protein that guides the development of certain system cells immune and turns on the activity of others. the gene encoding this protein is mutated in some human patients with inflammatory bowel disease, and mice lacking the gene NFIL3, the team found, had more so-called T _H 17 cells in their intestines.

These cells are a type of immune cell known as a T cell. they derive their name a signal they produce, called interleukin 17, which points to other T cells to increase the immune response. in normal numbers, T _H 17 cells, which live in the intestines, helping the body fight against bacterial and fungal infections. But when there are too many, the immune defense begins to cause the disease rather than prevent it. Stimulate NFIL3 levels in T cells growing in laboratory cultures resulted in fewer transform T _H 17 cells, the researchers found, suggesting that the work of the protein is prevent T cells from entering this area of ​​specialization. The absence of the protein, the team concluded, led to runaway T _H 17 activity.

At this point, researchers had no reason to suspect a connection System- internal timing of our body also known as our circadian clock that responds to daily cycles of light and darkness . But as they continued to explore the link between NFIL3 and T _H 17 cells, they found that some of the proteins produced by the "clock genes" of the body attach to genes NFIL3. In addition, cultured cells and mice whose clock genes have been experimentally produced tampered least T _H 17 cells. researchers hypothesize that a key protein in the clock network binds to the gene NFIL3 to maintain the production of T _H 17 cells synchronized with periods of light and darkness. and the team found that normal mice produce less NFIL3 and therefore more T _H 17 cells during the day and night.

in a final experiment, the researchers gave the offset jet mouse. "We did not steal everywhere, "Hooper jokes. instead of this, the team shifted light / dark cycles of 6 hours rodents every 4 days. "It would be like stealing the United States to Europe, India and Japan and spent 4 days in each country," she explains. Mice with altered light cycles were almost twice as T _H 17 cells in their spleens and intestines, compared with mice having a normal day, reports online today in Science of team. Mice schedule also mounted offset a stronger inflammatory response to irritation by chemical of an experimental test used to measure the sensitivity of the immune system which refers to animals may be more prone to inflammatory disease.

The finding adds to a body of research shows that a healthy pattern of light and darkness, sleep and waking, is essential for maintaining the immune system in balance more and more, says Hooper. It notes that inflammation is the basis of many chronic diseases, like heart disease, asthma, chronic pain, and many things ending in "-itis" as bursitis and dermatitis. Inflammatory conditions are more prevalent in developed countries, where circadian rhythms of people are chronically disturbed. Even people who do not work shifts or cross areas still wake schedules and sleep with shift light and darkness, Hooper said. "We all messed light cycles. We stay late, keep the lights on, look at our iPhones illuminated at 2 am"

Immunologist Dan Littman of New York University in New York found the results in cultured cells convincing. He cautions, however, that the carefully defined way of clock gene in T _H 17 deletion may not be so tidy in a living animal. "Although NFIL3 is involved in how they show circadian disruption affects many other things." Stress hormones, bacteria of the intestine, and the actions of other types of T cells may also explain effects of experimental jet lag, he said.

Littman also notes that increased inflammation in animals jetlag was a response to an induced chemical irritation, and more research is needed to prove a link to an inflammatory disease or autoimmune disease.

Hooper agreed that this study is probably the tip of the iceberg, and more research will give deeper insight into the relationship between immune cells circadian rhythms. It hopes to collaborate with other researchers to determine whether T _H 17 cells are increased in men with chronically altered light cycles. for now, she said, she tries to keep his own habits sleep longer aligned with nature, starting by limiting exposure to artificial light at night. "I turn off the lights, I draw the curtains, and I keep my iPhone off."

After 4 decades of vetting clinical trials of gene therapy for new risks, it is time to relax a bit, according to a report released today by a group of experts. But senior government officials welcomed the recommendation with caution.

Gene therapy has proved its worth and its leaders have managed the ethical issues, according to a panel convened by the Institute of Medicine (IOM) to the US National Academies. The long-term risks of gene therapy may not be clear yet, but the general risks seem no more than in other areas of experimental medicine, the report says, it is time to eliminate the American outfit created in 1974 which is dedicated to examining gene therapy, recombinant DNA Advisory Committee, or RAC.

"[M] no initial fears about gene transfer" -like concerns about the creation of new pathogens, modification of the human germ line, or hurt the company in other ways- "has not been confirmed," the panel concludes IOM. at the same time, he notes that "public perception has largely transition from negative to positive" thanks to the success of gene therapy in the treatment disorders such as hereditary blindness and hemophilia. The Committee urges the National Institutes of Health (NIH), home to the RAC and uses his advice, stop having RAC examining individual gene therapy protocols.

The report covers IOM This recommendation, however. While the former RAC should go out of business, the panel said, another RAC-like body should take his place, and with a broader mandate to consider all clinical research forms at risk than other organizations can not be able to adequately veterinarian. The IOM group also urges the government of the United States to maintain RAC will until a successor is created. During the transition, the IOM report said RAC examinations should be streamlined to make life easier for researchers and individual protocols should be considered only "in exceptional circumstances, for example where technology innovative gene therapy and treatment strategies to move forward in the field of clinical trials. "

gene therapists have long complained about the burden of RAC exams. Like other clinical researchers, they must get approval for the ethics of testing and biosecurity panels to their own institutions; they also have clear clinical trials in advance with the US Food and Drug Administration (FDA). But gene therapists have an additional duty to other researchers do not have: They must submit a detailed description of the proposed experiences with RAC. Unlike the FDA, RAC releases these proposals and may hold a public hearing before approving them a trial. Last year, the leading professional society of gene therapists issued a public call to end dual examination of the CARs. NIH asked IOM to address this issue, and today's report is the result of the application of the NIH.

The chair of the IOM panel, Lawrence Gostin, professor of public health and law at Georgetown University in Washington, DC, said he was well aware of the misfortune of gene therapists on multiple critical. Dismay "came loud and clear," during the public consultation sessions, Gostin said. The panel report IOM says that most gene therapy trials should now be reviewed by the FDA, it also recommends that the proposed gene therapy trials continue to be recorded in a record. But researchers should be required to file a single protocol, one prepared for review by the FDA. It seemed "prudent" to keep the tradition of free access to information in this area, said Gostin. RAC served an "extremely useful purpose," Gostin said, reassuring the public about the safety of this new field and once disturbing and aggregating the data each is precious, especially clinicians.

NIH Director Francis Collins, after being informed of the IOM report, issued a non-binding statement today to thank the panel for its work and said that NIH "will take a look closely the conclusions and recommendations and the study will determine the best way forward in light of our common interest to do what is best for patients and for the continued progress in the field. "American Society of Gene & Cell Therapy in a statement equally cautious, said today that he" welcomes "Collins" review and make decisions based on the results of the IOM. "

BEIJING Another new strain of bird flu has made the jump from birds to humans. But virologists believe that the deceased patient is likely to have been an isolated case

The November 30, a woman of 73 years originally from Jiangxi province in southern China has been hospitalized with symptoms of pneumonialike serious. she succumbed to respiratory failure, 6 December. A few days later, Chinese authorities notified the World Health Organization (WHO) doctors had isolated the H10N8 virus from the patient's blood. Although H10 virus arose occasionally in people, this is the first human infection known H10N8, said Malik Peiris, a virologist at Hong Kong University.

influenza experts are not hitting the panic button. For starters, they are not convinced that H10N8 was the main cause of death of women. She was a cancer patient whose thymus has been removed. The thymus produces T cells that help fight infections. "Her immune system was already seriously compromised," said George Gao, deputy general manager of the Chinese Center for Disease Control and Prevention (China CDC) here. "There is still no evidence that [virus] is direct cause of death. " For this reason, Peiris said, "I do not think this necessarily means that we will see many more cases" H10N8 may eventually follow a similar pattern to other newly emerging strain, H6N1 has been detected in May.. Taiwan, a woman who recovered after antiviral therapy. Since then, no other H6N1 human infection have been reported.

However, public health officials are taking no chances with H10N8. China CDC advised Jiangxi authorities to temporarily close a live poultry market where it is believed the woman to have contracted H10N8. and scientists are now probing the genome of H10N8 for "any unusual characteristics, and how it is similar to H7N9 "says Peiris. H7N9 is considered a serious threat: This strain has infected 143 people and killed 45 since its release in southern China in March. Four of these cases were reported during the past month. "The more cases there are, the more chances there are for the virus to adapt to human transmission," Peiris said. "This is the main concern."

WASHINGTON, DC With human cases of avian influenza H7N9 stacking, the Chinese authorities have ordered the closure of markets live poultry in three cities in the east in an attempt to stem the spread of the virus. So far, the Chinese Center for Control and Prevention (China CDC) indicates that it has not detected sustained transmission from human to human virus. But experts see no reason to breathe easy. If H7N9 were to acquire the ability to spread, warns Chen Hualan, director of the National Reference Laboratory for avian influenza in Harbin, China, "it will be a disaster."

So far in January, there have been 105 confirmed human cases, according to the Chinese CDC, compared to 144 in all of 2013 after the virus emerged in China last February . Scientists agree that the wearing of the H7N9 poultry, and some suspect that quail can be the main tank. But confused monitoring, the virus does not cause noticeable symptoms in poultry. While some human infections are mild, Chen noted, the mortality rate was nearly 30% of hospitalized cases in 2013. The death rate has tapered and 2014 event is running about 20%, according to the Chinese CDC.

the time of the slight increase in cases is alarming: tens of millions of Chinese are about to embark on an annual migration to their hometowns to celebrate the Lunar New Year, a holiday of a week starting from January 31. As a preventive measure, the Zhejiang provincial authorities ordered the immediate closure of all live poultry markets in the cities of Hangzhou, Ningbo and Jinhua, according to state news agency Xinhua. Hangzhou officials would step up checks at poultry farms and try to stop "the flight of pigeons." Shanghai, meanwhile, plans to close its live poultry markets from January 31 to April 30.

the situation is dangerous, warns Chen, who spoke here today at the American Society for Biodefense Research Meeting and emerging microbiological diseases. His team and others reported last year that some H7N9 strains can be transmitted by airborne droplets from infected to naïve ferrets, an animal used to model the spread of influenza in humans. "I'm pretty sure it was human to human transmission in Zhejiang," Chen said the meeting. She said afterward to Science Insider she was referring to reports of three people infected from the same family in Zhejiang.

Other researchers point out that the human transmission of evidence to man is tenuous. "There are some family clusters" in which investigators could not rule out limited human to human transmission, said George Gao, director of Key Laboratory of Pathogenic Microbiology and Immunology at the Chinese Academy of Sciences in Beijing. But the exposure to live poultry in these families could not be ruled out either, he said. "it's too early to say anything for the moment," he said.

the H7N9 pandemic could . be dark indeed the high mortality rate is a major concern; another is that H7N9 presents a formidable challenge to vaccinemakers the virus is stealthier than other flu strains, "able to evade the cellular immune response. human humoral, "reported a team led by Anne de Groot of the University of Rhode Island, Providence, in the May 2013 issue human Vaccines & immunotherapies .

" We will continue watching "signs of human transmission in sustainable human, Gao said," and a look of almost all cases. "

Platelets are the sandbags of the circulatory system, accumulate in the wounds to create clots and minimize bleeding. Now, researchers in Japan have shown that they can produce large quantities of human platelets starting with the stem cells. Scaled up, the technique could provide a reliable source of replacement pads for patients

Platelets are the cells. they are fragments of bone marrow cells called megakaryocytes. patients and those suffering from diseases such as aplastic anemia cancer often do not produce enough of the blood-clotters, so they may require additional infusions, sometimes more than once a week. Platelets gleaned from blood donations are the source of these transfusions, but they have several drawbacks that have stimulated researchers to seek alternative. Because the fragments of cells can not be refrigerated, low temperatures damage-their life is only a few days, weeks against the red blood cells and platelets are more likely to be contaminated with dangerous bacteria. Denisa Wagner vascular biologist at Harvard Medical School in Boston highlights another motivation to identify new sources of platelets: the aging of the world population. Older people are more likely to need transfusions because they naturally produce fewer platelets, she notes.

In recent years, two teams reported having high human megakaryocytes and platelets from embryonic stem cells, called induced pluripotent stem cells (iPS) cells, adult cells returned to stem cells. However, neither technical provide enough platelets for transfusion. To increase efficiency, Koji Eto of Kyoto University in Japan, who led one of the teams, and colleagues have refined their recipe. By prodding human iPS cells and embryonic stem cells with drugs, they cranked the activity of three genes that prompt cells to divide and prevent them from committing suicide. This step resulted in megakaryocyte precursors, cells that can give rise to megakaryocytes. The team found that megakaryocytes precursors could survive and continue to divide in culture for more than five months, even after being frozen and thawed.

When the researchers switched off the three genes in removing drugs, cells matured into megakaryocytes and platelets started pumping. online today Cell Stem Cell , Eto and colleagues estimated that within 5 days of the method could produce enough platelets for transfusion. To test the platelets clotting capacity, researchers injected into mice who had blood vessel injury. The clots formed lab made pads in animals, the researchers showed.

To use this strategy medically Eto provides that megakaryocytes precursors were stored frozen. If necessary, they can be thawed and coaxed to specialize in wafer makers. Although megakaryocytes induced by the team are not as productive as those in the bone marrow, the growth of cells on a large scale could compensate for this inefficiency and allow the generation of large quantities of chips, he added. Eto said he plans to start clinical trials to laboratory wafers produced in 2 or 3 years.

Other researchers agree that this study brings closer field goal to derive usable platelets from stem cells. "I'm very impressed," said Nicolas Pineault stem cell biologist Canadian Blood Services in Ottawa. "I think it's very close" to be convenient for humans, said Wagner.

The quality of laboratory pads fact could be a stumbling block, however. for example, they are not as sticky as platelets born in the bone marrow, which may limit their clotting ability. "this is good chips, but they platelets are not excellent, "said Pineault. Researchers still have much work to do before that laboratory cultured platelets can replace those derived from donor says hematologist Poncz Mortimer of the University of Pennsylvania Perelman School of Medicine. "Are we still here? No. "

molecular geneticist Benjamin Kile of the Walter and Eliza Hall Institute of Medical Research in Australia recognized that many questions remain on laboratory plates made, including their ability to coagulation and lifespan in humans. But he said Eto and colleagues have the merit of showing that it is possible to produce large quantities of cell fragments. "you can not do clinical trials until you have managed to grow enough pads, "he said.

When we speak of the human microbiome, bacteria generally get all the press. But fungi live in and on us, too. New research shows that a little-known fungus called Pichia lives in the mouth healthy and can play an important role in protecting us against infection by the harmful fungus Candida . The friendly fungus makes a substance that can even lead to a new antifungal drug.

Most of the time, Candida is a peaceful passenger who lives with other harmless bacteria in our mouth, but when the immune system of a person is affected, the fungus can crack, what causes a yeast infection in the mouth known as thrush name. This infection is common in people living with HIV, where it can make swallowing difficult and contribute to poor nutrition. Any difference in microbiomes mouth of people living with HIV and those without the virus could give scientists clues about how a healthy population of oral microbes can help keep Candida in check, said medical mycologist Mahmoud Ghannoum of Case Western Reserve University in Cleveland, Ohio. "If you have a disturbance in the community, you're likely to have a disease."

So the group Ghannoum compared the microbes, both bacterial and fungal, in the mouths of 12 people living with HIV and 12 healthy controls. One hypothesis is that bacteria keep fungi in check, but the team Ghannoum found no major differences between the bacterial populations in both groups. Mushrooms, however, were another story: healthy people have more species of fungi in their mouth, and a particular fungus stand out as a possible competitor of Candida . His name is Pichia .

Mouths where many Pichia has lived tended to have lower levels of Candida Ghannoum team found. If a lack of Pichia fails to keep Candida in check in people living with HIV, which could help explain why they are more susceptible to thrush. To confirm that Pichia is killing Candida and not the reverse, the researchers studied the fungal rivalry by mixing the cultures of the two microbes in the laboratory. When the two were incubated together Pichia flourished and Candida withered.

Researchers suspected Pichia was the production of a chemical that has poisoned Candida , so they filtered fungal cells Pichia cultures. The chemical soup out remains to be a powerful antifungal, interfering with The growth of Candida and its ability to form biofilms sticky mat. When administered to mice with Candida infections, Pichia concoction -produced killed Candida their language , researchers reported online this week in PLoS Pathogens . The Pichia Treatment with the same outperformed the standard treatment for thrush, an antifungal called Nystatin.

"The other fascinating thing is that it is able to inhibit another fungus that causes the disease," said Ghannoum, including Aspergillus and Fusarium . This means that the Pichia -derived promising solution as a broad-spectrum antifungal. Ghannoum also provides a live containing mouthwash Pichia which could be used as a probiotic by HIV patients or other people at risk Candida infection.

"This is a tremendous advance in the field," says Anna-Dongari Bagtzoglou, an oral microbiologist at the University of Connecticut Health Center in Farmington. Besides being the first study of fungal microbiome in people living with HIV, it is also the first study to compare bacterial and fungal populations in the same patients, she said. "These correlations are important because for many years we thought that the two kingdoms were competing," she said, adding that research from his laboratory showed that some bacteria can even combine with Candida to more serious infections.

Although Pichia inhibits clearly Candida in the laboratory, more work is needed to tell if a lack of Pichia is the reason HIV patients are at a higher risk for thrush. the greatest mystery in the field of microbiome is whether microbial changes are a cause or a problem of effect with the immune system, said Dongari-Bagtzoglou. "It is a chicken or the egg question."

Entamoeba histolytica is a small pathogen that takes a terrible toll. The parasite unicellular amoeba about a tenth of the size of a dust mite infects 50 million people worldwide and kills as many as 100,000 each year. Now, a new report reveals how the microbe proved its fatal damage: eating live cells, piece by piece. The discovery provides a potential target for new drugs to treat E. histolytica infections, and transforms the understanding of the researchers how parasites work.

"This process of whittling cells went undetected by all in this area, including me, for over a hundred years," says infectious disease specialist William Petri University of Virginia in Charlottesville, a co-author who has studied E. histolytica for more than two decades.

Although scientists have studied E. histolytica for over a century many of the parasite remains a mystery. part of the problem is that it behaves unpredictably. many infected people have no symptoms at all-amoeba lives quietly in their gut, feeding on bacteria without cause trouble. But in others the parasite attacks the intestine itself and may cause life-threatening diarrhea, ulcers of the intestine, and liver abscesses. This disease called amoebiasis, is a major cause of parasitic death in humans. Common in parts of the developing world, including Africa, Latin America and South Asia, it is transmitted through food and water contaminated. But researchers knew only bits of how the disease plays in the intestine. They knew, for example, that the amoeba has only killed cells with which he had direct contact, and it binds to these cells using specific sugars, called lectins.

"We thought they somehow caused the death of cells and parasites eat the dead cells," says microbiologist Katherine Ralston of the University of Virginia. Because amoebas are known to feed by phagocytosis, a process in which an engulfing cell and "eats" other researchers have speculated amoeba ingested dead cells together.

But Ralston wondered if new live microscopy techniques that allow scientists to capture video cells in action, could be more. Working with Petri and colleagues at the University of Virginia and Jawaharlal Nehru University in New Delhi, Ralston has parasitic amoeba and human cells that have fluorescent made so they would be easier to locate in a dish and examined their interaction. what saw the team surprised.

"It is remarkable to see the amoeba taking bites, "Ralston said. Within a minute of contact, the parasites were torn and ingestion of fragments of human cells, which were visible as bits of fluorescent material in the ameba. The bite was like trogocytosis, a process in which immune cells extract bits of other immune cells, but was unique in that it took place between a parasite and its host and eventually cause cell death. Once the amoeba took his first bite, he continued to consume more and more of the cell until the cell is dead about 10 minutes later.

"A little nibbling caused more snacking," says Ralston, "and this was happening when human cells were alive."

When the cells were dead, amoeba arrested snacking, detached cells, and is past. human red blood cells have the same gruesome end. (See video-human cell appears in pink, green amoeba.) the team then repeated the experiment with fabric intestinal live from mice engineered to have fluorescent intestinal cells and found the parasites have invaded the tissue and caused damage similar to that seen in samples of E. histolytica infected colon tissue human.

the researchers could not be sure that snacking was actually caused the death of cells, however, so they used a drug that interferes with the ability of the amoeba to remodel to bite observe its effect on cell death. Drug amoeba hampered nibbled less and did not kill the cells. Nor amoebas the GM team, so they could not produce the proteins and lectins often found where the parasites come into contact with human cells.

Together, the results suggest that this fragmentary snacking causes cell death and damage often seen in E. histolytica 'of the suite, and that lectins can induce or regulate the behavior of bite, reports the online team today Nature . If further studies confirm that E. histolytica actually kills cells in this way in people suffering from amoebiasis, Ralston said, they could open the way to new treatments for the disease. "If we could understand how the amoeba takes a bite, it would be a good target for therapeutic drugs."

The discovery of the team could change the game E. histolytica research, said Upi Singh, a physician and infectious disease researcher at Stanford University in California who was not involved in the study. "It is fantastic for the area to have a study of this caliber come, "she said." This changes the paradigm. "