Women's immune genes are regulated differently to men's, study finds

a happy Couple

Researchers have found that there’s a big difference between the way that immune system genes are switched off and on in females and the way they’re regulated in males, and it seems to be environmental factors, not DNA, that’s driving the variation. The discovery could help explain why women are so much more susceptible to autoimmune conditions such as lupus and rheumatoid arthritis than men.

Even though our genetic code contains lots of different genes, not all of these are ‘active’ all the time. “Some genes are virtually always on, like the clock light on a microwave; others sit unused for years at a time, like some regrettable appliance you bought, stuffed into the back of the closet and forgot. Some genes can be always on in one person and always off in another,” Jennie Dusheck wrote in a release for Stanford University in the US, where the research was conducted.

The study used a new technique called ATAC-seq, which for the first time ever provides scientists with the ability to study the molecules that regulate all that gene switching on and off. And it revealed that the process varies vastly between individuals – particularly between males and females.

“We were interested in exploring the landscape of gene regulation directly from live people and look at differences,” lead researcher Howard Chang told Dusheck. “We asked, ‘How different or similar are people?’ This is different from asking if they have the same genes.”

To work this out, they tested the blood of 12 healthy volunteers, and looked at the expression of 500 genes in immune cells called T cells. They found that 7 percent of the T-cell genes were switched on in different patterns from person to person. And these patterns persisted over time, forming a ‘fingerprint’ that was unique to each person. 

But even though there were differences between all individuals, “the single greatest predictor for genes’ tendency to turn on and off was the sex of the person,” said Chang. “In terms of significance, sex was far more important than all the other things we looked at, perhaps even combined.”

They also found that more than a third of the differences in gene expression patterns between individuals couldn’t be explained by genetics, suggesting that they’re caused by environmental factors such as diet or stress levels instead. This could explain why one twin can have an autoimmune condition, which causes someone’s immune system to attack their own cells, while their identical twin can be healthy.

The goal of the study was to use the new technique to find the baseline difference between healthy people’s gene expression patterns, so that in future researchers will be able to compare healthy people to those who are unwell.

It’s still very early days for this type of research, but in the future, by better understanding how and why certain genes are switched on and off, we could find new treatment pathways for a range of diseases.

Maybe it could also explain why the man flu is so much worse than the regular flu. The results have been published in the journal Cell Systems.



This article was originally published on PNAS.  Read the original article.

Cell transplant 'regenerates' liver


Transplanting cells into livers has the potential to completely regenerate them, say scientists.

The Medical Research Council team showed severely damaged organs in mice could be restored to near-normal function.

They say the findings, published in Nature Cell Biology, could eventually help people stuck on a waiting list for a transplant.

Further tests are now taking place with human tissue.

The liver does have a remarkable ability to heal itself. Even if half of the organ is removed, it can grow back.

The team, based at the University of Edinburgh, has been investigating the regenerative potential of the liver.

Normally, the main type of cell in the liver – hepatocytes – is able to restore the organ.

But one of the researchers, Prof Stuart Forbes, said: “The hepatocytes normally divide beautifully, but eventually they give up that ability to keep dividing, they become senescent, and that is something we see in all forms of severe liver injury.”


So the Edinburgh team turned to a closely related group of stem cells from the biliary duct.

Injecting these cells into damaged mouse livers led to near compete regeneration.

Prof Forbes added: “The big aim would be to develop a clinically applicable cell therapy for patients with severe liver failure where transplantation is not an option.”

The team say tissue from livers unsuitable for transplant could be a source of these cells.

However, Prof Forbes said liver transplants would remain the main option for patients and encouraged people to join the donor register.

Further studies will now focus on repeating the results with human tissue.

Dr Rob Buckle, the director of science programmes at the Medical Research Council, said: “This research has the potential to revolutionise patient care by finding ways of co-opting the body’s own resources to repair or replace damaged or diseased tissue.”



This article was originally published on Nature.  Read the original article.

No One Is Denying a "Right to Know What's in My Food"

lead in food

On Thursday, the U.S. House of Representatives passed a bill that would ban states from requiring special labels for all “genetically modified” foods. Known as the Safe and Accurate Food Labeling Act of 2015, it advanced by a vote of 275 to 150.

A deeply concerned contingent of detractors, meanwhile, calls it the Denying Americans the Right to Know Act. Which sounds much worse. And it accurately recapitulates the case for mandatory labeling, which consistently returns to the argument that people have a “right to know what’s in their food.”

“What’s the problem with letting consumers know what they are buying?” arguedPeter Welch, a Democratic representative from Vermont, one of three states that has already passed mandatory “GMO labeling” laws.

Who doesn’t want to know what’s in their food? As pro-rights arguments go, that sounds pretty airtight.

Except that the act doesn’t deny people that right. Nothing will stop food manufacturers who avoid “genetically modified” ingredients from labeling and marketing their products accordingly. People who object to genetic modification—either because of concerns about the prudence of introducing certain crops into certain ecosystems, or because of patent laws and corporate business practices, or because these people are among the majority of Americans who now believe any and all “genetically modified” foods to be inherently unhealthful to consume (despite assurances to the contrary from The World Health Organization, Food and Drug Administration, American Medical Association, National Academy of Sciences, and American Association for the Advancement of Science, among others)—can continue to pay premiums for products that are marketed as “GMO free,” which implies health and safety, even while the implication is without merit. Some go so far as to call it fraud.

The central and debilitating fallacy of the “right to know” argument is the meaninglessness and misleading nature of what is being known. Humans have been practicing bioengineering for centuries with selective breeding and cultivation. The Non-GMO Project defines “genetically modified organisms” as those “artificially manipulated in a laboratory” as opposed to “traditional cross-breeding methods,” wherein a laboratory is the nidus of transgression. It was only as recently as 1979 that Gallatin Valley Seed won the All American Selection Award for creating a variety of pea known as sugar snap, which is now ubiquitous, but carries no Franken-crop warning label. Indeed, most any act of agriculture could be considered an imposition of “unnatural” human activity into malleable, unassuming ecosystems. The domain of bioengineering is too vast and complex to know what exactly to make of blanket “GMO” labels; the hopeful premise that this is a binary indicator of good or evil is false. Should I have the “right to know” if my food contains ghosts?

Long-term effects of introducing certain crops into certain ecosystems, and the business practices with which they are grown and sold, are enormously important and remain to be seen and carefully considered. Some effects of agriculture will be desirable, some untoward, and effects of both kinds will come from crops that run the gamut of what has been “modified” by human intervention, and to what degree. But “GMO-free” does not mean fair trade, and it does not mean sustainable, and it does not mean monoculture-averting, and it does not mean rainforest-enabling, and it does not mean labor-friendly, and it does not mean healthy, though it puffs its chest and carries itself alongside those claims. Activists march with signs that say “I AM NOT AN EXPERIMENT.” But the state of having 7 billion food-consuming humans on this planet—6 billion more than there were two centuries ago—is an unprecedented experiment.

It’s because of this meaninglessness, and fear perpetuated by a “natural” food industry, that a right to know is in this case a right to be misled. And this act continues to give food companies the right to tout and sell “GMO-free” as some halo of wholesome virtue, which would be lovely and elegant if it meant progress toward sustainably feeding the world healthful food, but it does not.



Younger Adults With Alzheimer's Are Key To Drug Search

tal and giedre

The face of Alzheimer’s isn’t always old. Sometimes it belongs to someone like Giedre Cohen, who is 37, yet struggles to remember her own name.

Until about a year ago, Giedre was a “young, healthy, beautiful” woman just starting her life, says her husband, Tal Cohen, a real estate developer in Los Angeles. Now, he says, “her mind is slowly wasting away.”

People like Giedre have a rare gene mutation that causes symptoms of Alzheimer’s to appear before they turn 60.

Until recently, people who inherited this gene had no hope of avoiding dementia and an early death. Now there is a glimmer of hope, thanks to a project called DIAN TUthat is allowing them to take part in a study of experimental Alzheimer’s drugs.

The project also could have a huge payoff for society, says Dr. Randall Bateman, a professor of neurology at Washington University in St. Louis. “It’s highly likely,” he says, that the first drug able to prevent or delay Alzheimer’s will emerge from studies of people genetically destined to get the disease.

Giedre Cohen enrolled in the DIAN TU study in 2013, when she still had no symptoms of Alzheimer’s, her husband says. Their story began more than a decade earlier.

In 2002, Tal Cohen was on a trip to Miami to attend a wedding. He met Giedre, who was born in Lithuania, and the two fell in love.

“I spent the next, basically, two years, flying back and forth every two weeks or so in a long-distance relationship, until I finally convinced her to come out to Los Angeles,” Cohen says.


What was wrong was that Giedre’s sister had the gene mutation that causes Alzheimer’s to develop very early. Cohen says he consulted a neurologist who told him the odds were 50-50 that his wife also had the mutation.

Tal and Giedre decided they had to do something. And pretty soon they found DIAN, the Dominantly Inherited Alzheimer Network, an international research project based at Washington University in St. Louis.

The network was created specifically for members of families affected by the mutation that causes early Alzheimer’s. “Virtually 100 percent of the mutation carriers, even if they’re asymptomatic now, are going to become symptomatic,” says Dr. John Morris, DIAN’s principal investigator and a professor of neurology at Washington University.

At first, DIAN’s purpose was to study participants to learn more about Alzheimer’s. But when potential drugs for Alzheimer’s were ready to be tested in people, the network created DIAN TU (the TU stands for Trials Unit) to help participants get access to experimental drugs.

That effort now includes drug companies, the National Institute on Aging, the Alzheimer’s Association and more than 400 members of families with the mutation.

(From left) Tal and Giedre Cohen chat with Carrie Richardson and Mary Salter during a break at the Alzheimer's Association International Conference in Washington, D.C., on Saturday.

(From left) Tal and Giedre Cohen chat with Carrie Richardson and Mary Salter during a break at the Alzheimer’s Association International Conference in Washington, D.C., on Saturday.

Manuel Balce Ceneta/AP

When drug companies began to focus on preventing Alzheimer’s a few years ago, they became very interested in people who had no symptoms but were certain to develop the disease. And DIAN TU gave them a way to reach these people.

Alzheimer’s prevention trials would be very hard to carry out in the general population because Alzheimer’s can take decades to develop, and many people never get it. People with this mutation, however, are virtually certain to develop Alzheimer’s around the same age that one of their parents did.


This type of genetically targeted drug testing has been done before: Several decades ago, for example, drug companies tested the first cholesterol-lowering drugs in a population of people who had a huge genetic risk for heart disease.

“These families had mutations that caused them to have heart attacks and strokes in their 30s, 40s and 50s,” Bateman says. But the cholesterol drugs were able to “melt away cholesterol deposits” in these people and extend their lives by decades.

Now, people with the Alzheimer’s mutation need a similar success, Bateman says.

“Time is running out for these families,” he says. “As they and their siblings and their children advance in age, they’re marching toward that inevitable certainty of Alzheimer’s disease and death.”

So far, the DIAN TU study has included two different drugs intended to reduce amyloid, the sticky substance that builds up in the brains of people with Alzheimer’s.

Because of the way the study is structured, 75 percent of people participating are getting one of the candidate drugs, while 25 percent are getting a placebo. The study is “blinded,” which means that Giedre and Tal Cohen don’t yet know which of the drug candidates she’s getting, if any.

They do know that Giedre’s symptoms have continued to progress, her husband says.

“Every time Giedre gets dosed, I anguish,” Tal says, “wondering if she is getting something that will help her — or just a saline solution that will do nothing, and I’m putting her through this needlessly.”

Last weekend, the couple traveled to Washington, D.C., to attend the first ever meeting of DIAN families. It was held just before the annual Alzheimer’s Association International Conference, which took place this week.

Cohen says it was comforting to meet families with the same tragic problem he and his wife are facing. But the meeting also gave him a forum to make an impassioned plea for better access to the latest experimental Alzheimer’s drugs — drugs that might yet help his wife.

“We had the FDA there, the regulators; we had the pharma guys, we had the researchers,” he says. “They heard me loud and clear.”



This article was originally published on NPR.  Read the original article.

Researchers frustrated by failure to roll out 'game-changing' Ebola test

Researchers frustrated

A test kit that diagnoses Ebola rapidly using just a finger prick of blood could save lives in the ongoing epidemic in West Africa. But researchers are perplexed as to why the diagnostic kit has not been deployed in the field, despite both the World Health Organization (WHO) and the US Food and Drug Administration approving it four months ago for emergency use.

“A lot of people are frustrated,” says Nira Pollock, an infectious-diseases researcher at the Boston Children’s Hospital in Massachusetts, and the senior author of an independent field-validation study of the test kit, published on 26 June1 in The Lancet. The results were presented to the WHO and health ministries in affected countries in March. “Many groups on the ground would like to deploy the test, but can’t, because national regulators haven’t approved it.”

The test, developed by the medical-diagnostics company Corgenix, of Broomfield, Colorado, detects Ebola specific proteins that are in the blood. Like a pregnancy test kit, it shows a positive result by coloured bands; it is simple enough to use that healthcare workers with minimal training could deploy it in remote villages and get a fast result. Existing ‘gold-standard’ methods of diagnosis require blood samples to be drawn and transported to sophisticated central laboratories for processing — which can result in long delays. The Corgenix test could not replace lab confirmation, but it would allow workers to identify infected people and isolate them faster, greatly reducing the spread of disease, says Nahid Bhadelia, an infectious-diseases physician at the Boston University School of Medicine and the Boston Medical Center in Massachusetts.


At the peak of the epidemic, delays and bottlenecks in testing at centralized labs meant that people who were infectious were going undetected for around 5–6 days before being diagnosed, which had devastating effects, says Bhadelia, who is about to return to Sierra Leone for her fourth stint working in an Ebola treatment centre.

Sensitive test

One concern was that the test might fail to detect the virus in some cases of Ebola. But the independent field-validation1 (in Sierra Leone) shows that the kit was as sensitive at catching cases as the gold-standard comparison — a real-time polymerase chain reaction (RT-PCR) test that amplifies and detects genetic sequences that are specific to Ebola in blood and other bodily fluids.

Robert Garry, a virologist at Tulane University in New Orleans, Louisiana, who helped to develop the Corgenix test, blames the delays on what he says are overly restrictive and ambiguous sets of guidelines released by WHO in March and June. They state, for example, that the rapid “antigen-detection” tests “have no role in the routine management of Ebola in settings where PCR (molecular) testing is available; however, they may have utility in settings without laboratory infrastructure if their benefits and limitations are understood”.

Many people have misunderstood that to mean “if you have PCR, you don’t need the test”, Garry says. But the Ebola epidemic has shown that use of a centralized testing model alone is badly flawed, he says, and that additional decentralized testing is needed in the places where outbreaks occur to slash delays in identifying those infected. “We need to rethink the conventional wisdom about PCR being the only answer,” he adds.

False positives

But Mark Perkins, chief scientific officer of the non-profit organization Foundation for Innovative New Diagnostics (FIND) in Geneva, Switzerland, defends the thrust of the WHO’s guidelines, which FIND contributed to developing. The concern with the rapid-antigen tests, he says, is that they report too many false positives. In the independent validation, 6 of 77 people who tested negative for Ebola using PCR were declared positive by the Corgenix kit. “To roll out an assay with so many false positives is unthinkable,” Perkins says.

That is less of a problem in this instance, argues Bhadelia, as researchers are proposing to use the test only to speed up the identification of those who are positive for Ebola, before confirming the results in the lab a few days later.

Moreover, the independent validation has raised questions over the quality of some of the PCR testing that was done during the epidemic. In the study, researchers used a routinely employed, partly-automated PCR kit made by altona Diagnostics, of Hamburg, Germany. But some of the samples that the altona test scored as negative — and which the Corgenix kit scored as positive — were later confirmed to be positive using a reference-standard test kit. That is a concern, says Bhadelia, as false negatives by the altona test might have allowed people with Ebola to return to the community while they were still infectious. It also suggests the possibility that the Corgenix kit might not be as prone to false positives as Perkins suggests — though further research would be needed to clarify the kit’s performance.

Field research

Perkins says that although a rapid test would have helped to triage people at the peak of the Ebola epidemic last year, when PCR labs were overwhelmed, the drastic fall in the number of cases since then has meant that labs can now easily handle the load. Rapid tests are now of “reduced relevance”, he says.

But researchers say that this misses the point. Although most Ebola cases are currently close to urban PCR labs, sporadic outbreaks still occur in rural areas. Should Ebola flare up again, it would be beneficial to have gained experience using the kits in the field, says Pollock. Deploying the kits would also provide much more data about their real-world performance, useful both for this and further outbreaks, says Mara Jana Broadhurst, a co-author of The Lancet study. who works on Ebola diagnostics for Partners in Health, a global-health organization in Boston, Massachusetts.

Ebola in West Africa clearly exposed the “logistical constraints” of using PCR alone and its weaknesses as a frontline tool in a serious epidemic, says Broadhurst. “We need to consider all options.”


This article was originally published on Nature.  Read the original article.