Schizophrenia’s Genetic ‘Skyline’ Rising

“While the suspect variation identified so far only explains only about 3.5 percent of the risk for schizophrenia, these results warrant exploring whether using such data to calculate an individual’s risk for developing the disorder might someday be useful in screening for preventive interventions,” explained Thomas R. Insel, M.D., director of the NIH’s National Institute of Mental Health, one funder of the study. “Even based on these early predictors, people who score in the top 10% of risk may be up to 20-fold more prone to developing schizophrenia.”

The newfound genomic signals are not simply random sites of variation, say the researchers. They converge around pathways underlying the workings of processes involved in the disorder, such as communication between brain cells, learning and memory, cellular ion channels, immune function and a key medication target.

The Schizophrenia Working Group of the Psychiatric Genomic Consortium (PGC) report on their genome-wide analysis of nearly 37,000 cases and more than 113,000 controls in the journal Nature. The NIMH-supported PGC represents more than 500 investigators at more than 80 research institutions in 25 countries.

Prior to the new study, schizophrenia genome-wide studies had identified only about 30 common gene variants associated with the disorder. Sample sizes in these studies were individually too small to detect many of the subtle effects on risk exerted by such widely shared versions of genes. The PGC investigators sought to maximize statistical power by re-analyzing not just published results, but all available raw data, published and unpublished. Their findings of 108 illness-associated genomic locations were winnowed from an initial pool of about 9.5 million variants.

A comparison of the combined study data with findings in an independent sample of cases and controls yielded a high degree of replication, suggesting that considerably more such associations of this type are likely to be uncovered with larger sample sizes, say the researchers.

There was an association confirmed with variation in the gene that codes for a receptor for the brain chemical messenger dopamine, which is known to be the target for antipsychotic medications used to treat schizophrenia. Yet evidence from the study supports the view that most variants associated with schizophrenia appear to exert their effects via the turning on and off of genes rather than through coding for proteins.

The study found a notable overlap between protein-related functions of some linked common variants and rare variants associated with schizophrenia in other studies. These included genes involved in communication between neurons via the chemical messenger glutamate, learning and memory, and the machinery controlling the influx of calcium into cells.

“The overlap strongly suggests that common and rare variant studies are complementary rather than antagonistic, and that mechanistic studies driven by rare genetic variation will be informative for schizophrenia,” say the researchers.

Among the strongest associations detected, as in in previous genome-wide genetic studies, was for variation in tissues involved in immune system function. Although the significance of this connection for the illness process remains a mystery, epidemiologic evidence has long hinted at possible immune system involvement in schizophrenia.

Findings confirm that it’s possible to develop risk profile scores based on schizophrenia-associated variants that may be useful in research — but, for now, aren’t sensitive or specific enough to be used clinically as a predictive test, say the researchers.

They also note that the associated variations detected in the study may not themselves be the source of risk for schizophrenia. Rather, they may be signals indicating the presence of disease-causing variation nearby in a chromosomal region.

Researchers are following up with studies designed to pinpoint the specific sequences and genes that confer risk. The PGC is also typing genes in hundreds of thousands of people worldwide to enlarge the sample size, in hopes of detecting more genetic variation associated with mental disorders. Successful integration of data from several GWAS studies suggests that this approach would likely be transferrable to similar studies of other disorders, say the researchers.

“These results underscore that genetic programming affects the brain in tiny, incremental ways that can increase the risk for developing schizophrenia,” said Thomas Lehner, Ph.D., chief of NIMH’s Genomics Research Branch. “They also validate the strategy of examining both common and rare variation to understand this complex disorder.”

Sea Rising in Western Pacific: Human Activity


The study authors combined past sea level data gathered from both satellite altimeters and traditional tide gauges as part of the study. The goal was to find out how much a naturally occurring climate phenomenon called the Pacific Decadal Oscillation, or PDO, influences sea rise patterns in the Pacific, said Assistant Professor Benjamin Hamlington of Old Dominion University in Norfolk, Va., a former CU-Boulder postdoctoral researcher and lead study Read more →


The PDO is a temperature pattern in the Pacific Ocean akin to El Niño but which lasts roughly 20 to 30 years and contributes significantly to the decadal trends in regional and global sea level, said CU-Boulder Research Professor Robert Leben, a study co-author. The research team performed sea level reconstructions going back to 1950 by fitting patterns of satellite altimeter data to tide gauge data, then stripped away the effects of the PDO to better understand its influence on current sea level increases in the Pacific.

“The conventional wisdom has been that if the Pacific Decadal Oscillation was removed from the equation this sea level rise in parts of the Pacific would disappear,” said Hamlington, who received his doctorate from CU-Boulder. “But we found that sea level rise off the coasts of the Philippines and northeastern Australia appear to be anthropogenic and would continue even without this oscillation.”

A paper on the subject was published online in the July 20 issue of Nature Climate Change. Other co-authors on the study included CU-Boulder doctoral student Matthew Strassburg, CU-Boulder Associate Professor Weiqing Han, CU-Boulder Professor R. Steven Nerem and Seoul National University faculty member K.Y. Kim. The study was funded primarily by NASA and the National Science Foundation.

The team also used NASA climate models to assess sea level rise in the tropical Pacific that included data on the warming tropical Indian Ocean, which has been shown in previous studies to be caused by increases in greenhouse gases. The climate modeling portion of the new study also showed sea level rise near the Philippines and Australia is caused at least in part by anthropogenic, or human-caused, warming said Hamlington, who got his doctorate under Leben.

The research team estimated that areas of the ocean near the Philippines and northeast Australia are being raised by about 1 centimeter per year due to anthropogenic warming, which can increase the intensity of severe weather. “When water starts piling up there and typhoon-like storms are traveling over higher sea levels, it can be a bad situation,” said Hamlington.

Although global sea level patterns are not geographically uniform — sea level rise in some areas correlate with sea level fall in other areas — the average current global sea level rise is roughly 3 millimeters per year. Some scientists are estimating global seas may rise by a meter or more by the end of the century as a result of greenhouse warming.

“When the current PDO switches from its warm phase to its cool phase sea levels on the western coast of North America likely will rise,” said Leben of CU-Boulder’s aerospace engineering sciences department. “I think the PDO has been suppressing sea level there for the past 20 or 30 years.”

In a broader sense, the new study shows that scientists may be able to look at other regions of the world’s oceans and extract the natural climate variability in order to measure human-caused effects, said Hamlington, a researcher at CU-Boulder’s Cooperative Institute for Research in Environmental Sciences. “This kind of research may start revealing patterns that we might not expect.”

Most of the satellite altimeter data for the study came from NASA’s Topex-Poseidon and Jason satellite series missions. Satellite altimetry measures sea level rise by bouncing radar pulses off the surface of the ocean at particular points and calculating the round-trip time it takes the pulse to return to the spacecraft said Leben, also a faculty member of CU-Boulder’s Colorado Center for Astrodynamics Research, or CCAR.

A 2010 study led by CU-Boulder’s Han published in Nature Geoscience concluded that greenhouse gases were responsible for rising seas in parts of the Indian Ocean. The changes are believed to be at least partially a result of the roughly 1 degree Fahrenheit increase in the Indo-Pacific warm pool — an enormous, bathtub-shaped area stretching from the east coast of Africa to the International Date Line in the Pacific — during the past 50 years.

Bone marrow transplant cleared two men of HIV



More than three years ago, Australian researchers at St Vincent’s Hospital and the Kirby Institute at the University of New South Wales (UNSW) transplanted bone marrow to two HIV-positive men. Now, the men are apparently HIV-free.

The researchers have highlighted the fact that the bone marrow used did not contain both copies of the gene CCR5 delta32, a mutation that protects against the HIV virus, which suggest that bone marrow without this gene could also be used to afford protection againts the virus. Both men, however, have continued antiretroviral therapy—a combination of drugs that stops the progression of the disease—as a protective measure.

“It’s very possible that the Australian men would relapse if they Read more →

were to stop antiretroviral therapy,” explained Timothy Henrich, an infectious-disease specialist at Brigham and Women’s Hospital in the US, to Nature. That’s why the Australian researchers have been very careful and haven’t said that the men are cured.

So far the only person who has been cured of HIV is Timothy Ray Brown, also known as the ‘2008 Berlin patient’. Ray Brown received a bone marrow transplant too and has been HIV-free for six years. He has stopped taking antiretrovirals.

Bone marrow transplant is a difficult and costly procedure. And the researchers explained over at the UNSW website that the transplants shouldn’t be considered as a ‘functional cure.’

“This is a terrific unexpected result for people with malignancy and HIV. It may well give us a whole new insight into HIV, using the principles of stem cell transplantation,” said Dr Sam Milliken, Director of St Vincent’s Haematology & Bone Marrow Transplantation and study co-author, in a UNSW press release.

The researchers are still working with the Sydney patients to discover if there is any residual virus and where it’s hiding. Finding where the virus hides is essential to finding a potential cure for HIV.

Although the researchers still don’t know why the patients have undetectable HIV loads, Dr Kersten Koelsch from UNSW’s Kirby Institute explained that one theory suggests the bone marrow therapy helps destroy cells infected with the virus and that remaining infected cells are then destroyed by the patient’s immune system.

“We need more research to establish why and how bone marrow transplantation clears the virus. We also want to explore the predictors of sustained viral clearance and how this might be able to be exploited without the need for bone marrow transplantation,” says Dr Koelsch.

Is the Universe a Bubble? Multiverse Hypothesis

Never mind the big bang; in the beginning was the vacuum. The vacuum simmered with energy (variously called dark energy, vacuum energy, the inflation field, or the Higgs field). Like water in a pot, this high energy began to evaporate — bubbles formed.

Each bubble contained another vacuum, whose energy was lower, but still not nothing. This energy drove the bubbles to expand. Inevitably, some bubbles bumped into each other. It’s possible some produced secondary bubbles. Maybe the bubbles were rare and far apart; maybe they were packed close as foam.

But here’s the thing: each of these bubbles was a universe. In this picture, our universe is one bubble in a frothy sea of bubble universes.

That’s the multiverse hypothesis in a bubbly nutshell.

It’s not a bad story. It is, as scientists say, physically motivated — not just made up, but rather arising from what we think we know about cosmic inflation.

Cosmic inflation isn’t universally accepted — most cyclical models of the universe reject the idea. Nevertheless, inflation is a leading theory of the universe’s very early development, and there is some observational evidence to support it.

Inflation holds that in the instant after the big bang, the universe expanded rapidly — so rapidly that an area of space once a nanometer square ended up more than a quarter-billion light years across in just a trillionth of a trillionth of a trillionth of a second. It’s an amazing idea, but it would explain some otherwise puzzling astrophysical observations.

Inflation is thought to have been driven by an inflation field — which is vacuum energy by another name. Once you postulate that the inflation field exists, it’s hard to avoid an “in the beginning was the vacuum” kind of story. This is where the theory of inflation becomes controversial — when it starts to postulate multiple universes.

Proponents of the multiverse theory argue that it’s the next logical step in the inflation story. Detractors argue that it is not physics, but metaphysics — that it is not science because it cannot be tested. After all, physics lives or dies by data that can be gathered and predictions that can be checked.

That’s where Perimeter Associate Faculty member Matthew Johnson comes in. Working with a small team that also includes Perimeter Faculty member Luis Lehner, Johnson is working to bring the multiverse hypothesis firmly into the realm of testable science.

“That’s what this research program is all about,” he says. “We’re trying to find out what the testable predictions of this picture would be, and then going out and looking for them.”

Specifically, Johnson has been considering the rare cases in which our bubble universe might collide with another bubble universe. He lays out the steps: “We simulate the whole universe. We start with a multiverse that has two bubbles in it, we collide the bubbles on a computer to figure out what happens, and then we stick a virtual observer in various places and ask what that observer would see from there.”

Simulating the whole universe — or more than one — seems like a tall order, but apparently that’s not so.

“Simulating the universe is easy,” says Johnson. Simulations, he explains, are not accounting for every atom, every star, or every galaxy — in fact, they account for none of them.

“We’re simulating things only on the largest scales,” he says. “All I need is gravity and the stuff that makes these bubbles up. We’re now at the point where if you have a favourite model of the multiverse, I can stick it on a computer and tell you what you should see.”

That’s a small step for a computer simulation program, but a giant leap for the field of multiverse cosmology. By producing testable predictions, the multiverse model has crossed the line between appealing story and real science.

In fact, Johnson says, the program has reached the point where it can rule out certain models of the multiverse: “We’re now able to say that some models predict something that we should be able to see, and since we don’t in fact see it, we can rule those models out.”

For instance, collisions of one bubble universe with another would leave what Johnson calls “a disk on the sky” — a circular bruise in the cosmic microwave background. That the search for such a disk has so far come up empty makes certain collision-filled models less likely.

Meanwhile, the team is at work figuring out what other kinds of evidence a bubble collision might leave behind. It’s the first time, the team writes in their paper, that anyone has produced a direct quantitative set of predictions for the observable signatures of bubble collisions. And though none of those signatures has so far been found, some of them are possible to look for.

The real significance of this work is as a proof of principle: it shows that the multiverse can be testable. In other words, if we are living in a bubble universe, we might actually be able to tell.


Study shows exercise really is the best medicine



Researchers at Queensland University of Technology in Australia have published the results of a five-year study that looked into the impact of exercise in women over the age of 50.

The study, published in the journal Maturitas, suggests that moderate to vigorous activity has many mental and physical benefits for mature women.

The researchers also found that 30 minutes of exercise a day aren’t enough to reap all the benefits. “Research is now telling Read more →

us that older women should be doing at least 30 to 45 minutes five times a week of moderate to high-intensity exercise and by that we mean exercise that leaves you huffing and puffing,” explained professor Debra Anderson, who works at QUT’s Institute of Health and Biomedical Innovation, in a news release. The exercise should also be tailored to the women’s needs to ensure that its intensity is enough for them.

Jogging, running, walking, riding and swimming are some of the high-intensity activities that some women in this age group regularly practise. And the QUT scientists believe that doctors should be developing home-based exercise programs that are easy to incorporate into daily life.

Promoting a healthy lifestyle has become an important strategy for reducing morbidity and mortality, explained the researchers in a release, because high-intensity exercise over a sedentary lifestyle can reduce the risk of death.

So next time you’re avoiding heading to the gym or out for a run, just remember that 30 to 45 minutes of high-intensity exercise five days a week, can help you stay fit and healthy for longer.


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