Culture

ANN ARBOR--People often react to stress by binging on sweets or fattening comfort foods, cravings fueled by the appetite-stimulating stress hormone cortisol.

But overweight adolescents--considered particularly susceptible to stress eating--actually ate less when exposed to a lab stressor, and the foods they eschewed were the high fat and sugar options, according to a University of Michigan study.

Even more surprising, kids who produced the most cortisol after the stressor saw the biggest appetite reduction, eating about 35% fewer calories in the two hours after the stressor, said principal investigator Rebecca Hasson, associate professor of movement science at the U-M School of Kinesiology.

Results were similar whether adolescents in the study were monitoring their food intake or not. This matters because people who restrict calories are more likely to stress eat.

That didn't happen among these dieters, and the results suggest that a biological response--such as the flood of cortisol or the satiety hormone leptin--drove the adolescents' reduced appetite.

Hasson and colleague Matthew Nagy, the study's first author and an alumnus of the U-M School of Public Health, wanted to understand how biology and behavior impacted the eating patterns of overweight kids.

"These are really exciting findings because they give us a chance to observe eating patterns when adults are exposed to stress, which is a very important factor in childhood obesity, long-term cardiovascular risk and type 2 diabetes risk," said Hasson, who also leads the U-M Childhood Disparities Research Lab and is an associate professor of nutritional sciences in the School of Public Health.

"This doesn't mean stress kids out and they'll lose weight. This is in the short term only. They may eat more calories later. Typically, many kids did say they turned to food when stressed, so maybe this was a time effect."

Also, even if the cortisol spike didn't cause overeating, it's still metabolically unhealthy, she said.

The study, which appears in Psychosomatic Medicine, involved about 60 kids.

Hasson said much work remains to see who's susceptible to big cortisol spikes and the long-term effects of stress. Previous studies have found that overweight adults with high cortisol responses after stress also experience short-term calorie reduction.

New research at the University of Kentucky has confirmed that the presence of XX sex chromosomes increases the amount of fat circulating in the blood, which leads to narrowing of the arteries and ultimately a higher risk of heart attacks and coronary artery disease.

The research was published in June 2019 in Nature Communications.

The leading cause of death in women is coronary artery disease (CAD), but women develop CAD almost 10 years later than men. For many years, scientists attributed this decade-long delay in disease development to the protective effects of sex hormones. There is a lot of evidence that hormones like estrogen and progesterone protect the heart, but scientists had little data on the influence of the genetic component--the X chromosome--on the heart.

A team led by Lisa Cassis, a researcher in the UK College of Medicine's pharmacology and nutritional sciences department, set out to understand the role of sex chromosomes in the cardiovascular system. Cassis's team studies chromosome effects in mice, and for this most recent discovery they were able to zero in on XX chromosomes by removing hormones.

According to Yasir Al-Siraj, a postdoctoral scholar and the paper's first author, if the levels of circulating lipids transported by the blood are too high, they will start to accumulate in and on the artery wall, leading to plaque buildup. These plaques harden and narrow the artery, reducing blood flow to the vital organs.

The team looked at lipids absorbed from the diet and made in the liver. Cassis, who also serves as the UK vice president for research, said, "We looked at how our X sex chromosomes were influencing the levels of lipids in the blood and in the arteries." What they found is that an XX sex chromosome combination promotes efficient use of fat.

Women need fat to bear and feed babies, Cassis explained: "We're set up, potentially through our XX sex chromosomes, so that we can effectively absorb that lipid from the diet and put it into our fat cells and maybe even make it in the liver."

Everything is fine until women hit menopause and the protective effects of hormones disappear, leaving women with what Cassis calls "that XX thrifty, fat-absorbing kind of genotype."

The team is looking at genes that are changed in the liver and in the intestine to find novel targets for drug development. If they can find target genes that influence atherosclerosis, scientists can then explore the effects of existing drugs or develop new ones.

Al-Siraj said his next step is to study the role of the number of X chromosomes in atherosclerosis. "We don't know if our findings are due to the presence of two X chromosomes or due to the absence of the Y chromosome," he said.

These findings may also drive choice of diet for post-menopausal women. Cassis said, "For example, if they're very effective fat absorbers, obviously, once they get post-menopausal, they need to be careful about the fat content."

COLUMBUS, Ohio - If you want to achieve a goal, make sure you share your objective with the right person.

In a new set of studies, researchers found that people showed greater goal commitment and performance when they told their goal to someone they believed had higher status than themselves.

It didn't help people at all to tell their goals to someone they thought had lower status, or to keep their objectives to themselves.

These results run counter to a widely reported 2009 study that suggested telling other people your goals is actually counterproductive, said Howard Klein, lead author of the new study and professor of management and human resources at The Ohio State University's Fisher College of Business.

"Contrary to what you may have heard, in most cases you get more benefit from sharing your goal than if you don't - as long as you share it with someone whose opinion you value," Klein said.

Results showed that people were motivated by sharing a goal with someone they thought had higher status because they cared about how that higher-status person would evaluate them.

"You don't want them to think less of you because you didn't attain your goal," Klein said.

In these studies, higher-status people were those who the participants thought had more prestige and respect than they did.

The study was published online recently in the Journal of Applied Psychology and will appear in a future print edition.

In one study, the researchers found that working adults frequently do share their personal career goals and that their commitment to attaining those goals was higher when those goals were shared with someone higher in status.

In another study, 171 undergraduate students were seated at computers and told they had to move a slider on the screen to the number 50 as many times as possible within the allotted time.

After counting how many times they successfully did this, they had to do it again, but this time they were told to set and write down a goal.

The experimenter then informed participants that a lab assistant would come around and check on their goals. The same person always checked on the participants' goals - but there were two different versions of this assistant.

In some cases, the lab assistant was dressed in a suit and introduced himself as a doctoral-level student in the business school who was an expert on today's study topic. That was someone the undergraduate participants agreed was a higher-status person than themselves.

For other participants, the same lab assistant dressed in casual clothing and introduced himself as a student at a local community college who was working part time at the business school. In this case, the students rated the assistant as lower in status than themselves.

A third group of participants didn't share their goals with the lab assistant.

Results showed that participants who shared their goals with the higher-status lab assistant reported that they were more committed to achieving the goal they set for themselves than were those who told the lower-status assistant.

And, in fact, those whose goals were seen by the higher-status assistant did perform better on the task than did the others.

Participants who shared their goal with the lower-status assistant performed no better than those who told no one about their goal.

"If you don't care about the opinion of whom you tell, it doesn't affect your desire to persist - which is really what goal commitment is all about," Klein said.

"You want to be dedicated and unwilling to give up on your goal, which is more likely when you share that goal with someone you look up to."

A third similar study also asked participants about their "evaluation apprehension" - how much they cared about what the lab assistant thought of them.

The results showed that participants who cared more about what the lab assistant thought of them were more committed to their goal and were more likely to achieve it. In addition, evaluation apprehension was higher when the lab assistant was viewed as having higher status.

Evaluation apprehension may be one key to why it helps to tell a higher-status person about your goals, Klein said.

But it may be possible to take that too far.

"We didn't find it in this study, but it is possible that you may create so much anxiety in trying to impress someone that it could interfere with your performance," Klein said.

A final, more long-term study examined 292 college students over the course of an entire semester. The participants set challenging grade goals at the beginning of the semester and shared them.

As in the other studies, students who told higher-status people about their goal showed more goal commitment and were more likely to achieve their target grade than those who told lower-status people.

These findings provide evidence that counters popular media recommendations - including a TED talk with more than 6 million views - that one should stay silent about a goal, Klein said.

Those recommendations are based on an oversimplification of one journal article, the results of which run counter to the majority of studies in the field, he said.

So whom should you share your goals with?

For work goals, a supervisor is an obvious choice, but it depends on the situation, Klein said. If your goal is to get a better job or if you have another goal you would not want your supervisor to know, a mentor may be a better choice. You can even look to someone you admire outside of work to tell.

No matter what kind of goal you're talking about, one thing matters when sharing, according to Klein.

"The important thing is that you need to care about the opinion of who you are telling," he said.

Osaka, Japan - Researchers in Japan have found that the structure of Parkinson's disease-associated protein aggregates can tell us, for the first time, about their movement through the brain. These new findings indicate that Parkinson's disease is a kind of amyloidosis, which has implications for its diagnosis and treatment.

Lewy bodies, primarily composed of α-synuclein proteins (α-syn), are the neuropathological hallmark of Parkinson's disease. However, we don't yet fully understand how or why they appear in the brain. Using state-of-the-art imaging techniques, researchers at Osaka University have found that Lewy bodies in Parkinson's disease brains contain α-syn protein aggregates (called amyloid fibrils) that can propagate through the brain. These findings, published this week in PNAS, support the new idea that Parkinson's disease is a kind of amyloidosis, which is a group of rare diseases caused by abnormal protein accumulation.

"Our work follows on from in vitro findings that aggregates of α-synuclein that can propagate through the brain have a cross-β structure," says lead author of the study Dr Hideki Mochizuki. "Our study is the first to find that aggregates in Parkinson's disease brains also have this cross-β structure. This could mean that Parkinson's disease is a kind of amyloidosis that features the accumulation of amyloid fibrils of α-synuclein."

While immunostaining can tell us about the localization of a protein of interest, it doesn't tell us about its conformation. Electron microscopy can tell us about morphological features, but not about protein structure. Similarly, Fourier-transform infrared spectroscopy can tell us about the secondary structure of proteins, but not about their fibrillary organization.

The researchers therefore teamed up with the large-scale synchrotron radiation facility, SPring-8, and used microbeam X-ray diffraction to visualize the ultrastructure of Lewy bodies in the post mortem brain slices of three patients with Parkinson's disease. Some of the α-syn aggregates did indeed have a cross-β structure, but there was quite a bit of variety in the state of amyloid proteins.

"One possibility is that this variability could indicate the different maturity stages of Lewy bodies," says Dr Katsuya Araki, first author of the paper. "This has obvious implications in the diagnosis of Parkinson's disease, and could also have therapeutic implications in the long run."

The researchers suggest that Parkinson's disease is a systemic (whole-body) amyloidosis rather than one that is localized to one part of the brain. This fits with the non-motor symptoms that patients experience before the onset of motor dysfunction and the multiple organ involvement of α-syn pathology. The findings from this work are highly applicable to the development of new diagnostic and therapeutic tools for the treatment of Parkinson's disease.

Findings show that a decline in cardiovascular deaths has been offset by an increase in the number of deaths from infections and respiratory problems, highlighting the importance of focusing on patients' overall health rather than individual diseases.

The advanced age at which heart failure develops is also a factor. Survival has improved among young and middle-aged patients, but prolonging life in people older than 80 - who account for about half of all heart failure patients - remains very difficult.

An estimated 920,000 people are currently living with a diagnosis of heart failure in the UK. A host of new treatments, device therapies such as implantable defibrillators, and remodelled clinical teams introduced in recent years would be expected to reduce premature death among heart failure patients.

Dr Nathalie Conrad from The George Institute for Global Health, UK at the University of Oxford, who led the research, said: "Despite considerable improvements in heart failure care since the early 2000s, overall mortality rates in the UK have changed very little. We wanted to understand the underlying reasons for this to help develop more targeted therapies and public health strategies."

The research team tracked the death rate for 86,000 UK adults with heart failure in the year following their diagnosis, using information from the Clinical Practice Data Link. Overall, they found that the risk of death from cardiovascular causes declined by 27% over the 12-year study period, but this was offset by a 22% increase in the death rate from non-cardiovascular causes.

By 2013, the majority of deaths and hospitalisations among heart failure patients were due to non-cardiovascular causes, the major ones being: cancer (15% of all deaths); infections (13%); and respiratory conditions (12%).

As the population of the UK ages, more individuals will experience co-existing morbidities, i.e. multiple health conditions that impact life expectancy. Current heart failure treatment is intrinsically disease-centred and almost exclusively focuses on patients' cardiovascular health. To boost survival rates, future research and management strategies must address patient health in the round.

"Our evidence highlights that a broader perspective must be taken in approaching heart failure management; one that considers not only patients' cardiovascular health, but also the range of associated co-morbities they are likely to experience," said Conrad.

Technology developed using artificial intelligence (AI) could identify people at high risk of a fatal heart attack at least 5 years before it strikes, according to new research funded by the British Heart Foundation (BHF). The findings are being presented at the European Society of Cardiology (ESC) Congress in Paris and published in the European Heart Journal.

Researchers at the University of Oxford have developed a new biomarker, or 'fingerprint', called the fat radiomic profile (FRP), using machine learning. The fingerprint detects biological red flags in the perivascular space lining blood vessels which supply blood to the heart. It identifies inflammation, scarring and changes to these blood vessels, which are all pointers to a future heart attack.

When someone goes to hospital with chest pain, a standard component of care is to have a coronary CT angiogram (CCTA). This is a scan of the coronary arteries to check for any narrowed or blocked segments. If there is no significant narrowing of the artery, which accounts for about 75 per cent of scans [1], people are sent home, yet some of them will still have a heart attack at some point in the future. There are no methods used routinely by doctors that can spot all of the underlying red flags for a future heart attack.

In this study, Professor Charalambos Antoniades and his team firstly used fat biopsies from 167 people undergoing cardiac surgery. They analysed the expression of genes associated with inflammation, scarring and new blood vessel formation, and matched these to the CCTA scan images to determine which features best indicate changes to the fat surrounding the heart vessels, called perivascular fat.

Next, the team compared the CCTA scans of the 101 people, from a pool of 5487 individuals, who went on to have a heart attack or cardiovascular death within 5 years of having a CCTA with matched controls who did not, to understand the changes in the perivascular space which indicate that someone is at higher risk of a heart attack. Using machine learning, they developed the FRP fingerprint that captures the level of risk. The more heart scans that are added, the more accurate the predictions will become, and the more information that will become 'core knowledge'.

They tested the performance of this perivascular fingerprint in 1,575 people in the SCOT-HEART trial, showing that the FRP had a striking value in predicting heart attacks, above what can be achieved with any of the tools currently used in clinical practice.

The team hope that this powerful technology will enable a greater number of people to avoid a heart attack, and plan to roll it out to health care professionals in the next year, with the hope that it will be included in routine NHS practice alongside CCTA scans in the next 2 years.

Professor Charalambos Antoniades, Professor of Cardiovascular Medicine and BHF Senior Clinical Fellow at the University of Oxford, said:

"Just because someone's scan of their coronary artery shows there's no narrowing, that does not mean they are safe from a heart attack.

"By harnessing the power of AI, we've developed a fingerprint to find 'bad' characteristics around people's arteries. This has huge potential to detect the early signs of disease, and to be able to take all preventative steps before a heart attack strikes, ultimately saving lives.

"We genuinely believe this technology could be saving lives within the next year."

Professor Metin Avkiran, Associate Medical Director at the British Heart Foundation said:

"Every 5 minutes, someone is admitted to a UK hospital due to a heart attack. This research is a powerful example of how innovative use of machine learning technology has the potential to revolutionise how we identify people at risk of a heart attack and prevent them from happening.

"This is a significant advance. The new 'fingerprint' extracts additional information about underlying biology from scans used routinely to detect narrowed arteries. Such AI-based technology to predict an impending heart attack with greater precision could represent a big step forward in personalised care for people with suspected coronary artery disease."

Fleets of microscopic machines toil away in your cells, carrying out critical biological tasks and keeping you alive. By combining theory and experiment, researchers have discovered the surprising way one of these machines, called the spindle, avoids slowdowns: congestion.

The spindle divides chromosomes in half during cell division, ensuring that both offspring cells contain a full set of genetic material. The spindle is made up of tens of thousands of stiff, hollow tubes called microtubules connected by biological motors.

Microtubules are only propelled forward when connected to a neighbor pointed in the opposite direction. Previous observations, however, showed microtubules cruising at full speed even when linked only to neighbors facing the same way. In a new paper published September 2 in Nature Physics, the researchers provide an answer to this puzzle. The microtubules are so entangled with one another that even those not actively launched forward get dragged along at full speed by the crowd.

"It's like a New York City crosswalk," says study lead author Sebastian Fürthauer, a research scientist at the Flatiron Institute's Center for Computational Biology (CCB) in New York City. "People walking different ways are all mixed together, yet everyone is able to move at full speed and flow smoothly past one another."

The findings will help scientists better understand the cellular machinery that segregates chromosomes during cell division and why this process sometimes goes wrong. If a spindle does its job incorrectly, it can introduce errors such as missing or extra chromosomes that can lead to complications like infertility and cancer, Fürthauer says.

Fürthauer and CCB director Michael Shelley, both applied mathematicians, worked on the project alongside an interdisciplinary team of experimental biologists and physicists from Harvard University, the Massachusetts Institute of Technology, Indiana University, and the University of California, Santa Barbara.

One of the overarching goals of biophysics is to link the activity of small-scale components to the large-scale dynamics of cells and organisms. The properties of the main spindle components are relatively well studied. Microtubules are long, stiff polymer rods akin to drinking straws, each with a 'minus' end and a 'plus' end. Molecular motors latch onto and move along microtubules using a pair of molecular 'feet.' Kinesin motors, for instance, have two pairs of feet, one at either end. Kinesin molecules can attach to two different microtubules, with each pair of feet marching from the minus end to the plus end of each microtubule.

If the plus and minus ends of both microtubules are aligned, the two pairs of feet walk in the same direction and the microtubules don't move relative to one another. If the microtubules are anti-aligned, the feet move in opposite directions, causing the microtubules to slide past one another. The collective motion of all the microtubules determines the spindle's growth and form.

Previous studies mostly focused on situations where motors were scarce. Scientists had assumed that this was an accurate representation of what happens in actual cells. In such a scenario, a microtubule's movement would depend on its neighbors' orientation. Microtubules aligned with their neighbors would stay put while those that defied the crowd would zoom forward.

Real spindles, however, don't exhibit this expected behavior. Microtubules surrounded by neighbors facing the same way still move at full speed. So what's pushing them forward?

Fürthauer and colleagues investigated how the microtubules would collectively move if the system were packed with lots of motors, resulting in lots of connections between microtubules. They developed a mathematical theory of how mechanical stresses develop in the collective when microtubules are pushed and pulled against each other by the numerous motors.

Their theory predicts that the microtubules line up, with every microtubule facing one of two opposing directions. Where microtubules of opposite orientation mingle, they are propelled forward as expected. Microtubules elsewhere, the theory states, are so entangled with their neighbors that they too are pulled along for the ride. Every microtubule, therefore, moves at precisely the speed of the walking motors regardless of its place in the crowd.

Experiments conducted by the researchers using microtubules and abundant kinesin motors matched these predictions. Additionally, the theory and experiments matched real-world spindles: In the eggs of African clawed frogs, microtubules in spindles move at roughly the same speed that the motors connecting them are known to walk.

The frog spindle behavior is "very suggestive that the actual biology lives in the regime we see in our experiments," Fürthauer says. "With this new understanding, we can now ask: How can we build a spindle? Can we reconstruct this complex biological machine in a computer simulation, or even in the test tube?" He and his colleagues are hopeful that they are getting closer.

Immunity against mumps virus appears insufficient in a fraction of college-aged people who were vaccinated in childhood, research from Emory Vaccine Center and the Centers for Disease Control and Prevention indicates. The findings highlight the need to better understand the immune response to mumps and mumps vaccines.

The results of the study are scheduled for publication in PNAS.

In the last 15 years, several mumps outbreaks have occurred among college students, sports teams and in close-knit communities across the United States. Two possible contributing factors include waning vaccine-induced immunity and differences between the strain of mumps virus now circulating and the vaccine strain, which is part of the standard measles, mumps, and rubella (MMR) childhood vaccine.

"Overall, the MMR vaccine has been great, with a 99 percent reduction in measles, mumps and rubella disease and a significant reduction in associated complications since its introduction," says Sri Edupuganti, MD, MPH, associate professor of medicine (infectious diseases) at Emory University School of Medicine and medical director of the Hope Clinic of Emory Vaccine Center. "What we're seeing now with these mumps outbreaks is a combination of two things - a few people were not making a strong immune response to begin with, and the circulating strain has drifted away from the strain that is in the vaccine."

Emory and CDC scientists collaborated on a study that included 71 people, aged 18 to 23, in the Atlanta area - the largest study so far of mumps memory B cells in vaccinated people. Recruitment of participants took place in 2010. Although almost all (69/71) had received two MMR doses, 80 percent of the participants received their second MMR more than ten years before enrolling in the study.

Most participants (93 percent) had antibodies against mumps, but ten percent of people in the study had no detectable mumps-specific memory B cells, which would normally be capable of producing antiviral antibodies as part of a memory response after exposure to mumps virus. On average, the frequency of memory B cells in participants' blood was 5 to 10 times lower for cells making antibodies against mumps, compared with cells making antibodies to measles or rubella.

In addition, antibodies from the participants did not neutralize wild-type mumps virus as efficiently as the vaccine virus. At least six study participants may have been potentially susceptible to infection with the currently circulating wild-type mumps strain, the paper concludes. The researchers did not see a clear relationship between the timing of vaccination and low antibody or memory B cell levels.

Other research has shown that a third MMR dose resulted in increased neutralizing antibody responses to mumps in some individuals with low neutralization titers; however, the antibody levels declined toward baseline by 1 year so the effect was not long-lasting. In 2017, the CDC's Advisory Committee on Immunization Practices approved a third dose of MMR vaccine for groups of people who are at risk because of an ongoing mumps outbreak.

The Jeryl Lynn mumps vaccine strain in the MMR vaccine was originally cultured from a scientist's daughter's throat in the 1960s. Though there is only one serotype of mumps virus, the current circulating strain ("genotype G") is genetically distinct from the vaccine strain. How these genetic changes affect the antigenic properties of the wild-type strain is not fully understood.

Additional studies to characterize the immune response to wild-type and vaccine strains of mumps are clearly needed to determine if developing a new mumps vaccine is warranted. Developing a new mumps vaccine would take a large investment in clinical trials needed to demonstrate safety and efficacy.

Symptoms of mumps include those common to viral illnesses - fatigue, body aches, headache - but a distinctive aspect is often swelling of the salivary glands. More severe cases can lead to encephalitis or deafness. The disease is spread by direct contact, droplets, or contaminated objects. It usually takes 16 to 18 days for mumps symptoms to show up after infection starts.

The human digestive tract is home to thousands of different strains of bacteria. Many of these are beneficial, while others contribute to health problems such as inflammatory bowel disease. Researchers from MIT and the Broad Institute have now isolated and preserved samples of nearly 8,000 of these strains, while also clarifying their genetic and metabolic context.

This data set (BIO-ML), which is available to other researchers who want to use it, should help to shed light on the dynamics of microbial populations in the human gut and may help scientists develop new treatments for a variety of diseases, says Eric Alm, director of MIT's Center for Microbiome Informatics and Therapeutics and a professor of biological engineering and of civil and environmental engineering at MIT.

"There's a lot of excitement in the microbiome field because there are associations between these bacteria and health and disease. But we're lacking in being able to understand why that is, what's the mechanism, and what are the functions of those bacteria that are causing them to associate with disease," says Alm, who is the senior author of the study.

The researchers collected stool samples from about 90 people, for up to two years, allowing them to gain insight into how microbial populations change over time within individuals. This study focused on people living in the Boston area, but the research team is now gathering a larger diversity of samples from around the globe, in hopes of preserving microbial strains not found in people living in industrialized societies.

"More than ever before, modern techniques allow us to isolate previously uncultured human gut bacteria. Exploring this genetic and functional diversity is fascinating -- everywhere we look, we discover new things. I'm convinced that enriching biobanks with a large diversity of strains from individuals living diverse lifestyles is essential for future advancements in human microbiome research," says Mathilde Poyet, a senior postdoc at MIT and one of the lead authors of the study.

MIT research associate Mathieu Groussin and former postdoc Sean Gibbons are also lead authors of the study, which appears in the Sept. 2 issue of Nature Medicine. Ramnik Xavier, a professor of medicine at Harvard Medical School and member of the Broad Institute, is a senior author of the study along with Alm.

Microbiome dynamics

Humans have trillions of bacterial cells in their digestive tracts, and while scientists believe that these populations change and evolve over time, there has been little opportunity to observe this. Through the OpenBiome organization, which collects stool samples for research and therapeutic purposes, Alm and his colleagues at MIT and the Broad Institute had access to fecal samples from about 90 people.

For most of their analysis, the researchers focused on microbes found in about a dozen individuals who had provided samples over an extended period, up to two years.

"That was a unique opportunity, and we thought that would be a great set of individuals to really try to dig down and characterize the microbial populations more thoroughly," Alm says. "To date there hadn't been a ton of longitudinal studies, and we wanted to make that a key focus of our study, so we could understand what the variation is day-to-day."

The researchers were able to isolate a total of 7,758 strains from the six major phyla of bacteria that dominate the human GI tract. For 3,632 of these strains, the researchers sequenced their full genomes, and they also sequenced partial genomes of the remaining strains.

Analyzing how microbial populations changed over time within single hosts allowed the researchers to discover some novel interactions between strains. In one case, the researchers found three related strains of Bacteroides vulgatus coexisting within a host, all of which appeared to have diverged from one ancestor strain within the host. In another case, one strain of Turicibacter sanguinis completely replaced a related strain of the same species nearly overnight.

"This is the first time we're getting a glimpse of these really different dynamics," Alm says.

Population variation

The researchers also measured the quantities of many metabolites found in the stool samples. This analysis revealed that variations in amino acid levels were closely linked with changes in microbial populations over time within a single person. However, differences between the composition of microbial populations in different people were more closely associated with varying levels of bile acids, which help with digestion.

The researchers don't know exactly what produces these differences in amino acid and bile acid levels, but say they could be influenced by diet -- a connection that they hope to investigate in future studies. They have also made all of their data available online and are offering samples of the strains of bacteria they isolated, allowing other scientists to study the functions of these strains and their potential roles in human health.

"Comprehensive and high-resolution collections of bacterial isolates open the possibility to mechanistically investigate how our lifestyle shapes our gut microbiome, metabolism, and inflammation. We aim to provide such a resource to the research community worldwide, including to lower-income research institutions," Groussin says.

The researchers have also begun a larger-scale project to collect microbiome samples from a greater diversity of populations around the world. They are especially focusing on underrepresented populations who live in nonindustrialized societies, as their diet and microbiomes are expected to be very different from those of people living in industrialized societies.

"It may be that as populations that have been living traditional lifestyles start to switch to a more industrialized lifestyle, they may lose a lot of that biodiversity. So one of the main things we want to do is conserve it, and then later we can go back and characterize it as well," Alm says.

Diversity is a hallmark of life and it shows up in unexpected places. A multi-national team of evolutionary biologists investigated how two types of poison frog co-exist when we expect only one. Their innovative study uncovers conditions where diversity flourishes against the odds, and offers new perspectives on chemical defense. The project was a collaboration between the University of Jyvaskylä, the University of Mississippi, Centre national de la recherche scientifique (CNRS) and John Carroll University. The findings were published in the Proceedings of the National Academy of Sciences (PNAS) on September 2nd 2019.

Many creatures carry warning colors that signal toxicity, such as wasps with yellow bands. The Dyeing Poison Frog (Dendrobates tinctorius) of French Guiana also has yellow stripes to keep predators away, but some have white stripes instead. This is an anomaly of evolution because predators learn to avoid warning colors through bad experience, and rare warning colors are harder to learn.

The team headed by Doctors Bibiana Rojas from University of Jyvaskyla and J.P Lawrence from the University of California Irvine propose evolutionary explanations for how nature allows rare warnings to persist.

Firstly, rare or weak signals can persist under the protection of stronger signals. The researchers show that predators learn to avoid more distasteful yellow frogs and generalize this avoidance to white frogs. Although the stronger defenses of yellow frogs should allow them to out-compete the whites over time, genomic analysis revealed that the population of white frogs is genetically separate from the yellows. Thus, diversity can exist within a single population (due to generalized learning) and between different populations (due to genetic isolation).

New methods to measure chemical defence were developed

The initial experiments were modest in scope, but strange results inspired the researchers to develop new methods.

"We faced the difficulty of not having an established method to quantify predator reaction to the chemical defenses. However, that difficulty turned into one of the biggest assets of our study, as we eventually succeeded at developing a method", says Doctor Bibiana Rojas from University of Jyvaskyla.

The new method improves the ecological relevance and precision of measuring predator-prey interactions. Past studies have assumed that toxicity is everything, and measure it by injecting mice with defensive chemicals. But prey survival and evolution depends on whether they are eaten or spat out, not the blood chemistry of their predators. Thus, the researchers used skin extracts mixed with oats to get a separate measure of distastefulness. They show that toxicity and distastefulness are better considered independently.

"The biggest surprise came from the fact that the frogs [with] higher amount of toxins in their skin are not necessarily the ones that birds find most distasteful. This finding challenges previous assumptions that most toxic equals most unpalatable", says Rojas.

Even if you are a non-smoker who exercises and has no genetic predisposition to cardiovascular disease, skimping on sleep - or getting too much of it - can boost your risk of heart attack, according to a new University of Colorado Boulder study of nearly a half-million people.

The research, published Sept. 2 in the Journal of the American College of Cardiology, also found that for those at high genetic risk for heart attack, sleeping between 6 and 9 hours nightly can offset that risk.

"This provides some of the strongest proof yet that sleep duration is a key factor when it comes to heart health, and this holds true for everyone," said senior author Celine Vetter, an assistant professor of Integrative Physiology.

For the study, Vetter and co-authors at the Massachusetts General Hospital and the University of Manchester analyzed the genetic information, self-reported sleep habits and medical records of 461,000 UK Biobank participants age 40 to 69 who had never had a heart attack, then followed them for seven years.

Compared to those who slept 6 to 9 hours per night, those who slept fewer than six hours were 20 percent more likely to have a heart attack during the study period. Those who slept more than nine hours were 34 percent more likely.

When the researchers looked only at people with a genetic predisposition to heart disease, they found that sleeping between six and nine hours nightly cut their risk of having a heart attack by 18 percent.

"It's kind of a hopeful message, that regardless of what your inherited risk for heart attack is, sleeping a healthy amount may cut that risk just like eating a healthy diet, not smoking, and other lifestyle approaches can," said lead author Iyas Daghlas, a medical student at Harvard.

Previous research has long suggested an association between sleep and heart health, but because those studies were observational - looking at different groups to see who develops disease - it's been difficult to determine whether poor sleep causes heart problems or vice-versa.

Many factors can influence both heart health and sleep, making it even more difficult to determine cause and effect.

For the new study, the researchers used the massive UK Biobank dataset and combined observational and genetic research to ask the question in a different way.

After taking into account 30 other factors - including body composition, physical activity, socioeconomic status and mental health - they found that sleep duration, in and of itself, influenced heart attack risk independently of these other factors.

The farther people fell outside the 6 to 9-hour range, the more their risk increased. For instance, people who slept five hours per night had a 52 percent higher risk of heart attack than those who slept 7 to 8, while those who slept 10 hours nightly were twice as likely to have one.

Using a method called Mendelian randomization, the researchers then looked at participant's genetic profiles to determine whether those who were genetically predisposed to short sleep were more likely to have heart attacks. Twenty-seven genetic variants have been associated with short sleep.

They saw similar patterns emerge and found that genetically influenced short sleep duration was a risk factor for heart attack.

"This gives us even more confidence that there is a causal relationship here - that it is sleep duration, not something else, influencing heart health," Vetter said.

The study did not explore the mechanism by which short or long sleep may boost heart attack risk, but previous studies have pointed to a few explanations. Sleeping too little can impact the lining of the arteries, or endothelium, impact bone marrow development of inflammatory cells, but also lead to poor dietary choices and ill-timed eating (which can in turn impact weight and, thus, heart health). Sleeping too much may also boost inflammation in the body, which is also associated with cardiovascular disease.

The authors hope the study will increase awareness about sleep's heart-health benefits among physicians, public health agencies and the public.

"Just as working out and eating healthy can reduce your risk of heart disease, sleep can too," said Vetter.

ITHACA, NY, SEPTEMBER 2, 2019 -- Over-fertilization of agricultural fields is a huge environmental problem. Excess phosphorus from fertilized cropland frequently finds its way into nearby rivers and lakes. A resulting boom of aquatic plant growth can cause oxygen levels in the water to plunge, leading to fish die-offs and other harmful effects.

Researchers from Boyce Thompson Institute have uncovered the function of a pair of plant genes that could help farmers improve phosphate capture, potentially reducing the environmental harm associated with fertilization.

The work was published in Nature Plants on September 2.

The discovery stems from Maria Harrison's focus on plants' symbiotic relationships with arbuscular mycorrhizal (AM) fungi. Harrison is the William H. Crocker Professor at BTI and an adjunct professor in Cornell University's School of Integrative Plant Science.

AM fungi colonize plant roots, creating an interface where the plant trades fatty acids for phosphate and nitrogen. The fungi also can help plants recover from stressful conditions, such as periods of drought.

But feeding the AM fungi with fatty acids is costly, so plants don't let this colonization go unchecked.

To discover how plants control the amount of fungal colonization, Harrison and Lena Müller, a postdoctoral scientist in her lab, looked at genes that encode short proteins called CLE peptides in the plants Medicago truncatula and Brachypodium distachyon.

CLE peptides are involved in cellular development and response to stress, and they are present throughout the plant kingdom, from green algae to flowering plants.

The researchers found that two of these CLE genes are key modulators of AM fungal symbiosis. One gene, called CLE53, reduces colonization rates once the roots have been colonized. Another gene, CLE33, reduces colonization rates when there is plenty of phosphate available to the plant.

"Being able to control fungal colonization levels in plant roots and maintain the symbiosis even in higher phosphate conditions might be useful to a farmer," Harrison said. "For example, you may want the other beneficial effects of AM fungi, like nitrogen uptake and recovery from drought, as well as further uptake of phosphate"

"You might be able to achieve these benefits by altering the levels of these CLE peptides in the plants," Harrison added.

Müller found that the CLE peptides act through a receptor protein called SUNN. In collaboration with Harro Bouwmeester and Kristyna Flokova of the University of Amsterdam, she found that the two CLE peptides modulate the plant's synthesis of a compound called strigolactone.

Plant roots exude strigolactone into the soil, and the compound stimulates AM fungi to grow and colonize the root. Once the roots are colonized or there is plenty of phosphate, the CLE genes suppress the synthesis of strigolactone, thus reducing any further colonization by the fungi.

"In the early 2000's, researchers found that plants had a way to measure and then reduce colonization," Müller said. "But until now, nobody really understood the molecular mechanism of that dynamic."

The researchers' next steps will include figuring out the molecules that turn on the CLE genes in response to colonization and high phosphate levels.

Müller also plans to compare the two CLE peptides from this study with additional CLE peptides that have different functions.

"The CLE peptides are all so similar but they have completely different functions," Müller said. "It will be very interesting to see why that is."

Any effect that assisted reproduction technology has on babies' genes is largely corrected by adulthood, new research led by the Murdoch Children's Research Institute has found.

Published in the latest edition of Nature Communications, the study* found events that occur in early development, including ovarian stimulation, manipulation of the embryo and the extra hormones common in fertility treatment cycles, can impact gene health or epigenetics but these effects are short lived.

Epigenetics is a process that controls how genes are turned on and off. Diet and other external environmental influences can play a role in this gene expression.

The study was designed to see how often epigenetic changes occur due to assisted reproduction technology and whether there were any differences in these changes from birth to adulthood.

"In two independent groups, we found the same effects of assisted reproduction on genes when examining heel prick blood spots collected soon after birth," study senior MCRI Professor Richard Saffery says. "These epigenetic changes were not evident in the adult blood samples."

MCRI Professor Jane Halliday, who established the cohort, and has studied the health of these individuals in adulthood, said assisted conception is linked to a small increased risk of preterm birth, low birth weight, being small for gestational age or perinatal mortality.

"Given the interventions associated with assisted reproduction technology at the time of conception, there were concerns that epigenetic changes may be taking place, silencing important genes and resulting in a heightened risk of health problems," she says.

More than seven million people around the world, including more than 200,000 people in Australia have been conceived through assisted reproduction technology since 1978.

Dr Boris Novakovic, who performed most of the analysis for the study, says that despite the expansion of assisted reproduction technology worldwide, few studies have investigated the potential underlying effects on genes.

"Previous studies have found some epigenetic changes in embryos grown in labs. However, no study has looked for these changes in the same individuals at birth and adulthood as we have done," he says.

"Our results are reassuring for families as they suggest that environment and lifestyle experienced from birth can repair any epigenetic deviations associated with fertility treatments."

The study looked at a cohort of 158 Australians aged 22-35 years conceived through assisted reproduction technology (IVF and GIFT**) and 75 people conceived naturally.

Dr Novakovic says more studies of larger sample sizes are needed in order to replicate the current findings.

Researchers from the University of Melbourne, Monash University, University of Turku, Turku University Hospital, Victorian Assisted Reproductive Treatment Authority, The Royal Women's Hospital, The Royal Children's Hospital, Hudson Institute of Medical Research, and the Monash IVF Group also contributed to the findings.

*Publication: Boris Novakovic, Sharon Lewis, Jane Halliday, Joanne Kennedy, David P Burgner, Anne Czajko, B Kim, Alex Sexton-Oates, Markus Juonala, Karin Hammarberg, David J Amor, Lex W Doyle, Sarah Ranganathan, Liam Welsh, Michael Cheung, John McBain, Robert McLachlan and Richard Saffery. 'Assisted reproductive technologies induce limited epigenetic variation at birth that largely resolves by adulthood', Nature Communications.

**80 per cent of participants were born using IVF and 20 per cent using GIFT. GIFT involves removing a woman's eggs, mixing them with sperm, and immediately placing them into a fallopian tube, unlike IVF where the fertilised egg is grown in a lab for a few days before being transferred to the womb.

Protein variations that result from the process of alternative splicing control the identity and function of nerve cells in the brain. This allows organisms to build a highly complex neuronal network with only a limited number of genes. The study describing a detailed map of neuronal splicing conducted by a research team at the Biozentrum, University of Basel, has now been published in Nature Neuroscience.

Our brain consists of hundreds, if not thousands, of different types of nerve cells that control our brain functions due to their individual characteristics. But how do the different cell types manage to develop their diverse traits? In a genome-wide analysis, the team led by Prof. Peter Scheiffele at the Biozentrum, University of Basel, has now discovered that alternative splicing leads to a broad range of variants of individual proteins, which ultimately allows to distinguish types of nerve cells.

Alternative splicing determines cell types

Alternative splicing can generate multiple different protein variants from a single gene. In the mouse model, Scheiffele's team investigated splice variants in a panel of neuronal cell types. "We have been able to identify hundreds of splice variants that enable us to differentiate between different types of neurons," says Scheiffele. "There are unique repertoires of variants in each nerve cell type."

These repertoires of splice variants significantly shape the identity and function of nerve cells. "Although all neuronal cell types contain the same set of genes, even closely-related cell types produce different splice variants," explains Scheiffele. In particular, proteins located at the neuronal contact points - the synapses, which mediate the transmission and processing of information - are extremely diverse. Thus, the splicing process also controls the function of the neuronal circuits in the brain.

Data platform for scientists

The generation and analysis of the extensive data sets is part of the EU-funded project "SPLICECODE". In collaboration with the "Center for Scientific Computing" (sciCORE), a user-friendly website has been set up which allows scientists worldwide to investigate the role of individual splice variants in brain function.

Drug-resistant bacteria responsible for deadly hospital-acquired infections shut out antibiotics by closing tiny doors in their cell walls.

The new finding by researchers at Imperial College London could allow researchers to design new drugs that 'pick the locks' of these closed doors and allow antibiotics into bacterial cells. The result is published today in Nature Communications.

The bacterium Klebsiella pneumoniae causes infections in the lungs, blood and wounds of those in hospitals, and patients that have compromised immune systems are especially vulnerable. More than 20,000 K. pneumoniae infections were recorded in UK hospitals in the past year.

Like many bacteria, K. pneumoniae is becoming increasingly resistant to antibiotics, particularly a family of drugs called Carbapenems. Carbapenems are used as antibiotics in hospitals when others have failed or are ineffective.

Therefore, rising resistance to Carbapenems could dramatically affect our ability to cure infections. For this reason, Carbapenem-resistant K. pneumoniae and are classified as 'critical' World Health Organization Priority 1 organisms.

Now, the team from Imperial has discovered one mechanism by which K. pneumoniae is able to resist Carbapenems. Antibiotics usually enter the K. pneumoniae bacteria through surface doorways known as pores. The team investigated the structure of the pores and showed that by shutting these doorways K. pneumoniae becomes resistant to multiple drugs, since antibiotics cannot enter and kill them.

First author, Dr Joshua Wong, from the Department of Life Sciences at Imperial, said: "The prevalence of antibiotic resistance is increasing, so we are becoming more and more reliant on drugs like Carbapenems that work against a wide range of bacteria.

"But now with important bacteria like K. pneumoniae gaining resistance to Carbapenems it's important we understand how they are able to achieve this. Our new study provides vital insights that could allow new strategies and drugs to be designed."

The team compared the structures of K. pneumoniae bacteria that were resistant to Carbapenems to those that weren't, and found the resistant bacteria had modified or absent versions of a protein that creates pores in the cell wall. Resistant bacteria have much smaller pores, blocking the drug from entering.

The closed doors aren't all good news for bacteria. They also mean that the bacteria can take in fewer nutrients, and tests in mice showed that the bacteria grow slower as a result.

However, the advantage in terms of avoiding antibiotics outweighed the negative impact of slower growth for the bacteria, allowing them to maintain a high level of infection.

The project was conducted in close collaboration with Dr Konstantinos Beis from the Department of Life Sciences, who is based at the Research Complex at Harwell in Oxfordshire.

The team was led by Professor Gad Frankel, from the Department of Life Sciences at Imperial, who said: "The modification the bacteria use to avoid antibiotics is difficult to get around. Any drugs to counteract this defence mechanism would likely also get blocked out by the closed doors.

"However, we hope that it will be possible to design drugs that can pick the lock of the door, and our data provides information to help scientists and pharmaceutical companies make these new agents a reality."

As resistant bacteria are weaker, these results suggest that the pressure posed by the extensive use of Carbapenems in hospital settings is a major driver in the spread of these superbugs. The study provides a direct scientific basis for the implementation of restrictive prescribing policies that would minimise the use of broad-spectrum agents such as Carbapenems.

The team are all part of the Antimicrobial Research Collaborative at Imperial, a multidisciplinary centre that addresses antibiotic resistance by advancing basic research, translating research into new prevention strategies and healthcare interventions, and informing public health policy.