Culture

Breakthrough in understanding of magnetic monopoles could signal new technologies

A breakthrough in understanding how the quasi-particles known as magnetic monopoles behave could lead to the development of new technologies to replace electric charges.

Researchers at the University of Kent applied a combination of quantum and classic physics to investigate how magnetic atoms interact with each other to form composite objects known as 'magnetic monopoles'.

Basing the study on materials known as Spin Ices, the team showed how the 'hop' of a monopole from one site in the crystal lattice of Spin Ice to the next can be achieved by flipping the direction of a single magnetic atom.

Although in theory at low temperatures the magnetic atoms do not have enough energy to do this, the team found that as a monopole arrives in a lattice site, it induces changes in the fields acting on the magnetic atoms surrounding it which enable them to 'tunnel' through the energy barrier.

Dr Quintanilla of the University's School of Physical Sciences said: 'We found evidence that this mysterious low-temperature hopping is achieved through quantum tunnelling: a phenomenon that allows a quantum object to overcome an obstacle which would, according to the classical laws of physics, require more energy than the system has available to it.

'We showed that the magnetic atoms forming a monopole experience fields that are transverse to their own, which in turn induce the tunnelling. We compute the monopole hopping rates resulting from this scenario and find them to be broadly consistent with available observations.'

The researchers suggest that this better understanding of monopole motion in spin ice materials may enable future technologies based on moving magnetic monopoles, rather than electric charges.

First study to examine the association of physical activity with patient survival in advanced, metastatic colorectal cancer

Even low-intensity exercise was associated with a reduction in progression free survival

BOSTON - Patients with metastatic colorectal cancer who engaged in moderate exercise while undergoing chemotherapy tended to have delayed progression of their disease and fewer severe side effects from treatment, according to the results of a new study.

Even low-intensity exercise, such as walking four or more hours a week, was associated with a nearly 20 percent reduction in cancer progression or death over the course of the six-year study, said researchers from Dana-Farber Cancer Institute and Brigham and Women's Hospital, reporting in the Journal of Clinical Oncology. The analysis hinted at a possible lengthening of survival in patients who reported greater physical activity, but the data were not statistically significant.

"What we found was that people who engaged in some type of physical activity had a statistically significant improvement in progression-free survival (PFS)," said Jeffrey A. Meyerhardt, MD, MPH, of Dana-Farber, senior author of the study. "While there may also be an impact on overall survival, it was not statistically significant - and should be studied further."

"Physically active patients in our study also appeared to tolerate chemotherapy better," said Brendan Guercio, MD, first author of the study which was conducted while he was working as a hospitalist at Brigham and Women's. "Total physical activity equivalent to 30 or more minutes of moderate daily activity was associated with a 27 percent reduction in severe treatment-related toxicities."

Previous studies have found that regular exercise can reduce the risk of disease recurrence and death from colon cancer that has not metastasized to other parts of the body. Researchers say this is the first study to examine associations of physical activity with survival in advanced, metastatic colorectal cancer. Patients participated in a phase 3 study of chemotherapy for advanced colorectal cancer conducted by the Alliance for Clinical Trials in Oncology and sponsored by the National Cancer Institute. Within a month after beginning treatment, patients were invited to complete a questionnaire about their average physical activity over the previous two months. The final number of participants included 1,218 patients. While the data are significant, further research with a randomized prospective trial will help validate the results, the researchers said.

Based on the patients' descriptions, researchers quantified their physical activity in terms of metabolic equivalent task (MET)-hours per week - a standard measure used in research studies of exercise. Vigorous activity was defined as any activity requiring six or more METs, such as running, biking, tennis, skiing, or lap swimming. Non-vigorous activities included walking, climbing stairs, or yoga.

Analysis of the data revealed a statistically significant difference in PFS - the length of time after the patient completed the questionnaire before the cancer progressed or the person died. The difference in PFS was almost 20 percent in favor of those who exercised more.

Meyerhardt added that the findings "help justify encouraging patients to exercise and referring patients to physical therapists or programs like the YMCA LIVESTRONG program that does small group training for patients with cancer."

The analysis also found that patients who engaged in 18 or more MET-hours per week of activity had a 15 percent improvement in overall survival (death from any cause) than patients who engaged in less than three MET-hours per week of activity. However, that difference was not statistically significant, meaning it could have resulted from chance.

A higher standard of wastewater treatment in the UK has been linked to substantial improvements in a river's biodiversity over the past 30 years, ensuring a welcome success story for wildlife, say scientists.

The Centre for Ecology & Hydrology analysed data from the regular monitoring of both chemicals and invertebrates in the River Ray in Wiltshire by the Environment Agency and its predecessors between 1977 and 2016. This Thames tributary is downstream from Swindon's large wastewater treatment plant.

The Defra-funded study found that, since 1991, there has been a steady increase in both the diversity and abundance of freshwater invertebrates, which play a vital and varied role in an ecosystem's food chain1.

The water is cleaner due to a reduction in ammonia (a chemical present in human sewage that is potentially toxic to animals) plus an increase in oxygen levels (as a result of less organic matter being discharged into the river).

The findings, published in the journal Environmental Toxicology & Chemistry, echo other research2 which indicates there has been an increase in the biodiversity of many rivers across the UK. This latest analysis, which carefully examines four decades of chemistry and invertebrates data, offers an explanation why this has happened.

Professor Andrew Johnson of the Centre for Ecology & Hydrology, who led the study, explains: "There was a marked increase in the diversity and abundance of freshwater invertebrates on the River Ray immediately after 1991 and there has been a steady improvement since then. Therefore, we have identified Thames Water's investment in improved treatment to comply with the EU Urban Wastewater Directive, which was adopted that year, as the crucial turning point."

In practice, the implementation of the directive in the UK3 meant many large wastewater treatment plants including that at Swindon had to switch to the 'activated sludge' process, which is a more efficient way of dealing with large amounts of sewage water than the older 'trickling filter' system.

Professor Johnson says the previously lower standard of wastewater treatment, exacerbated by the increase in sewage produced by rapidly growing populations of towns like Swindon, had a negative impact on biodiversity. Many UK rivers had a low abundance of invertebrates and fish back in the 1960s, 70s and 80s.

Professor Johnson adds: "The fact there has been a continual increase in biodiversity in the Ray despite it being a small river taking the entire treated wastewater of a large town of 200,000 residents is extremely encouraging. It indicates that even for rivers with a very high wastewater content their fortunes can be turned around.

"It is wonderful to think that people walking by the Ray are seeing returning species of damselflies and caddisflies that they weren't seeing 30 years ago."

The privatisation of the UK water industry in 1989 meant the new water companies could borrow money to invest in their treatment plants to comply with higher standards, overseen by independent regulators. The industry spent £26 billion on various wastewater improvements between 1990 and 2015, according to Defra figures.

The European Union had been considering the merits of charcoal filtering as an additional, final stage of the wastewater treatment process to remove pharmaceuticals - a measure that could cost a total of £30 billion to introduce at treatment plants in England and Wales.4

However, the analysis by CEH found the trial introduction of charcoal filtering at Swindon between 2008 and 2014 resulted in no significant increase in the diversity and abundance of freshwater invertebrates, over and above the existing improving trend.

New Rochelle, NY, August 12, 2019--An optimized and newly engineered form of the adeno-associated vector 9 (AAV9) vector used to deliver the galactosylceramidase gene to a mouse model of the inherited neurogenerative and rapidly fatal form of Krabbe dis-ease improved clinical symptoms and prolonged median survival by 275%. Two-day old mice treated with a single injection of the systemic gene therapy had a significant increase in median life span to 150 days, compared to 41 days for the untreated mice, as reported in the study published in Human Gene Therapy, a peer-reviewed journal from Mary Ann Liebert, Inc., publishers. Click here to read the full-text article free on the Human Gene Therapy website through September 12, 2019.

The article entitled "An Engineered Galactosylceramidase Construct Improves AAV Gene Therapy for Krabbe Disease in Twitcher Mice" was coauthored by Dongsheng Duan, Steven LeVine, and colleagues from the University of Missouri (Columbia), Uni-versity of Missouri School of Medicine and College of Veterinary Medicine, and Univer-sity of Kansas Medical Center (Kansas City).

The researchers describe the construction and characterization of the specially engineered AAV9 vector, built on the codon-optimized mouse galactosylceramidase coding se-quence, and designed for improved protein delivery to the central nervous system and enhanced secretion of the galactosylceramidase enzyme. At 5 weeks of age, the treated mice had better body weight and motor function than the untreated mice. The longest-lived treated mouse survived to 180 days.

"This work shows dramatic in vivo proof-of-principle, indicating a robust therapeutic ef-fect from this optimized vector," says Editor-in-Chief Terence R. Flotte, MD, Celia and Isaac Haidak Professor of Medical Education and Dean, Provost, and Executive Deputy Chancellor, University of Massachusetts Medical School, Worcester, MA.

Research reported in this publication was supported by the National Institutes of Health un-der Award NumbersP30HD02528, 9P2OGM104936, and S10RR027564. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

"Birds of a feather flock together" or rather "opposites attract"? The recently published study on male macaques in Thailand speaks for the former: Behavioral biologists from the German Primate Centre - Leibniz Institute for Primate Research and psychologists from the University of Göttingen have observed that the more similar male Assamese macaques are in their personality, the closer they get and the stronger their social bonds. The scientists were able to rule out the possibility that the causality works the other way round, i.e. that close partners would become more and more similar over time, because the males' personality remained stable even if they migrated between groups and thus changed their social partners. It is suggested that this behavior provides an evolutionary advantage: If the friend has a similar personality, this facilitates communication and coordination and thus cooperation in critical situations (Animal Behaviour).

Social bonds in animals are defined as stable, equal and cooperative relationships, comparable to human friendships. Such bromance among unrelated adult males has been described in a few species. A close relationship with another male can be advantageous, as it promises support in critical situations, such as aggressive conflicts with other group mates. Personality homophily, i.e. the tendency to like others if they are similar, has been described both in humans and in a few species of animals. The advantage is obvious: The more similar our counterpart is to us, the better we can predict his reactions. This creates trust. But what are the characteristics that should be particularly similar for a relationship to succeed?

Within the framework of the Research Training Group "Understanding Social Relationships" of the German Primate Centre and the University of Göttingen, the team around PhD student Anja Ebenau obtained data on 24 free-living male Assamese macaques in the Phu Khieo Wildlife Sanctuary in Thailand over a period of almost two years. In close cooperation with the psychologists Lars Penke and Christoph von Borell, the individual personality of the males was described from detailed quantitative behavior protocols and questionnaires like those used in human psychology. The analyses demonstrate that the similarity of two males in the emergent personality dimensions gregariousness, aggressiveness, sociability, vigilance and confidence could be determined. It was found that the stronger the bond between two males, the more similar the animals were in terms of gregariousness. Notably, it did not matter whether the individuals are highly gregarious or not, they only had to be similar: Two rather solitary animals that avoid others can be just as close friends as two socially very central individuals.

In order to exclude the possibility that it is not the other way around, i.e. that friends become more and more similar in their personality over time, the characteristics of monkeys were examined before and after they had migrated to a new group and found new social partners there. It turned out that the personality of the animals remained rather stable, i.e. did not change with a new friend.

"We assume that personality homophily is a general biological principle that is deeply rooted in the evolution of humans and animals," said Oliver Schülke, scientist in the Department of Behavioral Ecology at the University of Göttingen and head of the study. Individuals whose friends have a similar character have an advantage. "One reason might be that similar personalities also have similar needs, understand each other particularly well, communicate effectively and are therefore more successful cooperation partners," said Schülke. A follow-up study will investigate whether coalitions of similar personalities are actually more successful in in conflicts with other males and thus defend a high rank of dominance for a longer period of time.

The hippocampus is a part of the brain that plays an important role in memory

How hippocampal time cells are generated to remember the sequence of items in our memory has been found by researchers at the University of Warwick

Now that we understand how the order events is stored in the brain, we now have a better foundation for exploring brain dysfunctions relating to memory, including the changes in memory in healthy ageing, Alzheimer's disease, and the memory for sad events in depression.

For centuries understanding how the order of events is stored in memory has been a mystery. However, researchers from the Department of Computer Science at the University of Warwick have worked out how the order of events in memory could be stored and later recalled in the hippocampal memory system in the brain.

The new research published in the journal 'Cell Reports' titled 'The Generation of Time in the Hippocampal Memory System' builds on the discovery by Nobel prize winners May-Britt and Edvard Moser that an input region to the hippocampus - the lateral entorhinal cortex (LEC) - has time ramping cells that slowly change their rates of activity over hundreds of seconds; and on the discovery that hippocampal time cells fire at separate times in a sequence.

In the new research a theory and model was developed of how entorhinal time ramping cells produce hippocampal time cells which can be associated with places and people to help remember the sequence in which the people and places occurred during the remembered episode.

The theory demonstrates how we can remember what happened to us during the day in the correct order, and how we can provide an eye witness memory for a series of events.

The researchers show how the transformation of the code of the memory between the two brain areas - the LEC and the hippocampus - is achieved by a well-known type of neural network present in the brain, a competitive network.

The competitive network learns to allocate hippocampal neurons to respond to different combinations of the firing of the time ramping cells, and thus a temporal sequence can be formed.

The theory also accounts for the slow activity changes in time ramping cells by adaptation mechanisms, and shows how spontaneous memory recall can occur with the correct order of items in the memory.

Understanding the brain's memory and related mechanisms is helping not only to understand disorders of memory, but also is providing new approaches to understanding and treating mental disorders including depression and schizophrenia.

Further details of Prof. Rolls' approach to a better understanding of depression building on these foundations is provided in his new book, 'The Brain, Emotion and Depression' published in 2018. It shows for example how sad memories dominate in depression, and provides suggestions for treatment.

Professor Edmund Rolls from the Department of Computer Science at the University of Warwick comments:

"This is an exciting time for research on the brain: we are starting to understand the underlying brain mechanisms for many types of behaviour including memory and emotion, and this has great potential for better treating brain disorders."

New research, published today in Nature, reveals how increasing brain stiffness as we age causes brain stem cell dysfunction, and demonstrates new ways to reverse older stem cells to a younger, healthier state.

The results have far reaching implications for how we understand the ageing process, and how we might develop much-needed treatments for age-related brain diseases.

As our bodies age, muscles and joints can become stiff, making everyday movements more difficult. This study shows the same is true in our brains, and that age-related brain stiffening has a significant impact on the function of brain stem cells.

A multi-disciplinary research team, based at the Wellcome-MRC Cambridge Stem Cell Institute (University of Cambridge), studied young and old rat brains to understand the impact of age-related brain stiffening on the function of oligodendrocyte progenitor cells (OPCs).

These cells are a type of brain stem cell important for maintaining normal brain function, and for the regeneration of myelin - the fatty sheath that surrounds our nerves, which is damaged in multiple sclerosis (MS). The effects of age on these cells contributes to MS, but their function also declines with age in healthy people.

To determine whether the loss of function in aged OPCs was reversible, the researchers transplanted older OPCs from aged rats into the soft, spongy brains of younger animals. Remarkably, the older brain cells were rejuvenated, and began to behave like the younger, more vigorous cells.

To study this further, the researchers developed new materials in the lab with varying degrees of stiffness, and used these to grow and study the rat brain stem cells in a controlled environment. The materials were engineered to have a similar softness to either young or old brains.

To fully understand how brain softness and stiffness influences cell behavior, the researchers investigated Piezo1 - a protein found on the cell surface, which informs the cell whether the surrounding environment is soft or stiff.

Dr Kevin Chalut, who co-led the research, said: "We were fascinated to see that when we grew young, functioning rat brain stem cells on the stiff material, the cells became dysfunctional and lost their ability to regenerate, and in fact began to function like aged cells. What was especially interesting, however, was that when the old brain cells were grown on the soft material, they began to function like young cells - in other words, they were rejuvenated."

"When we removed Piezo1 from the surface of aged brain stem cells, we were able to trick the cells into perceiving a soft surrounding environment, even when they were growing on the stiff material", explained Professor Robin Franklin, who co-led the research with Dr Chalut. "What's more, we were able to delete Piezo1 in the OPCs within the aged rat brains, which lead to the cells becoming rejuvenated and once again able to assume their normal regenerative function".

Dr Susan Kohlhaas, Director of Research at the MS Society, who part funded the research, said: "MS is relentless, painful, and disabling, and treatments that can slow and prevent the accumulation of disability over time are desperately needed. The Cambridge team's discoveries on how brain stem cells age and how this process might be reversed have important implications for future treatment, because it gives us a new target to address issues associated with aging and MS, including how to potentially regain lost function in the brain."

Bottom Line: This observational study examined whether daytime and nighttime blood pressure (BP) levels measured outside a clinical setting are associated with cardiovascular disease (CVD) and risk of death. Blood pressure levels measured at a clinic may not accurately reflect levels that a person experiences at home, work or while asleep. Using data from the Jackson Heart Study, which is designed to identify CVD risk factors among African American individuals, this analysis included 1,034 adults who had average daytime and nighttime BP levels calculated based on measurements from a BP monitor on their arm that took readings every 20 minutes during a 24-hour period. During follow-up there were 113 CVD events (including coronary heart disease and stroke) and 194 deaths. The authors report that individuals with higher levels of daytime and nighttime systolic BP had an associated increased risk for CVD events and death, independent of BP levels measured in the clinic. The increase in CVD risk was larger among participants not taking BP medication. The findings suggest monitoring daytime and nighttime BP outside the clinic during a 24-hour period may help to identify African Americans at increased risk for CVD. A limitation of the study to consider is that 24-hour BP monitoring was performed only once among participants, and the researchers were unable to assess whether changes in daytime and nighttime BP during follow-up were associated with outcomes.

Authors: Yuichiro Yano, M.D., Ph.D., Duke University, Durham, North Carolina, and coauthors.

(doi:10.1001/jamacardio.2019.2845)

Editor's Note: The article includes conflict of interest and funding/support disclosures. Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.

Bottom Line: Whether the experience of being a refugee increases the probability of developing a mental disorder such as schizophrenia was the focus of this study, a systematic review and meta-analysis that combined the results of nine studies involving 540,000 refugees in Denmark, Sweden, Norway and Canada. The relative risk of refugees developing nonaffective psychosis (which includes several mental disorders such as schizophrenia) was compared with the risk of natives of the host country and nonrefugee migrants there. Study authors report the refugee experience may be a risk factor in nonaffective psychosis in migrants. Limitations of the research include that with the exception of Canada, the studies included in the analysis were all from Scandinavian countries, which may limit the generalizability of the findings to other countries.

Authors: Lasse Brandt, M.D. and Jonathan Henssler, M.D., Charité University Medicine Berlin, Germany, and coauthors

(doi:10.1001/jamapsychiatry.2019.1937)

Editor's Note: The article includes conflict of interest disclosures. Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.

In high school chemistry, we all learned about chemical reactions. But what brings two reacting molecules together? As explained to us by Einstein, it is the random motion of inert molecules driven by the bombardment of solvent molecules. If brought close enough together, by random chance, these molecules may react.

Capturing the motion of single molecules is achieved by a method known as Fluorescence Correlation Spectroscopy (FCS). The catch? It takes very many detections of light particles, photons, emitted by single molecules to get a clear picture of molecular motion.

As an illustration, think of a political poll. At any given time in a campaign cycle, polls are used to predict the outcome of an upcoming election. But how many voters must we interrogate to get an accurate prediction and, given how time-sensitive polling information is, how quickly can we probe the nation's political leanings? Asking every voter in every state would yield accurate results but be too costly in time and dollars. For practical reasons, we need to take a sample of voters and efficiently exploit all information contained in that sample. The voters in this illustration are our proverbial photons here.

The long times needed to acquire data in FCS is just like the naïve polling strategy highlighted earlier. It takes too long, and the chemistry we care about learning might already be done. Furthermore, exposing samples to the laser for long periods of time may result in the photochemical damage of molecules under study, preventing the widespread use of FCS in biological research.

"Single-molecule fluorescence techniques have revolutionized our understanding of the dynamics of many critical molecular processes, but signals are inherently noisy and experiments require long acquisition times," explained Marcia Levitus, an associate professor in the School of Molecular Sciences and the Biodesign Institute.

This work leverages new tools from data science in order to make every photon detected count and refine our picture of molecular motion.

"New mathematical tools make it possible to think about old but powerful experiments in a new light," said Steve Pressé, lead author on the study and joint professor in the Department of Physics and School of Molecular Sciences at ASU at Arizona State University.

A paper published in Nature Communications by Pressé and collaborators now addresses these issues using tools from data science and, more specifically, Bayesian nonparametrics -- a type of statistical modeling tool so far largely used outside the natural sciences. Levitus adds "Old strategies limited our ability to probe anything but slow processes, leaving a vast number of interesting biological questions involving faster chemical reactions out of reach. Now we can begin asking questions on processes resolved in short order."

Whether they're aiming to avoid high financial management fees, control their own investments, or enjoy the thrill of playing the market, more consumers are opening investment accounts and making their own stock picks.

But a new study from the UBC Sauder School of Business has found that less experienced investors are failing to diversify -- and could be putting themselves at serious financial risk. The effect is so pronounced that many amateur investors would be better off choosing stocks at complete random.

For the study, researchers first asked participants to create portfolios of financial assets using tables of previous returns, and then assessed the participants' level of financial literacy. The researchers found the investors with poor financial literacy tended to choose positively correlated assets - for example, stocks in oil companies and forestry -- which tend to fluctuate in value together.

"An amateur investor might buy stocks in lumber, mining, oil and banks, and believe they are diversifying because they're investing in different companies and sectors," said David Hardisty, study co-author and assistant professor at UBC Sauder. "But because all of those equities tend to move in unison, it can be quite risky, because all the assets can potentially plunge at the same time."

More experienced investors know to hedge their bets by including negatively correlated assets, which are likely to move down when others go up -- or uncorrelated assets (ones that move up and down independently of the others) in order to mitigate losses.

The researchers also found that the amateur investors were actively preferring correlated assets because they seemed less complicated and more predictable.

"If it seems predictable, it seems safer and easier to track," explains Hardisty. "Whereas if you have a combination of assets that all go in different directions, it seems chaotic, unpredictable and riskier."

Ironically, when the study participants were encouraged to take more risk when creating a portfolio, the amateur investors ended up making safer, more diversified selections, compared to when they were encouraged to avoid risk.

"This shows that amateur investors rely on a definition of risk that greatly differs from the objective definition of portfolio risk," said Yann Cornil, assistant professor at UBC Sauder and co-author of the study. "This can lead them to make objectively low-risk investments when they intend to take risk, or to make high-risk investments when they intend to reduce risk."

The researchers found that when amateur investors are shown the aggregate returns of portfolios (and not merely the returns of each asset composing the portfolio), they can see that having negatively correlated or uncorrelated assets is the winning investment strategy -- even if it might seem counterintuitive to play both sides.

"If you don't diversify, when one asset does well the other ones are also going to do well. But if one does badly it's likely the others will all do badly -- and in investing, you want to avoid those worst-case scenarios," says Hardisty, who hopes the research will encourage investors to educate themselves on investment strategies, and use the diversification tools that online investment services provide to properly balance their portfolios.

"In the best-case scenario you could make lots of money and have an extra vacation or buy a car or something like that," he explains of the positively correlated accounts. "But if your whole portfolio crashes you could risk losing your life savings. So, the best-case scenario isn't that much better, but the worst-case scenario is a whole lot worse."

How many stars are there in the observable universe? It was once deemed an impossible question, but astronomers have gleaned an answer--about one billion trillion of them.

Now, scientists at Harvard Medical School and Joslin Diabetes Center have embarked on what could be a similarly daunting quest: How many genes are there in the human microbiome?

In a study published Aug. 14 in the journal Cell Host & Microbe, a team of microbiologists and bioinformaticians offer a first glimpse of the array of genes that make up the bacterial universe residing in each of us.

The findings thus far: There may be more genes in the collective human microbiome than stars in the observable universe, and at least half of these genes appear to be unique to each individual--a diversity far exceeding the researchers' expectations.

The research is believed to be the largest analysis of its kind to date and the first one to include DNA samples from bacteria that reside both in the mouth and the gut. Past studies have focused on one or the other.

Even so, the work marks only the beginning of efforts to analyze the entire genome of the human microbiome.

"Ours is a gateway study, the first step on a what will likely be a long journey toward understanding how differences in gene content drive microbial behavior and modify disease risk," said study first author Braden Tierney, a graduate student at Harvard Medical School.

Microbial fingerprinting for more precise therapies

Scientists estimate that the human microbiome--the collective body of microbes that populate our guts, mouths, skin and other parts of the body--contains trillions of bacteria, most of them harmless, many beneficial and some disease causing. Mounting evidence has revealed the role of these microbes as powerful modulators of disease and health. Changes in both bacterial count and bacterial content have been linked to development of conditions ranging from garden variety dental caries and gut infections to more serious ones, including chronic inflammatory bowel disease, diabetes and multiple sclerosis.

Most research to date has focused on mapping the types of bacteria that inhabit our bodies in an effort to determine whether and how the presence of a given bacterial species might affect disease risk. By contrast, the new research delves far deeper, looking at the genes that make up the various microbial species and strains.

Studying bacterial species alone is bound to provide only partial clues into these microorganisms' role in disease and health, the researchers say. Given that genetic content varies greatly between the same microbes, understanding how and whether individual microbial genes affect disease risk is just as important.

"Just like no two siblings are genetically identical, no two bacterial strains are genetically identical, either," said study co-senior author Chirag Patel, assistant professor of biomedical informatics at Harvard Medical School's Blavatnik Institute. "Two members of the same bacterial strain could have markedly different genetic makeup, so information about bacterial species alone could mask critical differences that arise from genetic variation."

Cataloguing the array of microbial genes could inform the design of precision-targeted treatments, said study senior co-author Alex Kostic, assistant professor of microbiology at Harvard Medical School and an investigator at the Joslin Diabetes Center.

"Such narrowly targeted therapies would be based on the unique microbial genetic make-up of a person rather than on bacterial type alone," Kostic said.

Additionally, profiling the unique genes that make up a person's microbiome could act as a form of microbial fingerprinting that provides valuable clues about past exposures to different pathogens or environmental influences, as well as disease predispositions, Kostic added.

A microbe's evolutionary organ

In the study, the researchers set out to estimate the size of the universe of microbial genes in the human body, gathering all publicly available DNA sequencing data on human oral and gut microbiomes. In total, they analyzed the DNA of some 3,500 human microbiome samples, of which more than 1,400 were obtained from people's mouths and 2,100 from people's guts.

There were nearly 46 million bacterial genes in the 3,500 samples--about 24 million in the oral microbiome and 22 million in the gut microbiome, the researchers found.

More than half of all the bacterial genes (23 million) occurred only once, rendering them unique to the individual. The researchers termed these unique genes "singletons." Of the 23 million singletons, 11.8 million came from oral samples and 12.6 million came from intestinal samples.

Compounding the intrigue, these singleton genes also appeared to behave differently from other genes, the researchers observed: they performed different functions.

Commonly shared genes, the analysis showed, appeared to be involved in more or less basic functions critical to a microbe's day-to-day survival, such the consumption and breakdown of enzymes, energy conversion and metabolism. Unique genes, by contrast, tended to carry out more specialized functions, such as gaining resistance against antibiotics and other pressures and helping to build a microbe's protective cell wall, which shields it from external assaults.

This finding, the team said, suggests that singleton genes are key parts of a microbe's evolutionary survival kit.

"Some of these unique genes appear to be important in solving evolutionary challenges," Tierney said. "If a microbe needs to become resistant to an antibiotic because of exposure to drugs or suddenly faces a new selective pressure, the singleton genes may be the wellspring of genetic diversity the microbe can pull from to adapt."

But what fuels such gene diversity?

The answer to this question remains the subject of further research, the investigators said, but they believe there are at least two important drivers of genetic variation.

One is the microbes' love of freely swapping DNA material with their neighbors--a phenomenon known as horizontal gene transfer. To test this hypothesis, the researchers performed a special type of analysis that detects the shared molecular content between two organisms. To their surprise, they found little evidence that horizontal gene transfer was a main source of genetic uniqueness. Indeed, less than 1 percent of unique genes detected in oral samples and just under 2 percent of those found in the gut appeared to have arisen through this neighborly gene exchange.

Therefore, the researchers hypothesize, another, more powerful, driver of genetic diversity could be bacteria's ability to evolve their DNA rapidly in response to changes in the host environment. The current study was not designed to detect the precise environmental changes that drive this variation, but examples of such changes may include what type of food a person consumes, what medication they use, the lifestyle choices they make, what environmental exposures they encounter and any physiologic changes in the host, including upregulation and downregulation in various host genes or whether a person develops a disease.

So how many genes in the collective human microbiome?

By one calculation, that number could be around 232 million, the study estimated. Another estimate, however, yielded a number comparable to the number of atoms in the universe.

Indeed, the true number may be unknowable, Patel said.

"Whatever it may be, we hope that our catalog, along with a searchable web application, will have many practical uses and seed many directions of research in the field of host-microbe relationships."

Facing the threat of domestic violence, being a survivor of sexual assault, struggling with depression or thoughts of suicide are four topics that are difficult to broach with anyone. Including those who can help you.

A new study reveals up to 47.5 percent of patients who feel they face one or more of these four threats do not disclose this critical information to care providers out of embarrassment, fear of judgement or the possible long-term implications of sharing such information.

Scientists at University of Utah Health, Middlesex Community College, University of Michigan and University of Iowa collaborated on the study, which was published online in JAMA Network Open on August 14.

Understanding how to make patients feel more comfortable with clinicians is key to helping patients address such life-threatening risks, says the study’s senior author Angela Fagerlin, Ph.D.

“For primary care providers to help patients to achieve their best health, they need to know what the patient is struggling with,” says Fagerlin. Patients who withhold they have been sexually assaulted are potentially at risk for post-traumatic stress disorder and sexually-transmitted diseases, she explains. “These are numerous ways providers can help patients with such as getting resources, therapy and treatment.” She is chair of the department of Population Health Sciences at U of U Health and an investigator with the VA Salt Lake City Health System’s Informatics Decision-Enhancement and Analytic Sciences (IDEAS) Center for innovation.

The study reflects responses from over 4,500 people in two national online surveys from 2015. Participants in one survey averaged 36 years old, while participants from the second had a median age of 61. They reviewed a list of types of medically relevant information and asked to indicate whether they had ever withheld this information from a clinician. They were also asked to recall why.

The surveys show that 40 to 47.5 percent of participants chose not to tell their provider that they had experienced at least one of the four threats. Over 70 percent said the reason why was embarrassment or fear of being judged or lectured.

If the patient was female or younger then the odds were higher they would keep this information to themselves. What compounds this issue is that multiple studies in recent years have highlighted how health care providers downplay or fail to take seriously women’s medical complaints.

One limitation noted by the study’s first author Andrea Gurmankin Levy, Ph.D., MBe, a professor in social sciences at Middlesex Community College in Middletown, Connecticut, is that study participants may have not shared in their survey responses all the information they withheld, meaning that this phenomenon may be even more prevalent than the study reveals.

Levy says the survey reinforces the point that there is discomfort and a lack of trust between patients and providers. If patients filled out a questionnaire about sensitive information when they arrive at the provider’s office, might that improve the information flow? She wonders, “Is it easier to tell a piece of paper something sensitive than to look into your clinician’s eyes and say it?”

The next step in Fagerlin and Levy’s research may be contacting patients as they leave an appointment with their provider. Person-to-person interviews would permit the research team to get patients to respond while their memories are still clear.

“If we are there, we can ask them right in the moment so they can more easily put their finger on exactly what was at issue - why they didn’t share such crucial information,” Levy says.

This is the second article by this team to draw upon the 2015 surveys. The first, published in November 2018 revealed that 60 to 80 percent of those surveyed did not share pertinent information with their provider regarding daily issues like diet and exercise. One third did not speak up when they disagreed with their provider’s recommendations.

Both surveys raise concerns about communication and trust between patients and their care givers. Improving rapport falls both on providers’ and patients’ shoulders, the authors say. Providers need to establish an atmosphere where the patient feels neither judged nor rushed but rather are able to share concerns fundamental to their well-being. In addition, patients will benefit by sharing sensitive information with their providers.

Journal

JAMA Network Open

However, while too much inequality is harmful, the researchers also find that complete equality isn't always needed either, in order to bring about the greatest benefits to the public. Some inequality within groups can actually help to ensure that everyone contributes sufficiently to the group, according to the findings. The results could help policy-makers who are responsible for ensuring continuing support for public goods and services such as taxes, healthcare and education.

The research, including co-first authors Dr Oliver Hauser (University of Exeter) and Dr Christian Hilbe (IST Austria), developed a mathematical theory, which took into account to what extent people with differing incomes and productivities were able to cooperate with one another by measuring their willingness to contribute part of their income to the public good.

They discovered that in a very unequal society, those people with higher incomes were less inclined to contribute their proportional share towards public goods and services. This, in turn, also led people on the lowest incomes to contribute less. The breakdown of cooperation under high inequality has implications for funding of essential services for society.

"To ensure our public goods are maintained we need to understand what impact inequality plays," said Dr Hauser. "Many people view inequality as either categorically bad or good, but our research demonstrates that it is more complicated than that. We looked at it in a slightly different way - under what conditions does inequality become harmful and are there cases where it can also be beneficial? The main take-away from our research is that if inequality runs away with us, we are threatening the maintenance of public services. Eventually, too much inequality negatively affects everyone's outcomes - both for the poorest but even the rich."

The researchers showed that in groups of two people with unequal incomes, high inequality reduces the willingness to cooperate. Yet when people have different productivities (such as more experience or skills on a work task), some inequality in incomes can be beneficial to ensure they both continue to contribute.

"We found that when there is some inequality, both people still have enough influence to hold each other accountable for their contributions. We also discovered that those who are highly productive in the task are more motivated to contribute. They will give more of their income - even if that is a large amount," said Dr Hilbe.

"But there is a limit: once the inequality between the two people becomes too large, the influence over the other person is lost and the poorer player is at the mercy of the more powerful rich player. Neither of them has much incentive to cooperate anymore and cooperation breaks down quickly."

The research was also carried out by Professor Martin Nowak (Harvard University) and Professor Krishnendu Chatterjee (IST Austria). The team used game theory, computer simulations and a behavioural experiment to develop their model and find empirical support for its conclusions. Where previous studies have typically looked at individual interactions, the team's modelling technique looked at group interactions across millions of different scenarios which makes the finding of this study unique -- particularly towards understanding societal interaction.

"Our research demonstrates the impact that inequality can have on support for public goods," said Dr. Chatterjee. "We hope that more research will be carried out in this area in the future to better understand the forces that affect our decision-making, particularly in the critical area of supporting the goods and services which serve society. Now we have a more realistic model to emulate societal interaction and the analytical, theoretical and behavioural results are all in excellent agreement. To me, this is the greatest aspect of this paper."

CORVALLIS, Ore. - Researchers at Oregon State University are paving the way toward greater safety for coastal residents and infrastructure by developing a better means of modeling the destructive force of tsunami waves.

Rare but potentially devastating, tsunamis can cause huge damage to coastal infrastructure, with part of the problem tracing to unstable soil around the structures.

Understanding the processes through which a tsunami destabilizes soil is a key to developing engineering techniques that can make buildings, roads and bridges better able to withstand the complicated forces at work within a tsunami.

Collaborators led by Ben Mason and Harry Yeh of the OSU College of Engineering used a centrifuge that once tested Apollo astronauts' resistance to G-forces, attaching a container apparatus filled with soil and water for a scalable simulation of the effects of inundation.

The centrifuge technique replicates inundation physics over a parcel of soil 21 meters long, nearly 10 meters deep and more than 14 meters wide - much larger than can be simulated in a traditional wave tank.

"This is the first time anything like this has been done," Mason said. "The challenge of figuring out the logistics and mechanical engineering to design the container is a pretty striking aspect of this research."

Findings were published in Nature Scientific Reports.

A centrifuge is a device that puts something in rotation around a fixed axis, i.e. swings it in a circle.

"Imagine holding a 5-gallon bucket of water that you start spinning around with, and if you spin fast enough, the water will stay in the bucket regardless of its position, and if you slow down, it will pour out," Mason said. "That's exactly the concept we were working with."

The centrifuge in the study, housed at the UC Davis Center for Geotechnical Modeling after originally being part of NASA's Ames Research Center, has a radius of 9.1 meters. Attached to the arm was the apparatus Mason and collaborators built, part of it filled with water, the other part with soil, with gates to allow for flow simulating a tsunami wave.

"We're trying to mimic the entire process of a tsunami coming onshore and then drawing back," Mason said. "If you're putting soil in a wave flume to try to do that, it gets really, really expensive, and also because at Earth's gravity, you can't have a very deep layer of soil - tsunamis' spatiotemporal scales make it hard to do lab experiments that scale up. That's our key advantage: We can simulate a much larger expanse of earth, and once the box is built, it's much quicker to build soil models in the centrifuge."

"In the centrifuge, we can use high-speed video to learn a lot about what's happening in the soil, such as scouring, and under the surface, how pore water pressure changes with time as the water moves across," Mason said. "All of these things are important for understanding what we can expect the soil around coastal infrastructure to do, and then how do we protect that infrastructure when the next tsunami occurs."