Culture

According to a genome-wide association study involving more than 470,000 people, a person's genetic variants do not meaningfully predict whether they will engage in same-sex sexual behavior. The findings suggest same-sex sexual behavior is influenced by a complex mix of genetic and environmental influences, similar to what's seen for most other human traits. There is no single "gay gene," the study's authors say, and instead there are thousands of genetic variants linked to the trait, each with small effects. Andrea Ganna et al. examined the genetics of individuals who self-reported on whether they had ever engaged in same-sex sexual behavior. The authors analyzed survey responses and performed genome-wide association studies (GWAS) on data from over 470,000 people in the UK Biobank and 23andMe, Inc. The researchers could not find any patterns among genetic variants that could be used to meaningfully predict or identify a person's sexual behavior, they say. "[M]any loci with individually small effects...additively contribute to individual differences in predisposition to same-sex sexual behavior," they write, describing genetic patterns consistent with many personality, behavioral, and physical traits. In their study, only five genetic variants were "significantly" associated with same-sex behavior, and thousands more appear to also be involved, but taken together these variants had only small effects and are far from being predictive, the authors emphasize. They note that some among these variants are linked to the biological pathways for sex hormones and olfaction, providing clues into mechanisms influencing same-sex behavior. "Our findings provide insights into the biological underpinnings of same-sex sexual behavior," say Ganna et al., "but [they] also underscore the importance of resisting simplistic conclusions because the behavioral phenotypes are complex, because our genetic insights are rudimentary, and because there is a long history of misusing genetic results for social purposes."
In a Perspective, Melinda Mills emphasizes the limitations of the study results: "...although they did find particular genetic loci associated with same-sex behavior, when they combine the effects of these loci together into one comprehensive score, the effects are so small (under 1%) that this genetic score could not be reliably used to predict same-sex sexual behavior of an individual." She adds that "using these results for prediction, intervention or a supposed 'cure' is wholly and unreservedly impossible."

A global archaeological assessment of ancient land use reveals that prehistoric human activity had already substantially transformed the ecology of Earth by 3,000 years ago, even before intensive farming and the domestication of plants and animals. The results of this "big-data" approach to understanding humans' legacy on Earth suggest that early hunter-gatherers, farmers and pastoralists have had a far greater effect on Earth's landscapes - much earlier and more broadly than previously thought - which challenges the emerging Anthropocene paradigm suggesting that large-scale, human-caused environmental change is but a recent phenomenon. From the advent of agriculture and domesticated animals to increased pressures on wild animals and plants, the "heavy hand" of human activity is often written in the landscapes. It is widely recognized in archaeological sites across the globe. However, the details concerning the global extent, trajectory and environmental consequences of human land use aren't well-understood, largely due to the various incompatibilities of disparate, often qualitative, archaeological datasets. Lucas Stephens and colleagues compiled a comprehensive, global picture of ancient land use and human impacts from the early Holocene 10,000 years ago to the dawn of the modern industrial era using data from the ArchaeoGLOBE project, a crowdsourced synthesis of global archaeological knowledge from 255 researchers worldwide. Through a large-scale meta-analysis, Stephens et al. were able to generate worldwide regional assessments of land use over time. The results uncovered the deep roots of Earth's dramatic and sometimes irreversible transformation due to human activities, even before the domestication of plants and animals and intensive agriculture. "The results of these collaborative 'big data' analyses are impressive, and they tell us that human transformation of our planet began well before the first atomic bomb test, the invention of the steam engine or other proposed markers for the onset of the Anthropocene," writes Neil Roberts in a related Perspective.

Aug 29, 2019 - The obesity epidemic affects nearly half a billion people worldwide, many of them children. Obesity-related diseases including heart disease, stroke, type 2 diabetes, and cancer are a leading cause of preventable death. Obesity is caused by both genetic and environmental factors, confounding the development of effective anti-obesity drugs, which exhibit severe off-target effects. In a study published today in Genome Research, researchers developed a gene therapy that specifically reduces fat tissue and reverses obesity-related metabolic disease in obese mice.

To overcome the side effects of current anti-obesity drugs, researchers Jee Young Chung and colleagues developed a specific gene silencing therapy against a fatty acid metabolism gene, Fabp4. Researchers used a CRISPR interference system wherein catalytically dead Cas9 protein and single guide RNA was targeted to white adipocytes with a tissue-specific fusion peptide. The complex is internalized with little toxicity to the cells and upon internalization, the molecule complex decreases the expression of Fabp4 and reduces lipid storage in adipocytes. Demonstrating that this delivery method performed well in cells, Chung and colleagues tested their therapy on obese mice. Mice were fed a diet high in fat leading to obesity and insulin resistance. Fabp4 repression resulted in a 20% reduction of body weight and improved insulin resistance and inflammation after just six weeks of treatment. Additional systemic improvements were observed, including a reduction in fatty lipid deposition in the liver and reduced circulating triglycerides.

The current standard FDA-approved treatment showed just 5% of body weight loss after one year of treatment in humans. However, while this therapy displays promising results in mice, further studies are required before it can be used in clinical treatment against human disease. Importantly, this work highlights the advances in precision gene editing technology, which can be translated to other types of therapies.

Land use by early farmers, pastoralists and even hunter-gatherer societies was extensive enough to have created significant global landcover change by 3,000-4,000 years ago. This is much earlier than has been recognised, and challenges prevailing opinions concerning a mid-20th century start date for the Anthropocene. These are the findings of a new study published this week in Science, by a large international team of archaeologists and environmental scientists.

This study brought together several hundred archaeologists from around the world, who pooled extensive datasets summarising decades of archaeological research. Nicole Boivin, Director of the Department of Archaeology at the Max Planck Institute for the Science of Human History and a lead author on the study, notes that "archaeologists possess critical datasets for assessing long-term human impacts to the natural world, but these remain largely untapped in terms of global-scale assessments". She observes that "this novel crowd-sourcing approach to pooling archaeological data is extremely innovative, and has provided researchers with a unique perspective".

Unique collaboration allows for creation of large database of archaeological data to study past environmental change

The ArchaeoGLOBE project was coordinated by an international team of researchers who developed an online survey to gather past land-use estimates from archaeologists with regional expertise. The current study offers a novel way to assess archaeological knowledge on human land use across the globe over the past 10,000 years. By incorporating online archaeological crowdsourcing, the study was able to incorporate the local expertise of 255 archaeologists to reach an unprecedented level of global coverage. This global archaeological assessment, and the collaborative approach it represents, will help stimulate and support future efforts towards the common goal of understanding early land use as a driver of long-term global environmental changes across the Earth system, including changes in climate.

"This type of work causes us to rethink the role of humans in environmental systems, particularly in the way we understand 'natural' environments," said Lucas Stephens of the University of Maryland Baltimore County, University of Pennsylvania and Max Planck Institute for the Science of Human History, who led the global collaboration of archaeologists that produced the study. "It also allows us to identify patterns in the distribution of our data and prioritize future collection areas to improve the reliability of global datasets."

Study of archaeological data reveals huge impact of humans over thousands of years

"While modern rates and scales of anthropogenic global change are far greater than those of the deep past, the long-term cumulative changes wrought by early food producers are greater than many realize," said Andrea Kay of the Max Planck Institute for the Science of Human History and The University of Queensland, a lead author on the study. "Even small-scale or shifting agriculture can cause global change when considered at large scales and over long time-periods," she adds.

By acknowledging the deep time impact of humans on this planet and better understanding human-environment interactions over the long term, the researchers believe we can better plan for future climate scenarios and possibly find ways of mitigating negative impacts on soils, vegetation, and climate. "It's time to get beyond the mostly recent paradigm of the Anthropocene and recognize that the long-term changes of the deep past have transformed the ecology of this planet, and produced the social-ecological infrastructures - agricultural and urban - that made the contemporary global changes possible," said Erle Ellis of University of Maryland Baltimore County, a senior author who initially proposed and helped design the study. "These past changes produced the social-ecological infrastructures - agricultural and urban - that made the contemporary global changes possible."

A day is the time for Earth to make one complete rotation on its axis, a year is the time for Earth to make one revolution around the Sun -- reminders that basic units of time and periods on Earth are intimately linked to our planet's motion in space relative to the Sun. In fact, we mostly live our lives to the rhythm of these astronomical cycles.

The same goes for climate cycles. The cycles in daily and annual sunlight cause the familiar diel swings in temperature and the seasons. On geologic time scales (thousands to millions of years), variations in Earth's orbit are the pacemaker of the ice ages (so-called Milankovi? cycles). Changes in orbital parameters include eccentricity (the deviation from a perfect circular orbit), which can be identified in geological archives, just like a fingerprint.

The dating of geologic archives has been revolutionized by the development of a so-called astronomical time scale, a "calendar" of the past providing ages of geologic periods based on astronomy. For example, cycles in mineralogy or chemistry of geologic archives can be matched to cycles of an astronomical solution (calculated astronomical parameters in the past from computing the planetary orbits backward in time). The astronomical solution has a built-in clock and so provides an accurate chronology for the geologic record.

However, geologists and astronomers have struggled to extend the astronomical time scale further back than about fifty million years due to a major roadblock: solar system chaos, which makes the system unpredictable beyond a certain point.

In a new study published in the journal Science, Richard Zeebe from the University of Hawai'i at Manoa and Lucas Lourens from Utrecht University now offer a way to overcome the roadblock. The team used geologic records from deep-sea drill cores to constrain the astronomical solution and, in turn, used the astronomical solution to extend the astronomical time scale by about 8 million years. Further application of their new method promises to reach further back in time still, one step and geologic record at a time.

On the one hand, Zeebe and Lourens analyzed sediment data from drill cores in the South Atlantic Ocean across the late Paleocene and early Eocene, ca. 58-53 million years ago (Ma). The sediment cycles displayed a remarkable expression of one particular Milankovi? parameter, Earth's orbital eccentricity. On the other hand, Zeebe and Lourens computed a new astronomical solution (dubbed ZB18a), which showed exceptional agreement with the data from the South Atlantic drill core.

"This was truly stunning," Zeebe said. "We had this one curve based on data from over 50-million-year-old sediment drilled from the ocean floor and then the other curve entirely based on physics and numerical integration of the solar system. So the two curves were derived entirely independently, yet they looked almost like identical twins."

Zeebe and Lourens are not the first to discover such agreement -- the breakthrough is that their time window is older than 50 Ma, where astronomical solutions disagree. They tested 18 different published solutions but ZB18a gives the best match with the data.

The implications of their work reach much further. Using their new chronology, they provide a new age for the Paleocene-Eocene boundary (56.01 Ma) with a small margin of error (0.1%). They also show that the onset of a large ancient climate event, the Paleocene-Eocene Thermal Maximum (PETM), occurred near an eccentricity maximum, which suggests an orbital trigger for the event. The PETM is considered the best paleo-analog for the present and future anthropogenic carbon release, yet the PETM's trigger has been widely debated. The orbital configurations then and now are very different though, suggesting that impacts from orbital parameters in the future will likely be smaller than 56 million years ago.

Zeebe cautioned, however, "None of this will directly mitigate future warming, so there is no reason to downplay anthropogenic carbon emissions and climate change."

Regarding implications for astronomy, the new study shows unmistakable fingerprints of solar system chaos around 50 Ma. The team found a change in frequencies related to Earth's and Mars' orbits, affecting their amplitude modulation (often called a "beat" in music).

"You can hear amplitude modulation when tuning a guitar. When two notes are nearly the same, you essentially hear one frequency, but the amplitude varies slowly -- that's a beat," Zeebe explained. In non-chaotic systems, the frequencies and beats are constant over time, but they can change and switch in chaotic systems (called resonance transition). Zeebe added, "The change in beats is a clear expression of chaos, which makes the system fascinating but also more complex. Ironically, the change in beats is also precisely what helps us to identify the solution and extend the astronomical time scale".

Nearly 15 million babies are born prematurely, or before 37 weeks of pregnancy, around the world each year. When born too early, a baby's immature respiratory center in the brain often fails to signal it to breathe, resulting in low oxygen levels, or hypoxia, in the brain.

Research published in the Journal of Neuroscience shows that even a brief 30-minute period of hypoxia is enough to persistently disrupt the structure and function of the brain region known as the hippocampus, which is vital for learning and memory.

"Our findings raise new concerns about the vulnerability of the preterm brain to hypoxia. They are concerning for the long-term impact that oxygen deprivation can have on the ability of these preterm babies to learn as they grow to school age and adulthood," said the study's principal investigator, Stephen Back, M.D., Ph.D., Clyde and Elda Munson Professor of Pediatric Research and Pediatrics, OHSU School of Medicine, OHSU Doernbecher Children's Hospital.

In the neonatal intensive care unit, preemies can experience up to 600 short, but impactful periods of hypoxia each week. Consequently, more than one-third of babies who survive preterm birth are likely to have smaller brains, presumably due to brain cell loss, compared with the brains of full-term infants. This can increase the risk of significant life-long neurodevelopmental challenges that will affect learning, memory, attention and behavior.

Using a twin preterm fetal sheep model, Back and colleagues studied the impact of both hypoxia alone, as well as in combination with ischemia -- or insufficient blood flow -- on the developing hippocampus. The results confirm that, similar to human preterm survivors, growth of the hippocampus is impaired. However, brain cells do not die as previously believed. Rather, hippocampal cells fail to mature normally, causing a reduction in long-term potentiation, or the cellular basis of how the brain learns.

Remarkably, the severity of the hypoxia predicted the degree to which cells in the hippocampus failed to mature normally, explains Back. These findings are all the more unexpected because it was not appreciated that the preterm hippocampus was already capable of these learning processes.

"We want to understand next how very brief or prolonged exposure to hypoxia affects the ability for optimal learning and memory, " says Back. "This will allow us to understand how the hippocampus responds to a lack of oxygen, creating new mechanisms of care and intervention both at the hospital, and at home."

LOS ANGELES (Aug. 28, 2019) -- A new study gives insight into how immunotherapies, treatments that help the body's immune system fight cancer, might one day be delivered directly to the brain in order to treat brain tumors.

The study, published this week on the peer-reviewed open access journal Nature Communications, demonstrated that a new type of nano-immunotherapy traversed the blood-brain barrier in laboratory mice, inducing a local immune response in brain tissue surrounding the tumors. The tumor cells stopped multiplying, and survival rates increased.

For patients with glioblastoma, the most common and also most deadly form of brain cancer, immunotherapies like this could hold the key to longer survival, said Julia Ljubimova, MD, PhD, senior author of the study and professor of Neurosurgery and Biomedical Sciences at Cedars-Sinai.

"This study showed a promising and exciting outcome," Ljubimova said. "Current clinically proven methods of brain cancer immunotherapy do not ensure that therapeutic drugs cross the blood-brain barrier. Although our findings were not made in humans, they bring us closer to developing a treatment that might effectively attack brain tumors with systematic drug administration."

Harnessing the power of the body's own immune system to attack tumors is a concept that has intrigued investigators for decades. Scientists have been studying ways to persuade the immune system to attack tumors in the same way that it attacks, for example, a virus.

While promising, this idea presents a few key challenges, especially when it comes to brain tumors. The environment of the brain can be hard to penetrate with drugs or other therapies. The blood-brain barrier, which the body uses to naturally block toxins and other harmful substances in the bloodstream from getting into the brain, can keep out potentially lifesaving treatments.

In addition, brain tumors seem to have the effect of suppressing their local immune systems. Tumors accumulate immunological guards such as T regulatory cells (Tregs) and special macrophages, which block the body's anti-cancer immune cells, protecting the tumor from attack, Ljubimova said. In order to allow tumor-killing immune cells to activate, investigators needed to find a way to arrest or deactivate the tumor-protecting Tregs and macrophages.

Other immunotherapies have been successful in triggering an immune response in the whole body, which can slow the growth of tumors and extend the life of patients, but this treatment is one of the first of its kind to demonstrate the activation of both whole body and local immune systems around the tumor in laboratory mice.

The immunotherapy tested in this study works by delivering checkpoint inhibitors, a type of antibody drug that can arrest and block Tregs and macrophages, so the tumor can't use them to block the incoming tumor-killing immune cells.

Those checkpoint inhibitors are attached with a biodegradable polymer to a protein or peptide that enables the drug to traverse the blood-brain barrier.

"The checkpoint inhibitors can then block the Tregs and macrophages, allowing the local immune cells to get activated and do their job-fight the tumor," Ljubimova said.

With the tumor-shielding cells blocked, immune cells like cytotoxic lymphocytes and microglial cells can then attack and destroy the cancer cells.

"Drug delivery is the major obstacle for the treatment of central nervous system diseases, including brain conditions," Ljubimova said. "The horizon for treatment of brain cancer is getting clearer. We hope that by delivering multifunctional new-generation drugs through the blood-brain barrier, we can explore new therapies for many neurological conditions."

Ljubimova says that further tests are needed before this therapy can be tested in humans.

NEW YORK, NY (August 29, 2019)--Biologists at Columbia University Vagelos College of Physicians and Surgeons have leveraged a computational method to map protein-protein interactions between all known human-infecting viruses and the cells they infect. The method, along with the data that it generated, has generated a wealth of information about how viruses manipulate the cells that they infect and cause disease. Among the study's findings are the role of estrogen receptors in regulating Zika virus infection and how human papillomavirus (HPV) causes cancer.

The study, led by Sagi Shapira, PhD, assistant professor of systems biology at Columbia University Vagelos College of Physicians and Surgeons, was published today in the journal Cell.

LIMITED UNDERSTANDING OF HOW VIRUSES WORK

At the molecular level, viruses invade cells and manipulate them to replicate, survive, and cause disease. Since they depend on human cells for their life cycle, one way viruses co-opt cellular machinery is through protein-protein interactions within their cell host. Similarly, cells respond to infection by initiating immune responses that control and limit viral replication - these too, depend on protein-protein interactions.

To date, considerable effort has been invested in identifying these key interactions - and many of these efforts have resulted in many fundamental discoveries, some with therapeutic implications. However, traditional methods are limited in terms of scalability, efficiency, and even access. To address this challenge, Dr. Shapira and his collaborators developed and implemented a computational framework, P-HIPSTER, that infers interactions between pathogen and human proteins--the building blocks of viruses and cells.

Until now, our knowledge about many viruses that infect people is limited to their genome sequences. Yet for most viruses, little has been uncovered about the underlying biological interactions that drive these relationships and give rise to disease.

"There are over 1,000 unique viruses that are known to infect people," says Dr. Shapira. "Yet, despite their unquestionable public health importance, we know virtually nothing about the vast majority of them. We just know they infect human cells. The idea behind this effort was to systematically catalogue the interactions that viruses have with the cells they infect. And, by doing so, also reveal some really interesting biology and provide the scientific community with a resource that they can use to make interesting observations of their own."

Using a novel algorithm, P-HIPSTer exploits protein structural information to systematically interrogate virus-human protein-protein interactions with remarkable accuracy. Dr. Shapira and his collaborators applied P-HIPSTer to all 1,001 human-infecting viruses and the approximately 13,000 proteins they encode. The algorithm predicted roughly 280,000 likely pairs of interacting proteins that represent a comprehensive catalogue of human virus protein-protein interactions with an accuracy rate of almost 80 percent.

"This is the first step towards building a comprehensive cartography of physical interactions between different organisms," Dr. Shapira says.

ZIKA, HPV, VIRAL EVOLUTION

In addition to defining pan-viral protein interactions, P-HIPSTer has yielded new biological insights into Zika virus, HPV, and the impact of viruses in shaping human genetics.

Among their discoveries, the researchers found that Zika virus interacts with estrogen receptor, the protein that allows cells to effectively respond to the estrogen hormone. Importantly, they found estrogen receptor has potential to inhibit Zika virus replication. Says Dr. Shapira, "And, in fact, estrogen receptor inhibits viral replication even more than interferon, a protein that is the body's first line of defense to viral infection and our gold standard for anti-viral defense."

The finding is particularly relevant to clinical disease as pregnant women are most susceptible to Zika during their first trimester, which is when estrogen levels are at their lowest. This period also is when the fetus is most susceptible to Zika, a virus for which there is no vaccine or specific treatment and that can cause sever birth defects.

Dr. Shapira and his team also explored interactions between HPV, the leading cause of cervical cancer, and the cells that it infects. HPV is the most common sexually transmitted viral infection with approximately 80 percent of sexually active individuals contracting one of the 200 different types of HPV at some point in their lives. Dr. Shapira and his team used the data generated by P-HIPSTer to identify protein-protein interactions that distinguish HPV infections associated with cancer from those that are not. In addition to providing insights into how HPV may cause disease, the finding could lead to improved diagnostics for those infected with HPV, and P-HIPSTer could potentially be used to help predict whether or not any particular virus is likely to be highly pathogenic.

The researchers also examined whether the interactions mediated by viruses have impacted human genetics. The researchers found evidence of strong selection pressure for several dozen cellular proteins have been shaped by viral infection, unlocking new insights into how our genome has been impacted by viruses.

"One of the things we can do with this data is drill down and ask whether virus infection has changed the history of human genetics," notes Dr. Shapira. "That is certainly not a novel idea but to have a catalogue of what those proteins are is significant. There are a lot of areas that we can explore now that we couldn't before."

FUTURE WORK

Dr. Shapira and his team intend to apply P-HIPSTer on more complex pathogens, such as parasites and bacteria, and use it to better understand how bacteria in the human gut communicate with each other. In the future, the algorithm could also be used to explore viruses or pathogens that effect agricultural plants or livestock.

The Shapira Laboratory at Columbia University is working to decipher the genetic and molecular circuitry at the interface of host-pathogen interactions. A deeper understanding of these relationships provides important insights into cellular machinery that control basic cell biology and has broad implications in human translational immunology and infectious disease research.

EVANSTON, Ill. -- After Brazil's 2018 presidential election, international political pundits and journalists wondered if social media platform WhatsApp enabled far-right candidate Jair Bolsonaro's rise to power. Northwestern University computer scientists now confirm that WhatsApp use played a key role in the electoral process.

After performing the first large-scale analysis of partisan WhatsApp groups in the context of Brazil's 2018 election, the researchers found that right-wing users were more effective in using the social media tool to spread news, disinformation and opinions.

More specifically, right-wing groups in Brazil were much more numerous and shared substantially more multimedia content and YouTube videos than left-wing groups.

"Our ultimate goal is to understand how information and misinformation spreads, so we can find technological interventions," said Larry Birnbaum, the study's senior author. "We want to find ways to help people better evaluate the information they receive. Media literacy has not caught up with rapid changes in technology."

Victor Bursztyn, the paper's first author and a doctoral student in computer science at Northwestern, will present their findings at 11 a.m. EDT on Friday, Aug. 30, at the IEEE/ACM International Conference on Advances in Social Networks Analysis and Mining in Vancouver. Their paper is titled "Thousands of small, constant rallies: A large-scale analysis of partisan WhatsApp groups."

With more than 120 million users, Brazil is the second-largest WhatsApp market in the world, trailing India. While Americans tend to use WhatsApp for one-to-one or small group text messaging, Brazilians use WhatsApp for most everything: text messaging, large group chats, and sending and receiving news. WhatsApp allows users to join public and private groups with up to 256 members to share text and multimedia messages, transforming chat groups into highly active social spaces.

"More than half of Brazil's population uses WhatsApp," Bursztyn said. "WhatsApp's large groups are often targeted for political outcomes."

From Sept. 1 to Nov. 1, 2018, Birnbaum and Bursztyn followed 232 partisan groups. During that time, they collected 2.8 million messages from more than 45,000 users. (This is 3.5 times as many messages and 2.4 times as many users than the largest competing dataset to date.)

The team discovered multiple differences between right- and left-wing groups. In the studied sample, right-wing groups shared 5.5 times as many messages as left-wing users. Of the messages shared by right-wing users, 46.5% were multimedia messages, such as photos, audio and video files. Just 30% of left-wing messages included multimedia.

"It's hard to say whether multimedia is more effective in influencing opinions, but right-wingers are more savvy in using them," said Birnbaum, professor of computer science in Northwestern's McCormick School of Engineering. "Images are always more compelling than text."

Birnbaum and Bursztyn also found that the most-shared news by WhatsApp groups during the 2018 presidential election campaign came from websites that spread disinformation, as identified by several fact-checking agencies. Right-wing groups tended to spread disinformation from four popular, skewed sites. Left-wing groups shared news from one popular, skewed site.

"Data suggests that both sides consume this content, but it's a more prevalent problem on the right," Birnbaum said.

In a new study published 29th August in PLOS Genetics, Federico Rey of the University of Wisconsin - Madison and colleagues identified genetic variants in mice that impact the levels of different bile acids as well as the size of a specific population of microbes in the gut.

The complex assortment of microbes that live in the intestines are the result of poorly understood interactions between a person's individual genetics and environmental influences like diet and drugs. One factor that links these two are bile acids, which the body produces to help absorb vitamins and fat in the small intestine, and which encourage some bacterial populations and suppress others. Additionally, bacteria metabolize bile acids to create secondary bile acids, which the body also uses for digestion. To identify genetic variants that affect bile acid levels and the microbial community in the gut, researchers profiled a population of 400 genetically diverse mice. The analysis pointed to a gene that codes for the ileal bile acid transporter, a protein that takes up bile acids from the final section of the small intestine for recycling back to the liver. Genetic variants in this transporter not only affect the abundance of bacterial species belonging to a group called Turicibacter but also alter levels of a bile metabolite that the researchers detected in the blood.

This study reveals novel interactions between Turicibacter species and bile acids and is the first to use genetic mapping to integrate the community of microbes living in the gut with the profile of bile acid metabolites. "We are interested in identifying the microbial functions that are under host genetic control," said author Federico Rey, "and future studies will integrate additional metabolomic, metagenomic and transcriptional data derived from the host intestine."

More broadly, the work shows the power of systems genetics to identify novel interactions between microbes and metabolites in the intestine. It also provides multiple leads on host-microbe-metabolite interactions that with additional study can help dissect the complex factors that shape microbial communities in the gut.

Scientists have mapped the DNA of bacteria found within a chronic disease affecting grapevines, a feat they hope will ultimately help protect the multibillion-dollar grape industry that produces juice, jelly, wine and other important products.

Researchers including several Rochester Institute of Technology faculty and alumni sequenced the microbiome found within tumors of grapevines afflicted with crown gall disease. The study spanned four continents and sheds light on the complex interaction between the grapevine and its microbial community, which could lead to better management of the crown gall disease in the future.

"The research is important given that the Finger Lakes region is such a large producer of wine," said Professor André Hudson, head of RIT's Thomas H. Gosnell School of Life Sciences. "Crown gall disease is caused by the plant pathogen Allorhizobium vitis and is one of the most debilitating diseases of grapes that impacts production and quality."

The disease occurs when bacteria infect grapevines at the crown of the plant, where the root and the shoot meet.

"Bacteria transfer genes into the cells of the grapevine at the crown of the plant," explained Michael Savka, professor at RIT's Thomas H. Gosnell School of Life Sciences. "The piece of DNA that's transferred into the grape cells basically encodes enzymes that allow for the plant cells to overproduce two hormones. Unregulated production of these two hormones leads to the crown gall tumor, a chronic disease that degrades the vigor of the plant."

The international team of researchers conducted next-generation DNA sequencing of 73 tumor samples taken from grapevines from as close as Geneva, N.Y., and as far as Hungary, Tunisia and Japan. Han Ming Gan '08 (biotechnology), a senior research fellow in genomics at Deakin University, said the study provides researchers a database that can be used to assess the disease stage of crown gall tumors in the future. The fundamental research can pave the way for more advances to combat the disease.

"Moving forward, what would be nice is to look at the functional aspect that can be attained using whole metagenome sequencing," said Gan. "So far, the information that we obtained is on the 'who' but not the 'how.' In other words, we know which bacteria are in the galls but not what they are capable of doing."

The famed quantum physicist Max Planck had an idiosyncratic view about what spurred scientific progress: death. That is, Planck thought, new concepts generally take hold after older scientists with entrenched ideas vanish from the discipline.

"A great scientific truth does not triumph by convincing its opponents and making them see the light, but rather because its opponents eventually die, and a new generation grows up that is familiar with it," Planck once wrote.

Now a new study co-authored by MIT economist Pierre Azoulay, an expert on the dynamics of scientific research, concludes that Planck was right. In many areas of the life sciences, at least, the deaths of prominent researchers are often followed by a surge in highly cited research by newcomers to those fields.

Indeed, when star scientists die, their subfields see a subsequent 8.6 percent increase, on average, of articles by researchers who have not previously collaborated with those star scientists. Moreover, those papers published by the newcomers to these fields are much more likely to be influential and highly cited than other pieces of research.

"The conclusion of this paper is not that stars are bad," says Azoulay, who has co-authored a new paper detailing the study's findings. "It's just that, once safely ensconsed at the top of their fields, maybe they tend to overstay their welcome."

The paper, "Does Science Advance one Funeral at a Time?" is co-authored by Azoulay, the International Programs Professor of Management at the MIT Sloan School of Management; Christian Fons-Rosen, an assistant professor of economics at the University of California at Merced; and Joshua Graff Zivin, a professor of economics at the University of California at San Diego and faculty member in the university's School of Global Policy and Strategy. It is forthcoming in the American Economic Review.

To conduct the study, the researchers used a database of life scientists that Azoulay and Graff Zivin have been building for well over a decade. In it, the researchers chart the careers of life scientists, looking at accomplishments that include funding awards, published papers and the citations of those papers, and patent statistics.

In this case, Azoulay, Graff Zivin, and Fons-Rosen studied what occurred after the unexpected deaths of 452 life scientists, who were still active in their disciplines. In addition to the 8.6 percent increase in papers by new entrants to those subfields, there was a 20.7 percent decrease in papers by the rather smaller number of scientists who had previously co-authored papers with the star scientists.

Overall, Azoulay notes, the study provides a window into the power structures of scientific disciplines. Even if well-established scientists are not intentionally blocking the work of researchers with alternate ideas, a group of tightly connected colleagues may wield considerable influence over journals and grant awards. In those cases, "it's going to be harder for those outsiders to make a mark on the domain," Azoulay notes.

"The fact that if you're successful, you get to set the intellectual agenda of your field, that is part of the incentive system of science, and people do extraordinary positive things in the hope of getting to that position," Azoulay notes. "It's just that, once they get there, over time, maybe they tend to discount 'foreign' ideas too quickly and for too long."

Thus what the researchers call "Planck's Principle" serves as an unexpected -- and tragic -- mechanism for diversifying bioscience research.

The researchers note that in referencing Planck, they are extending his ideas to a slightly different setting than the one he himself was describing. In his writing, Planck was discussing the birth of quantum physics -- the kind of epochal, paradigm-setting shift that rarely occurs in science. The current study, Azoulay notes, examines what happens in everyday "normal science," in the phrase of philosopher Thomas Kuhn.

The process of bringing new ideas into science, and then hanging on to them, is only to be expected in many areas of research, according to Azoulay. Today's seemingly stodgy research veterans were once themselves innovators facing an old guard.

"They had to hoist themselves atop the field in the first place, when presumably they were [fighting] the same thing," Azoulay says. "It's the circle of life."

Or, in this case, the circle of life science.

DURHAM, N.C. -- Thousands of marine species could be at risk if a new United Nations high-seas biodiversity treaty, now being negotiated in New York, does not include measures to address the management of all fish species in international waters, not just the commercial species, warns an analysis by American, Dutch, Swiss and French researchers.

"Of the 4,018 known species of fish in the deep ocean, more than 95% are non-targeted species whose populations are not assessed by regional fisheries management organizations and are currently not being considered as part of the high-seas biodiversity to be monitored and protected under the new treaty," said Guillermo Ortuño Crespo, a doctoral candidate at Duke University's Nicholas School of the Environment and lead author of the new analysis.

"We found that only 4.8% of high-seas fish species have stock assessments or analogous forms of population models," he said. "For more than 85%, we have no information at all on their population trends. We simply don't know enough to know if or how they are being affected."

"These findings make a compelling case for covering the full scope of high-seas fish biodiversity in the new agreement," Ortuño Crespo said.

"We are not arguing that the emerging treaty should infringe on the current management mandate of regional fisheries management organizations, but we are calling for negotiators to address biodiversity concerns for the species that are not currently being managed and are slipping through the governance net," emphasized Patrick N. Halpin, professor and director of the Marine Geospatial Ecology Lab at Duke's Nicholas School.

"Fisheries management and the management of overall fish biodiversity are uniquely different processes and activities," Halpin noted.

Ortuño Crespo, Halpin and their colleagues published their analysis August 26 in the journal Nature Ecology & Evolution.

The UN General Assembly has been meeting at its New York headquarters for two weeks to hammer out the final text of the new treaty on marine biodiversity -- first proposed almost 20 years ago -- under the UN Law of the Sea.

"This is an opportunity of a lifetime to increase the sustainability of human activities in the high seas, which cover 46% of our planet, so we must get it right," Ortuño Crespo said.

Early in the discussion process, parties to the negotiations agreed that any new treaty should not undermine existing agreements or management organizations. Some nations have used this pretext as a way to exclude already managed commercial fisheries and other human activities from the treaty, Ortuño Crespo said. But by excluding such species, the majority of non-commercial fish species in the high seas might not be effectively managed under the treaty.

Fears that expanding the scope of the treaty to include all fish biodiversity would undermine existing agreements and management organizations are unfounded, he added.

"We believe that the new treaty, with the expanded scope we propose, could help regional fisheries management organizations fulfil their conservation and management mandates, and encourage research, monitoring and management of all forms of biodiversity that are currently not being monitored by existing bodies or treaties," he said.

UNIVERSITY PARK, Pa.--The Christian church can provide an important social support community for international college students in the United States, according to researchers at Penn State. Specifically, the team found that the church also may help to provide culturally sensitive counseling to international students. The team focused its investigation on Chinese international students.

"Church activities are often carefully and purposefully designed to nurture relationships among students from different backgrounds," said Chi Nguyen, Ph.D. candidate in education policy studies and data analyst at the Schreyer Honors College, "and many international students respond positively to this."

For example, one student participant in the study said of her first day in town, "I still remember my feeling after arriving at [the local] airport, I felt lost and unfamiliar. Everything was new to me. I thought that no one would pick me up at the airport. I didn't know how to take a bus or a taxi to my dorm. Suddenly, I saw Jiahe, ... It was my first time to see him. He stood right beside the exit door and held a flag that read 'Chinese Home Church welcomes new students.' I still remember my feeling at that moment. I knew that I was home. I had a sense of belonging here."

According to their research, students from Mainland China comprise more than a third of international students in the United States.

"These students are important contributors to higher education institutions academically, financially and culturally," she said. "Overall, international students contribute some $40 billion to the U.S. economy each year, according to the U.S. Department of Commerce."

However, these students often lack access to adequate support issues related to culture shock, language barriers and academic challenges caused by unfamiliar teaching styles and learning environments, she added.

"A recent study found that nearly half of Chinese international students interviewed reported depression symptoms and slightly fewer reported anxiety symptoms," said Nguyen. "Many on-campus counseling centers lack culturally knowledgeable staff to cater their services to a diverse international student population."

Nguyen and her colleagues Anke Li, Ph.D. candidate in education policy studies, and Jinhee Choi, Ph.D. candidate in learning and performance systems, conducted an ethnographic study--in which they observed the subjects directly--of the effects of participation in a Christian church community on Chinese international undergraduate students' social experiences.

Li came up with the idea of doing research on Christian international students after conducting interviews with Christian and non-Christian Chinese undergraduate students for a prior research project.

"It seemed that students who participated in Christian communities were more peaceful and satisfied with their experiences of studying abroad," Li recalled. "This intrigued me to explore the reasons behind their different experiences."

Soon after, Nguyen and Choi joined Li in her investigation.

Together, the team spent approximately six hours per week for 13 months observing students' interactions and conversations within the worship services, bible studies, weekly dinners and informal gatherings of the "Chinese Home Church," a Chinese Christian church in a university town in the Northeast.

Additionally, the team interviewed Chinese international undergraduate students who participated in this church and its fellowship. Specifically, the researchers asked the students to share their stories and experiences of participating in the church community and how these experiences have shaped their lives in the United States. They also asked participants to reflect on how the church has helped them develop their social networks and academic skills. Finally, they asked for the students' opinions about friendship inside and outside of the church. They report their results in the Aug. 7 issue of Social Sciences.

"From both our observations and interviews, it is clear that the 'Chinese Home Church' provided a welcoming and caring environment for Chinese international students, helping them to enrich their lives socially and, to some extent, academically," said Choi. "For some Chinese students, most of whom grew up in the Chinese one-child policy era, this is their first time living away from their parents. Therefore, our participants often rely on the church community in times of difficulty. The church's pastor and senior mentors, whose cumulative knowledge and experience in the ministry well equips them for this role, often serve as parental figures to Chinese students and offer them trustworthy judgments and advice."

According to Choi, the church also functioned as an informal counseling center, where students could share their emotional and mental distress and receive practical and culturally relevant advice.

Li added that the church provided this environment without proselytizing.

"The focus was more on building community than on teaching Christianity," said Li. "It was about offering care for the feelings and experiences of new students."

The authors conclude that higher education institutions should aim to understand the struggles that international students face during their process of adaptation and use this knowledge to design counseling services. For example, they could hire counselors with international and/or multicultural personal and professional backgrounds who may have more in common with international students. Likewise, universities could also consider creating other supportive communities or organizations for their international students.

"Most international students do not have access to family-like communities such as those provided by religious organizations," said Li. "It is important for higher education institutions to learn from this model."

When a chemical spills in the environment, it's important to know how quickly the spill will spread. If a farmer irrigates a crop, the person will need to know how fast the water should move through the soil and be absorbed by the roots. In both cases, a good understanding of water pore structure is necessary.

A new method to measure pore structure and water flow is described in a study published in the journal Water Resources Research. With it, scientists should be able to more accurately determine how fast water, contaminants, nutrients and other liquids move through the soil--and where they go.

The mathematical model was validated by researchers at the University of California, Davis, California State University, Northridge and University of North Carolina at Chapel Hill.

"This will open a whole new direction that will help us use our resources more efficiently and better understand the flow of water, contaminants and nutrients," said corresponding author and UC Davis assistant professor Majdi Abou Najm, who developed the model when he was at the American University of Beirut.

NOT ONE-SIZE-FITS ALL

One of the most important equations in hydrology, Darcy's law, has long been used to describe the flow of fluids through a porous medium, like rocks and soil. But that equation assumes a one-size-fits all estimation of pore size, when the reality is more complicated.

"Our model finds a middle ground between reality, which has an infinite number of pore sizes, and the current model, which represents them with one average pore size," said Abou Najm.

CHEAP AND ACCESSIBLE

The new model, which was tested on four sands for the study, has the added benefit of being relatively cheap and accessible to use in a variety of environments. The study said that most pore size measurement methods require collecting samples of limited size for lab analysis. This new method provides a simple, inexpensive approach to measuring a variety of pore sizes directly in the field using items that can be bought in a typical grocery store, such as soup thickeners or food additives.