Culture

Researchers at San Diego State University have found a new way to harness food as medicine, which has far reaching implications to control harmful microbes in our gut while balancing microbial diversity by fostering the growth of beneficial bacteria.

Foods we eat commonly affect our gut microbiota. New research shows they do so by triggering the production of bacteriophage - viruses that infect and replicate inside bacteria. Compounds in these foods have an antimicrobial effect which causes the phage to replicate.

The researchers began by identifying which foods were antimicrobial, then analyzed them before narrowing it down to a shortlist. When examining growth curves of bacteria, they observed that while bacteria multiply over time, eventually their numbers plateau. However, if phages are activated, then bacterial growth stops altogether and their numbers drop dramatically until they're depleted.

Foods they tested that had antimicrobial effects include honey, licorice, stevia (a sugar substitute derived from the stevia plant), aspartame, hot sauce, herbs such as oregano, spices such as cinnamon and clove, rhubarbs, uva ursi (bear berry), and neem extract. They also tested toothpaste, since it's known to contain antimicrobial compounds. Of these, honey, stevia, aspartame, neem and uva ursi had the most impact in triggering phage production.

"The microbiome is composed of hundreds of different bacteria and the phages they host," said Lance Boling, an SDSU molecular biologist and research associate. "We could actually tackle certain conditions by adjusting the foods we consume, that will affect microbial diversity which in turn will influence health and diseases."

"We also found some foods acted as phage inhibitors and could be used to control pathogenic viruses," Boling added.

Our gut microbiome can affect cognitive ability, metabolism, weight gain or loss, our moods, and even cause depression. It can also cause inflammation that could lead to cancer, diabetes, Crohn's disease and irritable bowel syndrome. With careful analysis and planning, food could be used as medicine to correct imbalances.

"This shows we could sculpt the human gut microbiome with common dietary compounds," said Forest Rohwer, an SDSU microbial ecologist and pioneer of viromics research. "The ability to kill specific bacteria, without affecting others, makes these compounds very interesting."

Boling works on microbiome research in Rohwer's lab. Their findings will be published Jan. 13 in Gut Microbes.

Identifying phage triggers

When phage replicate they kill the host cell and exit into the environment, which can lead to a cascade effect where they infect bacterial cells around them. Each bacterial cell that bursts - when the phage grows inside them - can have hundreds of new phages that emerge. When they release in the microbiome, if there are more bacteria present, they will continue to infect the bacteria.

"There aren't many known chemical triggers, and we wanted to find these 'prophage' inducers - or what causes the phage DNA to detach and replicate," Boling said.

Once the researchers chose foods with known and perceived antimicrobial effects, they then selected bacteria representative of the two major gut phyla, Bacteroidetes and Firmicutes, including strains of pathogenic as well as beneficial bacteria. They narrowed the food compounds down to 28 from 117 candidates on which they conducted the prophage induction assay. Bacterial growth was observed with and without food compounds, for comparison. The samples were processed using flow cytometry, a sensitive method for detecting particles as tiny as viruses.

Future applications

While other studies have focused on increasing the abundance of therapeutic phages, this research goes further to explore the reductive effect of 117 commonly consumed foods, chemical additives, and plant extracts on the growth and phage production capacity of common gut bacteria.

This reductive approach is "akin to pulling weeds from a garden so that more desirable plants have room to grow," Boling explained, hence the term 'landscaping' the gut.

Conversely, over-consumption of broad-spectrum antimicrobial foods could contribute to the same metabolic states correlated with low gut diversity that may be produced by the administration of antibiotic medicines. Proper understanding and utilization of these food compounds could aid in the treatment or prevention of conditions associated with gut imbalances, and promote overall health.

"We are excited about finding more prophage inducers and determining the molecular mechanisms by which they work," Rohwer said. "There are probably thousands of compounds that would be useful for eliminating unwanted bacteria."

The researchers recommend that foods found to be prophage inducers should be studied further to elucidate their molecular mechanisms. While the importance of phages and the fact that they are the most prolific biological entity in the biosphere is well-established, little is understood about the triggers that cause bacteria to produce phage and release them into the environment. Elucidating these mechanisms will further our understanding of how bacteria and phage shape the ecosystems that they populate.

Whether it be a brisk walk around the park or high intensity training at the gym, exercise does a body good. But what if you could harness the benefits of a good workout without ever moving a muscle?

Michigan Medicine researchers studying a class of naturally occurring protein called Sestrin have found that it can mimic many of exercise's effects in flies and mice. The findings could eventually help scientists combat muscle wasting due to aging and other causes.

"Researchers have previously observed that Sestrin accumulates in muscle following exercise," said Myungjin Kim, Ph.D., a research assistant professor in the Department of Molecular & Integrative Physiology. Kim, working with professor Jun Hee Lee, Ph.D. and a team of researchers wanted to know more about the protein's apparent link to exercise. Their first step was to encourage a bunch of flies to work out.

Taking advantage of Drosophila flies' normal instinct to climb up and out of a test tube, their collaborators Robert Wessells, Ph.D. and Alyson Sujkowski of Wayne State University in Detroit developed a type of fly treadmill. Using it, the team trained the flies for three weeks and compared the running and flying ability of normal flies with that of flies bred to lack the ability to make Sestrin.

"Flies can usually run around four to six hours at this point and the normal flies' abilities improved over that period," says Lee. "The flies without Sestrin did not improve with exercise."

What's more, when they overexpressed Sestrin in the muscles of normal flies, essentially maxing out their Sestrin levels, they found those flies had abilities above and beyond the trained flies, even without exercise. In fact, flies with overexpressed Sestrin didn't develop more endurance when exercised.

The beneficial effects of Sestrin include more than just improved endurance. Mice without Sestrin lacked the improved aerobic capacity, improved respiration and fat burning typically associated with exercise.

"We propose that Sestrin can coordinate these biological activities by turning on or off different metabolic pathways," says Lee. "This kind of combined effect is important for producing exercise's effects."

Lee also helped another collaborator, Pura Muñoz-Cánoves, Ph.D., of Pompeu Fabra University in Spain, to demonstrate that muscle-specific Sestrin can also help prevent atrophy in a muscle that's immobilized, such as the type that occurs when a limb is in a cast for a long period of time. "This independent study again highlights that Sestrin alone is sufficient to produce many benefits of physical movement and exercise," says Lee.

Could Sestrin supplements be on the horizon? Not quite, says Lee. "Sestrins are not small molecules, but we are working to find small molecule modulators of Sestrin."

Additionally, adds Kim, scientists still don't know how exercise produces Sestrin in the body. "This is very critical for future study and could lead to a treatment for people who cannot exercise."

Every language has cases in which two or more concepts are expressed by the same word, such as the English word fly, which refers to both the act of flying and to the insect. By comparing patterns in these cases, which linguists call colexifications, across languages, researchers can gain insights into a wide range of issues, including human perception, language evolution, and language contact. The third installment of the CLICS database significantly increases the number of languages, concepts, and data sources available in earlier versions, allowing researchers to study colexifications on a global scale in unprecedented detail and depth.

With detailed computer-assisted workflows, CLICS facilitates the standardization of linguistic datasets and provides solutions to many of the persistent challenges in linguistic research. "While data aggregation was generally based on ad-hoc procedures in the past, our new workflows and guidelines for best practice are an important step to guarantee the reproducibility of linguistic research," says Tiago Tresoldi.

Effectiveness of CLICS demonstrated in research applications

The ability of CLICS to provide new evidence to address cutting-edge questions in psychology and cognition has already been illustrated in a recent study published in Science, which concentrated on the world-wide coding of emotion concepts. The study compared colexification networks of words for emotion concepts from a global sample of languages, and revealed that the meanings of emotions vary greatly across language families.

"In this study, CLICS was used to study differences in the lexical coding of emotion in languages around the world, but the potential of the database is not limited to emotion concepts. Many more interesting questions can be tackled in the future," says Johann-Mattis List.

New standards and workflows allow for the reproducible harvesting of global lexical data

Building on the new guidelines for standardized data formats in cross-linguistic research, which were first presented in 2018 (DOI: 10.1038/sdata.2018.205), the CLICS team was able to increase the amount of data from 300 language varieties and 1200 concepts in the original database to 3156 language varieties and 2906 concepts in the current installation. The new version also guarantees the reproducibility of the data aggregation process, conforming to best practices in research data management. "Thanks to the new standards and workflows we developed, our data is not only FAIR (findable, accessible, interoperable, and reproducible), but the process of lifting linguistic data from their original forms to our cross-linguistic standards is also much more efficient than in the past," says Robert Forkel.

The effectiveness of the workflow developed for CLICS has been tested and confirmed in various validation experiments involving a large range of scholars and students. Two different student tasks were conducted, resulting in the creation of new datasets and the progressive improvement of the existing data. Students were tasked with working through the different steps of data set creation described in the study, e.g. data extraction, data mapping (to reference catalogs), and identification of sources. "Having people from outside of the core team use and test your tools is essential and helps tremendously in fine-tuning all processes," says Christoph Rzymski.

With CLICS and its workflow being accessible to a wider audience, scholars cannot only directly contribute to the database in the future; they can also profit from the established machinery and start their own targeted collections. "The number of linguists who actively use our standards and workflows is constantly increasing. We hope that the release of this new version of CLICS will propagate them further," says Simon Greenhill.

Researchers at the University of South Florida (USF) have discovered a novel feedback pathway from the brain to the eye that modulates eye pressure – a significant advancement in the effort to diagnose and treat glaucoma. Glaucoma is associated with increased pressure in the eye due to a reduce ability of the eye to maintain proper fluid drainage. The heightened pressure applies mechanical strain to the optic nerve as the nerve exits the eye, resulting in vision loss and potential blindness.

It has long been hypothesized that brain pressure might also play a role in glaucoma because the amount of strain on the optic nerve depends not just on eye pressure, but the difference in pressure between the eye and brain. The groundbreaking study published in the Journal of Physiology shows, for the first time, that eye and brain pressure are physiologically connected. The neuroscientists came to this conclusion by altering brain pressure in animal models and noting changes in the fluid drainage properties of the eye that could be blocked by chemicals that eliminate feedback signals from the brain. Interestingly, the eye's ability to clear fluid changed in a manner that restored a healthy pressure difference across the optic nerve.

"The drainage control system may service to protect the optic nerve from swings in eye or brain pressure," said Chris Passaglia, PhD, professor in the USF Department of Medical Engineering. "Its discovery offers a new target for glaucoma treatment, wherein the modulatory mechanisms of the system might be exploited to help lower eye pressure and impede disease progression in glaucoma patients."

Glaucoma is the leading cause of blindness in people over the age of 60. Since symptoms often don't arise until the condition has advanced, ophthalmologists check the eye pressures of patients during routine exams by administering an "air puff test." However, Passaglia says there are more complex aspects of the disease that make diagnosis a challenge. Some patients exhibit symptoms of glaucoma yet have normal eye pressure. While others with high eye pressure, don't always show signs of the condition.

Researchers are now trying to pinpoint the location of the brain cells that are sending signals to the eye and find which nerve fibers in the eye are being mediated by the brain. This will help physicians better diagnose glaucoma and have a greater understanding of what's causing it to develop.

Members of collective leadership groups can maintain cohesion and act decisively when faced with a crisis, in spite of lacking the formal authority to do so, according to new research from Cass Business School.

The study 'Ambiguous Authority and Hidden Hierarchy: Collective Leadership in an Elite Professional Service Firm' examines the distinctive power dynamics revealed among peers in a professional service firm as they responded to an acute organisational crisis - the substantial reduction in the size of the partnership when the global banking crisis forced a decline in the firm's revenue.

As they dealt with the crisis, members in the firm's collective leadership group exercised considerable informal power under the cloak of ambiguity, highlighting the hidden hierarchy that existed within the collective. Their response also emphasised the significance of an individual 'heroic' leader within the collective - in this case, the Senior Partner.

The author Professor Laura Empson said professional service firms provided an ideal example of collective leadership.

"Professional service firms have a partnership form of governance, with an extended network of professional peers collectively owning the firm. As a result, peers expect considerable autonomy and consultation about how their business is managed," she said.

The firm is ranked in its sector's top five globally in terms of revenue, profitability, and number of staff. At the time of the study (2009-10), it generated revenue of US$1,500 million, had 500 partners and employed 5,000 staff.

In 2008, the collapse of Lehman Brothers and the subsequent banking crisis caused a significant threat to the firm's core business, with the firm facing a sharp decline in income and limited scope to reduce costs as partner remuneration formed a substantial part of the cost base.

"There was no facility within the Partnership Agreement to reduce a partner's profit share and as a co-owner of the firm, a partner could only be compelled to leave following a vote of the full partnership. In addition to this, a large reduction in partner numbers would threaten the social embeddedness of the partnership as a whole," said Professor Empson.

Using interviews, institutional archives and observation, Professor Empson's research focused on three specific aspects of the collective leadership group: composition, interaction and situation (the response to the financial crisis).

The composition and authority of the collective leadership group was ambiguous, including the senior executive pair of Senior and Managing Partner, whose roles were deliberately not distinguished and had considerable overlap. Power relations between the two were ambiguous but not contested. The group also included joint heads of practice, Board members and an unofficial management team.

"The prevailing pattern of interaction within the group was of an instinctive, intuitive mutual adjustment which was demonstrated by how the group built consensus, created collective responsibility, attempted to avoid conflict and worked to maintain harmony," said Professor Empson.

"This was facilitated by high levels of social interaction within the group which members suggested was associated with the characteristics of career tenure, with people building close relationships over time, as well as shared values and mutual trust."

Professor Empson found that when dealing with the crisis, the Senior Partner mobilised a hidden hierarchy within the group, recognising that the group's ambiguous authority, which had worked until this point, represented a major difficulty in dealing with the crisis.

"The Senior Partner first organised an initial highly confidential meeting to discuss the firm's response with a smaller group including some joint heads of practice and some Board members. He and the Managing Partner said they didn't have all the answers and wanted to get the 'best minds' round the table to share thoughts and ideas".

After this meeting, the Managing Partner and Finance Director commenced formal contingency planning to develop a list of partners for restructuring. Their list of selected partners was then rejected by the practice heads and the Board and was further refined by a subset of the leadership group, with practice heads challenging each other's lists. This caused conflict and disagreement but was ultimately resolved after forceful interventions from the Senior and Managing Partner.

The Senior and Managing Partner then sought to build support for decisive action within the wider collective leadership group and other influential colleagues within the partnership by establishing consensus for the decision and extending collective responsibility.

It was decided that 50 partners (10 per cent of the total) would be asked to leave and offered a substantial compensation package. A further 35 partners were asked to accept a reduction in their partnership equity. All 'restructured' partners accepted their packages.

Professor Empson said the interviewees praised the Senior Partner for his deliberate yet unobtrusive leadership which resolved the crisis.

"Echoing Winston Churchill's famous speech during a bleak period of World War II, a Board member told me: "(The Senior Partner) managed to bring a tricky group of people to unity. It was his finest hour."

Professor Empson said the study suggests that collective leadership requires effective individual leaders who can nurture the context in which collective leadership can flourish.

"Whilst they may avoid the rhetoric and personality cult of the conventional 'heroic' leader, their ability to mobilise and direct individuals can be seen as a subtle and nuanced version of heroism. It is perhaps ironic that this study has highlighted to extent to which collective leadership ultimately ends and begins with the individual."

PITTSBURGH--Complete the following sentence: Rohingya refugees should go to¬¬¬ --

A. Pakistan.
B. Bangladesh.
C. Hell.

These aren't good choices, but all are sentiments that have been expressed repeatedly on social media. The Rohingyas, who began fleeing Myanamar in 2017 to avoid ethnic cleansing, are ill-equipped to defend themselves from these online attacks, but innovations from Carnegie Mellon University's Language Technologies Institute (LTI) could help counter the hate speech directed at them and other voiceless groups.

The LTI researchers have developed a system that leverages artificial intelligence to rapidly analyze hundreds of thousands of comments on social media and identify the fraction that defend or sympathize with disenfranchised minorities such as the Rohingya community. Human social media moderators, who couldn't possibly manually sift through so many comments, would then have the option to highlight this "help speech" in comment sections.

"Even if there's lots of hateful content, we can still find positive comments," said Ashiqur R. KhudaBukhsh, a post-doctoral researcher in the LTI who conducted the research with alumnus Shriphani Palakodety. Finding and highlighting these positive comments, they suggest, might do as much to make the internet a safer, healthier place as would detecting and eliminating hostile content or banning the trolls responsible.

Left to themselves, the Rohingyas are largely defenseless against online hate speech. Many of them have limited proficiency in global languages such as English, and they have little access to the internet. Most are too busy trying to stay alive to spend much time posting their own content, KhudaBukhsh said.

To find relevant help speech, the researchers used their technique to search more than a quarter of a million comments from YouTube in what they believe is the first AI-focused analysis of the Rohingya refugee crisis. They will present their findings at the Association for the Advancement of Artificial Intelligence annual conference, Feb. 7-12, in New York City.

Similarly, in an as-yet unpublished study, they used the technology to search for antiwar "hope speech" among almost a million YouTube comments surrounding the February 2019 Pulwama terror attack in Kashmir, which enflamed the longstanding India-Pakistan dispute over the region.

The ability to analyze such large quantities of text for content and opinion is possible because of recent major improvements in language models, said Jaime Carbonell, LTI director and a co-author on the study. These models learn from examples so they can predict what words are likely to occur in a given sequence and help machines understand what speakers and writers are trying to say.

But the CMU researchers developed a further innovation that made it possible to apply these models to short social media texts in South Asia, he added. Short bits of text, often with spelling and grammar mistakes, are difficult for machines to interpret. It's even harder in South Asian countries, where people may speak several languages and tend to "code switch," combining bits of different languages and even different writing systems in the same statement.

Existing machine learning methods create representations of words, or word embeddings, so that all words with a similar meaning are represented in the same way. This technique makes it possible to compute the proximity of a word to others in a comment or post. To extend this technique to the challenging texts of South Asia, the CMU team obtained new embeddings that revealed language groupings or clusters. This language identification technique worked as well or better than commercially available solutions.

This innovation has become an enabling technology for computational analyses of social media in that region, Carbonell noted.

Samplings of the YouTube comments showed about 10% of the comments were positive. When the researchers used their method to search for help speech in the larger dataset, the results were 88% positive, indicating that the method could substantially reduce the manual effort necessary to find them, KhudaBukhsh said.

"No country is too small to take on refugees," said one text, while another argued "all the countries should take a stand for these people."

But detecting pro-Rohingya texts can be a double-edged sword: some texts can contain language that could be considered hate speech against their alleged persecutors, he added.

Antagonists of the Rohingya are "really kind of like animals not like human beings so that's why they genocide innocent people," said one such text. Though the method reduces manual efforts, comments such as this indicate the continuing need for human judgment and for further research, the scientists concluded.

CORVALLIS, Ore. - For the first month and a half after receiving a modified toy car designed for children with disabilities, the kids and their families seemed motivated to use driving as a means of exploration and socialization.

But in the month and a half after that, most kids' driving time fell off to almost nothing.

Sam Logan, an Oregon State University kinesiologist who conducts research using the cars in his lab, said families who use the "Go Baby Go" ride-on cars require more robust support to push past barriers and keep using the cars over time. Otherwise, instead of helping young children with mobility issues explore their world, the cars end up forgotten in a closet.

OSU is one of several Go Baby Go chapters around the country working with children ages 3 and younger who experience limited mobility. OSU students take the off-the-shelf cars that kids can ride in and modify them with large easy-to-press activation buttons and PVC pipe frames to keep children sitting safely upright inside the car.

In previous studies, researchers made frequent home visits and were able to troubleshoot any problems families faced in using the cars. Logan said their aim has always been to be as inclusive as possible, so that even children with complex medical needs are able to drive.

This latest study used an electronic tracking system developed by two former high school students to record participants' car usage. Now freshmen at Brown University, twins Benjamin and Joshua Phelps started working in Logan's lab when they were freshmen at South Eugene High School and used open-source coding to craft a system that logged every push of the ignition button and the length of each use.

"The reason behind this study was to figure out what happens when families get cars and they're not part of a research study and they're not getting systematic support," said Logan, a kinesiologist in OSU's College of Public Health and Human Sciences. "Turns out, when we gave the cars out for three months and tracked their use, the average was about seven days out of 90 that they were used."

The drop-off in usage was significant: In the more hands-on studies, kids used the cars for an average of 1,060 minutes over three months; in this one, they averaged only 171 minutes, most of which occurred in the first 45 days. Half of the 14 participants saw less than 100 total minutes of use, including one child who never used the car.

In a companion study, families said the two biggest barriers to usage were their environment and the kids' responses to the device. The noise, speed and lack of finesse-steering posed challenges for some kids, and limited space or bad weather kept some families from making the car part of their regular routine.

To overcome those barriers, as the cars become more widespread, Logan sees the need for a welcome kit to help families get started, telling them what to expect and how to approach specific problems, as well as offering ideas for fun ways to use the cars, like driving to the mailbox or setting up a play car wash.

Community-based support is also crucial. Families in similar situations could share their knowledge with newcomers, and public recreational spaces could better accommodate the Go Baby Go cars.

"What we haven't figured out yet is, what can that support look like in a way that's sustainable across the country," Logan said.

Thanks to some astrophysical sleuthing, researchers have pinpointed an early galactic merger that helped shape the Milky Way.

The merger -- a collision, actually -- happened 11.5 billion years ago. That's when a small galaxy called Gaia-Enceladus slammed into what then existed of the Milky Way, Earth's home galaxy, which is about 13.5 billion years old.

"We know today that the Milky Way was formed by the merger of many small galaxies. This is the first time we have been able to determine when such a merger happened," said Sarbani Basu, professor and chair of astronomy at Yale and co-author of a new study reporting the discovery. "This is an important step in understanding when the Milky Way accreted, or collected, its mass."

The study appears Jan. 13 in the journal Nature Astronomy. Dozens of astronomers from around the world, led by the University of Birmingham in the U.K., conducted the work. Yale graduate student Joel Ong is also a co-author.

The research team followed the life story of a single, bright star in the Indus constellation, visible today from Earth's southern hemisphere. The scientists said this star, nu Indi, was already orbiting inside the Milky Way prior to the Gaia-Enceladus collision, which unfolded over millions of years. As the merger progressed, it altered nu Indi's orbit around the center of the Milky Way, providing a marker for when the merger happened. (Stars have orbits, just as planets do.)

"My role was to determine the age of the star (nu Indi) using seismic data," Basu said. "Like many low-mass stars, this star pulsates, or quakes, continuously. The quakes can be described as a series of tones and overtones."

Basu and her colleagues calculated "frequencies" from nu Indi's tones and overtones. Those frequencies, in turn, indicated the star's physical structure and properties. From there, the researchers were able to gauge nu Indi's stage of development, factor in its brightness, and estimate its age.

Knowing nu Indi's age provided a limit for when the merger could have taken place, the researchers said.

Some of the world's latest technology aided researchers in their detective work. They got data on nu Indi's quakes from NASA's Transiting Exoplanet Survey Satellite (TESS). Launched in 2018, TESS is surveying stars across most of the sky to search for planets orbiting those stars and to study the stars themselves. The researchers also used information collected from the European Space Agency (ESA) Gaia Mission.

University of Birmingham astrophysicist Bill Chaplin, lead author of the study, said determining the natural oscillations of stars -- called asteroseismology -- is a way to better understand the history of stars and the environments in which they formed.

"This study demonstrates the potential of asteroseismology with TESS, and what is possible when one has a variety of cutting-edge data available on a single, bright star," Chaplin said.

Houston Methodist scientists identified a protein found in ovarian cancer that may contribute to declining brain function and Alzheimer's disease, by combining computational methods and lab research.

"Our finding suggests another known protein may be coming into play here, which could help us identify a new therapeutic target one day," said Stephen T.C. Wong, Ph.D., lead author and Associate Director of Bioinformatics and Biostatistics Cores at Houston Methodist Cancer Center. "These findings may suggest a different role of the protein amyloid beta in neurodegeneration. Many Alzheimer's researchers have focused on amyloid beta alone, or connections between amyloid beta and another protein, tau."

In a study published online in the journal EBiomedicine, Wong and his team at the Ting Tsung and Wei Fong Chao Center for BRAIN of Houston Methodist, reported on a new role of OCIAD1 (ovarian cancer immune-reactive antigen domain containing 1). Originally discovered for its effect on ovarian cancer metastasis and stem cell metabolisms, Wong's group found the OCIAD1 protein in human brain cells--and determined it impairs neurons and damages synapses in the brain, contributing to neurodegeneration in Alzheimer's disease.

"Our research addresses a fundamental question of Alzheimer's disease--how, or if, amyloid beta accumulation that can be seen up to two decades prior to brain function decline is involved in progressive neurodegeneration," said Wong, who is John S Dunn Sr. presidential distinguished chair in biomedical engineering and professor of computer science and bioengineering in oncology at Houston Methodist. "Examining factors that contribute to the progressive decline in people with Alzheimer's will help us develop diagnostic biomarkers and new therapeutics."

The scientists culled through archived bioinformatics data of brain tissue from deceased Alzheimer's patients, as well as mouse models by blending computational methods with laboratory research. They determined that OCIAD1 plays a role in the disease's progressive neurodegeneration by impairing mitochondria function. Known as the powerhouse of cells, damage to mitochondria results in the trickle-down cell death effect in the brain leading to neuron damage.

"We applied a system biology strategy to see if we could find a different mechanism of neurodegeneration in Alzheimer's disease. We identified OCIAD1 as a new neurodegeneration-relevant factor, predicted its function, and demonstrated it mediates the long-term impact of amyloid beta on cells and synaptic damages by impairing mitochondria function," said Xuping Li, Ph.D., co-corresponding author and an instructor in Wong's group.

Alzheimer's research has traditionally focused on a few major themes - the role of the amyloid protein on neuronal loss and how this toxic protein causes injury by interacting with tau. More recently, however, other research considers amyloid beta a bystander and questions whether it causes neuronal degeneration at all.

Wong's group next intends to examine whether OCIAD1 plays a role in the interplay between two known changes in Alzheimer's - amyloid beta and tau aggregates. If so, additional research would focus on the potential of OCIAD1 as a biomarker or therapeutic target.

The epidemic of Alzheimer's, a disease affecting more than 5.8 million Americans, is expected to increase as the aging population lives longer. According to the Alzheimer's Association and the Center for Disease Control and Prevention, Alzheimer's is the most expensive disease in the United States, costing an estimated $290 billion in 2019.

Climate is an important factor in determining a plant species' growing zone. Some studies suggest that by the turn of the next century, climate change will have caused some species to spread several dozen kilometres north of their current distribution areas.

Such changes could have major consequences on how land-based ecosystems function.

But a northern migration isn't in the cards for sugar maples, according to Alexis Carteron, who recently published his doctoral research findings in the Journal of Ecology. His work is supervised by Professor Etienne Laliberté of Université de Montréal and co-supervised by Mark Vellend of Université de Sherbrooke.

Carteron and his colleagues at Université de Montréal's Department of Biological Sciences and the Institut de recherche en biologie végétale reached this conclusion after conducting experiments in greenhouses at the Jardin botanique de Montréal using soil samples harvested from Mont-Mégantic National Park.

The importance of soil composition
Climate - and the rising temperatures recorded in recent decades - contributes substantially to tree migration, but so does soil composition. However, we know much less about the effects of soil compared to climate.

That's why Carteron and his colleagues decided to study the effects that microorganisms and soil chemistry have on sugar maple (Acer saccharum) seedlings' performance (survival and biomass).

The researchers first collected soil samples from the eastern slope of Mont Saint-Joseph in Mont-Mégantic National Park in June 2016. The samples were taken at different altitudes to reflect the two types of forest that grow at the site.

"Mont Saint-Joseph has a substantial variation in altitude with a temperate forest of mostly sugar maple trees growing next to a boreal forest populated with conifers," said Carteron. "When you look at the mountain from a distance, it's easy to see where one forest starts and the other one ends."

Different soil experiments
The next step involved sprouting maple seeds, also known as samaras, planting them in greenhouses at the Jardin botanique and allowing them to grow over the summers of 2016 and 2017 (interrupted by a dormant phase in winter).

The researchers then applied various sterilization and inoculation treatments to the soil samples to better understand and differentiate the effects of biotic (microorganisms, fungi) and abiotic (acidity, nutrients) factors on sugar maple survival and growth.

Lower survival rates and biomass in boreal forests
At the end of summer 2017, Carteron and his colleagues assessed how well the young sugar maples had grown (based on survival rates and biomass) in different soil types.

They found that sugar maples grown in soil from the boreal forest had substantially poorer performance than those grown in the transition zone between temperate and boreal forests.

Likewise, sugar maple trees grown in boreal forest soil and inoculated boreal forest soil performed 37 per cent and 44% worse respectively than those grown in temperate forest soil.

The researchers also noted that the pH of boreal forest soil might have negatively affected sugar maple survival rates. Meanwhile, soil from temperate forests--which is where sugar maples typically grow--allowed for better arbuscular mycorrhizal fungal colonization in the trees' roots, which can promote tree survival and growth.

"Due to the interaction of biotic and abiotic factors, boreal forest soil seems to offer a less hospitable environment for sugar maple trees than other soil types," said Carteron. "While global warming might have made it physiologically possible for sugar maple trees to grow in more northern areas, the soil conditions in these areas make a northern migration less likely."

But shouldn't soil composition also change as the climate heats up? "It's certainly possible that the soil's biotic and abiotic properties could change and allow for the sugar maple's growing zone to expand, but that type of change would take a very long time to occur," said Carteron, who's won many research awards in recent years.

A single cell contains the genetic instructions for an entire organism. This genomic information is managed and processed by the complex machinery of chromatin -- a mix of DNA and protein within chromosomes whose function and role in disease are of increasing interest to scientists.

A Northwestern University research team -- using mathematical modeling and optical imaging they developed themselves -- has discovered how chromatin folds at the single-cell level. The researchers found chromatin is folded into a variety of tree-like domains spaced along a chromatin backbone. These small and large areas are like a mixed forest of trees growing from the forest floor. The overall structure is a 3D forest at microscale.

Chromatin is responsible for packing DNA into the cell nucleus. In humans, that's about six feet of DNA in each cell. The new work suggests that chromatin is more structured and hierarchical in single cells than previously thought. Learning how chromatin correctly operates will help scientists understand what goes wrong with it in cancer and other diseases.

"By integrating theoretical and experimental work, we have produced a new chromatin folding picture that helps us see how the 3D genome is organized at the single-cell level," said Igal Szleifer, the Christina Enroth-Cugell Professor of Biomedical Engineering at Northwestern's McCormick School of Engineering. He co-led the research team with Vadim Backman.

Details of the interdisciplinary study will be published Jan. 10 in the journal Science Advances.

"If genes are the hardware, chromatin is the software," said Backman, the Walter Dill Scott Professor of Biomedical Engineering and director of the Center for Physical Genomics and Engineering. "If the structure of chromatin changes, it can alter the processing of the information stored in the genome, but it does not alter the genes themselves. Understanding chromatin folding holds the key to understanding how cells differentiate and how cancer happens."

Advances in genomic, imaging and information technologies are just beginning to enable scientists to better understand how chromatin works. The Northwestern researchers used a Partial Wave Spectroscopic (PWS) microscope, optical imaging developed by Backman and colleagues, to peer deep into live cells and "sense" alterations in chromatin packing. They also used electron imaging.

"Our paradigm-shifting picture of chromatin folding is an important missing piece in the holistic view of genomic structure," said Kai Huang, the study's first author. Huang is a postdoctoral fellow in Backman's research group. "The results should inspire new strategies to fight cancer."

The expansion of Medicaid coverage for low-income adults permitted by the Affordable Care Act (ACA) was associated with a six percent reduction in total opioid overdose deaths nationally, according to new research from NYU Grossman School of Medicine and University of California, Davis.

Published online January 10 in JAMA Network Open, the study is the first to look at whether the ACA-related Medicaid expansion is associated with county-level opioid overdose mortality. The researchers analyzed cause-of-death data from the National Vital Statistics System from 3,109 counties within 49 states and the District of Columbia between 2001 and 2017--looking at changes in opioid overdose rates in counties that expanded Medicaid and compared those to changes that occurred in the same time period in counties within states that did not expand Medicaid.

Drug overdose remains a leading cause of injury death in the United States and is responsible for more than 70,000 deaths annually. After examining the association of Medicaid expansion with county-by-year counts of opioid overdose deaths and by class of opioid, the researchers found that:

Medicaid expansion may have prevented between 1,678 and 8,132 opioid overdose deaths in 2015 to 2017 in the 32 states that expanded Medicaid between 2014 and 2016.

Adoption of Medicaid expansion was associated with a six percent lower rate of total opioid overdose deaths, 11 percent lower rate of death involving heroin, and a 10 percent lower rate of death involving synthetic opioids other than methadone (such as fentanyl).

Unexpectedly, an 11 percent increase in methadone overdose mortality was observed with Medicaid expansion.

"Our findings suggest that as states invest more resources in addressing the opioid overdose epidemic, policymakers should pay attention to the role that expanding Medicaid can play in reducing opioid overdose deaths by providing greater access to health care, and in particular, to treatment for opioid use disorder," said Magdalena Cerdá, DrPH, associate professor and director of the Center for Opioid Epidemiology and Policy in the Department of Population Health at NYU Langone Health, and the study's senior author. "At a broader level, the findings of this study suggest that providing expanded access to health care may be a key policy lever to address the opioid overdose crisis."

One concerning finding from the study was the association of Medicaid expansion with an 11 percent increase in overdose deaths involving methadone. According to Cerdá, Medicaid beneficiaries are more likely to receive prescriptions for methadone to treat pain, compared to the general population. While the dispensing of methadone to treat opioid use disorder is highly effective and standardized, the use of methadone to treat pain is associated with greater risk of overdose reflecting in part wide variation in prescribing practices.

"Past research has found Medicaid expansion is associated with not only large decreases in the number of uninsured Americans, but also considerable increases in access to opioid use disorder treatment and the opioid overdose reversal medication naloxone," said Nicole Kravitz-Wirtz, PhD, MPH, assistant professor with the Violence Prevention Research Program in the Department of Emergency Medicine at UC Davis, and the study's lead author. "Ours was the first study to investigate the natural follow-up question: Is the expansion associated with reductions in local opioid overdose deaths? On balance, the answer appears to be yes."

Study Limitations

Cerdá and colleagues cite a number of study limitations. First, the research relies on coding of death certificate data. Since coding has changed over time, some deaths due to opioid overdoses may be misclassified. A second limitation is that the investigators looked at deaths among the whole population as opposed to just Medicaid beneficiaries. Any effect detected may be an underestimate of the effect that would be observed among Medicaid beneficiaries, says Cerdá.

Finally, although the researchers looked at the relationship of Medicaid expansion and overdose mortality, they did not directly examine pathways such as how Medicaid expansion affects access to treatment for opioid use disorder, how it affects opioid misuse and nonfatal overdoses, or how it affects access to naloxone, a medication used to counter the effects of opioid overdose. Each of these additional pathways are worthy of future study and are likely important levers to pull in terms of addressing the opioid overdose crisis, says Cerdá.

Congenital Zika Syndrome (CZS) refers to a collection of developmental malformations associated with Zika virus (ZIKV) congenital infection. This syndrome includes devastating conditions that have a huge impact on the rest of the life of the individual and their family, such as smaller (microcephaly) and unfolded (lissencephalic) brains, retinal abnormalities, enlarged ventricles of the heart, a lack of the inter-hemispheric connections and calcifications in the brain.

Brazil has been widely affected by ZIKV, but ~75% of CZS have been found in the socio-economically disadvantaged region of the Northeast.

In a new study, researchers from the University of Oxford and the Federal University of Rio de Janeiro have found that this rise in cases of CZS is linked to poor diet among the infants' mothers.

Professor Zoltán Molnár of the University of Oxford's Department of Physiology, Anatomy & Genetics, who participated in the study and has a long-term collaboration with the lead author Associate Professor Patricia Garcez of the Federal University of Rio de Janeiro Brazil partially supported by the Medical Research Council and Royal Society, said: 'We knew that areas of Brazil with the lowest socioeconomic status had the highest level of developmental impairment in babies due to CZS, which is why we looked at the possible link between ZIKV and one of the potentially most important co-factors, nutrition.

'This study showed that developmental impairment caused by ZIKV congenital infection is made much worse by environmental co-factors, specifically diets poor in protein, which explains why the devastating effects of CZS vary across ZIKV endemic regions.'

The link between Zika virus infection and the CZS has been demonstrated in previous studies, which helped researchers understand how the infection affected brain growth and development of blood vessels. These showed that ZIKV infects the cells that develop into the brain and alter genes and proteins related to the normal cell cycle and blood vessel development.

The current study also used a mouse model to replicate the effects of Zika infection in mice that had a low-protein diet, and found that several of the pathological signs found in humans appeared in the undernourished mice in a similar way.

Professor Molnár added: 'When we replicated the effects seen in humans who had poor diets in mice we saw similar effects in the foetuses, such as placental damage as well as poor embryonic body growth and a reduction in brain size of newborns born to undernourished pregnant mouse.

'The mouse mothers were clearly less able to fight against ZIKV, which was shown by a robust and persistent ZIKV infection in the spleens of undernourished mothers, in contrast to healthy mice. Our undernourished mouse model helped us to identify the cellular mechanisms that are responsible for the differences in humans.'

'Improving diet alone will not protect against ZIKV infections, but it can determine the severity of the CZS.

'While we need more work to translate these findings to human disease, our mouse model helped us to identify significant differences in the regulation patterns of key molecular pathways, and particular genes identified within developing brains reflect how a poor nutritional status increases the adverse effects of ZIKV infection.'

The study was partially funded by a joint MRC Grant between Professor Zoltán Molnár of the University of Oxford and Associate Professor Patricia Garcez of the Federal University of Rio de Janeiro.

Computational biologists led by Prof. Yvan Saeys (VIB-UGent Center for Inflammation Research) developed a new bioinformatics method to better study communication between cells. This method, called NicheNet, helps researchers to gain insight into how the gene expression of cells is regulated by interacting cells. NicheNet has a broad range of potential applications in fields like immunology and tumor biology, and was already successfully used by the collaborating group of Prof. Martin Guilliams (VIB-UGent Center for Inflammation Research).

Cell neighbors

In multicellular organisms cells don't function on their own, but they produce signaling molecules that influence gene expression in interacting cells. This intercellular communication plays an important role in many biological processes, such as the development and functioning of cells. Studying intercellular communication is not only important to understand fundamental biology, but also to gain insights into diseases like cancer. Interactions between cancer cells and other cells in the microenvironment of the tumor are crucial for its growth.

An example of a process in which intercellular communication is essential, is the differentiation of macrophages, a type of immune cell. This process is affected by other cell types in the environment, or 'niche', of the macrophage.

Researchers from the group of Martin Guilliams (VIB-Ghent University), who work in close collaboration with the Saeys lab, wanted to study this process for Kupffer cells, a macrophage in the liver blood stream. They generated a lot of gene expression data of all cells involved.

"But, using this type of data to unravel how cells communicate is not a trivial task'', says Yvan Saeys. "We needed to develop a new sophisticated algorithm to tackle this problem."

Machine learning for talking cells

Guided by post-doc Wouter Saelens and Yvan Saeys, PhD student Robin Browaeys started developing such a new method to analyze how cells might signal each other.

Browaeys explains: "Our idea was to make use of the enormous amount of available knowledge on intercellular signaling that was acquired over the years, and use this knowledge to find out which intercellular communication processes are going on in the data we had. To do this, we had to apply several machine learning and statistical techniques, including network algorithms that are also used to analyze social networks, for example."

Saelens summarizes: "In essence, you can compare our newly developed method, NicheNet, with a hypothetical biologist who not only knows everything that is already published about intercellular communication, but who can also apply all this knowledge on complex, big datasets. Making reasonable predictions on intercellular communication is something that would have required weeks of literature study in the past, but this can now be done with the push of a button."

Testing NicheNet

A first test case for NicheNet was the Kupffer cell niche data generated by the Guilliams lab. Researchers from that lab were able to experimentally validate some of the signals that NicheNet predicted. "Thanks to NicheNet, we looked into factors that we would not have thought about ourselves", confirms Martin Guilliams. "For us, NicheNet was an essential tool to help unravel the Kupffer cell niche".

"In addition to the Kupffer cell story, we have also been applying NicheNet to investigate cell-cell communication in the tumor microenvironment", adds Saeys. "We used NicheNet on single-cell data that was published earlier, but we are now working on novel single-cell datasets generated by collaborating research groups. How different types of treatment affect the cellular interactions within the tumor microenvironment, and how this influences the tumor, are some of the questions we are trying to address with NicheNet."

These different applications illustrate the value of NicheNet for generating novel hypotheses about how cells communicate in fundamental biological processes and diseases.

Stellar black holes form when massive stars end their life in a dramatic collapse. Observations have shown that stellar black holes typically have masses of about ten times that of the Sun, in accordance with the theory of stellar evolution. Recently, a Chinese team of astronomers claimed to have discovered a black hole as massive as 70 solar masses, which, if confirmed, would severely challenge the current view of stellar evolution. The publication immediately triggered theoretical investigations as well as additional observations by other astrophysicists. Among those to take a closer look at the object was a team of astronomers from the Universities of Erlangen-Nürnberg and Potsdam. They discovered that it may not necessarily be a black hole at all, but possibly a massive neutron star or even an 'ordinary' star. Their results have now been published as a highlight-paper in the renowned journal Astronomy & Astrophysics*.

The putative black hole was detected indirectly from the motion of a bright companion star, orbiting an invisible compact object over a period of about 80 days. From new observations, a Belgian team showed that the original measurements were misinterpreted and that the mass of the black hole is, in fact, very uncertain. The most important question, namely how the observed binary system was created, remains unanswered. A crucial aspect is the mass of the visible companion, the hot star LS V+22 25. The more massive this star is, the more massive the black hole has to be to induce the observed motion of the bright star. The latter was considered to be a normal star, eight times more massive than the Sun.

A team of astronomers from Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU) and the University of Potsdam had a closer look at the archival spectrum of LS V+22 25, taken by the Keck telescope at Mauna Kea, Hawaii. In particular, they were interested in studying the abundances of the chemical elements on the stellar surface. Interestingly, they detected deviations in the abundances of helium, carbon, nitrogen, and oxygen compared to the standard composition of a young massive star. The observed pattern on the surface showed ashes resulting from the nuclear fusion of hydrogen, a process that only happens deep in the core of young stars and would not be expected to be detected at its surface.

'At first glance, the spectrum did indeed look like one from a young massive star. However, several properties appeared rather suspicious. This motivated us to have a fresh look at the archival data', said Andreas Irrgang, the leading scientist of this study and a member of the Dr. Karl Remeis-Observatory in Bamberg, the Astronomical Institute of FAU.

The authors concluded that LS V+22 25 must have interacted with its compact companion in the past. During this episode of mass-transfer, the outer layers of the star were removed and now the stripped helium core is visible, enriched with the ashes from the burning of hydrogen.

However, stripped helium stars are much lighter than their normal counterparts. Combining their results with recent distance measurements from the Gaia space telescope, the authors determined a most likely stellar mass of only 1.1 (with an uncertainty of +/-0.5) times that of the Sun. This yields a minimum mass of only 2-3 solar masses for the compact companion, suggesting that it may not necessarily be a black hole at all, but possibly a massive neutron star or even an 'ordinary' star.

The star LS V+22 25 has become famous for possibly having a massive black hole companion. However, a closer look at the star itself reveals that it is a very intriguing object in its own right, as whilst stripped helium stars of intermediate mass have been predicted in theory, only very few have been discovered so far. They are key objects to understanding binary star interactions.