Culture

Washington, DC - January 23, 2020 - Government and academic investigators have developed a vaccine against African swine fever that appears to be far more effective than previously developed vaccines. The research appears this week in the Journal of Virology, a publication of the American Society for Microbiology.

Currently, there is no commercially available vaccine against African swine fever, which has been devastating the swine industry in Eastern Europe and Southeast Asia. African swine fever virus (ASFV) is highly contagious and often lethal to domestic and wild pigs. Outbreaks have been quelled--more or less--"by animal quarantine and slaughter," according to the report. (Humans are not susceptible to ASFV.)

In the study, both low and high doses of the vaccine were 100% effective against the virus when the pigs were challenged 28 days post-inoculation.

The research was motivated by the 2007 outbreak of African swine fever in the Republic of Georgia, said principal investigator Douglas P. Gladue, PhD, Senior Scientist, Plum Island Animal Disease Center, Agricultural Research Service, US Department of Agriculture. "This was the first outbreak in recent history outside of Africa and Sardinia--where swine fever is endemic--and this particular strain has been highly lethal and highly contagious, spreading quickly to neighboring countries." This is also a new strain of the virus, now known as ASFV-G (the G stands for Georgia).

The 2007 outbreak was also the genesis of the African swine fever that has been spreading through Eastern Europe and east Asia, said Manuel V. Borca, PhD, also a Senior Scientist at the Plum Island Animal Disease Center.

There is limited cross-protection between strains of African swine fever, likely because the antigens and degree of virulence differ among them, and none of the historical experimental vaccines have been shown to be effective against ASFV-G, said Dr. Gladue.

So the investigators at Plum Island Animal Disease Center set out to develop a vaccine. Part of the process of developing whole virus vaccines involves deleting virulence genes from the virus. But when the researchers deleted genes similar to those that had been deleted in older ASFV strains to attenuate them, "it became clear that ASFV-G was much more virulent" than the other, historical isolates, because it retained a higher level of virulence, said Dr. Gladue. The investigators then realized they needed a different genetic target in order to attenuate ASFV-G.

They used a predictive methodology called a computational pipeline to predict the roles of proteins on the virus. The computational pipeline predicted that a protein called I177l could interfere with the immune system of the pig. When they deleted this gene, ASFV-G was completely attenuated.

More work needs to be done to meet regulatory requirements for commercialization, said Dr. Gladue. But "This new experimental ASFV vaccine shows promise, and offers complete protection against the current strain currently producing outbreaks throughout Eastern Europe and Asia."

EAST LANSING, Mich. - The United States currently averages 20 mass shootings per year. Researchers from Michigan State University measured the extent to which mass shootings are committed by domestic violence perpetrators, suggesting how firearm restrictions may prevent these tragedies.

Under federal law, when people are convicted of domestic violence misdemeanor crimes, they are prohibited from purchasing and possessing guns for the rest of their lives. However, holes in the system allow potential mass shooters to slip through the cracks.

"We found that 38% of known mass shooters had a history of domestic violence, either known to the justice system or mentioned in the media," said April Zeoli, associate professor of criminal justice at MSU and lead author of the research. "Very few of those who committed mass shootings seemed to have firearm restrictions due to domestic violence; the fact that some of them had those restrictions suggests that we are not actually preventing purchase or possession of a gun as well as we could or need to be."

Zeoli explained that some cases of domestic violence never result in firearm restrictions because law enforcement is never involved, because the cases were not referred to prosecutors, because the charges that were filed didn't qualify for firearm restrictions or because the case didn't meet a relationship requirement for the gun restrictions to be applied.

"In more than 20 states, a person convicted of misdemeanor domestic violence against a dating partner will not be restricted from firearm access - you must have lived together, be married or have a child together to qualify for the restriction," Zeoli said.

The research, published in Criminology & Public Policy, looked at the nearly 90 mass shootings that took place between 2014 and 2017. Zeoli and co-author Jennifer Paruk cross-checked four separate mass shooting databases - compiled by Every Town for Gun Safety, USA Today, Gun Violence Archives and Mother Jones - and then used publicly available criminal records to see what other criminal charges the shooters had against them.

"The public sees media reports of mass shootings happening in movie theaters, schools, night clubs and beyond - these are the ones that keep us all up at night," Zeoli said. "But the majority of these mass shootings involved intimate and family member victims."

The researchers pinpointed ways - called "exit points" in the paper - that firearm restrictions failed to prevent a shooter from buying a gun, which include purchases made through private sales and a failure to report gun disqualifications to the criminal background check system.

"In the case of the Sutherland Springs Baptist church shooting, the shooter did in fact qualify for a gun restriction under federal law because of domestic violence," Zeoli said. "However, the conviction was in military court, and the military never sent the conviction records to the background check system; so, when he went to buy a gun, nothing showed up on his record."

Zeoli hopes that the findings inspire both the public and lawmakers to learn about their states' laws, as well as the exit points she and Paruk found that can lead to a gun landing in the hands of the wrong type of person.

"The image you get of mass shootings in the media isn't always the full picture," Zeoli said. "People should determine, in their state, whether it may be possible for people convicted of domestic violence to obtain a firearm. Many of those exit points can be closed through legislation and better implementation of the law. My feeling - and my hope - is that we'll continue to see states work to implement restrictions to dangerous individuals from gaining access to guns and prevent gun violence from happening."

Family caregivers of the deceased rated the quality of end-of-life care in the intensive care unit (ICU) higher than the end-of-life care in other hospital departments (also called wards), according to new, large Penn Medicine study in the American Journal of Respiratory and Critical Care Medicine. The research challenges a common belief that dying in the ICU is a less favorable experience than dying elsewhere in the hospital.

The findings don't suggest that more dying patients should be moved to the ICU, rather that more efforts should be made to learn about the elements in the ICU that potentially improve end-of-care experiences, such as higher staffing ratios. These lessons could then be applied to other clinical settings.

What's more, ICU use - often associated with unfavorable end-of-life experiences by clinicians, researchers, and policymakers - may not be an appropriate measure of poor quality end-of-life care.

"It has been assumed that dying in an ICU is even worse than a ward because it's more expensive and more intensive. But that has been never been based on any sound evidence - it's just based on traditional ways of looking at the problem," said senior author Scott D. Halpern, MD, PhD, a critical care physician and professor of Medicine, Epidemiology, and Medical Ethics and Health Policy in Penn's Perelman School of Medicine, and director of the Palliative and Advanced Illness Research (PAIR) Center. "So, we wanted to better understand the difference in the care. Are the doctors getting it right? Are the researchers getting it right? Are policymakers getting it right? Turns out, none of those parties were getting it right."

The study analyzed clinical data and bereavement surveys from the family members of more than 28,000 patients who died in 106 Veterans Administration (VA) acute-care hospitals between 2010 and 2016 in and outside the ICU, including those who experienced care in both.

Compared with ward-based care, the researchers found ICU care was associated with higher ratings by family caregivers of overall care, pain management, clinician-family communication, emotional support, and spiritual support during patients' final 30 days.

Reducing ICU use has been a longstanding research and policy objective. In many surveys, ICU care has received lower ratings for cancer patients, likely because they underwent aggressive treatments. Driven by this and other factors, researchers have used ICU deaths as an outcome measure in their studies, with the idea that lower rates of ICU death represent better end-of-life care. Policymakers have also clung to this notion, with some pushing for ICU utilization as a measure of low-quality care - a move that could adversely affect hospital patient and safety scores. However, few studies exist to support this view.

To better understand the quality of end-of-life care inside and outside the ICU, Penn Medicine researchers analyzed patient and hospitalization characteristics from VA records and results from the Bereaved Family Survey, which are distributed to family members or close contacts of every veteran who dies in a VA acute care hospital or other VA institutional setting.

The study found that "ICU-only care" was associated with more frequent optimal ratings than "no ICU care," including overall excellent care (56.6 percent vs. 48.1 percent), care consistent with preferences (78.7 percent vs. 72.4 percent), and having pain controlled (51.3 percent vs. 46.7 percent).

Among patients with mixed care, increasing ICU time was associated with higher ratings on these same measures.

"Instead of just looking at people who got all of their care in the ICU and people who did not, we looked at all people in the hospital," Halpern said. "That actually provides the most compelling evidence that ICU care is associated with better end-of-life quality because we found that the greater the proportion of time spent in the ICU, the higher the quality of end-of-life care. It was a classic 'dose-response' relationship."

The higher ratings may be explained by the more favorable staffing ratios in the ICU and other features that can improve symptom management and other facets of care. ICUs have been the focus of significant research and guidelines on end-of-life care, so greater experience among clinicians and nurses may translate into improved communication and symptom management. And family members of patients receiving ICU care may take solace in knowing that all reasonable efforts to extend life were attempted - which may affect their ratings.

"The implication is that we should work to improve end-of-life care in acute care settings like hospital wards. And because moving people from ICUs to wards may not be a good strategy to improve their end-of-life experience, we need to focus instead on getting people out the hospital entirely for end of life care when feasible," said first author Joshua A. Rolnick, MD, a physician in Penn's division of General Internal Medicine and at the Philadelphia VA Medical Center.

A noteworthy secondary finding was the high rate of uncontrolled pain among patients: more than 50 percent. This finding is consistent with prior work suggesting high unmet needs for symptom management near the end of life that deserves further study and attention.

According to the researchers, further studies are warranted to not only better understand how factors in ICU may improve end-of-life care outside the ICU in the hospital, but also assisted-care settings, including home hospice care, and to help reduce overall hospitalizations.

The BioScience Talks podcast features discussions of topical issues related to the biological sciences.

Agricultural areas are often considered distinct from local ecosystems, and in many cases, such an assessment rings true. Single-crop farmlands, reliant on the liberal use of pest- and herbicides, often limit local biodiversity and species interactions. However, in other agricultural settings, robust ecosystems thrive, intermingled with crops and supporting a diversity of species.

One such acroecosystem is coffee's. On shade-coffee farms, the coffee plant is consumed by numerous pests, including the green coffee scale, coffee berry borer, and coffee rust disease. In turn, these species are regulated by a variety of natural enemies, through processes of often staggering complexity. In a major BioScience Overview article, John Vandermeer of the University of Michigan and his colleagues aim to untangle such complexities and get at the heart of pest control in the coffee system, emphasizing the intersection of ecology with "the burgeoning field of complex systems, including references to chaos, critical transitions, hysteresis, basin or boundary collision, and spatial self-organization."

Dr. Vandermeer joins us on this episode of BioScience Talks to discuss the coffee agroecosystem--and the many species and dynamics that underlie it.

The International Sweeteners Association (ISA) welcomes the publication this month of a new scientific report* by Ashwell et al. in Nutrition Research Reviews.(1)

This new publication points to the extensive body of robust scientific evidence that shows that low/no calorie sweeteners:

- Are safe: all of them have undergone an extensive safety evaluation process by food safety authorities globally prior to being approved for use on the market;
- Have no adverse effect on blood glucose regulation in people with and without diabetes and lead to a lower blood glucose rise compared to sugar;(2) they have therefore a role to play in the dietary management of diabetes when used as substitutes for sugars;
- Can help reduce net calorie intake while providing the desired sweet taste, when used in place of sugar to reduce energy density of foods and drinks; and
- Can be part of the strategies to consider to reduce sugars intake, in line with public health recommendations worldwide aimed at reducing the risk and prevalence of obesity, a major public health concern.

While reduction in the intake of sugars is being recommended around the world to address the increasing rates of obesity, the authors agree on the need for evidence-based communication to ensure more informed public health decisions and public attitudes towards low/no calorie sweeteners.

Commenting on the paper, lead author Dr Margaret Ashwell highlighted that: "The aim of our workshop was to stimulate forward thinking as well as to restate principles. It is the consensus of the panel that the substantial body of evidence around low calorie sweeteners' safety and role in helping people reduce their sugar and calorie intake, a public health priority, should be communicated in a consistent manner". Co-author Sigrid Gibson added: "We [the 17 panel experts] came together to discuss and debate what we really do know, what we don't yet know, and what should be done in relation to research on low calorie sweeteners, in light of current public health policies. This experts' consensus is important because it provides clarity to communicators, so that they know they can give a message with confidence. So, we hope that the recommendations arising from this workshop will assist policy makers and other stakeholders including NGOs, health professionals, research funding bodies and the food and beverage industry".

Provided that they are used in place of sugar and in the context of a healthy diet and lifestyle, the experts agree that low/no calorie sweeteners have a beneficial role to play in helping achieve sugar and calorie intake reduction, which associated health gains cannot be ignored. They clarified that the benefit of using low/no calorie sweeteners will depend on the amount of sugars replaced in the diet as well as the overall diet quality. As also stated by the experts' panel, the "Use of LCS [low calorie sweeteners] alone cannot be expected to act as a 'silver bullet' for weight loss". Nevertheless, and based on the robust scientific evidence considered, the authors concluded that low/no calorie sweeteners can be useful in dietary approaches to both prevent and manage diabetes and obesity, and can facilitate reduction in energy intake and weight loss.

Having discussed research priorities, and in line with other consensus of experts published recently(3,4), the panel agreed that future research should include well-designed, high-quality human studies to confirm long-term benefits of low/no calorie sweeteners. Furthermore, the report indicated the need for studies to model low/no calorie sweeteners' impact on sugar reduction and diet quality. With regard to suggested actions, the group of experts pointed to the importance of effective communication strategies to inform consumers - to tackle misperceptions - as well as NGOs, health professionals, research funding bodies and the food and beverage industry. They further concluded that: "Efforts should be made to understand and, where possible, reconcile policy discrepancies between organisations and reduce regulatory hurdles that impede product development and reformulation designed to reduce sugars and/or calories."

CORVALLIS, Ore. - People with facial paralysis are more likely to face depression and anxiety than the general population, especially if the paralysis occurs later in life rather than at birth, according to a recent study from Oregon State University.

OSU College of Liberal Arts researcher Kathleen Bogart surveyed people around the world with different forms of facial paralysis, both congenital and acquired, to understand socioemotional issues affecting them. She looked at emotional clarity - the ability to identify and understand one's own emotions - as well as stigma, attachment and psychological distress.

About 225,000 people per year develop facial paralysis in the U.S., whether from injury or illness like Bell's palsy, or from congenital issues like Moebius syndrome or birth trauma. Bogart's study focused on peripheral facial paralysis, which affects only the face and is caused by facial nerve problems, rather than paralysis from other cognitive conditions that affect multiple parts of the body.

The study tested two competing ideas: The "acquired advantage" hypothesis theorized that people who acquire paralysis later in life would fare better on emotional clarity, as they completed their early developmental stages with a full range of motion and expression. The "congenital advantage" hypothesis countered that people born with paralysis were able to adapt from a young age and thus developed their own alternative ways of expressing themselves, such as body language and tone of voice.

Contrary to popular opinion, it's people who acquire paralysis later in life that struggle the most, study results showed.

"It seemed that people assumed that people who went through their initial development not having facial paralysis would be doing better; like 'having a so-called normal early childhood would give you the emotional fundamentals,'" Bogart said. "But these findings are actually really neat, because lots of people have disabilities, and this suggests the ones who have them from birth actually seem to have an advantage. They're learning how to function in the world for the first time, alongside that disability, at a time of great cognitive flexibility. People with congenital disabilities have a lot to teach us about adaptation."

When people acquire paralysis later in life, she said, there's a real sense of loss or a change in identity that those born with paralysis don't experience.

Facial paralysis can affect people in a variety of ways, including difficulty with facial expressions, vision, speech, eating and drinking. It can also cause physical discomfort and pain.

And because people with facial paralysis have visibly different faces, regardless of when they acquired the paralysis, they also deal with a lot of stigma and discrimination, Bogart said.

The shock of suddenly experiencing stigma, or experiencing stigma in that way, also contributes to the challenges faced by people with acquired paralysis, she said.

People with acquired paralysis reported higher rates of depression and anxiety, as well as more problems with emotional clarity and attachment, likely stemming from the newfound difficulty in conveying emotions to other people.

But both groups still experienced greater stigma than the norm, even though the norms for this question were calculated from people with other stigmatized neurological conditions - just without visible facial paralysis.

Published in the journal Health Psychology, this was the largest psychological study of people with peripheral facial paralysis to date. After contacting participants through facial paralysis organizations and social media, Bogart surveyed 112 adults with congenital paralysis and 434 people with acquired paralysis, which is much more common. Participants were from 37 countries, with the majority in the U.S., and the vast majority were white women. The average age was about 45 years old.

To address these issues and alleviate psychological distress, Bogart says, there need to be greater protections against discrimination and bullying toward people with visibly different faces. People with facial paralysis often report being turned down for public-facing jobs or leadership roles, as well as being perceived as unfriendly or uninterested because of their facial appearance. Though the Americans with Disabilities Act prohibits this type of discrimination, it is not well enforced, Bogart said.

"We found that stigma was the main predictor of anxiety and depression," she said. "This is a socially created problem that can be acted upon."

There are currently no specialized therapies to support people with facial paralysis experiencing psychological distress. Bogart calls for the development of these therapies, which could include support groups and communication skills training.

High-protein diets may help people lose weight and build muscle, but a new study in mice suggests they have a down side: They lead to more plaque in the arteries. Further, the new research shows that high-protein diets spur unstable plaque -- the kind most prone to rupturing and causing blocked arteries. More plaque buildup in the arteries, particularly if it's unstable, increases the risk of heart attack.

The new study, by researchers at Washington University School of Medicine in St. Louis, appears Jan. 23 in the journal Nature Metabolism.

"There are clear weight-loss benefits to high-protein diets, which has boosted their popularity in recent years," said senior author Babak Razani, MD, PhD, an associate professor of medicine. "But animal studies and some large epidemiological studies in people have linked high dietary protein to cardiovascular problems. We decided to take a look at whether there is truly a causal link between high dietary protein and poorer cardiovascular health."

The researchers studied mice fed a high-fat diet to deliberately induce atherosclerosis, or plaque buildup in the arteries. According to Razani, mice must eat a high-fat diet to develop arterial plaque. Therefore, some of the mice received a high-fat diet that was also high in protein. And others were fed a high-fat, low-protein diet for comparison.

"A couple of scoops of protein powder in a milkshake or a smoothie adds something like 40 grams of protein -- almost equivalent to the daily recommended intake," Razani said. "To see if protein has an effect on cardiovascular health, we tripled the amount of protein that the mice receive in the high-fat, high-protein diet -- keeping the fat constant. Protein went from 15% to 46% of calories for these mice."

The mice on the high-fat, high-protein diet developed worse atherosclerosis -- about 30% more plaque in the arteries -- than mice on the high-fat, normal-protein diet, despite the fact that the mice eating more protein did not gain weight, unlike the mice on the high-fat, normal-protein diet.

"This study is not the first to show a telltale increase in plaque with high-protein diets, but it offers a deeper understanding of the impact of high protein with the detailed analysis of the plaques," Razani said. "In other words, our study shows how and why dietary protein leads to the development of unstable plaques."

Plaque contains a mix of fat, cholesterol, calcium deposits and dead cells. Past work by Razani's team and other groups has shown that immune cells called macrophages work to clean up plaque in arteries. But the environment inside plaque can overwhelm these cells, and when such cells die, they make the problem worse, contributing to plaque buildup and increasing plaque complexity.

"In mice on the high-protein diet, their plaques were a macrophage graveyard," Razani said. "Many dead cells in the core of the plaque make it extremely unstable and prone to rupture. As blood flows past the plaque, that force -- especially in the context of high blood pressure -- puts a lot of stress on it. This situation is a recipe for a heart attack."

To understand how high dietary protein might increase plaque complexity, Razani and his colleagues studied the path protein takes after it has been digested -- broken down into its original building blocks, called amino acids.

Razani and his team found that excess amino acids from a high-protein diet activate a protein in macrophages called mTOR, which tells the cell to grow rather than go about its housecleaning tasks. The signals from mTOR shut down the cells' ability to clean up the toxic waste of the plaque, and this sets off a chain of events that results in macrophage death. The researchers found that certain amino acids, especially leucine and arginine, were more potent in activating mTOR -- and derailing macrophages from their cleanup duties, leading to cell death -- than other amino acids.

"Leucine is particularly high in red meat, compared with, say, fish or plant sources of protein," Razani said. "A future study might look at high-protein diets with different amino acid contents to see if that could have an effect on plaque complexity. Cell death is the key feature of plaque instability. If you could stop these cells from dying, you might not make the plaque smaller, but you would reduce its instability.

"This work not only defines the critical processes underlying the cardiovascular risks of dietary protein but also lays the groundwork for targeting these pathways in treating heart disease," he said.

Chronic alcohol abuse and hepatitis can injure the liver, often leading to a buildup of collagen and scar tissue. Understanding this process, known as liver fibrosis, could help researchers develop new ways to prevent or treat conditions such as alcoholic liver disease, non-alcoholic steatohepatitis (NASH) and nonalcoholic flatty liver disease (NAFLD).

In a study published January 23, 2020 by Gastroenterology, researchers at University of California San Diego School of Medicine demonstrated for the first time that liver fibrosis progression could potentially be addressed by manipulating a special population of liver cells called hepatic stellate cells (HSCs).

In the liver, HSCs are found in three forms: naïve in healthy people, activated in people with liver disease and inactivated in people who have recovered from liver fibrosis. In both mouse and human liver tissue, the researchers discovered they can control this cellular switch by activating or inhibiting specific transcription factors, molecules that turn genes "on" or "off."

"We are excited to discover that HSCs have this flexibility, and that we can change their type by manipulating the molecules involved," said Tatiana Kisseleva, MD, PhD, associate professor of surgery at UC San Diego School of Medicine. "These insights may allow us to develop new ways to stop the progression of liver fibrosis." Kisseleva led the study with first author Xiao Liu, a researcher in her lab.

In healthy people, naïve HSCs store vitamin A and support normal liver function -- filtering blood, metabolizing drugs and producing bile acids to aid digestion. But in alcoholic liver disease or hepatitis, HSCs become activated and start producing collagen, a hallmark of fibrosis.

The goals of the study, Kisseleva said, were to 1) understand the mechanism that switches HSCs from their naïve to their active state and 2) find ways to stop the process and inactivate collagen-producing HSCs.

Kisseleva and her team identified several transcription factors that distinguish active HSCs from naïve HSCs, and studied them in human liver samples and mouse models. Some of the transcription factors they found prevent activation of HSCs or inactivate them. When the levels of each of these naïve-associated transcription factors were reduced in mouse HSCs, the cells became activated, increased their collagen production and promoted fibrosis. Liver fibrosis was more severe in mice lacking these transcription factors.

The researchers also took the opposite approach, stimulating one of these transcription factors, PPARγ, with a chemical called rosiglitazone. In mice treated with rosiglitazone, the researchers observed liver fibrosis regression and faster resolution of fibrous scars than in untreated mice.

"We essentially found that we can help PPARγ put a stop to collagen production by activated HSCs," Kisseleva said.

New therapeutic targets are urgently needed for liver fibrosis, she said. According to the US National Institutes of Health, weight loss is the only known method for reducing liver fibrosis associated with NAFLD and NASH. Therapeutic drugs to slow the progression of disease are only available in advanced stages, where NASH has led to liver cirrhosis. Alcoholic liver disease is most commonly treated with corticosteroids, but they are not highly effective. Early liver transplantation is the only proven cure, but is offered only at select medical centers to a limited number of patients.

To further their efforts, Kisseleva and team are now exploring the role of other transcription factors involved in maintaining HSC naïveté, and searching for activators and inhibitors. They also plan to take a closer look at the genes these transcription factors are regulating, and determine if they can be directly targeted to inactivate HSCs.

LOS ALAMOS, N.M., January 23, 2020--Take biomass-derived acetone--common nail polish remover--use light to upgrade it to higher-mass hydrocarbons, and, voila, you have a domestically generated product that can be blended with conventional jet fuel to fly while providing environmental benefits, creating domestic jobs, securing the nation's global leadership in bioenergy technologies, and improving U.S. energy security.

"This process allows us to transform a natural product into a fuel additive, improving the performance of petroleum-based jet fuel," said Courtney Ford Ryan, a postdoctoral fellow at Los Alamos National Laboratory and lead author of a paper out in preprint form in the journal Sustainable Energy and Fuels.

"We converted bio-derived acetone to isophorone and then used a UV lamp to convert it to a cyclobutane, a type of hydrocarbon with high energy density for fuels applications," Ryan said.

There are many challenges in using acetone for fuels applications, the paper's authors note. Its volatility precludes its direct use as a fuel, and it requires chemical upgrading to be suitable for introduction into the fuel supply, as acetone has a nasty habit of dissolving engine parts and O-rings. So by upgrading the initial product to a cyclobutane, a potentially safer and more energy-dense fuel is created, while reducing the hydrogen input required for upgrading a bio-derived feedstock.

"Reducing high-pressure hydrogen treatment in synthesizing renewable fuels is important, because most hydrogen is derived from using steam to reform natural gas, which generates carbon dioxide," she said. Next, more work is needed to make a catalyst that could do it using sunlight, Ryan noted.

WOODS HOLE, Mass. -- A scientific discovery often starts with a chance observation made by open minds who realize its potential. This happens over and over again in the MBL's Advanced Research Training courses. A fresh insight leads to a course research project that, after the course is over, can blossom into a full-scale scientific collaboration that continues to connect course participants across the globe.

In 2014, students and faculty in the MBL's Microbial Diversity course made such a serendipitous observation. A team followed up on it in the coming years and last week, published their insights in the journal Environmental Microbiome.

The story started at Trunk River lagoon, near the Shining Sea Bike Path in Falmouth, Mass., which for decades has been a "natural laboratory" for the Microbial Diversity course along with other local field sites, such as Sippewissett Marsh. (The course, established at MBL in 1971 by Holger Jannasch, will celebrate its 50th anniversary this year).

"A few days after we had waded through the shallow section of Trunk River lagoon, our footprints turned yellow," says senior author Emil Ruff, a course teaching assistant in 2014-15 and now a scientist in the MBL's Ecosystems Center and Josephine Bay Paul Center.

Ruff hypothesized that the yellow suspension (which the course participants called microbial "lemonade") was a sulfur bloom generated by microorganisms that couple photosynthesis to the oxidation of sulfur. The students' footsteps likely stirred up decaying sea grass and other organic material, releasing sulfide into the water and creating a habitat suitable for rare microbes to bloom.

Blooms of microorganisms are not uncommon in water bodies. Some are so huge that they are visible from satellites. Some are harmful, because they can be toxic for animals, or lead to oxygen depletion in certain areas of the ocean. Blooms generated by high sulfide concentrations are generally a concern, as they can become toxic for fish, mussels and birds. There are many open questions about what triggers bloom formation and collapse.

The next year, Ruff and a team from the Microbial Diversity course returned to Trunk River with the goal of intentionally creating and tracking blooms to study how microbial communities form and change over time. They dug holes in the lagoon and added poles that allowed them to sample daily from several depths without disturbing the water column.

"Often in microbial ecology, we try to understand an ecosystem in its steady state. But it remains unclear how long it takes for an ecosystem to recover after a disturbance and what it takes to establish a diverse [microbial] community," says Ruff. The experimental design allowed the research team to follow the microbial community as it began to assemble, matured and stratified over time, and collapsed at the end of the bloom.

Understanding these dynamics is particularly important in estuarine ecosystems, such as Trunk River lagoon, that are exposed to natural and human disturbances. Estuaries not only provide important protection from coastal erosion, they also capture carbon from the atmosphere and sequester it. They also serve as a food source and breeding ground for much of the coastal biodiversity.

"The ecology and biogeochemistry causing the sulfur-driven blooms showed us how quickly things can turn, and how ecosystems and microbiomes can rapidly change upon disturbances," says Ruff.

One surprising finding was where the bloom's microbes -- called anoxygenic phototrophs -- found optimal living conditions. Prior to the study, it was generally thought that many of the bloom microbes could not grow in the presence of oxygen. Finding them in mildly oxic waters led the researchers to examine their genomes. They found that certain species of Chlorobiales - the bacterial lineage responsible for most of the bloom biomass and the yellow color -- encode enzymes that combat oxygen stress, which could explain the microbes' oxygen tolerance. This and other insights have already initiated new course research projects.

Like the different functions of the microbes in the Trunk River estuarine community, the Microbial Diversity course brings together teaching fellows, faculty and students with diverse backgrounds and research foci.

"What I found remarkable is the range of expertise in the course," says Ruff. "You can assemble a group of researchers that can look at all aspects of an ecosystem, including microbiology, physics, chemistry and everything in between. This holistic approach is what the course stands for and passes on to its students each year, for the past 49 years."

BOSTON - Newborns face unique immunological challenges immediately after birth. As they depart a relatively sterile fetal environment, they are abruptly exposed to a multitude of foreign antigens, the major burden of which is in the form of the microbiota newly colonizing the gastrointestinal tract. These rapidly multiplying foreign invaders represent, by far, the biggest threat to the neonatal immune system, which has to recognize and classify these organisms as benign, commensal or pathogenic.

Research shows that effective "crosstalk" or communication between early microbes and mucosal immune cells is essential to the formation of healthy microbial communities and promotion of a well-functioning immune system. The cells of the immune system that participate in mucosal immunity develop in an organ called the thymus located under the breastbone above the heart. Until now, it has been unclear if intestinal microbes influence the development of these cells in the thymus in early life.

Researchers at the Mucosal and Immunology Biology Research Center (MIBRC) at Massachusetts General Hospital now report that gut microbes regulate the development of specialized immune cells in the thymus that play a critical role in mucosal tolerance. The findings of their extensive research were published in Proceedings of the National Academy of Science, USA this week. Nitya Jain, PhD, and colleagues focused their studies on a subset of immune cells that express the transcription factor PLZF. These cells, collectively called innate and innate-like lymphocytes, typically function at the gut mucosal barrier interface and provide immune protection at mucosal sites.

To study the development of these immune cells in the context of gut microbes, researchers monocolonized germ-free mice with a model human commensal, Bacteroides fragilis, and demonstrated that this single species of bacteria could restore the development of PLZF+ innate and innate-like lymphocytes in the thymus of infant mice. In further proof-of-concept studies, they showed that a mutant B. fragilis lacking expression of Polysaccharide A (PSA) was unable to do the same, suggesting that specific microbial antigens could regulate this early life developmental process. A similar deficit in these cells was observed in mutant mice that lacked the expression of Toll like receptor 2, a receptor that recognizes bacteria and bacterial components, including B. fragilis PSA, to initiate host protective immune responses.

To understand how this microbial message was delivered to developing thymic cells, Jain's group used a novel mouse model to track the migration of cells from the colon to the thymus. The photo-conversion strategy, developed with the help of MGH's Guillermo "Gary" Tearney's group at the Wellman Center for Photomedicine, was highlighted in the Journal of Visualized Experiments in 2018.

Researchers showed that a class of antigen-presenting cells called plasmacytoid dendritic cells (pDCs) are imprinted by intestinal microbes and migrate from the gut to the thymus in early life to regulate the development of thymic lymphocytes. For the first time, Jain's group has revealed "a novel communication between intestinal microbes and developing cells in the thymus," says Jain. "It shapes the immune 'repertoire' in early life and affects how the host will respond to disease throughout the lifespan."

The unbalanced development of an infant's gut microbiome is thought to play a role in disease development later in life. Disturbing the microbiota in infancy by antibiotics or diet, for example, has been linked to increased risk of allergies, asthma and autoimmune disorders including celiac disease and Inflammatory Bowel Disease (IBD). Jain's group demonstrates one mechanistic basis for this observation. They show that thymic PLZF+ cells did not develop efficiently in mice treated with broad-spectrum antibiotics in early life, but mice treated in later life were spared.

Jain says there "appeared to be an early-life time window when developing immune cells in the thymus were particularly susceptible to microbial influence." Additionally, the study shows that microbe-induced altered development of thymic innate and innate-like cells in early life persists into adulthood and leads to increased susceptibility to experimental colitis. Importantly, disease severity could be moderated by the transfer of PLZF+ cells from mice that developed with normal microbiota in early life, says Jain. She adds, "This has significant implications for the design of strategies to treat autoimmune disorders such as IBD. Our studies point to a previously unexplored pathway that may be developed as an adoptive cell therapy for patients."

MIBRC Director Alessio Fasano, MD notes that growing evidence shows that early development of a healthy immune state requires an ideal symbiotic relationship between developing infants and their community of microorganisms. "How we 'choose' our ideal microbiome to teach our immune system to defend us rather than harm us is still a big question mark. Nitya and her group--for the first time--have shed light on the very early mechanisms that are in charge of establishing a healthy relationship between the human host and the microbiome," says Fasano.

SAN DIEGO--A Tactile Internet is potentially the next phase of the Internet of Things, in which humans can touch and interact with remote or virtual objects while experiencing realistic haptic feedback.

A team of researchers led by Elaine Wong at the University of Melbourne, Australia, developed a method for enhancing haptic feedback experiences in human-to-machine applications that are typical in the Tactile Internet. The researchers believe their method can be used for forecasting proper feedback in applications ranging from electronic healthcare to virtual reality gaming.

Wong and her colleagues will present their proposed module, which uses an artificial neural network to forecast the material touched, at the Optical Fiber Communication Conference and Exhibition (OFC), to be held 8-12 March 2020 at the San Diego Convention Center, California, U.S.A.

Depending on the dynamicity of the interaction, an optimum human-to-machine application may require a network response time as short as one millisecond.

"These response times impose a limit on how far apart humans and machines can be placed," said Wong. "Hence, solutions to decouple this distance from the network response time is critical to realizing the Tactile Internet."

As a step toward this goal, the team trained a reinforcement learning algorithm to guess the appropriate haptic feedback in a human-to-machine system before the correct feedback is known. The module, called the Event-based HAptic SAmple Forecast (EHASAF), speeds up the process by providing a touch response based on a probabilistic prediction of the material the user is interacting with.

"To facilitate human-to-machine applications over long distance networks, we rely on artificial intelligence to overcome the effects of long propagation latency," said Sourav Mondal, an author on the paper.

Once the actual material is identified, the unit adapts and updates its probability distribution to help choose the proper feedback looking forward.

The group tested the EHASAF module with a pair of virtual reality gloves used by a human to touch a virtual ball. The gloves contain sensors on the fingers and wrists to detect touches and track movements, forces and the orientation of the hand.

Depending on which material ball the user chooses to touch of the four virtual options provided, the feedback from the glove should vary. For example, a metal ball will be firmer than a foam ball. When a neural network determines that one of the fingers has touched the ball, the EHASAF module begins cycling through feedback options to generate until it resolves the actual material of the chosen ball.

Currently, with four materials, the prediction accuracy of the module is about 97%.

"We think it is possible to improve prediction accuracy with a greater number of materials," said Mondal. "However, more sophisticated artificial intelligence-based models are needed to achieve that."

"More and more sophisticated models with improved performance can be developed based on the fundamental idea of our proposed EHSAF module," Mondal said.

These results and additional research will be presented onsite at OFC 2020.

Engineered human capillaries are providing an astounding view of how red blood cells transit ultra-small blood vessels.

This new platform was used in a recent study to learn how severe malaria infection causes red cells to get stuck in blood microvessels. As they accumulate, the parasite-infected red cells obstruct the narrowest routes of blood flow in the body.

The way the 3D microvessel model was created with living cells, and the findings it helped glean on the mechanisms of microcirculatory obstruction by severe malaria infection, are reported in a paper in the current issues of Science Advances.

Researchers at the University of Washington, Seattle Children's Research Institute, and the UW Medicine Institute for Stem Cell and Regenerative Medicine conducted the project.

The corresponding authors of the resulting paper are Ying Zheng, associate professor of bioengineering, Joseph D. Smith, affiliate professor of global health and a Seattle Children's infectious disease researcher, and Cole A. DeForest, assistant professor of chemical engineering and bioengineering

The 3D capillary system their team developed holds promise for research on several other diseases that cause blockage or damage to human capillaries. These include sickle cell anemia, diabetes, and cardiovascular problems.

The system might also be an initial step toward engineering microcirculation for regenerative medicine purposes, such as to supply sufficient blood flow to organ-repairing patches derived from stem cells or to laboratory-grown organs.

In the human body, capillaries are the smallest blood vessels. They are important conduits for the transfer of oxygen and nutrients from the blood stream to tissues, in exchange for carbon dioxide and waste products.

Human capillaries are so narrow that red blood cells pass through them one-by-one.

The scientists were able to construct their capillary system through a type of biological printing of vessels 100 micrometers in size engraved into a collagen base. Multiphoton technology from the DeForest lab was employed to etch the channels and to disturb cells from larger blood vessels, thereby encouraging them to move into the channels and form capillaries.

With their 3D engineered microvessel, which resembles an hourglass, the scientists could analyze how red blood cells navigate tight bottlenecks. Normal red blood cells, which are shaped like a round rubber raft, get through smoothly by contorting themselves to look like slippers, parachutes or bells. They somehow seem to avoid touching the inside of the capillary.

However, red blood cells infected with malaria are more rigid and knobby. When transversing the capillary region, they do not elongate very much. They also roll and tumble. Both their shape and motion increase their risk of adhering to the capillary and becoming trapped.

Encountering the forces present in blood flow, infected red blood cells tend to be pushed more toward the capillary wall compared to their uninfected counterparts. This shoving aside also raises their likelihood of sticking.

While most normal red blood cells passed through the narrowest regions of the capillary model without a hitch, those infected with certain malaria parasite variants steadily accumulate. Within minutes they can dam the capillary and stop the flow, trapping some normal red blood cells with them.

The researchers performed additional analysis of the possible detrimental contributions of the knobs that appear on malaria-infected red blood cells.

They concluded that the dynamic forces of blood flow on the infected cells, and the modifications in the red blood cells induced by the malaria parasite might play independent roles in the events leading to blockage of microvessels. So, for example, there is more gathering of infected cells near the exit from the capillaries, which is the spot where blood flow slows down and shear stresses are reduced.

The scientists mentioned that two possible shortcomings of their 3D human microvessel model is that it was derived from cell types originating in larger blood vessels and that studying single-cell dynamics is challenging due to imprecise flow control.

They hope that, with modifications, this fundamentally new approach to investigating obstruction of microvessels will assist in future therapeutic developments for blood-stage malaria, in the study of other conditions that might damage small blood vessels, and in transfusion medicine research on blood products.

Most diseases have a genetic component. To better understand disease, researchers led by the Garvan Institute of Medical Research are analysing genetic information to determine what keeps us healthy.

In a world first, the team has compiled a genome reference database of thousands of healthy older Australians, which has the potential to predict disease-linked gene variants more accurately than has been previously possible.

The researchers released the first 2,570 genomes of the Medical Genome Reference Bank (MGRB) and published their analysis in the journal Nature Communications.

The MGRB is a collaboration led by Garvan, Monash University's ASPREE study and the Sax Institute's 45 and Up Study.

"By doing a comprehensive analysis of healthy individuals, we can get a much clearer understanding of which genes are and which are not linked to disease. The Medical Genome Reference Bank will provide an ideal background for the future of genomic research in Australia," says Professor David Thomas, Garvan Cancer Research Theme Leader and Director of The Kinghorn Cancer Centre.

A baseline of healthy ageing

Every person has around 6 billion DNA 'letters' in their genome, which encodes all of the information needed to make and run every cell in the body. Between any two unrelated people, there are millions of single letter differences, or variations.

Variations make us different, but some of them can cause disease - the challenge for researchers is to pinpoint which these are.

The authors of the current paper publish the genomic data of 2,570 healthy older Australians (64 - 95 years old) that were free from cancer, cardiovascular disease or neurodegenerative disease until the age of at least 70. These individuals were participants of the ASPREE study and the 45 and Up Study.

"This first release of data from the Medical Genome Reference Bank gives researchers a much more statistically powerful framework to identify new disease-causing gene variants," says Professor Thomas.

"For instance, when we analysed genomes of prostate cancer patients, we found that using the MGRB as a 'control' gave us a 25% higher predictive power of disease-linked gene variants than another genome database that is commonly used by researchers to find such variants."

Determining biological age from DNA

Using whole genome sequencing, the researchers were able to detect genetic changes associated with ageing, including shorter telomeres, the 'caps' at the ends of chromosomes, and less mitochondrial DNA, which codes for the energy generators of cells. Interestingly, the researchers found that the amount of mitochondrial DNA was associated with a higher grip strength in men.

"We were able to detect changes in the genomes that could distinguish between healthy older individuals that share the same age, but have different physical function. This indicates that the DNA in an individual's blood sample may provide a better indicator of their 'biological age' than their chronological age," says Professor Thomas.

"The ability to derive a measure of biological age may better predict health outcomes for individuals. As our population ages, understanding the genetic basis for healthy ageing will become more and more important," says Professor Thomas.

The first release of the data is available to researchers via the Vectis platform. Once completed, the Medical Genome Reference Bank will contain genomic data from over 4,000 older Australians.

WASHINGTON--Women with polycystic ovary syndrome (PCOS) experience poor health and quality of life into their late forties, according to new research published in the Endocrine Society's Journal of Clinical Endocrinology & Metabolism.

PCOS is a common yet underdiagnosed condition affecting 6-18 percent of women at reproductive age, but its side effects extend beyond infertility and menstrual irregularities. Women with PCOS experience psychological issues like anxiety and depression that continue well beyond fertile age.

"Most PCOS studies focus on women during reproductive age, but symptoms like mental health issues and excess hair growth continue into the late forties," said the study's principal investigator, Terhi Piltonen, M.D., Ph.D. of the University of Oulu in Finland. "Our study focuses on this population and shows that women with PCOS have lower life satisfaction and poorer health up to their late reproductive years."

The researchers studied a longitudinal cohort of 5,889 women at ages 31 and 46 and identified women with PCOS from this Northern Finland Birth Cohort 1966. The investigators found women with PCOS have poor health and quality of life compared to those without the condition. Mental distress was the strongest contributing factor to poor quality of life.

"More interventions are needed to improve the quality of life for women with PCOS who are in their late thirties and forties. These women should be screened regularly for mental health issues and treated for other distressing symptoms like excess hair growth," Piltonen said.