Culture

Researchers from Charité - Universitätsmedizin Berlin and the University of California in San Francisco were able to show for the first time that a very low calorie diet significantly alters the composition of the microbiota present in the human gut. In a current Nature* publication, the researchers report that dieting results in an increase of specific bacteria - notably Clostridioides difficile, which is associated with antibiotic-induced diarrhea and colitis. These bacteria apparently affect the body's energy balance by exerting an influence on the absorption of nutrients from the gut.

The human gut microbiome consists of trillions of microorganisms and differs from one person to the next. In persons who are overweight or obese, for instance, its composition is known to be different to that found in individuals with a normal body weight. Many of us will, at some point in our lives, try dieting in order to lose weight. But what effect does such a drastic change in diet have on our bodies? An international team of researchers co-led by Charité has addressed this question. "For the first time, we were able to show that a very low calorie diet produces major changes in the composition of the gut microbiome and that these changes have an impact on the host's energy balance," says Prof. Dr. Joachim Spranger, Head of Charité's Department of Endocrinology and Metabolic Diseases and one of the study's lead authors.

To explore the effects of dieting, the team studied 80 older (post-menopausal) women whose weight ranged from slightly overweight to severely obese for a duration of 16 weeks. The women either followed a medically supervised meal replacement regime, consuming shakes totaling less than 800 calories a day, or maintained their weight for the duration of the study. The participants were examined at the Experimental and Clinical Research Center (ECRC), a facility jointly operated by Charité and the Max Delbrück Center for Molecular Medicine (MDC). Regular stool sample analysis showed that dieting reduced the number of microorganisms present in the gut and changed the composition of the gut microbiome. "We were able to observe how the bacteria adapted their metabolism in order to absorb more sugar molecules and, by doing so, make them unavailable to their human host. One might say we observed the development of a 'hungry microbiome'," says the study's first author, Dr. Reiner Jumpertz von Schwartzenberg, a researcher and clinician at the Department of Endocrinology and Metabolic Diseases whose work on the study was funded by the Clinician Scientist program operated by Charité and the Berlin Institute of Health (BIH).

Stool samples, which had been collected before and after dieting, were then transferred into mice which had been kept under germ-free conditions and, as a result, lacked all gut microbiota. The results were staggering: Animals which received post-dieting stools lost more than 10 percent of their body mass. Pre-diet stools had no effect whatsoever. "Our results show that this phenomenon is primarily explained by changes in the absorption of nutrients from the animals' guts," says Prof. Spranger. He adds: "This highlights the fact that gut bacteria have a major impact on the absorption of food."

When the researchers studied stool composition in greater detail, they were particularly struck by signs of increased colonization by a specific bacterium - Clostridioides difficile. While this microorganism is commonly found in the natural environment and in the guts of healthy human beings and animals, its numbers in the gut can increase in response to antibiotic use, potentially resulting in severe inflammation of the gut wall. It is also known as one of the most common hospital-associated pathogens. Increased quantities of the bacterium were found both in participants who had completed the weight loss regimen and in mice which had received post-dieting gut bacteria. "We were able to show that C. difficile produced the toxins typically associated with this bacterium and that this was what the animals' weight loss was contingent upon," explains Prof. Spranger. He adds: "Despite that, neither the participants nor the animals showed relevant signs of gut inflammation."

Summing up the results of the research, Prof. Spranger says: "A very low calorie diet severely modifies our gut microbiome and appears to reduce the colonization-resistance for the hospital-associated bacterium Clostridioides difficile. These changes render the absorption of nutrients across the gut wall less efficient, notably without producing relevant clinical symptoms. What remains unclear is whether or to which extent this type of asymptomatic colonization by C. difficile might impair or potentially improve a person's health. This has to be explored in larger studies." Results from the current study, which also received funding from the German Center for Cardiovascular Disease (DZHK), might even give rise to treatment options for metabolic disorders such as obesity and diabetes. For this reason, the researchers will now explore how gut bacteria might be influenced in order to produce beneficial effects on the weight and metabolism of their human hosts.

A new article published in the Journal of the Association for Consumer Research presents a neural model of maladaptive consumption.

Consumption (of, for instance, substances, food, and online media) is driven mainly by expected rewards that stem from the ability of the consumption act to satisfy intrinsic (e.g., curiosity) and extrinsic (e.g., job performance) needs. In the article, "A Triple-System Neural Model of Maladaptive Consumption," the authors define maladaptive consumption as a state of compulsive seeking and consumption of rewarding products or experiences, which are sustained despite the negative consequences of such behaviors.

"Understanding the neural basis of maladaptive consumption is important because it can serve as a basis for developing policies that minimize the chances of maladaptive consumption and serve to protect consumers, especially vulnerable populations, like children," note authors Ofir Turel and Antoine Bechara. Getting into the brain networks that govern maladaptive decision making in response to rewarding products/services can lead to interventions that reduce maladaptive consumption post hoc and ethical guidelines for marketers and service providers to decide when it is ethical to use habit-forming mechanisms, such as reward variability, to entice consumers into maladaptive consumption.

The proposed model includes three neural systems, among which the interaction may drive maladaptive behaviors. These include the impulsive system which mediates reward expectation and management, in form of dopamine release; the reflective system, which largely engages the prefrontal cortex (which is responsible for self-control and long-term planning); and the interoceptive-awareness system (which includes that insula, that responds to body interoceptive signals elicited by withdrawal and reward deprivation, leading to urges).

Since these brain regions often operate in an interrelated neural network rather than in isolation, a holistic perspective focusing on the interactions among these brain regions would help provide a better understanding of underlying mechanisms of consumption decisions. The paper proposes that maladaptive behaviors may arise from abnormal activity in any one or a combination of these three neural systems or connectivity among the brain systems.

This model can inform other neural representations of maladaptive consumption, which assumes that maladaptive behaviors results from an overactive reward system and/or an underactive self-control system, and the consequent transitioning from goal-directed to automatic and habitual behaviors. "The triple model supplements this view and suggests that situational conditions, such as deprivation, can exacerbate the reliance on habit-controlled processes," write the authors.

The model extends the neuro-marketing view of the brain underpinnings of normal consumption to the case of maladaptive consumption and provides insights for marketers, consumer rights advocates, and regulators. Such a model may inform research on binge-watching and other common excess consumptions, such as pornography, and help explain why some people engage in such behaviors and how they respond to advertising.

Newspapers regularly carry stories of terrifying shark attacks, but in a paper published today, Oxford-led researchers reveal their discovery of a 3,000-year-old victim - attacked by a shark in the Seto Inland Sea of the Japanese archipelago.

The research in Journal of Archaeological Science: Reports, shows that this body is the earliest direct evidence for a shark attack on a human and an international research team has carefully recreated what happened - using a combination of archaeological science and forensic techniques.

The grim discovery of the victim was made by Oxford researchers, J. Alyssa White and Professor Rick Schulting, while investigating evidence for violent trauma on the skeletal remains of prehistoric hunter-gatherers at Kyoto University. They came upon No24, from the previously excavated site of Tsukumo, an adult male riddled with traumatic injuries.

'We were initially flummoxed by what could have caused at least 790 deep, serrated injuries to this man,' say the Oxford pair. 'There were so many injuries and yet he was buried in the community burial ground, the Tsukumo Shell-mound cemetery site.'

They continue, 'The injuries were mainly confined to the arms, legs, and front of the chest and abdomen. Through a process of elimination, we ruled out human conflict and more commonly-reported animal predators or scavengers.'

Since archaeological cases of shark reports are extremely rare, they turned to forensic shark attack cases for clues and worked with expert George Burgess, Director Emeritus of the Florida Program for Shark Research. And a reconstruction of the attack was put together by the international team.

The team concluded that the individual died more than 3,000 years ago, between 1370 to 1010 BC. The distribution of wounds strongly suggest the victim was alive at the time of attack; his left hand was sheared off, possibly a defence wound.

Individual No 24's body had been recovered soon after the attack and buried with his people at the cemetery. Excavation records showed he was also missing his right leg and his left leg was placed on top of his body in an inverted position.

According to the pair, 'Given the injuries, he was clearly the victim of a shark attack. The man may well have been fishing with companions at the time, since he was recovered quickly. And, based on the character and distribution of the tooth marks, the most likely species responsible was either a tiger or white shark.'

Co-author Dr Mark Hudson, a researcher with the Max Planck Institute, says, 'The Neolithic people of Jomon Japan exploited a range of marine resources... It's not clear if Tsukumo 24 was deliberately targeting sharks or if the shark was attracted by blood or bait from other fish. Either way, this find not only provides a new perspective on ancient Japan, but is also a rare example of archaeologists being able to reconstruct a dramatic episode in the life of a prehistoric community.'

By José Tadeu Arantes | Agência FAPESP – Mathematical models that describe the physical behavior of magnetic materials can also be used to describe the spread of the novel coronavirus that causes COVID-19.

This is the conclusion of a study conducted in Brazil by researchers affiliated with São Paulo State University (UNESP) in Rio Claro and Ilha Solteira and reported in an article published in Physica A: Statistical Mechanics and its Applications.

The study was part of a project led by Mariano de Souza, a professor at UNESP’s Rio Claro Physics Department, and of the PhD research of Isys Mello, whose thesis advisor is Souza, last author of the article. Another co-author is Antonio Seridonio, a professor at UNESP’s Ilha Solteira Physics and Chemistry Department.

The central idea of the study was an analogy between concepts in magnetism and epidemiology in which electron interaction is compared with interaction among people. “We used the Ising model, widely used in several areas of physics, to demonstrate the importance of social distancing and isolation in reducing the rate at which the virus spreads,” Souza told Agência FAPESP.

The magnetic behavior intrinsic to electrons is associated with spin. Simply put, spin can be imagined as a tiny magnet “pointing up” toward the sky or “down” to the ground, so that an electron may spin up or spin down. Spins may interact, depending on the material, and this interaction is quantified in terms of exchange energy.

“We imagined that infected people were ‘spin-up’ and non-infected people were ‘spin-down’. We considered contact between an infected person and a non-infected person analogous to energy exchange in magnetism,” Souza explained.

Using other more complex concepts from physics such as the Bethe lattice (see figure) and percolation theory, the group demonstrated the key role played by social distancing and quarantine in mitigating transmission of the virus.

“We considered that all those who come into contact with each other form a network, and that contact between infected and non-infected people is likely to spread the virus. For example, imagine the first infected person [patient zero] is in contact with other people and fails to take proper precautions [social distancing, face covering, hand hygiene etc]. The members of this group who are infected by the virus may transmit it to relatives, friends and other contacts, and these, in turn, may spread it to others, forming a ‘contact network’ that corresponds to a Bethe lattice in condensed matter physics,” Souza said.

“If patient zero had taken all the necessary precautions, they would have avoided transmitting the virus to all these people who were indirectly infected by them,” he added.

Flavoring can change how the brain responds to e-cigarette aerosols that contain nicotine, according to Penn State College of Medicine researchers. Andrea Hobkirk and her team used functional magnetic resonance imaging (MRI) to understand how the brain's reward areas react to e-cigarette aerosol with and without flavor.

"There are nearly 12 million e-cigarette users in the United States," Hobkirk, an assistant professor of psychiatry and behavioral health at Penn State College of Medicine, said. "The vast majority use e-cigarettes with menthol, mint, fruity and dessert-type flavors. Although regulations that limit the sale of flavored e-cigarettes may help curb use among youth, they might also stop adults from using e-cigarettes as a smoking reduction or cessation aid. We are trying to understand how flavor influences e-cigarette reward and satisfaction for smokers and the risk of nicotine addiction for non-smokers."

The team first developed a device to deliver e-cigarette aerosols during brain scanning. Next, the research team used this new device to deliver aerosols containing a low dose of nicotine to nine adult female smokers during a single laboratory visit. One aerosol had a strawberry-vanilla flavor, and the other aerosol was flavorless. The team compared the strength of brain activation and reward brain region involvement between flavored and unflavored aerosols.

"For our study, we were interested in looking first at, for smokers, how flavor might affect their response to nicotine e-cigarettes," Hobkirk said. "We recruited smokers who had never used e-cigarettes before or were not regular e-cigarette users. What we were interested in is figuring out whether or not flavor changed how they perceived or how their brain responded to this e-cigarette use."

The researchers found that the strawberry-vanilla aerosol engaged the brain's taste region. In contrast, the unflavored aerosol engaged the brain's reward region, similar to observations during cigarette smoking. The researchers published their results in the journal Experimental and Clinical Psychopharmacology.

The researchers also assessed patterns of neural activity between brain regions. Stronger connectivity between two brain regions typically means that these regions are working together. They found that key brain reward regions were strongly connected with flavored aerosol and not unflavored.

The findings suggest that, for smokers, unflavored e-cigarettes may mimic the typical smoking experience more than flavored e-cigarettes.

"We found that for smokers who had never really used e-cigarettes before, the flavor did not make the experience more rewarding for them, at least in terms of what we saw in the brain," Hobkirk said. "It did not make the experience of breathing in these aerosols more like a smoking experience. Typically, that's what smokers are looking for when they're trying to transition over to a healthier product. They want something that gives all the similar rewarding and sensory-motor effects of their regular combustible cigarette, but without all the harmful effects that come in the toxins of a cigarette. We found that adding flavor doesn't necessarily do that for these smokers, at least what we saw in their response to them in the brain. This could suggest that, potentially, smokers do not necessarily need these flavors to make the transition from a combustible cigarette to an e-cigarette."

Researchers from Bentley University have been exploring how readers at partisan news sites respond to news events that challenge their worldview.

In a forthcoming paper in the journal ACM Transactions on Social Computing, they report results of a study that examines reader comments on stories surrounding the 2017 Roy Moore Alabama senate race at two partisan news sites: a left-leaning news site (Daily Kos) and a right-leaning news site (Breitbart). They consider the alleged sexual misconduct of Mr. Moore as a challenging news event for the right-leaning readers; and the subsequent nomination of Mr. Moore as the Republican candidate as a challenging news event for the left-leaning readers.

Their analysis identifies the obstacles that readers face as they try to make sense of news events they find challenging. The comments they contribute show that some readers question the motives of different actors in the story, others provide erroneous arguments to diffuse the story, yet others engage in personal attacks. The researchers describe these as breakdowns that prevent a group from acknowledging the new event.

The study adds to our understanding of political discourse and polarization. "We are still trying to understand the causes of disinformation and political echo chambers. Our study provides a window into how deliberation can break down in closed groups," says Dr. Sandeep Purao, one of the lead researchers.

"The processes underlying social representations are difficult to examine. The reader comments allow us this opportunity," says Dr. David Murungi, a professor who also participated in the study. "The reader comments tend to be complex. Although we can judge them to be problematic, it is often hard to name what the problems are," says Dr. David Yates, another professor who participated in the study.

The results of the study are being published in the journal ACM Transactions on Social Computing. The team continues to empirically investigate the problem of disinformation and political discourse, and is moving to explore potential solutions to combat misinformation.

NEW YORK CITY, June 23, 2021 -- From amoebas to zebras, all living things evolve. They change over time as pressures from the environment cause individuals with certain traits to become more common in a population while those with other traits become less common.

Cancer is no different. Within a growing tumor, cancer cells with the best ability to compete for resources and withstand environmental stressors will come to dominate in frequency. It's "survival of the fittest" on a microscopic scale.

But fitness -- how well suited any particular individual is to its environment -- isn't set in stone; it can change when the environment changes. The cancer cells that might do best in an environment saturated with chemotherapy drugs are likely to be different than the ones that will thrive in an environment without those drugs. So, predicting how tumors will evolve over time, especially in response to treatment, is a major challenge for scientists.

A new study by researchers at Memorial Sloan Kettering in collaboration with researchers at the University of British Columbia/BC Cancer in Canada suggests that one day it may be possible to make those predictions. The study, published June 23, 2021, in the journal Nature, was led by MSK computational biologist Sohrab Shah and BC Cancer breast cancer researcher Samuel Aparicio. The scientists showed that a machine-learning approach, built using principles of population genetics that describe how populations change over time, could accurately predict how human breast cancer tumors will evolve.

"Population genetic models of evolution match up nicely to cancer, but for a number of practical reasons it's been a challenge to apply these to the evolution of real human cancers," says Dr. Shah, Chief of Computational Oncology at MSK. "In this study, we show it's possible to overcome some of those barriers."

Ultimately, the approach could provide a means to predict whether a patient's tumor is likely to stop responding to a particular treatment and identify the cells that are likely to be responsible for a relapse. This could mean highly tailored treatments, delivered at the optimal time, to produce better outcomes for people with cancer.

A Trifecta of Innovations

Three separate innovations came together to make these findings possible. The first was using realistic cancer models called patient xenografts, which are human cancers that have been removed from patients and transplanted into mice. The scientists analyzed these tumor models repeatedly over extended timeframes of up to three years, exploring the effects of platinum-based chemotherapy treatment and treatment withdrawal.

"Historically, the field has focused on the evolutionary history of a cancer from a single snapshot," Dr. Shah says. "That approach is inherently error prone. By taking many snapshots over time, we can obtain a much clearer picture."

The second key innovation was applying single-cell sequencing technology to document the genetic makeup of thousands of individual cancer cells in the tumor at the same time. A previously developed platform allowed the team to perform these operations in an efficient and automated fashion.

The final component was a machine-learning tool, dubbed fitClone, developed in collaboration with UBC statistics professor Alexandre Bouchard-Côté, which applies the mathematics of population genetics to cancer cells in the tumor. These equations describe how a population will evolve given certain starting frequencies of individuals with different fitnesses within that population.

With these innovations in place, the scientists were able to create a model of how individual cells and their offspring, or clones, will behave. When the team conducted experiments to measure evolution, they found close agreement between these data and their model.

"The beauty of this model is it can be run forwards to predict which clones are likely to expand and which clones are likely to get outcompeted," Dr. Shah says.

In other words, how the cancer will evolve is predictable.

A Foundation for the Future

The particular types of genetic changes the team looked at are called copy number changes. These are differences in the number of particular DNA segments in cancer cells. Up until now, the significance of these sorts of changes hasn't been clear, and researchers have had doubts about their importance in cancer progression.

"Our results show that copy number changes have a measurable impact on fitness," Dr. Shah says.

For example, the scientists found that, in their mouse models, treatment of tumors with platinum chemotherapy led to the eventual emergence of drug-resistant tumor cells -- similar to what happens in patients undergoing treatment. These drug-resistant cells had distinct copy number variants.

The team wondered: What would happen to the tumor if they stopped treatment? Turns out the cells that took over the tumor in the presence of chemotherapy declined or disappeared when the chemotherapy was taken away; the drug-resistant cells were outmatched by the original drug-sensitive cells. This behavior indicates that drug resistance has an evolutionary cost. In other words, the traits that are good for resisting drugs aren't necessarily the best for thriving in an environment without those drugs.

Ultimately, Dr. Shah says, the goal is to one day be able to use this approach on blood samples to identify the particular clones in a person's tumor, predict how they are likely to evolve, and tailor medicines accordingly.

"This study is an important conceptual advance," Dr. Shah says. "It demonstrates that the fitness trajectories of cancer cells are predictable and reproducible."

Toronto - Last winter, Goldman Sachs reported it was working to make things better after a group of junior analysts revolted against 100-hour work weeks.

That's a smart thing to do, suggests a new study from the University of Toronto's Rotman School of Management. Drawing from more than 6,000 employee reviews of their workplaces and data on their firms' forecasting accuracy, the research shows that making improvements to hardworking analysts' work-life balance produces dividends for the company and for the analysts' careers.

"There is a lot of anecdotal evidence, but here we provide large-scale evidence that supports the recent push to grant these employees at least some reprieve from the extremes of their jobs," said Ole-Kristian Hope, who is the Deloitte Professor of Accounting at the Rotman School, and worked on the research with three colleagues.

Too much of a good thing is possible, however. The study found there was a limit to the positive performance impact of improving work-life balance.

An analyst's forecast accuracy -- that is, how correct their forecasts are about a company's future earnings and whether it's a recommended stock pick -- maxed out once analysts' work-life balance hit about 3.5, or "okay," on a 5-point review scale.

Investment returns based on those stock recommendations showed a similar effect, with returns maxing out when work-life balance reached about 3 out of 5 points. It's thought that this is because people need a certain amount of mental stimulation and demand to process information efficiently.

"If you have too much work-life balance, that means you're not focusing enough on work," said Prof. Hope. "A little bit of stress is probably a good thing but if it's too much then the pressure becomes daunting and you can't do anything."

Optimized work-life balance was also found to support analysts' career advancement, based on job mobility and promotion data and information from a recognized industry awards recognition program. Such awards influence analysts' compensation and career opportunities.

This is the first study to examine the role of work-life balance in financial analysts' performance and career advancement. It was made possible by the availability of employee reviews about the companies they work for via a social media platform called Glassdoor.

The researchers chose these employees to measure the impacts of work-life balance because of their reputation for being more professionally aggressive, career-oriented and having a higher tolerance for stress. Financial analysts can put in as much as 70 to 110 hours a week during quarterly earnings seasons, when companies are issuing their reports. "They're not your typical animals," said Prof. Hope, making it less obvious that work-life balance would affect them the same as it does other workers.

Financial analysts are also important to study because the information they provide contributes significantly to the operation of capital markets. "Learning about the source of variations in their work performance is important by itself," said Prof. Hope.

The Gerontological Society of America's highly cited, peer-reviewed journals are continuing to publish scientific articles on COVID-19. The following were published between May 4 and June 14; all are free to access:

Cardiometabolic therapy and mortality in very old patients with diabetes hospitalized due to COVID-19: Research article in The Journals of Gerontology, Series A: Biological Sciences and Medical Sciences by Jose Manuel Ramos-Rincón, MD, PhD, Luis M. Pérez-Belmonte, MD, PhD, Francisco Javier Carrasco-Sánchez, MD, PhD, Sergio Jansen-Chaparro, MD, PhD, Mercedes De-Sousa-Baena, MD, José Bueno-Fonseca, MD, Maria Pérez-Aguilar, MD, Coral Arévalo-Cañas, MD, Marta Bacete Cebrian, MD, Manuel Méndez-Bailón, MD, PhD, Isabel Fiteni Mera, MD, PhD, Andrés González García, MD, PhD, Francisco Navarro Romero, MD, PhD, Carlota Tuñón de Almeida, MD, Gemma Muñiz Nicolás, MD, Amara González Noya, MD, Almudena Hernández Milian, MD, Gema María García García, MD, José Nicolás Alcalá Pedrajas, MD, Virginia Herrero García, MD, Luis Corral-Gudino, MD, PhD, Pere Comas Casanova, MD, Héctor Meijide Míguez, MD, PhD, José Manuel Casas-Rojo, MD, Ricardo Gómez-Huelgas, MD, PhD, and the SEMI-COVID-19 Network
The Role of Media Sources for COVID-19 Information on Engaging in Recommended Preventive Behaviors among Medicare Beneficiaries Aged ≥ 65 Years: Research article in The Journals of Gerontology, Series B: Psychological Sciences and Social Sciences by Boon Peng Ng, PhD, and Chanhyun Park, PhD
Impact of Negative and Positive Age Stereotypes in Media on Older Individuals’ Mental Health during the COVID-19 Pandemic: Article in The Journals of Gerontology, Series B: Psychological Sciences and Social Sciences by Becca R. Levy, PhD, E-Shien Chang, MA, Sarah Lowe, PhD, Natalia Provolo, BA, and Martin D Slade, MPH
Network-exposure severity and self-protective behaviors: The case of COVID-19: Original research article in Innovation in Aging by Howard Litwin, PhD, and Michal Levinsky, MA
COVID-19 and its Impacts on Older Adults: Global Perspectives: Editorial in The Journals of Gerontology, Series B: Psychological Sciences and Social Sciences by Danan Gu and Qiushi Feng
The Lived Experience of Already-Lonely Older Adults During COVID-19: Research article in The Gerontologist by Henry Bundy, PhD, Heather M. Lee, BSW, CCM, Kim N. Sturkey, BA, ACM-SW, CCM, CMC, and Anthony J. Caprio, MD
Purpose in life, loneliness, and protective health behaviors during the COVID-19 pandemic: Research article in The Gerontologist by Yoona Kang, PhD, Danielle Cosme, PhD, Rui Pei, PhD, Prateekshit Pandey, MA, José Carreras-Tartak, BA, and Emily B. Falk, PhD

Beekeepers across the United States lost 45.5% of their managed honey bee colonies from April 2020 to April 2021, according to preliminary results of the 15th annual nationwide survey conducted by the nonprofit Bee Informed Partnership (BIP). These losses mark the second highest loss rate the survey has recorded since it began in 2006 (6.1 percentage points higher than the average annual loss rate of 39.4%). The survey results highlight the continuing high rates of honey bee colony turnover. The high loss rate was driven by both elevated summer and winter losses this year, with no clear progression toward improvement for beekeepers and their colonies. BIP hopes to use the survey results to better understand how colony losses are experienced by beekeepers, and what can be done to reduce losses in future seasons.

Since beekeepers began noticing higher losses in their colonies in the early 2000s, agricultural agencies, researchers, and the beekeeping industry have been working together to understand why and develop best management practices to reduce their losses. The BIP annual colony loss survey, which has been conducted since 2006, has been integral to that process.

"This year's survey results show that colony losses are still high," says Nathalie Steinhauer, BIP's science coordinator and a post-doctoral researcher in the University of Maryland Department of Entomology. "Not all beekeepers are affected at the same intensity, but the turnover rate of colonies is still overall higher than beekeepers deem acceptable [normal or acceptable turnover is defined at about 20%]. We should remember, however, that loss rates are not the same as population decline. The recent numbers of honey bee colonies in the U.S. are relatively stable despite those high losses, but that's because beekeepers invest a lot of time and effort to increase their operation size to mitigate their losses."

Commercial honey bee operations are essential to agricultural production in the U.S., pollinating $15 billion worth of food crops each year. Honey bee colonies are moved around the country to pollinate important agricultural crops such as almonds, blueberries, and apples. Minimizing their losses and ensuring the health of both commercial and backyard colonies is critical to food production and supply.

"Beekeepers of all types consistently lose a high number of colonies each year, which puts a heavy burden on many of them to recoup those losses in time for major pollination events like California almonds," says Geoffrey Williams, assistant professor of entomology at Auburn University and co-author of the survey. "Colony losses remain elevated, and this year's annual and summer loss rates are among the highest recorded."

This past year, winter losses were reported at 32.2%, which is 9.6 percentage points higher than last year and 3.9 points higher than the survey average. Summer losses were some of the highest ever reported again this year at 31.1%, which is 0.9 percentage points lower than last year, but 8.6 points higher than the survey average.

The survey asks beekeeping operations of all sizes to track the survival or turnover rates of their honey bee colonies. This year, 3,347 beekeepers managing 192,384 colonies across the country responded to the survey, representing about 7% of the nation's estimated 2.71 million managed colonies. This effort helps to keep a finger on the pulse of what is going on with beekeepers to identify why high losses are persisting.

"Though we see fluctuations from year to year, the worrisome part is we see no progression towards a reduction of losses," says Steinhauer.

"The long-term efforts of the BIP's annual survey are so important to monitoring honey bee colony losses and beekeeper management over time, and hopefully to identifying key practices that are protective for colonies," stresses Williams. "Because of the close connection of honey bees to the environment, the survey's long-term data may lend itself to insights into how changes in land-use and weather impact the beekeeping industry too. These are really understudied areas at the moment."

This year, to get a better understanding of different management practices that may lead to loss fluctuations, the BIP team delivered two versions of the survey to cater to different beekeepers. The two surveys found that backyard (managing 50 or fewer colonies) and sideliner (managing 51-500 colonies) beekeeping operations face both similar and distinct challenges to commercial beekeepers managing more than 500 colonies. While parasitic varroa mites continue to be a major issue for beekeepers regardless of operation size, queen management might be a factor that can lead to variation in seasonal colony losses.

"A colony needs a healthy, fully functioning queen before major pollination events to be productive," explains Williams. "A preliminary look into survey data reveals that commercial beekeepers almost always replace old queens with new ones during the summer, whereas only about half of backyard beekeepers do. Could this explain why commercial beekeepers lose fewer colonies in the subsequent winter than backyard beekeepers? Perhaps, but we need to dig deeper and possibly perform experiments to shed more light on this."

While the survey suggests that beekeepers are remaining responsive to the current best management practices and health concerns of their colonies, the loss data shows little progress.

"We see in the survey signs that beekeepers are adjusting their practices over time," says Steinhauer. "We also see that their perception of risk is changing. The level of acceptable loss, which was originally around 15% in earlier years of the survey, has crept up to 23% this year. So that tells us beekeepers are thinking about those factors that affect honey bee health more actively. We also see some beneficial changes in agricultural practices that could affect honey bee health, like changes in spray recommendations. But there are still a lot of issues that are left unaddressed. It seems we're running to stand still because beekeepers are changing their practices, and yet we still don't see a clear improvement in their loss rates."

BIP stresses that the lack of improvement in losses is a clear call for more attention and efforts to be paid on finding solutions, especially concerning varroa mites. The BIP annual loss survey continues to be an important part of documenting the data necessary to drive future research, best management practice recommendations, and support for honey bee health.

"We hope to continue BIP's survey effort to record colony losses experienced by U.S. beekeepers and explore beekeepers' management practices," ensures Steinhauer. "We have a general idea of what practices are associated with higher success, but the devil is in the details, and we need to understand why the implementation of some practices are more successful in some cases than others. Of course beekeepers also need the support of the public and political sectors. We need to recreate environments that are conducive to healthy bees, and that will benefit both honey bees and native bees or other wild pollinators."

The survey is conducted by the Bee Informed Partnership with data collected and analyzed by the University of Maryland and Auburn University. Survey results are available here on the Bee Informed Partnership website, with a summary provided below.

Winter Loss Estimates:

1 October 2020 - 1 April 2021: 32.2% losses

9.6 percentage points higher than winter 2019-2020: 22.6%

3.9 percentage points higher than average winter loss (2006-2021): 28.3%

Summer Loss Estimates:

1 April 2020 - 1 October 2020: 31.1% losses

0.9 percentage points lower than summer 2019: 32.1%

8.6 percentage points higher than average summer loss (2010-2020): 22.8%

Total Annual Loss Estimates:

1 April 2020 - 1 April 2021: 45.5% losses

1.8 percentage points higher than 2019-2020: 43.7%

6.1 percentage points higher than average annual loss (2010-2021): 39.4%

Loss Comparison by Beekeeper Category:

Backyard beekeepers (manage 50 or fewer colonies): 27.0% summer vs. 42.0% winter losses

Sideliner (manage 51-500 colonies): 19.5% summer vs. 31.9% winter losses

Commercial (manage more than 500 colonies): 30.9% summer vs. 32.9% winter losses

A human genetic mechanism hijacked by SARS-CoV-2, the coronavirus behind the COVID-19 pandemic, to help it spread also makes it vulnerable to a new class of drug candidates, a new study finds.

Led by researchers at NYU Grossman School of Medicine, a research team showed that coronavirus reproduction in infected human cells requires chemical changes made by the human protein METTL3 to RNA, a key form of genetic material. Additional human proteins involved in the recognition of modified RNA, YTHDF1 and YTHDF3, were also found to be important to the process.

Published online in Genes and Development on June 24, the study showed for the first time that a molecular inhibitor of METTL3, designed by Storm Therapeutics Ltd and called STM2457, dramatically reduced in cell cultures the replication of both pandemic SARS-CoV-2 and, a less severe, seasonal coronavirus, HCoV-OC43, one cause of the common cold.

"Our results represent the first time a chemical inhibitor of METTL3 has been shown to have an anti-viral effect for coronaviruses, or any virus," says senior study author Ian Mohr, PhD, professor in the Department of Microbiology at NYU Langone Health. "This represents a necessary step in drug development, identifies new targets, and reveals an unexpected strategy to halt the coronavirus lifecycle."

Turning Virus' Weaknesses Against Them

The current study builds on a growing understanding of gene regulation. It has long been established that sequences of As, Gs, Cs and Ts, the molecular letters in the DNA code of genes, are copied into messenger RNA (mRNA) molecules that carry the information to the machinery that determines which proteins are made. Only recently has the importance of chemical modification to mRNAs become apparent in the control of protein production. In some instances this process is controlled by the attachment of a methyl group (one carbon and three hydrogens) to an RNA chain, which turns that genetic message off.

Crucially, coronaviruses that replicate inside human cells are known to encode the complete set of their genetic instructions (their genomes) in RNA chains, raising the question of whether human RNA modification enzymes, including those that attach methyl groups, could impact the production of viral proteins that enable them to multiply.

Past work in Mohr's lab had revealed the enzymes that determine whether an A (adenosine), one of the chemical "letters" making up mRNA, is methylated at the N6 position (m6A) is important for replication of human cytomegalovirus (HCMV), with regulation by human m6A enzymes of mRNAs shaping the immune response to that virus.

In the current study, the research team showed for the first time that the reproduction of SARS-CoV-2 and HCoV-OC43 requires the action, not only of the human enzyme that installs the m6A methylation on RNA, METTL3, but human proteins that bind to this unusual arrangement of methylated RNA, YTHDF1 and YTHDF3. Remarkably, the researchers also found that the RNA genomes of both study coronaviruses contained this m6A modification.

For the next step, the NYU Langone team partnered with the UK-based Storm Therapeutics, which had run a medicinal chemistry program to develop a compound that best inhibited the action of METTL3. The current study compared the effects of the METTL3 inhibitor STM2457 and an inactive control compound, STM2120, on cultures of human lung cells infected with the seasonal coronavirus or SARS-CoV-2. The researchers then used an imaging technology to track viral infection in thousands of cells treated with different doses of STM2457.

Compared with the same concentration of the inactive control compound, the highest dose of STM2457 reduced the number of HCoV-OC43 infected cells in culture by more than 80 percent, while the same dose of STM2457 reduced SARS-CoV-2 reproduction by more than 90 percent. Further experiments revealed that STM2457 reduced viral RNA and protein levels, but not by affecting the same human immune response mRNAs previously found to be important for HCMV.

"The inhibition of coronaviruses by this molecule is really encouraging but understanding exactly why coronaviruses need m6A RNA modification is important and might enable the design of compounds that work even better," says study first author Hannah Burgess, PhD, an assistant research scientist in the Department of Microbiology at NYU Langone Health.

Moving forward, the research team plans to further investigate precisely how m6A modification influences virus and host gene expression in cells infected with pandemic or seasonal coronaviruses and whether STM2457 can interfere with coronavirus replication and prevent severe disease outcomes in non-human animals.

"We went into it hoping to learn about the differences between the biology of innocuous and pandemic coronavirus infections," says co-corresponding author Angus Wilson, PhD, associate professor in the Department of Microbiology at NYU Langone Health. "If anything we found that both share a dependence upon the m6A methylation machinery. That creates the hope that inhibiting METTL3 may also be useful against future pandemic coronaviruses."

Those with power, such as the wealthy are more likely to blame others for having shortcomings and they are also less troubled by reports of inequality, according to recent research from the University of California San Diego's Rady School of Management.

The study published in Social Psychological and Personality Science defines power as control over valuable resources. The paper finds that people in positions of power are more likely to adopt a "choice-mindset," which means that although they have more choices (the definition of power in many cases) they still see others with less power as having lots of choice, regardless of their situation. Consequently, high-power individuals are more likely to blame others if they perform poorly and they are also more likely to punish them.

"Being in a choice-mindset changes how individuals think, feel and behave," said Yidan Yin, the first author of the paper and recent PhD graduate from the Rady School. "Compared to low-power people, high-power people are less likely to be aware of others' constraints. As a result they assign more blame when people make mistakes or have shortcomings. Thus, they see the current hierarchy as more justified."

The results from the research were derived from three different studies the authors conducted to replicate the findings in different settings.

Research findings hold up in three robust study settings

The first study was conducted via a survey in which the researchers measured the sense of power of 363 members of the general public recruited through the platform Prolific. They also asked the participants to complete a separate survey, claiming it was unrelated, in which they were crowdsourcing how to resolve a human resources issue at the university. The survey explained that their academic department was weighing whether to give an administrative assistant a bonus though they had missed a deadline on a big project due to conflicting priorities. The survey participants who measured as having a greater sense of power overwhelming responded the administrative assistant did not deserve the bonus and that their excuses were without merit.

The second study was conducted with the platform Amazon Mechanical Turk involving 393 members of the general public who were randomly assigned to roles as supervisors and subordinates in completing various tasks. Though the assigned ranks were random, supervisors were told they earned the role for their proficiencies and subordinates were told they were designated as such because they were outperformed by supervisors.

The two groups had to judge the performance of an anonymous individual, who by design, made mistakes in completing their tasks. Once again, the researchers found that those with a greater sense of power (supervisors) were harsher, less understanding with their judgment and recommended punishment more than subordinates.

The third study was done in a lab with UC San Diego undergraduates and mirrored the second experiment. The main difference was that both supervisors and subordinates knew that the target person they had to judge had the rank of a subordinate and therefore less choices. The results from the first two studies held up with subjects that had more power assigning more blame and recommending more punishment.

"Each study was designed to build on the others," Yidan and co-author Pamela K. Smith, associate professor of economics and strategic management at the Rady School write. "In study one, we were measuring power, in study two, we manipulated power and in study three, we created a world in which the judges knew the target person had less power and less choices. We wanted to see if the perceptions remained consistent in all three settings. It was a combination of replication and adding these additional twists and turns."

Implications for more equitable public policy and workplace environments

The results from the study have significant implications for public policy, according to the authors.

"Policymakers are in a position of power and privilege and may be less sensitive to the disadvantages of their constituents," the authors write. "This is especially important as we come out of the pandemic when there are big discussions in the political domain on pulling back on unemployment benefits, or rent assistance. If you are in a position of power, you may assume people are choosing to stay home and not work and they can make better choices. However, you may need to think much more carefully about how many choices citizens have and if you are missing constraints they face."

In addition, the implications are far-reaching for the workplace.

"Mangers should be aware of how many more choices they have than their subordinates and their tendency to project their own choices onto others, especially when employees make mistakes." Yin said.

Smith added, "It might require having more discussion with employees and being cognizant of their situation because sometimes lack of choice and constraints can be invisible to someone from the outside."

Irvine, CA - June 23, 2021 - A new University of California, Irvine-led study finds that the persistence of a marker of chronic cellular stress, previously associated with neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), also takes place in the brains of Huntington's disease (HD) patients.

Chronic cellular stress results in the abnormal accumulation of stress granules (SGs), which are clumps of protein and RNAs that gather in the cell. Prior to this study, published in the Journal of Clinical Investigation, it was not known if these types of granules were a pathological feature of HD, an inherited and progressive neurodegenerative disorder that typically strikes in the prime of life.

In addition to identifying SGs as a pathological feature of HD, researchers made several other discoveries including that extracellular vesicles, which float in cerebrospinal fluid (CSF) and act as a messaging system between cells in the brain, can potentially alter the behavior of other cells and impact the abnormal accumulation of the granules. They also found that TAR DNA-binding protein 43 (TDP43) is mislocalized, which has emerged as a critical feature of multiple neurodegenerative diseases.

"We were initially interested in whether the profile of these messages could serve as a biomarker for HD and investigated whether the vesicles from HD patients contain messages that are different from those of unaffected individuals," said first author Isabella I. Sanchez, PhD, from the Thompson Laboratory at UCI School of Medicine.

Researchers found that the CSF of HD patients carried messages in the form of small non-coding RNAs (miRNAs) that did were predicted to alter the production of proteins that are indispensable for SG formation. They soon identified a key player in SG dynamics, GTPase-activating protein-binding protein 1 (G3BP1), as a predicted target.

"This finding regarding the miRNAs was very exciting, as we had simultaneously started investigations to characterize SGs in HD brain tissues. SGs can be very difficult to detect in brain tissues, and it just so happened that we had narrowed down the adequate conditions and were ready to being characterizing G3BP1 SGs in HD mouse and HD patient brains," said Leslie M. Thompson, PhD, Donald Bren and UCI Chancellor's professor in the Departments of Psychiatry & Human Behavior and Biological Chemistry at the UCI School of Medicine, and Neurobiology and Behavior at the UCI School of Biological Sciences.

While SG formation is a normal physiological process that enables cells to overcome stressful conditions, the SG pathology in HD may result from an accumulation G3BP1 SGs that initially served a protective function, but develop into hyper-stable structures over time.

"We hope that our findings will inform future studies aimed at understanding how SG accumulation affects HD progression, and whether targeting SG pathology is a viable therapeutic avenue in the fight against HD," said Robert Spitale, PhD, professor in the Department of Pharmaceutical Sciences and also a lead author of the study.

In a groundbreaking study, a team of UC Davis researchers has discovered a special type of stem cell that can reduce the amount of the virus causing AIDS, boosting the body's antiviral immunity and repairing and restoring the gut's lymphoid follicles damaged by the simian immunodeficiency virus (SIV), the equivalent of the human immunodeficiency virus (HIV) in non-human primates.

The study, published June 22 in JCI Insight, showed the mechanism through which mesenchymal stem/stromal cells (MSCs) enhance the body's immune response to the virus. It also provides a roadmap for developing multi-pronged HIV eradication strategies.

"Impaired immune functions in HIV infection and incomplete immune recovery pose obstacles for eradicating HIV," said Satya Dandekar, senior author of this paper. "Our objective was to develop strategies to boost immunity against the virus and empower the host immune system to eradicate the virus. We sought to repair, regenerate and restore the lymphoid follicles that are damaged by the viral infection."

The lymphoid tissue in the gut is an early site for viral replication and the establishment of viral reservoirs. Dandekar's group has previously shown that an HIV infection causes severe loss of gut mucosal T immune cells and disrupts the gut epithelial barrier lining, leading to a leaky gut.

"The lymphoid follicles are organized structures where the long-term immune attack is launched against pathogens by generating antibody response targeting the virus. These important regions are functionally impaired very early following HIV infection," Dandekar said.

While antiretroviral drugs effectively suppress viral replication, they do not repair the damage caused by the virus to the immune system. On their own, these drugs cannot restore the functionality of the lymphoid follicles damaged by HIV infection.

Can stem cells counteract the gut damage caused by HIV?

The researchers administered bone marrow-derived MSC in a rhesus macaque model of AIDS that had impaired immunity and disrupted gut functions due to the viral infection.

"We are starting to recognize the great potential of these stem cells in the context of infectious diseases. We have yet to discover how these stem cells can impact chronic viral infections such as AIDS," Dandekar said. She is a professor at and the chairperson of the Department of Medical Microbiology and Immunology at UC Davis and affiliated with the California National Primate Research Center.

The study found that the MSCs can modulate, alter and remodel the damaged mucosal site. There were immediate benefits, with a rapid rise in antibodies and T-immune cells targeting the virus. The stem cells were instrumental in the recovery and restoration of these lymphoid follicles.

MSCs also offer an opportunity for an innovative, multi-pronged HIV cure strategy by complementing current HIV treatments.

"Stem cells are good synergistic partner components with drugs. The antiretroviral drugs can stop the fire of the viral infection but cannot restore the forest of the lymphoid tissue compartment. The MSCs would rejuvenate the field and bring back immune vitality," Dandekar said.

Even without the use of antiviral drugs, MSCs were able to increase the host's antiviral response by repairing the lymphoid follicles, restoring the mucosal immunity and reviving what has been targeted by the virus very early on.

MSC treatments

MSC treatments require well defined cell quality controls and specific delivery mechanisms. The UC Davis Stem Cell Program, a center for excellence for stem cell research, is leading multiple clinical trials on MSC use in treating diseases such as spina bifida and Huntington's disease. Findings from this study provide a scientific basis for investigating MSC in treating HIV and other infectious diseases in the clinical setting.

Adult corals that survive high-intensity environmental stresses, such as bleaching events, can produce offspring that are better suited to survive in new environments. These results from a series of experiments conducted at the Bermuda Institute of Ocean Sciences (BIOS) in 2017 and 2018 are deepening scientists' understanding of how the gradual increase of sea surface temperatures and other environmental disturbances may influence future coral generations.

Researchers on the project included BIOS marine ecologists Samantha de Putron and Gretchen Goodbody-Gringley (now with the Central Caribbean Marine Institute), ecophysiologist Hollie Putnam at the University of Rhode Island (URI), and Kevin Wong, then a first-year doctoral student at URI. Primary funding came from the Heising-Simons Foundation International, Ltd. with additional funding from the National Geographic Society and the Canadian Associates of BIOS (CABIOS).

The team spent last year working the data into a manuscript, which was published this month in the journal Global Change Biology and listed Wong as the first author. Wong, now nearing the end of his fourth year of studies at URI under the mentorship of Putnam, plans to graduate in May 2022.

"We know parental history influences the characteristics of offspring in corals, however the experimental design used in this study provides us with a unique perspective on how multiple types of thermal events can accumulate over time and have lasting consequences across generations," Wong said.

Coral Collection and Study
The multi-year field and lab-based study began in the summer of 2017. Departing from BIOS on a small boat with diving gear, the team collected 40 adult Porites astreoides (mustard hill) corals from two different reef sites northwest of Bermuda: a patch reef (Crescent Reef), which is located in a shallower lagoon environment, and a rim reef (Hog Reef) which is a barrier reef more exposed to open ocean conditions.

They next placed the live corals in the then newly-constructed BIOS mesocosm facility, where large outdoor aquaria "flow-through" seawater systems allowed researchers to control and adjust water temperature in the tanks for completing the study.

A variety of baseline data were collected on the corals in each colony, such as metabolic rates and the density of Symbiodinaceae, the symbiotic algae that live within the coral tissues. To simulate a thermal stress event, the adult corals were exposed to two different temperature treatments--ambient (84°F or 29°C) or heated (88°F or 31°C)--for a period of 21 days over their reproductive period. Afterward, the team assessed the physiology of the adult corals, looking at key functions such as respiration and photosynthetic rates. They also monitored the release of coral larvae and assessed its physiology, measuring the larval size and density of Symbiodinaceae within each larva, among other factors.

Upon completion of the experiment, the adult corals were divided in half and reciprocally transplanted, with half of the fragments positioned in the new environments and half returned to their originating environments. All of the fragments remained in place until the summer of 2018, when they were re-collected, and the physiologies of both adult corals and coral larvae were assessed in the same manner as in 2017.

A Stronger Coral Generation
The results of this two-year investigation showed that adult corals that experienced the thermal stress event produced offspring more capable of thriving in their current environment. This means that parent corals that experience stressors may be able to "pre-condition" their offspring to survive in new environments in the following year. The results also indicate that high-intensity environmental stress events, such as bleaching, can have lasting impacts on adult colonies and how they produce their offspring.

"The coral used in this study is a notoriously resilient coral and these findings potentially demonstrate how this species is so persistent across the Caribbean," Putnam said. "Not all coral species are this robust to environmental stressors. However, this system allows us to unravel the mechanisms leading to resilience and identify which corals are most sensitive to climate change."

Long-time Member of BIOS Community
Wong, 27, is a familiar face at BIOS, having first arrived on campus in the summer of 2014 as a CABIOS intern when he spent 12 weeks working with de Putron on a research project investigating the role of temperature and light on the growth and survivorship of juvenile mustard hill corals from two different reef zones. The following year, he received CABIOS funding to work with then-faculty member Gretchen Goodbody-Gringley on a project focused on the reproductive ecology of corals from mesophotic reef ecosystems, deeper-water reefs which typically extend from 100 to almost 500 feet (30 to 150 meters) in depth.

While presenting the results of his research at the 2016 International Coral Reef Symposium meeting in Hawaii, he had the opportunity to interview with Putnam for URI's Biological and Environmental Sciences doctoral program. Wong then returned to BIOS to spend six months in 2016 as a teaching assistant for several summer and fall courses. He also received BIOS Grants-in-Aid funding for a research project with Goodbody-Gringley and de Putron focused on the reproductive ecology of mustard hill coral from various reef sites around Bermuda, resulting in a publication in the journal Coral Reefs.

"It is wonderful to see an undergraduate intern progress to a successful graduate student who is publishing manuscripts," de Putron said. "Many years of hard work and plenty of exhausting, yet fun, days in the field and laboratory all culminated in interesting and critically relevant discoveries that further our understanding of coral resilience."

Now, a year from graduation, Wong is diving deeper into the mechanisms that drive environmental memory within and across coral generations at a molecular level. By using approaches such as metabolomics (the identification and quantification of metabolic by-products), transcriptomics (quantification of gene expression), and epigenetics (features that regulate gene expression), Wong aims to determine the key linkages between metabolism and coral bleaching phenotypes at a cellular level.