Culture

Inspired by work on infants, researchers at the Eötvös Loránd University (ELTE ) investigated whether dogs' behaviors are guided by human displays of preference or by the animals' own choices. They found that dogs' looking times, but not fetching behavior, were influenced by the owner's expression of preference. Although the studies did not demonstrate that dogs override their own preferences for an object, the results suggested that the owners' expressed preference was perceived by the dogs and guided their perceptual focus.

Studies on animal cognition deepen our understanding of the human mind's evolution and help inform policy makers in the production of legislation around animal keeping. Whether dogs have any idea that their humans have thoughts and emotions of their own, is one of the hot topics in dog research. The answer could have interesting implications, but it has been challenging to find a decisive way to test it so far.

„There is no shortage of attempts to unveil the putative mind-reading abilities of dogs" says Dr. Ádám Miklósi, head of the Department of Ethology at Eötvös Loránd University, Budapest, „but no single study has been convincing enough on its own, so over the years we have broken down the big question into smaller, more tangible goals."

One of these goals has been to investigate how dogs respond to expressions signaling the preferences of humans. A new study published in Frontiers in Psychology follows up on previous efforts in this direction. „We knew that dogs respond to humans signalling their preference, but in previous studies, the dogs' own priorities were not accounted for. In particular, we did not know how conflicting preferences between the dogs and the owner influence the behavior of dogs." says Eniko Kubinyi, leading author of the study, senior researcher at Eötvös Loránd University. „18-month-old children recognize that their own preference might differ from that of others and they understand how desire can be inferred from emotional expressions, but 14-month-olds do not. We wanted to test where dogs are on this scale."

The researchers first tested a subset of dogs on their spontaneous preference for either a dog toy or a bracelet. The toy was without exception the more desirable object. Next, owners displayed happy expressions towards the bracelet and made disgusted faces towards the toy. Then the owner asked the dog to fetch, without providing additional guiding cues. All dogs fetched the toy, indicating that their own choice was not overcome by the emotional expressions of the owner. "Thus dogs either are not able to distinguish between their own and the owners' preference or they failed to inhibit the "wrong" response" explains Flóra Szánthó, co-author.

The researchers decided to dig deeper. „Fetching was clearly not a good choice to measure dogs' sensitivity to others' preferences for several reasons" notes Kubinyi, „since their own favorite object was in reach, the dogs had little incentive to factor in the owner's choice in their responses. We assumed that if the same objects were out of reach, they would stimulate what appears to be "showing" behavior in the dogs and they would direct more attention towards their owners' pick, thereby also weakening the affordance provided by their preferred object." To test this hypothesis, the researchers decided to put the objects up on the laboratory's windowsill where the dogs could not reach them.

Fifty-one dogs were assigned to one of two experimental groups: a matching/congruent condition where owners displayed happy expressions towards the toy and made disgusted faces towards the bracelet, and a non-matching/incongruent condition, where owners showed happiness toward the bracelet and disgust toward the toy. After the emotion display, the toy and the bracelet were placed out of reach and the researchers now measured how much time the dogs looked at each object. "In this case", says Ivaylo Iotchev, postdoc at Eötvös Loránd University, and co-author, "the dogs looked at the favored toy when their owner had previously responded to it with a happy face. In the other group they looked the same amount of time at the bracelet and the toy."

The demonstration of the owners' preference affected the dogs' behavior. „It is not certain that this influence is the result of inferred and shared representations" warns Kubinyi. "We have not found conclusive evidence that dogs, similarly to one and a half.year-old toddlers, understand the subjectivity of the desire, i.e., that different people can have different attitudes toward the same object. If they indeed infer the owner's preference, they might not understand fetching as an act of offering an object to a human, or response inhibition, an important aspect of cognitive control, was not sufficiently strong to overwrite the animals' own preference." What is certain, is that this study is the first to show that dogs are sensitive to their owners' choice even though they prefer to fetch their favorite toy when it is in reach."

URBANA, Ill. ­­- Food insecurity in America is reaching an all-time high during the COVID-19 pandemic. But large regional differences exist in the severity of the impact.

Experts project over 50 million Americans will be food insecure in 2020, including about 17 million children, says Craig Gundersen, ACES distinguished professor in the Department of Agricultural and Consumer Economics at the University of Illinois.

Gundersen estimated food insecurity using Map the Meal Gap, an interactive model he developed for Feeding America, a nationwide network of more than 200 food banks in the U.S. For the current report, he combined MMG data with projected unemployment numbers.

"One of the key things about COVID-19 is how there's differential impacts across the country and by demographic groups. People with college education generally have not seen much of an impact on either unemployment rates or incomes. However, people in lower-wage jobs tend to be impacted a lot more," Gundersen states. "We would expect greater impact of COVID-19 in areas with a high concentration of service industry jobs."

The report finds the hardest hit states are the same as before the pandemic - Mississippi, Arkansas, Alabama, Louisiana, and New Mexico ­- but with higher rates. Jefferson County, Mississippi, has the highest food insecurity rate, 30.4%, in the country.

However, the pandemic disproportionately affected other states. For example, Nevada jumped from 20th to eighth highest food insecurity rate by state.

"Areas like Nevada, which has a strong emphasis on the service industry and tourism, will have substantially higher rates of increase in food insecurity than areas with fewer service sector workers," Gundersen says.

These findings can help direct relief efforts, he notes.

"Resources should continue to be directed towards those areas with greater needs before, during, and after COVID-19. But we also have to recognize that during the pandemic situation there are areas of the country, such as Nevada, which may need more emergency assistance in the near term," Gundersen says.

"Furthermore, some of these jobs may not come back; tourism may be permanently down in the United States. So these impacts could also have longer term ramifications," he concludes.

LOS ANGELES (Nov. 12, 2020) -- Older adults who joined group exercise classes experienced decreased loneliness and social isolation, according to a new Cedars-Sinai study conducted before the COVID-19 pandemic. The classes have continued virtually since March, and early results suggest the online versions are also effective.

Seniors face increased risk for developing serious health issues or even death if they lack social connections or feel alone. Loneliness is connected to higher rates of depression, anxiety and suicide. Experts say social isolation can have the same impact on an older person's health as smoking 15 cigarettes a day.

Both loneliness and social isolation are widespread issues in the U.S., where more than a third of adults 45 and older feel lonely and nearly a quarter of those 65 and older are socially isolated, according to the National Academies of Sciences, Engineering, and Medicine. But few studies have examined the most effective ways to improve social connectedness among seniors.

"As the demographics of our country shift, more people are living alone than ever before," said the study's lead author, Allison Moser Mays, MD, a Cedars-Sinai geriatrician. "The number of adults over the age of 65 in the U.S. is expected to reach more than 70 million by 2030 - double what it is now. We need sustainable ways to help this burgeoning population thrive as they age, or there will be widespread consequences."

Mays and her co-investigators partnered with local community groups to enroll participants in evidence-based exercise and health management classes for people over 50 at nine sites in Los Angeles neighborhoods with a known concentration of low-income older adults. All locations - which included libraries, senior centers and recreation centers - were accessible for those with mobility limitations and had access to parking and public transit.

The study tracked 382 participants ages 52 to 104 from July 2018 through March 2020, when the pandemic forced the classes to move online. Some people were referred by their Cedars-Sinai physician during an office visit. Others found the program through community outreach.

All participants met with a health coach who assessed their needs and helped them select one of four courses, which research has shown improve other aspects of health: Arthritis Exercise, EnhancedFitness, Tai Chi for Arthritis, and Chronic Disease Self-Management. The three exercise classes proved the most popular, and individuals had to attend at least one session to be included in the study.

Participants completed questionnaires about their social connections and loneliness prior to starting their course and after six months. At the end of that period, investigators found a 6.9% decrease in loneliness and a 3.3% improvement in social connectedness, after adjusting for age, gender and other characteristics. The study was published in the American Journal of Geriatric Psychiatry.

"These classes had already been shown to reduce the risk of falls in seniors, and this was the first demonstration that they also reduce social isolation, to the best of our knowledge," Mays said.

The Leveraging Exercise to Age in Place (LEAP) classes have been supported by a three-year grant from the AARP Foundation. Cedars-Sinai has adopted the successful programming under the Community Engagement Department.

"The results of this study are very exciting because we've provided a model that other health systems can easily replicate by integrating evidence-based programs in the community with their organizations. They don't need to reinvent the wheel," said senior study author Sonja Rosen, MD, chief of Geriatric Medicine at Cedars-Sinai. "The health coach is the key ingredient because they make sure that nobody falls through the cracks."

The health coach has been especially crucial since the pandemic began when classes moved online and participants sometimes have needed help figuring out how to log on to the platform. That effort has been paying off.

Of the 59 participants who continued with the virtual workouts, there has not been a statistically significant change in loneliness or social isolation one month after stay at home orders began, according to data Mays presented over the weekend at the Gerontological Society of America's annual meeting. The investigators will analyze further data as the classes continue. They're also piloting another program that pairs older adults with younger participants for one-on-one workout sessions online.

"Cedars-Sinai treats more patients over the age of 80 than any other academic health system in the country," Rosen said. "We're really at the epicenter of this growing population of older adults and figuring out the best ways to care for them so they can successfully age in place."

Rosen said efforts like the LEAP program helped Cedars-Sinai earn its designation as an Age-Friendly Health System Committed to Care Excellence earlier this year. The distinction, which highlights care tailored to older adults, is part of a national initiative of The John A. Hartford Foundation and the Institute for Healthcare Improvement, in partnership with the American Hospital Association and the Catholic Health Association of the United States.

CHARLOTTE, N.C. - NOV. 12, 2020 - A new comprehensive study from UNC Charlotte's Urban Institute, College of Health and Human Services and School of Social Work shows an effective approach to ending chronic homelessness that helps those in need and benefits communities.

The Housing First Charlotte-Mecklenburg initiative, an innovative multi-sector collaboration that's been working to end chronic homelessness in Charlotte for five years, has placed more than 1,000 people in the Charlotte community in stable housing. This is the largest and most comprehensive local effort to address chronic homelessness. Nationwide, on any given night, more than 550,000 Americans are experiencing homelessness, and this research could offer guidance to cities around the U.S. struggling with this issue.

"The Housing First Charlotte-Mecklenburg effort led to major housing wins during a time of increasing housing scarcity, and the vast majority of those who were able to access housing through the effort did not return to emergency shelters," said Lori Thomas, associate professor at UNC Charlotte's School of Social Work and Director of Research and Faculty Engagement at the UNC Charlotte Urban Institute.

Thomas has completed an evaluation of the first phase of the program, the most rigorous and in-depth study to date in Charlotte and one of the few reports in the country that examines a community's overall response to chronic homelessness. Findings highlighted in Thomas' research may have a significant impact throughout the country in other cities working to expand Housing First programs such as Atlanta, Denver, San Francisco and Washington, D.C.

Key findings from the first phase of the Housing First program include:

Housing First works. Almost three-quarters of study participants housed through the Housing First program either retained their housing or moved into other housing during the study period. That means a large majority of people who get housed, stay housed.

Housing First impacts participants. Clients who gained housing showed reductions in trauma, mental illness and substance use. Additionally, housed participants scored significantly higher on standardized overall quality of life indicators.

Housing First impacts the community. People who were housed were less likely to be arrested or visit the emergency department. Additionally, the average number of visits to the Mecklenburg County Health Departments and the average number of nights spent in emergency shelters all decreased.

Costs of housing are partially offset through other community services. Based on the changes in service utilization, there is a $2.54 reduction in community services for every $10 invested in housing first permanent supportive housing. This savings reduces the average annual cost of housing first permanent supportive housing from $17,256 to $12,688.

There were also lessons learned that can improve the initiative. Among those:

Housing First participants experienced persistent and worsening food insecurity. Rates of food insecurity remained high for clients who gained housing. Research suggests people might have more difficulty accessing food once they gain housing, perhaps because they do not have transportation to free resources where they previously got food, or because they now live in a "food desert."

Housing First participants continued to report poor perceptions of physical health. The impact of years without housing and access to preventative care, as well as the fact that the majority of study participants have two or more disabilities, may account for this finding.

Housing First and the focus on homelessness highlighted the need for better coordination, representation and communication among stakeholders across various sectors (government, nonprofit, academic and business). Additionally, the initiative drove home the need to connect homelessness to the community-wide affordable housing challenges facing Charlotte and Mecklenburg.

"With the release of the Housing First Evaluation report, we are able to share information with the community about the results and impact of a public-private, community initiative to end chronic homelessness," said Stacy Lowry, director of community support services for Mecklenburg County. "In addition to outcomes, this report also provides an in-depth analysis of the initiative, itself. By looking at the relationship between outcomes and process, Charlotte-Mecklenburg can use this report to expand and strengthen existing efforts to prevent and end homelessness as well as inform new, systemic solutions to address complex problems comprehensively and effectively."

HOUSTON - (Nov. 12, 2020) - "Position 4" didn't seem important until researchers took a long look at a particular peptide.

That part of the peptide drawn from a SARS-CoV virus turned out to have an unexpected but significant influence on how it stably binds with a receptor central to the immune system's ability to attack diseased cells.

In a study published by the Proceedings of the National Academy of Sciences, researchers at Rice University's Brown School of Engineering and the University of Texas MD Anderson Cancer Center revealed models at atomic resolution that detail not only the binding but also, for the first time, the unbinding mechanisms that underlie a key component of the immune system.

They say better understanding of the entire mechanism could lead to advancements in immunotherapy that boosts the body's ability to fight disease.

Rice computer scientist Lydia Kavraki, alumnus Jayvee Abella and postdoctoral researcher Dinler Antunes, led the study.

"Finding good targets to trigger a protective immune response is very challenging, especially in cancer research," Antunes said. "The fact that this particular peptide was predicted not to bind to HLAs (human leukocyte antigens) by sequence-based methods highlights a blind spot in our current prediction capacity.

"By incorporating structural analysis, we can detect the contribution of these secondary interactions to peptide binding and stability, hopefully enabling us to find better targets for antiviral vaccine development and T-cell-based cancer immunotherapy," he said.

The researchers used their simulations to illuminate details of how the intracellular SARS peptide, QFKDNVILL, binds to an MHC receptor protein known as HLA-A?24:02, primarily at dominant anchors on both ends of the peptide (at positions 2 and 9) and presents them for inspection to the immune system's T cells.

Stable binding of a peptide and MHC is a prerequisite to the activation of T cells, which look for peptides not normally found in healthy cells. If the peptide and protein don't bind, the T cell is not prompted to attack.

"That much was known from previous studies of the bound and unbound states of many such complexes," Kavraki said. "What they didn't capture was the intermediate states and the transitions that lead from one state to another, especially the unbinding.

"I think this is the only analysis that shows the unbinding of peptides from the MHC with atomic resolution," Kavraki said. "Other peptides have similar characteristics and we think they would have similar behaviors."

All of these interactions were revealed in great detail through Markov state models that analyze how systems change over time. In this case, the models revealed the importance of secondary sites that support the peptide's primary anchors. That's where position 4 stood out.

"There are the main, canonical anchors that people know, but there are these secondary interactions that contribute to the binding and the stability," Antunes said. "These are harder to capture, but in this study, it seems that position 4 plays a very important role. When you mutate it, it affects the behavior of the peptide as it unbinds from the molecule."

The researchers modeled mutations of the MHC to see how they would influence binding and found they supported the importance of position 4 to the stability of the complex.

"Our computational approach was able to make predictions on the effect of mutations that are then experimentally verified," said co-author Cecilia Clementi, a former Rice professor who recently became Einstein Professor of Physics at the Free University of Berlin.

The researchers developed a two-stage process to simplify the computational complexity of atom-scale analysis of large molecules. The first stage used a technique called umbrella sampling to accelerate the initial exploration of the molecules. The second, exploratory stage used adaptive sampling, in which simulations are driven to accelerate the construction of the Markov model.

"The challenge is that these MHCs are pretty large systems for computational chemists to simulate," said Abella, whose research on the topic formed much of his doctoral thesis. "We had to make some approximations and leverage advances in these classes of methods to move forward.

"We're not the first one to study unbinding, but what characterizes our work over others is that we keep full atomic resolution in our simulations," he said. "Other works use a technique known as a Markov chain Monte Carlo, whereas we use molecular dynamics, which lets us incorporate time into our computation to capture the kinetics."

Their methods can be applied to other peptide-MHC complexes with existing 3D models. "This was, in some sense, a feasibility study to show we can use molecular dynamics and build a Markov state model of a system this size," Abella said.

The researchers also noted the study's relevance to the current fight against COVID-19, as the SARS peptide they viewed, QFKDNVILL, is highly similar to the NFKDQVILL peptide in SARS-CoV-2, with the same binding pockets in positions 2, 4 and 9.

"These results suggest that both peptides can bind to HLA-A*2402 and provide targets for anti-viral T-cell responses, which are of great interest in light of the current pandemic," said co-author Gregory Lizée, a professor in the Department of Melanoma Medical Oncology at MD Anderson. "But these results also shed light on many other potential immune targets, including those of other viruses and even human cancers."

Kavraki noted that experimental work by longterm collaborator Lizée and Kyle Jackson, a graduate research assistant at Lizée's lab who produced the mutant proteins, were critical to validate their simulations. Kavraki's own lab won a National Science Foundation (NSF) Rapid Response Research grant to help identify fragments of SARS-CoV-2 viral proteins as possible targets for vaccine development.

MADISON, Wis. -- Researchers have discovered a previously unknown way that pancreatic cells decide how much insulin to secrete. It could provide a promising new target to develop drugs for boosting insulin production in people with Type 2 diabetes.

In a pair of papers recently published in Cell Metabolism, scientists from the University of Wisconsin-Madison and their colleagues point to an overlooked enzyme known as pyruvate kinase as the primary way pancreatic beta cells sense sugar levels and release the appropriate amount of insulin.

From several proof-of-concept experiments in rodents and on human pancreatic cells, the team found that drugs stimulating pyruvate kinase not only increase the secretion of insulin but have other metabolically protective effects in the liver, muscle and red blood cells. The findings suggest that activating pyruvate kinase could be a new way to increase insulin secretion to counter Type 2 diabetes, but more research would be required before any new treatments were available.

"Too much insulin can lower blood sugar to dangerous levels, and too little insulin can lead to diabetes," says Matthew Merrins, a professor of medicine at the UW School of Medicine and Public Health who led the work. "The question we're asking here is: How do nutrients like glucose and amino acids turn on beta cells in the pancreas to release just the right amount of insulin?"

The work was accomplished by carefully dissecting the paradoxical timing of key biochemical events in the prevailing understanding of how pancreatic beta cells respond to nutrients in the blood. The researchers point to a new, richer model to understand how this important process is controlled that resolves these inconsistencies.

For decades, scientists believed that mitochondria, the energy generators in cells, initiated insulin secretion. It was a natural explanation, because mitochondria produce the high-energy molecule ATP, in the process depleting ATP's low-energy version, ADP. The drop in ADP stimulates calcium -- the ultimate trigger to release stored insulin.

But the timing didn't make sense. Mitochondria are most active after insulin secretion has already begun, not before. Plus, mitochondria would stall out before exhausting enough ADP to trigger insulin secretion.

A clue to solving these apparent paradoxes came from studies in the 1980s on heart muscle cells. At the time, scientists found that the enzyme pyruvate kinase -- which converts sugar into energy, independently of mitochondria -- could also severely deplete ADP. This process happens near ADP-sensing proteins involved in insulin release in the pancreas. Maybe, Merrins' team thought, the pancreas took advantage of this proximity to fine-tune the release of insulin.

In initial experiments, the researchers supplied sugar and ADP to sections of pancreatic cells containing pyruvate kinase. The enzyme gobbled up both components, depleting ADP. Because pyruvate kinase was located near the ADP-sensing protein that triggers insulin secretion, it had a big effect.

"That's one of the important concepts in our paper: the location of metabolism is critical to its function," says Merrins.

Using mouse and human pancreatic islets, the clusters of cells that release insulin, the researchers tried stimulating pyruvate kinase activity. Drugs that activate the enzyme quadrupled the release of insulin, but only when there was enough sugar around -- a sign that pyruvate kinase can't be forced to release too much insulin.

"Pyruvate kinase doesn't change how much fuel comes into the cell, it just changes how that fuel is used," says Merrins. "Drugs that active pyruvate kinase strongly boost insulin secretion without causing too much insulin release that can lead to hypoglycemia."

In all, they discovered evidence of a more complex way in which pancreatic beta cells decide when and how much insulin to release, akin to a two-cycle engine. In the first cycle, blood sugar gets processed by pyruvate kinase, depleting ADP. Mitochondria keep the process going by feeding pyruvate kinase even more material, which causes ADP levels to crash, ultimately stimulating enough calcium entry into the cell to release insulin.

In the second cycle, mitochondria switch from feeding pyruvate kinase with material to producing the high-energy molecule ATP, which is needed to fully release insulin. Then the process resets.

In the companion study, led by Merrins' colleagues at Yale University, the researchers examined how pyruvate kinase activators affected metabolism in healthy and obese rats. In a series of experiments, they found that activating pyruvate kinase increased both insulin secretion and insulin sensitivity while improving sugar metabolism in liver and red blood cells. Such treatments could be helpful for people with Type 2 diabetes, who don't produce enough insulin and have dysfunctional sugar metabolism as a result.

"The therapeutic idea here is we could rewire metabolism to more efficiently trigger insulin secretion while improving the function of other organs at the same time," says Merrins.

Little is understood about how cilia, the tiny hairlike organelles that in humans are often the first lines of defense against pathogens in our lungs and respiratory tracks and even help push sperm along, move in coordination. New research from USC scholars identifies the mechanisms in play for cilia to work effectively and productively to push particles and fluid along, which is especially important given their critical role in health and in even ensuring reproduction.

Given the difficulty of accessing cilia in locations such as the lung, brain, and reproductive tract, researchers often study aquatic microorganisms to get insight into cilia motion because the structure of cilia is conserved across species. In a healthy body, motile cilia coordinate with each other to achieve specific modes of motion, so they can direct fluid flows in a certain direction (without coordinated movement of cilia in the lung for example, lung tissues risk buildup of bacteria and viruses). USC researchers performed computational experiments to better understand how cilia transition between different modes of coordination such as rowing together in the same direction versus moving in different directions. The researchers found that these changes in movement direction occur in one of two ways: changing the level of in sync activity between cilia or shifting the activity level of the cilia. Results were published in Physical Letters Review.

This is critical, says Eva Kanso, the Zohrab A. Kaprielian Fellow in Engineering and professor of Aerospace and Mechanical Engineering, because cilia, in mammalian tissue, are in places like the upper respiratory tracts, where they form the first line of defense against environmental particles, viruses and bacteria--thus making understanding how they work all the more important. Cilia can force mucus to be pushed from the lungs or help sperm move along the reproductive tract to meet with an egg.

"When cilia are not coordinated, each is moving in a different direction. Their purpose is to push fluids and if every cilium is working against every other cilium, they won't be able to achieve this in a consistent, coherent manner," Kanso said.

But beyond coordination, Kanso said, the next biggest consideration is how cilia transition from one coordinated mode of motion to the next. "The fate of the cell is dependent on these transitions."

The environment could also play a role. In the lungs, a shift in the environment--perhaps the result of diseased tissue--could trigger a shift in the activity level of the cilia. As a result, the cilia may be less coordinated and this transition to an uncoordinated state could be detrimental to the health of the lung. Without appropriate motion sweeping harmful bacteria and particles out of the lung, it may build up within the lung. In turn, this could change the cilia's environment, causing a feedback loop that continues to suppress normal cilia function, Kanso said.

Kanso said that the study also suggests that the level of coupling between cilia can change transitional behavior--and this could change the progression of certain diseases, for example lung disease. Given this, her team is hoping to translate the tools and techniques they acquire from a broader study of ciliary beds to a collaboration with Dr. Amy Ryan, assistant professor, and Dr. Janna Nawroth, senior research scientist, both at the Keck School of Medicine at USC.

The study Kanso and post-doctoral scholar Yi Man, conducted focused on the interaction of a pair of cilia. In the future, they hope to look at a whole ciliary bed, with the hopes of further understanding not only how cilia function, but also the greater implications for how their coordination reflects on the health of an organism.

"The long-term vision is that maybe there will be some way to not just look at individual cilia but grow ciliated tissue--for instance based on a swab of human cells--and to look at its coordination. How well the cells coordinate could be used as a diagnostic tool to better understand how far a disease has progressed and what a patient's prognosis is," Kanso said.

Current research and applications in the field of artificial intelligence (AI) include several key challenges. These include: (a) A priori estimation of the required dataset size to achieve a desired test accuracy. For example, how many handwritten digits does a machine have to learn before being able to predict a new one with a success rate of 99%? Similarly, how many specific types of circumstances does an autonomous vehicle have to learn before its reaction will not lead to an accident? (b) The achievement of reliable decision-making under a limited number of examples, where each example can be trained only once, i.e., observed only for a short period. This type of realization of fast on-line decision making is representative of many aspects of human activity, robotic control and network optimization.

In an article published today in the journal Scientific Reports, researchers show how these two challenges are solved by adopting a physical concept that was introduced a century ago to describe the formation of a magnet during a process of iron bulk cooling.

Using a careful optimization procedure and exhaustive simulations, a group of scientists from Bar-Ilan University has demonstrated the usefulness of the physical concept of power-law scaling to deep learning. This central concept in physics, which arises from diverse phenomena, including the timing and magnitude of earthquakes, Internet topology and social networks, stock price fluctuations, word frequencies in linguistics, and signal amplitudes in brain activity, has also been found to be applicable in the ever-growing field of AI, and especially deep learning.

"Test errors with online learning, where each example is trained only once, are in close agreement with state-of-the-art algorithms consisting of a very large number of epochs, where each example is trained many times. This result has an important implication on rapid decision making such as robotic control," said Prof. Ido Kanter, of Bar-Ilan's Department of Physics and Gonda (Goldshmied) Multidisciplinary Brain Research Center, who led the research. "The power-law scaling, governing different dynamical rules and network architectures, enables the classification and hierarchy creation among the different examined classification or decision problems," he added.

"One of the important ingredients of the advanced deep learning algorithm is the recent new bridge between experimental neuroscience and advanced artificial intelligence learning algorithms," said PhD student Shira Sardi, a co-author of the study. Our new type of experiments on neuronal cultures indicate that an increase in the training frequency enables us to significantly accelerate the neuronal adaptation process. "This accelerated brain-inspired mechanism enables building advanced deep learning algorithms which outperform existing ones," said PhD student Yuval Meir, another co-author.

The reconstructed bridge from physics and experimental neuroscience to machine learning is expected to advance artificial intelligence and especially ultrafast decision making under limited training examples as to contribute to the formation of a theoretical framework of the field of deep learning.

People of Black ethnicity are twice as likely to be infected with COVID-19 compared to those of White ethnicity, according to researchers at the Universities of Leicester and Nottingham, supported by the National Institute for Health Research (NIHR) Leicester Biomedical Research Centre. The findings are published in EClinical Medicine by The Lancet today (Thursday 12 November 2020).

People from Asian backgrounds are also 1.5 times more likely to become infected with the virus compared to White individuals.

In the first meta-analysis of the effect of ethnicity on clinical outcomes in patients with COVID-19, which screened over 1500 articles, the research team pooled data from more than 18 million people who had taken part in 50 studies in the United Kingdom and United States of America. All the studies included in the analysis were published between 1 December 2019 and 31 August 2020 in peer-reviewed journals or as pre-prints waiting for peer-review.

All the patients included in the study who had COVID-19 were defined as such by a positive nasal swab test or clinical signs and symptoms of the virus, along with radiology and laboratory tests.

Researchers also found those of Asian ethnicities to be at higher risk of admission to an intensive therapy unit (ITU) and death. However, all studies investigating ITU admission that were included in the meta-analysis had not yet been peer-reviewed, and the risk of death was only of borderline statistical significance. This is in contrast to the strong evidence of increased risk of infection in Black and Asian ethnic groups.

Dr Manish Pareek, Associate Clinical Professor in Infectious Diseases at the University of Leicester, Consultant in Infectious Diseases at the University Hospitals of Leicester NHS Trust and a senior author on the paper, said: "Our findings suggest that the disproportionate impact of COVID-19 on Black and Asian communities is mainly attributable to increased risk of infection in these communities.

"Many explanations exist as to why there may be an elevated level of COVID-19 infection in ethnic minority groups, including the greater likelihood of living in larger household sizes comprised of multiple generations; having lower socioeconomic status, which may increase the likelihood of living in overcrowded households; and being employed in frontline roles where working from home is not an option."

Dr Shirley Sze, NIHR Academic Clinical Lecturer and Specialist Registrar in Cardiology at the University of Leicester, and a lead author of the paper, said: "The clear evidence of increased risk of infection amongst ethnic minority groups is of urgent public health importance - we must work to minimise exposure to the virus in these at-risk groups by facilitating their timely access to healthcare resources and target the social and structural disparities that contribute to health inequalities."

Dr Daniel Pan, Specialist Registrar in Infectious Diseases at the University Hospitals of Leicester NHS Trust and an NIHR Clinical Academic Fellow at the University of Leicester is a lead author of the paper. He said: "Future papers must try to adjust for the risk of infection when looking at the risk of ITU admission and death in COVID-19 patients, in order for us to accurately assess the impact of ethnicity on an individual's risk of death once they are infected".

After six years of research, a team of scientists at the University of California, Santa Cruz has developed a cost-effective new aquaculture feed that eliminates conventional fish meal and fish oil ingredients while also providing better fish weight gain and higher nutritional value in the filet for humans. The new fish-free feed is the first to demonstrate across-the-board gains in sustainability, performance, economic viability, and human health.

"This is a potential game-changer for shifting aquaculture to more sustainable practices," said Pallab Sarker, lead author of a Scientific Reports article on this research published Nov. 12.

Sarker, an associate research professor in environmental studies, works alongside Professor Anne Kapuscinski to co-lead an ecological aquaculture research facility at the UCSC Farm. Their lab focuses on integrating circular economy concepts into aquatic food systems, particularly as a means of breaking aquaculture's reliance on wild-caught forage fish for feed ingredients.

Sarker and Kapuscinski developed their new feed by replacing fish oil with whole cells from a marine microalga called Schizochytrium sp. and swapping out fish meal for leftover biomass from oil-extracted marine Nannochloropsis oculata microalga, a protein-rich waste product from commercial omega-3 dietary supplement production.

The new fish-free feed formula was then tested against a conventional feed and a few other blends in an experiment where 480 Nile tilapia were cultivated for six months. By the end of the trial, tilapia on the fish-free diet showed 58 percent higher weight gain percentages, compared to those on conventional feed. Tilapia on the fish-free diet also had the highest amount of heart-healthy DHA omega-3 fatty acids in their filets, which is a key improvement over other feed formulations currently available on the market.

"You can develop fish-free feed using soy and corn and other ingredients, but the problem is, you compromise the fatty acid profile of the filet," Sarker explained. "Terrestrial vegetable oils lack long-chain omega-3 fatty acids, but from the combination of these microalgae, we found a higher amount of deposition from DHA into tilapia filets, which is good for human health."

Feed produced using agricultural crops can also have an imbalance of limiting amino acids and lower palatability and digestibility, resulting in reduced fish health. But another improvement the new microalgae-based formula offers over crop-derived ingredients is that it reduces the myriad sustainability issues associated with producing agricultural products for animal feed, rather than direct human consumption. And the team's research shows promising results for the potential cost-competitiveness of their new formula, too.

Despite some of the ingredients in the fish-free feed being slightly more expensive compared to conventional feed, the tilapia on the fish-free diet grew so efficiently that the production cost per kilogram of tilapia was actually lower for the new formula.

That outcome, in particular, is likely to pique interest across the aquaculture industry, since tilapia is one of the most popular farmed fish in the world. The insights from this successful feed formula may have applications for other species, too. Sarker and Kapuscinski now hope to leverage what they've learned to develop fish-free aquaculture feed for rainbow trout.

If successful, those efforts would be another major milestone, since salmonids are highly valued in aquaculture and consume enormous quantities of fish meal and fish oil. Aquaculture will need to continue expanding to support the protein demands of a growing human population, but through continued research, UC Santa Cruz scientists see an opportunity to help shape a more sustainable future in that process.

"Aquaculture is the fastest growing food sector in the world, but it's still a young industry compared to agriculture," Sarker said. "We have an opportunity to not make the same mistakes. This research could be a key leverage point for reforming aquaculture to ensure sustainable growth in ways that don't damage terrestrial or aquatic ecosystems."

Scientists at Sanford Burnham Prebys Medical Discovery Institute, University of California San Diego School of Medicine and Hopp Children's Cancer Center Heidelberg (KiTZ) have demonstrated that personalized drug screens can be used to identify new therapeutic candidates for medulloblastoma, the most common malignant brain cancer in children. The approach measures the effectiveness of therapeutics using tumor cells obtained from a biopsy and can be performed in a few days--making it one of the quickest sources of information used in clinical decision-making. Based on this proof-of-concept study, which was published in Cancer Research, a clinical trial using the approach is now planned.

"Our findings show that personalized drug screens can help us move away from a one-size-fits-all approach to treating medulloblastoma patients," says Robert Wechsler-Reya, Ph.D., corresponding author of the study, professor and director of the Tumor Initiation and Maintenance Program at Sanford Burnham Prebys, and program director of the Joseph Clayes III Research Center for Neuro-Oncology and Genomics at the Rady Children's Institute for Genomic Medicine. "We have shown that we can identify therapies that cannot be predicted using other methods, and that the results can be used in clinical decision-making to improve outcomes for patients. For children diagnosed with medulloblastoma and their parents, better treatments can't arrive fast enough."

Efforts to find personalized treatments for medulloblastoma, which comprises four distinct subgroups--WNT, Sonic hedgehog (SHH), Group 3 and Group 4--have not been successful to date. Most patients still receive the same treatments--brain surgery to remove the tumor followed by radiation and chemotherapy--in spite of the different molecular characteristics of the tumors. As a result, one-third of children succumb to the cancer; and the children who do survive often have severe, lifelong side effects from the treatment, including cognitive impairment and a greater likelihood of developing cancer again.

"Precision medicine has revolutionized the treatment of certain cancers. Now, we hope that personalized drug screens will expand these benefits to children with brain cancer," says John Crawford, M.D., a co-author of the study and director of the Neuro-Oncology Program at Rady Children's Hospital-San Diego. "Personalized drug screens allow us to tailor therapy to each patient's tumor, potentially saving the lives of more children and protecting others from the devastating long-term side effects of receiving chemotherapy and radiation at such a young age."

Expanding the "medicine cabinet" for medulloblastoma

In the study, the scientists initially screened medulloblastoma tumors from patient-derived xenografts (PDX), models created by transplanting a patient's brain tumor into mice, against a drug library containing nearly 5,000 compounds. The screen identified several drugs that halted the growth of cells from Group 3 medulloblastoma, the deadliest form of the disease; and one of these drugs, actinomycin D, extended the survival of mice harboring the corresponding PDX model.

"We are very excited that this screen revealed a drug that may be effective against Group 3 medulloblastoma, which is the most aggressive subtype," says Jessica Rusert, Ph.D., lead author of the study and postdoctoral researcher in the Wechsler-Reya lab. "Actinomycin D has been used since the 1950s to treat other pediatric cancers, which means we have extensive information about its safety in children, and thus it could be moved relatively quickly into human testing."

Actinomycin D also appeared to work better than some of the standard-of-care chemotherapies, offering a glimmer of hope that it might be able to replace the harsh treatment regimen that leaves some children with serious long-term side effects.

A leap from lab to clinic

To confirm that this approach could be used in the real world, the scientists completed a "test run" using a brain tumor removed from an 8-year-old boy newly diagnosed with metastatic medulloblastoma. A personalized drug screen identified several drugs that may work for his tumor type, and the results were reviewed by a molecular tumor board--a panel of physicians and scientists who work together to discuss treatment options. Although per protocol, the child continued with standard-of-care treatment, the results showed that a personalized treatment plan could have been created in time to guide care decisions.

"We want to move toward a future where a doctor will say, 'You have medulloblastoma; now here is your specific treatment plan,'" says Wechsler-Reya. "Our study suggests that it can be done. Now we need to demonstrate that the method works in a clinical setting."

PULLMAN, Wash. - A team of researchers for the first time has found a correlation between the levels of bacteria and fungi in the gastrointestinal tract of children and the amount of common chemicals found in their home environment.

The work, published this month in Environmental Science and Technology Letters, could lead to better understanding of how these semi-volatile organic compounds may affect human health.

Courtney Gardner, assistant professor in the Washington State University Department of Civil and Environmental Engineering, is lead author on the paper, which she completed as a postdoctoral researcher in collaboration with Duke University.

The gut microbiome, the community of microbes that live in our intestinal tract, has become of increasing interest to researchers in recent years. The microbes in our gut, which include a large variety of bacteria and fungi, are thought to affect many processes, from nutrient absorption to our immunity, and an unhealthy microbiome has been implicated in diseases ranging from obesity to asthma and dementia.

In the study, the researchers measured levels of ubiquitous semi-organic compounds in the blood and urine of 69 toddlers and preschoolers and then, using fecal samples, studied the children's gut microbiomes. The semi-volatile organic compounds they measured included phthalates that are used in detergents, plastic clothing such as raincoats, shower curtains, and personal-care products, such as soap, shampoo, and hair spray, as well as per- and polyfluoroalkyl substances (PFASs), which are used in stain- and water-repellent fabrics, coatings for carpets and furniture, nonstick cooking products, polishes, paints, and cleaning products. People are exposed daily to such chemicals in the air and dust in their homes, especially young children who might ingest them by crawling on carpets or frequently putting objects in their mouths.

When the researchers looked at the levels of fungi and bacteria in the gut, they found that children who had higher levels of the chemicals in their bloodstream showed differences in their gut microbiome.

Children with higher levels of PFASs in their blood had a reduction in the amount and diversity of bacteria, while increased levels of phthalates were associated with a reduction in fungi populations.

The correlation between the chemicals and less abundant bacterial organisms was especially pronounced and potentially most concerning, Gardner said.

"These microbes are perhaps not the main drivers and may have more subtle roles in our biology, but it might be the case that one of these microbes does have a unique function and decreasing its levels may have significant health impacts," she said.

The researchers also found, surprisingly, that the children who had high levels of chemical compounds in their blood also had in their gut several types of bacteria that have been used to clean up toxic chemicals. Dehalogenating bacteria have been used for bioremediation to degrade persistent halogenated chemicals like dry cleaning solvents from the environment. These bacteria are not typically found in the human gut.

"Finding the increased levels of these type of bacteria in the gut means that, potentially, the gut microbiome is trying to correct itself," Gardner said.

Gardner hopes to use the information gathered from the study to develop a diagnostic tool for people and perhaps future probiotic interventions to improve health outcomes.

"While these data do not denote causation, they offer an indication of the types of organisms that may be impacted by exposure to these compounds and provide a springboard for future research," she said. "Gaining a more holistic understanding of the interactions between man-made chemicals, the gut microbiome, and human health is a critical step in advancing public health."

Scientists have developed a bilayer passive cooling technology inspired by the way camels stay cool in the hot desert sun. The technology's bottom hydrogel layer acts like a camel's sweat glands, lowering the temperature through evaporating water, whereas the top aerogel layer functions like fur, insulating against outside heat while letting water vapor pass through. The research, published November 11 in the journal Joule, demonstrates that the design keeps products cool five times longer than conventional single-layer approaches.

"While previous passive cooling research focused on mimicking the evaporation from sweat glands in mammals, in this work we identified the crucial role of the fur insulation," says Jeffrey Grossman, head of the Department of Materials Science and Engineering at Massachusetts Institute of Technology and a senior author of the study. "By mimicking the dual fur/gland system in camels, we designed an evaporation-insulation bilayer, which, like for the camel, allows for a significant extension of the passive evaporative cooling time for the same amount of water consumption."

As the climate warms and technology becomes increasingly necessary to keep buildings cool and preserve food and pharmaceuticals, scientists are in hot pursuit of passive cooling methods that do not require external energy sources. Although approaches based on evaporation from hydrogels present one of the most promising passive cooling solutions, they tend to require significant amounts of water and have limited potential for long-term use.

By thinking about these issues in terms of desert-animal physiology, Grossman and colleagues realized that a key component was missing from existing evaporative cooling technologies.

"Zoologists have reported that a shorn camel has to increase the water expenditure for sweating by 50% in the daytime compared to the one with a natural woolly coat," says Grossman. "And so, to minimize water loss while preserving the cooling power of evaporation, and therefore extend the cooling capabilities over longer periods of times, we turned our attention to nature."

To mimic a camel's fur layer, the researchers synthesized highly porous, hydrophobic silica aerogels with about half the thermal conductivity of air, then combined them with sweat gland-mimicking hydrogels. The team then tested a sample of the resulting bilayer in an enclosed chamber with controlled ambient temperature and relative humidity, demonstrating that the sample could maintain a temperature 7 degrees Celsius lower than its surroundings. A cooling technology with only the hydrogel layer could maintain a slightly lower temperature, but the bilayer technology lasted far longer. A 5-millimeter layer of hydrogel covered by a 5-millimeter aerogel maintained its temperature for 200 hours before its moisture was depleted and it needed to be recharged with water, whereas a hydrogel layer alone persisted for only 40 hours.

Because of its ability to keep objects cool for an extended period of time without electricity, the bilayer passive cooling technology could enable distributors to ship, transport, and temporarily store products without air conditioning--a service that would be especially useful in regions of the world where electricity remains scarce.

"This technology could also allow for significant miniaturization of conventional evaporation technologies, as it provides move effective cooling for longer times for any given amount of water provided," says Grossman. "It can also potentially assist thermal management of buildings where the demand for cooling has rapidly increased."

However, the aerogel layer that gives the technology its edge currently limits its ability to be scaled up for widespread use. "While the material cost of our aerogel is low, the manufacture cost is currently the bottleneck for scalability due to a critical-point drying step," says Grossman, noting that one of the coauthors, Elise Strobach, has co-founded a start-up company to pursue scalable production of transparent aerogels for building window applications.

Since the first bird evolved more than 150 million years ago, its descendants have adapted to a vast range of ecological niches, giving rise to tiny, hovering hummingbirds, plunge-diving pelicans and showy birds-of-paradise. Today, more than 10,000 species of birds live on the planet--and now scientists are well on their way to capturing a complete genetic portrait of that diversity.

In the Nov. 11 issue of the journal Nature, scientists from the Smithsonian Institution, the University of Copenhagen, BGI-Shenzen, the University of California, Santa Cruz and approximately 100 other institutions report on the genomes of 363 species of birds, including 267 that have been sequenced for the first time. The studied species--from widespread, economically important birds such as the chicken to the lesser known Henderson crake, which lives only on one small island in the Pacific Ocean--represent more than 92% of the world's avian families. The data from the study will advance research on the evolution of birds and aids in the conservation of threatened bird species.

Together, the data constitute a rich genomic resource that is now freely available to the scientific community. The release of the new genomes is a major milestone for the Bird 10,000 Genomes Project (B10K), an international collaboration organized by researchers at the Smithsonian's National Museum of Natural History, the Kunming Institute of Zoology, the Institute of Zoology in Beijing, the University of Copenhagen, The Rockefeller University, BGI-Shenzen, Curtin University (Perth), the Howard Hughes Medical Institute, Imperial College London and the Natural History Museum of Denmark, which aims to sequence and share the genome of every avian species on the planet.

"B10K is probably the single most important project ever conducted in the study of birds," said Gary Graves, curator of birds at the National Museum of Natural History and one of B10K's seven organizers. "We're not only hoping to learn about the phylogenetic relationships among the major branches of the tree of life of birds, but we're providing an enormous amount of comparative data for the study of the evolution of vertebrates and life itself."

Comparing genomes across bird families will enable B10K researchers and others to explore how particular traits evolved in different birds, as well as to better understand evolution at the molecular level. Ultimately, B10K researchers aim to build a comprehensive avian tree of life that charts the genetic relationships between all modern birds. Such knowledge will not only reveal birds' evolutionary past but will also be vital in guiding conservation efforts in the future.

More than 150 ornithologists, molecular biologists and computer scientists came together to obtain specimens and analyze more than 17 trillion base pairs of DNA for the family-level phase of the B10K project. Sequencing and analysis began in 2011, but the data represent several decades of work by field collectors and collections management staff who have collected and preserved birds from every continent, Graves said.

Approximately 40% of the newly sequenced bird genomes were obtained using tissue samples preserved in the National Museum of Natural History's Avian Genetic Resources Collection, which Graves started in 1986 and has since become part of the museum’s biorepository in support of the its broader Global Genome Initiative. Also contributing to the project were Michael Braun, a research zoologist at the National Museum of Natural History; Rebecca Dikow, who leads the Smithsonian Data Science Lab; and researchers with the Smithsonian's National Zoo and Conservation Biology Institute and the Smithsonian Tropical Research Institute in Panama.

"It might seem that having a genome for each bird family or species is a bit like stamp collecting, but this massive cooperative effort has given us a set of very important genomic resources for conservation," said Rob Fleischer, one of the authors and head of the Smithsonian Conservation Biology Institute's Center for Conservation Genomics. "For example, it provides a ready source of genetic markers useful to map population declines, identify kin and reduce inbreeding when managing rescue populations of endangered species. Having the genomes simplifies the search for genes responsible for important survival traits such as resistance to deadly introduced diseases."

"Through 34 years of field work and dozens of expeditions, we were able to get the stockpile of high-quality DNA that actually makes this project possible," Graves said. "Many of those resources were stored long before DNA sequencing technology had been developed, preserved for future analyses their collectors could not have imagined at the time. It's one of the many reasons why natural history museum collections and museum-based research programs are so important!"

With 363 genomes complete, B10K is expanding its efforts to encompass the next level of avian classification. In this phase, the team will sequence thousands of additional genomes, aiming to represent each of the approximately 2,300 genera of birds.

Three papers published November 11 in Nature present major advances in understanding the evolution of birds and mammals, made possible by new methods for comparing the genomes of hundreds of species.

Comparative genomics uses genomic data to study the evolutionary relationships among species and to identify DNA sequences with essential functions conserved across many species. This approach requires an alignment of the genome sequences so that corresponding positions in different genomes can be compared, but that becomes increasingly difficult as the number of genomes grows.

Researchers at the UC Santa Cruz Genomics Institute developed a powerful new genome alignment method that has made the new studies possible, including the largest genome alignment ever achieved of more than 600 vertebrate genomes. The results provide a detailed view of how species are related to each other at the genetic level.

"We're literally lining up the DNA sequences to see the corresponding positions in each genome, so you can look at individual elements of the genome and see in great detail what has changed and what's stayed the same over evolutionary time," explained Benedict Paten, associate professor of biomolecular engineering at UC Santa Cruz and a corresponding author of two of the new papers.

Identifying DNA sequences that are conserved, remaining unchanged over millions of years of evolution, enables scientists to pinpoint elements of the genome that control important functions across a wide range of species. "It tells you something is important there--it hasn't changed because it can't--and now we can see that with higher resolution than ever before," Paten explained.

The previous generation of alignment tools relied on comparing everything to a single reference genome, resulting in a problem called "reference bias." Paten and coauthor Glenn Hickey originally developed a reference-free alignment program called Cactus, which was state-of-the-art at the time, but worked only on a small scale. UCSC graduate student Joel Armstrong (now at Google) then extended it to create a powerful new program called Progressive Cactus, which can work for hundreds and even thousands of genomes.

"Most previous alignment methods were limited by reference bias, so if human is the reference, they could tell you a lot about the human genome's relationship to the mouse genome, and a lot about the human genome's relationship to the dog genome--but not very much about the mouse genome's relationship to the dog genome," Armstrong explained. "What we've done with Progressive Cactus is work out how to avoid the reference-bias limitation while remaining efficient enough and accurate enough to handle the massive scale of today's genome sequencing projects."

Armstrong is a lead author of all three papers, and first author of the paper that describes Progressive Cactus and presents the results from an alignment of 605 genomes representing hundreds of millions of years of vertebrate evolution. This unprecedented alignment combines two smaller alignments, one for 242 placental mammals and another for 363 birds. The other two papers focus separately on the mammal and bird genome alignments.

This international collaborative effort was coordinated by an organizing group led by coauthors Guojie Zhang at the University of Copenhagen and China National GeneBank, Elinor Karlsson at the Broad Institute of Harvard and MIT, and Paten at UCSC. The genomic data used in these analyses were generated by two broad consortia: the 10,000 Bird Genomes (B10K) project for avian genomes and the Zoonomia project for mammalian genomes.

Scientists have been making plans for years to sequence and analyze the genomes of tens of thousands of animals. Coauthor David Haussler, director of the UCSC Genomics Institute, helped initiate the Genome 10K project in 2009. Related efforts include the Vertebrate Genome Project and the Earth BioGenome Project, and all of these projects are now gathering steam.

"These are very much forward-looking papers, because the methods we've developed will scale to alignments of thousands of genomes," Paten said. "As sequencing technology gets cheaper and faster, people are sequencing hundreds of new species, and this opens up new possibilities for understanding evolutionary relationships and the genetic underpinnings of biology. There is a colossal amount of information in these genomes."