Culture

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 However, all studies investigating ITU admission that were included in the meta-analysis had not yet been peer-reviewed, and the risk of death was only of borderline statistical significance.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."

Bo Li, Kai Kou, Research Fellows of IBS Center for Soft and Living Matter, Walter Kob, Professor of University of Montpellier and Institute Universitaire de France and Steve Granick, Director of the IBS Center for Soft and Living Matter report together in the 7833 issue of the journal Nature that onset of glass transition is a highly non-trivial process involving complex non-linear responses.

As a substance that has been giving remarkable impetus to both the convenience of our daily life and the advance of modern science and technology, glasses puzzle us, however, on the basic science level. "Glasses see much incremental study but rarely a breakthrough, regardless of the endeavors from generations of scientists," commented Granick.

The reported non-monotonic dynamical length scale peaking at the onset temperature subverts the prevalent understanding that cage formation is a simple crossover between liquid and glass. "One central question in glass science is the cage formation process that gives the glassy materials their unique optical and mechanical properties," said Kob, "and we directly hit the problem by locally exciting a colloidal glass using laser beams" said Li.

The emergence of the non-monotonic length scale results from the buildup of domains with cooperative dynamics that become increasingly rigid and start to dominate the particle dynamics. "Just like the painting of Seurat, the mosaic of the dynamical grains," Kob commented with enthusiasm, "and the cage formation is directly related to the merging of them." "The beauty of science here is that we are able to see how glasses germinate from the liquids microscopically," Li said.

The simple physical picture of the enhanced cooperative dynamics for the non-monotonic response suggests the finding should be general. Kob said, "It's amazing that the physical rule behind such rich dynamics is so concise." "And our findings in a well-defined model system will help better understanding other glassy or disordered systems like polymer, granular and atomic glasses, etc." Li remarked.

In addition to the non-monotonic behavior, a scaling relation between the morphology and size of the excitation pattern is extracted based on huge amount of experimental data. "The deviation of this relation reflects the degree of a material's heterogeneity at certain condition" said Li. And Granick remarked, "This scaling law, besides its theoretical importance for physicists, will interest chemists and material scientists as well by offering them a 'ruler' that guides the design and synthesis of glass materials."

Beyond enlightening the first step of glass transition, this proof-of-concept experiment paves the way for the fundamental understanding of glasses eventually. "Using laser as a lancet, a glass sample can be precisely anatomized," said Granick. "More and more exotic yet puzzling behaviors in glasses will be assessed in this way," remarked Kob.

This work is motivated by the long-standing challenges in glass science. The sluggish and highly coupled dynamics always burry the key effect. "If only I can shrink myself, jump into the system and stir the surroundings", once Li conceived, "perhaps laser is a good choice". The femtosecond holographic laser system originally developed by Lou perfectly satisfy the needs of the local excitation. Valuable theoretical support is obtained from Kob for refining the complex experimental observations into concise physical principles. "The highly interdisciplinary environment in our center and successful international collaboration makes a once improbable brainstorm real", commented Granick.

Granick and Kob concluded: "The field of glass science, being classic but constantly challenging, is promoted by this experiments that elucidating the onset of glass transition. The conceptual importance of cage-formation for the properties of glassy materials is revealed. And the micro-rheological approach taken here opens the door to the thorough understanding of the glasses one day."

Scientists can now select individual cells from a population that grows on the surface of a laboratory dish and study their molecular contents. Developed by University of Toronto researchers, the new tool will enable a deeper study of stem cells and other rare cell types for therapy development.

The method is the first to marry cell microscopy with omics platforms to link the cells' physical parameters that are visible by eye, such as appearance, the presence of surface markers or cell-cell contacts, to their molecular makeup.

"We give the user the power to take beautiful fluorescence microscopy images to learn everything that can be learned about cells growing in situ and then connect that information with the cell's genome, transcriptome and proteome," says Aaron Wheeler, a professor of chemistry and biomedical engineering in the Donnelly Centre for Cellular and Biomolecular Research who led the work.

The platform is described in a paper out today in the journal Nature Communications.

Named DISCO, for Digital microfluidic Isolation of Single Cells for -Omics, the method allows researchers to select single cells in their local environment and analyse their contents with the DNA and protein sequencing technologies to read the cell's DNA (genome), the genes' RNA transcripts (transcriptome) and protein molecules (proteome).

The rise of single-cell analyses over the past five years has enabled researchers to measure tens of thousands of molecules in each cell, transforming their ability to study tissues and organs on a granular level. But these approaches miss important information about the cells' physical features and local environment because the cells have to be placed in suspension and separated from each other prior to analysis.

"There's a revolution going on right now with single cell omics," says Wheeler, who is Canada Research Chair in Microfluidic Bioanalysis. "But I came across people who were disappointed that there weren't able to capture phenotypic information about the cell in its in situ environment."

"And I thought we might be able to come up with a way to select particular cells from that population and analyse them," he says.

DISCO is composed of a microscope fitted with a high frequency laser and a microfluidic chip for the collection of cellular material. The microscope allows the user to take detailed images of the target cell before shining the laser on it. The energy from the laser causes a tiny bubble to form and pop in the proximity of the cell, rupturing its membrane and shooting its contents up into a droplet on the microfluidic chip, from where it is retrieved for molecular sequencing.

"Our platform focuses on the metadata that you lose when you do single cell suspension, things like cell position, what were its morphological properties, who were its neighbours? Those are all the things that we can capture before we do the single cell sequencing ," says Erica Scott, a postdoctoral fellow in the lab who spearheaded the work along with two PhD students in the lab, Julian Lamanna and Harrison Edwards.

"To our knowledge, this is the only platform that can take cells in culture and do this kind of thing," she says.

In proof of principle experiments, the researchers demonstrated DISCO's ability to faithfully relate omics data to individual human and mouse brain cancer cells that were cultured side by side.

But the findings also brought into sharp focus the extent to which the contacts between cells can influence their molecular states. The expression of a whopping 5,000 mouse genes--about a fifth of the genome-- was altered in individual mouse cells that had been surrounded by human cells instead of their own kin.

The findings could have important implications for many labs that seek to gain a better understanding of healthy and diseased human tissue, such as tumours, by growing them in mice so that they can be studied in a whole-body environment. If gene expression is similarly affected in the human graft, these changes could have ramification for treatment development, said Wheeler.

Fortunately, DISCO may soon offer a window into the cells in their natural environment as the researchers are working to adapt it to the analysis of tissue slices. Their ultimate goal is to apply DISCO to the study of rare cell types, such as stem cells, whose regenerative potential is in large part regulated by their immediate environment, to help advance new therapies.

Looking for a bird's-eye view of human impact? A new study published in the journal Nature provides the most comprehensive picture yet of how human noise and light pollution affect birds throughout North America, including how these factors may interact with or mask the impacts of climate change.

Recent troubling findings suggest bird populations have declined by more than 30% in the last few decades. To develop effective strategies to reverse this trend, scientists and land managers need to understand what caused the decline.

The effects of noise and light pollution on the health of bird populations had been largely overlooked until some recent studies suggested that these stressors can harm individual species. With this new study, a continent-wide picture has emerged.

"Our study provides the most comprehensive evidence that noise and light can profoundly alter reproduction of birds, even when accounting for other aspects of human activities," said Clint Francis, a biologist at California Polytechnic State University and one of the lead study authors.

Researchers looked at a huge collection of data sets -- including those collected by citizen scientists through the NestWatch Program -- to assess how light and noise affected the reproductive success of 58,506 nests from 142 species across North America. The team considered several factors for each nest, including the time of year breeding occurred and whether at least one chick fledged from the nest.

Birds time their reproduction to coincide with peak food availability to feed their young, using daylight cues to breed about the same time each year. The researchers found that light pollution causes birds to begin nesting up to a month earlier than normal in such open environments as grasslands or wetlands and 18 days earlier in forested environments. The consequence could be a mismatch in timing -- hungry chicks may hatch before their food is readily available. If that happens, these early season nests may be less successful at fledging at least one chick, but the situation is complicated by climate change.

As the planet warms, birds' food is available earlier due to warmer weather. Birds that maintain their historical breeding times because their internal clocks are set to changes in day length may have fewer chicks survive because the food source they rely on already came and went.

"We discovered that the birds that advanced the timing of their reproduction in response to increased light pollution actually have better reproductive success," Francis said. "A likely interpretation of this response is that light pollution actually allows these birds to 'catch up' to the shift towards earlier availability of food due to climate change."

These findings suggest two conclusions about how birds respond to climate change. First, at least temporarily, birds in areas impacted by light pollution may track climate change better than those in in natural habitats that are darker. Second, when scientists thought birds were adjusting their reproductive timing to climate change, birds actually may have been responding instead to the light cues because many studies were done in areas exposed to some light pollution.

When considering noise pollution, results showed that birds living in forested environments tend to be more sensitive to noise than birds in open environments.

Researchers delved into greater detail for 27 species looking for physical traits that could explain the variations in species' responses to light and noise. A bird's ability to see in low light and the pitch of its call were related to species' responses to light and noise pollution, respectively.

The more light a bird's eye is capable of taking in, the more that species moved its breeding time earlier in the year in response to light pollution and the more that species experienced improved nest success as a result of light pollution. Noise pollution delayed nesting for birds' whose songs are at a lower frequency and thus more difficult to hear through low-frequency human noise. Mating decisions are made based on the male's song, and in some cases, females need to hear the male's song to become physically ready to breed.

These trait and environment-specific results have strong implications for managing wildlands.

"We show convincingly across a lot of species that noise and light pollution are having strong effects on wild populations," Francis said. "If there's a proposed development and land managers are worried about a bird that they have no information on, they can use this study to see whether the development is likely to affect the bird. Is it a forest bird? If so, it is likely that it is more sensitive to light and noise."

The study is the first step toward a larger goal of developing a sensitivity index for all North American birds. The index would allow managers and conservationists to cross-reference multiple physical traits for a species to assess how factors such as light and noise pollution would affect it and each species.

EMBARGOED FOR RELEASE UNTIL 11 A.M. ET, WEDNESDAY, NOV. 11, 2020

PITTSBURGH, Nov. 11, 2020 - Researchers from the Pittsburgh Center for Pain Research at the University of Pittsburgh School of Medicine announced today in the journal Neuron that they've uncovered additional complexities behind mechanical allodynia--the sensation of pain from innocuous stimuli, such as light touch.

Different types of injury that cause mechanical allodynia activate distinct spinal circuits that process the information from the skin to the brain, scientists discovered. The finding may explain why pain medications don't alleviate an adverse sensation in all patients. It also suggests that new treatment strategies for pain management need to consider ways in which pain signals are processed in the spinal cord.

"Even though the pain outcome is the same, the neural circuits that conduct the signal are different depending on the kind of injury you have--say, arthritis or nerve trauma," said senior author Rebecca Seal, Ph.D., associate professor in Pitt's Department of Neurobiology. "And if you have different neural pathways depending on the type of injury, that might explain why therapies sometimes don't work."

For patients who experience mechanical allodynia, even the most mundane actions can hurt: Putting on clothes or even tossing in bed can be excruciatingly painful. The condition currently has no cure.

While recent studies identified the critical role of skin receptors for the perception of pain after a light touch, little was known about the way information is transferred from the nerve endings in the skin to the central nervous system where the pain sensation forms.

"People typically think of mechanical allodynia as a condition that is uniform in terms of its underlying neural circuitry in the central nervous system," said Seal. "We now show that is not the case."

Pitt researchers used several pain models to determine if calretinin-expressing (CR) neurons located in the outermost layer of the dorsal horn--one of the three gray columns of the spinal cord--are important to convey mechanical allodynia.

Experiments in mice showed that these neurons are critical for transmitting pain signals induced by inflammatory injuries but not by nerve injury.

Conversely, another subset of neurons of the spinal cord--this time PKC-gamma neurons, which lay adjacent to CR neurons at the border between the second and third layer of the dorsal horn--were responsible for animals feeling neuropathic-induced pain but not pain of inflammatory origin.

Lastly, researchers found that Cholecystokinin (CCK) neurons located deeper within the layers of the dorsal horn are important for both types of injuries.

"Now that we know more about how spinal circuitry of pain is organized, we can use gene therapy to shut it off," said Seal. Her lab currently is working on developing ways to target neurons in the spinal cord using viral gene therapy and chemogenetics in patients experiencing mechanical allodynia.

"A lot of work has been done to understand how sensory neurons transmit pain signals, but we didn't know much about what happens in the spinal cord," she added. "Cracking that black box open in this unique way feels particularly exciting."

In a manuscript published in the same issue of Neuron and co-authored by Seal, Graziana Gatto, Ph.D., and Martyn Goulding, Ph.D., both of The Salk Institute for Biological Sciences in California, use similar experimental approaches to describe the wiring of the motor behavioral responses to acute pain and touch sensation in the spinal cord.

Carbon dioxide fuels photosynthesis, the process by which plants generate their food in the form of carbohydrates. The atmosphere's carbon dioxide levels are rapidly increasing, but there is uncertainty about whether plants can turn these extra resources into higher yields while retaining nutritional quality.

A team from the University of Illinois and Monash University studied how the root crop cassava, which feeds over 1 billion people, will adapt to the amount of carbon dioxide expected by the second half of this century. They grew the crop in an outdoor research facility called SoyFACE that artificially boosts carbon dioxide to understand how increasing levels will impact crops in the coming decades.

This study is the result of a partnership between two international research projects that are supported by the Bill & Melinda Gates Foundation. Cassava Source-Sink is focused on improving the yield of cassava; Realizing Increased Photosynthetic Efficiency (RIPE) is improving photosynthesis to boost crop yields with support from the Gates Foundation, Foundation for Food and Agriculture Research, and U.K. Foreign, Commonwealth & Development Office.

In the Journal of Experimental Botany, they reported significant yield increases ranging from 22 to 39 percent in seven out of eight varieties of cassava. Each cultivar selected for the study is 'farmer preferred' in Africa, where cassava makes up a quarter or more of diets in several countries. Counter to past studies on other crops, they found no decrease in protein quality nor nitrogen content in the leaves, which are consumed by humans and livestock in addition to the starchy tubers.

"We wanted to know how cassava copes with elevated carbon dioxide," said RIPE Deputy Director Donald Ort, Robert Emerson Professor of Crop Sciences and Plant Biology at Illinois' Carl R. Woese Institute for Genomic Biology. "Sometimes, plants cannot make use of extra carbohydrates, which then triggers the plant to down-regulate photosynthesis. We found cassava could maintain photosynthetic efficiency and nutritional quality."

To take in carbon dioxide, plants open tiny pores in their leaves (called stomata) that allow water to exit through transpiration. This study found that when carbon dioxide levels increase from 400 to 600 ppm, cassava leaves could conserve 58 percent more water on average by optimizing stomatal conductance, which is the rate that carbon enters compared to water exiting the leaf.

"Cassava's natural ability to produce high yields with little water is part of what makes this crop a staple in drought-prone regions across sub-Saharan Africa," said co-author Amanda De Souza, a postdoctoral researcher for the RIPE project at Illinois. "It is not surprising to see this trait magnified in C3 crops, but it is encouraging since we predict water scarcity to be a major barrier to food security."

While the team did not find much difference in how well the eight varieties photosynthesized, they discovered differences in their growth and development due to how the plants distributed carbohydrates to their roots, stems, and leaves--which is called partitioning. Cassava plant breeders try to maximize the resources allocated to the roots, referred to as the 'sink' where the plant stores carbon.

"We can capitalize on these differences in partitioning to develop cassava varieties that sink more carbon into their roots to boost yields," said Ursula Ruiz Vera, a postdoctoral researcher for both projects, who led the study at Illinois. "We aim to enhance the natural resilience and productivity of this crop that is uniquely situated to help smallholder farmers withstand pressures from our changing climate."

Researchers can now more accurately and precisely target specific proteins in yeast, mammalian cells and mice to study how knocking down specific protein traits can influence physical manifestation in a cell or organism.

The Japan-based team published their results on November 11th in Nature Communications.

"Conditional gene knockout and small interfering RNA (siRNA), which is used to silence proteins without knocking them out completely, has been employed in many studies," said Masato T. Kanemaki, professor at the National Institute of Genetics in the Research Organization of Information and Systems (ROIS). "However, these technologies are not ideal for studying highly dynamic processes, such as cell cycle, differentiation, or neural activity, because of the slow rate of depletion of the protein of interest."

Kanemaki and his team had previously developed an approach called the AID system, which uses a small protein tag, known as a degron, fused to proteins to induce degradation. To initiate the degradation process, the researchers administered auxin, a plant hormone that helps regulate plant growth. In previous conditional gene knockout and siRNA studies, according to Kanemaki, it typically takes two or three days for a target protein to deplete. The AID system allows for a general, more efficient approach by which the target protein can be depleted in less than a few hours.

"The original AID system has two major drawbacks: leaky degradation and the requirement for a high dose of auxin," Kanemaki said. "These negative features make it difficult to control precisely the expression level of a protein of interest in living cells and apply this method to mice."

The ability to knockout genes in mice is a critical step in genetic research and therapeutics. According to Kanemaki, an approach may work well in cultured cells, but it must work in a whole model system, such as a mouse. The "leaky degradation" of the AID system meant that a targeted protein would only degraded weakly without auxin, but the level of auxin required to induce full degradation appeared to have long-term negative effects on cell growth.

"In this paper, we describe the AID2 system, which overcomes all the drawbacks of the original AID system," Kanemaki said, noting that they did not detect leaky degradation with the system, the degradation was quicker, and the required dose of auxin was much lower.

To establish the AID2 system, the researchers employed what is known as a "bump-and-hole" strategy to create an empty space in a mutant version of a plant protein (called TIR1) that recognizes and induces the degradation of degron-fused proteins. An auxin analog can bind directly to the TIR1 mutant and initiate the degradation process. Since the approach is very efficient, less auxin analog is needed. The researchers found that depletion could be induced at a concentration about 670 times lower than in the original system.

"With the AID 2 system, it is possible to rapidly deplete a protein of interest in cultured cells and mice," Kanemaki said. "Next, we plan to use the system to find something new in chromosome biology, and to apply the AID2 system to other model organisms."

A large international consortium led by scientists at Uppsala University and the Broad Institute of MIT and Harvard has sequenced the genome of 130 mammals and analysed the data together with 110 existing genomes to allow scientist to identify which are the important positions in the DNA. This new information can help both research on disease mutations in humans and how best to preserve endangered species. The study is published in Nature.

When scientists and medical doctors want to understand which mutations give rise to diseases such as cancer, heart disease or schizophrenia, they compare the genomes from many patients and matched control individuals. They often find tens to hundreds of regions that predispose to disease. These regions typically do not overlap genes, but lie outside genes, and each region may contain hundreds of mutations among which it is hard to pinpoint the one predisposing to disease.

During evolution, the majority of positions in the DNA mutate randomly many times. If a position has not changed in 100 million years (since the first mammal), that specific position is very likely to have an important function in the genome. With the help of this concept, evolutionary constraint, it is much easier to find the regulatory elements that govern when, where and how much of a protein is made from a gene.

"The comparison of the genomes from the 240 mammals will help geneticists to identify the mutations that lead to human diseases," says Professor Kerstin Lindblad-Toh of Uppsala University, SciLifeLab and the Broad Institute of MIT and Harvard.

In addition to understanding the human genome, all these genomes together, sampled broadly across mammals, can be used to study how specific species adapt to different environments. For example, some otters have a thick, water-resistant coat, and some mice, but not all, have adapted to hibernation. These animal traits can help us understand human traits such as metabolic diseases.

With climate change and more animal habitats being affected by human activities, it is becoming more and more important to defend endangered species. Traditionally, scientists study many individuals in different populations of a species to understand the genetic diversity that exist in it. This is important for understanding how to protect specific species. In this study, animals on the IUCN (International Union for Conservation of Nature) red list of endangered species had less variation in their genome, which is consistent with their endangered status.

"We hope that our extensive data set, which is available to all scientists in the world, will be used for understanding disease genetics and the protection of biodiversity," says Lindblad-Toh.

In 2030, one in three people in Europe will be over the age of 65, and all of these people will want to enjoy their old age and lead an active lifestyle. To be able to do so, however, it is crucial that people maintain their physical and mental health.

Wanted: simple and inexpensive prevention

Published last year, the VITAL study in the US indicated that vitamin D and omega-3 fatty acids did not lower the risk of developing new cancer or major cardiovascular diseases in men and women aged between 50 and 60. Now, the largest European study on old age, DO-HEALTH, has investigated the effects of these supplements on aging. The EU-funded project is led by Heike A. Bischoff-Ferrari, professor of geriatric medicine and aging research at the University of Zurich, head of clinic at the UniversityHospital Zurich and senior physician at the university clinic for geriatrics at the Waid and Triemli hospitals in Zurich.

The first findings of the three-year clinical trial published by the international team of researchers has found no effects on lower extremity function, memory or bone fracture incidence. However, the study's findings suggest that, compared to the control group, some subgroups experienced increased benefits of vitamin D and omega-3 supplementation when it comes to lowering infection rates and systolic blood pressure.

Largest randomized double-blind study on old age

For their study, the researchers recruited 2,157 relatively healthy men and women aged 70 or older who lived at home and had no significant pre-existing conditions. About half of the participants came from Switzerland, followed by Austria, Germany, France and Portugal.

They were randomized into eight groups and received none, one, two or all three of the following interventions: supplementation of omega-3 fatty acids (1 gram/day), supplementation of vitamin D (2,000 IU/day) and/or a simple home-exercise program. Neither the trial centers nor the participants knew which group they were in. The control groups were given placebos and carried out control exercises focused on joint flexibility.

In each of the study's three years, the seven European trial centers conducted comprehensive full-day visits to observe participants' health and functions, while also carrying out extensive surveys over the phone every three months. The researchers examined, for example, bone and muscle density, blood pressure, memory functions, walking speed as well as important biomarkers. Moreover, they recorded events such as new diseases, infections, falls, visits to the doctor and hospital stays.

Significant positive effects for some subgroups only

"Our findings suggest that supplementation of vitamin D and omega-3s in adults aged 70 or older who lead an active lifestyle and have no pre-existing conditions does not provide any benefits when it comes to bone health, memory and muscle function. However, we believe there is an effect on infections, such as Covid-19," says Bischoff-Ferrari.

Omega-3s reduced the risk of infections by 11% in total, in particular for upper respiratory (10%) and urinary tract infections (62%), while vitamin D lowered systolic blood pressure in men by 2.5 mmHg and the risk of infections in younger participants (70 to 74-year-old) by 16%.

"Given the high safety and low costs of these supplements as well as the high mortality associated with infections in older adults, these findings are very relevant for the health of the general population," says Bischoff-Ferrari. The gender-specific effects of vitamin D on lowering systolic blood pressure also warrant additional research.

Placing findings in the right context

The researchers attribute the lack of effect on bone health, muscle function and memory to the relatively good health of the study's participants, most of whom took regular exercise. Moreover, about half of the participants were so-called healthy agers, with no pre-existing conditions or vitamin D insufficiency. In addition to the supplementation prescribed by the study, they were also allowed to take 800 IUs of vitamin D daily. "The results therefore do not contradict the Federal Office of Public Health's current recommendation on vitamin D supplementation and fall prevention for older people, nor the proven preventive effects of exercise programs," says Bischoff-Ferrari.

Unique database for research on old age

The study team is now expecting the results on the DO-HEALTH interventions when it comes to cancer prevention, cholesterol levels, cardiovascular diseases, falls, frailty and health costs. "Then we'll be able to fully assess the role of supplementation in preventive geriatrics," says Bischoff-Ferrari. Going forward, the comprehensive database and biobank set up for the DO-HEALTH study is also expected to help assess the aging process and health risks for each person early on and individually, with the aim of personalized prevention. "Ultimately, the goal of DO-HEALTH is to enable more people to age in a healthy and active way," says Bischoff-Ferrari.