Culture

At the beginning of the month, 60 percent still restricted themselves in this regard. At the same time, the proportion of people concerned about the impact of the virus on their social relationships fell to 15 percent. "It becomes clear that for many people life is returning more strongly back to the usual pattern of everyday life", says Professor Dr. Dr. Andreas Hensel, president of the German Federal Institute for Risk Assessment.

https://www.bfr.bund.de/cm/349/200915-bfr-corona-monitor-en.pdf

Nevertheless, the majority of people still consider an infection through proximity to other people to be probable. However, a clear difference can be observed between the age groups: While 78 percent of people under the age of 40 consider an infection via this pathway to be probable, this proportion is only 41 percent among those aged 60 and over. One reason for this may be that elderly people often have fewer social contacts and thus encounter considerably fewer people in their everyday lives than younger people.

In contrast, most of the legal regulations on dealing with other people in public still find broad approval, regardless of age. Both the mandatory use of masks and the mandatory distance are considered appropriate by around 90 percent of the respondents - and a similar number of people state that they implement these measures in their everyday lives.

The BfR continually adapts its FAQs on the topic of coronavirus to the current state of science:

https://www.bfr.bund.de/en/can_the_new_type_of_coronavirus_be_transmitted_via_food_and_objects_-244090.html

IIASA researchers have developed a novel measurement framework to track energy poverty that better aligns with the services people lack rather than capturing the mere absence of physical connections to a source of electricity. This alternative framework can aid better tracking of Sustainable Development Goal (SDG) 7 by virtue of its simplicity and sensitivity to the diversity in service conditions among the poor.

Despite significant efforts and progress made across the developing world to provide households with electricity, close to 800 million people, mainly in sub-Saharan Africa, still have no access to electricity services. According to a new study published in the journal Progress in Energy, accurately measuring energy poverty requires distinguishing poor electricity supply conditions from service deprivations within the home. For instance, availability of power is a condition related to electricity supply, whereas whether a person enjoys a comfortable temperature level in their home depends on their ability to afford cooling equipment and its running costs. Tracking energy poverty in this way can help direct policy efforts towards energy suppliers and households, and thereby accelerate efforts to achieve the targets of SDG7: Ensuring universal access to affordable, reliable, sustainable, and modern energy for all.

Currently, two indicators are recommended to track Target 7.1 - Indicator 7.1.1: Proportion of population with access to electricity, and Indicator 7.1.2: Proportion of population with primary reliance on clean fuels and technology. These binary indicators, while easy to communicate and quantify, mask several service shortcomings among those that have connections to electricity, which underestimates the challenge of eradicating energy poverty.

"Our main objective in this research was to try to design a better but simple framework for measuring energy poverty, and apply this to actual data from Ethiopia, India, and Rwanda to test how well it captures energy poverty in comparison to other multidimensional frameworks, such as the World Bank's Multi-Tier Framework (MTF)," explains Shonali Pachauri, acting director of the IIASA Transitions to New Technologies Program and a senior researcher in the Energy Program.

According to the authors, the World Bank MTF - while being a significant improvement over binary indicators - is overly complicated, and conflates electricity supply characteristics with household service conditions. The alternative framework the authors propose prunes the dimensions of energy poverty measures to those specified in the SDG 7 target and defines thresholds to mark fewer tiers. It also distinguishes electricity supply indicators from those that relate to household poverty. For instance, the authors propose to use appliance ownership as an indicator of households' access to energy services rather than electricity consumption, which could be misleading if caused by poor energy efficiency. The affordability indicator is also expanded to include appliance purchase costs in addition to the recurrent electricity costs. When applied to real data, the new framework suggests that affordability is even more of a constraint to gaining access to modern electric services for households in Ethiopia, India, and Rwanda.

"Making the normative foundations of measurement frameworks more explicit make it easier to communicate what they capture. Such frameworks also need to strike a balance between accuracy of measurement with simplification and conceptual clarity for application on a global scale. Further refinements of the alternative framework we propose, through applications to other nations, can help improve how we identify the most vulnerable and design and target policies to improve energy access for all," concludes Narasimha Rao a senior researcher in the IIASA Energy Program and a faculty member at the Yale School of the Environment.

The traditional rice-based diet of some east-Asian population has brought to a number of genomic adaptations that may contribute to mitigating the spread of diabetes and obesity. An international study led by the University of Bologna and published in the journal Evolutionary Applications has recently suggested this interesting hypothesis. Researchers analysed and compared the genomes of more than 2,000 subjects from 124 south-east-Asian populations.

"We suggest that it may be possible that some east-Asian populations, whose ancestors started eating rice on a daily basis at least 10,000 years ago, have evolved genomic adaptations that mitigate the harmful effects of high-glycaemic diets on metabolism", confirms Marco Sazzini, study coordinator and professor at the Department of Biology, Geology and Environmental Sciences of the University of Bologna. "Furthermore, these adaptations plausibly continue to play a pivotal role in protecting them from the negative effects that derive from major dietary alterations brought about by the globalisation and westernization of their lifestyles. These alterations dramatically increased their consumption of food rich in processed sugar and with a high glycaemic index".

RICE AND GLYCAEMIC INDEX

Among the so-called domesticated cereals, rice presents a high glycaemic index and is rich in carbohydrates. This means that once ingested and digested, it causes sugar in the blood to increase. If eaten regularly and in large quantities, rice may represent a potential risk factor for developing insulin resistance and related metabolic diseases such as type 2 diabetes.

However, if we compare east-Asian people having used rice as a staple food for over 10,000 years with those in the Indian sub-continent, we soon find out that the latter show higher rates of diabetes and obesity than east-Asians. Why are these two groups different?

A 10,000-YEAR-OLD DIET

Archaeology may provide a hint to answering that question. Archaeobotanical findings in some eastern regions of Asia show that wild rice had been part of the inhabitants' diets in the past starting 12,000 years ago. After rice domestication and the introduction of rice farming techniques, between 7,000 and 6,000 years ago, rice spread rapidly across Korea and Japan. In northern regions of the Indian sub-continent, an independent domestication process had started 4,000 years ago and brought to the selection of rice varieties presenting a lower glycaemic index if compared to east-Asian rice.

"Different rice varieties and a head start of millennia may have put populations in China, Korea, and Japan under a more pressing metabolic stress than that experienced by south Asian populations", explains Arianna Landini, first author of this study and a PhD student at the University of Edinburgh. "This might have allowed them to evolve genomic adaptations that mitigate the risk of becoming ill with metabolic diseases linked with a high-sugar diet".

RICE AND GENOMIC ADAPTATIONS

To test such a hypothesis, researchers analysed the genome of more than 2,000 subjects from 124 east-Asian and south-Asian populations. Then, they compared the adaptive evolution observed in Chinese Han and Tujia ethnic groups, as well as in people of Korean and Japanese ancestry (with a long-standing tradition of rice-based diets) with that of people from regions of Pakistan, Bangladesh, Myanmar, Vietnam, and south-east Asia. Southeast Asian subjects were used as control groups because their adoption of cereal-based diets occurred many thousand years later.

"The genomic adaptations observed in control groups differ greatly from those of east Asian populations and are not related to metabolic stress due to a specific diet", says Claudia Ojeda-Granados, one of the authors and a research fellow at the University of Bologna. "Chinese Han and Tujia ethnic groups, as well as people of Korean and Japanese ancestry show instead similar metabolic genomic adaptations".

Some of the genetic modifications the researchers identified are associated with a lower BMI and a weaker risk of cardiovascular diseases thanks to a reduced conversion of carbohydrates into cholesterol and fatty acids. Some other adaptations favour a reduced insulin resistance as they negatively modulate the glucogenesis in the liver. Finally, some others stimulate the production of retinoic acid, which is a metabolite of vitamin A. Deficiency in this nutritional organic compound often causes health-issues in people eating a rice-based diet.

"Our results demonstrate once again how studying evolutionary history may successfully inform biomedical research, eventually leading to the identification of the mechanisms underlying the different susceptibility of human populations to different diseases", concludes Sazzini.

When veterinarian Cynthia Otto was in Manhattan in the wake of the 9/11 attacks helping support the search and rescue dogs, she heard rumors about the possible impact on the dogs' long-term health.

"I was at Ground Zero and I would hear people make comments like, 'Did you hear that half of the dogs that responded to the bombing in Oklahoma City died of X, Y, or Z?' Or they'd say dogs responding to 9/11 had died," she recalls. "It was really disconcerting."

It also underscored to her the importance of collecting rigorous data on the health of dogs deployed to disaster sites. An initiative that launched in the weeks after the Sept. 11, 2001, terrorist attacks did just that, and this week, 19 years later, Otto and colleagues' findings offer reassurance. Dogs that participated in search-and-rescue efforts following 9/11 lived a similar length of time, on average, compared to a control group of search-and-rescue dogs and outlived their breed-average life spans. There was also no discernable difference in the dogs' cause of death.

"Honestly this was not what we expected; it's surprising and wonderful," says Otto, director of the School of Veterinary Medicine's Working Dog Center, who shared the findings in the Journal of the American Veterinary Medical Association.

While postmortem results showed that dogs that deployed after the 9/11 attacks had more particulate material in their lungs upon their death, it seems this exposure didn't cause serious problems for the animals in life. The most common cause of death were age-related conditions, such as arthritis and cancer, similar to the control group.

During and in the immediate aftermath of the 9/11 response, Otto and colleagues reached out to handlers to recruit search-and-rescue dogs into a longitudinal study that would track their health, longevity, and cause of death. They recruited 95 dogs that had worked at the World Trade Center, Fresh Kills Landfill, or Pentagon disaster sites. As a control group, they also included in the study 55 search-and-rescue dogs that had not deployed to 9/11.

As part of being involved, the dogs received annual medical examinations, including chest X-rays and bloodwork. When the dogs died, the researchers paid for the handlers to have veterinarians collect samples of various organ tissues and send them for analysis at Michigan State University. Forty-four of the 9/11 dogs and 19 of the control group dogs underwent postmortems. For most of the other dogs in the study, the research team obtained information on cause of death from medical records or the handlers themselves.

While the team had expected to see respiratory problems in the exposed dogs--conditions that have been reported by human first responders to 9/11--they did not.

"We anticipated that the dogs would be the canary in the coal mine for the human first responders since dogs age faster than humans and didn't have any of the protective equipment during the response," Otto says. "But we didn't see a lot that was concerning."

In fact, the median age at death for 9/11 dogs was about the same as the control group: 12.8 compared to 12.7 years. The most common cause of death for the dogs that deployed was degenerative causes--typically euthanasia due to severe arthritis--followed closely by cancer, though the risk of cancer was about the same as in control group dogs.

Otto and her colleagues have ideas for why the foreign particulate matter found in some of the dog's lungs did not translate to ill health, though they emphasize that they're speculations, not yet based in data.

"For the pulmonary effects, it's somewhat easier to explain because dogs have a really good filtering system," Otto says. "Their lungs are different--they don't get asthma, for example--so it seems like there is something about their lungs that's more tolerant than in humans."

She notes that working dogs tend to be extremely physically fit compared to pet dogs, perhaps counteracting any ill effects of the deployment conditions on health. But working dog handlers and trainers can always do more to focus on fitness and conditioning, especially because doing so could slow the progression of arthritis, a disease which played a role in the death of many dogs in the study.

"We know when people stop moving, they gain weight and that puts them at a higher risk of arthritis, and arthritis makes it painful to move, so it's a vicious cycle," she says. "The same can be true of dogs."

The mind-body connection may also help explain the difference between humans and dogs and the longevity of the working dogs, Otto says, as dogs don't necessary worry and experience the same type of stress in the wake of a disaster.

"These dogs have an incredible relationship with their partners," Otto says. "They have a purpose and a job and the mental stimulation of training. My guess is that makes a difference, too."

ANN ARBOR, Mich. - A new paper suggests three solutions to addressing the backlog of non-urgent surgeries delayed due to the COVID-19 pandemic.

"As a surgeon, I understand why hospitals needed to delay many elective surgeries to ensure there was enough space and health care workers available to take care of the sickest patients with COVID-19," says Jessica Billig, M.D., a resident physician of plastic surgery at Michigan Medicine and lead author of the paper published in Annals of Surgery. "But we know that continuing to delay these surgeries could result in poor health outcomes for our patients. Which makes us ask, how can we start to work through the backlog of surgeries efficiently and swiftly?"

Billig and her co-author, Erika Sears, M.D., an assistant professor of plastic surgery at Michigan Medicine, provide three strategies to address the need for surgical care:

1. Continue to grow telemedicine. The pair notes that broadly adopting the way telehealth appointments were implemented for postoperative care in the past, and expanding it to some initial surgical consultations, could continue to grow the service and make medical appointments easier on the patient.

2. Expand operating room schedules and ambulatory surgery center capacity. They suggest operating outside of normal working hours, accommodating more outpatient surgical patients at ambulatory surgery center sites and performing minor procedures in the clinic setting to free up operating room space for more complex procedures.

3. Be transparent with patients about surgical billing. Billig and Sears note that many patients are experiencing unemployment and monetary strains due to the pandemic. They encourage surgeons, practices and health care systems to provide patients with access to transparent pricing. Surgeons should also consider location when they are performing a procedure. For example, if it was performed in a clinic, could it result in less out-of-pocket expenses for the patient?

"It should be noted, that if many of these surgeries continue to be put off, many of these health conditions will continue to progress and could cause the patient to become sicker," Billig says. "We hope these strategies offer our colleagues across the country some thoughts to consider so we can accommodate the patients that need our surgical care."

Oak Brook, IL - The October edition of SLAS Discovery features the cover article, "A Critical and Concise Review of Mass Spectrometry Applied to Imaging in Drug Discovery" by Richard J. A. Goodwin Ph.D. (AstraZeneca), Zoltan Takats Ph.D. (Imperial College London), and Josephine Bunch, Ph.D. (National Physical Laboratory).

Mass spectrometry imaging (MSI) has increasingly become a versatile methodology to support pharmaceutical research and development over the past decade. MSI efficiently provides data on drug delivery throughout the human body while simultaneously mapping endogenous metabolites, lipids and proteins on a molecular level, allowing researchers to make both pharmacokinetic and pharmacodynamic measurements at cellular resolution in tissue. The increasing development costs of new and emerging therapeutic modalities and the associated risks of late-stage program attrition are unique challenges associated with MSI, along with the increasing number of complex and challenging bioanalytical questions within drug discovery. The cover article by Goodwin, Takats and Bunch provides an updated concise review of the use of MSI for drug discovery, while critically considering what is required to immerse MSI into the greater pharmaceutical research and development industry. In addition to the cover article and 10 original research articles, the October issue features a technical brief entitled, "In Silico Selection of Gp120 ssDNA Aptamer to HIV-1."

Articles of Original Research include:

Direct Comparison of Label-Free Biosensor Binding Kinetics Obtained on the Biacore 8K and the Carterra LSA

A High-Throughput Cellular Screening Assay for Small-Molecule Inhibitors and Activators of Cytoplasmic Dynein-1-Based Cargo Transport

Z' Does Not Need to Be > 0.5

Controlling the Reproducibility of AC50 Estimation during Compound Profiling through Bayesian β-Expectation Tolerance Intervals

High-Throughput Fluorescence-Based Activity Assay for Arginase-1

Identification of Novel Carbonic Anhydrase IX Inhibitors Using High-Throughput Screening of Pooled Compound Libraries by DNA-Linked Inhibitor Antibody Assay (DIANA)

A Robust and Cost-Effective Luminescent-Based High-Throughput Assay for Fructose-1,6-Bisphosphate Aldolase A

A Pilot Screen of a Novel Peptide Hormone Library Identified Candidate GPR83 Ligands

Development of a High-Throughput Screening Assay to Identify Inhibitors of the Major M17-Leucyl Aminopeptidase from Trypanosoma cruzi Using RapidFire Mass Spectrometry

Two Forms of Tyrosyl-tRNA Synthetase from Pseudomonas aeruginosa: Characterization and Discovery of Inhibitory Compounds

For decades, scientists have urged policymakers to take prompt action to address climate change, but their calls have largely gone unanswered. Now, as wildfires ravage the west and hurricanes batter the Atlantic and Gulf coasts with greater intensity, a new study involving Washington University in St. Louis researchers finds consumers across the United States and in some European countries are ready to start paying for it now.

One reason why governments have been slow to react is because of the cost-participation dilemma. In order to be effective, a climate policy must raise the price of carbon and include most countries in the world, explained Michael Bechtel, associate professor of political science in Arts & Sciences. But that's a challenge because participation is voluntary, and raising energy costs -- no matter how necessary -- is never popular.

As policymakers debate the best way to fund climate action, Bechtel -- along with Kenneth Scheve at Yale University and Elisabeth van Lieshout at Stanford University -- wanted to better understand the public's perspective.

In a study published Sept. 21 in Nature Climate Change, they asked more than 10,000 people in the United States, United Kingdom, Germany and France to consider four different methods of funding climate policies:

Should the prices start low and gradually increase over time?

Should prices start high and decrease over time as progress is made?

Should prices start low, increase over time and then come back down?

Or, would consumers prefer a constant-cost plan?

Policymakers and pundits have generally assumed that ramping up climate action and costs over time would be the most attractive approach as it would allow consumers to prepare and adjust their energy usage. Instead, they found the majority in all four countries preferred a simpler, constant-cost plan -- even if average household costs are high.

Policymakers take note: The constant-cost plan also significantly reduced opposition to climate action, as compared with the ramp-up plan.

According to Bechtel, understanding the public's preference for funding climate action is important because these costs would likely be passed on to the consumer.

"Carbon taxes are meant to change energy-intense production as well as consumption patterns, and they would be paid by businesses and consumers," Bechtel said. "An example is a fuel tax that would directly increase the price of gasoline. A second type of a carbon tax is an emissions tax, which would raise the price of industrial activities that emit greenhouse gases. But even with this type of activity, consumers will ultimately incur higher prices because the increased production costs will require raising the price of such emission-intense goods."

Researchers began by introducing the notion of an international agreement, which would entail certain average costs per month and household. Respondents were given the four different options of distributing the costs of implementing the agreement over time and asked to indicate which cost schedule they would select in a referendum given a certain cost level average -- low or high.

Across the four countries, 58% of respondents preferred the constant-cost plan, whereas only 12% preferred an increasing-cost plan.

Those who favored the constant-cost plan stressed the desire to simplify budgeting and plan for the future. It also encouraged people to reduce their energy usage over time. Even when average household costs were substantial -- adding up to 2% of GDP -- most respondents still preferred the certainty of the constant plan.

In comparison, those who preferred the ramp-up approach said this plan allowed people to gradually adjust to rising costs. Respondents also chose this option in the hope that delayed costs would leave less of a consumer impact because of wage increases, inflation, etc.

Essential to tackling climate change

Respondents who preferred higher costs up front emphasized the need to make investments now, which they said were essential to tackling climate change.

"Credible climate policies will have to raise the price of carbon, and the public are concerned about these costs even when they believe the science of climate change and generally want governments to address the issue," the researchers wrote.

"As policymakers seek to design policies that are transparent and meet meaningful emission reduction goals, our research indicates that constant-cost plans promise more support for climate action relative to ramping-up approaches.

"Moreover, due to the delay in large-scale policy responses to climate change, countries will likely have to pursue more progressive and costly climate action to limit the adverse effects of global warming. The drop in support due to higher costs associated with these more ambitious policy efforts may be at least partially mitigated by selecting a set of attractive design features such as the constant distribution of costs."

Progress appears challenging, but it is possible. The 2016 Paris Agreement created a global framework to address climate change with countries committing to work together to limit the global average temperature increase to 2°C or less. But it stopped short of prescribing which policy instruments countries could use to reach the collective goal.

"Countries have agreed that domestic mitigation measures that reduce greenhouse gas emissions are needed," Bechtel said. "This is the goal of carbon pricing: Incentivizing societies to produce less GHG emissions. There are several policy instruments that promise to get us closer to this goal. A carbon tax is one of these instruments, but countries can also use emission trading systems or emission reduction funds, for example. They could also rely on a combination of these policies."

HOUSTON - (Sept. 21, 2020) - A dose of artificial intelligence can speed the development of 3D-printed bioscaffolds that help injuries heal, according to researchers at Rice University.

A team led by computer scientist Lydia Kavraki of Rice's Brown School of Engineering used a machine learning approach to predict the quality of scaffold materials, given the printing parameters. The work also found that controlling print speed is critical in making high-quality implants.

Bioscaffolds developed by co-author and Rice bioengineer Antonios Mikos are bonelike structures that serve as placeholders for injured tissue. They are porous to support the growth of cells and blood vessels that turn into new tissue and ultimately replace the implant.

Mikos has been developing bioscaffolds, largely in concert with the Center for Engineering Complex Tissues, to improve techniques to heal craniofacial and musculoskeletal wounds. That work has progressed to include sophisticated 3D printing that can make a biocompatible implant custom-fit to the site of a wound.

That doesn't mean there isn't room for improvement. With the help of machine learning techniques, designing materials and developing processes to create implants can be faster and eliminate much trial and error.

"We were able to give feedback on which parameters are most likely to affect the quality of printing, so when they continue their experimentation, they can focus on some parameters and ignore the others," said Kavraki, a renowned authority on robotics, artificial intelligence and biomedicine and director of Rice's Ken Kennedy Institute.

The team reported its results in Tissue Engineering Part A.

The study identified print speed as the most important of five metrics the team measured, the others in descending order of importance being material composition, pressure, layering and spacing.

Mikos and his students had already considered bringing machine learning into the mix. The COVID-19 pandemic created a unique opportunity to pursue the project.

"This was a way to make great progress while many students and faculty were unable to get to the lab," Mikos said.

Kavraki said the researchers -- graduate students Anja Conev and Eleni Litsa in her lab and graduate student Marissa Perez and postdoctoral fellow Mani Diba in the Mikos lab, all co-authors of the paper -- took time at the start to establish an approach to a mass of data from a 2016 study on printing scaffolds with biodegradable poly(propylene fumarate), and then to figure out what more was needed to train the computer models.

"The students had to figure out how to talk to each other, and once they did, it was amazing how quickly they progressed," Kavraki said.

From start to finish, the COVID-19 window let them assemble data, develop models and get the results published within seven months, record time for a process that can often take years.

The team explored two modeling approaches. One was a classification method that predicted whether a given set of parameters would produce a "low" or "high" quality scaffold. The other was a regression-based approach that approximated the values of print-quality metrics to come to a result. Kavraki said both relied upon a "classical supervised learning technique" called random forest that builds multiple "decision trees" and "merges" them together to get a more accurate and stable prediction.

Ultimately, the collaboration could lead to better ways to quickly print a customized jawbone, kneecap or bit of cartilage on demand.

"A hugely important aspect is the potential to discover new things," Mikos said. "This line of research gives us not only the ability to optimize a system for which we have a number of variables -- which is very important -- but also the possibility to discover something totally new and unexpected. In my opinion, that's the real beauty of this work.

"It's a great example of convergence," he said. "We have a lot to learn from advances in computer science and artificial intelligence, and this study is a perfect example of how they will help us become more efficient."

"In the long run, labs should be able to understand which of their materials can give them different kinds of printed scaffolds, and in the very long run, even predict results for materials they have not tried," Kavraki said. "We don't have enough data to do that right now, but at some point we think we should be able to generate such models."

Kavraki noted The Welch Institute, recently established at Rice to enhance the university's already stellar reputation for advanced materials science, has great potential to expand such collaborations.

"Artificial intelligence has a role to play in new materials, so what the institute offers should be of interest to people on this campus," she said. "There are so many problems at the intersection of materials science and computing, and the more people we can get to work on them, the better."

In a review paper published in Frontiers in Plant Science, scientists urge the importance of combining the knowledge harbored by farmers of diverse crop varieties - which is often overlooked by scientists - with high-tech breeding done in laboratories.

Authors argue that farmers' knowledge and high-tech breeding to improve crops can be effectively combined to unlock more resilient and nutritious food supplies in the face of climate threats. They say that involving farmers in crop improvement enhances the chance that new varieties will be adopted, making crop improvement more efficient.

"Modern breeding under a microscope in the lab can speed up breeding of 'elite' varieties able to provide significant yield increase," says Carlo Fadda, a co-author from the Alliance of Bioversity and International Center for Tropical Agriculture. "But are those varieties and traits most important to farmers? Do they plant them? On the other hand, traditional varieties can better withstand changing climatic conditions, but are these varieties high-yielding enough?"

This Seeds for Needs approach, first trialed in Ethiopia to speed up durum wheat breeding, has already yielded surprising results. When scientists took a selection of elite and traditional durum wheat varieties obtained from Ethiopia Biodiversity Institute (EBI) to farmers to get their feedback, traditional varieties outperformed elite ones, producing double the average national durum wheat yield while also resistant to major diseases.

"Rather than mass-producing seed to cope in a broad range of conditions, we need to find varieties for local contexts in order to maximize yields at each site," says Fadda. "Traditionally, farmers grow a portfolio of crops to withstand different conditions and make different products. Some will plant wheat for bread, for local-brewed beer, for injera - the local flatbread - to minimize their risk."

The 'Seeds for Needs' approach further integrates scientific rigor and cutting-edge breeding to fast-track climate-resilient traits and crop varieties. Combined with farmer selection of varieties, which can cope in field conditions, the result is a better-adapted food supply, more resilient to the impacts of the impending climate crisis, say authors.

"Climate change is a shifting target, and to address it we need a dynamic process," says Fadda. "This approach provides a constant injection of new material adapted to a broader set of conditions within one locality. With this approach, as climate change advances, there will always be well-adapted crop varieties for local conditions, bringing together high tech approaches and traditional knowledge."

Matteo Dell'Acqua, a co-author and geneticist at the Institute of Life Sciences, Scuola Superiore Sant'Anna, in Pisa in Italy, adds: "This approach shows the value of combining the most advanced genomics approaches with traditional knowledge of farmer communities. In this framework, modern breeding and crowd-sourcing methods can complement each other in supporting local adaptation of farming systems to the impacts of climate change."

With the advent of digital tools, the researchers say farmer 'citizen scientists' can provide adequate, reliable information identifying varieties with superior traits tolerant to climate-induced stress. Research conducted with farmers in Ethiopia, Honduras and India shows they are keen to be part of trials, to contribute to research or in exchange for advice.

In Ethiopia, two wheat varieties bred using the 'Seeds for Needs' approach have already been released four years faster than the average time required to release new varieties. Now, the approach is being used across Africa, Asia and Latin American and the Caribbean.

A druggable pocket in the SARS-CoV-2 Spike protein that could be used to stop the virus from infecting human cells has been discovered by an international team of scientists led by the University of Bristol. The researchers say their findings, published today [21 Sep] in the journal Science, are a potential 'game changer' in defeating the current pandemic and add that small molecule anti-viral drugs developed to target the pocket they discovered could help eliminate COVID-19.

SARS-CoV-2 is decorated by multiple copies of a glycoprotein, known as the 'Spike protein', which plays an essential role in viral infectivity. Spike binds to the human cell surface, allowing the virus to penetrate the cells and start replicating, causing widespread damage.

In this ground-breaking study, the team headed by Professor Christiane Schaffitzel from Bristol's School of Biochemistry and Professor Imre Berger from the Max Planck-Bristol Centre for Minimal Biology, used a powerful imaging technique, electron cryo-microscopy (cryo-EM), to analyse SARS-CoV-2 Spike at near atomic resolution. Enabled by Oracle high-performance cloud computing, a 3D structure of SARS CoV-2 Spike protein was generated allowing the researchers to peer deep inside the Spike identifying its molecular composition.

Unexpectedly, the research team's analysis revealed the presence of a small molecule, linoleic acid (LA), buried in a tailor-made pocket within the Spike protein. LA is a free fatty acid, which is indispensable for many cellular functions. The human body cannot produce LA. Instead, the body absorbs this essential molecule through diet. Intriguingly, LA plays a vital role in inflammation and immune modulation, which are both key elements of COVID-19 disease progression. LA is also needed to maintain cell membranes in the lungs so that we can breathe properly.

Professor Berger said: "We were truly puzzled by our discovery, and its implications. So here we have LA, a molecule which is at the centre of those functions that go haywire in COVID-19 patients, with terrible consequences. And the virus that is causing all this chaos, according to our data, grabs and holds on to exactly this molecule - basically disarming much of the body's defences."

Professor Schaffitzel explained: "From other diseases we know that tinkering with LA metabolic pathways can trigger systemic inflammation, acute respiratory distress syndrome and pneumonia. These pathologies are all observed in patients suffering from severe COVID-19. A recent study of COVID-19 patients showed markedly reduced LA levels in their sera."

Professor Berger adds: "Our discovery provides the first direct link between LA, COVID-19 pathological manifestations and the virus itself. The question now is how to turn this new knowledge against the virus itself and defeat the pandemic."

There is reason for hope. In rhinovirus, a virus causing the common cold, a similar pocket was exploited to develop potent small molecules that bound tightly to the pocket distorting the structure of the rhinovirus, stopping its infectivity. These small molecules were successfully used as anti-viral drugs in human trials and show promise for treating rhinovirus clinically. The Bristol team, based on their data, is optimistic that a similar strategy can now be pursued to develop small molecule anti-viral drugs against SARS-CoV-2.

Professor Schaffitzel said: "COVID-19 continues to cause widespread devastation and in the absence of a proven vaccine, it is vital that we also look at other ways to combat the disease. If we look at HIV, after 30 years of research what worked in the end is a cocktail of small molecule anti-viral drugs that keeps the virus at bay. Our discovery of a druggable pocket within the SARS-CoV-2 Spike protein could lead to new anti-viral drugs to shut down and eliminate the virus before it entered human cells, stopping it firmly in its tracks."

Alison Derbenwick Miller, Vice President, Oracle for Research, added: "Oracle for Research unites researchers and cloud computing to help bring about beneficial change for our planet and its people. SARS-CoV-2 and COVID-19 are causing global devastation, and research efforts to find vaccines and treatments cannot move quickly enough. We are so pleased that Oracle's high-performance cloud infrastructure enabled Professors Berger and Schaffitzel to examine the molecular structures of the coronavirus spike protein and make this powerful and unexpected new discovery that could help curb the pandemic and save lives."

September 21, 2020--(BRONX, NY)--The first study comparing the immune responses of adults and children with COVID-19 has detected key differences that may contribute to understanding why children usually have milder disease than adults. The findings also have important implications for vaccines and drugs being developed to curb COVID-19. The study was published today in Science Translational Medicine and was conducted by scientists at Albert Einstein College of Medicine, Children's Hospital at Montefiore (CHAM), and Yale University.

The study involved 60 adult COVID-19 patients and 65 pediatric COVID-19 patients (less than 24 years old) hospitalized at CHAM and Montefiore Health System between March 13 and May 17, 2020; 20 of the pediatric patients had the novel multi-system inflammatory syndrome (MIS-C). The patients' blood was tested for the presence of several types of immune cells, antibody responses, and the inflammatory proteins, known as cytokines, that immune cells produce.

Children with COVID-19 fared significantly better than adults. Twenty-two adults (37%) required mechanical ventilation compared with only five (8%) of the pediatric patients. In addition, 17 adults (28%) died in the hospital compared with two (3%) of the pediatric patients. No deaths occurred among pediatric patients with MIS-C.

"Our findings suggest that children with COVID-19 do better than adults because their stronger innate immunity protects them against SARS-CoV-2, the novel coronavirus that causes the disease," said co-senior author Betsy Herold, M.D., chief of infectious diseases and vice chair for research in the department of pediatrics at Einstein and CHAM. Kevan C. Herold, M.D., C.N.H. Long Professor of Immunology and of Medicine at Yale School of Medicine, was the other co-senior author on the study.

People have two types of immunity--innate and adaptive. Innate immunity, in which immune cells respond rapidly to invading pathogens of all kinds, is more robust during childhood. Adaptive immunity, the second type of immune response, is more specific and features antibodies and immune cells that target specific viruses or other microbes.

Compared with adult patients, pediatric COVID-19 patients in the study possessed significantly higher levels of certain cytokines associated with the innate immune response. This suggests that young people's more robust innate response protects them from developing acute respiratory distress syndrome (ARDS)--the hallmark of severe and often fatal COVID-19 cases. One cytokine in particular, known as IL-17A, was found at much higher levels in pediatric patients than in adults. "The high levels of IL-17A that we found in pediatric patients may be important in protecting them against progression of their COVID-19," said Dr. K. Herold.

Both pediatric and adult COVID-19 patients were found to make antibodies against the coronavirus' spike protein, which the virus uses to latch onto and infect cells. Those spike-protein antibodies include neutralizing antibodies, which block the coronavirus from infecting cells. Counterintuitively, the researchers found that neutralizing antibody levels in adult COVID-19 patients who died or required mechanical ventilation were higher than in those who recovered--and significantly higher than levels detected in pediatric patients.

"These results suggest that the more severe COVID-19 disease seen in adults is not caused by a failure of their adaptive immunity to mount T-cell or antibody responses," said Dr. K. Herold. "Rather, adult patients respond to coronavirus infection with an over-vigorous adaptive immune response that may promote the inflammation associated with ARDS."

The findings have important implications for COVID-19 therapies and vaccines. "Our adult COVID-19 patients who fared poorly had high levels of neutralizing antibodies, suggesting that convalescent plasma--which is rich in neutralizing antibodies--may not help adults who have already developed signs of ARDS," said Dr. B. Herold. "By contrast, therapies that boost innate immune responses early in the course of the disease may be especially beneficial."

As for vaccines, Dr. B. Herold notes that most vaccine candidates for protecting against SARS-CoV-2 infection are aimed at boosting neutralizing-antibody levels. "We may want to consider assessing vaccines that promote immunity in other ways, such as by bolstering the innate immune response," she said.

New research suggests that the impact of natural and vaccine-induced immunity will be key factors in shaping the future trajectory of the global coronavirus pandemic, known as COVID-19. In particular, a vaccine capable of eliciting a strong immune response could substantially reduce the future burden of infection, according to a study by Princeton researchers published in the journal Science Sept. 21.

"Much of the discussion so far related to the future trajectory of Covid-19 has rightly been focused on the effects of seasonality and non-pharmaceutical interventions [NPIs], such as mask-wearing and physical distancing,", said co-first author Chadi Saad-Roy, a Ph.D. candidate in Princeton's Lewis-Sigler Institute for Integrative Genomics. "In the short term, and during the pandemic phase, NPIs are the key determinant of case burdens. However, the role of immunity will become increasingly important as we look into the future."

"Ultimately, we don't know what the strength or duration of natural immunity to SARS-CoV-2 -- or a potential vaccine -- will look like," explained co-first author Caroline Wagner, an assistant professor of bioengineering at McGill University who worked on the study as a postdoctoral research associate in the Princeton Environmental Institute (PEI).

"For instance, if reinfection is possible, what does a person's immune response to their previous infection do?" Wagner asked. "Is that immune response capable of stopping you from transmitting the infection to others? These will all impact the dynamics of future outbreaks."

The current study builds on Princeton research published in Science May 18 that reported that local variations in climate are not likely to dominate the first wave of the COVID-19 pandemic and included many of the same authors, who are all affiliated with PEI's Climate Change and Infectious Disease initiative.

In the most recent paper, the researchers used a simple model to project the future incidence of COVID-19 cases -- and the degree of immunity in the human population -- under a range of assumptions related to how likely individuals are to transmit the virus in different contexts. For example, the model allows for different durations of immunity after infection, as well as different extents of protection from reinfection. The researchers posted online an interactive version of model's predictions under these different sets of assumptions.

As expected, the model found that the initial pandemic peak is largely independent of immunity because most people are susceptible. However, a substantial range of epidemic patterns are possible as SARS-CoV-2 infection -- and thus immunity -- increases in the population.

"If immune responses are only weak, or transiently protective against reinfection, for example, then larger and more frequent outbreaks can be expected in the medium term," said co-author Andrea Graham, professor of ecology and evolutionary biology at Princeton.

The nature of the immune responses also can affect clinical outcomes and the burden of severe cases requiring hospitalization, the researchers found. The key question is the severity of subsequent infections in comparison to primary ones.

Importantly, the study found that in all scenarios a vaccine capable of eliciting a strong immune response could substantially reduce future caseloads. Even a vaccine that only offers partial protection against secondary transmission could generate major benefits if widely deployed, the researchers reported.

Factors such as age and superspreading events are known to influence the spread of SARS-CoV-2 by causing individuals within a population to experience different immune responses or transmit the virus at different rates. "Our models show that these factors do not affect our qualitative projections about future epidemic dynamics," said Bryan Grenfell, the Kathryn Briger and Sarah Fenton Professor of Ecology and Evolutionary Biology and Public Affairs and an associated faculty member in PEI. Grenfell is a co-senior author on the paper with C. Jessica Metcalf, associate professor of ecology and evolutionary biology and public affairs and also a PEI associated faculty member.

"As vaccine candidates emerge, and more detailed predictions of future caseloads with vaccination are needed, these additional details will need to be incorporated into more complex models," Grenfell said.

The study authors also explored the effect of "vaccine hesitancy" on future infection dynamics. Their model found that people who decline to partake in pharmaceutical and non-pharmaceutical measures to contain the coronavirus could nonetheless slow containment of the virus even if a vaccine is available.

"Our model indicates that if vaccine refusal is high and correlated with increased transmission and riskier behavior such as refusing to wear a mask, then the necessary vaccination rate needed to reach herd immunity could be much higher," said co-author Simon Levin, the James S. McDonnell Distinguished University Professor in Ecology and Evolutionary Biology and an associated faculty member in PEI. "In this case, the nature of the immune response after infection or vaccination would be very important factors in determining how effective a vaccine would be."

"When so much uncertainty in the underlying processes exists, it can be challenging to make accurate projections about the future," Grenfell said. "We argue in this study that ultimately, a family of both simple and more complex models is the best way to proceed under these circumstances. Comparing the predictions of these models carefully and then coming up with a carefully averaged picture of the future -- as with weather prediction -- can be very helpful."

One of the main takeaways of the study is that monitoring population-level immunity to SARS-CoV-2, in addition to active infections, will be critical for accurately predicting future incidence.

"This is not an easy thing to do accurately, particularly when the nature of this immune response is not well understood," said co-author Michael Mina, an assistant professor at the Harvard School of Public Health and Harvard Medical School. "Even if we can measure a clinical quantity like an antibody titer against this virus, we don't necessarily know what that means in terms of protection."

"Studying the effects of T-cell immunity and cross-protection from other coronaviruses are important avenues for future work," Metcalf said.

Researchers who adapted standard epidemiological models to explore how the COVID-19 pandemic trajectory might unfold in the next five years report diverse scenarios ranging from recurring severe epidemics to elimination. Their work emphasizes how dependent the future course of the pandemic is on the nature of the adaptive immune response to this virus and on the efficacy of future potential vaccines. The duration and severity of future COVID-19 cases will depend on the strength of both natural and vaccine-derived immunity against the SARS-CoV-2 pathogen. However, there is still uncertainty about both. Here, to explore how variations in immune responses could impact the magnitude and timing of COVID-19 cases in the next five years, Chadi Saad-Roy and colleagues adapted a series of standard epidemiologic models of the spread of infection (the SIR and SIRS models, respectively). They used these adapted models to evaluate results of four future scenarios that consider different outcomes for the nature of the adaptive immune response to SARS-CoV-2 infection, the effect of transmission rate seasonality, the adoption of non-pharmaceutical interventions, and the availability and effectiveness of a vaccine. Depending on these variations, dramatically different immunity landscapes and burdens of critically severe cases could emerge, they say, ranging from sustained epidemics to near elimination. The results underscore that understanding the immunology of secondary infection - which impacts the number of those susceptible to the virus - is critical. They also reveal how the pandemic trajectory will be substantially altered by mass deployment of vaccines, though, this is strongly dependent on vaccine efficacy. Their work also shows that relying on the status of infection of an individual as the main "observable" during an ongoing epidemic is not sufficient to characterize the complex immune landscape generated by the pandemic. Regular testing of antibody presence and correlates of protection such as T cell immunity are critical, to accurately characterize population-level natural and vaccinal immunity to this pathogen. The authors note that in order to focus on immune dynamics, they made several simplifying assumptions.

A comparison of children and adults hospitalized with COVID-19 reveals pediatric patients, who had better outcomes and shorter hospital stays, displayed altered immune responses and more limited production of antibodies against infection. While these preliminary findings are descriptive and do not establish a causative relationship, the study hints that these immune differences could help explain why children have consistently developed less severe cases of COVID-19 than adults during the pandemic. COVID-19 has caused more than 29 million cases and 929,000 deaths globally, and high hospitalization rates from the disease have overwhelmed healthcare systems in many cities. Clinicians have noted that children and young people have milder symptoms and rarely progress to life-threatening respiratory complications - the opposite of what has been observed with other viral infections such as respiratory syncytial virus. However, the basis for these clinical differences has been unclear. Carl Pierce and colleagues compared data from 65 children and youths (under 24 years of age) and 60 adults hospitalized with COVID-19 in metropolitan New York. The infected children - including some who had the emerging complication known as multisystem inflammatory syndrome - were less likely to require mechanical ventilation (8% vs 37%) and had lower mortality (3% vs 28%) than the adults. However, adults showed higher antibody production and T cell responses to the viral spike protein, but lower amounts of inflammatory molecules like IL-17A and IFNγ that are involved in innate immunity. "The results provide new insights into potential mechanisms that may contribute to age-related differences in disease resolution ... and may have implications for ongoing efforts with convalescent plasma and the development of therapeutic antibodies," Pierce et al. write.

WASHINGTON, D.C. - September 21, 2020 - Although people of any age can become infected with SARS-CoV-2, the virus that causes COVID-19, elderly patients face a higher risk of severity and death than younger patients. New research comparing the immune response among age groups, published this week in mBio, an open-access journal of the American Society for Microbiology, may help explain why. Older patients with the disease have lower frequencies of the immune cells needed to expel the virus from the body, the researchers found.

"Elderly people have more severe diseases compared to young people, and we found that the cytotoxic part of immune control is not as efficient to respond to the virus in older people," said virologist Gennadiy Zelinskyy, Ph.D., at the University Hospital Essen, in Germany. Zelinskyy led the new study.

He and his colleagues analyzed blood samples from 30 people with mild cases of COVID-19 to observe how T cells, which are necessary for recognition and elimination of infected cells, respond during SARS-CoV-2 infection. Patient ages ranged from the mid-20s to the late 90s. In all patients, the investigators found that acute SARS-CoV-2 infections led to lower numbers of T cells in the blood of the patients, compared to healthy individuals.

This reduction has been one of many unwelcome surprises from COVID-19, said Zelinskyy. Most viruses, once inside the body, trigger an uptick in the immune system's expansion of T cells. These include "killer" T cells, which play a critical role in eradicating virus-infected cells. They produce cytotoxic molecules that destroy infected cells in the body. But if a person's immune system produces fewer of these T cells, said Zelinskyy, it will be less successful at fighting off a viral infection.

In the COVID-19 patient group studied by Zelinskyy and his colleagues, the researchers similarly found that the number of CD8+ T cells producing cytotoxic molecules in response to virus diminished with increased age, and that reduction was significantly higher, on average, in patients over 80. Moreover, the "killer" T cells from patients aged 80-96 produced cytotoxic molecules at a lower frequency than similar cells from younger patients.

The SARS-CoV-2 virus attaches to cells in the nose or mouth. From there, it may spread to the lungs and move on to other organs, triggering a life-threatening infection. "Cytotoxic T cells really fight for control during this acute phase of infection," Zelinskyy said. If an elderly patient's immune system produces fewer killer T cells, and these cells are inadequately armed, he said, they may be mounting an insufficient defense against SARS-CoV-2. The viral particles can continue to spread and, as a result, the infection worsens.

The new data suggest that cytotoxic T cells play a key role in control of early infections, but Zelinskyy cautioned that it's too soon to know if that connection can be harnessed to design an effective immunotherapy that uses these cells. In previous studies on viral infections in mice, his group found that a checkpoint inhibitor--an immunotherapy that activates killer T cells and effectively releases the brakes on the immune system--improved virus control at first but had the potential to later cause damage to the lungs and other organs. Further studies are warranted, he said, to better understand the potential risks and benefits of interfering with T cells as a way to control SARS-CoV-2 and other viruses.