Culture

It is largely unknown why influenza infections lead to an increased risk of bacterial pneumonia. Researchers at Karolinska Institutet in Sweden have now described important findings leading to so-called superinfections, which claim many lives around the world every year. The study is published in the journal PNAS, Proceedings of the National Academy of Sciences, and can also contribute to research on COVID-19.

The Spanish Flu was an influenza pandemic that swept across the world in 1918-20 and unlike many other pandemics disproportionately hit young otherwise healthy adults. One important reason for this was so-called superinfections caused by bacteria, in particular pneumococci.

Influenza is caused by a virus, but the most common cause of death is secondary bacterial pneumonia rather than the influenza virus per se. Pneumococcal infections are the most common cause of community-acquired pneumonia and a leading global cause of death. A prior influenza virus infection sensitizes for pneumococcal infections, but mechanisms behind this increase susceptibility are not fully understood. Researchers at Karolinska Institutet have now identified influenza-induced changes in the lower airways that affect the growth of pneumococci in the lungs.

Using an animal model, the researchers found that different nutrients and antioxidants, such as vitamin C and other normally cell protective substances leak from the blood, thereby creating an environment in the lungs that favours growth of the bacteria. The bacteria adapt to the inflammatory environment by increasing the production of the bacterial enzyme HtrA.

The presence of HtrA weakens the immune system and promotes bacterial growth in the influenza-infected airways. The lack of HtrA stops bacterial growth.

"The ability of pneumococcus to grow in the lower airways during an influenza infection seems to depend on the nutrient-rich environment with its higher levels of antioxidants that occurs during a viral infection, as well as on the bacteria's ability to adapt to the environment and protect itself from being eradicated by the immune system," says principal investigator Birgitta Henriques Normark, professor at the Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet.

The results provide valuable information on how bacteria integrate with their environment in the lungs and could be used to find new therapies for double infections between the influenza virus and pneumococcal bacteria.

"HtrA is an enzyme, a protease, which helps to weaken the immune system and allows pneumococcal bacteria to penetrate the protective cell layer on the inside of the airways," explains the paper's first author Vicky Sender, researcher at the same department. "A possible strategy can therefore be use of protease inhibitors to prevent pneumococcal growth in the lungs."

It is still not known if COVID-19 patients are also sensitive to such secondary bacterial infections, but the researchers think that similar mechanisms could potentially be found in severely ill COVID-19 patients.

"It's likely that acute lung inflammation, regardless of cause, gives rise to leakage of nutrients and antioxidants, and to an environment that fosters bacterial growth," says Professor Henriques Normark.

Why do so many Republicans still believe that the recent US presidential election was fraudulent? Is it possible to reach coronavirus deniers with factual arguments? A study by researchers at the Max Planck Institute for Human Development and the University of Amsterdam provides insights into what it is that stops people from changing their minds. Their findings have been published in the journal Proceedings of the Royal Society of London B.

By talking to other people and observing their behavior, we can learn new things, acquire new skills, and adapt to changing conditions. But what if the information provided by the social environment is inconsistent or contradictory? In a recent study, researchers from the Max Planck Institute for Human Development and the University of Amsterdam have investigated how people deal with information from diverse social sources, and how they use that information to form beliefs. "The internet, in particular, has dramatically changed the structure and dynamics of social interactions. The availablility of social sources is to some extent controlled by algorithms--what we see is biased in favor of our own preferences. At the same time, the internet gives us access to potentially conflicting views," says lead author Lucas Molleman, associate research scientist in the Center for Adaptive Rationality at the Max Planck Institute for Human Development and postdoc at the University of Amsterdam.

The researchers first conducted an experimental study with 95 participants from the United States. Participants completed an adapted version of the Berlin Estimate AdjuStment Task (BEAST), which reliably measures individuals' use of social information. They were shown images of groups of animals and asked to estimate the number of animals. They were then shown the estimates of three other participants and asked to make a second estimate. The more participants adjusted their estimates to those of their peers, the more account they had taken of social information.

Across 30 rounds of the task, the researchers varied the conditions of the study, presenting participants with estimates that deviated to a greater or lesser extent from their own estimate, and that were more or less extreme. The results showed that whether participants integrated information from the social environment in their second estimate depended on whether and how strongly their peers' estimates deviated from each other and from their own estimate. Participants were most likely to adjust their estimates when their peers were in close agreement with each other and their estimates were not too different from the participant's own. Higher variation in peers' estimates reduced their impact on the participant's own judgment. In general, participants gave more weight to their own initial estimate than to their peers' estimates. Overall, three adjustment strategies were identified: (1) sticking to one's original estimate, (2) adopting the estimate of one of the three peers, or (3) compromising between one's original estimate and the peer estimates. The relative frequency of these strategies differed significantly between study conditions. When participants observed a single peer who closely agreed with them, they were more likely to stick to their original estimate or to adopt the estimate of the near peer. When none of the peers were in close agreement with them, participants were more likely to compromise by adjusting their estimate towards, but rarely beyond, that of the nearest peer.

"Our experiment quantifies how people weigh their own prior beliefs and the beliefs of others. In our context, there is actually no reason to assume that one's own estimate is better than anyone else's. But what we see here is an effect known in psychology as 'egocentric discounting' - namely that people put more weight on their own beliefs than on those of others," explains co-author Alan Noveas Tump, postdoc at the Center for Adaptive Rationality of the Max Planck Institute for Human Development. "What's more, our study reveals that this weighting is strongly impacted by the consistency of others' beliefs with one's own: people are more likely to heed information that confirms their own beliefs."

Building on these findings, the researchers developed a model that integrates the observed adjustment strategies and captures that people pay particular attention to social information that confirms their personal judgements. Using simulations, they then investigated how people would behave in real-life situations. For example, they simulated a typical filter bubble, where social information tends to come from like-minded people. They also simulated typical attempts to change people's minds by confronting them with information inconsistent with their own beliefs. Finally, they investigated how people react to being simultaneously exposed to different groups with extreme beliefs. Their simulations suggest that confirmation effects can lead to divergent social information being ignored, filter bubble effects being exacerbated, and people becoming more extreme in their attitudes.

"Although our study was experimental in design, our model helps explain many contemporary phenomena. It shows how the way people process social information can exacerbate filter bubbles on the internet, and why public debates often become polarized as people quickly become impervious to opposing arguments. As interactions increasingly often take place online, people can often find information that confirms their existing beliefs, making them less willing to listen to alternatives," says co-author Wouter van den Bos, adjunct research scientist in the Center for Adaptive Rationality at the Max Planck Institute for Human Development and associate professor at the University of Amsterdam.

In future studies, the researchers want to integrate further aspects of reality into the model to find out, for example, whether it matters whether social information comes from a friend, a stranger, an expert, or someone with the same or different political partisanship. They are also investigating how other people influence individuals' altruistic giving and compliance with social norms.

Modern microscopes used for biological imaging are expensive, are located in specialized laboratories and require highly qualified staff. To research novel, creative approaches to address urgent scientific issues -- for example in the fight against infectious diseases such as Covid-19 -- is thus primarily reserved for scientists at well-equipped research institutions in rich countries. A young research team from the Leibniz Institute of Photonic Technology (Leibniz IPHT) in Jena, the Friedrich Schiller University and Jena University Hospital wants to change this: The researchers have developed an optical toolbox to build microscopes for a few hundred euros that deliver high-resolution images comparable to commercial microscopes that cost a hundred to a thousand times more. With open-source blueprints, components from the 3D printer and smartphone camera, the UC2 (You. See. Too.) modular system can be combined specifically in the way the research question requires -- from long-term observation of living organisms in the incubator to a toolbox for optics education. The research team presents its development on November 25, 2020 in the renowned journal Nature Communications (DOI: 10.1038/s41467-020-19447-9).

The basic building block of the UC2 system is a simple 3D printable cube with an edge length of 5 centimeters, which can host a variety of components such as lenses, LEDs or cameras. Several such cubes are plugged on a magnetic raster base plate. Cleverly arranged, the modules thus result in a powerful optical instrument. An optical concept according to which focal planes of adjacent lenses coincide is the basis for most of the complex optical setups such as modern microscopes. With the UC2 toolbox, the research team of PhD students at the lab of Prof. Dr. Rainer Heintzmann, Leibniz IPHT and Friedrich Schiller University Jena, shows how this inherently modular process can be understood intuitively in hands-on-experiments. In this way, UC2 also provides users without technical training with an optical tool that they can use, modify and expand -- depending on what they are researching.

Monitor pathogens -- and then recycle the contaminated microscope

Helge Ewers, Professor of Biochemistry at the Free University of Berlin and the Charité, is investigating pathogens usind the UC2 toolbox. "The UC2 system allows us to produce a high-quality microscope at low cost, with which we can observe living cells in an incubator", he states. UC2 thus opens up areas of application for biomedical research for which conventional microscopes are not suitable. "Commercial microscopes that can be used to examine pathogens over a longer period of time cost hundreds or thousands of times more than our UC2 setup," says Benedict Diederich, PhD student at Leibniz-IPHT, who developed the optical toolbox there together with René Lachmann. "You can hardly get them into a contaminated laboratory from which you may not be able to remove them because they cannot be cleaned easily". The UC2 microscope made of plastic, on the other hand, can be easily burned or recycled after its successful use in the biological safety laboratory. For a study at Jena University Hospital, the UC2 team observed the differentiation of monocytes into macrophages in the incubator over a period of one week in order to gain insights into how the innate immune system fights off pathogens in the body.

Building according to the Lego principle: From the idea to the prototype

Building according to the Lego principle -- this not only awakens the users' inner play instinct, observes the UC2 team, but it also opens up new possibilities for researchers to design an instrument precisely tailored to their research question. "With our method, it is possible to quickly assemble the right tool to map specific cells," explains Benedict Diederich. "If, for example, a red wavelength is required as excitation, you simply install the appropriate laser and change the filter. If an inverted microscope is needed, you stack the cubes accordingly. With the UC2 system, elements can be combined depending on the required resolution, stability, duration or microscopy method and tested directly in the "rapid prototyping" process.

The Vision: Open Science

The researchers publish construction plans and software on the freely accessible online repository GitHub, so that the open-source community worldwide can access, rebuild, modify and expand the presented systems. "With the feedback from users, we improve the system step by step and add ever new creative solutions," reports René Lachmann. The first users have already started to expand the system for themselves and their purposes. "We are eager to see when we can present the first user solutions".

The aim behind this is to enable open science. Thanks to the detailed documentation, researchers can reproduce and further develop experiments anywhere in the world, even beyond well-equipped laboratories. "Change in Paradigm: Science for a Dime" is what Benedict Diederich calls this vision: to herald a paradigm shift in which the scientific process is as open and transparent as possible, freely accessible to all, where researchers share their knowledge with each other and incorporate it into their work.

UC2 experiment box brings science to schools

In order to get especially young people interested in optics, the research team has developed a sophisticated tool set for educational purposes in schools and universities. With "The Box" UC2 introduces a kit that enables users to learn about and try out optical concepts and microscopy methods. "The components can be combined to form a projector or a telescope; you can build a spectrometer or a smartphone microscope," explains Barbora Maršíková, who developed experiments and a series of ready-to-use documentations that the UC2 team already tested in several workshops in and around Jena as well as in the US, in Great Britain and Norway. In Jena, the young researchers have already used the UC2 toolbox in several schools and e.g. supported pupils to build a fluorescence microscope to detect microplastics. "We have combined UC2 with our smartphone. This enabled us to build our own fluorescence microscope cost-effectively without any major optical knowledge and to develop a comparably simple method for detecting plastic particles in cosmetics," reports Emilia Walther from the Montessori School in Jena, who together with her group is pursuing an innovative interdisciplinary learning approach.

"We want to make modern microscopy techniques accessible to a broad public," says Benedict Diederich, "and build up an open and creative microscopy community". This build-it-yourself approach to teaching has a huge potential, especially at times of the Corona pandemics, when access to teaching material at home is severely limited.

MANHATTAN, KANSAS -- In a paper published Wednesday, Nov. 25, in Nature, Kansas State University researchers, in collaboration with the international 10+ Genome Project led by the University of Saskatchewan, have announced the complete genome sequencing of 15 wheat varieties representing breeding programs around the world -- an invaluable resource to improve global wheat production.

This effort gained momentum in 2018 when the Kansas State University team, in collaboration with the International Wheat Genome Sequencing Consortium, published the genome assembly of Chinese Spring, the first complete reference genome of bread wheat. With rapid advances in DNA sequencing technology, and with experience from assembling the first wheat genome, the 10+ Genome Project brought together the expertise and resources of more than 95 scientists from universities and institutes in Canada, Switzerland, Germany, Japan, the U.K., Saudi Arabia, Mexico, Israel, Australia and the U.S.

This study represents the start of a larger effort to generate thousands of genome sequences of wheat, including genetic material brought in from wheat's wild relatives.

"It's like finding the missing pieces for your favorite puzzle that you have been working on for decades," said project leader Curtis Pozniak, wheat breeder and director of the University of Saskatchewan Crop Development Centre. "By having many complete gene assemblies available, we can now help solve the huge puzzle that is the massive wheat pan-genome and usher in a new era for wheat discovery and breeding."

"Our team was uniquely suited to represent U.S. wheat in this effort here in America's breadbasket and as a land-grant institution with a strong history in wheat research," said Jesse Poland, associate professor at Kansas State University and director of the Feed the Future Innovation Lab for Applied Wheat Genomics and the Wheat Genetics Resource Center. "We are fortunate to have world leaders in breeding and genetics under one roof, and generous support from the National Science Foundation, Kansas Wheat and many others."

The Kansas team was responsible for sequencing and analyzing the hard red winter wheat variety Jagger, released in 1994 by the Kansas State University breeding program, now led by Allan Fritz. Jagger was a landmark wheat variety in the Great Plains and covered millions of acres for many years. It was selected for this project because of its relevance as a breeding parent as it is found in the pedigrees of current varieties across the U.S.

"Because of our collaboration in this project, we've had access to this phenomenal genomics resource as it's been built, which has already led to tremendous discovery," Poland said. "K-State plant genetics graduate student Emily Delorean is using data from the 10+ Genomes Project to develop a comprehensive analysis of important quality genes and develop better molecular breeding tools, which will have a huge impact on bread making."

In a companion publication published in Theoretical and Applied Genetics, Kansas State University scientists Liangliang Gao, Dal-Hoe Koo and team completed detailed characterization of the 2N introgression, a chromosome segment that was transferred from wild wheat relative Aegilops ventricosa, which is found in Jagger, but was not present in the original Chinese Spring reference genome. The 2N segment possesses resistance genes to multiple wheat diseases, including stem and leaf rust, nematodes and the emerging wheat blast disease. The team found that this chromosome segment is present in about 80% of Kansas wheat lines and also a large proportion of wheat around the world, marking its importance toward addressing global wheat improvement.

"Progress of this magnitude is only possible because of the strength of the international wheat breeding network and strong international collaborations in wheat research," said Justin Gilpin of Kansas Wheat. "It is exciting for the Kansas wheat growers to be part of this excellent work."

RENO, Nevada - Freshwater fish reserves are extraordinarily successful at protecting multiple species of fish, a new study of a network of community-based reserves in Thailand has found.

Aaron Koning, a postdoctoral research fellow at the University of Nevada, Reno's Global Water Center, spent seven years studying a network of freshwater protected areas (fish reserves) that communities established in one branch of the Salween River Basin in northern Thailand.

He mapped more than 50 reserves, all community organized and managed independently of government support, throughout the river and its branches. The area supports more than 40 species of fish, ranging from large minnows to catfish to needlefish. The results are published today in the scientific journal Nature in the article "A network of grassroots reserves protects tropical river fish diversity."

"The conservation benefits of each reserve established independently by local Pgagayaw, or Karen, indigenous communities are remarkable, and the collective benefits for fish within the entire network of reserves are even greater," Koning said. "Twenty-seven years ago, one community created a reserve in an effort to protect their fish, and since then reserves have spread among communities throughout the valley. It's a great story of effective community-based resource management."

Koning worked with a team of scientists who he had known from his work at the University of Wisconsin-Madison: Martin Perales from the University of Wisconsin-Madison; Etienne Fluet-Chouinard, now from Stanford University, and aquatic conservation ecologist and Associate Professor Peter McIntyre of Cornell University.

"During six weeks of fieldwork related to this study, Martin and I lived with friends in riverside villages, but made the 90 minute drive to Mae Sarieng for internet access on a couple of weekends."

They bounced around the study area of the 50-mile-long Mae Ngao River in a 1999 Toyota Hilux 4X4 truck, through the various regions and communities, including teak forests and upland agricultural areas with rice paddies and soybean crops.

"When I initially started documenting the locations of reserves several years ago, I tried to find the locations of as many reserves within the basin as I could by exploring every road and trail on the map, and many that weren't on any map," he said. "For our fish surveys, we selected a set of 23 reserves distributed throughout the river basin that broadly represented all of the reserves. While there are probably 40 species within this river valley, in this study we regularly observed 33 species of fish."

Intensive fisheries have reduced fish biodiversity and abundance in aquatic ecosystems worldwide. No-take reserves have become a cornerstone of marine ecosystem-based fisheries management. The team used the knowledge gained from decades of study on marine reserves to test if the same principles of success might apply to this network of riverine reserves, where one might not think reserves would work.

"The applicability of this marine reserve network paradigm to riverine biodiversity and inland fisheries remains largely untested," Koning said. "Our research shows that freshwater reserves created by 23 separate communities in Thailand's Salween basin have dramatically increased fish richness, density and biomass when compared to adjacent areas. One river reserve is 1,000 feet long and just 12 feet wide in dry season, but you can see fish everywhere."

Underwater fish surveys were done using masks and snorkels with lots of crawling over and around rocks underwater. In many reserves, the abundance and size of fish seeking protection was evident by eye from the river bank in the dry season.

McIntyre, now Koning's colleague in this research, was once his doctoral advisor at the University of Wisconsin, and co-advisor for his postdoctoral work at Cornell. McIntyre said he was shocked that the reserves worked so well.

"When you see piles of fish in each of these reserves, it is clear that something big is happening," he said. "Questions remain about whether the fish populations are viable in the long run, and how durable the governance approach will prove, but this unique experiment in conservation still has much to teach us."

Despite their small size, grassroots reserves enhanced the species richness, density and biomass of protected fish communities enormously. Relative to adjacent fished areas with comparable water depth and substrate composition, reserves held 27% more fish species; 124% higher fish density and an astounding 2,247% higher biomass on average.

"Our results demonstrate that small reserves have great benefits for intensively harvested fishes in this tropical river, even though their collective area encompasses only 2% of the channel in our study catchment," Koning said. "The area of individual reserves ranged from just a half acre up to six acres."

"One of the most important findings is that the network of reserves adds benefits beyond those arising from any single reserve," McIntyre said. "Another key lesson is that communities have the power to protect the resource themselves, in a way that doesn't prevent them from using it intensively outside of the reserve boundary."

This study demonstrates that fish reserves can work well in subsistence fisheries targeting rivers, thereby offering a model for protecting fish biodiversity and offsetting overfishing in rivers worldwide. The study is especially timely given that overharvest of fisheries threatens thousands of species and the food security of hundreds of millions of people around the world.

"Freshwaters are under-represented among the world's protected areas, and our findings suggest that networks of small, community-based reserves offer a generalizable model for protecting biodiversity and augmenting fisheries as the world's rivers face unprecedented pressures," Koning said.

In Southeast Asia, riverine reserves are commonplace; hundreds of communities have designated no-fishing zones that together form de facto reserve networks in rivers throughout the region.

The idea has the potential to be a big step forward in terms of freshwater biodiversity protection, not just in Thailand but worldwide. These results and the model could be applied in freshwater ecosystems worldwide - including highly diverse and highly threatened tropical rivers such as the Amazon, Congo and Mekong Rivers.

McIntyre echoed Koning's take on the potential for worldwide implementation.

"Aaron's findings offer a great model for other parts of the world, "he said. "The role of cultural traditions and governance structure can't be overstated, so we do not expect simplistic transferability. However, many of the principles identified could be applicable to subsistence fisheries elsewhere."

Koning is currently a postdoctoral researcher working with Zeb Hogan and based at the University of Nevada, Reno's Global Water Center in the College of Science.

Koning and Hogan, an aquatic conservation ecologist, along with Sudeep Chandra, the Director of the Global Water Center at the University of Nevada, Reno will be replicating the Thailand study on Cambodian rivers as part of their Wonders of the Mekong project, a comprehensive approach to fish conservation, economics and cultural values.

Boston, Mass. - Even as tens of thousands of Americans test positive for COVID-19 each day, physicians still aren't sure why some people experience mild to no symptoms while others become critically ill. New research led by Robert E. Gerszten, MD, Chief of the Division of Cardiovascular Medicine at Beth Israel Deaconess Medical Center (BIDMC) sheds new light on the genetic risk factors that make individuals more or less susceptible to severe COVID-19. The findings, published in a letter in the New England Journal of Medicine, illuminate the mechanisms underlying COVID-19, and potentially open the door to novel treatments for the disease.

"Patients with COVID-19 display a wide array of clinical manifestations and degrees of severity, ranging from flu-like symptoms to acute respiratory distress," said Gerszten, who is also Professor of Medicine at Harvard Medical School. "While pre-existing conditions, particularly cardiovascular and metabolic disease, are risk factors for disease severity and outcomes, the underlying reasons that some people develop life threatening disease while others remain asymptomatic are not well understood."

A growing body of genetic evidence from patients in China, Europe and the Unites States links COVID-19 outcomes to variations in two regions of the human genome, findings which were published in the NEJM. But the statistical association doesn't explain how the differences modulate disease. To do that, scientists need to understand which proteins these sections of the genome code for and the role these proteins play in the body in the context of disease.

Over the last decade, Gerszten and colleagues have generated just such a database -- an immense library of all the proteins and metabolites associated with various regions of the human genome. When they looked up one genomic "hot spot" found to be associated with COVID-19 disease severity, they quickly realized that the very same region was linked to a protein that has recently been implicated in the process by which the SARS-CoV-2 virus infects human cells.

"Groups are increasingly finding genomic hotspots related to diseases, but it's often not clear how they impact the mechanisms of disease," said Gerszten. "We leveraged our huge database -- it's more than 100 terabytes' worth of data -- to very quickly determine that the protein most highly expressed by that region turned out to be a co-receptor for the virus that causes COVID-19, suggesting that this might be a target for therapeutic interventions. The so-called antibody cocktails currently available mostly target the spike proteins on the virus. In turn, our work identifies which proteins in the human body that SARS-CoV-2 and other coronaviruses latch on to."

The second region was linked to a poorly understood protein that appears to play a role attracting immune cells called lymphocytes to sites of infection, which also merits further study. Early analyses from their work also suggest that these genetic variants and proteins may vary across races. Taken together, these findings provide important contributions as the scientific community works rapidly to understand the mysteries of COVID-19.

Wheat researchers at the John Innes Centre are pioneering a new technique that promises to improve gene discovery for the globally important crop.

Crop breeding involves assembling desired combinations of traits that are defined by underlying genetic variation. Part of this genetic variation often stays the same between generations, with certain genes being inherited together. These blocks of genes - very rarely broken up in genetic recombination - are called haplotype blocks. These haplotypes are the units that breeders switch and select between plants to create new crop lines.

In the new study which appears in Communications Biology John Innes Centre researchers led by the group of Professor Cristobal Uauy show that current platforms used by breeders do not provide the resolution needed to distinguish between haplotypes, potentially leading to inaccurate breeding decisions.

They defined shared haplotype-blocks across the 15 bread wheat cultivars assembled in the 10+ Wheat Genome Project a major international collaboration published today in Nature.

To illustrate the application of this haplotype-led approach to support crop improvement, they focused on a specific region of the wheat genome on chromosome 6A.

Through detailed genetic studies and extensive field experiments, they showed that UK breeders are maintaining multiple genes as an intact chromosome 6A haplotype to maximise the expression of desirable traits including flowering time and yield.

Given the low diversity on chromosome 6A, they tested the haplotype approach to discover and introduce novel haplotypes from wheat landraces not subjected to modern breeding.

Combining haplotype knowledge, genetics and field studies, they identified three novel haplotypes in the landraces associated with improved productivity traits in UK environments.

As these haplotypes are not present in modern germplasm, they represent novel variations that could be targeted for yield improvement in elite cultivars, using modern genomic tools.

Lead author Dr Jemima Brinton says: "We used strict criteria to distinguish these shared haplotype blocks from near-identical sequences. We argue that this stringency is essential for crop improvement. The breeding process is poised to undergo an improvement in precision and efficiency through haplotype-led breeding."

The knowledge generated in the study directly affect the breeding and discovery process by allowing scientists to:

Perform focused discovery of novel haplotypes and use breeding strategies to introduce this genetic diversity into modern germplasm.

Prioritise research targets to understand the biological functions of sequences selected by breeders

Perform more precise selection of parents to maximise genetic gains within breeding programmes

Intentionally assemble optimised haplotype combinations

To make the work more accessible to readers, scientists and breeders, the group developed a new haplotype visualisation interface at http://www.crop-haplotypes.com.

The lives of patients hospitalised with COVID-19 are being saved by doctors who are using an existing medical treatment at an earlier stage.

Dr Luigi Sedda of Lancaster University analysed the results from the team at Wrightington, Wigan and Leigh Teaching Hospitals NHS Trust (WWL). Their research has now been published in the prestigious medical journal BMJ Respiratory Open.

He said: "We show that Continuous Positive Airway Pressure (CPAP) in the first days of hospitalisation seems to save between 10% to 20% of patients. However it is important to underline that this was a pilot study with a small sample size, although comforting evidence is starting to emerge elsewhere."

According to NHS England, 96% of people who died with Covid had at least one serious health condition and the majority are over the age of 80.

The team led by Dr Abdul Ashish used the CPAP machines on patients with COVID-19 admitted to the Royal Albert Edward Infirmary in Wigan.

In the case of patients with severe acute respiratory syndrome, COVID-19 may cause the lungs to swell and collapse. Using CPAP treatment, which is often used at home to help people with sleep problems, helps to keep the lungs open and makes breathing easier.

The research conducted by the team showed how CPAP treatment can be delivered effectively in a ward setting, with low resources both across the country and worldwide where intensive care bed availability is limited.

The research has so far helped almost a hundred patients at the Royal Albert Edward Infirmary.

Consultant Respiratory Physician Dr Ashish said: "When you use CPAP early in the admission it stops the patient getting worse, therefore avoiding invasive ventilation techniques. As CPAP is readily available and can be used in a ward setting, we have demonstrated that, when used early, it can be very effective way of treating severe COVID-19 pneumonia.

"We are one of the early adopters of ward based CPAP in the North West and have developed local protocols and pathways by modifying our existing CPAP machines to deliver good outcomes for our patients."

The researchers also found that the early use of CPAP potentially reduces lung damage during the worst of the COVID-19 infection and allows the patient to recover from the inflammatory effects. However, when used later, CPCP does not prevent lung damage thus leading to additional inflammation and a reduction in survival chances.

Dr Martin Farrier, Associate Medical Director, said: ""We are at the forefront of developing care for COVID-19 patients and have developed a very effective treatment strategy for our population who develop lung failure following COVID-19 infection. The people of Wigan can be sure that they are going to get the best care at WWL because we have helped to develop the best care."

He praised Dr Luigi Sedda and his team at Lancaster University.

"This collaboration with Lancaster University has been remarkable and allowed us to deliver high quality research.

"The BMJ Respiratory Open is a very significant journal, but more than that, the results of the work are important in terms of our response to COVID-19 and for our organisation. This is the most important publication on the use of CPAP in treating COVID-19 patients and shows a significant association with a fall in mortality. The way that we treat patients here in Wigan has been influential in the way that patients are now treated in other organisations."

The quantum sensing abilities of nanodiamonds can be used to improve the sensitivity of paper-based diagnostic tests, potentially allowing for earlier detection of diseases such as HIV, according to a study led by UCL researchers in the i-sense McKendry group.

Paper-based lateral flow tests work the same way as a pregnancy test in that a strip of paper is soaked in a fluid sample and a change in colour - or fluorescent signal - indicates a positive result and the detection of virus proteins or DNA. They are widely used to detect viruses ranging from HIV to SARS-CoV-2 (lateral flow tests for Covid-19 are currently being piloted across England) and can provide a rapid diagnosis, as the results do not have to be processed in a lab.

The new research, published in Nature, found that low-cost nanodiamonds could be used to signal the presence of an HIV disease marker with a sensitivity many thousands of times greater than the gold nanoparticles widely used in these tests.

This greater sensitivity allows lower viral loads to be detected, meaning the test could pick up lower levels of disease or detect the disease at an earlier stage, which is crucial for reducing transmission risk of infected individuals and for effective treatment of diseases such as HIV.

The research team are working on adapting the new technology to test for COVID-19 and other diseases over the coming months. A key next step is to develop a hand-held device that can "read" the results, as the technique was demonstrated using a microscope in a laboratory. Further clinical evaluation studies are also planned.

Lead author Professor Rachel McKendry, Professor of Biomedical Nanotechnology at UCL and Director of i-sense EPSRC IRC, said: "Our proof-of-concept study shows how quantum technologies can be used to detect ultralow levels of virus in a patient sample, enabling much earlier diagnosis.

"We have focused on the detection of HIV, but our approach is very flexible and can be easily adapted to other diseases and biomarker types. We are working on adapting our approach to COVID-19. We believe that this transformative new technology will benefit patients and protect populations from infectious diseases."

The researchers made use of the quantum properties of nanodiamonds manufactured with a precise imperfection. This defect in the highly regular structure of a diamond creates what is called a nitrogen-vacancy (NV) centre. NV centres have many potential applications, from fluorescent biomarking for use in ultra-sensitive imaging to information processing qubits in quantum computing.

The NV centres can signal the presence of an antigen or other target molecule by emitting a bright fluorescent light. In the past, fluorescent markers have been limited by background fluorescence, either from the sample or the test strip, making it harder to detect low concentrations of virus proteins or DNA that would indicate a positive test. However, the quantum properties of fluorescent nanodiamonds allow their emission to be selectively modulated, meaning the signal can be fixed at a set frequency using a microwave field and can be efficiently separated from the background fluorescence, addressing this limitation.

The optical results showed up to a five orders of magnitude (100,000 times) improvement in sensitivity compared to gold nanoparticles (that is, a much lower number of nanoparticles were required to generate a detectable signal). With the inclusion of a short 10-minute constant-temperature amplification step, in which copies of the RNA were multiplied, the researchers were able to detect HIV RNA at the level of a single molecule in a model sample.

The work was demonstrated in a laboratory setting but the team hopes to develop the tests so that the results could be read with a smartphone or portable fluorescence reader. This means that the test could, in future, be performed in low-resource settings, making it more accessible to users.

First author Dr Ben Miller (i-sense Postdoctoral Research Associate at the London Centre for Nanotechnology at UCL) said: "Paper-based lateral flow tests with gold nanoparticles do not require laboratory analysis, making them particularly useful in low resource settings and where access to healthcare is limited. They are low cost, portable, and user friendly.

"However, these tests currently lack the sensitivity to detect very low levels of biomarkers. By replacing commonly used gold nanoparticles with fluorescent nanodiamonds in this new design, and selectively modulating their (already bright) emission of light, we have been able to separate their signal from the unwanted background fluorescence of the test strip, dramatically improving sensitivity."

Co-author Professor John Morton, Director of UCL's Quantum Science and Technology Institute (UCLQ), said: "This interdisciplinary collaboration between UCLQ and the i-sense team in the LCN is a fantastic illustration of how foundational work on quantum systems, such as NV centre in diamond, can evolve from the lab and play a crucial role in real-world applications in sensing and diagnostics. Researchers at UCLQ are exploring and enabling the impact of these and other quantum technologies by working with industry and other academic research groups."

DES PLAINES, IL -- Advanced practice providers (APPs) have lower productivity compared with emergency department physicians, seeing fewer and less complex patients and generating less relative value units per hour, and having no apparent impact on patient satisfaction and safety metrics. That is the conclusion of a study to be published in the November 2020 issue of Academic Emergency Medicine (AEM), a journal of the Society for Academic Emergency Medicine (SAEM). This is the first known study to examine the impact of ED APP staffing on productivity, flow, safety, and experience

The lead author of the study is Dr. Jesse Pines, the national director for clinical innovation at US Acute Care Solutions (USACS) and a professor of emergency medicine at Drexel University, Philadelphia. In this role, he focuses on developing and implementing new care models including telemedicine, alternative payment models, and also leads the USACS opioid programs.

The study suggests that advanced practice providers can be effectively integrated into EDs with staffing models accounting for the lower productivity of advanced practice providers compared to physicians with no apparent negative impact on ED flow, clinical quality, or patient experience. Greater levels of advanced practice provider coverage appear to allow physicians to care for higher?acuity cases while also allowing advanced practice providers to care for a lower, but significant number of patients requiring hospital admission and other critical care services.

While advanced practice providers are currently utilized primarily for low?acuity cases, the finding of advanced practice providers independently evaluating critically ill ED patients suggests the potential for enhanced use of advanced practice providers in EDs. However, advanced practice provider use did not result in economies of scale given the higher productivity of physicians even when accounting for their similarly higher salary.

The findings are discussed with the author in a recent AEM podcast, "Taking Care of Patients Everyday With Physician Assistants and Nurse Practitioners." An accompanying invited commentary by Zane and Michael, "The Economics and Effectiveness of Advanced Practice Providers Are Decidedly Local Phenomena," provides expert perspective of APPs in contemporaneous emergency care.

The next time you visit a lake or the seashore, take a deep breath. As you exhale, take a moment to be thankful for the little things: specifically, for the microscopic, single-celled algae in the soil and waters all around you that are extracting the carbon dioxide you just exhaled and incorporating it into sugars that will eventually be used by every other organism in the biosphere. About 30% of this activity, globally, is carried out by a specialized structure in algae called the pyrenoid.

To visualize a pyrenoid, think of a pomegranate. The pyrenoid contains kernels of Rubisco, the enzyme that carries out the molecular work of incorporating carbon dioxide into sugars. These kernels are embedded in a supportive flesh, or matrix, of other proteins, that is itself surrounded by an outer shell made of starch. The fruit is a bit worm-eaten; it is riddled with fingerlike channels -- actually, tubules enclosed by membrane -- that deliver concentrated carbon dioxide to the Rubisco kernels. The tubules are important to pyrenoid function because waterborne algae such as Chlamydomonas reinhardtii would otherwise struggle to get enough carbon dioxide to keep Rubisco operating at peak capacity.

The pyrenoid presents several enigmas for scientists. For example, how the proteins that make up the pyrenoid are routed there, and how they organize into such a complex arrangement, has been an enduring mystery. New work from the laboratory of Martin Jonikas, an Assistant Professor in the Department of Molecular Biology at Princeton, and collaborators, has now solved this riddle.

"The key initial discovery was made by chance," says Jonikas.

Research Molecular Biologist Moritz Meyer and colleagues were trying to identify what proteins are present in the pyrenoid besides Rubisco. To do this, they used an antibody: a protein that, like a key, attaches to other proteins that possess a specific, matching lock. Meyer and colleagues planned to crack open algae and then add an antibody that binds a particular matrix protein to the resulting molecular soup. By pulling on the antibody, the scientists could drag that protein out. Any other proteins that bind to the antibody's target protein would come along for the ride, and the scientists could then determine whether any of them were previously unknown pyrenoid components. But the experiment didn't turn out as expected.

"We noticed that the antibody directly bound to several pyrenoid-localized proteins," says Jonikas. In other words, they'd just discovered that all these proteins possess a lock matching their antibody's key. Closer examination of the proteins revealed the existence of a sequence of amino acids, or motif, that is present in the antibody's original target and also appears in all of the other proteins.

"We hypothesized that this motif may serve as a signal that targets the proteins to the pyrenoid, and the experiments we did support this hypothesis," explains Jonikas. "Removing the motif from one of the motif-containing proteins caused it to no longer localize to the pyrenoid, while adding it to non-pyrenoid proteins caused them to localize to the pyrenoid."

Meyer and colleagues found that the motif binds to Rubisco. This explains how the pyrenoid forms: its component proteins remain loose in the cell until they bump into Rubisco and become trapped.

"Several of the proteins do not simply localize to the pyrenoid matrix, but rather appear to localize to the interfaces between the matrix and the pyrenoid's two other sub-compartments, the pyrenoid tubules and the starch sheath," notes Jonikas. This may allow the proteins to self-organize into the complex pyrenoid structure.

"The study represents an exquisite example of investigative science," says Dr. Howard Griffiths, Professor of Plant Science at Cambridge University in the United Kingdom. Dr. Griffiths has collaborated with Jonikas's group on other studies, but he was not involved in this work.

"They used clever experimental manipulations to prove that a common motif could allow the specific linker to form the Rubisco matrix, and anchor other key elements both internally to the thylakoid tubules, and the starch sheath towards the periphery," says Griffiths. "Overall, the report by Meyer and colleagues has made a significant contribution to our understanding of pyrenoid form and function, with relevance both for understanding aquatic primary productivity, and to underpin approaches seeking to incorporate such a mechanism to 'turbocharge' photosynthesis in terrestrial crop plants."

Despite their reputation, rats are surprisingly sociable and actually regularly help each other out with tasks. Researchers at the Universities of Göttingen, Bern and St Andrews have now shown that a rat just has to smell the scent of another rat that is engaged in helpful behaviour to increase his or her own helpfulness. This is the first study to show that just the smell of a cooperating individual rat is enough to trigger an altruistic and helpful response in another. The research was published in the Proceedings of the Royal Society B.

It is well known that rats will help each other out. What the researchers wanted to know was whether the rat's odour during this behaviour had any effect on another rat's helpfulness. They therefore carried out a series of tests to study the importance of the scent of a rat while making cooperative decisions. The rats being studied could choose to help another rat by pulling a platform containing a reward towards the other rat's cage. This provided food for the other rat but did not have any immediate benefit for them personally. The researchers then provided the test rats either with the smell of a rat that was being helpful to another rat in a different room or with the smell of a rat that was not engaged in helpful behaviour. The researchers were surprised to find that just the scent of a rat engaged in helpful behavior was enough to illicit helpful behaviour in the other.

Dr Nina Gerber from the Wildlife Sciences at the University of Göttingen, who led the research, says: "Test rats increased their own helping behaviour when they were presented with the smell of a helpful rat. Remarkably, this holds true even though they did not experience this helpful behaviour themselves." She goes on to say, "Furthermore, such a 'smell of cooperation' depends on the actual activity of helping and is not connected to an individual rat. There isn't a "special smell" for certain nice rats: the same individual can release the scent of being helpful or not, depending solely on their behaviour."

The researchers concluded that physical cues - such as smell - might be even more important for rats to encourage cooperation than actual experiences. Gerber adds, "Even though people do not seem to rely on communication through scent in the way rats do, some studies indicate that scent is key for finding partners, or that smelling certain chemicals can increase trust in others. Whether there is such a 'smell of cooperation' in humans, however, would be an interesting question for future studies."

Astrophysicists from Far Eastern Federal University (FEFU) joined the international research team for explaining the difference in the results of observation of the comet 41P/ Tuttle - Giacobini - Kresak. Researchers believe that data obtained by three independent teams are complementary and its complex analysis helps to unravel the mystery of dust chemical composition of comet 41P and other conundrums of the Universe. A related article appears in Astronomy & Astrophysics.

The activity of comets is more complex than it appeared to be, one of the research outcomes says. The chemical composition of a cometary coma (gas-dusty environment of the nucleus) is able to change very rapidly, literally during the day. That is because of the Sun affects the nucleus of a comet approaching.

Researchers all over the Globe try to get data on the chemical composition of comets via analyses of the light refracted by its dust particles. However, the information about the color spectrum of comets differs every time, depending on different observation epochs and different phase angles (angle Earth-comet-Sun).

The present research paper postulates the controversial data sets obtained due to different sets of photometric filters and areas (apertures) of research are steady.

"At least three groups of researchers who observed comet 41P in 2017 came up with different results. The comet color ranged from red to blue. We have explained in detail why this happened", Anton Kochergin says", one of the authors of the study, a PhD student FEFU School of Natural Sciences. "Usually, the final color is normalized by taking into account the different bandwidths of the photometric filters applied. However, in many studies, the color of celestial bodies is interpreted independently of a particular set of photometric filters. We show that this is not valid for all cases. The reason the comet color differs is exactly sets of various photometric filters. In addition, the choice of the size of the calculation area, i.e. aperture, is of great importance. This is a certain radius around the cometary coma in the pictures from observatories, which scientists define as an area of research. Having decided on the aperture, they analyze only the signal inside this field".

The choice of the aperture determines which processes and results are included in the analysis. For example, a gas from a diatomic carbon molecule (C2): there are parent molecules (called CHON particles in the literature), which become a source of C2 upon photodissociation. This dissociation occurs at a certain distance from the comet's nucleus, which in turn depends on the comet's distance from the Sun. With the right aperture chosen, one can exclude most of the signals that C2 molecules give focusing on analyses of the dust component of the coma.

Anton Kochergin emphasized that the opposite data about the color of the comet, collected by different groups using different sets of photometric filters, only benefits the researchers. It is impossible to give a thorough description of the color (the color is directly related to the chemical composition of the dust of a cometary coma), and the chemical composition after just one observation. It is necessary to observe and determine the characteristics in dynamics. The more measurements made, the more accurate the conclusions are.

"In practice, this allows us to probe into the microphysical properties of cometary dust, and the processes run in a cometary coma. With such information, we will shed light on the evolutionary processes of the Solar system. Many scientific groups around the world are working inside this fundamental area", explains Anton Kochergin.

Scientists were able to model the results of color measurements of comet 41P, receives almost simultaneously via different photometric filters in different locations. Although the blue color was gained in one case and the red in the other, the researchers found that both results were consistent with the actual behavior of cometary dust particles in coma 41P. One can copy these results via simulating light scattering by dust particles of the pyroxene mineral. Pyroxene is a silicate material that is part of the lunar soil and was also delivered from the asteroid Itokawa and discovered in the comet 81P / Wild 2. Pyroxenes are a part of cometary matter and are well studied in laboratories.

Researchers to further cooperate in observing celestial bodies from different Earth locations. The routine helps to catch up with the object under investigation in case of adverse weather conditions at the location of one of the observatories. This also brings additional data in the case of different sets of filters applied by different teams. In the observation schedule of the international collaborators, all comets and asteroids their gear is capable of tracing.

The present results became possible due to the collaboration of scientists from Astronomical Observatory, Taras Shevchenko National University of Kyiv, Humanitas College, Kyung Hee University (South Korea), Space Science Institute (USA), Astronomical Institute of the Slovak Academy of Sciences, Main Astronomical Observatory of National Academy of Sciences, School of Natural Sciences, Far Eastern Federal University, Ussuriysk Observatory of the Institute of Applied Astronomy of the Russian Academy of Sciences.

Previously, FEFU astrophysicists teamed up with Russian and foreign colleagues to observe the ATLAS comet, which disintegrated when approaching the Sun. They brought up a conclusion that carbon found in the nucleus of the comet would help to determine the age of comets in the Solar system.

Bottom Line: Among patients with glioblastoma receiving an immune checkpoint inhibitor, those who received the corticosteroid dexamethasone at baseline for cerebral edema had significantly worse overall survival.

Journal in Which the Study was Published: Clinical Cancer Research, a journal of the American Association for Cancer Research

Author: David A. Reardon, MD, clinical director of the Center for Neuro-Oncology at Dana-Farber Cancer Institute in Boston

Background: "Dexamethasone is a potent corticosteroid that is often prescribed to patients with glioblastoma to treat symptoms related to cerebral edema, or swelling in the brain," said Reardon. "Cerebral edema is a common yet potentially life-threatening complication for patients with glioblastoma, and treatment with corticosteroids can help to suppress the inflammation in the brain," he added.

"Historically, patients with glioblastoma have been empirically treated with dexamethasone, even without symptoms, with many clinicians prescribing steroids for prolonged periods of time, out of a concern that patients may start to develop edema," Reardon continued. "Our study was designed to look at that paradigm of clinical practice, particularly in the immunotherapy era, and determine if there could be negative consequences associated with dexamethasone use among patients with glioblastoma treated with immune checkpoint inhibitors."

How the Study was Conducted & Results: Reardon and colleagues evaluated the effect of concurrent dexamethasone administration with an immune checkpoint inhibitor (anti-PD-1 therapy) in syngeneic murine glioblastoma models. In an immunosensitive mouse model, which is inherently responsive to immune checkpoint blockade, the researchers found that the addition of dexamethasone to anti-PD-1 therapy resulted in reduced survival in a dose-dependent manner. Additionally, in an immunoresistant mouse model, which Reardon noted is more representative of human glioblastoma, the addition of dexamethasone to anti-PD-1 therapy or anti-PD-1 therapy plus radiotherapy also resulted in reduced survival.

"In our preclinical studies, we found that steroids had a significant detrimental effect on the efficacy of anti-PD-1 therapy, even in an immunosensitive model, which over-predicts the benefit of immune checkpoint blockade in glioblastoma patients," said Reardon.

The researchers next analyzed overall survival data from 181 patients with glioblastoma treated with either anti-PD-1 or anti-PD-L1 therapy at Dana-Farber Cancer Institute who were diagnosed before April 1, 2019. This patient population was heterogeneous, with patients receiving treatment through a clinical trial or on a compassionate use basis; roughly 76 percent were treated for recurrence, and roughly 24 percent were treated for a new diagnosis. Of these 181 patients, around 35 percent were taking dexamethasone at baseline.

Reardon and colleagues evaluated the potential detrimental effect of dexamethasone using multivariable analysis, where they adjusted for a variety of factors, including disease setting (newly diagnosed versus recurrent), tumor volume at treatment initiation, age, and extent of resection, among the 163 patients that had complete annotated data for relevant prognostic factors. Compared with patients who were not taking dexamethasone at baseline, patients treated with dexamethasone had roughly twice the risk of death. Further, baseline use of dexamethasone was the strongest identified negative risk factor for overall survival.

Author's Comments: "Our results suggest that we should try to avoid dexamethasone among patients with glioblastoma who are treated with immunotherapy, and if corticosteroids are clinically required, we should use these drugs judiciously," Reardon said. "Further, our results highlight that other strategies for the treatment of cerebral edema that do not have such a broad anti-inflammatory effect critically need to be investigated."

Study Limitations: Limitations of the study include the retrospective nature of the clinical analyses. Further, in their preclinical studies, the researchers solely evaluated the effect of dexamethasone on the efficacy of anti-PD-1 treatment. "Whether the same observations would occur with other immunomodulatory checkpoint targeting agents, or even other immunotherapy treatments--such as vaccines, adoptive cellular therapies, or genetically engineered oncolytic viruses--remains to be evaluated," Reardon said.

Funding & Disclosures: This study was sponsored by The Jennifer Oppenheimer Cancer Research Initiative; The Ben and Catherine Ivy Foundation; Hope It's A Beach Thing, an annual 5K for brain tumor research; and the Pan- Mass Challenge, a bike-a-thon that raises money for the Dana-Farber Cancer Institute. This study was also funded by the National Institutes of Health.

OTTAWA, ON - NOV. 25, 2020 - A new study published in The BMJ shows that people who had surgery to improve blood flow in their legs under spinal or epidural anesthesia were less likely to die than those who were given general anesthesia.

General anesthesia involves using drugs to make a patient unconscious and inserting a tube into their windpipe to help with breathing. Spinal and epidural anesthesia directly freeze the nerves to the legs and can be combined with lighter forms of sedation which do not involve a breathing tube.

This study, the largest of its kind, looked at medical records of 20,988 people who had leg artery bypass surgery in Ontario, Canada, between 2002 and 2015. Approximately two thirds of these surgeries used general anesthesia and a third used spinal or epidural anesthesia.

The researchers found that 646 of the patients who had general anesthesia (4.4 percent) died within 30 days of their surgery compared to 204 of the patients who had spinal or epidural anesthesia (3.2 per cent). The results remained the same after the researchers adjusted for differences between the groups, such as how sick the patients were before surgery.

"We estimate that this finding could save at least 100 of the patients' lives who undergo leg artery bypass surgeries every year both in Canada and the United States," said lead author Dr. Derek Roberts, a vascular and endovascular surgeon at The Ottawa Hospital and incoming assistant professor at the University of Ottawa. "We hope to conduct a randomized controlled trial to confirm these results, but in the meantime our findings suggest that we should increasingly perform more of these types of surgeries using spinal or epidural anesthesia techniques."

"We were surprised to find that some hospitals did these types of surgeries under spinal or epidural anesthesia more than 90 per cent of the time, while in others it was less than one per cent," said senior author Dr. Daniel McIsaac, associate scientist and anesthesiologist at The Ottawa Hospital, associate professor at the University of Ottawa, and adjunct scientist at ICES. "We hope this study will help patients and physicians make more informed decisions about what type of anesthetic is best for each patient."

The study also found that patients who had spinal or epidural anesthesia were able to leave the hospital half a day earlier than those who had general anesthesia.

The researchers estimate that if all leg artery bypass surgeries were done with spinal or epidural anesthesia, it could save $50 million in health care costs each year in Canada. In Ontario, the vast majority of these surgeries are done in specialty centres that can easily perform spinal or epidural anesthesia.

Close to 20,000 people have leg artery bypass surgery in Canada and the United States every year.