Weather Extremes by 2060

In this visualization, based on weather and climate observations from NASA's MERRA dataset, the northern hemisphere's polar jet stream is seen as a meandering, fast-moving belt of westerly winds traversing the lower layers of the atmosphere. Credit: NASA

 New research provides insights into how the position and intensity of the North Atlantic jet stream has changed during the past 1,250 years. The findings suggest that the position of the jet stream could migrate outside of the range of natural variability by as early as the year 2060 under unabated greenhouse gas emissions, with potentially drastic weather-related consequences for societies on both sides of the Atlantic.

Matthew Osman steadies an ice core
drilling barrel into the Greenland Ice Sheet
Credit: Sarah Das/Woods Hole Oceanographic Institution

Led by Matthew Osman, a postdoctoral research associate at the University of Arizona Climate Systems Center, the study is published in Proceedings of the National Academy of Sciences.

Familiar to air travelers flying between North America and Europe, the North Atlantic jet stream is the ribbon of prevailing westerly winds circling the Arctic. Often called the "polar jet," these high-altitude winds impact weather and climate across eastern North America and western Europe, accounting for between 10% and 50% of variance in annual precipitation and temperature in both regions. However, little is known about how the jet stream varied during the past, or how it might change in the future.  

Osman's research team collected glacial ice core samples from nearly 50 sites spanning the Greenland ice sheet to reconstruct changes in windiness across the North Atlantic dating back to the eighth century.  The reconstructions suggest that natural variability has thus far masked the effect of human-caused warming on mid-latitude atmospheric dynamics across annual and longer timescales.

"For most places on Earth, direct climate observations typically do not span more than a few decades," Osman said. "So, we haven't had a great sense of how or why the jet stream changes over longer periods of time. What we do know is that extraordinary variations in the jet stream can have severe societal implications, such as floods and droughts, due to its impacts on weather patterns and so, in terms of thinking about the future, we can now begin to use the past as a sort of a prologue."

The work reveals that although natural variability has largely controlled the position of the North Atlantic jet stream, continued warming could cause significant deviations from the norm. In particular, model projections forecast a northward migration of the North Atlantic jet stream under 21st-century warming scenarios. Such migration could render the jet stream significantly different within a matter of decades.

Although the polar jet stream blows most swiftly near the typical cruising altitudes of planes, the band of winds actually extends all the way to the ground. While of lesser intensity, Osman explained, near the ground the winds are often referred to as storm tracks. Storm tracks impact weather and climate across Greenland, affecting the island's precipitation and temperature changes. By analyzing year-to-year variations in the amount of

snowfall archived in Greenland ice cores, as well as the chemical makeup of the water molecules comprising those annual snow layers, the researchers were able to extract centuries-old clues into how the jet stream changed.

"These layers tell us about how much precipitation fell in a given year and also about the temperatures that air masses were exposed to," Osman said.

Weather events like this summer's heat wave in the Pacific Northwest and the floods in Europe are some recent examples of how the jet stream affects weather patterns based on its intensity or location in the short term, Osman said. But societally significant changes also occur across longer time scales; reconstructing the jet stream's past revealed that in some years, it could be far north, only to venture more than 10 degrees farther south a few years later.

"Such variations have huge implications on the types of weather that people might experience at a given place," Osman said. "For example, when the jet stream is situated farther south, the normally dry Iberian Peninsula tends to experience milder, moister conditions. But, as the jet stream migrates northward, much of that moisture also moves away from Iberia towards already-wet regions of Scandinavia. A poleward-shifted jet stream in the future thus might have similar, but more permanent, consequences."

The team was able to match certain changes in wind speed and geographical shifts to historical weather-related calamities. For example, during a famine that gripped the Iberian Peninsula in 1374, the jet stream was situated unusually far north. Similarly, two famine events in the British Isles and Ireland in 1728 and 1740 coincided with years that winds blew at nearly half their usual intensity, dramatically cooling temperatures and reducing precipitation. The latter of these events, in 1740, is estimated to have cost the lives of nearly half a million people.

Osman and his co-authors expect that any future shifts in the North Atlantic jet stream would also have dramatic implications on day-to-day weather and ecosystems, with trickle-down effects impacting national economies and societies.

"Our results serve as a warning: Although pushing the jet stream beyond its natural range would be problematic, its ultimate trajectory is still largely in our control," he said.

Source/Credit: University of Arizona/Daniel Stolte

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Pandemic proofing our future

Dr Kirsty Short Credit: University of Queensland

A project developing a test and treatments that would be effective against multiple viral threats could become a cornerstone of the world’s response to future pandemics.

University of Queensland virologist Dr Kirsty Short has been awarded $1.37 million from the National Health and Medical Research Council (NHRMC) to use her understanding of the immune response in COVID-19 and influenza to investigate a future pandemic response.

“The reality is the world was not prepared for COVID-19, so our aim is start developing broad spectrum diagnostics and drugs that work against multiple viruses,” Dr Short said.

“If we develop these things now, we can stockpile them so that any time there’s a viral outbreak, we have them on hand, ready to deploy.”

Dr Short said the project would look for a genetic marker or ‘signature’ in people with COVID-19 that could be used in a rapid test that can be picked up before the viral genetic material can be detected by standard diagnostic PCR.

“We’re working with health authorities to access samples from people going through hotel quarantine and we’re combining that with machine learning to try and identify a signature that will then allow for the development of early diagnostics.”

While existing anti-viral therapies are developed for a specific virus, Dr Short’s project will investigate a treatment that targets the immune response to multiple viruses.

“An out-of-control inflammatory response is the reason some people become seriously ill in a coronavirus infection, in a flu infection and in many other pandemic viruses,” she said.

“By targeting that response, we can develop an effective therapy that is useful against any pandemic virus that you could anticipate.”

Dr Short said identifying a ‘host signature of infection’ would also allow for earlier detection of any virus, benefiting both the public health response and individual patients.

“If we take SARS-COV-2 as an example, you can be infected with the virus but initially get a negative PCR test and maybe five days later you test positive.

“With an early diagnostic test, we could determine whether an individual carries the ‘host signature’, which would allow us to identify those likely to come down with an infection.

“If you didn’t have the signature, you might be released earlier from quarantine or maybe allowed to home quarantine, making the process less arduous for everyone.”

The test and therapies would initially be rolled out in Australia, but Dr Short hoped they would also make a difference elsewhere.

“Ideally, we could have this as part of a global pandemic preparedness plan, because ultimately there will be another,” Dr Short said.

 “What I really fundamentally hope is that this project will ensure that the next outbreak will be of much reduced severity and consequences compared to the COVID-19 pandemic.”

UQ received NHMRC grants for five Centers for Research Excellence (CRE), two Partnership Projects and 29 Investigator Grants in the latest round of funding.

Source/Credit: University of Queensland

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Molecular Achilles heel of cancer cells discovered

Tissue samples from 144 patients with colorectal cancer were analyzed
by mass spectrometry as part of the study. Image: W. Filser / TUM

 Changes in fat metabolism of colorectal cancer cells demonstrated for the first time Molecular Achilles heel of cancer cells discovered

Where does a malignant tumor obtain the energy to keep growing? That is a key question in cancer research. If the energy source were known, the tumor could be “starved”. Researchers have now laid the foundation for this approach: For the first time, they have demonstrated a fundamental difference in the fat metabolism of healthy cells in the inner lining of the intestinal tract and colorectal cancer cells. This could point the way to new treatment options targeting the changed metabolism of the tumor.

Some past measurements have also indicated significant differences in how fat is metabolized by healthy and cancerous cells. However, the results of this work have been highly inconsistent. Some investigations appeared to support such differences while others reported contrary results. “This question has been hotly debated”, says Prof. Klaus-Peter Janssen, a biologist at TUM’s university hospital Klinikum rechts der Isar.

To obtain clarity, surgeons at Klinikum rechts der Isar took tissue samples from the surgically removed tumors of 144 colorectal cancer (CRC) patients. The samples were immediately prepared onsite and then analyzed using mass spectrometry at the Institute for Food & Health (ZIEL) in Freising and at the University Hospital Regensburg. This is a biochemical procedure for the quantitative measurement of the type and mass of certain molecules in specially prepared tissue samples – in this case around 200 different fat molecules.

To prove that the results were reproducible, and not merely accidental, the patients were divided into two cohorts. The tissue samples were then analyzed separately and the results compared. In addition, the researchers incorporated the analysis of samples from another cohort of 20 CRC patients investigated independently at the University of Dresden.

In all three cohorts, the researchers were able to show that “CRC cells indeed have a specific lipid signature,” says Janssen. This means that they show a certain pattern of different lipid molecules – “A fingerprint, in a sense, with which we can distinguish between cancer cells and normal cells with a high degree of certainty. This signature also has prognostic relevance. In other words, it can be used to predict the course of the illness.”

The changes in the lipidome – i.e. the totality of lipids in a cell – related mainly to sphingo- and glycerolipids. These differences were also reflected at the genomic level: The team showed that the activity of certain genes that provide the blueprint for various enzymes was also significantly altered. Enzymes are functional proteins that play an important role in the production of metabolic products such as lipids, for example. This might be a starting point for cutting off the energy supply to cancer cells and thus slowing their growth – by finding drugs to activate or inhibit individual enzymes in order to starve the cancer.

“Lipids in tissue samples are highly sensitive molecules that are sometimes subject to rapid change or decay,” says Janssen. Unless tissue samples are shock-frozen immediately after dissection and properly handled and stored, some of the highly sensitive lipids will already be destroyed. This will invalidate the results of the analysis. That could be a reason for the inconsistent results of past studies: This kind of close cooperation is not guaranteed everywhere.

Janssen and his team were also able to clearly demonstrate that the lipid profile of the tissue samples undergoes changes when stored under sub-optimal conditions and over extended periods. They showed that some lipids remain stable in tissue samples and are therefore suitable as biomarkers, while others rapidly deteriorate and in some cases are entirely degraded within just an hour of the operation.

The metabolisms of healthy and diseased cells are different – and thus the types and quantity of the molecules produced in them such as sugars, proteins and lipids - i.e. fatty molecules. Lipids are important for obtaining and storing energy in cells, but also as important building blocks for cell membranes and as signaling molecules.

As the totality of all lipids in a cell is referred to as the lipidome, this term gives rise to “lipidomics” – an entirely new field of research. It compares the lipidome of different cells and seeks to draw conclusions based on the differences and changes: For example, how does the lipid profile of a CRC cell differ from that of a healthy cell in the lining of the intestinal tract? Are there changes typically seen in cancerous cells – and how can this knowledge be used to develop new drugs?

Lipidomics a subfield of the better-known area of metabolomics, which includes all metabolic products of a cell – the “metabolome”. Many research groups working in this area have generally focused on sugars, nucleic acids (DNA, RNA) and proteins, which are easier to analyze. Lipids are not only more sensitive. “For a long time, it was also difficult and time-consuming to measure them with conventional methods,” says Janssen. “They have become a focal point of research only since that changed.”

Publications:

Josef Ecker, Elisa Benedetti, Alida S.D. Kindt, Marcus Höring, Markus Perl, Andrea Christel Machmüller, Anna Sichler, Johannes Plagge, Yuting Wang, Sebastian Zeissig, Andrej Shevchenko, Ralph Burkhardt, Jan Krumsiek, Gerhard Liebisch, Klaus-Peter Janssen: The Colorectal Cancer Lipidome: Identification of a Robust Tumor-Specific Lipid Species Signature, Gastroenterology, Volume 161, Issue 3 (2021).

Source/Credit: Technical University of Munich

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Flipping the “genetic paradox of invasions”

A close-up look at a green crab. Image credit: Ted Grosholz

The green crab, Carcinus maenas, is considered a globally distributed invasive species, an organism introduced by humans that eventually becomes overpopulated, with increased potential to negatively alter its new environment. Traditionally, it’s been assumed that successful populations contain high genetic diversity, or a variety of characteristics allowing them to adapt and thrive. On the contrary, the green crab - like many successful invasive populations - has low genetic diversity, while still spreading rapidly in a new part of the world.

A new study led by Carolyn Tepolt, an associate scientist of biology at Woods Hole Oceanographic Institution, is investigating the adaptive mechanisms of the green crab along the west coast of North America, where it has shown extensive dispersal in the last decade despite minimal genetic diversity. The study was published recently in Molecular Ecology and is a collaboration between WHOI, the University of California at Davis, Portland State University, and the Smithsonian Environmental Research Center.

“Invasive species like these are generally unwelcome. Green crabs can compete with native species, rip up eelgrass ‘nurseries’, and eat small shellfish before they have a chance to be harvested. Green crabs can be an ecological menace and an economic burden,” Tepolt said. “In this study, we found that one of the world's most serious marine invasive species has evolved specific genetic variation that likely helps it adapt to new environments really quickly, even when it's lost a lot of genetic diversity overall.”

Genetic diversity refers to small individual-to-individual differences in DNA, and often translates into a range of different inherited traits within a species. A population with high genetic diversity is more likely to include individuals with a wide range of different traits. In order for a population to adjust to changing environments, this variation can be crucial - or so scientists have often thought. Invasive species often challenge this assumption, successfully spreading in new regions despite low genetic diversity caused by descending from a small number of initial colonists.

This study focuses on a northwest Pacific population of green crab that has spread within the last 35 years from a single source. High-profile marine invasive species, such as green crabs, often live across thousands of kilometers of ocean, spanning countless environmental differences, both small and large. Using six U.S. west coast locations spanning over 900 miles from central California to British Columbia, Tepolt and her team examined the species’ genetic structure at thousands of places across its genome. While this population has lost a large amount of overall genetic diversity relative to its European source, a piece of DNA associated with cold tolerance in a prior study appears to be under strong selection from north to south across its invasive West Coast range.

This may represent a type of genetic feature - a balanced polymorphism - that evolved to promote rapid adaptation in variable environments despite high gene flow, and which now contributes to successful invasion and spread in a novel environment. Researchers do occasionally find incredibly successful populations that have passed through severe bottlenecks, dramatically decreasing their genetic diversity relative to their source. This study is amplifying the need to consider that diversity at specific parts of the genome (rather than genome-wide diversity) may play a critical role in resilience in new or changing environments.

“This is exciting for two main reasons. First, the study tests a partial resolution to ‘the genetic paradox of invasions’, demonstrating that variation at key parts of the genome permits rapid adaptation even in a population with low overall genetic diversity. Second, it suggests that high gene flow in a widespread species’ native range may generate evolutionary mechanisms, like this one, which provide that species with the substrate for rapid adaptive change as it spreads across new environments,” Tepolt explained.

Identifying invasive species spread can also be a job for non-scientists. As the climate changes and as humans get better and better at moving stuff around the globe, there’s more potential for species to come along for the ride and expand into new environments. Tepolt says it’s important to keep an eye out for cues, changes in the environment and possible new species in places they haven’t been before. She recommends seizing the opportunity to tell officials and researchers if there is something unusual at the coastline. There may be signs at beaches and boat ramps asking people to keep a lookout for particular species and giving contact information. If there are suddenly green crabs in an area for the first time, for example, on the West Coast in the Salish Sea and in Alaska, they likely should not be there and should be reported.

Source/Credit: Woods Hole Oceanographic Institution

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New global dashboard sheds light on reasons behind COVID vaccine hesitancy, refusal

 

A woman works in a face mask manufacturing in factory in Harare, Zimbabwe. 
Credit: INTERNATIONAL LABOUR ORGANIZATION

In an ongoing global survey, more than half of those who are unvaccinated in more than 50 countries indicated in August that they definitely or probably won't get a COVID-19 vaccine. A new dashboard, launched today by the Johns Hopkins Center for Communication Programs, unpacks that survey data to help explain why—and how experts can work to increase acceptance rates.

The researchers found that the primary reasons around the world for resisting vaccination include fears about side effects, a desire to wait until more people have had the shots so they know they are safe, and a lack of confidence in whether the vaccine really works.

"Our analysis of this large trove of data finds that while vaccine hesitancy is real, there are many people around the globe who can be encouraged to get their doses—if public health officials can build and share their messages to address their concerns."

Dominick Shattuck
Johns Hopkins Center for Communication Programs

These latest survey results, based on responses gathered between Aug. 16 and 31, can be found in the new COVID Behaviors dashboard, an interactive tool created with data collected from more than 12 million people from 115 countries. The survey—believed to be the world's largest daily survey of global COVID knowledge, attitudes, and practices—has been fielded every day since May 20, 2021. It is expected to continue until the end of this year, and new data will become available every two weeks.

The dashboard is intended to be used by policymakers, government officials, and public health practitioners at national and sub-national levels to better understand the behavioral drivers behind vaccine uptake, masking, and physical distancing that can prevent the spread of COVID-19.

"Our analysis of this large trove of data finds that while vaccine hesitancy is real, there are many people around the globe who can be encouraged to get their doses—if public health officials can build and share their messages to address their concerns," says Dominick Shattuck, CCP's director of monitoring evaluation and learning and one of the leaders of the COVID behaviors project.

Adds Marla Shaivitz, CCP's director of digital strategy: "The dashboard can be used as a roadmap for policymakers to identify and engage with citizens to encourage them to be vaccinated to protect themselves and their families from COVID-19. In many countries, this dashboard fills an important data gap. It offers the most comprehensive data some governments have access to on how COVID behaviors are changing and what they can do to intervene."

The dashboard is the product of a collaboration among CCP, the World Health Organization's Global Outbreak Alert and Response Network, and Facebook. The data are generated from the COVID-19 Trends and Impact Survey, which is administered in the United States by the Delphi Group at Carnegie Mellon University and in other countries by the University of Maryland Social Data Science Center. The two universities collect the survey data from a random sample of Facebook users and CCP analyzes the responses.

A previous COVID behaviors dashboard, also led by CCP, was based on smaller, less frequent surveys from June 2020 through March 2021.

In this latest survey, reasons for vaccine hesitancy vary by country. In Senegal, the two most common reasons for hesitancy are concerns about side effects and whether the vaccine will work. Education around vaccine science and side effects could work to encourage vaccine uptake in Senegal. In the Netherlands, however, unvaccinated respondents were most likely to say that they don't believe they need a vaccine. When asked why not, their main reasons were because they are not a member of a high-risk group, or they don't believe COVID-19 is a serious illness. Each underlying perception requires a different messaging response.

The dashboard sheds light on how other behaviors have evolved over the last four months as well. In the United States, for example, 65% of those who responded to the survey between Aug. 16 and 31 said they had been shopping indoors in the previous 24 hours, and two-thirds those who had been shopping said they wore masks. Mask wearing steadily decreased in the U.S. until the middle of July but has been rising since the highly transmissible Delta variant became the dominant strain, and case counts and hospitalizations began rising again to record levels in many states.

In India, where an outbreak has fallen from its May peak, only 29% of respondents had been shopping indoors in the previous 24 hours and the vast majority of them (87%) were wearing masks, suggesting there is a long way to go before things get back to normal.

Since March 2020, a staggering 223 million COVID cases—and 4.6 million deaths—have been reported around the world, according to Johns Hopkins University's COVID-19 dashboard. More than 5.3 billion vaccine doses have been administered globally, though just over 2% of those doses have been administered in Africa.

USAID has sent more than 110 million doses to low- and middle-income countries and COVAX, a worldwide initiative aimed at equitable access to COVID-19 vaccines, has distributed more than 236 million doses. As vaccine access increases, governments will need to develop strategies to sensitize citizens to accurate information and the benefits of vaccines.

In addition to findings about vaccine hesitancy, the dashboard also features data on why many people who want vaccines can't seem to access them. In Brazil, for example, where 65% of the unvaccinated respondents in the Aug. 16-31 survey period said they probably or definitely want a vaccine, 23% of those who want one said they couldn't get a shot because they are not eligible for one, and 34% said there were no appointments available.

Armed with knowledge from the dashboard, officials in those countries can aim to work with local communities to make vaccine appointments more accessible—once vaccines are widely available—and to better spread the word about appointments that are available and when, where, and how to secure them.

"We are at a critical time for global COVID-19 vaccine rollouts, yet populations are oversaturated with information, disinformation, and rumors," says Jeni Stolow of WHO's Global Outbreak Alert and Response Network. "Continuously producing timely evidence-based and effective health communication is a major challenge in this second year of the pandemic. This dashboard can support public health practitioners around the globe in their endeavors to tailor, target, and reinvigorate their local COVID-19 vaccine outreach efforts."

While many unvaccinated people around the world say they are unlikely to get vaccinated, in many countries, large percentages of the population say they would choose to get their children vaccinated once a vaccine becomes available. In India and Guatemala, well over 90% of survey respondents said they would definitely or probably vaccinate their children. Data from Aug. 16 through 31 show the figure was 86% in Mozambique, 72% in the United States, and 47% in Serbia.

"The volume of data that has and will continue to be collected on COVID-19 will be of great value to policymakers and health practitioners, if the data are strategically used," says Douglas Storey, CCP's director for communication science and research. "This dashboard offers deep insights into behaviors around the world and will be a guide for those aiming to stop the spread of this devastating disease."

Source/Credit: Johns Hopkins University

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New tool for analyzing large superconducting circuits

The next generation of computing and information processing lies in the intriguing world of quantum mechanics. Quantum computers are expected to be capable of solving large, extremely complex problems that are beyond the capacity of today’s most powerful supercomputers.

New research tools are needed to advance the field and fully develop quantum computers. Now Northwestern University researchers have developed and tested a theoretical tool for analyzing large superconducting circuits. These circuits use superconducting quantum bits, or qubits, the smallest units of a quantum computer, to store information.

Circuit size is important since protection from detrimental noise tends to come at the cost of increased circuit complexity. Currently there are few tools that tackle the modeling of large circuits, making the Northwestern method an important contribution to the research community.

“Our framework is inspired by methods originally developed for the study of electrons in crystals and allows us to obtain quantitative predictions for circuits that were previously hard or impossible to access,” said Daniel Weiss, corresponding and first author of the paper. He is a fourth-year graduate student in the research group of Jens Koch, an expert in superconducting qubits.

Koch, an associate professor of physics and astronomy in Weinberg College of Arts and Sciences, is a member of the Superconducting Quantum Materials and Systems Center (SQMS) and the Co-design Center for Quantum Advantage (C2QA). Both national centers were established last year by the U.S. Department of Energy (DOE). SQMS is focused on building and deploying a beyond-state-of-the-art quantum computer based on superconducting technologies. C2QA is building the fundamental tools necessary to create scalable, distributed and fault-tolerant quantum computer systems.

“We are excited to contribute to the missions pursued by these two DOE centers and to add to Northwestern’s visibility in the field of quantum information science,” Koch said. 

In their study, the Northwestern researchers illustrate the use of their theoretical tool by extracting from a protected circuit quantitative information that was unobtainable using standard techniques. 

Details were published in the open access journal Physical Review Research.

The researchers specifically studied protected qubits. These qubits are protected from detrimental noise by design and could yield coherence times (how long quantum information is retained) that are much longer than current state-of-the-art qubits.  

These superconducting circuits are necessarily large, and the Northwestern tool is a means for quantifying the behavior of these circuits. There are some existing tools that can analyze large superconducting circuits, but each works well only when certain conditions are met. The Northwestern method is complementary and works well when these other tools may give suboptimal results.

The research was supported by the Army Research Office (Contract No. W911NF-17-C-0024).

Source/Credit: Northwestern University/Megan Fellman

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Fountain of youth for ageing stem cells in bone marrow

Stained calcium (dark brown) in stem cells from the bone marrow: 

Young stem cells (left) produce more material for bone than old stem cells (center). 

They can be rejuvenated by adding sodium acetate (right).

Credit/Source: Pouikli/Max Planck Institute for Biology of Ageing

As we age, our bones become thinner, we suffer fractures more often, and bone-diseases such as osteoporosis are more likely to occur. One responsible mechanism involves the impaired function of the bone-marrow stem cells, which are required for the maintenance of bone integrity. Researchers from the Max Planck Institute for Biology of Ageing and CECAD Cluster of Excellence for Ageing Research at the University of Cologne have now shown that the reduced stem cell function upon ageing is due to changes in their epigenome. They were able to reverse these changes in isolated stem cells by adding acetate. This fountain of youth for the epigenome could become important for the treatment of diseases such as osteoporosis.

Ageing Researchers have been looking at epigenetics as a cause of ageing processes for some time. Epigenetics looks at changes in genetic information and chromosomes that do not alter the sequence of the genes themselves, but do affect their activity. One possibility is changes in proteins called histones, which package the DNA in our cells and thus control access to DNA. The Cologne research group of Peter Tessarz has now studied the epigenome of mesenchymal stem cells. These stem cells are found in bone marrow and can give rise to different types of cells such as cartilage, bone and fat cells.

The epigenetic changes of ageing stem cells

"We wanted to know why these stem cells produce less material for the development and maintenance of bones as we age, causing more and more fat to accumulate in the bone marrow. To do this, we compared the epigenome of stem cells from young and old mice," explains Andromachi Pouikli, first author of the study. "We could see that the epigenome changes significantly with age. Genes that are important for bone production are particularly affected."

Rejuvenation of the epigenome

The researchers then investigated whether the epigenome of stem cells could be rejuvenated. To do this, they treated isolated stem cells from mouse bone marrow with a nutrient solution which contained sodium acetate. The cell converts the acetate into a building block that enzymes can attach to histones to increase access to genes, thereby boosting their activity. "This treatment impressively caused the epigenome to rejuvenate, improving stem cell activity and leading to higher production of bone cells," Pouikli said.

To clarify whether this change in the epigenome could also be the cause of the increased risk in old age for bone fractures or osteoporosis in humans, the researchers studied human mesenchymal stem cells from patients after hip surgery. The cells from elderly patients who also suffered from osteoporosis showed the same epigenetic changes as previously observed in the mice.

A new therapeutic approach against osteoporosis?

"Sodium acetate is also available as a food additive, however, it is not advisable to use it in this form against osteoporosis, as our observed effect is very specific to certain cells. However, there are already first experiences with stem cell therapies for osteoporosis. Such a treatment with acetate could also work in such a case. However, we still need to investigate in more detail the effects on the whole organism in order to exclude possible risks and side effects," explains Peter Tessarz, who led the study.

Source/Credit: Max-Planck-Gesellschaft

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Engineers grow pancreatic organoids

MIT and Cancer Research UK Manchester Institute researchers have
developed a synthetic gel that can be used to grow tiny
pancreatic organoids, seen here, from human pancreatic cells.
Credits: Courtesy of the researchers.

MIT engineers, in collaboration with scientists at Cancer Research UK Manchester Institute, have developed a new way to grow tiny replicas of the pancreas, using either healthy or cancerous pancreatic cells. Their new models could help researchers develop and test potential drugs for pancreatic cancer, which is currently one of the most difficult types of cancer to treat.

Using a specialized gel that mimics the extracellular environment surrounding the pancreas, the researchers were able to grow pancreatic “organoids,” allowing them to study the important interactions between pancreatic tumors and their environment. Unlike some of the gels now used to grow tissue, the new MIT gel is completely synthetic, easy to assemble and can be produced with a consistent composition every time.

Researchers Create Materials for Shape-Shifting Architecture

 

Source/Credit: North Carolina State University

Researchers at North Carolina State University have developed materials that can be used to create structures capable of transforming into multiple different architectures. The researchers envision applications ranging from construction to robotics.

“The system we’ve developed was inspired by metamorphosis,” says Jie Yin, corresponding author of a paper on the work and an associate professor of mechanical and aerospace engineering at NC State. “With metamorphosis in nature, animals change their fundamental shape. We’ve created a class of materials that can be used to create structures that change their fundamental architecture.”

Kirigami is a fundamental concept for Yin’s work. Kirigami is a variation of origami that involves cutting and folding paper. But while kirigami traditionally uses two-dimensional materials, Yin applies the same principles to three-dimensional materials.

The metamorphosis system starts with a single unit of 3D kirigami. Each unit can form multiple shapes in itself. But these units are also modular – they can be connected to form increasingly complex structures. Because the individual units themselves can form multiple shapes, and can connect to other units in multiple ways, the overall system is capable of forming a wide variety of architectures.

“Think of what you can build with conventional materials,” Yin says. “Now imagine what you can build when each basic building block is capable of transforming in multiple ways.”

Yin’s lab previously demonstrated a similar concept, in which 3D kirigami units were stacked on each other. In that system, the units could be used to assemble a structure – but the structure could also then be disassembled.

The metamorphosis system involves actually connecting the kirigami units. In other words, once the units are connected to each other they cannot be disconnected. However, the larger structures they create are capable of transforming into multiple, different architectures.

“There are two big differences between our first kirigami system and the metamorphosis system,” Yin explains.

“The first kirigami system involved units that could be assembled into architectures and then disassembled, which is an advantage. However, when the units were assembled, the architecture wouldn’t be capable of transforming. Because the sides of the unit were not rigid and fixed at 90-degree angles, the assembled structure could bend and move – but it could not fundamentally change its geometry.

“The metamorphosis kirigami system does not allow you to disassemble a structure,” Yin says. “And because the sides of each cubic unit are rigid and fixed at 90-degree angles, the assembled structure does not bend or flex very much. However, the finished structure is capable of transforming into different architectures.”

In proof-of-concept testing, the researchers demonstrated that the metamorphosis system was capable of creating many different structures that are capable of bearing significant weight while maintaining their structural integrity.

That structural integrity is important, because Yin thinks construction is one potential application for the metamorphosis system.

“If you scale this approach up, it could be the basis for a new generation of construction materials that can be used to create rapidly deployable structures,” Yin says. “Think of the medical units that have had to be expanded on short notice during the pandemic, or the need for emergency housing shelters in the wake of a disaster.”

The researchers also think the metamorphosis system could be used to create a variety of robotic devices that can transform in order to respond to external stimuli or to perform different functions.

“We also think this system could be used to create a new line of toys – particularly toys that can help people explore some fundamental STEM concepts related to physics and engineering,” Yin says. “We’re open to working with industry collaborators to pursue these and other potential applications for the system.”

The paper, “Metamorphosis of three-dimensional kirigami-inspired reconfigurable and reprogrammable architected matter,” is published in the journal Materials Today Physics. First author of the paper is Yanbin Li, a Ph.D. student at NC State. The work was done with support from the National Science Foundation, under grant 2005374.

Source/Credit: North Carolina State University

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Crop-eating moths will flourish as climate warms

 

The top map shows the distribution of diamondback moths as of 2016. Overwintering regions are shown in red. The bottom map shows regions where the diamondback moth’s range has expanded in the past 50 years, based on a climate change model in which mean global temperatures will increase 2 degrees Celsius this century. Darker colors indicate a greater chance for overwinter survival.
(Image courtesy of V. Rudolf/Rice University)

Climate change in this century will allow one of the world’s costliest agricultural pests, the diamondback moth, to both thrive year-round and rapidly evolve resistance to pesticides in large parts of the United States, Europe and China where it previously died each winter, according to a study by U.S. and Chinese researchers.

The moth, Plutella xylostella, which is also known as the cabbage moth, already causes more than $4 billion in damage worldwide each year to broccoli, cauliflower, cabbage, kale, mustard, radishes, turnips, watercress, Brussels sprouts and other crops. It is also one the world’s most pesticide-resistant species, with a documented resistance to at least 97 insecticides.

In a first-of-its-kind study published in the open-access journal Nature Communications, researchers from Rice University and the Chinese Academy of Agricultural Sciences combined results from years of laboratory and field experiments, computer simulations of future climate warming scenarios and a meta-analysis of decades of prior moth research.

“It’s well-documented that climate change is shifting the distribution and ranges of species, but the challenge is trying to predict where species will go,” said study co-author Volker Rudolf, an ecologist, evolutionary biologist and professor of biosciences at Rice University.

Rudolf said the team, which was led by co-lead authors Chun-Sen Ma and Wei Zhang, began with laboratory experiments aimed at isolating a specific mechanism that could be used to accurately predict how the range of diamondback moths would evolve in response to climate change. Previous experiments had found the coldest temperature individual moths could survive, but it was also well-known the moths died out each winter in places where temperatures were considerably higher. Rudolf said the lab studies allowed the team to predict where the moths can “overwinter,” or survive year-round, based on the daily accumulated low temperatures below a critical threshold in winter, a metric they dubbed “low temperature degree days.”

“That variable alone predicts over 90% of mortality, which is pretty nuts,” Rudolf said. “You don’t normally get correlations that strong.”

That gave the researchers “a simple variable that was both mechanistically linked to the survival of the species and really easy to calculate from either past climate data or future-climate models,” he said.

Diamondback moth
(This work, “Plutella.xylostella.7383,” by of Olaf Leillinger
is used and provided under
CC BY SA 2.5 courtesy of Wikimedia Commons)

The researchers found climate change over the past 50 years has increased the overwintering range of the diamondback moth by more than 925,000 square miles. They also showed each increase in mean global temperature of 1 degree Celsius will allow the moth’s overwintering range to expand by about 850,000 square miles. Current climate models predict mean global temperatures will increase by 2-6 degrees Celsius during the coming 100-150 years, the study said.

Rudolf said the overwintering data combined with a meta-analysis of decades of previous studies of diamondback moth pesticide resistance allowed the team to show how climate change could dramatically worsen the problem of evolved pesticide resistance in parts of the U.S., China, Japan and the Mediterranean that are currently “marginal” overwintering regions for the moth.

“We care about overwintering because if they survive winters and stay year-round that allows for rapid evolution of pesticide resistance,” Rudolf said.

Diamondback moths and many other crop pests like armyworms, planthoppers, leafrollers and some species of aphids overwinter in warm regions and migrate annually, causing significant damage to crops in regions where they cannot overwinter. Where these species cannot overwinter, they are slower to evolve pesticide resistance, Rudolf said.

“Because they always come from somewhere else to recolonize a particular site, the individuals are most likely coming from different ancestors every year,” he said. “So, you can have within-season selection for pesticide resistance, but selection across-seasons gets interrupted.”

The researchers’ global meta-analysis of pesticide resistance in diamondback moths illustrated the critical difference between these two types of evolutionary processes: Mean pesticide resistance was 158 times higher at overwintering sites compared to non-overwintering sites, the research showed.

The double whammy of an expanded year-round range and more rapid evolution of pesticide resistance could severely impede control efforts and allow diamondback moths to cause greater economic losses for farmers, the study found.

But the study’s authors said the research also presents an opportunity, both as a template for studying similar crop pests and as a guide to designing and coordinating more effective control efforts.

The findings could be used to “develop proactive pest management in a changing world, reduce costs of control efforts and assure food security while minimizing impacts on natural enemies and other aspects of the ecosystem,” they wrote in the study. “In practice, our results emphasize the importance of adjusting pest management strategies to adapt to differences in winter survival across regions and how this will change under future climate scenarios.”

Study co-authors include Yu Peng, Liang Zhu and Gang Ma of the Chinese Academy of Agricultural Sciences in Beijing, Fei Zhao and Kun Xing of both the Chinese Academy of Agricultural Sciences and Shanxi Agricultural University in Shanxi, Xiang-Qian Chang of both the Chinese Academy of Agricultural Sciences and Hubei Academy of Agricultural Sciences in Wuhan, and He-Ping Yang of the National Meteorological Information Centre in Beijing.

The research was supported by the National Natural Science Foundation of China (31471764, 31620103914, 31501630), the National Key R&D Program of China (2018YFD0201400, 2019YFD1002100), the Chinese Academy of Agricultural Sciences’ Fundamental Research Fund (Y2017LM10) and the Chinese Academy of Agricultural Sciences’ Innovation Program (CAAS-ZDRW202012).

Source/Credit: Rice University

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Fat matters more than muscle for heart health, research finds

 

Photo by Polina Tankilevitch from Pexels

New research has found that changes in body fat impact early markers of heart health more than changes in body muscle, suggesting there are greater benefits to be expected from losing fat than from gaining muscle.

The observational study, led by researchers from the University of Bristol, was published in PLoS Medicine.

More than 3,200 young people in Bristol’s Children of the 90s birth cohort study were measured repeatedly for levels of body fat and lean mass using a body scanning device. These scans were performed four times across participants’ lives, when they were children, adolescents, and young adults (at ages 10, 13, 18 and 25 years). Handgrip strength was also tested when they were aged 12 and 25 years.

When the participants were 25 years old, blood samples were collected and a technique called “metabolomics” was used to measure over 200 detailed markers of metabolism including different types of harmful cholesterol, glucose, and inflammation, which together indicate one’s susceptibility to developing heart disease and other health conditions.

Dr Joshua Bell, senior research associate in epidemiology and lead author of the report, said: “We knew that fat gain is harmful for health, but we didn’t know whether gaining muscle could really improve health and help prevent heart disease. We wanted to put those benefits in context.”

The findings showed that gaining fat mass was strongly and consistently related to poorer metabolic health in young adulthood, as indicated, for example, by higher levels of harmful cholesterol. These effects were much larger (often about 5-times larger) than any beneficial effect of gaining muscle. Where there were benefits of gaining muscle, these were specific to gains that had occurred in adolescence – suggesting that this early stage of life is a key window for promoting muscle gain and reaping its benefits.

Dr Bell added: “Fat loss is difficult, but that does seem to be where the greatest health benefits lie. We need to double down on preventing fat gain and supporting people in losing fat and keeping it off.

“We absolutely still encourage exercise – there are many other health benefits and strength is a prize in itself. We may just need to temper expectations for what gaining muscle can really do for avoiding heart disease – fat gain is the real driver.”

The study also found that improving strength (based on handgrip) has slightly greater benefits for markers of heart health than gaining muscle itself, suggesting that the frequent use of muscle, rather than the bulking up of muscle, may matter more.

Professor Nic Timpson, the Principal Investigator of the Children of the 90s and one of the study’s authors, said: “This research provides greater clarity in the relative roles of fat and lean mass in the basis of cardio-metabolic disease. This is an important finding and clearly part of a complex picture of health that involves weight gain, but also the other indirect costs and benefits of different types of lifestyle. It is only through detailed, longitudinal, studies like Children of the 90s that these relationships can be uncovered. We extend our thanks to the participants of the Children of the 90s who make all of this work possible.”

Source/Credit: University of Bristol

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Mapping project completed, helping to save world’s reefs

 

Ailinginae Atoll - Ailinginae Atoll in the Marshall Islands.
Photo credit: Greg Asner

All of the world’s shallow coral reefs have been digitally mapped, thanks to a three-year project combining two million satellite images, enormous amounts of field data and University of Queensland-developed mapping techniques.

The Allen Coral Atlas project has officially launched its high-resolution maps of the world’s reefs which, together with the Atlas’s coral monitoring tool launched in May, will revolutionize reef management.

The project is an international research collaboration led by Arizona State University in partnership with UQ, Planet Ltd, National Geographic and Vulcan Inc.

UQ’s Remote Sensing Research Centre researcher Dr Chris Roelfsema said the digital atlas is a comprehensive and continually updated tool, perfect for scientists, policy makers and planners.

“To manage environmental assets like the world’s reefs, you need to know what’s happening at any given time,” Dr Roelfsema said.

“The Allen Coral Atlas provides maps that accurately describe the composition and extent of our reefs globally, and at a level of detail not seen before.

“These maps are connecting people with the data they need to save our reefs – it’s momentous.”

The Allen Coral Atlas, now available online, has been a global effort with UQ scientists playing the leading role in gathering verification data, developing and implementing the mapping approach for the world’s coral reefs.

“The verification and mapping approaches we’ve developed are based on 20 years of experience UQ has in combining reef knowledge, field data and earth observation processes to map and monitor coral reefs,” Dr Roelfsema said.

“This work combined 450 field data sets from global collaborators with machine learning and automated contextual-editing approaches, which helps us achieve the highest spatial and thematic resolution of coral reefs anyone has ever seen.”

The data is needed now more than ever, with models predicting 70 to 90 per cent of coral reefs will be lost by 2050, because of warming, polluted and acidic oceans.

Professor Greg Asner, Director of Arizona State University's Center for Global Discovery and Conservation Science and Managing Director of the Atlas project, said he was thrilled to announce the platform.

“It is a gratifying milestone after years of dedicated non-stop teamwork to bring this global map to fruition,” Dr Asner said.

“But the true value of the work will come when coral conservationists are able to better protect coral reefs based on the high-resolution maps and monitoring system.

“We must double down and use this tool as we work to save coral reefs from the impacts of our climate crisis and other threats.”

The Allen Coral Atlas is named for the late Microsoft co-founder Paul G. Allen, and founder of Vulcan Inc.

Source/Credit: University of Queensland

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Silicon, Subatomic Particles and Possible ‘Fifth Force’

 

As neutrons pass through a crystal, they create two different standing waves – one along atomic planes and one between them. The interaction of these waves affects the path of the neutron, revealing aspects of the crystal structure.  Credit: NIST

Using a groundbreaking new technique at the National Institute of Standards and Technology (NIST), an international collaboration led by NIST researchers has revealed previously unrecognized properties of technologically crucial silicon crystals and uncovered new information about an important subatomic particle and a long-theorized fifth force of nature.

By aiming subatomic particles known as neutrons at silicon crystals and monitoring the outcome with exquisite sensitivity, the NIST scientists were able to obtain three extraordinary results: the first measurement of a key neutron property in 20 years using a unique method; the highest-precision measurements of the effects of heat-related vibrations in a silicon crystal; and limits on the strength of a possible “fifth force” beyond standard physics theories.

The researchers report their findings in the journal Science.

In a regular crystal such as silicon, there are many parallel sheets of atoms, each of which forms a plane. Probing different planes with neutrons reveals different aspects of the crystal.  Credit: NIST

To obtain information about crystalline materials at the atomic scale, scientists typically aim a beam of
particles (such as X-rays, electrons or neutrons) at the crystal and detect the beam’s angles, intensities and patterns as it passes through or ricochets off planes in the crystal’s lattice-like atomic geometry.

That information is critically important for characterizing the electronic, mechanical and magnetic properties of microchip components and various novel nanomaterials for next-generation applications including quantum computing. A great deal is known already, but continued progress requires increasingly detailed knowledge.

“A vastly improved understanding of the crystal structure of silicon, the ‘universal’ substrate or foundation material on which everything is built, will be crucial in understanding the nature of components operating near the point at which the accuracy of measurements is limited by quantum effects,” said NIST senior project scientist Michael Huber.

Neutrons, Atoms and Angles

Like all quantum objects, neutrons have both point-like particle and wave properties. As a neutron travels through the crystal, it forms standing waves (like a plucked guitar string) both in between and on top of rows or sheets of atoms called Bragg planes. When waves from each of the two routes combine, or “interfere” in the parlance of physics, they create faint patterns called pendellösung oscillations that provide insights into the forces that neutrons experience inside the crystal.

“Imagine two identical guitars,” said Huber. “Pluck them the same way, and as the strings vibrate, drive one down a road with speed bumps — that is, along the planes of atoms in the lattice — and drive the other down a road of the same length without the speed bumps — analogous to moving between the lattice planes. Comparing the sounds from both guitars tells us something about the speed bumps: how big they are, how smooth, and do they have interesting shapes?”

The latest work, which was conducted at the NIST Center for Neutron Research (NCNR) in Gaithersburg, Maryland, in collaboration with researchers from Japan, the U.S. and Canada, resulted in a fourfold improvement in precision measurement of the silicon crystal structure.

Not-Quite-Neutral Neutrons

Each neutron in an atomic nucleus is made up of three elementary particles called quarks. The three quarks’ electrical charge sum to zero, making it electrically neutral. But the distribution of those charges is such that positive charges are more likely to be found in the center of the neutron, and negative charges toward the outside.  Credit: NIST

In one striking result, the scientists measured the electrical “charge radius” of the neutron in a new way with an uncertainty in the radius value competitive with the most-precise prior results using other methods. Neutrons are electrically neutral, as their name suggests. But they are composite objects made up of three elementary charged particles called quarks with different electrical properties that are not exactly uniformly distributed.

As a result, predominantly negative charge from one kind of quark tends to be located toward the outer part of the neutron, whereas net positive charge is located toward the center. The distance between those two concentrations is the “charge radius.” That dimension, important to fundamental physics, has been measured by similar types of experiments whose results differ significantly. The new pendellösung data is unaffected by the factors thought to lead to these discrepancies.

Measuring the pendellösung oscillations in an electrically charged environment provides a unique way to gauge the charge radius. “When the neutron is in the crystal, it is well within the atomic electric cloud,” said NIST’s Benjamin Heacock, the first author on the Science paper.

“In there, because the distances between charges are so small, the interatomic electric fields are enormous, on the order of a hundred million volts per centimeter. Because of that very, very large field, our technique is sensitive to the fact that the neutron behaves like a spherical composite particle with a slightly positive core and a slightly negative surrounding shell.”

Vibrations and Uncertainty

A valuable alternative to neutrons is X-ray scattering. But its accuracy has been limited by atomic motion caused by heat. Thermal vibration causes the distances between crystal planes to keep changing, and thus changes the interference patterns being measured.

The scientists employed neutron pendellösung oscillation measurements to test the values predicted by X-ray scattering models and found that some significantly underestimate the magnitude of the vibration.

The results provide valuable complementary information for both x-ray and neutron scattering. “Neutrons interact almost entirely with the protons and neutrons at the centers, or nuclei, of the atoms,” Huber said, “and x-rays reveal how the electrons are arranged between the nuclei. This complementary knowledge deepens our understanding.

“One reason our measurements are so sensitive is that neutrons penetrate much deeper into the crystal than x-rays – a centimeter or more – and thus measures a much larger assembly of nuclei. We have found evidence that the nuclei and electrons may not vibrate rigidly, as is commonly assumed. That shifts our understanding on the how silicon atoms interact with one another inside a crystal lattice.”

Force Five

The Standard Model is the current, widely accepted theory of how particles and forces interact at the smallest scales. But it’s an incomplete explanation of how nature works, and scientists suspect there is more to the universe than the theory describes.

The Standard Model describes three fundamental forces in nature: electromagnetic, strong and weak. Each force operates through the action of “carrier particles.” For example, the photon is the force carrier for the electromagnetic force. But the Standard Model has yet to incorporate gravity in its description of nature. Furthermore, some experiments and theories suggest the possible presence of a fifth force.

“Generally, if there’s a force carrier, the length scale over which it acts is inversely proportional to its mass,” meaning it can only influence other particles over a limited range, Heacock said. But the photon, which has no mass, can act over an unlimited range. “So, if we can bracket the range over which it might act, we can limit its strength.” The scientists’ results improve constraints on the strength of a potential fifth force by tenfold over a length scale between 0.02 nanometers (nm, billionths of a meter) and 10 nm, giving fifth-force hunters a narrowed range over which to look.

The researchers are already planning more expansive pendellösung measurements using both silicon and germanium. They expect a possible factor of five reduction in their measurement uncertainties, which could produce the most precise measurement of the neutron charge radius to date and further constrain — or discover — a fifth force. They also plan to perform a cryogenic version of the experiment, which would lend insight into how the crystal atoms behave in their so-called “quantum ground state,” which accounts for the fact that quantum objects are never perfectly still, even at temperatures approaching absolute zero.

Source/Credit: National Institute of Standards and Technology

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How land birds cross the open ocean

 

Terrestrial birds are capable of flying for hundreds of kilometers over the open sea. Nourani et al. show that the autumn migration trajectories of some of these birds correspond with uplift over the sea surface. Suitable uplift means less drag, making sea-crossing less energetically demanding. Moreover, strong uplift can allow the birds to soar.
© Elham Nourani / Max Planck Institute of Animal Behavior

Migrating birds choose routes with the best wind and uplift conditions, helping them to fly nonstop for hundreds of kilometers over the sea

Researchers at the Max Planck Institute of Animal Behavior and University of Konstanz in Germany have identified how large land birds fly nonstop for hundreds of kilometers over the open ocean—without taking a break for food or rest. Using GPS tracking technology, the team monitored the global migration of five species of large land birds that complete long sea crossings. They found that all birds exploited wind and uplift to reduce energy costs during flight—even adjusting their migratory routes to benefit from the best atmospheric conditions. This is the most wide-ranging study of sea-crossing behavior yet and reveals the important role of the atmosphere in facilitating migration over the open sea for many terrestrial birds.

Flying over the open sea can be dangerous for land birds. Unlike seabirds, land birds are not able to rest or feed on water, and so sea crossings must be conducted as nonstop flights. For centuries, bird-watchers assumed that large land birds only managed short sea crossings of less than 100 kilometers and completely avoided flying over the open ocean.

However, recent advances in GPS tracking technology have overturned that assumption. Data obtained by attaching small tracking devices on wild birds has shown that many land birds fly for hundreds or even thousands of kilometers over the open seas and oceans as a regular part of their migration.

But scientists are still unraveling how land birds are able to accomplish this. Flapping is an energetically costly activity, and trying to sustain nonstop flapping flight for hundreds of kilometers would not be possible for large, heavy land birds. Some studies have suggested that birds sustain such journeys using tailwind, a horizontal wind blowing in the bird’s direction of flight, which helps them save energy. Most recently, a study revealed that a single species—the osprey—used rising air thermals known as “uplift” to soar over the open sea.

Now, the new study has examined sea-crossing behavior of 65 birds across five species to gain the most wide-ranging insight yet into how land birds survive long flights over the open sea. The researchers analyzed 112 sea-crossing tracks, collected over nine years, with global atmospheric information to pinpoint the criteria that the birds use for selecting their migration routes over the open sea. A large international collaboration of scientists shared their tracking data to make this study possible.

The findings not only confirm the role of tailwind in facilitating sea-crossing behavior, but also reveal the widespread use of uplift for saving energy during these nonstop flights. Suitable uplift means less drag, making sea crossing less energetically demanding.

“Until recently, uplift was assumed to be weak or absent over the sea surface. We show that is not the case,” says first author Elham Nourani, a DAAD PRIME postdoctoral fellow at the Department of Biology at the University of Konstanz, who did the work when she was at the Max Planck Institute of Animal Behavior.

Terrestrial birds are capable of flying for hundreds of kilometers over the open sea. Nourani et al. show that the autumn migration trajectories of

some of these birds correspond with uplift over the sea surface. Suitable uplift means less drag, making sea-crossing less energetically demanding. Moreover, strong uplift can allow the birds to soar.

“Instead, we find that migratory birds adjust their flight routes to benefit from the best wind and uplift conditions when they fly over the sea. This helps them sustain flight for hundreds of kilometers,” says Nourani.

The oriental honey buzzard, for example, flies 700 kilometers over the East China Sea during its annual migration from Japan to southeast Asia. The roughly 18-hour nonstop sea crossing is conducted in autumn when the air movement conditions are optimal. “By making use of uplift, these birds can soar up to one kilometer above the sea surface,” says Nourani.

The study also raises the question of how migration will be affected by a changing climate. “Our findings show that many land birds are dependent on atmospheric support to complete their migrations over the open sea, indicating their vulnerability to any changes to the Earth’s atmospheric circulation patterns,” says Nourani. “Collaborative studies like this are important to unravel general patterns about how migratory birds depend on the weather patterns. This enables future studies to make robust predictions about how these birds will be impacted by climate change.”

Source/Credit: Max-Planck-Gesellschaft

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The development of non-opioid painkillers to treat chronic pain

 

An image of the cryogenic electron microscopy structure of the human adenosine
A1 receptor (colored blue) bound to its signaling protein
(colored pink, green, and purple), adenosine (purple spheres)
and a proof-of-concept non-opioid analgesic (colored as orange spheres).

Monash University researchers have made a breakthrough discovery that could pave the way for the development of novel non-opioid painkillers (analgesics) to safely and effectively treat neuropathic pain.

The research was published today in the prestigious journal Nature.

Neuropathic pain is a type of chronic pain that can occur if your nervous system is damaged or not working correctly, and can be caused by injury, virus infection or cancer treatment, or be a symptom or complication of conditions such as multiple sclerosis and diabetes.

The new study, led by world-renowned drug researchers from the Monash Institute of Pharmaceutical Sciences (MIPS) and the Monash Biomedicine Discovery Institute (BDI), has demonstrated a new mode of targeting the adenosine A1 receptor protein, which has long been recognized as a promising therapeutic target for non-opioid painkillers to treat neuropathic pain but for which the development of painkillers had failed due to a lack of sufficient on-target selectivity, as well as undesirable adverse effects.

In the study, Monash researchers used electrophysiology and preclinical pain models to demonstrate that a particular class of molecule, called a ‘positive allosteric modulator’ (PAM), can provide much more selective targeting of the A1 receptor by binding to a different region of the protein than traditional, previously investigated, activators.

Another breakthrough in the study was facilitated by the application of cryo electron microscopy (cryoEM) to solve the high-resolution structure of the A1 receptor bound to both its natural activator, adenosine, and an analgesic PAM, thus providing the first atomic level snapshot of where these drugs bind.

Chronic pain remains a widespread global health burden, with lack of current therapeutic options leading to an over-reliance on opioid painkillers, which provide limited relief in patients with chronic (particularly neuropathic) pain, while exhibiting severe adverse effects, such as respiratory depression and addiction.

The new Monash discovery provides the opportunity for researchers to develop non-opioid drugs that lack such side effects.

Co-corresponding author of the study and Dean of the Faculty of Pharmacy and Pharmaceutical Sciences (home to MIPS), Professor Arthur Christopoulos said: “The world is in the grip of a global opioid crisis and there is an urgent need for non-opioid drugs that are both safe and effective.”

Associate Professor Wendy Imlach, who is the head of the Pain Mechanisms lab at Monash BDI and a co-corresponding author of the work, stated: “This study has helped us to better understand mechanisms underpinning allosteric drug actions. One of the exciting things we found is that not only were the PAMs able to decrease neuropathic pain with minimal unwanted effects, but they actually increase their level of effectiveness as the pain signals in the spinal cord get stronger – thus highlighting the potential for allosteric medicines that are uniquely sensitive to disease context”.

Professor Christopoulos added: “This multidisciplinary study now provides a valuable launchpad for the next stage in our drug discovery pipeline, which will leverage structure-based insights for the design of novel non-opioid allosteric drugs to successfully treat chronic pain.”

This work was performed in collaboration with researchers from the Universities of Sydney, Kansas and Tokyo, Uppsala University, and the ARC Centre for cryo-Electron Microscopy of Membrane Proteins. It was supported by the National Health and Medical Research Council of Australia, the Australian Research Council, the Australian Heart Foundation, the American Heart Association and the National Institutes of Health, and the Swedish Research Council.

Source/Credit: Monash University

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