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Top biomedical engineering researcher develops synthetic scaffolds for tendon and ligament regeneration

Previous synthetic tendon grafts have led to poor outcomes and implant rejection

Australia has one of the highest rates of anterior cruciate ligament (ACL) injuries in the world - and up to 25 percent of surgeries require revision

Australia's love of sport means it has one of the highest rates of knee anterior cruciate ligament (ACL) injury and reconstruction in the world.

Worldwide, the costs of tendon and ligament rupture repair and surgery revision represent tens of billions of dollars of the clinical orthopaedic market.

A team of biomedical engineering researchers from the University of Sydney, working with Columbia University's Regenerative Engineering Laboratory and FAU Erlangen-Nurnberg Institute of Medical Biotechnology (Germany), are hoping to improve the outcomes of tendon and ligament repair by developing a new synthetic scaffold for their regeneration.

Led by the Head of the Biomaterials and Tissue Engineering Research Unit and Director of the Australian Research Centre for Innovative BioEngineering, Professor Hala Zreiqat, working with postdoctoral researcher Dr Young No, the researchers are the first to develop and patent novel fibre-reinforced hydrogel scaffolds, a synthetic substance that has the ability to mimic and replace human tendon and ligament tissue.

"Ruptures to tendons and ligaments mostly occur in accidents and when playing sport. Worldwide and particularly in Australia, there is an immense clinical need for the development of readily available, off-the-shelf, mechanically strong synthetic tendon scaffolds," said Professor Zreiqat.

"Conservative methods using immobilisation casts and movement restricting splints and braces often require several weeks of rehabilitation to achieve minimal functional recovery, while current implants carry a higher risk of rejection and infection," she said.

"Our technology hopes to fast-track the restoration of tendons' and ligaments' mechanical function and support the growth of collagen tissue, without compromising the body's biological response," she said.

Tested on patellar tendon models in rats, the synthetic scaffold has been developed with a stress resistance and water volume similar to real tendons and ligaments, allowing for the improved in-growth of collagen tissue.

"Until now, synthetic scaffolds have come with a significant risk of implant failure, as well as poor biological tissue integration and abrasion," she said.

"Human tendons and ligaments are 70 percent water - they are complicated structures that include blood vessels, nerves and lymphatic vessels and perform the task of linking bone to muscle and moving the body," she said.

"For synthetic scaffolds to be accepted by the body, their physical and chemical architecture must align with human tendons and ligaments," she said.

The researchers now hope to investigate the long-term behaviour of these scaffolds in both internal and external bodily conditions, as well as to observe tissue integration and biomechanics in larger animal models.

Since the first discovery of photocatalytic water splitting on a TiO2 electrode under ultraviolet (UV) light, TiO2 materials have been widely investigated over the past few decades due to their unique properties such as nontoxicity, abundance, easy availability, and stability. For the moment, TiO2 materials present great potentials in the applications from the conventional areas (e.g., pigment, cosmetic, and toothpaste) to the latest developed areas including catalysis, energy storage and conversion, biomedicine, environmental remediation and so on. Beyond all question, TiO2 materials render new candidates to overcome the energy, environment, and health challenges facing humanity today.

Recently, various TiO2 nanomaterials with different structures have been fabricated and applied in different areas and reveal excellent performances. Among them, mesoporous TiO2 materials, especially with hierarchically mesoporous structures, have received increasing interest due to their attractive features, such as high surface areas, large pore volumes, tunable pore structures, and nano-confined effects. Those features enable the high performance of hierarchically mesoporous TiO2 materials in many areas. The high surface area can provide abundant active-sites for surface- or interface-related processes such as adsorption and catalysis. The large pore volume has shown great potential in the loading of guest species and the accommodation of structural change. And the porous structure can facilitate the diffusion of reactants and products, which is benefit for the reaction kinetics.

In a new review published in National Science Review, scientists at the Department of Chemistry in Fudan University, China, present the latest advances in the synthesis of hierarchically mesoporous TiO2 materials for energy and environmental applications. Co-authors Wei Zhang, Yong Tian, Haili He, Li Xu, Wei Li, and Dongyuan Zhao summarize the general synthetic strategies (template-free, soft-template, and hard-template and multiple-template routes) for hierarchically mesoporous TiO2 materials firstly. After that, they review the representative morphologies of hierarchically mesoporous TiO2 materials (nanofibers, nanosheets, microparticles, films, spheres, core-shell structures, and multi-level architectures), meanwhile, the corresponding synthetic mechanisms and the key factors for the controllable synthesis of hierarchically mesoporous TiO2 materials with different architectures are highlighted. Moreover, they discuss the applications of hierarchically mesoporous TiO2 materials in terms of energy storage and environmental protection, including photocatalytic degradation of pollutants, photocatalytic fuel generation, photoelectrochemical water splitting, chemical catalysis, lithium-ion batteries and sodium-ion batteries. Finally, the author outline the challenges and future directions of research and development in this area.

As instances of antibiotic resistance increase in the medical field, scientists are reexamining natural materials for their potential use in medicine. Honey has been used for thousands of years, from the time of Pharaohs for their effectiveness in treating wounds and burns.

Manuka is honey made by bees out of the pollen of Leptospermum scoparium, a type of tea tree native to southeast Australia and New Zealand. Manuka is the Maori name for the flowering tea tree plant. Manuka honey contains multiple bioactive ingredients including hydrogen peroxide, methylglyoxal (MGO), polyphenols, sucrose and maltose that aid in healing.

All types of honey contain peroxide which kills bacteria on contact, however peroxide is also damaging to human cells. What makes the hydrogen peroxide in honey special is that it is produced slowly, enough to keep the bacterial growth at bay while being gentle on human cells. What makes manuka honey more sought after than other honeys is that it contains MGO which inhibits bacterial growth by limiting the swarming and swimming mobility of bacterial strains. Even the sugars in honey contributes to healing! Sucrose and maltose can be direct sources of energy for cells on the wound surface.

Dressings provide a shield between pathogens in the environment and the open wound. Appendages must be robust enough to protect the body from the outside elements, but also gentle on healing flesh. Researchers at Shinshu University lead by Azeem Ullah decided to produce a novel wound dressing comprised of manuka honey using electrospun cellulose acetate nanofiber.

Cellulose is used to make paper and is 90% of what makes cotton. Cellulose acetate is a hydrophilic biodegradable material with high tensile strength, biocompatible and suitable for protecting susceptible wounds.

Electrospinning is a technique in fiber engineering that uses electrostatic repulsion to counteract surface tension and dispel the "dope" or fiber mixture to spin nano-sized fibers made of desirable ingredients. It is often used when producing fibers made of complex polymers, in this case with the added ingredient of manuka honey.

Corresponding author of this study, Professor Ick Soo Kim of Shinshu University's Institute for Fiber Engineering stated that it was difficult to "prepare a spinning dope for electrospinning. As we used cellulose acetate as a polymer carrier for our bioactive ingredient, it was very important to determine an amount of manuka honey which should show its bioactivity in the composite nanofiber mats without altering the electrospinning dope properties."  So, the balance of adding the manuka honey with enough anti-bacterial properties without changing the electrospinning mixture properties needed tinkering and proved to be the key to the success of this research.

The research successfully showed that the composite nanofibrous mats demonstrated antimicrobial activity against the Gram-positive S. aureus and Gram-negative E. coli bacterial strains. The cellulose acetate manuka honey nanofibrous mats also are breathable and promote wound healing in vitro.

The scientists were happy to discover that including the honey in the nanofiber mats decreased the water contact angle which helps the proliferation and migration of cells during the healing process. This property of the nanofiber mats can also be used for tissue engineering and regenerative medicine.

The researchers hope to soon bring this to market. In order to do so, extensive in vivo analysis is needed. More information can be found in their paper, Manuka honey incorporated cellulose acetate nanofibrous mats: Fabrication and in vitro evaluation as a potential wound dressing.

New York, NY--April 13, 2020--Photosynthesis on Earth is regulated by plant phenology--how plant life cycles interact with the climate--and environmental conditions, both of which changed substantially in recent decades. Unlike early-season photosynthesis which is mostly driven by warming temperatures or the onset of the wet season, late-season photosynthesis can be limited by several factors, such as plant life cycle and radiation, and its underlying mechanisms are less understood. Late-season photosynthesis on land contributes greatly to annual total carbon fixation and is sensitive to climate. Scientists generally agree that temperature limitation on late-season photosynthesis will alleviate with warming but the effects of water availability are highly uncertain.

A new Columbia Engineering study shows that increased water stress--higher frequency of drought due to higher temperatures, is going to constrain the phenological cycle: in effect, by shutting down photosynthesis, it will generate a lower carbon uptake at the end of the season, thus contributing to increased global warming. The researchers used both remote sensing data and in-situ observations to analyze the temperature and water limitations on the end of photosynthesis date. They found that water limitation on late-season photosynthesis is regulated by both soil water and mean annual temperature. Earth system models have predicted warming and soil drying over most of the land surface by 2100, and so it is clear that water availability will become increasingly important as a limiting factor for late-season photosynthesis and carbon uptake.

"We wanted to understand what the driving factor of plant photosynthesis is during the late growing season, and how it will change in the future," says Pierre Gentine, associate professor of earth and environmental engineering and affiliated with the Earth Institute, who led the study published today in Proceedings of National Academy of Sciences. "Our study is a very good example of how advances in remote sensing technologies can be used to solve long-lasting questions like this one."

The team used both machine learning and remote sensing to generate a new dataset for mapping global plant photosynthesis. They found a contrasting spatial pattern of temperature and water limitations on photosynthesis at the end of the growing season. The threshold separating these was determined by the balance between energy availability and soil water supply. Precipitation and temperature had important yet opposite impacts on the end of the growing season photosynthesis for ecosystems at different locations: if plant photosynthesis in some areas is limited by precipitation (positive relationship with precipitation), temperature is likely to have a negative effect, and vice versa.

"We are the first to show that the balance between soil water and energy input into the ecosystem determines whether the system is limited by precipitation or by temperature," says the study's lead author Yao Zhang, a former postdoc research scientist with Gentine and now a postdoc scholar at Lawrence Berkeley National Laboratory. "As temperature limitation diminishes, more soil water is needed to support increased vegetation activity, especially during the late growing season. CMIP5 models project future warming and drying especially during late season, both of which should further expand the regions with limited water, causing large variations and potential decreases in photosynthesis."

Scientists at the University of Alberta have shown that the drug remdesivir is highly effective in stopping the replication mechanism of the coronavirus that causes COVID-19, according to new research published today in the Journal of Biological Chemistry.

The paper follows closely on research published by the same lab in late February that demonstrated how the drug worked against the Middle East Respiratory Syndrome (MERS) virus, a related coronavirus.

"We were optimistic that we would see the same results against the SARS-CoV-2 virus," said Matthias Götte, chair of medical microbiology and immunology at U of A.

"We obtained almost identical results as we reported previously with MERS, so we see that remdesivir is a very potent inhibitor for coronavirus polymerases."

Götte's new paper demonstrates how remdesivir, developed in 2014 to fight the Ebola epidemic, works in detail. He likens the polymerase to the engine of the virus, responsible for synthesizing the virus' genome.

"If you target the polymerase, the virus cannot spread, so it's a very logical target for treatment," Götte said.

The lab's work shows how remdesivir tricks the virus by mimicking its building blocks.

"These coronavirus polymerases are sloppy and they get fooled, so the inhibitor gets incorporated many times and the virus can no longer replicate," Götte explained.

He said the evidence from his group, along with previously published studies in animal and cell culture models, means that remdesivir can be classified as a "direct-acting antiviral" against SARS-CoV-2, a term first used to describe newer classes of antivirals that interfere with specific steps of the hepatitis C virus (HCV) life cycle.

He said the discovery of that direct action reinforces the promise of clinical trials for remdesivir in COVID-19 patients, which are already underway around the world.

While Götte said the evidence justifies clinical trials, he cautioned that the results obtained in the lab cannot be used to predict how the drug will work with people.

"We've got to be patient and wait for the results of the randomized clinical trials," said Götte, whose research was funded by the Canadian Institutes of Health Research, Alberta's Major Innovation Fund and Gilead Sciences, which manufactures remdesivir.

The Götte lab previously worked on human immunodeficiency virus (HIV) and HCV, but a couple of years ago switched to focus on viruses with the highest epidemic potential. The World Health Organization (WHO) issued its list of the top pathogens likely to cause severe outbreaks, including Ebola, Lassa and coronaviruses, in 2015.

"In that sense we were prepared because my lab specializes in viral polymerases," said Götte, adding that his next step will be to use his lab's tools to evaluate other promising antivirals.

He is optimistic that the unprecedented amount of research going on worldwide and the high level of co-operation between researchers will lead to the discovery of one or more effective treatments for COVID-19.

"We are desperate, but we still have to keep the bar high for anything that we put into clinical trials," he said.

Remdesivir is one of several drugs being fast-tracked into trials by the World Health Organization, comparing potential treatments in hospitalized COVID-19 patients in a dozen countries, including Canada. Götte said we can expect results from important clinical trials as early as April or May.

Götte said it is disappointing that antivirals discovered at the time of the severe acute respiratory syndrome (SARS) outbreak of 2003--which might have been effective against COVID-19 too--were never translated into widely available treatments, largely because of the huge cost involved in developing new drugs.

"This time around it's obvious that we have to cross the finish line," he said.

"Ten billion dollars, it seems a lot, a huge amount," Götte said. "But in the context of this pandemic and the costs associated with this pandemic, it's nothing."

UNIVERSITY PARK, Pa. -- Commercially prepared baby foods that purport to be loaded with dark green vegetables are sweetened with fruit puree and often don't contain a high percentage of dark green vegetable content, according to a team of researchers.

The resulting lack of dark green vegetable taste matters, said team leader John Hayes, associate professor of food science at Penn State, because young children don't learn to like the taste of broccoli, spinach, brussels sprouts and kale, to name a few, unless they repeatedly are exposed to them. So, they may not want to eat them later.

"Other research indicates young kids need to be exposed to the flavor of vegetables to learn to like them," he said. "If true, this new work is key because it shows that current commercial products on the market fail to meet this need, as they cover up and hide the flavor of vegetables -- even when vegetables are on the ingredient list."

Because vegetables are an important but under-consumed part of a healthy diet, there is growing interest in promoting vegetable acceptance and consumption among infants to help establish life-long healthy eating patterns, noted Hayes, director of the Sensory Evaluation Center in Penn State's College of Agricultural Sciences.

He suggested that many well-meaning parents who want their young children to eat and like dark green vegetables may be fooled by misleading content descriptions.

"If parents don't stop and taste these foods themselves, the front of the package may lead them to think these products taste like vegetables rather than a fruit puree," he said.

A recent survey of commercial baby food products in the United States conducted by some researchers on the team revealed a lack of variety in the types of vegetables offered. Most notably, there were no commercially available single, dark green vegetable products. Instead, dark green vegetables often were mixed with fruits or red/orange vegetables -- such as squash -- that provide additional sweetness.

For the liking of vegetables to be learned, the flavors from the vegetables must be perceptible within the mixture, explained Alyssa Bakke, staff sensory scientist in Penn State's Department of Food Science, who spearheaded the research. She pointed out that the study was an effort to understand the sensory profiles of vegetable-containing, stage 2 infant products commercially available in the United States, and how ingredient composition affects flavor profiles.

In the study, recently published in Appetite, researchers performed descriptive analyses to quantitatively profile the sensory properties of 21 commercial vegetable-containing infant foods and one prepared in Hayes' laboratory. Eleven experienced adult panelists, after 14 1/2 hours of training, rated all 22 products -- in triplicate -- for 14 taste, flavor and texture attributes.

Panelists found that products containing fruit not only were sweeter than products that did not contain fruit but also were higher in fruit flavors and lower in vegetable flavors. In general, sensory profiles were driven by the first or majority ingredient in the product. Because few products had dark green vegetables as a first ingredient, dark green vegetable flavor was not prevalent.

"This suggests the sensory profiles of commercially available infant vegetable foods may not be adequate to facilitate increased acceptance of green vegetables," Bakke said. "This is a huge concern right now -- how can we promote the liking of vegetables? From infants to adults, people tend not to like vegetables."

There are understandable reasons why vegetables are not preferred, Bakke said. They tend to be more bitter than other foods, and they tend to have less intense, more subtle flavors than most other foods. Sensory attributes that, unfortunately, are innate drivers of liking, she said, are salt and fat.

"Vegetables, of course, just don't have those things, so we have to learn to like them, and sometimes we have to overcome things like bitterness," she said. "The number one way we do that is just repeated trial -- trying it over and over and over again. If this is done early on, we can prepare people to have a liking for vegetables throughout their whole lifetimes."

ABERDEEN PROVING GROUND, Md. -- Materials used for a Soldier's personal protection gear may be tough enough for vehicles too, according to a new Army study.

Findings, released April 10 in the journal Polymer, show that polymers filled with carbon nanotubes could potentially improve how unmanned vehicles dissipate energy.

A team led by the U.S. Army's Combat Capabilities Development Command's Army Research Laboratory is conducting theoretical research through computer modeling.

"Our motivation for this research is that there could potentially be a use, as matrix material, for incorporation into lightweight composites in unmanned vehicle systems," said Dr. Yelena R. Sliozberg, a computational materials scientist at the laboratory.

Researchers said polyurethanes are versatile materials used in a broad variety of applications, including coatings, foams and solid elastomers. As film adhesives, for example, they are commonly used as bonding agents between layers of glass and as polymer back layers in the transparent glass or plastic composites such as vision blocks on side windows used in the tactical vehicles. In particular, high-performance segmented PUU polymers exhibit versatile physical and mechanical properties.

In this research, the team used computer modeling to look into the nature of the materials.

Sliozberg said hierarchical composites are a promising area of research for the Army vehicles as they are less susceptible to corrosion, leading to early component death.

"In contrast to traditional thermoset composites performance poly(urethaneurea) elastomers are far less brittle and they offer unparalleled control over material architecture," Sliozberg said. "Carbon nanotube/polymer composites have desirable electrical and thermal characteristics that exhibits behaviors superior to conventional fiber materials."

Sliozberg said they need to have deeper understanding of the nature of molecular level interactions in these materials in order to enhance the maximum stress levels it can withstand and tailor energy dissipation mechanisms.

Chemical modification of nanofillers is nontrivial and typically diminish their properties by changing their structure and chemistry. For example, the Young modulus could be lower, she explained.

This team's results strongly indicate the effectiveness of incorporation of aligned carbon nanotubes for microstructure optimization of hierarchical PUU polymers in the matrix as well as at the interface without any filler surface modification, Sliozberg said.

"It shows that the presence of high affinity of poly(urethane-urea) to carbon nanotubes would lead to a novel green synthesis pathway without the need of any surface functionalization of nanotubes for fabrication of carbon nanotube reinforced poly(urethane-urea) nanocomposites hierarchical composites," she said.

Sliozberg's co-authors for the paper, "Dissipative particle dynamics simulation of microphase separation in polyurethane urea nanocomposites" are Jeffrey L. Gair Jr., Scinetics, Inc., and Dr. Alex J. Hsieh, from the lab's Institute for Soldier Nanotechnologies at the Massachusetts Institute of Technology.

Future Army vehicles could see an improvement in their structural materials since they are less susceptible to corrosion, lightweight and have higher electrical conductivity than traditional elastomers. The materials also show great potential to protect vehicles against static build-up and discharge and lightning strikes.

"Certain military vehicles such as Army helicopters must withstand intense vibration and fatigue and the conductive nature of these materials could lead to an unprecedented level of multifunctionality with potential in real-time structural health monitoring through embedded strain sensing and damage monitoring that will lead to safely and accurately assessing the remaining life in vehicle components," Sliozberg said.

Collaborators at Drexel University are furthering the research by investigating the potential uses of PUU polymers with carbon nanotubes as filament materials for 3-D printing. The laboratory is not currently conducting these studies on any vehicles. Researchers plan to collaborate with other Army teams for testing in the near future.

CCDC Army Research Laboratory is an element of the U.S. Army Combat Capabilities Development Command. As the Army's corporate research laboratory, ARL discovers, innovates and transitions science and technology to ensure dominant strategic land power. Through collaboration across the command's core technical competencies, CCDC leads in the discovery, development and delivery of the technology-based capabilities required to make Soldiers more lethal to win our nation's wars and come home safely. CCDC is a major subordinate command of the U.S. Army Futures Command.

DALLAS - April 13, 2020 - Cancer cells avoid an immune system attack after radiation by commandeering a cell signaling pathway that helps dying cells avoid triggering an immune response, a new study led by UTSW scientists suggests. The findings, published in a recent issue of Nature Immunology, could eventually lead to new ways to augment existing treatments to fight this disease.

Researchers have long known that radiation - a mainstay of treatment protocols for many types of cancerous tumors - kills cancer cells in two different ways: The high-energy beams smite some cells directly, and these dead cells leak DNA that triggers a tumor-fighting immune response through proteins known as interferons (IFNs). But even though cancerous cells make up the vast majority of a tumor, explains study leader Yang-Xin Fu, Ph.D., studies have shown that these cells secrete very little IFN themselves, muting the immune response that could eradicate them.

"We figured that tumor cells must have some mechanism to escape interferon production," Fu says.

To figure out what that mechanism might be, he and his colleagues tested 42 FDA-approved drugs that block various parts of cell signaling on mouse colon cancer cells growing in petri dishes, searching for any that might be able to prompt these cells to secrete abundant interferons after radiation. Their search identified a drug known as emricasan, often prescribed to liver transplant recipients to help prevent rejection. This drug broadly inhibits production of a family of enzymes known as caspases, which not only help trigger cell death but also muffle the immune system's response to dying cells.

Further experiments indicated that one particular member of this family known as caspase-9 (CASP9) was key for preventing the cancer cells from secreting IFN. When the researchers genetically manipulated cancer cells to turn off CASP9 production, radiation increased their IFN production thousands-fold compared with "wild type" cancer cells that hadn't been modified.

When the researchers placed these CASP9-deficient cancer cells into mice, their tumors completely regressed after radiation, compared with those carrying tumors made of wild type cells. Additional experiments showed that a particular population of immune cells, known as CD8+ T cells, were recruited by the secreted interferon and were responsible for this dramatic regression.

Peering deeper into the mechanism behind how CASP9 helps protect tumor cells from the immune system, the researchers looked for the molecular trigger behind the production of this enzyme. Because cells secrete DNA from the nucleus only after they're dead, the researchers looked to an event that occurs earlier after radiation damage: the secretion of DNA from mitochondria, the cell's power-generating organelles. When the researchers removed mitochondrial DNA from cancer cells, they no longer produced IFN when they were irradiated, suggesting that this was the triggering event.

Although blocking CASP9 production appears to be a promising way to boost the anti-tumor immune response, it comes with a significant drawback: When tumors in animal models lost CASP9 signaling, these masses found a new way to evade immune attack by stepping up production of a protein called programmed death-ligand 1 (PD-L1), which shields cancer cells from immune discovery. However, when the researchers administered an antibody that blocked PD-L1, the tumors regressed again. Using a combination of CASP9 inhibitors with anti-PD-L1 could offer a new strategy for boosting the effects of radiation, Fu says.

"This approach could eventually give doctors the confidence that they're irradiating the tumor that they can see and using the immune system to knock out other tumor cells that they can't see," he adds. "Together, this may be able to give some patients long-lasting survival that's not yet achievable."

What The Study Did: Transgender adolescents often seek hormonal intervention to achieve a body consistent with their gender identity and those interventions affect reproductive function. This research letter examined the use of fertility preservation among transgender adolescents receiving hormonal intervention at a pediatric gender practice in Australia.

Authors: Kenneth C. Pang, M.B.B.S.(Hons), B.Med.Sc., Ph.D., of the Royal Children's Hospital in Melbourne, Australia, is the corresponding author.

To access the embargoed study: Visit our For The Media website at this link https://media.jamanetwork.com/

(doi:10.1001/jamapediatrics.2020.0264)

Editor's Note: The article includes conflict of interest disclosures. Please see the article for additional information, including other authors, author contributions and affiliations, conflicts of interest and financial disclosures, and funding and support.

What The Study Did: Risks for obesity and type 2 diabetes in adulthood were compared among 33,000 women born by cesarean or vaginal delivery between 1946 and 1964 in this observation study that included participants in the Nurses' Health Study II.

Authors: Jorge E. Chavarro, M.D., Sc.D., of the Harvard T.H. Chan School of Public Health in Boston, is the corresponding author.

To access the embargoed study: Visit our For The Media website at this link https://media.jamanetwork.com/

(doi:10.1001/jamanetworkopen.2020.2605)

Editor's Note: The article includes conflict of interest and funding/support disclosures. Please see the articles for additional information, including other authors, author contributions and affiliations, conflicts of interest and financial disclosures, and funding and support.

What are the most effective ways to achieve desired sustainable development outcomes across all aspects of wellbeing, and how might the pursuit of some of these goals affect progress toward others? A new study by an international team of researchers aims to address these questions to help understand possible synergies and tradeoffs among these goals.

The importance of pursuing sustainable development poses a challenge to scientists in terms of determining the most effective ways to achieve desired outcomes across health, education, poverty, energy, the environment, and many other aspects of wellbeing, as well as how the pursuit of some of these goals might affect the achievement of others. A study published in the journal Nature Sustainability brings together several different connections between particularly education and climate change and evaluates them together.

"We examined how changes in educational attainment simultaneously affect population growth, economic growth, greenhouse gas emissions, and vulnerability to climate change impacts. Previous studies have looked at the role of education in vulnerability to climate change impacts and its relationship to population increase, and also separately to economic growth. Our study however brings these multiple effects together in a single analysis," explains Shonali Pachauri, a study coauthor and Acting IIASA Transitions to New Technologies Program Director.

The team wanted to address two main questions through their research: Firstly, they wanted to determine the net effect of increased educational attainment on the emissions that drive climate change, as there is reason to believe that it could lead either to higher or to lower emissions. Second, they asked how much less vulnerable people in less developed countries might be if educational attainment is improved.

The findings indicate that increasing the level of educational attainment in a population leads to a large improvement in vulnerability - in other words, populations are significantly less vulnerable to climate change if efforts are made to improve their level of education. Conversely, populations are quite a bit more vulnerable if educational improvements slow substantially.

According to the researchers, one of the more surprising results of the study is that increasing educational attainment tends to lead to a small increase in emissions that drive climate change. Many other studies have found that slower population growth leads to lower emissions. In this case however, the authors found that if increased educational attainment is taken into account, the reductions in emissions from a smaller population can be more than offset by the boost to economic growth that education also provides.

A second unexpected finding was the size of the positive effect of education on vulnerability. If optimistic increases in educational attainment can be achieved in developing countries in the future, the reduction in vulnerability, as measured by the Human Development Index, can be quite large.

The authors point out that the study's results are preliminary, especially because education can affect people and society in many ways that matter to climate change, and they only examined a few of them. Improved education may, for instance, speed up the development of new technologies to lower greenhouse gas emissions, or it may change consumption patterns or political behavior. These possible effects were not included in the analysis.

The study's results will help to inform discussions around policies aimed at fostering sustainable development and improve human wellbeing, while also preserving the environment. Not all policies will off course achieve these multiple aims equally well.

"The world is complicated, so we shouldn't expect policy solutions to be simple. Improving education has overwhelmingly positive consequences for people and society in many different ways, and we find that is true for reducing vulnerability to climate change impacts as well. At the same time, we shouldn't expect it to also reduce the emissions driving climate change. We will still need other approaches to accomplish that goal. Reducing emissions requires shifting the global energy system to be largely free of fossil fuels. Improved education may even help with that task in ways that we did not examine as part of our study," concludes study lead author Brian O'Neill, a researcher at the Josef Korbel School of International Studies and Pardee Center for International Futures at the University of Denver.

Can women in menopause get the benefits of hormone replacement therapy without the risks? A new UCLA study conducted with mice points in that direction, but additional research is necessary.

Women commonly experience hot flashes and weight gain, among other changes, during and after menopause. Hormone therapy, which gives women additional estrogen, can help alleviate some of these symptoms, but it has been linked to a higher risk of heart disease and breast cancer.

UCLA life scientists now report that a gene called reprimo, which is expressed by certain neurons in the brain, may play a role in menopause-related weight gain, a phenomenon not linked to increased eating. Their findings are published today in the journal Nature Metabolism.

"We want to figure out which neurons are mediating the beneficial portions of hormone therapy and mimic them without hormones," said senior author Stephanie Correa, a UCLA assistant professor of integrative biology and physiology and a member of UCLA's Brain Research Institute. "Hormone therapy can be beneficial, but it treats the entire brain and body with hormones. We may be able to bypass the hormone. That's our goal, and it's a big one. We haven't achieved it yet, but we're learning."

Correa and her research team show that the reprimo gene is important for regulating temperature. Changes in temperature are known to affect body weight and may contribute to the weight gain often seen in menopause.

"It's possible that reprimo is involved in the weight gain that accompanies menopause," said co-lead author Edward van Veen, a project scientist in Correa's laboratory. "If equivalent neurons exist in humans and we can find some way to tweak them, it might relieve much of the weight gain without the side effects of hormone therapy."

A brain region called the hypothalamus is essential for survival in many species, from mice to humans; it controls eating, drinking, reproduction and body-temperature regulation, among other vital functions. Correa and her research team studied dozens of genes in the hypothalami of more than 50 mice, both female and male, starting at about eight weeks of age, shortly after they reach reproductive age.

The team used a technique known as single-cell RNA-seq, which allows biologists to study individual cells one at a time, to investigate which neurons in an area of the hypothalamus known as the ventromedial hypothalamus might mediate these different functions.

"We had hints there were different types of neurons in the ventromedial hypothalamus, and this region is very different in males and females, so we studied hundreds of cells in males and females to identify the different types of neurons and determine whether there are sex differences," Correa said.

The biologists were most interested in neurons that have estrogen receptors. These receptors bind to the hormone and are subsequently able regulate to the activity of specific genes in the neuron, a process known as gene expression. The team's most significant findings centered on the reprimo gene, which is expressed in one group, or population, of these estrogen-responsive neurons, restricted almost entirely to females.

"We were excited to find not only populations of estrogen-responsive neurons but also differences in these populations between males and females," said co-lead author Laura Kammel, a former UCLA doctoral student in Correa's laboratory.

"The difference between females and males in reprimo in the ventromedial hypothalamus is like night and day," Correa said. "The females express a ton of it, and males express little, if any, reprimo in this brain region. Of the dozens of genes I have studied in this region, this is easily the strongest sex difference I have ever seen."

In a series of experiments, the biologists interfered with the function of reprimo in the ventromedial hypothalamus in about two dozen mice. In one experiment, they shut off reprimo in female mice by using an RNA molecular compound that interferes with how the gene works in neurons. In another, they increased reprimo expression in male mice by removing an estrogen receptor from the neurons. In both cases, body temperature changed substantially, demonstrating a link between reprimo's role in temperature and the effects of estrogen.

"We know that reprimo is important in regulating body temperature, but we don't know what it is actually doing in neurons," van Veen said. "We want to find out."

Correa and her team also report that estrogen acts on another gene, Tac1, that is significantly increased in the ventromedial hypothalamus of female mice, although the difference is not nearly as dramatic as with reprimo. Tac1 has been shown to promote physical activity in female mice.

Estrogen receptor alpha, one of three estrogen receptors, is found in neurons in the same region of the ventromedial hypothalamus as Tac1 and reprimo. When the researchers removed that estrogen receptor, they found it led to obesity and reduced movement in female mice.

The results, the researchers said, not only aid in their understanding of the interplay between genes and estrogen but may also have implications for understanding obesity.

Summarizing the research, van Veen said: "The ventromedial hypothalamus is involved in movement and temperature regulation. We know estrogen affects movement and temperature. From Stephanie Correa's previous research, we learned the estrogen response of neurons that affect movement, and now we think we know the estrogen response of neurons that affect temperature. It's interesting that they are in the same location but distinct."

"Our findings suggest reprimo is controlling some of the effects of estrogen on temperature," Correa said. "If it is controlling the beneficial effects, then maybe we can manipulate it -- with a drug that targets reprimo or the neurons that express reprimo -- as an alternative to hormone therapy and get around the requirement for estrogen. We are studying the brain in a nuanced way and trying to learn which cells or which genes are important to target for potential therapies."

Toxoplasmosis is a parasitic disease caused by the Toxoplasma gondii parasite, which can be passed from animals to human beings (zoonosis). It is widely spread all over the world and, though it does not generally present symptoms, it is considered to be a major cause of reproductive disorders in a variety of species, including human beings. Although felines are definitive hosts (the only species that eliminates the infectiousness of the parasite), all warm-blooded species are potentially susceptible to infection. This disease has great significance in animal health and public health, and is primarily associated with reproductive disorders as well as alterations in the nervous and respiratory systems in immunosuppressed people.

The results were obtained from a recent study performed in different zoos around Spain by the Infectious Diseases research group at the Animal Health Department at the University of Cordoba. These results indicate that 42% of the 393 zoo animals under analysis showed T. gondii antibodies, meaning that at some point in their lives they had contact with this parasite. Moreover, animals tested positive at all the zoos included in the study.

The study, in which blood serum samples were taken from 393 animals belonging to 91 different species, was made possible by a collaboration agreement among zoos around Spain.

"The results are not alarming from a public health perspective, since many people are already immune and the risk of a zoo animal infecting a person is quite low", explains Ignacio García, one of the study's authors along with researchers David Cano, Sonia Almería, Javier Caballero, Débora Jiménez, Sabrina Castro and Jitender P. Dubey.

Nevertheless, in light of these results, infection from this parasite could become a conservation issue in certain endangered species living in zoos, especially during pregnancy or in certain species that are particularly prone to infection. Thus, as Ignacio García points out, it is necessary for zoos to take preventative measures aimed at keeping this parasite from moving around these establishments.

Some alternatives to limiting this spread, explains the researcher, range from creating effective rodent control programs to keeping stray cats out of zoos, as well as properly washing produce and freezing meat before feeding these species.

A team of Chinese scientists has reported the high-resolution crystal structure of the main protease (Mpro) of the COVID-19 virus and has identified drugs that may hold promise in combating the virus.

Prof. RAO Zihe and Prof. YANG Haitao from the Shanghai Institute for Advanced Immunochemical Studies of ShanghaiTech University, Prof. JIANG Hualiang from the Shanghai Institute of Materia Medica of the Chinese Academy of Sciences and their collaborators conducted the research, which was published online in Nature on April 9.

Mpro, a key coronavirus enzyme, plays a pivotal role in mediating viral replication and transcription, making it an attractive antiviral drug target. To identify new drug leads for targeting Mpro in the COVID-19 virus, the researchers initiated a program of combined structure-assisted drug design, virtual drug screening and high-throughput screening.

Using computer-aided drug design, the researchers identified a mechanism-based inhibitor, N3, and subsequently determined the crystal structure of COVID-19 virus Mpro in complex with this compound on Jan. 26. The subsequent publication of this information represents the first 3D structure from the COVID-19 virus available in the public domain.

Using a combination of structure-based virtual and high-throughput screening, the scientists then assayed over 10,000 compounds, including approved drugs, drug candidates in clinical trials, and other pharmacologically active compounds, as potential inhibitors of Mpro. Among the compounds studied, six inhibited Mpro with IC50 values ranging from 0.67 to 21.4 μM. The compound ebselen also exhibited promising antiviral activity in cell-based assays.

In this study, the convergence of structure-based ab initio drug design, virtual screening and high-throughput screening was proved to be an efficient strategy for finding antiviral leads to combat the COVID-19 virus. The methods presented can greatly accelerate finding drug leads with clinical potential to fight new emerging infectious diseases that currently lack specific drugs and vaccines.

The team publicly released the list of candidate drugs on Jan. 25 and the structure of the COVID-19 virus Mpro on Jan. 26, in advance of officially releasing the results.

Before the Mpro structure was officially released on the Protein Data Bank (PDB), the team decided to provide its research data to over 300 research teams from academia to industry worldwide to help to accelerate the global research combating pandemic. By doing this, the team propelled research efforts around the world by helping clinicians, vaccine researchers and other professionals get a better understanding of the new virus.

In February, the crystal structure of COVID-19 virus Mpro (also known as 3CL protease) was selected as the February Molecule of the Month by PDB and was featured in PDB news. The PDB press release noted that the "rapid public release of this structure of the main protease of the virus (PDB 6lu7) will enable research on this newly recognized human pathogen."

MIPT scientists and their colleagues from Japan and the U.S. have calculated the parameters of photodetectors comprised by layers of graphene and a combination of black phosphorus and black arsenic. These sensors are able to detect radiation with energy less than the band gap of the constituent layers without graphene. It is also easy to modify them in order to increase their sensitivity to the required wavelength of light. Such sensors could replace any far-infrared and terahertz radiation detectors. The research findings were published in the journal Optics Express.

The new sensors will benefit many areas of science and technology. The far-infrared band is substantial both for household applications and for fundamental science. These waves are emitted by cosmic dust, whose study reveals the evolution of galaxies. Infrared light sensors are used in night vision equipment, remote controls, homing missiles, and heartbeat sensors. Terahertz radiation offers a less dangerous alternative to X-ray baggage scanners.

The researchers considered far-infrared interband photodetectors based on a graphene monolayer. The graphene was surrounded by layers made of black phosphorus and black arsenic in varying proportions. By changing the ratio of these substances, it is possible to shift the working range of the photodetector. The energies inaccessible to electrons in black phosphorus and arsenic are different. The detector operates by registering an electron or hole entering the conduction band of black phosphorus or arsenic following a transition between two energy bands of graphene. However, temperature effects cause infrared and terahertz sensors to detect signal even "in the dark," in the absence of radiation. The layered structures examined in the study turned out to experience a dark current much lower than in those used today.

"We calculated the parameters of the light-sensitive elements for far-infrared detection based on a graphene monolayer. Such devices can replace almost any far-infrared and terahertz radiation sensors used today. The decreased dark current and the high photosensitivity significantly improve the signal-to-noise ratio even for low-intensity radiation. By applying a carefully calibrated voltage, the working range of the detectors can be changed without affecting signal reception quality. Such sensors could enhance the performance of infrared telescopes. According to calculations, at high temperatures the detectors will produce a much cleaner signal than the detectors used now," adds Victor Ryzhii, the head of the 2D Materials and Nanodevices Laboratory.