Tech

An international group of scientific experts co-directed by CNRS oceanographer Jean-Pierre Gattuso* has stated the requirements for coral reef survival in an article published in Biological Conservation. Over 500 million people rely on coral reefs for the protection they confer against submersion, the fishing resources they offer, and the tourism they help attract. Yet these ecosystems are among the most threatened by global warming: since the 1980s, there has been a rise in the number of bleaching episodes, during which corals expel the microscopic algae that keep them alive. While these events are reversible if the temperature change is only brief, prolonged bleaching can kill corals and the ecosystems associated with them.

The team of scientists, which comprises members of the Pew Marine Fellows Programme and of the Ocean Solutions Initiative, modelled future reef changes for two CO2 emission scenarios: the worst case and a scenario acceptable under the Paris Agreement. The former would lead to near extinction of reefs in 30 to 50 years, while the latter would give some corals time to adapt. Of the 16 possible actions for limiting the decline of coral reefs presented in the scientific literature, a massive energy transition is the most effective and the only plausible one on the global scale. Actions that may be taken on regional and local levels--e.g. designation of marine protected areas or selection of species best suited to new environmental conditions--may increase the adaptation potential of corals. The group asserts that saving reefs accordingly requires international political support, comparable to that rallied for campaigns against certain diseases.

Scientists have developed a new biomaterial that regrows blood vessels and bone, potentially providing a single-stage approach when repairing large bone defects.

The study, led by researchers from RCSI University of Medicine and Health Sciences and SFI AMBER Centre, is published in the Journal of Controlled Release.

Previous RCSI-led research had found that activating a mechanosensitive gene, called placental growth factor (PGF), at different doses promoted bone regeneration and grew new blood vessels. Using this knowledge, the researchers developed a biomaterial that delivers PGF at different concentrations.

Inspired by the natural way in which bone defects regenerate, the biomaterial first releases a high dose of PGF, promoting blood vessel growth, and follows it with a more sustained lower dose, which promotes bone regeneration. When tested in a pre-clinical model, the biomaterial successfully repaired large bone defects while also regrowing blood vessels.

Current biomaterials that promote both blood vessel and bone growth typically require using more than one therapeutic drug, which means designing a more complex system that faces more challenges. Furthermore, drugs that have been approved for use in the clinic have been controversially associated with dangerous side-effects, highlighting the need for new strategies.

"More testing is needed before we can begin clinical trials, but if proven successful, this biomaterial could benefit patients when repairing bone defects by providing an alternative to current systems," said Professor Fergal O'Brien, the study's principal investigator and RCSI's Director of Research and Innovation.

"In addition to repairing bone defects, our approach to regenerative medicine executed in the study provides a new framework for evaluating regenerative biomaterials for other tissue engineering applications. We are now applying this concept of 'mechanobiology informed regenerative medicine' to identify new therapeutics in other areas, including cartilage and spinal cord repair."

The biomaterial was developed by researchers from the Tissue Engineering Research Group (TERG) based at RCSI and the SFI AMBER Centre. Their work was supported by the Irish Research Council, the EU BlueHuman Interreg Atlantic Area Project, the European Community's Horizon 2020 research and innovation programme under European Research Council Advanced Grant agreement n° 788753 (ReCaP) and the Health Research Board of Ireland under the Health Research Awards - Patient-Oriented Research Scheme.

"By using a mechanobiology-informed approach, we were able to identify a promising new therapeutic candidate for bone repair and also determine the optimal concentrations required to promote both angiogenesis and osteogenesis within a single biomaterial," said Dr Eamon Sheehy, the study's first author and researcher in TERG.

"The regeneration of large bone defects remains a significant clinical challenge, but hopefully our new biomaterial will continue to prove beneficial in further trials."

In a study conducted at the University of Helsinki, researchers found a cause for severe epilepsy resulting in death in Parson Russell Terrier puppies at a few months of age. A change in the PITRM1 gene can lead to a dysfunction of mitochondria, the cellular energy pumps. Concurrently, amyloid-β accumulation and widespread neurodegeneration associated with Alzheimer's disease were identified in the puppies' brains. Changes to the PITRM1 gene in humans also cause a severe but slowly progressing brain disease.

Some Parson Russell Terrier puppies were seen to suddenly develop epileptic seizures at 6 to 12 weeks of age. The disease progressed very rapidly, in a matter of hours in the worst cases, to a situation where the seizures were continuous and unresponsive to medication.

"All of the sick dogs either died spontaneously or had to be euthanised. On the tissue level, neuronal necroses, or dead neurons, were identified throughout the brains of the deceased dogs. In the neurons, we observed crowding of mitochondria, the cellular energy pumps, and accumulation of amyloid-β typical of Alzheimer's disease. Such an accumulation is expected to be found in old dogs only," says Docent Marjo Hytönen from the University of Helsinki and the Folkhälsan Research Center.

With the help of several research groups at the University of Helsinki and international partners, samples were collected from around Europe, making it possible to pinpoint the gene defect underlying the disease to the PITRM1 gene. This gene encodes an enzyme that is important to mitochondrial function. Due to their responsibility for cellular energy metabolism, mitochondria are key to the functioning of cells.

"In the study, we determined the presence of the variant in nearly 30,000 dogs from 374 breeds, identifying the gene defect only in Parson Russell Terriers. Fortunately, the carrier frequency was low, only 5%. The findings will benefit dogs immediately, as a gene test made available based on the results helps identify carriers and avoid breeding them to produce sick puppies. We have already previously reported the gene test results for the roughly 700 dogs tested in the study," says Professor Hannes Lohi from the University of Helsinki.

The disease associated with Parson Russell Terriers is a recessive trait, which means that, for the disease to develop, the defective gene must be copied from both parents to the offspring. The defect is found in this specific breed only.

"The PITRM1 protein serves as a kind of mitochondrial cleaner that breaks up unnecessary pieces of protein and also the harmful amyloid-β. The accumulation of these substances in mitochondria disturbs their function, while neurons in particular tolerate deficient cellular respiration poorly, which explains the early-onset neurodegeneration in dogs. The gene defect results in the disappearance of two amino acids in the PITRM1 enzyme and inhibits it from functioning normally," Hytönen says.

In humans, changes in the same PITRM1 gene also cause neurodegeneration that results in cerebellar ataxia with psychiatric and cognitive abnormalities.

"The human disease progresses slower, but the clinical picture and mechanisms are similar. Our canine study confirms the significance of PITRM1 to mitochondrial and neuronal function, also strengthening the link between mitochondrial dysfunction and neurodegeneration. For now, there are few human patients diagnosed with this disease, which makes the canine model groundbreaking in terms of understanding it," says Professor Lohi.

A new type of COVID-19 testing strategy could help streamline the process of identifying cases, tracking variants and detecting co-infecting viruses.

At present, separate assays and complex workflows are involved in each of these three diagnostic procedures, with analyses typically performed in highly specialized facilities. KAUST researchers have now combined all three kinds of tests into a single procedure that should allow for point-of-care tracking of COVID-19 and the many emerging variants of SARS-CoV-2.

"Our all-in-one test provides a promising integrated solution for rapid field-deployable detection and mutational surveillance of pandemic viruses," says stem cell biologist Mo Li, who led the study.

The test involves a portable briefcase-sized mini-laboratory that avoids all the slow and expensive techniques that are standard for COVID-19 screening and monitoring. The new test takes advantage of a recent genetic method (called recombinase polymerase amplification) and a next-generation portable sequencer to quickly detect the presence of viral sequences and provide read-outs -- in up to 96 patient samples at a time.

Li's team, in collaboration with researchers from Saudi Arabia, the United States and Spain, designed the test to decode five segments of the SARS-CoV-2 genome, each chosen to help guide variant tracking. They also incorporated assays for three common respiratory viruses that can cause symptoms similar to COVID-19.

Working with clinical collaborators from hospitals in Mecca, Medina and Jeddah, the team validated the technique -- termed NIRVANA -- using nose and throat swabs from people suspected of having SARS-CoV-2 infections. They also tested wastewater samples collected from municipal sewage at KAUST to show how the method could allow for population-level surveillance of SARS-CoV-2 and other viruses.

"NIRVANA can rapidly diagnose multiple viral infections in a high-throughput manner," notes Chongwei Bi, a Ph.D. student in Li's lab. What's more, when it comes to SARS-CoV-2 monitoring, "it can simultaneously detect the virus and report its mutations," he adds.

With support from the Rapid Research Response Team (part of the university's Smart Health Initiative), Li and his lab group are continuing to refine the NIRVANA platform for large-scale deployment.

One limitation of the test is that it can only detect SARS-CoV-2 mutations in selected genomic regions, and as new variants of concern keep cropping up around the world, those regions might need to be updated to reflect the evolving nature of the virus.

"At the same time," Li says, "we are seeking to collaborate with hospitals to test NIRVANA in the clinic."

Researchers assessing the impact of solar energy development across Europe have come up with ten ways in which the expansion of solar can be shaped to ensure pollinators benefit.

Space-hungry solar photovoltaic (PV) is set to dominate future global electricity supply, but with careful decision making, efforts to secure clean energy need not come at the expense of biodiversity - particularly pollinators which are in sharp decline.

Bees, hoverflies, wasps, beetles, butterflies and moths play a key role in food production, with around 75% of the leading global food crops and 35% of global crop production relying on them to some extent.

Writing in the journal Renewable and Sustainable Energy Reviews, a Lancaster-led team of environmental scientists systematically reviewed the available evidence on how land management practices relating to solar parks in North West Europe could enhance pollinator biodiversity.

Along with colleagues from the University of Reading, they highlighted ten evidence-based ways to protect and even enhance pollinator biodiversity ranging from sowing wildflowers to connecting solar parks to nearby areas of semi-natural habitat.

Their findings are timely as, in a bid to tackle climate change and reduce greenhouse gas emissions, more power is being generated from renewable sources - at the beginning of 2020 a record breaking 47% of the UK's electricity came from renewables, including wind, solar, hydro, wave and biomass.

Solar parks can produce large amounts of power, with the UK's largest solar park set to power 91,000 homes once complete. But, solar parks also take up land, with potential impacts on the environment. In the UK approximately half of PV has been installed as ground-mounted solar parks, ranging in size from 1-40 hectares.

Shading caused by rows of solar panels affects air temperature, rainfall and evaporation which has a knock on effect on soil, vegetation and biodiversity.

However, in the UK solar parks are often built in intensively managed agricultural landscapes and thus are poor for biodiversity. In this scenario, solar parks may in fact provide opportunities to establish hotspots of pollinator biodiversity which in turn can help pollinate local crops such as oilseed, strawberries and apples.

Lancaster University's Hollie Blaydes said: "Many pollinators are in decline both in the UK and in other parts of the world. Actions to conserve pollinators include reversing agricultural intensification and maintaining natural habitat, both of which can be achieved within solar parks. Often built amongst agricultural land, solar parks offer a unique opportunity to provide pollinator resources where they are most needed."

Prof Simon Potts, University of Reading, said: "As well as promoting biodiversity, pollinator-friendly solar parks also have the potential to provide tangible economic benefits to farmers through enhancing pollination services to adjacent agricultural land, boosting crop yields.

"Imagine a world where solar parks not only produced much needed low carbon electricity but were also diverse and attractive wildflower meadows buzzing with insect life."

Dr Alona Armstrong, Lancaster University Environment Centre said: "Land use change for solar parks could cause further degradation of our environment but, if done well, offers much potential to improve our environment. If we transition well, we could use energy system decarbonisation to also address the ecological crisis. Given where we are, can we afford not to?"

Researchers at the TUM have demonstrated a way to efficiently study molecular mechanisms of disease resistance or biomedical issues in farm animals. Researchers are now able to introduce specific gene mutations into a desired organ or even correct existing genes without creating new animal models for each target gene. This reduces the number of animals required for research..

CRISPR/Cas9 enables desired gene manipulations

CRISPR/Cas9 is a tool to rewrite DNA information. Genes can be inactivated or specifically modified using this method. The CRISPR/Cas9 system consists of two components.

The gRNA (guide RNA) is a short sequence that binds specifically to the DNA segment of the gene that is to be modified. The Cas9 nuclease, the actual "gene scissors", binds to the gRNA and cuts the respective section of the target DNA. This cut activates repair mechanisms that can inactivate gene functions or incorporate specific mutations.

Healthy chickens and pigs with integrated gene scissors

"The generated animals provide the gene scissors, the Cas9 protein, right along with them. So all we have to do is to introduce the guide RNAs to get animals which have specific genetic characteristics," explains Benjamin Schusser, Professor of Reproductive Biotechnology at the TUM. "The initial generation of these animals took about three years. Cas9 can now be used at all stages of animal development, since every cell in the body permanently possesses the Cas9 protein. We have been successfully able to utilize this technique in chicken embryos as well as in living pigs."

The healthy chickens and pigs produced by the researchers thus possess the Cas9 nuclease in all organs studied. This is particularly useful in biomedical and agricultural research.

Analytical tool to fight viral or cancer diseases

Pigs are used as disease models for humans because their anatomy and physiology are much more similar to humans in comparison to mice (currently a common disease model). Thus, a modified pig may help to better understand the mechanism of carcinogenesis in humans. Potential new treatments for humans can also be tested in animal models.

"Due to the presence of Cas9 in the cells the processes are significantly accelerated and simplified," says Angelika Schnieke, Professor of Livestock Biotechnology at the TUM. "Cas9-equipped animals make it possible, for example, to specifically inactivate tumor-relevant genes and to simulate cancer development."

Cas9 pigs and chickens enable researchers to test which genes might be involved in the formation of traits, such as disease resistance, directly in the animal. "The mechanism of the CRISPR/Cas9 system may also be useful for combating infections using DNA viruses. Initial cell culture experiments showed that this already works for the avian herpes virus," says Prof. Schusser.

Important resource for biomedical and agricultural research

Prof. Schnieke notes, "Our Cas9-expressing chickens and pigs represent an innovative resource for genome editing in the biomedical and agricultural sciences, but beyond that, these animals are also available to other research groups. Hence, efficient genome editing in living animals has the potential to significantly advance biomedical and agricultural research."

Diodes are widely used electronic devices that act as one-way switches for current. A well-known example is the LED (light-emitting diode), but there is a special class of diodes designed to make use of the phenomenon known as “quantum tunneling”. Called resonant-tunneling diodes (RTDs), they are among the fastest semiconductor devices and are used in countless practical applications, such as high-frequency oscillators in the terahertz band, wave emitters, wave detectors, and logic gates, to take only a few examples. RTDs are also sensitive to light and can be used as photodetectors or optically active elements in optoelectronic circuits.

Quantum tunneling (or the tunnel effect) is a phenomenon described by quantum mechanics in which particles are able to transition through a classically forbidden energy state. In other words, they can escape from a region surrounded by a potential barrier even if their kinetic energy is lower than the potential energy of the barrier.

“RTDs consist of two potential barriers separated by a layer that forms a quantum well. This structure is sandwiched between extremities formed by semiconductor alloys with a high concentration of electrical charges, which are accelerated when a voltage is placed across the RTD. The tunnel effect occurs when the energy in the electrical charges accelerated by application of the voltage coincides with the quantized energy level in the quantum well. As the voltage is applied, the energy of the electrons retained by the barrier increases, and at a specific level, they are able to cross the forbidden region. However, if an even higher voltage is applied, the electrons can no longer get through because their energy exceeds the quantized energy in the well,” said Marcio Daldin Teodoro, a professor in the Physics Department of the Federal University of São Carlos (UFSCar), in the state of São Paulo, Brazil.

Teodoro was the principal investigator for a study that determined charge buildup and dynamics in RTDs throughout the applied voltage range. A paper describing the study is published in Physical Review Applied. The study was supported by FAPESP via four projects (13/18719-1, 14/19142-2, 14/02112-3 and 18/01914-0).

“The operation of RTD-based devices depends on several parameters, such as charge excitation, accumulation and transport, and the relationships among these properties,” Teodoro said. “Charge carrier density in these devices has always been determined before and after the resonance area, but not in the resonance area itself, which carries the key information. We used advanced spectroscopy and electronic transport techniques to determine charge accumulation and dynamics throughout the device. The tunneling signature is a peak current followed by a sharp drop to a specific voltage that depends on the RTD’s structural characteristics.”

Magnetic field

Previous studies measured charge carrier density as a function of voltage using the magneto-transport technique, which correlates current intensity and magnetic field. However, magneto-transport tools may not be able to characterize charge accumulation throughout the operating range, and there can be blind spots for certain voltage values. As a result, the researchers also used a technique called magneto-electroluminescence, which investigates the light emission induced by the voltage applied as a function of the magnetic field.

“Magneto-electroluminescence enabled us to study voltage bands that were magneto-transport blind spots. The results matched at points where charge density can be measured by both techniques,” said Edson Rafael Cardozo de Oliveira, first author of the paper. “These two experimental techniques proved complementary for a complete investigation of charge density across the entire RTD operating voltage range.”

Cardozo de Oliveira earned a PhD in physics with Teodoro as his thesis advisor, after a sandwich doctorate in Germany at the University of Würzburg’s Department of Technical Physics. Among his other contributions to the study was writing the software used to process the huge amount of data, on the order of gigabytes, produced by the experiments.

“The study can guide further research on RTDs, potentially leading to the production of more efficient optoelectronic devices,” he said. “By monitoring charge buildup as a function of voltage, it will be possible to develop novel RTDs with optimized charge distribution to enhance photodetection efficiency or minimize optical losses.”

Because RTDs are such complex structures, knowing how charges are distributed in them is important. “We now have a more complete map of RTD charge distribution,” said Victor Lopez Richard, a professor at UFSCar and a co-author of the paper.

The paper “Determination of carrier density and dynamics via magneto-electroluminescence spectroscopy in resonant-tunneling diodes” is at: journals.aps.org/prapplied/abstract/10.1103/PhysRevApplied.15.014042.

Journal

Physical Review Applied

DOI

10.1103/PhysRevApplied.15.014042

Current national strategies for bridge maintenance favor replacement over maintenance. A fairly simple depreciation formula is used, resulting in overly conservative assessments of a bridge's long-term health. In a study published in the American Society of Civil Engineers' Journal of Performance of Constructed Facilities, researchers from UGA's College of Engineering propose a new model for the first time. This new approach considers the interaction of 60 to 80 bridge components in predicting long-term bridge performance and focuses on maintenance instead of replacement.

"Rather than considering a bridge as a monolithic structure, the bridge coactive model assesses a bridge as a system in which changes in the condition of each coactive element not only directly affects the overall bridge performance but indirectly influences the performance of the other dependent elements," said Brian Oyegbile, one of the study's authors.

Oyegbile earned his Ph.D. in engineering from UGA in 2020 and now works with the California Department of Transportation.

As an example, Oyegbile says replacing a damaged bridge expansion joint is inexpensive and has marginal impact on the overall performance of the bridge in the short term. However, salt from de-icing or contaminated water can seep through a damaged expansion joint over time, accelerating the deterioration of more critical elements below, such as a column. Likewise, a bridge deck may deteriorate more quickly when debris accumulates in an expansion joint and restricts the normal expansion and contraction of the deck.

According to the UGA researchers, proactively replacing elements at the right time - even one as small as an expansion joint - can have a big impact on long-term bridge health. They say their model can provide stronger data and more accurate depreciation predictions for state transportation agencies as they schedule bridge maintenance, repair and replacement. Nationally, bridges last an average of 75 years. With timely and efficient application of available resources, the researchers say these bridges can serve for more than 100 years.

"In my eyes, the co-activeness is apparent in the bridge inspection data and we can scientifically leverage data analytics in bridge service-life predictions, saving money for the country's infrastructure maintenance and construction," said Oyegbile.

Regular upkeep would save money

Stephan Durham, a professor in the College of Engineering and one of the study's co-authors, says your home's heating and cooling system serves as a good analogy.

"Like clockwork, I replace my air filters every two months whether the system has been in heavy use or not because it keeps the system operating efficiently," he said. "It's the same thing with a bridge. If you're replacing an expansion joint on a regular basis, whether it's completely worn out or not, your bridge is going to perform better than if you let it degrade to the point a component absolutely must be replaced."

The researchers analyzed data in the Federal Highway Administration's National Bridge Inventory for Alabama, Florida and Georgia to build and test their model. Georgia alone has more than 15,000 bridges. The NBI database includes inspection reports on individual bridge elements, proving a wealth of information for the researchers.

"Prior to our work, we hadn't seen a mathematical model that considers the interaction between bridge elements," said Mi Geum Chorzepa, an associate professor and the study's principal investigator. "We need a more realistic way to assess bridge conditions and prioritize preventive maintenance, particularly in such a challenging budget environment."

The researchers estimate a $10 billion investment in timely and appropriate preventive maintenance on the nation's bridges over three years would generate $20 billion in recurring savings by 2024. Those savings could be devoted elsewhere, such as new infrastructure construction, and help drive economic growth, according to the team.

The Georgia Department of Transportation, which funded the study, recently approved a grant for the researchers to expand their work. In the second phase of the project, the team will work with GDOT's Offices of Transportation Data, Research, and Bridge Maintenance to develop a bridge life-cycle assessment tool for use by GDOT and county governments across the state.

The research team also includes S. Sonny Kim, an associate professor in the College of Engineering.

Durham, NC - A study released today in STEM CELLS Translational Medicine suggests a new way to correct facial atrophy of localized scleroderma (LoS) in patients. It shows how applying grafts made up of the patient's own fat enhanced with adipose-derived stem cells (ADSCs) is a safe, feasible and attractive alternative to conventional fat grafting or fat grafting combined with stromal vascular fraction in treating this condition.

LoS is a rare autoimmune disease caused when the body makes too much collagen, which results in the skin becoming stiff and hard. "Presenting mainly as subcutaneous tissue atrophy and hyperpigmentation, this disorder seriously affects the life quality and mental health of patients," said the study's first corresponding author, Xiaojun Wang, M.D., chief of the plastic surgery department at Peking Union Medical College Hospital (PUMCH). Along with Prof. Wang and her PUMCH colleagues, the study team included researchers at Jimo Traditional Chinese Medicine Hospital, Shanghai University, Chinese Academy of Medical Sciences, and the University of Oxford.

Autologous fat grafting (AFG) is currently the primary surgical treatment used to improve facial atrophy in LoS patients, but for various reasons most of the fat graft does not survive. "As a result, the patient has to undergo numerous rounds of grafting procedures to maintain their appearance, which is not only hard on them physically and mentally but poses a financial burden as well," said the study's first authors, Chenyu Wang, M.D., and Xiao Long, M.D.

Some studies indicate that SVF-assisted fat grafting can improve fat graft retention by about 35 percent in healthy people, but it hasn't been proven to induce a similar increase in people with LoS. "However, ADSCs have shown potential for improving fat retention," Prof. Long said. ADSCs, which are harvested from adult fat, have many advantages, researchers believe. They have been proven to be safe, they have self-renewal capacity and can undergo differentiation to mature cells. These cells also are very easy to propagate in cell culture, compared to other cell types.

The Wang team's study is believed to be the first clinical study employing ADSCs-assisted fat grafting to treat facial atrophy of LoS. It is also the first to perform a side-by-side comparison of these grafting therapies, revealing significant differences in graft retention. It was performed on 18 LoS patients exhibiting facial atrophy on their foreheads and cheeks. One group received conventional AFG; a second group was treated with SVF-assisted AFG; and a third group received fat grafting with ex vivo-enriched ADSCs. The mixture of ADSCs-enriched fat grafts was supplemented with 5 × 105 ADSCs/ml fat, a concentration chosen based on the protocols of previous clinical studies of ADSC transplantation.

Magnetic resonance imaging was then used to measure the facial atrophy volume of each participant preoperatively, as well as postoperatively at intervals of three and six months. Clinical photographs also were taken for outcome evaluation.

"The results showed that the fat graft retention of the ADSCs-assisted group was significantly higher than that of the SVF-assisted and the conventional fat grafting groups," Prof. Wang said. "The ADSCs-assisted group showed notable graft retention over the rest of the groups at an early stage and exhibited the highest level of graft retention among the three groups in the long run.

"Although this pilot study was with a limited number of participants and relatively brief follow-up, it showed that the ADSCs-assisted fat grating was not only safe and well-tolerated in LoS patients, but it also may be more feasible and superior to conventional fat grafting or SVF-assisted fat grafting in improving facial atrophy," she added.

"Longer-term, larger and controlled clinical trials will be important to confirm the efficacy of this novel cell therapy for improving fat retention in LoS patients."

"This pilot study suggests that fat grafts combined with their stem cells potentially provide for a safe and feasible alternative to conventional treatment methods to correct facial atrophy that can occur for scleroderma patients," said Anthony Atala, M.D., Editor-in-Chief of STEM CELLS Translational Medicine and Director of the Wake Forest Institute for Regenerative Medicine. "We look forward to the continuation of this research to further document clinical efficacy."

The next time you go for a hike, take an extra moment to appreciate the seemingly ordinary life all around you. A house fly, humble yarrow weed and other "generalist" plants and pollinators play a crucial role in maintaining biodiversity and may also serve as buffers against some impacts of climate change, finds new University of Colorado Boulder research.

The findings, published this month in Ecology, provide valuable insights for prioritizing the conservation of species that contribute to the strength of ecological communities.

"A lot of times, conservation efforts are geared toward things that are rare. But oftentimes, species that are common are also in decline and could go extinct, and that could have really big repercussions for maintaining biodiversity," said Julian Resasco, lead author on the study and assistant professor of ecology.

A "generalist" simply refers to a species that interacts with a lot of other species. For example: A bee that visits many different species of flowers, or conversely, a flower that's visited by many species of bees and other pollinators, said Resasco.

Bumblebees are well-known generalists, their fuzzy, cute bumbling bodies having garnered a large fan base of admirers over the years. But there are unsung heroes among generalist pollinators, including an insect that we often consider with disdain: flies. According to Resasco, some flies are the most common visitors to flowers, and they visit lots of different flowers.

Generalist plants that Colorado residents may recognize include mountain parsley (Pseudocymopterus montanus), which are made up of bunches of small yellow flowers, and common yarrow (Achillea millefolium), which looks similar but are usually white. These plants may not be the famous, brightly colored specimens that wildflower enthusiasts go looking for in summer, but this research finds their role is important to the ecological stability of the meadows where beloved columbine, fireweed and Indian paintbrush grow.

Ecologists have long studied networks of interactions between plants and pollinators, and previous research has shown that generalists can be found time and time again within and across landscapes, and during warm seasons or over several years. What this new study finds is that within seasons, over the span of many years and across the landscape, generalists are able to persist and act as anchors for their communities.

Because so many species rely on generalists, having healthy populations of them helps support a robust community of plants and pollinators that are less susceptible to local extinctions, said Resasco. This robustness may also be important for buffering against increasing unequal shifts in the seasonal timing of species interaction due to climate change, known as phenological mismatch.

What's common is crucial

For the past six years, Resasco has returned to the same mountain meadow in the morning each week, between snowmelt in May and the return of snowfall in September, to observe bumblebees, flies and beetles dance and hop between daisies, roses and asters at six different marked plots.

There's nothing particularly unique about this east-facing meadow, surrounded by aspen and spruce-fir forest. But here, just below Niwot Ridge at 9,500 feet above sea level, near the CU Boulder Mountain Research Station, Resasco counted 267 different species of pollinators that visited the flowers of 41 species of plants--and an encouragingly healthy number of generalists.

Even Resasco, an experienced ecologist recently selected as an early career fellow by the Ecological Society of America (ESA), was surprised by the biodiversity that this meadow supports. Returning year after year to the same place, he found himself noticing more and more about the place.

"Every year teaches you something different," he said.

And these findings teach us that what is common could be crucial to help ecosystems weather current and future environmental change. From setting conservation priorities that protect generalists to leaving your local flies and flowers in peace, there are many ways to support these critical but common species.

Between late June and late July, these plants and pollinators will bloom and bustle in our backyards and nearby mountain meadows, awaiting hikers eager to see them. But if there aren't Instagram-worthy columbines waiting for you when you go, don't despair.

"If you just take some time to stop and observe what's around you, it's always interesting," said Resasco. "Don't overlook the common generalists."

Researchers and physicians from the Occupational Safety and Health Administration (OSHA) and UC San Francisco have found that deaths of workers using methylene chloride paint strippers are on the rise. The solvent is widely used in paint strippers, cleaners, adhesives and sealants.

The study is the first comprehensive review of fatalities linked to the deadly chemical in the United States and identified more deaths than previously reported.

The Environmental Protection Agency (EPA) has acknowledged 53 fatalities connected to the chemical from 1980 to 2018. The new study identified 85 deaths over the same period, most of them occurring in occupational settings (87 percent). The study is published April 19, 2021, in JAMA Internal Medicine.

The authors urged action from the EPA to limit use of the chemical and prevent future deaths.

"It is unacceptable that these workers died simply because they were doing their job," said lead author Annie Hoang, a UCSF medical student and research fellow at UCSF's Program on Reproductive Health and the Environment. "I hope the EPA will do its job to protect our workers and save lives."

The researchers believe that methylene chloride fatalities are undercounted in the United States due to fragmented public health reporting. To identify deaths from the chemical, the researchers undertook a massive search of different sources, including published scientific papers and government databases, compiling information that included medical records and autopsy findings, where available. Their analysis found an increase since 2000 in occupational fatalities related to both paint stripping and to bathroom construction, due to stripping bathtubs.

In early 2017, EPA proposed a rule banning almost all methylene chloride strippers in both the workplace and for consumer use. But in 2019 under new leadership, EPA limited the ban to consumer products while still allowing commercial use to continue unchecked.

"Based on our findings, workers are still at risk from methylene chloride products," said Kathleen Fagan, MD, MPH, former Medical Officer in the Office of Occupational Medicine and Nursing at OSHA and one of the study's researchers. "Health care providers have a critical role to play in preventing deaths by counseling at-risk patients on risk reduction and providing resources on safer alternatives to methylene chloride."

The paper reported that while regulatory policies over the last 25 years mandated product labeling and worker protections, fatalities continued during that time, with a higher proportion of recent deaths tied to the use of paint stripping products. The vast majority of deaths were among men (93.8 percent). Of the 85 fatalities, in 70 cases that had specific information about age, the median age was 31.

The researchers concluded that despite regulatory efforts to address the toxicity of methylene chloride for consumers and workers, fatalities are continuing in the U.S., particularly in occupational settings. They said that prevention should emphasize safer substitutes, not hazard warnings or reliance on personal protective equipment.

"Safer alternatives to methylene chloride are available and in widespread use," said senior author Veena Singla, PhD, a senior scientist at the Natural Resources Defense Council. Previously, she was director of science and policy with UCSF's Program on Reproductive Health and the Environment.

"The science is clear," Singla said. "It is past time to eliminate this deadly chemical and prevent any further tragic loss of life."

Japan -- Next to cat videos, watching small and cuddly rabbits is probably one of the most popular internet pastimes. Plus they appear in literature as well as in traditional folklore spanning numerous cultures, thanks likely to the fact that rabbits reside on every continent except Antarctica.

Yet despite their ubiquity, lagomorphs -- including rabbits, hares, and pikas -- are rather limited in their size diversity. Compare this to their evolutionary sisters, the rodents, which vary in size from the four-gram pygmy mouse to capybaras weighing as much as 50 kilograms.

So why don't we see rabbits rivaling the sizes of horses?

To answer this question, a research team led by Kyoto University's Primate Research Institute investigated the fossil record and evolutionary history of lagomorphs. In a study in the journal Evolution, the team reports that larger herbivore competitors were one evolutionary constraint limiting rabbits' size.

"The largest living wild lagomorphs weigh only about 5 kg on average, a tenth of the largest living rodent, the capybara," says first author Susumu Tomiya.

"But some breeds of domestic rabbits and other extinct species can weigh up to 8 kg. We were surprised by this, and so began to investigate what sort of external forces keep wild lagomorphs across the world from evolving larger body sizes."

The scientists began by analyzing ecological factors, discovering that the body sizes of ungulates -- hoofed animals -- are the most influential predictor.

"We next compared how much energy is used by populations of lagomorphs and ungulates relative to their body sizes," continues Tomiya, "finding that lagomorphs weighing more than six kilograms are energetically at a competitive disadvantage to ungulates of the same size."

The team lastly went through the lagomorph fossil record in North America, discovering that the best predictor for maximum body size was that of the smallest contemporaneous ungulate.

"We see this pattern today across numerous eco-regions, suggesting that there is an evolutionary 'ceiling' placed on lagomorphs by their ungulate competitors," explains Tomiya.

These findings suggest that competitive biotic processes can play an important role in shaping the evolutionary history of mammalian orders, acting in hand with abiotic processes such as changes in climate.

"An ongoing debate in evolutionary biology concerns whether biological or environmental processes are more important in shaping biological diversity," states Tomiya, "as characterized by the 'red queen' and 'court jester' hypotheses."

"For some time, the court jester model -- ascribing diversity to abiotic forces such as the climate -- has been dominant, due to the difficulty of studying biological interactions in the fossil record."

The team's results show that biotic interactions do play an important role in guiding the evolutionary trajectories of some species, within the larger context of abiotic influences.

The production of nanomaterials involves self-assembly processes of functionalized (organic) molecules on inorganic surfaces. This combination of organic and inorganic components is essential for applications in organic electronics and other areas of nanotechnology.

Until now, certain desired surface properties were often achieved on a trial-and-error basis. Molecules were chemically modified until the best result for the desired surface property was found. However, the processes controlling the self-assembly of molecules at interfaces are so complex that small molecular changes can lead to completely different motifs. Physicists from TU Graz explain this unexpected structure formation in a study published in the renowned journal ACS Nano. For this purpose, the researchers studied quinoid compounds on a silver surface. First author Andreas Jeindl from the Institute of Solid State Physics explains: "Naively, one might expect molecules with slightly different sizes but the same functionalization to form similar motifs. In striking contrast, our joint theoretical and experimental study shows that quinones can form diverse structures. Despite constant initial conditions, the formation of these structures cannot be predicted and planned without detailed knowledge of the relevant interactions."

Three opposing driving forces

The researchers in Graz, together with a team from the FSU Jena, have now started to break down this unpredictability. They found that the structure formation is the result of a trade-off between three opposing driving forces: The interaction between molecules and the metal attempts to force all molecules into the same orientation, while the interaction between molecules sometimes favours different orientations. The geometric shapes of the molecules then act as a third factor, preventing or only partially permitting certain interactions.

Based on this, they were able to establish a design principle with which the structures that form at the interfaces, and subsequently their properties, can be predicted - at least for a first class of molecules. An essential role is played by a search algorithm (SAMPLE) based on machine learning. Jeindl elaborates: "We were able to show in this publication that the structures predicted by our algorithm are in excellent agreement with experimental characterizations of organic-inorganic interfaces - both in how the molecules orient themselves on the surface and in how the motifs repeat on the surface. Moreover, our analysis, for the first time, allowed a detailed and quantitative break down of the driving forces, not only of the experimentally formed structures, but de facto of all conceivable structures. This is an important look behind-the-scenes of structure formation."

Interfacial properties with modular building blocks

The non-intuitive interplay of similarly important interaction mechanisms remains a challenge for the design of functional interfaces. With a detailed investigation of all the driving forces, however, the physicists at TU Graz are nevertheless able to devise a design principle for the self-assembly of functionalized molecules for a given class of molecules. Once there are enough analyses for different classes of molecules, the right molecules for the desired interfacial properties can be easily assembled on the computer from modular building blocks.

Liquid Crystals (LC) are widely deployed in display technology and optical fibres. From smartphones in your pockets to large screen TVs, LCs are everywhere, as this special state of matter has been found in colorful soap bubbles as well as certain living tissues.

But LCs are by no means limited to use in gadgets or electronic devices. For quite some time, scientists have been studying the possibility of creating "active nematics", a particular class of active LCs, which consist of self-driven units capable of converting chemical or other forms of energy into motion. When administered the proper stimuli, scientists have found that they can generate a predictable response from different LCs, which allows for design of smart, multifunctional materials systems, such as a bacteria-killing multiphase systems capable of self-regulating and reporting the presence and elimination of pathogens. Previous studies have demonstrated that light patterns can be harnessed to direct the creation and motion of topological defects in LCs, which could serve as cargo carriers or signal transmitters that further enhance the response of the material.

Their findings were published in the journal Nature Materials on February 18,2021. The work was a successful collaboration between several research groups, including Professors Juan de Pablo, Margaret Gardel, Vincenzo Vitelli and Aaron Dinner from the University of Chicago and Professor Zev Bryant from Stanford University.

Sculpting well-defined structures in liquids could in principle enable the engineering of functionalities that are otherwise only possible in solid materials. Existing efforts towards this goal often-times rely on multiple components or phases that are far from equilibrium and difficult to control, thereby limiting their application.

Introducing local activity into such liquid structures could therefore open opportunities for a wide range of applications, for example, mimicking the behavior of cells. However, manipulating these embedded or sculpted structures remains difficult. Thanks to the underlying local molecular orientational field, topological defects in LCs represent stable inhomogeneous structures, which may allow the embedding of flexible structures into a liquid medium.

"Active LCs are a nascent field, and many phenomena remain to be elucidated and applied," said Prof. ZHANG Rui, Assistant Professor in the Department of Physics, HKUST, who is one of the co-authors of the research. "Our study investigated different active LC systems, including natural systems, such as cell colonies, biopolymers and bacteria, as well as synthetic systems, which mimic the adaptive and autonomous behaviors found in living matter."

The study, which was recently published in Nature Reviews Materials, reveals that distinct types of active LC systems all exhibit striking similarities with one another but, more importantly, these systems exhibit a high sensitivity to the environment, such as interfacial events, which makes them potentially programmable and autonomous for a wide range of applications.

"The sensitivity to interfacial events, such as temperature gradients and hydrodynamic flows, can be exploited for the detection of ionic species, gases, toxins, and bacteria," noted Zhang. "By engineering the corresponding interfaces, we can impart a transient activity to these LC systems, which would make these self-propelling LCs a potential candidate for applications such as microreactor design and targeted drug delivery".

"We knew these active materials were beautiful and interesting, but now we know how to manipulate them and use them for interesting applications," says Professor Juan de Pablo, the vice President and Professor of Molecular Engineering of the University of Chicago, a corresponding author of the study said. "That's very promising."

"Active materials are promising in the sense that they don't need real-time communications, human intervention, and external power supply", says Zhang. In the future, Zhang group will continue to collaborate with the Chicago group to explore the possibility of logic operations through these active liquid crystals, which could lead to an applicable autonomous material that can compute and take necessary actions based on their calculations. "With the realization of such intelligent materials, we don't have to read the manual of a medicine, and the capsule would decide how much dose to be released while inside your body; or your window can decide its color and whether to open even in a catastrophic event including an electricity blackout", says Zhang.

A simple dietary supplement reduces behavioral symptoms in mice with a genetic mutation that causes schizophrenia. After additional experiments, including visualizing the fluorescently stained dancing edge of immature brain cells, researchers concluded that the supplement likely protects proteins that build neurons' cellular skeletons.

The supplement betaine was first isolated from sugar beets and is often associated with sweetness or umami flavor. Healthy levels of betaine come from both external food sources and internal synthesis in the body. Betaine supplements are already used clinically to treat the metabolic disease homocystinuria.

"I don't encourage anyone to take betaine for no reason, if a doctor has not recommended it. But, we know this drug is already used clinically, so repurposing it to treat schizophrenia should be safe," said Project Professor Nobutaka Hirokawa, M.D., Ph.D., from the University of Tokyo Graduate School of Medicine who led the recent research project. Hirokawa has been a member of the Japan Academy, a national honorary organization recognizing scientific achievement, since 2004 and received a Person of Cultural Merit award from the Japanese government in 2013.

Schizophrenia is estimated to affect about 1 in 100 people globally and is one of the top 15 leading causes of disability worldwide.

"There are treatments for schizophrenia, but they have side effects and unfortunately there is still no effective drug for patients to take that we can explain biochemically why it works," explained Hirokawa.

Genetic studies of people diagnosed with schizophrenia have found possible links between the disease and variations in the kinesin family 3b (kif3b) gene as well as another gene involved in the body's internal synthesis of betaine.

Hirokawa and his lab members have categorized all 45 members of the kinesin superfamily of genes in mammals, most of which encode motor proteins that move materials throughout the cell. Normally, the KIF3B protein links together with another kinesin superfamily protein and transports cargo throughout a neuron by traveling up and down the cell's skeleton.

Mice used in the recent research had only one functional copy of the kif3b gene and are often used as an animal model of schizophrenia. These mice avoid social interactions and show the same weak response as human patients with schizophrenia in a test called prepulse inhibition, which measures how startled they are by a sudden, loud sound preceded by a quieter sound.

Kif3b mutant mice raised on a diet supplemented with three times the normal amount of betaine had normal behavior, indicating that betaine supplements could treat schizophrenia symptoms.

To figure out why betaine had this effect on mice, researchers grew nerve cells with the kif3b mutation in the laboratory and added fluorescent labels so they could watch the cellular skeleton take shape.

The shape of a healthy neuron is reminiscent of a tree: a cell body surrounded by branches, the dendrites, attached to a long trunk, the axon. Kif3b mutant neurons grown in the lab have an unusual, hyperbranched structure with too many dendrites. Similar hyperbranched neurons are also seen in brain samples donated by people with schizophrenia, regardless of what treatments or medications they took while they were alive.

During healthy neuron development, the main body of the cell fills with a skeleton component called tubulin. Meanwhile, the front growth cone of the cell builds outwards in a spiky, erratic dance due to the movements of another skeleton component called filamentous actin. In kif3b mutants, this dancing movement, which experts refer to as lamellipodial dynamics, is noticeably reduced and the division between tubulin and actin is blurred.

The actin in a neuron's cellular skeleton is assembled in part by another protein called CRMP2. Chemical analyses of the brains of kif3b mutant mice and human schizophrenia patients reveal significant chemical damage to CRMP2, which causes the proteins to clump together.

Betaine is known to prevent the type of chemical damage, carbonyl stress, that causes this CRMP2 dysfunction.

"In postmortem brains of schizophrenia patients, CRMP2 is the protein in the brain with the most carbonyl stress. Betaine likely eliminates the carbonyl stress portion of the schizophrenia equation," said Hirokawa.

By protecting CRMP2 from damage, betaine treatment allows kif3b mutant neurons to build proper structures. With a structurally sound skeleton to navigate, the remaining functional KIF3B protein can shuttle cargo around the cell. Other test tube experiments revealed that KIF3B and CRMP2 can bind together, but their exact relationship remains unclear.

"We know that the amount of betaine decreases in schizophrenia patients' brains, so this study strongly suggests betaine could be therapeutic for at least some kinds of schizophrenia," said Hirokawa.

The UTokyo research team is planning future collaborations with pharmaceutical companies and clinical studies of betaine supplements as a treatment for schizophrenia.