Brain

Warming at the Third Pole has increased vegetation growth that can, in turn, slow down warming.

The Third Pole has seen an increase in vegetation over the past three decades. This phenomenon, also known as "greening," may help slow rapid local warming, according to an invited review paper published in the inaugural issue of Nature Reviews Earth & Environment.

The review finds that CO2 fertilization is the main driver of greening on the global scale. However, in places with a lighter human footprint, such as the Third Pole, global warming is the main cause of greening. "This greening is likely to persist well into the future, because the optimum air temperature for ecosystem productivity is still well below the present-day growing-season air temperature at the Third Pole," said lead author PIAO Shilong, professor at the Institute of Tibetan Plateau Research (ITP) of the Chinese Academy of Sciences (CAS).

Prof. PIAO was invited to lead this comprehensive review of global vegetation change and its climate feedback covering the period from the 1980s to the present. Studying biosphere changes and their impacts is crucial for understanding and adapting to the dramatic changes taking place in the Earth system.

"The greening of the Third Pole has both local and remote impacts on climate change," said PIAO, noting that such vegetation growth may contribute to a slowdown of rapid local warming.

"It would also modify the atmospheric heat source of the Third Pole through evaporative cooling, and induce a remote effect on downstream Asian climate," said PIAO. "But the quantification of this teleconnection needs exploration in the future."

It is still too early to tell if this greening will have an overall positive outcome, though. Another study by PIAO's team has found that warming-induced earlier greening may induce more water loss through enhanced evapotranspiration. This would create drier summer soils across the northern hemisphere, which might result in more frequent heat waves.

These studies are supported by the Second Tibetan Plateau Expedition and Research (STEP), a TPE-related scientific project.

Men pose more risk to other road users than women do and they are more likely to drive more dangerous vehicles, reveals the first study of its kind, published online in the journal Injury Prevention.

The findings prompt the researchers to suggest that greater gender equity in road transport jobs, overall, might help lessen these risks.

Road safety analysis has traditionally focused on an individual's injury risk from their own use of a particular type of transport rather than the risk that might be posed to others.

To try and plug this knowledge gap, the researchers drew on four sets of official data for England for the period 2005-15: police injury statistics (Stats19); Road Traffic Statistics; National Travel Survey data; and Office for National Statistics population/gender figures.

They used the data to analyse the risks posed to other road users from bicycles, cars and taxis, vans, buses, lorries and motorbikes per billion vehicle kilometres travelled, and categorised by road type--major and minor roads in urban and rural areas--and gender.

In terms of absolute numbers, cars and taxis were associated with most (two-thirds) of fatalities to other road users. But a comparison of fatalities per distance travelled shows that other vehicles might be even more dangerous.

Lorries were associated with one in six deaths to other road users: each km driven was associated with more than five times the number of such deaths than each km driven in a car. There was a similarly high death toll for buses per km driven.

Despite their small size, motorbikes also put other road users at high risk. Each km driven was associated with around 2.5 times more deaths to other parties than was each km driven in a car.

In urban areas, most of those deaths--173 over the entire study period--were pedestrians. Policy-makers should ensure that measures to discourage car use don't inadvertently encourage a shift to motorbike transport, suggest the researchers.

At the other end of the scale, cycling seems relatively safe for others: it was associated with fewer deaths to other parties per km ridden than all the other types of transport, with just one other death per billion km cycled.

Analysis of the data by gender showed that men posed a significantly higher risk to other road users for five of the six vehicle types studied.

For cars and vans, the risk posed by male drivers was double that posed by women per km driven, rising to four times higher for lorry drivers, and more than 10 times higher for motorbike riders.

In a linked podcast, lead researcher Dr Rachel Aldred, points out that driving jobs tend to be male dominated, citing the high death toll to other road users associated with lorries, 95% of which are driven by men.

While lorries in general are dangerous vehicles, male lorry drivers pose a particularly high risk compared to female lorry drivers, she adds.

"Greater gender equity would have a positive impact on these injuries," she suggests, adding that: "Policy-makers should be looking to measure the risk posed to others, and how to reduce it."

The researchers conclude: "We suggest policy-makers consider policies to increase gender balance in occupations that substantially involve driving, given the greater likelihood that other road users will be killed if men rather than women are driving or riding."

New research in JNeurosci explores how a particular region of the brainstem might explain differences in attention in people with autism.

In day-to-day life, we are confronted with an abundance of information, and have to be able to selectively attend to the most relevant aspects of our environment. A region of the brainstem called the locus coeruleus is involved in controlling attention. Because people with autism spectrum disorder show differences in how they regulate their attention, Granovetter et al. explored how the locus coeruleus behaves in individuals with autism. Researchers had participants perform an attention-demanding task and monitored their pupil dilation, which provides information about locus coeruleus activity.

Adult participants watched letters flash on a screen and pushed a button if the same letter appeared twice in a row. They then repeated this task with a distraction -- auditory tones played at random times. All participants performed equally well on the task, but participants with autism had atypically smaller pupil dilations compared to controls during the more distracting condition, suggesting a dysregulation in locus coeruleus activity. This dysregulation might explain exaggerated responses to environmental stimuli as well as fixated behaviors and interests that characterize autism spectrum disorder.

There's a new disease-detecting technology in the lab of Sanjiv "Sam" Gambhir, MD PhD, and its No. 1 source of data is number one. And number two.

It's a smart toilet. But not the kind that lifts its own lid in preparation for use; this toilet is fitted with technology that can detect a range of disease markers in stool and urine, including those of some cancers, such as colorectal or urologic cancers. The device could be particularly appealing to individuals who are genetically predisposed to certain conditions, such as irritable bowel syndrome, prostate cancer or kidney failure, and want to keep on top of their health.

"Our concept dates back well over 15 years," said Gambhir, professor and chair of radiology. "When I'd bring it up, people would sort of laugh because it seemed like an interesting idea, but also a bit odd." With a pilot study of 21 participants now completed, Gambhir and his team have made their vision of a precision health-focused smart toilet a reality.

Gambhir's toilet is an ordinary toilet outfitted with gadgets inside the bowl. These tools, a suite of different technologies, use motion sensing to deploy a mixture of tests that assess the health of any deposits. Urine samples undergo physical and molecular analysis; stool assessment is based on physical characteristics.

The toilet automatically sends data extracted from any sample to a secure, cloud-based system for safekeeping. In the future, Gambhir said, the system could be integrated into any health care provider's record-keeping system for quick and easy access.

A paper describing the research will be published April 6 in Nature Biomedical Engineering. Gambhir is the senior author. Seung-min Park, PhD, senior research scientist; David Won, MD, PhD, former visiting scholar in the Molecular Imaging Program at Stanford; and postdoctoral scholar Brian Lee, PhD, share lead authorship.

Pulling double duty

The toilet falls into a category of technology known as continuous health monitoring, which encompasses wearables like smart watches. "The thing about a smart toilet, though, is that unlike wearables, you can't take it off," Gambhir said. "Everyone uses the bathroom -- there's really no avoiding it -- and that enhances its value as a disease-detecting device."

Although the idea may take some getting used to, Gambhir, who holds the Virginia and D.K. Ludwig Professorship for Clinical Investigation in Cancer Research, envisions the smart toilet as part of the average home bathroom. In facilitating that broad adaption, Gambhir designed the "smart" aspect as an add-on -- a piece of technology that's readily integrated into any old porcelain bowl. "It's sort of like buying a bidet add-on that can be mounted right into your existing toilet," he said. "And like a bidet, it has little extensions that carry out different purposes."

These extensions sport an array of health-monitoring technologies that look for signs of disease. Both urine and stool samples are captured on video and are then processed by a set of algorithms that can distinguish normal "urodynamics" (flow rate, stream time and total volume, among other parameters) and stool consistencies from those that are unhealthy.

Alongside physical stream analysis, the toilet also deploys uranalysis strips, or "dipstick tests," to measure certain molecular features. White blood cell count, consistent blood contamination, certain levels of proteins and more can point to a spectrum of diseases, from infection to bladder cancer to kidney failure. In its current stage of development, Gambhir said, the toilet can measure 10 different biomarkers.

It's still early days, though, with a total of 21 participants having tested the toilet over the course of several months. To get a better feel for "user acceptance" more broadly, the team surveyed 300 prospective smart-toilet users. About 37% said they were "somewhat comfortable" with the idea, and 15% said they were "very comfortable" with the idea of baring it all in the name of precision health.

ID please

One of the most important aspects of the smart toilet may well be one of the most surprising -- and perhaps unnerving: It has a built-in identification system. "The whole point is to provide precise, individualized health feedback, so we needed to make sure the toilet could discern between users," Gambhir said. "To do so, we made a flush lever that reads fingerprints." The team realized, however, that fingerprints aren't quite foolproof. What if one person uses the toilet, but someone else flushes it? Or what if the toilet is of the auto-flush variety?

They added a small scanner that images a rather camera-shy part of the body. You might call it the polar opposite of facial recognition. In other words, to fully reap the benefits of the smart toilet, users must make their peace with a camera that scans their anus.

"We know it seems weird, but as it turns out, your anal print is unique," Gambhir said. The scans -- both finger and nonfinger -- are used purely as a recognition system to match users to their specific data. No one, not you or your doctor, will see the scans.

By no means is this toilet a replacement for a doctor, or even a diagnosis, Gambhir said. In fact, in many cases, the toilet won't ever report data to the individual user. In an ideal scenario, should something questionable arise -- like blood in the urine -- an app fitted with privacy protection would send an alert to the user's health care team, allowing professionals to determine the next steps for a proper diagnosis. The data would be stored in a secure, cloud-based system. Data protection, both in terms of identification and sample analyses, is a crucial piece of this research, Gambhir said. "We have taken rigorous steps to ensure that all the information is de-identified when it's sent to the cloud and that the information -- when sent to health care providers -- is protected under HIPAA," he said, referring to the Health Insurance Portability and Accountability Act, which restricts the disclosure of health care records.

Smart toilet 2.0

As Gambhir and his team continue to develop the smart toilet, they're focusing on a few things: increasing the number of participants, integrating molecular features into stool analysis and refining the technologies that are already working. They're even individualizing the tests deployed by the toilet. For example, someone with diabetes may need his or her urine monitored for glucose, whereas someone else who is predisposed to bladder or kidney cancer might want the toilet to monitor for blood.

Gambhir's other goal is to further develop molecular analysis for stool samples. "That's a bit trickier, but we're working toward it," Gambhir said. "The smart toilet is the perfect way to harness a source of data that's typically ignored -- and the user doesn't have to do anything differently."

The Casimir Force is a well-known effect originating from the quantum fluctuation of electromagnetic fields in a vacuum. Now an international group of researchers have reported a counterpoint to that theory, adding to the understanding of energy fluctuations within fluids.

Ultimately, said Rodolfo Ostilla-Mónico, the goal is to apply the findings to better understand the collective behavior of bacteria and other organisms. Ostilla-Mónico, assistant professor of mechanical engineering at the University of Houston, is co-corresponding author of a paper describing the discovery, published Friday in Science Advances.

The customary effect of the Casimir Force is well understood, Ostilla-Mónico said. "This is an analog to this force in a non-quantum system. We are especially interested in the biological implications."

In addition to Ostilla-Mónico, researchers involved in the project include Daniel Putt, a graduate student at UH; Vamsi Spandan from Harvard University; and Alpha A. Lee of the University of Cambridge.

The work builds upon the Casimir Force, one of the governing principles of physics which describes a force arising from the unending electromagnetic waves found in a vacuum. It suggests that a vacuum, rather than being empty, is filled with energy, and this is demonstrated by measuring the force as two plates placed in the vacuum are attracted and move closer to one another because they confine the fluctuations of the electromagnetic field. Dutch physicist Hendrick Casimir first predicted the effect in 1948.

The current work similarly focused on the study of fluctuation-induced force between two plates; in this case the plates were immersed in isotropic turbulence, a scenario in which turbulent fluctuations are the same in all directions. It was designed to illustrate how hydrodynamic turbulence generates force between objects even when the flow has no preferred direction.

The work, the researchers wrote, "sheds light on how length scale-dependent distributions of energy and high-intensity vortex structures determine Casimir forces."

Ostilla-Mónico said they were able to quantify that Casimir forces depend on specific parameters, including turbulence and positioning of the plates.

The findings have implications for micro and nanomanufacturing, but Ostilla-Mónico said the work grew out of the researchers' interest in learning more about the behavior of bacteria. Bacteria are more complex to study, even computationally, but they determined that the study of turbulence would offer some parallels, because both continuously consume energy and generate similar flow fields.

"Turbulence needs energy to keep going," he said. "Bacteria need to be constantly fed in order to keep moving."

Some substances are known to exist in several different structurally disordered solid states, a phenomenon known as polyamorphism.

The first and perhaps most celebrated example of polyamorphic behavior was discovered in water ice in 1984 by Mishima et al. Two different forms of amorphous water ice were identified, known as low-density amorphous and high-density amorphous ices. Later on, similar phenomena were also observed in other important systems such as Si, SiO2, and GeO2.

In condensed matter physics, polyamorphism is a very interesting but poorly understood phenomenon.

Recently, a team of scientists from Institute of Solid State Physics of Hefei Institutes of Physical Science in China and their international collaborators from Comenius University in Slovakia, European Laboratory for Non-Linear Spectroscopy in Italy, The University of Edinburgh in UK and et al. , examined polyamorphism in the molecular substance SO2.

While exploring phase transition in dense SO2, they found pressure-induced amorphization in dense sulfur SO2 and a reversible pressure-induced structural transformation between the molecular amorphous and polymeric amorphous forms of SO2. This work was published in PNAS on April 4, 2020.

SO2 plays a significant part in chemistry research and in the physics of the Earth and atmosphere. While properties of similar solid molecular systems such as CO2 or N2 at high pressures have been extensively studied, more research on dense SO2, especially its behavior and properties, still needs to be done.

In this study, scientists took a closer look at this simple molecule through a combined experimental and computational effort that tried to describe some new and unexpected phenomena.

By using experimental techniques of Raman spectroscopy and X-ray diffraction at high pressures, they compressed SO2 up to 60 GPa with a diamond anvil cell and explored the phase transitions and structures of SO2 up to 60 GPa and at temperatures ranging from 77-300 K.

At 77 K and below 16 GPa, sulfur dioxide was crystalline. When compressed to 16 GPa, the sulfur dioxide in the crystalline phase went through pressure-induced amorphization and entered the amorphous phase of the molecular state. When further compressed to above 26 GPa, a phase transition occurred from the molecular amorphous phase (two-coordinated sulfur) to the chain polymeric amorphous phase (three-coordinated sulfur).

The researchers studied several different temperature paths and found that the phase transition path in dense SO2 proceeded from the crystalline to the molecular amorphous phase and then to the polymeric amorphous phase over the entire temperature range of 77-300 K. They also discovered that the phase transition path was reversible.

Furthermore, the amorphization pressure changed with temperature, ranging from 10-16 GPa across the 77-300 K temperature range.

To test their observations, the team used molecular dynamics simulations and the same phenomenon was also observed. In particular, the high-pressure polymeric amorphous form was found to consist mainly of disordered polymeric chains made of three-coordinated sulfur atoms connected via oxygen atoms, and few residual intact molecules.

The amorphous molecular to amorphous polymeric transition identified in this research may also suggest the possible existence of a similar transition in the liquid state.

BIRMINGHAM, Ala. - Human cells respond to stresses like DNA damage, metabolic imbalance and starvation by first trying to repair the problem. If that does not work, the cells then induce programmed cell death, called apoptosis. Apoptosis is a highly regulated cell fate decision that removes about 50 billion to 70 billion cells each day in adults.

The regulators of apoptosis watch over cell functions, especially cell replication and the decision to enter the cell cycle. This portion of the life of a cell requires accurate DNA replication and error-free chromosome separation. At multiple checkpoints during this process, pathways exist to induce apoptosis as needed.

Now University of Alabama at Birmingham researchers William Placzek, Ph.D., and Robert Whitaker have found a direct link between the protein MCL1 -- a member of the large BCL2 protein family known as the gatekeepers of apoptosis -- and a cell-cycle checkpoint protein called P18. Through this link, they show the first demonstration that MCL1, which functions in the decision between either cell survival or programmed death, can also directly initiate cell proliferation, via the CDK4/6-RB pathway.

Their study is published in the journal Cell Death & Disease, the official journal of the Cell Death Differentiation Association. Placzek is an assistant professor in the UAB Department of Biochemistry and Molecular Genetics and an associate scientist in the O'Neal Comprehensive Cancer Center at UAB. Whitaker is a graduate student in the Placzek lab.

The BCL2 family includes pro-apoptotic proteins and anti-apoptotic proteins that compete via direct protein-to-protein binding to determine cell fate. These detailed interactions have significance in human health because the anti-apoptotic BCL2-family proteins turn out to be key regulators of cancer tumorigenesis and/or anti-cancer therapeutic responses. Upregulation of the proteins is a common event in various types of cancer. In particular, overexpression of the anti-apoptotic BCL2-family protein MCL1 is a mechanism used by solid tumors to evade some standard cancer chemotherapies.

Besides its role in cancer, Placzek said, "we expect this communication between the BCL2 family and the CDK4/6-RB pathway exists and will have significant impact in normal cellular proliferation, in stem cell growth and in differentiation. Of particular interest is how this interaction impacts hematopoietic and neuronal progenitor cell speciation, where MCL1 has been identified as a key mediator of differentiation."

Study details

Nine years ago, Placzek and colleagues at the Sanford-Burnham Medical Research Institute identified a novel protein motif that could bind to the mouse version of MCL1. A protein structural motif is a secondary structure on the protein that can interact with a secondary structure on another protein, akin to a space capsule docking to the International Space Station. The novel motif found by Placzek and colleagues was a reversal of the known binding motif BH3, so they called it reverse BH3, or rBH3.

Search of the human genome DNA sequence identified several proteins that putatively had an rBH3 motif, including P18, a regulator acting at the G1/S stage of the mammalian cell cycle.

The current study shows biological significance for the rBH3 motif.

"We have demonstrated that the rBH3 motif is more than a unique peptide sequence," Placzek said. "It is a natural protein motif that is able to mediate direct protein-to-protein interactions between MCL1 and an rBH3-containing protein."

Using a variety of biological chemistry tools like pull-down experiments, co-immunoprecipitation, chimeric proteins, small molecule inhibitors, protein expression knockdown and protein overexpression, the two researchers detailed the mechanism of MCL1-P18 binding and its biological significance.

They showed that the two proteins bind together in vitro and endogenously inside cells of two solid tumor cell lines; they also showed that the rBH3 motif on P18 was necessary and sufficient to mediate that binding. In the two solid tumor cell lines, they showed that overexpression of MCL1 induced a loss of P18 through a transcriptionally independent cysteine-protease degradation process. That overexpression of MCL1 also affected the cell cycle, as shown by a decrease in the G1 cell population and corresponding increases in the S and G2/M populations, and those changes are RB1-dependent. Finally, they showed that those changes occur because of increased cell proliferation, rather than the alternate possibility, a G2/M block.

A previous study has shown that a type of squill growing in Madeira produces a chemical compound that may be useful as a medicinal drug. But a new study from researchers at Uppsala University has shown that this is probably not true: instead, the plant had likely accumulated antibiotics from contaminated soil.

All chemical compounds in nature are built through biosynthesis, a process where plants, animals and microorganisms produce complex compounds from simpler structures. Some of these are produced with the goal of protecting the organism, e.g. the toxic compounds produced by plants to poison herbivores. The fields of pharmacognosy and natural products chemistry are focussed on taking these compounds from nature and repurposing them for use in human medicine.

Today, we know quite a lot about biosynthesis within different organisms. Using this knowledge, we can even predict the kinds of chemical compounds that we expect to find within nature - and the ones we do not.

This knowledge led Luke Robertson, postdoctoral fellow working between the Department of Ecology and Genetics and the Department of Medicinal Chemistry, to question the proposed structure of a chemical compound discovered within the Madeiran Squill (Scilla madeirensis, Asparagaceae). A previous study had reported that a compound produced by the plant might be useful for the treatment of prostate hyperplasia. But the structure of the compound looked strange: it did not fit with any known biosynthetic pathway. Closer examination led Robertson to the conclusion that the researchers had not only misidentified the chemical structure - but that they had found a substance that was not produced by the plant at all. They had discovered a synthetic antibiotic: sulfadiazine.

"The tools we use to identify the structures of organic compounds can be complex; we don't just put data into a computer and it then spits out a chemical structure back at us. It's like solving a riddle - and two people might have different answers to the same riddle" said Luke Robertson.

But where did the sulfadiazine come from? While the compound was clearly isolated from within the plant, we know that sulfadiazine is synthetic; that is, produced only by humans. The only reasonable explanation, according to Robertson, is that the drug had contaminated the plant and the surrounding area through polluted fertilizer. Sulfadiazine is widely used within the livestock industry and is known to be spread throughout the environment via animal manure. The compound then builds up within soil and is later accumulated within plants.

"It is incredibly important that we identify chemical structures correctly. Drug companies stand to lose millions by discovering a compound with potential to be used as a human drug, but then patenting the incorrect chemical structure. If another company figures this out, they can effectively 'steal' the compounds patent".

The end-Permian mass extinction (EPME), approximately 252 million years ago (Ma), caused a serious marine and terrestrial ecosystem crisis, and about 75% of terrestrial biological species disappeared. How long did it take for terrestrial ecosystems to recover?

A research team led by Prof. WANG Bo from the Nanjing Institute of Geology and Palaeontology of the Chinese Academy of Sciences (NIGPAS) found that both lake and peat-forming forest ecosystems probably took as long as 10 million years to recover after the EPME. Results were published in Geology on March 30. 

Marine ecosystems are thought to have recovered substantially by the middle to late Anisian (about 8-10 million years later) and their restoration was still ongoing in the latter part of the Late Triassic (200 Ma). However, the pattern of recovery of lacustrine ecosystems is still unclear due to the highly fragmentary freshwater fossil record.

The researchers conducted a systematic study of the Middle Triassic lacustrine sediments in the Ordos Basin of China, including stratigraphy, sedimentology, and palaeontology in three outcrops on the southern edge of the basin.

U-Pb isotopic ages of tuffaceous layers in three outcrops dated the Triassic organic-rich shale to 242 Ma in the Middle Triassic Tongchuan Formation. The organic-rich shale in the lower part of the Tongchuan Formation represents the first known appearance of a deep perennial lake after the EPME and is 5 million years earlier than any previous record.

The shales have yielded abundant fossils, including microalgae, macroalgae, notostracans, ostracods, insects, fishes, and fish coprolites. They provide data on the earliest known Triassic complex lacustrine ecosystem. Such an ecosystem is a key component of Mesozoic lakes, which were different from pre-Mesozoic lakes in which dipteran larvae were absent and aquatic beetles were rare. 

The restoration of a complex lacustrine ecosystem was coincident with the termination of the "coal gap," which was an interval of approximately 10 million years during which no coals were deposited worldwide.

It is generally believed that the reoccurrence of the Middle Triassic coal seam represents a significant restoration of the forest ecosystem after the EPME. Therefore, both lake and peat-forming forest ecosystems probably took up to 10 million years to recover, much longer than the period of recovery of plant communities inferred from palynological data.

Australian Scientists have shown that an anti-parasitic drug already available around the world can kill the virus within 48 hours.

Scientists from Monash University in Melbourne showed that a single dose of the drug, Ivermectin, could stop the SARS-CoV-2 virus growing in cell culture - effectively eradicating all genetic material of the virus within 48 hours.

The next steps are to determine the correct human dosage - ensuring the doses shown to effectively treat the virus in the test tube are safe levels for humans.

The use of Ivermectin to combat COVID-19 depends on pre-clinical testing and clinical trials, with funding urgently required to progress the work.

Ivermectin is an FDA-approved anti-parasitic drug that has also been shown to be effective in vitro against a broad range of viruses including HIV, Dengue, Influenza and Zika virus.

The findings of the study were published today in Antiviral Research.

A collaborative study led by Monash University's Biomedicine Discovery Institute (BDI) in Melbourne, Australia, with the Peter Doherty Institute of Infection and Immunity (Doherty Institute), has shown that an anti-parasitic drug already available around the world kills the virus within 48 hours.

The Monash Biomedicine Discovery Institute's Dr Kylie Wagstaff, who led the study, said the scientists showed that the drug, Ivermectin, stopped the SARS-CoV-2 virus growing in cell culture within 48 hours.

"We found that even a single dose could essentially remove all viral RNA by 48 hours and that even at 24 hours there was a really significant reduction in it," Dr Wagstaff said.

Ivermectin is an FDA-approved anti-parasitic drug that has also been shown to be effective in vitro against a broad range of viruses including HIV, Dengue, Influenza and Zika virus.

Dr Wagstaff cautioned that the tests conducted in the study were in vitro and that trials needed to be carried out in people.

"Ivermectin is very widely used and seen as a safe drug. We need to figure out now whether the dosage you can use it at in humans will be effective - that's the next step," Dr Wagstaff said.

"In times when we're having a global pandemic and there isn't an approved treatment, if we had a compound that was already available around the world then that might help people sooner. Realistically it's going to be a while before a vaccine is broadly available.

Although the mechanism by which Ivermectin works on the virus is not known, it is likely, based on its action in other viruses, that it works to stop the virus 'dampening down' the host cells' ability to clear it, Dr Wagstaff said.

Royal Melbourne Hospital's Dr Leon Caly, a Senior Medical Scientist at the Victorian Infectious Diseases Reference Laboratory (VIDRL) at the Doherty Institute where the experiments with live coronavirus were conducted, is the study's first author.

"As the virologist who was part of the team who were first to isolate and share SARS-COV2 outside of China in January 2020, I am excited about the prospect of Ivermectin being used as a potential drug against COVID-19," Dr Caly said.

Dr Wagstaff made a previous breakthrough finding on Ivermectin in 2012 when she identified the drug and its antiviral activity with Monash Biomedicine Discovery Institute's Professor David Jans, also an author on this paper. Professor Jans and his team have been researching Ivermectin for more than 10 years with different viruses.

Dr Wagstaff and Professor Jans started investigating whether it worked on the SARS-CoV-2 virus as soon as the pandemic was known to have started.

The use of Ivermectin to combat COVID-19 would depend on the results of further pre-clinical testing and ultimately clinical trials, with funding urgently required to keep progressing the work, Dr Wagstaff said.

Using a machine learning algorithm to analyze mouse facial expressions, Nejc Dolensek and colleagues have uncovered the neurological origins of emotional states. Their work "provides an objective analysis tool that is essential to be able to understand the neurobiological mechanisms of emotions, to identify species-specific emotions, and to identify their variability across individuals," say Benoit Girard and Camilla Bellone in a related Perspective. The neurobiological origins of emotions remain mysterious to researchers. Scientists still do not fully understand how emotions arise in the complex circuitry of the human brain, and attempts to understand emotions in animals like mice have been held back by a lack of precise tools for gauging emotional states. To better understand the emotional states of our furry cousins, Dolensek et al. used an advanced machine vision technique to precisely classify facial expressions in mice reacting to emotion-inducing events. The researchers recorded the mice as they exposed them to sensory stimuli such as sweet and bitter tastes and fearful events and identified several facial expressions that consistently correlated with emotional descriptors such as pleasure, disgust and malaise. These facial expressions showed properties such as valence (engendering positive or negative reactions) and scaled with the strength of the stimulus, suggesting that they corresponded to internal emotional states and were not merely reflexive reactions. Using two-photon calcium imaging, the authors also characterized "face" neurons in the brain whose activity correlated to specific facial expressions in the mice. The work, the authors say, may assist in moving towards a more universal and evolutionary based definition of emotions and their neural underpinnings across species.

In a study published this week in Science, Université de Montreal researchers report key structural and biochemical differences among a class of anti-cancer drugs known as PARP inhibitors. These distinguishing differences were linked to differing capacities of PARP inhibitors to kill cancer cells. The research resolves a long-standing and perplexing quandary over differences between the effectiveness of PARP inhibitors used in cancer clinics.

Moreover, the researchers used their structural and biochemical insights to introduce modifications to an existing PARP inhibitor, and thereby increased its capacity to kill cancer cells. "The principle behind this tailoring of PARP inhibitor molecules also has applications beyond cancer therapy, for example in other indications such as cardiovascular disease and inflammation, where PARP inhibitor use is also being evaluated," says John Pascal, a senior author on the study.

PARP inhibitors target the enzyme PARP-1. PARP-1 is a primary responder to breaks in the structure of DNA, a chronic form of genome damage that is under constant surveillance and repair. PARP-1 has two major activities: binding to DNA breaks, and creating a molecule known as poly(ADP-ribose). PARP inhibitors all bind to the same region of PARP-1 and prevent PARP-1 from making poly(ADP-ribose), and this activity interferes with PARP-1 contribution to the repair of DNA damage. The loss of PARP-1 contribution to DNA repair is acceptable in healthy cells; however, cancer cells with re-configured DNA repair mechanisms, such as those deficient in the repair protein BRCA1 or BRCA2, have become dependent on PARP-1 and are selectively killed by PARP inhibitors.

Prior to the study in Science, it was unclear whether PARP inhibitors could also affect the second activity of PARP-1, binding to damaged DNA. The PARP inhibitors that are most effective in the clinic tend to "trap" PARP-1 on DNA, which is thought to prevent cancer cells from dividing. The authors of the study asked whether there could be a structural aspect of PARP inhibitors that increases PARP-1 interaction with DNA. "We were quite surprised to find that some PARP inhibitors actually decreased PARP-1 interaction with damaged DNA," says Marie-France Langelier, a lead author of the study. One of these PARP inhibitors, Veliparib, decreased PARP-1 binding to DNA and is poor at killing cancer cells compared to other PARP inhibitors. Veliparib thus seems to work against the PARP-1 "trapping" process by weakening PARP-1 interaction with DNA. This result provided a key clue to the puzzle: By comparing the structure of Veliparib to clinical PARP inhibitors that do trap PARP-1 on DNA, the authors were able to identify differences in the structures that could account for the ability of the inhibitors to trap versus weaken interactions with DNA.

Using Veliparib as a starting molecule, the researchers engineered a new PARP inhibitor that did have the capacity to increase PARP-1 interaction with DNA, and this new PARP inhibitor showed greater cancer cell killing relative to Veliparib. "It was rewarding to see that the biochemical and structural studies were consistent and predictive of the behaviors that I observed in the cell killing assays" continued Langelier.

The results of this study also open up new avenues to designing PARP inhibitors for treating other diseases. While PARP inhibitors used in cancer treatment are selected for their ability to kill cancer cells, there are others used to treat inflammation or cardiovascular disease where the goal is to preserve cells and guard against tissue damage associated with hyper activation of PARP-1. Thus, the ability to tailor PARP inhibitors to reduce PARP-1 trapping on DNA could be important in these applications. The study provides the design principles for tailoring PARP inhibitors to specific applications. "PARP inhibitors have generated excitement in the medical community and they have established new prospects for treating disease. We are thrilled that our structural and biochemical approach to understanding PARP-1 can guide the continued development of PARP inhibitors," says John Pascal.

Recent years have brought unusually large and damaging wildfires to the Pacific Northwest - from the Carlton Complex Fire in 2014 that was the largest in Washington's history, to the 2017 fire season in Oregon, to the 2018 Maple Fire, when normally sodden rainforests on the Olympic Peninsula were ablaze. Many people have wondered what this means for the region's future.

A University of Washington study, published this winter in Fire Ecology, takes a big-picture look at what climate change could mean for wildfires in the Northwest, considering Washington, Oregon, Idaho and western Montana.

"We can't predict the exact location of wildfires, because we don't know where ignitions will occur. But based on historical and contemporary fire records, we know some forests are much more likely to burn frequently, and models can help us determine where climate change will likely increase the frequency of fire," said lead author Jessica Halofsky, a research scientist at the UW School of Environmental and Forest Sciences and with the U.S. Forest Service.

The review was done in response to a survey of stakeholder needs by the Northwest Climate Adaptation Science Center, a UW-hosted federal-university partnership. State, federal and tribal resource managers wanted more information on the available science about fire and climate change.

"We're on the cusp of some big changes. We expect that droughts will become more common, and the interaction of climate and fire could look very different by the mid-21st century," said David Peterson, professor at the UW School of Environmental and Forest Sciences. "Starting the process of adapting to those changes now will give us a better chance of protecting forest resources in the future."

The greatest increased risk was found for low-elevation ponderosa pine forests, of the type found at lower elevations on the east side of the Cascade Range in Washington, Oregon, Montana and Idaho. This ecosystem has the highest fire risk today and also has the highest increase in risk due to climate change. The authors predict with high confidence that wildfires in this region will become larger and more frequent.

"We can't attribute single fire events to climate change. But the trends in large fire events that have been occurring in the region are consistent with expected trends in a warming climate," said co-author Brian Harvey, assistant professor at the UW School of Environmental and Forest Sciences. His UW research group studies forests and fires in the Pacific Northwest and Northern Rockies.

The authors also summarize how other Northwest ecosystems might experience the combined threats of drought, warmer temperatures and insect outbreaks. Moist, coniferous forests -- found on the Olympic Peninsula, in Western Washington and in Northern Idaho -- will likely burn more often, but fires won't be significantly larger than they were historically. Fires in subalpine, high-elevation forests, found in mountainous terrain, will similarly become more frequent but only slightly larger or more severe.

After describing the threats, the authors evaluate potential strategies to prepare. Land managers could remove dry organic material, or fuels, and maintain forest densities at lower levels to reduce the severity of fires, since the severity of wildfire is more controllable than the frequency or total area burned. Thinning would also help the remaining trees to withstand drought. Planting genetically diverse seedlings could also help with regeneration after fires -- an important step for long-term survival of forests.

Rural landowners can also play a role, the authors write.

"Individual landowners can reduce hazardous fuels, promote species that can survive fire and drought, and increase diversity of species and structures across the landscape," Peterson said.

Historically the Northwest has had lower risk of wildfire than other states, such as California, but that may be changing.

"In general, the climate in the Northwest is cooler and wetter than in most low-elevation areas of California," Halofsky said. But the Northwest summers are dry and warm. "Climate change will accentuate dry summers, and Northwest climate will become more similar to current-day California climate, leading to more and bigger fires."

Over the past few decades, the critically endangered whooping crane (Grus Americana) has experienced considerable recovery. However, in a report appearing April 2 in the journal Heliyon, researchers found that habitat loss and within-species attraction have led whooping cranes to gather in unusually large groups during migration. While larger groups are a positive sign of species recovery, the authors say that these large groups mean that a disease outbreak or extreme weather event could inadvertently impact a substantial portion of this still fragile population.

"Whooping crane conservation is one of North America's great success stories," says Andrew Caven, Director of Conservation Research at Crane Trust, a non-profit organization dedicated to the protection of critical habitat for whooping cranes and other migratory birds. During the 1940s the whooping crane population fell to 16 birds, largely due to overhunting. However, after concerted conservation efforts, their numbers have increased 30-fold. "We had this species at the brink of extinction, and now there are over 500 birds. As conservation biologists, we've been extremely inspired by that."

Even with this boom in whooping crane numbers, researchers are observing larger migratory flocks than they would expect from population growth alone. Historically, groups of migrating whooping cranes seldom exceeded a family unit. "Twenty years ago, a group of nine was notable; something you'd write in your natural history notes about. But now it's becoming something quite regular. In the recent years we've seen bird groups over seventy multiple times."

With a total population of only around 500 birds, groups of this size could potentially put the whole species at risk. "The largest group detected was about 150 birds near Marcelin, Saskatchewan, which represents over one-fourth of the population. In a group that size, extreme weather like hailstorms or an outbreak of avian cholera could be catastrophic for the species," says Caven.

So Caven and his research team set out to understand why traveling groups of whooping cranes had grown so large. They collected sightings data from state, federal, and private conservation organizations as well as the public along the whooping cranes migratory path from their Texas wintering grounds to their breeding grounds in Alberta, Canada.

Results indicated that the larger flocks of whooping crane roosted most frequently in the Southern Great Plains, where wetland habitats are sparse, but a few, high-quality conserved wetlands still stand.

"Many wetland habitats in the Great Plains have disappeared due to sedimentation or have been drained for farming" says Caven. "The rate of wetland loss has actually been quite high, particularly in these basins south of the Platte River." With limited access to quality habitat in the southward part of their migration, it appears whooping crane have adjusted by gathering in proportionally larger assemblages.

As a sort of snowball effect, the authors say these gatherings can also be promoted by conspecific attraction or attraction to like individuals. The presence of birds in a location can make it more desirable for other cranes. "Conspecific attraction helps birds indicate optimal forging resources in these patchy environments and provide vigilance in situations that could be risky. These benefits could be a major reason we are seeing the emergence of these new behaviors as the cranes recover from near extinction," he says.

Based on these findings, Caven suggests the best way to disperse these groups is to provide more wetland habitat throughout their migration path. "Supporting conservation groups that are restoring habitats south of the Platte River, particularly wetlands, can have a serious impact. Increasing the scale of wetland restoration within the migration corridor could break up these aggregations and provide foraging space for a ton of birds, not just whooping crane."

The Crane Trust research team also plans to evaluate how habitat quality affects the length of time whooping cranes stay at stopover locations before continuing on in their migration. This will help determine those sites that are most essential in providing necessary resources for the birds to complete their 3,000-mile journey.

Learning from nature, scientists from the Center for Sustainable Resource Science in Japan and the Korean Basic Science Institute (KBSI) have found a catalyst that efficiently transforms nitrate into nitrite--an environmentally important reaction--without requiring high temperature or acidity, and now have identified the mechanism that makes this efficiency possible.
Nitrogen is an important element for various biological processes, but it is often necessary to convert it into one form or another, in a system known as the nitrogen cycle. In nature, this is usually carried out by bacteria and other microorganisms, which can perform the feat at ambient temperature and mild pH conditions. Recently, the excessive use of nitrogen fertilizers in response to population growth has led to serious water pollution due to the presence of nitrate (NO3-) ions in fertilizers. Runoff from agriculture can lead to nitrate pollution of drinking water, and the eutrophication of lakes and marshes, leading to algae growth. As a result, it has become necessary to reduce the emission of nitrate ions into the environment.

Wastewater cleaning using microbes is currently performed, but it is not always possible to do this, as the concentration of nitrate can make it impossible for microorganisms to survive. There have been attempts to create catalysts that can perform the same task done by bacteria. Unfortunately, due to the high stability of nitrate, these expensive rare metal catalysts require high temperature, ultraviolet photolysis, or strongly acidic environments. Thus the development of catalysts that could cheaply perform the transformation at ambient temperatures was a major goal of research.

Recently, an international team led by Ryuhei Nakamura of the RIKEN Center for Sustainable Resource Science (CSRS), decided to try to use the same method as nitrate reductase, an enzyme used by microorganisms, and succeeded in chemically synthesizing oxo-containing molybdenum sulfide, which was able to catalyze nitrate into nitrite in an aqueous electrolyte at neutral pH.

Now, in research published in Angewandte Chemie International Edition, they have used a variety of methods to determine that their catalyst contains a reaction active site similar to what is found in natural nitrate reductase. They had identified oxo-containing molybdenum sulfide as a promising candidate, and knew that it worked better than other catalysts, but they did not know why. They went on to study it by observing chemical species on its surface in the presence of a reducing agent--in this case dithionite ions--using molecular spectroscopy (electron paramagnetic resonance spectroscopy (EPR) and Raman spectroscopy. "We hypothesized," says first author Yamei Li, who did the work at RIKEN CSRS and is currently at the Tokyo Institute of Technology, "that the oxo-molybdenum sulfide catalysts may have active sites similar to those in enzymes. To test this hypothesis, we attempted to track how chemical species on the catalyst surface change using molecular spectroscopy."

Their main finding was that pentavalent molybdenum with oxygen ligands--one of the intermediate products--functioned as an active species that accelerated the reaction, and showed that this active species has a structure similar to the active core of natural nitrate reductase. Their studies using EPR spectroscopy confirmed this, finding that the oxygen and sulfur, ligands of the molybdenum also play an important role in efficiently producing the pentavalent oxo-molybdenum species on the catalyst surface.

According to Nakamura, "This result shows that nitrate ions can be detoxified in a mild environment without depending on rare metal catalysts. We hope that this will make possible the development of new technology for synthesizing ammonia from waste liquid."