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Biophysicists from the MIPT Center for Molecular Mechanisms of Aging and Age-Related Diseases have teamed up with colleagues from Canada, the U.S., Japan, France, and Germany to shed light on the structure and functioning mechanism of the CysLT receptors, which regulate inflammatory responses associated with allergic disorders. Their findings are reported in Nature Communications.

Cellular communication refers to the interactions between cells in an organism. It allows millions of cells to work together, managing bodily processes that are crucial for survival. Cells communicate via protein molecules called receptors, which exist on the cell and organelle surfaces, as well as in the cytoplasm. When a receptor binds a particular molecule, this triggers a specific response. A molecule that binds to a specific receptor is called a ligand.

G protein-coupled receptors, or GPCRs, are molecular machines incorporated into cell membranes. CysLT1R and CysLT2R are members of the GPCR family. Their ligands are highly potent lipids called peptide (cysteinyl) leukotrienes, or CysLTs.

Both of the receptor subtypes CysLT1 and CysLT2 are known to regulate allergic inflammatory responses. For over two decades, asthma and associated conditions have been treated with drugs that inhibit the CysLT1 receptor. Many patients, however, do not respond to this treatment. At the same time, the role of the CysLT2 receptor in the physiology and pathogenesis of the inflammatory response remains poorly studied. It was not until recently that CysLT2R was suggested as a potential drug target in the treatment of atopic asthma, brain injury, and central nervous system disorders, as well as certain cancers.

As of today, the development of more effective medications for asthma and associated conditions is hindered by the lack of information on how and to what ligands the CysLT receptors bind. Their functioning mechanisms have not been clearly understood either, as this requires high-resolution structural biology data. Once these are available, researchers can proceed using computer simulations.

In molecular modeling, docking is a method for determining the preferred orientation and conformation of the ligand within the protein binding site. Knowing the spatial structure of a given receptor with angstrom precision, as well as the chemical structure of the ligand, enables biologists to predict the spatial structure of the corresponding receptor-ligand complex and calculate the free energy of its formation. Hence, determining the spatial structure of such complexes is crucial to understanding their function.

In their recent study, researchers from the Moscow Institute of Physics and Technology identified the most critical ligand-binding determinants of the CysLT1 and CysLT2 receptors based on the structural analysis the team performed for CysLT2R and the structural data on CysLT1R published by the laboratory in October.

"The new structures have greatly improved the accuracy of ligand docking and helped us better understand the properties of ligands with respect to both receptors. Now we know how to alter drug design templates to inhibit the activity of both the CysLT1 and CysLT2 receptors or do that selectively for either of them," commented Anastasiia Gusach, a PhD student at MIPT and a junior researcher at the MIPT Laboratory of Structural Biology of G Protein-Coupled Receptors.

In the future, these structures could be further developed to serve as drug candidates or tool compounds, aiding in understanding the specific role of each of the CysLT receptor subtypes in various physiological and pathological processes.

"Recently obtained results suggest that addressing both the CysLT1 and CysLT2 receptors as a drug target or even inhibiting CysLT2R alone will offer a more effective alternative to CysLT1R-selective drugs, especially in severe asthma cases. In addition, CysLT2R is emerging as a potential drug target for patients with brain injury and neurodegenerative disorders. All of the above makes CysLT2R promising for research. In this study, we described four crystal structures of CysLT2R in complex with three ligands blocking the CysLT1 and CysLT2 receptors," said Alexey Mishin, a senior researcher at the MIPT Laboratory of Structural Biology of G Protein-Coupled Receptors.

Another great application of the structural information obtained in the study is the possibility to rationalize the effects of point mutations in which a "foreign" amino acid appears in the amino acid sequence of a protein, which in turn influences receptor activity. For this reason, the researchers accumulated information on mutations in the sequence of the CysLT2 receptor from 60,000 healthy individuals and mapped the positions of the new amino acids on the receptor structure. They found that about a quarter of these mutations were located in functionally important regions and may influence what processes the receptor will activate or deactivate when it interacts with its ligand.

This implies that with the rapid development of genome sequencing technologies and the accumulation of large volumes of statistical data, structure-function studies will not only allow accurate prediction of disease for every patient but will also enable predicting drug efficacy and improving patient safety based on how these variations in genes affect the response to certain medications.

Hershey, Pa. -- Patient enrollment in clinical trials as the first course of treatment after cancer diagnosis is low, despite the fact that enrollment may increase life expectancy, according to researchers at Penn State. They also found that white males with private health insurance and metastatic cancers treated at academic medical centers are more likely than other groups to enroll in clinical trials.

Dr. Nicholas G. Zaorsky, an assistant professor of radiation oncology, Penn State College of Medicine, led a team of Penn State Cancer Institute researchers who analyzed data from more than 12 million patients with 46 different types of cancer between 2004 and 2015 in the National Cancer Database. They found that only 11,576 (0.1%) of those patients were enrolled in clinical trials as their first course of therapy following diagnosis.

According to Dr. Niraj J. Gusani, professor of surgery, Penn State College of Medicine, and senior author of the study, which published in the Journal of the National Comprehensive Cancer Network in November 2019, the low enrollment is troubling because clinical trials may be beneficial for patients.

"Major advances in cancer treatment have been supported by clinical trials," Gusani said. "By volunteering to participate in a trial, patients may help further the field of research and gain access to new treatments."

Zaorsky, Gusani and their team found that patients with cancer treated in clinical trials, when matched and compared to similar patients not treated on trials, lived longer. They report that patients with cancer in clinical trials at the first course of therapy had a median survival of seven and half months more than those not enrolled in a trial.

According to Zaorsky, previous evaluations of whether clinical trials improved survival compared patients who were enrolled in trials against those not enrolled in trials -- but didn't account for factors like age, race, gender and cancer type.

The researchers performed a stratified analysis in which they matched each patient who participated in a clinical trial with another patient who was not enrolled in a trial that had ten similar characteristics -- including cancer type, age, race, insurance type, disease stage, and whether or not surgery or chemotherapy were part of the treatment plan.

"If you're going to evaluate whether clinical trial enrollment is beneficial for patients, you have to try and match each patient to someone who has a similar cancer and sociodemographic profile," Zaorsky said. "Otherwise, it is like comparing apples to oranges."

While the survival trend was evident across cancer types, the researchers said that this may not necessarily be true for the general population. In their analysis, they determined that the patients who enrolled in clinical trials at first course of therapy tended to be white males with private insurance, metastatic disease, who had no other chronic medical conditions and were treated at academic medical centers.

"If clinical trials are going to be used to determine standards of care for the general population, then the study participants need to be representative of the general population -- and this study shows that often this isn't the case," Gusani said.

According to Zaorsky, increasing patient enrollment in clinical trials cannot happen without first improving the infrastructure of clinical trial design and management. Patients may not live close to locations where clinical trials are offered. Even if they are in close proximity to a center offering clinical trials, the trials may not be for their type or stage of cancer.

Gusani suggests that the biggest barrier to clinical trial enrollment is the stigma around them. Patients may feel they are 'guinea pigs' in experiments and that they are receiving substandard care. In reality, trials emphasize patient safety at every stage and are carefully regulated and monitored by institutional review boards.

"The increased level of quality control in clinical trials may be beneficial for patients," Zaorsky said. "Patients who go onto a clinical trial must be treated per protocol, meaning that there are many quality measures that must be met, and that there are many other health care providers looking over the patient's care."

Allegedly, they should not exist in the brain, the so-called precapillary sphincters - a kind of squeezing 'muscle clamp' between the larger and smaller vessels of the bloodstream.

Nevertheless, Assistant Professor Søren Grubb from the Department of Neuroscience at the University of Copenhagen has indeed shown the sphincters in mice.

'In the early '10s, a Japanese review study concluded that there was no evidence that pre-capillary sphincters should exist in the heart, brain and muscular connective tissue,' he says and continues:

'Since then, scientists have focused a lot on pericytes - muscle cells that can regulate the resistance in the smallest blood vessels. At the same time, however, they have somehow missed a great resistance right between some arterioles and capillaries: The sphincters. Perhaps because the discovery of the pericytes has received more attention among all the blood vessels of the brain'.

Functions as a water faucet or a sluice system

As blood flows through the brain, it flows from arteriole to vein through the capillaries. The latter are the smallest blood vessels in the body, but incredibly important. It is here that the blood and the brain exchange oxygen and nutrients.

Søren Grubb explains that the precapillary sphincters may be compared to a kind of thermostat that distributes the pressure between the branches of the blood vessels. A bit like a faucet adjusting the pressure between a water pipe and a garden hose.

As the muscle clamp relaxes, more blood cells will flow through its passage and the pressure in the following blood vessels will increase. When the clamp contracts, a bottleneck forms, which lowers the pressure further down the blood flow.

'In this way, it also works a bit like a sluice system to irrigate fields: You may have a roaring river, but by diverting water from the river and making sluices that can regulate the amount of water for each field, you can distribute the water to many areas, says Søren Grubb.

'Conversely, if the sluice shuts down or is clogged, the field will quickly dry out', he adds.

Potential for dementia and migraine

Based on that picture, Søren Grubb assumes that the pre-capillary sphincters may play a major role for disturbances of the brain's blood supply and blood pressure.

If the assumption holds true, the discovery of the clamping muscles in the brain will potentially affect the treatment of diseases such as migraine, Alzheimer's and vascular dementia - all associated with an accumulation of waste products that may stem from blood vessel defects.

Already, the research group Lauritzen Lab, of which Søren Grubb is part, has tested a model for migraine with aura. The model confirms the hypothesis, but the Assistant Professor emphasises that further research is still needed in connection with disorders:

'We have shown that the precapillary sphincter is found in the brain. The rest is still speculative. But perhaps more researchers will start working on it, now that they know that the sphincters are there'.

Scientists at UCL have discovered how immune cells, essential for tackling life-threatening infections and cancers, are able to 'recycle' material within themselves in order to stay healthy and function, a breakthrough finding which could lead to more effective immunotherapies.

In the study, published in Cell Reports, researchers investigated how 'autophagy' - the natural physiological process of 'self-eating' which allows intracellular components, such as mitochondria, to be degraded and replaced - takes place in liver-based T cells.

T cells are a subset of lymphocytes (white blood cells) that play a key role in protecting against chronic liver infection and tumours.

Researchers discovered that T cells in the liver had an enhanced rate of autophagy and that this is enabled by the presence and action of a soluble messenger protein found in the liver: the cytokine 'interleukin-15' (IL-15).

This is the first study to identify that IL-15 can boost autophagy in human T cells and researchers believe this new understanding could enable emerging immunotherapies, such as CAR T cell therapy, to be positively manipulated to boost T cell health and survival.

Corresponding author, Dr Leo Swadling (UCL Infection & Immunity), said: "The liver is a common site for chronic viral infection and tumours and T cells play a key role in protecting against these.

"T cells living within the liver must adapt to the stressful microenvironment, with low levels of oxygen and an abundance of inhibitory signals, to find ways of maintaining prolonged survival and functionality.

"We discovered that a population of T cells able to live exclusively within the human liver can switch on autophagy to maintain nutrient supply and renew organelles like mitochondria to maintain their fitness. We could imprint this same adaptation on T cells taken from blood by exposing them to the cytokine IL-15."

The research team were assisted by surgeons and the Tissue Access for Patient Benefit project (TAPb) at The Royal Free Hospital, London, and gained rare access to live immune cells from human liver samples.

Several cutting-edge single cell technologies were used to compare autophagy in the T cells from these liver samples to T cells in the blood.

Lead author, Professor Mala Maini (UCL Infection & Immunity), said: "Understanding how human T cells are adapted for autophagy opens up the possibility of manipulating this dynamic process, which could enable a wide range of new and effective therapeutic possibilities.

"For instance, we can now investigate whether modulating autophagy rates can be used to improve emerging immunotherapies for cancer and chronic viral infection (such as TCR-redirected T cells and CAR T cells), where T cells must persist and function in diverse tumour and tissue microenvironments."

Quebec City, January 20, 2020--To better treat people with depression, not only must we treat the neurons affected by the disease, but we must also restore the integrity of the barrier that regulates exchanges between blood circulation and the brain. This is the conclusion of a study published today in PNAS by Université Laval researchers and their international collaborators.

"Between 30% and 50% of those suffering from depression respond either poorly or not at all to antidepressants," says main author Caroline Ménard, professor at Université Laval's Faculty of Medicine and researcher at the Cervo Brain Research Centre. "This suggests that biological mechanisms other than those directly affecting neurons are at play," adds professor Ménard, who also holds the Sentinel North Research Chair on the Neurobiology of Stress and Resiliency.

Caroline Ménard and her colleagues showed in 2017 that the appearance of depressive symptoms in mice subjected to social stress was linked to increased permeability of the blood-brain barrier. They also discovered that this permeability is due to a decrease in a protein called claudin-5.

"In the study published today, we wanted to find out what causes the decrease in claudin-5 in mice under social stress and why some mice are resilient to social stress while others exhibit depressive symptoms," explains Professor Ménard.

The researchers examined blood-brain barrier cells in depressed stressed mice, resilient stressed mice, and control mice. Their observations show that the epigenetic processes that allow the expression of the claudin-5 gene are more readily activated in resilient mice. They also observed that the resilient mice produce less of one of the proteins that inhibit expression of the claudin-5 gene.

Conversely, depressed stressed mice express more of an enzyme called HDAC1 that triggers a loss of claudin-5. "When a chemical compound is used to block HDAC1, the depressive mice produce more claudin-5 and their social interactions spontaneously increase," says Professor Ménard.

Thanks to the Douglas Bell Canada Brain Bank, the researchers were able to verify whether the same mechanisms were present in humans. "We found that expression of HDAC1 was greater in depressed people without treatment at the time of death than in subjects who were taking antidepressants or in the control group. This increase correlated with a decrease in claudin-5."

These results suggest that efforts to develop better treatments for depression should not be limited to finding new molecules that target affected neurons. Researchers must also find a way to close the gaps in the blood-brain barrier to ensure its proper functioning. "For now, we don't know of any molecules that increase the expression of claudin-5 and would allow us to directly restore the barrier's impermeability," adds Professor Ménard. "Our future work will focus on evaluating the effect of different pharmacological approaches and lifestyle habits on the integrity of this barrier in order to promote resilience."

Cross-linked polymers are structures where large molecular chains are linked together, allowing exceptional mechanical properties and chemical resistance to the final product. However, their modification is not easy. Now, scientists at Tokyo Institute of Technology develop a method that allows the fusion of different polymers together easily, allowing the precise tuning of the properties of the final material by selecting appropriate base polymers and mixing them at the right proportion.

Polymers, large molecular chains composed of small repeating subunits, can be found all around us and also within us. DNA and proteins are some familiar natural polymers. In contrast, synthetic polymers, such as plastics, were first produced about a century ago, but have since then found their way into our everyday lives because of their amazing properties. Polymers can be tailored according to their constituent subunits to confer them with many desirable characteristics, such as mechanical strength, stretchability, permeability, and so on.

Another way to obtain even more functionalities in polymers is by cross-linking them. Cross-linked polymers (CPLs) are polymers that are linked together using special cross-linker molecules. Certain CPLs exhibit outstanding properties due to their interlocked tridimensional structures. Motivated by the potential applications, a research team from Tokyo Institute of Technology (Tokyo Tech) led by Professor Hideyuki Otsuka has recently achieved a breakthrough in this field: they managed to cross-link different CPLs together through an unprecedented approach. "The development of a novel method to fuse different CPLs would bring a revolution in the field, as their mechanical properties can be easily and systematically tuned in an operationally simple process," explains Otsuka.

The researchers achieved this feat by switching things up in the cross-linker molecule they used. For a CPL to have self-healing capabilities, which is very attractive for many applications, the polymers have to be joined by what is known as dynamic covalent bonds. These bonds also allow for fusing different types of CPLs, but the carbon molecules used in currently available linkers are prone to oxidizing, which complicates the fusion and processing of CPLs in bulk. What this research team did was employ a linker molecule, called BiTEMPS, that cross-links polymers through a central sulfur-sulfur (S-S) covalent bond. This bond can be temporarily cleaved in half at temperatures higher than 80°C, which allows for exchange among different polymer at the free ends, called TEMPS radicals (see Figure 1). Through this cleaving and re-joining process, different CPLs can be fused together. One of the main advantages of the TEMPS radicals is that they are highly stable against oxygen, meaning that all the processing can be done without requiring oxygen care.

To prove the usefulness of their approach, the researchers cross-linked two types of CPLs, one of them much more elastic than the other. By hot-pressing their mixture, they managed to fuse the CPLs together, and the mechanical properties of the final material were dependent on the ratio of the raw CPLs used. "The mechanical properties of the fused samples could be widely tuned to make them as soft and elastic as desired. As the variety of available polymers is almost infinite, it should be possible to generate materials that exhibit a broad spectrum of physical properties using our method by judiciously choosing appropriate polymer compositions and mixing ratios," concludes Otsuka. This innovative method will significantly advance the field of CPLs, allowing for the development of highly tailored materials for specialized applications.

Camas, a seed-producing forb, grows in prairie and wetland habitats in the Pacific Northwest (PNW) and carries profound prehistoric and current significance as a food resource and article of commerce among indigenous cultures of the PNW. The forb once flourished among the region but decreased in population after the conversion to modern forms of agricultural production.

The establishment of new camas populations in prairie and wetland restoration sites in the PNW has become challenging, though. According to plant pathologist Gretchen Freed, camas populations are readily established when grown in a monoculture setting for seed increase and bulb production at the nursery.

"Camas is a keystone component of native plant restoration efforts in ephemeral wetland and prairie ecosystems in the PNW," says Freed. "Fungal communities associated with camas seeds may provide inoculum for colonization of seedling tissues to support the establishment of camas populations in diverse plant communities. Yet little is known about the composition of the fungal communities associated with camas."

"Seeds likely harbor communities that co-occur with camas plants and facilitate the annual growth cycle of plant tissues and the decomposition of plant debris in the soil," says Freed. "Seed taxa may influence the local adaptation of camas seedlings to new wetland environments."

To learn more, Freed and colleagues conducted the first comprehensive study of above- and below-ground fungal communities associated with camas using samples from wetland habitats in Oregon, Idaho, and a home garden plot in Washington. They found that the local environment of each sampled camas population had a significant impact on above-ground fungal community diversity. However, the below-ground fungal communities detected in plant tissues and closely associated soils are similar among the camas sampled in the wetland habitats.

Additionally, they found that camas plant roots may be preferentially colonized by endophytic fungi recruited from nearby soil communities suggesting that plants limit complexity of fungal communities.

The discovery of the diversity among fungal taxa present in the different types of tissues from a native plant that grows for many years is a unique opportunity to explore the endophytes that promote plant population longevity within diverse plant communities.

"What surprised us the most was the number of endophytic fungal taxa that are present among the camas seeds, roots, rhizospheres, and leaves. It is curious whether these taxa may be required for the establishment of camas populations."

This information may help native prairie and wetland restoration scientists restore camas populations in the PNW.

INFORMS Journal Marketing Science New Study Key Takeaways:

The shutdown of 'Google News' in Spain decreased the number of daily visits to Spanish news outlets between 8 and 14 percent.

The shutdown decreased online advertising revenue and advertising intensity at news outlets.

News aggregators increase consumers' awareness of news outlet contents, thereby increasing their number of visits.

CATONSVILLE, MD, January 20, 2020 - News aggregators help to simplify consumers' search for news stories by gathering content based on viewing history or other factors. Commonly used aggregators include Google News, Yahoo! News, and others. They offer links to news stories published by news outlets and save consumers considerable time and effort in finding news.

New research in the INFORMS journal Marketing Science examined the relationship between the two, specifically data compiled after the shutdown of 'Google News' in Spain in December 2014. The study, "What do news aggregators do? Evidence from 'Google News' in Spain and Germany," was conducted by Joan Calzada of the University of Barcelona and Ricard Gil of Queen's University. It found daily visits to Spanish news outlets dropped between 8 and 14%, relative to news outlets in France and Italy where Google News remained active.

"Amidst the growing importance of online platforms, news aggregators are one of the most successful new players in the Internet's new era, quickly rising to occupy top positions in audience rankings," said Calzada, a professor in the Department of Economics and BEAT at the University of Barcelona.

News outlets can opt out of aggregators by using software that blocks the links to the content, but most publishers want to be indexed even without receiving economic compensation for the use of their content.

Despite initial turmoil and initiative to impose indexing fees on news aggregators, traditional news outlets around the world have been silent about aggregators' indexing practices because of their potential effects on consumers' browsing behavior, and in conjunction, advertising revenues.

The research suggests measurable consequences of website activity without aggregators. News aggregators increase consumers' awareness of news outlet content, thereby increasing their number of visits.

"Aggregators create a market expansion effect by bringing visitors to news outlets, but they can also generate a substitution effect if some visitors switch from the news outlets to the aggregators," continued Calzada.

The data from the shutdown period showed sports and regional outlets were affected the most, while having a lower effect on national outlets and no significant effect on business outlets. The evidence suggests that smaller and geographically local outlets benefit the most from news aggregators. The study also shows that the shutdown decreased online advertising revenue and advertising intensity at news outlets.

Electrons are tough to pin down in biology. Learning how to harness electrons is no fool's errand because, when electrons move, they are the electricity that powers life.

Electrons power the production of fuel and medicine. Electron movement is behind photosynthesis, our main source of food and combustion. Moving electrons are the definition of an electric current, which is why you can read this story.

In a new study, scientists at the MSU-DOE Plant Research Laboratory report a new synthetic system that could guide electron transfer over long distances. The new system is made up of two components plucked from nature. One is a protein from bacteria and the other a molecule found in our blood.

Nature has figured out how to tame electrons. The trick is to split up their journeys into short pit stops that are easier to manage. Electrons then hop between stops as they are guided towards some final destination.

One of these natural pit stops is the heme, a molecule that contains iron. It is what gives our blood its color and it is found in many other biological molecules.

"In nature, multiple hemes have to be closely positioned and angled precisely to allow for fast electron hops. The hemes are fixed in place by attaching to protein structures," said Jingcheng Huang, a former graduate student in the lab of Danny Ducat. "Otherwise, if the distances between hemes become too large, an electron will hop out of control. It is lost."

Since hemes are found in almost all living beings, they can associate with many types of proteins. The science team used the protein BMC-H, from bacteria, to build their artificial electron pit stops.

The team identified four possible locations the heme can dock into. Specifically, the alpha helical region was the most promising host area.

"We didn't have to modify the BMC-H protein much," Huang said. "With only three amino acid substitutions, we can get a heme binding tightly to it. Because the modification is minimal, the protein's shape and functions remain intact."

The scientists have managed to produce these larger structures with hemes attached to them. Moreover, they can produce them inside of bacteria cells, which saves resources.

"We'd like to optimize this system into a functional nanowire," Huang said. "Someday, it could funnel electrons to power the production of new medicines, or biofuels or electronic devices made of biogoo; the possibilities are endless."

"The exciting part is that we played with what nature has already figured out: We took a protein that self-assembles into large structures but doesn't bind hemes and functionalized it so that it hosts them," Huang said. "Otherwise, if we had created a system from scratch, we would have added extra layers of difficulty. That's the essence of synthetic biology, taking natural ingredients and re-configuring them in new, unseen ways."

Esports has developed from relative obscurity into a billion dollar global industry, with an estimated 453 million viewers worldwide in 2019 - and its set to get even bigger.

Despite esports rapid rise in popularity, there has been a notable lack of research available to support the needs of esports athletes but this is starting to change.

A study has used sleep tracking devices and mood measures (anxiety and depression) to determine how well esports athletes around the world sleep, and the effect this has on their mental health and well being.

Preliminary results have shown that esports athletes are not getting the sleep (7-9hours p/night for young adults aged 18-25) needed to best support optimal mental health and performance.

Leading the way is a multinational sleep team that includes clinical psychologist and PhD candidate Daniel Bonnar and Professor Michael Gradisar (Flinders University), Associate Professor Aly Suh and PhD candidate Sangha Lee (Sungshin University), Associate Professor Brandy Roane (University of North Texas) and Dr Daniel Blum (Stanford University).

Daniel Bonnar says innovative esports organisations around the world are now starting to actively look at how they could better support the health needs of their players, with sleep being apart of that.

"Global esports giant Gen.G from South Korea, and Perth-based Ground Zero were the first two teams to sign up to our project, which really demonstrated their commitment to promoting player wellness and performance" says Daniel.

Other esports organisations now involved include Kanga Esports and Gravitas from Australia.

"The benefit of working with esports organisations from different countries is that it allows us to develop a global view of the sleep habits of esports athletes," Daniel added.

As to the study's findings, preliminary results have shown that esports athletes are not getting the sleep (7-9hrs p/night for young adults aged 18-25) needed to best support optimal mental health and performance.

"From the data we've collected so far, we can see a trend that many esports athletes obtain less than 7hrs of sleep p/night, have a tendency to want to sleep and wake very late, with mood impacted as a result in some players", says Professor Michael Gradisar. "Although these late sleeping patterns might be ok for some players, for others it could be an issue with conflicting daytime commitments encroaching on their sleep schedule".

Phase two of the project will be to improve players' sleep using a sleep intervention designed to address their specific sleep needs.

"If we can improve the sleep of esports athletes, this will translate into enhanced well being which can only be helpful for performance as well," says Professor Gradisar.

Gravitas team owner Sean Callanan says "I'm looking forward to Gravitas players understanding the importance of sleep and how it can affect their performance for practice and on game days. I know it's become a focus in traditional pro-sports, so esports should be following their lead".

Researchers at the Center for Cognition and Sociality, within the Institute for Basic Science (IBS) in South Korea, have engineered an improved biological tool that controls calcium (Ca2+) levels in the brain via blue light. Published in Nature Communications, this optogenetic construct, called monster-OptoSTIM1 or monSTIM1 for short, causes a change in mice's fear learning behavior without the need of optic fiber implants in the brain.

The brain utilizes Ca2+ signaling to regulate a variety of functions, including memory, emotion, and movement. Several evidences show correlation between abnormally regulated Ca2+ levels in certain brain cells and neurodegenerative diseases, but the details still remain obscure. For understanding the precise role of Ca2+ signaling, the IBS team is studying Ca2+-specific modulators that can be triggered in different parts of the brain at a designated time.

Optogenetics uses light to control Ca2+ signaling in the mouse brain. Since the brain is surrounded by hair, skin and skull, which prevent light from reaching deep tissues, optic fiber insertion in the brain used to be the norm in optogenetics. However, these implants can cause inflammation, morphological changes of neurons and disconnection of neural circuits. In this study, the research team improved their optogenetic tool so that it works with an external source of blue light, shone from the ceiling of the mouse cage, and without the need of brain implants.

MonSTIM1 is made of a part (CRY2) that responds to blue light and another part (STIM1) that activates calcium channels. Compared to the previously developed optogenetic techniques, the researchers were able to enhance CRY2's light-sensitivity approximately 55-fold and also avoid the increase of basal Ca2+ levels. The monSTIM1 construct was injected into the mouse brain through a virus, and was shown to activate Ca2+ signals in the cortex as well as in the deeper hippocampus and thalamus regions.

The team observed behavioral changes in mice with monSTIM1 expressed in excitatory neurons in the anterior cingulate cortex, a brain region that has a central function in empathic emotions. Mice with activated monSTIM1 froze with fear by looking at other mice, which experienced a mild electric foot shock. Twenty-four hours later the same mice remembered about it and showed again an enhanced fear response, indicating that Ca2+ signaling contributed to both short- and long-term social fear responses.

"MonSTIM1 can be applied to a wide range of brain calcium research and brain cognitive science research, because it allows easy manipulation of intracellular calcium signals without damaging the brain," says Won Do Heo (KAIST professor), leading author of this research.

The international team works on a computational model able to predict the properties of new molecules based on the analysis of fundamental chemical laws. The project was supported by the Russian Science Foundation (title "Using AI methods for the planning of chemical synthesis").

Co-author, Associate Professor Timur Madzhidov, explains, "We offered a way to insert the preexisting chemical equations into some frameworks of machine learning. It was tested on the predictions of tautomeric constants and acidity, which are linked by the Kabachnik equation. Using the functional interdependency between them, the neural network learns how to predict both these properties."

Prototropic tautomerism is the phenomenon of reversible isomerism, in which isomers (substances having the same qualitative and quantitative composition, but differing in structure and properties) easily transition into each other due to the transfer of a hydrogen atom.

"Tautomeric transformations are very common for organic compounds, being known for about half of all discovered compounds. For example, one of the mechanisms of spontaneous mutations is tied to the tautomeric transformations of DNA nucleic base. That why tautomerism must be taken into account when registering new compounds, during the computer design of new medications and the search for molecules with preconditioned properties," adds Madzhidov.

The results of this research can help increase the precision of prediction of physicochemical properties of designed medication and materials, as well as correctly forecast the parameters of chemical reactions.

Kazan Federal University, Lomonosov Moscow State University, the University of Hokkaido, and the University of Strasbourg contributed to the publication.

In 2009, 105 single-family homes in the city of Cordoba were demolished in order to expand the airport. At first, the debris from the demolition was going to be sent to a landfill, as is common procedure. But, the University of Cordoba came up with the idea to recycle all the debris in situ and use it to build an experimental stretch of road on the CH-2 highway that goes around the runway at the airport and also connects Cordoba with the town of Almodóvar. This stretch of road is used by over 9,000 vehicles on a daily basis. After ten years of research, the complete study was published. The results are very positive and the conclusion is that recycled materials from demolitions are a good alternative when building roadways.

Most research projects performed at a national or international level are done in the lab. "This research shows the feasibility of using these materials on a real project and for a long period of time", says José Ramón Jiménez, the researcher in charge of the study. This research was carried out with involvement from the company PLODER UICESA, contractor of the highway building project, and with the support of AENA and of the Guadalquivir Water Agency, owner of the highway.

One stretch of the road was built with natural aggregates, commonly used materials for these kinds of construction projects. In the experimental stretch of road two kinds of recycled materials were used: mixed recycled aggregates, from walls and structures of the homes, and recycled aggregates from concrete, which came from the foundations of the homes.

"The surface properties of the road were maintained in both cases", says the researcher. "In the case of mechanical properties, the development is even better in the case of recycled aggregates".

In addition to determining the good behavior of these materials, the research team wanted to do their part in contributing to sustainability in the construction sector. In order to do so, a mobile recycling plant was set up, which allowed for less carbon dioxide impact caused by transporting materials. The researcher highlights that in situ recycling is a viable alternative but "we have to be really careful" in this area. There are several cases in which these debris have been recycled illegally and without any kind of quality guarantee. Only materiales from recycling plants that can guarantee the quality of their materials should be used.

Building demolition generates a large amount of materials that usually end up in landfills. 2020 European regulations on waste make it compulsory to recycle 70% of construction and demolition waste. Nevertheless, Spain continues to fall far below that goal, with barely a 40% recycling rate. This study lays out a scientific basis to start repurposing these materials. "This is a real sample that can lead to government agencies and construction companies relying on recycled demolition and construction waste. We have no excuse to not reach the goals required by the EU", concludes José Ramón Jiménez.

Each year, an average of 120 gigatonnes of carbon dioxide (CO2) worldwide is released through soil and vegetation respiration. Plants are capable of taking in nearly 123 gigatonnes through photosynthesis in the same period. But as humans release another ten gigatonnes of carbon dioxide into this cycle, mainly by burning fossil fuels such as crude oil and natural gas, there are seven gigatonnes of excess CO2. "And these seven gigatonnes are our big problem," says Thomas Dandekar who holds the Chair of Bioinformatics at the University of Würzburg. They fuel global warming and cause global temperatures to rise at an alarming rate.

While searching for a solution to fix this problem, Dandekar and his colleagues believe to have discovered a promising way forward: They are studying plants which are capable of absorbing residual carbon dioxide more effectively thanks to a modified metabolism. The scientists have now published their findings in the current issue of the journal Trends in Biotechnology.

Modulated metabolic networks calculated

Bioinformatics researchers usually work with mathematical computer models. Over the past months, Thomas Dandekar and his team have been studying whether the metabolic networks of plants can be modulated so as to enable the plants to fix more carbon dioxide. To achieve this, the scientists combined two different methods to modulate the metabolism of the plant cell. By performing complex calculations, they found out that this combination enables plants to absorb five times more carbon dioxide than in the normal state.

Now their theoretical calculations need to be tested in practice. Muhammad Naseem, a colleague of Dandekar, is in charge of conducting these experiments. Born in Pakistan, Naseem has a PhD in molecular biology. He works both in Würzburg and at Zayed University in Abu Dhabi, the capital of the United Arab Emirates where he has been a professor for two years. On 4 January, Naseem returned to Abu Dhabi. He plans to start the practical test there in the course of this year. "We will experiment with tobacco plants and thale cress, also known as Arabidopsis thaliana, which are both easy to modify," the scientist explains.

Less carbon and more yield

"If we continue on our current path, climate change will have disastrous consequences," Dandekar warns. The scientist expects that the average temperature could rise by up to four degrees compared to pre-industrial levels. He believes that the next decade must be used to find new ways of removing the carbon dioxide that has already been released into the atmosphere, reducing CO2 emissions and developing strategies to adapt to the consequences of climate change. If successful in practice, the Würzburg research would kill two birds with one stone: Not only do the modulated plants absorb more carbon dioxide, they also deliver higher yields.

According to Thomas Dandekar, the research project funded by the Free State of Bavaria could help large companies offset their carbon dioxide emissions. The bioinformatics expert has the cement industry in mind, for example, which has a massive carbon dioxide problem. Cement production is estimated to be responsible for four to eight percent of global CO2 emissions. Modified diatoms could help reduce these high emissions as the professor explains: "These fast-growing algae could be cultivated directly in the sand pits."

Tackling two problems of humanity

Adapting to a changing climate is currently even more important for countries outside of Europe than for Germany, as Muhammad Naseem explains. The consequences are already clearly noticeable especially in the United Arab Emirates. Based on model forecasts, climate researchers warn that temperatures in the major cities on the Persian Gulf could rise to 50 or even 60 degrees Celsius. Such temperature levels would be unbearable even by Arabian standards. "The big problem is that the United Arab Emirates is among the countries with the highest carbon dioxide emissions per capita in the world," Muhammad Naseem says. He emphasises the urgency of curbing CO2 emissions.

Naseem considers the idea of combining two modulation methods a blessing because it would enable two problems of humanity to be addressed - provided that the computer analyses are congruous with the behaviour of the plants in the field. "The two problems of climate change and feeding the world population are closely connected," says the life scientist. Climate change causes scorched fields, withering plants and complete crop failure due to drought in some regions. Plants with modulated metabolic pathways could not only fix more CO2, they also produce more biomass due to the genetic modification.

More research funding is needed for active strategies against climate change

Of course, these new research findings are not the only strategy to mitigate climate change. Marine cloud brightening, which involves small, white, low altitude clouds that cool the ocean by reflecting the bright sun-light, or eco-diesel made from carbon dioxide using hydrogen from solar cells are two other promising approaches. "Whichever path or mix of strategies we choose has to be explored carefully for ten years before it is implemented," Dandekar cautions. It is imperative to boost funding of research and critical exploration of active strategies to combat climate change given the worldwide lack of willingness to actually cut carbon emissions. "Otherwise, come 2030, we will be powerless with no means of defending ourselves against the increasingly severe consequences of climate change and carbon dioxide increase."

New research from the Prevention Research Center of the Pacific Institute for Research and Evaluation suggests that legalization and greater retail availability of recreational marijuana is positively associated with marijuana use among adolescents.

The researchers investigated whether legalization of recreational marijuana sales in 2015 and retail availability of marijuana in Oregon counties were associated with higher levels of adolescent marijuana use and related beliefs.

Using survey data gathered every other year from 2010 to 2018 from 6th, 8th and 11th graders 35 Oregon counties, this study assessed changes in past-30-day marijuana use and beliefs, including:

perceived availability of marijuana,

perceived parent approval of marijuana use, and

lower levels of perceived risk of marijuana use.

Comparisons were made in counties that allowed recreational marijuana sales compared to counties that did not.

The results of the study show that:

Higher rates of past-30-day marijuana use and more favorable beliefs were found in counties that allow recreational marijuana sales both before and after legalization;

Prevalence of past-30-day marijuana use increased after legalization both in counties that did and did not allow sales;

The relationship between allowing recreational marijuana sales and adolescent marijuana use was accounted for by greater retail marijuana availability and favorable beliefs.

Overall, this study shows that there was a statewide increase in the prevalence of marijuana use among Oregon adolescents after legalization in 2015, and that greater retail availability of marijuana in counties that permit recreational marijuana sales is positively associated with both marijuana use and beliefs favorable toward its use among adolescents.

Said lead author, Dr. Paschall, "Our study indicates that statewide legalization of recreational marijuana use and greater retail availability of marijuana in Oregon communities may be contributing to an increase in marijuana use among adolescents. Greater local restrictions on numbers of licensed marijuana retail outlets, hours of operation and advertising, and higher taxes on marijuana products may help to reduce both retail and social availability of marijuana."