Culture

Ishikawa, Japan - Powering everything from smartphones to electric cars, lithium-ion batteries (LIBs) have evolved markedly with advances in technology and revolutionized our world. The next step in the progress of technology is developing even better batteries to power electronic devices for longer durations. One promising technique for increasing battery performance involves the atomic substitution of positively charged ions or "cations" in the cathode material. However, doing so systematically for different substituent cations to determine the ideal ones experimentally is complex and expensive, leaving us with simulations as the only viable option for narrowing down the choices.

Several studies have reported an improved battery life and thermal stability based on their findings using a simulation-based approach. However, such improvements have, in turn, lowered the discharge capacity of the battery, which is the amount of energy that a battery can supply in a single discharge. As a result, an extensive search must be performed for the cation substituent that enhances the discharge capacity.

Against this backdrop, a team of scientists led by Prof. Ryo Maezono from Japan Advanced Institute of Science and Technology (JAIST) conducted an extensive screening of different cations for partial substitution of nickel in a nickel-based LIB with the intent of enhancing the battery discharge capacity.

"The discharge capacity can be determined using the discharge profile, which is the voltage change during the charge-discharge process," explains Prof. Maezono. "We used first-principles calculations to evaluate the discharge profiles of materials that, in turn, determines their discharge capacities. However, these calculations are computationally costly, so we integrated other methods to narrow down the candidates for cation replacement. To the best of our knowledge, this is the first study that successfully predicts cation substitution to increase battery capacity." The groundbreaking study has been published in a recent issue of The Journal of Physical Chemistry C.

A prominent strategy for successfully predicting the discharge voltage profile is the "strongly constrained and appropriately normed" (SCAN) functional. However, due to the large computing costs involved, such methods are impractical for extensive screening. So, the team began by using relatively inexpensive techniques such as density functional theory and cluster expansion to identify suitable candidates for cation replacement and then applied SCAN functional to the inferred candidates to assure reliability and accuracy in voltage predictions.

The screening process revealed that the highest discharge capacity was obtained when nickel was partially substituted with platinum and palladium in nickel-based LIB. These results were consistent with the experimental data, validating the proposed methodology.

While Prof. Maezono emphasizes the need for additional research, he is optimistic about the future of their low-cost screening process. "Our findings indicate that substituents such as rhenium and osmium offer high discharge capacities. However, these elements are rare and costly, and putting them to practical use would be challenging. Further study is needed to achieve the same effect with less substitution, multiple element substitution, or anion substitution," he says. "Having said that, our novel computational technique will accelerate the search for optimal materials that improve battery performance at lower costs, allowing us to replace the bulk of our current electricity sources with carbon-free alternatives."

Hopefully, such advances will bring humankind one step closer to becoming an environment-friendly species in the near future!

The final stage of cataclysmic explosions of dying massive stars, called supernovae, could pack an up to six times bigger punch on the surrounding interstellar gas with the help of cosmic rays, according to a new study led by researchers at the University of Oxford. The work will be presented by PhD student Francisco Rodríguez Montero today (19 July) at the virtual National Astronomy Meeting (NAM 2021).

When supernovae explode, they emit light and billions of particles into space. While the light can freely reach us, particles become trapped in spiral loops by magnetic shockwaves generated during the explosions. Crossing back and forth through shock fronts, these particles are accelerated almost to the speed of light and, on escaping the supernovae, are thought to be the source of the mysterious form of radiation known as cosmic rays.

Due to their immense speed, cosmic rays experience strong relativistic effects, effectively losing less energy than regular matter and allowing them to travel great distances through a galaxy. Along the way, they affect the energy and structure of interstellar gas in their path and may play a crucial role in shutting down the formation of new stars in dense pockets of gas. However, to date, the influence of cosmic rays in galaxy evolution has not been well understood.

In the first high-resolution numerical study of its kind, the team ran simulations of the evolution of the shockwaves emanating from supernovae explosions over several million years. They found that cosmic rays can play a critical role in the final stages of a supernova's evolution and its ability to inject energy into the galactic gas that surrounds it.

Rodríguez Montero explains: "Initially, the addition of cosmic rays does not appear to change how the explosion evolves. Nevertheless, when the supernova reaches the stage in which it cannot gain more momentum from the conversion of the supernova's thermal energy to kinetic energy, we found that cosmic rays can give an extra push to the gas, allowing for the final momentum imparted to be up to 4-6 times higher than previously predicted."

The results suggest that gas outflows driven from the interstellar medium into the surrounding tenuous gas, or circumgalactic medium, will be dramatically more massive than previously estimated.

Contrary to state-of-the-art theoretical arguments, the simulations also suggest that the extra push provided by cosmic rays is more significant when massive stars explode in low-density environments. This could facilitate the creation of super-bubbles powered by successive generations of supernovae, sweeping gas from the interstellar medium and venting it out of galactic discs.

Rodríguez Montero adds: "Our results are a first look at the extraordinary new insights that cosmic rays will provide to our understanding of the complex nature of galaxy formation."

Researchers at the RIKEN Center for Integrative Medical Sciences (IMS) have discovered that acetate, a major metabolite produced by some intestinal bacteria, is involved in regulating other intestinal bacteria. Specifically, experiments showed that acetate could trigger an immune response against potentially harmful bacteria. The findings, published in the scientific journal Nature, will lead to the development of new ways to regulate the balance of intestinal bacteria.

You may be surprised to know that 40 trillion important bacteria live in our intestines. They help keep us healthy by producing essential nutrients and eliminating foreign pathogens. On the other hand, these commensal bacteria can harm your health if they are out of control. Therefore, understanding the way the body regulates the balance of intestinal bacteria is important issue for staying healthy.

Immunoglobulin A (IgA) is the most abundant antibody produced in the human body, mostly secreted from the mucosal surfaces of the intestinal tract. IgA is thought to regulate the growth, colonization, and function of intestinal bacteria by binding to them. However, until now, we didn't know what could trigger IgA responses to bacteria in a dynamically changing intestinal environment.

Intestinal bacteria help us break down what we eat into smaller pieces called metabolites. Recent studies suggest that these metabolites have a significant impact on immune function in the intestinal tract. In particular, short-chain fatty acids (SCFAs), a major metabolite of intestinal bacteria, are known to be involved in creating and regulating immune-cell function. They are thought to increase IgA production, but until now, nobody knew what could trigger this behavior.

A research group led by Hiroshi Ohno at RIKEN IMS fed mice food that can specifically increase SCFAs locally in the large intestine. Analysis of the mice showed that acetate, a type of SCFA, increases both the number of IgA-producing cells and the amount of IgA, and also regulates how much IgA is bound to each intestinal bacterium. "SCFAs including acetate are easily absorbed in the stomach and proximal small intestine, so it was difficult to investigate the effects of orally administered SCFAs in the distal intestine such as the colon, where the intrinsic SCFA levels are high," says Ohno. "Our collaborators have developed a method that can efficiently deliver the metabolites into the distal intestine, which enabled us to analyze the effects of SCFAs on the immune system there." Other SCFAs, such as propionic acid or butyric acid did not affect IgA.

The researchers also found that the type of bacteria to which IgA binds depends on whether acetate is present or not. Normally, IgA binds mostly to common symbiotic bacteria, but in mice treated with acetate, it tended to bind to potentially harmful bacteria such as E. coli. More detailed analysis showed that when acetate leads to IgA production in the colon, the IgA binds to those potentially harmful bacteria and prevents them from settling in and invading the mucus layer.

These findings were somewhat unexpected. "At first we thought that acetate simply increases IgA equally against all commensal bacteria," explains Ohno. "It was rather surprising to see that it preferentially enhances production of IgA against certain microbes through collaboration with other immune cells." In fact, the experiments showed that acetate only increased IgA production when potentially harmful bacteria were present.

Overall, this study revealed that acetate produced by bacteria can change the balance of IgA in the intestines. The process involves enhancing IgA production together with bacterial components. By increasing IgA production, especially IgA that will attack potentially harmful bacteria, acetate can alter the bacterial makeup of the intestines.

"Accumulating evidence suggests the involvement of gut microbiota in many human diseases. IgA is one of the most efficient ways to control the microbiota, and therefore we think our findings are a basis for this regulatory mechanism. Since the functions of metabolites remain largely unknown, we will keep focusing on host-microbe interactions through these small molecules to reveal how they affect human pathophysiology," says Ohno.

The carbon-hydrogen bonds in alkanes--particularly those at the ends of the molecules, where each carbon has three hydrogen atoms bound to it--are very hard to "crack" if you want to replace the hydrogen atoms with other atoms. Methane (CH(4)) and ethane (CH(3)CH(3)) are made up, exclusively, of such tightly bound hydrogen atoms. In the journal Angewandte Chemie, a team of researchers has now described how they break these bonds while forming new carbon-nitrogen bonds (amidation).

If it were possible to easily break the C-H bonds in hydrocarbons, it would be possible to synthesize complex organic molecules, such as pharmaceuticals, much more conveniently and directly from petroleum. This strategy could also provide more pathways for recycling plastic waste. The formation of carbon-nitrogen bonds is of particular interest because these play an important role in natural products. For example, amide bonds link individual amino acids into proteins.

Although there has been some success in the functionalization of heavy hydrocarbons, even at the end positions, the particularly strong C-H bonds of light alkanes, especially methane, can hardly be split at all. The use of these primary components of natural gas as synthetic building blocks is especially desirable, as it would allow for the use of this often wasted side-product of oil extraction.

A team led by Ana Caballero and Pedro J. Pérez (Universidad de Huelva, Spain), as well as John F. Hartwig (University of California, Berkeley, USA) has now successfully coupled amides (nitrogen-containing organic compounds) to light alkanes with loss of a hydrogen atom. The products of these dehydrogenative amidations are known as N-alkyl amides.

The starting point for this approach was the amidation of C-H bonds in heavy alkanes with a copper-based catalyst and di-tert-butyl peroxide as an oxidizing agent, as developed several years ago by the Hartwig group. Variation of the catalyst led to success. If the copper has phenanthroline-type ligands (an aromatic, nitrogen-containing system of three six-membered rings), it is possible to produce high yields in the reaction of ethane with benzamide--as well as a number of other amides--using benzene as a solvent. The reaction also worked when supercritical carbon dioxide--a more environmentally friendly option--was used as a solvent. The reaction with ethane is an unusual C-N bond formation with a non-activated primary C-H bond.

Propane, n-butane, and iso-butane gave similar results. In the light alkanes, reactivity correlates significantly more strongly with the dissociation energy of the C-H bonds than in higher alkanes.

And methane? Even the toughest candidate--amidation of methane has never previously been observed--could be coupled to the amide. Isotopic experiments were used to prove that methane reacts to form N-methylbenzamide.

The climate crisis will lead to changes in distribution and habitat loss of stony corals in the tropical Atlantic, shows a new study published by the open access publisher Frontiers. The loss of such coral species could have devastating consequences for the marine ecosystems they inhabit. The results of the study highlight an urgent need for coral reef management in the Atlantic.

Researchers at the University of São Paulo projected current and future distributions of three key reef building corals of the tropical Atlantic (Mussismilia hispida, Montastraea cavernosa and the Siderastrea complex). They conclude that all three species will experience changes in range due to the climate crisis, which will elicit negative cascading effects on the biodiversity of reef ecosystems. The results are published in the journal Frontiers in Marine Science.

Nature's engineers are threatened

Mussismilia hispida, Montastraea cavernosa and the Siderastrea complex are stony corals of the eastern and western Atlantic. They are ecosystem engineers: much like beavers who contribute to the structure of their terrestrial habitats by building dams, stony corals help build reefs by depositing calcium carbonate. They are vital for the health and function of these reefs, which are among the most diverse ecosystems on Earth.

"Coral reefs provide essential ecosystem services such as food provision, coastal protection and nutrient cycling, that benefit millions of people - including those who live far from any coral reef," says lead author and PhD candidate Silas Principe of the University of São Paulo.

"If species that are important in structuring the coral reefs are lost, the provision of all those services is consequently also threatened."

Human activity has long harmed corals worldwide, and coral reefs are already some of the most threatened ecosystems on the planet. Intense and long-lasting mass bleaching events, ocean acidification, pollution, urbanization, fisheries, and tourism are all leading to reduction and loss of coral cover. Now, the climate crisis is adding to those threats.

Climate change leads to changes in coral distribution, with key coral species moving within the tropics or to temperate waters at higher latitudes. Changes in distributions of these key species may have unprecedented cascading effects on entire marine wildlife communities, such as drastic changes in the structural complexity of reef ecosystems.

Concerning findings

Researching possible changes in stony coral distribution is important for planning and management of coral reef conservation. The researchers collected data on M. hispida, M. cavernosa and the Siderastrea complex from different databases and used species distribution models to model their suitability on their current habitat. They also modeled future changes in range under three different climate change scenarios (most pessimistic, most optimistic, and moderate).

They found that, even in the most optimistic scenario, all three species could experience changes in their distributions. Especially in the western Atlantic, decreases in the abundance of stony corals are expected under all three scenarios. Several areas along the Brazilian coast and the Caribbean will lose habitat suitability. These projections are especially critical for the Brazilian coast, where there are fewer habitat-building coral species.

The researchers urge conservation and management efforts to be focused on regions such as the Abrolhos region, northeast coast of Brazil, western Caribbean, and the Gulf of Mexico. "We show that important reef builder species of the Atlantic will face shifts in its distribution due to climate change," Principe said.

"Certain areas, such as the Abrolhos region in the coast of Brazil, will completely lose at least one of its species in any of the future scenarios. Major areas in the Caribbean will also lose species in the future, although in the coast of Africa some species may expand their current range."

But the results also indicate that there is hope for Atlantic stony corals. "Although our results predict major negative impacts on Atlantic shallow reefs, we also identified several areas where none or less changes are predicted. Managers and policy makers can use this to support the planning process of conservation areas." Principe concludes: "Researchers and conservationists can use these results to focus research efforts on the so-called 'refuge areas' that may constitute safe areas for coral species in the future."

To prepare for the next pandemic and provide a coordinated approach to vaccination across the country, Canada should create Canadian Immunization Services based on the Canadian Blood Services model, authors propose in CMAJ (Canadian Medical Association Journal).

The authors, including a leading health policy and immunization expert, a blood system expert and a former federal minister of health, are Dr. Kumanan Wilson, professor, Department of Medicine and member of the Centre for Health Law, Policy and Ethics, University of Ottawa; Dr. Graham Sher, CEO, Canadian Blood Services; and Dr. Jane Philpott, Dean, Faculty of Health Sciences, Queen's University.

"If we want to be better prepared for the next pandemic, it is time to chart a bold new path forward," said Dr. Kumanan Wilson. "We propose intergovernmental collaboration through an arms-length entity, which was successful after the tainted blood scandal, one of Canada's biggest public health crises. We have done this before, emerging stronger from a public health crisis and creating a world-class blood system. We can do it again."

Various reports, including from the federal auditor general, have documented the problems with how Canada's federal, provincial and territorial governments work together. Different vaccination schedules for each province and territory, different terminology and variations in immunization tracking have made Canada's system fragmented.

"It is challenging to coordinate pan-Canadian disease surveillance and mass immunization responses without harmonized data and systems," said Dr. Wilson. "Our response to COVID-19 has been plagued by many of the challenges facing public health over the last 20 years."

As the responsibility for managing public health threats is largely the responsibility of the provinces and territories, unilateral federal mandates are difficult to implement.

The authors propose an independent not-for-profit corporation -- Canadian Immunization Services -- funded by participating provinces and territories, and potentially the federal government, based on the Canadian Blood Services model.

"Twenty-three years ago, Canadian Blood Services assumed full responsibility for the operation of the national blood supply outside Quebec, taking over a system that was unquestionably broken," said Dr. Graham Sher. "We were founded to restore confidence in the blood system, and over the past two decades, our journey has been one from tragedy to trust. We now have one of the safest blood systems in the world. We believe that Canada can effectively prepare for the next pandemic by establishing a world-class vaccination system based on this model as well."

Canadian Immunization Services would provide:

Ability to procure vaccines in bulk for Canada

Vaccine surveillance and supply chain management by single entity versus many

Common data standard to enable data sharing between provinces and territories

Ability to access expertise rapidly without government barriers to hiring

"If we hope for public health to be better prepared for the next pandemic, now is the time to implement needed changes," the authors conclude.

"Preparing for the next pandemic by creating Canadian Immunization Services" is published July 19, 2021.

Philadelphia, July 19, 2021 - University of Minnesota School of Public Health researchers recently completed a study to determine how food-insecure young (emerging) adults (18-29 years of age) adapted their eating and child feeding behaviors during the COVID-19 pandemic. The researchers also sought to identify barriers to food access and opportunities to improve local access to resources for emerging adults. Their study results are published in the Journal of the Academy of Nutrition and Dietetics.

The steep rise in food insecurity during the COVID-19 pandemic has disproportionately impacted Black, Indigenous, and persons of color across the United States. Emerging adulthood is a time of particular vulnerability for experiencing food insecurity and when young people may begin providing meals for their own children. It is a public health concern that food insecurity among emerging adult populations has the potential to negatively impact the health trajectories of multiple generations.

Researchers used data from the COVID-19 Eating and Activity over Time (C-EAT) study, which collected survey data from 720 emerging adults from April to October 2020 and included interviews with a diverse subset of 33 food-insecure respondents.

The study found:

Nearly one-third of emerging adults surveyed experienced food insecurity in the past year.
One Earth A disproportionately high prevalence of food insecurity and food insufficiency among emerging adults living with children and those who identified as Black, Indigenous, or a person of color.

Many food-insecure emerging adults made changes to their eating and feeding behaviors to cope during the pandemic -- and several of the changes, such as consuming more fast food and processed foods or increased sporadic eating, could lead to negative health consequences.

Food-insecure emerging adults reported concerns regarding the implementation of measures used to reduce COVID-19 transmission in food retail stores and other notable barriers to local food access (e.g., reduced store hours, neighborhood safety concerns).

Interview participants of diverse ethnic/racial backgrounds commented on how food access had been recently impacted by racial justice uprisings and reported several forms of discrimination experienced while shopping in food retail stores. Concerns about discrimination and xenophobia, including excessive monitoring and verbal harassment, influenced how households managed shopping for food.

Barriers to accessing food assistance were also themes among the comments made by food-insecure emerging adults. Most services were provided in line with guidance for preventing COVID-19 transmission, but factors limiting eligibility for benefits and access to emergency food assistance were identified along with some concerns about food quality, physical distancing, and physical safety at food pantries.

"Our findings show an urgent need for research to address how the processes of racism that are embedded in the policies and practices of society and institutions are directly contributing to food insecurity," said study lead Nicole Larson, PhD, MPH, RDN, Senior Research Associate, Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, MN, USA. "The findings also support recent calls for expanding federal food assistance benefits for postsecondary students as the comments made by many emerging adult participants indicated that both students and workers were not eligible for adequate benefits to meet their food needs."

Dr. Larson remarked that even among households that reported receiving federal food assistance (e.g., SNAP), there were multiple emerging adults who reported needing to obtain food from local food pantries or distribution sites. The study results also highlighted the importance of ensuring that information about emergency food assistance sites is broadly distributed through multiple communication channels and varying the open hours of sites to address the needs of emerging adults who may need to visit outside of regular daytime hours.

"It is heartbreaking to learn about the high levels of food insecurity so close to home. It is incumbent upon all of us to work toward eliminating food insecurity and ensuring that all people have access to adequate amounts of healthful foods. As health care professionals, advocates, researchers, and members of society, we all have a role to play. We need to work now to prevent a widening of disparities following this global pandemic," added principal investigator Dianne Neumark-Sztainer, PhD, MPH, RD, Division Head and McKnight Presidential and Mayo Professor, Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, MN, USA.

Highlights

The results of a new study support the validity of a score that considers various patient-reported outcome measures and preferences for assessing health-related quality of life in individuals with kidney failure.

The score is calculated from assessments of cognitive function, depression, fatigue, pain interference, physical functioning, sleep disturbance, and ability to participate in social roles.

Washington, DC (July 16, 2021) -- Results from a new study support the validity of a score that considers various patient-reported measures and preferences for assessing health-related quality of life and promoting patient-centered care in individuals with kidney failure. The study appears in an upcoming issue of CJASN.

The score, called the Patient Reported Outcomes Measurement Information System (PROMIS®)-Preference (PROPr) Summary Score, is determined from 7 domains: cognitive function, depression, fatigue, pain interference, physical functioning, sleep disturbance, and ability to participate in social roles.

When investigators led by Istvan Mucsi, MD, PhD and Jing Zhang BSc, MPH (University Health Network and University of Toronto) correlated PROPr with other health-related measures, their findings supported the validity of PROPr among 524 patients who were undergoing hemodialysis or who had recently received kidney transplants.

"Up to 70% of patients with kidney failure experience persistent physical symptoms and emotional distress that substantially impair health-related quality of life. These concerns are under-reported, under-recognized and under-managed," said Dr. Mucsi. "Our results open the doors for the use of PROPr and PROMIS® tools in nephrology research and in the care of patients with kidney failure."

What The Study Did: The association between primary care payment models and the use of telemedicine for Medicare Advantage enrollees during the COVID-19 pandemic was examined in this study.

Authors: Brian W. Powers, M.D., M.B.A., of Humana Inc. in Louisville, Kentucky, is the corresponding author.

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

(doi:10.1001/jamahealthforum.2021.1597)

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

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Media advisory: The full study is linked to this news release.

Embed this link to provide your readers free access to the full-text article This link will be live at the embargo time https://jamanetwork.com/journals/jama-health-forum/fullarticle/10.1001/jamahealthforum.2021.1597?utm_source=For_The_Media&utm_medium=referral&utm_campaign=ftm_links&utm_term=071621

About JAMA Heath Forum: JAMA Health Forum has transitioned from an information channel to an international, peer-reviewed, online, open access journal that addresses health policy and strategies affecting medicine, health and health care. The journal publishes original research, evidence-based reports and opinion about national and global health policy; innovative approaches to health care delivery; and health care economics, access, quality, safety, equity and reform. Its distribution will be solely digital and all content will be freely available for anyone to read.

What The Study Did: Researchers investigated whether death, other hospital outcomes and processes of care differed between patients cared for by female and male physicians at hospitals in Canada.

Authors: Fahad Razak, M.D., M.Sc., of the University of Toronto in Ontario, Canada, is the corresponding author.

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

(doi:10.1001/jamahealthforum.2021.1615)

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

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Media advisory: The full study is linked to this news release.

Embed this link to provide your readers free access to the full-text article This link will be live at the embargo time https://jamanetwork.com/journals/jama-health-forum/fullarticle/10.1001/jamahealthforum.2021.1615?utm_source=For_The_Media&utm_medium=referral&utm_campaign=ftm_links&utm_term=071621

About JAMA Heath Forum: JAMA Health Forum has transitioned from an information channel to an international, peer-reviewed, online, open access journal that addresses health policy and strategies affecting medicine, health and health care. The journal publishes original research, evidence-based reports and opinion about national and global health policy; innovative approaches to health care delivery; and health care economics, access, quality, safety, equity and reform. Its distribution will be solely digital and all content will be freely available for anyone to read.

What The Study Did: National health care systems have different capacities to correctly identify people who died of COVID-19. Researchers in this study analyzed the gap between excess mortality and  COVID-19 confirmed mortality in 67 countries to determine the extent to which official data on COVID-19 deaths might be considered reliable.

Authors: Davide Golinelli, M.D.,  Alma Mater Studiorum-University of Bologna in Italy, is the corresponding author.

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

(doi:10.1001/jamanetworkopen.2021.17359)

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

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Media advisory: The full study is linked to this news release.

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About JAMA Network Open: JAMA Network Open is the new online-only open access general medical journal from the JAMA Network. On weekdays, the journal publishes peer-reviewed clinical research and commentary in more than 40 medical and health subject areas. Every article is free online from the day of publication.

Fear is an important reaction that warns and protects us from danger. But when fear responses are out of control, this can lead to persistent fears and anxiety disorders. In Europe, about 15 percent of the population is affected by anxiety disorders. Existing therapies remain largely unspecific or are not generally effective, because the detailed neurobiological understanding of these disorders is lacking.

What was known so far is that distinct nerve cells interact together to regulate fear responses by promoting or suppressing them. Different circuits of nerve cells are involved in this process. A kind of "tug-of-war" takes place, with one brain circuit "winning" and overriding the other, depending on the context. If this system is disturbed, for example if fear reactions are no longer suppressed, this can lead to anxiety disorders.

Recent studies have shown that certain groups of neurons in the amygdala are crucial for the regulation of fear responses. The amygdala is a small almond-shaped brain structure in the center of the brain that receives information about fearful stimuli and transmits it to other brain regions to generate fear responses. This causes the body to release stress hormones, change heart rate or trigger fight, flight or freezing responses.

Now, a group led by Professors Stephane Ciocchi of the University of Bern and Andreas Luthi of the Friedrich Miescher Institute in Basel has discovered that the amygdala plays a much more active role in these processes than previously thought: Not only is the central amygdala a "hub" to generate fear responses, but it contains neuronal microcircuits that regulate the suppression of fear responses. In animal models, it has been shown that inhibition of these microcircuits leads to long-lasting fear behaviour. However, when they are activated, behaviour returns to normal despite previous fear responses. This shows that neurons in the central amygdala are highly adaptive and essential for suppressing fear. These results were published in the journal Nature Communications.

"Disturbed" suppression leads to long-lasting fear

The researchers led by Stephane Ciocchi and Andreas Luthi studied the activity of neurons of the central amygdala in mice during the suppression of fear responses. They were able to identify different cell types that influence the animals' behaviour. For their study, the researchers used several methods, including a technique called optogenetics with which they could precisely shut down - with pulses of light - the activity of an identified neuronal population within the central amygdala that produces a specific enzyme. This impaired the suppression of fear responses, whereupon animals became excessively fearful. "We were surprised how strongly our targeted intervention in specific cell types of the central amygdala affected fear responses," says Ciocchi, Assistant Professor at the Institute of Physiology, University of Bern. "The optogenetic silencing of these specific neurons completely abolished the suppression of fear and provoked a state of pathological fear."

Important for developing more effective therapies

In humans, dysfunction of this system, including deficient plasticity in the nerve cells of the central amygdala described here, could contribute to the impaired suppression of fear memories reported in patients with anxiety and trauma-related disorders. A better understanding of these processes will help develop more specific therapies for these disorders. "However, further studies are necessary to investigate whether discoveries obtained in simple animal models can be extrapolated to human anxiety disorders", Ciocchi adds.

This study was carried out in partnership with the University of Bern, the Friedrich Miescher Institute and international collaborators. It was funded by the University of Bern, the Swiss National Science Foundation and the European Research Council (ERC).

Systems Neuroscience Group, Institute of Physiology, University of Bern

Neuronal diversity is a hallmark of cortical networks. In the hippocampus, distinct neuronal cell-types interact together by selective synaptic contacts and neural activity patterns. We investigate how different forms of emotional and cognitive behaviours emerge within intricate neuronal circuits of the ventral CA1 hippocampus, a brain region instrumental for context-specific emotional memories, anxiety and goal-directed actions. We hypothesize that distinct behavioural programs are implemented by the selective recruitment of micro- and large-scale neural circuits of the ventral CA1 hippocampus. To identify these circuit motifs, we are combining single-unit recordings of ventral CA1 GABAergic interneurons and projection neurons, selective optogenetic strategies, cell-type specific viral tracing and behavioural paradigms in rodents. The results of our experimental approaches will determine fundamental neural computations underlying learning and memory within higher cortical brain regions.

Neuro-evolutionary robotics is an attractive approach to realize collective behaviors for swarms of robots. Despite the large number of studies that have been devoted to it and although many methods and ideas have been proposed, empirical evaluations and comparative analyses are rare.

A publication in the journal Nature Communications, led by Mauro Birattari and his team at the research center IRIDIA, École Polytechnique de Bruxelles, Université Libre de Bruxelles, compares some of the most popular and advanced neuro-evolutionary methods for offline design of robot swarms.

"Concretely, these methods can enable the development of humanoid robot behavior, but to my knowledge, neuro-evolutionary robotics is not yet routinely adopted in real-world applications," explains Mauro Birattari.

All of these processes use evolutionary algorithms to generate a neural network that controls the robots, i.e., a neural network that takes sensor readings as input and outputs actuator commands. These methods use computer simulations to generate a neural network appropriate for the specific mission that the robots must accomplish. Once the neural network is generated (in simulation), it is installed on the physical robots and tested.

When comparing the different methods, the researchers observed a kind of "overfitting": the design process becomes too specialized in the simulation environment, and the neural network produced fails to "generalize" to the real world. This is a reality gap, i.e. the difference between reality and the simulator used in the design process. Although the simulator is fairly accurate, differences are inevitable.

"For example, if robots need to move back and forth between two areas, one solution that the evolutionary process might find in simulation is to produce a neural network that makes the robot move along a circular path that touches both areas. This solution is very elegant and works very efficiently in simulation. When applied to robots, this solution would fail miserably: for example, if the real diameter of (one of) the robot's wheels differs slightly from the nominal value, the radius of the trajectory will be different... the trajectory will no longer pass through the two given zones as desired and as predicted by the simulation," illustrates Mauro Birattari.

The Chocolate Solution ?

Although counter-intuitive, the solution seems to be to reduce the "power" of the design method: adopt a method that can produce a limited range of behaviors... This clearly means that researchers will have to accept that they will get worse results in simulation. This method will not perform as well in simulation as a "powerful" method because it will not be able to exploit all the characteristics of the simulator... yet, the result will be more general, less specialized to the simulator and therefore more likely to generalize well to reality. The simpler the better...

The chocolate method seems a good illustration of this idea. Chocolate is a process that researchers at the IRIDIA Center proposed a few years ago and that does not belong to neuro-evolutionary robotics but that, in a similar way to neuro-evolution, automatically generates control software for robots, under the same conditions. Chocolat operates on pre-existing software modules that are low-level behaviors (e.g., I go in the direction of the light, I stop, I move away from perceived peers...) and conditions for moving from one low-level behavior to another (e.g., I am surrounded by peers, the color of the floor I am on is black...).

Instead of playing with a very powerful neural network capable of producing a wide range of behaviors, chocolate plays with predefined building blocks that are (comparatively) much more "coarse". The working hypothesis is that by doing so, the risks of "over-fitting" will be reduced...

RUDN University biologists discovered the way how macrophages (the cells of the "first line" immune response) respond to inflammation and identified how the immune response depends on their origin. It turned out that when exposed to an inflammatory stimulus, two opposing mechanisms are activated in macrophages simultaneously -- inducing and inhibiting inflammation. These data can potentially be useful in the treatment of cancer, as targeted activation of macrophages will strengthen the immune response of the organism in the fight against a tumor. The results were published in the journal Biomedicine & Pharmacotherapy.

Macrophages are the cells responsible for phagocytosis -- they capture bacteria, the dead cells remains and other foreign particles. This is the first line of defense of immune system. Most macrophages are formed from blood monocytes, which in turn differ in the level of two proteins on their surface: CD14 and CD16. Until now, it was not known how macrophages derived from the two most polar types of monocytes -- called CD14+monocytes and CD16+monocytes-respond to inflammation. RUDN University biologists have identified these differences.

"Surprisingly, among the published data, there is practically no information about the activation of macrophages obtained from CD14+monocytes and CD16+monocytes. There have only been several published works devoted to the pro-inflammatory polarization of human macrophages with varying monocytic origin. Most data derived from mouse models. We decided to fill this gap and discover how macrophages obtained from CD14+ and CD16+monocytes are activated", said Polina Vishnyakova, PhD, researcher at Medical Biotechnology Laboratory at RUDN University.

The receptors on the surface of macrophages react, for example, to lipopolysaccharides (LPS) -- the main component of bacterial membranes. RUDN University biologists used blood samples from six healthy women aged 26 to 34 years and isolated CD14+monocytes and CD16+monocytes from the blood using magnetic separation. Then the monocytes were "turned" into macrophages - by cultivation with special differentiation factors. Macrophages obtained from different types of monocytes were subjected to LPS and analyzed using flow cytometry, secretome, transcriptomic and proteomic analysis.

The results demonstrated that, firstly, the traditional division of macrophages into pro-inflammatory and anti-inflammatory is not quite correct -- they switch their functions depending on the surrounding conditions. RUDN University biologists also found out that macrophages derived from CD14+monocytes are more prone to a pro-inflammatory response. Flow cytometry showed that these macrophages synthesize more CD86 protein, which is responsible for the activation of T-lymphocytes -- other cells of the immune response. At the same time, secretome analysis showed that macrophages derived from CD14+monocytes secrete more pro-inflammatory and anti-inflammatory cytokine molecules.

These results can be used in the future for the treatment of oncological diseases. The fact is that pro-inflammatory macrophages are able to fight tumors. Picking the most suitable monocytes of the patient (CD14 or CD16), turning them into pro-inflammatory macrophages and transplanting them back to the tumor, one can stimulate the organism's fight against cancer cells.

"The key issue is the choice of monocyte subset for further therapeutic application of macrophages. Thus, macrophages obtained from different populations of human monocytes are potentially relevant for cell therapy in case of malignant oncological diseases", said Polina Vishnyakova, PhD, researcher at Medical Biotechnology Laboratory at RUDN University.

JULY 15, 2021, NEW YORK - A Ludwig Cancer Research study has found that inducing random chromosome instability (CIN) events in mice for as little as one week is enough to trigger harmful chromosomal patterns in cells that spur the formation of tumors.

"We show that you don't need chronic, lifelong chromosomal mistakes to produce tumorigenesis at a quite respectable frequency," said Don Cleveland, Member of the Ludwig Institute for Cancer Research, San Diego, who led the study with Floris Foijer of the University of Groningen, in The Netherlands. "A very transient exposure would likely be sufficient to drive a very substantial increase in tumorigenesis."

The finding, detailed this week in the journal Genes & Development, confirms a nearly 120-year-old hypothesis by the German biologist Theodor Boveri that aneuploidy--an abnormal number of chromosomes--and tumorigenesis are linked.

"Boveri hypothesized that there would be specific combinations of gains and losses of chromosomes that could lead to cancer. We've now tested that and shown that not only was he right, but that even a short burst of chromosome instability is enough to induce these combinations," said Ofer Shoshani, a postdoctoral researcher in Cleveland's lab and the study's first author.

In the study, Shoshani and his colleagues overexpressed the gene polo-like kinase 4 (Plk4) in mice. Plk4 is a master regulator that controls the number of centrosomes present inside a cell. Centrosomes play an important role in cell division by helping separate replicated chromosomes into two daughter cells. Normally, two centrosomes are present inside a cell during division, one at each pole of the cell.

"However, when you overexpress Plk4, you have more than two, and this leads to chromosome missegregation, whereby the chromosomes are not being pulled correctly and the daughter cells inherit an unequal number of chromosomes," Shoshani explained.

The scientists overexpressed Plk4 in the mice for either one week, two weeks or four weeks, and found that one week was enough to cause the formation of aggressive T cell lymphomas. Whole genome sequencing of the mouse tumors revealed an increased recurrence of a particular chromosome pattern early in the tumor formation process. This "aneuploid profile" involved triple occurrences of chromosomes 4, 5, 14 and 15 (cells normally contain only two copies of each chromosome).

Scientists have long known that certain cancer types are associated with specific chromosome gains--for example, breast cancer often involves a gain of chromosome 1. "What our work potentially shows is that when you induce a transient pulse of chromosome instability, you accelerate the formation of such a recurrent aneuploidy profile," said Shoshani. "We identify the profile originating very early in the formation of cancer, either at, or very close to, the formation of the cell that generates the tumor."

Moreover, the researchers found that transient CIN events can drive tumorigenesis regardless of whether p53--a major tumor suppressor gene and the most commonly mutated gene in human cancer--is inactivated. "This tells you that transient CINs will enhance tumorigenesis independent of whether you have other genetic issues that might predispose you to cancer," Cleveland said.

The findings could be especially relevant to cancer patients undergoing anti-cancer therapy, particularly those being treated with chemotherapeutic agents known as aneugens, which work by driving chromosome instability and aneuploidy.

"Our work suggests that cancer patients who undergo therapy using aneugenic drugs might develop secondary cancers down the road," said Shoshani. "Of course, this would need to be further investigated, in both human patients and by using experimental models in the lab."