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Among adults with kidney failure who were referred for transplantation, 60% of black and 66% of white patients were waitlisted within the first year. Differences in socioeconomic status and comorbidities between black and white patients could explain up to 58% of the disparity in listing.

Fewer black patients on transplant wait lists received transplants compared with white patients, but differences in socioeconomic status and comorbidities did not explain this disparity.

Washington, DC (May 7, 2020) -- Among adults with kidney failure in need of a transplant, socioeconomic status and medical illnesses likely contribute to racial disparities in being put on transplant wait lists. The findings come from a study that will appear in an upcoming issue of CJASN.

Black adults are more likely than white adults to develop kidney failure, and yet their odds of being listed for and receiving a kidney transplant are lower. To assess whether socioeconomic status and illnesses besides kidney disease (comorbidities) affect these disparities, Mara McAdams-DeMarco, PhD, Karly Murphy, MD, MHS (Johns Hopkins Medical Institutions), and their colleagues examined information on 3,013 patients with kidney failure who were referred for and who started the transplant process between 2009 and 2018.

"We examined socioeconomic status--using income, education level, and employment status--and 17 medical comorbidities as potential mediators, both individually and combined, to explain racial disparities in listing for kidney transplant or for receiving a kidney transplant," said Dr. McAdams-DeMarco.

The team found that within the first year, 60% of black and 66% of white patients were waitlisted. Differences in socioeconomic status explained 36% of the disparity in listing, while differences in comorbidities explained 44% of the disparity in listing. Together, differences in socioeconomic status and comorbidities between black and white patients could explain up to 58% of the disparity in listing.

Among 2,109 listed candidates, transplants occurred at rates of 19 and 24 per 100 persons per year for black and white candidates, respectively. Differences in socioeconomic status and comorbidities did not explain the disparities in receipt of transplants between black and white transplant candidates.

"We found that socioeconomic status and medical history most likely influence the likelihood that a person would be listed for transplant but did not change the likelihood of receiving a kidney transplant," said Dr. McAdams-DeMarco.

With so many COVID-19 models being developed, how do policymakers know which ones to use? A new process to harness multiple disease models for outbreak management has been developed by an international team of researchers. The team describes the process in a paper appearing May 8 in the journal Science and was awarded a Grant for Rapid Response Research (RAPID) from the National Science Foundation to immediately implement the process to help inform policy decisions for the COVID-19 outbreak.

During a disease outbreak, many research groups independently generate models, for example projecting how the disease will spread, which groups will be impacted most severely, or how implementing a particular management action might affect these dynamics. These models help inform public health policy for managing the outbreak.

"While most models have strong scientific underpinnings, they often differ greatly in their projections and policy recommendation," said Katriona Shea, professor of biology and Alumni Professor in the Biological Sciences, Penn State. "This means that policymakers are forced to rely on consensus when it appears, or on a single trusted source of advice, without confidence that their decisions will be the best possible."

At the onset of an outbreak, particularly for a new disease, a large amount of information is often unavailable or unknown, and researchers must make decisions about how to incorporate this uncertainty into their models, leading to differing projections. For the COVID-19 outbreak, for example, uncertainty is present in a wide range of areas, from infection rate to details of transmission to the capacity of health care systems. The designers of each model bring their own perspective and approach to address these uncertainties.

"In order to improve modeling and analysis of epidemic disease, it is essential to develop protocols that deliberately generate and evaluate valuable individual ideas from across the modeling community," said Michael Runge, a research ecologist at the U.S. Geological Survey's Patuxent Wildlife Research Center who specializes in decision analysis for wildlife management. "We have identified best practices that allow the synthesis and evaluation of input from multiple modeling groups in an efficient and timely manner."

In the three-part process, multiple research groups first create models for specified management scenarios, for example, addressing how caseload would be affected if social isolation measures were lifted this summer, or how the duration of the outbreak would change if students return to school in the fall. The research groups work independently during this step to encourage a wide range of ideas without prematurely conforming to a certain way of thinking. Then, the modeling groups formally discuss their models with each other--an important addition to previous multiple model methods--which allows them to examine why their models might disagree. Finally, the groups work independently again to refine their models, based on the insights from the discussion and comparison stage.

After group discussion and individual model refinement, the models are combined into an overall projection for each management strategy, which can be used to help guide risk analysis and policy deliberation. At this stage, methods from the field of decision analysis can allow the decision maker, for example a public health agency, to understand the merits of different management options in the face of the existing uncertainty.

Additionally, the combined results can help identify which uncertainty--what pieces of missing information--are most critical to learn about in order to improve models and thus improve decision making, providing a way to prioritize research directions.

"This process allows us to embrace uncertainty, rather than hastening to a premature consensus that could derail or deflect management efforts," said Shea. "The process encourages a healthy conversation between scientists and decision makers, enabling policy agencies to more effectively achieve their management goals."

Even after initial decisions are made, the process can continue as new information about the outbreak and management becomes available. This "adaptive management" strategy can allow researchers to refine their models and make new predictions as the outbreak progresses. For COVID-19, this process might inform how and when isolation and travel bans are lifted, and if these or other measures might be necessary again in the future.

The research team plans to implement this process immediately for COVID-19. By taking advantage of the many research groups already producing models for the current outbreak, the strategy should be easy to implement while producing more robust results from the existing process. The team will share results with the U.S. Centers for Disease Control and Prevention as they are generated.

"We hope this process actively feeds into policy for the COVID-19 response in the United States," said Shea. "It also provides a framework for future outbreak settings, including emerging diseases and agricultural pest species, and management of endemic infectious diseases, including vaccination strategies and disease surveillance."

While an effective vaccine for the SARS-CoV-2 virus is likely many months away, development could be accelerated by conducting controlled human infection (CHI) studies - which are increasingly being considered by the scientific community due to the urgent need. In a Policy Forum, Seema Shah and colleagues outline an ethical framework for conducting CHI studies in response to the COVID-19 pandemic. In CHI studies, a small number of willing participants are deliberately exposed to infection to rapidly gather data on the efficacy of experimental vaccine candidates or treatments. Many CHI studies have a safe and successful track record in the clinical efforts to address many infectious diseases, however, they can be wrought with ethical concerns. Given the nature of the evolving global COVID-19 pandemic and its rapidly growing death toll, novel CHI studies are likely to advance, albeit amidst significant uncertainty and controversy. Here, Shah et al. apply a state-of-the-art ethical framework to address the considerations and concerns for potential novel coronavirus CHI investigations. The framework outlines the conditions under which CHI studies with SARS-CoV-2 would be ethically acceptable and provide guidance for the research community and participants considering them. Among the ethical considerations addressed in their framework, the authors argue that potential CHI studies must have sufficient social value to warrant their use and maintain reasonable risks to participants.

Controlling spatter during laser powder bed fusion - a form of 3D printing that uses metal as a medium - reduces random defects and increases the overall reliability of built parts. New technologies capable of 3D printing metallic materials are poised to revolutionize manufacturing, particularly for advanced aerospace and biomedical applications. One such technology - laser powder bed fusion (L-PBF) - uses a high-power laser to melt and fuse metallic powders layer-by-layer to produce an intricate 3D part. However, despite their promise, widespread application of metal 3D printing has yet to be realized, primarily due to their sub-optimal operational reliability. Due to an accumulation of various defects, such as pores randomly generated during the printing processes, L-PBF printed parts often do not consistently meet adequate standards. To solve these issues, critical gaps in the understanding of the physics underlying the L-PBF printing process - including the complex dynamics between the laser, powder layer and melt pool that occurs where the two meet - must be addressed. Using a predictive multi-physics model and x-ray synchrotron experiments to capture fast and fleeting laser-powder-melt pool dynamics, Saad Khairallah and colleagues explored how best to reduce variability and the defects in L-PBF prints. Khairallah et al. discovered several previously unknown effects caused by spatter - a common and likely underestimated occurrence in L-PBF printing - that can lead to the formation of defects and deformations. According to the results, spatter issues can be mitigated by carefully controlling laser power, which helps to minimize the random formation of defects and ensure reproducible, high-quality prints. Andrew Polonsky and Tresa Pollock discuss the study's findings further in a related Perspective.

In a world where movements of non-native animal species are drastically disrupting whole ecosystems and causing economic harm and environmental change, it is becoming increasingly important to understand the features that allow them to colonize new habitats.

A new study, published in Communications Biology, shows that the prolific comb jelly, a marine invertebrate invader from North America that now frequently washes up on Baltic shores, is able to expand their geographical range thanks to the use of its own young as nutrient stores through long and nutrient deprived winters.

As jellies trace their lineage back to the beginning of all animal life, this work furthers the view of cannibalism as a pervasive trait amongst the animal kingdom.

Mysterious success

With their translucent gelatinous bodies, they may not look like much, but the expansion of the comb jelly, Mnemiopsis leidyi, from the east coasts of North and South America to Eurasian coastal waters has wreaked havoc on local environments.

Their success has remained something of a mystery especially as, instead of storing resources before wintering, they seemed to counterproductively invest in massive 'blooms' of offspring unable to survive long and nutrient deprived winters.

It had been assumed that perhaps they were able to persist due to a lack of native predators, though both this, as well as the best conservation management strategies for this exotic species, have remained hazy.

A handy floating reservoir of food

That was until an international team of researchers, including authors at the University of Southern Denmark and the Max Planck Institute for the Science of Human History, performed the dedicated collection of comb jellies throughout the year at their northernmost range in the Baltic Sea off of northern Germany.

Lead author of the study, Jamileh Javidpour, Assistant Prof. at University of Southern Denmark states "we combined a study of the population dynamics of this species with experimental feeding and geochemical tracers to show, for the first time, that adult jellies were actually consuming the blooms of their own offspring".

This rather sinister realization behind the function of these blooms makes perfect sense. As a handy floating nutrient reservoir that lasted beyond the collapse of normal prey populations, the release of offspring provided adults with an additional 2-3 weeks window of growth which, ecologically, can be the difference between life and death.

Tackling their colonization

"In some ways, the whole jelly population is acting as a single organism, with the younger groups supporting the adults through times of nutrient stress", says Thomas Larsen, a co-author of the study at the Max Planck Institute for the Science of Human History.

"Overall, it enables jellies to persist through extreme events and low food periods, colonizing further than climate systems and other conditions would usually allow", he continues.

The novel data produced by the team may allow conservationists and governments to better combat the spread of these jellies which can disadvantage native species and bring local fisheries down. In their exotic ranges, the comb jellies have been particularly successful in seas impacted by rapid warming, overfishing and excessive nutrient loads.

Tackling these problems could potentially reduce the food sources for these gelatinous invaders and restore the ecological balance of Eurasian seas.

The study also suggests that this jelly may become a problematic species in its native ranges, with possible rapid bloom-and-bust cycles under the right conditions.

Was cannibalism an early trait?

This study also speaks to wider questions of cannibalism in the animal kingdom. Cannibalism has been recorded among over 1,500 species, including humans, chimpanzees, squirrels, fish, and dragonfly larvae.

Although sometimes cannibalism occurs during periods of extreme shortage or disaster, it can also occur under regular conditions.

"Because comb jellies trace their ancestry back to the beginning of most animal life as we know it during the Cambrian Period, 525 Million Years Ago, it remains possible that it is a basic, unifying feature across the animal kingdom", Jamileh Javidpour concludes.

More research is certainly required to clarify the role of cannibalism among the earliest members of the animal kingdom and the evolutionary origins of cannibalism and the reasons why it is particularly prominent in aquatic ecosystems.

Nevertheless, these gelatinous critters have provided a calculating window into the use of this behaviour during the invasion of new habitats. While it may seem abhorrent to us, 'investing in the future' certainly has a very different meaning for these invertebrates!

What The Study Did: The clinical characteristics of men with coronavirus disease 2019 (COVID-19) whose semen tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are examined in this observational study.

Authors: Weiguo Zhao, M.D., of the Eighth Medical Center of Chinese People's Liberation Army General Hospital in Beijing, and Shixi Zhang, M.D., of the Shangqiu Municipal Hospital in Shangqiu City, Henan Province, China, are the corresponding authors.

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

(doi:10.1001/jamanetworkopen.2020.8292)

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

NEW YORK, May 7, 2020 -- A newly published study in Current Biology reveals surprising findings about the function of circadian network neurons that undergo daily structural change. The research could lead to a better understanding of how to address circadian rhythm disruptions in humans and facilitate preventing a host of associated health problems, including increased risk for cancer and metabolic syndrome.

Circadian networks are collections of neurons that serve as master body clocks in all animals, helping them know when to sleep and when to be productive. Scientists have long studied the circadian networks of the Drosophila melanogaster (better known as the fruit fly) to gain insight into how the human body clock operates. Recently, investigators at the Advanced Science Research Center at The Graduate Center, CUNY (CUNY ASRC) and Barnard College examined the function of small regions of important neuronal clocks in the fly's brain. Some segments of the neurons in these regions undergo daily remodeling, displaying a highly branched structure at the beginning of the day and a simpler structure at the beginning of the night. Scientists previously believed that these segments -- called the dorsal medial termini -- served a critical output function, sending signals that tell the fruit fly's brain what time of day it is. But the research team discovered that they actually serve in an input capacity, receiving cues from the external environment about the time of day.

"The circadian network shapes the timing of sleep and activity through two key mechanisms: an endogenous clock, which runs on a cycle that is slightly longer or shorter than the Earth's 24-hour solar day; and the process of entrainment, which adjusts the endogenous clock every day to keep it in sync with the solar day," said Orie Shafer, a professor with the CUNY ASRC Neuroscience Initiative and the study's co-senior investigator. "For years, the field has assumed that the dorsal medial termini would be required for a strong endogenous clock. But when we tested this prediction in flies in which the formation of these segments was prevented, we found the flies' clocks were absolutely fine but that they had a difficult time synchronizing them to the rising and falling of environmental temperatures."

For their study, researchers bred fruit flies with undeveloped dorsal medial termini segments that completely lacked the structures that normally change throughout the day. The flies were then examined to see if this manipulation had effects on circadian timekeeping. Remarkably, the manipulated flies displayed completely normal circadian rhythms in sleep and activity. Given this surprising result, the researchers then asked if the loss of the dorsal medial termini segment might prevent the normal synchronization of the clock with daily changes environmental cues. The researchers observed that fruit flies lacking dorsal termini were unable to properly synchronize their sleep/activity rhythms to daily temperature cycles. Previous research has shown that temperature changes play a role in regulating circadian rhythms. These new findings strongly suggest that dorsal medial termini neurons likely input (receive) signals from regions of the brain that track environmental temperature.

"I have been curious for some time to know whether the structural plasticity that I characterized in clock neurons as a part of my graduate student work was an output mechanism for the clock to connect with downstream targets," said the study's first and co-senior author Maria Fernández, an assistant professor in the Department of Neuroscience and Behavior at Barnard College. "We were surprised to see that this site of plasticity seems to be involved in input, rather than output, pathways."

The neurons examined in the fruit fly serve timekeeping functions that are highly similar to neurons in mammals, so the researchers' results suggest that daily changes in neuronal segment structures may shape the sensitivity of circadian network neurons to cues from the environments in all animals, including humans. This finding is important for understanding how the body's internal clock is reset every day. This process, called "entrainment," appears to be challenged by modern lighting and social environments, contributing to a growing list of health issues including cancer and obesity.

Neural stem cells are not only responsible for early brain development - they remain active for an entire lifetime. They divide and continually generate new nerve cells and enable the brain to constantly adapt to new demands. Various genetic mutations impede neural stem cell activity and thus lead to learning and memory deficits in the people affected. Very little has hitherto been known about the mechanisms responsible for this.

Enzyme regulates brain stem cell activity

An international research team led by Sebastian Jessberger, professor at the Brain Research Institute at the University of Zurich (UZH), is now demonstrating for the first time that a lipid metabolism enzyme regulates the lifelong activity of brain stem cells, in a study published in Cell Stem Cell. This enzyme - known as fatty acid synthase (FASN) - is responsible for the formation of fatty acids. A specific mutation in the enzyme's genetic information causes cognitive deficits in affected patients.

Headed by postdoc Megan Bowers and PhD candidates Tong Liang and Daniel Gonzalez-Bohorquez, the researchers studied the genetic change of FASN in the mouse model as well as in human cerebral organoids - organ-like cell cultures of the brain that are formed from human embryonic stem cells. "This approach allows us to analyze the effects of the defective enzyme in the brains of adult mice and during early human brain development in parallel," explains Jessberger. The research involved altering the genetic information of both the mice and the human organoids experimentally so that the lipid metabolism enzyme exhibited the exact mutation that had been found in people with cognitive deficits.

Diminished stem cell activity reduces cognitive performance

The FASN mutation led to reduced division of stem cells, which constantly generate new nerve cells, both in mice and in human tissue. The hyperactivity of the mutated enzyme is responsible for this, since fats accumulate inside the cell, putting the stem cells under stress and reducing their ability to divide. Similar to cognitive deficits found in affected people, mice also displayed learning and memory deficits due to the mutation. "Our results provide evidence of the functional correlation between lipid metabolism, stem cell activity and cognitive performance," says Jessberger.

The mechanism now identified shows how lipid metabolism regulates neuronal stem cells activity and thus influences brain development. "The new discoveries regarding learning and memory deficits in people were only made possible by linking our research on animal models and in human cells," stresses Jessberger. According to the research scientists, their methodology provides a "blueprint" for conducting detailed research into the activity of brain stem cells and their role in cognitive processes, and therefore for achieving a better understanding of poorly understood diseases.

Stem cells as a therapeutic objective for brain diseases

"In addition, we hope that it will be possible to control stem cell activity therapeutically to use them for brain repair - for example for the future treatment of cognitive disorders or in association with diseases that involve the death of nerve cells, such as Parkinson's disease or Alzheimer's disease," says Sebastian Jessberger.

What The Viewpoint Says: The considerations and challenges affecting the palliative care specialty and delivery of palliative care in the COVID-19 era, as well as potential solutions, are discussed in this Viewpoint.

Authors: Ambereen K. Mehta, M.D., M.P.H., of the University of California, Los Angeles, in Santa Monica, 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/jamaoncol.2020.1938)

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

What The Article Says: This essay discusses similarities between a doctor's experiences with diagnoses of cancer and COVID-19.

Author: Urvi A. Shah, M.D., of Memorial Sloan Kettering Cancer Center in New York, is the author.

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

(doi:10.1001/jamaoncol.2020.1848)

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

Repurposing existing medicines focused on known drug targets is likely to offer a more rapid hope of tackling COVID-19 than developing and manufacturing a vaccine, argue an international team of scientists in the British Journal of Pharmacology today.

Since the emergence of the SARS-CoV-2 virus in late 2019, more than 3.5 million people are known to have been infected, leading to over 240,000 deaths worldwide from COVID-19, the disease caused by the novel coronavirus. The race is on to find new drugs to treat COVID-19 patients and to develop a vaccine to prevent infection in the first place.

A team of researchers representing the International Union of Basic and Clinical Pharmacology today say there will be no 'magic bullet' to treat the disease and argue that a multi-pronged approach is needed to find new drugs. They caution that an effective and scalable vaccine is likely to take over a year before it can used to tackle the global pandemic.

When a virus enters our body, unless we have already developed immunity from previous infection or vaccination, it will break into our cells, hijacking their machinery and using it to replicate and spread throughout the body. Often, the symptoms we see are a result of our immune system fighting back in an attempt to clear the infection. In severe cases, this immune response can become overactive, potentially leading to a so-called cytokine storm, causing collateral damage to organs along the way.

"Any drug to treat COVID-19 will need to focus on the three key stages of infection: preventing the virus entering our cells in the first place, stopping it replicating if it gets inside the cells, and reducing the damage that occurs to our tissues, in this case, the lungs and heart," said Professor Anthony Davenport from the University of Cambridge, one of the authors of the review.

The review looks at potential therapeutic drug targets - the chinks in the virus's own armour or weak spots in the body's defences. Two key targets appear to be proteins on the surface of our cells, to which SARS-CoV-2 binds allowing it entry - ACE2 and TMPRSS2. TMPRSS2 appears to be very common on cells, whereas ACE2 is usually present at low levels that increase depending on sex, age, and smoking history.

"As we know these two proteins play a role in this coronavirus infection, we can focus on repurposing drugs that already have regulatory approval or are in the late stages of clinical trials," said Professor Davenport. "These treatments will have already been shown to be safe and so, if they can now be shown to be effective in COVID-19, they could be brought to clinical use relatively quickly."

One promising candidate is remdesivir, a drug originally developed for Ebola. Although clinical trials found it to be insufficiently effective at treating Ebola, clinical trials in the USA have suggested the drug may be beneficial for treating patients hospitalised with COVID-19, and the FDA has now approved it for emergency use. There have also been promising findings from studies of monoclonal antibodies, but this type of drug is expensive to produce and therefore less likely to be scalable.

"While we're waiting for a vaccine, drugs currently being used to treat other illnesses can be investigated as treatments for COVID-19 - in other words repurposed," said Dr Steve Alexander from the University of Nottingham.

"There's unlikely to be a single magic bullet - we will probably need several drugs in our armoury, some that will need be used in combination with others. The important thing is that these drugs are cheap to produce and easy to manufacture. That way, we can ensure access to affordable drugs across the globe, not just for wealthier nations."

The team say that we need to move quickly to identify existing drugs that are effective in clinical trials so that we can begin treating patients as rapidly as possible, but also because cases are likely to fall during the summer meaning there will be fewer people who can be recruited to clinical trials ahead of an anticipated second wave of the disease in autumn. They estimate there are currently more than 300 clinical trials taking place worldwide, though many of these investigational drugs are unlikely to be effective for widespread use because either it is not clear which part of the disease pathway they are targeting or they cause unpleasant side-effects.

They also advise patience for the promise of developing an effective vaccine against the virus anytime soon. Even after a new vaccine candidate has been shown to offer immunity against the coronavirus in humans, it needs to be tested in larger numbers of people to ensure it is safe to use. Manufacturing and distributing a vaccine at the scale needed to tackle this pandemic will also present significant challenges.

"Although there are a lot of vaccines being developed around the world, which we hope will be successful, it's still going to take a long time before those vaccines are shown to be effective and can be manufactured at the scale needed to make an impact," said Dr Steve Alexander.

"Some of the vaccines may not work, so the more drugs that can be tested and the more we know about the targets, the more likely we are to get something which is effective. The very specificity of vaccines means they are limited in which viruses they can neutralise. The lessons we learn and the drugs we generate will hopefully provide a greater degree of protection, not just against the COVID-19 virus, but also against the next viral threat."

Tsukuba, Japan - Collective behaviors are the result of dynamic local interactions between individual members of the collective. While the actions of a collective are readily observable, the interactions remain hidden and have traditionally been difficult to analyze. Now, researchers from the University of Tsukuba applied integrated information theory to understand how varying sizes of a collective of fish affect the interactions between its individual members.

Originally developed to measure the degree of consciousness from brain activity, integrated information theory is an elaborate computational tool that enables the study of groups of elements within a system--like a biological network--whereby each element has the ability to affect another through the cause-effect principle. In this context, "integrated" means that the information that the biological network yields is more substantial and informative than the information derived from the individual elements of the network. By measuring integrated information, overarching systems such as consciousness can be quantified from empirical data, including electroencephalographic (EEG) or functional magnetic resonance imaging (fMRI) recordings. In the behavioral sciences, this overarching system could be seen as a collective of animals, whereby actions of individual members could yield data to help understand the collective.

"Collective behaviors like swarming, fish schooling and bird flocking function so smoothly and seemingly effortlessly," says lead author of the study Professor Takayuki Niizato. "The quintessential question is how these collectives function as efficiently and coherently as they do. The goal of our study was to further our understanding of the dynamics of collective behavior by applying integrated information theory to schools of two to five fish to understand the intrinsic differences between these groups."

To achieve their goal, the researchers studied groups of Plecoglossus altivelis, also known as sweetfish. They chose juvenile fish, as these display typical schooling behavior, whereas adult fish tend to show territorial behavior. The researchers randomly picked fish and moved them together without any prior training to ensure the formation of a school of a given size.

By analyzing the trajectories of the fish using integrated information theory and including the visual field, distance and turning rate of each member of the collective in their analysis, the researchers found a discontinuity between three- and four-fish schools. Interestingly, this means that there was a substantial change in group behavior when the number of fish was increased from three to four, an observation that had not been made before.

"Our findings underscore the dynamics of collective behavior with varying collective sizes," says Professor Niizato. "Specifically, as collective size increases, a leadership emerges that determines group integrity. Our study highlights the intricacies of group dynamics and could help improve our understanding of more complex patterns of collective behavior."

Tsukuba, Japan - The germline is the cell lineage of an organism that passes on its genetic material to its progeny. Genetic damage to the germline can cause developmental defects and even death of that same progeny. It is thought that biological mechanisms exist that ensure that aberrant germline cells are eliminated to maintain germline integrity, although the specific molecular basis for this is unknown. In a new study published in Communications Biology, researchers from the University of Tsukuba identified the transcription factor Myc as a central molecular actor within the process of preserving the genomic integrity of the germline after DNA damage.

To achieve their goal, the researchers studied the fruit fly Drosophila to understand how germline integrity is maintained. This fly model presents a sterility syndrome called P-M (paternal-maternal) hybrid dysgenesis (HD), which results from a high rate of mutations and rearrangements in the DNA, leading to germline-loss and sterility. At the molecular level, so-called P-elements are responsible for HD. P-elements are DNA segments of which the protein transposase. Transposases have an ability known as P-element mobilization wherein they move segments of DNA, which leads to mutations and DNA instability. When male fruit flies carrying P-elements are crossed with females lacking P-elements, P-element mobilization and thus DNA damage occurs in their progeny, resulting in sterility.

"The Drosophila P-M hybrid dysgenesis model has been known for decades, but the molecular basis of the resulting sterility is still not fully understood," says corresponding author Professor Satoru Kobayashi. "The goal of our study was to further our understanding of the molecular mechanisms governing the elimination of damaged germline cells during reproduction. Interestingly, in a separate set of experiments, we found that knockdown of the transcription factor Myc resulted in a similar germline-loss phenotype that we observe in hybrid dysgenesis. We wanted to know how Myc and hybrid dysgenesis were interconnected in the process of maintaining germline integrity."

The researchers first investigated the number of germline cells at different embryonic stages in HD progeny and in normal flies that did not produce Myc. They found that in both models the number of germline cells decreased at a similar stage of embryonic development, suggesting that both processes are connected. The researchers then followed the expression of Myc in HD progeny and found that it was reduced in germline cells before the number of germline cells decreased, suggesting that HD causes Myc downregulation to result in a germline-loss phenotype. They then examined what happens if Myc continued to be expressed in HD progeny by overexpressing the transcription factor. While Myc overexpression in the HD germline led to increased germline cell numbers, the resulting germline exhibited a higher DNA mutation frequency and a lower capacity to develop into adulthood.

"These are striking results that show that Myc-dependent germline cell reduction serves to eliminate aberrant germline cells in which the genetic material has been damaged," says Professor Kobayashi. "We think that Myc is a central molecular actor in this process, serving as a quality-control during embryonic development."

Scientific team found a new metabolism regulation system for the brown adipose tissue using the kallikrein-kinin hormonal system, so far related to the physiology of the renal and cardiovascular system and inflammation and pain processes. This molecular auto-control system of lipidic metabolism, so far unknown, could help prevent the damaging effects derived from an excessive activation of the brown adipose tissue.

The new study, published in the journal Nature Communications, is led by Professor Francesc Villarroya, from the Faculty of Biology and the Institute of Biomedicine of the University of Barcelona (IBUB), and member of the Physiopathology of Obesity and Nutrition Networking Biomedical Research Centre (CIBERobn) from the Health Institute Carlos III. Other participants in the study are the experts from the University of Santiago de Compostela, Maastricht University (the Netherlands), and Humboldt University, the Center for Cardiovascular Research and Berlin Institute of Health (Germany).

Brown adipose tissue: how to auto-control its activity

The brown adipose tissue's main function is to burn calories and create body heat using fat (thermogenesis). It also acts as an endocrine organ able to secrete factors that activate fat and carb metabolism and help prevent pathologies such as obesity and diabetes. However, an excessive and uncontrolled activity of the tissue could cause damaging effects such as cachexia -excessive loss of body weight- present in some types of cancer.

The new paper describes for the first time the relation of the kallikrein-kikin System with metabolic regulation systems in the brown adipose tissue. This tissue is activated as a reaction to environmental stimuli -temperature, diet, etc.- and its response is channelled through the sympathetic nervous system and hormonal factors. It was believed that the interruption of these inductors was the authentic limiting the thermogenic activity of fat.

"We now know that some active mechanisms can restrain this and that the own positive inductors can activate the Kallikrein-kinin system which acts as an auto-control mechanism to remove the brown adipose tissue activity", notes Professor Villarroya, head of the research group on Genetics and Molecular Biology of Mitochondrial Proteins and Associated Pathologies of the UB.

"Although it may look contradictory -the activator signals determine the self-control of the system- and this could be explained if we consider the importance of the fine regulation of thermogenesis to avoid too much metabolites to burn without any physiological aim for the body", notes the expert.

Thermogenesis: beyond providing cells with energy

The biochemical mechanism to burn calories and make body heat with fat -known mitochondrial uncoupling- is a process that alters the bioenergetics of the mitochondria, the cell organelle that obtains energy. In this specific mechanism, the activity of the mitochondria is not the common one -oxidising substrates to get ATP molecules to provide energy to cells- but it derives in the dissipation of metabolic energy in form of heat.

An excessive activity of the brown adipose tissue creates pathological picture associated to an uncontrolled energetic waste and fast weight loss (cachexia, etc.) in patients with tumours. There are many enigmas about a process, that despite being within the clinical field, hardens the recovery of the affected patients by burning when the energy waste and activity of the brown adipose tissue skyrockets.

Before knowing about the physiology of the brown adipose tissue, the mitochondrial uncoupling was the altered mechanism for the intoxication in workers in army factories during the World War I. Due to the exposure to dinitrophenol compound -toxic that generates mitochondrial uncoupling uncontrolledly in all body tissues- the temperature of the intoxicated workers increased and the weight loss was severe in the affected ones. During the 20th century's seventies, the scientific community could identify that mitochondrial uncoupling was a process that occurs in a controlled way in the mitochondria of the brown adipose tissue through the UCP1 protein.

"It is clear that such a mechanism should be highly controlled in order to prevent problems caused by an uncontrolled activity. Actually, it is possible for the evolution to have confined this mechanism within the mitochondria in a specialized cell -brown adipocyte- and not all body tissues as a security mechanism", says Villarroya.

The new study could shed light on strategies to moderate the thermogenic activity in pathological situations (cancer, etc.). In this context, the discovery of the local action of of the auto-control system of kallikrein-kinkin on the brown adipose tissue sheds lights on future pharmacological tools for the fight and control of metabolic diseases.

According to Carlos García Meca and Andrés Macho Ortiz, researchers at NTC-UPV, this new symmetry allows the conservation of the linear moment between dramatically different physical systems. This paves the way to designing pioneering optical, acoustic and elastic devices, including invisible omnidirectional, polarization-independent materials, ultra-compact frequency shifters, isolators and pulse-shape transformers.

"These devices allow us to unusually modify different properties of light signals inside photonic circuits to process the spread of information. This is vital in communication systems. Moreover, we can adapt the functionality of those devices to the requirements at any time, as they are dynamically configurable," explained Carlos García Meca.

For designing these new devices, the key lies in changing the refraction index, which in this case is not generated in space but in time. "The Supersymmetry technique tells us how to vary the refraction index of an object to have the light completely transmitted, avoiding undesired reflections," said Andrés Macho Ortiz.

The property of non-reflection is particularly useful for designing new photonic circuits. "Its implementation allows us to increase the speed of communications inside and makes them more compact and configurable without the signal that transports information bits being reflected back," explained Carlos and Andrés.

In general, the reflection of materials whose properties vary in time does not depend on the direction of light propagation. Therefore, "the absence of reflection in the proposed materials is linked to a total transparency, which results in the concept of omnidirectional invisibility: whatever the direction of light hitting those materials is, their presence is undetectable," concluded the authors.

Symmetries

The discovery of symmetries in the nature is a cornerstone in physics that allows us to find the conservation laws governing the universe. For example, electric charge, energy and mass conservation (coming from symmetries in physical laws governing electromagnetism, thermodynamics and chemistry) has allowed humans to have the ability to develop this technology (circuits, nuclear power stations, drugs...).

Exceptionally, supersymmetry was originally conceived in quantum physics as a hypothetical symmetry between particles that could explain all interactions in nature: nuclear forces, gravity and electromagnetism.