Culture

The Feinstein Institutes for Medical Research Professor and Senior Vice President Karina W. Davidson, PhD, MASc, reviews clinical practices for social determinants of health screening and referrals in the September 17 issue of The Journal of the American Medical Association (JAMA).

Conditions in the places where people live, learn, work and play affect a wide range of health risks and outcomes - these conditions are called social determinants of health. Screening for social determinants helps health care professionals better understand patient health risks and improves patient health. The health care community generally agrees that clinicians should screen social determinants for their patients.

"For optimal health of our patients, we must address and eventually eliminate patients' social determinants of health disparities," said Dr. Davidson, who heads the Center for Personalized Health at the Feinstein Institutes and is a professor of Behavioral Medicine at the Donald and Barbara Zucker School of Medicine at Hofstra/Northwell. "Continued advances and debate about how to best implement social determinants screening and referrals will ensure continued progress towards this goal and will give clinicians and patients hope for a healthier future."

Dr. Davidson, along with co-author Thomas McGinn, MD, MPH, Director of the Institute for Health Innovations and Outcomes Research at the Feinstein Institutes and senior vice president of physician network operations at Northwell Health, note in their JAMA review that it is well known in the clinic that disparities in the social determinants are harmful to health. But less is known about who should screen, identify and deliver programs to reduce these harms and successfully address patients' social determinants, either individually or at the societal level. The authors note that there have been successes in identifying social screening needs and implementing co-location care models, for example. They also note that, "identifying and addressing/improving patients' social determinants will only be successful if these clinical practices occur with broad structural, community, and societal changes to the determinants that currently perpetuate poor health."

Drs. Davidson and McGinn also note that there is a debate to implementing comprehensive and universal screening for social determinants. One of the debates is that doctors don't have time. In a 2019 survey, 70 percent of physicians reported "lack of time" as an issue that prevents social determinants screening. There is already concern that many physicians are spending too little time in meaningful patient care, and too much time on electronic health record entry and other administrative responsibilities, and that adding screening for social determinants of health many only exacerbate this issue.

"Dr. Davidson is a research leader in chronic disease management who exemplifies our mission to produce knowledge to cure disease," said Kevin J. Tracey, MD, president and CEO of the Feinstein Institutes. "This paper is another example of how she brilliantly applies research to find future cures."

Dr. Davidson joined the Feinstein Institutes last year. Her current research focuses on Personalized (N-of-1) trials to identify precise therapies that improve a single patients' symptoms, conditions, or behaviors. Dr. Davidson has been the principal investigator of more than 22 federally funded grants and authored over 200 peer reviewed articles. She was recently awarded a Transformative R01 grant to accomplish this vision of re-imagining the process by which therapies are tested in the clinical encounter, which helped identify maximal benefit and minimal harm for each individual patient. For more than 25 years, she has served in leadership roles with diverse teams focused on improving scientific and educational missions.

Encouraging citizens to take part in almost every step of scientific air quality research improves their understanding of how air pollution affects their health, finds a new study from the University of Surrey.

In a paper published in Sustainable Cities and Society journal, researchers from Surrey's Global Centre for Clean Air Research (GCARE) together with the IAAC Fab Lab Barcelona, Connected Places Catapult and T6 Ecosystems under the iSCAPE project, provide details about how introducing a multi-component, 'citizen science' approach that allows people to take part in the scientific process of research - e.g., finding research problems, methodologies and conclusions, in collaboration with the researchers - helps them to better understand their pollution exposure levels.

GCARE's strategy is based on three basic ideas:

Inclusion: introducing seminars and workshops to involve people from different genders, ages and ethnic groups

Collaboration: constant interaction between researchers, communities and policy makers

Reciprocation: citizen scientists are encouraged to debate their research with each other in a workshop setting.

Scientists from GCARE also used questionnaires and interactive quizzes to monitor people's perception of exposure levels and introduced low-cost sensors to allow individuals to conduct their own research studies.

The project allowed citizens to create detailed and well thought out investigations that looked into issues such as the air quality inside of their homes at different times of the day to explored when and how traffic jams worsen air quality in nearby residential areas.

Professor Prashant Kumar, Director of GCARE at the University of Surrey, said: "Until recently, citizens' involvement in air quality research has been limited to monitoring their environment and raising awareness of pollution in their local area, while tasks such as the design, planning and analysis of research were carried out by scientists. What we have found is that when local residents play an integral part in scientific research, they acquire knowledge that can more directly impact their day-to-day lives and actions.

"Citizens should no longer be treated as participants of a study; we should rather embrace them as partners. This work is an example of bringing together citizens and their representatives, public authorities and researchers for all-round actions against pollution."

Councillor Caroline Reeves, Leader of Guildford Borough Council, said: "The involvement of members of our community with the work done at the University of Surrey has highlighted the interest in the issues around air quality in a very strong and meaningful way. Residents and businesses have far greater awareness, and are keen to find resolutions to the problems rather than dismissing it at someone else's problem. It has meant that air quality is very high on the list of targets to be addressed locally as well as nationally."

Scientists at the Institute for Research in Biomedicine (IRB Barcelona) and the Molecular Biology Institute of Barcelona (IBMB-CSIC) have published a study in the journal Nature Communications revealing the structure of a key protein, known as a portal, in Epstein-Barr virus infection.

The Epstein-Barr virus, which belongs to the herpesvirus family, is one of the most widespread human viruses and the main cause of infectious mononucleosis (also known as glandular fever). In addition, it causes several kinds of cancer, including Burkitt and Hodgkins lymphoma, stomach cancer and nasopharyngeal cancer, as well as several autoimmune diseases. There is currently no treatment for infections caused by this virus.

"Understanding the structure of the portal protein could prove useful for the design of inhibitors for the treatment of herpesvirus infections such as Epstein-Barr. Also, given that this protein is found only in herpesviruses, these inhibitors would be virus-specific and may be less toxic for humans," says Miquel Coll, head of the Structural Biology of Protein & Nucleic Acid Complexes and Molecular Machines Lab at IRB Barcelona and professor at CSIC.

All herpesviruses have a similar infection mechanism. Having entered the cell and reached the nucleus, the viruses release their DNA, which can remain latent for years until certain conditions trigger its replication. After this process, DNA is then introduced into new viral capsids, thereby forming new viruses that can attack other cells. The portal protein is the route through which DNA enters the viral capsid and through which it leaves to infect cells.

In a second study recently published in the same journal, the researchers have also characterised the structure of the portal protein in bacteriophage T7. This phage is a virus that infects only bacteria and, interestingly, its DNA packaging system resembles that used by herpesviruses.

"By solving the structure of the portal protein of bacteriophage T7, we have been able to infer how the portal from Epstein-Barr virus works," explain Cristina Machón and Montserrat Fàbrega, postdoctoral fellows at IRB Barcelona and IBMB-CSIC, and first authors --together with Ana Cuervo, from the National Centre for Biotechnology (CNB-CSIC)--of the studies published.

"In both viruses, the portal protein comprises 12 subunits, forming a large mushroom-shaped structure, with a central channel through which DNA passes. This channel has a valve that regulates the entry and exit of the virus' genetic material," explains Coll.

To study the structure of this protein, the researchers used both synchrotron X-ray diffraction and high-resolution electron cryomicroscopy. Both studies were performed in collaboration with the CNB-CSIC and the University of Oxford (UK).

The expression of many genes that have previously been associated with autism is abnormal also in violent psychopathy, a new study shows. The researchers used stem cell technology to analyse the expression of genes and proteins in the brain cells of psychopathic violent offenders. Published in Molecular Psychiatry, the findings may open up new avenues for the treatment of psychopathy. The study was carried out in collaboration between the University of Eastern Finland, the University of Helsinki and Karolinska Institutet in Sweden.

Psychopathy is an extreme form of antisocial behaviour, with about 1% prevalence in the general population, and 10-30% prevalence among incarcerated criminal offenders. Psychopathy is known to be strongly hereditary, but whether or not it is associated with abnormal expression of genes or proteins in neurons has remained unclear- up until now.

In the newly published study, the researchers used stem cell technology to analyse the expression of genes and proteins that have been associated with psychopathy. The study participants' skin cells were used to create pluripotent stem cells, which were then differentiated into cortical neurons and astrocytes. The study population comprised psychopathic violent offenders and healthy controls. Since psychopathy was accompanied by substance abuse, the study population also included non-psychopathic substance abusers. This made it possible for the researchers to determine which abnormalities were associated exclusively with psychopathy.

The study shows that psychopathy is associated with robust alterations in the expression of genes and immune-response-related molecular pathways. Several of these genes have also been linked to autism. In neurons, psychopathy was associated with marked upregulation of RPL10P9 and ZNF132, and downregulation of CDH5 and OPRD1. In astrocytes, RPL10P9 and MT-RNR2 were upregulated. The expression of these genes explained 30-92% of the variance of psychopathic symptoms. Psychopathy was also associated with altered expression of proteins related to glucose metabolism and the opioid system.

Several earlier studies have suggested that violent and psychotic behaviour are associated with alterations in glucose metabolism and opioidergic neurotransmission. The new findings support the idea of abnormal opioid system function being a factor underlying psychopathy. This suggests that using long-lasting injections of naltrexone or buprenorphine to balance the opioid system could be a feasible treatment for psychopathy.

Opioid dependence has become a national crisis with serious impact on economic and social welfare, and numerous casualties. A big goal of ongoing research in combating opioid use disorder is understanding drug withdrawal. The physical and emotional symptoms of withdrawal can be life threatening and make up a powerfully negative experience; the fear of these symptoms strongly motivates addiction.

Researchers in the lab of James Schwaber at the Daniel Baugh Institute for Functional Genomics and Computational Biology at Thomas Jefferson University are studying how inflammation contributes to drug withdrawal and dependence. Their study was published in Frontiers of Neuroscience on July 3.

Opioids can cause inflammation in the brain by inducing immune cells to release inflammatory molecules called cytokines. The main immune cells in the brain are microglia and astrocytes. Inflammatory responses induced by opioids have been observed in the central amygdala, a brain region that has been strongly implicated in opioid dependence because of its role in emotion and motivation. The central amygdala can also be affected by inflammation in other parts of the body, like the gut. In fact, the communication between the gut and the brain can shape a variety of motivated behaviors and emotional states, including those associated with drug dependence and withdrawal.

The researchers including first author Sean O'Sullivan in Dr. Schwaber's lab isolated single neurons, microglia, and astrocytes from the central amygdala and studied their genetic profiles in normal, opioid-dependent, and withdrawn rats. They were surprised to find that the profile of astrocytes changed the most, shifting genetic expression to a more activated state. This shift correlated strongly with opioid withdrawal. Furthermore, all three cell types showed a considerable increase in an inflammatory cytokine called TNF alpha in withdrawn animals.

In addition, the researchers also assayed different types of bacteria in the gut of rats and found that certain anti-inflammatory bacteria were suppressed in withdrawn animals, shifting the ratio of gut microbiota and causing a phenomenon called dysbiosis, which can cause inflammation in the digestive system. It is unclear how these changes influence opioid withdrawal, but the authors propose that the simultaneous inflammation in the gut and central amygdala may be linked to the negative emotional experience of withdrawal.

The findings underscore the highly complex relationship between the gut and the brain, and suggest that inflammation in the gut and brain may exacerbate symptoms associated with withdrawal. Targeting inflammation in these regions may alleviate the negative experience of drug withdrawal, and therefore prevent dependence.

How active matter, such as assemblages of bacterial or epithelial cells, manages to expand into narrow spaces largely depends on their growth dynamics, as Ludwig-Maximilians-Universitaet (LMU) in Munich physicists demonstrate in a newly published study.

Biological forms of active matter, such as bacterial biofilms or sheets of epithelial cells, are often found in confined microspaces. Working out how such systems colonize their environment and extend their range by invading new territories will enhance our understanding of many of the normal functions and disease states observed in higher organisms. In cooperation with Dr. Amin Doostmohammadi (University of Oxford), LMU physicists Felix Kempf and Professor Erwin Frey have now demonstrated with the aid of computer simulations that cell collectives exhibit a variety of motility patterns as they approach and pass through local constrictions. The authors of the new study go on to show that the pattern adopted depends on the level of active motility that develops at the leading edge of the assemblage. The findings appear in the journal Soft Matter.

Several previous publications had suggested that the collective motions of biological matter are influenced by the nature of the terrain in which such systems find themselves. In particular, in-vitro experiments carried out with epithelial and bacterial cells, and with mixtures consisting of isolated intracellular biofilaments and molecular motors, have revealed that spatial boundaries have a significant impact on motility. "So far, this type of research has concentrated primarily on the interactions between the shape of the obstacle employed and the motile activity of the particles concerned," says Kempf, the lead author of the new paper. However, in most of these systems, the number of particles does not remain constant. Under natural conditions, epithelial or bacterial cells divide at regular intervals and, when confined in capillary tubes, they form an advancing invasion front. Therefore, in order to understand how these patterns form and evolve, it is necessary to take the growth dynamics of these systems into account. Kempf and colleagues used computer simulations to explore the effects of this factor.

They observed three fundamentally distinct modes of invasion, which can be distinguished on the basis of the overall activity of the growing system and the behavior of the invasion front as it approaches the constriction. If the level of motile activity is low, the invasion front retains its smooth and sharply defined outline as it advances at a constant speed. At higher levels of activity, the leading edge takes on an irregular outline. Finally, once the activity level exceeds a certain threshold, small clusters of cells detach from the advancing front, which can then worm their way through the narrow gap. The simulations also enabled the researchers to characterize the processes that drive the transitions observed as the invasion front evolves, and to quantify their impact on the speed with which the cells advanced into the ever more confined space. "These findings make a significant contribution to our understanding of active matter, and have several implications that can be tested in future experiments," says Kempf.

Plant genetic varieties in Central Europe could collapse due to temperature extremes and drought brought on by climate change. According to a new paper published in Nature today, only a few individuals of a species have already adapted to extreme climate conditions. These findings suggest that the overall species genetic diversity could be greatly diminished. The publication was led by Moises Exposito-Alonso, who joins Carnegie next month from the Max Planck Institute for Developmental Biology and the University of California Berkeley.

An international team of researchers from the Max Planck Institute for Developmental Biology, University of Tübingen, Technical University of Madrid, and UC Berkeley studied populations of the thale cress plant, Arabidopsis thaliana, collected from over 500 geographic locations in Europe, commonly used for biological research. Growing these plants in Spain and Germany under dry conditions revealed how individual plants responded to heat and drought.

The investigators were particularly interested in how the unique blend of genetic mutations enables the different individuals of the same species to resist experimentally simulated climates. As some of these mutations may confer physiological advantages, the main goal of this study was to rank their fitness for the future survival of the species.

Mathematical models forecast shrink potential of European biodiversity

This data was then combined with models predicting how temperatures and precipitation are expected to shift geographically in the next few decades in order to understand how plant biodiversity will be affected by climate change caused by human activity.

"On the basis of our calculations up to the year 2050, we can determine a significant change in the mutations that will be needed for the thale cress to survive in Southern to Central Europe," first author Moi Exposito-Alonso said. "It is remarkable how much individuals from different parts of Europe differ in their ability to withstand future climate conditions," added Detlef Weigel, Director at the Max Planck Institute, where the work was coordinated.

Many of the continent's predominant plant populations won't be able to survive

As precipitation decreases and temperatures rise, especially in so-called transition zones between the Mediterranean and northern Europe, the team's predictions indicate that many of the continent's predominant plant populations will not possess the necessary genetic mutations to survive. These patterns might be shared across many plant species of Europe. While genetic information for most species is still lacking, the rapid advance in modern genetic methods allows researchers to obtain such information for more and more species. With such information in hand, it will be possible to improve predictions of where a species is most at risk of suffering from the consequences of climate change.

Researchers at the German Center for Neurodegenerative Diseases (DZNE) and the Institute for Stroke and Dementia Research (ISD) at the University Hospital of the Ludwig-Maximilians-Universität (LMU) in Munich have found that a protein called TREM2 could positively influence the course of Alzheimer's disease. When TREM2 is present in the cerebrospinal fluid at higher concentrations, patients at any stage of the disease have a better prognosis. This observation provides a starting point for the development of new therapeutic strategies. The study was led by Prof. Christian Haass (DZNE) and Prof. Michael Ewers (ISD, LMU) and is published in the journal "Science Translational Medicine".

In the brain, TREM2 is exclusively produced by microglia, the immune cells of the brain. These cells patrol the brain and clear it from cellular waste products and debris to keep it healthy. In previous studies on mice, Haass and his colleagues demonstrated that TREM2 activates microglia to enclose and selectively destroy toxic protein aggregates typical for Alzheimer's disease. "These observations indicate that TREM2 can protect the brain from the degenerative effects of the disease - at least in animal models," said Haass.

But what about patients with Alzheimer's disease? Does TREM2 protect the human brain as well? To answer these questions, Haass, Ewers, and their colleagues correlated the concentration of TREM2 in the cerebrospinal fluid of Alzheimer patients with their respective disease progression over several years. To this end, they used data of 385 subjects from the Alzheimer's Disease Neuroimaging Initiative (ADNI), a large clinical dataset containing records and samples from patients and healthy seniors taken at regular checkups over many years. The study thus allows to establish associations between certain biochemical changes and disease progression.

Indeed, Haass and Ewers found that high levels of TREM2 improved the prognosis of subjects at all stages of the disease. Their memory remained more stable and the degradation of the hippocampus, a brain region responsible for learning and recollection, was less pronounced. "Our findings are clinically relevant because we found that higher levels of TREM2 were associated also with a reduced rate of the development of full blown dementia over a time period up to 11 years", explained Ewers. "Microglia activation is a double-edged sword, entailing both protective effects and neurotoxic inflammation. TREM2 signaling may play a key role in the regulation of the brain's protective immune response".

The concentration of TREM2 in the cerebrospinal fluid usually increases at early stages of the disease, when the first symptoms appear. "TREM2 production is a response to brain damage that has already occurred," said Haass. "It stimulates the microglia to protect the brain. However, this protection does not seem to be sufficient in patients with Alzheimer's disease". This is where Haass and his colleagues see an option for new therapeutic strategies. "We are currently developing a therapeutic antibody that stimulates the TREM2 function and thus improves its protective function," said Haass.

Jugglers are skilled at keeping several objects in motion at the same time using a combination of tossing motions and eye movement. As objects are added to a juggler's routine, their gaze moves as the juggler tries to focus on all of the objects and avoid dropping one or two.

People who often multitask at work might feel like a juggler at times. In a work setting -- such as an oil refinery -- where a person needs to keep tabs on multiple gauges and systems to keep systems working properly, a change in a person's eye movement could cause a mistake, and possibly cost a life. With the ever-increasing connectivity of today's society, the demand for a real-time way to evaluate how well an employee understands their current situation -- often called situational awareness -- has become a paramount safety issue for employers, especially those in industrial and manufacturing industries. Researchers at the University of Missouri believe studying a person's eyes could help with this.

"An employee with poor situational awareness will miss some critical things that happen in their work area," said Jung Hyup Kim, an assistant professor of industrial and manufacturing systems engineering in the MU College of Engineering. "If I am tired, burdened by other things, or my workload is beyond what I can handle, my awareness will go down, and there is no way to measure that in real-time."

Researchers said the current method to evaluate a person's situational awareness involves only asking questions; this is not enough. In the study, they created a simulated multitasking environment of an oil refinery control room. Participants had to monitor multiple gauges and other controls on a computer screen while simultaneously responding to unexpected events, such as alarms.

"We found a relationship between situational awareness and self-terminating visual search -- or once you find a solution, you end the search," Kim said. "So, if a person has a good understanding about the situation, then they can directly target the cause of the problem in a short amount of time. But if they do not have good awareness, then they may spend a long time searching randomly for the cause."

Kim and Xiaonan Yang, a graduate student at MU, hope to test their model in a real-life environment to see if any changes are observed between that situation and their simulation.

A medication that boosts the body's own cannabis-like substances, endocannabinoids, shows promise to help the brain un-learn fear memories when these are no longer meaningful. These results, obtained in an early-stage, experimental study on healthy volunteers at Linköping University in Sweden, give hope that a new treatment can be developed for post-traumatic stress disorder, PTSD. The study has been published in the scientific journal Biological Psychiatry.

"We have used a medication that blocks the way the body breaks down its own cannabis-like substances, or 'endocannabinoids'. Our study shows that this class of medications, called FAAH inhibitors, may offer a new way to treat PTSD and perhaps also other stress-related psychiatric conditions. The next important step will be to see if this type of medication works in patients, particularly those with PTSD", says Leah Mayo, senior post-doctoral fellow and lead investigator on the study, which was carried out in the laboratory of Professor Markus Heilig at the Center for Social and Affective Neuroscience, CSAN, Linköping University.

Post-traumatic stress disorder, PTSD, arises in some - but not all - people who have experienced life-threatening events. A person affected by PTSD avoids reminders of the trauma, even when the danger is long gone. Over time, these patients become tense, withdrawn, and experience sleep difficulties. This condition is particularly common among women, where it is often the result of physical or sexual abuse. It is highly debilitating, and current treatment options are limited.

PTSD is currently best treated using prolonged exposure therapy, PE. In this treatment, patients are repeatedly exposed to their traumatic memory with the help of a therapist. This ultimately allows patients to acquire new learning: that these memories no longer signal imminent danger. Although clinically useful, effects of PE are limited. Many patients do not benefit, and among those who do, fears frequently return over time. The scientists who carried out the current study examined whether fear extinction learning, the principle behind PE therapy, can be boosted by a medication.

The researchers tested a pharmaceutical that affects the endocannabinoid system, which uses the body's own cannabis-like substances to regulate fear and stress-related behaviors. The experimental medication results in increased levels of anandamide, a key endocannabinoid, in regions of the brain that control fear and anxiety. The medication accomplishes this by blocking an enzyme, FAAH (fatty acid amide hydrolase), that normally breaks down anandamide. The FAAH inhibitor tested by the researchers was originally developed for use as a pain killer, but was not effective enough when tested clinically.

This early-stage experimental study was randomised, placebo-controlled and double-blind, which means that neither the participants nor the scientists knew who was receiving the active drug (16 people) and who was receiving placebo (29 people). Participants were healthy volunteers. After taking the drug for 10 days, they underwent several psychological and physiological tests. In one of these, participants learned to associate a highly unpleasant sound, that of fingernails scraping across a blackboard, with a specific visual cue - an image of a red or blue lamp. Once they had learned to respond with fear to the previously innocuous image of the lamp, they were repeatedly re-exposed to it, but now in the absence of the unpleasant sound. This allowed them to unlearn the fear memory. The following day, the scientists measured how well participants remembered this new learning: that the lamp was no longer a threat signal. This process of un-learning fear is the same principle on which PE therapy for PTSD is based.

"We saw that participants who had received the FAAH inhibitor remembered the fear extinction memory much better. This is very exciting", say Leah Mayo.

"Numerous promising treatments coming out of basic research on psychiatric disorders have failed when tested in humans. This has created quite a disappointment in the field. This is the first mechanism in a long time where promising results from animal experiments seem to hold up when put to test in people. The next step, of course, is to see whether the treatment works in people with PTSD", adds professor Markus Heilig.

East Hanover, NJ. August 29, 2019. A recent study by Kessler Foundation researchers linked the deficits in social cognition in multiple sclerosis with symptoms in other domains. The article, "Relationship between social cognition and fatigue, depressive symptoms, and anxiety in multiple sclerosis," was epublished on June 1, 2019 by the Journal of Neuropsychology.

The authors are Helen Genova, PhD, Katie Lancaster, PhD, Jean Lengenfelder, PhD, Christopher Bober, John DeLuca, PhD, and Nancy Chiaravalloti, PhD, of Kessler Foundation. Link to abstract: https://doi.org/10.1111/jnp.12185

Researchers tested 28 individuals with multiple sclerosis for impairments of social cognition using tests of facial affect recognition and Theory of Mind, and looked for associations between deficits of social cognition with common conditions in this population by screening for fatigue, depression and anxiety. They also measured non-social cognitive ability, i.e., attention and processing speed, using the Symbol Digit Modality Test.

Preliminary findings showed consistent associations between poorer performance on measures of social cognition and increased symptoms of depression, anxiety, and fatigue, most notably psychosocial fatigue. Cognitive ability was not a factor in these associations.

The study raises issues of causality and reciprocal effects, according to Dr. Genova, the Foundation's assistant director of the Center for Neuropsychology and Neuroscience Research. "The nature of the relationships among these variables remains unclear," said Dr. Genova. "We cannot say whether deficits of social cognition worsen mood condition and fatigue, or vice versa," she explained. "The relationships may be reciprocal in nature," she observed. "Poor social cognition may worsen fatigue, depression and anxiety, leading to greater social isolation. That, in turn, may worsen social cognitive function."

The researchers emphasized the preliminary nature of their findings and recommended further research into the relationships among these factors in individuals with MS, as well in other populations with non-neurologic conditions, and healthy controls. "All of these conditions adversely affect quality of life," concluded Dr. Genova. "To alleviate their impact, we need to understand the interplay of social cognition, mood, and fatigue. Our study is an initial step toward understanding these dynamics in the population with MS.'

Engineers at the University of Birmingham have successfully designed a robotic system that can perform a key task in disassembling component parts.

The research is an important advance for manufacturers looking for more efficient ways to build products from a combination of reused, repaired and new parts.

Known as remanufacturing, this process is becoming increasingly commonplace in manufacturing and is attractive because it can use as little as 10 per cent of the energy and raw materials required to build the product from scratch. It can also reduce CO2 emissions by more than 80 per cent.

A key part of the process is the ability to disassemble the 'core', the returned product. It's a challenge because of the huge variety within these products, with lots of unknowns in the size, shape and condition of components.

The new study, published in Royal Society Open Science, demonstrates a process for removing pins from holes - components like these are extremely common in a wide variety of machines, such as internal combustion engines. The research is the first to investigate this operation in depth and identify the key parameters required to automate the process.

Yongquan Zhang, of the Autonomous Remanufacturing Laboratory at the University of Birmingham is lead author on the paper. "Processes currently used for automating disassembly are fairly ad hoc," he explained. "We need to be able to design robust systems that can handle the uncertainties that are inherent in disassembly processes - and to do that, we need a better fundamental understanding of disassembly."

"The results of this study demonstrate how that fundamental understanding can be used to design robotic systems for reliably performing one common disassembly operation."

LA JOLLA--(August 29, 2019) Iron is essential for plant growth, but with heavy rainfall and poor aeration, many acidic soils become toxic with excess iron. In countries with dramatic flood seasons, such as in West Africa and tropical Asia, toxic iron levels can have dire consequences on the availability of staple foods, such as rice.

Despite dozens of attempts in the last two decades to uncover the genes responsible for iron tolerance, these remained elusive until recently. Now, Salk scientists have found a major genetic regulator of iron tolerance, a gene called GSNOR. The findings, published in Nature Communications on August 29, 2019, could lead to the development of crop species that produce higher yields in soils with excess iron.

"This is the first time that a gene and its natural variants have been identified for iron tolerance," says Associate Professor Wolfgang Busch, senior author on the paper and a member of Salk's Plant Molecular and Cellular Biology Laboratory as well as its Integrative Biology Laboratory. "This work is exciting because we now understand how plants can grow in stressful conditions, such as high levels of iron, which could help us make more stress-resistant crops."

In plants such as rice, elevated soil iron levels cause direct cellular damage by harming fats and proteins, decreasing roots' ability to grow. Yet, some plants appear to have inherent tolerance to high iron levels; scientists wanted to understand why.

"We believed there were genetic mechanisms that underlie this resistance, but it was unclear which genes were responsible," says first author Baohai Li, a postdoctoral fellow in the Busch lab. "To examine this question, we used the power of natural variation of hundreds of different strains of plants to study genetic adaption to high levels of iron."

The scientists first tested a number of strains of a small mustard plant (Arabidopsis thaliana), to observe if there was natural variation in iron resistance. Some of the plants did exhibit tolerance to iron toxicity, so the researchers used an approach called genome-wide association studies (GWAS) to locate the responsible gene. Their analyses pinpointed the gene GSNOR as the key to enabling plants and roots to grow in iron-heavy environments.

The researchers also found that the iron-tolerance mechanism is, to their surprise, related to the activities of nitric oxide, a gaseous molecule with a variety of roles in plants including responding to stress. High levels of nitric oxide induced cellular stress and impaired the plant roots' tolerance for elevated iron levels. This occurred when plants did not have a functional GSNOR gene. GSNOR likely plays a central role in nitric oxide metabolism and regulates the plants' ability to respond to cellular stress and damage. This nitric oxide mechanism and the GSNOR gene also affected iron tolerance in other species of plants, such as rice (Oryza sativa) and a legume (Lotus japonicus), suggesting that this gene and its activities are likely critical in many, if not all, species of plants.

"By identifying this gene and its genetic variants that confer iron tolerance, we hope to help plants, such as rice, become more resistant to iron in regions with toxic iron levels," says Busch. "Since we found that this gene and pathway was conserved in multiple species of plants, we suspect they may be important for iron resistance in all higher plants. Additionally, this gene and pathway may also play a role in humans, and could lead to new treatments for conditions associated with iron overload."

Next, Li will be starting his own laboratory at Zhejiang University, in China. He plans to identify the relevant genetic variants in rice and observe if iron-tolerance variants could increase crop yields in flooded Chinese fields.

NEW YORK AND SEVILLE, SPAIN -- Every animal, from an ant to a human, contains in their genome pieces of DNA called Hox genes. Architects of the body, these genes are keepers of the body's blueprints; they dictate how embryos grown into adults, including where a developing animal puts its head, legs and other body parts.

Scientists have long searched for ways to decipher how Hox genes create this body map; a key to decoding how we build our bodies.

Now an international group of researchers from Columbia University and the Spanish National Research Council (CSIC) based at the Universidad Pablo de Olavide in Seville, Spain have found one such key: a method that can systematically identify the role each Hox gene plays in a developing fruit fly. Their results, reported recently in Nature Communications, offer a new path forward for researchers hoping to make sense of a process that is equal parts chaotic and precise, and that is critical to understanding not only growth and development but also aging and disease.

"The genome, which contains thousands of genes and millions of letters of DNA, is the most complicated code ever written," said Richard Mann, PhD, principal investigator at Columbia's Mortimer B. Zuckerman Mind Brain Behavior Institute and the paper's co-senior author. "Deciphering this code has proven so difficult because evolution wrote it in fits and starts over hundreds of millions of years. Today's study offers a key to cracking that code, bringing us closer than ever to understanding how Hox genes build a healthy body, or how this process gets disrupted in disease."

Hox genes are ancient; they can be found across all animal species. Even primitive jellyfish have them. Each type of organism has different combinations of these genes. Fruit flies have eight Hox genes, while humans have 39.

These genes work by producing special proteins called transcription factors, which work together with similar proteins called Hox cofactors to bind to different segments of DNA and turn many other genes on and off at just the right time -- a Rube Goldberg machine of microscopic proportions.

"Because these genes are intricately involved in many aspects of development, it has proven incredibly challenging to isolate individual Hox genes and trace their activity over time," said James Castelli-Gair Hombría, PhD, a principal investigator at the Centro Andaluz de Biología del Desarrollo at the Universidad Pablo de Olavide and the paper's co-senior author. "We had this incredibly complex equation to solve but too many unknowns to make significant progress."

Recently, Dr. Hombría and his team hit upon a bit of luck. While examining genetic activity in a developing fruit fly, they stumbled upon a small piece of regulatory DNA, called vvI1+2, that had an unusual -- and surprising -- attribute. Although it was active in cells across the fruit fly's entire developing body, it appeared to be regulated by all of the fruit fly's eight Hox genes.

"The ubiquity of the vvI1+2 DNA segment across the entire developing fruit fly, combined with the fact that every Hox gene touches it, made it an ideal system by which to study the Hox gene family," said Carlos Sánchez-Higueras, PhD, a postdoctoral researcher in the Hombría lab and the paper's first author. "In this single piece of DNA, we had the perfect tool; we could now devise a method to systematically manipulate vvI1+2 activity to see how each Hox gene functioned."

First, Dr. Sánchez-Higueras teamed up with Dr. Mann at Columbia's Zuckerman Institute and used a sophisticated computer algorithm called No Read Left Behind, or NRLB. NRLB was recently developed by Dr. Mann, his lab, and his collaborators, including Columbia systems biology professor Harmen Bussemaker, PhD. This powerful algorithm pinpoints the locations where transcription factors bind to a stretch of DNA, even if these binding sites are very weak and difficult to capture. For this study, the researchers focused on the Hox transcription factors and Hox cofactors that bind to vvI1+2.

"Our analyses provided a precise road map of Hox binding sites in vvI1+2, which we could then apply to a living fruit fly," said Dr. Mann, who is also the Higgins Professor of Biochemistry and Molecular Biophysics (in Systems Biology) at Columbia's Vagelos College of Physicians and Surgeons.

By employing a combination of elegant genetic manipulations in living, or in vivo, fly embryos, together with advanced biochemical and computational analysis, the researchers could then systematically manipulate Hox target activity with an unprecedented level of precision.

"We now had a starting point from which to systematically decode Hox gene regulation," said Dr. Hombría, "a kind of Rosetta Stone to help us decipher the genetics of body development."

The researchers' findings are especially promising because they can be applied to the entire genome. The steps that Hox genes undergo to regulate vvI1+2 can inform how Hox genes regulate other DNA, not just in fruit flies but beyond -- including in vertebrates, such as mammals, and even humans.

"While there is much about Hox genes that remains to be elucidated, our work is a significant step forward," said Dr. Sánchez-Higueras. "These continued efforts, combined with those of our peers, will help shed light on how the whole system works together in a growing embryo and how they contribute to disease."

On Aug 21st, Prof. MA Cheng from the University of Science and Technology of China (USTC) and his collaborators proposed an effective strategy to address the electrode-electrolyte contact issue that is limiting the development of next-generation solid-state Li batteries. The solid-solid composite electrode created this way exhibited exceptional capacities and rate performances.

Replacing the organic liquid electrolyte in conventional Li-ion batteries with solid electrolytes can greatly alleviate the safety issues, and potentially break the "glass ceiling" for energy density improvement. However, mainstream electrode materials are also solids. Since the contact between two solids is nearly impossible to be as intimate as that between solid and liquid, at present the batteries based on solid electrolytes typically exhibit poor electrode-electrolyte contact and unsatisfactory full-cell performances.

"The electrode-electrolyte contact issue of solid-state batteries is somewhat like the shortest stave of a wooden barrel," said Prof. MA Cheng from USTC, the lead author of the study. "Actually, over these years researchers have already developed many excellent electrodes and solid electrolytes, but the poor contact between them is still limiting the efficiency of Li-ion transport."

Fortunately, MA's strategy may overcome this formidable challenge. The study began with the atom-by-atom examination of an impurity phase in a prototype, perovskite-structured solid electrolyte. Although the crystal structure differed greatly between the impurity and the solid electrolyte, they were observed to form epitaxial interfaces. After a series of detailed structural and chemical analyses, researchers discovered that the impurity phase is isostructural with the high-capacity Li-rich layered electrodes. That is to say, a prototype solid electrolyte can crystallize on the "template" formed by the atomic framework of a high-performance electrode, resulting in atomically intimate interfaces.

"This is truly a surprise," said the first author LI Fuzhen, who is currently a graduate student of USTC. "The presence of impurities in the material is actually a very common phenomenon, so common that most of the time they will be ignored. However, after taking a close look at them, we discovered this unexpected epitaxial behavior, and it directly inspired our strategy for improving the solid-solid contact."

Taking advantage of the observed phenomenon, the researchers intentionally crystallized the amorphous powder with the same composition as the perovskite-structured solid electrolyte on the surface of a Li-rich layered compound, and successfully realized a thorough, seamless contact between these two solid materials in a composite electrode. With the electrode-electrolyte contact issue addressed, such a solid-solid composite electrode delivered a rate capability even comparable to that from a solid-liquid composite electrode. More importantly, the researchers also found this type of epitaxial solid-solid contact may tolerate large lattice mismatches, and thus the strategy they proposed could also be applicable to many other perovskite solid electrolytes and layered electrodes.

"This work pointed out a direction that is worth pursuing," MA said. "Applying the principle raised here to other important materials could lead to even better cell performances and more interesting science. We are looking forward to it."

The researchers intend to continue their exploration in this direction, and apply the proposed strategy to other high-capacity, high-potential cathodes.