Brain

The cover for issue 40 of Oncotarget features Figure 5, "miR-210 silences the proapoptosis member CASP8AP2," by Kling, et al. which reported that hypoxic Ewing's sarcoma cells release exosomes that promote sphere formation, a stem-like phenotype, in EWS cells by enhancing survival.

Analysis of the hypoxic exosomal miRNA cargo identified a HIF-1α regulated miRNA, miR-210, as a potential mediator of sphere formation in cells exposed to hypoxic exosomes.

The knockdown of HIF-1α in hypoxic EWS cells led to decreased exosomal miR-210 levels and reduced the capacity of hypoxic exosomes to form spheres.

Inhibition of miR-210 in hypoxic spheres attenuated sphere formation and overexpression of miR-210 in normoxic spheres significantly enhanced the number of EWS spheres.

Together, the findings in this Oncotarget study suggest that hypoxic exosomes promote stemness in EWS cells by delivering enriched miR-210 that is capable of down-regulating apoptotic pathways, resulting in the survival of cells with increased sphere formation.

This Oncotarget study suggest that hypoxic exosomes promote stemness in EWS cells by delivering enriched miR-210 that is capable of down-regulating apoptotic pathways.

Dr. Shantaram S. Joshi from The University of Nebraska Medical Center said, "Ewing's sarcoma (EWS) is an aggressive and highly malignant bone tumor that develops in children and adolescents."

HIF -1α has been demonstrated to regulate tumor formation and stem cell survival in hypoxic cancer cells by inhibiting apoptosis.

Emerging evidence indicates intercellular communication between tumor cells in hypoxic and normoxic regions contributes to functional differences associated with hypoxic tumors.

Other reports demonstrated that shCD99 EWS-derived exosomes could transfer enriched miR-34a to recipient EWS cells and stimulate neural differentiation while in another study, EWS-derived exosomes carrying EZH2 mRNA could be delivered intact to mesenchymal stem cells.

Studies in other cancer models investigating the role of hypoxic exosomes have provided insight into how hypoxic tumors can secrete exosomes that propagate an aggressive phenotype in cells outside the hypoxic niche.

Exosomes released from hypoxic prostate cancer cells enhanced sphere formation in normoxic cells, but the authors were unable to elucidate a mechanism describing how hypoxic exosomes promote stemness in normoxic cells.

The Joshi Research Team concluded in their Oncotarget Research Paper that this study describes a mechanism whereby EWS cells under hypoxic conditions release exosomes that enhance stemness in EWS cells.

The authors identified a hypoxia regulated miRNA significantly expressed in hypoxic cells and HypoxicEXO and characterized a potential target that facilitates an apoptotic pathway critical to sphere formation.

Ongoing studies are investigating the role of HIF-1α on regulating EWS stemness and together, the authors future aim is to investigate how HIF-1α selectively modulates the packaging of miRNAs into HypoxicEXO, and validate additional miRNAs that promote aggressive hypoxic phenotypes.

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DOI - https://doi.org/10.18632/oncotarget.27702

Full text - https://www.oncotarget.com/article/27702/text/

Correspondence to - Shantaram S. Joshi - ssjoshi@unmc.edu

Keywords -
exosomes,
hypoxia,
Ewing's sarcoma,
stemness,
miR-210

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New Rochelle, NY --Ableist language is often used by autism researchers, which assumes that autistic people are "broken" or inferior to non-autistic people. Strategies for avoiding ableist language are provided in Autism and Adulthood. Click here to read the full article.

"We provide practical guidance to help researchers make language choices that reduce stigmatization, misunderstanding, and exclusion of autistic people," state Kristen Bottema-Beutel, PhD, Boston College, and coauthors.

The authors assert that avoiding ableist language will result in better outcomes for the autistic community and improved communication in research.

"I am amazed at how often researchers inadvertently use ableist, dehumanizing language when speaking about autism. This thoughtful article challenges researchers to re-evaluate the language they use to talk about autism and gives them tools to do better. I expect it will set the standard for how autism, and autistic people, are discussed in the literature," says Editor-in-Chief of Autism in Adulthood, Christina Nicolaidis, MD, MPH, Portland State University and Oregon Health & Science University.

A scientist from RUDN University suggested a new physical model to describe the optical properties of dense plasma. The model was tested on available experimental data and does not require complex calculations. The work was published in the Annals of Physics journal.

Plasma is the fourth state of matter, along with solid matter, liquid, and gas. High-density (up to ~1 g/cm3) plasma is used in many technical and experimental installations such as heavy-current electrical discharge devices, control fusion targets, or laser targets that are used to study the properties of matter under extreme pressure.

An important feature of plasma is its light absorptance coefficient. Its value is to a great extent dependent on the photo effect (the transfer of energy from the photons to the electrons of a substance) and light absorptance in optical lines. Both of these processes, in turn, are due to the so-called microfield--an electric field inside plasma produced by the chaotic thermal movement of ions and free electrons. This field can fluctuate from its average value in time and space, and knowing its characteristics is important for solving numerous scientific and technical tasks.

"We have analyzed all models described in scientific literature and identified their disadvantages. Namely, these models provide for the infinite density of the electric field energy in an atomic cell which contradicts the laws of physics. The only model that doesn't have these disadvantages is the Quasi Independent Particle model or QUIP. We developed a generalized version of this model that takes into account the inhomogeneity of plasma microfield. This helped us extrapolate the model to high-density plasma for which homogeneous microfield approximations cannot be used. The generalized QUIP model is very simple and does not require complex calculations, because all formulas are presented in an explicit manner," said Alexander Belov, a Candidate of Physics and Mathematics and a senior lecturer at the Department of Applied Informatics and Probability Theory, RUDN University.

To confirm a theoretical model, one has to test it against experimental results. For this purpose, the team chose experiments on the fluorescence of laser-based plasma that have been going on since the 1980s. In these experiments, tiny glass bubbles were filled with a mix of deuterium, argon, krypton, neon, and other gases, covered with aluminum coating and then heated with a powerful multi-beam laser system. As a result, plasma with high temperature and density was formed inside the bubbles and emitted a series of lines in the X-ray range.

"The number of observable spectral lines can be theoretically predicted by a model. In the majority of works, this parameter was neither calculated nor compared to experimental data. Our analysis shows that all models except for QUIP gave wrong predictions that did not match experimental results. Therefore, our model is better at describing the experiment. This test is a convincing proof of the advantage that the generalized QUIP model has over other known models," added Alexander Belov.

Description of heterogeneous plasma microfield and optical properties of plasma by the QUIP model

A new study by University of California researchers shows the promise of high-throughput DNA-sequencing technologies to improve prenatal diagnosis and pregnancy outcomes for women who have experienced an abnormal prenatal ultrasound.

In the UCSF-led study, scientists used a technique called exome sequencing to identify genetic diseases as the underlying cause in 37 of 127 cases of nonimmune hydrops fetalis (NIHF), a life-threatening condition in which the fetus is overloaded with fluid. The study was published online Oct. 7, 2020, in The New England Journal of Medicine (NEJM).

Corresponding author Teresa Sparks, MD, MAS, a UCSF assistant professor in the Department of Obstetrics, Gynecology & Reproductive Sciences, led the study with senior study author Mary Norton, MD, a professor in the same department. "The cause of most cases of NIHF is not identified with standard testing, but when we apply exome sequencing, we find a genetic diagnosis in nearly 30 percent of cases of previously unknown cause," Sparks said.

NIHF affects about one in every 1,700 to 3,000 pregnancies in the United States and is associated with high risks of stillbirth, preterm birth, neonatal death and other complications. Although NIHF often leads to death, identifying the precise genetic cause is critical, as associated outcomes vary widely in severity.

NIHF can be a manifestation of many genetic diseases, but evidence of abnormal fluid accumulation in the fetus detected through an ultrasound exam -- whether it occurs under the skin, in the abdomen, or around the heart or lungs -- does not pinpoint an underlying cause.

Participants in the NEJM study were referred from throughout the United States after NIHF was identified with prenatal ultrasound but no underlying genetic disease was found using long established methods for detecting genetic abnormalities. These traditional genetic tests -- karyotype and chromosomal microarray analysis -- detect large abnormalities in chromosomes, not disorders caused by a defect in a single gene as are identified with exome sequencing.

Exome sequencing is the complete spelling out of the genetic code for DNA segments within the genome that serves as the blueprints for proteins. This has become possible to perform quickly and accurately in recent years, thanks to the continual refinement of technology that can sequence DNA strands that are thousands of nucleotide building blocks long, often in a massively parallel manner that helps ensure accurate results. Exome sequencing can identify even the smallest mutations, such as a change in a single building-block nucleotide base pair.

Importantly, many of the disorders identified in the study have not previously been reported in association with NIHF, so the findings broaden knowledge of genetic diseases that can present with the condition. Among the most common of 37 genetic disorders identified in the NEJM study were 11 cases affecting a key intracellular signaling pathway called RAS-MAPK, four cases of inborn errors of metabolism, four cases of musculoskeletal disorders, and three cases each of lymphatic, neurodevelopmental, cardiovascular and blood disorders. Many of these diagnoses would also have been missed by commercial gene panels, Sparks said.

Most mutations identified in the study newly arose in the fetus, but several were inherited, with the potential to affect future pregnancies with the same biologic mother or father.

"There is a very wide range in genetic diagnoses underlying NIHF, and identifying the diagnosis is essential for families and healthcare providers," Sparks said. "With advanced genetic testing, there is much more we can discover for families to help them understand the situation, for obstetricians and neonatologists to better take care of the pregnancy and anticipate the needs of the newborn, and ultimately to guide the development of novel prenatal management strategies such as in-utero therapies to improve health outcomes over the long term."

For some of the genetic disorders identified in the study, prenatal interventions that can improve or save lives already have been identified. For example, genetic causes of anemia in the fetus may be closely monitored, and the fetus may receive a blood transfusion if needed.

Similarly, for some of the inborn errors of metabolism identified in the study, enzyme therapies already are available after birth. Early diagnosis and treatment of these metabolic disorders leads to better outcomes. A co-author of the NEJM study, Tippi MacKenzie, MD, a professor with the UCSF Department of Surgery, is investigating in utero treatments for specific genetic disorders underlying NIHF in a new clinical trial. Sparks, Norton, and co-authors are also pursuing further investigations to identify additional genomic abnormalities underlying NIHF for the cases that remain unsolved.

The opioid crisis, in which addiction and harm are related to pain-relieving opioid drugs, has been well documented. It has been concentrated in the USA but is now affecting most Western nations and increasingly, developing countries also. In some cases, this addiction and subsequent harm begins when the patient is given these drugs for pain relief after surgery.

To help confront this, an international group of global experts including anaesthetists, surgeons and other healthcare professionals have come together to publish a consensus statement on the prevention of opioid-related harm in adult surgical patients. The consensus statement is published in Anaesthesia (a journal of the Association of Anaesthetists).

"Opioids are effective medicines that form an integral component of balanced multimodal painkilling strategies for the management of acute pain in postoperative patients," explain the statement co-authors, who include Professor Dileep Lobo, Nottingham University Hospitals NHS Trust and University of Nottingham, Queen's Medical Centre, Nottingham, UK. "However, over the past decade it has been increasingly appreciated that, in efforts to improve pain relief after surgery, doctors prescribing these drugs to help pain relief during and after surgery have unwittingly contributed to persistent postoperative opioid use, abuse and harm in some patients."

They add: "In addition to the social and economic costs of opioid misuse, there are personal costs, with many people dying from opioid overdose, or in accidents caused, for example, by driving under the influence of opioids."

Ways to reduce possible harm begin before surgery, since the strongest predictor of persistent postoperative opioid use post-surgery is pre-existing chronic opioid use. The incidence of persistent postoperative opioid use can be up to 10 times higher in those taking opioids long-term before surgery than in patients who have never used opioids.

The main points from the consensus statement are:

All patients undergoing surgery should be assumed to be at risk of developing persistent postoperative opioid use/addiction and may need interventions to mitigate those risks. However, some patients are at particularly high-risk of opioid related respiratory impairment, including older patients; those with sleep-disordered breathing; obesity; kidney disease; respiratory, cardiac and neurological diseases; diabetes; tolerance to opioids; and genetic variations in opioid metabolism.

Healthcare teams must consider optimising management of pre-operative pain and psychological risk-factors before surgery, including weaning patients off opioids they are already taking where possible. They should ensure realistic expectations of postoperative pain control, both in hospital and after discharge.

Provision of opioid painkillers should be guided by functional outcomes, rather than just a rating of the patient's pain using existing scales.

Multiple methods of pain management should be optimised, and patients educated about the use of non-pharmacological and non-opioid painkilling strategies to reduce the amount and duration of opioids required to restore function

Long-acting opioids should not be used routinely for acute postoperative pain. (e.g. modified-release oxycodone, transdermal fentanyl patches)

A patient-centred approach should be used to limit the number of tablets and the duration of usual discharge opioid prescriptions, typically to less than a week. (Post-discharge prescriptions of opioids, if necessary, should be limited to less than a week's duration. A small number of patients may need repeat prescriptions, but these should not be automatic).

Automated post-discharge repeat prescriptions for opioids should be avoided. Doctors, including those in outpatient clinics and general practice, should perform a patient review if more opioids are requested. Research has shown each additional repeat prescription has been found to increase the risk of opioid misuse (encompassing diagnoses of opioid dependence; abuse; or overdose) by 40%, with each additional week of opioids taken raising the risk of misuse by 20%. GPs should assess patients before re-prescribing opioids.

Patients should be advised on safe storage and disposal of unused opioids and directed to avoid opioid diversion to other individuals (e.g. sharing with friends and family). Addiction surveys have shown that around 50% of adults who misuse opioids obtain them from friends and family. This also avoids accidental deaths. Paediatric mortality from unintentional opioid overdose has increased three-fold in the last 20 years and has followed a similar time trend to adult overdose deaths

The authors also highlight the dangers of driving under the influence of opioids, that can impair driving skills and cognitive reasoning in a similar manner to alcohol. "Driving under the influence of drugs, including prescribed opioids, is now recognised to be a major cause of motor vehicle collisions and subsequent fatalities, particularly if the person commenced the opioid within the previous 30 days," explain the authors, who add that many countries have established laws making driving under the influence of opioids illegal.

They conclude: "While the use of opioids during and after surgery has the capacity to promote recovery after life-saving or life-enhancing surgery, their use can be associated with harm from persistent postoperative opioid use; opioid-induced respiratory impairment; opioid diversion to people they were not originally prescribed for; and driving under the influence of prescription opioids. Strict control of opioid use within hospitals (stewardship) is required to minimise the risk of opioid-related harm. This will require the multidisciplinary involvement of anaesthetists; surgeons; pain specialists; pharmacists; nursing staff; physiotherapists; primary care clinicians; hospital management; and patients to adopt the recommendations from this consensus statement to local practice."

A failure by governments to deliver on commitments under a global nature conservation treaty, the Convention on Biological Diversity, could have devastating effects.

The warning comes after a consortium of scientists, led by Dr Sean Maxwell and Professor James Watson from The University of Queensland, reviewed national area-based conservation efforts, including protected areas.

In 2010, almost all nations agreed that area-based conservation efforts must cover at least 17 per cent of land and 10 per cent of ocean by 2020, in areas that are important for biodiversity and ecosystem services.

"We reviewed progress toward this target by overlaying maps of protected areas on natural ecosystems, threatened species, carbon services on land and sea and fisheries productivity in the world's oceans," Dr Maxwell said.

"We found some welcome progress - particularly in the marine realm - since global environmental targets were agreed.

"But terrestrial protected area expansion needed to be double what it was in the past decade in order to achieve 17 per cent coverage for land and freshwater environments.

"There is also alarming shortfalls in ecological representation and management effectiveness, and measurable biodiversity outcomes persist in area-based conservation efforts.

"We found that 78 per cent of known threatened species and more than half of all ecosystems on land and sea remain without adequate protection.

"And seven of the world's most productive at-sea fisheries have no formal protected area coverage."

The researchers also reviewed how effective and equitable protected area management has been, given these criteria featured in the 2010 targets.

"We know that adequately funding protected areas are one of our best tools for reducing threats to biodiversity," Dr Maxwell said.

"Yet the current financial shortfall for area-based conservation likely exceeds the multi-billion dollar mark, and as much as 90 per cent have inadequate or below optimum on-site staff capacity.

Professor Watson, of UQ and the Wildlife Conservation Society, said the next round of conservation targets, which were meant to be set this year, is fundamental to the future of global biodiversity.

"It is obvious that governments have dramatically underinvested in protected areas and been weak in legally protecting them," Professor Watson said.

"For biodiversity to have any chance to survive climate change, nations must invest more resources in consolidating area-based conservation efforts and ensuring biodiversity conservation is a far stronger part of managed land and seas.

"There are significant opportunities to better recognise and support conservation by indigenous peoples, local communities and private actors, and we now need to embrace new models for land stewardship that rewards good behaviour by farmers, developers and miners."

In 2018, 701 cases of severe invasive listeriosis were communicated to the Robert Koch Institute (RKI), which translates into 0.8 cases per 100,000 inhabitants. Most listeriosis illnesses reported are severe and are associated with blood poisoning, meningitis or miscarriages, for example. In 2018, the disease was fatal in 5% of cases. Elderly people, people with weakened immune defences, pregnant women and their new-born babies are particularly vulnerable. Listeria can be found in a large variety of foods of plant and animal origin. Cold or hot-smoked fish are often contaminated and are, therefore, also suspected of transmitting this illness. Other fish products and seafood eaten raw, such as sushi, sashimi and oysters or cured products such as graved fish, may also be affected. "Pregnant women, elderly people or those with weakened immune defences should only eat fish and seafood that have been thoroughly heated," says BfR President Professor Dr. Dr. Andreas Hensel.

Link to the information sheet for consumers (in German):
https://www.bfr.bund.de/cm/350/verbrauchertipps-schutz-vor-lebensmittelinfektionen-mit-listerien.pdf

Not all Listeria bacteria cause illness. Of the 20 Listeria species described, only Listeria (L.) monocytogenes is a significant cause of infection in humans. Infections during pregnancy can lead to miscarriage, premature birth, stillbirth or the birth of a sick child. Furthermore, listeriosis mainly develops in people whose immune system is weakened by old age, pre-existing medical conditions or medication intake. They often suffer from blood poisoning, encephalitis or meningitis as well as e.g. from endocarditis or bacterial joint inflammation. Listeriosis is associated with relatively high mortality in risk groups. In healthy individuals who do not belong to one of the risk groups, an infection can lead to inflammation of the gastrointestinal tract plus a fever, with progression generally being mild.

The bacterium L. monocytogenes is widespread in the environment and can be found in many foods. High detection rates are found in minced meat, raw meat dishes (e.g. tartare), raw sausage meat (e.g. "Mettwurst" raw minced pork) and raw milk, for example. However, numerous other ready-to-eat foods of animal and plant origin, which are not subjected to further germicidal treatment (e.g. heating) after processing, may also contain L. monocytogenes. Examples include cheese (made from raw or pasteurised milk), pre-cut salads and vegetables, deli salads or sliced sausage products. This is because listeria can survive for a long time in food processing plants in recesses that are difficult to reach for cleaning and disinfection. As a result, the continuous entry of the germs during food production is possible.

Raw, smoked or cured fish products and seafood such as sushi, sashimi, oysters, cold or hot smoked fish (e.g. smoked salmon) and cured fish (e.g. graved salmon) are frequently contaminated with listeria. 7 to 18 % of the samples of cold-smoked or cured fish products examined by the food monitoring authorities in Germany between 2007 and 2017, and 3 to 9 % of the samples of hot-smoked fish products contained L. monocytogenes. Even low germ concentrations are hazardous to risk groups, for example when products are stored at home above the temperatures recommended by the manufacturer or when they are eaten after their best-before date. What's more, handling contaminated products risks transferring listeria to other foods.

The German Nutrition Society (DGE) recommends at least one fish meal every week. Fish notably contains special fatty acids and the long-chain omega-3 fatty acids docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA).

The BfR recommends that people who have an increased risk of developing listeriosis should not generally avoid fish, but rather only eat fish or seafood that has been thoroughly heated. Listeria can be reliably killed off by heating food to a core temperature of 70 °C for at least two minutes. Risk groups should refrain from eating raw, smoked and cured fish products and seafood.

A National Institutes of Health study in mice suggests that parents have an innate capacity to respond to an infant's cries for help and this capacity may serve as a foundation from which a parent learns to adjust to an infant's changing needs. The study was conducted by Robert C. Froemke, Ph.D., of New York University School of Medicine, and colleagues. It appears in Nature.

When housed with mice who have given birth, unmated female mice will assist with the care of the newborn pups. The researchers evaluated the ability of such babysitter mice to respond to a variety of recorded newborn distress cries. These included typical distress cries as well as a range of cries that had been digitally altered--sped up or slowed down to include more or fewer syllables than typical distress vocalizations.

Experienced babysitters responded to typical distress cries 80% of the time, compared to the 33% initial response rate of the novice babysitters. Both experienced and novice babysitters at first responded at only low rates to the altered cries, but both learned to recognize these cries with time. Eventually, even the novices responded to some types of altered calls as much as 75% of the time. Similarly, auditory centers in the babysitters' brains activated when the animals heard the calls, at levels corresponding to their initial responses, and increased as they became more responsive to the cries. The researchers also found that administering oxytocin improved the rate at which the mice responded to the cries, while blocking natural oxytocin in the brain reduced their response rate. Oxytocin has been implicated in maternal bonding and other behaviors.

These results provide evidence that new parents may be hard-wired to respond to certain kinds of cries from their infants, but also have the capacity to expand their repertoire to include other kinds of vocalizations as well.

As the pandemic persists, COVID-19 has claimed more than 200,000 lives in the United States and damaged the public health system and economy. In a study published on September 21 in the journal The Innovation, researchers at Emory University found that long-term exposure to urban air pollution may have made COVID-19 more deadly.

"Both long-term and short-term exposure to air pollution has been associated with direct and indirect systemic impact on the human body by enhancing oxidative stress, acute inflammation, and respiratory infection risk," says Donghai Liang of Emory University, co-first author on the paper along with Liuhua Shi.

The researchers analyzed key urban air pollutants, including fine particle matter (PM2.5), nitrogen dioxide (NO2), and ozone (O3), across 3,122 counties in the United States from January to July. To examine the association between ambient air pollutants and the severity of COVID-19 outcomes, they investigated two major death outcomes, the case-fatality rate (i.e., number of deaths among the people who are diagnosed with COVID-19) and the mortality rate (i.e., number of COVID-19 deaths in the population). The two indicators can imply the biological susceptibility to deaths from COVID-19 and offer information of the severity of the COVID-19 deaths in the general population, respectively.

Of the pollutants analyzed, NO2 had the strongest independent correlation with raising a person's susceptibility to death from COVID-19. A 4.6 parts per billion (ppb) increase of NO2 in the air was associated with 11.3% and 16.2% increases in COVID-19 case-fatality and mortality rate, respectively. Moreover, Liang and his colleagues discovered that just a 4.6 ppb reduction in long-term exposure to NO2 would have prevented 14,672 deaths among those who tested positive for the virus. The team also observed a margin-ally significant association between PM2.5 exposure and COVID case-fatality rate, whereas no notable associations were found with O3.

"Long-term exposure to urban air pollution, especially nitrogen dioxide, might enhance populations' susceptibility to severe COVID-19 death outcomes," says Liang. "It's es-sential to deliver this message to public health practitioners and policymakers in order for them to consider protecting vulnerable populations that lived in historically high NO2 pollution including the metropolitan areas in the state of New York, New Jersey, California, and Arizona."

Liang also noted that air pollution is a health equity issue: the burden of NO2 pollution is not evenly shared. People with lower income and people of color often face higher exposure to ambient air pollution and may experience a more significant impact from the pollutants. Not having many choices in residency, many live by highways or industrial sites, which makes them especially vulnerable to air pollution.

"The continuations and expansions of current efforts to lower traffic emissions and ambient air pollution might be an important component of reducing the population-level risk of COVID-19 case-fatality and mortality in the United States," says Liang.

DALLAS, Oct. 7, 2020 -- Feeling optimistic, that you have a sense of purpose in life and that you are in control of your environment - characteristics of psychosocial resilience - are associated with having better cardiovascular health among Black adults, independent of neighborhood context, according to a study published today in Circulation: Cardiovascular Quality and Outcomes, an American Heart Association journal.

Highlighting a relatively understudied area of research, this study shows that psychosocial well-being, or resilience, may positively affect cardiovascular health among Black people. One known factor that negatively impacts health in the Black community is the neighborhood itself, as people living in neighborhoods with more socioeconomic disadvantages have higher rates of heart attacks, strokes and deaths from these factors. Living in a neighborhood with fewer or limited socio-economic resources is recognized as one of a number of social determinants of health, which are factors that may affect one's risk of cardiovascular disease.

"Cardiovascular health differences between Black and white Americans have been documented for decades; however, individual factors within Black Americans that might contribute to better cardiovascular health are not well understood," said Tené T. Lewis, Ph.D., FAHA, a clinical psychologist and associate professor of epidemiology at the Rollins School of Public Health at Emory University in Atlanta, and one of the principal investigators of the study. "Almost everything we know about Black Americans and their health focuses on deficits, yet we really need to begin to identify strengths. Understanding which strengths matter most for Black Americans - and under which contexts - will allow us to develop the most appropriate and applicable public health interventions for this group.

The study investigated whether individual psychosocial resilience and neighborhood-level cardiovascular resilience were associated with better cardiovascular health in Black adults, based on the American Heart Association's Life's Simple 7® metrics. Life's Simple 7 are seven individual measures that quantify heart health: smoking status, physical activity, diet, weight, and levels of blood glucose, cholesterol and blood pressure.

Researchers recruited 389 adult volunteers with no prior history of CVD (ages 30-70, 39% male) who self-identified as Black or African American, living in the greater Atlanta region, as part of a substudy in the American Heart Association-funded Morehouse-Emory Cardiovascular (MECA) Center for Health Equity study. The MECA Study of 1,500 Black adults, conducted from 2016-2019, investigated socioenvironmental and individual behavioral measures that promote resilience to cardiovascular disease in Black adults by assessing biological, functional and molecular mechanisms in the greater Atlanta, metropolitan area.

Participants completed multiple standard questionnaires during in-person interviews that gauged their psychosocial health. The questionnaires were focused on their perceptions of control over their own environment; whether they feel they have a sense of purpose in life; their level of optimism; and assessing coping skills and depressive symptoms. Participants also received physical examinations and blood analysis. People with prior cardiovascular events, human immunodeficiency virus, lupus, cancer, substance abuse, psychiatric illness, or who were pregnant, or nursing were excluded from the study.

The psychosocial and physical data of participants were compared to the corresponding neighborhood data on heart and stroke disease and deaths rates according to the 2010 U.S. Census Tract.

Among the findings, Black adults with higher psychosocial resilience scores who lived in neighborhoods with high rates of heart disease and stroke had a 12.5% lower incidence of cardiovascular disease compared to those with lower psychosocial resilience in the same neighborhoods.

"It was somewhat surprising that our psychosocial resilience measures were more strongly associated with cardiovascular health than the neighborhood-level resilience measure. We assumed that being both high on psychosocial resilience and living in a resilient neighborhood would be the most beneficial for cardiovascular health, yet what we found was that psychosocial resilience demonstrated the most robust association regardless of the neighborhood resilience measure," Lewis said.

Among the study's limitations are that the small number of participants were from a single city, therefore, the results may not be generalizable to Black adults across the U.S. or in other countries. The study also did not assess structural characteristics of the neighborhoods, such

as walkability or access to food, or environmental factors like air pollution. Further research is needed to examine the factors within a community and how, together with and compared to other social determinants of health, they impact psychosocial well-being and overall health in Black Americans.

"As a result of the heartbreaking consequences of COVID-19 and the inhumanity of George Floyd's death, we are having a national conversation about the ways in which structural and interpersonal racism have shaped Black Americans' lives and deaths," Lewis added. "More studies like this are necessary to fully understand the factors that promote better health for Black Americans, who are, based on current numbers, at the highest risk for COVID-19 as well as cardiovascular disease. With this information, we can create new systems of support and care that can lead to improved psychosocial resilience, which could, in turn, improve health outcomes."

An editorial by Amber E. Johnson, M.D., M.S., M.B.A., and Jared W. Magnani, M.D., M.S., assistant professors of medicine in cardiology at the University of Pittsburgh School of Medicine, is publishing simultaneously with Lewis et. al's article.

They note the study "... complements the existing data describing LS7 [Life's Simple 7] among Black individuals by adding the association of resilience with health outcomes. Few studies of resilience have focused on Black individuals." While they noted several limitations of the study, they support that its findings "... underscore the importance of psychosocial support and empowerment for Black patients at risk for developing CVD. However, the factors that moderate the relationship between resilience and cardiovascular health have yet to be defined."

Notably, Johnson and Magnani comment, "Although resilience techniques can be taught, to do so requires intentional acknowledgement of the conditions and experiences from which the adversity originated. The community context in which resilience thrives not only includes psychosocial well-being. Economic well-being and health care accessibility are needed as well. Eliminating disparities in cardiovascular health will require community-engaged partnerships based on common goals to provide care and to rebuild health care systems. We advocate for promoting health equity and social justice first, thereby rendering interventions to bolster resilience unnecessary."

The number of proteins in the human body, collectively known as the proteome, is vast. Somewhere between 80,000 and 400,000 proteins circulate in our cells, tissues and organs, carrying out a broad range of duties essential for life. When proteins go awry, they are responsible for a myriad of serious diseases.

Now, researchers at the Biodesign Center for Applied Structural Discovery and ASU's School of Molecular Sciences, along with their colleagues, investigate a critically important class of proteins, which adorn the outer membranes of cells. Such membrane proteins often act as receptors for binding molecules, initiating signals that can alter cell behavior in a variety of ways.

A new approach to acquiring structural data of membrane proteins in startling detail is described in the new study. Cryogenic electron microscopy (or cryo-EM) methods, a groundbreaking suite of tools, is used. Further, use of so-called LCP crystallization and Microcrystal electron diffraction (MicroED) help unveil structural details of proteins that have been largely inaccessible through conventional approaches like X-ray crystallography.

The findings describe the first use of LCP-embedded microcrystals to reveal high-resolution protein structural details using MicroED. The new research graces the cover of the current issue of the Cell Press journal Structure.

"LCP was a great success in membrane protein crystallization, according to Wei Liu, a corresponding author of the new study. "The new extensive application of LCP-MicroED offers promise for improved approaches for structural determination from challenging protein targets. These structural blueprints can be used to facilitate new therapeutic drug design from more precise insights."

One class of membrane proteins of particular interest are the G-protein-coupled receptors (GPCRs), which form the largest and most varied group of membrane receptors found in eukaryotic organisms, including humans.

The physiological activities of GPCRs are so important that they are a major target for a wide range of therapeutic drugs. This is where problems arise however, as determining the detailed structure of membrane proteins--an essential precursor to accurate drug design-- often poses enormous challenges.

The technique of X-ray crystallography has been used to investigate the atomic-scale structures and even dynamic behavior of many proteins. Here, crystallized samples of the protein under study are struck with an X-ray beam, causing diffraction patterns, which appear on a screen. Assembling thousands of diffraction snapshots allows a high-resolution 3D structural image to be assembled with the aid of computers.

Yet many membrane proteins, including GPCRs, don't form large, well-ordered crystals appropriate for X-ray crystallography. Further, such proteins are delicate and easily damaged by X-radiation. Getting around the problem has required the use of special devices known as X-ray free electron lasers or XFELS, which can deliver a brilliant burst of X-ray light lasting mere femtoseconds, (a femtosecond is equal to one quadrillionth of a second or about the time it takes a light ray to traverse the diamere of a virus). The technique of serial femtosecond X-ray crystallography allows researchers to obtain a refraction image before the crystalized sample is destroyed.

Nevertheless, crystallization of many membrane proteins remains an extremely difficult and imprecise art and only a handful of these gargantuan XFEL machines exist in the world.

Enter cryogenic electron microscopy and MicroED. This ground-breaking technique involves flash-freezing protein crystals in a thin veneer of ice, then subjecting them to a beam of electrons. As in the case of X-ray crystallography, the method uses diffraction patterns, this time from electrons rather than X-rays, to assemble final detailed structures.

MicroED excels in collecting data from crystals too small and irregular to be used for conventional X-ray crystallography. In the new study, researchers used two advanced techniques in tandem in order to produce high-resolution diffraction images of two important model proteins: Proteinase K and the A2A adenosine receptor, whose functions include modulation of neurotransmitters in the brain, cardiac vasodilation and T-cell immune response.

The proteins were embedded in a special type of crystal known as a lipidic cubic phase or LCP crystal, which mimics the native environment such proteins naturally occur in. The LCP samples were then subjected to electron microscopy, using the MicroED method, which permits the imaging of extremely thin, sub-micron-sized crystals. Further, continuous rotation of LCP crystals under the electron microscope allows multiple diffraction patterns to be acquired from a single crystal with an extremely low, damage-free electron dose.

The ability to examine proteins that can only form micro- or nanocrystals opens the door to the structural determination of many vitally important membrane proteins that have eluded conventional means of investigation, particularly GPCRs.

Negative feelings resulting from perceived broken promises from employers within UK police forces are a major cause of workplace stress, according to new research at the University of Birmingham.

In a study of police officers, researchers from the University's School of Psychology found that employees who perceive a violation of their psychological contract - the negative emotional reactions in response to perceived broken promises at work - are at greater risk of job-related stress, anxiety and depression.

Existing research shows that these feelings of violation stem from inadequate staffing to meet work demands, as well as insufficient physical resources to successfully execute their role. As a result, employees perceive that their contributions at work are not fully reciprocated in the relationship they have with their employer.

The study, published in the International Journal of Stress Management, shows that these feelings are particularly pertinent to police officers because of the high pressure of their roles and the effects of austerity cuts.

"Breaching these psychological contracts might result in feelings of anger or frustration and influence their well-being," explains Dr Fazeelat Duran, lead author of the study. "It's a construct that is relevant to public sector workers such as police or firefighters because of the deep impact from austerity cuts leading to fewer resources and increased workloads."

In the study, the research team surveyed 126 men and women who had served with the police for between 3 and 29 years. Their results showed that psychological contract violation (PCV) correlated with feelings of depression, anxiety and stress.

The team also found that fairness and self-efficacy - an employee's belief that they are capable of doing their job - mediated the relationship between psychological contract violation and anxiety and stress.

"The links with fairness and self-efficacy are really important," explains Dr Duran. "They show, for example, how feelings of PCV resulting from unfairness and things like inadequate job resources may affect how competent an employee feels in fulfilling their job."

"Employers clearly need to take more responsibility for these psychological contracts, including providing honest explanations to their employees, as well as fostering officers' feelings of self-efficacy and ensuring transparency around decision-making in the workplace."

Scientists have made significant progress in understanding the sources of radiation events that could impact human space-flight operations. Relativistic Electron Precipitation (REP) events are instances when high energy electrons move through areas of space at significant fractions of the speed of light. These REP events may pose challenges to human spaceflight, specifically during extravehicular activity (EVA).

These hazards motivate the question of whether REP events can be forecasted in order to avoid unnecessary human exposure to radiation. In order to predict REP events, their cause must first be determined.

A scientific team led by researchers at the National Institute of Polar Research (NIPR) in Japan has made strides in answering that question. Their findings were published on August 14 in the Journal of Geophysical Research: Space Physics.

Ryuho Kataoka, the lead author of the study and an associate professor at NIPR, pinpointed the cause of REP events and emphasized that REP events must be accounted for in human spaceflight missions.

"The importance of understanding REP events has been increasing since the REP events have been clearly identified at International Space Station (ISS)," Kataoka said. "REP events are important because they cause radiation dose during EVAs."

It has been hypothesized that electromagnetic ion cyclotron (EMIC) waves play an important role in REP events at the ISS. It was still an open question, however, whether other mechanisms played a role in REP event generation. EMIC waves are electromagnetic waves that propagate through the plasma in Earth's magnetosphere, causing disturbances in the charged particles within the plasma.

Using multiple sensors aboard the ISS, as well as data from the Arase satellite, the research group was able to show that at least three separate processes contributed to REP events. One is indeed EMIC waves. But the data also suggested two other sources: Whistler mode chorus waves and electrostatic whistler waves. Whistler mode waves can be excited by high energy electrons associated with auroral activities, such as the Northern Lights.

"It turned out that REP events at the ISS are caused not only by EMIC waves but also by whistler mode waves, which makes the space weather forecast more difficult," Kataoka said.

With a better understanding of the physical causes of REP events, Kataoka and his team are working towards ways to predict future events. "The next step is the space weather forecast of REP events at the ISS by modeling different kinds of plasma wave activities. The ultimate goal is to obtain a unified theory to understand the interaction between energetic particles and plasma waves, and their impact of radiation dose on the atmosphere, space craft, and human beings."

"Eat your spinach," is a common refrain from many people's childhoods. Spinach, the hearty, green vegetable chock full of nutrients, doesn't just provide energy in humans. It also has potential to help power fuel cells, according to a new paper by researchers in AU's Department of Chemistry. Spinach, when converted from its leafy, edible form into carbon nanosheets, acts as a catalyst for an oxygen reduction reaction in fuel cells and metal-air batteries.

An oxygen reduction reaction is one of two reactions in fuel cells and metal-air batteries and is usually the slower one that limits the energy output of these devices. Researchers have long known that certain carbon materials can catalyze the reaction. But those carbon-based catalysts don't always perform as good or better than the traditional platinum-based catalysts. The AU researchers wanted to find an inexpensive and less toxic preparation method for an efficient catalyst by using readily available natural resources. They tackled this challenge by using spinach.

"This work suggests that sustainable catalysts can be made for an oxygen reduction reaction from natural resources," said Prof. Shouzhong Zou, chemistry professor at AU and the paper's lead author. "The method we tested can produce highly active, carbon-based catalysts from spinach, which is a renewable biomass. In fact, we believe it outperforms commercial platinum catalysts in both activity and stability. The catalysts are potentially applicable in hydrogen fuel cells and metal-air batteries." Zou's former post-doctoral students Xiaojun Liu and Wenyue Li and undergraduate student Casey Culhane are the paper's co-authors.

Catalysts accelerate an oxygen reduction reaction to produce sufficient current and create energy. Among the practical applications for the research are fuel cells and metal-air batteries, which power electric vehicles and types of military gear. Researchers are making progress in the lab and in prototypes with catalysts derived from plants or plant products such as cattail grass or rice. Zou's work is the first demonstration using spinach as a material for preparing oxygen reduction reaction-catalysts. Spinach is a good candidate for this work because it survives in low temperatures, is abundant and easy to grow, and is rich in iron and nitrogen that are essential for this type of catalyst.

Zou and his students created and tested the catalysts, which are spinach-derived carbon nanosheets. Carbon nanosheets are like a piece of paper with the thickness on a nanometer scale, a thousand times thinner than a piece of human hair. To create the nanosheets, the researchers put the spinach through a multi-step process that included both low- and high-tech methods, including washing, juicing and freeze-drying the spinach, manually grinding it into a fine powder with a mortar and pestle, and "doping" the resulting carbon nanosheet with extra nitrogen to improve its performance. The measurements showed that the spinach-derived catalysts performed better than platinum-based catalysts that can be expensive and lose their potency over time.

The next step for the researchers is to put the catalysts from the lab simulation into prototype devices, such as hydrogen fuel cells, to see how they perform and to develop catalysts from other plants. Zou would like to also improve sustainability by reducing the energy consumption needed for the process.

LOS ALAMOS, N.M., October 5, 2020--A new algorithm that fast forwards simulations could bring greater use ability to current and near-term quantum computers, opening the way for applications to run past strict time limits that hamper many quantum calculations.

"Quantum computers have a limited time to perform calculations before their useful quantum nature, which we call coherence, breaks down," said Andrew Sornborger of the Computer, Computational, and Statistical Sciences division at Los Alamos National Laboratory, and senior author on a paper announcing the research. "With a new algorithm we have developed and tested, we will be able to fast forward quantum simulations to solve problems that were previously out of reach."

Computers built of quantum components, known as qubits, can potentially solve extremely difficult problems that exceed the capabilities of even the most powerful modern supercomputers. Applications include faster analysis of large data sets, drug development, and unraveling the mysteries of superconductivity, to name a few of the possibilities that could lead to major technological and scientific breakthroughs in the near future.

Recent experiments have demonstrated the potential for quantum computers to solve problems in seconds that would take the best conventional computer millennia to complete. The challenge remains, however, to ensure a quantum computer can run meaningful simulations before quantum coherence breaks down.

"We use machine learning to create a quantum circuit that can approximate a large number of quantum simulation operations all at once," said Sornborger. "The result is a quantum simulator that replaces a sequence of calculations with a single, rapid operation that can complete before quantum coherence breaks down."

The Variational Fast Forwarding (VFF) algorithm that the Los Alamos researchers developed is a hybrid combining aspects of classical and quantum computing. Although well-established theorems exclude the potential of general fast forwarding with absolute fidelity for arbitrary quantum simulations, the researchers get around the problem by tolerating small calculation errors for intermediate times in order to provide useful, if slightly imperfect, predictions.

In principle, the approach allows scientists to quantum-mechanically simulate a system for as long as they like. Practically speaking, the errors that build up as simulation times increase limits potential calculations. Still, the algorithm allows simulations far beyond the time scales that quantum computers can achieve without the VFF algorithm.

One quirk of the process is that it takes twice as many qubits to fast forward a calculation than would make up the quantum computer being fast forwarded. In the newly published paper, for example, the research group confirmed their approach by implementing a VFF algorithm on a two qubit computer to fast forward the calculations that would be performed in a one qubit quantum simulation.

In future work, the Los Alamos researchers plan to explore the limits of the VFF algorithm by increasing the number of qubits they fast forward, and checking the extent to which they can fast forward systems. The research was published September 18, 2020 in the journal npj Quantum Information.