Culture

Boston, MA - Women with post-traumatic stress disorder (PTSD) and depression have an almost fourfold greater risk of early death from cardiovascular disease, respiratory disease, type 2 diabetes, accidents, suicide, and other causes than women without trauma exposure or depression, according to a large long-term study conducted by researchers at Harvard T.H. Chan School of Public Health.

"The study examines longevity--in a way, the ultimate health outcome--and the findings strengthen our understanding that mental and physical health are tightly interconnected," said Andrea Roberts, lead author of the study and a senior research scientist in the Department of Environmental Health. "This is particularly salient during the pandemic, which is exposing many Americans and others across the world to unusual stress while at the same time reducing social connections, which can be powerfully protective for our mental health."

The study, which is the first study of co-occurring PTSD and depression in a large population of civilian women, will be published online December 4, 2020 in JAMA Network Open. Previous research on PTSD and depression has primarily focused on men in the military.

Roberts and her colleagues studied more than 50,000 women at midlife (ages 43 to 64 years) and found that women with both high levels of PTSD and depression symptoms were nearly four times more likely to die from nearly every major cause of death over the following nine years than women who did not have depression and had not experienced a traumatic event.

The researchers examined whether health risk factors such as smoking, exercise, and obesity might explain the association between PTSD and depression and premature death, but these factors only explained a relatively small part. This finding suggests that other factors, such as the effect of stress hormones on the body, may account for the higher risk of early death in women with the disorders.

Treatment of PTSD and depression in women with symptoms of both disorders may reduce their substantial increased risk of mortality, the researchers said.

"These findings provide further evidence that mental health is fundamental to physical health--and to our very survival. We ignore our emotional well-being at our peril," said Karestan Koenen, senior author of the study and professor of psychiatric epidemiology in the Department of Epidemiology and Department of Social and Behavioral Sciences.

Other Harvard Chan School authors included Laura Kubzansky, Lori Chibnik, and Eric Rimm.

Tokyo Medical and Dental University (TMDU) researchers report a cross-linker for dental cement that breaks down under UV light, making treatments easier to reverse.

Tokyo - Everyone who has had tooth cavities filled knows that the best dental materials stay where the dentist puts them. The adhesion of currently available dental materials to tooth surfaces continues to improve, but what about short-term treatments that are not supposed to adhere indefinitely? TMDU researchers have developed a method of making dental materials easier to remove; their findings are published in ACS Applied Polymer Materials.

The continual improvement of long-lasting caries treatments can be regarded a triumph of dental material research. However, there are dental procedures that require non-permanent adhesion to the tooth surface, such as the fixing of orthodontic brackets. Removing adhered materials after such procedures generally requires mechanical detachment that can damage tooth enamel.

Efforts to improve removal processes have produced materials that are weakened by triggers, such as heat or electric currents. However, approved sources of these stimuli are not readily available in standard dental clinics. The researchers therefore focused on UV light-responsive materials that can be triggered by the UV sources widely used by dentists to cure resin cements and composites.

The toughness of many dental cements is a result of mixing them with a cross-linker that locks the cement molecules to each other to form a stable network. The researchers have introduced a chemical 'switch' into a new cross-linker that opens when UV light is shined on it.

"The cross-linker structure resembles rings threaded onto a piece of string with bulky stoppers at each end," study lead author Atsushi Tamura explains. "We have added a section to the string--an o-nitrobenzyl ester group--that breaks under UV light causing the rings to slide off. This has a significant effect on the stability of the cement material the cross-linker is holding in place."

The researchers used their cross-linker to stabilize a commercially available resin cement that was used to stick two polymer blocks together, or to attach a polymer block to a bovine tooth. After shining UV light on the cross-linked cement for just 2 minutes, the cement showed a significant reduction in adhesion strength in both tests, meaning separation of the bonded materials was easier following UV treatment.

"We are very encouraged by the initial findings using our cross-linker," study corresponding author Nobuhiko Yui explains. "Although the UV wavelength used to disrupt the material was not clinically appropriate in this case, we intend to develop the chemistry of our internal switch so that it can provide a facile and readily accessible method of removing adhesives in the clinic."

The article, "Light-Embrittled Dental Resin Cements Containing Photodegradable Polyrotaxane Cross-Linkers for Attenuating Debonding Strength", was published in ACS Applied Polymer Materials (DOI: https://doi.org/10.1021/acsapm.0c01024).

At the same time, the article was selected to be featured as ACS (American Chemical Society) Editors' Choice (on 25th November, 2020) based on recommendations by ca. 70 ACS journals' editors due to its potential for broad public interest, an honor given to only one article from the entire ACS portfolio each day of the year.

News at a Glance:

Analysis of Victorian data by the Murdoch Children's Research Institute suggests that COVID-19 cases in schools and childcare were mainly driven by community transmission

373 students possibly acquired COVID-19 via a school or early childhood education centre

The COVID-19 in Victorian Schools Report recommends prioritising opening schools and childcare for onsite learning as soon as community transmission levels fall and provides detailed mitigation plans for outbreaks

COVID-19 cases in schools, early childhood education centres and childcare are mainly driven by community transmission. Off-site learning should therefore be a last resort, a new Australian report has found.

The Murdoch Children's Research Institute (MCRI) prepared the COVID-19 in Victorian Schools Report at the request of the Victorian State Government. The report recommends schools and childcare centres should re-open as soon as community transmission of coronavirus falls and stays low.

Professor Fiona Russell, from MCRI and The University of Melbourne, who led the analysis team said, "School and childcare COVID-19 outbreaks were far more likely in those areas that also had high community levels, suggesting community transmission drives COVID-19 spread in schools."

"The single best policy to support school reopening prior to the development of a vaccine or treatment is suppression of COVID-19," she said.

The report analysed government data which included reported COVID-19 cases and outbreaks across all early childhood and primary and secondary educational settings in Victoria from 25 January to 31 August.

At the start of August 2020, Victoria and the United Kingdom were reporting similar numbers of new daily cases. By mid-November, Victoria had recorded 14 days of no new cases while the UK was experiencing 25,000 new cases every day.

Cases associated with schools accounted for eight per cent of all cases in Victoria. Of 373 students and 139 staff who were infected and linked to a childcare or school event, four students and four staff were admitted to hospital, all of whom subsequently recovered.

The report's senior co-author MCRI Professor Sharon Goldfeld said, "Childcare and schools play a critical role not only in providing education, but also offer critical support, especially for the most vulnerable of students, which makes them a priority for opening and remaining open."

"Closing schools should be a last resort, especially for childcare and primary school children as cases in this age group are less likely to transmit and be associated with an outbreak."

The report also provided detailed scenario plans for possible outbreaks following the staged easing of lockdown restrictions which would follow a traffic light system. These plans have drawn on experiences from international settings, designed to reduce day-to-day disruptions as far as possible, while ensuring that teachers, students and the wider community is kept as safe as possible.

Key findings:

373 students had an infection likely acquired at an ECEC or school event

There were 1,635 infections linked with ECECs and schools, out of a total of 19,109 infections in Victoria. Cases associated with schools accounted for nine per cent of all infections in Victoria.

Testing, Tracing and Isolation within 48 hours of a notification is the most important strategy to prevent an outbreak. In Victoria, the average time between confirmation of the first case in an ECEC or school and school closure was 1 day. This timely response prevented outbreaks from occurring as 66 percent of events in schools involved just a single infection in a staff member or student and 92 percent involved fewer than 10 cases.

Of 139 staff & 373 students who likely acquired COVID-19 at an ECEC or school event, 8 (4 staff and 4 students) admitted to hospital and all recovered

Infections in ECEC and schools were rarely linked to the most vulnerable population, the elderly

If the first case was aged 12 years or younger, an outbreak (2 or more cases) was very uncommon.

A group of researchers developed a promising fix to CRISPR-Cas9's problem with unwanted genetic changes using a method that allows them to turn off gene-editing until it reaches key cell cycle phases where more accurate repairs are likely to happen.

Researchers from Hiroshima University and Tokyo Medical and Dental University published on Communications Biology the results of their study which successfully demonstrated a more precise gene-editing and suppressed unintended genetic deletions, insertions, or mutations called off-target effects.

Although previous methods were developed that reported fewer off-target effects associated with the CRISPR technology, the researchers said these often exhibited lower editing efficiency.

"We aimed to develop the method to avoid the side effect called off-target effect which is one of the most challenging problems in the genome-editing field," said Wataru Nomura, one of the study's authors and a professor at HU's Graduate School of Biomedical and Health Sciences.

"Our method is like hitting two birds with one stone. We can improve the preciseness of genome editing and suppression of off-target effects at the same time."

More control in gene-editing

CRISPR-Cas9 has ushered in a new frontier in gene editing as a simpler and less expensive tool. Acting like scissors, it can snip genetic material you want to alter. The process, however, can also create off-target effects that limit its use in the field of therapeutics.

The newest method developed to eliminate off-target effects works by using the anti-CRISPR protein AcrIIA4 which works like an "off switch" that stops the genome editing activity of SpyCas9. The researchers fused AcrIIA4 with the N terminal region of human Cdt1 -- a gene that helps ensure DNA replication happens only once per cell division -- intending to deactivate gene editing until S and G2, phases of the cell cycle when homology-directed repair (HDR) is dominant.

HDR is one of the two DNA repair processes used by organisms along with non-homologous end joining (NHEJ). Of the two, however, HDR is the preferred method as the repair relies on the existence of two chromosome copies in each cell. HDR's use of the duplicate chromosome as a template for repair makes gene editing more precise as opposed to NHEJ which just tends to connect the broken ends of the DNA. HDR occurs during the S and G2 phases of the cell cycle while NHEJ operates in all phases, especially in G1 -- the first phase of the cycle's interphase stage where the cell grows in preparation for DNA replication.

The researchers found that the amount of ArIIA4-Cdt1 fusion is dependent on the cell cycle. It increases during the G1 phase which stops gene-editing from happening and, consequently, halts repairs through NHEJ. Meanwhile, it decreases during the S, G2, and M phases that follow.

"The efficiency of HDR using AcrIIA4-Cdt1 was increased approximately by 4.0-fold compared to that using SpyCas9 alone. At target or off-target site 1 (HCN1 gene), the mutation ratio was decreased by 86.5%. Moreover, the mutation ratio at off-target site 2 (MFAP1 gene) was decreased from 8.5% to 0.6% using AcrIIA4-Cdt1," the researchers said in the study.

"Co-expression of SpyCas9 and AcrIIA4-Cdt1 not only increases the frequency of HDR but also suppresses off-target effects. Thus, the combination of SpyCas9 and AcrIIA4-Cdt1 is a cell cycle-dependent Cas9 activation system for accurate and efficient genome editing."

Nomura said they want to further improve the preciseness of the system so it could be used safely in the therapeutic field.

"We envision to apply our system to other CRISPR/anti-CRISPR combinations as well as other CRISPR based gene editor such as base editors and targeted transcription mediators," he said.

"Our ultimate goal is to develop a genome editing system which can be used safely in the medical therapeutic field."

Reactive oxygen molecules, also known as "free radicals", are generally considered harmful. However as it now turns out, they control cellular processes, which are important for the brain's ability to adapt - at least in mice. Researchers from the German Center for Neurodegenerative Diseases (DZNE) and the Center for Regenerative Therapies Dresden (CRTD) at TU Dresden published the findings in the journal Cell Stem Cell.

The researchers focused on the "hippocampus", a brain area that is regarded as the control center for learning and memory. New nerve cells are created lifelong, even in adulthood. "This so-called adult neurogenesis helps the brain to adapt and change throughout life. It happens not only in mice, but also in humans," explains Prof. Gerd Kempermann, speaker of the DZNE's Dresden site and research group leader at the CRTD.

A trigger for neurogenesis

New nerve cells emerge from stem cells. "These precursor cells are an important basis for neuroplasticity, which is how we call the brain's ability to adapt," says the Dresden scientist. Together with colleagues he has now gained new insights into the processes underlying the formation of new nerve cells. The team was able to show in mice that neural stem cells, in comparison to adult nerve cells, contain a high degree of free radicals. "This is especially true when the stem cells are in a dormant state, which means that they do not divide and do not develop into nerve cells," says Prof. Kempermann. Current study shows that an increase in the concentration of the radicals makes the stem cells ready to divide. "The oxygen molecules act like a switch that sets neurogenesis in motion."

Free radicals are waste products of normal metabolism. Cellular mechanisms are usually in place to make sure they do not pile up. This is because the reactive oxygen molecules cause oxidative stress. "Too much of oxidative stress is known to be unfavorable. It can cause nerve damage and trigger aging processes," explains Prof. Kempermann. "But obviously this is only one aspect and there is also a good side to free radicals. There are indications of this in other contexts. However, what is new and surprising is the fact that the stem cells in our brains not only tolerate such extremely high levels of radicals, but also use them for their function."

Healthy aging

Radical scavengers, also known as "antioxidants", counteract oxidative stress. Such substances are therefore considered important components of a healthy diet. They can be found in fruits and vegetables. "The positive effect of antioxidants has been proven and is not questioned by our study. We should also be careful with drawing conclusions for humans based on purely laboratory studies," emphasizes Kempermann. "And yet our results at least suggest that free radicals are not fundamentally bad for the brain. In fact, they are most likely important for the brain to remain adaptable throughout life and to age in a healthy way."

A combined research team from the Universities of Portsmouth and Bournemouth and Portsmouth Hospitals University NHS Trust has shown that an assessment score used to measure a patient's severity of illness can be applied to patients with Covid-19 without modification.

The Portsmouth Academic ConsortIum For Investigating COVID-19 (PACIFIC-19) team has shown that the National Early Warning Score (NEWS) is equally good at predicting certain adverse clinical outcomes in patients with Covid-19 and other groups of patients admitted to hospital.

These results are important because they show that different techniques are not required for monitoring the severity of illness of patients with Covid-19. Developing new ways of working would require investment, take time and lead to extra demands on staff training, at a time when these are in short supply.

NEWS is used across the NHS to measure a patient's severity of illness. It takes commonly measured vital sign readings (pulse, blood pressure, temperature, breathing rate, etc) and converts them to a single value from 0 to 20. The higher the NEWS value the greater the patient's risk of developing certain adverse clinical outcomes.

The original work underpinning NEWS started in Portsmouth about 14 years ago. Since then, NEWS has been recommended by the Royal College of Physicians and NHS England. More recently, the World Health Organisation (WHO) has recommended its use for the close monitoring of clinical deterioration in patients with Covid-19.

In a separate study, the PACIFIC-19 team was also able to show that the Covid-19 outbreak, and the processes required to respond to it, did not adversely affect the ability of healthcare staff to monitor the vital signs of patients under their care.

Dr Ina Kostakis, Research Fellow at the University of Portsmouth's Centre for Healthcare Modelling and Informatics and the lead author of both studies, said: "We all know about the immense extra burdens that the Covid-19 outbreak has imposed on hospital staff, but we have shown that the tools and processes they already use to monitor deteriorating patients have stood up to the task."

Professor Anoop Chauhan, Executive Director of Research and Innovation at Portsmouth Hospitals University Trust and a senior author on the studies, said: "I'm immensely proud of the way the team came together rapidly at the start of the crisis and has now produced this important work. We look forward to producing even more insights that help us to look after our patients during this pandemic and beyond."

A new study from Karolinska Institutet and the Helmholtz Diabetes Research Center shows that primary cilia, hair-like protrusions on endothelial cells inside vessels, play an important role in the blood supply and delivery of glucose to the insulin-producing beta cells in the pancreatic islets. The findings are published in eLife and may be relevant for transplantation therapies in diabetes, as formation of functional blood vessels is important for the treatment to be successful.

When blood glucose levels rise, beta cells in pancreatic islets release insulin into the blood stream. Insulin triggers glucose uptake in a variety of tissues including fat and muscle. Glucose and other nutrients must cross the vascular barrier to reach beta cells inside pancreatic islets. Similarly, newly released insulin must cross the blood vessels into the blood stream to reach its target tissues.

Endothelial cells can be found on the inside of blood vessels. Vessels in the pancreatic islets form a dense network with many small pores in the endothelial cell membrane, facilitating the exchange of molecules across the vessel wall.

Now, researchers have investigated how pancreatic islet vessel formation and function are affected by primary cilia, small hair-like structures found on beta cells and endothelial cells. Professor Per-Olof Berggren's research group at The Rolf Luft Research Center for Diabetes and Endocrinology, the Department of Molecular Medicine and Surgery, Karolinska Institutet in Sweden and Dr. Jantje Gerdes' research group at the Helmholtz Diabetes Research Center in Munich, Germany, have previously shown that insulin secretion is modulated by cilia on beta cells.

In the new study, the researchers examined a mouse model of Bardet-Biedl Syndrome, a disease caused by cilia dysfunction. They were able to show that when endothelial cilia are dysfunctional, the blood supply to the pancreatic islets is less efficient. Newly formed vessels have larger diameters and fewer pores that allow nutrients to pass through the vessel wall.

"Consequently, the smallest blood vessels, the capillaries, become less efficient at delivering glucose to the beta cells," says Yan Xiong, assistant professor at the Department of Molecular Medicine and Surgery, Karolinska Institutet and first author of the study.

Signalling via the growth factor VEGF-A was identified as a key player in this process. Endothelial cells that lack functional cilia are less sensitive to VEGF-A compared to normal endothelial cells, resulting in impaired signalling via the VEGFR2 receptor.

"In summary, we have demonstrated that primary cilia, specifically those on endothelial cells, regulate pancreatic islet vascularisation and vascular barrier function via the VEGF-A/VEGFR2 signalling pathway," says Dr Gerdes, one of the senior authors of the study.

The formation of functional blood vessels is an important factor in transplantation therapies. Beta cell replacement therapy could potentially treat and cure type 1 diabetes, and the formation of a functional interface between beta cells and blood vessels is an important step towards longer graft survival and diabetes remission.

"This study improves the understanding of how primary cilia facilitate efficient blood vessel formation, and potentially offers novel therapeutic avenues to enable effective pancreatic islet transplantation in diabetes and possibly transplantation of other organs as well," says Dr Berggren, the other senior author of the study.

Emotions are complex phenomena that influence our minds, bodies and behaviour. A number of studies have sought to connect given emotions, such as fear or pleasure, to specific areas of the brain, but without success. Some theoretical models suggest that emotions emerge through the coordination of multiple mental processes triggered by an event. These models involve the brain orchestrating adapted emotional responses via the synchronisation of motivational, expressive and visceral mechanisms. To investigate this hypothesis, a research team from the University of Geneva (UNIGE) studied brain activity using functional MRI. They analysed the feelings, expressions and physiological responses of volunteers while they were playing a video game that had been specially developed to arouse different emotions depending on the progress of the game. The results, published in the journal PLOS Biology, show that different emotional components recruit several neural networks in parallel distributed throughout the brain, and that their transient synchronisation generates an emotional state. The somatosensory and motor pathways are two of the areas involved in this synchronisation, thereby validating the idea that emotion is grounded in action-oriented functions in order to allow an adapted response to events.

Most studies use passive stimulation to understand the emergence of emotions: they typically present volunteers with photos, videos or images evoking fear, anger, joy or sadness while recording the cerebral response using electroencephalography or imaging. The goal is to pinpoint the specific neural networks for each emotion. &laquoThe problem is, these regions overlap for different emotions, so they're not specific», begins Joana Leitão, a post-doctoral fellow in the Department of Fundamental Neurosciences (NEUFO) in UNIGE's Faculty of Medicine and at the Swiss Centre for Affective Sciences (CISA). &laquoWhat's more, it's likely that, although these images represent emotions well, they don't evoke them».

A question of perspective

Several neuroscientific theories have attempted to model the emergence of an emotion, although none has so far been proven experimentally. The UNIGE research team subscribe to the postulate that emotions are &laquosubjective»: two individuals faced with the same situation may experience a different emotion. &laquoA given event is not assessed in the same way by each person because the perspectives are different,» continues Dr Leitão.

In a theoretical model known as the component process model (CPM) - devised by Professor Klaus Scherer, the retired founding director of CISA- an event will generate multiple responses in the organism. These relate to components of cognitive assessment (novelty or concordance with a goal or norms), motivation, physiological processes (sweating or heart rate), and expression (smiling or shouting). In a situation that sets off an emotional response, these different components influence each other dynamically. It is their transitory synchronisation that might correspond to an emotional state.

Emotional about Pacman

The Geneva neuroscientists devised a video game to evaluate the applicability of this model. &laquoThe aim is to evoke emotions that correspond to different forms of evaluation», explains Dr Leitão. &laquoRather than viewing simple images, participants play a video game that puts them in situations they'll have to evaluate so they can advance and win rewards». The game is an arcade game that is similar to the famous Pacman. Players have to grab coins, touch the &laquonice monsters», ignore the &laquoneutral monsters» and avoid the &laquobad guys» to win points and pass to the next level.

The scenario involves situations that trigger the four components of the CPM model differently. At the same time, the researchers were able to measure brain activity via imaging; facial expression by analysing the zygomatic muscles; feelings via questions; and physiology by skin and cardiorespiratory measurements. &laquoAll of these components involve different circuits distributed throughout the brain», says the Geneva-based researcher. &laquoBy cross-referencing the imagery data with computational modelling, we were able to determine how these components interact over time and at what point they synchronise to generate an emotion».

A made-to-measure emotional response

The results also indicate that a region deep in the brain called the basal ganglia is involved in this synchronisation. This structure is known as a convergence point between multiple cortical regions, each of which is equipped with specialised affective, cognitive or sensorimotor processes. The other regions involve the sensorimotor network, the posterior insula and the prefrontal cortex. &laquoThe involvement of the somatosensory and motor zones accords with the postulate of theories that consider emotion as a preparatory mechanism for action that enables the body to promote an adaptive response to events», concludes Patrik Vuilleumier, full professor at NEUFO and senior author of the study.

Researchers from the Institute of Biomedicine of Seville (IBIS) have presented a study carried out in the Clinical Biochemistry Service of the Virgen del Rocío University Hospital which identifies the values for six biochemical biomarkers that indicate a patient may be infected with SARS-COV-2 (COVID-19). The key novelty of this study, led by Dr. Juan Miguel Guerrero, head of service and IR of the IBiS Molecular NeuroImmunoendocrinology group, lies in the fact that it was carried out using a blood test and can provide a determination in about 60 minutes.

The Coronavirus continues to concern society and occupy researchers and health professionals. Research remains key to achieving not only a vaccine but also a rapid diagnosis of the disease. The Laboratory of the Virgen del Rocío University Hospital in Seville has identified the values of six biochemical biomarkers which indicate the patient may be infected with the Coronavirus.

This was possible thanks to their cooperation with the specialists at the Clinical Biochemistry service, who evaluated the routine blood tests of more than 200 people conducted in the ED to detect infection. Specifically, they analysed the accuracy of each biomarker to differentiate between patients infected with COVID-19 and those who aren't. The researchers behind the study have established six criteria linked to suspected COVID-19 infection using the blood lymphocyte and eosinophil count, and the levels of ferritin, lactate dehydrogenase, C-reactive protein and d-dimer in plasma. Ninety-one percent of patients infected with COVID-19 met one or more of these biomarker criteria. It is thus possible to rule out a Coronavirus infection with a high degree of probability in patients who meet none of these criteria.

All hospitals have the facilities to test for these biomarkers using quick, automated analysers (in less than 60 minutes). These laboratory criteria, combined with medical history and imaging tests, can be very useful to screen patients with suspected COVID-19.

For this study, the researchers collaborated with the company Blueberry Diagnostics, creating an algorithm that uses artificial intelligence to identify patients infected with COVID-19 with a sensitivity of 100% and a specificity of 100%. A second algorithm has been developed that can detect those patients with a more serious prognosis from the disease, thus making it possible to prioritise their treatment and reduce the mortality rate. The algorithms have since been turned into decision trees which are to be released through a public license so that any hospital can analyse them in its own laboratory.

Neutrinos are chargeless particles with about a mass about a millionth that of an electron that are created by the nuclear processes that occur in the Sun and other stars. These particles are often colourfully described as the 'ghosts' of the particle zoo because they interact so weakly with matter. A paper published in EPJ C by the Borexino collaboration - including XueFeng Ding, Postdoc Associate of Physics at Princeton University, United States - documents the attempts of the Borexino experiment to measure low-energy neutrinos from the Sun's carbon-nitrogen-oxygen (CNO) cycle for the first time.

"This giant instrument, buried beneath the Gran Sasso mountains in the Gran Sasso National Laboratory in Italy, is capturing ghost-like neutrinos from a so-called CNO process in the very centre of the Sun," Ding explains. "We made tens of thousands of simulations and predicted that we would be able to prove these 'CNO' ghosts exist for the first time in human history ever."

The Sun produces energy by converting four hydrogen nuclei to one helium nucleus through two mechanisms. The majority of energy produced by the Sun is initiated by the direct fusion of two protons into a deuteron, starting the pp chain, the other mechanism is catalysed by heavier nuclei, such as carbon, nitrogen and oxygen, known as the CNO cycle - which produces about 1% of our star's energy output. As well as this small energy contribution, the CNO cycle should also produce about 1% of the neutrinos that stream from the Sun.

"Neutrinos from the CNO cycle process in the Sun had remained essentially hypothetical until the recent report of Borexino on the Neutrino 2020 conference," Ding says. "Borexino has been looking for CNO neutrinos since 2016 after the thermal insulation system and active temperature control system were installed. This paper reports a quantitative study on the Borexino sensitivity in searching for CNO neutrinos and explains the methodology."

Since the Sun itself only has a 1% CNO branch, and since neutrinos are already incredibly difficult to detect, there has been essentially no measurement yet of the CNO process itself, even though it is believed to be the dominate energy production avenue in stars much more massive than the Sun. Detecting neutrinos from the CNO cycle will teach researchers much more about it, in turn revealing the secrets locked beneath the surface of the Universe's most massive stars.

New Orleans, LA - A study by researchers at LSU Health New Orleans School of Public Health, believed to be the first study to investigate the role of neighborhood deprivation on COVID-19 in Louisiana, found that the more a neighborhood is deprived, the higher the risk for cases of COVID-19. They report that people living in the most deprived neighborhoods had an almost 40% higher risk of COVID-19 compared to those residing in the least deprived neighborhoods. Their findings are published online in PLOS ONE, available here.

Led by Edward S. Peters, DMD, SM, ScD, FACE, the team at LSU Health New Orleans School of Public Health sought to find more definitive answers about what contributed to the nation's highest per capita rate of COVID-19 cases in New Orleans during the summer of 2020 and the disproportionate number of African Americans affected. Few studies in the US had assessed the role of social determinants of health on COVID-19 disease. The studies that existed examined only a couple of specific risk factors, such as overcrowding and income. The LSU Health New Orleans team took a much more comprehensive approach to examine the relationship between neighborhood deprivation and COVID-19 in Louisiana.

The authors explain, "Risk factors leading to COVID-19 disease, hospitalization, and mortality exist not only at the individual or biological level; neighborhood-level factors and their interactions with individual-level factors are also responsible for the observed disparities. Lack of access to health care, unemployment, less education, and poor housing conditions significantly increase the risk of COVID-19 infection. These determinants of health can be studied collectively as neighborhood or area deprivation."

"We used a measurement called the Area Deprivation Index (ADI) to look at how relative deprivation of Louisiana neighborhoods is associated with the rate of COVID-19 cases," notes Dr. Peters, Professor and Chair of Epidemiology at LSU Health New Orleans School of Public Health. "The ADI uses 17 census-derived measures of poverty, education, housing, and employment indicators at the census tract level to classify neighborhoods. It is a robust metric measuring many relevant social determinants of health that may help explain the socio-biologic mechanisms of disease. We obtained the cumulative number of Louisiana COVID-19 case counts from the Louisiana Department of Health on July 31, 2020. We estimated COVID-19 risk for five categories of deprivation, ranging from least to most deprived neighborhoods."

The authors noted that non-Hispanic African Americans are more likely to have vulnerable and low-paying jobs that do not allow remote work, are more likely to rely on public transportation and to live in crowded housing or work in crowded worksites that place them an increased risk for COVID-19. African Americans exhibit a greater burden of chronic medical conditions such as hypertension, diabetes, heart disease, chronic disease, and obesity that increase the severity of COVID-19 illness. In Louisiana, 2.9 million people have at least one chronic condition, and 68% of Louisiana adults are overweight or obese. Furthermore, the poverty rate is much higher among African Americans compared to Non-Hispanic Whites, and African Americans tend to live in neighborhoods with high poverty. Neighborhood socioeconomic status is linked to access to health care services, and people residing in low socioeconomic status neighborhoods are less likely to have access to health care services, which further increases the risk of adverse health outcomes related to COVID-19, such as a higher rate of hospitalizations and mortality.

"We observed a great disparity in deprivation among Louisiana neighborhoods," Peters says. "We also found an association between neighborhood deprivation and cumulative COVID-19 cases per 1,000 persons in Louisiana. Neighborhoods with greater deprivation should be especially targeted with public health prevention measures such as wearing a mask while in public, social distancing, and considered as a priority for COVID-19 vaccine delivery."

The research team also included Drs. Evrim Oral, Susanne Straif-Bourgeois, and Ariane L. Rung, along with PhD student Madhav KC, all at LSU Health New Orleans School of Public Health.

The world's largest solar observatory, the U.S. National Science Foundation's Daniel K. Inouye Solar Telescope, just released its first image of a sunspot. Although the telescope is still in the final phases of completion, the image is an indication of how the telescope's advanced optics and four-meter primary mirror will give scientists the best view of the Sun from Earth throughout the next solar cycle.

The image, taken January 28, 2020, is not the same naked eye sunspot currently visible on the Sun. This sunspot image accompanies a new paper by Dr. Thomas Rimmele and his team. Rimmele is the associate director at NSF's National Solar Observatory (NSO), the organization responsible for building and operating the Inouye Solar Telescope. The paper is the first in a series of Inouye-related articles featured in Solar Physics. The paper details the optics, mechanical systems, instruments, operational plans and scientific objectives of the Inouye Solar Telescope. Solar Physics will publish the remaining papers in early 2021.

Read Daniel K. Inouye Solar Telescope - Observatory Overview, by Thomas R. Rimmele et al. - Solar Physics volume 295, issue 12, 2020

"The sunspot image achieves a spatial resolution about 2.5 times higher than ever previously achieved, showing magnetic structures as small as 20 kilometers on the surface of the sun," said Rimmele.

The image reveals striking details of the sunspot's structure as seen at the Sun's surface. The streaky appearance of hot and cool gas spidering out from the darker center is the result of sculpting by a convergence of intense magnetic fields and hot gasses boiling up from below.

The concentration of magnetic fields in this dark region suppresses heat within the Sun from reaching the surface. Although the dark area of the sunspot is cooler than the surrounding area of the Sun, it is still extremely hot with a temperature of more than 7,500 degrees Fahrenheit.

This sunspot image, measuring about 10,000 miles across, is just a tiny part of the Sun. However, the sunspot is large enough that Earth could comfortably fit inside.

Sunspots are the most visible representation of solar activity. Scientists know that the more sunspots that are visible on the Sun, the more active the Sun is. The Sun reached solar minimum, the time of fewest sunspots during its 11-year solar cycle, in December 2019. This sunspot was one of the first of the new solar cycle. Solar maximum for the current solar cycle is predicted in mid-2025.

"With this solar cycle just beginning, we also enter the era of the Inouye Solar Telescope," says Dr. Matt Mountain, president of the Association of Universities for Research in Astronomy (AURA), the organization that manages NSO and the Inouye Solar Telescope. "We can now point the world's most advanced solar telescope at the Sun to capture and share incredibly detailed images and add to our scientific insights about the Sun's activity."

Sunspots, and associated solar flares and coronal mass ejections, cause many space weather events, which frequently impact the Earth, a consequence of living inside the extended atmosphere of a star. These events affect technological life on Earth. The magnetic fields associated with solar storms can impact power grids, communications, GPS navigation, air travel, satellites and humans living in space. The Inouye Solar Telescope is poised to add important capabilities to the complement of tools optimized to study solar activity particularly magnetic fields.

NSF's Inouye Solar Telescope is located on the island of Maui in Hawai?i. Construction began in 2013 and is slated to be completed in 2021.

"While the start of telescope operations has been slightly delayed due to the impacts of the COVID-19 global pandemic," said Dr. David Boboltz, NSF Program Director for the Inouye Solar Telescope, "this image represents an early preview of the unprecedented capabilities that the facility will bring to bear on our understanding of the Sun."

The Daniel K. Inouye Solar Telescope is a facility of the National Science Foundation operated by the National Solar Observatory under a cooperative agreement with the Association of Universities for Research in Astronomy, Inc. The Inouye Solar Telescope is located on land of spiritual and cultural significance to Native Hawaiian people. The use of this important site to further scientific knowledge is done so with appreciation and respect.

Vanderbilt University Medical Center researchers have discovered individuals with type 1 and type 2 diabetes infected with COVID-19 are three times more likely to have a severe illness or require hospitalization compared with people without diabetes.

Because of this amplified impact, they are urging policymakers to prioritize these individuals for COVID-19 vaccination. Their findings were published in Diabetes Care, the journal of the American Diabetes Association.

While studies have suggested that those with type 2 diabetes are at higher risk for more serious complications and being hospitalized if they get COVID-19, little is known about the risk for individuals with type 1 diabetes. In the U.S. alone, an estimated 1.6 million individuals have type 1 diabetes.

"I think these data support prioritizing individuals with type 1 or individuals with type 2 diabetes for immunization alongside other high-risk medical conditions that increase the risk of getting very sick with COVID-19, such as heart or lung disease," said Justin Gregory, MD, MSCI, lead investigator for the study.

The team of investigators identified electronic health records (EHRs) of more than 6,000 patients across 137 Vanderbilt Health clinical sites who had a COVID-19 diagnosis during the period from mid-March until the first week of August. The team then closely reviewed the patients' medical records and contacted many individuals by telephone to identify additional risk factors and gather more information on how COVID-19 had impacted their health.

They compared the overall impact of COVID-19 for three populations: individuals with type 1 diabetes, individuals with type 2 diabetes and those who did not have diabetes. The study was a prospective cohort study, meaning researchers identified the study subjects soon after their infection with COVID-19 and followed these individuals as they progressed through the illness. Prospective studies have lower risk of investigator bias as the outcome is not known when study subjects are identified.

"People with type 1 diabetes don't need to live in fear and have undue anxiety, but they need to be really diligent in doing the things we all should be doing," Gregory said. "All of us should be washing our hands and staying 6 feet apart. We should be conscientious about limiting the time spent with people outside our household. I'm not asking people with type 1 diabetes to do anything that all of us shouldn't already be doing. I just think they need to be the most diligent about doing it day in and day out."

Biologists from RUDN University working together with their colleagues from the Institute of Molecular Biology of the Russian Academy of Sciences and the Institute of Flax studied the genes that determine the fatty acid composition in flaxseed oil and identified polymorphisms in six of them. The team also found out what gene variations could extend the shelf life of flaxseed oil. This data can be used to improve the genetic selection of new flax breeds. The results were published in the BMC Plant Biology journal.

Linum usitatissimum or common flax has been known as an oil crop since the early Neolithic Age. Its seeds are used to produce oil, paints, lacquers, biofuel, resins, linseed oil varnish, linoleum, and pet food, while its stocks are a source of fiber for textiles and sealing materials. Breeds and lines of flax differ by fatty acid content and composition. The lines that contain less than 5% of linolenic acid but have a high content of linolic acid are known for long shelf life which is important for the food industry. The synthesis of fatty acids in flax is determined by genes that belong to the SAD and FAD families. A team of biologists including specialists from RUDN University used deep DNA sequencing to study the genome of flax and confirmed that SAD and FAD genes and their polymorphisms directly affect the fatty acid content in flax seeds and the shelf life of flaxseed oil.

"We created a representative set of 84 flax breeds and lines with different fatty acid content in their oil. Using deep sequencing, we identified the sequences of six genes: SAD1, SAD2, FAD2A, FAD2B, FAD3A and FAD3B," said Parfait Kezimana, a postgraduate student at the Agrarian and Technological Institute of RUDN University.

The team studied the genetic material of 50 flax germs from each breed and line to find polymorphisms allowing for intraparietal heterogeneity. Using the Illumina platform (MiSeq sequencer) with 400? coverage, the team managed to accurately identify the sequence of the genes.

Based on the content of fatty acids in flaxseed oil and different polymorphisms in the studied genes, the team found out which genes and their allelic variants determined the quantities of certain acids. All but one breed with low linolenic acid content had a polymorphism that substituted the amino acid histidine in FAD3B with tyrosine and the amino acid tryptophan in FAD3A with a stop codon. Thanks to these mutations, the oil made from these breeds of flax has a longer shelf life and is better preserved.

"We have evaluated the polymorphisms of SAD and FAD genes in a set of flax breeds and lines with different oil compositions and identified the polymorphisms that determine the content of fatty acids in them. Our results could be used to develop markers for the genetic selection of new flax breeds. In the future, breeds could be certified based on their DNA sequences," added Parfait Kezimana from RUDN University.

In the last five decades, we've learned a lot about the secret lives of proteins -- how they work, what they interact with, the machinery that makes them function -- and the pace of discovery is accelerating.

The first three-dimensional protein structure began emerging in the 1970s. Today, the Protein Data Bank, a worldwide repository of information about the 3D structures of large biological molecules, has information about hundreds of thousands of proteins. Just this week, the company DeepMind shocked the protein structure world with its accurate, AI-driven predictions.

But the 3D structure is often not enough to truly understand what a protein is up to, explains Ken Dill, director of the Laufer Center for Physical and Quantitative Biology at Stony Brook University and a member of the National Academy of Sciences. "It's like somebody asking how an automobile works, and a mechanic opening the hood of a car and saying, 'see, there's the engine, that's how it works.'"

In the intervening decades, computer simulations have built upon and added to the understanding of protein behavior by setting these 3D molecular machines in motion. Analyzing their energy landscapes, interactions, and dynamics has taught us even more about these prime movers of life.

"We're really trying to ask the question: how does it work? Not just, how does it look?" Dill said. "That's the essence of why you want to know protein structures in the first place, and one of the biggest applications of this is for drug discovery."

Writing in Science magazine in November 2020, Dill and his Stony Brook colleagues Carlos Simmerling and Emiliano Brini shared their perspectives on the evolution of the field.

"Computational Molecular Physics is an increasingly powerful tool for telling the stories of protein molecule actions," they wrote. "Systematic improvements in forcefields, enhanced sampling methods, and accelerators have enabled [computational molecular physics] to reach timescales of important biological actions.... At this rate, in the next quarter century, we'll be telling stories of protein molecules over the whole lifespan, tens of minutes, of a bacterial cell."

SPEEDING SIMULATIONS

Decades after the first dynamic models of proteins, however, computational biophysicists still face major challenges. To be useful, simulations need to be accurate; and to be accurate, simulation needs to progress atom by atom and femtosecond (10^-12 seconds) by femtosecond. To match the timescales that matter, simulations must extend over microseconds or milliseconds -- that is, millions of time-steps.

"Computational molecular physics has developed at a fast clip relatively speaking, but not enough to get us into the time and size and motion range we need to see," he said.

One of the main methods researchers use to understand proteins in this way is called molecular dynamics. Since 2015, with support from the National Institutes of Health and the National Science Foundation, Dill and his team have been working to speed up molecular dynamics simulations. Their method, called MELD, accelerates the process by providing vague but important information about the system being studied.

Dill likens the method to a treasure hunt. Instead of asking someone to find a treasure that could be anywhere, they provide a map with clues, saying: 'it's either near Chicago or Idaho.' In the case of actual proteins, that might mean telling the simulation that one part of a chain of amino acids is near another part of the chain. This narrowing of the search field can speed up simulations significantly -- sometimes more than 1000-times faster -- enabling novel studies and providing new insights.

PROTEIN STRUCTURE PREDICTIONS FOR COVID-19

One of the most important uses of biophysical modeling in our daily lives is drug discovery and development. 3D models of viruses or bacteria help identify weak spots in their defenses, and molecular dynamics simulations determine what small molecules may bind to those attackers and gum up their works without having to test every possibility in the lab.

Dill's Laufer Center team is involved in a number of efforts to find drugs and treatments for COVID-19, with support from the White House-organized COVID-19 HPC Consortium, an effort among Federal government, industry, and academic leaders to provide access to the world's most powerful high-performance computing resources in support of COVID-19 research.

"Everyone dropped other things to work on COVID-19," Dill recalled.

The first step the team took was to use MELD to determine the 3D shape of the coronavirus' unknown proteins. Only three of the 29 of the virus' proteins have been definitively resolved so far. "Most structures are not known, which is not a good beginning for drug discovery," he said. "Can we predict structures that are not known? That's the primary thing that we used Frontera for."

The Frontera supercomputer at the Texas Advanced Computing Center (TACC) -- the fastest at any university in the world -- allowed Dill and his team to make structure predictions for 19 additional proteins. Each of these could serve as an avenue for new drug developments. They have made their structure predictions publicly available and are working with teams to experimentally test their accuracy.

While it seems like the vaccine race is already close to declaring a winner, the first round of vaccines, drugs, and treatments are only the starting point for a recovery. As with HIV, it is likely that the first drugs developed will not work on all people, or will be surpassed by more effective ones with fewer side-effects in the future.

Dill and his Laufer Center team are playing the long game, hoping to find targets and mechanisms that are more promising than those already being developed.

REPURPOSING DRUGS AND EXPLORING NEW APPROACHES

A second project by the Laufer Center group uses Frontera to scan millions of commercially available small molecules for efficacy against COVID-19, in collaboration with Dima Kozakov's group at Stony Brook University.

"By focusing on the repurposing of commercially available molecules it's possible, in principle, to shorten the time it takes to find a new drug," he said. "Kozakov's group has the ability to quickly screen thousands of molecules to identify the best hundred ones. We use our physics modeling to filter this pool of candidates even further, narrowing the options experimentalists need to test."

A third project is studying an interesting cellular protein known as PROTAC that directs the "trash collector proteins" of human cells to pick up specific target proteins that they would not usually remove.

"Our cell has smart ways to identify proteins that needs to be destroyed. It gets next to it, puts a sticker on it, and the proteins who collect trash take it away," he explained. "Initially PROTAC molecules have been used to target cancer related proteins. Now there is a push to transfer this concept to target SARS-CoV-2 proteins."

Collaborating with Stony Brook chemist Peter Tonge, they are working to simulate the interaction of novel PROTACS with the COVID-19 virus. "These are some of our most ambitious simulations, both in term of the size of the systems we are tackling and in terms of the chemical complexity," he said. "Frontera is a crucial resource to give us sufficient turnaround times. For one simulation we need 30 GPUs and four to five days of continuous calculations."

The team is developing and testing their protocols on a non-COVID test system to benchmark their predictions. Once they settle on a protocol, they will apply this design procedure to COVID systems.

Every protein has a story to tell and Dill, Brini and their collaborators are building and applying the tools that help elucidate these stories. "There are some problems in protein science where we believe the real challenge is getting the physics and math right," Dill concluded. "We're testing that hypothesis on COVID-19."