Culture

MINNEAPOLIS/ST. PAUL (06/24/2021) -- A study led by researchers at the University of Minnesota Medical School sheds new light on boys' weapon-carrying behaviors at U.S. high schools. The results indicate that weapon-carrying is not tied to students' race or ethnicity but rather their schools' social climates.

The study was published in the journal Pediatrics and led by Patricia Jewett, PhD, a researcher in the Department of Medicine at the U of M Medical School.

"Narratives of violence in the U.S. have been distorted by racist stereotyping, portraying male individuals of color as more dangerous than white males," Jewett said. "Instead, our study suggests that school climates may be linked to an increase in weapon-carrying at schools."

The study analyzed self-reported weapon-carrying behaviors among 88,000 young males at U.S. high schools between 1993 and 2019 based on data from the Youth Risk Behavior Surveillance System. From that data, they identified four key findings:

- Since 1993, weapon-carrying in schools has declined among all males.

- Over the last 20 years, in schools perceived as safer, Non-Hispanic, white males have been more likely to bring weapons into schools than Non-Hispanic Black/African American or Hispanic males.

- Between 2017 and 2019, while comparing all schools, no significant differences in weapon-carrying behaviors existed by race or ethnicity.

- More frequent weapon-carrying is associated with experiences of unsafety or violence at school. Males who experienced violence or felt unsafe at school brought weapons at least twice as often, and such negative school experiences were more common among males of color (8-12%) than among Non-Hispanic white males (4-5%).

"Our work underscores the association of experiences of unsafety at school with weapon-carrying at school and highlights large knowledge gaps in the field of gun violence research in the U.S.," Jewett said. "This is an important foundation for much needed research to disentangle the intertwined phenomena of racism, toxic environments of violence and gun- and weapon-culture in the U.S. We are currently reaching out to other researchers who work in the field to collaborate on this urgent public health topic."

Dmitry Blinov is a co-author of the article and Senior Research Associate in the Department of Astrophysics, St Petersburg University. He notes that researchers have been studying the optical polarisation from active galactic nuclei for more than 50 years. Some of the first academic papers on this topic were published back in the 1960s by Vladimir Hagen-Thorn, Professor in the Department of Astrophysics, St Petersburg University, and Viktor Dombrovskiy, Associate Professor in the Department of Astrophysics, Leningrad State University.

In the Universe, the main material is concentrated in galaxies with hundreds of billions of stars: there are about 200-400 of them in the Milky Way. At the centre of galaxies there are supermassive black holes, whose mass ranges from millions to billions of those of the Sun. Around black holes there is a large number of stars, gas and dust, which, being too close to the black hole, 'fall' into it. However, a black hole cannot ingest these completely and throws out part of the matter into intergalactic space in the form of extremely fast plasma jets.

The best objects for studying this phenomenon are blazars. They are active galactic nuclei with very high luminosity, whose plasma flow (jet) is directed towards the Earth at an angle of no more than 15 degrees. Such objects are the main sources of cosmic gamma rays, the nature and properties of which are understudied. Additionally, blazars puzzle astronomers by other phenomena, including the rotation of polarisation plane.

The polarisation plane of a wave is the plane in which a vector (for example, the electric field vector) oscillates and changes. In the figure below, the oscillations of the electric vector are in blue; the polarisation plane is in red.

The light that we see in nature, as a rule, consists of many such waves directed in different directions. In this case, the orientation of polarisation is random (in the figure on the left). Fully polarised light (in the figure on the right) propagates with the oscillations of the electric vector in only one plane. Such a phenomenon can be observed in some lasers. However, physical processes mainly create partially polarised light, while electromagnetic waves in a light beam often oscillate along one of the directions. For example, the figure in the middle shows electromagnetic waves in a beam of partially polarised light directed towards the reader. It is this kind of light that scientists observe when studying blazars. For this purpose, they study active galactic nuclei through a telescope with a special polarising filter, similar to sunglasses, which transmits oscillations only in one plane.

Decades of observations have testified that the polarisation plane of visible light in blazars sometimes rotates. Scientists have put forward several hypotheses that could describe the mechanism of such rotations, but none of them have had sufficient evidence. The research group from the Laboratory of Observational Astrophysics at St Petersburg University drew attention to one of the theoretical models. It was proposed back in 2010 in an academic paper. Researchers from St Petersburg University also took part in that study. It considered a rotation of the polarisation plane and predicted that such rotations should coincide with repeated gamma ray bursts.

The research group from St Petersburg University tested this hypothesis in collaboration with scientists from: the Boston University Institute for Astrophysical Research, the Max Planck Institute for Radio Astronomy; and other research institutions. They analysed publicly available data from: the Fermi Gamma-ray Space Telescope, which had observed one of the most active blazars 3C 279; the St Petersburg University Observatory; the Crimean Astrophysical Observatory; the Perkins telescope; and others.

'We have compared the results of numerous observations of the polarisation of optical emission from blazar 3C 279 with open data from the Fermi Gamma-ray Space Telescope. It has been regularly scanning the entire sky since 2008 and showing gamma-ray flux distribution. We have managed to find a pattern of bursts in this blazar, which has repeated at least three times along with the rotations of the optical polarisation. This confirms the previously proposed model explaining rotations of polarisation,' says Dmitry Blinov.

Additionally, based on the data obtained, the researchers have managed to describe the structure of the inner part of the jets. It is found that the fast spine, the centre of the jet, is surrounded by a slower sheath, which consists of ring condensations. When a plasmoid moves along the spine of the jet at high speed, it scatters low-energy photons from the sheath to energies of the gamma-ray band. This causes the bursts that the scientists have observed. Since the ring-shaped structures of the sheath have been stable over the years of observations, such bursts have repeated several times.

The research findings have become the basis for 3D animation, which gives an idea of the processes taking place in the inner parts of active galactic nuclei. According to Dmitry Blinov, in the future, similar patterns of bursts in the gamma band might help clarify other issues. For example, according to one of the hypotheses, it is jets with fast spines and a slow sheaths that can produce fundamental cosmic particles - neutrinos. Repeating patterns of bursts might indicate blazars that emit cosmic neutrinos.

An international team of researchers co-led by the University of Adelaide and the University of Arizona has analysed the genomes of more than 2,500 modern humans from 26 worldwide populations, to better understand how humans have adapted to historical coronavirus outbreaks.

In a paper published in Current Biology, the researchers used cutting-edge computational methods to uncover genetic traces of adaptation to coronaviruses, the family of viruses responsible for three major outbreaks in the last 20 years, including the ongoing pandemic.

"Modern human genomes contain evolutionary information tracing back hundreds of thousands of years, however it's only in the past few decades geneticists have learned how to decode the extensive information captured within our genomes," said lead author Dr Yassine Souilmi, with the University of Adelaide's School of Biological Sciences.

"This includes physiological and immunological 'adaptions' that have enabled humans to survive new threats, including viruses.

"Viruses are very simple creatures with the sole objective to make more copies of themselves. Their simple biological structure renders them incapable of reproducing by themselves so they must invade the cells of other organisms and hijack their molecular machinery to exist."

Viral invasions involve attaching and interacting with specific proteins produced by the host cell known as viral interacting proteins (VIPs).

In the study researchers found signs of adaptation in 42 different human genes encoding VIPs.

"We found VIP signals in five populations from East Asia and suggest the ancestors of modern East Asians were first exposed to coronaviruses over 20,000 years ago," said Dr Souilmi.

"We found the 42 VIPs are primarily active in the lungs - the tissue most affected by coronaviruses - and confirmed that they interact directly with the virus underlying the current pandemic."

Other independent studies have shown that mutations in VIP genes may mediate coronavirus susceptibility and also the severity of COVID-19 symptoms. And several VIPs are either currently being used in drugs for COVID-19 treatments or are part of clinical trials for further drug development.

"Our past interactions with viruses have left telltale genetic signals that we can leverage to identify genes influencing infection and disease in modern populations, and can inform drug repurposing efforts and the development of new treatments," said co-author Dr Ray Tobler, from the University of Adelaide's School of Biological Sciences.

"By uncovering the genes previously impacted by historical viral outbreaks, our study points to the promise of evolutionary genetic analyses as a new tool in fighting the outbreaks of the future." said Dr Souilmi.

The researchers also note that their results in no way supersede pre-existing public health policies and protections, such as mask wearing, social distancing, and vaccinations.

Rheumatologists are familiar with the everyday use of immunomodulatory drugs. These are designed to treat the inflammation caused by autoimmune diseases such as rheumatoid arthritis. A EULAR taskforce was set up to develop a set of new points to consider to give guidance and advice on the best way to use these medicines to treat COVID-19. The taskforce included rheumatologists, immunologists, haematologists, paediatricians, patients and other health professionals. They looked at the published evidence on the use of immunomodulatory therapies to treat severe COVID-19.

In total, there are two overarching principles and 14 points to consider. The principles stress that the picture of SARS-CoV-2 infection can be very different in different people. Infections range from asymptomatic or mild disease to severe or fatal. People with COVID-19 may need different treatment approaches, including antiviral medicines, oxygen therapy, anticoagulation and/or immunomodulatory treatment at different stages of the disease. The 14 points to consider are split into two categories: pathophysiology, and immunomodulatory therapy. Pathophysiology is about the disease itself. Immunomodulatory therapy is about how we might use existing medicines from the field of rheumatology to treat severe COVID-19. These give specific advice about which treatments to use at what stages of the disease. The picture is changing very quickly, which means there are some areas of uncertainty. EULAR intends to update the advice
in response to increasing knowledge and evidence both about the disease, and the impact of COVID-19 vaccines.

These findings do not apply to people living with RMDs who are taking immunomodulatory treatments for their rheumatic disease. Separate recommendations are available for the management of people with RMDs in the context of the pandemic.

The cells of simple organisms, such as bacteria, as well as human cells are surrounded by a membrane, which fulfills various tasks including protecting the cell from stress. In a joint project, teams from Johannes Gutenberg University Mainz (JGU) and Forschungszentrum Jülich, with participation of Heinrich Heine University Düsseldorf (HHU), have now discovered that a membrane protein found in bacteria has a similar structure and function as a group of proteins that are responsible for remodeling and rebuilding the cell membrane in humans. No connection between the two protein groups was known before. The team's research work has been published recently in the renowned journal Cell.

PspA plays a key role in bacterial stress response

The phage shock protein (Psp) system was discovered in bacteria approximately 30 years ago. At the time, it was identified to be a response of Escherichia coli bacteria to infection with special viruses called bacteriophages. Later it became clear that its function in protecting the cell membrane exceeds the specific response to bacteriophage infection. Osmotic stress, heat, cell toxins, or defects in the membrane envelope can also trigger the stress reaction.

"Today, we know that the Psp system is activated in response to numerous types of membrane stress. However, several molecular details still remain puzzling," explained Professor Dirk Schneider, head of the Membrane Proteins group at JGU. "That's why we decided to take a closer look at core proteins of the Psp system." Together with his team, he has recently discovered how the Psp representative IM30 forms a protective carpet-like structure on a cell membrane in order to cope with membrane stress.

In their new work, the scientists scrutinized the phage shock protein A (PspA), which has a key role in the Psp system. Specifically, by using cryo-electron microscopy, it became visible how PspA forms long, spiral-shaped tubes that can enclose a biomembrane in the inner cavity. The high-resolution images now show for the very first time how PspA dissolves individual membranes locally and then reshapes them into larger units or even mediates the formation of new membrane structures.

"Thousands of PspA building blocks can be assembled to form large helical structures. Therefore, they are an ideal research object for our cryo-electron microscopic structural analysis," said Professor Carsten Sachse from Forschungszentrum Jülich and HHU Düsseldorf. The studies were performed at Jülich together with Dr. Benedikt Junglas, a former doctoral student of Professor Dirk Schneider at JGU. At the Ernst Ruska-Centre for Microscopy and Spectroscopy with Electrons (ER-C), Forschungszentrum Jülich operates some of the most powerful electron microscopes in Europe and, as of recently, cryo-microscopes for the study of flash-frozen biological samples.

PspA remodels membranes

Under the microscope, the researchers were able to recognize or - in jargon - "resolve" the structure of PspA. The structure of a protein is essential for its function and a defect in the structure can impair the protein function. "Under the microscope, we realized that PspA has a structure similar to ESCRT-III proteins, which our laboratory had already been working on. This came as a complete surprise and showed how important it is to elucidate protein structures in detail," said Sachse. "After billions of years, the two groups of proteins have genetically diverged so far that their similarities could only be detected based on their structure."

ESCRT-III proteins are found in all living organisms with a true cell nucleus, including human cells. Here, the ESCRT-III protein complexes are involved in cell membrane remodeling and repair but also play a key role in a number of other cell processes. In bacteria, no proteins of the ESCRT-III family were previously known. "Therefore, PspA and ESCRT-III belong to the same group of proteins. These two perform similar tasks at membranes inside of cells," said Schneider.

"Based on the similar structural and functional properties of PspA and the eukaryotic ESCRT-III proteins, we have identified PspA as a bacterial member of the evolutionarily conserved ESCRT-III superfamily of membrane remodeling proteins," the authors wrote in their article for Cell.

Researchers at the Niels Bohr Institute, University of Copenhagen, together with epidemiologist Lone Simonsen from Roskilde University form part of the panel advising the Danish government on how to tackle the different infection-spreading situations we have all seen unfold over the past year. Researchers have modelled the spread of infections under a variety of scenarios, and the Coronavirus has proven to not follow the older models of disease spreading. An increasingly varied picture of its behaviour and thus its impact on society has emerged. In several scientific articles, researchers have described the knowledge accrued to date, most recently around the concept of "superspreaders". It turns out that only approximately 10% of those infected account for roughly 80% of the spread of the infection. The results have been published in the scientific journal Proceedings of the National Academy of Sciences, PNAS.

Where does our knowledge of infections spreading stem from?

The data researchers use to" feed" and develop computer models comes from a wide range of different sources. The Danish municipalities have kept inventories of the spread of the infection, and this data has the advantage that it stems from units that are not overly large. There is a high degree of detail and this means that one can trace local development more clearly and thus construct parameters for superspreading, which Postdoc Julius Kirkegaard has contributed to. Contact tracing is another source of information. In that case, the focus is on localising and limiting the individual's transmission of the virus. The third source is slightly more complicated as it seeks to follow the chain of infections via the gene sequence of the virus.

Who are the superspreaders?

Regardless of which source researchers examine, the results deliver roughly the same: 10% of all those infected account for as much as 80% of the spread of the infection. It is therefore crucial, in relation to the spread of the virus to locate the so-called superspreaders and uncover how superspreading occurs. Researchers stress that, at the moment, we are not quite sure what constitutes a person as a superspreader. It may purely be down to personal, physiological characteristics. In addition, there are varying degrees of superspreading in the population, so it is not necessarily just one or the other. Some people simply spread the virus more than others and the variation from persons with almost no transmission to superspreaders is great.

How do researchers model a population of just under 6 million individuals?

Three basic categories are considered important when modelling the population's behaviour, when calculating a scenario for the spread of infection: 1. The family context, 2. Work context and 3. The random contexts people find themselves in - in other words, people in proximity on public transport, at leisure activities etc. The time factor in all three is crucial, as it takes time to infect other people. In terms of time, these three categories are somewhat identical when it comes to common diseases, but not a superpreader coronavirus variant.

But this is where the individual characteristics of the virus come into play: Superspreaders are quite different when handled in a computer model. Methods known from physics become important here, as it is necessary to model individuals and their contacts. Researchers have set up computer models both for scenarios with and without superspreaders, and it transpires that shutting down workspaces as well as sporting events, and public transport has the same effect when the model does not take superspreaders into account. But when we include superspreaders, there is a pronounced difference, and the shutdown of public events has a much greater effect.

Disease modelling faces new challenges and strong interdisciplinary collaboration

Diseases can behave very differently and it is therefore incredibly important to be both ready and capable of rapid change in relation to the development of new models that reflect the characteristics of different diseases as accurately as possible, if we hope to contain them. Professor Kim Sneppen explains:" The biological variation of different viruses is enormous. SARS-CoV-2 contains a special feature in that it is at its most contagious just before one develops symptoms. This is the exact opposite of an earlier disease that threatened to become a pandemic, namely SARS, which is mostly contagious after one displays symptoms. Viruses are extremely advanced machines that each find specific weak points to exploit. A new field of research is rapidly developing, which examines how viruses attack the cells in our body. COVID-19 has proven to lead to very different sickness progressions for different patients. In that senses, it behaves chaotically, as we say in physics.".

Ph.D. student Bjarke Frost Nielsen and Professor Kim Sneppen see a large open field of research within the collaboration between physics and biology. Gathering as much possible information about different viruses is crucial thus enabling physists to deploy this knowledge in mapping scenarios to respond to them.

The potential for research into the spread of infections is great

Bjarke Frost Nielsen says:" We need to create a toolbox that contains a wide variation in the way we tackle the spread of transmission, in our computer programs. This is the immediate perspective we can see in front of us, at the moment. Mathematical disease modelling has been around for almost 100 years, but unfortunately not a lot of headway has been made over that period. To put it bluntly, the same equations from the 1930's are still in use today. In relation to some diseases, they can be correct, but in relation to others they can be way off. This is where, as physicists, we have a completely different approach. There are numerous parameters, i.e., social dynamics and much more varied interactions between individuals that we can build our scenarios upon. This is badly needed, when we see the enormous variations in the different diseases".

While invasive zebra mussels consume small plant-like organisms called phytoplankton, Michigan State University researchers discovered during a long-term study that zebra mussels can actually increase Microcystis, a type of phytoplankton known as "blue-green algae" or cyanobacteria, that forms harmful floating blooms.

"Microcystis literally means small cell, but numerous cells cluster together in colonies that can float to the surface to form scums," said Orlando Sarnelle, a professor emeritus with the Department of Fisheries and Wildlife within the College of Agriculture and Natural Resources. "It is one of the most common causes of nuisance algal blooms in nutrient-enriched waters, including Lake Erie where it is a concern for municipal water supplies."

In the 1990s, researchers observed the appearance of dime-sized zebra mussels in Gull Lake, Michigan. Shortly after the mussels arrived, the researchers noticed an increase in Microcystis, which was surprising because the lake has low levels of phosphorus and Microcystis has a well-documented need for high-nutrient waters.

"Lakes colonized by zebra mussels tend to have about three times more Microcystis," said Stephen Hamilton, a professor at the W.K. Kellogg Biological Station and the Department of Integrative Biology within the College of Natural Science, who was also curious to see if there was a relationship between the Microcystis and zebra mussels.

"We observed that zebra mussels can filter out the Microcystis with other particles, but then they spit out the Microcystis because evidently it is unpalatable to them," Hamilton said.

Sarnelle collaborated with Hamilton on a multiyear study that was part of the National Science Foundation's Long-Term Ecological Research Network. Forty years ago, the NSF recognized the need for research studies that lasted more than a few years and launched the LTER Network. This study is one of five projects highlighted in a recent issue of the Ecological Society of America's journal, Ecosphere.

"Long-term measurements are essential to our understanding of many ecological phenomena," Sarnelle said. "There are many things you can't answer in the typical two- to four-year grant cycle."

The researchers suspected the zebra mussels were consuming competitors of Microcystis, which paved the way for the cyanobacteria to flourish under lower nutrient availability than it usually needs. In 2010, an unexpected summer die-off of zebra mussels in Gull Lake during prolonged warm temperatures provided a whole-lake test of the relationship, an opportunity that scientists sometimes call a "natural experiment."

"Normally, Microcystis thrives in warmer water," said Jeffrey White, who was a graduate student advised by Sarnelle at the time and is now a faculty member at Framingham State University in Framingham, Massachusetts. "Instead, we saw an 80% decrease in the Gull Lake Microcystis population when the zebra mussels died despite optimal temperatures for its growth."

The researchers were able to use the long-term study data to confirm their hypothesis.

"This fortuitous observation following years of sampling strengthens the argument that there is a cause-and-effect relationship, and not just a correlation, between zebra mussels and increased Microcystis," Hamilton said. "Multiyear studies can catch slow, unusual or extreme events that could be making important changes resulting in long-term lasting effects in the ecosystems."

A new study could lead to improved decision making in assigning treatments for children with the aggressive cancer rhabdomyosarcoma after revealing key genetic changes underlying development of the disease.

In the largest and most comprehensive study of rhabdomyosarcoma to date, scientists found that specific genetic changes in tumours are linked to aggressiveness, early age of onset and location in the body.

All these factors affect the chances that children will survive their disease - and understanding how they are driven by a cancer's genetics could lead to new ways of tailoring treatment for each patient.

Rhabdomyosarcoma is a rare type of cancer that resembles muscle tissue and mostly affects children. Less than 30 per cent of children with rhabdomyosarcoma who have relapsed or whose cancer has spread will survive.

The new international study, led by researchers at The Institute of Cancer Research, London, could help pick out children with particularly aggressive cancers in need of intense treatment and close monitoring. It could also identify other children who could benefit from less aggressive therapy and could be spared some of the most severe side effects of treatment.

The researchers are already planning to incorporate the new insights into the design of upcoming clinical trials aiming to improve the management of the disease.

The international group of researchers analysed the DNA from 641 patients with rhabdomyosarcoma. The study was published today (Thursday) in the Journal of Clinical Oncology and was funded by Cancer Research UK and several charities who fundraise specifically for research into rhabdomyosarcoma - the Chris Lucas Trust, Talan's Trust and Alice's Arc.

Two main sub-types of rhabdomyosarcoma exist - fusion gene-positive and fusion gene-negative, depending on the presence of a 'fusion gene'. A fusion gene is a hybrid gene formed from two previously separate genes - in this case, a PAX gene and a gene called FOXO1.

When looking at children with fusion-negative rhabdomyosarcoma, researchers found that children whose tumours had faults in the genes MYOD1 and TP53 had significantly poorer response to treatment and worse survival outcomes. TP53 was altered in 69 out of 515 children and was linked to worse survival outcomes.

Approximately half the children whose cancers had TP53 mutations succumbed to their disease compared with one in four children with cancers that were not TP53 mutant - indicating that those without the mutation had a better chance of survival.

The researchers found mutations in MYOD1 in 17 out of 515 children and linked these to both worse outcomes and rapid progression of the disease. The findings suggest that children with these mutations could benefit from more aggressive treatment.

A small number of children with fusion-positive rhabdomyosarcoma - five out of 126 - also had changes in TP53. None of these children survived their cancer and, as a consequence, researchers have identified TP53 as a 'high risk' indicator in this sub-group too.

Researchers believe having too many copies of the genes CDK4 or MYCN may also be linked to a poorer outcome in fusion-positive rhabdomyosarcoma, with 16 and 13 cases, respectively, showing these genetic changes. However, as the number of cases in the study was small this needs to be explored further in future research.

The new study challenges previous findings that the presence of a fault in the RAS gene is linked to poor outcomes. Researchers did however find that some RAS mutations seemed to be correlated with particular ages of onset - with HRAS mutations arising in babies, KRAS mutations in toddlers and NRAS mutations in adolescence.

Babies have previously been shown to have lower survival than older children, which may be because clinicians avoid using more aggressive treatments like radiation in the youngest patients. Taking into account findings from this study, researchers believe that using targeted drugs such as tipifarnib, which blocks HRAS, may be particularly beneficial for these young, vulnerable and high-risk patients.

Study leader Professor Janet Shipley, Professor of Molecular Pathology at The Institute of Cancer Research, London, said:

"Our findings shed light on the genetic changes that underlie rhabdomyosarcoma, a rare and aggressive childhood cancer. By looking at the genetic features of different tumours, we can divide children into different risk groups to help guide their treatment.

"Decades of clinical trials have led to the current complicated system for assigning risk to children with rhabdomyosarcoma - but we know that the current system is not accurate enough to properly assign treatment for individual children. Our findings should refine the current system and treatments clinicians provide to more effectively match each child's genetic profile and risk. Ultimately, further research may highlight new drugs to tailor treatment for patients with high-risk rhabdomyosarcomas that have specific genetic defects."

Professor Paul Workman, Chief Executive of The Institute of Cancer Research, London, said:

"This international collaborative effort has linked specific genetic changes in cancers to the ways that children respond to treatment. It should help clinicians to treat children according to the particular features of their cancer and the risk they face of their cancer progressing. The findings have the potential to have a real impact not only on survival but also on quality of life, by picking out those children who need the most aggressive treatment, but also sparing others with lower-risk disease from the side effects of intensive interventions."

Alice's Arc was inspired by Sara's and David's daughter Alice who, at the age of three, was diagnosed with rhabdomyosarcoma. Alice's Arc was established just after her diagnosis. Alice died four and half years later, aged just seven. Sara Wakeling, Co-founder of Alice's Arc, said:

"We believe the future of treating rhabdomyosarcoma effectively and kindly is reliant on understanding the features of each individual's tumour and tailoring treatment accordingly. We are delighted to have played a role in helping to build understanding of these genetic features of rhabdomyosarcoma tumours and how they play a part in predicting outcomes and influencing treatment pathways. We look forward to continuing to work with the team at the ICR to uncover more clinically translatable research discoveries to defeat this devastating childhood cancer."

Philadelphia, June 24, 2021 - After beginning treatment with remdesivir for COVID-19, a patient experienced significant bradycardia, or low heart rate. Her physicians used a dopamine infusion to stabilize her through the five-day course of remdesivir treatment, and her cardiac condition resolved itself at the end of the treatment. The case is discussed in Heart Rhythm Case Reports, an official journal of the Heart Rhythm Society, published by Elsevier.

"Remdesivir has become the standard of care for COVID-19 pneumonia and there is a paucity of data on its cardiac effects," explained lead author Jomel Patrick Jacinto, DO, HCA Healthcare/USF Morsani College of Medicine GME Programs at Regional Medical Center Bayonet Point, Hudson, FL, USA. "While it is known to be well tolerated and effective, it's critical to note its potential adverse effects on the cardiovascular system. To our knowledge, this is the first reported case of remdesivir-induced hemodynamically unstable sinus bradycardia."

The patient arrived at the hospital in respiratory distress with abnormally rapid breathing, and she tested positive for COVID-19. She was admitted to the intensive care unit and was started on standard COVID-19 treatment protocol, including antiviral therapy with remdesivir. Twenty hours after administration of the first dose, her vitals revealed very low blood pressure and a heart rate as low as 38 beats per minute. An electrocardiogram found marked sinus bradycardia. She lacked any prior cardiac history and had normal telemetry monitor and ECG findings prior to receiving remdesivir. She was started on a dopamine drip and maintained normal sinus rhythm with a heart rate of 60-65 beats per minute. Eighteen hours after her last dose of remdesivir, the dopamine was titrated off, and the patient was stable, with normal ECG findings.

Dr. Jacinto observed that remdesivir has an important role in the fight against severe COVID-19 because it has been shown to improve mortality rates and shorten the total time to recovery. In this case, completion of the five-day course of remdesivir was imperative to the patient's treatment despite the adverse effects as concurrent medical treatment with pressors such as dopamine was adequate support.

"Most hospitals have the ability to support the patient through the five-day treatment course to completion, using medications such as dopamine to nullify severe bradycardia," Dr. Jacinto said. "Having a heightened awareness of its cardiac safety profile is essential to make effective clinical decisions in treatment of patients with remdesivir." He added that remdesivir should be used cautiously in patients with known cardiovascular disease.

Motions of a remarkable cosmic structure have been measured for the first time, using NASA's Chandra X-ray Observatory. The blast wave and debris from an exploded star are seen moving away from the explosion site and colliding with a wall of surrounding gas.

Astronomers estimate that light from the supernova explosion reached Earth about 1,700 years ago, or when the Mayan empire was flourishing and the Jin dynasty ruled China. However, by cosmic standards the supernova remnant formed by the explosion, called MSH 15-52, is one of the youngest in the Milky Way galaxy. The explosion also created an ultra-dense, magnetized star called a pulsar, which then blew a bubble of energetic particles, an X-ray-emitting nebula.

Since the explosion the supernova remnant - made of debris from the shattered star, plus the explosion's blast wave - and the X-ray nebula have been changing as they expand outward into space. Notably, the supernova remnant and X-ray nebula now resemble the shape of fingers and a palm.

Previously, astronomers had released a full Chandra view of the "hand," as shown in the main graphic. A new study is now reporting how quickly the supernova remnant associated with the hand is moving, as it strikes a cloud of gas called RCW 89. The inner edge of this cloud forms a gas wall located about 35 light-years from the center of the explosion.

To track the motion the team used Chandra data from 2004, 2008, and then a combined image from observations taken in late 2017 and early 2018. These three epochs are shown in the inset of the main graphic.

The rectangle (fixed in space) highlights the motion of the explosion's blast wave, which is located near one of the fingertips. This feature is moving at almost 9 million miles per hour. The fixed squares enclose clumps of magnesium and neon that likely formed in the star before it exploded and shot into space once the star blew up. Some of this explosion debris is moving at even faster speeds of more than 11 million miles per hour. A color version of the 2018 image shows the fingers in blue and green and the clumps of magnesium and neon in red and yellow.

While these are startling high speeds, they actually represent a slowing down of the remnant. Researchers estimate that to reach the farthest edge of RCW 89, material would have to travel on average at almost 30 million miles per hour. This estimate is based on the age of the supernova remnant and the distance between the center of the explosion and RCW 89. This difference in speed implies that the material has passed through a low-density cavity of gas and then been significantly decelerated by running into RCW 89.

The exploded star likely lost part or all of its outer layer of hydrogen gas in a wind, forming such a cavity, before exploding, as did the star that exploded to form the well-known supernova remnant Cassiopeia A (Cas A), which is much younger at an age of about 350 years. About 30% of massive stars that collapse to form supernovas are of this type. The clumps of debris seen in the 1,700-year-old supernova remnant could be older versions of those seen in Cas A at optical wavelengths in terms of their initial speeds and densities. This means that these two objects may have the same underlying source for their explosions, which is likely related to how stars with stripped hydrogen layers explode. However, astronomers do not understand the details of this yet and will continue to study this possibility.

A paper describing these results appeared in the June 1, 2020, issue of The Astrophysical Journal Letters, and a preprint is available online. The authors of the study are Kazimierz Borkowski, Stephen Reynolds, and William Miltich, all of North Carolina State University in Raleigh.

In a study in Nature Plants, Yiping Qi, associate professor of Plant Science at the University of Maryland (UMD), introduces a new and improved CRISPR 3.0 system in plants, focusing on gene activation instead of traditional gene editing. This third generation CRISPR system focuses on multiplexed gene activation, meaning that it can boost the function of multiple genes simultaneously. According to the researchers, this system boasts four to six times the activation capacity of current state-of-the-art CRISPR technology, demonstrating high accuracy and efficiency in up to seven genes at once. While CRISPR is more often known for its gene editing capabilities that can knock out genes that are undesirable, activating genes to gain functionality is essential to creating better plants and crops for the future.

"While my lab has produced systems for simultaneous gene editing [multiplexed editing] before, editing is mostly about generating loss of function to improve the crop," explains Qi. "But if you think about it, that strategy is finite, because there aren't endless genes that you can turn off and actually still gain something valuable. Logically, it is a very limited way to engineer and breed better traits, whereas the plant may have already evolved to have different pathways, defense mechanisms, and traits that just need a boost. Through activation, you can really uplift pathways or enhance existing capacity, even achieve a novel function. Instead of shutting things down, you can take advantage of the functionality already there in the genome and enhance what you know is useful."

In his new paper, Qi and his team validated the CRISPR 3.0 system in rice, tomatoes, and Arabidopsis (the most popular model plant species, commonly known as rockcress). The team showed that you can simultaneously activate many kinds of genes, including faster flowering to speed up the breeding process. But this is just one of the many advantages of multiplexed activation, says Qi.

"Having a much more streamlined process for multiplexed activation can provide significant breakthroughs. For example, we look forward to using this technology to screen the genome more effectively and efficiently for genes that can help in the fight against climate change and global hunger. We can design, tailor, and track gene activation with this new system on a larger scale to screen for genes of importance, and that will be very enabling for discovery and translational science in plants."

Since CRISPR is usually thought of as "molecular scissors" that can cut DNA, this activation system uses deactivated CRISPR-Cas9 that can only bind. Without the ability to cut, the system can focus on recruiting activation proteins for specific genes of interest by binding to certain segments of DNA instead. Qi also tested his SpRY variant of CRISPR-Cas9 that greatly broadens the scope of what can be targeted for activation, as well as a deactivated form of his recent CRISPR-Cas12b system to show versatility across CRISPR systems. This shows the great potential of expanding for multiplexed activation, which can change the way genome engineering works.

"People always talk about how individuals have potential if you can nurture and promote their natural talents," says Qi. "This technology is exciting to me because we are promoting the same thing in plants - how can you promote their potential to help plants do more with their natural capabilities? That is what multiplexed gene activation can do, and it gives us so many new opportunities for crop breeding and enhancement."

LA JOLLA--(June 24, 2021) When looking at a complex landscape, the eye needs to focus in on important details without losing the big picture--a charging lion in a jungle, for example. Now, a new study by Salk scientists shows how inhibitory neurons play a critical role in this process.

The study, published May 25, 2021, in the journal Cell Reports, shows that inhibitory neurons do more than just inhibit neuron activity like an off-switch; paradoxically, they actually increase the amount of information transmitted through the nervous system when it needs to be flexible. To make this possible, inhibitory neurons need to be integrated into the circuit in a specific way. These observations could help scientists better understand and treat disorders involving our ability to focus and modulate signals based on the bigger picture, which are altered in conditions such as anxiety and attention deficit disorders.

"This work points to a new role for inhibitory neurons, which are usually just thought to be suppressors and organizers of activity," says Professor Tatyana Sharpee, who led the study. "The role of inhibitory neurons extends much further. By targeting only the most sparsely responding neurons, inhibitory neurons make it possible for the whole circuit to function well. That's completely new."

The new work was motivated by unanswered questions from a previous study of the diversity of response rates among neurons in the retina. The retina is a part of the eye that converts lights to electrical signals to be sent to the brain. "Remarkably, when we looked at retina cells that were not responding very much, their rates of information transfer actually increased in the presence of modulation," says first author Wei-Mien Hsu, a postdoctoral fellow in the Sharpee lab. "The trick for making this unexpected phenomenon possible is to apply the modulation signal via inhibitory neurons."

While the researchers tested the theory in neurons involved in vision, the findings could apply widely to neurons found throughout the brain and nervous system, adds Sharpee, who holds the Edwin K. Hunter Chair at Salk.

The next step in this line of research is to study how the phenomenon works in large sets of neurons.

UNIVERSITY PARK, Pa. -- It can be difficult to get young kids to eat enough vegetables, but a new Penn State study found that simply adding more veggies to their plates resulted in children consuming more vegetables at the meal.

The researchers found that when they doubled the amount of corn and broccoli served at a meal -- from 60 to 120 grams -- the children ate 68% more of the veggies, or an additional 21 grams. Seasoning the vegetables with butter and salt, however, did not affect consumption.

The daily recommended amount of vegetables for kids is about 1.5 cups a day, according to the official Dietary Guidelines for Americans as set by the U.S. Departments of Agriculture and Health and Human Services.

"The increase we observed is equal to about one third of a serving or 12% of the daily recommended intake for young children," said Hanim Diktas, graduate student in nutritional sciences. "Using this strategy may be useful to parents, caregivers and teachers who are trying to encourage kids to eat the recommended amount of vegetables throughout the day."

Barbara Rolls, Helen A. Guthrie Chair and director of the Laboratory for the Study of Human Ingestive Behavior at Penn State, said the findings -- recently published in the journal Appetite -- support the MyPlate guidance from the U.S. Department of Agriculture, which recommends meals high in fruits and vegetables.

"It's important to serve your kids a lot of vegetables, but it's also important to serve them ones they like because they have to compete with the other foods on the plate," Rolls said. "Parents can ease into this by gradually exposing kids to new vegetables, cooking them in a way their child enjoys, and experimenting with different flavors and seasonings as you familiarize them."

According to the researchers, the majority of children in the U.S. don't eat the recommended daily amount of vegetables, which could possibly be explained by children having a low preference for them. And while serving larger portions has been found to increase the amount of food children eat -- called the "portion size effect" -- kids tend to eat smaller amounts of vegetables in response to bigger portions compared to other foods.

For this study, the researchers were curious if increasing just the amount of vegetables while keeping the portions of other foods the same would help increase veggie consumption in kids. They also wanted to experiment with whether adding light butter and salt to the vegetables would increase their palatability and also affect consumption.

For the study, the researchers recruited 67 children between the ages of three and five. Once a week for four weeks, the participants were served lunch with one of four different preparations of vegetables: a regular-sized serving of plain corn and broccoli, a regular-sized serving with added butter and salt, a doubled serving of plain corn and broccoli, and a doubled serving with added butter and salt.

During each meal, the vegetables were served alongside fish sticks, rice, applesauce and milk. Foods were weighed before and after the meal to measure consumption.

"We chose foods that were generally well-liked but also not the kids' favorite foods," Rolls said. "If you offer vegetables alongside, say, chicken nuggets you might be disappointed. Food pairings are something you need to be conscious of, because how palpable the vegetables are compared to the other foods on the plate is going to affect the response to portion size. You need to make sure your vegetables taste pretty good compared to the other foods."

After analyzing the results, the researchers found that while the larger portions of vegetables were associated with greater intake, the addition of butter and salt was not. The children also reported liking both versions -- seasoned and unseasoned -- about the same. About 76% of kids rated the vegetables as "yummy" or "just ok."

"We were surprised that the butter and salt weren't needed to improve intake, but the vegetables we served were corn and broccoli, which may have been already familiar to and well-liked by the kids," Diktas said. "So for less familiar vegetables, it's possible some extra flavoring might help to increase intake."

Diktas said that while serving larger portions may increase vegetable consumption, it also has the potential to increase waste if kids don't eat all of the food that is served.

"We're working on additional research that looks into substituting vegetables for other food instead of just adding more vegetables," Diktas said. "In the future, we may be able to give recommendations about portion size and substituting vegetables for other foods, so we can both limit waste and promote veggie intake in children."

GRAND RAPIDS, Mich. (June 24, 2021) -- The same taste-sensing molecule that helps you enjoy a meal from your favorite restaurant may one day lead to improved ways to treat diabetes and other metabolic and immune diseases.

TRPM5 is a specialized protein that is concentrated in the taste buds, where it helps relay messages to and from cells. It has long been of interest to researchers due to its roles in taste perception and blood sugar regulation.

Now, a team led by scientists at Van Andel Institute has published the first-ever high-resolution images of TRPM5, which reveal two areas that may serve as targets for new medications. The structures also may aid in the development of low-calorie alternative sweeteners that mimic sugar. The findings were published today in Nature Structural and Molecular Biology.

"TRPM5 is the cornerstone of taste signaling, which itself has a much larger role in the body than often recognized," said Wei Lü, Ph.D., an associate professor at VAI and co-corresponding author of the study. "We hope our structures of TRPM5 will serve as blueprints for designing new medications that help control blood sugar in diabetes, while also providing a template for development of low-calorie sweeteners that activate sensory circuits in the brain and the gut -- a key distinction that mimics sugar."

There are five types of taste that the body senses: sweet, sour, salty, bitter and umami. When the tongue encounters a taste, specialized cells on the tongue called taste receptors send messages about that taste to the brain. TRPM5 is a key part of the complex process that ushers these important signals on their way to the brain's sensory processing center.

But taste perception goes far beyond helping us sense the subtle flavors of a tiramisu. It helps protect the body by detecting bitter and acidic tastes, which commonly are associated with harmful substances. Taste perception also occurs beyond the tongue; for example, the process of taste perception in certain pancreatic cells regulates insulin secretion, which keeps blood sugar levels in check. Similar cells, called tuft cells, also coat the linings of the intestine, lungs and gallbladder, where they use TRPM5 and related proteins to sense the sugar-like byproducts of parasitic infections and trigger immune responses to deal with the threat.

"Targeting TRPM5 and taste-signaling throughout the body has two major potential benefits: it may help us improve treatment for a number of metabolic and immune disorders while also providing a path toward improved sweeteners," said Juan Du, Ph.D., an associate professor at VAI and co-corresponding author of the study. "While the body needs sugar to survive, too much of it can be harmful. We're hopeful a more thorough understanding of TRPM5 will lead to better alternatives."

TRPM5 belongs to the TRP superfamily, a group of proteins that mediate responses to sensory stimuli, such as pain, pressure, vision, temperature and taste. Broadly known as ion channels, proteins like TRP nestle within cells' membranes, acting as gatekeepers for chemical signals passing into and out of the cell. The eight proteins that comprise the TRPM subfamily are part of this broader group.

To date, Lü and Du laboratories have solved the structures of three of the eight known TRPM proteins as well as an ion channel called CALHM2, which belongs to the calcium homeostasis modulator family. Another member of this molecular family is CALHM1, also an important component of taste signaling.

Rude behavior at work has come to be expected, like donuts in the breakroom. Two decades of research on employee relationships shows that 98 percent of employees experience rude behavior at work, but now a new study suggests a large majority of workplace relationships are not characterized by rudeness. Isolated incidents of rude behavior at work, although somewhat common, do not point to widespread incivility between employees and their colleagues, according to a new UCF study.

"Because prior research suggests workplace mistreatment is harmful and widespread, it is often called an epidemic, but our findings show that rude behavior is less like the flu and more like cholera," says Shannon Taylor, an associate professor of management and co-author of the report. "It is still harmful, but far less common, and outbreaks are often traced to a single source - much like a contaminated water pump."

While the study was conducted prior to the COVID-19 pandemic, Taylor says his team's findings are just as applicable to remote work environments. Collaborating remotely presents a variety of challenges that can lead to miscommunication and misinterpretation.

"As employees return to work on-site, our study suggests developing and maintaining good relationships with co-workers is important now more than ever," Taylor says.

The study, co-authored by UCF doctoral student Lauren Locklear, was published this month in the Journal of Applied Psychology. The project takes a closer look at the influence of workplace relationships on disrespectful behavior in the office.

The study examined rude behavior among restaurant, manufacturing, and office workers. Researchers found that while most employees experience rudeness at work, these experiences came from a small number of co-workers. Although 70% of employees experienced rudeness at work, only 16 percent of workplace relationships were characterized by rude behavior.

An employee's individual personality, position and other traits are major factors in determining the level of incivility present in a given workplace. Across all study groups, researchers found that unique relationships between colleagues have just as strong an influence in determining whether workers will be rude to one another.

"Even if one employee is a jerk to everyone and their co-worker is the office punching bag, there is still something about their unique relationship that explains how well they get along together," Taylor says. "Most people do experience rude behavior, but most of their relationships are not characterized by rudeness."

Behavioral expectations and workplace culture also play a key role in influencing employee mistreatment. But an employee's perceptions about how their colleagues should treat each other have a stronger impact on rude behavior than an employee's perceptions about how their colleagues actually treat each other.

"Employees' beliefs about what is 'right and wrong' at work have a big impact on what happens on the job," says Locklear. "Employers should ensure there are strong norms for respect and civility in the workplace. Having a zero-tolerance policy for these rude behaviors is key to stopping mistreatment in its tracks."

Being clear and encouraging positive interactions will be key, the study's authors say.

"Our prior work shows gratitude and appreciation are important aspects to fostering positive employee relationships and decreasing negative workplace behavior," Locklear says. "Expressing these positive behaviors will be essential in determining how smoothly we return to in-person work environments."