Culture

A pioneering study, published in Scientific Reports, found that the Parkinon's gene PINK1 is important for the generation of dopamine-producing neurons throughout life, and is not just responsible for the premature death of these neurons
The international research, led by University of Sheffield's Neuroscience Institute, used two model systems to examine how neurons are produced throughout our lifetime
Parkinson's disease is a relentlessly progressive neurodegenerative disorder that affects around 145,000 people in the UK
A gene defect linked to Parkinson's disease may not only cause the early death of neurons, but also impair the process that generates neurons in the brain throughout our lifetime, a new study has revealed.

The international study, led by the University of Sheffield's Neuroscience Institute, may have a significant impact on the future treatment of Parkinson's patients who develop the illness due to PINK1 defect or similar gene defects.

The development of novel treatments and therapies to slow down disease progression, halt or reverse Parkinson's may now focus on enhancing the generation of new dopamine-producing neurons, rather than just trying to protect these neurons from dying later.

The findings, published today (23 March 2021) in Scientific Reports, used two model systems to measure how inactivation of the PINK1 gene affects dopamine-producing neurons in the adult brain.

Dopamine-producing neurons are the most severely affected brain cells in Parkinson's disease. It is typically thought that Parkinson's genes, such as PINK1, cause early death of these neurons, with symptoms developing when neuron numbers fall. However, here, researchers found that a deficiency in PINK1 resulted in fewer dopamine-producing neurons being made throughout life.

Professor Oliver Bandmann, Professor of Movement Disorders Neurology at the Sheffield Institute for Translational Neuroscience (SITraN), said: "Neurogenesis is the process by which new neurons are formed in the brain. Recent evidence suggests that this process is ongoing throughout life but the relevance of this is poorly understood in neurodegenerative disorders such as Parkinson's disease."

"We know that mutations in the PINK1 gene cause an early onset, inherited form of Parkinson's disease. If we can further our understanding about the impact of this genetic mutation on the dopamine-producing neurons we can develop new therapeutic approaches that aim to mitigate those effects."

In collaboration with the University of Luxembourg, researchers used two complementary model systems to examine how neurons are reproduced throughout our lifetime.

Professor Marysia Placzek, Professor of Developmental Neurobiology in the Department of Biomedical Science, said: "This study attests to the power of using simple model organisms for pre-clinical translational research. We used the zebrafish to demonstrate that dopamine-producing neurons are generated into adulthood at a rate that decreases with age and that PINK1-deficiency impairs neurogenesis of these neurons, significantly in early adult life. Our international collaborators then confirmed these results in a human organoid cell model."

The observation of impaired adult dopaminergic neurogenesis in PINK1 deficiency in two complementing model systems may have significant consequences for future therapeutic approaches in Parkinson's disease. Future research will aim to identify the precise mechanisms that link Parkinson's genes to neurogenesis. This will allow us to explore the development of gene therapy or small molecule approaches to enhance neurogenesis in the brain of patients with Parkinson's. The development of new therapies for brain diseases like Parkinson's is the main focus of the Sheffield Institute for Translational Neuroscience (SITraN).

The research was funded by the Medical Research Council (MRC), Parkinson's UK and the Wellcome Trust.

Parkinson's disease is the second most common neurodegenerative disease, with approximately 10 million people affected worldwide. Currently, only symptomatic treatment options are available to patients.

The University of Sheffield launched a sustained fundraising effort for Parkinson's disease research at the end of 2019. Since then, Sheffield staff, students, alumni and the general public have come together to raise more than £350,000 so far. The ongoing efforts of this campaign are set to continue as Sheffield dedicates itself to backing the next breakthrough.

Uncovering detailed travel patterns and habitat use of sharks along and across shelf territories has been historically challenging - especially for most pelagic shark species - which remain offshore for most of their lives. Their vertical diving behavior has been a subject of inquiry for a long time, and for young sharks in particular, has remained elusive.

Using cutting-edge 3D satellite technology, a study led by Florida Atlantic University's Harbor Branch Oceanographic Institute, in collaboration with NOAA's National Marine Fisheries Service; OCEARCH; The South Fork Natural History Museum and Nature Center; and the Wildlife Conservation Society, is providing a unique look into how young white sharks in the North Atlantic Ocean travel and use their habitats. The study also is the first to provide fine-scale analysis of vertical movement behavior in young-of-year (1 to 2 years) and juvenile white sharks (Carcharodon carcharias) in the New York Bight, the only confirmed white shark nursery area in the entire North Atlantic Ocean.

Results published in the journal Frontiers in Marine Science, showed that across multiple years, the tagged young white sharks consistently displayed horizontal movements parallel to Long Island's southern shoreline and the New Jersey coast and likely cling to these waters due to their summertime productivity. Horizontal movements ranged from the surf zone to more than 130 kilometers from shore; however, more than 90 percent of the sharks were positioned within 20 kilometers of Long Island's southern shoreline, which further confirms the importance of this region to baby white sharks.

Data from the study simultaneously address many questions on the ecology, behavior and conservation of a highly mobile marine species that has been challenging to explore, and will inform ongoing preservation strategies for this vulnerable white shark population.

"We have known about the importance of nurseries for young sharks for some time, however, knowledge of the finer scale use of shelf systems by these animals has been limited. This lack of information impacts our understanding of potential shark 'hotspots' within these large ecosystems," said Rachel Shaw, lead author, and a recent graduate from the Fisheries Ecology and Conservation (FEC) Lab, led by Matt Ajemian, Ph.D., co-author and an assistant research professor at FAU Harbor Branch.

Between 2016 and 2019, 21 young-of-year and juvenile white sharks were fitted with satellite and acoustic tags to examine their distribution and habitat selection during late summertime (August to October) in the New York Bight - the coastal region between Montauk, New York and Cape May, New Jersey. Movement data from the 21 young white sharks were collected (11 males and 10 females ranging in size from 54 to 61 inches in length) and linked to environmental measurements from remote sensing platforms.

These data sets produced the first-ever glimpse into the 3D movements for these young white sharks alongside oceanographic features like bathymetry (submarine topography), sea surface temperature, chlorophyll-a levels, and sea surface salinity.

"Undoubtedly, our research shows that young white sharks traverse variable oceanographic features across the continental shelf in the New York Bight, but they certainly have their habitat preferences," said Shaw.

The vertical diving behavior and accompanying measurements showed that sharks encountered several areas across the shelf with thermally stratified water column structure. This was most evident around the Hudson Shelf Valley region where some of the coldest bottom temperatures were recorded during the summertime, and is indicative of the "cold pool" that sets up in this region. Further, young white sharks also selected areas with relatively high levels of productivity (i.e., mesotrophic waters) as reflected by salinity and chlorophyll-a concentration. Tagged individuals selected sea surface salinities slightly less saline than oceanic waters, which are typically associated with coastal areas.

Altogether, the research suggests young white sharks prefer nearshore habitats, but can exhibit connectivity between the immediate shoreline and mid-continental shelf region, where they play important ecological roles as apex predators on a variety of species. The study improves characterization of essential habitat for young white sharks and provides new insights into their reliance on this productive continental shelf ecosystem, which may provide them with the resources needed to grow quickly as well as a refuge from predators.

"While the northwest Atlantic white shark population appears to be recovering from historical overfishing, there is considerable uncertainty in their population dynamics, seasonal habitat preferences, ecological roles, and exposure to environmental impacts," said Ajemian. "Understanding species-habitat relationships is critical for predicting the potential impacts of long-term environmental changes including climate change, which is disproportionately affecting this region."

More extroverted people suffered mood declines while more introverted people saw mood improvements during the early COVID-19 pandemic, in survey of students at a U.S. university.

In Slovakia, in counties subject to two rounds of rapid antigen testing for SARS-CoV-2 where those who tested positive then isolated, the approach helped decrease the prevalence of positive tests by more than 50% in a week - all while primary schools and workplaces remained open. "While it was impossible to disentangle the precise contribution of control measures and mass testing," the authors said, mass testing is likely to have had a substantial effect, their modeling showed. Applying mass testing may provide a valuable tool in future containment of SARS-CoV-2 elsewhere, they say. Compared to mandating closure of schools and non-essential businesses, which has had an unprecedented economic effect worldwide during the COVID pandemic, mass testing campaigns for SARS-CoV-2 - which can be conducted while such places remain open - are an alternative way to identify and target infectious individuals without much added burden to those who are not infectious. In October and November 2020, to identify cases at scale and rapidly reduce transmission, in order to ease the conditions of lockdown, Slovakia used rapid antigen tests in a campaign targeting the whole population. More than five million rapid antigen tests were conducted in a pilot, a first round of national testing, and in a second round targeted to high prevalence counties. More than 50,000 participants tested positive. Combining the pilot results with the ones from the two rounds of testing, each round of mass testing was estimated to have reduced observed infection prevalence by 56%, say Martin Pavelka et al. The 41 counties with two rounds of testing likely reduced infection prevalence by 81% within two weeks. Further modelling by Pavelka et al. suggests the observed reductions could not be explained solely by infection control measures but required the additional impact of isolation of those who tested positive. "The observational nature of this study made it difficult to separate the effects of the mass testing campaigns from the other non-pharmaceutical interventions introduced over the same period," say the authors. "Nevertheless, a greater than 50% decline in infection prevalence within one week is striking, particularly while primary schools and workplaces were mostly open." For comparison, a month-long lockdown in November in the United Kingdom led to just a 30% decrease in prevalence.

BEER-SHEVA, Israel, March 23, 2021 - Ben-Gurion University of the Negev (BGU) researchers have found that the Pfizer Coronavirus vaccine is moderately less effective against the South African variant, but still neutralizes the British variant and the original SARS-CoV-2 strain.

Their research was just published in the prestigious journal Cell Host and Microbe.

"Our findings show that future variants could necessitate a modified vaccine as the virus mutates to increase its infectivity," says principal investigator Dr. Ran Taube of the Shraga Segal Department of Microbiology, Immunology and Genetics in the Faculty of Health Sciences.

The BGU scientists evaluated the vaccine effectiveness against the original viral strain, the British and the South African variants, as well as strains that harbor combined changes in the viral spike.

Dr. Taube and his team also evaluated neutralizing antibody levels following administration of one and two vaccine doses. They found that vaccination provided optimal protection when compared with the levels observed in recovered patients. The researchers are continuing to test other circulating variants as they emerge, consisting of mutations that could possibly compromise the vaccine.

Glioma is a fatal neurological disorder that has limited interventional treatment, despite extensive research over the past several decades. A research team led by Dr. Gong Chen, a former professor at Penn State University and now leading a brain repair center at Jinan University in China, has developed a novel gene therapy to reprogram glioma cells into functional neurons, shedding new light on glioma treatment. The work has been published in Cancer Biology & Medicine on March 22, 2021

Glioma is a common malignant cancer growing in the central nervous system. For patients with a type of severe glioma called glioblastoma, the median survival time is typically less than 15 months. Surgical removal followed with chemotherapy and/or radiation therapy are the major ways of treatment but their effectiveness is limited. Several clinical trials are ongoing using engineered immune cells to target primary or recurrent glioma, but still meet with serious hurdles to be solved.

Glioma is caused by aggressive proliferation of glial cells. Chen's team has previously published a series of work demonstrating that brain internal glial cells can be directly converted into functional neurons after overexpressing neural transcription factors such as NeuroD1 and Dlx2. In this work, the team further extended their research from glial cells to glioma cells and discovered that neural transcription factors can also efficiently convert glioma cells into neurons.

"Our cell conversion therapy for glioma is quite unique and distinct from conventional cancer therapies that typically aim at killing cancer cells," commented by Prof. Chen. "One major side effect caused by killing cancer cells is the inevitable collateral damage on normal cells. In contrast, when we use gene therapy technology to convert glioma cells into neurons, normal cells are minimally affected", Prof. Chen explained why they developed this new technology.

"Another important advantage of our gene therapy approach is that after overexpressing neural transcription factor(s) such as NeuroD1 or other transcription factors into glioma cells, the glioma cells stop proliferation immediately before being converted into neurons. Therefore, this transcription factor-based gene therapy may provide a new strategy to prolong the time window of treatment by arresting rapid proliferation of malignant glioma cells," added Dr. Xin Wang, the first author of this work.

While excited about their new findings, Prof. Chen and colleagues also acknowledge that this new technology of treating glioma with transcription factor-based gene therapy is still in its infant stage. Many technical issues still need to be considered, such as developing a safe viral delivery system, targeting glioma cells in a specific way, and potential side effects induced by neural transcription factors. They also plan to combine their cell conversion therapy together with other interventions to achieve synergistic effects to treat glioma.

Scientists have developed a pioneering new procedure that will help diagnose a potentially lethal fungal lung disease with greater speed and accuracy, and with less distress to the patient.

A team of international scientists, including Professor Chris Thornton from the University of Exeter, has created a new diagnostic procedure for pulmonary aspergillosis.

Aspergillus is a common mold readily found worldwide in a variety of environments, such as soil and decaying plant material, and can easily be inhaled as air-borne spores in everyday life.

While people with healthy immune systems are able to combat these spores when inhaled, those who have a weakened immune system from illness or medications have fewer infection-fighting cells. This allows Aspergillus to take hold, invading the lungs and, in the most serious cases, other parts of the body.

For COVID-19 patients admitted in intensive care units in particular, the infection has become a significant problem - an estimated 30 percent of them develop COVID-19-Associated Pulmonary Aspergillosis.

The diagnosis of the infection is extremely difficult, and current diagnostic procedures are unpleasant for the already weakened patients. Medical professionals rely on highly invasive techniques such as lung biopsies or broncho-alveolar lavages - where fluid is injected directly into the lungs through the nose or mouth.

Now, the team of researchers have conducted a study, using a mouse model of infection, and utilizing a patent-pending Aspergillus-specific monoclonal antibody, JF5, developed by ground-breaking University of Exeter spin-out company, ISCA Diagnostics.

The research shows that the humanised JF5 antibody can specifically and rapidly recognize the infection in the lungs of infected animals without the need for the invasive procedures.

Using a radiotracer injected only intravenously, advanced molecular imaging techniques developed at the University of Tübingen were able to provide a rapid and specific diagnosis of the disease while allowing for precise monitoring of therapy.

The imaging results were then be complemented by 3D microscopy performed at the University of Duisburg-Essen, which underlined the accuracy of the developed imaging method with a precise (quantitative) evaluation of the infection.

This innovative dual approach proved that all sites of infection could be accurately uncovered, a crucial step to not only provide an estimate of the severity of the infection, but also as a first step in monitoring the success of its treatment.

The researchers demonstrated the potential of therapy monitoring using molecular imaging during administration of the front-line antifungal drug Voriconazole.

Professor Thornton, an expert in Fungal Immunology at the University of Exeter and co-author of the published work said: "This highly innovative and ground-breaking diagnostic technology is a step-change in the way we diagnose this devastating disease of immunocompromised patients, eliminating our current reliance on unpleasant invasive procedures."

"We strongly expect," says Dr. Nicolas Beziere of the Department of Preclinical Imaging and Radiopharmacy at Tübingen University Hospital and senior author of the study, "that the performance of the newly developed radiotracer will be similar in humans and hope that future clinical trials will show a highly positive impact on survivability with a far lower risk and higher comfort for the patient."

Serious complications due to blood clots, such as heart attacks and strokes, that are experienced by some COVID-19 survivors may be caused by a lingering immune response in the blood vessels after recovery, suggests a study published today in eLife.

The findings may help explain why some COVID-19 survivors, so-called 'long-haulers', report lasting COVID-19 symptoms or why some experience strokes or heart attacks weeks or months after recovery. They may also suggest potential strategies to help prevent these complications.

"During the initial stages of infection, SARS-CoV-2, the virus that causes COVID-19, may attack the lining of the blood vessels which can trigger inflammation and an immune response. This can result in blood vessel damage in the short term," explains first author Florence Chioh, Research Assistant at the Lee Kong Chian School of Medicine (LKCMedicine), Nanyang Technological University, Singapore. "For our study, we wanted to investigate what happens in the blood vessels of COVID-19 survivors over the longer term."

Chioh and colleagues collected blood samples from COVID-19 survivors within a month of their recovery and discharge from the hospital. They found that, in comparison with healthy individuals, COVID-19 survivors have twice as many damaged blood vessel cells, called circulating endothelial cells, floating in their blood. Even more of these damaged blood vessel cells were found in survivors who had conditions such as hypertension or diabetes that can also damage the blood vessels.

In addition to signs of blood vessel damage, the team found that survivors had an abundance of inflammatory proteins called cytokines that are produced by immune cells. They also found unusually high numbers of immune cells called T cells, which help destroy viruses, despite the fact that the virus was already gone.

"We show that an overactive immune system is the likely cause of blood vessel damage seen in some COVID-19 survivors," Chioh says. "This may cause 'leakiness' in the blood vessels that increases the risk of blood clots."

"Our work suggests that COVID-19 patients, especially those with underlying chronic conditions, may benefit from close post-recovery monitoring," adds senior author Christine Cheung, Assistant Professor and Provost's Chair in Medicine at LKCMedicine. "This would help identify high-risk individuals who may need blood thinners or preventative therapy to protect them from debilitating blood-clotting complications."

A study of young men with COVID-19 has revealed a genetic variant linked to disease severity.

The discovery, published recently in eLife, means that men with severe disease could be genetically screened to identify who has the variant and may benefit from interferon treatment.

For most people, COVID-19, the disease caused by the virus SARS-CoV-2, causes only mild or no symptoms. However, severe cases can rapidly progress towards respiratory distress syndrome.

"Although older age and the presence of long-term conditions such as cardiovascular disease or diabetes are known risk factors, they alone do not fully explain differences in severity," explains first author Chiara Fallerini, Research Fellow in Medical Genetics at the Department of Medical Biotechnologies, University of Siena, Italy. "Some younger men without pre-existing medical conditions are more likely to be hospitalised, admitted to intensive care and to die of COVID-19, which suggests that some factors must cause a deficiency in their immune system."

Recent research has suggested that genes controlling interferon are important in regulating the immune response to COVID-19. Interferon is produced by immune cells during viral infection. It works alongside molecules on the surface of immune cells called Toll-like receptors (TLR) which detect viruses and kickstart the immune response. "When a recent study identified rare mutations in a TLR gene, TLR7, in young men with severe COVID-19, we wanted to investigate whether this was an ultra-rare situation or just the tip of the iceberg," says co-senior author Mario Mondelli, Professor of Infectious Diseases at the Division of Clinical Immunology and Infectious Diseases, Fondazione IRCCS Policlinico San Matteo and University of Pavia, Italy.

The team studied a subset of 156 male COVID-19 patients younger than 60 years old, selected from a large multicentre study in Italy, called GEN-COVID, which started its activity on March 16, 2020. GEN-COVID is a network of more than 40 Italian hospitals coordinated by co-senior author Alessandra Renieri, Full Professor of Medical Genetics at the University of Siena, and Director of Medical Genetics at Azienda Ospedaliero-Universitaria Senese, Siena, Italy.

The team first analysed all the genes on the X chromosome of men with both mild and severe cases of COVID-19, and identified the TLR7 gene as one of the most important genes linked to disease severity. They then searched the entire GEN-COVID database, and selected for younger men (less than 60 years old). This identified rare TLR7 missense mutations in five of 79 patients (6.3%) with life-threatening COVID-19 and no similar mutations in the 77 men who had few symptoms. They also found the same mutation in three men aged over 60: two who had severe COVID-19 and one who had few symptoms - although the mutation found in the man with few symptoms had little effect on TLR function.

To link these mutations to the immune cell response, they treated white blood cells from recovered patients with a drug that switches TLR7 genes on. They found that the TLR7 genes were dampened down in immune cells from patients with mutations, compared to the TLR7 activity seen in normal immune cells. They also found lower levels of interferon in the cells containing the mutation compared to normal white blood cells. This confirmed that the mutations identified directly affect the control of interferon as part of the innate immune response.

To confirm the impact of the mutations on COVID-19 response, the team studied two brothers, one with a mutation in an interferon gene and one without. The levels of interferon gene activity were much lower in the man with the missense mutation, compared with his brother. Moreover, the brother with the mutation had severe COVID-19, while his brother with normal interferon genes was asymptomatic.

"Our results show that young men with severe COVID-19 who have lost function in their interferon-regulating genes represent a small but important subset of more vulnerable COVID-19 patients," says co-senior author Elisa Frullanti, Researcher of Medical Genetics at the University of Siena.

Co-senior author Alessandra Renieri adds: "These mutations could potentially account for disease severity in up to 2% of young men with COVID-19. We believe that screening for these mutations in men who are admitted with severe disease and promptly treating them with interferon could prevent more deaths."

New research from Copenhagen Business School finds sexual harassment in the workplace severely hurts company value.

"Sexual harassment has serious consequences for the victim. But it is also something managers and investors should be interested in for purely financial reasons, as it can wipe off enormous amounts of market value in a matter of days," says Associate Professor Ulf Nielsson from the Department of Finance at Copenhagen Business School.

The research found that the stock market value of a listed company drops by 1.5% following sexual harassment reports, which corresponds to an average impact of $450m million for the companies. In the long term the affected firms recovered only about half of that lost value.

The study looked at nearly 200 sexual harassment incidents, many of them taking place in well-known companies such as Disney, Tesla, Amazon, Google, and Facebook, financial firms like Goldman Sachs and Morgan Stanley, and popular media brands such as The New York Times, Fox, and CBS.

The researchers found that this was amplified if the CEO was involved. If the incident received high news coverage, then the effect could be up to 6.5% of the share price, whereas the impact was mitigated if the firm itself reported on the incident before the media attention.

The study is published in the Journal of Corporate Finance.

New insight

To assemble their data the researchers scoured through English-language news archives from January 2005 to February 2019 in the Nexis Uni research database to identify sexual harassment incidents, ranging from verbal abuse comments to unwanted physical advances and forced sexual relations. Moreover, they made a combined Nexis Uni and Google News search from Standard & Poor's 500 Index companies.

This returned almost 200 incidents worldwide with 78% of the scandals taking place in the USA. They also identified it was a female who came forward to report the harassment in 88% of all cases.

In contrast to the fields of psychology and sociology, which have widely documented the negative consequences of sexual harassment on the individual, the instant impact of sexual harassment on company value has not been separately studied. Moreover, sexual harassment scandals are different from typical corporate scandals such as fraud or labour violations in that they are arguably not motivated by profit or monetary betterment.

"This research moves things forward by offering new insight into quantifying the size of the financial impact a sexual harassment scandal has on company value," adds Ulf Nielsson.

The bottom line

The researchers recommend that it makes good business sense for companies to have a preventive strategy in place as sexual harassment is a real business risk and the impact is economically significant. The potential detrimental impact will justify considerable cost and effort from businesses to prevent such cases occuring and to react swiftly and firmly if they do happen.

"Companies need to realise that it is also in their benefit (not only in the victim's benefit) to prevent and react to incidents of sexual harassment as this ultimately affects their bottom line," concludes Ulf Nielsson.

Maps generally indicate elevation in meters above sea level. But sea level is not the same everywhere. A group of experts headed by the Technical University of Munich (TUM), has developed an International Height Reference System (IHRS) that will unify geodetic measurements worldwide.

How high is Mount Everest? 8848 meters? 8844 meters? Or 8850 meters? For years, China and Nepal could not agree. In 2019, Nepal sent a team of geodesists to measure the world's highest mountain. A year later a team from China climbed the peak. Last December the two governments jointly announced the outcome of the new measurement: 8848.86 meters.

The fact that both China and Nepal recognize this result must be seen as a diplomatic success. It was made possible by the new International Height Reference System (IHRS), used for the first time by the geodetic specialists conducting the new measurement. Scientists from TUM played a leading role in developing the new system. It establishes a generally agreed zero level as a basis for all future measurements. It thus replaces the mean sea level, which has traditionally served as the zero level for surveyors and thus for all topographical maps. A paper in the Journal of Geodesy, jointly authored by TUM scientists and international research groups, outlines the scientific background and theoretical concept of the IHRS as well as the strategy for implementing it.

When zero is not always zero

The standard used until now - the mean sea level - was flawed from the outset: There was never a fixed definition. Every country could use arbitrary tide gauges to define its own zero level. As a result, Germany's official sea level is 31 centimeters higher than Italy's, 50 cm higher than that used in Spain and actually 2.33 m higher than in Belgium, where the zero height is based on low water in Ostend.

When topographical maps are only used for hiking, no one is bothered by such differences. But for geodetics specialists trying to arrive at a universally agreed height - for Mount Everest, for example, half in Nepal and half in China - the inconsistent zero levels are a bigger problem. And it can be very costly when planners of cross-border structures such as bridges and tunnels forget to check the different coordinates used by the teams and convert them as needed. On the Hochrheinbrücke, a bridge connecting Germany and Switzerland, a discrepancy of this kind was noticed just in time.

Surveys from orbit

"The introduction of an internationally valid height reference system was long overdue," says TUM researcher Dr. Laura Sánchez of the Deutsches Geodätisches Forschungsinstitut (DGFI-TUM), who has headed working groups studying theoretical aspects and implementing the new global height reference system at the International Association of Geodesy for several years.

What is needed is obvious: a universally accepted zero level. The new International Height Reference System (IHRS) defines how it can be calculated: It takes into account the shape of the Earth - which is close to spherical, but flattened at the poles and bulging slightly at the equator due to its rotation - and the uneven distribution of masses in the interior and on the surface. The resulting irregularities in the gravity field are the basis for calculating the height system because the strength and direction of the force determine the distribution of water in the oceans. If we assume that the Earth's surface is completely covered with water, the height of a hypothetical sea level and thus the zero level for the entire globe can be calculated precisely.

In construction projects, even the smallest deviations can be crucial

"It became possible to realize the IHRS only with the availability of global data from satellite missions such as the ESA earth observation satellite GOCE (Gravity field and steady-state Ocean Circulation Explorer)," says Prof. Roland Pail of the TUM Chair of Astronomical and Physical Geodesy (APG). His team played an integral role in analyzing the GOCE measurements and using them to calculate global models of the Earth's gravity field. "The information gained in this way provides the basis to calculate the mean sea level for every point on Earth with the new International Height Reference System, regardless of whether it is on a continent or in an ocean, and thus to compute the internationally accepted zero level," explains Sánchez.

Does every map have to be redrawn? "It won't be that dramatic," says Sánchez. "In the industrial countries, where they have been making gravity measurements for decades, the deviations are quite small - only in the decimeter range." But with construction projects, for example, even small deviations can cause serious troubles. Consequently, the scientist is confident that the new reference system will gain acceptance quickly.

WINSTON-SALEM, N.C. - March 22, 2021 - The fear, anxiety and stress associated with the COVID-19 pandemic has taken a toll on mental health. But a new study suggests these symptoms may be alleviated through safe and convenient online mindfulness practices.

The study, which was recently published in the journal Global Advances in Health and Medicine, shows that an online mindfulness intervention may reduce momentary stress, anxiety and COVID-19 concern.

At the onset of the pandemic, Rebecca Erwin Wells, M.D., M.P.H., associate professor of neurology at Wake Forest School of Medicine, part of Wake Forest Baptist Health, and principal investigator for this study, recognized the tremendous impact of this pandemic on emotional health and wanted to evaluate how a safe, online mindfulness meditation strategy might help.

In creating this study, Wells was inspired by Mindfulness for Milan, a program created by co-author Licia Grazzi, M.D., an Italian physician who led free daily mindfulness sessions to help the public manage stress and anxiety during lockdown.

Mindfulness means maintaining a moment-by-moment, non-judgmental awareness of thoughts, feelings, bodily sensations and surrounding environment.

"We are all born with the capacity for mindfulness," said Wells. "It can help reduce stress and anxiety, and mindfulness meditation practice can help enhance this ability."

There were 233 participants from across the world in this non-randomized clinical trial, which included a pre-session survey, a single 15-minute online mindfulness meditation session and a post-session survey. The study ran from March to August 2020. Pre- and post-session surveys evaluated momentary stress, anxiety and COVID-19 concern. Most of the participants (63%) had never practiced mindfulness before, and 89% of participants said the session was helpful, and that the online platform was effective for practicing mindfulness. 76% of participants reported decreased anxiety, 80% reported decreased stress, and 55% had decreased COVID-19 concern. Of note, 21% of participants were retired, suggesting that age did not prevent accessibility.

Participants were also surveyed on how they were helping others during the pandemic. Responses varied with common themes including following public health guidelines, conducting acts of service and connection such as reaching out to elderly neighbors, and self-care activities such as staying positive and calm.

Investigators also assessed online mindfulness resources across time during the pandemic and found a 52% increase in search results of "Mindfulness + COVID" from May to August 2020. "People are searching for ways to help target the stress and anxiety of the pandemic," Wells said. "Mindfulness teachers and programs have expanded offerings, eliminated fees, and converted offerings to online to meet this huge need."

According to Wells, the study shows that a virtual platform can be effective for practicing mindfulness.

"We found that online mindfulness interventions may improve psychological health at a time of uncertainty. We were also encouraged by the survey responses, which showed a sense of connectedness and a desire to help others," Wells said. "Helping others during the pandemic demonstrates the beautiful capacity of the human spirit to find positivity despite the extraordinary negative circumstances."

Wells said that additional research is needed to evaluate the pandemic's effects on post-traumatic growth, the positive psychological change experienced following a challenging life circumstance.

Fatigue, depression, sleep disorders, burnout: the number of cases where employees are unable to work for mental health-related reasons has increased dramatically in recent years. Professor Sascha Alavi, Chair at the Sales Management Department (SMD), has long been keeping a critical eye on this development in society, especially in the corporate world. Together with his former PhD student Dr. Kim Linsenmayer and Professor Johannes Habel from the University of Houston, Alavi has now demonstrated in the Journal of Marketing the negative effects that pressure in the form of performance-based remuneration schemes can have on health. Rubin, the science magazine from RUB, reports on this.

In a field experiment, the research team studied a medium-sized company in Germany that sells consumer goods, tools and services to customers in the construction and automotive industries. Over a period of twelve months, the team monitored the transition of the company's remuneration model from 80 per cent variable to 80 per cent fixed remuneration and analysed the data of more than 800 employees for this purpose. The result of their time series analysis: stronger performance incentives go hand in hand with more sick days.

The J-effect

"If the percentage of variable remuneration in total salary increases, this initially has a positive effect on employee performance," points out Alavi. The incentive provided by sales commissions and bonus payments is motivating. However, the empirical data also show that as variable pay increases, so do stress levels. "This in turn results in more sick leave and reduced performance," as Alavi elaborates the J-shaped progression of the curve. "We call this the J-effect," the economist continues. When variable remuneration accounts for about 30 per cent of total remuneration, the pressure to perform increases rapidly and performance decreases. "Our data thus reflect that incentive schemes in the form of variable remuneration can have harmful consequences on health. They can create stress and insecurity and thus generate pressure," the researcher concludes.

Pressure to perform leads to emotional exhaustion

In subsequent studies, the research team confirmed the observed J-effect and expanded on existing stress theories. For example, a survey of 400 salespeople from different companies and industries found that an increase in variable remuneration is also associated with an increase in emotional exhaustion. "Above a share of variable remuneration of about 30 per cent of total remuneration, the survey participants increasingly reported suffering from symptoms of fatigue, feeling drained, burnt out, frustrated or tired at the end of a workday or workweek", Alavi explains.

Coping strategies

The survey results also show that there are differences between individual employee groups. Not everyone finds the performance incentives stressful; some remain unaffected. In particular, employees who had very specific personal, mental and social skills or considerable experience were more resilient. "The pressure to perform is less of a problem for those who, for example, have delivered fairly consistent performance in the past or have many years of work experience," as Alavi explains the finding. Employees who maintain a good relationship with their supervisor and team also cope better with increased pressure levels. "The pressure to perform is less of a problem for those who, for example, have delivered fairly consistent performance in the past or have many years of work experience," as Alavi explains the finding. Employees who maintain a good relationship with their supervisor and team also cope better with increased pressure levels. The results thus can also be used to draw pragmatic conclusions and recommendations for managerial circles.

The possibly oldest cephalopods in the earth's history stem from the Avalon Peninsula in Newfoundland (Canada). They were discovered by earth scientists from Heidelberg University. The 522 million-year-old fossils could turn out to be the first known form of these highly evolved invertebrate organisms, whose living descendants today include species such as the cuttlefish, octopus and nautilus. In that case, the find would indicate that the cephalopods evolved about 30 million years earlier than has been assumed.

"If they should actually be cephalopods, we would have to backdate the origin of cephalopods into the early Cambrian period," says Dr Anne Hildenbrand from the Institute of Earth Sciences. Together with Dr Gregor Austermann, she headed the research projects carried out in cooperation with the Bavarian Natural History Collections. "That would mean that cephalopods emerged at the very beginning of the evolution of multicellular organisms during the Cambrian explosion."

The chalky shells of the fossils found on the eastern Avalon Peninsula are shaped like a longish cone and subdivided into individual chambers. These are connected by a tube called the siphuncle. The cephalopods were thus the first organisms able to move actively up and down in the water and thus settle in the open ocean as their habitat. The fossils are distant relatives of the spiral-shaped nautilus, but clearly differ in shape from early finds and the still existing representatives of that class.

"This find is extraordinary," says Dr Austermann. "In scientific circles it was long suspected that the evolution of these highly developed organisms had begun much earlier than hitherto assumed. But there was a lack of fossil evidence to back up this theory." According to the Heidelberg scientists, the fossils from the Avalon Peninsula might supply this evidence, as on the one hand, they resemble other known early cephalopods but, on the other, differ so much from them that they might conceivably form a link leading to the early Cambrian.

The former and little explored micro-continent of Avalonia, which - besides the east coast of Newfoundland - comprises parts of Europe, is particularly suited to paleontological research, since many different creatures from the Cambrian period are still preserved in its rocks. The researchers hope that other, better preserved finds will confirm the classification of their discoveries as early cephalopods.

The research results about the 522 million-year-old fossils were published in the Nature-journal "Communications Biology". Logistic support was given by the province of Newfoundland and the Manuels River Natural Heritage Society located there. The publication in open-access format was enabled in the context of Project DEAL.

In the hours after we die, certain cells in the human brain are still active. Some cells even increase their activity and grow to gargantuan proportions, according to new research from the University of Illinois Chicago.

In a newly published study in the journal Scientific Reports, the UIC researchers analyzed gene expression in fresh brain tissue -- which was collected during routine brain surgery -- at multiple times after removal to simulate the post-mortem interval and death. They found that gene expression in some cells actually increased after death.

These 'zombie genes' -- those that increased expression after the post-mortem interval -- were specific to one type of cell: inflammatory cells called glial cells. The researchers observed that glial cells grow and sprout long arm-like appendages for many hours after death.

"That glial cells enlarge after death isn't too surprising given that they are inflammatory and their job is to clean things up after brain injuries like oxygen deprivation or stroke," said Dr. Jeffrey Loeb, the John S. Garvin Professor and head of neurology and rehabilitation at the UIC College of Medicine and corresponding author on the paper.

What's significant, Loeb said, is the implications of this discovery -- most research studies that use postmortem human brain tissues to find treatments and potential cures for disorders such as autism, schizophrenia and Alzheimer's disease, do not account for the post-mortem gene expression or cell activity.

"Most studies assume that everything in the brain stops when the heart stops beating, but this is not so," Loeb said. "Our findings will be needed to interpret research on human brain tissues. We just haven't quantified these changes until now."

Loeb and his team noticed that the global pattern of gene expression in fresh human brain tissue didn't match any of the published reports of postmortem brain gene expression from people without neurological disorders or from people with a wide variety of neurological disorders, ranging from autism to Alzheimer's.

"We decided to run a simulated death experiment by looking at the expression of all human genes, at time points from 0 to 24 hours, from a large block of recently collected brain tissues, which were allowed to sit at room temperature to replicate the postmortem interval," Loeb said.

Loeb and colleagues are at a particular advantage when it comes to studying brain tissue. Loeb is director of the UI NeuroRepository, a bank of human brain tissues from patients with neurological disorders who have consented to having tissue collected and stored for research either after they die, or during standard of care surgery to treat disorders such as epilepsy. For example, during certain surgeries to treat epilepsy, epileptic brain tissue is removed to help eliminate seizures. Not all of the tissue is needed for pathological diagnosis, so some can be used for research. This is the tissue that Loeb and colleagues analyzed in their research.

They found that about 80% of the genes analyzed remained relatively stable for 24 hours -- their expression didn't change much. These included genes often referred to as housekeeping genes that provide basic cellular functions and are commonly used in research studies to show the quality of the tissue. Another group of genes, known to be present in neurons and shown to be intricately involved in human brain activity such as memory, thinking and seizure activity, rapidly degraded in the hours after death. These genes are important to researchers studying disorders like schizophrenia and Alzheimer's disease, Loeb said.

A third group of genes -- the 'zombie genes' -- increased their activity at the same time the neuronal genes were ramping down. The pattern of post-mortem changes peaked at about 12 hours.

"Our findings don't mean that we should throw away human tissue research programs, it just means that researchers need to take into account these genetic and cellular changes, and reduce the post-mortem interval as much as possible to reduce the magnitude of these changes," Loeb said. "The good news from our findings is that we now know which genes and cell types are stable, which degrade, and which increase over time so that results from postmortem brain studies can be better understood."