Culture

Unraveling the genome in 3D-space

image: Proper folding of extremely long chromosomal DNA molecules is crucial for the correct functioning of the cell. Scientists from the Gerlich lab at IMBA - Institute of Molecular Biotechnology of the Austrian Academy of Sciences - developed a groundbreaking method to map contact points between replicated DNA molecules, thereby elucidating how the genome is folded inside the nucleus of human cells.

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©IMBA

The cells that make up our body are tiny, each of them measuring only micrometers in diameter. The ensemble of chromosomal DNA molecules that encode the genome, on the other hand, measures almost 2 meters. In order to fit into cells, chromosomal DNA is folded many times. But the DNA is not merely squeezed into the nucleus in a random manor but folded in a specific and highly regulated structure. The spatial organization of chromosomal DNA enables regulated topological interactions between distant parts, thereby supporting proper expression, maintenance, and transport of the genome across cell generations.

Breaks in our DNA, which can occur spontaneously or result from irradiation or chemical insults, can lead to severe problems since they foster mutations and can ultimately lead to cancer. But not every DNA break has disastrous consequences, since our cells have ingenious ways of repairing the damage. One of the main DNA repair pathways involves copying the missing information on the damaged DNA from the replicated sister chromatid. For this to occur, the two DNA molecules of sister chromatids need to come close together at the exact same genomic position. How the two DNA molecules are organized relative to each other to support this important repair pathway, however, has remained unclear.

The team around Daniel Gerlich developed a method that solves this problem. "Current methods to map the folding of DNA have a serious blind spot: They are not able to distinguish identical copies of DNA molecules. Our approach to solve this was to label DNA copies in a way such that we can discriminate them by DNA sequencing" explains Michael Mitter, doctoral student in Dr. Gerlich's lab and first author of the current publication in Nature. Using this approach, the researchers were able to create the first high resolution map of contact points between replicated chromosomes.

"With this new method, we can now study the molecular machinery regulating the conformation of sister chromatids, which will provide insights into the mechanics underlying the repair of DNA breaks and the formation of rod-shaped chromosomes in dividing cells, which is required for proper transport the genome to cell progeny," says Daniel Gerlich about the project, which is financed by the Vienna Science and Technology Fund (WWTF) and was a fruitful collaboration of several research groups at the Vienna BioCenter, including the Ameres and Goloborodko labs at IMBA, and the Peters lab at the neighboring Institute of Molecular Pathology (IMP).

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IMBA- Institute of Molecular Biotechnology of the Austrian Academy of Sciences

Study: Death counts fail to capture full mortality effects of COVID-19

TAMPA, Fla. (Sept. 23, 2020)- More than 200,000 people in the U.S. have died from COVID-19. Some argue that statistic is inaccurate due to inconsistencies in how deaths are being reported. But researchers from the University of South Florida claim that even if those deaths have been correctly measured, the number doesn't fully convey the true mortality effects of COVID-19.

A study published in the Journal of Public Health finds that for each person in the U.S. who died after contracting COVID-19, an average of nearly 10 years of life had been lost. Researchers claim "years of life lost" is a more insightful measure than death count since it accounts for the ages of the deceased. The tool is often used to determine the effects of non-communicable disease, drug misuse and suicide. They believe "years of life lost" is especially appropriate given the range of ages at which individuals have died of COVID-19.

"While death counts are a vital initial measure of the extent of COVID-19 mortality, they do not provide information regarding the age profile of those who died," said lead author Troy Quast, professor of health economics in the USF College of Public Health. "By contrast, years of life lost tell us the extent to which deaths are occurring across age groups and can potentially help healthcare providers and policymakers better target clinical and governmental responses to reduce the number of deaths."

Quast and his research team obtained data from the Centers for Disease Control and Prevention that report COVID-19 death counts by sex, age and state. The study focused on data from Feb. 1 to July 11, during which there had been roughly 130,000 COVID-19 deaths reported. They then compared the ages at death to life expectancies by age and gender from the U.S. Social Security Administration and to population data from the U.S. Census Bureau. When taking those factors into account, they calculated that COVID-19 had caused 1.2 million years of life lost during that timeframe. While the analysis only covered the period through mid-July, if past trends were to have continued, that figure at this point would approach 2 million.

Nearly 80 percent of deaths nationwide occurred among people ages 65 and older. Therefore, geographical areas with a younger population had more years of life lost due to COVID-19. For example, one-sixth of the nation's years of life lost is attributed to New York City, the then-epicenter of the outbreak. Another significant factor is pre-existing medical conditions. Males generally have more pre-existing medical conditions than females and accounted for roughly 55 percent of deaths attributed to COVID-19. Researchers adjusted for the higher rate of pre-existing conditions among COVID-19 decedents by reducing expected life expectancy by 25 percent.

Measuring COVID-19 deaths has been difficult due to evolving diagnostic criteria, testing supply constraints and the uncertainties that occur in over-burdened intensive care units. Quast says it's vital to continue monitoring years of life lost due to COVID-19 to help policy makers and health care providers better understand the extent of the outbreak.

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University of South Florida

New tool mimics human skin to allow detailed study of mosquito biting

image: The biteOscope tool is used to record a mosquito as it feeds on a human skin mimic.

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Felix Hol (CC BY 4.0)

Scientists have developed a tool for studying the biting behaviour of common pathogen-carrying mosquitoes, according to new research published this week in eLife.

The tool, which uses an artificial blood meal and a surface that mimics human skin, will provide detailed understanding of blood feeding without using human subjects as bait. It can also fit conveniently into a backpack, allowing the study of mosquitoes in laboratory and natural environments.

Blood feeding is essential for mosquitoes to reproduce, but it is during blood feeds on human hosts that they pass on pathogens such as malaria.

"Although the initial step in obtaining a blood meal - flying towards a host - is relatively well characterised, the steps that unfold after a mosquito has landed on a host are less well understood," explains first author Felix Hol, a researcher at Institut Pasteur and the Center for Research and Interdisciplinarity, Paris, France. "There is a lack of tools available to measure mosquito biting behaviour, and those that do exist rely on using human hosts which limits the number and type of experiments you can do - you cannot study pathogen-carrying mosquitoes in this way."

This is important because it is thought that factors such as infection can affect a mosquito's feeding behaviour, including the number of feeding attempts they make and the size of the meal they take. In turn, these aspects can alter the transmission dynamics of pathogens. To address this, Hol and colleagues from Stanford University, California, US, Institut Pasteur and CRI (Universite de Paris/INSERM), Paris, France, developed the biteOscope - a tool that allows the high-resolution study of how mosquitoes explore and probe host skin surfaces before taking a meal.

It consists of a bite 'substrate' - a transparent, temperature-controlled surface that mimics body temperature to attract mosquitoes. An artificial meal is applied on top of this and covered with a commonly used membrane that mosquitoes can pierce. The meal resembles blood, allowing mosquitoes to engorge and increase their weight by two to threefold. This bite substrate is then placed in a transparent cage, and an external camera records the mosquitoes' behaviour.

The team tested biteOscope with four medically important species of mosquito and built a computer model to analyse behaviours from images captured of the mosquitoes as they landed on the 'skin'. "We found that the time a mosquito spends exploring skin that does not lead to a successful feed is rarely longer than the duration of a successful feed," says author Louis Lambrechts, Research Director at the Department of Virology, Institut Pasteur. "This suggests that if blood is not found within a certain time, the mosquitoes give up and move on."

They next demonstrated how the tool can track body parts to understand how the mosquitoes 'sense' the surface they are exploring. When they coated the skin mimic with the insect repellent DEET, they found that mosquitoes tended to land and immediately take off, only making contact with their legs, which suggests repulsion is mediated by leg contact.

"We have used the biteOscope to describe the behavioural patterns of four key mosquito species, providing a useful knowledge base for future studies of blood feeding behaviour," concludes author Manu Prakash, Assistant Professor of Bioengineering at Stanford University. "More broadly, we hope that the tools presented here will provide a fresh perspective on mosquito behaviours that are relevant to pathogen transmission and enable researchers to gain a detailed understanding of blood feeding without having to sacrifice their own skin."

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eLife

How a single protein in non-neuronal cells controls brain development

Tsukuba, Japan - Normal brain development requires a precise interplay between neuronal and non-neuronal (also called glial) cells. In a new study, researchers from the University of Tsukuba revealed how the loss of protein arginine methyltransferase (PRMT) 1 causes disruptions in glial cells and affects proper brain development.

PRMTs modify specific amino acids of other proteins regulating key cellular functions, such as survival, proliferation and development. Of the many members of the PRMT family that have been identified to date, PRMT1 is one of the most common and controls tissue development and lifespan, as well as stress responses. Because total knockout of PRMT1, i.e., the loss of the protein in all tissues during development, results in failure of embryonic development, recently tissue-specific knockout of PRMT1 has been under increasing scrutiny, in an effort to understand how PRMT1 contributes to tissue development and function.

"We previously discovered that PRMT1 is critical for the function of one type of glial cell, oligodendrocytes, during brain development," says corresponding author of the study Professor Akiyoshi Fukamizu. "The goal of this study was to understand how other glial cells may contribute to the hypomyelination phenotype we observe in PRMT1 conditional knockout mice."

To achieve their goal, the researchers used the same mouse model as in their previous study, in which PRMT1 was knocked out in neural stem cells (NSCs) and cells that are derived from NSCs. These include oligodendrocytes and astrocytes, but not microglia, all of which are important glial cell types in the brain. The researchers performed RNA-sequencing of the outer region of the brain, called the cortex, where these cells reside in neonatal PRMT1 knockout mice. By doing so, they were able to survey changes in gene expression in the brain of mice lacking PRMT1. Interestingly, the researchers found increased expression of genes regulating inflammation, pointing towards the involvement of astrocytes and microglia. Looking closer at markers of inflammation, the researchers found that among a panel of inflammation markers the expression of Interleukin-6 in particular was significantly increased in PRMT1 knockout mice.

The researchers next asked how there is increased inflammation in the brain of neonatal mice lacking PRMT1 and looked closer at astrocytes and microglia. By assaying the brains for markers of astrocytes and microglia, they found signs of severe ongoing inflammation: massive astrogliosis, which is an increase in astrocyte numbers, and an increase in the number of microglia. The latter is particularly intriguing because microglia are not derived from NSCs and hence showed normal expression of PRMT1.

"These are striking results that show how a single protein controls such essential developmental processes in the brain. Our results provide a novel insight into the molecular control of brain development," says first author of the study Assistant Professor Misuzu Hashimoto (Gifu University).

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University of Tsukuba

Neurotic college students could benefit from health education

College students are under a lot of stress, even more so lately due to the COVID-19 pandemic. Based on certain personality types, especially neurotic personalities, college health courses could help students develop a more positive stress mindset, according to research from faculty at Binghamton University, State University of New York.

A research team including Binghamton University Health and Wellness Studies Lecturer Jennifer Wegmann sought to evaluate the impact of health education on the change of stress mindset and also to explore the role of personality in the change of stress mindset when there is a specific focus on improving individual health and well-being. Specifically, they sought to assess the relationship between each personality dimension (i.e., neuroticism, extraversion, openness, agreeableness and conscientiousness) and stress mindset change over time.

"The findings surrounding specific personality dimensions were interesting," said Wegmann. "It appears that engaging in health education is beneficial in changing perceptions of stress for some students but not all -- based on personality. For example, significant changes were elicited in students who scored high on the neuroticism scale but no significance was shown for students on the extroversion scale. Neurotic students tend to be worriers with high anxiety. The findings of this research show how focusing on their health, in general, can change these typically high-stressed students' beliefs about the stress they experience."

The researchers conducted an online survey with a group of 423 students taking a college health education course. They asked students to rate the extent to which they agreed with a series of statements. Analyzing the data, the researchers found that students with specific personality types, especially neurotic students, were more likely to improve their stress mindset by engaging in health education.

Wegmann said the most interesting thing about these findings is that change in stress mindset was elicited not through focusing on stress and changing mindsets specifically, but rather by students focusing on their overall health and wellness. Colleges may not have the faculty, space or funding to provide stress-specific courses, but this research shows there is another avenue to help students navigate their stress, Wegmann said.

"This is important for several reasons," said Wegmann. "First, helping students develop a more positive or enhancing stress mindset has been associated with improved mental health, increased performance and productivity. Second, general health education courses are available to large numbers of students. There typically are few, if any, stress-specific courses offered on college campuses,' and if they are offered, many are limited in student capacity."

Wegmann said that the next step is to work on discovering what approach will be helpful for all students.

"According to our research, this approach was not helpful for everyone," said Wegmann. "While these findings are providing novel and interesting information, as a stress researcher who works to help students become more productive and healthy, I want to know what other avenues will reach our students."

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Binghamton University

Women orthopaedic surgeons report high rates of sexual harassment

September 23, 2020 - More than two-thirds of women orthopaedic surgeons report experiencing sexual harassment during their residency training, according to a survey study in Clinical Orthopaedics and Related Research® (CORR®), a publication of The Association of Bone and Joint Surgeons®. The journal is published in the Lippincott portfolio by Wolters Kluwer.

Sexual harassment of women during orthopaedic training appears pervasive, and its frequency has hardly improved over the past several decades, reports the study by Emily Whicker, MD, of University of Pittsburgh Medical Center and colleagues. "Sexual harassment as reported by women orthopaedic trainees remains pervasive across training programs throughout the United States," the researchers write.

A 'Wake-up Call' for Orthopaedic Surgery: Women Surgeons Say #MeToo

The anonymous online survey targeted members of a professional society for women orthopaedic surgeons. Adapted from a general questionnaire about sexual harassment in the workplace, the survey included questions about the nature of the harassment, who the harasser was, and whether the incident was reported.

Two hundred fifty women orthopaedic surgeons completed the survey, representing a 37 percent response rate. While surveys are susceptible to non-response bias, even if all non-responders had nothing to report in terms of harassment, the proportion of women who experienced harassment would still be one in four. In addition, a large number of women's experiences were represented: of the 250 surgeons responding, 20 percent were current residents and the balance had trained sometime in the past 30 years.

Overall, 68 percent of women said they were sexually harassed during their orthopaedic training. Harassment was reported by 59 percent of current trainees compared to 71 percent for practicing surgeons. The authors had thought that current residents might be less likely to report harassment -at a time of growing awareness including the #MeToo movement. "However, this was not the case, and our results suggest that increased awareness has not yet translated to a decrease in proportion," Dr. Whicker and coauthors write.

Common types of harassment included obscene images, unwanted touching, and unwanted sexual invitations. While about 70 percent of women reporting harassment said they were harassed by other residents who were men, over 40 percent reported harassment by attending surgeons who were men. Rates of reported harassment were similar across US regions.

Only 15 percent of women who were harassed reported the incident. Current residents were more likely to report harassment than past residents: 26 versus 11 percent. The women's reasons for not reporting included negative impact on their careers, feeling that reporting was "pointless" because no action would be taken, or because the harasser was a superior.

The survey adds to previous evidence that women experience high rates of sexual harassment during medical training, and specifically in orthopaedic surgery: a specialty that historically has had low proportions of women surgeons. "In light of these findings, training programs should consider implementing specific training and awareness programs that target not only the trainees, but also attending surgeons," Dr. Whicker and coauthors write. They believe that efforts to recruit more women to orthopaedic surgery and to increase the number of women in leadership and mentorship positions will also be essential.

The new research "has clearly documented and confirmed that sexual harassment exists to a meaningful degree in orthopaedic surgery," according to a CORR Insights® perspective piece by Joseph D. Zuckerman, MD, of NYU Langone Orthopedic Hospital, and professor and chair of the Department of Orthopedic Surgery at NYU Grossman School of Medicine, New York City.. He outlines an approach to correcting the problem - including his experience in recognizing and addressing sexual harassment in his own department.

Dr. Zuckerman believes the survey findings should be a "wake-up call" throughout orthopaedic surgery. "We need to listen to what our female colleagues have described and we need to learn from the experiences they have reported," he concludes. "And most importantly, we need to make it much, much better."

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Wolters Kluwer Health

Genome duplications as evolutionary adaptation strategy

image: Genome duplications describe an exceptional process in land plants to make available additional genetic variability

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Photo: Marcus Koch

Genome duplications play a major role in the development of forms and structures of plant organisms and their changes across long periods of evolution. Heidelberg University biologists under the direction of Prof. Dr Marcus Koch made this discovery in their research of the Brassicaceae family. To determine the scope of the different variations over 30 million years, they analysed all 4,000 species of this plant family and investigated at the genus level their morphological diversity with respect to all their characteristic traits. The results of this research were published in the journal Nature Communications.

The external form of a plant, also known as its morphology, notably depends on environmental factors and their influences. This is true over short time scales of individual development as well as over the long term on an evolutionary scale. "A plant species always embodies only a portion of the possible breadth of morphological variation in evolution, thus allowing related evolutionary lines to be studied as a group for their morphological disparity," stresses Prof. Koch, who leads the Biodiversity and Plant Systematics research group at the Centre for Organismal Studies (COS) of Heidelberg University. The extent of this disparity can be viewed as evolutionary potential for adaptations to altered environments and an associated differentiation.

To measure the morphological variation, the researchers first recorded the characteristic traits of the 4,000 Brassicaceae species in a checklist describing the identity and correlations of the species. They then constructed a family tree on genus level from next generation sequencing DNA data to visualise and test the underlying evolutionary dynamics. The tree facilitates the study of complex traits and their development over the course of evolution and places them in the context of other processes and events such as genome duplications or major changes in speciation rates. Genome duplications, that is the multiplication of the whole genome in a cell, describe an exceptional process in land plants to make available additional genetic variability.

"One surprising result of our study is that there is no key innovation with respect to the morphological characteristics studied. The character traits constantly change and appear to be arbitrarily assembled over and over. The old evolutionary lines make use of the morphological potential in a different way but do not differ from one another in terms of their disparity. In this way, evolution can proceed quickly and divergently," states Marcus Koch.

These patterns are associated with genome duplications, which reflect the genetic components, as well as a rapid increase in speciation rates as an expression of selection pressure of past and changing environments. Accordingly, present-day Brassicaceae exhibit more than 40 percent polyploid species, which underwent genome duplications and carry a multiple set of chromosomes. "That means that a species like thale cress, Arabidopsis thaliana, has gone through at least three genome duplications over the course of evolution of the flowering plants in the last 160 million years. Yet this species still has only ten chromosomes because the genomes have to be subsequently stabilised and usually scaled back down over the long term," explains Prof. Koch.

The research was conducted mainly in the framework of the DFG priority program "Evolutionary Plant Solutions to Ecological Challenges" (SPP 1529). The data are available in a public access database.

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Heidelberg University

Fructose made in the brain could be a mechanism driving Alzheimer's disease

New research released from the University of Colorado Anschutz Medical Campus proposes that Alzheimer's disease may be driven by the overactivation of fructose made in the brain.

The study was published in the Frontiers in Aging Neuroscience and outlined the hypothesis that Alzheimer's disease is driven largely by Western culture that has resulted in excessive fructose metabolism in the brain.

The paper brought together an interdisciplinary team of neurologists, neuorscientists and experts on sugar metabolism, and presents evidence from extensive data and research conducted in Alzheimer's disease that links high fructose levels in the brain to the disease. It also helps explain associations, such as why diabetes and obesity are associated with an increased risk for Alzheimer's disease.

"In essence, we propose that Alzheimer's disease is a modern disease driven by changes in dietary lifestyle in which fructose can disrupt cerebral metabolism and neuronal function," said author Richard Johnson, MD, professor at the University of Colorado School of Medicine on the CU Anschutz Medical Campus.

Johnson outlines data that showcases the overactivation of cerebral fructose metabolism that can drive Alzheimer's disease. The source of fructose is largely from endogenous production in the brain. Thus, the reduction in mitochondrial energy production is hampered by neuronal glycolysis that is inadequate, resulting in progressive loss of cerebral energy levels required for neurons to remain functional and viable.

"By outlining consistent evidence, we're hoping to inspire researchers to continue exploring the relationship between fructose in the brain and Alzheimer's disease. New treatments aimed at inhibiting intracerebral fructose metabolism could provide a novel way to prevent and treat this disease," Johnson adds.

In one of the scenarios outlined by Johnson and his collaborators, glucose hypometabolism increased oxidative stress, and a progressive loss of mitochondria occured, leading eventually to neuronal dysfunction and death. In this scenario, the amyloid plaques and neurofibrillary tangles are part of the inflammatory response and participate in injury, but are not the central factors driving the disease. Johnson mentions that theoretically, inhibiting enzymes in the brain that are involved in fructose production or metabolism might provide novel ways to prevent and treat Alzheimer's disease.

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University of Colorado Anschutz Medical Campus

Tiny worlds reveal fundamental drivers of abundance, diversity

The natural world is astonishingly complex. After centuries of study, scientists still have much to learn about how all the species in an ecosystem coexist, for example. New research on microbial communities published in Nature Communications helps light the way to answering this fundamental question in ecology.

"What I wanted to know is, sure communities are very complicated, there are many species interacting, but if we try to describe the most important forces shaping this community, what are they?" says author Jacopo Grilli, a biological physicist at the International Center for Theoretical Physics in Trieste, Italy and a former Omidyar Fellow at the Santa Fe Institute in the U.S.

Grilli, whose work focuses on understanding complex phenomena by using simple rules, knew that to begin to answer that question, he needed to focus on ecological communities from many different environments, and for which a wealth of data already existed. It's far easier to study a glass of ocean water or a spoonful of soil than a patch of forest, he explains. "Ecology is traditionally a data-poor discipline. But in the case of microbial communities, it's much easier to get a lot of data on these communities, across several conditions," Grilli says. "Microbial communities are everywhere. They are all around us, outside and inside us. So they contribute to many fundamental ecological processes around the world, and they determine in some part our health and well-being. Their impact on our lives and on our planet is immense."

In parsing the abundance and diversity of bacteria in a variety of tiny worlds using a simple mathematical model, Grilli's research suggests that environmental variability is the main determinant of whether a species is present or absent in a microbial community, and that environmental change -- such as a change in temperature or nutrients -- is the primary driver of fluctuations in the abundance of a species. "That sort of suggests the players are different -- the species that are in our gut versus the species that are in the ocean are different -- but the forces that shape them are the same," Grilli says.

He also identified three key laws that help explain how the number of species in an ecosystem fluctuates over time. These laws can be used to predict a species presence or absence and the diversity in a system.

While the size, complexity, and dearth of data for, say, a forest ecosystem makes it difficult to extrapolate the findings to other systems, Grilli says these laws can be used as a starting point for investigations of bigger ecosystems.

"When we look at these bacterial communities, the number of individuals is huge compared to the forest next to our backyard," he says. For example, the number of bacterial cells in our colon is ten times the number of trees in the world. "So when we understand something about the ecology of bacteria, we are looking at the ecology of something that is at the spatial and temporal scale of our planet. Every hypothesis in the context of micro-communities provides a starting point for other communities. And it's obvious why, in a time when we see a huge decline in biodiversity at the global scale, understanding something more about ecology and in such a large scale is important."

Grilli is now building on this work to better understand interactions among microbial species.

Grilli adds that while he is the sole author of the paper, the research was informed by input from the many scientists from diverse disciplines he met while he was a fellow at SFI. "If I didn't spend the time at SFI, where I had the opportunity to discuss and collaborate, I don't think this paper would have existed," he says. "It's the result of many conversations and the environment."

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Santa Fe Institute

SARS-CoV-2 during pregnancy was not associated with complications in neonates

image: Mia Ahlberg, midwife at Theme Women's Health, Pregnancy and Childbirth, Karolinska University Hospital, and researcher at the Department of Medicine, Karolinska Institutet (Solna). Photo: Elisabeth Ubbe

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Elisabeth Ubbe

In a new study published in the esteemed journal JAMA researchers at Karolinska Institutet and Karolinska University Hospital have examined the association between a positive SARS-CoV-2 test during pregnancy and complications in mothers and their newborn babies. Almost two out of three pregnant women who tested positive for SARS-CoV-2 were asymptomatic and the researchers found no higher prevalence of complications during delivery or of ill-health in the neonates. However, preeclampsia was more common in infected women.

On 25 March, Karolinska University Hospital in Sweden launched a screening programme (PCR test) for the new coronavirus for all women admitted for delivery. The researchers behind the present study have collected these data and linked them to data from the Swedish Pregnancy Register for all 2,682 women who gave birth at the hospital between March 25 and July 24, 2020.

In order to investigate the association between test positivity and medical outcomes in both mother and neonate, the researchers compared test-positive women with test-negative women, matching the two groups for age, BMI, parity, educational level, country of birth, smoking status, co-habitation and pre-pregnancy health status.

A total of 156 women (5.8 per cent) tested positive for SARS-CoV-2. Out of these women, 65 per cent were asymptomatic. That the majority of test-positive pregnant women were asymptomatic is in line with other research results where screening has been used. There was no statistically significant difference in terms of mode of delivery, haemorrhage, use of epidural, preterm birth, length of hospital stay or breastfeeding between infected and not infected women. Nor was there any difference between the groups regarding the infants' Apgar scores or birth weight.

Women who tested positive for the new coronavirus had, for reasons that remain unclear, a lower prevalence of induced labour (18.7 per cent, as opposed to 29.6 per cent in the test-negative women) and a higher prevalence of preeclampsia (7.7 per cent versus 4.3 per cent).

"One possible reason for the latter is that both preeclampsia and COVID-19 impact several organs and can present similar symptoms," says the study's lead author Mia Ahlberg, midwife at Theme Women's Health, Pregnancy and Childbirth, Karolinska University Hospital, and researcher at the Department of Medicine, Karolinska Institutet (Solna).

The fact that the majority of the test-positive women were asymptomatic likely affect the results of the study, Dr Ahlberg explains.

"The proportion of women with symptoms was too small to be able to investigate if these women have a higher risk of complications," she says. "There are several reports of pregnant women who develop severe COVID-19 with adverse outcomes. Larger studies should be conducted to be able to identify if women with symptoms and different degrees of symptoms constitute a risk group for adverse outcomes such as preterm birth."

The study also showed that the prevalence of SARS-CoV-2 was higher in women with lower education (14.2 per cent with 12 years' schooling) and higher in women born in Africa or the Middle East (10.0 per cent) than in women born in the Nordic countries, including Sweden (3.9 per cent).

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Karolinska Institutet

Poll: Americans' views of systemic racism divided by race

LOWELL, Mass. - In the wake of outrage across the nation and racial justice protests spurred by the deaths and injuries of George Floyd, Breonna Taylor, Jacob Blake and other Black Americans, more than half of Americans believe policing in the country is not fair, according to a new national poll released today by the UMass Lowell Center for Public Opinion.

The center conducted an independent, nonpartisan national survey asking 1,000 respondents about race, discrimination and systemic racism and found from policing, to the economy to the workplace, race divides Americans' views of many issues.

A majority of American adults polled think that policing in this country is not fair - 51 percent say that Blacks are treated less fairly than whites in their interactions with police, compared to 41 percent who say they are treated the same. Another 7 percent say whites are treated less fairly than Blacks. Among Black respondents, the perception that Blacks are treated less fairly is higher, at 73 percent, while nearly half of white respondents, 48 percent, think Blacks are treated less fairly than whites.

Among white respondents, there is a clear split in answers to this question by party identification, ideology, age and how a respondent scores on racial resentment, a metric political scientists often use to represent symbolic racism. Democrats, liberals, Americans younger than 50, and those who score low on the racial resentment scale are all far more likely than Republicans, conservatives, Americans older than 50, and those scoring high in racial resentment to think that Blacks are treated less fairly than whites by the police, the poll found.

When asked about police shootings and the effect on public discourse, Americans are divided: About 44 percent believe such an incident raises important issues about race that should be discussed, but 43 percent said police shootings are getting too much attention. Only 14 percent of Blacks surveyed said shootings are getting more attention than they deserve and 70 percent of Blacks thought shootings raised important issues on race. Four in 10 whites say shootings raise important issues but 49 percent say they are receiving undue attention. Racially resentful white Americans overwhelmingly (88 percent) said shootings caused race to get attention that was overblown. Racially progressive white Americans almost unanimously agreed that such incidents raised important issues about race.

The poll found many different experiences reported by respondents in their interactions with police based on race, whether white, Black or Latino. Fifteen percent of all respondents said they were treated poorly by police because of their race, nearly equal numbers said they received preferential treatment (12 percent) because of their race, while the vast majority reported no difference in treatment because of their race. However, Black respondents (38 percent) were more than five times as likely as white respondents (7 percent) to say they were treated poorly by the police because of their race. Similar results were seen for Hispanic/Latino respondents, 31 percent of whom reported being treated poorly by police because of their race. Only 7 percent of white respondents said they were treated poorly because of their race.

"This finding is particularly noteworthy. The idea in this country that there is discrimination in law enforcement does not come from the news for many people of color - it comes from personal experiences," said Joshua Dyck, director of the Center for Public Opinion and associate professor of political science.

As a remedy to such issues, a majority of Americans polled do not support efforts to defund the police. Fifty-four percent said police budgets should be left as they are. However, a majority of Blacks polled, 52 percent, support reallocating funds from police budgets.

When asked about creating a citizen review board at the municipal level made up of racially representative community members to review police actions, the majority of Americans polled - 65 percent - favor or strongly favor the idea. The idea is more popular among Blacks (52 percent) vs. whites (33 percent).

A central tenet of the American Dream is that hard work brings about professional success, but Blacks are less likely to say they can access jobs and Black respondents were twice as likely to say that they strongly disagree with the notion that their hard work directly contributes to their success (18 percent of Blacks vs. 9 percent of whites).

Blacks surveyed also reported having to work harder to get their jobs.

Overall, a slight majority of all Americans polled said that Blacks often face hurdles such as discrimination when looking for a job. Fifty-three percent of Americans say Blacks face job discrimination, 13 percent are unsure and 34 percent say there is no discrimination. Eighty-three percent of Blacks polled said that Blacks face discrimination and only 7 percent say Blacks have the same chance as whites, compared to 41 percent of whites who said Blacks and whites have the same chance.

Overall, 56 percent of Americans polled favor affirmative action programs and 44 percent oppose them. Eighty-four percent of Blacks polled are in favor of affirmative action.

A third of Americans, overall, believe that Blacks and whites are treated differently on the job and 58 percent said there is equal treatment. There was marked difference in the opinions of Blacks and whites polled: 64 percent of whites said everyone receives equal treatment, compared to 21 percent of blacks. Seventy-three percent of Blacks polled said Blacks are treated less fairly, compared to 26 percent of whites. Asked if they were ever treated differently at work because of their race, 76 percent of whites said no compared to 40 percent of Black respondents. Fifty-two percent of Black respondents said they have at some point on the job been treated poorly because of their race, compared to 15 percent of white respondents.

When asked how Blacks and whites are treated in shops or businesses, 60 percent of Americans said they feel both are treated the same, but while 66 percent of whites believe that is the case, only 25 percent of Blacks agree. Sixty-three percent of Blacks polled said they are treated less fairly.

Thirty-four percent of Americans said they believe that the educational playing field is equal. Eighty-one percent of Black respondents said they see education as unequal and only 10 percent said their children have the same opportunity as white children. Whites are four times as likely to believe America's children start out on equal footing: 41 percent of whites believe the quality of education is the same for Black and white students and less than a majority (44 percent) recognizes education as a cause of inequality.

The poll found Americans are divided about government action to improve the social and economic condition of Blacks. A slight plurality of respondents says some help is needed (43 percent), but the majority (57 percent) are either undecided or opposed to systemic help. Blacks are more likely than whites to support government intervention on their behalf (66 percent vs. 40 percent) and are half as likely to say no government help is warranted (21 percent vs. 40 percent).

"To me the biggest take-away from this survey is that our data show that whites do not connect the disadvantages faced by Blacks to their own advantage. Whites have yet to understand the full extent of the privileges structural racism bestows upon them. While many whites readily say that Blacks are discriminated against, they do not see how the lack of opportunity for Blacks translates into more opportunities for whites," said Mona Kleinberg, assistant professor of political science who designed and analyzed the poll, along with political science major Lindsey Kilpatrick of Manilus, N.Y., and Maddi Hertz, a 2020 graduate from Andover. "Making the connection that when one group receives less another group gets more is what whites need to see more clearly if we want to end white dominance in the U.S."

"By studying what people believe and highlighting differences through in-depth scientific public opinion polling, we are seeking to add to ongoing and much-needed discussions in this country of racism, social justice and discrimination. Our poll uncovers much in the different perspectives and experiences of whites and Blacks, and in the varying policy attitudes of Americans who believe that we have serious problems with racism and discrimination in this country and those who do not. We hope that this information is useful to the ongoing discourse on how to make our society a more just and equitable one," said Dyck.

More detailed poll results - including how ideology and the concept of "racial resentment" affect views - are available at http://www.uml.edu/polls, along with topline and methodology. The independent, nonpartisan poll was conducted by the UMass Lowell Center for Public Opinion using the latest technology and highest standards. The center is a member of the American Association for Public Opinion Research's Transparency Initiative and presents events and polls on political and social issues that provide unique opportunities for civic engagement, experiential learning and research.

The poll surveyed 1,000 American adults. The poll was designed and analyzed by the Center for Public Opinion and fielded by YouGov from Aug. 20 through Aug. 25. The adjusted margin of error is plus or minus 4.0 percent. Full poll methodology is available at http://www.uml.edu/polls.

UMass Lowell is a national research university offering its more than 18,000 students bachelor's, master's and doctoral degrees in business, education, engineering, fine arts, health, humanities, sciences and social sciences. UMass Lowell delivers high-quality educational programs and personal attention from leading faculty and staff, all of which prepare graduates to be leaders in their communities and around the globe. http://www.uml.edu

Credit: 
University of Massachusetts Lowell

Likely molecular mechanisms of SARS-CoV-2 pathogenesis are revealed by network biology

image: Researchers have built an interactome that includes the lung-epithelial cell host interactome integrated with a SARS-CoV-2 interactome. Applying network biology analysis tools to this human/SARS-CoV-2 interactome has revealed potential molecular mechanisms of pathogenesis for SARS-CoV-2, the virus responsible for the COVID-19 pandemic. The research identified 33 high-value SARS-CoV-2 therapeutic targets, which are possibly involved in viral entry, proliferation and survival to establish infection and facilitate disease progression.

Image: 
UAB

BIRMINGHAM, Ala. - Viral and bacterial pathogens wield pathogenic or virulent proteins that interact with high-value targets inside human cells, attacking what is known as the host interactome. The host interactome is the network map of all the protein-protein interactions inside cells.

Such networks have been studied in organisms as diverse as plants, humans and roundworms, and they show a similarity to social networks like Facebook or airline route maps. In Facebook, a few people will have a huge number of friend connections, some will have many, and a vast majority will have much fewer. Similarly, airlines have a few hubs that many passengers pass through on the way to their destinations.

Host interactomes show a limited number of high-powered hubs -- where a protein has a large number of connections -- and a limited number of important bottlenecks, which are sites with a large number of short paths to a node. These are key targets for pathogens as they seek to seize control of the infected cell, so it can rewire the cell's flow of information and cause disease.

University of Alabama at Birmingham researchers, led by Shahid Mukhtar, Ph.D., associate professor of biology in the UAB College of Arts and Sciences, have now built an interactome that includes the lung-epithelial cell host interactome integrated with a SARS-CoV-2 interactome. Applying network biology analysis tools to this human/SARS-CoV-2 interactome has revealed potential molecular mechanisms of pathogenesis for SARS-CoV-2, the virus responsible for the COVID-19 pandemic. The UAB research, published in the journal iScience, identified 33 high-value SARS-CoV-2 therapeutic targets, which are possibly involved in viral entry, proliferation and survival to establish infection and facilitate disease progression. These molecular insights may foster effective therapies, using combinations of existing drugs, for patients with COVID-19.

So far in 2019, the SARS-CoV-2 virus has killed nearly 1 million people worldwide and 200,000 in the United States.

The UAB researchers took many steps to generate the Calu-3-specific human-SARS-CoV-2 interactome, or CSI, that was the starting point for their network biology analyses.

They began from a comprehensive human interactome of experimentally validated protein-protein interactions, posted online in 2015, and then manually curated other protein-protein interactions from four subsequent interactome studies. The resulting human interactome contained 18,906 nodes and 444,633 "edges" -- the term for the links between protein nodes.

From two 2020 studies, the researchers compiled an exhaustive list of 394 host proteins that interact with the novel human coronavirus; these host proteins were called SARS-CoV-2 interacting proteins, or SIPs. The SIPs included 332 human proteins associated with the peptides of SARS-CoV-2 and 62 host proteins interacting with the viral factors of other human coronaviruses, including SARSCoV and MERS-CoV, the causes of SARS and MERS, which could also aid understanding the molecular pathogenesis of SARS-CoV-2

By querying these 394 SIPs in the human interactome, they generated a subnetwork of 12,852 nodes and 84,100 edges that covered first and second neighbors of the 373 SIPs.

Finally, they filtered these interactions in the context of temporal changes during COVID-19 infection, using a high-resolution temporal transcriptome derived from cultured human airway epithelial cells, or Calu-3, treated with SARSCoV and SARS-CoV-2 over time. Integrating this Calu-3 expression data with the SIPs-derived protein-protein interaction subnetwork resulted in a Calu-3-specific human-SARS-CoV-2 interactome, or CSI, that contained 214 SIPs interacting with their first and second neighbors, and forming a network of 4,176 nodes and 18,630 edges.

The CSI had a power law degree distribution with a few nodes harboring increased connectivity compared to a random network, and thus exhibited properties of a scale-free network, similar to the other, previously generated human-viral interactomes.

The robust, high-quality CSI was then further utilized for network-aided architectural and functional pathway analyses.

Topological clustering and pathway enrichment analysis showed that the SARS-CoV-2 virus attacks central nodes of the host-viral network that participate in core functional pathways. Network centrality analyses discovered 33 high-value SARS-CoV-2 targets for possible drug therapy; these targets are possibly involved in viral entry, proliferation and survival to establish infection and facilitate disease progression. A probabilistic modeling framework elucidated critical regulatory circuitry and molecular events pertinent to COVID-19, particularly the host modifying responses and cytokine storm.

"In summary," Mukhtar said, "our integrative network topology analyses led us to elucidate the underlying molecular mechanisms and pathways of SARS-CoV-2 pathogenesis." Mukhtar's lab continues to work on network medicine and artificial intelligence to battle COVID-19 and other human inflammatory diseases.

Credit: 
University of Alabama at Birmingham

GSA publishes seven articles on COVID-19 and aging

The Gerontological Society of America's highly cited, peer-reviewed journals are continuing to publish scientific articles on COVID-19. The following were published between August 28 and September 21; all are free to access:

Societal Views of Older Adults as Vulnerable and a Burden to Society During the COVID-19 Outbreak: Results from an Israeli Nationally Representative Sample: Research report in The Journals of Gerontology, Series B: Psychological Sciences and Social Sciences by Ella Cohn-Schwartz, PhD, and Liat Ayalon, PhD

A Thematic Analysis of Weibo Topics (Chinese Twitter Hashtags) regarding Older Adults During the COVID-19 Outbreak: Research report in The Journals of Gerontology, Series B: Psychological Sciences and Social Sciences by Wanyu Xi, Wenqian Xu, Xin Zhang, and Liat Ayalon

Older Adults’ Experience of the COVID-19 Pandemic: A Mixed-Methods Analysis of Stresses and Joys: Research article in The Gerontologist by Brenda R. Whitehead, PhD, and Emily Torossian, BA

Caremongering and Assumptions of Need: The Spread of Compassionate Ageism During COVID-19: Forum article in The Gerontologist by Deanna Vervaecke, BSc (Hons), and Brad A. Meisner, PhD

Challenges Experienced by Older People During the Initial Months of the COVID-19 Pandemic: Research article in The Gerontologist by Allison R. Heid, PhD, Francine Cartwright, BS, Maureen Wilson-Genderson, PhD, and Rachel Pruchno, PhD

COVID-19 as a Stressor: Pandemic Expectations, Perceived Stress, and Negative Affect in Older Adults: Research report in The Journals of Gerontology, Series B: Psychological Sciences and Social Sciences by Brenda R. Whitehead, PhD

Estimating older adult mortality from COVID-19: Research report in The Journals of Gerontology, Series B: Psychological Sciences and Social Sciences by Andy Sharma, PhD

Credit: 
The Gerontological Society of America

UAlberta researchers pinpoint how iron deposits form

image: Iron oxide-apatite ore from one of the study areas at Iron Springs, Utah.

Image: 
Wyatt M. Bain.

University of Alberta scientists have uncovered the formation mechanism behind a class of mineral deposits that have been hotly contested until now. The findings shed new light on how iron deposits, among others, form--and this new understanding can aid geologists in the hunt for more ore.

"Most mineral deposits are formed by circulation of hot water; whereas some are formed by crystallization from a magma," said Matthew Steele-MacInnis, assistant professor in the Department of Earth and Atmospheric Science. "In the case of Iron oxide-apatite deposits, nobody has been able to agree on how they are deposited, but our study now shows they are deposited from a very unusual liquid dominated by calcium carbonate and sulfate."

The substance is a magma in a sense, explains Steele-MacInnis, but an unusual one and a formation process unknown until this study--led by PhD student Wyatt Bain under MacInnis' supervision-- and this context gives geologists new clues to guide the hunt for ore.

"The origins and chemical properties of ore-forming fluids are key parameters that determine whether a mineral deposit will form. In this case, our results show that the fluids that form iron oxide-apatite deposits are sourced by a very particular process: melting of limestones and/or salt deposits by injection of magma," said Steele-MacInnis.

The results can be directly applied in exploration, explains Steele-MacInnis. Geologists looking for iron oxide-apatite deposits should target areas where magmatic rocks have been emplaced into sedimentary basins containing limestones or salt deposits.

And while the findings have the most immediate relevance for the hunt for iron deposits, Steele-MacInnis explains that this new understanding also has implications for some of our most cutting-edge technology.

"Iron oxide-apatite deposits have been mined for some years as sources of iron, which is probably the single most important metal for industrial applications and infrastructure," said Steele-MacInnis. "But in recent years, these deposits have become even more attractive, because they commonly are enriched in key high-tech metals like rare Earth elements, which are critical to green-energy production and electronics."

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University of Alberta

Study shows weighted blankets can decrease insomnia severity

DARIEN, IL - Weighted blankets are a safe and effective intervention in the treatment of insomnia, according to Swedish researchers who found that insomnia patients with psychiatric disorders experienced reduced insomnia severity, improved sleep and less daytime sleepiness when sleeping with a weighted chain blanket.

Results of the randomized, controlled study show that participants using the weighted blanket for four weeks reported significantly reduced insomnia severity, better sleep maintenance, a higher daytime activity level, and reduced symptoms of fatigue, depression and anxiety. Participants in the weighted blanket group were almost 26 times more likely to experience a decrease of 50% or more in their insomnia severity compared with the control group, and they were nearly 20 times more likely to achieve remission of their insomnia. Positive results were maintained during a 12-month, open follow-up phase of the study.

"A suggested explanation for the calming and sleep-promoting effect is the pressure that the chain blanket applies on different points on the body, stimulating the sensation of touch and the sense of muscles and joints, similar to acupressure and massage," said principle investigator Dr. Mats Alder, consultant psychiatrist in the department of clinical neuroscience at the Karolinska Institutet in Stockholm, Sweden. "There is evidence suggesting that deep pressure stimulation increases parasympathetic arousal of the autonomic nervous system and at the same time reduces sympathetic arousal, which is considered to be the cause of the calming effect."

The study is published in the Sept. 15 issue of the
Journal of Clinical Sleep Medicine.

The study involved 120 adults (68% women, 32% men) previously diagnosed with clinical insomnia and a co-occurring psychiatric disorder: major depressive disorder, bipolar disorder, attention deficit hyperactivity disorder, or generalized anxiety disorder. They had a mean age of about 40 years.

Participants were randomized to sleep for four weeks at home with either a chain-weighted blanket or a control blanket. Participants assigned to the weighted blanket group tried an 8-kilogram (about 17.6 pounds) chain blanket at the clinic. Ten participants found it to be too heavy and received a 6-kilogram (about 13.2 pounds) blanket instead. Participants in the control group slept with a light plastic chain blanket of 1.5 kilograms (about 3.3 pounds). Change in insomnia severity, the primary outcome, was evaluated using the Insomnia Severity Index. Wrist actigraphy was used to estimate sleep and daytime activity levels.

Nearly 60% of weighted blanket users had a positive response with a decrease of 50% or more in their ISI score from the baseline to the four-week endpoint, compared with 5.4% of the control group. Remission, a score of seven or less on the ISI scale, was 42.2% in the weighted blanket group, compared with 3.6% in the control group.

After the initial four-week study, all participants had the option to use the weighted blanket for a 12-month follow-up phase. They tested four different weighted blankets: two chain blankets (6 kilograms and 8 kilograms) and two ball blankets (6.5 kilograms and 7 kilograms). After the test, and they were freely allowed to choose the blanket they preferred, with most selecting a heavier blanket. Only one participant discontinued the study due to feelings of anxiety when using the blanket. Participants who switched from the control blanket to a weighted blanket experienced a similar effect as patients who used the weighted blanket initially. After 12 months, 92% of weighted blanket users were responders, and 78% were in remission.

"I was surprised by the large effect size on insomnia by the weighted blanket and pleased by the reduction of levels of both anxiety and depression," said Adler.

In a related commentary, also published in the September issue of JCSM, Dr. William McCall writes that the study results support the psychoanalytic "holding environment" theory, which states that touch is a basic need that provides calming and comfort. McCall urges providers to consider the impact of sleeping surfaces and bedding on sleep quality, while calling for additional research into the effect of weighted blankets.

Credit: 
American Academy of Sleep Medicine