Culture

DURHAM, N.C. -- Close bonds with the opposite sex can have non-romantic benefits. And not just for people, but for our primate cousins, too.

Drawing on 35 years of data, a new study of more than 540 baboons in Amboseli National Park in Kenya finds that male baboons that have close female friends have higher rates of survival than those who don't.

Researchers have often assumed that when a male is friendlier to certain females, it's for the reproductive perks: to better protect his offspring, or to boost his chances of mating with her. But the new study points to an additional potential benefit: female friends may help him live a longer life.

The team's findings will appear Sept. 21 in a special issue of the journal Philosophical Transactions of the Royal Society B.

It's well known that people who have close friendships are more likely to live a long life than those who don't. In fact, human studies show that making and keeping friends can be as important for longevity as losing weight and getting exercise.

In the last decade, similar patterns have been found in animals ranging from monkeys and horses to dolphins and killer whales. However most of this research has focused on females, whereas males are more of a mystery. The reason is that, in most social mammals, females typically spend their entire lives in the same group, while males come and go, leaving researchers with only a partial snapshot of their lives.

"It means there are lots of gaps in our understanding of male social life," said senior author Susan Alberts, chair of the evolutionary anthropology department at Duke University.

Using statistical techniques to infer mortality risk at each age from sparse data, Alberts and colleagues looked at whether the link between survival and friendship was the same for male and female baboons.

Since 1971, researchers have followed individual baboons in southern Kenya on a near-daily basis, noting who they socialized with and how they fared over their lifetimes as part of the Amboseli Baboon Research Project.

Baboon besties don't catch up for coffee or bare their souls over beers. But they do spend time together grooming -- a give-and-take that involves sitting close together and stroking and picking through each other's fur, looking for ticks and other parasites. "It's a baboon's way of bonding and relieving stress, as well as providing some help with hygiene," Alberts said.

Males spend very little time grooming each other, but they do groom with females, and not just when the females are fertile.

Analyzing data for 277 males and 265 females, the team estimated the 'strength' of the bonds in each baboon's inner circle by measuring how often they spent time grooming with their closest friends.

The researchers showed for the first time in a wild primate that, not surprisingly, both sexes benefit from having strong social ties. Just like humans, "baboon males live longer lives if they're socially connected," Alberts said.

Males that maintained strong female friendships were 28% more likely to make it to their next birthday than their socially isolated counterparts.

Indeed, the team found that the flip side of the friendship coin, social isolation, can be a bigger threat to male survival than the stress and dangers of fighting their way up the pecking order.

Alberts says more work needs to be done to confirm that the link in baboons is in fact a causal one, and if so, to figure out exactly how the bonds of friendship affect physiology to lengthen their lifespans.

But the researchers say their work on baboon social behavior suggests that the power of friendship may have deep evolutionary roots in the primate family tree.

"How do primate friendships get 'under the skin' to lengthen life?" Alberts said. "We still don't know; it's one of the most wonderful black boxes in my life."

DURHAM , N.C. -- Many humans live to see their 70s and 80s, some even reach 100 years old. But life is much shorter for our closest animal relatives. Chimpanzees, for example, rarely make it past age 50, despite sharing almost 99% of our genetic code.

While advances in medicine and nutrition in the last 200 years have added years to human lifespans, a new study suggests there could be a more ancient explanation why humans are the long-lived primate.

Part of the secret to human longevity, researchers say, may lie in chemical changes along the DNA within our cells that slowed the rate of human aging in the 7 to 8 million years since our ancestors went their separate ways from chimps.

The findings will appear Sept. 21 in the journal Philosophical Transactions of the Royal Society B.

In the last decade, researchers have found that chemical marks on the human genome -- modifications that can affect gene activity without altering the underlying DNA sequence -- actually change as we age.

Studies have shown that certain sites along our DNA gain or lose chemical tags called methyl groups in a way that marks time, like a metronome. The changes are so consistent that they can be used as an "aging clock" to tell a person's age to within less than four years.

The new study, led by researchers at Duke University and George Washington University, marks the first time such age-related changes have been analyzed in chimpanzees, said lead author Elaine Guevara, an assistant research professor of evolutionary anthropology at Duke.

Guevara and colleagues analyzed some 850,000 of these sites in blood from 83 chimpanzees aged 1 to 59.

Sure enough, they found that aging leaves its mark on the chimpanzee genome, just as it does in humans. More than 65,000 of the DNA sites the scientists scrutinized changed in a clock-like way across the lifespan, with some gaining methylation and others losing it.

"A lot of their genome shows an age-related pattern," Guevara said.

The pattern was so reliable that the researchers were able to use DNA methylation levels to tell a chimpanzee's age to within 2.5 years, which is much more accurate than current methods for estimating a wild animal's age by the amount of wear on their molars.

When the researchers compared the rates of change they found in chimps with published data for humans, the epigenetic aging clock ticked faster for chimpanzees.

It's unknown whether these changes merely track the aging process or actively contribute to it, Guevara says.

But the researchers hope such work could eventually offer clues to the gene regulatory mechanisms behind the physical and cognitive decline that often accompanies aging,
and lead to new ways to fight aging-related diseases.

University of Cincinnati researchers have found that certain treatments for cancer may increase the chance of death if they contract COVID-19.

These findings from a multicenter study, presented at the European Society for Medical Oncology Virtual Congress 2020, shed light on ways standard anti-cancer treatments may impact outcomes for patients with both cancer and the coronavirus.

"Patients with cancer are susceptible to infection from COVID-19 and subsequent complications," says Trisha Wise-Draper, MD, associate professor of medicine in the Division of Hematology Oncology at the UC College of Medicine and lead author. "They experience higher rates of hospitalization, up to 40%, severe respiratory illness and death. Treatment for cancer, within four weeks of [the diagnosis of] COVID-19, was suggested to be associated with higher rates of complications, but less is known about treatment before or after that time frame.

"In a previous study from the COVID-19 and Cancer Consortium, with a smaller group of patients, we found that several factors increased the chance of death including age, sex, history of smoking and other health conditions, including active cancer. However, recent cancer treatment was not associated with poor outcomes in the smaller cohort. Now, we're investigating the correlation between timing of anti-cancer treatment and COVID-19 related complications as well as death in 30 days of a larger number of patients -- over 3,000."

"Of the 3,600 patients analyzed from 122 institutions across the country, we found that 30-day mortality was highest among cancer patients treated one to three months prior to COVID-19 diagnosis and was highest for those treated with a chemotherapy/immunotherapy combination," continues Wise-Draper, a UC Health oncologist and member of the UC Cancer Center. "Death was especially high in those receiving anti-CD20 monoclonal antibodies, which are normally used to deplete abnormal B cells common for certain lymphomas, one to three months prior to COVID-19 infection - a time period for which significant B-cell depletion develops."

She adds that death was higher for those undergoing active cancer treatment, except for endocrine therapy, when compared to patients untreated within a year prior to COVID-19 diagnosis.

"Any way you slice it, this is not good news for patients who are fighting cancer," she says. "Targeted therapies, especially those causing immune cell depletion, used one to three months before [the diagnosis of] COVID-19, are associated with very high mortality, up to 50%. Also, death from any condition or reason in patients with cancer is higher than the general population, including those who have been in remission and have not received treatment in the last year.

"We previously reported that immunotherapy was safe for use in patients with cancer and COVID-19, but this reveals more about anti-cancer treatments for patients, showing that immunotherapy combinations and immune-depleting drugs, but not immunotherapy alone, may lead to worse outcomes. More research is needed on this topic as we continue to investigate the effect of the pandemic on this group of patients."

Situated between Africa and Eurasia, the Arabian Peninsula is an important yet understudied region for understanding human evolution across the continents. Recent research highlighting the role of the Arabian Peninsula in human prehistory shows that humans repeatedly dispersed into the peninsula's interior at times when its harsh deserts were transformed into lush grasslands. However, the nature and timing of these dispersals have remained elusive, due to a scarcity of datable material and poor-resolution paleoecological data associated with evidence for humans.

In a new study published in Science Advances, researchers from the Max Planck Institutes for Chemical Ecology (MPI-CE) and the Science of Human History (MPI-SHH) in Jena, Germany and Royal Holloway University of London, UK, together with a team of international partners, describe a large assemblage of fossilized footprints discovered in an ancient lake deposit in Saudi Arabia's Nefud Desert. The footprints, dated to roughly 120 thousand-years-ago, include those of humans, elephants and horses, among other animals. These findings represent the earliest dated evidence for human movements into this part of the world, contemporary with well-known human dispersals from Africa to the Levant. In addition, it appears that the movements and landscape use patterns of humans and large mammals were tightly linked, perhaps in response to dry conditions and diminishing water supplies.

A Green Arabia in Human Prehistory

Because the Arabian Peninsula is characterized by large, hyper-arid deserts inhospitable to early humans and the animals they relied on, Arabia has received considerably less attention than Africa or Eurasia, neighboring regions that are vital to understanding human prehistory. However, research over the last decade has shown that this was not always the case, and it is now well-understood that conditions in Arabia have fluctuated significantly over the past million years.

"At certain times in the past, the deserts that dominate the interior of the peninsula transformed into expansive grasslands with permanent freshwater lakes and rivers," explains Richard Clark-Wilson of Royal Holloway, one of the lead authors of the study. "It was during these periods of climatic upturn that human and animal populations dispersed into the interior, as shown by the archaeological and fossil record."

Footprints as a High-Resolution Proxy

The footprints described in the new study were discovered during a recent survey of the Nefud Desert in Saudi Arabia. At an ancient lake deposit dubbed 'Alathar' (meaning "the trace" in Arabic) by the team, hundreds of human and animal footprints were discovered embedded in the surface, having been exposed following the erosion of overlying sediments.

"We immediately realized the potential of these findings," says Mathew Stewart of MPI-CE, one of the study's lead authors. "Footprints are a unique form of fossil evidence in that they provide snapshots in time, typically representing a few hours or days, a resolution we tend not get from other records."

Researchers were able to identify a number of animals from the footprints, including elephants, horses, and camels. The presence of elephants was particularly notable, as these large animals appear to have gone locally extinct in the Levant by around 400 thousand-years-ago.

"The presence of large animals such as elephants and hippos, together with open grasslands and large water resources, may have made northern Arabia a particularly attractive place to humans moving between Africa and Eurasia," says Michael Petraglia of MPI-SHH, who has been conducting research in the region for over a decade.

The dense concentration of footprints and evidence from the lake sediments suggests that animals may have been congregating around the lake in response to dry conditions and diminishing water supplies. Humans, too, may have been utilizing the lake for water and the surrounding area for foraging.

"We know people visited the lake, but the lack of stone tools or evidence of the use of animal carcasses suggests that their visit to the lake was only brief," says Stewart. Human movements and landscape use patterns, therefore, may have been closely linked to the large animals they shared the area with.

Early Human Dispersals into Arabia

The age of the footprints is of particular interest. They date to a period known as the last interglacial, a time of relatively humid conditions across the region and an important moment in human prehistory. Environmental changes during the last interglacial would have allowed humans and animals to disperse across otherwise desert regions, which normally acted as major barriers to dispersal during the less humid periods. Fossil and archaeological records indicate that these conditions also facilitated human dispersal from Africa into the Levant.

"It is only after the last interglacial with the return of cooler conditions that we have definitive evidence for Neanderthals moving into the region," says Stewart. "The footprints, therefore, most likely represent humans, or Homo sapiens."

These findings suggest that human movements beyond Africa during the last interglacial extended into northern Arabia, highlighting the importance of Arabia for the study of human prehistory.

Prices paid to hospitals nationally during 2018 by privately insured patients averaged 247% of what Medicare would have paid, with wide variation in prices among states, according to a new RAND Corporation study.

Some states (Arkansas, Michigan and Rhode Island) had relative prices under 200% of Medicare, while other states (Florida, Tennessee, Alaska, West Virginia and South Carolina) had relative prices that were above 325% of Medicare.

The study notes a steady increase in hospital prices, rising to the 2018 average level from an average of 224% of Medicare costs in 2016 and 230% of Medicare costs in 2017.

The analysis, which includes information from more than half of the nation's community hospitals, is a broad-based study of prices paid by private health plans to hospitals. A study from RAND last year looked at similar metrics from hospitals in 25 states.

"This analysis provides the most-detailed picture ever of what privately insured individuals pay for hospital-based care relative to what the government pays for people insured through Medicare," said Christopher Whaley, the study's lead author and a policy researcher at RAND, a nonprofit research organization. "Especially during the COVID-19 pandemic, employers need transparent information on the prices that they and their employees are paying for health care services."

If employers and health plans participating in the study had paid hospitals using Medicare's payment formulas, total payments over the 2016-2018 period would have been reduced by $19.7 billion, a potential savings of 58%.

"The rising gap between public and private hospital prices is a cause for concern and raises questions about the efficiency of the employer market," said Katherine Hempstead, senior policy adviser at the Robert Wood Johnson Foundation, which sponsored the project. "The goal of this work is to arm employers with data so they can negotiate more effectively. Curbing excessive spending on employer health insurance is in the public interest."

Spending on hospital services accounts for approximately 44% of total personal health care spending for the privately insured, and hospital price increases are key drivers of recent growth in per capita spending among the privately insured.

While recent price transparency initiatives have increased information about procedure-level prices available to patients, employers (who provide most private insurance) typically do not have usable information about the prices negotiated with hospitals on their behalf.

The RAND study is based on information from 49 states and Washington, D.C. (Maryland was excluded because it long has had a system in place where the privately insured and Medicare recipients pay the same price). Data sources include $33.8 billion in spending from 3,112 hospitals nationally, including approximately 750,000 claims for inpatient hospital stays and 40.2 million claims for outpatient services.

Researchers analyzed health care claims obtained from self-insured employers, six state all-payer claims databases and records from health insurance plans that chose to participate. For each private claim, researchers re-priced the service using Medicare's grouping and pricing formulas. Medicare is the federal insurance plan for Americans aged 65 and older.

Other findings from the study include an observation that hospital costs within individual states and hospital systems vary widely. Researchers also examined whether the observed differences in prices could be explained by differences in the quality of care. However, they did not find a strong relationship between prices and two widely-recognized metrics of quality and patient safety, or that variation in hospital prices is explained by differences in Medicare and Medicaid patient populations.

A large portion of private health insurance contracting for hospitals is done on a discounted-charge basis where the insurer agrees to pay a percentage of billed charges. By contrast, Medicare issues a fee schedule that determines the price it will pay for each service, with adjustments for inflation, hospital location, the severity of a patient's illness and other factors.

RAND researchers suggest that private insurers may want to move away from discounted-charge contracting for hospital services and shift to contracting based on a percent of Medicare or another similar fixed-price arrangement, often called reference-based pricing.

In both Montana and Oregon, the health plan for state employees has transitioned to a multiple-of-Medicare contracting arrangement. Employers in Indiana recently pushed to implement a reference-based pricing approach for outpatient services.

"In the case of specific high-priced hospitals, there may be justification for the unusually high prices, such as offering specialized services or a well-deserved reputation for higher-quality care," Whaley said. "However, if two hospitals have similar quality, then any difference in prices may be harder to justify. Employers can use the information in this report to help inform these comparisons and to make judgments about appropriate pricing."

A detailed list of both relative and standardized prices for each facility, identified by name and Medicare Provider Number, is included in the report's supplemental material. The supplemental material also includes CMS Hospital Compare star ratings for those hospital facilities.

Who are we? Where did we come from? How did we get here? Throughout the ages, humans have sought answers to these questions, pursuing wisdom through religion, philosophy, and eventually science. Evolutionary analyses published by Genome Biology and Evolution (GBE) allow us to peer into the mirror and better understand ourselves as a species, bringing us closer than ever to uncovering the answers to these long-held questions. GBE's latest virtual issue on human genetics highlights some of the most exciting research published in the journal within the last year and a half, demonstrating the wide variety of evolutionary approaches to this avenue of research as well as a number of fascinating insights into our own biology.

Taking over a decade to complete, the original Human Genome Project cost nearly $3 billion and involved the collective effort of hundreds of scientists. Since then, advances in sequencing technology have resulted in an explosion in human genetics and genomics research, with an estimated one million human genomes sequenced to date. While this wealth of data has the potential to answer some of our most fundamental questions, unlocking its mysteries has necessitated the invention of new analytic and computational methods and the integration of techniques and ideas from diverse biological sciences, including physiology, anatomy, medicine, population genetics, bioinformatics, and computational, molecular, and evolutionary biology.

A key area of investigation involves identifying ways in which humans differ from other primates--in other words, what makes us human? Several studies published over the last 18 months suggest that part of the answer may be found in transcriptional regulation and changes in gene expression. Edsall et al. (2019) evaluated differences in chromatin accessibility, which impacts access of the transcriptional machinery to the DNA, across five primates including humans. They found high levels of differentiation across species, as well as classes of sites that differed based on selection, genomic location, and cell type specificity. More specifically, Swain-Lenz et al. (2019) found that differences in chromatin accessibility near genes involved in lipid metabolism may provide a mechanistic explanation for the higher levels of body fat observed in humans compared to other primates. Arakawa et al. (2019) showed that human-specific increases in the transcription of four structural protein genes may give rise to morphological features specific to human skin, including increased thickness and strength compared to the skin of other primates. Finally, a catalog of proteins involved in transcriptional regulation by Perdomo-Sabogal and Nowick (2019) showed that certain types of transcription factors are associated with genes under positive selection, including those associated with schizophrenia, eye development, and fertility in humans.

Another area of interest is the role of mutation in shaping the human genome and our evolutionary history. For example, there has been considerable debate over how much of the human genome is subject to natural selection. It has been argued that this fraction cannot be too large, or else humans would suffer a loss of fitness due to the number of deleterious mutations. However, Galeota-Sprung et al. (2020) countered this argument by showing that the mutational load would be tolerable even if much of the human genome were subject to selection. Additional analyses by Castellano et al. (2020) revealed how the recombination rate, gene density, and mutation rate interact to shape patterns of DNA diversity across humans and other closely related homininae. A study by Prendergast et al. (2019) further uncovered unique biases in mutations that occur at adjacent nucleotide sites in humans, suggesting the existence of distinct evolutionary forces acting on such sites and identifying differences in these forces across human populations.

A particularly fascinating topic in this field is concerned with investigating genetic differences between human populations and their association with the natural history of these groups. For example, Harris et al. (2019) found that the ancestors of Native Americans carried the ancestral, rather than the derived, version of an ancient polymorphism that predates the split with Neanderthals. This polymorphism encompasses the fatty acid desaturase genes, and thus those with Native American ancestry may be at risk for low levels of nutrients derived from dietary omega-3 and omega-6 fatty acids. Jonnalagadda et al. (2019) identified a number of alleles associated with iris color and skin pigmentation in South Asians, while Vicuña et al. (2019) discovered genetic variants that may have helped the Andean Native American ancestors of people living in the Atacama Desert in northern Chile to adapt to high arsenic levels in the water. Analysis of another desert-dwelling population by Eaaswarkhanth et al. (2020) showed evidence for positive selection of a genomic region encompassing the TNKS gene in Kuwaiti individuals. Because this gene influences metabolic traits and hypertension risk, selection for this haplotype may have provided an advantage to Kuwaiti ancestors living in the desert of the Arabian Peninsula but has health implications for their modern day descendants.

Indeed, as revealed by these studies, one of the greatest potential benefits of this line of inquiry is the elucidation of new knowledge that informs our understanding of human health and disease. Reher et al. (2019) found that genes of the major histocompatibility complex, which helps the immune system recognize foreign substances, retain higher levels of diversity than other genes. This was true in both archaic and modern humans, even though archaic humans and Neanderthals had reduced levels of genetic diversity compared to modern humans. Lin and Gokcumen (2019) characterized fine-scale structural variation in the human genome and revealed hotspots that were associated with both adaptive and biomedically relevant variants. For example, they identified hotspots associated with alpha and beta hemoglobin gene clusters as well as idiopathic short stature. Finally, a study by Liu et al. (2019) of samples taken from within a single tumor of a patient with hepatocellular carcinoma showed that the mitochondrial genome was evolving neutrally, providing evidence that refutes the hypothesis that selection acts on mitochondrial DNA to promote tumor development.

Together, this selection of manuscripts highlights some of the latest findings and new approaches in the study of human genetics, a field that promises to help define who we are as a species and to reveal mysteries of human migration and adaptation that may otherwise have been lost to human history.

Researchers from the Singapore University of Technology and Design (SUTD) developed a method to perform direct ink writing (DIW) 3D printing of milk-based products at room temperature, while maintaining its temperature sensitive nutrients.

3D printing of food has been achieved by different printing methods, including the widely used selective laser sintering (SLS) and hot-melt extrusion methods. However, these methods are not always compatible with temperature-sensitive nutrients found in certain types of food. For instance, milk is rich in both calcium and protein, but as these nutrients are temperature sensitive, milk is unsuitable for 3D printing using the aforementioned printing methods which require high temperature. While the cold-extrusion is a viable alternative, it often requires rheology modifiers or additives to stabilize printed structures. Optimizing these additives is a complex and judicious task.

To tackle these limitations, the research team from SUTD's Soft Fluidics Lab changed the rheological properties of the printing ink and demonstrated DIW 3D printing of milk (refer to image) by cold-extrusion with a single milk product - powdered milk. The team found that the concentration of milk powder allowed for the simple formulation of 3D-printable milk inks using water to control the rheology. Extensive characterizations of the formulated milk ink were also conducted to analyse their rheological properties and ensure optimal printability.

"This novel yet simple method can be used in formulating various nutritious foods including those served to patients in hospitals for their special dietary needs," said the lead author and Ph.D. candidate from SUTD, Mr Lee Cheng Pau.

"Cold-extrusion does not compromise heat-sensitive nutrients and yet offers vast potential in 3D printing of aesthetically pleasing, nutritionally controlled foods customized for individual requirements," added Assistant Professor Michinao Hashimoto, the principal investigator of the study.

This research was published by RSC Advances, a leading journal that encourages high quality, well conducted studies which contribute to the advancement of chemistry and its applications. Rahul Karyappa, a research fellow at SUTD, also participated in this project.

Researchers from Peter the Great St.Petersburg Polytechnic University (SPbPU) developed a new mathematical model to predict economic performance of crops. It can assist the breeders to obtain the plants with the highest possible quality. The research results were presented at the fifth "Plant genetics, genomics, bioinformatics, and biotechnology" (PlantGen2019) conference as well as published in BMC Genetics and supported by the Russian Foundation for Basic Research, project 18-29-13033.

"We have developed a new mathematical model for predicting crop phenotypic traits as a function genotype," notes Maria Samsonova, head of the Laboratory of Mathematical Biology and Bioinformatics at SPbPU. She added, that such models in agriculture are called genomic selection models. It is very difficult to create a new variety of plants, it usually takes 10-12 years. Using genomic selection models, this process can be accelerated several times. "Our mathematical model, based on machine learning methods, performs better than modern analogs as it contains a significantly smaller number of parameters.

Scientists applied the model to predict phenotypic traits of an important crop, soybean. Among the traits, they analyzed plant height, number of seeds per plant, yield, protein and oil content in seeds.

"For breeders, it is very important to select parental plants able to produce offspring of high quality," says Anna Igolkina, engineer of the Laboratory of Mathematical Biology and Bioinformatics at SPbPU. "Due to the small number of parameters in our model, we can rank breeding pairs according to offspring quality and selected advanced parental pairs representing new potentially interesting donors of desired traits."

Scientists from the Department of Cell Biology of the University of Malaga (UMA) and the Andalusian Centre for Nanomedicine and Biotechnology (BIONAND) have made progress in finding new rapid implementation therapies to combat the COVID-19 pandemic, identifying a new drug that could prevent or mitigate the consequences derived from SARS-CoV-2 infection.

In the coming year, a team led by the researchers of the UMA Iván Durán and Fabiana Csukasi will study how 4-Phenylbutiric acid (4-PBA) treatment modulates the inflammatory response produced in severe cases of COVID-19. The project has been financed by the COVID-19 Fund of the Government of Andalusia, with an initial endowment of EUR 90,000 and the possibility of a three-year renewal. First results have already been published in the scientific journal Cytokine and Growth Factors Review.

The inflammatory process identified in severe cases of coronavirus causes an uncontrolled and excessive release of cytokines -molecules in charge of organizing the body's defenses- which could even trigger vascular hyperpermeability and multiorgan failure. Controlling such cytokine "storm", through those controlling them, that is, the infected cells, is precisely what these researchers of the UMA propose.

"When cells are stressed by infection, they call the cytokines, and the more stressed they are, the more persistent they become, provoking this uncontrolled inflammation. Hence, one possible treatment for COVID-19 is to reduce cellular stress", explains Durán.

According to the researcher, repurposing the 4-PBA anti-stress drug, approved for clinical use against other diseases and, hence, easy to apply clinically, could modulate such cellular stress, which is also present in pathologies like diabetes, aging or carcinogenesis, which, in turn, are classified as risk factors for COVID-19.

Identifying risk groups

"Our preliminary results conducted on animal models have demonstrated that 4-PBA fully curbs mortality caused by respiratory failure derived from cellular stress", says the professor of the UMA, who further explains that these first studies have also identified the endoplasmic reticulum resident protein "BiP" (Binding Immunoglobulin Protein) -a stress blood marker- as indicator of cellular stress situations, likely to be explored and measured in affected patients.

This way, as Durán points out, BiP levels, apart from determining the efficacy of 4-PBA treatment, could serve as early indicators of COVID-19 risk groups, establishing a correlation between high levels and the inflammatory severity after the viral infection.

"There are people already suffering from diseases that cause cellular stress, and when they become infected with coronavirus, they are more likely to fall ill or die. Therefore, if we know that the patient suffers from cellular stress, we can kill two birds with one stone: we can detect susceptibility before infection occurs and know how to treat it in due time", remarks the scientist of the UMA.
In order to confirm the effectiveness and security of 4-PBA treatment through in vitro and in vivo studies of cytokine storm and SARS-CoV-2 infection, the scientists Csukasi and Durán work at the Biomedical Research Institute of Malaga (IBIMA) in collaboration with Dr. José María Reguera and Dr. Javier Sánchez from the Regional University Hospital of Malaga and Virgen de la Victoria University Hospital, respectively, and Deborah Krakow, researcher of the University of California, Los Angeles, as well as the researchers Manuel Mari-Beffa, Gustavo Rico, José Miguel Tejeiro, Rick Visser and David Bagllieto, members of the Bioengineering and Tissue Regeneration Laboratory (LABRET), directed by Professor José Becerra, who are also members of the Cellular Therapy Network, CIBER-BBN and CIBER-NED.

In March 2020, Covid-19 was declared a global pandemic, and governments around the world imposed restrictions to reduce the spread of the Coronavirus. Some countries chose stricter measures than others. But what effect does social distancing and similar measures have on our mental health? How do we adapt?

Researchers at UiT have compared corona restrictions in six countries, and looked at psychological reactions among the population, their confidence in the restrictions and belief that the government is in control over Covid-19 in their countries.

They found that those who were satisfied with how the country fought the outbreak had better well-being and a lower perceived risk of getting Coronavirus.

Dissatisfaction created fear

- We found that those who were dissatisfied with the country's Covid-19 response saw the risk of getting the virus as greater, were more concerned and expressed reduced faith in the possibility of controlling the outbreak, says professor at the Department of Psychology, Gerit Pfuhl.
Together with colleague Martin Mækelæ, and international research colleagues, Dr. Phuhl now present the recent results of the study in the journal Royal Society Open Science.

- Dissatisfaction with the government's reactions to Covid-19 led to increased stress levels and psychological reactions, Pfuhl says about the results.

- Regardless of which country they lived in, those who were dissatisfied with the measures were more tense and perceived the risk of getting Covid-19 over the next two months as higher than those who were satisfied with how the country fought the outbreak, the researcher says.

Pfuhl explains that if you experience that your country is not doing enough, then you have more fear, if you think your country is doing enough to fight the outbreak, then you are more relaxed about it and have less fear.

These new research results provide important insights for decision-makers on how to take care of the well - being of their population during a global crisis.

Large survey

The researchers sent out questionnaires via social media in Norway, Germany, Israel, Colombia, Brazil and the USA, countries that had varying degrees of strict and mild restrictions. 2285 people are included in the analysis. The survey was voluntary, and the participants were asked questions about restrictions and reactions, psychological factors, fear and knowledge, and general demographics.

Gerit Pfuhl emphasizes that this study has looked at the measures that were used early in the pandemic, namely 12-31 March.

- At that time Colombia and Israel, with a full lockdown, that had the strictest measures. The mildest, in comparison with the other five countries we examined, was the USA, says Dr. Pfuhl.

Most people coped well

So how did ordinary people cope with the situation that arose in March?

- Most people coped well. Older people better than younger people. And in Norway better than other countries, says Gerit Pfuhl.

- Among the countries we compared, Norway did very well in many areas. We had little problems with mental health, and we had confidence in that our own actions and the actions of the authorities were effective, says Martin Mækelæ who is a psychology student that has worked in the project.

He says that a large proportion of Norwegians expressed that they were satisfied with how the authorities handled the situation.

- There were very few in Norway who were very scared. But we should not ignore those few, says the Dr. Pfuhl. Some people wrote to us by email, or used an open response field in the survey to express their anxiety. Among other things, some were afraid that their partner would die of Covid-19 due to for instance heart disease, says Pfuhl.

She thinks it agrees well with what other researchers have found out, i.e. that a few are very scared but most coped quite well with the situation.

Trust in society is good for health

- The vast majority reported that they believed that infection control measures were effective, says Mækelæ.

- It's nice to see that we adapt. This means that despite the fact that the closure of society has changed the way of life, most people stayed calm and collected, and especially those who believe that their country will succeed in fighting the outbreak.

In other words, the more trust you have in society, the government, fellow citizens, and your own self-efficacy, the better it is for your own mental health.

- More than 90 percent of the population, perform infection-reducing actions, and most have self-efficacy, says Pfuhl.

When asked which restrictions are the most effective and which affect mental health the least, Pfuhl answers:

- Measures that prevent physical gatherings of people indoors are very effective. That is, fewer meetings or digital meetings - because this only creates physical distance but not social distance.

Important to communicate well

If we experienced the start of the pandemic again, and if you were part of the Norwegian government, would you do something different?

- It is hard to say. On the one hand, Norway reacted late, as did the whole of Europe, Pfuhl believes.

- On the other hand, Norway was quite good at communicating about the pandemic. The authorities were honest about the uncertainty about how serious it was.

- The government communicated well, but it could always have been better, given that the number of deaths is in itself not very informative.

She believes one must look relatively at such figures.

- That is, how many of those who tested positive died, and whether they died with or because of Coronavirus. This can reduce the fear that it is a very serious, deadly disease, the researcher concludes.

The BioScience Talks podcast features discussions of topical issues related to the biological sciences.

In the latest installment of the journal BioScience's In Their Own Words oral history series, acclaimed astrophysicist Neil deGrasse Tyson shared insights on a number of topics, including Mars exploration, the COVID-19 pandemic, and numerous themes discussed in the most recent season of his show COSMOS: Possible Worlds.
Over the course of the career-spanning interview, the Frederick P. Rose Director of the Hayden Planetarium at the American Museum of Natural History and renowned science communicator also weighed in on the numerous challenges presently facing humanity. "Every disaster movie ends with important people ignoring scientists," said Tyson, who also highlighted the cyclical nature of history, comparing the current political climate with that preceding the Second World War.
In the interview, which is also published in the pages of BioScience, Tyson shed light on his views on space exploration and the role of commercial enterprise therein. While broadly endorsing public-private partnership, he underscored the continued importance of NASA in pressing the frontiers of human discovery: "The private relationship to the moving frontier of space is historically a second-wave phenomenon," he said, because "the first wave is hugely expensive."

To hear the whole discussion, visit this link for this latest episode of the BioScience Talks podcast.

A group of scientists from Russia studied the trends in the evolution of amino acid sequences of proteins in vertebrates and insects and traced the factors influencing the process of evolution. The research results are published in the Nature Communications.

Proteins provide for the majority of the most crucial functions of the body. Hence, changes in the amino acid sequences of proteins are a real mirror of evolution, in which scientists can track evolutionary changes and their implications for the body.

The evolution of protein sequences can occur under the influence of two factors. The first one is external (for example, changes in the environment or the impact of pathogens), and it is the classic engine of evolution. The second factor is related to the changes within the genome, usually in this case, they mean epistasis, the interaction between different genes.

A group of scientists from Skoltech, the Institute for Information Transmission Problems of the Russian Academy of Sciences, Moscow State University, and the Institute of Epidemiology under the leadership of Georgii Bazykin, Professor of the Skoltech Life Sciences Center, showed that these two forces lead to opposite patterns of sequence evolution. Thus, looking at these patterns, it is possible to estimate the contribution of the external environment and epistasis to the evolution of proteins.

"Patterns are such that due to external changes, the variant of the gene currently entrenched in the course of evolution will become less profitable over time. On the contrary, under the influence of epistasis, coevolution occurs, the interacting regions of the genome "adjust" to each other. As a result, their successful combination becomes more and more evolutionarily advantageous," says the first author of the study, Skoltech graduate student Anastasia Stolyarova.

Using bioinformatics analysis of protein sequences from the genomes of vertebrates and insects, scientists were able to describe new universal evolutionary patterns. External factors can be considered as a reason for positive selection affecting certain genomic positions and serve as an essential aspect for the rapid evolution of these positions. But the effect of epistasis is manifested in positions under negative selection, as a result of which substitutions from one option to another occur less often in them - they evolve more slowly.

Why does the mouse sleep five times longer than the elephant? Why do babies sleep longer than adults? If these sound like riddles, that's because they have been. Sleep, in spite of its ubiquity, holds mysteries that have perplexed scientists for decades.

Now, using data from humans and other mammals, a team of scientists including researchers from the Santa Fe Institute has developed one of the first quantitative models that explains why sleep times across species and during development decrease as brains get bigger. Crucially, the model identifies a sharp transition at around 2.4 years of age, where sleep patterns change in humans as the primary purpose of sleep shifts from reorganization to repair.

"By looking at sleep, and looking how it changes, you get insight into something truly fundamental about brain development," says Geoffrey West, a theoretical physicist who is Shannan Distinguished Professor and a past president of SFI.

Previous work done by West and Van Savage, a physicist and biologist who is a professor at UCLA and an external professor at SFI, looked at differences in sleep times among mammals. The new research in Science Advances ties phylogeny -- the evolutionary relationships between species -- and ontogeny -- the development of an organism as it ages -- into a unified framework.

Although experts have proposed many possible reasons for sleep, the two most prominent are neural reorganization, which is essentially learning, and repair. During waking hours, the brain experiences wear and tear from blood flow and the everyday production of harmful chemicals; sleep cleans this up. The brain reorganizes and repairs mainly when asleep - - West likens it to subway repairs that take place at night to avoid disrupting normal traffic.

Time asleep can roughly be divided into REM (random eye movement) and NREM (non-REM). Colloquially, REM sleep is often known as "deep sleep," but its purpose has remained an open question.

To answer questions about REM and NREM, the new model reduces the brain to a series of simple equations that capture how the brain uses energy to process information (which it must then reorganize). Then the authors input data from a variety of studies that looked at sleep time, metabolic rate, and brain size for dozens of participants who ranged from infants to adolescents.

By determining the ratios of REM and NREM to total sleeping time -- among other factors like brain size -- the researchers were able to use the model to predict their respective purposes. It turns out REM sleep is primarily responsible for reorganization/learning that dominates early development, while NREM handles the everyday repair that occurs throughout life.

Around 2.4 years old, the researchers observed a sudden change, where the majority of sleep shifts from REM to NREM -- a phase shift from sleeping to reorganize to sleeping to repair. In other words, humans sleep less in part because they no longer need to form as many new neural connections. This transition point has not been pinpointed before, but it could have important implications for development, according to Savage.

"The brain is doing something really amazing and very different during that period," he says. "What are the consequences of that, in terms of our ability to learn languages or adapt our brains to different situations?"

Preliminary measurements of other animals in development (rabbits, rats, and guinea pigs) show similarities to human sleep, but it's too soon to say if all mammal babies follow the same sharp transition.

"I'm very interested to see if our framework also can be extended to other mammals," says Junyu Cao, a researcher at the University of Texas at Austin and the paper's lead author.

The research was initiated at SFI in 2007, when Savage was a postdoctoral fellow working with West. It has since evolved through a series of workshops and working groups as part of the Institute's ongoing research on biological scaling laws and complex time.

Prolonged sleep deprivation can lead to severe health problems in humans and other animals. But why is sleep so vital to our health? A UCLA-led team of scientists has answered this question and shown for the first time that a dramatic change in the purpose of sleep occurs at the age of about 2-and-a-half.

Before that age, the brain grows very rapidly. During REM sleep, when vivid dreams occur, the young brain is busy building and strengthening synapses -- the structures that connect neurons to one another and allow them to communicate.

"Don't wake babies up during REM sleep -- important work is being done in their brains as they sleep," said senior study author Gina Poe, a UCLA professor of integrative biology and physiology who has conducted sleep research for more than 30 years.

After 2-and-a-half years, however, sleep's primary purpose switches from brain building to brain maintenance and repair, a role it maintains for the rest of our lives, the scientists report Sept. 18 in the journal Science Advances. This transition, the researchers say, corresponds to changes in brain development.

All animals naturally experience a certain amount of neurological damage during waking hours, and the resulting debris, including damaged genes and proteins within neurons, can build up and cause brain disease. Sleep helps repair this damage and clear the debris -- essentially decluttering the brain and taking out the trash that can lead to serious illness.

Nearly all of this brain repair occurs during sleep, according to senior author Van Savage, a UCLA professor of ecology and evolutionary biology and of computational medicine, and his colleagues.

"I was shocked how huge a change this is over a short period of time, and that this switch occurs when we're so young," Savage said. "It's a transition that is analogous to when water freezes to ice."

The research team, which included scientists with expertise in neuroscience, biology, mathematics and statistics, conducted the most comprehensive statistical analysis of sleep to date, using data from more than 60 sleep studies involving humans and other mammals. They examined data on sleep throughout development -- including total sleep time, REM sleep time, brain size and body size -- and built and tested a mathematical model to explain how sleep changes with brain and body size.

The data were remarkably consistent: All species experienced a dramatic decline in REM sleep when they reached the human developmental equivalent of about 2-and-half years of age. The fraction of time spent in REM sleep before and after that point was roughly the same, whether the researchers studied rabbits, rats, pigs or humans.

REM sleep decreases with the growth in brain size throughout development, the scientists found. While newborns spend about 50% of their sleep time in REM sleep, that falls to about 25% by the age of 10 and continues to decrease with age. Adults older than 50 spend approximately 15% of their time asleep in REM. The significant dropoff in REM sleep at about 2-and-a-half happens just as the major change in the function of sleep occurs, Poe said.

"Sleep is as important as food," Poe said. "And it's miraculous how well sleep matches the needs of our nervous system. From jellyfish to birds to whales, everyone sleeps. While we sleep, our brains are not resting."

A chronic lack of sleep likely contributes to long-term health problems such as dementia and other cognitive disorders, diabetes, and obesity, to name a few, Poe said. When you start to feel tired, she said, don't fight it -- go to bed.

"I fought sleep and pulled all-nighters when I was in college, and now think that was a mistake," Savage said. "I would have been better off with a good night's sleep. Now when I feel tired, I don't have any guilt about sleeping."

For most adults, a regular seven-and-a-half hours of sleep a night is normal -- and time lying awake doesn't count, Poe says. While children need more sleep, babies need much more, roughly twice as much as adults. The large percentage of REM sleep in babies is in stark contrast to the amount of REM sleep observed in adult mammals across an enormous range of brain sizes and body sizes. Adult humans have five REM cycles during a full night of sleep and can have a few dreams in each cycle.

A good night's sleep is excellent medicine, Poe says. And it's free.

The removal of one gene renders poxviruses - a lethal family of viral infections that are known to spread from animals to humans - harmless, a new study in the journal Science Advances reports.

During this ground-breaking study, scientists from the Spanish National Research Council and the University of Surrey investigated the immune response of cells to poxviruses. Poxviruses, such as cowpox and monkeypox, can spread to humans from infected animals, causing skin lesions, fever, swollen lymph nodes and even death.

Viruses contain genetic material which helps them outsmart host cells, enabling replication and the spread of the infection. Cells in the body are comprised of molecules that sense the presence of viruses, sometimes via the recognition of their genetic material, and alert the immune system of an upcoming infection. Poxviruses, unlike other viruses, are highly unusual in that they have large DNA genomes that are replicated exclusively in the cell cytosol, an area of the cell full of sensors. How poxviruses manage to stay undetectable has remained unknown.

Resembling human smallpox, scientists in this study used ectromelia virus (ECTV), a member of the poxvirus family that causes mousepox. ECTV spreads through the lymphatic system of mice to vital organs, where massive replication of the virus takes place, resulting in the rapid death of the animal.

During their investigations, scientists identified a gene, viral Schlafen (vSLFN), which was found to block the cell response to the virus genome making the infection silent to the immune system. Remarkably, disabling this one gene made the infection detectable, triggering a potent immune response that protected animals against doses one million times higher than the regular lethal quantity.

Following the removal of vSLFN, it was found that animals with the modified virus were protected from subcutaneous, respiratory and intravenous infection and all survived. Scientists also found that the protection was mediated by interferon, a known molecule with powerful anti-viral properties, and natural killer cells, which play a major role in the host-rejection of virally infected cells.

Researchers believe that these findings will shed light into how we combat microbial infections and will improve the efficacy and safety of vaccines, anti-cancer agents and gene therapies that are based on poxviruses.

Dr Carlos Maluquer de Motes, Senior Lecturer in Molecular Virology at the University of Surrey, said: "Viruses, although minuscule, are very complex agents with very sophisticated strategies contained in their genetic material. But it is also this same genetic material that makes them vulnerable to cell recognition. The removal of vSLFN gene protected animal against mousepox, and we believe that that we may see the same results for other poxviruses.

"Our findings reveal the importance of activating the molecules responsible for the detection of the genetic material of microbes in the fight against viruses. In addition, they also suggest that mimicking the action of vSLFN may be a valid strategy to prevent auto inflammatory and autoimmune diseases that are caused when the genetic material of cells is sensed by the immune system, promoting a reaction."

Dr Antonio Alcami from the Spanish National Research Council, said: "Viral inhibition of DNA sensing prevents the induction of the type I IFN response and complements another viral mechanism to sequester type I IFN through the secretion of soluble IFN decoy receptors. This highlights the importance of the type I IFN response in the control of immunity."