Culture

An international team of plant scientists have shown the potential to rapidly improve the quality of barley grain through a genetic tool known as CRISPR or gene editing.

Published in The Plant Journal, researchers from the University of Adelaide's Waite Research Institute working with the James Hutton Institute in Scotland and other colleagues in the UK and Melbourne, describe how the levels of beta-glucan in barley grain can be influenced through gene editing.

Joint senior author Associate Professor Matthew Tucker, Deputy Director of the Waite Research Institute, says: "Barley grain is comparatively rich in beta-glucan, a source of fermentable dietary fibre that protects against various human health conditions. However, crops with a low content of this compound are preferred for brewing and distilling.

"The research has given us further insight into key genes responsible for barley grain composition and, by using CRISPR gene editing, plant breeders will have the potential to accelerate plant breeding and deliver new crop varieties that are best suited to their target markets."

This work was carried out by Dr Guillermo Garcia-Gimenez during his PhD at the James Hutton Institute and the University of Adelaide. It is the first published use of the CRISPR technique to influence barley grain quality in Australia and Scotland.

Dr Garcia-Gimenez says: "We used what's called a reverse genetics approach, using CRISPR to generate changes in members of the gene superfamily responsible for making beta-glucan. The results led to specific differences in grain quality, composition and content of beta-glucan.

"We hope this work will contribute to creating awareness about the potential of this technique and we look forward to trialling the new plants in field conditions."

Associate Professor Tucker says: "This study has brought real immediate benefit in terms of understanding how gene editing can help improve the quality of barley crops. And it's part of our overall ongoing efforts to apply the latest genetic techniques to deliver improvements for the food and feed industries."

Professor Matthew Gilliham, Director of the Waite Research institute, says: "Barley is Australia's second most important cereal crop behind wheat, contributing around $3 billion to the economy. Despite recent market fluctuations, this discovery is important and opens the door to significant economic impact for breeders and growers.

"The Waite Research Institute, in partnership with The International Barley Hub, is showing again that research in this area can yield great returns on investment in the basic understanding of barley."

A study conducted by Hiroshima University researchers found that using Ultraviolet C light with a wavelength of 222 nanometers which is safer to use around humans effectively kills SARS-CoV-2 -- the first research in the world to prove its efficacy against the virus that causes COVID-19.

Other studies involving 222 nm UVC, also known as Far-UVC, have so far only looked at its potency in eradicating seasonal coronaviruses that are structurally similar to the SARS-CoV-2 but not on the COVID-19-causing virus itself. A nanometer is equivalent to one billionth of a meter.

An in vitro experiment by HU researchers showed that 99.7% of the SARS-CoV-2 viral culture was killed after a 30-second exposure to 222 nm UVC irradiation at 0.1 mW/cm2. The study is published in the American Journal of Infection Control.

Tests were conducted using Ushio's Care222TM krypton-chloride excimer lamp. A 100 microliter solution containing the virus (ca. 5 × 106 TCID50/mL) was spread onto a 9-centimeter sterile polystyrene plate. The researchers allowed it to dry in a biosafety cabinet at room temperature before placing the Far-UVC lamp 24 centimeters above the surface of the plates.

222 nm vs 254 nm UVC

A wavelength of 222 nm UVC cannot penetrate the outer, non-living layer of the human eye and skin so it won't cause harm to the living cells beneath. This makes it a safer but equally potent alternative to the more damaging 254 nm UVC germicidal lamps increasingly used in disinfecting healthcare facilities.

Since 254 nm UVC harms exposed human tissues, it can only be used to sanitize empty rooms. But 222 nm UVC can be a promising disinfection system for occupied public spaces including hospitals where nosocomial infections are a possibility.

The researchers, however, suggest further evaluation of the safety and effectiveness of 222 nm UVC irradiation in killing SARS-CoV-2 viruses in real-world surfaces as their study only investigated its in vitro efficacy.

Changing skins

Cells are surrounded by a layer of membrane lipids that protect them from changes in their environment such as temperature, much in the same way that our skin changes when we are cold or exposed to the sun. Lead author and NIOZ senior scientist Laura Villanueva explains why they make such interesting biomarkers. 'When a cell dies, these lipids preserve like fossils and hold ancient-old information on Earths' early environmental conditions.' Our tree of life includes small and simple cells (Bacteria and Archaea) and more complex cells (Eukaryotes), including animals and humans. Bacteria and Eukaryotes share a similar lipid membrane. Looking at Archaea, their 'skin' or membrane looks very different and is primarily designed to help these microorganisms to survive in extreme environments. Villanueva: 'This "lipid divide", or difference in membranes between Bacteria and Eukaryotes on the one hand and Archaea on the other, is believed to have happened after the emergence of Bacteria and Archaea from the last universal cellular ancestor (LUCA).'

Missing piece hidden in the deep Black Sea

The leading theory is that Eukaryotes evolved from a symbiosis event between archaeal and bacterial cells in which the archaeal cell was the host. But how does this work when their 'skins' are so different and share no sign of common ancestry? Villanueva: 'To explain the creation of more complex life-forms, the archaeal membrane must have made a switch to a bacterial type membrane. Such a switch likely needed a transition period in which the two membrane types were mixed.' However, mixed lipid membranes had never been found in microbes until the team of Villanueva made an unexpected discovery in de deep waters of the Black Sea.

Villanueva: 'We found a possible missing piece of this puzzle in the Black Sea. Here, an abundant group of bacteria thrive in the deep-sea, absent of oxygen and with high sulfide concentration. We discovered that the genetic material of this group did not only carry pathway genes for bacterial lipids but archaeal ones as well.' The peculiarity was also found in the genetic material of other, closely related Bacteria and supports the idea that this ability to create 'mixed' membranes is more widespread than previously thought. This discovery sheds new light on the evolution of all cellular life forms and may have important consequences for the interpretation of archaeal lipid fossils in the geological record and paleoclimate reconstructions.

Climate changes associated with global warming can affect astronomical observations. That is the result of a study involving scientists from the University of Cologne. The international research team investigated a range of climate parameters at the Very Large Telescope (VLT) at the Paranal in the Atacama Desert in Chile, where the European Southern Observatory (ESO) operates its telescopes. Among other things, the team evaluated the data for temperature, wind speed and wind direction, and the water vapour content in the atmosphere over a period of several decades. This revealed an increase in temperatures above the world average and also increasing image blur due to air turbulence - so-called seeing.

The study 'The impact of climate change on astronomical observations' was published in the current issue of Nature Astronomy and can be viewed online. Its results are not only important for astronomers to adapt their observations to changing environmental conditions, but must also be taken into account when planning new large telescopes - such as the Extremely Large Telescope (ELT), which is currently being built near the Paranal.

The Cologne-based scientists Professor Dr Susanne Crewell and Christoph Böhm from the Institute of Geophysics and Meteorology were involved in the study. In the past, they had already explored various aspects of the past, present and future climate at the telescope's site in the framework of Collaborative Research Centre 1211 'Earth - Evolution at the Dry Limit'. The first author of the article is Faustine Cantalloube from the Max Planck Institute for Astronomy in Heidelberg.

The researchers investigated the extent to which climate change affects astronomy and in particular the quality of observations. The team focused on the Paranal Observatory in northern Chile because it has a whole range of environmental sensors that document local meteorological conditions. These measurements yielded one of the most comprehensive data sets over the last three decades at a largely untouched location.

Based on this data set, astronomers, climate researchers, atmosphere scientists, and meteorologists joined forces to identify important meteorological parameters that play a role in the quality of astronomical observations. The data allowed them to analyse long-term trends over a period of more than thirty years to determine the impact of climate change on future observations. Using four examples, they showed how climate change is already affecting, or might affect the operation of an astronomical observatory in future. The VLT, operated by ESO, was served as an example.

'The data showed a 1.5 ° C increase in near-ground temperature over the last four decades at the Paranal Observatory. This is slightly higher than the worldwide average of 1°C since the pre-industrial age,' said Susanne Crewell. Since the original telescope cooling system was not designed for such warm conditions, the quality of observations is increasingly endangered by more frequent turbulences - a consequence of the rise in temperature. The expected rise of 4° C (the most pessimistic scenario of the ICCP climate simulations) within the next century thus has to be taken into account in the construction of the 39-metre Extremely Large Telescope (ELT) at a nearby site.

In particular, astronomers face the challenge of a reduction in the so-called 'dome seeing', a reduction in resolution due to turbulence within the telescope dome. The researchers furthermore noticed an increase in turbulence in the air layer near the ground, making images blurred since cold and warm air layers with different refractive indices alternate more quickly. However, attributing this to climate change is difficult, since there were also constructional changes. The increase in wind shear in the upper troposphere in connection with the jet stream also leads to a so-called 'wind-driven halo'. This phenomenon appears when atmospheric turbulence conditions vary faster than the telescope's control system can correct them. This limits the contrast capabilities of the instrument and could potentially limit exoplanet studies. An increase in water vapour in the atmosphere moreover could lead to a reduction of the astronomical signal.

Through their unique perspective on the universe, astronomers know that the origin of life on Earth was a complex process made possible only by the coincidence of extremely rare circumstances. There is no second Earth in our neighbourhood. For this reason, the current issue of Nature Astronomy, published on September 10, is dedicated to the topic climate. The special issue aims to raise awareness in astronomy for climate aspects that are important for the work of astronomers.

The spike protein on the surface of the SARS-CoV-2 coronavirus can adopt at least ten distinct structural states, when in contact with the human virus receptor ACE2, according to research from the Francis Crick Institute published in Nature today (Thursday).

This new insight into the mechanism of infection will equip research groups with the understanding needed to inform studies into vaccines and treatments.

The surface of SARS-CoV-2, the virus that causes COVID-19, is covered in proteins called spikes, which enable the virus to infect human cells. The infection begins when a spike protein binds with ACE2 cell surface receptors and, at later stages, catalyses the release of the virus genome into the cell.

However, the exact nature of the ACE2 binding to the SARS-CoV-2 spike remains unknown.

In the first study to examine the binding mechanism between ACE2 and the spike protein in its entirety, researchers in the Crick's Structural Biology of Disease Processes Laboratory, have characterised ten distinct structures that are associated with different stages of receptor binding and infection.

The team incubated a mixture of spike protein and ACE2 before trapping different forms of the protein by rapid freezing in liquid ethane. They examined these samples using cryo-electron microscopy, obtaining tens of thousands of high-resolution images of the different binding stages.

They observed that the spike protein exists as a mixture of closed and open structures., Following ACE2 binding at a single open site, the spike protein becomes more open, leading to a series of favourable conformational changes, priming it for additional binding. Once the spike is bound to ACE2 at all three of its binding sites, its central core becomes exposed, which may help the virus to fuse to the cell membrane, permitting infection.

"By examining the binding event in its entirety, we've been able to characterise spike structures that are unique to SARS-CoV-2," says Donald Benton, co-lead author and postdoctoral training fellow in the Structural Biology of Disease Processes Laboratory at the Crick.

"We can see that as the spike becomes more open, the stability of the protein will reduce, which may increase the ability of the protein to carry out membrane fusion, allowing infection."

The researchers hope that the more we can uncover about how SARS-CoV-2 differs from other coronaviruses, the more targeted we can be with the development of new treatments and vaccines.

Antoni Wrobel, co-lead author and postdoctoral training fellow in the Structural Biology of Disease Processes Laboratory at the Crick, says: "As we unravel the mechanism of the earliest stages of infection, we could expose new targets for treatments or understand which currently available anti-viral treatments are more likely to work."

Steve Gamblin, group leader of the Structural Biology of Disease Processes Laboratory at the Crick says: "There's so much we still don't know about SARS-CoV-2, but its basic biology contains the clues to managing this pandemic.

"By understanding what makes this virus distinctive, researchers could expose weaknesses to exploit."

The team are continuing to examine the structures of spikes of SARS-CoV-2 and related coronaviruses in other species to better understand the mechanisms of viral infection and evolution.

A milk-tooth found in the vicinity of "Riparo del Broion" on the Berici Hills in the Veneto region bears evidence of one of the last Neanderthals in Italy. This small canine tooth belonged to a child between 11 and 12 that had lived in that area around 48,000 years ago. This is the most recent Neanderthal finding in Northern Italy.

The study uncovering this tooth was carried out by a group of researchers from the Universities of Bologna and Ferrara, who have recently published a paper in the Journal of Human Evolution. "This work stems from the synergy between different disciplines and specializations", says Matteo Romandini, lead author of this study and researcher at the University of Bologna. "High-resolution prehistoric field-archaeology allowed us to find the tooth, then we employed virtual approaches to the analyses of its shape, genome, taphonomy and of its radiometric profile. Following this process, we could identify this tooth as belonging to a child that was one of the last Neanderthals in Italy".

The genetic analysis reveals that the owner of the tooth found in Veneto was a relative, on their mother's side, of Neanderthals that had lived in Belgium. This makes this site in Veneto a key-area for comprehending the gradual extinction of Neanderthals in Europe.

"This small tooth is extremely important", according to Stefano Benazzi, professor at the University of Bologna and research coordinator. "This is even more relevant if we consider that, when this child who lived in Veneto lost their tooth, Homo Sapiens communities were already present a thousand kilometres away in Bulgaria".

Researchers analysed the tooth by employing highly innovative virtual methods. "The techniques we employed to analyse the tooth led to the following discovery: this is an upper canine milk-tooth that belonged to a Neanderthal child, aged 11 or 12, that lived between 48,000 and 45,000 years ago", as report Gregorio Oxilia and Eugenio Bortolini, who are co-authors of the study and researchers at the University of Bologna. "According to this dating, this little milk-tooth is the most recent finding of the Neanderthal period in Northern Italy and one of the latest in the entire peninsula".

The findings retrieved from the "Riparo del Broion" are still being analysed. However, preliminary results show that this site had been used for a long period of time as there are signs of hunting activities and butchering of large prays. "The manufacturing of tools, mainly made of flint, shows Neanderthals' great adaptability and their systematic and specialized exploitation of the raw materials available in this area", adds Marco Peresanti, a professor of the University of Ferrara who contributed to the study.

Up to one in four Danes has an unhealthy accumulation of fat in the liver, also known as fatty liver. Fatty liver is rarely the cause of symptoms in itself, but people with fatty liver have an increased risk of developing diabetes. Exactly how the two diseases are linked has, however, so far been unknown.

Now, a new study from the Faculty of Health and Medical Sciences at the University of Copenhagen shows that people with fatty liver have reduced sensitivity to glucagon which increases the glucagon secretion and leads to increased amounts of glucagon in the blood. The same is seen in patients with type 2 diabetes, the vast majority of whom have increased fat in the liver.

'The reduced glucagon sensitivity means that the secretion of glucagon is increased via a so-called feedback system between the liver and the pancreas. An elevated level of glucagon is undesirable as it increases sugar production in the liver and thus creates a high blood sugar level', says Nicolai J. Wewer Albrechtsen, Assistant Professor at the Novo Nordisk Center for Protein Research and Resident at the Department of Clinical Biochemistry, Rigshospitalet.

With the study, the researchers are introducing an entirely new concept within the field of diabetes: glucagon resistance. They believe that the concept is so fundamental to the understanding of diabetes that it should not be limited to laboratories and research environments.

'Glucagon resistance is an entirely new biological concept that we will include in the future teaching of medical students, just as we do today with insulin resistance', says Nicolai J. Wewer Albrechtsen.

Potential New Treatment

The decreased glucagon sensitivity may help to explain the connection between fatty liver and type 2 diabetes. And with new knowledge come new opportunities. If you can detect decreased glucagon sensitivity, you can start treatment earlier. That way, you can stop the glucagon level and thus the blood sugar from running wild.

'Our study points to a new biomarker (the glucagon-alanine index) that may be useful in identifying persons with impaired glucagon sensitivity. If we can detect glucagon resistance from a blood test, we can start treatment early and thus prevent the development of type 2 diabetes', says PhD student at the Novo Nordisk Foundation Center for Protein Research and the Department of Biomedical Sciences, Marie Winther-Sørensen.

The treatment consists primarily of weight loss, which will limit the amount of fat in the liver, but may also include drugs that go in and inhibit the hormone glucagon.

'We know that the pharmaceutical industry has just started using our marker for glucagon sensitivity in studies where new treatments are tested. Our study has the potential to demonstrate glucagon resistance in fatty liver based on a simple blood test, and we must now investigate this in a so-called lottery experiment', says Marie Winther-Sørensen.

An international consortium of researchers under the aegis of CMIP6 has calculated new estimates for the melting of Earth's ice sheets due to greenhouse gas emissions and its impact on sea levels, showing that the ice sheets could together contribute more than 40 cm by the end of 2100.

One of the many effects of global warming is the increase of sea levels due to the melting and retreat of the ice sheets in the Arctic and the Antarctic. As the sea level rises, large areas of densely populated coastal land will become uninhabitable. It is vital that we understand the impact climate change interventions could have on the rate of melting and, consequently, changes in sea level.

The Ice Sheet Model Intercomparison Project for CMIP6 (ISMIP6), consisting of more than 60 scientists from 36 institutions across the world - including Dr. Christopher Chambers and Professor Ralf Greve from the Institute of Low Temperature Science at Hokkaido University - has used the latest generation of models to estimate the impact of global warming on ice sheets. Their results were published in a special issue of the journal The Cryosphere on September 17.

The ISMIP6 team projected the changes of the Greenland and Antarctic Ice Sheets (GrIS/AIS) between 2015 and 2100 under global warming conditions predicted by climate modelling. The advantage of ISMIP6 was that it used fourteen different models to estimate the changes in the ice sheet under two greenhouse gas (GHG) emissions pathways: the pessimistic scenario, where there is no change in current trends, leading to a rapid increase in GHG emissions; and the optimistic scenario, where comprehensive steps are taken to reduce GHG emissions. Using different models to estimate the changes was vital to this endeavour, as they have different baselines and assumptions.

Ralf Greve and Christopher Chambers modelled the behavior of ice sheets using the SICOPOLIS model. The first version was released in 1995 by Greve, and since then it has been continuously developed and used for a large number of studies. The SICOPOLIS model uses data from 1990 as a baseline for the experiments. As the model has a 25-year history with an uninterrupted development and publication record, it brought a unique perspective to ISMIP6.

The rate of ice sheet change was modelled under different forcings provided by climate models: future changes of precipitation, surface melting over the ice sheets, surface and ocean temperatures. The goal was to estimate how much the mass loss of the ice sheets would contribute to the rise in average sea levels beyond what has already been put in motion. The study found that, by 2100, the GrIS would raise sea levels by 4-14 cm under the pessimistic scenario, but only 1.5-5 cm under the optimistic scenario. For the AIS, the results point to a greater range of possibilities, from ice sheet change that decreases sea level by 7.8 cm to increasing it by 30 cm under the pessimistic scenario, and an increase of 0-3 cm under the optimistic scenario.

"Mass change from the AIS is notoriously difficult to predict: Increasing ocean temperatures erode the bottom of large floating ice shelves, causing loss; while the AIS can also gain mass by increased snowfall due to warmer air temperatures. However, we are constantly improving our understanding of the ice sheets and their interaction with the Earth's climate system. Modelling intercomparison studies like ISMIP6 are an effective tool to provide society with the necessary information, including uncertainties, for rational decisions", said Ralf Greve.

This effort took over six years of collaboration, and the findings of ISMIP6 will help inform the Sixth Assessment Report (AR6) of the Intergovernmental Panel on Climate Change (IPCC), scheduled for release in 2022. ISMIP6 is part of the sixth phase of the Coupled Model Intercomparison Project (CMIP6). CMIP6 currently has a total of 23 endorsed Model Intercomparison Projects (MIPs), and has been invaluable in assessing our understanding of climate and climate change.

Women with a longer reproductive period had an elevated risk for dementia in old age, compared with those who were fertile for a shorter period, a population-based study from the University of Gothenburg shows.

"Our results may explain why women have a higher risk of developing dementia and Alzheimer's disease than men after age 85, and provide further support for the hypothesis that estrogen affect the risk of dementia among women", says Jenna Najar, a medical doctor and doctoral student at Sahlgrenska Academy who also works at AgeCap, the Centre for Ageing and Health at the University of Gothenburg.

The study, now published in the journal Alzheimer's & Dementia, covers 1,364 women who were followed between 1968 and 2012 in the population studies collectively known as the "Prospective Population-based Study of Women in Gothenburg" (PPSW) and the "Gothenburg H70 Birth Cohort Studies in Sweden" (the H70 studies). The "reproduction period" spans the years between menarche (onset of menstruation) and menopause, when menstruation ceases.

Of the women studied with a shorter reproductive period (32.6 years or less), 16 percent (53 of 333 individuals) developed dementia. In the group of women who were fertile a longer period (38 years or more), 24 percent (88 of 364) developed dementia. The difference was thus 8 percentage points.

The study shows that risk for dementia and Alzheimer's disease increases successively for every additional year that the woman remains fertile. The association was strongest for those with dementia onset after age 85, and the effect was most strongly associated with age at menopause.

These results persisted after adjustment for other factors with an influence, such as educational attainment, physical activity, BMI, smoking, and cardiovascular disease. On the other hand, no association was found between dementia risk and age at menarche, number of pregnancies, duration of breastfeeding, or exogenous estrogen taken in the form of hormonal replacement therapy (HRT) or oral contraceptives.

Several studies have investigated how estrogen in the form of HRT affects dementia risk. Some studies show that dementia risk falls and others that it rises, especially in women who take estrogen late in life.

In the current study Jenna Najar has, instead, investigated the long-term association between factors related to endogenous estrogen and dementia.

"What's novel about this study, too, is that we've had access to information about several events in a woman's life that can affect her estrogen levels. Examples are pregnancies, births, and breastfeeding. Being pregnant boosts estrogen levels tremendously; then they decline once the baby is born, and if women breastfeed the levels fall to extremely low levels. The more indicators we capture, the more reliable our results are," Najar says.

Ingmar Skoog, professor of psychiatry at Sahlgrenska Academy, University of Gothenburg and head of AgeCap, led the study.

"The varying results for estrogen may be due to it having a protective effect early in life but being potentially harmful once the disease has begun."

At the same time, Skoog points out that the duration of women's fertile periods is one risk factor for dementia among many.

Most women whose menopause is delayed do not develop dementia because of this factor alone. However, the study may provide a clue as to why women are at higher risk than men for dementia after age 85, the most common age of onset. Alzheimer's disease, on the other hand, starts developing some 20 years before symptoms of the disorder become apparent.

"Most people affected are over 80 and female," Najar says.

"As a result of global ageing, the number of people affected by dementia will increase. To be able to implement preventive strategies, we need to identify people with an elevated risk of dementia."

A paper published in the Proceedings of the National Academy of Science (PNAS) explains the advantage that animals have of using a specific type of chaotic type of movement called a "Lévy walk," and how this type of behavior emerges. Using computer modeling, the author shows that this type of movement can allow animals to make flexible decisions between "exploitation" and "exploring" in an environment.

"Lévy walks"--a type of behavior where an organism makes a mixture of small random-like movements and an occasional larger movement--are very common in biological systems. They are seen in the behavior of many animal species including humans, as well as in reptiles, fish, birds, and even individual cells. They are different from what is called a "Brownian walk"--which resembles the random movements of molecules in a gas or liquid, as the organism will occasionally take long movements which bring it to another location. However, the mechanisms through which these movements take place and the advantages they offer are not well understood.

To tackle this, Masato S. Abe of the RIKEN Center for Advanced Intelligence Project, the author of the paper, began by creating a mathematical model that imitate the motion of the lava of a fruit fly--a commonly used model organism--using two oscillators, which are connected together. When the link between the oscillators was very weak, the larvae basically followed random Brownian motion, and when they were tightly linked together, the larvae just walked in straight lines. When there was a weak linkage, however, they exhibited precisely what a Lévy walk would look like.

An interesting observation of the model was that Lévy walks emerged suddenly near points known as "critical points"--places where the behavior undergoes a rapid transformation. He wondered if this could be beneficial in some way, and found that in these areas, actors were able to respond strongly to even mild environmental stimuli, so it could help animals make finely tuned decisions over whether to exploit the food in one area or explore other areas. Abe then used observations of the actual movements of fruit fly larva to show that they were indeed carrying out behavior that fit with the model.

"Thanks to this model, we can now explain why Lévy walks, emerging near critical points in a system, make sense for organisms performing tasks such as foraging for food, as well as searching for words in their memory. This work will also help us in the field of artificial intelligence to create autonomous agents that can behave more closely like living organisms."

Since the start of the COVID-19 pandemic, scientific and medical journals have published over 100,000 studies on SARS-CoV-2. But according to data scientists who created a machine-learning tool to analyze the deluge of publications, basic lab-based studies on the microbiology of the virus, including research on its pathogenesis and mechanisms of viral transmission, are lacking. Their analysis appears September 16 in the journal Patterns.

"In a crisis like this pandemic, we would expect research outside the lab to happen at a faster pace than lab research," says first author Anhvinh Doanvo (@AnhvinhDoanvo), a volunteer data scientist with the COVID-19 Dispersed Volunteer Research Network. "Nevertheless, the relative lack of lab-based studies seems to be unique to SARS-CoV-2, compared to other human coronaviruses. This shortage of lab-based research means that the scientific community may miss key aspects of the virus that could impact our ability to contain this pandemic and to counter future ones."

The investigators used research abstracts obtained from CORD-19 (COVID-19 Open Research Dataset). CORD-19 is updated daily and includes peer-reviewed studies from PubMed Central, as well as preprints from bioRxiv and medRxiv. At the time they conducted their first analysis at the end of May, the dataset included more than 137,000 studies. The analysis was later updated with data through July 31.

The team used two computational methods to analyze the data. The first was dimensionality reduction, which helps to find big patterns across many documents, such as abstracts from scientific studies, and to identify trends based on those patterns. The second method, topic modeling, allowed them to group the documents into different topics and to compare research on SARS-CoV-2 to research on other coronaviruses. Unlike previous studies that have focused only on keywords, both of these tools enabled them to review the full text of the abstracts.

"Broadly speaking, we found that the research community has produced a lot of work on the clinical manifestations of the virus, epidemiological models of its spread, and other work based on data collected from the field," says senior author Maimuna Majumder (@maiamajumder), a computational epidemiologist at Harvard Medical School and Boston Children's Hospital's Computational Health Informatics Program.

The researchers also note that research has changed over time, with an acceleration in studies examining public health responses, clinical issues related to the virus, the societal impact of the outbreak, and how the disease spreads across populations, while reporting on the status of the outbreak has begun to plateau. "This is a positive development, as it indicates that the scientific community has transitioned from the role of a passive observer of the virus into a group studying ways to fight its spread," Majumder says.

"But basic microbiological research has been slow to pick up the pace, leaving potential knowledge gaps in its wake," Doanvo says. "It's possible that stronger resourcing in these time- and resource-intensive efforts would better enable the scientific community to respond quickly to this virus."

The researchers hope this analysis will help raise awareness about the importance of prioritizing lab-based studies on SARS-CoV-2 moving forward. They plan to conduct another analysis of scientific studies in about a year, using the tools they have already developed.

When it comes to metabolic health, it's not just what you eat, it's when you eat it. Studies have shown that one effective means of losing weight and tackling obesity is to reduce the number of hours in the day that you eat. Time-restricted feeding - otherwise known as intermittent fasting - has also been shown to improve health even before weight loss kicks in.

The biological explanation for the phenomenon remains poorly understood. So scientists from the University of Copenhagen, the Australian Catholic University and Karolinska Institutet investigated the body's early adaptations to time-restricted feeding. Their study identified a number of key changes in the genetic activity of muscles, as well as the content of muscle fats and proteins, which could explain the positive impact of time-restricted feeding.

Novel insights on short-term time-restricted feeding

The study is the first time scientists have examined the oscillations of metabolites in skeletal muscle and in blood, as well as gene expression in skeletal muscle after time-restricted feeding. By focusing on the short-term and early effects of time-restricted feeding, the goal was to disentangle the signals that govern health from those associated with weight loss.

"We observe that the rhythm of skeletal muscle core clock genes is unchanged by time-restricted feeding, suggesting that any differences are driven more by diet, rather than inherent rhythms," says Postdoc Leonidas Lundell, from the Novo Nordisk Foundation Center for Basic Metabolic Research (CBMR) at the University of Copenhagen.

"We also see that the metabolite profile of skeletal muscle switches from being predominantly lipid based, to amino acid based, after time-restricted feeding. This coincides with changes in rhythmicity of amino acid transporters, indicating that part of the amino acid profile could be due to absorption from the blood."

Research Fellow Evelyn Parr from the Mary MacKillop Institute for Health Research at the Australian Catholic University, adds: "Our research is an important step towards understanding how time-restricted eating can improve metabolic health, while bridging the gap between animal models and human intervention studies. It was important to capture these early metabolic responses before assessing what changes might occur after a longer period following a time-restricted feeding pattern."

Eating behavior does not impact the body's core clock

In the study, 11 men with overweight/obesity were assigned one of two eating protocols for a period of five days, either unrestricted feeding, or eight-hours of time restricted feeding. On the fifth day, samples were taken every four hours for a full day. After a 10-day break, they repeated the experiment following the other eating protocol.

After each intervention, the team of scientists studied the gene expression in muscles, as well as the profile of metabolites - molecules that are formed through metabolic processes - in the blood and muscles.

They discovered that time-restricted feeding changed the rhythmic concentration of metabolites in blood and muscle. Time-restricted feeding also influenced the rhythmic expression of genes expressed by muscle, particularly those responsible for helping the transport of amino acids, the building blocks of proteins.

Critically, the study showed that time-restricted feeding did not alter the muscle's core clock - the cell's inbuilt metronome that regulates its daily cycle of activity. This suggests that the altered rhythmicity of metabolite and gene expression caused by time-restricted feeding could be responsible for the positive health impact.

"Our findings open new avenues for scientists who are interested in understanding the causal relationship between time-restricted feeding and improved metabolic health. These insights could help develop new therapies to improve the lives of people who live with obesity," says Professor Juleen Zierath from Karolinska Institutet and CBMR at the University of Copenhagen.

Scientists from Sechenov University interviewed Russian healthcare experts to find out what problems impeded the development of medical tourism in the country most and what measures would help attract foreigners. The results of the work can form the basis of the state policy in this field. Details of the study were published in the journal Frontiers in Psychology.

Medical tourism (that is, providing medical care to foreign citizens) helps to develop the host country's healthcare system: in addition to the money paid for treatment by patients or insurance companies, it receives investment and an incentive to improve the service quality and the qualifications of its staff. However, to prefer to leave their country for treatment, foreigners must be sure that they will get an appointment with professionals, that it will not be very difficult to issue documents, including a visa, and that treatment itself will not be ruinous.

'Earlier, people came to places where they got better treatment, but now they look at where it is cheaper, comparing the price-quality ratio and service quality. And we began to be late with this. The issues of medical tourism in our country were taken up only a few years ago: the first research on this topic appeared in 2010-2011, and the state's interest in this issue was shown just two years ago, in the decree of President Vladimir Putin dated May 7, 2018,' said Vladimir Reshetnikov, one of the study authors, head of the Semashko Department of Public Health and Healthcare, Sechenov University.

The authors of the article asked experts to list the main problems that hinder the development of medical tourism, the measures that clinics and authorities need to take to improve the situation and the advantages of Russia that will allow it to compete with other countries. 36 heads of medical organisations took part in the survey.

The three most important problems, according to the experts, were the low awareness of foreigners about medical services, the lack of doctors and staff who know a foreign language and the lack of resources (specialists, equipment, etc). Respondents also noted that it is difficult to accommodate patients and obtain the necessary documents and visas, not all clinics have international certificates, and patients sometimes cannot continue to pay for treatment in the case of complications.

The largest number of experts - a quarter of them - agreed that first of all it is necessary to solve the problem of the lack of personnel and equipment. This group of measures also includes the use of the latest technologies, standards and recommendations. In the second place is informing potential patients about the services of medical organisations. This requires maintaining the clinic's website in good condition, translating materials into foreign languages, placing ads on foreign sites and offering online consultations. Experts consider word of mouth - recommendations from doctors and other patients - as well as advertising in search engines and social networks to be an effective way to promote clinic services. Another area of work is the creation of an organisation that supports the export of medical services at the federal level as well as the development of programmes for regional projects.

'The fastest thing to do is to build an organisation, create a structure that will deal with management, advertising and patient logistics. You can quickly change the legal framework, for example, to introduce medical visas. Of course, staff training will require more time,' Vladimir Reshetnikov explained.

Experts named the relatively low cost of services, well-equipped clinics and highly qualified staff as well as geographical location (proximity to the CIS countries) as competitive advantages of Russian healthcare.

'The goal of our work was to understand how to organise the development of medical tourism, to determine where our niche was, and what our strengths and weaknesses were, in order to outline the plan of action. The results are already being implemented in two regions (Sverdlovsk and Moscow regions) and discussed in the Civic Chamber of Russia,' the co-author of the study added.

Research being presented at the ESCMID Conference on Coronavirus Disease (ECCVID, held online from 23-25 September) shows that persistent fatigue occurs in more than half of patients recovered from COVID-19, regardless of the seriousness of their infection. The study is by Dr Liam Townsend, St James's Hospital and Trinity Translational Medicine Institute, Trinity College, Dublin, Ireland, and colleagues.

As the global COVID-19 pandemic continues to grow worldwide, the number of patients recovering, and also experiencing post-infection problems, is also growing. "Fatigue is a common symptom in those presenting with symptomatic COVID-19 infection. Whilst the presenting features of SARS-CoV-2 infection have been well-characterised, the medium and long-term consequences of infection remain unexplored," explains Dr Townsend.

"In particular, concern has been raised that SARS-CoV-2 has the potential to cause persistent fatigue, even after those infected have recovered from COVID-19. In our study, we investigated whether patients recovering from SARS-CoV-2 infection remained fatigued after their physical recovery, and to see whether there was a relationship between severe fatigue and a variety of clinical parameters. We also examined persistence of markers of disease beyond clinical resolution of infection."

The authors used a commonly-used scale to determine fatigue in recovered patients, called the Chalder Fatigue Score (CFQ-11). They also looked at the severity of the patient's initial infection (need for admission, and critical/intensive care), and also their pre-existing conditions including depression. They also looked at various markers of immune activation (white cell counts, C-reactive protein, Interluekin-6, and sCD25).

The study included 128 participants (mean age 50 years; 54% female) who were recruited consecutively at a median of 10 weeks following clinical recovery from SARS-CoV-2 infection. More than half reported persistent fatigue (52.3%; 67/128) at this point.

The researchers offered an outpatient appointment to anyone who had a COVID-19 positive swab test in their laboratory at St James Hospital. This included all admitted patients as well as any hospital staff (including cleaning staff, caterers, etc) since the service was also offered to staff that thought they had COVID-19 symptoms. The majority of those in the non-admitted group had a mild illness but had a swab test performed at St James's Hospital rather than at a community testing facility, as they were employed by St James's Hospital.

Of the patients assessed in this study,71/128 (55.5%) were admitted to hospital and 57/128 (44.5%) were not admitted. "Fatigue was found to occur independent of admission to hospital, affecting both groups equally," explains Dr Townsend.

There was no association between COVID-19 severity (need for inpatient admission, supplemental oxygen or critical care) and fatigue following COVID-19. Additionally, there was no association between routine laboratory markers of inflammation and cell turnover (white blood cell counts or ratios, lactate dehydrogenase, C-reactive protein) or pro-inflammatory molecules (IL-6 or sCD25) and fatigue post COVID-19. Female gender and those with a pre-existing diagnosis of depression/anxiety were over-represented in those with fatigue. Although women represented just over half of the patients in the study (54%), two-thirds of those with persistent fatigue (67%) were women. And while only 1 person of the 61 (1.6%) without fatigue had a history of anxiety or depression, this proportion was 13.4% (9/67) in those with persistent fatigue.

The authors conclude: "Our findings demonstrate a significant burden of post-viral fatigue in individuals with previous SARS-CoV-2 infection after the acute phase of COVID-19 illness. This study highlights the importance of assessing those recovering from COVID-19 for symptoms of severe fatigue, irrespective of severity of initial illness, and may identify a group worthy of further study and early intervention. It also supports the use of non-pharmacological interventions for fatigue management. These interventions will need to be tailored to the individual needs of the patients, and may include lifestyle modification, cognitive behavioural therapy and self-pacing exercise, where tolerated."

A study investigating SARS-CoV-2 infections across 16 mink farms in the Netherlands, being presented at the ESCMID Conference on Coronavirus Disease (ECCVID, held online from 23-25 September) shows that the virus likely jumped between people and mink and back, providing strong evidence that animal to human (zoonotic) transmission is possible.

The study is by a group of Dutch veterinary science experts including Dr Bas Oude Munnink (ErasmusMC), Professor Wim van der Poel (Wageningen University and Research Centre), Professor Arjan Stegeman (Utrecht University) Prof Marion Koopmans (ErasmusMC) and Reina Sikkema (ErasmusMC).

The exact origin of SARS-CoV-2 is still unknown, although various theories have been put forward. Animal experiments have shown that non-human primates, ferrets, hamsters, rabbits and bats can be infected by SARS-CoV-2 as well as cats, dogs, lions and tigers. Recently, multiple outbreaks in mink farms (containing mink of the Neovison vison species) in the Netherlands have demonstrated that mink are also susceptible for SARS-CoV-2.

The authors did an in-depth investigation of outbreaks on 16 mink farms and humans living or working on these farms, using whole genome sequencing to underpin sources of transmission. They describe SARS-CoV-2 infections on 16 farms, with over 720,000 animals. In total, 66 of 97 (67%) persons tested had evidence for SARS-CoV-2 infection, either by PCR or serology. All people tested had a direct link to an infected mink farm.

The authors say: "Due to longitudinal follow up of the first 4 farms, we have strong evidence that at least two people on those farms were infected by minks. Unfortunately, based on our research we cannot make definite conclusions on the direction of most of the infections, so we do not know the total number of people that were infected by minks. We conclude that initially the virus was introduced from humans and has evolved on mink farms, most likely reflecting widespread circulation among mink in the first SARS-CoV-2 mink farms, several weeks prior to detection."

They add: "Genetic analysis of SARS-CoV-2 from the human employees on the farms showed they were the same as those found in mink, and were not identical to those found in unrelated SARS-CoV-2 patients living in the vicinity of farms. Genetic sequences from each of the infected mink farms fell into one of five distinct clusters, showing transmission between different mink farms."

They conclude: "Additional research will be needed to determine the routes of transmission. We conclude that at least some of these employees are very likely to have been infected directly from infected mink and thereby describe the first proven zoonotic transmission of SARS-CoV-2 to humans. Close collaboration between human and animal health departments is essential for early identification and control of SARS-CoV-2 infections."