Culture

Somnambulism - otherwise known as sleepwalking - is a phenomenon which has fascinated the public and neurologists for decades, but a lot of what causes it remains a mystery.

Affecting up to 4% of adults, sleepwalking is a non-rapid-eye movement (NREM) sleep parasomnia that not only gives someone a poor night's sleep, but also puts them at serious risk of injury and, in some cases, lead to unintended violence against others.

The following day can also prove challenging as the sleepwalker will feel unrested and a strong desire to fall asleep (somnolence).

Unfortunately for those predisposed to sleepwalking episodes, prolonged sleep deprivation increases both their frequency and complexity, making it harder for them to achieve the deep sleep the body needs to function healthily.

Now, in a paper published to Frontiers in Neurology, researchers at the University of Montréal and Montréal Sacred Heart Hospital, Canada aimed to further investigate the hypothesis that sleepwalking is a disorder of arousal and poorly regulated deep sleep (slow-wave sleep).

More specifically, they examined how the autonomic nervous system - measured via the heart rate - influences deep sleep in sleepwalkers.

Challenges of a sleepwalking study

14 adult sleepwalkers were recruited for the study as well as 14 sex- and age-matched normal controls. They were evaluated using video-polysomnography for one night and during recovery sleep following 25 hours of sleep deprivation.

According to corresponding authors Prof Antonio Zadra and Dr Andrée-Ann Baril of the University of Montréal, it can be a challenge to put together a study investigating the mysterious inner workings of sleepwalking.

"One challenge in studying large cohorts of sleepwalkers is the relatively low prevalence of the disorder in the adult population," they said.

"Fortunately, the Center for Advanced Research in Sleep Medicine, where this research was conducted, is a one-of-a-kind clinical and research facility in Canada affiliated with one of the country's largest and highly specialized sleep disorders clinics that assesses over 1,000 patients a year. As a general rule, however, adult sleepwalkers are readily willing to take part in research studies aiming to better understand the underlying causes and possible treatments of the sleep disorder."

Wakefulness and deep sleep at the same time

The autonomic nervous system regulates the body's physiological functions and is composed of the sympathetic branch, which underlies the 'fight or flight' response, and the parasympathetic branch, which underlies the 'rest and digest' response. Zadra, Baril, and the rest of their team found that sleepwalkers show an elevated rest-and-digest response and a lower fight-or-flight response during deep sleep.

"While the causes of sleepwalking remain unclear, we know that while asleep, sleepwalkers can experience an abnormal interplay between processes linked to arousal and to deep sleep, even outside of their episodes," Zadra and Baril said.

"In other words, sleepwalkers can present evidence of both wakefulness and deep sleep at the same time; a state out of which episodes of sleepwalking can arise. Our findings indicate that when compared to healthy adults, sleepwalkers' autonomic nervous system favors their parasympathetic activity, or rest-and-digest response, during sleep. This paves a new and broader way to understand the biological processes implicated in sleepwalking."

Surprising discovery

The results were "surprising", they added, as it had been assumed that the deep sleep of sleepwalkers would show an elevated fight-or-flight response that would predispose them to higher risks of experiencing sleepwalking episodes.

One limitation of the study is that measuring the influence of the sympathetic and parasympathetic branches on a person's heartbeat is an indirect approach and can be confounded by other factors.

"While our results indicate the presence of an altered autonomic nervous system during sleepwalkers' deep sleep, whether and how this atypical activity is involved in the occurrence of actual sleepwalking episodes remains to be determined," Zadra and Baril said.

"Since several pharmaceutical agents can be used to modulate autonomic effects, such treatment venues could be explored if our results are replicated and expanded upon."

The cultivated planet is withstanding record-breaking pressure to ensure food security. To meet the rising demand of food, energy, and fiber, a 70%-100% increase in crop commodities will be needed globally by 2050. However, rapid urbanization and industrialization have caused dramatic loss of high-quality cropland and hence threatened food security. To stabilize cropland area, cropland expansion to marginal lands has become a widespread phenomenon worldwide. This study developed a systems framework to represent the trade-off among crop yield, production, and environmental cost, according to the competitive relationship of production, settlement, and ecological space and the link of "land - food - environment - policy". Using China as a case study, the authors validated the systems framework by assessing the associated food benefits and environmental costs from large-scale cropland redistribution driven by economic development and policy implementation.

The environmental impacts of cropland redistribution in China were invesgated. Due to urbanization-induced loss of high-quality croplands in south China (~8.5 t ha-1), croplands were expanded to marginal lands in northeast (~4.5 t ha-1) and northwest China (~2.9 t ha-1) during 1990-2015 to pursue food security. However, the reclamation in these low-yield and ecologically vulnerable zones considerably undermined local environmental sustainability, e.g., increasing wind erosion (+3.47%), irrigation water consumption (+34.42%), fertilizer use (+20.02%), and decreasing natural habitats (-3.11%). Forecasts show that further reclamation in marginal lands per current policies would exacerbate environmental costs by 2050. The future cropland security risk will be remarkably intensified due to the conflict between food production and environmental sustainability. Kuang et al.'s results suggest that globally emerging reclamation of marginal lands should be restricted and crop yield boost should be encouraged for both food security and environmental benefits.

The findings in this paper reveal that, under the influence of national macro policies, the competition of urban, agriculture and ecology systems driven by "the supplement of marginal lands and loss of high-quality croplands in the future" lead to the trade-off relationship between food production and environmental sustainability. The paper also confirms that the global or specific regional marginal lands beyond a certain threshold will not increase grain production, but will cause environmental unsustainability.

The rarity of these syndromes, caused by damage to a gene named HUWE1, means very few children are affected. Of course, the low absolute numbers are little consolation for children who are born with a severe intellectual disability as a result of gene mutation.

Many affected children have distinctive facial features, some struggle to learn to walk, and many never learn to speak. Some have an abnormally small head and have stunted growth.

There is no cure. Parents mainly focus on learning enough about how to cope to make everyday life workable.

A lot of parents struggle with guilt. Why did their child turn out like this? Could it be their fault?

Marte Gjøl Haug is the senior consultant in medical genetics at St. Olavs Hospital in Trondheim, Norway, and has met with many despairing parents.

In recent years, the number of referrals has increased significantly as genetic testing has become cheaper and more readily available.

"Many parents are afraid that the cause of their child's condition stems from something they could have avoided. A lot of parents have thought this for years before the child is referred and given a genetic diagnosis, which often adds an extra burden to their situation. Once they know that damage to a gene is the cause, many of them are hugely relieved. It wasn't the one glass of wine during the pregnancy that was the cause after all," says Haug.

The problems that result from the damaged HUWE1 gene have names like Juberg-Marsidi, Say-Meyer or Brooks syndrome.

The gene in question is one of more than 900 found on the X chromosome, the female sex chromosome. Girls have two X chromosomes. Boys have an X chromosome and a Y chromosome. Syndromes that are associated with the X chromosome, such as HUWE1, can therefore have differing degrees of severity in both girls and boys.

The damage to the gene occurs when a mutation occurs.

All genes have to be copied, but in instances when DNA fails to copy accurately, a mutation results that can lead to a number of diseases.

Damage to HUWE1 is known to lead to various syndromes, but this is the first time that anyone has figured out that all of the different syndromes have a common cause.

Professor Barbara van Loon is the researcher behind the discovery. She is a graduate of MIT and the University of Zurich, and came to NTNU, the Norwegian University of Science and Technology in Trondheim, from Switzerland. Her expertise is in the field of DNA repair.

Studying these syndromes is challenging because the number of individuals affected by each syndrome is very low.

The low number makes it difficult for researchers to obtain a large enough number of samples to be able to draw conclusions.

"Individually, many of the syndromes are rare, but a lot of people are affected if you combine all the rare syndromes," says van Loon.

Van Loon obtained blood cells from five boys with rare syndromes. In this way, she gathered enough genetic material to find a link.

To recreate the development of the disease, she created stem cells from skin cells from a child with a rare syndrome, and cultured mini-brains of these cells.

Her research allowed her to see that the cause of the syndromes was a protein called p53. This protein plays a major role in very basic neurological mechanisms.

If p53 gets out of control, a cell can develop into a cancer cell. It is well known that this gene is important in the development of cancer. Now, for the first time, van Loon and her colleagues have documented that it can also lead to such great problems with the brain's development to cause intellectual disabilities.

"Our findings don't mean that we can come up with a quick cure, but being able to explain the very basic mechanisms behind an illness is an important prerequisite for developing diagnostics and serving as a basis for future treatment. It's also important in itself to give the affected families more information about the disease and how it's developed," says van Loon.

Barbara van Loon works on basic research, which focuses on the very basic and fundamental processes in human beings. Her research is driven by the goal to discover completely new cell connections.

Van Loon's research findings are important pieces in the large puzzles that could result in a future breakthrough in how disease should be treated.

Knowledge gained through basic research is the most important source of major breakthroughs in medical treatment, but it can be years between a basic research discovery and clinical applications.

A study from the Centre for Nutraceuticals at the University of Westminster found that plant-based protein shakes may be potential viable alternatives to milk-based whey protein shakes, particularly in people with need of careful monitoring of glucose levels.

The study, published in the journal Nutrients, is the first to show potato and rice proteins can be just as effective at managing your appetite and can help better manage blood glucose levels and reduce spikes in insulin compared to whey protein.

During the study the blood metabolic response of participants was measured after drinking potato, rice and whey protein shakes. Appetite was also monitored in the following three hours to understand how these drinks may affect the participants' hunger and their desire to eat.

The research observed that vegan protein shakes led to a lower rise in blood insulin compared to whey, while potato protein prevented any rise in insulin. This may explain the better blood glucose control following consumption of the plant-based protein and poses the question of whether vegan protein shakes are more suitable for individuals who need to need control their blood glucose levels such as diabetic and obese individuals.

Interestingly, release of the key appetite regulating hormone GLP-1 was greater after drinking the whey protein shake. However, the greater GLP-1 response did not translate to an increased feeling of fullness as there were no differences observed in appetite perception between the three different protein shakes.

Consumer trends in protein intake are on the rise with milk protein derivatives such as whey extensively used in consumer products such as protein shakes, fortified food and beverage products.

There are alternative protein products available for vegetarians and vegans such as soy, rice, wheat and pea proteins but there is a relative lack of evidence on their health benefits in comparison to milk proteins. Potato protein is a novel plant-based protein product that is obtained from the waste material from potato starch production and is a sustainable economic protein source. This study provides the first evidence to suggest that it may be an alternative to whey protein sources.

Professor M Gulrez Zariwala, corresponding author and Director of the Centre for Nutraceuticals at the University of Westminster, said: "Global concerns on sustainability have led to consumer shifts towards ethical eating and a change in dietary habits with increased adoption of vegetarian and vegan diets.

"However, research in this area is still lacking and it would be interesting to clarify whether proteins from plant sources can provide identical metabolic health benefits as those with traditional sources such as milk.

"Our results shed new light in this area and improves our understanding of how plant source proteins can be a more sustainable yet nutritionally beneficial food source. We plan to conduct follow-up studies further research this exciting area."

New research has uncovered a novel trick employed by the bacterium Staphylococcus aureus to thwart the immune response, raising hopes that a vaccine that prevents deadly MRSA infections is a little closer on the horizon.

Immunologists from Trinity College Dublin, working with scientists at GSK - one of the world's largest vaccine manufacturers - discovered the new trick of the troublesome Staphylococcus aureus, which is the causative agent of the infamous "superbug" MRSA.

They found that the bacterium interferes with the host immune response by causing toxic effects on white blood cells, which prevents them from engaging in their infection-fighting jobs.

Importantly, the study also showed in a pre-clinical model system that the toxicity could be lessened following vaccination with a mutated version of a protein specifically engineered to throw a spanner in the MRSA works. Ultimately, this suggests a vaccine could one day do the same thing in people.

The research was recently published in journal, mBio.

MRSA - a global killer

An estimated 700,000 deaths occur annually due to infections against which antibiotics are no longer effective. If this is allowed to continue, modern medicine as we know it will cease to exist; a common childhood infection or routine surgical procedure could become fatal, with the threat of AMR infection likened to that of climate change in some circles.

Immediate and significant action is required to turn the tide of AMR and the development of novel vaccines to prevent these types of infection in the first place, are an attractive and potentially very effective option.

Rachel McLoughlin, Professor in Immunology in Trinity's School of Biochemistry and Immunology and the Trinity Biomedical Sciences Institute (TBSI), said:

"As a society we are witnessing first-hand the powerful impact that vaccination can have on curbing the spread of infection. However, on the backdrop of the COVID-19 epidemic we must not lose sight of the fact that we are also waging war on a more subtle epidemic of antimicrobial resistant infection, which is potentially equally deadly."

"In this study we have identified a mechanism by which a protein made by the bacterium - known as Staphylococcal Protein A (SpA) - attacks and rapidly kills white blood cells. This protein has been widely studied for its immune evasion capacity and has a well-documented role in rendering antibodies raised against the bacterium non-functional.

"Here we uncover a previously undocumented strategy by which SpA forms immune complexes through its interaction with host antibodies, that in turn exert toxic effects on multiple white blood cell types. This discovery highlights how important it will be for effective vaccines to be capable of disarming the effects of protein A."

Dr Fabio Bagnoli, Director, Research & Development Project Leader, GSK, said:

"Our collaboration with Trinity College Dublin and in particular with Professor Rachel McLoughlin, a worldwide recognised expert on staphylococcal immunology, is critical for increasing our knowledge on protective mechanisms against S. aureus."

The study documents the latest discovery made by this group at Trinity under an ongoing research agreement with GSK Vaccines (Siena, Italy) in which PhD students from Trinity have the unique opportunity to obtain training in applied vaccine research at the world's largest vaccine research company, thus equipping them with the skills to pursue world class discovery research in both academia and industrial settings.

Overall, this collaboration aims to increase understanding of the immunology of Staphylococcus aureus infection to advance development of next-generation vaccines to prevent MRSA infections.

Scientists using computer modelling to study SARS-CoV-2, the virus that caused the COVID-19 pandemic, have discovered the virus is most ideally adapted to infect human cells - rather than bat or pangolin cells, again raising questions of its origin.

In a paper published in the Nature journal Scientific Reports, Australian scientists describe how they used high-performance computer modelling of the form of the SARS-CoV-2 virus at the beginning of the pandemic to predict its ability to infect humans and a range of 12 domestic and exotic animals.

Their work aimed to help identify any intermediate animal vector that may have played a role in transmitting a bat virus to humans, and to understand any risk posed by the susceptibilities of companion animals such as cats and dogs, and commercial animals like cows, sheep, pigs and horses.

The scientists, from Flinders University and La Trobe University, used genomic data from the 12 animal species to painstakingly build computer models of the key ACE2 protein receptors for each species. These models were then used to calculate the strength of binding of the SARS-CoV-2 spike protein to each species' ACE2 receptor.

Surprisingly, the results showed that SARS-CoV-2 bound to ACE2 on human cells more tightly than any of the tested animal species, including bats and pangolins. If one of the animal species tested was the origin, it would normally be expected to show the highest binding to the virus.

"Humans showed the strongest spike binding, consistent with the high susceptibility to the virus, but very surprising if an animal was the initial source of the infection in humans," says La Trobe University Professor David Winkler.

The findings, originally released on the ArXiv preprint server, have now been peer reviewed and published in Scientific Reports (Springer Nature).

"The computer modelling found the virus's ability to bind to the bat ACE2 protein was poor relative to its ability to bind human cells. This argues against the virus being transmitted directly from bats to humans. Hence, if the virus has a natural source, it could only have come to humans via an intermediary species which has yet to be found," says Flinders affiliated Professor Nikolai Petrovsky.

The team's computer modelling shows the SARS-CoV-2 virus also bound relatively strongly to ACE2 from pangolins, a rare exotic ant-eater found in some parts of South-East Asia with occasional instances of use as food or traditional medicines. Professor Winkler says pangolins showed the highest spike binding energy of all the animals the study looked at - significantly higher than bats, monkeys and snakes.

"While it was incorrectly suggested early in the pandemic by some scientists that they had found SARS-CoV-2 in pangolins, this was due to a misunderstanding and this claim was rapidly retracted as the pangolin coronavirus they described had less than 90% genetic similarity to SARS-CoV-2 and hence could not be its ancestor," Professor Petrovsky says.

This study and others have shown, however, that the specific part of the pangolin coronavirus spike protein that binds ACE2 was almost identical to that of the SARS-CoV-2 spike protein.

"This sharing of the almost identical spike protein almost certainly explains why SARS-CoV-2 binds so well to pangolin ACE2. Pangolin and SARS-CoV-2 spike proteins may have evolved similarities through a process of convergent evolution, genetic recombination between viruses, or through genetic engineering, with no current way to distinguish between these possibilities," Professor Petrovsky says.

"Overall, putting aside the intriguing pangolin ACE2 results, our study showed that the COVID-19 virus was very well adapted to infect humans."

"We also deduced that some domesticated animals like cats, dogs and cows are likely to be susceptible to SARS-CoV-2 infection too," Professor Winkler adds.

The extremely important and open question of how the virus came to infect humans has two main explanations currently. The virus may have passed to humans from bats through an intermediary animal yet to be found (zoonotic origin), but it cannot yet be excluded that it was released accidently from a virology lab. A thorough scientific, evidence-based investigation is needed to determine which of these explanations is correct.

How and where the SARS-CoV-2 virus adapted to become such an effective human pathogen remains a mystery, the researchers conclude, adding that finding the origins of the disease will help efforts to protect humanity against future coronavirus pandemics.

In the animal kingdom, specific growth factors control body axis development. These signalling molecules are produced by a small group of cells at one end of the embryo to be distributed in a graded fashion toward the opposite pole. Through this process, discrete spatial patterns arise that determine the correct formation of the head-foot axis. A research team at the Centre for Organismal Studies (COS) at Heidelberg University recently discovered an enzyme in the freshwater polyp Hydra that critically shapes this process by limiting the activity of certain growth factors.

In particular, the proteins of the so-called Wnt signalling pathway play an important role in the pattern formation of the primary body axis. Wnt proteins, which arose early during evolution, are considered to be universal developmental factors. "Misregulation of Wnt factors can cause serious malformations during embryonic development and give rise to diseases such as cancer," explains Prof. Dr Özbek, a member of the "Molecular Evolution and Genomics" department led by Prof. Dr Thomas Holstein at the COS.

Now, the researchers have discovered an enzyme in the freshwater polyp Hydra that can break down Wnt proteins, thereby deactivating them. Hydra is a basal multicellular organism of the phylum Cnidaria that has long been used as a model organism to study the Spemann-Mangold organizer, an embryonic signalling centre in charge of forming the body's longitudinal axis. The Wnt proteins responsible for this process are continually produced in the mouth region of the adult polyp to maintain the body axis.

The researchers determined that the newly discovered HAS-7 enzyme develops in a ring-shaped zone below Hydra's tentacle wreath. This region separates the head from the body. If HAS-7 production is experimentally interrupted by suppressing the gene expression, a fully formed second head and a second body axis spontaneously develop. According to Prof. Özbek, something similar occurs when Wnt proteins are artificially produced in the animal's entire body.

In cooperation with Prof. Dr Walter Stöcker's group at Mainz University, the Heidelberg researchers were able to show that the HAS-7 enzyme is capable of specifically cleaving the Wnt protein to suppress its activity beyond the head. Without this inhibitory mechanism, the Wnt emanating from the head floods the body, creating a two-headed animal. The HAS-7 enzyme is a member of the astacin family of proteases, which were first identified in crayfish. "Members of the astacin protease family are also found in higher vertebrates. It is therefore likely that we have found a mechanism here that may play a role in humans as well," states Prof. Holstein.

In a follow-up project within the Collaborative Research Centre 1324 "Mechanisms and Functions of Wnt Signaling", the researchers will collaborate with Prof. Dr Irmgard Sinning of the Heidelberg University Biochemistry Center to study the molecular mechanism of Wnt cleavage by astacin. "We hope to be able to find clues on the precise point of attack in the Wnt protein," states Prof. Özbek.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

PspA plays a key role in bacterial stress response

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

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

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

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

PspA remodels membranes

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

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

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

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

Where does our knowledge of infections spreading stem from?

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

Who are the superspreaders?

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

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

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

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

Disease modelling faces new challenges and strong interdisciplinary collaboration

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

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

The potential for research into the spread of infections is great

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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