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New research published in Diabetologia (the journal of the European Association for the Study of Diabetes [EASD]) shows that antibody responses to SARS-CoV-2 are similar in COVID-19 patients with and without diabetes, and thus are unlikely to be responsible for the higher death rates in patients with diabetes.

Furthermore, they found that a particular antibody response related to the 'spike' protein of the SARS-CoV-2 virus is strongly associated with improved survival, boosting hopes that vaccines involving this same protein will have a high chance of being as effective in vulnerable patients with diabetes as they will be in the general population. The study also found that higher blood glucose levels were strongly associated with COVID-19 mortality in patients whether or not they had diabetes.

Patients with diabetes, especially type 2 diabetes, are over-represented in COVID-19 deaths and severe disease. In countries such as the UK, around 30% of people who have died with COVID-19 infection have also had diabetes, with similar numbers reported in other countries.

"Demonstrating the ability to mount an appropriate antibody response in the presence of abnormally high blood sugar (hyperglycaemia) is relevant to understand the mechanisms related to the observed worse clinical outcome of COVID-19 pneumonia in patients with diabetes and for the development of any future vaccination campaign to prevent SARS-CoV-2 infection," explain the authors, who include Professor Lorenzo Piemonti, Director of the San Raffaele Diabetes Research Institute, IRCCS Hospital San Raffaele, Milan, Italy, and colleagues.

The authors analysed the presence of three types of antibody to COVID-19 in their study: immunoglobulin G (IgG), which is evidence of past infection; IgM, which indicates more recent or current infection, and IgA, which is involved in the mucosal immune response, for example in the nose and respiratory tract where the virus enters the body.

They analysed the IgG, IgM and IgA response against multiple antigens of SARS-CoV-2 in a cohort of 509 patients with documented diagnosis of COVID-19, prospectively followed at the IRCCS Hospital San Raffaele. These patients were all adults (aged 18 years or over) and admitted between 25 February and 19 April 2020. These patients had all signed consent forms to have blood samples taken and stored, in order to help with COVID-19 research efforts. The researchers analysed the patients' clinical outcomes and antibody levels according to the presence of hyperglycaemia, including either diagnosed or undiagnosed diabetes, at the time of, or during, hospitalisation.

Among patients with confirmed COVID-19, 139 (27.3%) had diabetes: 90 (17.7%) had diabetes diagnosed prior to the hospital admission while 49 (9.6%) had diabetes diagnosed at the time of admission (newly diagnosed). Diabetes was associated with increased levels of inflammatory biomarkers and hypercoagulopathy (increased blood clotting), as well as leucocytosis (increased leukocytes, a type of white blood cell in the immune system) and neutrophilia (high levels of neutrophils, another type of white blood cell).

Diabetes was independently associated with 2.3 times increased risk of death, even after adjustment for age, sex and other relevant comorbidities. Furthermore, a strong association between higher glucose levels and risk of death was found, irrespective of diabetes diagnosis, with statistical modelling showing that each increase in blood sugar of 1.1 mmol/l resulted in a 14% increased risk of COVID-19 related death, regardless of whether the patient had diabetes. The range of blood sugar values in patients without diabetes was 4.1 to 6.6 mmol/l, while in those with diabetes the range was much greater, from 5.1 to 14.3 mmol/l.

The immune response in terms of the above antibodies against SARS-CoV-2 in patients with diabetes was present and almost identical, in both timing and antibody levels, to that of patients without diabetes, with only marginal differences. The response was also not influenced by blood glucose levels.

Of the measured antibody responses, positivity for IgG against the SARS-CoV-2 spike receptor-binding domain (RBD) (which the virus uses to enter human cells) was predictive of survival rate, both in the presence or absence of diabetes. Overall, the presence of these particular antibodies was associated with a 60% reduction in the death rate of patients with COVID-19, with a 63% reduction death risk in patients with diabetes, and a 57% reduction in those without. This is important, say the authors, because many SARS-CoV-2 vaccines currently in development are targeting this so-called 'spike protein' in the virus.

The authors say: "Patients with either diagnosed or undiagnosed diabetes are more likely to experience severe symptoms and death from COVID-19 pneumonia. Frailty, pre-existing comorbid conditions and a potential underlying immune system dysfunction could contribute to a poorer outcome."

They conclude: "We found that diabetes or high blood sugar does not impair the immune response against SARs-CoV-2. The evidence that presence of IgG antibodies against the so-called 'spike protein' is associated with a remarkable protective effect - about a 60% reduction - in COVID-19 mortality in patients with diabetes allows for cautious optimism on the efficacy of future vaccines against SARs-COV-2 in people with diabetes, who are particularly vulnerable in this deadly pandemic."

Tokyo, Japan - Researchers in the Institute of Industrial Science at The University of Tokyo studied a new method for creating semisolid colloidal systems with less internal mechanical stress by delaying network formation. This work may help scientists better understand biological processes involving cytoplasm.

Within soft-matter physics, gels are a relatively familiar sight. Certain particle suspensions can be turned into a semisolid when particles join to form a stiff network. Think of Jell-O, in which a soupy mix of gelatin proteins sets into a delicious, free-standing dessert. Gels play important roles in biology, and may be involved in how cells move and respond to changing external conditions.

Scientists at The University of Tokyo studied the mechanism by which dispersed particles, called colloids, join together during gelation. Most gel networks are thought to form before dynamical motion stops, which leads to built-in mechanical stress. If the creation of the networks could be delayed, they could be made free from such stress and more stable .

"A net under mechanical tension is stretched and sometimes broken. Conventional colloidal gels suffer from such stress, and thus, are not so stable. Stress-free gels are free from this problem," first author Hideyo Tsurusawa explains.

The team found that network formation (percolation) occurs after the formation of a mechanically stable structure and the cessation of particle motion for a lower concentration of colloidal particles compared with the one at which traditional gels form. The researchers used confocal microscopy and computer simulations to better understand both conventional and stress-free gelation. Systems with fluorescently-labeled poly(methyl methacrylate) colloids could be monitored to see how long it took for networks to form and for particle motion to be arrested.

The choice between these two types of gelation is determined by the large and small relationship between the two characteristic times, i.e., "time until the mechanically stable structure is formed" and "time to percolation". Furthermore, when the interaction between the particles is short-range, the large and small relationship is determined solely by the volume fraction of the colloid.

"We found that colloidal gelation can universally be grouped into the two types. This universal classification of the gelation of particle systems is expected to make a significant contribution to the understanding of gelation in the field of soft matter and biology.," senior author Hajime Tanaka says. "Our findings could be applied to developing new industrial processes that create semisolid products, including foodstuffs, more efficiently."

Researchers from Tokyo Medical and Dental University (TMDU) show that laser irradiation inhibits expression of the osteogenesis inhibitor protein sclerostin without causing inflammation, providing a potential therapeutic option for osteoporosis

Tokyo, Japan - Osteoporosis is a disease in which bone loses mass as a result of age or other influences. This weakening is the leading cause of fractures in the elderly, often after trivial injuries, and makes treating these "pathological fractures" a challenge. Bone health is a dynamic process of continual remodeling controlled by multiple factors. Sclerostin, a glycoprotein coded by the gene SOST, is produced by bone cells and suppresses bone formation. Now, researchers at Tokyo Medical and Dental University (TMDU) have shown that laser irradiation, by inhibiting sclerostin expression without inducing inflammation, shows promise as a new treatment modality for osteoporosis.

Lasers have been used in medical and dental practice for their beneficial photo-biomodulation effects on tissue healing. The benefits of low-level laser therapy are now gaining increased attention in spheres of medicine and dentistry that require enhanced bone regeneration.

The team knew that in periodontal surgery, bone that underwent controlled destruction using a specific type of laser known as an Er:YAG laser healed faster than bone subjected to conventional bur drilling. Thus, they wondered whether Er:YAG laser irradiation modified SOST expression in bone. "We set out to compare comprehensive and sequential gene expression and biological healing responses in laser-ablated, bur-drilled, and untreated bone, as well as investigating the bio-stimulation effect of an Er:YAG laser on osteogenic cells," explains Yujin Ohsugi, lead author.

Using microarray analysis, the researchers first studied gene expression patterns in rat skull bones during healing at 6, 24, and 72 hours after drilling or laser treatment. Immunohistochemical analysis at 1 day was performed to detect sclerostin expression. Additionally, oseteogenic cell cultures were irradiated in vitro and assessed for cell death and sclerostin concentration.

"We confirmed decreased sclerostin expression after laser irradiation both in vivo and in vitro," affirms Sayaka Katagiri, corresponding author. "Interestingly, sequential microarray analysis revealed a clear distinction in the gene expression pattern between bur-drilled and laser-ablated bones at 24 hours, with the former alone showing enriched inflammation-related pathways. Significantly, at 6 hours following laser ablation, the Hippo signaling pathway that limits tissue overgrowth was enriched but inflammation-related pathways remained unaffected, suggesting that laser irradiation worked thorough mechanical bio-stimulation."

The finding that mechanical stimulation of laser irradiation inhibits the pathways that suppress bone regeneration without provoking inflammation may aid development of laser-based therapeutic methods. Such methods might be used in treatments for osteoporosis and to induce or promote bone regeneration in medical and dental procedures.

Everyone has to call in sick at work at some point. With caseworkers at the employment office, however, a sudden absence has direct economic consequences for a third party: The people they support are unemployed on average five percent longer if a meeting is canceled, which corresponds to a period of twelve days. This may sound rather trivial, but it can entail considerable costs for both the welfare state and the individual concerned.

Amelie Schiprowski, economist of the Cluster of Excellence ECONtribute at the Universities of Cologne and Bonn (Germany), evaluated Swiss unemployment insurance data from 2010 to 2012 and investigated how much the personal interaction with caseworkers matters for unemployed individuals. She found out: The duration of unemployment depends to a large extent on how reliable and committed the support provided by the employment office is.

Regular support important for reintegration

Caseworkers at the employment office help to reintegrate unemployment benefit recipients into the labor market. A spontaneous absence of a caseworker reduces the average number of meetings that an unemployed individual can attend. As there are only about two to three meetings per half-year, one missed meeting corresponds in the analyzed data to about 40 percent of support time. The cancellation of a meeting results on average in a five percent longer unemployment spell. This means in turn that regular support is very important for successful reintegration.

Quantity and quality are important

The economist divided the observed caseworkers into two groups according to their productivity; productivity means how quickly, on average, the people they supported found a job again. The result: Absences of less productive caseworkers have no negative effect, while the absence of a more productive caseworker extends unemployment by an average of 13 percent. The negative impact of a canceled appointment therefore depends on the quality of the support.

Investment in human capital can reduce duration of unemployment

The paper highlights the economic importance of staff at the employment office. "Caseworkers are underestimated as an important resource for welfare states," says Amelie Schiprowski. Every day of additional unemployment is expensive for the state. Unemployment could be decreased by reducing the workload of individual caseworkers to facilitate more individual meetings, and by investing into the quality of the support provision.

Twenty shacks destroyed in five minutes. That's how quickly fires can spread in informal settlements.

This is one of the major results of the world's largest informal settlement fire experiment consisting of twenty homes.

The experiment was conducted by the Fire Engineering Research Unit at Stellenbosch University (FireSUN) in collaboration with the Western Cape Disaster Management, Fire & Rescue Services and the Breede Valley Municipality (BVM) Fire Department who hosted the experiment and provided significant assistance to the overall research efforts. The work forms part of a collaborative project with the University of Edinburgh looking at how to reduce the impact of such fires, which has been funded by the UK-based Global Challenges Research Fund.

The results of the experiment have been published recently in Fire Technology, one of the leading academic journals in fire safety.

[A video of the experiment can be watched at https://youtu.be/kkXr6ueakAU with the technical details being found at https://rdcu.be/b7Z9e.]

"People often criticise the Fire Department for not acting swiftly, but our experiment showed that a fire can move really, really fast. Firefighters have always known this, but now we have better experimental data to understand the problem and analyse interventions," says Prof Richard Walls from FireSUN who managed the overall project.

"From our experiment we could see that certain interventions currently being implemented would have been ineffective for slowing down this fire. For instance, fire-resistant paint would have had little impact due to the intensity of the fire and the fact that the fire ignited homes through any small openings in these structures, negating the influence of coatings. Also, doors and windows in a densely-packed settlement will always provide an easy entrance for fire."

The experiment was designed by Walls' colleague Dr Nico de Koker who also analysed the results.

He says the experiment was designed to simulate a 'fire line' which would be found in a dense settlement as a large fire moves through it. "We included extensive instrumentation, thermal-imaging cameras, a drone and other equipment in the experiment to provide data on flame lengths, temperatures experienced, spread rates and details regarding when homes ignited."

Walls points out that from the time the first homes were ignited until the time the last homes caught alight was around five minutes.

"This is a frightening figure when it is considered that often it can take many minutes for a resident to notice a fire, to contact the local fire brigade (often the wrong number is called), a fire truck to be dispatched and then possibly has to drive a long distance, for fighters to find the burning dwellings (in the midst of a settlement with no street names), to setup and finally extinguish the fire."

"After around 16 minutes there were almost no homes left standing in the experiment, there was simply a pile of scrap metal lying on the floor. Temperatures of up to around 1200°C were measured, and flames many meters long emerged from dwellings."

Highlighting the value of the experiment, Deputy Fire Chief Josephus Pretorius of the BVM notes that their firefighters regularly risk their lives to fight these very dangerous fires. "It is exciting that our municipality has been able to make this research possible, so that we can better understand how these fires spread and behave."

Echoing his sentiments, Marlu Rust of the Western Cape Disaster Management, Fire & Rescue Services explains that "We have been actively working on ways to improve fire safety in informal settlements, and have worked closely with Stellenbosch University over the past years. Our fire departments have major challenges in trying to fight such fires so it is important that government, academia and communities are working together to find solutions."

Walls says that from this research experiment, and many others, the team has been developing a good understanding of fire spread in settlements.

"Although there are no easy solutions to the problem, at least the data is immediately showing what sort of interventions are likely to be less effective. Computer models have been developed to simulate fire spread through settlements, and may soon be useful decision-making tools for analysing risk in settlements, and potentially for developing fire safety strategies."

Walls adds that this experiment, amongst others, also helped to shed light on the performance of products (e.g. detectors, fire-resistant paints, extinguishers and warning systems to municipalities) used to prevent an informal settlement fire; how fast these fires spread; and how to suppress them as efficiently as possible and how communities can assist.

He says a final set of experiments conducted after this large-scale test are currently being analysed to provide further insight on a number of aspects. Also, a series of tests have been undertaken to understand the effectiveness of community-based suppression systems.

Epileptic seizures often originate in small, localized areas of the brain where neurons abnormally fire in unison. These electrical impulses disrupt proper brain functioning and cause seizures. But what makes regions where seizures start different from parts of the brain where electrical impulses remain normal? More importantly, what prevents these epileptic centers from growing?

The answer to these questions may lie in a new discovery by researchers at the University of Illinois Chicago. Dr. Jeffrey Loeb and his colleagues found that a protein -- called DUSP4 -- was increased in healthy brain tissue directly adjacent to epileptic tissue. Their research suggests that boosting levels of DUSP4 could be a novel way of preventing or treating epilepsy.

Their findings are reported in the journal Neurobiology of Disease.

"If epileptic brain regions spread throughout the brain with nothing to stop them, the seizures would overwhelm the brain, it would not be survivable," said Loeb, UIC professor and head of neurology and rehabilitation at the College of Medicine and corresponding author on the study. "We wondered if there were natural ways that epileptic brain areas are quarantined. We searched for genes at the border between epileptic and normal brain tissue that may help prevent the spread of epilepsy."

Loeb and colleagues analyzed thousands of genes in tissues from 20 patients who underwent surgery to treat their epilepsy. During these surgical procedures, brain tissue from epileptic areas and directly adjacent, non-epileptic tissue was removed. Tissue not required for pathological evaluation was stored in the University of Illinois NeuroRepository -- a human brain tissue bank and research database that links clinical, radiological, physiological, histological and molecular/genomic data to thousands of human tissue samples.

The researchers used a mathematical modeling technique called cluster analysis to sort through huge numbers of genes from the epileptic versus the nonepileptic tissue. They identified a number of genes that were increased -- or "upregulated" -- in or near epileptic tissues and the observed that DUSP4 fell into a different cluster than most of the pro-epileptic genes.

In previous research, Loeb and colleagues identified a signaling pathway that was highly upregulated in areas of the brain where epileptic seizures started. In an animal model, suppression of the pathway --known as the mitogen-activated protein kinase, or MAPK, pathway -- reduced epileptic electrical activity in the brain.

"We were excited about DUSP4 because it is known to be a potent MAPK pathway inhibitor in cancer cells," Loeb said. "Seeing this gene activated at the borders and shutting off MAPK signaling genes in the human brain led us to believe that the protein cordons off epileptic regions so that they don't enlarge or spread, similar to how in a ship you might get a leak in one area, but you can close and seal off doors to keep the leak isolated. That's how we think DUSP4 is working to keep epileptic focal points from enlarging."

In addition to the gene, when the researchers went back to look at the protein's levels in their tissue samples, they found that tissue from brain regions with lower epileptic activity had lower MAPK activity and higher levels of the DUSP4 protein.

Loeb and colleagues currently are investigating potential drugs that can upregulate or augment the activity of DUSP4 to help treat or even prevent epilepsy.

"These DUSP4-targeting drugs would represent a new kind of 'disease-modifying' treatment for epilepsy, which currently does not exist," Loeb said.

Coronavirus antibodies can last at least three months after a person becomes infected with the virus that causes COVID-19, according to a new study published today in Science Immunology.

Researchers from the Lunenfeld-Tanenbaum Research Institute (LTRI) at Sinai Health and the Temerty Faculty of Medicine at the University of Toronto used both saliva and blood samples from COVID-19 patients to measure and compare antibody levels for over three months post-symptom onset.

They found that antibodies of the IgG class that bind to the SARS-CoV-2 spike protein are detectable for at least 115 days, representing the longest time interval measured. The study is also the first to show these antibodies can also be detected in the saliva.

"Our study shows that IgG antibodies against the spike protein of the virus are relatively durable in both blood and saliva," said Jennifer Gommerman, professor of immunology at the University of Toronto and leader of the saliva testing effort. "Our study suggests saliva may serve as an alternative for antibody testing. While saliva is not as sensitive as serum, it is easy to collect."

The saliva assay was developed at the University of Toronto, while a team at LTRI, led by senior investigator Anne-Claude Gingras, a professor of molecular genetics at the University of Toronto, executed the serum assay.

"The LTRI platform for detection of antibodies in serum, or blood, is incredibly robust and well suited for assessing the prevalence of infection within the community," said Gingras. "This is another tool that can help us better understand and even overcome this virus."

Most people who recover from COVID-19 develop immune agents in their blood called antibodies that are specific to the virus. These antibodies are useful in indicating who has been infected, regardless of whether they had symptoms or not.

A large team of scientists collaborated on the study. Dr. Allison McGeer, a senior clinician scientist at LTRI and principal investigator of the Toronto Invasive Bacterial Diseases Network, along with Dr. Mario Ostrowski at St. Michael's Hospital of Unity Health Toronto provided access to the paired saliva and serum samples from dozens of patients for the study.

The study was co-led by graduate students Baweleta Isho, Kento Abe, Michelle Zuo and Alainna Jamal. Dr. James Rini, a professor of biochemistry and molecular genetics at the University of Toronto, and Yves Durocher from the National Research Council of Canada provided key protein reagents for the saliva studies.

The durability of the antibody response to SARS-CoV-2 has been debated in recent months. An earlier study published in Nature Medicine suggested the antibodies can disappear after two months for some individuals who had the virus but did not experience symptoms.

This study led by the Toronto team is in agreement with findings from leading immunologists in the U.S. in describing the antibody response as longer lasting.

While the team admits there is a lot they still don't know about antibody responses to SARS-CoV-2 infection, including how long the antibodies last beyond this period or what protection they afford against re-infection, this research could have broader implications in the development of an effective vaccine.

"This study suggests that if a vaccine is properly designed, it has the potential to induce a durable antibody response that can help protect the vaccinated person against the virus that causes COVID-19," Gommerman said.

Researchers from the RIKEN Cluster for Pioneering Research have made observations of a new magnetar, called Swift J1818.0-1607, which challenges current knowledge about two types of extreme stars, known as magnetars and pulsars. The research, just published in The Astrophysical Journal, was done using the Neutron star Interior Composition Explorer (NICER), an X-ray instrument aboard the International Space Station.
Magnetars are a subtype of pulsars, which are neutron stars--degenerate stars that failed to become black holes but instead became extremely dense bodies composed mostly of neutrons. Magnetars as well as some young rotation-powered pulsars--another type of pulsar--emit powerful X-ray beams, but the mechanism is believed to be different. With magnetars, the beams are believed to be powered by extremely strong magnetic fields, whereas in canonical pulsars they are powered by the rapid rotation of the star. However, there is much that is not well understood about these phenomena. Recently, several magnetars have been shown to emit radio waves--a property that was formerly thought to be limited to canonical rotation-powered pulsars--blurring the boundary between the two.

For the current study, work done by Chin-Ping Hu, a visiting researcher at the Extreme Natural Phenomena RIKEN Hakubi Research Team in the RIKEN Cluster for Pioneering Research and colleagues, has revealed a missing link between the two types of pulsar.

On March 12, a new gamma-ray burst was detected by the Burst Alert Telescope (BAT) aboard the Neil Gehrels Swift Observatory, a space-based gamma ray observatory. The object, believed to be a magnetar, was dubbed Swift J1818.0-1607. The RIKEN group and NICER team quickly moved into action. Four hours after the alert, they began making X-ray follow-up observations with NICER.

They found that the magnetar had a pulsation period of 1.36 seconds, the shortest among magnetars observed until now. Their observations showed that it was showing spin-down behavior--suggesting that the emissions were to some extent being powered by rotations--and that it had a magnetar-level surface magnetic field of 2.7×1014 Gauss, indicating that it is a young magnetar, formed about 420 years earlier. Studies of "glitches"--sudden changes in the rotational frequency that are important of understanding neutron stars--as well as the noisy timing behavior of its stellar rotation showed that it is indeed young. However, its X-ray emission was found to be lower than that of other magnetars, indicating that the star has attributes of both magnetars and rotation powered pulsars.

According to Hu, "Our study has given us new understanding of the neutron stars with high magnetic fields. Recent radio observations suggest that magnetars may be a cause of mysterious phenomena called fast radio bursts, so we look forward to investigating further."

According to Teruaki Enoto, team leader of the Extreme Natural Phenomena RIKEN Hakubi Research Team, "The discovery of a new magnetar is exactly what our magnetar and magnetosphere science team of NICER was waiting for. The NICER observatory is very well suited to monitoring X-ray pulsations from magnetars, and the bridge between the two types of pulsars that we discovered has contributed to our understanding of these mysterious objects."

The work was done by scientists from RIKEN CPR in collaboration with colleagues from Kyoto University and a number of other institutes around the world.????

Zoologists from Trinity College Dublin, working in tropical Southeast Asia, have uncovered a modern-day example of rapid evolution in action.

The zoologists have discovered that male and female Sulawesi Babblers (Pellorneum celebense, a species of bird) have evolved to attain different sizes on small islands, and in quick-fire time. They believe this is most likely due to evolutionary pressure favouring such "dimorphism" because the birds are able to reduce competition with each other by feeding on different, scarce resources.

The research, completed with the support of the Irish Research Council and collaborators in Universitas Halu Oleo, is published today in the journal Biotropica. The research shows that the males of the Sulawesi Babbler grow to be up to 15% larger than the females - with this difference particularly marked on the smaller islands.

Fionn Ó Marcaigh, first author on the paper and a PhD Candidate in Trinity's School of Natural Sciences, said:

"Tropical regions are home to more species of plants and animals than anywhere else, but many of these remain poorly understood even as they face imminent extinction. This is especially true of relatively non-descript species like the babblers, which are shy birds that feed in dense bushes all over the islands of Southeast Asia.

"Because male and female babblers have the same dull brown plumage, unlike familiar birds such as pheasants or peacocks, scientists previously thought that they did not show sexual dimorphism. Our discovery proves this wrong and provides another timely reminder that we have so much more to learn about tropical species if we are to understand how they are evolving on all the world's marvellous and diverse islands.

"We can't protect them if we don't understand them."

The kind of sexual dimorphism in size displayed by the babblers is important because it enables the males and females to fill different "niches" in the ecosystem.

There is an evolutionary theory stating that dimorphic species are likely to become more strongly dimorphic on islands than they are on the mainland, as it prevents them having to compete for scarcer resources. However, this is usually seen on very isolated islands where there has been ample time for populations to evolve separately.

Fionn Ó Marcaigh added:

"Our research is significant for showing the same process to have occurred on much younger islands, which were connected to the mainland by land-bridges only 30,000 years ago. This means that the difference in sexual dimorphism between mainland and island birds must have evolved quite rapidly, showing its importance for the ecology of the species."

Samples from the lungs of patients show a runaway immune system reaction could be one mechanism behind severe COVID-19 cases.

When infected with the SARS-CoV-2 coronavirus, many people experience mild and moderate symptoms, but for some people infection can be severe or fatal. Scientists are urgently seeking to understand how COVID-19 can become severe.

Now, a study led by Imperial College London researchers has revealed how an overreaction of part of the immune system could be linked to severe cases of COVID-19.

When we are infected with pathogens like bacteria and viruses, our bodies mount several types of immune system response. One of the major components are T cells, which come in several different forms that coordinate the immune response, from killing infected cells to recruiting more T cells to the fight.

Sometimes, our immune system overreacts to invaders, for example during an allergic reaction, resulting in T cells killing normal, healthy cells and causing tissue damage. However, there is a 'brake mechanism' that should kick in, causing T cells to reduce their activity and calming inflammation.

The new research, published today in Frontiers in Immunology, shows how this brake mechanism does not appear to kick in in severe COVID-19 cases.

Lead researcher Dr Masahiro Ono, from the Department of Life Sciences at Imperial, said: "We desperately need new ways to reduce the impact of COVID-19 in severely affected patients. This starts with understanding exactly what is going wrong and causing them damage. We hope this study will go some way to answering this question, and lead to new tools to fight the disease."

The researchers tested samples from the lungs of six COVID-19 patients in China with severe symptoms and compared them to samples from three moderate COVID-19 patients and three healthy individuals.

Although the samples were from relatively few patients, the team investigated gene usage in single cells, gaining fine detail on the immune system response. This method allowed them to analyse rare cells and their dynamics, which cannot be achieved with conventional methods.

The found that the lungs of severe COVID-19 patients had accumulated a broad range of 'hyperactivated' T cells, suggesting the brake mechanism had failed. This overreaction 'paralyses' the overall T cell system, causing it to fail at fighting the virus, as well as causing more damage to the lungs through severe inflammation and tissue destruction.

On closer inspection of the mechanism, the researchers found that the protein 'Foxp3', which usually induced the brake mechanism, is inhibited in lungs of severe COVID-19 patients. They are unsure why Foxp3 is inhibited, but further study could reveal this, and potentially lead to a way to put the brakes back on the T cell response, reducing the severity of the disease.

First author Dr Bahire Kalfaoglu, from the Department of Life Sciences at Imperial, said: "Our study looked at just a few patients, but analysed thousands of their cells in great detail, revealing a new mechanism of COVID-19 worsening. With more study, we hope to further understand the mechanism of Foxp3 inhibition, and potentially, how to reverse it."

The CRISPR/Cas9 gene-editing tool is one of the most promising approaches to advancing treatments of genetic diseases - including cancer -, an area of research where progress is constantly being made. Now, the Molecular Cytogenetics Unit led by Sandra Rodríguez-Perales at the Spanish National Cancer Research Centre (CNIO) has taken a step forward by effectively applying this technology to eliminate so-called fusion genes, which in the future could open the door to the development of cancer therapies that specifically destroy tumours without affecting healthy cells. The paper is published in Nature Communications.

Fusion genes are the abnormal result of an incorrect joining of DNA fragments that come from two different genes, an event that occurs by accident during the process of cell division. If the cell cannot benefit from this error, it will die and the fusion genes will be eliminated. But when the error results in a reproductive or survival advantage, the carrier cell will multiply and the fusion genes and the proteins they encode thus become an event triggering tumour formation. "Many chromosomal rearrangements and the fusion genes they produce are at the origin of childhood sarcomas and leukaemias," explains Sandra Rodríguez-Perales, lead co-author of the study now published by the CNIO. Fusion genes are also found in among others prostate, breast, lung and brain tumours: in total, in up to 20% of all cancers.

Because they are only present in tumour cells, fusion genes attract a great deal of interest among the scientific community because they are highly specific therapeutic targets, and attacking them only affects the tumour and has no effect on healthy cells.

And this is where the CRISPR technology comes into play. With this technology, researchers can target specific sequences of the genome and, as if using molecular scissors, cut and paste DNA fragments and thus modify the genome in a controlled way. In the study carried out by the CNIO team, the researchers worked with cell lines and mouse models of Ewing's sarcoma and chronic myeloid leukaemia, in which they managed to eliminate the tumour cells by cutting out the fusion genes causing the tumour.

The tumour cell repairs itself... and destroys itself

This is the first time that CRISPR has been successfully applied for the selective elimination of fusion genes in tumour cells. Earlier strategies by other research teams were based on modifying the junction between the two genes involved in the fusion to introduce a DNA sequence that induces cell death. The problem is that the introduction of foreign sequences has proven to be very ineffective in eliminating tumours.

The CNIO researchers used a completely different approach to induce the tumour cell to destroy itself. "Our strategy was to make two cuts in introns, non-coding regions of a gene, located at both ends of the fusion gene," explains Raúl Torres-Ruiz, co-author of the paper. "In that way, in trying to repair those breaks on its own, the cell will join the cut ends which will result in the complete elimination of the fusion gene located in the middle". As this gene is essential for the survival of the cell, this repair automatically causes the death of the tumour cell.

"Our next steps will be to carry out more studies to analyse the safety and efficiency of our approach," continues Rodríguez-Perales. "These steps are essential to know if our approach can be translated in the future into a potential clinical treatment. Furthermore, we will study whether our strategy, which we have already seen works in Ewing's sarcoma and chronic myeloid leukaemia, is also effective in other types of cancer caused by fusion genes and for which there are currently no effective therapies," he concludes.

Point-of-care-testing for suspected COVID-19 reduces time to results and may improve infection control, suggesting these tests might have clinical advantages over widely used laboratory PCR methods.

An interventional study tracking SARS-CoV-2 testing on admission to a UK hospital finds that the wait for results was just 1.7 hours using point-of-care testing (POCT) close to the patient's bedside, compared with 21.3 hours using the standard process of PCR testing in a centralised lab within the hospital.

The study is the first to assess real-world impact of POCT and is published in The Lancet Respiratory Medicine journal. It was conducted between 20 March and 29 April 2020 (the peak of the first wave of COVID-19 in the UK).

The findings from 1054 patients in the UK using the QIA-stat-Dx POCT platform suggest that testing suspected COVID-19 at the point-of-care could help health-care providers better manage a surge in cases and reduce infection spread within the hospital.

During the first wave of the coronavirus pandemic, health-care systems across the world relied on PCR testing of patient samples in centralised hospital laboratories, an approach that is lengthy and resource intensive. Delays in results means that it takes longer for patients to be admitted to the correct COVID/non-COVID wards, so they are waiting in mixed assessment rooms, increasing the possibility of transmission between positive and negative patients.

In recent months, a number of molecular POCT testing platforms have been developed, promising rapid results from testing in the area where the patient is being seen, such as A&E. Swab samples are placed into test cartridges that take up little physical space and can be operated by health-care staff, unlike the standard laboratory PCR test where samples are sent off to centralised labs and dealt with by specialist staff. Although there are data to support the speed and accuracy of POCT kits, there remains a lack of insight into their impact on hospital care and transmission.

Reducing diagnosis time is key to tackling COVID-19 as it allows patients to be quickly isolated and for treatment to be started immediately. Furthermore, rapidly identifying cases allows patients to avoid assessment areas, resulting in less need for decontamination of beds and reduced staff exposure.

As hospitals prepare for a second wave of the pandemic, rapid testing of suspected cases of COVID-19 will be key to containment and preventing hospitals from becoming overwhelmed.

"Our findings are the first to suggest the clinical benefits of molecular point-of-care COVID-19 testing in hospitals, demonstrating reduced delays, bed moves, and time in assessment areas, which all lead to better infection control," says Dr Tristan William Clark, lead author from Southampton General Hospital, UK. "We believe that molecular POCTs should be urgently integrated into care pathways to reduce coronavirus transmission within hospitals to prevent the next wave of the pandemic overwhelming health services around the world." [1]

The non-randomised trial took place in the Acute Medical Unit and Emergency Department of Southampton General Hospital and included adults with COVID-19 symptoms.

Nose and throat swabs were taken from all patients and tested for infection with SARS-CoV-2 virus. Around half (499/1054) of the patients were tested using POCT in a dedicated hub in the Acute Medical Unit, using a kit known as QIAstat-Dx Respiratory SARS-CoV-2 Panel, which detects SARS-CoV-2 and other respiratory viruses, including influenza. They were also tested using the standard laboratory PCR test. The remaining control patients (555/1054) were tested only using standard PCR testing.

197 (39%) of 500 patients in the POCT group were found to be PCR-positive for SARS-CoV-2 compared with 155 (28%) of 555 in the control group.

The authors compared how long it took to receive results with the two types of testing. Secondary analyses (planned outcome measures that are not as important as the primary outcome measure but are still of interest in evaluating the effect of an intervention [2]) looked at infection control and diagnostic accuracy.

Median time to results with POCT was 1.7 hours compared with 21.3 hours and the difference remained large after taking into account factors such as disease severity, age, and sex.

After testing, patients were transferred to definitive COVID-positive or negative wards. This took 8 hours in the POCT group, compared with 28.8 hours in the control group, with 13.7% transferred directly to the correct ward (bypassing assessment areas) in the POCT group and 0% in the control group. The mean number of bed moves between admission and final ward arrival was lower in the POCT group at 0.9 moves than in the control group at 1.4 moves.

These improvements were seen without compromising diagnostic accuracy. 469 POCT tests were assessed for diagnostic accuracy and had 99.4% sensitivity (176/177 participants) and 98.6% specificity (288/292 participants), outperforming central lab PCR (85.9% [152/177] sensitivity and 98.9% [289/292] specificity).

The findings provide evidence that POCT for SARS-CoV-2 is feasible in the context of appropriate infection control and staff training. The study could inform decision making around patient diagnostics and containment as the pandemic continues.

Most COVID-positive patients were recruited into a further COVID-19 clinical trial that took place during the first wave (63% in the POCT group and 67% in the control group). Patients in the POCT group were enrolled in clinical trials 2 days quicker than those in the PCR group, with a median wait of 1 day versus 3 days.

"Recruiting patients into clinical trials remains an international priority throughout this pandemic and is vital to accelerating the search for effective treatments", says Dr Clark. "This is especially true when researchers are investigating the potential of anti-virals, which have to be administered at early disease stages to have the greatest benefit." [1]

The authors caution that there are limitations to the study, most notably that they were unable to randomise the groups due to staffing resources, and there were differences in baseline measures of a number of factors, with the POCT group showing more severe disease. They further caution that POCT must always be carried out under appropriate infection control guidelines and with trained staff, and that the findings may not extend to non-hospital settings.

Writing in a linked Comment, Dr Luke Moore (who was not involved in the study), from Chelsea and Westminster Hospital NHS Foundation Trust, UK, says: "Brendish and colleagues focus on clinical outcomes and find that the QIAstat-Dx SARS-CoV-2 turnaround time leads to shorter time to patient placement in an appropriate care area, fewer bed moves, and faster time to enrolment into other COVID-19 clinical trials--all significant advantages...Although independent, prospective, controlled, in-situ evaluations of respiratory virus diagnostics such as that by Brendish and colleagues are essential, we need to push even further for clear analyses of implementation and impact, to best understand and leverage the value added from point-of-care platforms during this pandemic and beyond."

Two separate studies have documented the persistence of antibodies that target SARS-CoV-2 in hundreds of patients with COVID-19 at least 3 months after symptom onset. Both studies point to the IgG class of antibodies as the longest-lasting antibodies detectable in the blood and saliva of patients during this timeframe, suggesting that SARS-CoV-2-specific IgG antibodies may serve as promising targets to detect and evaluate immune responses against the virus. That these antibodies could be detected at similar levels in both blood and saliva suggests that saliva could be used as an alternative biofluid for antibody testing.

In the first study, Anita Iyer and colleagues measured antibody responses in the blood of 343 patients with COVID-19 for up to 122 days after symptom onset - and compared these responses to those of 1,548 control individuals sampled before the pandemic. The researchers focused only on antibodies specific to the SARS-CoV-2 spike protein's receptor binding domain. To provide a baseline, the researchers estimated sensitivities of IgG, IgA, and IgM antibody types at 95%, 90%, and 81%, respectively, for detecting infected individuals between 15 to 28 weeks after symptom onset. Among these antibodies, spike protein-specific IgM and IgA were short-lived, dropping beneath detection levels at around 49 and 71 days, respectively, after the appearance of symptoms. In contrast, spike protein-targeted IgG responses decayed slowly over a period of 90 days, with only 3 individuals losing them within this timeframe. Levels of spike protein-specific IgG strongly correlated with levels of neutralizing antibodies in the patients. The researchers also did not observe cross-reactivity of any SARS-CoV-2-targeting antibodies with other "common cold" coronaviruses.

Similar to Iyer et al., Baweleta Isho and colleagues found that while IgA and IgM antibodies targeting the spike protein's receptor binding domain rapidly decayed, IgG antibodies remained relatively stable for up to 105 days after symptom onset in 402 patients with COVID-19. The researchers detected spike protein-specific antibodies in the saliva, as well as the blood, of these patients. They charted the patients' antibody responses from 3 to 115 days after symptom onset, and compared their profiles with 339 pre-pandemic controls. Patients with COVID-19 showed peak IgG levels at 16 to 30 days after the appearance of symptoms. Levels of all spike protein-specific IgG, IgM, and IgA antibodies in the blood positively correlated with levels observed in matched saliva samples. "Given that the virus can also be measured in saliva by PCR, using saliva as a biofluid for both virus and antibody measurements may have some diagnostic value," the authors say.

In plants, many proteins are found at only one end of a cell, giving them a polarity like heads and tails on a coin.

Often, cells next to each other have these proteins at the same end, like a stack of coins with heads all facing up. This protein patterning is critical for how plant cells orient and coordinate themselves to produce the leaves, flowers, stems and roots that adorn our gardens and provide us with all our food and the oxygen we breathe.

Previously it's been unclear how this head-to-tail protein patterning is produced: can it arise within each cell, or does it depend on a collective effort of many cells working together?

A new paper, published in Current Biology has found that even cells in isolation can become polarised to create the head to tail pattern, and that this polarity can orient how the cell grows.

The team, from the John Innes Centre, studied a protein called BASL that is normally found at only one end of the cells giving rise to leaf pores. By tagging the BASL protein with fluorescence and introducing it into cultured plant cells they could see where the protein went.

They showed that even if the cells were stripped of their walls, to create membrane-enclosed spheres, the BASL protein went to only one end of the cell, forming a cap. Time-lapse movies showed that position of BASL labelling changed over time, like a polar ice cap wandering over the earth's surface. However, when cells reformed their walls, the BASL cap could become fixed, and cells elongated into sausage shapes, with the cap remaining at one of the rounded ends.

Lead author Dr Jordi Chan says, "It was incredibly exciting to see polarity in isolated plant cells for the first time. It was like seeing a boring-looking planet suddenly light up to reveal a cap, and then elongating while keeping the cap at one end."

The results show that cell polarity can arise within cells and likely orients their growth. Signalling between cells may then coordinate polarity, aligning the heads and tails of different cells in a tissue, guiding how they grow collectively and develop into a plant.

Athletes using legal performance enhancing and medical sport supplements are more likely to dope than those using sport foods and superfoods, a new study reveals.

While some sport supplements may be necessary for an athlete's programme, taking ergogenic and medical sport supplements may inadvertently lead to sports people developing favourable attitudes towards doping

Researchers at the University of Birmingham and Canterbury Christ Church University are calling for bespoke anti-doping education for athletes using such supplements to prevent them turning to banned substances.

In the first study of its kind, the researchers surveyed 573 athletes competing at club, country, national and international level about their use of four types of sport supplements:

Ergogenic, such as creatine - used to improve performance;

Medical, such as iron - used to treat clinical issues and nutrient deficiencies;

Sport foods/drinks, such as protein bars - providing a source of nutrients; and

Superfoods, such as goji berries - which claim to optimise health and performance.

Publishing their findings in Journal of Science and Medicine in Sport, the researchers note that athletes using ergogenic and medical sport supplements to improve performance, through boosting strength and shortening recovery between training sessions can develop the belief that doping is another means to improve performance.

Co-author Christopher Ring, Professor in Psychology at the University of Birmingham, commented: "Our results have important implications for coaches, nutritionists and sport doctors - they must appreciate that athletes who are administered ergogenic and medical sport supplements may develop more favourable attitudes towards doping.

"An athlete using these supplements may come to believe that using chemically active substances is an acceptable way of enhancing sport performance. This belief could then later develop into a rationalisation that doping is just another means to enhance performance."

Two in five athletes surveyed (42%) used ergogenic supplements, whereas one in five used medical sport supplements (18%) and sport foods and drinks (21%). Superfoods were rarely used (2%). Over half (53%) used at least one sport supplement.

Researchers note that future research such explore how use of one supplement type may lead to another and eventually the use of banned substances - for example, superfood use leads to ergogenic and medical supplement use, which may in turn, lead to doping.