Culture

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.

While the world waits eagerly for a safe and effective vaccine to prevent infections from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus behind the COVID-19 pandemic, researchers also are focusing on better understanding how SARS-CoV-2 attacks the body in the search for other means of stopping its devastating impact. The key to one possibility -- blocking a protein that enables the virus to turn the immune system against healthy cells -- has been identified in a recent study by a team of Johns Hopkins Medicine researchers.

Based on their findings, the researchers believe that inhibiting the protein, known as factor D, also will curtail the potentially deadly inflammatory reactions that many patients have to the virus.

Making the discovery even more exciting is that there may already be drugs in development and testing for other diseases that can do the required blocking.

The study is published in the Sept. 2, 2020, issue of the journal Blood.

Scientists already know that spike proteins on the surface of the SARS-CoV-2 virus -- making the pathogen look like the spiny ball from a medieval mace -- are the means by which it attaches to cells targeted for infection. To do this, the spikes first grab hold of heparan sulfate, a large, complex sugar molecule found on the surface of cells in the lungs, blood vessels and smooth muscle making up most organs. Facilitated by its initial binding with heparan sulfate, SARS-CoV-2 then uses another cell-surface component, the protein known as angiotensin-converting enzyme 2 (ACE2), as its doorway into the attacked cell.

The Johns Hopkins Medicine team discovered that when SARS-CoV-2 ties up heparan sulfate, it prevents factor H from using the sugar molecule to bind with cells. Factor H's normal function is to regulate the chemical signals that trigger inflammation and keep the immune system from harming healthy cells. Without this protection, cells in the lungs, heart, kidneys and other organs can be destroyed by the defense mechanism nature intended to safeguard them.

"Previous research has suggested that along with tying up heparan sulfate, SARS-CoV-2 activates a cascading series of biological reactions -- what we call the alternative pathway of complement, or APC -- that can lead to inflammation and cell destruction if misdirected by the immune system at healthy organs," says study senior author Robert Brodsky, M.D., director of the hematology division at the Johns Hopkins University School of Medicine. "The goal of our study was to discover how the virus activates this pathway and to find a way to inhibit it before the damage happens."

The APC is one of three chain reaction processes involving the splitting and combining of more than 20 different proteins -- known as complement proteins -- that usually gets activated when bacteria or viruses invade the body. The end product of this complement cascade, a structure called membrane attack complex (MAC), forms on the surface of the invader and causes its destruction, either by creating holes in bacterial membranes or disrupting a virus' outer envelope. However, MACs also can arise on the membranes of healthy cells. Fortunately, humans have a number of complement proteins, including factor H, that regulate the APC, keep it in check and therefore, protect normal cells from damage by MACs.

In a series of experiments, Brodsky and his colleagues used normal human blood serum and three subunits of the SARS-CoV-2 spike protein to discover exactly how the virus activates the APC, hijacks the immune system and endangers normal cells. They discovered that two of the subunits, called S1 and S2, are the components that bind the virus to heparan sulfate -- setting off the APC cascade and blocking factor H from connecting with the sugar -- and in turn, disabling the complement regulation by which factor H deters a misdirected immune response.

In turn, the researchers say, the resulting immune system response to chemicals released by the lysing of killed cells could be responsible for the organ damage and failures seen in severe cases of COVID-19.

Most notably, Brodsky says, the research team found by blocking another complement protein, known as factor D, which works immediately upstream in the pathway from factor H, they were able to stop the destructive chain of events triggered by SARS-CoV-2.

"When we added a small molecule that inhibits the function of factor D, the APC wasn't activated by the virus spike proteins," Brodsky says. "We believe that when the SARS-CoV-2 spike proteins bind to heparan sulfate, it triggers an increase in the complement-mediated killing of normal cells because factor H, a key regulator of the APC, can't do its job."

To better understand what happens, Brodsky says think of the APC like a car in motion.

"If the brakes are disabled, the gas pedal can be floored without restraint, very likely leading to a crash and destruction," he explains. "The viral spike proteins disable the biological brakes, factor H, enabling the gas pedal, factor D, to accelerate the immune system and cause cell, tissue and organ devastation. Inhibit factor D, and the brakes can be reapplied and the immune system reset."

Brodsky adds that cell death and organ damage from a misdirected APC associated with factor H suppression is already known to occur in several complement-related human diseases, including age-related macular degeneration, a leading cause of vision loss for people age 50 and older; and atypical hemolytic uremic syndrome (aHUS), a rare disease that causes clots to block blood flow to the kidneys.

Brodsky and his colleagues hope that their work will encourage more study into the potential use against COVID-19 of complement-inhibiting drugs already in the pipeline for other diseases.

"There are a number of these drugs that will be FDA-approved and in clinical practice within the next two years," Brodsky says. "Perhaps one or more of these could be teamed with vaccines to help control the spread of COVID-19 and avoid future viral pandemics."

The intertidal mudflats of Barr Al Hikman, a nature reserve at the south-east coast of the Sultanate Oman, are crucial nursery grounds for numerous crab species. In return, these crabs are a vital element of the ecology, as well as the regional economy, a new publication in the scientific journal Hydrobiologia shows. 'These important functions of the crabs should be considered when looking at the increasing human pressure on this nature reserve', first author and NIOZ-researcher Roeland Bom says.

Blue swimming crab

The mudflats of Barr Al Hikman are home to almost thirty crab species. For his research, Bom, together with colleagues in The Netherlands and at the Sultan Qaboos University in Oman, looked at the ecology of the two most abundant species. Bom: 'Barr Al Hikman is also home to the blue swimming crab Portunus segnis. That is the species caught by local fishermen. This crab uses the mudflats of Barr Al Hikman as nursery grounds.'

The counts of Bom and his colleagues show, that there are millions and millions of these crabs in Barr Al Hikman. They are food to hundreds of thousands of birds, both migrating species, as well as birds breeding in the area, such as crab plovers. The crabs live in holes in the ground. They forage on the seagrass beds that are still abundant in Barr Al Hikman. 'Apart from the high primary production (algae) in Barr al Hikman, this reserve is also well suited for crabs because of the vastness of the area', Bom assumes. 'The slopes of the mudflats are very gentle, so at low tide, the crabs have an immense area at their disposition.'

Eco value

The value of the crabs is not just ecological, Bom stresses. "Local fishermen that catch the blue swimming crabs, distribute them not only through Oman, but also through the rest of the Arabian Peninsula and even to Japan. At approximately € 2,- per kilo, these crabs represent an important economic pillar, both under the region around Barr Al Hikman, as well as for the whole of Oman.'

Reserve

The protection of the reserve of Barr Al Hikman is limited to national legislation. Efforts to acknowledge this reserve under the international Ramsar-convention were never effectuated. There is, however, increasing human pressure on the mudflats of Barr Al Hikman, the authors describe, that would justify further protection. For example, there are well-developed plans to start shrimp farming around this intertidal area. 'When looking at the cost and benefits of these activities, it is important to look at the role of this reserve in the local ecology, as well as in the broader ecology of the many migratory birds that use the area', Bom says. 'Moreover, our research shows that the unique ecosystem of Barr Al Hikman plays a key role in the economy as well.'

It is only 120 millionths of a millimetre in size but can bring entire countries to a standstill: the Corona virus. Even if it were to disappear one day, viral infections will still be among the most frequent and difficult-to-treat diseases in humans. Even decades of research have only produced a few standardized vaccines and strategies for treatment to combat just a small number of viruses. Nor has there been much research into viral mechanisms of action - which was a reason for Prof. Guiscard Seebohm and his team at the Institute for the Genetics of Heart Diseases of Münster University to focus their attention on precisely this topic. And the team has now succeeded in making a groundbreaking development: it has created a viral expression model which can be used to simulate and analyse a large number of viral infections - including the one with SARS-CoV-2. The results can be read in the current issue of Scientific Reports published by the "Nature" journal.

One virus that is much less well-known than SARS-CoV-2, but which can be transmitted in the same way, is the Coxsackie virus B3 (CVB3). "Its symptoms," explains Guiscard Seebohm, "are mostly similar to those for flu, as is the recovery time: after two or three weeks, any patients with a CVB3 infection are, as a rule, well again, and don't have any obvious long-term impairment." But - not always, says Guiscard Seebohm, who heads the Cellular Electrophysiology and Molecular Biology department. Apart from any acute infections, he explains, a viral infection also contains the risk of a chronic infection, with the consequence of continuous damage to certain internal organs - which can lead to death. This means that months or even years later, an inflammation of the heart muscle, or type 1 diabetes, can occur in some patients who had CVB3 in the past. Histological examinations of patients showed, in some cases, serious damage to the tissue structure. Also: even years after the acute infection occurred, tissue analyses prove the existence of a virus in the genes.

So far there has been an insufficient amount of study devoted to the question of how a CVB3 infection becomes chronic and how exactly an acute infection progresses. In this respect, the Guiscard Seebohm team has succeeded in taking a great step forward. It developed an expression model for CVB3, based on stem cells, in order to get to the bottom of the mechanisms of action in this virus - as a prototype for the effects of viruses in general. In a study, the model was tested for its controllability in heart muscle cells cultured from stem cells. In the process, the team of researchers was able to achieve a stable integration of the genetic information from a non-infectious variant of CVB3 into the genetic material in human stem cells. The latter can be converted into any kind of human tissue in the laboratory, making it possible to precisely investigate viral mechanisms. The CVB3 expression can be specifically activated by means of a chemical signal.

Guiscard Seebohm is delighted at this success, because, as he says, "As a result of this unique human viral expression system based on stem cells, it will now be possible to simulate a large number of diseases in their progression and, for the first time, analyse them with the utmost precision." In Guiscard Seebohm's view there is something else that is just as important: the system is completely controllable. The team of researchers managed to steer the CVB3 expression in the expression model time-wise, both in stem cells and in differentiated heart muscle cells. At the same time, the researchers were able to vary the quantity of viral proteins produced as well as their localization. In other words, the extent of the viral infection, the infection pattern and the time progression can all be adapted to whatever topics researchers are working on.

The production of the first fully controllable viral expression model in human cells, its proven functionality, and the transferability to patients all open up numerous new approaches for research. It is not only that any infection with CVB3 and other viruses such as Corona and influenza can be examined with a very high resolution; this new method also means that the borders of what can be researched can be extended. Follow-up studies on the controlled expression of CVB3 in hiPSC are already underway and showing promising results. Last but not least, Dr. Stefan Peischard, the lead author of the study now published, and his colleagues in the Seebohm team hope that their work will lead to significant benefits for patients.

Unforeseen circumstances force low-income families to quickly move from one home to the next, a process that helps to perpetuate racial and economic segregation in the United States, research shows.

Author Johns Hopkins University sociologist Stefanie DeLuca analyzed 17 years of her team's field work with 1,200 low-income households in five different cities. They found that low-income families are forced by urgent crises to choose the safest, most convenient locations necessary for immediate survival rather than take the time to find neighborhoods with great schools and job opportunities. These unpredictable shocks often include housing quality failure, housing policy changes, landlord behaviors, income changes and neighborhood violence.

"By listening to how low-income families make their housing decisions we can develop better policies to target what is really getting in their way of moving to higher opportunity neighborhoods with less racial and economic segregation," DeLuca said. "They're not making that move because there is seldom enough time before the next emergency arises and forces them out and demands an immediate solution."

The current pandemic will only exacerbate that pattern if evictions escalate amid record unemployment, say authors of the new paper, published this week in City & Community.

The findings of DeLuca and co-author Christine Jang-Trettien, a former Johns Hopkins graduate student who's now at Princeton University, demonstrate that lawmakers need to reconsider the extent to which federal, state and local policies make assumptions about how low-income families decide where to live and where to send their children to school. Decision-makers often assume that personal preferences and structural impediments such as racial discrimination in housing markets are the primary impediments to reducing segregation by income and race.

The researchers found that people who experience a lifetime of exposure to economically disadvantaged and racially segregated schools and neighborhoods make repeated reactive moves without first considering options for school.

DeLuca and her team conducted interviews over 17 years in Baltimore, Seattle, Cleveland, Dallas and Mobile, Alabama. They revealed how shocks that lead to reactive decision-making affect whether to move, where to move, what schools to choose and whether to rent or own. Residents shared that they did not have the luxury of waiting for the "package deal" of a home in a high-opportunity community. Instead, time and again, they took a "trial and error approach" that they hoped would improve their housing and school situation.

The federal government is already incorporating insights from the research into developing policies that could help support families' ability to choose higher opportunity areas that have been proven to improve physical and mental health and end the cycle of poverty by exposing children to better schools and more jobs.

The U.S. Department of Housing and Urban Development is currently considering applications from public housing authorities through December for a test program that seeks to expand on findings from public housing authorities in Seattle and King County, Washington. Pilot programs there show families with federal housing subsidies are often forced to live in higher poverty areas because of barriers, including "inadequate time to find a unit," not preferences.

The program is building upon research highlighted by DeLuca in this paper and other work conducted collaboratively with colleagues at Harvard, MIT and Columbia.

"The COVID-19 pandemic has deepened the already existing housing crisis in the United States; with unemployment rates more than tripling in the first three months of the pandemic, an enormous eviction wave looms on the horizon," the paper states. "As more families are forced to make 'reactive' moves under duress and financial constraints, our research has potential to highlight the consequences for households and neighborhoods, as well as provide guidance on how to respond to such a fast-moving crisis."

DALLAS - Oct. 8, 2020 - The COVID-19 pandemic has led to new rules and expectations for clinical trials. Following guidance from federal agencies, institutions such as UT Southwestern adjusted clinical trial operations. To protect patient safety, changes such as utilizing remote consents, conducting telehealth study visits, and shipping oral study treatment to patients' homes have streamlined the clinical trial participation process.

A survey of UTSW clinical research professionals found that most clinical trial coordinators, managers, and nurses report positive experiences with these COVID-related adjustments. In fact, a majority are in favor of keeping the new protocols even after the pandemic ends.

"With COVID-19, we've seen more changes to clinical trial practices than at any other time in my career," says David Gerber, M.D., a professor of internal medicine at UTSW, associate director of clinical research in the Harold C. Simmons Comprehensive Cancer Center, and first author of an article on the survey results published online this week in the Journal of the National Comprehensive Cancer Network. "My hope is that this whole ordeal leads to long-term simplification of the clinical research process."

On March 16, UT Southwestern announced restrictions on clinical trials in response to COVID-19, halting new enrollments and cutting back on in-person, nonessential research visits for ongoing trials. Two days later, the Food and Drug Administration issued its own guidance, allowing clinical researchers to make temporary changes to trial conduct, including implementing telehealth appointments and allowing electronic signatures. This guidance remains in effect until the official COVID-19 national emergency is ended by the federal government. The National Institutes of Health also issued revised trial guidance.

"Shutting everything down for new enrollment was a hard decision for us, but ultimately we had to consider what was best for patients," says Erin Williams, associate director of clinical research operations at the Simmons Cancer Center. "Our goal was to get everything reactivated as quickly as possible, but we needed time to figure out how to make clinical trials work in the wake of COVID-19."

Before ramping clinical trials back up, Williams' team had to cross many technical barriers. Those included putting systems into place for researchers and patients to remotely access documents and information, as well as new ways for researchers to communicate virtually with patients.

From April 27 to June 1, the Simmons Cancer Center gradually resumed clinical trial enrollments, but with new measures in place. For instance, patients no longer had to visit in person to consent to participate in a trial - a lengthy process that involves learning about the risks and benefits of participation. That process was shifted to video calls and electronic signatures. Moreover, some patients who previously had to visit the Simmons Cancer Center to receive drugs could now have them shipped to their homes. And some visits to check on patients' progress or symptoms were converted to telehealth calls.

"Things behind the scenes changed, too," says Williams. "Our workflow and that of any sponsoring pharmaceutical company are very different now."

Gerber, Williams, and their colleagues saw the changes as an opportunity for research. On May 22 - roughly a month after the new procedures were launched - they invited 108 UTSW clinical research professionals to participate in a webinar and respond to an emailed survey about the changes.

Ninety-four responded to the survey, including administrative professionals who coordinate trial logistics and finances, research nurses, research managers and coordinators, and data specialists. Of those, 58 percent had more than five years of professional experience with clinical research and 56 percent had personal experience with a COVID-19-related change.

Overall, survey respondents said that the changes had a positive impact on patient safety, treatment efficacy, patient and staff experience, and communication with patients, investigators, and sponsors. More than 90 percent thought that it was pretty important, important, or very important to continue any positive COVID-19-related clinical research adjustments after the pandemic ends.

For some specific changes, those who had firsthand experience with the new protocols were more likely to recommend continuation. For instance, 61 percent of respondents who had used telehealth were in favor of keeping it going, compared with 36 percent of those who had not used this technology. Similarly, 63 percent of those who had been involved in shipping therapies were in favor of the practice continuing, while only 29 percent of those without experience shipping therapies suggested the practice continue.

"It goes to show that things that might look or sound complicated from the outside are actually less scary when you're the one who gets it worked out and does it," Williams says.

Research professionals with more than five years of experience in the field also were more open to keeping the changes in place. "I think the longer someone works in clinical research, the more they tend to question the status quo," Gerber says.

Researchers from the Center for Algorithmic Biotechnology at St Petersburg University, as part of a group of Russian and American scientists, have developed the metaFlye assembler. It is designed to assemble DNA samples from microbial communities. With its help, it is possible to solve a wide range of fundamental and applied problems, among which is the control of the process of treating patients and even the creation of new drugs.

At present, to study the DNA of any living organism, scientists around the world use complex biotechnological instruments - DNA sequencers. These special machines cannot 'read' the genome from start to finish (like people read books). They do it in separate short fragments - reads. Combining reads into longer fragments, and ideally into a single sequence of the original genome, is an extremely complex computational problem. It is like assembling a million-piece puzzle. The problem is complicated by the fact that genomes often contain a large number of identical repetitive sequences, which often exceed the length of reads. It is possible to cope with this challenging problem using specialised software - genome assemblers.

Several dozen different assemblers are being developed in leading bioinformatics laboratories around the world, and they are available to scientists. This diversity is because the algorithms that assemblers are based on need to be adapted to: different types of input data obtained on different types of DNA sequencers; and different organisms. For example, approaches for assembling bacterial genomes may not be suitable at all for assembling the human genome and vice versa. Additionally, the developers of genomic assemblers are constantly striving to improve their solutions so that: their programmes run faster and use less memory; and the resulting assemblies are longer and more accurate than those produced by the competing software.

The new metaFlye assembler is designed for assembling metagenomes. These are DNA samples from microbial communities obtained from various environments, such as the deep sea, soil in a park, or human gut. Having received an assembly of such a sample, it is possible to determine what kind of and how many organisms are presented in it. Using additional assembly analysis, it is often possible to find out: what these organisms can feed on; how they interact; and what substances they synthesise. All this information can be used in the future, for example: to search for new drugs of natural origin; to determine the reasons underlying the extreme soil fertility; when checking the course of treating patients; and in solving many other fundamental and applied problems.

The metaFlye assembler is designed for data obtained using the current state-of-the-art sequencing technology - long-read sequencing. There are already several metagenomic assemblers working with short-read sequencing, or next-generation sequencing (NGS) data generated on Illumina instruments. Among these assemblers there is the metaSPAdes assembler. It was developed at the Center for Algorithmic Biotechnology at St Petersburg University in 2016. There are also software for assembling isolate genomes from long reads. metaFlye makes it possible to take advantage of the new technology for complex metagenomic data. It is the first metagenome assembler specially designed to work with Oxford Nanopore and PacBio technologies.

'The impetus to develop metaFlye was the absence of a specific metagenomic assembler for long-read technology,' says Mikhail Rayko, one of the project's authors, a senior research fellow at the Center for Algorithmic Biotechnology at St Petersburg University. 'This technology has already changed dramatically the whole modern genomic science. We have learned to obtain much more complete assemblies. For example, with its help, many missing fragments of the human genome have recently been sequenced and localised. The original Flye tool was used for that, and the members of our laboratory also took part in this project. However, such data have just begun to appear for metagenomes, and, of course, special tools are needed for processing it.'

Work on metaFlye started about two years ago. It is four years if we count from the creation of its predecessor, the genomic assembler Flye, on the basis of which the new project was implemented.

'In our study, published in the journal Nature Methods, we used metaFlye and other assemblers to analyse several simulated (i.e., computer generated, without real DNA sequencing) and real metagenomic samples from the gastrointestinal tract of a human, a cow and a sheep,' says Alexey Gurevich, a co-author of the assembler and a senior research fellow at the Center for Algorithmic Biotechnology at St Petersburg University. 'A sample of the sheep microbiome is perhaps of principal interest. It was first obtained and studied in this work, while the initial sequencing data for the other two samples were taken from the works of third-party authors. metaFlye made it possible to assemble an order of magnitude more viral genomes and one and a half times more plasmids in this sample than when using the best existing analogue programmes.'

Another intriguing result was that it was possible to assemble in the sample the genomes of not only bacteria and archaea, but also eukaryotes. At the same time, bioinformatics analysis revealed that almost half of eukaryotic genomic fragments belong to representatives of nematodes, or roundworms. This result fully complies with the autopsy report of the animal, which showed signs of parasitic infection.

'The metaFlye assembler is a tool for solving a wide range of tasks. It will be available to all researchers working with such data. Of the specific projects carried out in our laboratory, we use the assembler to study the soil composition in Chernevaya taiga - a unique biocoenosis of Western Siberia with abnormally high fertility,' says Alexey Gurevich.

The publication about metaFlye is the result of a collaboration of 11 Russian and American scientists from: St Petersburg University; the University of California San Diego (UCSD); Bioinformatics Institute (St Petersburg); and US Research Centers for Dairy Forage and Meat Animal. The metaFlye assembler itself is being mainly developed in UCSD. Its developer and main author of the publication is Mikhail Kolmogorov, a postdoc at UCSD. The research supervisor of the project is Pavel Pevzner, Professor at UCSD and Chief Advisor of the Center for Algorithmic Biotechnology at St Petersburg University.

New research from the University of California San Diego reveals that Democratic control of state houses leads to substantial improvement in women's incomes, wages and unemployment relative to men.

The study, to be published in Legislative Studies Quarterly, finds that especially in the recent period of pronounced partisan polarization, Democratic house control helps close the gender inequality gap. Across all states, women's wages averaged only 70 percent of men's wages in 2018, but just a few years after Democrats are elected in a state, that gap typically declines by 3.6 percentage points. Additionally, the researchers estimate that a slim Democratic majority in the house--as opposed to a slim Republican majority--leads to a 2.6 percent point reduction in the overall income gap between men and women.

"No voting bloc is more important in American elections than women," said first author Zoltan Hajnal, a professor of political scientist at UC San Diego's School of Global Policy and Strategy. "With women accounting for more than half of all votes, small shifts in the female vote can and likely will determine who wins in November."

Hajnal and co-author John Seungmin Kuk of the University of Oklahoma also assessed whether Democratic or Republican control of the White House could be linked to gains or declines in gender inequality, and the same pattern emerged. Over the last half century, women's incomes grew almost twice as fast under Democratic administrations than they did when Republicans held the Oval Office. The average gain in income for women was $443 per year under Democrats but only $284 per year under Republicans. And, poverty as well as unemployment rates also fell among females under Democratic administrations.

To test whether Democratic or Republican control of state houses impacts gender inequality, the authors tracked male and female wages, income, poverty, and employment in each state annually for the last five decades. Specifically, they looked to see if women were catching up to men faster when Democrats controlled the levers of state power then when Republicans did.

Their assessment was made by comparing changes in gender equality in states where Democrats barely won a majority in the House to states where Republicans barely won a majority. Further comparisons revealed that that Democratic control of the state House leads to significant improvement in female income (relative to male income), significant declines in female unemployment (relative to male unemployment), and near significant declines in the wage and poverty gaps.

"Just one year of Democratic control leads to a one percentage point increase in the female-male income ratio, a 0.7 percentage point decline in the wage gap, a 0.4 percent decline in the female-male employment gap, and a .28 percent decline in the male-female poverty gap," the authors wrote.

A gender gap that is no longer narrowing

These trends could be critical in closing the gender wage gap. The study points to ample evidence that women who work in the same job with the same level of experience still get paid considerably less than men. For example, National Women's Law Center recently estimated that women typically have to work 50 years to make what a man earns in 40 years. Moreover, there is evidence that after declining for many decades, the gap is no longer narrowing.

Several factors contribute to pronounced inequity, such as the fact that women are much more likely than men to be family caregivers means that the gender gap widens after women become mothers. However, 38 percent of the gender wage gap cannot be explained by factors that are easily measured such as occupation, educational attainment, or years of experience.

So, what do Democrats do differently to help close the gender the gap? While the researchers could not definitively answer this question, they find two factors are associated with the gains for women under Democrats.

"The first is gender policy," they write. "Democratic control of the state houses leads to significantly more liberal policies on gender discrimination and access to family planning. The other factor is female representation. We find that having more women in office also leads to more liberal gender policy and likely contributes to improvement on basic economic indicators for women."

However, just having more women hold office isn't necessarily the answer, according to the data.

"Any impact of female legislators is entirely contingent on having Democrats control the house majority," they write. "Having women in office greatly matters for gender policy, but only when Democrats control the agenda."

While Democratic vs. Republican control has meaningful effects for gender equality in some cases, it does not in others. Partisan control of the governor's office appears to have no clear impact on gender equality, and the same could be inferred regarding state senates. Data limitations prevented the authors from directly assessing the effect of Democratic control of the state senate, but their exploratory analysis revealed no clear effects.

Yet, they conclude that parties appear to have more meaning now as polarization has increased, relative to how a less-divided political system operated for much of the 20th Century.