Capturing the structure of large molecular complexes

SMN or in full Survival Motor Neuron: Professor Utz Fischer has been analyzing this protein and the large molecular complex of the same name, of which SMN is one of the building blocks, for many years. He holds the Chair of the Department of Biochemistry at the Julius-Maximilian’s University of Würzburg (JMU), and he first discovered the molecule during his search for the root cause of spinal muscular atrophy. As scientists found out a few years ago, this disease is caused by a lack of the SNM complex.
The work group around Prof. Fischer has now succeeded in presenting a first three-dimensional model of the entire SNM complex. Once the structure of the complex is known, it is possible to understand the way how the complex works, and why the loss of its function leads to muscular atrophy. The scientists have published their findings in the current issue of the journal Nucleic Acids Research.
The new findings have been made possible by an integrative structural-biological approach that combines biochemical, genetic and biophysical technologies.
Resolution up to a millionth of a millimeter
“The structural analysis of large and complex molecules in atomic detail has been made possible by the ‘revolution-resolution’, which was primarily brought about by the developments in cryo-electron microscopy,” says Utz Fischer. The only snag about the technology, however, is the fact that it works best on structures that are more or less rigid and have few flexible sections.
Unfortunately, many molecular entities are not built like this, including the SMN complex. “This complex is of central importance for our cells because it supports the formation of molecular machines required for the expression of our genes,” says Prof. Fischer. However, in order to serve its function in the cell, it must be highly flexible and dynamic. As a result, a structural analysis by traditional strategies has been impossible so far.

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Do you know the way to Berkelium, Californium?

Heavy elements known as the actinides are important materials for medicine, energy, and national defense. But even though the first actinides were discovered by scientists at Berkeley Lab more than 50 years ago, we still don’t know much about their chemical properties because only small amounts of these highly radioactive elements (or isotopes) are produced every year; they’re expensive; and their radioactivity makes them challenging to handle and store safely.
But those massive hurdles to actinide research may one day be a thing of the past. Scientists at the U.S. Department of Energy’s Lawrence Berkeley National Laboratory (Berkeley Lab) and UC Berkeley have demonstrated how a world-leading electron microscope can image actinide samples as small as a single nanogram (a billionth of a gram) — a quantity that is several orders of magnitude less than required by conventional approaches.
Their findings were recently reported in Nature Communications, and are especially significant for co-senior author Rebecca Abergel, whose work on chelators — metal-binding molecules — has resulted in new advances in cancer therapies, medical imaging, and medical countermeasures against nuclear threats, among others. Abergel is a faculty scientist who leads the Heavy Element Chemistry program in the Chemical Sciences Division at Berkeley Lab, and assistant professor in nuclear engineering at UC Berkeley.
“There are still so many unanswered questions with regards to chemical bonding in the actinide series. With such state-of-the art instrumentation, we are finally able to probe the electronic structure of actinide compounds, and this will allow us to refine molecular design principles for various systems with applications in medicine, energy, and security,” Abergel said.
“We demonstrated that you can work with less material — a nanogram — and get the same if not better data without having to invest in dedicated instruments for radioactive materials,” said co-senior author Andy Minor, facility director of the National Center for Electron Microscopy at Berkeley Lab’s Molecular Foundry, and professor of materials science and engineering at UC Berkeley.
Allowing researchers to work with just a nanogram of an actinide sample will significantly reduce the high costs of experiments conducted using previous methods. One gram of the actinide berkelium can cost a jaw-dropping $27 million, for example. An actinide sample that is only a nanogram also reduces radiation exposure and contamination risks, Minor added.

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Copper foam as a highly efficient, durable filter for reusable masks and air cleaners

During the COVID-19 pandemic, people have grown accustomed to wearing facemasks, but many coverings are fragile and not easily disinfected. Metal foams are durable, and their small pores and large surface areas suggest they could effectively filter out microbes. Now, researchers reporting in ACS’ Nano Letters have transformed copper nanowires into metal foams that could be used in facemasks and air filtration systems. The foams filter efficiently, decontaminate easily for reuse and are recyclable.
When a person with a respiratory infection, such as SARS-CoV-2, coughs or sneezes, they release small droplets and aerosolized particles into the air. Particles smaller than 0.3 µm can stay airborne for hours, so materials that can trap these tiny particles are ideal for use in facemasks and air filters. But some existing filter materials have drawbacks. For example, fiberglass, carbon nanotubes and polypropylene fibers are not durable enough to undergo repeated decontamination procedures, while some further rely on electrostatics so they can’t be washed, leading to large amounts of waste. Recently, researchers have developed metallic foams with microscopic pores that are stronger and more resistant to deformation, solvents, and high temperatures and pressures. So, Kai Liu and colleagues wanted to develop and test copper foams to see if they could effectively remove submicron-sized aerosols while also being durable enough to be decontaminated and reused.
The researchers fabricated metal foams by harvesting electrodeposited copper nanowires and casting them into a free-standing 3D network, which was solidified with heat to form strong bonds. A second copper layer was added to further strengthen the material. In tests, the copper foam held its form when pressurized and at high air speeds, suggesting it’s durable for reusable facemasks or air filters and could be cleaned with washing or compressed air. The team found the metal foams had excellent filtration efficiency for particles within the 0.1-1.6 µm size range, which is relevant for filtering out SARS-CoV-2. Their most effective material was a 2.5 mm-thick version, with copper taking up 15% of the volume. This foam had a large surface area and trapped 97% of 0.1-0.4 µm aerosolized salt particles, which are commonly used in facemask tests. According to the team’s calculations, the breathability of their foams was generally comparable to that of commercially available polypropylene N95 facemasks. Because the new material is copper-based, the filters should be resistant to cleaning agents, allowing for many disinfection options, and its antimicrobial properties will help kill trapped bacteria and viruses, say the researchers. In addition, they are recyclable. The researchers estimate that the materials would cost around $2 per mask at present, and disinfection and reuse would extend their lifetime, making them economically competitive with current products.
The authors acknowledge funding from the Georgetown Environmental Initiative Impact Program Award, the McDevitt bequest to Georgetown University and Tom and Ginny Cahill’s Fund for Environmental Physics at University of California Davis.
Story Source:
Materials provided by American Chemical Society. Note: Content may be edited for style and length.

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Coronavirus: 'Double mutant' Covid variant found in India

SharecloseShare pageCopy linkAbout sharingA new “double mutant” variant of the coronavirus has been detected from samples collected in India.Officials are checking if the variant, where two mutations come together in the same virus, may be more infectious or less affected by vaccines.Some 10,787 samples from 18 Indian states also showed up 771 cases of known variants – 736 of the UK, 34 of the South African and one Brazilian.Officials say the variants are not linked to a spike in cases in India.India reported 47,262 cases and 275 deaths on Wednesday – the sharpest daily rise this year.The Indian SARS-CoV-2 Consortium on Genomics (INSACOG), a group of 10 national laboratories under India’s health ministry, carried out genomic sequencing on the latest samples. Genomic sequencing is a testing process to map the entire genetic code of an organism – in this case, the virus. The genetic code of the virus works like its instruction manual. Mutations in viruses are common but most of them are insignificant and do not cause any change in its ability to transmit or cause serious infection. But some mutations, like the ones in the UK or South Africa variant lineages, can make the virus more infectious and in some cases even deadlier.Virologist Shahid Jameel explained that a “double mutation in key areas of the virus’s spike protein may increase these risks and allow the virus to escape the immune system”.The spike protein is the part of the virus that it uses to penetrate human cells.Delhi orders Covid tests at airports as cases surgeSharp rise in India Covid cases ‘alarming’The government said that an analysis of the samples collected from India’s western Maharashtra state showed “an increase in the fraction of samples with the E484Q and L452R mutations” compared with December last year. “Such [double] mutations confer immune escape and increased infectivity,” the health ministry said in a statement. Dr Jameel added that “there may be a separate lineage developing in India with the L452R and E484Q mutations coming together”.Are double mutants a worry?Smitha Mundasad, BBC health reporterA “double mutant virus” – it’s a scary phrase. Breaking it down, the words suggests that Indian scientists have discovered two significant mutations – or changes – in different locations in a single variant of the virus. That is not so surprising. Viruses mutate all the time but the questions that need answering are: does the presence of this double mutation change how the virus behaves? Will this variant be more infectious now, or cause more severe disease? And importantly, will current vaccines still work well against it? Scientists will now be busy doing the detective work needed to find out the answers. Officials say because the proportion of tests that have come back with this double mutation is currently low, there is currently nothing to suggest this is behind the current surge in cases.What is clear is that this double mutation, as different as it sounds, requires the same public health response. Increased testing, tracking of close contacts, the prompt isolation of cases, as well as masks and social distancing will all help. Reducing the pressure on India’s over-burdened healthcare system is key. In terms of vaccines – so far, for many variants of concern around the world they have been shown to be effective, though sometimes less so when compared to the original viruses they were designed against. Scientists are confident that if needed, existing vaccines can be modified to target new mutations.The Indian government denies that the rise in cases is linked to the mutations. “Though VOCs [variants of concern] and a new double mutant variant have been found in India, these have not been detected in numbers sufficient to either establish a direct relationship or explain the rapid increase in cases in some states,” the health ministry said. The recent report comes after several experts had asked the government to step up genome sequencing efforts. “We need to constantly monitor and make sure none of the variants of concern are spreading in the population. The fact that it is not happening now doesn’t mean it will not happen in the future. And we have to make sure that we get the evidence early enough,” Dr Jameel told the BBC’s Soutik Biswas earlier this month.India became the fifth country in the world to sequence the genome of the novel coronavirus after isolating it from some of the first cases recorded in January last year. More than 11.7 million cases and 160,000 deaths later, efforts are continuing to identify mutations. The latest surge – which began this month – comes during what some experts have called a “delicate phase” for India – the healthcare system is already exhausted from a year-long battle against the coronavirus.States have already begun re-introducing restrictions, including curfews and intermittent lockdowns. Two major cities, Delhi and Mumbai, have also ordered randomised rapid tests at airports, railway stations and crowded areas such as shopping malls.

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Coronavirus: EU plans tougher controls on vaccine exports

SharecloseShare pageCopy linkAbout sharingimage copyrightEPAThe European Commission is to call for tougher controls on Covid vaccine exports after it accused UK-Swedish firm AstraZeneca of failing to honour its contract to supply EU countries.The proposals, to go before EU leaders on Thursday, stop short of a ban but could enflame tensions with the UK.Under the plans any shipment of vaccine would be assessed on the country’s rate of vaccinations and vaccine exports.Meanwhile, millions of AZ doses have reportedly been found in Italy.La Stampa website says some 29 million vaccine doses due to be shipped to the UK were being stored at the Catalent plant in Anagni near Rome but were discovered by Italian inspectors as part of an investigation by the European Commission.When asked by the BBC about the report, the foreign ministry in Rome and the Italian prime minister’s office refused to comment. The plant has a contract with AstraZeneca to “fill and finish” its vaccines and is set to do the same for the Johnson & Johnson vaccine, also approved for use in the EU.The reported discovery comes weeks after the Italian government blocked the export of 250,000 doses of the Oxford-AstraZeneca vaccine to Australia, as part of new EU regulations allowing a shipment to be stopped if a company is seen as failing to meet its obligations to the 27 member states.Italy blocks AstraZeneca shipment to AustraliaThe latest proposals, which go further than January’s regulations, come as EU countries try to speed up Covid vaccination campaigns after a sluggish start, blamed partly on delayed deliveries of the AZ drug as well as safety checks.Italian Prime Minister Mario Draghi said on Wednesday that on average 170,000 daily vaccinations had been carried out this month and that the objective was to increase that to half a million. He highlighted the large number of sites and people taking part in the UK vaccination drive.image copyrightEPA”We must ask pharmaceutical companies to fully respect their commitments on a European level,” Mr Draghi said, calling for a supply chain that was not vulnerable to shocks and decisions made elsewhere. Italy is one of several European countries seeing a rise in Covid infections. Poland has reported a record 29,978 cases in the past 24 hours. Germany has announced a strict five-day lockdown over Easter, but Chancellor Angela Merkel has called a summit of 16 state leaders amid pressure to change the plan.What the Commission is planningThe European Commission was due to update its plans to tighten up export controls on Wednesday but they are likely to affect vaccine-exporting countries that have higher vaccination rates than the EU, such as the UK and US.Officials say the criteria will focus on “reciprocity” and “proportionality”, but will not include outright export bans which are opposed by countries such as the Netherlands and Belgium. Vaccine manufacturers would be assessed to see if they were fulfilling their contract with the EU.Last week, European Commission President Ursula von der Leyen complained that the EU had exported more than 10 million doses to the UK but the UK had so far exported none in return.Why is the EU having vaccine problems?EU tussle with UK over AstraZeneca jabs escalatesPM’s vaccines comments set tongues waggingUK sources insist vital components are being sent to the continent, for example for the Pfizer vaccine, and they have emphasised the UK’s role in investing early in vaccine development, BBC correspondent Nick Beake reports.The EU’s 27 leaders will assess the proposals at a summit on Thursday, in which US President Joe Biden will also take part via video.

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The Next Trick: Pulling Coronavirus Out of Thin Air

Thermo Fisher Scientific’s new air sampler can help monitor for airborne pathogens, and signals renewed interest in bioaerosol surveillance.A decade ago, when the firefighter John Burke earned his master’s degree in health care emergency management, he wrote his thesis on pandemic planning. So when the coronavirus hit last spring, Mr. Burke, now the fire chief in Sandwich, Mass., was ready.“I had my playbook ready to go,” Mr. Burke said.Testing for the virus was a top priority, so he connected with a private laboratory to ensure that his firefighters, who were transporting coronavirus patients to hospitals, could be regularly tested.And then he heard that Thermo Fisher Scientific, a Massachusetts company that makes laboratory equipment and materials, was beta testing an air sampler that could help him detect airborne coronavirus particlesBy December, he had installed one in a fire station hallway. The device, about the size of a toaster oven, sucked in ambient air and trapped airborne virus particles — if there were any to be found — in a specialized cartridge. Each afternoon, an employee would remove the cartridge and walk it to the UPS drop box across the street, sending it off for laboratory analysis.Before the month was out, the air sampler had turned up traces of the virus. Officials ultimately traced it back to a town employee who had been working in the station, without a mask, during a quiet holiday period.It was proof of concept for Thermo Fisher Scientific’s AerosolSense Sampler, which the company was making publicly available on Wednesday. The device, the company says, can be used to detect a variety of airborne pathogens, including the coronavirus. It could be deployed in hospitals, offices, schools and other buildings to monitor for signs of the virus as society begins to reopen.The AerosolSense, which will sell for $4,995, is not the first air sampler capable of capturing the coronavirus; scientists have used several other models to study the pathogen over the past year. But the new device appears to be simpler and more accessible, experts said.“I’m not sure that there’s anything else on the market that’s as easy to use,” said Linsey Marr, an expert in airborne viruses at Virginia Tech. “This will enable collection of air samples by almost anyone.”Thermo Fisher Scientific is likely to face competition. The pandemic has galvanized interest in a once-niche area of disease surveillance — pulling pathogens out of thin air. Experts in the field say they have been inundated with calls and emails from companies, organizations and other laboratories interested in developing or using coronavirus-collecting air samplers. (Dr. Marr is consulting with one company, whose name she could not disclose, to develop an air sampler that would monitor for the virus in public places.)And in November, the Defense Advanced Research Projects Agency began soliciting proposals for research to develop a coronavirus-detecting air sensor.“There’s a tremendous amount of interest,” said John Lednicky, a virologist at the University of Florida.The approach has real potential, experts say. But it also raises a thicket of logistical questions, they add, and must be deployed carefully, with a clear understanding of what the technology can and cannot do.Air samplers are already widely used to detect a variety of pollutants. But capturing airborne viruses is considerably more difficult. Viral aerosols are tiny and compose just a small fraction of the detritus that floats around in the air.“You’re looking for a needle in a haystack in a field of haystacks,” Dr. Marr said.That means that most air samplers need to inhale a lot of air to capture bits of virus, and even then they may not capture viruses present at low levels.The technology is improving, experts said, but remains complicated and labor-intensive. “There are very few places that have the knowledge, the equipment and the virology capability to do this properly,” Dr. Lednicky said.The AerosolSense sampler was designed to be easy to use. The device draws air into a collection pipe and directs it toward a replaceable, cylindrical cartridge. The cartridge, which is about the size of a 10-milliliter syringe, contains a proprietary foamlike substance that traps viral particles.After a few hours, or longer, the cartridge can be pulled out of the machine and sent to a lab for analysis. Technicians can use P.C.R., the polymerase chain reaction technique that underlies the gold-standard test for Covid-19, to determine whether genetic material from the coronavirus is present.It can take a day or two to receive results if the cartridge needs to be shipped to a third-party laboratory, but hospitals, universities and nursing homes that have labs on site can process the cartridges within a few hours, Thermo Fisher Scientific says.The company has also conducted “initial feasibility testing” with a rapid P.C.R. test that returns results in 30 minutes. (The test is made by Mesa Biotech, which Thermo Fisher Scientific recently acquired.)An air sampler at the University of Massachusetts Memorial Medical Center. Though the device shows promise, it can’t be seen as a silver bullet, Chief Burke said.Thermo Fisher ScientificA series of studies — performed in an enclosed box, a 9-by-14-foot room and the hospital rooms of Covid-19 patients — suggested that the AerosolSense sampler could capture the coronavirus even when present at low levels, said Kevin Van Den Wymelenberg, who conducted the research and directs the Biology and the Built Environment Center at the University of Oregon.“We’re confident that this is sensitive enough to use in real-world environments with Covid-positive individuals,” he said.(The research, which has not yet been published in a scientific journal, was funded by Thermo Fisher Scientific.)Thermo Fisher Scientific also piloted the samplers in a Covid-19 field hospital in Worcester, Mass. The hospital deployed the devices in patient care areas, where the virus was expected to be found, and in staff break rooms, where it was not.“Our cold zones were indeed cold,” said Dr. John Broach, an emergency physician at UMass Memorial Medical Center and the medical director of the field hospital. “And our hot zone had heavy contamination, which was expected.”Thermo Fisher Scientific, which will focus on hospitals in the first phase of its rollout, says other health care facilities could use the samplers to make sure that their Covid protocols are working — and that the virus is not making its way out of patient rooms.“We see the facilities asking, are their scheduling and pre-screening activities effective?” said Mark Stevenson, the executive vice president and chief operating officer of Thermo Fisher Scientific. “Are their cleaning and ventilation procedures adequate? And consequently, can I give my patients confidence in their visit to the facility?”Of course, detecting the virus in the hospital room of a Covid-19 patient is one thing, said Alex Huffman, an aerosol scientist at the University of Denver: “It’s another step to go into an environment that likely has much lower concentrations still, surveilling a classroom or a medical clinic where you have no idea if there’s going to be somebody positive or not.”And an air sampler is not a silver bullet, said Mr. Burke, who made sure that his firefighters continued to wear masks, socially distance and get regular Covid tests even after he installed the air sampler.“It can’t be like a smoke detector in your house where you’re, like, ‘I’m just going to have the machine, I’m not going to do anything else, it will let me know when there’s a problem,’” he said.There are not yet any truly autonomous viral samplers, which still require humans to remove and analyze the samples. That takes time — and means that the results provided by these samplers are not real-time snapshots but composite portraits of a building over the previous two or 12 or 24 hours.And although P.C.R. analysis can reveal whether genetic material from the coronavirus is present, it cannot distinguish between intact, infectious virus and viral fragments that pose no risk.None of these drawbacks are dealbreakers, said Dr. Marr, who noted that it was still useful to know whether airborne coronavirus particles were in a space recently.“If they’ve detected it in air, then it’s probably fairly freshly emitted,” she said. “And I’d be willing to bet that there is some infectious virus in there.”But the results need to be interpreted with care. A negative result does not mean that there is no virus present — simply that the air sampler did not collect any.“There’s a high chance for false negatives, because viruses are in notoriously low concentrations in the air,” said Kristen Coleman, an expert in bioaerosols at Duke-NUS Medical School in Singapore.Figuring out how to respond to a positive sample might prove even trickier. “I don’t think the answer is just evacuate the building,” Dr. Van Den Wymelenberg said.Instead, he imagined a suite of more measured responses — from increasing ventilation rates to strategic testing and tracing — that organizations could adopt when they found signs of the virus.But convincing office workers that a temporary ventilation boost makes it safe to come into an office where the virus has been found could be a hard sell. And even these modest measures could prompt concerns about privacy and legal liability.“I have been talking with several large building owners about indoor environmental surveillance throughout this pandemic, and the question of how is this information going to be used and who holds liability for any misapplication of the information always comes up,” Dr. Van Den Wymelenberg said.(Mr. Burke made sure to clear use of the air sampler with the local unions, which were, he said, “100 percent supportive.”)Another approach might be to use air sampling for larger-scale surveillance. If public health authorities see a spike in viral levels in a certain region or neighborhood, this could be an early warning sign that a surge of new Covid-19 cases is coming — and that officials need to step up their testing and contact tracing.Easily available, user-friendly air samplers could also make it possible for more scientists to conduct research on viral aerosols, Dr. Huffman said.“In the medium and long term, I think technology like this has a tremendous role to play in continuing to push forward the state of knowledge about these things such that we can make better decisions that help with other viral aerosols, like influenza and the next pandemic that comes along,” he said. “That’s not to say it can’t help now, but I think its real influence may be even greater as we go further and further into the future.”

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Too Much High-Intensity Exercise May Be Bad for Your Health

A new study hints that excessive HIIT may harm your mitochondria, the energy generators found in every cell of your body.If high-intensity exercise is good for us, is more necessarily better?Maybe not, according to an admonitory new study of the molecular effects of high-intensity interval training, also known as HIIT. In the study, people who began working out strenuously almost every day developed sudden and severe declines in the function of their mitochondria, which are the energy powerhouses inside of cells, along with incipient signs of blood sugar dysfunction.Their metabolic issues started to reverse when they dialed back on their workouts but did not disappear, suggesting that the benefits of extremely vigorous exercise may depend on just how much we do.At this point, almost anyone with an interest in fitness is familiar with the concept and appeal of high-intensity interval training. Consisting of repeated, brief spurts of hard exercise interspersed with a few minutes of rest, HIIT workouts can be quite short but are still able to improve substantially our aerobic fitness and many other aspects of our health. Studies show, for example, that intense bursts of exercise increase the number of mitochondria in our muscle cells, and more mitochondria are thought to contribute to better cellular and metabolic health.But recent research has begun to hint that HIIT also may have unexpected downsides. In a study I wrote about in January, people who worked out with HIIT routines three times a week for six weeks did not improve their blood pressure or body fat as much as people who exercised far more moderately five times a week.The authors of that study speculated that, by being sedentary for four days each week, the intense exercisers in the study may have undermined the otherwise potent effects of their HIIT sessions. On a weekly basis, they were not exercising enough.But whether it would be advisable to do more HIIT sessions in a single week has not been clear. Most past studies and formal recommendations about intense workouts top out at three sessions a week, and few researchers have looked into how HIIT-ing harder or more often might affect health.So, for the new study, which was published recently in the journal Cell Metabolism, researchers at the Swedish School of Sport and Health Sciences and the Karolinska Institute, both in Stockholm, set out, like Goldilocks, to sample different amounts of weekly hard exercise and see if any might be just right.They began by recruiting 11 healthy men and women who exercised but were not competitive athletes. These volunteers visited the researchers’ lab for tests of their current fitness and metabolic health, including blood-sugar levels over the course of a day.Then the volunteers began an ambitious exercise program. During the first week, they performed two sessions of HIIT, repeating four-minute-long intervals five times on a stationary bicycle, with three minutes of rest in between. The riders pedaled as hard as they could during each four-minute surge, while researchers monitored their power output. Afterward, the researchers biopsied leg muscles and rechecked the riders’ fitness and 24-hour blood-sugar control.During week two, the riders added a third HIIT session and ramped up the length of some of their intervals to a draining eight minutes. In week three, they worked out five times, with a mix of four-minute and eight-minute spurts of all-out pedaling. Finally, in week four, for recovery, they effectively halved the amount and intensity of their exercise. Each week, the researchers repeated all testing.Then they compared how people’s bodies had changed week over week.At first, the findings were encouraging. By the end of week two, the riders were pedaling harder and appeared to be getting fitter, with better daily blood-sugar control and more total mitochondria in their muscle cells. Each of these mitochondria was also more efficient now, producing greater amounts of energy than at the start.But something began to go wrong during week three. The volunteers’ ability to generate power while cycling flattened, and their subsequent muscle biopsies showed sputtering mitochondria, each of which was now producing only about 60 percent as much energy as during the previous week. The riders’ blood-sugar control also slipped, with seesawing spikes and dips throughout the day.After a week of lower-intensity riding, their mitochondria started to bounce back, producing more energy, but still 25 percent less than during week two. Their blood-sugar levels also stabilized, but again, not to the same extent as before. The riders could pedal, however, with the same — or even greater — vigor as in week two.Taken as a whole, the monthlong experiment suggests that “HIIT exercise should not be excessive if increased health is a desired outcome,” says Mikael Flockhart, a doctoral student at the Swedish School of Sport and Health Sciences, who conducted the study with his adviser, Filip Larsen, and others.The study was not focused on athletic performance, but even for serious athletes, he says, piling on multiple, intense, interval workouts each week, with little rest between them, is likely to lead to a tipping point, after which performance, as well as indicators of metabolic health, slip.The researchers are not sure precisely what changes within their volunteers’ bodies and muscles precipitated the negative results in week three. They tested multiple potential molecular causes, Mr. Flockhart says, but did not isolate an obvious, single instigator. He and his colleagues suspect that a cascade of biochemical changes within people’s muscles during the hardest week of exercise overwhelmed the mitochondria then, and the weakened mitochondria contributed to the disruptions in people’s blood-sugar control.This study was small, though, and quite short-term, with barely a week of each exercise routine. It also featured healthy volunteers, so does not show whether results would be the same, better or worse in people with existing metabolic problems.Even so, the findings strongly suggest that anyone interested in high-intensity interval training start small, Mr. Flockhart says. Train a few times a week and on the remaining days, maybe take a walk.

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Lockdown anniversary: Hospital workers on a year of Covid

For a year we have all lived under Covid-19 restrictions. But how have hospital staff dealt with fighting the pandemic at work and living under lockdown at home?Four staff from University Hospital Southampton tell the BBC about the impact of the last year on their home and work lives. Filmed/edited by Rachel PriceProduced by Alexander Littlewood

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Rugby study identifies new method to diagnose concussion using saliva

A University of Birmingham-led study of top-flight UK rugby players — carried out in collaboration with the Rugby Football Union (RFU), Premiership Rugby, and Marker Diagnostics — has identified a method of accurately diagnosing concussion using saliva, paving the way for the first non-invasive clinical test for concussion for use in sport and other settings.
Following the team’s previous research, which identified that the concentration of specific molecules in saliva changes rapidly after a traumatic brain injury, the researchers embarked on a three-year study in elite rugby to establish if these ‘biomarkers’ could be used as a diagnostic test for sport-related concussion.
Using DNA sequencing technology in the laboratory at the University of Birmingham, the research team tested these biomarkers in saliva samples from 1,028 professional men’s rugby players competing in English rugby’s top two leagues — the Premiership and Championship.
The results of SCRUM (Study of Concussion in Rugby Union through MicroRNAs), published today (March 23) in the British Journal of Sports Medicine, has for the first time shown that specific salivary biomarkers can be used to indicate if a player has been concussed. Additionally, the research has found these biomarkers provide further insights into the body’s response to injury as it evolves from immediately after trauma, to several hours and even days later.
The scientific breakthrough provides a new laboratory-based non-invasive salivary biological concussion test, which could have wide-reaching use and potential to reduce the risk of missing concussions not only in sport — from grassroots to professional levels — but also in wider settings such as military and healthcare.
In community sport, these biomarkers may provide a diagnostic test that is comparable in accuracy to the level of assessment available in a professional sport setting. While, at an elite level of rugby, the concussion test may be used in addition to the existing World Rugby Head Injury Assessment (HIA) protocol.

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Neutrons reveal unpredicted binding between SARS-CoV-2, hepatitis C antiviral drug

Scientists have found new, unexpected behaviors when SARS-CoV-2 — the virus that causes COVID-19 — encounters drugs known as inhibitors, which bind to certain components of the virus and block its ability to reproduce.
Published in the Journal of Medicinal Chemistry, the research provides key insights for advancing drug design and drug repurposing efforts to treat COVID-19.
Researchers at the Department of Energy’s Oak Ridge National Laboratory used neutron scattering to investigate interactions between telaprevir, a drug used to treat hepatitis C viral infection, and the SARS-CoV-2 main protease, the enzyme responsible for enabling the virus to reproduce.
They discovered unforeseen changes in the electric charges in the drug binding site of the protease enzyme that were not predicted by prevailing computer simulations.
“We found this particular protein — the SARS-CoV-2 main protease — which a lot of researchers are studying by computational methods, is behaving in a surprising way,” said lead author Daniel Kneller. “Our findings provide critical experimental data needed to improve computer modeling so that simulations more closely match reality.”
The virus reproduces by assembling long chains of proteins, or polyproteins, made from almost 2,000 amino acids that must be cut into smaller chains by the main protease. Finding a drug that effectively blocks or inhibits the protease function is paramount to preventing the virus from replicating and spreading to other healthy cells in the body.

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