Publisher Health

Physical inactivity is linked to more severe COVID-19 infection and a heightened risk of dying from the disease, finds a large US study published online in the British Journal of Sports Medicine.
Patients with COVID-19 who were consistently inactive during the 2 years preceding the pandemic were more likely to be admitted to hospital, to require intensive care, and to die than were patients who had consistently met physical activity guidelines, the findings show.
As a risk factor for severe disease, physical inactivity was surpassed only by advanced age and a history of organ transplant.
Several risk factors for severe COVID-19 infection have been identified, including advanced age, male sex, and certain underlying medical conditions, such as diabetes, obesity, and cardiovascular disease.
But physical inactivity is not one of them, even though it is a well known contributory risk factor for several long term conditions, including those associated with severe COVID-19, point out the researchers.
To explore its potential impact on the severity of the infection, including hospital admission rates, need for intensive care, and death, the researchers compared these outcomes in 48,440 adults with confirmed COVID-19 infection between January and October 2020.

SharecloseShare pageCopy linkAbout sharingimage copyrightGetty ImagesA leading Israeli doctor believes the country may be close to reaching “herd immunity”.This happens when enough of a population has protection against an infection that it stops being able to spread – and even people who don’t themselves have immunity are indirectly protected.For Covid the estimated threshold for herd immunity is at least 65%-70%. But scientists in the UK are more cautious. Dr Sarah Pitt, a virologist at the University of Brighton, urged “extreme caution” in concluding that herd immunity had been reached – something she believes will be difficult even at high vaccination rates. She said it was still too early to tell: “We need to see whether the cases in Israel continue to fall and stay at low levels.” Reaching this level of population immunity is important to protect people who can’t be vaccinated or whose immune system is too weak to produce a good, protective response. In Israel, more than half (5.3 million) its residents have been vaccinated and an additional 830,000 people have tested positive for the virus in the past, which should give them some natural immunity. That works out as roughly 68% of the population who are likely to have antibodies in their blood which can fight off the virus. Prof Eyal Leshem, a director at Israel’s largest hospital, the Sheba Medical Center, said herd immunity was the “only explanation” for the fact that cases continued to fall even as more restrictions were lifted. “There is a continuous decline despite returning to near normalcy,” he said. “This tells us that even if a person is infected, most people they meet walking around won’t be infected by them.” And cases are falling in all age groups including children, even though under-16s are not generally being vaccinated. How does herd immunity work?Experts think that with no restrictions in place, someone infected with the original strain of the virus that causes Covid-19, will infect, on average three to four other people.If it’s three, then, in theory, once two-thirds of the population becomes immune to the virus, an infected person will, on average, only pass it to one other person. That’s enough for the virus to spread, but not enough for it to grow.You’ve eliminated two of those three people from the chain of transmission. It sounds simple on paper. In reality, though, it’s a little more complicated.The vaccines are not 100% effective, and even when they stop people from getting sick they don’t completely block infections in everyone. That means some vaccinated people might still be able to pass on the virus.Not everyone with a past Covid infection has strong or long-lasting natural immunity, and newer variants of the virus are more transmissible.This means we may have to inoculate many more people before we reach that magic threshold. But it’s not all bad news. “I would say that we should not be looking for ‘herd immunity’ alone as a sign that we can lift all public health measures and get back to ‘normal’,” Dr Pitt explained. “Rather we should be looking for consistently low levels of Covid-19 infection”. Is the UK close to herd immunity?The UK is a way off this milestone – if it is ever reached. Only about half the population has Covid antibodies, either from infection or vaccination. But the country is already starting to see the impact of vaccination on hospitalisations and deaths, with the biggest declines seen in the most vaccinated age groups.There have been big falls in infection and illness among younger people too which might suggest the vaccine is blocking some transmission – although lockdown will have had a major effect too. After herd immunity, what’s next?So far, new variants don’t seem to be resistant to the vaccine. But a future variant which does show resistance to the virus, Prof Leshem explained, could mean people have less protection and the country could dip below the herd immunity threshold. This isn’t insurmountable – it could be tackled with tweaks to the vaccine, as already happens with the annual flu jab. It serves as an important reminder, though – even if Israel has reached herd immunity, and if the UK follows, this is not necessarily a permanent state.We can look at what’s happened with measles in recent years. The virus was considered to have been eliminated in the UK, but the World Health Organization revoked this status in 2019 after a “marked increase” in measles cases driven by a fall in the proportion of vaccinated people. Measles is highly contagious – each infected person infects roughly 15 other people – so vaccination coverage needs to be over 90% to prevent outbreaks. Follow Rachel on Twitter

Health departments scrambled to postpone vaccine clinics and rebook patients after the one-dose offering from Johnson & Johnson was sidelined.CHICAGO — The student union had been converted into a vaccination center. The doses had arrived on campus. The first appointments were minutes away. Then, at 7:23 a.m. on Tuesday, news of the pause in Johnson & Johnson vaccinations reached Youngstown State University.“We were ready to go,” said Shannon Tirone, an associate vice president at the university, in eastern Ohio, who instead started calling students to tell them they would not be able to get the vaccine after all.Similar scenes played out across the country as the abrupt halt in the use of the Johnson & Johnson vaccine because of concerns about potential blood clots upended plans to vaccinate some of the country’s hardest-to-reach populations.In California, mobile vaccine clinics in rural areas were canceled. In Chicago, vaccination events for restaurant employees and aviation workers were postponed indefinitely. And at colleges in Ohio, New York and Tennessee, where the one-dose vaccine offered a chance to quickly inoculate students before they left campus for the summer, appointments were called off en masse.“It really fit into this kind of tight deadline we were doing,” Ms. Tirone said of the Johnson & Johnson vaccine. She said she hoped to offer another on-campus clinic in Youngstown with one of the two-dose alternatives, but she worried that students would not be eligible for a second dose until finals week or later.At the White House, Biden administration officials played down the effect of the Johnson & Johnson pause and pledged to help states with the logistics involved in rescheduling patients to receive shots from Pfizer and Moderna, the two other coronavirus vaccine manufacturers authorized by the Food and Drug Administration.Federal health officials said the Johnson & Johnson vaccine could be returned to use in days after a review by the Food and Drug Administration and the Centers for Disease Control and Prevention.“The most important thing is that the supply exists to continue to vaccinate three million Americans a day, and there’s enough supply to actually accelerate that,” Jeffrey D. Zients, the Covid response coordinator at the White House, told reporters on Tuesday.In much of the country, public health officials said they were able to offer other vaccines to people who had been scheduled to receive a Johnson & Johnson shot.The Albany County Health Department in New York said it would provide Pfizer doses for a Johnson & Johnson clinic on Tuesday at a local university. The chief public health officer in Detroit said people who had appointments for a Johnson & Johnson vaccine at a city-run site would be allowed to keep their times and receive a Pfizer or Moderna shot. And officials in New Hampshire, who had planned to use the Johnson & Johnson vaccine on Tuesday at clinics and for homebound patients, said they were working to find Pfizer or Moderna doses to use instead.“This news will not slow down New Hampshire,” Gov. Chris Sununu said in a statement. “While the federal government has directed a brief pause in the J&J vaccine, the state is already working with our partners to ensure that they have an alternative supply of Pfizer or Moderna to help continue their efforts today.”But in some places, there was no immediate alternative. In Aurora, Ill., a mass vaccination clinic planned for Tuesday was called off, leaving 1,000 patients without appointments. In Riverside County, Calif., mobile clinics that had planned to vaccinate about 400 people in less populous areas on Tuesday were canceled. And in rural Jefferson County, in southeast Iowa, a Johnson & Johnson clinic targeting manufacturing workers was scrapped at the last minute.“It was so heartbreaking to me,” said Christine Estle, the county’s public health nurse administrator, who said she and her colleagues had encouraged the roughly 140 people scheduled to attend to make appointments at local pharmacies or hospitals.The Johnson & Johnson vaccine had long been seen as a key to the country’s vaccination effort because it requires only one shot, unlike the two-dose Moderna and Pfizer regimens, and because it can be stored more easily. In cities around the country, public health experts had begun using the vaccine in places where hesitancy about one shot — much less two — is high..css-1xzcza9{list-style-type:disc;padding-inline-start:1em;}.css-rqynmc{font-family:nyt-franklin,helvetica,arial,sans-serif;font-size:0.9375rem;line-height:1.25rem;color:#333;margin-bottom:0.78125rem;}@media (min-width:740px){.css-rqynmc{font-size:1.0625rem;line-height:1.5rem;margin-bottom:0.9375rem;}}.css-rqynmc strong{font-weight:600;}.css-rqynmc em{font-style:italic;}.css-yoay6m{margin:0 auto 5px;font-family:nyt-franklin,helvetica,arial,sans-serif;font-weight:700;font-size:1.125rem;line-height:1.3125rem;color:#121212;}@media (min-width:740px){.css-yoay6m{font-size:1.25rem;line-height:1.4375rem;}}.css-1dg6kl4{margin-top:5px;margin-bottom:15px;}.css-16ed7iq{width:100%;display:-webkit-box;display:-webkit-flex;display:-ms-flexbox;display:flex;-webkit-align-items:center;-webkit-box-align:center;-ms-flex-align:center;align-items:center;-webkit-box-pack:center;-webkit-justify-content:center;-ms-flex-pack:center;justify-content:center;padding:10px 0;background-color:white;}.css-pmm6ed{display:-webkit-box;display:-webkit-flex;display:-ms-flexbox;display:flex;-webkit-align-items:center;-webkit-box-align:center;-ms-flex-align:center;align-items:center;}.css-pmm6ed > :not(:first-child){margin-left:5px;}.css-5gimkt{font-family:nyt-franklin,helvetica,arial,sans-serif;font-size:0.8125rem;font-weight:700;-webkit-letter-spacing:0.03em;-moz-letter-spacing:0.03em;-ms-letter-spacing:0.03em;letter-spacing:0.03em;text-transform:uppercase;color:#333;}.css-5gimkt:after{content:’Collapse’;}.css-rdoyk0{-webkit-transition:all 0.5s ease;transition:all 0.5s ease;-webkit-transform:rotate(180deg);-ms-transform:rotate(180deg);transform:rotate(180deg);}.css-eb027h{max-height:5000px;-webkit-transition:max-height 0.5s ease;transition:max-height 0.5s ease;}.css-6mllg9{-webkit-transition:all 0.5s ease;transition:all 0.5s ease;position:relative;opacity:0;}.css-6mllg9:before{content:”;background-image:linear-gradient(180deg,transparent,#ffffff);background-image:-webkit-linear-gradient(270deg,rgba(255,255,255,0),#ffffff);height:80px;width:100%;position:absolute;bottom:0px;pointer-events:none;}#masthead-bar-one{display:none;}#masthead-bar-one{display:none;}.css-1pd7fgo{background-color:white;border:1px solid #e2e2e2;width:calc(100% – 40px);max-width:600px;margin:1.5rem auto 1.9rem;padding:15px;box-sizing:border-box;}@media (min-width:740px){.css-1pd7fgo{padding:20px;width:100%;}}.css-1pd7fgo:focus{outline:1px solid #e2e2e2;}#NYT_BELOW_MAIN_CONTENT_REGION .css-1pd7fgo{border:none;padding:20px 0 0;border-top:1px solid #121212;}.css-1pd7fgo[data-truncated] .css-rdoyk0{-webkit-transform:rotate(0deg);-ms-transform:rotate(0deg);transform:rotate(0deg);}.css-1pd7fgo[data-truncated] .css-eb027h{max-height:300px;overflow:hidden;-webkit-transition:none;transition:none;}.css-1pd7fgo[data-truncated] .css-5gimkt:after{content:’See more’;}.css-1pd7fgo[data-truncated] .css-6mllg9{opacity:1;}.css-1rh1sk1{margin:0 auto;overflow:hidden;}.css-1rh1sk1 strong{font-weight:700;}.css-1rh1sk1 em{font-style:italic;}.css-1rh1sk1 a{color:#326891;-webkit-text-decoration:underline;text-decoration:underline;text-underline-offset:1px;-webkit-text-decoration-thickness:1px;text-decoration-thickness:1px;-webkit-text-decoration-color:#ccd9e3;text-decoration-color:#ccd9e3;}.css-1rh1sk1 a:visited{color:#333;-webkit-text-decoration-color:#ccc;text-decoration-color:#ccc;}.css-1rh1sk1 a:hover{-webkit-text-decoration:none;text-decoration:none;}“I just want to do everything we can to have those people who signed up for appointments still come for them with Pfizer or Moderna,” said Dr. Allison Arwady, the Chicago public health commissioner, who said she worried that the pause would undermine vaccine confidence and that she had already heard of skeptical patients asking whether the other shots were safe.Dr. Arwady said her department had been using the Johnson & Johnson vaccine to reach people who might otherwise be unlikely to seek one out by offering it at workplaces, churches and even along bus lines.“A lot of our more creative planning has been with J&J,” she said. “People who have a lot of barriers to get vaccinated, a single-dose vaccine can be very good.”In Colorado, state officials had expressed optimism that the Johnson & Johnson vaccine would help reach residents who lived far outside cities like Denver or Boulder. Gov. Jared Polis recently kicked off a program using blue and red buses to carry the one-dose vaccine to rural communities around the state.That effort was suspended as the mobile vaccination clinics were shut down for at least Tuesday and Wednesday. Officials did not say when the buses might begin rolling again, or whether they would eventually switch to distributing the Pfizer or Moderna vaccines.The situation was similarly uncertain in Ithaca, N.Y., where officials at Ithaca College canceled their College Student Vaccination Day.“Although unfortunate that we will be unable to provide our students with Thursday’s planned vaccine opportunity, Ithaca College will continue to work with its local partners to identify future clinic opportunities for the two-dose Pfizer and Moderna vaccine series,” the college said in an email.“Thank you for your understanding,” they added.Mitch Smith reported from Chicago, and Michael D. Shear from Washington. Danielle Ivory contributed reporting from New York.

Wheezing, coughing that doesn’t stop, a pale and sweaty face: clinically, severe asthma attacks look very similar from patient to patient. But biologically, not all severe asthma is the same — and a team of scientists has, for the first time, identified the key difference in people, a finding that has important implications for treatment.
In a paper published today in Cell Reports, a group of scientists led by immunologists and pulmonologists at the University of Pittsburgh, in collaboration with Stanford University, used advanced tools of immunology, molecular biology and unbiased computational and bioinformatic approaches to characterize immune profiles of patients with severe asthma. These findings invite a new appreciation for the complexity of disease mechanisms and can lead to improved treatments.
“We started this study to better understand immune mediators of inflammation in asthma,” said lead author Matthew Camiolo, M.D., Ph.D., clinical instructor of medicine at Pitt. “We found that despite being grouped broadly as ‘clinically severe,’ these asthma patients actually had very different and distinct immune profiles.”
Asthma is a debilitating condition that affects millions of people each year. According to the Centers for Disease Control and Prevention, 25 million Americans, or 1 in 13 people suffer from asthma. And while current standards of treatment — inhaled immunosuppressive corticosteroids, such as beclomethasone and budesonide — are effective in most patients, clinical markers that can help identify those who are likely to be resistant to treatment are lacking.
For patients who do not respond to standard corticosteroid treatment or respond to it poorly, there is no ‘one size fits all’ approach to treat severe disease. Because of that, while severe asthma accounts for 5 to 10 percent of all asthma cases, it consumes 50 percent of associated health care costs, amounting to $28 billion annually.
“Although breakthroughs in asthma therapy have greatly improved our ability to treat patients, many people still continue with disease that greatly diminishes their quality of life,” said co-senior author Sally Wenzel, M.D., director of Pitt’s Asthma and Environmental Lung Health Institute, and chair of Pitt Public Health’s Department of Environmental and Occupational Health.
To characterize immune cells within the airways of severe asthma patients, the researchers, in collaboration with Kari Nadeau, M.D., Ph.D., director of the Sean N Parker Center for Allergy & Asthma Research at Stanford University School of Medicine, used mass cytometry, RNA-sequencing and machine learning, and established a novel algorithm that links immune cells to cellular pathways potentially related to disease pathogenesis.
The research team found that lung aspirates from one group of patients were enriched with T cells polarized to fight infections, while the other group had a much lower level of T cells. At the same time, the second group had an increased number of innate immune cells expressing an inflammatory molecule IL-4 — a cytokine known to be elevated in asthma.
“We have identified two clusters of severe asthma patients with very similar biomarkers but with strikingly distinct immune profiles and associated biological pathways,” said senior author Anuradha Ray, Ph.D., professor of medicine and immunology at Pitt. “These findings identify new targets for therapy, which are distinct in the two subgroups of severe asthma patients who otherwise would be indistinguishable based on biomarker profiles.”
“We believe that the cell types expressing IL-4 in the airways of one of the groups have not been previously identified in humans in any setting,” Ray added.
Researchers are optimistic that these findings will enhance precision medicine approaches to treating severe asthma patients.
“These important findings are the result of a successful team effort among physician-scientists and basic scientists across institutions that has established a new frontier in asthma research,” said Ray. “We hope the new knowledge gained will be used to develop new therapeutics to treat severe asthma patients and also allow improved stratification of patients for better efficacy of existing therapies.”

A sex ed teacher talks about how young people can try to keep themselves safe from sexual assault and be allies to others.I was making lunch when my 17-year-old son sat down at the kitchen table. “Hey Mom, is this real?” he asked, and showed me an Instagram post that read: “97% of young women have experienced sexual harassment. If you are surprised, then you’re probably not listening.”I asked to take a closer look and he handed me his phone. The statistic wasn’t completely accurate but it was close. It was pulled from a British study that found that among women aged 18 to 24, 86 percent had been harassed in public spaces, 3 percent didn’t recall ever having experienced sexually harassing behavior, and 11 percent chose not to answer the question. There was more to the post; when I swiped left, it demanded: “Boys do better.”“What do I do with that?,” my son asked. “What does that mean?”It was a good question.Posts like the one my son showed me have been all over social media since the death of Sarah Everard, the young British woman who was kidnapped and killed several weeks ago (a police officer has been charged).As a high school sex educator, working both in person and remotely as a national consultant, I talk to young people all over the country. The posts they see include statistics about sexual harassment, sexual assault and rape that my students describe as “devastating” and “terrifying.”When I asked some of my students and other teens I know about the statement “Boys do better,” several boys said they felt “attacked” or “hopeless” because it feels as if they are being accused of perpetrating crimes they haven’t committed. Many say they consider themselves a “good guy” and want to help, but don’t know how.According to another survey, this one done in the United States, 87 percent of 18- to 25-year-old women reported having experienced sexual harassment. The report found that 76 percent of respondents (72 percent male, 80 percent female) had never had a conversation about how not to harass, or express other forms of misogyny. The National Violence Resource Center concluded that one in four girls and one in six boys is sexually abused by the age of 18. We also know that boys experience sexual abuse not only at the hands of men, but in some cases, girls and women. And a large number of those who experience sexual assault are gay, lesbian, bisexual or transgender.So, yes, sexual violence is a significant problem. Chalina Morgan-Lopez, 17, from Raleigh, N.C., who told me she had been repeatedly harassed and grabbed at school, said: “It made me feel powerless and like an object. I felt uncomfortable and unsafe in my classes with my harassers.”When I teach, there are certain questions about sexual assault that teenagers always ask. They want to know, “How do I keep myself safe?” “How can I be a supportive friend and ally?” They also want to know, “What’s the deal with drunk sex?” Here are some answers to those questions.Promote respectSpeak up about objectifying and dehumanizing language, whether in the media or in school hallways. During Donald Trump’s presidential campaign in 2016, he dismissed his vulgar comments about grabbing women as “locker room banter.” The incident heightened awareness of the way that talking about women as sex objects normalizes sexual harassment and may contribute to sexual assault.Amanda Ehrenhalt, a 16-year-old who lives in Philadelphia and plays field hockey and track and field, said, “Locker room talk isn’t made up. It’s for real. As an athlete who is around other athletes, I hear it all of the time.” If you hear someone talking about sex in a demeaning way, you might say, “Hey, let’s keep it respectful,” or “What do you mean by that?”Take care of yourselfAs you go through adolescence, it’s important to understand consent. Your body and sexuality belong to you. Just because you say yes to one form of sexual activity, doesn’t mean you’ve said yes to another. You and your partner have to agree about what you’re doing together and whether to take things to a new level. You also have the right to change your mind at any time and choose not to move on or even to stop the activity altogether.If you choose to be sexual with someone else, know how to manage what’s going on. You can say “No,” “This is making me uncomfortable,” or “Let’s go back to what we were doing before.” If you don’t feel you can say something directly, you can make up an excuse: “I forgot that I’m supposed to be home early — I have to go.” If the person you are with continues to try and persuade you or is just not listening, you can say, “If you continue you will be assaulting/raping me.”We all deserve to be treated with dignity and enjoy our romantic and sexual relationships with others. If you are sexually active, you have to ask the person you’re with to make sure your interactions are welcome, and keep on asking. It can be as simple as, “you good?” or “this OK?” Pressuring, manipulating, pushing or talking someone into saying yes to sexual activity is not a “yes” or consent. It is coercion and potentially illegal.Remember that federal law recognizes that someone who is incapacitated by alcohol or drugs is legally incapable of giving consent. Each state has its own laws, as well.Put simply, getting someone drunk so they will have sex with you could land you with a criminal charge or in jail.And, if you are the one who is assaulted, no matter what choices you make, what you are wearing or consuming, it is not your fault.Step in to help othersThere are several ways to be a supportive friend or an ally to someone who has experienced sexual harassment or assault. They include raising awareness, speaking up when you see or hear suspicious, risky or dangerous behavior and being compassionate to survivors.Ramis Banuri, 19, of Salt Lake City, Utah, said he speaks up whenever he can, and tries to get others to do the same. “People don’t necessarily want to intervene because there’s this notion that it’s not your business and they don’t want to embarrass themselves if they misread a situation, he said. “I tell them ‘would you rather be embarrassed for a moment about a small situation that nobody will really remember, or be sorry because you were right and could have prevented someone from getting hurt?’”Bystander intervention is a strategy for preventing harassment and assault from happening or continuing. The goal is to disrupt what feels like a loaded moment before things can escalate. Every situation is different and there is no single way to intervene, but here are some guidelines from the Green Dot program, a widely used bystander intervention training system, which encourages people to act using what are called the Three Ds.Direct intervention is straightforward. If someone uses sexist language or makes someone uncomfortable with sexual comments or jokes, you could say, “Hey, that’s making people uncomfortable — that’s harassment. Stop.” Or “You’ve had way too much to drink. You’re in no shape to even think about hooking up — let’s get you home.”You can also interrupt a risky dynamic with a distraction. If someone is making another person uncomfortable with their attention, you could say, “Hey, the guys are looking for you downstairs. Let’s go see what’s up.”In other situations, you may delegate to someone else who has more training, authority or social leverage and may be more effective at intervening.If you see someone you don’t know well acting inappropriately, tell the people they came with and encourage them to intervene. If you witness a couple fighting and it seems to be getting physical, find a trusted adult or authority figure, or call the police.If you or a friend are harassed or assaulted, the National Sexual Assault Hotline can provide information and guidance.Ms. Morgan-Lopez took steps to be proactive: “I began by forming a small group of students at my school who were also passionate about targeting this issue, and we connected with local organizations who offered us trainings in sexual assault.”Mr. Banuri also had training through a peer-led sex education program. He said what inspires him is knowing that “I am doing the right thing — that reaffirms my values: community, connection, family and friendship. That’s affirming and strong — helping people stay safe.”Shafia Zaloom is the author of “Sex, Teens and Everything in Between.”

Violent blows or jolts to the head can cause traumatic brain injury (TBI), and there are currently about five million people in the U.S. living with some form of chronic impairment after suffering a TBI. Even in a mild form, TBI can lead to lifelong nerve cell deterioration associated with a wide array of neuropsychiatric conditions. Tragically, there are no medicines to protect nerve cells after injury. Behind aging and genetics, TBI is the third leading cause of Alzheimer’s disease (AD), yet the link between these two conditions is not understood.
In a new study, published online today in Cell, researchers have discovered a new way to prevent brain nerve cells from deteriorating after injury, which also revealed a potential mechanistic link between TBI and AD. Their discovery also yielded a new blood biomarker of nerve cell degeneration after injury, which is significant because there is an urgent need for mechanism-based blood biomarkers that can diagnose TBI and stage its severity.
Prior to this study, it had been previously reported that a small protein in nerve cells, called tau, was modified by a chemical process called acetylation in the post-mortem brains of AD patients. But how this modification came about, as well as its role in the disease process, was not understood.
“Normally, tau functions in nerve cells to maintain the appropriate structure of the axon, which is the nerve cell extension required for nerve cells to communicate with one another,” said Andrew A. Pieper, MD, PhD, senior author on the study, Harrington Discovery Institute (HDI) Investigator and Director of the HDI Neurotherapeutics Center at University Hospitals (UH), Morley-Mather Chair in Neuropsychiatry at UH, Director of the Translational Therapeutics Core of the Cleveland Alzheimer’s Disease Research Center, and VA Geriatric Research, Educational and Clinical Care (GRECC) Investigator. “Given the relationship between AD and TBI, we wondered whether elevated acetylated-tau (ac-tau) might also occur in TBI, and if so, then whether this could provide an experimental platform to study its potential role in nerve cell deterioration.”
Dr. Pieper’s lab discovered that ac-tau increased rapidly in multiple forms of TBI in mice and rats, and persisted chronically when nerve cell degeneration was untreated. They also showed that the increased ac-tau in human AD brain was further exacerbated when the AD patient also had a prior history of TBI.
“Our research showed that after ac-tau rises, a specific structure at the junction of the nerve cell body and its axon, called the axon initial segment, breaks down,” explained Min-Kyoo Shin, PhD, co-first author of the study. “As a result, tau is no longer appropriately sequestered in axons. This leads to axonal degeneration, followed by neurologic impairment.”
The team tested therapeutic interventions after TBI at each of the three nodal points in the new signaling pathway that they identified as leading to increased nerve cell ac-tau after injury. Using known medicines or experimental drugs, they saw that all three points provided effective therapeutic opportunity.

Almost all bacteria rely on the same emergency valves — protein channels that pop open under pressure, releasing a deluge of cell contents. It is a last-ditch effort, a failsafe that prevents bacteria from exploding and dying when stretched to the limit. If we understood how those protein channels worked, antibiotic drugs could be designed to open them on demand, draining a bacterium of its nutrients by exploiting a floodgate common to many species.
But these channels are tricky to operate in the lab. And how precisely they open and close, passing through a sub-conducting state and ending in a desensitized state under the influence of mechanical forces, remains poorly understood. Now, new research from the laboratory of Rockefeller’s Thomas Walz introduces a novel method to activate and visualize these channels, making it possible to explain their function. The findings shed light on key membrane proteins in bacteria, and the same method can be used to improve our understanding of similar channels in humans.
“We were actually able to see the entire cycle of the protein channel passing through a series of functional stages,” Walz says.
Walz has long focused upon MscS, a protein embedded in bacterial membranes that opens in response to mechanical force. MscS proteins exist in a closed state while resting in a thick membrane. Scientists once suspected that, when fluid build-up causes the cell to swell and puts tension on the membrane, it stretches so thin that its proteins protrude. Thrust into an unfamiliar environment, the protein channels snap open, releasing the contents of the cell and relieving pressure until the membrane returns to its original thickness and its channels slam shut.
But when Yixiao Zhang, a postdoctoral associate in the Walz group, tested this theory over five years ago, reconstituting MscS proteins into small custom-designed membrane patches, he discovered that it was impossible to prise the channel open by thinning membranes within the natural range. “We realized that membrane thinning is not how these channels open,” Walz says.
These custom patches, called nanodiscs, allow researchers to study proteins in an essentially native membrane environment and to visualize them with cryo-electron microscopy. Walz and Zhang resolved to push the limits of nanodisc technology, removing membrane lipids with ?-cyclodextrin, a chemical used to excise cholesterol from cell cultures. This induced tension in the membrane, and Walz and his team could observe with cryo-electron microscopy as the channel reacted accordingly — eventually snapping closed for good, a phenomenon known as desensitization.
What they observed matched computer simulations, and a new model for the function of MscS emerged. When fluid builds up inside the cell, they found, lipids are called in from all corners to help ease tension throughout the membrane. If the situation becomes dire, even lipids associated with the MscS channels flee. Without lipids keeping them closed, the channels have the legroom to pop open.
“We could see that, when you expose the membranes to ?-cyclodextrin, the channels open and then close again,” Walz says.
Walz and Zhang’s new method of manipulating nanodiscs with ?-cyclodextrin will allow researchers studying dozens of similar mechanosensitive protein channels to, at long last, test their hypotheses in the lab. Many such proteins play key roles in humans, from hearing and sense of touch to the regulation of blood pressure. Of more immediate interest, however, is the prospect of exploiting protein channels that many different bacteria rely upon to survive. Novel drug targets are a particular necessity, given the rise of dangerous antibiotic resistant bacteria such as MRSA.
MscS and the related bacterial protein channel MscL are “extremely interesting drug targets,” Walz says. “Almost every bacterium has one of these proteins. Because these channels are so widely distributed, a drug that targets MscS or MscL could become a broad-spectrum antibiotic.”
Story Source:
Materials provided by Rockefeller University. Note: Content may be edited for style and length.

A study done in rooms where COVID-19 patients were isolated shows that the virus’s RNA — part of the genetic material inside a virus — can persist up to a month in dust.
The study did not evaluate whether dust can transmit the virus to humans. It could, however, offer another option for monitoring COVID-19 outbreaks in specific buildings, including nursing homes, offices or schools.
Karen Dannemiller, senior author of the study, has experience studying dust and its relationship to potential hazards like mold and microbes.
“When the pandemic started, we really wanted to find a way that we could help contribute knowledge that might help mitigate this crisis,” said Dannemiller, assistant professor of civil, environmental and geodetic engineering and environmental health sciences at The Ohio State University.
“And we’ve spent so much time studying dust and flooring that we knew how to test it.”
The study, published today (April 13, 2021) in the journal mSystems, found some of the genetic material at the heart of the virus persists in dust, even though it is likely that the envelope around the virus may break down over time in dust. The envelope — the crown-like spiked sphere that contains the virus’s material — plays an important role in the virus’s transmission to humans.

Researchers have identified molecular signatures of the aging process in mice, publishing their results today in the open-access eLife journal.
Their analyses provide one of the most comprehensive characterisations of the molecular signatures of aging across diverse types of cells from different tissues in a mammal, and will aid future studies on aging and related topics.
Aging leads to the decline of major organs and is the main risk factor for many diseases, including cancer, cardiovascular and neurodegenerative diseases. While previous studies have highlighted different hallmarks of the aging process, the underlying molecular and cellular mechanisms remain unclear.
To gain a better understanding of these mechanisms, the Tabula Muris Consortium created the single-cell transcriptomic dataset, called Tabula Muris Senis (TMS). The TMS contains over 300,000 annotated cells from 23 tissues and organs of male and female mice. “These cells were collected from mice of diverse ages, making the data a tremendous opportunity to study the genetic basis of aging across different tissues and cell types,” says first author Martin Jinye Zhang, Postdoctoral Researcher in the Department of Epidemiology, Harvard University, Boston, US.
The original TMS study mainly explored the cell-centric effects of aging, aiming to characterise changes in the composition of cell types within different tissues. In the current gene-centric study, Zhang and colleagues focused on changes in gene expression that occur during the aging process across different cell types.
Using the TMS data, they identified aging-dependent genes in 76 cell types from 23 tissues. They then characterised the aging behaviours of these genes that were both shared among all cell types (‘globally’) and specific to different tissue cells.
“We found that the cell-centric and gene-centric perspectives of the previous and current studies are complementary, as gene expression can change within the same cell type during aging, even if the composition of cells in the tissue does not vary over time,” explains co-senior author Angela Oliveira Pisco, Associate Director of Bioinformatics at the Chan Zuckerberg Biohub, San Francisco, US. “The identification of many shared aging genes suggests that there is a coordinated global aging behaviour in mice.”
The team then used this coordinated activity to develop a single-cell aging score based on the global aging genes. This new high-resolution aging score revealed that different tissue-cell types in the same animal can have a different aging status, shedding light on the diverse aging process across different types of cells.
“Taken together, our results provide a characterisation of aging genes across a wide range of tissue-cell types in the mouse,” concludes senior author James Zou, Assistant Professor of Biomedical Data Science at Stanford University, Stanford, US, and a Chan Zuckerberg Biohub Investigator. “In addition to providing new biological insights on the aging process, this work serves as a comprehensive reference for researchers working in related fields.”
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A gene therapy protects eye cells in mice with a rare disorder that causes vision loss, especially when used in combination with other gene therapies, shows a study published today in eLife.
The findings suggest that this therapy, whether used alone or in combination with other gene therapies that boost eye health, may offer a new approach to preserving vision in people with retinitis pigmentosa or other conditions that cause vision loss.
Retinitis pigmentosa is a slowly progressive disease, which begins with the loss of night vision due to genetic lesions that affect rod photoreceptors — cells in the eyes that sense light when it is low. These photoreceptors die because of their intrinsic genetic defects. This then impacts cone photoreceptors, the eye cells that detect light during the day, which leads to the eventual loss of daylight vision. One theory about why cones die concerns the loss of nutrient supply, especially glucose.
Scientists have developed a few targeted gene therapies to help individuals with certain mutations that affect the photoreceptors, but no treatments are currently available that would be effective for a broad set of families with the disease. “A gene therapy that would preserve photoreceptors in people with retinitis pigmentosa regardless of their specific genetic mutation would help many more patients,” says lead author Yunlu Xue, Postdoctoral Fellow at senior author Constance Cepko’s lab, Harvard Medical School, Boston, US.
To find a widely effective gene therapy for the disease, Xue and colleagues screened 20 potential therapies in mouse models with the same genetic deficits as humans with retinitis pigmentosa. The team chose the therapies based on the effects they have on sugar metabolism.
Their experiments showed that using a virus carrier to deliver a gene called Txnip was the most effective approach in treating the condition across three different mouse models. A version of Txnip called C247S worked especially well, as it helped the cone photoreceptors switch to using alternative energy sources and improved mitochondria health in the cells.
The team then showed that giving the mice gene therapies that reduced oxidative stress and inflammation, along with Txnip gene therapy, provided additional protection for the cells. Further studies are now needed to confirm whether this approach would help preserve vision in people with retinitis pigmentosa.
“The immediate next step is to test Txnip for safety in animals beyond mice, before moving on to a clinical trial in humans,” explains senior author and Howard Hughes Institute Investigator Constance Cepko, the Bullard Professor of Genetics and Neuroscience at Harvard Medical School. “If it ultimately proves safe in people, then we would hope to see it become an effective approach for treating those with retinitis pigmentosa and other forms of progressive vision loss, such as age-related macular degeneration.”
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