How do different parts of the body communicate? Scientists at St. Jude are studying how signals sent from skeletal muscle affect the brain.
The team studied fruit flies and cutting-edge brain cell models called organoids. They focused on the signals muscles send when stressed. The researchers found that stress signals rely on an enzyme called Amyrel amylase and its product, the disaccharide maltose.
The scientists showed that mimicking the stress signals can protect the brain and retina from aging. The signals work by preventing the buildup of misfolded protein aggregates. Findings suggest that tailoring this signaling may potentially help combat neurodegenerative conditions like age-related dementia and Alzheimer’s disease.
“We found that a stress response induced in muscle could impact not only the muscle but also promote protein quality control in distant tissues like the brain and retina,” said Fabio Demontis, PhD, of St. Jude Developmental Neurobiology. “This stress response was actually protecting those tissues during aging.”
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Materials provided by St. Jude Children’s Research Hospital. Note: Content may be edited for style and length.

For people with tooth decay, drinking a cold beverage can be agony.
“It’s a unique kind of pain,” says David Clapham, vice president and chief scientific officer of the Howard Hughes Medical Institute (HHMI). “It’s just excruciating.”
Now, he and an international team of scientists have figured out how teeth sense the cold and pinpointed the molecular and cellular players involved. In both mice and humans, tooth cells called odontoblasts contain cold-sensitive proteins that detect temperature drops, the team reports March 26, 2021, in the journal Science Advances. Signals from these cells can ultimately trigger a jolt of pain to the brain.
The work offers an explanation for how one age-old home remedy eases toothaches. The main ingredient in clove oil, which has been used for centuries in dentistry, contains a chemical that blocks the “cold sensor”protein, says electrophysiologist Katharina Zimmermann, who led the work at Friedrich-Alexander University Erlangen-Nürnberg in Germany.
Developing drugs that target this sensor even more specifically could potentially eliminate tooth sensitivity to cold, Zimmermann says. “Once you have a molecule to target, there is a possibility of treatment.”
Mystery channel
Teeth decay when films of bacteria and acid eat away at the enamel, the hard, whitish covering of teeth. As enamel erodes, pits called cavities form. Roughly 2.4 billion people — about a third of the world’s population — have untreated cavities in permanent teeth, which can cause intense pain, including extreme cold sensitivity.

University of Maryland School of Medicine (UMSOM) researchers have identified the most toxic proteins made by SARS-COV-2 — the virus that causes COVID-19 — and then used an FDA-approved cancer drug to blunt the viral protein’s detrimental effects. In their experiments in fruit flies and human cell lines, the team discovered the cell process that the virus hijacks, illuminating new potential candidate drugs that could be tested for treating severe COVID-19 disease patients. Their findings were published in two studies simultaneously on March XX in Cell & Bioscience, a Springer Nature journal.
“Our work suggests there is a way to prevent SARS-COV-2 from injuring the body’s tissues and doing extensive damage,” says senior author of the study Zhe “Zion” Han, PhD, Associate Professor of Medicine and Director of the Center for Precision Disease Modeling at UMSOM. He notes that the most effective drug against Covid-19, remdesivir, only prevents the virus from making more copies of itself, but it does not protect already infected cells from damage caused by the viral proteins.
Prior to the pandemic, Dr. Han had been using fruit flies as a model to study other viruses, such as HIV and Zika. He says his research group shifted gears in February 2020 to study SARS-COV-2 when it was clear that the pandemic was going to significantly impact the U.S.
SARS-COV-2 infects cells and hijacks them into making proteins from each of its 27 genes. Dr. Han’s team introduced each of these 27 SARS-CoV-2 genes in human cells and examined their toxicity. They also generated 12 fruit fly lines to express SARS-CoV-2 proteins likely to cause toxicity based on their structure and predicted function.
The researchers found that a viral protein, known as Orf6, was the most toxic killing about half of the human cells. Two other proteins (Nsp6 and Orf7a) also proved toxic, killing about 30-40 percent of the human cells. Fruit flies that made any one of these three toxic viral proteins in their bodies were less likely to survive to adulthood. Those fruit flies that did live had problems like fewer branches in their lungs or fewer energy-generating power factories in their muscle cells.
For the remaining experiments, the researchers focused on just the most toxic viral protein, so they could figure out what cell process the virus hijacks during infection. Dr. Han’s team found that the virus’ toxic Orf6 protein sticks to multiple human proteins that have the job of moving materials out of the cell’s nucleus — the place in the cell that holds the genome, or the instructions for life.
They then discovered that one of these human moving proteins, targeted by the virus, gets blocked by the cancer drug selinexor. The researchers tested selinexor on human cells and fruit flies making the toxic viral protein to see if the drug could help reverse the damage. Selinexor, like many cancer drugs is itself toxic. However, after accounting for its toxic effects, the drug improved human cell survival by about 12 percent. Selinexor prevented early death in about 15 percent of the flies making the toxic viral protein. The drug also restored branches in the lungs and the energy-generators in the muscle cells. Selinexor is FDA-approved to treat certain blood cancers.
“More than 1,000 FDA-approved drugs are in clinical trials to test as treatments for Covid-19, and luckily a trial testing selinexor, the drug used in our study, is being performed already,” says Dr. Han. “If this trial proves to be successful, our data will have demonstrated the underlying mechanism for why the drug works.”
Albert Reece, MD, PhD, MBA, Executive Vice President for Medical Affairs, University of Maryland Baltimore, and the John Z. and Akiko K. Bowers Distinguished Professor and Dean, University of Maryland School of Medicine, commented, “Although we now have vaccines, it may still be a while before we will have Covid-19 infections under control, especially with the new variants emerging. We will need to tap into every tool in the arsenal available to protect people from needless sickness, disability or even death, and this study guides us towards a new target for potential therapeutics.”
These two studies were funded by a University of Maryland COVID-19 Accelerated Translational Incubator Pilot Grant, the University of Maryland, the Baltimore Institute for Clinical and Translational Research, and the University of Maryland School of Pharmacy Mass Spectrometry Center.
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Materials provided by University of Maryland School of Medicine. Original written by Vanessa McMains. Note: Content may be edited for style and length.

Researchers figured out how a jolt of discomfort gets from the damaged outside of your tooth to the nerves inside it.There’s nothing quite like the peculiar, bone-jarring reaction of a damaged tooth exposed to something cold: a bite of ice cream, or a cold drink, and suddenly, that sharp, searing feeling, like a needle piercing a nerve.Researchers have known for years that this phenomenon results from damage to the tooth’s protective outer layer. But just how the message goes from the outside of your tooth to the nerves within it has been difficult to uncover. On Friday, biologists report in the journal Science Advances that they have identified an unexpected player in this painful sensation: a protein embedded in the surface of cells inside the teeth. The discovery provides a glimpse of the connection between the outer world and the interior of a tooth, and could one day help guide the development of treatments for tooth pain.More than a decade ago, Dr. Katharina Zimmerman, now a professor at Friedrich-Alexander University in Germany, discovered that cells producing a protein called TRPC5 were sensitive to cold. When things got chilly, TRPC5 popped open to form a channel, allowing ions to flow across the cell’s membrane.Ion channels like TRPC5 are sprinkled throughout our bodies, Dr. Zimmerman said, and they are behind some surprisingly familiar sensations. For instance, if your eyes start to feel cold and dry in chilly air, it’s a result of an ion channel being activated in the cornea. She wondered which other parts of the body might make use of a cold receptor such as TRPC5. And it occurred to her that “the most sensitive tissue in the human body can be teeth” when it comes to cold sensations.Within the protective shell of their enamel, teeth are made of a hard substance called dentin that’s threaded with tiny tunnels. At the heart of the dentin is the tooth’s soft pulp, where nerve cells and cells called odontoblasts, which manufacture dentin, are intertwined.The prevailing theory for how teeth sense cold had been that temperature changes put pressure on the fluid in dentin’s tunnels, somehow provoking a response in those concealed nerves. But there was little detail about how exactly that could be happening and what could be bridging the gap between them.Dr. Zimmerman and her colleagues looked to see whether mice engineered to lack the TRPC5 channel still felt tooth pain as normal mice did. They were intrigued to find that these mice, when they had damage to their teeth, did not behave as if anything was amiss. They looked, in fact, about the same as if they had been given an anti-inflammatory painkiller, Dr. Zimmerman said.Her co-author Dr. Jochen Lennerz, a pathologist at Massachusetts General Hospital, checked human teeth for signs of the ion channel and found it in their nerves and other cells. That suggested that the channel might have a role in a person’s perception of cold.Over many years, the researchers constructed a way to precisely measure the nerve signals traveling out of a mouse’s damaged molar. They tested their ideas with molecules that could block the activity of various channels, including TRPC5.The picture they slowly assembled is that TRPC5 is active in the odontoblasts. That was a bit of a surprise, as these supporting cells are best known for making and maintaining dentin, not aiding in perception. Within the odontoblasts, Dr. Lennerz said, TRPC5 pops open when the signal for cold comes down the dentin tunnels, and this results in a message being sent to the nerves.As it happens, one substance that keeps TRPC5 from opening is eugenol, the main ingredient in oil of cloves, a traditional treatment for toothache. Though the Food and Drug Administration in the United States is equivocal about eugenol’s effectiveness, if it does lessen the pain for some people, it may be because of its effect on TRPC5.Perhaps the knowledge that this channel is at the heart of cold-induced pain will lead to better treatments for dental pain down the road — better ways to keep that message from becoming overwhelming.

A slew of new ads show sloppy kisses. Air travel is ticking back up. And impending vaccination can seem like a ticket back to normalcy for 20-somethings in the United States, many of whom feel desperate to get back to their 2019 social lives. Cramped parties. Strobe-lit dance floors. The ability to spontaneously text a friend: Want to grab a drink?Younger adults have played a disproportionate role in spreading the coronavirus. A report from the Centers for Disease Control and Prevention showed that from June to August 2020, Covid infections among 20- to 29-year-olds surged, accounting for more than 20 percent of the country’s total cases. Shortly after, data showed that those cases then led to an increase in infections among middle-aged and older people, potentially contributing to a national surge in cases.Now, as older adults have been prioritized for vaccination and about two-thirds of those over 65 have received at least one dose, their risk of getting severely ill after catching the virus from an infected young person has decreased significantly.But that doesn’t mean it’s completely safe to party like it’s 2019.How you calculate your risk of passing the virus onto more vulnerable people will hinge on your individual circumstances: whether you live with parents or people in their 20s, whether there are people at risk for severe outcomes of Covid in your social circle. “There’s not a simple red light, green light,” said Dr. William Schaffner, an infectious disease expert at Vanderbilt University.Here are some answers to common questions about what, in general, younger adults who are low risk can do when they’re fully vaccinated.Can we just go back to normal?A return to a kind of normal is coming, experts stressed, but there are still many unknowns about how the next few months will play out. While rising vaccination rates and falling cases are encouraging, said Dr. Schaffner, there are three situations that could hamper or negate that progress: if people refuse vaccination, if community transmission rates stay high and if virus variants render vaccines less effective.“If the older and younger adults get vaccines, and the variants are not too variant, then we could have lots of pool parties,” he said. “Bars could open up.”“The movement back to normal life should be a slow step-by-step,” said Tara Kirk Sell, a senior associate at the Johns Hopkins Center for Health Security, who researches large-scale health events. She recommended that people pick out one riskier activity they’ve been craving during the pandemic — seeing friends, going out to eat — and do that to celebrate their vaccination. “Then it should be a gradual move forward, rather than this huge explosion of, ‘I’m free!’,” she said.Lelanie Foster for The New York TimesLelanie Foster for The New York TimesBut much of that is dependent on how much virus is circulating in your community.“Once you get to a combination of hardly any cases in the community and a high proportion of people vaccinated — then, everything changes,” said Dr. Paul E. Sax, an infectious disease specialist at Brigham and Women’s Hospital in Boston. “That’s really what we’re looking forward to. Then you say, ‘Sure, I’ll take the chance of going to a restaurant. My chance of going to a restaurant and getting sick from Covid is no higher than the risk of getting sick from a regular cold.’ That’s a risk people should be very willing to take.”“People have to keep their eyes on the Covid landscape the way they do the weather,” said Dr. Peter Chin-Hong, an infectious disease expert at the University of California, San Francisco. He recommended that people monitor vaccination rates in their community and cases per 100,000. Dr. Carlos del Rio, an infectious disease specialist at Emory University, recommended the Covid ActNow site to check case numbers per county; The New York Times also tracks risk level by county.If your area has fewer than 10 cases per 100,000, it’s safer to go to a party or hang out indoors in a larger group of all vaccinated people. A far less safe scenario would be to participate in the kinds of spring break-related parties that are drawing attention in Florida, which reported 22 cases per 100,000 in the past seven days and is thought to have a large concentration of B.1.1.7, the more contagious and possibly more lethal virus variant first identified in Britain.Can we make out with strangers?Experts interviewed for this piece said that kissing and other intimate contact with someone you don’t know once you’ve been vaccinated is likely to be safe as long as you can confirm that they are also vaccinated.Even without that confirmation, making out with a stranger is likely to be a lower risk activity than going into a crowded setting like a club or party, said Dr. David Rubin, a professor of pediatrics at the Perelman School of Medicine at the University of Pennsylvania. “It’s one of those events best left to the individual person, to make that choice and not judge it,” he said.“If you’re in a controlled setting and you’re just with that person, and you want to take a chance on making out with that person and you think that person doesn’t have any risk of getting bad Covid — from the C.D.C. guidance, you can go ahead and make out with that person all you want,” said Dr. Chin-Hong.If you’re vaccinated but can’t confirm the vaccination or medical status of the person you want to kiss, it will be OK for most young people, he said.“The name of the game here is control,” he said. “The more noses and mouths that get together, the potentially riskier it is for transmission.”There’s also the obvious logistical quandary: It can be hard to casually and quickly verify that someone is fully vaccinated and low-risk. One dating app, Coffee Meets Bagel, recently added an option to include vaccine status on dating profiles, although it does not require verification.Can we gather in groups?The C.D.C. released recommendations earlier this month that said that it’s safe for vaccinated adults to gather in small groups without masks or social distancing. A C.D.C. spokeswoman said in an email that those guidelines applied to all people living in the United States, and that there were no additional considerations for younger adults.Practically, that means it’s OK for a group of about five to 10 vaccinated friends to hang out without precautions. But the larger the gathering, the more likely it is that someone in the group will be unvaccinated. While all three vaccines seem to be effective at preventing severe illness from the virus, we don’t yet know if they’ll prevent people from transmitting the virus to others.What about indoor bars?Dr. Ashish K. Jha, dean of the Brown University School of Public Health, predicted that most bars will be open across the country this summer. He also predicted that they’ll be a major source of viral spread among unvaccinated people, though they should be mostly safe for those who have received the vaccine.“The bottom line is, if you want to go to a bar, you want to go to a club — you can, and you’ll be pretty safe” once you’ve been vaccinated, Dr. Jha said. But other experts cautioned that there are still too many unknowns — about variants, about whether you can still transmit the virus after you’ve been vaccinated — to fully encourage people to flock back to indoor bars.Outdoor bars can be safer, depending on their setup and particularly if community transmission is low. Just be sure to stick to a small group of friends, rather than a large crowd.What about outdoor concerts?Experts agreed that outdoor concerts could be safe, particularly if attendees wear masks and keep distanced. Outdoor activities can support much larger groups of vaccinated people, Dr. Sax said.“People were wondering why there weren’t more cases after the protests this summer,” he said. “Well, it’s because they took place outside. That’s going to be true about outdoor concerts, also — I’d be very surprised if there were any major spreader events linked to an outdoor concert.”Do young people need to get vaccinated?Experts expressed concerns about vaccine hesitancy among young people. In January, the U.S. Census Bureau released survey data that showed that Americans under 44 were most reluctant to get vaccinated.“We’ve been selling the vaccine to older individuals as a way to protect against hospitalization and death,” Dr. del Rio said. “Most young people, if they get infected, they get a mild disease. We need to be able to communicate very clearly that there’s an advantage to getting the vaccine for young people, besides saying, ‘You’re not going to die.’”“The faster we vaccinate people, the more likely we are to have a more normal life,” he said.

Scientists at the University of Bonn and the caesar research center have isolated a molecule that might open new avenues in the fight against SARS coronavirus 2. The active ingredient binds to the spike protein that the virus uses to dock to the cells it infects. This prevents them from entering the respective cell, at least in the case of model viruses. It appears to do this by using a different mechanism than previously known inhibitors. The researchers therefore suspect that it may also help against viral mutations. The study will be published in the journal Angewandte Chemie but is already available online.
The novel active ingredient is a so-called aptamer. These are short chains of DNA, the chemical compound that also makes up chromosomes. DNA chains like to attach themselves to other molecules; one might call them sticky. In chromosomes, DNA is therefore present as two parallel strands whose sticky sides face each other and that coil around each other like two twisted threads.
Aptamers, on the other hand, are single-stranded. This allows them to form bonds with molecules to which conventional DNA would not normally bind and to influence their function. This makes them interesting for research into active ingredients, especially since it is now very easy to produce huge libraries of different aptamers. Some of these libraries contain millions of times more potential active ingredients than there are people living on Earth. “We used such a library to isolate aptamers that can attach to the spike protein of SARS coronavirus 2,” explains Prof. Dr. Günter Mayer of the LIMES Institute (the acronym stands for “Life and Medical Sciences”) at the University of Bonn.
Spike is essential for the infection
The spike protein is essential for the virus: It uses it to dock onto the cells it attacks. In the process, the protein binds to a molecule on the surface of its victims called ACE2, which effectively locks into the spike protein, much like a ski boot in a ski binding. The virus then fuses with the cell and reprograms it to produce numerous new viruses. “The vast majority of antibodies we know today prevent docking,” Mayer explains. “They attach to the part of the spike protein responsible for recognizing ACE2, which is the receptor binding domain, or RBD.”
The now isolated aptamer with the abbreviation SP6 also binds to the spike protein, but at a different site. “SP6 does not prevent viruses from docking to target cells,” explains Prof. Dr. Michael Famulok of the LIMES Institute, who also works at the caesar research center in Bonn. “Nevertheless, it reduces the level of cell infection by the virus; we do not yet know which mechanism is responsible for this.” The researchers did not use real coronaviruses in their experiments, but so-called pseudoviruses. These carry the spike protein on their surface; however, they cannot cause disease. “We now need to see if our results are confirmed in real viruses,” Famulok therefore emphasizes.
New Achilles heel of coronavirus?
If so, in the medium term the work could for instance result in a kind of nasal spray that protects against coronavirus infection for a few hours. The necessary studies will certainly take months to complete. Irrespective of this, however, the results may help to better understand the mechanisms involved in infection. This is all the more important because the existing active ingredients mainly target the receptor domain. In the so-called “British mutation,” this domain is altered so that it binds more strongly to ACE2. “The more such mutations accumulate, the greater the risk that the available drugs and vaccines will no longer work,” stresses Günter Mayer. “Our study may draw attention to an alternative Achilles’ heel of the virus.”
The results are also evidence of successful cooperation: Mayer and his postdoctoral researcher Dr. Anna Maria Weber were primarily responsible for characterizing the aptamer. Prof. Famulok’s group at the caesar research center was responsible for conducting the pseudovirus experiments, which were led by his colleague Dr. Anton Schmitz. Famulok and Mayer are members of the Transdisciplinary Research Areas “Life & Health” and “Building Blocks of Matter and Fundamental Interactions.” Mayer also heads the Center of Aptamer Research and Development (CARD) at the University of Bonn.
The study was funded by the German Federal Ministry of Education and Research (BMBF) and the German Research Foundation (DFG).
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Materials provided by University of Bonn. Note: Content may be edited for style and length.

Research has found that obesity and mental disorders such as depression and anxiety seem to often go hand in hand. Researchers at Baylor College of Medicine and collaborating institutions are providing new insights into this association by identifying and characterizing a novel neural circuit that mediates the reciprocal control of feeding and psychological states in mouse models.
Similar to human patients, mice that consumed a high-fat diet not only became obese, but also anxious and depressed, a condition mediated by a defective brain circuit. When the researchers genetically or pharmacologically corrected specific disruptions they had observed within this circuit, the mice became less anxious and depressed and later lost excess body weight.
Interestingly, weight loss was not the result of lack of appetite, but of the animals’ change of food preference. Before the treatment, the mice naturally preferred to eat a high-fat diet, but after the treatment they turned their preference toward a healthier diet with reduced fat and abundant protein and carbohydrates. The findings, published in the journal Molecular Psychiatry, for the first time, not only reveal a key regulatory mechanism for coinciding obesity and mental disorders, but also suggest the possibility of a pharmacological treatment.
“Reports indicate that 43% of adults with depression are obese and that adults with mental illness are more likely to develop obesity than those who are mentally healthy,” said corresponding author Dr. Qi Wu, a Pew Scholar for Biomedical Sciences, Kavli Scholar and assistant professor in pediatrics-nutrition at Baylor’s Children’s Nutrition Research Center. “Factors such as hormonal dysregulation, genetic deficiency and inflammation have been proposed to be involved in the connection between obesity and mental disorders. Here we provide evidence that supports the involvement of a neural component.” To investigate the neuronal circuits that could be involved in reciprocally regulating weight gain and depression or anxiety, the researchers provided mice with a high-fat diet. As expected, the animals became obese. They also developed anxiety and depression. In these mice, the team studied the function of neuronal circuits.
“We discovered in normal mice that two groups of brain cells, dBNST and AgRP neurons located in separate brain areas, form a circuit or connection to each other by extending cellular projections,” said co-first author Dr. Guobin Xia, postdoctoral associate in the Wu lab. “This newly discovered circuit was malfunctioning in mice that were both obese and depressed.”
“Using genetic approaches, we identified specific genes and other mediators that were altered and mediated the circuit’s malfunction in the obese and depressed mice,” said co-first author Dr. Yong Han, postdoctoral associate in the Wu lab.
“Importantly, genetically restoring the neural defects to normal eliminated the high fat diet-induced anxiety and depression and also reduced body weight,” Xia said. “We were surprised to see that the animals lost weight, not because they lost their appetite, but because genetically-aided readjustment of the mental states changed their feeding preference from high-fat to low-fat food.”
“Keeping in mind translational applications of our findings to the clinic, we investigated the possibility of restoring the novel circuit pharmacologically,” Wu said. “We discovered that the combination of two clinically-approved drugs, zonisamide and granisetron, profoundly reduced anxiety and depression in mice and promoted weight loss by synergistically acting upon two different molecular targets within our newly identified brain circuit. We consider that our results provide convincing support for further studies and future clinical trials testing the value of a cocktail therapy combining zonisamide and granisetron (or a selection of their derivatives) to treat metabolic-psychiatric diseases.”
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Materials provided by Baylor College of Medicine. Original written by Homa Shalchi. Note: Content may be edited for style and length.

When Laura Drager contracted Covid-19 in July, it was as though someone had suddenly muted her olfactory system.One morning she was sipping her favorite Gatorade (the yellow one), and two hours later the drink was completely flavorless. She immediately lit a candle and blew it out, but she couldn’t smell the smoke.Her sense of smell had disappeared. Now, she said, “everything either tastes like bleach or tastes like nothing.”Over the past few months she has lost 19 pounds. “I don’t have that ‘I’m hungry’ feeling,” said Ms. Drager, 41, who lives in Sevierville, Tenn., about 45 minutes from Knoxville. “I think you forget how much smell and taste is a part of your life until it goes away.”As the coronavirus continues to spread, there are increasing numbers of people who have either lost their senses of smell after contracting Covid or are struggling with parosmia, a disturbing disorder that causes previously normal odors to develop a new, often unpleasant aroma.One meta-analysis published in September found that as many as 77 percent of those who had Covid were estimated to have some form of smell loss as a result of their infections.The recommended treatment for these conditions is smell training. But how exactly do you do it, and why should you bother?We spoke with several experts to demystify the process.What is smell training?First, let’s talk about what smell training is not. If the words conjure up images of a “Rocky” training montage — as they did for Tejal Rao, a New York Times restaurant critic who lost her sense of smell after contracting Covid last year — the reality is very different. Smell training is more akin to physical therapy for your nose: tedious and repetitive. It involves sniffing several potent scents twice a day, sometimes for months, to stimulate and restore the olfactory system — or at the very least to help it function better.“It’s not a quick fix,” said Chrissi Kelly, a member of the Global Consortium for Chemosensory Research and the founder of AbScent, a nonprofit based in England and Wales that offers support and education to people around the world who have smell disorders. “You have to keep up with it.”If it has been a couple of weeks since you lost your sense of smell and it hasn’t started to come back, then it makes sense to start smell training. When your smell starts to come back, it might happen gradually rather than all at once. At first, scents might seem distorted or foul.Scientists are still learning about all of the mechanisms by which the coronavirus affects the olfactory system, but they believe parosmia occurs because the neural pathways from the nose to the brain have been disrupted, “kind of like a telephone operator from the 1950s connecting the wrong party to another line,” said Pamela Dalton, a faculty member at the Monell Chemical Senses Center, a nonprofit research institute in Philadelphia.For most people, parosmia is a symptom of recovery, and that’s why experts believe smell training can be beneficial as you continue to heal.Patricia Voulgaris for The New York TimesWhy smell training?Even if you’re devastated over having lost your sense of smell, you might be thinking: Do I really need to add smell training to my to-do list? Won’t my sense of smell return eventually all by itself?For many people, it appears to come back within weeks of being infected.A study published in January that recruited patients from 18 European hospitals found that among 1,363 coronavirus patients with olfactory dysfunction, most recovered their senses of smell within two months and 40 percent saw their ability to smell return within two weeks. All patients were encouraged to follow two daily sessions of smell training at home, said Dr. Jerome R. Lechien, a professor of otolaryngology at the University Hospital of Brussels and one of the authors of the study. Though it’s unclear how many patients did the training, nearly one-quarter were still experiencing smell dysfunction 60 days after the onset of their symptoms. By the six-month mark, 95 percent of the patients had recovered their senses of smell.Robust studies examining the efficacy of olfactory training among Covid survivors have not yet been published. Several studies, however, have demonstrated that smell training can help people who have lost some or all of their senses of smell to other viral illnesses like sinus infections — that’s why it is widely considered the best option for those who can no longer smell properly after contracting Covid.“It has no risk — except boredom,” Dr. Dalton said wryly.Before you begin, however, it is wise to rule out other conditions that could be affecting your sense of smell.“I saw somebody recently who had smell dysfunction following Covid-19, and it turned out they had inflammatory nasal polyps,” said Dr. Sunthosh K. Sivam, an ear, nose and throat specialist and an assistant professor at the Baylor College of Medicine in Houston. Once he removed the polyps, which were unrelated to Covid, his patient’s sense of smell improved greatly.“Seeing an E.N.T. is a good way to make sure nothing else is missed,” he added.How do you choose your scents?To start, decide on four scents that are familiar to you and that evoke strong memories, the experts said. These are the fragrances that you will stick with throughout the initial phase of your training. Maybe one of them is a scented shampoo, a favorite cologne or lemons from the tree in your backyard. An avid home cook, for example, might use certain spices from his pantry.Alternatively, “some people have had a lot of success with things that smell bad,” Dr. Dalton said.At one point during her smell training, Ms. Rao, the restaurant critic, used spoiled milk. Ms. Drager, who had Covid-19 over the summer, extinguishes a candle every day and tries to smell the smoke.If that doesn’t sound appealing, you can choose to buy a smell kit that contains essential oils: the classic scents are rose, eucalyptus, clove and lemon. The kits usually retail for under $50.Or you can purchase these oils yourself at a place like Whole Foods. Ms. Kelly includes instructions on how to make your own scent kit on the AbScent website.If you buy your own oils and you want to smell them directly from the open container, first ask someone who isn’t smell impaired to try it. Then ask whether the person can easily smell the fragrance when the scent is a few inches below his or her nose. (Some containers have such small openings that it might be difficult to get a good whiff.) In the process, avoid getting any of the oils on your skin because they are highly concentrated.How does smell training work?There is not one uniform, universal way of undergoing smell training, but the experts we spoke with offered similar advice.They recommend keeping your scents in an easily accessible location — such as by your bedside — and smelling each scent for about 20 seconds so that the entire smell-training session lasts approximately one minute.While you’re doing this, take short sniffs rather than deep inhales, recommended Ms. Kelly of AbScent as she demonstrated a series of repetitive whiffs that she referred to as “bunny sniffs.”While you’re smelling the fragrances, it often helps to look at a picture of the thing that you’re smelling, said Dr. Nicholas R. Rowan, an assistant professor of otolaryngology-head and neck surgery at the Johns Hopkins University School of Medicine in Baltimore.Then, try to imagine what the item used to smell or taste like to you.“It’s not simply the act of smelling something, but it’s also this sort of mindful imagining of what that smelled like when you were eating it or when you put it on your skin — if it was a lotion, for example,” Dr. Dalton said. “It just makes it more enjoyable to continue with the process.”Smelling something that is connected to a memory or emotion is ideal, she said, because the brain plays such a big role in how we perceive smell.How long do you need to do it?Generally, doctors advise their patients to do smell training twice a day for three months.“Keep on training for a year if you have to,” said Dr. Thomas Hummel, a researcher at the Smell and Taste Clinic of the otorhinolaryngology department at the Technical University of Dresden in Germany, whose work has informed the odor training methods now used around the world.The success of your training depends on a variety of factors, including your age. In general, younger people recover their sense of smell after a viral illness at a higher rate than older people, Dr. Hummel added. This is partly because older people tend to have fewer olfactory receptor neurons — the cells that detect and transmit information about smells to the central nervous system — and their receptor neurons do not regenerate as quickly.“When you’re older, everything is slower,” he said.How do you stay motivated?As with any process that doesn’t yield immediate results, you may find it difficult to stick with the plan.“It’s very frustrating for patients,” Dr. Rowan said. “They seek out this care because they can’t smell and want it fixed and then we say, ‘Hey, use this sensory function that you don’t have.’” But, he added, “this is the best thing out there.”He suggested using a calendar to record each scent training session in order to build the habit.Keeping a diary can also be helpful, Ms. Kelly said, so that you can take notes on what you’re experiencing during each session. For further motivation, the AbScent website offers an app called Snif that can help you track your progress.Finally, if you don’t know many people who have a smell dysfunction, consider joining an online community for support and inspiration. The AbScent Facebook group for people with Covid has grown to more than 25,000 people, Ms. Kelly said.As for Ms. Drager, although she is still working to heal her olfactory system, she did smell a lemon scent this year for the first time since her sense of smell disappeared.She cried with relief.“I’m making slow progress,” she said.

When the brain suffers injury or infection, glial cells surrounding the affected site act to preserve the brain’s sensitive nerve cells and prevent excessive damage. A team of researchers from Charité — Universitätsmedizin Berlin have been able to demonstrate the important role played by the reorganization of the structural and membrane elements of glial cells. The researchers’ findings, which have been published in Nature Communications, shed light on a new neuroprotective mechanism which the brain could use to actively control damage following neurological injury or disease.
The nervous system lacks the ability to regenerate nerve cells and is therefore particularly vulnerable to injury. Following brain injury or infection, various cells have to work together in a coordinated manner in order to limit damage and enable recovery. ‘Astrocytes’, the most common type of glial cell found in the central nervous system, play a key role in the protection of surrounding tissues. They form part of a defense mechanism known as ‘reactive astrogliosis’, which facilitates scar formation, thereby helping to contain inflammation and control tissue damage. Astrocytes can also ensure the survival of nerve cells located immediately adjacent to a site of tissue injury, thereby preserving the function of neuronal networks. The researchers were able to elucidate a new mechanism which explains what processes happen inside the astrocytes and how these are coordinated.
“We were able to show for the first time that the protein ‘drebrin’ controls astrogliosis,” says study lead Prof. Dr. Britta Eickholt, Director of Charité’s Institute of Biochemistry and Molecular Biology. “Astrocytes need drebrin in order to form scars and protect the surrounding tissue.” By switching off the production of drebrin inside astrocytes, the researchers were able to study its role in brain injury in an animal model. They used electron microscopy and high-resolution light microscopy to investigate cellular changes in the brain, in addition to undertaking real-time investigations using isolated astrocytes in cell culture. “Loss of drebrin results in the suppression of normal astrocyte activation,” explains Prof. Eickholt. She adds: “Instead of engaging in defensive reactions, these astrocytes suffer complete loss of function and abandon their cellular identity.” Without protective scar formation, normally harmless injuries will spread, and more and more nerve cells will die.
To enable scar formation, drebrin controls the reorganization of the actin cytoskeleton, an internal scaffold responsible for maintaining astrocyte mechanical stability. By doing so, drebrin also induces the formation of long cylindrical membrane structures known as tubular endosomes, which are used in the uptake, sorting and redistribution of surface receptors and are needed for the defensive measures of astrocytes. Summing up the researchers’ findings, Prof. Eickholt says: “Our findings also show how drebrin uses the dynamic and versatile cytoskeleton as well as membrane structures to control astrocyte functions which are fundamental to the defense mechanism against injury.” She continues: “In particular, the membrane tubules which are formed during this process have not previously been described in this manner, neither in cultured astrocytes nor in the brain.”
“Drebrin’s role as a cytoskeletal regulator suggests that it may be a risk factor for severe outcomes in both neurological and other disorders, because loss of the protein can produce similar changes in astrocytes,” says Prof. Eickholt. She adds: “It is also possible that individuals with defects in the drebrin gene — comparable to those in the animal model — might remain without symptoms until triggers like cellular stresses, environmental toxins or diseases occur.” It is hoped that investigations involving patient samples will elucidate the extent to which drebrin also plays a role in degenerative brain disorders, such as Alzheimer’s disease.
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Scientists at the Institute for Integrated Cell-Material Sciences (iCeMS) and colleagues in Japan have revealed molecular mechanisms involved in eliminating unwanted cells in the body. A nuclear protein fragment released into the cytoplasm activates a plasma membrane protein to display a lipid on the cell surface, signalling other cells to get rid of it. The findings were published in the journal Molecular Cell.
“Every day, ten billion cells die and are engulfed by blood cells called phagocytes. If this didn’t happen, dead cells would burst, triggering an auto-immune reaction,” explains iCeMS biochemist Jun Suzuki, who led the study. “It is important to understand how dead cells are eliminated as part of our body’s maintenance.”
Scientists already know that dead cells display an ‘eat me’ signal on their surface that is recognized by phagocytes. During this process, lipids are flipped between the inner and outer parts of the cell membrane via a variety of proteins called scramblases. Suzuki and his team have already identified several of these lipid-scrambling proteins, but some of their activation mechanisms have been unclear.
To solve this, the team used an array of screening approaches to study the scrambling protein called Xkr4. The broad aim was to single out the genes that are active during cell death and to specifically zoom in on Xkr4 and its associated proteins to understand how they interact.
“We found that a nuclear protein fragment activates Xkr4 to display the ‘eat me’ signal to phagocytes,” says iCeMS cell biologist Masahiro Maruoka, the first author of the study.
Specifically, the scientists found that cell death signals lead to a nuclear protein, called XRCC4, getting cut by an enzyme. A fragment of XRCC4 leaves the nucleus, activating Xkr4, which forms a dimer: the linking of identical pieces into configurations. Both XRCC4 binding and dimer formation are necessary for Xkr4 to ultimately transfer lipids on the cell surface to alert phagocytes.
Xkr4 is only one of the scrambling proteins. Others are activated much faster during cell death. The team now wants to understand when and why the Xkr4 pathway is specifically activated. Since it is strongly expressed in the brain, it is likely important for brain function. “We are now studying the elimination of unwanted cells or compartments in the brain to understand this process further,” says Maruoka.
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Materials provided by Kyoto University. Note: Content may be edited for style and length.