Publisher Health

An immune signal promotes the production of energy-burning “beige fat,” according to a new study publishing Aug. 5 in the open-access journal PLOS Biology by Zhonghan Yang of Sun Yat-Sen University, Guangzhou, China, and colleagues. The finding may lead to new ways to reduce obesity and treat metabolic disorders.
The beige color in beige fat comes from its high concentration of mitochondria, the cell’s powerhouses. Mitochondria burn high-energy molecules like fats and sugars with oxygen, releasing energy. Normally, that energy is stored as ATP, the energy currency that the cell uses for almost all its activities. But in beige fat, mitochondria accumulate a protein called “uncoupling protein-1” that limits ATP production, generating heat instead.
Babies are born with “brown fat,” a similar tissue concentrated in the shoulder region, which helps them stay warm, but brown fat is gradually lost with age. Not so beige fat, which is more widely distributed and which can be generated throughout life in response to both cold and neuronal or hormonal stimulation.
Recent work, including by the authors of the new study, has revealed that cytokines — immune system signaling molecules — play a role in regulation of beige fat. To explore that regulation further, the authors manipulated levels of the cytokine interleukin-25, and showed that an increase in the cytokine could mimic the effects of both cold and stimulation of a hormone receptor in increasing the production of beige fat in mice. They traced the signaling chain further, showing that IL-25 exerted its effects through two other cytokines, which in turn regulated immune cells called macrophages. Those cells acted on neurons that terminate in the beige fat tissue, promoting an increase in production of the neurotransmitter norepinephrine, which was already known to promote beige fat production. Thus, the authors’ work revealed the sequence of regulatory signals that begins with IL-25 and ends with release of norepinephrine and an increase in beige fat.
Finally, the authors showed that administering IL-25 to mice that were eating a high-fat diet prevented them from becoming obese and improved their ability to maintain their responsiveness to insulin, which is impaired in chronic obesity.
“Our results show that interleukin-25 plays a key role in production of beige fat,” Yang said, “and point toward increasing interleukin-25 signaling as a potential treatment for obesity.”
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Fasting before and during exposure to Salmonella enterica bacteria protects mice from developing a full-blown infection, in part due to changes in the animals’ gut microbiomes,according to new research published in PLOS Pathogens by Bruce Vallance and colleagues at University of British Columbia, Canada.
When people or animals develop an infection, they often lose their appetite. However it remains controversial whether fasting protects a host from infection, or increases their susceptibility. In the new study, mice were fasted for 48 hours before and during oral infection with the bacteria Salmonella enterica serovar Typhimurium, a common cause of foodborne illness in people.
Fasting decreased the signs of bacterial infection compared to fed mice, including nearly eliminating all intestinal tissue damage and inflammation. When fasted animals were re-fed for a day after their fast, there was a dramatic increase in Salmonella numbers and invasion into the intestinal walls, although the associated inflammation was still attenuated compared to normal. The results did not hold true when mice were exposed to Salmonella intravenously instead of orally, and analyses of the microbiomes of mice showed significant changes associated with fasting and protection against infection. Moreover, fasting did not fully protect germ-free mice — bred to lack a normal microbiome — from Salmonella, suggesting that some of the protection was due to fasting’s effect on the microbiome. Experiments using the bacteria Campylobacter jejuni confirmed that the effect of fasting was not limited to Salmonella, with similar results seen.
“These data suggest that therapeutic fasting or calorie restriction has the potential to beneficially modulate infectious and potentially non-infectious gastrointestinal diseases,” the researchers conclude.
The researchers add, “Our research highlights the important role that food plays in regulating interactions between the host, enteric pathogens and the gut microbiome. When food is limited, the microbiome appears to sequester the nutrients that remain, preventing pathogens from acquiring the energy they need to infect the host. While more research is needed, fasting or otherwise adjusting food intake could be exploited therapeutically to modulate infectious diseases in the future.”
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Frequent, rapid testing for COVID-19 is critical to controlling the spread of outbreaks, especially as new, more transmissible variants emerge.
While today’s gold standard COVID-19 diagnostic test, which uses qRT-PCR — quantitative reverse-transcriptase-polymerase chain reaction (PCR) — is extremely sensitive, detecting down to one copy of RNA per microliter, it requires specialized equipment, a runtime of several hours and a centralized laboratory facility. As a result, testing typically takes at least one to two days.
A research team led by scientists in the labs of Jennifer Doudna, David Savage and Patrick Hsu at the University of California, Berkeley, is aiming to develop a diagnostic test that is much faster and easier to deploy than qRT-PCR. It has now combined two different types of CRISPR enzymes to create an assay that can detect small amounts of viral RNA in less than an hour. Doudna shared the 2020 Nobel Prize in Chemistry for invention of CRISPR-Cas9 genome editing.
While the new technique is not yet at the stage where it rivals the sensitivity of qRT-PCR, which can detect just a few copies of the virus per microliter of liquid, it is already able to pick up levels of viral RNA — about 30 copies per microliter — sufficient to be used to surveil the population and limit the spread of infections.
“You don’t need the sensitivity of PCR to basically catch and diagnose COVID-19 in the community, if the test’s convenient enough and fast enough,” said co-author David Savage, professor of molecular and cell biology. “Our hope was to drive the biochemistry as far as possible to the point where you could imagine a very convenient format in a setting where you can get tested every day, say, at the entrance to work.”
The researchers will report their results online August 5 in the journal Nature Chemical Biology.

When new mothers complain that all those sleepless nights caring for their newborns are taking years off their life, they just might be right, UCLA research published this summer in the journal Sleep Health suggests.
Scientists studied 33 mothers during their pregnancies and the first year of their babies’ lives, analyzing the women’s DNA from blood samples to determine their “biological age,” which can differ from chronological age. They found that a year after giving birth, the biological age of mothers who slept less than seven hours a night at the six-month mark was three to seven years older than those who logged seven hours or more.
Mothers who slept less than seven hours also had shorter telomeres in their white blood cells. These small pieces of DNA at the ends of chromosomes act as protective caps, like the plastic tips on the ends of shoelaces. Shortened telomeres have been linked to a higher risk of cancers, cardiovascular and other diseases, and earlier death.
“The early months of postpartum sleep deprivation could have a lasting effect on physical health,” said the study’s first author, Judith Carroll, UCLA’s George F. Solomon Professor of Psychobiology. “We know from a large body of research that sleeping less than seven hours a night is detrimental to health and increases the risk of age-related diseases.”
While participants’ nightly sleep ranged from five to nine hours, more than half were getting less than seven hours, both six months and one year after giving birth, the researchers report.
“We found that with every hour of additional sleep, the mother’s biological age was younger,” said Carroll, a member of the Cousins Center for Psychoneuroimmunology at UCLA’s Jane and Terry Semel Institute for Neuroscience and Human Behavior. “I, and many other sleep scientists, consider sleep health to be just as vital to overall health as diet and exercise.”
Carroll urged new mothers take advantage of opportunities to get a little extra sleep, like taking naps during the day when their baby is asleep, accepting offers of assistance from family and friends, and, when possible, asking their partner to help with the baby during the night or early morning. “Taking care of your sleep needs will help you and your baby in the long run,” she said.

People with autism spectrum disorder have difficulty interpreting facial expressions.
Using a neural network model that reproduces the brain on a computer, a group of researchers based at Tohoku University have unraveled how this comes to be.
The journal Scientific Reports published the results on July 26, 2021.
“Humans recognize different emotions, such as sadness and anger by looking at facial expressions. Yet little is known about how we come to recognize different emotions based on the visual information of facial expressions,” said paper coauthor, Yuta Takahashi.
“It is also not clear what changes occur in this process that leads to people with autism spectrum disorder struggling to read facial expressions.”
The research group employed predictive processing theory to help understand more. According to this theory, the brain constantly predicts the next sensory stimulus and adapts when its prediction is wrong. Sensory information, such as facial expressions, helps reduce prediction error.
The artificial neural network model incorporated the predictive processing theory and reproduced the developmental process by learning to predict how parts of the face would move in videos of facial expression. After this, the clusters of emotions were self-organized into the neural network model’s higher level neuron space — without the model knowing which emotion the facial expression in the video corresponds to.
The model could generalize unknown facial expressions not given in the training, reproducing facial part movements and minimizing prediction errors.
Following this, the researchers conducted experiments and induced abnormalities in the neurons’ activities to investigate the effects on learning development and cognitive characteristics. In the model where heterogeneity of activity in neural population was reduced, the generalization ability also decreased; thus, the formation of emotional clusters in higher-level neurons was inhibited. This led to a tendency to fail in identifying the emotion of unknown facial expressions, a similar symptom of autism spectrum disorder.
According to Takahashi, the study clarified that predictive processing theory can explain emotion recognition from facial expressions using a neural network model.
“We hope to further our understanding of the process by which humans learn to recognize emotions and the cognitive characteristics of people with autism spectrum disorder,” added Takahashi. “The study will help advance developing appropriate intervention methods for people who find it difficult to identify emotions.”
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Researchers have conducted a new trial to identify how an existing psychological therapy can be adapted to help people cope with and manage frequent Bipolar mood swings.
A subgroup of those with Bipolar Spectrum Disorders experience ongoing mood fluctuations outside of full episodes. These shifts in mood can sometimes make it difficult to live life to the full, and can be a source of difficulties in relationships with others. There are currently few therapy options available for people living with dramatic weekly, daily or even hourly mood swings.
The ThRIVe-B programme, carried out by researchers at the University of Exeter, involved taking an existing psychological therapy for another group of people that aims to help with emotion regulation, known as Dialectical Behaviour Therapy (DPT), and adapting it for people who have these frequent Bipolar mood swings.
DPT teaches skills both in acceptance of situations and emotional responses and is currently offered to people who have a diagnosis of Emotionally Unstable Personality Disorder.
“We have psychological therapies that can be helpful for people with Bipolar but there’s less available for people who have very frequent and ongoing mood swings within Bipolar” said lead author Dr Kim Wright, of the University of Exeter.
“We wanted to see how acceptable the therapy would be to the people who received it and do a test run to identify what changes need to be made before conducting a larger trial.”
The study took place in Devon and Cumbria and 43 participants were placed randomly into two groups.

Facial recognition software can be used to spot a face in a crowd; but what if it could also predict where someone else was in the same crowd? While this may sound like science fiction, researchers from Japan have now shown that artificial intelligence can accomplish something very similar on a cellular level.
In a study published in Frontiers in Cell and Developmental Biology, researchers from Nara Institute of Science and Technology (NAIST) have revealed that a machine learning program can accurately predict the location of proteins related to actin, an important part of the cellular skeleton, based on the location of actin itself.
Actin plays a key role in providing shape and structure to cells, and during cell movement helps form lamellipodia, which are fan-shaped structures that cells use to “walk” forwards. Lamellipodia also contain a host of other proteins that bind to actin to help maintain the fan-like structure and keep the cells moving.
“While artificial intelligence has been used previously to predict the direction of cell migration based on a sequence of images, so far it has not been used to predict protein localization,” says lead author of the study, Shiro Suetsugu. This idea came in during the discussion with Yoshinobu Sato at the Data Science Center in NAIST. “We therefore sought to design a machine learning algorithm that can determine where proteins will appear in the cell based on their relationship with other proteins.”
To do this, the researchers trained an artificial intelligence system to predict where actin-associated proteins would be in the cell by showing it pictures of cells in which the proteins were labeled with fluorescent markers to show where they were located. Then, they gave the program pictures in which only actin was labeled and asked it to tell them where the associated proteins were.
“When we compared the predicted images to the actual images, there was a considerable degree of similarity,” states Suetsugu. “Our program accurately predicted the localization of three actin-associated proteins within lamellipodia; and, in the case of one of these proteins, in other structures within the cell.”
On the other hand, when the researchers asked the program to predict where tubulin, which is not directly related to actin, would be in the cell, the program did not perform nearly as well.
“Our findings suggest that machine learning can be used to accurately predict the location of functionally related proteins and describe the physical relationships between them,” says Suetsugu.
Given that lamellipodia are not always easy for non-experts to spot, the program developed in this study could be used to quickly and accurately identify these structures from cell images in the future. In addition, this approach could potentially be used as a sort of artificial cell staining method to avoid the limitations of current cell-staining methods.
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Biological engineers at MIT have devised a new way to efficiently edit bacterial genomes and program memories into bacterial cells by rewriting their DNA. Using this approach, various forms of spatial and temporal information can be permanently stored for generations and retrieved by sequencing the cells’ DNA.
The new DNA writing technique, which the researchers call HiSCRIBE, is much more efficient than previously developed systems for editing DNA in bacteria, which had a success rate of only about 1 in 10,000 cells per generation. In a new study, the researchers demonstrated that this approach could be used for storing memory of cellular interactions or spatial location.
This technique could also make it possible to selectively edit, activate, or silence genes in certain species of bacteria living in a natural community such as the human microbiome, the researchers say.
“With this new DNA writing system, we can precisely and efficiently edit bacterial genomes without the need for any form of selection, within complex bacterial ecosystems,” says Fahim Farzadfard, a former MIT postdoc and the lead author of the paper. “This enables us to perform genome editing and DNA writing outside of laboratory settings, whether to engineer bacteria, optimize traits of interest in situ, or study evolutionary dynamics and interactions in the bacterial populations.”
Timothy Lu, an MIT associate professor of electrical engineering and computer science and of biological engineering, is the senior author of the study, which appears today in Cell Systems. Nava Gharaei, a former graduate student at Harvard University, and Robert Citorik, a former MIT graduate student, are also authors of the study.
Genome writing and recording memories
For several years, Lu’s lab has been working on ways to use DNA to store information such as memory of cellular events. In 2014, he and Farzadfard developed a way to employ bacteria as a “genomic tape recorder,” engineering E. coli to store long-term memories of events such as a chemical exposure.

In a recent study from University of Gothenburg, it has been shown that all participants achieve normalization of CNS injury biomarkers, regardless of previous disease severity or persistent neurological symptoms, indicating that post-COVID-19 neurological sequalae are not due to active brain injury.
Central nervous system involvement and signs of brain injury have been described since the beginning of the SARS-CoV-2 pandemic. A previous study from the same group showed that hospitalized patients receiving oxygen therapy or ICU care often had signs of brain damage by measuring blood-based biomarker of brain injury.
In addition, in recent months it has been increasingly evident that after the acute phase of COVID-19, many patients still suffer from persisting neurologic disability. This often includes lethargy, fatigue, or impaired cognitive function. This consequence is now termed post COVID condition.
The mechanism behind how COVID-19 causes persisting neurological symptoms is still not fully understood. In a follow-up study, the researchers aimed to investigate the longitudinal trajectories of the same plasma biomarkers in patients who have recovered from COVID-19, with and without persisting neurological symptoms.
Normalization of markers
The study presented in EBioMedicine recruited 100 COVID-19 patients from the Sahlgrenska University Hospital in Gothenburg, Sweden. The study population was divided into groups according to disease severity: mild, moderate, and severe COVID-19. Blood samples were collected at an interval of acute phase of the disease, 3- and 6-months post-infection. At the acute phase, patients who required hospitalization and were receiving oxygen therapy or mechanical ventilation showed an increase of NfL (neurofilament light chain protein), a biomarker that increases with neuronal injury, and GFAp (glial fibrillary acidic protein), a biomarker that indicates astrocytic injury or overactivation. At follow-up, all biomarkers returned to their normal baseline values.
In addition, at 3- and 6-months clinical follow-up, 50 patients out of the 100 recruited individuals reported one or more neurological symptoms, the most common symptoms were fatigue, “brain-fog,” and cognitive impairment, such as memory loss and lack of concentration. Remarkably, there were no difference in frequency of any symptoms among the disease severity groups.
Further research important
“The findings in this study puts an emphasis on the importance of further research that needs to validate the scale of persisting neurological symptoms and recovery, but also to investigate the true cause of this condition. This is of high importance from a scientific and public health point of view in search for better care of this patient group,” says the first author Nelly Kanberg, PhD student at the Infectious Disease at Sahlgrenska Academy, University of Gothenburg and resident medical doctor at the Department of Infectious Disease, Sahlgrenska University Hospital.
Magnus Gisslén, Professor of Infectious Diseases at the Sahlgrenska Academy and chief physician at the Department of Infectious Diseases, Sahlgrenska University Hospital, leads the Academy’s clinical research on COVID-19. The results of this study are, in his view, of great importance and encouraging for patients with long-lasting symptoms after COVID-19.
“Neurological complications are common in COVID-19 and can in some patients continue several months after the acute phase. It is reassuring that elevated concentrations of brain-injury markers return to normal 3-6 months after the acute phase of COVID-19 indicating that no continuous brain damage is present and that there is a good chance for recovery also in patients with remaining post-acute neurologic and cognitive symptoms,” Gisslén says.
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The rise of the Delta variant and the uncertainty over schools and child care are keeping these parents from applying for jobs.Brianna McCain left her job as an office manager when the pandemic started, to care for her two young daughters. By last spring, she was ready to go back to work. But she hasn’t been able to, because her children are still at home.She has been searching for a job with flexible hours and the ability to work from home, but these are hard to find, especially for new hires and for hourly workers. She can’t take an in-person job until school opens for her 6-year-old, and her district, in Portland, Ore., has not announced its plans. She also needs child care for her 2-year-old that costs less than she earns, but child care availability is far below prepandemic levels, and prices have increased to cover the costs of Covid safety measures.“When you’re getting into a new job especially, there isn’t flexibility,” said Ms. McCain, whose partner, a warehouse worker, cannot work from home. “And with the unknowns of Covid, I don’t know if my kid’s going to get pulled out of school for a quarantine or school’s going to stop.”Especially as the Delta variant spreads, many parents of young children — those under 12 who cannot yet be vaccinated — say they’re unable to return to workplaces or apply for new jobs as long as there is uncertainty about when their children can safely return to full-time school or child care.Companies have been struggling to hire and retain workers for other reasons, too, and many parents have had no choice but to work. (In a recent Census Bureau survey, 5 percent of parents said their children were not currently attending child care for pandemic-related reasons.) But for the group of parents who still have children at home — they’re disproportionately Black and Latino, and some have medically vulnerable family members — it’s a significant challenge.“You cannot divorce the child care issue and the pandemic,” said AnnElizabeth Konkel, an economist at the Indeed Hiring Lab. “It’s important that we don’t forget about the workers who are wrestling with this day in and day out.”In an Indeed survey this summer, one-third of those looking for a job said they wouldn’t want to start in the next month, and a significant share said they were waiting for schools to open. Among those who were unemployed but not urgently looking, nearly one-fifth said care responsibilities were the reason. Those without college degrees were more likely to cite such a reason — and more likely to be unable to work from home or to afford nannies.Summer is always a challenge for working parents, and this year that is especially true. To meet safety guidelines, many camps have opened with shorter schedules and fewer children. Others have shut down because of the hiring shortage. And many parents don’t feel comfortable sending their children because of the risk of Covid exposure.Fall is looking increasingly uncertain. Some workplaces have paused reopening plans because of Delta, and parents worry schools may follow. Certain companies, including McDonald’s, and states, like Illinois, are trying to get ahead of this by offering child care benefits to help parents get back to work. According to Bright Horizons, the employer-based child care company, 75 companies have started offering backup child care this calendar year and others, like PayPal, have extended their pandemic expanded benefits through this year.Parents also have questions about whether in-person school is still safe. Children have been at much lower risk of serious disease from Covid, and schools were not a major source of transmission last year. Scientists and doctors have said they should open, despite Delta. But there is not solid data on whether Delta affects children differently, and some schools have dropped mask mandates and distancing. Vaccines for children under 12 are expected by late fall or early winter, if all goes as planned.Ms. McCain said uncertainty about child care this fall is keeping her home: “I don’t know if my kid’s going to get pulled out of school for a quarantine or school’s going to stop.”Leah Nash for The New York TimesMost school districts are still saying they plan to open full time, without the shortened schedules many had last spring. And the five largest nationally have released reopening plans, according to the Center on Reinventing Public Education at the University of Washington, which has been tracking districts’ responses to the pandemic. But some plans are still sparse on details, and districts where union negotiations are still taking place have not been able to answer all of parents’ questions.“What we’ve been most surprised by this summer is the lack of publicly available clarity on what to expect,” said Bree Dusseault, who leads the data effort. “Families need to know so they can structure their lives.”Even parents in districts that have already announced reopening plans face uncertainty. Will there be child care before and after school, and extracurricular activities? Will families need to quarantine for two weeks when there are cases at schools? Could schools close again if cases continue to rise?For Alexis Lohse, a mother of two in St. Paul, Minn., Delta feels like one detour too many. She lived in poverty as a single mother. In her 30s, she went to college, the first in her family to do so, and earned a master’s degree. She got a job in state government, and just before the pandemic she had a chance at a long-awaited promotion.But when schools closed, she could not pursue it. She kept working, but put aside all advancement opportunities and reduced her hours. (Her husband, a letter carrier, couldn’t.) Now, her county is identified by the C.D.C. as at substantial risk level, and with school set to open right after large gatherings at the Minnesota State Fair, she’s skeptical that full-time school will happen.“I don’t know how I get back on track, especially with the questions out there — how schools reopen; when; variants; the way everybody else is behaving; having the schools open and close at bizarre random hours,” she said.She says the safety net she built for herself has been torn away: “I know how difficult it is and how lacking in infrastructure our country is in supporting parents. And it just feels so frustrating that the same brick walls I hit 16 years ago, I hit again in the pandemic.”Many parents of preschool-aged children face a shortage of child care openings. One-third of child care centers never reopened, research shows; those that are still closed disproportionately served Asian, Latino and Black families. Those that opened are operating at 70 percent capacity, on average. They have struggled to hire qualified teachers; must keep classes small to limit exposure to the virus; and have raised prices to cover new health and cleaning measures.Daphne Muller, a mother of two in Los Angeles and a consultant to tech companies, said she calls preschools almost every week to find out if there is room for her youngest: “I don’t feel like I can plan anything career-wise for myself. I don’t want to take a job and have to quit.”Parents must also plan for disruptions, like quarantine periods after exposures or when community case rates rise.Bee Thorp, a mother of two in Richmond, Va., said her children’s child care center closed three times last year for two weeks each, and also shortened its hours for cleaning. Her husband, a lawyer, had much less flexibility than she did, so the extra care fell to her.“What that has meant is me not really job searching,” she said. “I can’t ask in an interview: ‘Do you mind if I take off two weeks with no notice?’ It’s frustrating to hear comments about how people aren’t applying for jobs. Maybe people do want those jobs; they just can’t right now.”Other parents aren’t yet ready to send their unvaccinated children to school. Amy Kolev is a mother of three and a construction project manager in Glen Burnie, Md. When virtual school became too hard, she and her husband, a software programmer, decided she would quit. She is yearning to return, but won’t risk exposing her children.“I’m going to go back when my kids are vaccinated and not a day before,” she said.