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People with depression have higher body temperatures, suggesting there could be a mental health benefit to lowering the temperatures of those with the disorder, a new UC San Francisco-led study found.
The study, publishing today in Scientific Reports, doesn’t indicate whether depression raises body temperature or a higher temperature causes depression. It’s also unknown whether the higher body temperature observed in people with depression reflects decreased ability to self-cool, increased generation of heat from metabolic processes or a combination of both.
Researchers analyzed data from more than 20,000 international participants who wore a device that measures body temperature, and also self-reported their body temperatures and depression symptoms daily. The seven-month study began in early 2020 and included data from 106 countries.
The results showed that with each increasing level of depression symptom severity, participants had higher body temperatures. The body temperature data also showed a trend toward higher depression scores in people whose temperatures had less fluctuation throughout a 24-hour period, but this finding didn’t reach significance.
The findings shed light on how a novel depression treatment method might work, said Ashley Mason, PhD, the study’s lead author and associate professor of psychiatry at UCSF Weill Institute for Neurosciences. A small body of existing, causal studies has found that using hot tubs or saunas can reduce depression, possibly by triggering the body to self-cool, for example, through sweating.
“Ironically, heating people up actually can lead to rebound body temperature lowering that lasts longer than simply cooling people down directly, as through an ice bath,” said Mason, who is also a clinical psychologist at the UCSF Osher Center for Integrative Health. “What if we can track the body temperature of people with depression to time heat-based treatments well?”
“To our knowledge, this is the largest study to date to examine the association between body temperature — assessed using both self-report methods and wearable sensors — and depressive symptoms in a geographically broad sample,” added Mason. “Given the climbing rates of depression in the United States, we’re excited by the possibilities of a new avenue for treatment.”

Published1 hour agoShareclose panelShare pageCopy linkAbout sharingImage source, BBC/Larissa TairoBy Larissa TairoBBC NewsA woman who discovered she had HIV after a routine health check is backing calls for more people to get tested.Becky, 37, from Sheffield, South Yorkshire, was diagnosed and treated shortly after transmission, with her HIV now undetectable.The UK Health Security Agency (UKHSA) said while the number of people taking a test had increased, it was still below pre-pandemic levels.It said there was “an urgent need” to improve the uptake of HIV testing.According to the latest available statistics, the overall number of HIV diagnoses in England rose by 6% from 2,313 in 2021 to 2,444 in 2022.The rise was caused by an increase in diagnoses among heterosexual people, a report showed. It saw a 14% rise within London and an 11% rise outside the capital. HIV Testing Week, which runs until Sunday, is a campaign by the Terrence Higgins Trust charity on behalf of the Office for Health Improvement and Disparities.Throughout the week, people can order a free HIV self-test which provides a result in 15 minutes.Becky told the BBC she began online dating after going through a divorce in 2015 and later discovered she had contracted HIV. “I didn’t even know HIV was an option,” she said.”People like to ask me if I was risky or unlucky – everyone with HIV is unlucky,” she said.She said a diagnosis so soon after she caught the virus enabled her to get the treatment she needed, with Becky recently giving birth to a healthy baby girl. “HIV campaigns were never targeted at me,” she said.”I knew nothing about it other than what I learned at school in the ’90s, which is that it kills you.”Becky works for Leeds Skyline, a branch of the Black Health Agency for Equality charity which provides HIV support services across Leeds, Wakefield, Manchester and Liverpool.She said many people still lack basic knowledge about the virus. “You can show someone all the science behind HIV and how being undetectable works,” she said.”There is a deep ingrained stigma people have and they don’t even know it.”Image source, Getty ImagesWhat is HIV?HIV stands for Human Immunodeficiency Virus – the immunodeficiency is the weakening of the immune system by the virusIf untreated it can lead to late-stage HIV or Aids, the name for a collection of illnesses caused by the virusMedication helping those with HIV to live long, healthy lives has been available for decadesModern medication reduces the viral load to undetectable levels, meaning someone can’t pass on HIV and their health is protectedSources: Terrence Higgins Trust and NHSAkhona, a 44-year-old Leeds Skyline volunteer, was diagnosed in 2016 and said she still faced discrimination despite her HIV being undetectable.Her former housemates asked her to eat from different tableware and use a different fridge, she recalled.”Even back then I understood they lacked knowledge about HIV,” she said. “But it is very depressing”.While dating, she said a date was scared to talk to her in fear of catching HIV after she disclosed her status. She said experiences like these had made her feel isolated. “The only time I deal with HIV is when I take my medication and when other people remind me that I have it,” she said.Image source, BBC/Larissa TairoAkhona decided to become an HIV awareness advocate and regularly holds talks aiming to help end HIV discrimination. Aydin Djemal, Black Health Agency for Equality’s chief executive officer, said a lot of people they see “lack adequate knowledge” of HIV.”People do not tend to understand HIV generally, or how HIV will affect them specifically, and that’s what we would like to start chipping away at,” he said.The most recent government figures show the number of people having an HIV test in sexual health services rose by 10% in 2022, but it was still 15% lower than in 2019.HIV testing levels among heterosexual men and women remained lower than those observed in 2019, the figures show.Mr Djemal said he would like to see more heterosexual men engaging with their services.”There could be 101 reasons why people do not test, what we see is that men tend to wait longer to seek help,” he said.Follow BBC Yorkshire on Facebook, X (formerly Twitter) and Instagram. Send your story ideas to yorkslincs.news@bbc.co.ukMore on this storyHIV blood tests to be rolled out to more hospitalsPublished29 November 2023’HIV home tests can help remove stigma’Published6 February 2023Free DIY home HIV tests offered in EnglandPublished6 February 2023Get tested more, urges sexual health charityPublished5 October 2022Related Internet LinksIt Starts With MeHome – Challenging inequality in Health care │ BHA for EqualityUK Health Security Agency – GOV.UKHome – Terrence Higgins TrustThe BBC is not responsible for the content of external sites.

A recent re-emergence and outbreak of Mpox brought poxviruses back as a public health threat, underlining an important knowledge gap at their core. Now, a team of researchers from the Institute of Science and Technology Austria (ISTA) lifted the mysteries of poxviral core architecture by combining various cryo-electron microscopy techniques with molecular modeling. The findings, published in Nature Structural & Molecular Biology, could facilitate future research on therapeutics targeting the poxvirus core.
Variola virus, the most notorious poxvirus and one of the deadliest viruses to have afflicted humans, wreaked havoc by causing smallpox until it was eradicated in 1980. The eradication succeeded thanks to an extensive vaccination campaign using another poxvirus, the aptly named Vaccinia virus. The 2022-2023 re-emergence and outbreak of Mpox virus reminded us once more that viruses find ways to return to the forefront as public health threats. Importantly, this has highlighted the fundamental questions about poxviruses that have remained unanswered to this day.
One such fundamental question lies, quite literally, at the core of the matter: “We know that for poxviruses to be infective, their viral core must be properly formed. But what is this poxviral core made of, and how do its individual components come together and function?” asks ISTA Assistant Professor Florian Schur, the corresponding author of the study. Schur and his team now put their finger on the missing link: a protein called A10. Interestingly, A10 is common to all clinically relevant poxviruses. In addition, the researchers found that A10 acts as one of the main building blocks of the poxviral core. This knowledge could be instrumental for future research on therapeutics targeting the poxviral core.
“The most advanced cryo-EM techniques available today”
The viral core is one of the factors common to all infectious poxvirus forms. “Previous experiments in virology, biochemistry, and genetics suggested several core protein candidates for poxviruses, but there were no experimentally-derived structures available,” says ISTA PhD student Julia Datler, one of the co-first authors of the study. Thus, the team started by computationally predicting models of the main core protein candidates, using the now-famous AI-based molecular modeling tool AlphaFold. In parallel, Datler was setting the project’s biochemical and structural foundations by drawing on her background in virology and the Schur group’s main expertise: cryogenic electron microscopy, or cryo-EM for short. “We integrated many of the most advanced cryo-EM techniques available today with AlphaFold molecular modeling. This gave us, for the first time, a detailed overall view of the poxviral core-the ‘safe’ or ‘bioreactor’ inside the virus that encloses the viral genome and releases it in infected cells,” says Schur. “It was a bit of a gamble, but we eventually managed to find the right mix of techniques to examine this complex question,” says postdoc Jesse Hansen, the study’s co-first author whose expertise in various structural biology techniques and image processing methods was pivotal for the project.
A global 3D view of the poxvirus
The ISTA researchers examined “live” Vaccinia virus mature virions and purified poxviral cores under every possible angle-quite literally. “We combined the ‘classic’ single-particle cryo-EM, cryo-electron tomography, subtomogram averaging, and AlphaFold analysis to gain an overall view of the poxviral core,” says Datler. With cryo-electron tomography, researchers can reconstitute 3D volumes of a biological sample as large as an entire virus by acquiring images while gradually tilting the sample. “It’s like doing a CT scan of the virus,” says Hansen. “Cryo-electron tomography, our lab’s ‘specialty,’ allowed us to gain nanometer-level resolutions of the whole virus, its core, and interior,” says Schur. In addition, the researchers could fit the AlphaFold models into the observed shapes like a puzzle and identify molecules that make up the poxviral core. Among these, the core protein candidate A10 stood out as one of the major components. “We found that A10 defines key structural elements of the core of poxviruses,” says Datler. Schur adds, “These findings are a great resource to interpret bits of structural and virological data generated over the last decades.”
A rugged path to uncovering poxviral cores
The path to these findings was all but straightforward. “We needed to find our own way from the start,” says Datler. Leveraging her expertise in biochemistry, virology, and structural biology, Datler isolated, propagated, and purified samples of Vaccinia virus and established the protocols to purify the complete viral core, all while optimizing these samples for structural studies. “Structurally, it was extremely hard to study these virus cores. But luckily, our perseverance and optimism paid off,” says Hansen.
The ISTA researchers are convinced that their findings could provide a knowledge platform for future therapeutics that seek to target poxviral cores. “For example, one could think of drugs that prevent the core from assembling — or even disassembling and releasing the viral DNA during infection. Ultimately, fundamental virus research, as done here, allows us to be better prepared against possible future viral outbreaks,” concludes Schur.

The new weight loss medication tirzepatide significantly lowered the systolic blood pressure (the top number in a blood pressure reading) for nearly 500 adults with obesity who took the medication for about eight months, according to new research published today in Hypertension, an American Heart Association journal.
Systolic blood pressure, or the top number in the blood pressure reading, is a stronger predictor for cardiovascular death than diastolic, or bottom number, blood pressure. According to the American Heart Association’s 2024 Heart Disease and Stroke Statistics, more than 122 million adults in the United States, or 47% of adults have hypertension, and nearly 42% of adults have obesity.
Tirzepatide works by mimicking two metabolic hormones in the body: it acts as a glucagon-like peptide-1 (GLP-1) receptor agonist and also as a glucose dependent insulinotropic polypeptide (GIP) receptor agonist. These hormones stimulate insulin secretion and sensitivity after a person eats. Together, they have been found so far to help regulate the body’s blood sugar levels, slow down digestion and reduce appetite, which makes a person feel more full and eat less, leading to weight loss. In contrast, semaglutide has only the GLP-1 hormone; it does not contain a GIP receptor agonist.
In 2022, the Food and Drug Administration approved tirzepatide for prescription as a treatment for Type 2 diabetes. In late 2023, the FDA also approved it for chronic weight management for people with obesity (body mass index of 30 kg/m2 or higher) or overweight (body mass index of 27-29 kg/m2) and at least one weight-related health condition, such as high blood pressure, Type 2 diabetes or high cholesterol.
“Our findings indicate treating obesity with the weight loss medication tirzepatide may be an effective strategy for preventing or treating high blood pressure,” said lead study author James A. de Lemos, M.D., FAHA, the Kern Wildenthal, M.D., Ph.D., distinguished chair of cardiology and a professor of medicine at UT Southwestern Medical Center in Dallas. “Although tirzepatide has been studied as a weight loss medication, the blood pressure reduction in our patients in this study was impressive. While it is not known if the impact on blood pressure was due to the medication or the participants’ weight loss, the lower blood pressure measures seen with tirzepatide rivaled what is seen for many hypertension medications.”
The current research was a planned sub-study including 600 of the participants from the SURMOUNT-1 weight loss study to determine if there was an effect on blood pressure. The sub-study was designed to assess the effects of tirzepatide on blood pressure levels as measured by 24-hour ambulatory blood pressure monitoring in people with obesity but without Type 2 diabetes.
Participants received either a placebo or a dose of tirzepatide in one of three strengths (5 mg, 10 mg or 15 mg). About one-third of participants reported they had high blood pressure at the beginning of the study and were taking one or more hypertension medications. When the sub-study began, all of the participants had blood pressure levels that were less than 140/90 mm Hg, and if they used blood pressure medications, they were required to have been taking their blood pressure medications for at least three months. The sub-study included participants who had hypertension and who had normal blood pressure.

The study was conducted from December 2019 to April 2022, and the participant results after 36 weeks of taking tirzepatide indicate: For participants taking 5 mg of tirzepatide, there was an average reduction in systolic blood pressure of 7.4 mm Hg. For participants taking 10 mg of tirzepatide, there was an average reduction in systolic blood pressure of 10.6 mmHg. For participants taking 15 mg of tirzepatide, there was an average reduction in systolic blood pressure of 8.0 mm Hg. The blood-pressure lowering effects of tirzepatide were evident in blood pressure measures taken during both the day and night. Nighttime systolic blood pressure is a stronger predictor for cardiovascular death and all-cause death than daytime blood pressure readings.The reductions in systolic blood pressure were consistent across subgroups of participants in the study who were categorized by additional factors, including age, sex, body mass index and hypertension-related risk factors.
Study background and details: SURMOUNT-1 was a randomized study on the effect of increasing doses of tirzepatide on weight loss. It found that in participants with overweight or obesity (body mass index (BMI) ≥27 kg/m2), once-weekly injections of 5 mg, 10 mg or 15 mg of tirzepatide led to mean weight reductions of 15%, 19.5% and 20.9%, respectively, compared to placebo. The sub-study included 600 adults from SURMOUNT-1: 155 participants received placebo; 145 were taking tirzepatide 5 mg; 152 were taking tirzepatide 10 mg; and 148 were taking tirzepatide 15 mg. Blood pressure measurements were available and analyzed for 494 participants who valid ambulatory blood pressure monitoring data at the beginning of the study and at week 36. Only the study participants with at least 70% valid readings on ambulatory monitoring and a minimum of 20 daytime and seven nighttime readings were included in the data analyses. This was 494 out of 600 initial participants. 69% of study participants self-identified as female, and 31% self-identified as male. 66.8% self-identified as white adults, 11.8% self-identified as Black adults and 25% self-identified as Hispanic ethnicity. The average age of the participants was 45.5 years, and their average BMI was 37.4 kg/m2, which meets the criteria for obesity (obesity is BMI≥30). People with obesity have an increased risk of high blood pressure, heart disease, stroke and Type 2 diabetes, as well as other health conditions. Ambulatory blood pressure monitoring used in this study included blood pressure measurements every 30 minutes during the day and every hour at night, providing a more comprehensive assessment of blood pressure than in office or daily home blood pressure measurements. For ambulatory blood pressure monitoring, study participants wore a blood pressure monitoring device for a 24- to 27-hour period that measured blood pressure throughout waking and sleeping hours. Ambulatory blood pressure monitoring was conducted when participants first began taking tirzepatide at the start of the study and after 36 weeks of being enrolled in the study.The 2017 ACC/AHA Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults classifies hypertension, or high blood pressure, as having top and bottom blood pressure measures greater than or equal to 130/80 mm Hg.
Study limitations include that it was only conducted in a subset of the original 2,539 SURMOUNT-1 participants; the ambulatory blood pressure monitoring was only measured at two points in the study — baseline and at 36 weeks; and measurements were only taken once per hour at night to minimize the burden on study participants. In addition, changes in food intake and 24-hour urine sodium excretion were not assessed, meaning the contribution of dietary modifications including salt intake or other changes that may help to reduce blood pressure are unknown and cannot be estimated.
“Overall, these data are encouraging that novel weight-loss medications are effective at reducing body weight and they are also effective at improving many of the cardiometabolic complications of obesity including hypertension, Type 2 diabetes and dyslipidemia, among others. While the impact of each of these beneficial effects is individually important, many of these obesity-related complications act synergistically to increase the risk of cardiovascular disease. Thus, strategies that mitigate multiple obesity-related complications may reduce the risk of cardiovascular events,” said Michael E. Hall, M.D., M.S., FAHA, chair of the writing group for the Association’s 2021 scientific statement on weight-loss strategies for prevention and treatment of hypertension and chair of the department of medicine at the University of Mississippi Medical Center in Jackson, Mississippi.
“Additional studies will be necessary to determine the long-term impact on cardiovascular events such as heart attack and heart failure. Also, studies are needed to investigate what happens to blood pressure when medications like tirzepatide are discontinued — does the blood pressure rebound and go back up, or does it remain lowered?” Hall concluded.
The study was funded by Eli Lilly and Company, the manufacturer of tirzepatide.

Researchers from Queen Mary University of London have found that the molecule RvT4 enhances the body’s natural defences against atherosclerosis (hardening of the arteries) in patients with rheumatoid arthritis.
Studies in mice undertaken by researchers from Queen Mary University of London’s William Harvey Research Institute and Centre for Inflammation and Therapeutic Innovation, and funded by the European Research Council (ERC) and Barts Charity, shows that increasing levels of the RvT4 molecule in the body improves the ability of the body’s own defence mechanisms [macrophages] to reduce local inflammation and remove blockages in blood vessels. This breakthrough in understanding the processes involved could lead to better treatments for people who have rheumatoid arthritis (RA), and who are at higher risk of developing cardiovascular disease.
Rheumatoid arthritis (RA) is the most common form of inflammatory arthritis in the UK and affects around 1% of the population. Approximately 10,000 people receive a diagnosis of RA every year. Alongside the more widely-known symptoms of joint inflammation, people with the condition are also twice as likely as others to develop blood vessel disease. This can lead to serious complications and an increased risk of premature death.
One type of blood vessel disease seen in people with RA is atherosclerosis, which is caused by a build-up of fatty material called ‘plaque’ along the artery walls. This build-up causes the arteries to harden and narrow, making it more difficult to circulate blood around the body. These blockages can also break free, causing heart attacks and strokes. Understanding the reasons why RA patients are at increased risk of these cardiovascular problems is critical in developing better treatments for this group and others.
To gain a better understanding of the causes of blood vessel disease in patients with RA, researchers explored the role of a group of molecules called 13-series resolvins (RvTs). In experimental arthritis the levels of one of these molecules, RvT4, are markedly reduced, a phenomenon that associates with a higher degree of blood vessel disease. This study was designed to explore why this might be the case.
The findings
The study found that treating arthritic mice with RvT4 reduced blood vessel inflammation by re-programming macrophages — a group of white blood cells that accumulate in the diseased vessels — to release stored lipids. Researchers observed that these lipids were preventing the macrophage from carrying out their usual work of clearing dead cells and reducing localised inflammation in blood vessels. Once freed of their lipid burden, the macrophages were able to move and work much more effectively to reduce the causes of atherosclerosis. The observation that RvT4 restores protective macrophage biological activities is an exciting finding.

RA patients also often present with metabolic dysfunction and this is thought to exacerbate vascular disease. The study found that administration of RvT4 to mice engineered to develop characteristics of metabolic dysfunction, advanced atherosclerosis, and arthritis led to an overall decrease in lipoprotein-associated cholesterol in plasma and an increase in the ratio of HDL-associated cholesterol to total cholesterol.
Jesmond Dalli, Professor in Molecular Pharmacology and Lipid Mediator Unit Director at the William Harvey Institute, Queen Mary University of London, said: “The study is important because it identifies for the first time the loss of RvT4 production as a potential new cause of blood vessel inflammation in the context of arthritis, offering a mechanistic explanation on the cause of this important disease in RA patients. It also showed that RvT4 restores the biological activities of lipid loaded macrophages by promoting lipid breakdown and efflux from the cells, an observation that can guide the development of new treatments to limit the incidence and/or severity of cardiovascular disease in patients with RA.”
Victoria King, Director of Funding and Impact at Barts Charity said: “This exciting new discovery helps to explain why certain patients with rheumatoid arthritis are more likely to develop blood vessel disease. This could pave the way for the development of new treatments for these patients to help them live longer and healthier lives.”
Dysregulation of macrophage biological responses by lipid accumulation is also involved in the onset and development of many other conditions, including obesity. Medicines derived from RvT4 or RvT4-based compounds may therefore be useful to limit inflammation and promote the release of accumulated lipids out of macrophages in patients with a number of other medical conditions.

For years, there has been a long-held belief that acute viral infections like Zika or COVID-19 are directly responsible for neurological damage, but researchers from McMaster University have now discovered that it’s the immune system’s response that is behind it.
The research, published on Feb. 5, 2024 in Nature Communications, was led by Elizabeth Balint, a PhD student at McMaster, and Ali Ashkar, a professor with the Department of Medicine and the Canada Research Chair in Natural Immunity and NK Cell Function.
“We were interested in trying to understand why so many viral infections are associated with neurological diseases,” says Balint. “Our evidence suggests that it’s not the virus itself that causes the damage, but a unique population of T cells, which are part of the immune system, that are actually responsible for the damage.”
To come to this conclusion, the McMaster team focused on Zika virus. During laboratory testing, researchers, as expected, found T cells that were specific for Zika and designed to eliminate infected cells. They found something else, too.
“What was interesting in our study is that although we did find some T cells specific for Zika, we identified cells that weren’t functioning like a normal T cell and were killing lots of cells that weren’t infected with Zika.”
These cells are called NKG2D+CD8+ T cells and researchers say their aggressive response is responsible for neurological damage suffered from infections beyond just Zika, like COVID-19 and even septic shock.
The aggressive response is the result of the body producing large amounts of inflammatory proteins called cytokines, which in moderation help to coordinate the body’s response in battling an infection or injury by telling immune cells where to go and what to do when they arrive.

“If our body’s immune cells overreact and over produce inflammatory cytokines, this condition will lead to non-specific activation of our immune cells which in turn leads to collateral damage. This can have severe consequences if it happens in the brain,” Ashkar says.
The discovery offers researchers and scientists a new target for treatments of neurological diseases sparked by acute viral infections. In fact, Balint has already found a treatment that holds promise.
“Elizabeth has experimented with an antibody that can completely block and treat devastating neurotoxicity in the animal model, which is already in clinical trials for different uses in humans,” says Ashkar.
Balint hopes to continue her work towards finding a treatment that would be effective in humans.
“There are a few different other viruses we’re interested in studying, which will aid us in creating the best treatment options,” Balint says.
Funding for this study was provided by the Canadian Institutes of Health Research. Balint is also a recipient of a Canada Graduate Scholarship Doctoral Award.

A new computer program allows scientists to design synthetic DNA segments that indicate, in real time, the state of cells. Reported by the Gargiulo lab in “Nature Communications,” it will be used to screen for anti-cancer or viral infections drugs, or to improve gene and cell-based immunotherapies.
All the cells in our body have the same genetic code, and yet they can differ in their identities, functions and disease states. Telling one cell apart from another in a simple manner, in real time, would prove invaluable for scientists trying to understand inflammation, infections or cancers. Now, scientists at the Max Delbrück Center have created an algorithm that can design such tools that reveal the identity and state of cells using segments of DNA called “synthetic locus control regions” (sLCRs). They can be used in a variety of biological systems. The findings, by the lab of Dr Gaetano Gargiulo, head of the Molecular Oncology Lab, are reported in Nature Communications.
“This algorithm enables us to create precise DNA tools for marking and studying cells, offering new insights into cellular behaviors,” says Gargiulo, senior author of the study. “We hope this research opens doors to a more straightforward and scalable way of understanding and manipulating cells.”
This effort began when Dr Carlos Company, a former graduate student at the Gargiulo lab and co-first author of the study, started to invest energy into making the design of the DNA tools automated and accessible to other scientists. He coded an algorithm that can generate tools to understand basic cellular processes as well as disease processes such as cancers, inflammation and infections.
“This tool allows researchers to examine the way cells transform from one type to another. It is particularly innovative because it compiles all the crucial instructions that direct these changes into a simple synthetic DNA sequence. In turn, this simplifies studying complex cellular behaviors in important areas like cancer research and human development,” says Company.
Algorithm to make a tailored DNA tool
The computer program is named “logical design of synthetic cis-regulatory DNA” (LSD). The researchers input the known genes and transcription factors associated with the specific cell states they want to study, and the program uses this to identify DNA segments (promoters and enhancers) controlling the activity in the cell of interest. This information is sufficient to discover functional sequences, and scientists do not have to know the precise genetic or molecular reason behind a cell’s behavior; they just have to construct the sLCR.

The program looks within the genomes of either humans or mouse to find places where transcription factors are highly likely to bind, says Yuliia Dramaretska, a graduate student at the Gargiulo lab and co-first author. It spits out a list of 150-basepair long sequences that are relevant, and which likely act as the active promoters and enhancers for the condition being studied.
“It’s not giving a random list of those regions, obviously,” she says. “The algorithm is actually ranking them and finding the segments that will most efficiently represent the phenotype you want to study.”
Like a lamp inside the cells
Scientists can then make a tool, called a “synthetic locus control region” (sLCR), which includes the generated sequence followed by a DNA segment encoding a fluorescent protein. “The sLCRs are like an automated lamp that you can put inside of the cells. This lamp switches on only under the conditions you want to study,” says Dr Michela Serresi, a researcher at the Gargiulo lab and co-first author. The color of the “lamp” can be varied to match different states of interest, so that scientists can look under a fluorescence microscope and immediately know the state of each cell from its color. “We can follow with our eyes the color in a petri dish when we give a treatment,” Serresi says.
The scientists have validated the utility of the computer program by using it to screen for drugs in SARS-CoV-2 infected cells, as published last year in “Science Advances.” They also used it to find mechanisms implicated in brain cancers called glioblastomas, where no single treatment works. “In order to find treatment combinations that work for specific cell states in glioblastomas, you not only need to understand what defines these cell states, but you also need to see them as they arise,” says Dr Matthias Jürgen Schmitt, the researcher at the Gargiulo lab and co-first author, who used the tools in the lab to showcase their value.
Now, imagine immune cells engineered in the lab as a gene therapy to kill a type of cancer. When infused into the patient, not all these cells will work as intended. Some will be potent and while others may be in a dysfunctional state. Funded by an European Research Council grant, the Gargiulo lab will be using this system to study the behavior of these delicate anti-cancer cell-based therapeutics during manufacturing. “With the right collaborations, this method holds potential for advancing treatments in areas like cancer, viral infections, and immunotherapies,” Gargiulo says.

Virus family history could help scientists identify which strains have potential to become the so-called Disease X that causes the next global pandemic.
A study has identified 70 virus lineages — groups of related viruses — that pose the biggest risk. Viruses from other genetic backgrounds are unlikely to cause a high number of infections in humans, the research shows.
The findings will support ongoing efforts to monitor and prepare for future pandemics, including guiding vaccine and diagnostic development, experts say.
Disease X is the generic term used by the World Health Organization to represent a hypothetical, unidentified pathogen that could pose a significant threat to people.
RNA viruses carry their genetic information as RNA, a structure similar to DNA. They cause many diseases, including the common cold, Covid-19 and measles, and have been responsible for most epidemics, or global pandemics, in recent history.
Monitoring RNA viruses in animal populations could help to identify those that are most likely to emerge and spread rapidly in humans. However, the huge number in circulation makes this extremely challenging and expensive.
The University of Edinburgh-led research team traced the lineage, or family tree, of 743 distinct RNA virus species to track how they evolved, including all species currently known to infect humans.

Researchers compared the development of strictly zoonotic viruses — those that spread from animals to humans, but not between people — with human-transmissible viruses, which can spread within human populations.
The findings showed that viruses that can spread within human populations typically evolve separately from strictly zoonotic viruses.
Human-transmissible viruses often emerge when related viruses from the same lineage can already spread between humans.
Strictly zoonotic viruses have historically not led to epidemics in human populations. Having a close relative that can infect humans, but not spread between them, does not appear to increase the risk of epidemic potential.
The research team caution that there is still a chance the next pandemic could come as the result of a strictly zoonotic virus — such as bird flu — or an entirely new virus. However, the findings offer a route to help streamline surveillance for Disease X among the vast number of RNA viruses in existence.
The study is published in the journal Molecular Biology and Evolution. The research team included scientists from the Universities of Edinburgh and Liverpool and Peking University in China. The study was funded by the EU Horizon 2020 programme and the BBSRC.
Professor Mark Woolhouse, Professor of Infectious Disease Epidemiology at the University of Edinburgh, said: “Viruses without the right ancestry don’t seem to cause epidemics. Out of potentially huge numbers of mammal and bird viruses in circulation, we should concentrate on the ones that are related to existing human viruses with epidemic potential. This research narrows the search for the next Disease X enormously.”

The research team investigated the four extracellular matrix proteins Brevican, Neurocan, Tenascin-C and Tenascin-R, which occur in the cell environment of nerve cells of the retina. “Their precise role in the retina has not yet been sufficiently investigated,” explains Jacqueline Reinhard-Recht. The researchers therefore studied the visual function of so-called knockout mice, which were genetically modified in such a way that their bodies could not produce the four mentioned proteins.
Through electroretinogram analyses, the research team was able to show that rod photoreceptors and bipolar cells in the knockout mice exhibit functional deficits in visual processing. “Interestingly, we were also able to find significant limitations in visual movement processing in the knockout mice compared to control animals,” says Jacqueline Reinhard-Recht. Mice lacking only the proteins tenascin-C or tenascin-R also display losses in visual motion processing, but much weaker. “This shows that the cumulative loss of four matrix proteins reinforces optomotor limitations,” says the researcher.
Matrix remodeling and imbalance in synaptic signaling
Studies on the retina of knockout mice also revealed changes in various matrix molecules and synapses. “In particular, there was an imbalance of inhibitory and excitatory synapses,” says Jacqueline Reinhard-Recht. “Overall, the research data indicate that the four matrix proteins Brevican, Neurocan, Tenascin-C and Tenascin-R are important modulators of synaptic signaling in the retina.”
“The research data contribute to a much better understanding of the complex molecular mechanisms of visual processing. In the future, these findings could offer new approaches for the development of therapeutic interventions for visual function disorders.”

Football players (and anyone else who takes hard hits) may want to breathe a sigh of relief.
In recent research, engineers at the University of Colorado of Boulder and Sandia National Laboratories have developed a new design for padding that can withstand big impacts. The team’s innovations, which can be printed on commercially available 3D printers, could one day wind up in everything from shipping crates to football pads — anything that helps to protect fragile objects, or bodies, from the bumps of life.
The team described the technology in January in the journal “Advanced Materials Technologies.”
“Impact mitigation is something that’s important everywhere,” said Robert MacCurdy, corresponding author of the study and assistant professor in the Paul M. Rady Department of Mechanical Engineering at CU Boulder. “It’s in highway crash barriers, knee pads and elbow pads, and in packaging equipment.”
The research takes a fresh look at something most people encounter all the time but rarely notice: foams. They’re squishy materials filled with countless tiny holes and channels. Picture packing peanuts or stress balls. MacCurdy said that foams can be good at absorbing blows, but they have a major drawback: If you squeeze a foam hard enough, it will eventually compress down into a rigid wad.
He and his colleagues think they can do better.
In the new study, the group wrote computer algorithms to meticulously redesign the interior of cushioning materials — allowing them to buckle under force, but only following a careful pattern. When the group put their designs to the test in the lab, they discovered that their padding could absorb as much as 25% more force than current state-of-the-art technologies.

“The material you use for absorbing impacts matters,” MacCurdy said. “But what really matters is the geometry.”
Zooming in
To understand why some cushions work well, and others don’t, it helps to look deep inside.
What gives a foam its spring, for example, are all those little nooks and crannies. When you squeeze a sponge, MacCurdy explained, those empty spaces will begin to close up, which, in turn, absorbs energy.
Some engineers have moved beyond that basic design. Instead, they make padding out of a network of hexagonal towers, or “plate lattices,” that look a bit like honeycombs. If a linebacker, perhaps, crashes into this kind of cushion, the impact will cause the honeycombs to collapse in a wave-like pattern. That’s a more efficient way to absorb forces.
But, MacCurdy noted, researchers have long strived for padding that meets a gold standard — technology that doesn’t just absorb a lot of force, but can also absorb many different kinds of forces with the same finesse.

“If you’re riding your bike and get into a crash, you don’t know if that’s going to be a low-speed impact or a high-speed impact. But regardless, you expect your helmet to perform well,” he said. “We’re trying to develop a geometry that performs well under all of those scenarios.”
Giving the squeeze
To make a more versatile cushion, the engineer and his colleagues opted to rearrange the interior of these objects, down to the scale of a millimeter or less.
The group first used custom software to lay out a network of honeycombs, then tweaked them to include a few kinks, a bit like the bellows in an accordion. Those kinks help to guide the honeycombs as they crunch down during an impact, allowing for a much smoother collapse.
“The moment you start to compress these structures, they absorb a certain amount of force,” MacCurdy said. “The best absorber designs maintain a constant force across the whole range of compression.”
In other words, unlike a foam, these cushions will behave the same no matter how much you squish them down — or, at least, up to a certain maximum.
The researchers also wanted to make sure their padding could stand up to bumps and bruises in the real world. They used a 3D printer to create blocks the size of a small brick out of a springy material called thermoplastic polyurethane. Then they squeezed them with an impact-testing machine.
The group discovered that its blocks could absorb roughly six times more energy than standard foams made out of the same material, and up to 25% more than other honeycomb designs. MacCurdy and his colleagues are currently working to improve on their structures even further. He added that engineers can make these kinds of designs out of many different types of materials, from bouncy plastics to harder substances like aluminum.
The world, in other words, could soon be a much softer place.