Simply asking patients to get the flu vaccine, and combining it with helpful video and print messages, is enough to persuade many who visit emergency departments to roll up their sleeves, according to a new study led by UC San Francisco.
Researchers found a 32% vaccine uptake in patients who were asked if they’d be interested in getting the flu shot and told their health providers would be informed. They saw a 41% uptake for those who were asked about receiving a flu shot and received a pamphlet, watched a three-minute video of a physician with a similar ethnic background discussing the vaccine and were told about the benefits of the vaccine.
The study published March 26, 2024 in NEJM Evidence.
The researchers say this type of systematic approach could lead to more underserved people receiving vaccines, especially those whose primary health care occurs in emergency departments.
Flu can be fatal
Flu leads to considerable mortality in the United States — annual death rates are typically in the tens of thousands, especially when combined with pneumonia — but vaccination is particularly low among underserved populations and those whose primary care occurs in emergency departments. Such patients often face general vaccine hesitancy or a lack of opportunities for the flu shot.
“This research arose from our desire to address the health disparities that we see every day in our emergency department, especially among homeless persons, the uninsured and immigrant populations,” said first author, Robert M. Rodriguez, MD, a professor of Emergency Medicine with the UCSF School of Medicine.
Investigators in the study created flu vaccine messaging — including a brief video, flyer and a scripted health provider question, “Would you be willing to accept the influenza vaccine?” — and assessed their effectiveness among nearly 800 patients in five cities: San Francisco, Houston, Philadelphia, Seattle and Durham, North Carolina. The median age was 46. More than half the participants in the trial were Black or Latino, 16 % lacked health insurance, nearly a third had no primary care and 9% were homeless or living in severely inadequate housing. These demographic characteristics are similar to patient populations often served by urban emergency departments.
The researchers designed the clinical trial to span a single flu season between Oct. 2022 and Feb. 2023.
“Overall, our study adds to the growing body of knowledge showing that a number of important public health interventions can and should be delivered to underserved populations in emergency departments,” said Rodriguez, whose previous research has found the effectiveness of delivering similar COVID-19 vaccine messaging to emergency department patients.

A majority of the Supreme Court seemed inclined on Tuesday to reject a bid to sharply limit access to abortion pills.During about 90 minutes of argument, most of the justices seemed doubtful that the plaintiffs, who do not prescribe abortion pills or regularly treat abortion patients, even had standing to bring the challenge. The justices, including several in the conservative majority, questioned whether the plaintiffs could show that they faced the moral harm they claimed to suffer from the availability of the pill, mifepristone.The case centers on whether changes the Food and Drug Administration made in 2016 and 2021, which broadened access to the drug, would have to be rolled back.Those changes made it possible for patients to obtain prescriptions for mifepristone by telemedicine and receive abortion pills in the mail, which has greatly increased the availability of medication abortion.Several justices questioned the remedy the plaintiffs seek: to apply nationwide restrictions to the drug in a case that would have very broad implications because it would be the first time a court had second-guessed the F.D.A.’s regulatory authority.“This case seems like a prime example of turning what could be a small lawsuit into a nationwide legislative assembly on an F.D.A. rule or any other federal government action,” said Justice Neil Gorsuch, an appointee of President Donald J. Trump.We are having trouble retrieving the article content.Please enable JavaScript in your browser settings.Thank you for your patience while we verify access. If you are in Reader mode please exit and log into your Times account, or subscribe for all of The Times.Thank you for your patience while we verify access.Already a subscriber? Log in.Want all of The Times? Subscribe.

When the skeletal remains of a giant ground sloth were first unearthed in 1796, the discovery marked one of the earliest paleontological finds in American history.
The animal, named Megalonyx by Thomas Jefferson in 1799, was the first genus of fossil named from the United States. Thought to have roamed North America during one of the last ice ages, the extinct giant ground sloth was an herbivorous mammal resembling a large bear — at full size, it likely reached nearly 10 feet tall (3 meters) and weighed about as much as a small elephant.
The report made by Jefferson, an avid fossil collector who was known to keep bones at the White House, was among the earliest papers in the scientific field that would eventually become paleontology, and may have played a role in the development of certain zoological naming conventions.
Though Jefferson named only the genus Megalonyx, public misinterpretation of the spelling of the scientific name began with the second published paper on this giant ground sloth. Later on, confusion about the true author and timing of the report caused paleontologists to debate over what the specimen’s true name should be.
In an effort to settle the dispute, Loren Babcock, a professor of earth sciences at The Ohio State University, reviewed the nomenclatural history of the animal and argues that misinterpretation or spelling errors of the original harm the scientific process and disregard the importance of early paleontological work.
In an article published recently in the journal ZooKeys, Babcock asserts that since Jefferson fulfilled all the necessary requirements for establishing the formal zoological name of the giant ground sloth, he should be recognized as the true author of the genus. And because Jefferson’s original moniker was spelled as Megalonyx, any other subsequent spellings of the name, like some that utilize the -onix suffix, are incorrect. Additionally, the report notes that the original spelling of the animal’s species-group name, Megalonyx jeffersonii, is only correct when written with an -ii ending.
“At the time, there were no standards for publication of new names in zoology,” said Babcock. “There was a binomial system of nomenclature, a genus and species name that would be attached to things, but there were no rules other than that.”
Today, when a new species is discovered, scientists give it a name with two parts: The first name describes the animal’s genus, or group, and the second is its species name. Until the mid-1800s, it was common practice to label animals with only a genus name, which is how Jefferson’s original paper described Megalonyx. Although his observations were published more than a quarter century before paleontology was considered a formal science, it does meet modern naming requirements — meaning his authorship of it is valid, said Babcock.

“We have rules in science just like we do in other aspects of our culture,” said Babcock. “They ensure that the correct procedures are followed and we can give credit where it is due.”
Resolving some of these long-standing issues is important, Babcock said, and it’s worth setting the record straight. “I want to set the original usage in stone because Jefferson had done it correctly from the start,” said Babcock. “It’s pretty black and white. There’s not much room for ambiguity when you go back and read the original manuscripts.”
In the long run, having strict naming conventions also helps scientists accurately document the history of life on Earth, because what paleontologists choose to call a specimen can have profound implications for how it’s studied and how those findings are communicated.
Megalonyx jeffersonii, for instance, was initially mistaken as a carnivore when its “giant claw” was compared to that of a large African lion. Jefferson soon corrected this, but his initial observations of the giant ground sloth’s remains contributed to the way that Megalonyx would later be reconstructed and influenced some of the earliest developments of the discipline, and earned him the title of father of American paleontology, said Babcock.
Decades later, the first relatively complete skeleton of Megalonyx jeffersonii was found in 1890 in Holmes County, Ohio. “This skeleton has had a major impact on the history of science,” Babcock said. “It’s really influenced so much of the perception of paleontology and paleontological art over time.”
Asone of the earliest free-standing prehistoric specimens to be mounted and displayed in an American museum, it’s been used as a unique learning tool for past and future paleontologists alike. It was also a model that was later applied for dinosaur skeleton reconstructions, said Babcock. This popularity has led many other versions of Megalonyx jeffersonii to appear across digital media and pop culture throughout the past century, most notably in the “Ice Age” films as Sid the ground sloth.

Today, the reconstructed skeleton of Megalonyx jeffersonii resides in Ohio State’s Orton Geological Museum, where it has been on display since April 13, 1896. And for decades, it’s been known by many as simply “Jeff” for short.
Although few truly know all the details of its backstory, Babcock, who is the current director of the Orton Museum, remains confident that the legacy of Thomas Jefferson’s Megalonyx jeffersonii will stand tall for centuries to come.
“Understanding the history of paleontology casts light not just on the evolution of organisms, but on the evolution of science and how we interpret that evolutionary history,” he said. “So names are something that I think historians will always pay attention to.”

Researchers at Weill Cornell Medicine have discovered a protein called SEL1L that plays a critical role in clearing collagen from tissue, and which may be a therapeutic target to help prevent fibrosis, scar tissue that interferes with organ function. The paper, published on Feb. 20 in Nature Communications, provides clues that could lead to drug development for diseases like lung fibrosis which have no therapeutic options currently.
Corresponding author, Dr. Michael J. Podolsky, assistant professor of medicine at Weill Cornell Medicine, has led a team that searched the human genome for genes involved in the process that triggers specialized cells to engulf and digest excess collagen from tissue. Cells called fibroblasts and macrophages pick up collagen fragments for degradation in lysosomes, the trash compactors of cells.
Normal lungs continuously synthesize collagen and degrade excess collagen, keeping the two processes precisely balanced to maintain healthy tissue architecture. Even when lungs are injured and the body responds by increasing the rate of collagen production, simultaneously collagen degradation is increased to prevent the formation of permanent scar tissue. However, when the two processes are uncoupled, the result is disease. In pulmonary fibrosis, for instance, collagen degradation does not keep pace with collagen production, resulting in an excess accumulation.
The researchers discovered a mechanism that cells use to detect collagen production internally and regulate clearance of excess collagen in tissues. The protein SEL1L acts as a sensor that responds to collagen production by triggering another protein called MRC2 which is involved in the uptake and disposal of collagen.
This study suggests that a defective collagen clearing pathway based on MRC2 is a key part of the imbalance in fibrotic disease. The data show when SEL1L is overproduced in cells, it leads to increased MRC2 production and thereby prevents the accumulation of collagen. This pathway could eventually be therapeutically targeted to drive increased clearance of collagen to improve fibrosis when it is impaired. Next, Dr. Podolsky, who is also an attending physician at NewYork Presbyterian/Weill Cornell Medical Center, plans to investigate how SEL1L is impaired in fibrotic human lungs. The lab is also exploring the molecular consequences of when MRC2 is inadequately triggered in pulmonary fibrosis.
This research was supported in part by the National Institutes of Health grant K08 HL145015 and a Grant-in-aid from The Stony Wold-Herbert Fund.

By 2030, the World Health Organization (WHO), the Global Fund and UNAIDS are hoping to end the human immunodeficiency virus (HIV) and AIDS epidemic. An international team of researchers led by Eric Arts, professor at the Schulich School of Medicine & Dentistry, and Jamie Mann, senior lecturer at the University of Bristol (U.K.), has brought us another step closer to meeting this goal, by finding an effective and affordable targeted treatment strategy for an HIV cure.
In a first, the study published in the journal Emerging Microbes and Infections demonstrated the team’s patented therapeutic candidate, an HIV-virus-like-particle (HLP), is 100 times more effective than other candidate HIV cure therapeutics for people living with chronic HIV on combined antiretroviral therapy (cART). If successful in clinical trials, HLP could be used by millions of people living around the world to free them of HIV. This study was done using blood samples from people living with chronic HIV.
HLPs are dead HIV particles hosting a comprehensive set of HIV proteins that increase immune responses without infecting a person. When compared with other potential cure approaches, HLP is an affordable biotherapeutic and can be administered by intramuscular injection — similar to the seasonal flu vaccine.
“The development of this HIV cure was ten years in the making but with strong support from our collaborators in the U.S., Canada and Uganda, we have observed a striking ability of HLP to drive out the last remnants of HIV-1, which we hope will provide an affordable cure for all,” said Arts, who is a Canada Research Chair in HIV Pathogenesis and Viral Control. “To live HIV-free is a goal for the 39 million infected. It is also the priority of the UN and WHO to end the HIV pandemic by 2030.”
HIV is a retrovirus that attacks the body’s immune system and if left untreated, can lead to acquired immunodeficiency syndrome (AIDS). The virus weakens a person’s immune system by destroying CD4-T white blood cells, which are tasked with helping the immune system fight infections. Approximately 95 per cent of people living with HIV have chronic HIV — where the virus is slowly causing a slow destruction of the patients’ immune systems when they initiated lifelong cART.
While cART is effective at treating HIV, it has been unable to completely eliminate the virus from the body. This is because of the virus’ ability to create a “latent reservoir” — where it hides dormant inside of cells, safe from detection. Using blood samples from 32 participants living with chronic HIV from the U.S., Uganda and Canada, who were on stable cART for a median of approximately 13 years, researchers found that HLP was able to specifically target just the immune cells containing latent HIV reservoir and purge these cells of their HIV, a critical step towards an HIV-1 cure. An HIV cure is typically described as therapy and approach that eliminates all HIV without the need of continuous antiretroviral therapy.
“Over time, the virus grows more diverse within a single individual that is not on treatment which makes it more difficult to target,” said co-lead author Ryan Ho, master’s student in the department of microbiology and immunology. “This formulation we’ve crafted covers the theoretical diversity so it can reach the HIV-1 in all those people living with HIV.”
Minh Ha Ngo, lead author and postdoctoral scholar in the department of microbiology and immunology, says one concern expressed among people living with HIV for years is that continued use of cART could lead to the virus becoming unreachable and unable to be eliminated. The results of this study, by contrast, demonstrate that combining HLP with cART is still able to trigger the latent reservoir, even in chronic cases. If these dormant latent reservoirs can be awakened, then they can be eliminated from the body.

“Owing to its high mutation rate, HIV exhibits remarkable genetic diversity, resulting in different viral subtypes; some of which predominate in particular regions of the globe,” said Mann. “We were excited to see preliminary evidence that our HLP cure therapy reverses latency irrespective of the subtype of the individual’s infection. Whilst this needs to be explored further, it hints at the global applicability of our approach.”
In the future, researchers plan to test HLP on a larger representative HIV cohort with subtype C infections, which includes people living in South Africa, Ethiopia, Vietnam and India. This would help determine if the treatment strategy is effective for most people living with acute and chronic HIV.
Current studies involve confirming a lack of toxicity in preparation for human clinical trials.
These studies will be made possible with the advanced Pathogen Research Centre at Schulich Medicine & Dentistry. This study was conducted in collaboration with University of Bristol, University of Toronto, Case Western Reserve University, Rakai Health Sciences Program, Johns Hopkins University School of Medicine and the U.S. National Institutes of Health.
The study was funded by the American Foundation for AIDS Research, and by the Canadian Institutes of Health Research, U.S. National Institute of Allergy and Infectious Diseases; part of the National Institutes of Health, and the Canada Research Chairs Program.

A study by researchers at the UCLA Health Jonsson Comprehensive Cancer Center suggests that injecting engineered dendritic cells directly into cancerous lung tumors can help promote a stronger immune response, causing more T cells to become active and attack the cancer more effectively. When tested in mice with non-small cell lung cancer, the team discovered that combining this therapy with immune checkpoint blockade, a type of immunotherapy, made the treatment even more effective.
Immune checkpoint blockade has been revolutionary for treating patients with non-small cell lung cancer. However, the majority of patients with lung cancer do not benefit from the treatment, and many experience disease progression after an initial response. This can occur because the immune system doesn’t recognize the tumor as a threat or the environment around the tumor suppresses the immune response. Scientists have found that certain molecules called chemokines, specifically CXCL9 and CXCL10, play a crucial role in attracting immune cells, particularly activated T cells, to the tumor site. When these molecules are present in high amounts, they can help the immune system fight cancer more effectively.
To help enhance the effectiveness of immune checkpoint blockade, the UCLA team explored an approach called in situ vaccination with gene modified dendritic cells, which involves injecting immune-stimulating, chemokine gene-engineered dendritic cells directly into the tumor, which can boost the body’s immune response against cancer.
In this study, scientists genetically modified dendritic cells to produce CXCL9 and CXCL10 to help increase T cell infiltration and activation within the tumor. They then injected the modified dendritic cells directly into the tumors in mouse models of non-small cell lung cancer. They found that this approach increased the number and activity of T cells in the tumor and slowed down tumor growth in these models, even in cases where tumors were resistant to standard immunotherapy. Additionally, they observed that this therapy helped to establish a long-lasting immune response against the cancer. Studies analyzing genetic data from lung cancer patients suggest that the CXCL9/10-DC therapy could be particularly beneficial for patients with certain genetic characteristics associated with resistance to standard-of-care immunotherapy.
The results of the UCLA study suggest that using CXCL9 and CXCL10-producing dendritic cells alongside immunotherapy can be a promising strategy to overcome treatment resistance and improve clinical outcomes for patients with non-small cell lung cancer.

Brain development is a highly orchestrated process involving numerous parallel and sequential steps. Many of these steps depend on the activation of specific genes. A team led by Christian Mayer at the Max Planck Institute for Biological Intelligence discovered that a protein called MEIS2 plays a crucial role in this process: it activates genes necessary for the formation of inhibitory projection neurons. These neurons are vital for motion control and decision-making. A MEIS2 mutation, known from patients with severe intellectual disability, was found to disrupt these processes. The study provides valuable insights into brain development and consequences of genetic mutations.
Nerve cells are a prime example for interwoven family relations. The specialized cells that form the brain come in hundreds of different types, all of which develop from a limited set of generalized progenitor cells — their immature ‘parents’. During development, only a specific set of genes is activated in a single progenitor cell. The precise timing and combination of activated genes decide which developmental path the cell will take. In some cases, apparently identical precursor cells develop into strikingly different neurons. In others, different precursors give rise to the same nerve cell type.
The complexity is mind-blowing and not easy to disentangle in the lab. Christian Mayer and his team set out to do so nevertheless (Diversity research in the brain). Together with colleagues in Munich and Madrid, they now added another puzzle piece to our understanding of neuron development.
Inhibitory cell relations
The scientists studied the formation of inhibitory neurons that produce the neurotransmitter GABA — cells, which are known to display a broad range of diversity. In the adult brain, inhibitory neurons can act locally, or they can extend long-range axons to remote brain areas. Locally connected “interneurons” are an integral part of the cortical circuit, reciprocally linking cortical neurons. Long-range “projection neurons,” on the other hand, primarily populate subcortical regions. They contribute to motivated behavior, reward learning and decision-making. Both types, interneurons and projection neurons, originate in the same area of the developing brain. From here, the newborn neurons migrate to their final locations in the brain.
Using a barcoding approach, Christian Mayer and his team followed the family relationships between precursor cells and young inhibitory neurons. They discovered that a protein called MEIS2 plays an important role when a precursor cell ‘decides’ whether it should turn into an interneuron or into a projection neuron: MEIS2 assists the cellular machinery to activate the genes that are required for a precursor cell to become a projection neuron.
A protein with a far-reaching impact
To advance this development, MEIS2 works together with another protein, known as DLX5. When MEIS2 is missing or doesn’t function correctly, the development of projection neurons is stalled and a larger fraction of precursor cells turns into interneurons instead. However, MEIS2 can’t do the job by itself. “Our experiments show that MEIS2 and DLX5 have to come together at the same time, and in the same cells,” explains Christian Mayer. “Only the combination of the two will fully activate the genes that drive projection neuron development.”

The importance of this process is underscored by previous reports on a MEIS2 variant that was found in patients with intellectual disabilities and a delayed development. Due to a small change in the MEIS2 gene, a slightly different protein is produced. The team around Christian Mayer tested this MEIS2 variant in their experiments and found that it leads to a failure to induce the specific genes needed to form projection neurons. “The inability of MEIS2 to activate the genes essential for the formation of projection neurons may contribute to neurodevelopmental disorders, such as those observed in patients with mutations in the gene encoding this protein,” says Christian Mayer.
The complex control by genes
Intrigued by this discovery, the researchers delved into the mechanism by which MEIS2 activates projection neuron specific genes. “Patients with mutations in MEIS2 suffer from a diverse range of effects, like irregularities in digits, impaired lung to brain development, or intellectual disabilities. At a first look, these symptoms have nothing in common,” relates Christian Mayer. “This shows, how important it is to understand that genes often have very different roles in different parts of the body.”
The genome has millions of non-coding regulatory elements like enhancers, promoters, and insulators. These elements don’t actually code for proteins themselves, but they act like switches, controlling when and where genes turn on and off. “Enhancers, which are part of the genome, are like interpreters in the cell. If MEIS2 and DLX5 are present together, a specific set of enhancers becomes active. It is this specific set of enhancers that induces projection neuron genes in the brain. In other parts of the body, MEIS2 interacts with other proteins to induce different sets of enhancers,” explains Christian Mayer.
Recent large-scale whole exome sequencing studies in patients have provided a systematic and highly reliable identification of risk genes for neurodevelopmental disorders. Future studies focusing on the molecular interactions between the proteins encoded by these risk genes, such as MEIS2, will pave the way for a comprehensive understanding of the biological mechanisms underlying neurodevelopmental disorders.

An international research team led by RMIT University has designed and manufactured a virus-killing surface that could help control disease spread in hospitals, labs and other high-risk environments.
The surface made of silicon is covered in tiny nanospikes that skewer viruses on contact.
Lab tests with the hPIV-3 virus — which causes bronchitis, pneumonia and croup — showed 96% of the viruses were either ripped apart or damaged to the point where they could no longer replicate to cause infection.
These impressive results, featured on the cover of top nanoscience journal ACS Nano, show the material’s promise for helping control the transmission of potentially dangerous biological material in laboratories and healthcare environments.
Spike the viruses to kill them
Corresponding author Dr Natalie Borg, from RMIT’s School of Health and Biomedical Sciences, said this seemingly unsophisticated concept of skewering the virus required considerable technical expertise.
“Our virus-killing surface looks like a flat black mirror to the naked eye but actually has tiny spikes designed specifically to kill viruses,” she said.

“This material can be incorporated into commonly touched devices and surfaces to prevent viral spread and reduce the use of disinfectants.”
The nano spiked surfaces were manufactured at the Melbourne Centre for Nanofabrication, starting with a smooth silicon wafer, which is bombarded with ions to strategically remove material.
The result is a surface full of needles that are 2 nanometers thick — 30,000 times thinner than a human hair — and 290 nanometers high.
Specialists in antimicrobial surfaces
The team led by RMIT Distinguished Professor Elena Ivanova has years of experience studying mechanical methods for controlling pathogenic microorganisms inspired by the world of nature: the wings of insects such as dragonflies or cicadas have a nanoscale spiked structure that can pierce bacteria and fungi.
In this case, however, viruses are an order of magnitude smaller than bacteria so the needles must be correspondingly smaller if they are to have any effect on them.

The process by which viruses lose their infectious ability when they contact the nanostructured surface was analysed in theoretical and practical terms by the research team.
Researchers at Spain’s Universitat Rovira i Virgili (URV), Dr Vladimir Baulin and Dr Vassil Tzanov, computer simulated the interactions between the viruses and the needles.
RMIT researchers carried out a practical experimental analysis, exposing the virus to the nanostructured surface and observing the results at RMIT’s Microscopy and Microanalysis Facility.
The findings show the spike design to be extremely effective at damaging the virus’ external structure and piercing its membranes, incapacitating 96% of viruses that came into contact with the surface within six hours.
Study first author, Samson Mah, who completed the work under an RMIT-CSIRO Masters by Research Scholarship and has now progressed to working on his PhD research with the team, said he was inspired by the practical potential of the research.
“Implementing this cutting-edge technology in high-risk environments like laboratories or healthcare facilities, where exposure to hazardous biological materials is a concern, could significantly bolster containment measures against infectious diseases,” he said.
“By doing so, we aim to create safer environments for researchers, healthcare professionals, and patients alike.”
The project was a truly interdisciplinary and multi-institutional collaboration carried out over two years, involving researchers from RMIT, URV (Spain), CSIRO, Swinburne University, Monash University and the Kaiteki Institute (Japan).
This study was supported by the ARC Research Hub for Australian Steel Manufacturing and by the ARC Industrial Transformational Training Centre in Surface Engineering for Advanced Materials.

Researchers at the University of Leeds and Lancaster University in the UK have identified a new potential target for the treatment of Alzheimer’s disease — PDE4B.
Alzheimer’s disease is the leading cause of dementia and disability in old age. As the number of people diagnosed with Alzheimer’s disease is on the increase, new treatments are urgently needed to improve the quality of life for people living with the disease.
PDE4B is an enzyme inside cells that breaks down a molecule known as cyclic AMP, which regulates a range of cellular processes. Based on an Australian study that identified the PDE4B gene as a risk factor for developing Alzheimer’s disease, the UK team investigated whether reducing PDE4B activity might protect against Alzheimer’s disease pathology and be a useful treatment approach. To this end, they introduced a gene for reduced PDE4B activity into an Alzheimer’s disease (AD) mouse model that develops amyloid plaques in the brain, a key pathological feature of the disease.
The researchers observed that AD mice showed memory deficits in maze tests, but memory was unimpaired in AD mice with genetically reduced PDE4B activity. Using functional brain imaging, the team found the metabolism of glucose, the main source of energy in the brain, was impaired in AD mice, like that seen in patients with the disease. However, AD mice with genetically reduced PDE4B activity showed healthy levels of glucose metabolism in the brain.
To understand the mechanisms involved, the researchers next looked at gene and protein expression levels in the brain. This identified increased inflammation in the brains of AD mice, like that seen in Alzheimer’s disease patients, but inflammation was lower in AD mice with genetically reduced PDE4B activity. Similar effects were seen for a range of other proteins involved in Alzheimer’s disease pathology. Overall, these data suggest that reducing PDE4B activity might be a useful approach for the treatment of Alzheimer’s disease, although more research is needed to validate the use of drugs that target the enzyme.
Dr Steven Clapcote, the lead researcher, from the University of Leeds, said, “Reducing the activity of the PDE4B enzyme had a profound protective effect on memory and glucose metabolism in the AD mouse model, despite these mice showing no decrease in the number of amyloid plaques in the brain. This raises the prospect that reducing PDE4B activity may protect against cognitive impairment not only in Alzheimer’s disease but also in other forms of dementia, such as Huntington’s disease.”
Dr Neil Dawson, a co-author of the paper, from Lancaster University, echoed these sentiments: “These results offer real hope for the development of new treatments that will benefit patients with Alzheimer’s disease in the future. It was intriguing to find that reducing PDE4B activity by just 27% could dramatically rescue memory, brain function and inflammation in the AD mice. The next stage is to test whether PDE4B inhibiting drugs have similar beneficial effects in the AD mouse model, to test their potential efficacy in Alzheimer’s disease.”
The research was published in the Nature Portfolio journal Neuropsychopharmacology and was supported by the Dunhill Medical Trust, BBSRC, Alzheimer’s Research UK, and the Scientific and Technological Research Council of Turkey.

Our bodies can maintain body temperature in cold environments. However, the detailed mechanism remains unclear. Researchers from University of Tsukuba elucidated the molecular mechanism by which macrophages, a type of immune cells, control heat production in brown adipose tissue to increase the body temperature in response to cold.
Maintaining body temperature in cold environments is critical for survival. However, the detailed mechanisms remain elusive. The body employs two methods for heat production: shivering-mediated heat production by skeletal muscle and non-shivering thermogenesis by brown adipose tissue. The latter is particularly significant for long-term adaptation to cold.
Recently, researchers investigated the role of the transcription factor MAFB in macrophages — an immune cell type involved in non-shivering thermogenesis within brown adipose tissue. This tissue can generate heat to increase the body temperature in response to cold, primarily regulated by the sympathetic nervous system. Therefore, the researchers bred Mafb-deficient mice and exposed them to cold conditions, monitoring their body temperature changes. They found that heat production by brown adipose tissue was reduced in Mafb-deficient mice, leading to a decrease in body temperature. Additionally, the density of sympathetic nerve fibers in the brown adipose tissue of Mafb-deficient mice was notably lower than that in wild-type mice. Further analysis revealed that MAFB inhibits the expression of the inflammatory cytokine IL-6, consequently reducing the expression of nerve growth factor in brown adipose tissue and impairing the development of sympathetic nerve fibers. These results suggest that MAFB-mediated regulation of sympathetic nerve fiber density plays a key role in the thermogenic capacity of brown adipose tissue.
These findings contribute to a novel understanding of how body temperature maintenance is associated with macrophages, with potential implications for health preservation in cold climates and obesity treatment through enhanced energy expenditure.
This work was supported by the Ministry of Education and Sports of Japan (MEXT); the Ministry of Education, Culture, Sports, Science and Technology of Japan under grants No. 26221004, 25860205, 23118504, 16K18398, 19K07499, and 19H00966, 23K05586, 19K07499; the Uehara Memorial Foundation; the Takeda Science Foundation; the Takamatsunomiya Cancer Foundation under grant No. 15-24724 (M. Hamada); and the World Premier International Research Center Initiative (WPI), MEXT, Japan.