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Published10 hours agocommentsCommentsShareclose panelShare pageCopy linkAbout sharingImage source, Getty ImagesBy Kate Whannel & Sam FrancisPolitical reporters, BBC NewsMPs have backed a plan to ban anyone born after 2009 from buying cigarettes, effectively ensuring it will become law.The measures, championed by Prime Minister Rishi Sunak, survived despite opposition from several leading Tory figures – including two ex-PMs.Health Secretary Victoria Atkins told MPs “there is no liberty in addiction” as she defended the plans.The Tobacco and Vapes Bill passed by 383 votes to 67.If they become law, the UK’s smoking laws will be among the strictest in the world.The UK’s approach is thought to have been inspired by a similar law in New Zealand, which was later repealed after a change in government.Speaking in the House of Commons, Ms Atkins said the plan would create a “smoke free generation”.However, several Tory MPs, including former prime minister Liz Truss, voted against the bill, arguing it would limit personal freedom.Last week, ex-prime minster Boris Johnson called the smoking ban “absolutely nuts” during a speech at a Conservative conference in Ottawa, Canada.”When the party of Winston Churchill wants to ban cigars, donnez-moi un break as they say in Quebec, it’s just mad,” he said.Read more about the smoking banWill Rishi Sunak’s plan to ban smoking in UK work?Sunak’s smoking ban is nuts, says Boris Johnson Smoking ban for those born after 2009 moves aheadA quick guide to smoking bans across the worldShould vaping have same restrictions as tobacco?Conservative MPs were given a free vote on the bill, meaning they were not ordered to vote with the government. But full support by Labour’s front bench ensured the measures passed. There are still several more steps needed before it becomes law, such as votes in the House of Lords, but it is possible that the bill could now become law before the general election, expected in the second half of 2024.Labour’s shadow health and social care secretary Wes Streeting accused Mr Sunak of “putting the bill at risk” by granting a free vote “because he is too weak to stand up to the Liz Truss-wing of his party”.”If we are privileged enough to form the next government, Labour will implement this ban, so young people today are even less likely to smoke than they are to vote Conservative,” he added.In total, 178 Tory MPs voted to support the plan but 57 voted against, including Business Secretary Kemi Badenoch and Conservative Party Deputy Chair Jonathan Gullis. Foreign Office minister Anne-Marie Trevelyan also signalled her opposition but ultimately abstained on the vote.She was one of some 106 Tories listed as having “no vote recorded”, including Penny Mordaunt, the leader of the House of Commons.Not all those listed in this way will have abstained, as some will have received permission to miss the vote.Lee Anderson, an ex-deputy chair of the Conservative Party who defected to Reform UK last month, also voted against the bill. Mr Sunak used his conference speech in October of last year to unveil his plans to ban people born after 1 January 2009 from buying tobacco products. ‘Free society’The debate on Tuesday was MPs’ first chance to debate the legislation implementing the ban.Ms Truss was one of the first to speak against the bill, telling the House of Commons it risked infantilising people. “It is very important that until people have decision-making capability while they are growing up that we protect them but I think the whole idea that we can protect adults from themselves is hugely problematic.”Her concern was echoed by some of her fellow Conservative MPs.Former immigration minister Robert Jenrick, tipped as a potential contender to run for the Tory leadership, also came out against the policy.On social media he said he was against the bill because he “believes in personal freedom”.”I also believe in the principle of equality under the law. A phased ban of smoking would be an affront to that,” he added.Former minister Sir Jake Berry said he was more concerned about “the addiction of the government to telling people what to do” than he was about people addicted to nicotine. “I want to live in a free society where I am free to make both good and bad decisions.”Ms Atkins said she understood their concerns about “banning things” but defended the bill arguing: “Nicotine robs people of their freedom to choose.””The vast majority of smokers start when they are young, and three quarters say that if they could turn back the clock they would not have started.”Earlier in the day, England’s chief medical officer Sir Chris Whitty said once people become addicted to smoking “their choice is taken away”.He said: “When I was a junior doctor doing surgery I remember the tragedy of seeing people, whose legs had had to be cut off because of the smoking that had damaged their arteries, outside the hospital weeping as they lit up because they were trapped by addiction – that is not choice.”Tobacco use is the UK’s single biggest preventable cause of death, killing two-thirds of long-term users and causing 80,000 deaths every year.On top of that, a patient is admitted to hospital with a smoking-related condition, such as heart disease, strokes and lung cancer, almost every minute in England.The bill also aims to make vapes less appealing to children, with new restrictions on flavours and packaging. Trading standards officers would also get new powers to issue on-the-spot £100 fines to shops selling tobacco or vapes to children, with all the money raised going towards further enforcement.Figures show that one in five children has tried vaping despite it being illegal for under-18s, while the number of children using vapes has tripled in the past three years.More on this storyWhat is the smoking ban and how will it work?Published13 hours agoDisposable bans will not work, says vape bossPublished26 MarchSunak’s smoking ban is nuts, says Boris JohnsonPublished5 days ago

Alzheimer’s disease (AD) currently afflicts nearly seven million people in the U.S. With this number expected to grow to nearly 13 million by 2050, the lack of meaningful therapies represents a major unmet medical need. Scientists at Sanford Burnham Prebys have now identified promising real-world links between common HIV drugs and a reduced incidence of AD. The study, led by Jerold Chun, M.D., Ph.D., was published in Pharmaceuticals.
Chun’s new research builds on his lab’s landmark publication in Nature in 2018 that described how somatic gene recombination in neurons can produce thousands of new gene variants within Alzheimer’s disease brains. Importantly, it also revealed for the first time how the Alzheimer’s-linked gene, APP, is recombined by using the same type of enzyme found in HIV.
The enzyme, called reverse transcriptase (RT), copies RNA molecules and changes them into complementary DNA duplicates that can then be inserted back into DNA, producing permanent sequence changes within the cell’s DNA blueprint.
HIV and many other viruses rely on RT to hijack a host’s cells to establish a chronic infection, so drugs that block the RT enzyme’s activity have become a common part of treatment cocktails for keeping HIV at bay.
The brain appears to have its own RTs that are different from those in viruses, and the research team wondered if inhibiting brain RTs with HIV drugs actually helps AD patients.
To assess the link between real-world RT inhibitor exposure and AD in humans, the team analyzed anonymized medical records with prescription claims from more than 225,000 control and HIV-positive patients, and found that RT inhibitor exposure was associated with a statistically significant reduced incidence and prevalence of AD.
“Thus, we looked at HIV-positive individuals taking RT inhibitors and other combined antiretroviral therapies as they aged, and asked the question: How many of them got Alzheimer’s disease?” says Chun. “And the answer is that there were many fewer than might have been expected compared to the general population.”
Of the more than 225,000 individuals with claims data in the study, just shy of 80,000 were HIV-positive individuals over the age of 60. More than 46,000 had taken RT inhibitors during a nearly three-year observation period from 2016 to 2019. The data was obtained through a collaboration with health information technology and clinical research firm IQVIA, led by Tiffany Chow, M.D.

In living persons with HIV, there were 2.46 Alzheimer’s disease diagnoses per 1,000 persons among HIV-positive individuals taking these inhibitors, versus 6.15 for the general population. This control group was represented by more than 150,000 HIV-negative patients over the age of 60 with medical insurance claims related to treatment for the common cold.
“You cannot feasibly run a prospective clinical trial with this number of patients,” Chun adds. “This approach is a way to look at how a drug can act on a large patient population.”
Chun underscores that the drugs patients took in this retrospective study were designed to counter RT activity in HIV and likely only had a limited effect on many different possible forms of the enzyme active in the brain.
“What we’re looking at now is very crude,” says Chun. “The clear next step for our lab is to identify which versions of RTs are at work in the AD brain so that more targeted treatments can be discovered, while prospective clinical trials of currently available RT inhibitors on persons with early AD should be pursued.”
Jerold Chun, M.D. Ph.D., is a professor in the Center for Genetic Disorders and Aging Research at Sanford Burnham Prebys.
Additional authors on the study include Tiffany W. Chow, Mark Raupp, Matthew W. Reynolds, Siying Li and Gwendolyn E. Kaeser.
The work was supported by the National Institute on Aging — NIH (R01AG071465, R01AG065541 and R56AG073965), the Shaffer Family Foundation and the Bruce Ford & Anne Smith Bundy Foundation.

A milestone study led by University of Queensland researchers has identified the main types of E. coli bacteria that cause neonatal meningitis, and revealed why some infections recur despite being treated with antibiotics.
Professor Mark Schembri and Dr Nhu Nguyen from UQ’s Institute for Molecular Bioscience and Associate Professor Adam Irwin from UQ’s Centre for Clinical Research led a team which discovered that around 50 per cent of neonatal meningitis infections are caused by two types of E. coli.
“Neonatal meningitis is a rare but life-threatening disease that occurs when a newborn baby is infected with bacteria,” Professor Schembri said.
“E. coli is the most common cause of meningitis in babies born pre-term, but knowing which types allows us to test for those strains and treat them appropriately.”
The study was the largest ever of its type, examining the genomes of 58 different E. coli bacteria across four continents and using samples collected over 46 years.
It found two types of the bacteria were responsible for the majority of neonatal infections.
Associate Professor Irwin, who is also a paediatric infectious disease specialist at the Queensland Children’s Hospital, said meningitis can have a devastating impact on families.

“Parents may lose their child, or in a significant proportion of cases the child can suffer ongoing complications such as a brain injury, leading to developmental problems,” Dr Irwin said.
“While antibiotics can be effective in treating the infection, this relies on rapid diagnosis.
“Also, antibiotics don’t always eliminate the bacteria — some of the babies we tracked showed signs of a complete recovery before suffering repeated invasive E. coli infections.”
The researchers discovered the bacteria causing subsequent infections were the same as in the initial infection.
“It’s most likely that bacteria hide out in the intestinal microbiome,” Professoe Schembri said.
“This tells us we need to keep monitoring these babies after their first infection, as they are at a high risk of subsequent infection.”
Professor Schembri said the E. coli that can lead to meningitis also cause urinary tract infections and colonise the intestinal tract.

“There is something about these types of E. coli that equips them to cause both infections,” he said.
“Our next step is to examine the bacteria’s pathway from the intestinal tract or urinary tract into the bloodstream, and then to the brain, so we can consider new ways to stop them.”
Professor Schembri is a co-affiliate of UQ’s School of Chemistry & Molecular Biosciences.
Australian collaborators on the research included Dr Brian Forde (UQ’s Institute for Molecular Bioscience), Dr Patrick Harris (UQ Centre for Clinical Research), Associate Professor Scott Beatson (School of Chemistry and Molecular Biosciences), Dr Sanmarie Schlebusch (UQ Centre for Clinical Research) and Dr Haakon Bergh (Pathology Queensland).
The research was funded by the Children’s Hospital Foundation, the National Health and Medical Research Foundation, the Wellcome Trust and The University of Queensland.
The research paper was published in eLife.

Patients with suspected inflammatory bowel disease (IBD) could benefit from better testing protocols that would reduce the need and lengthy wait for potentially unnecessary colonoscopies, a new study has found.
In a paper published in Frontline Gastroenterology, researchers from the Birmingham NIHR Biomedical Research Centre (BRC) at the University of Birmingham tested a new protocol to improve IBD diagnosis combining clinical history with multiple home stool tests.
In the two-year study involving 767 participants, patients were triaged and had repeated faecal calprotectin (FCP) tests and the research team found that the use of serial FCP tests were able to strongly predict possible IBD as well as Crohn’s Disease and Ulcerative Colitis.
The team observed that a second FCP test was a strong indicator of a potential need for further investigation including colonoscopy; although the researchers observed that only 20% of patients had two samples submitted prior to referral to secondary care.
Dr Peter Rimmer from the Birmingham NIHR Biomedical Research Centre at the University of Birmingham and corresponding author of the study said:
“Patients who experience symptoms associated with inflammatory bowel diseases often have a long wait until getting a diagnosis, and current testing is under immense strain.
“Using a comprehensive 13-point symptom checker and multiple FCP tests, we have been able to identify much more accurately patients who had IBD and other diseases. The rollout of this protocol could reduce the time taken to get a diagnosis and start treatment for IBDs as much more of the screening and testing can be done through primary care. The sensitivity of multiple FCP tests can be used to flag those patients who urgently need referral into secondary care.”
Dr Rachel Cooney, Consultant Gastroenterologist at University Hospitals Birmingham NHS Foundation Trust, researcher at the NIHR Birmingham BRC and co-author of the study, added:
“In its simplest form, this study may help improve referral triage for IBD patients. But as we plan new care pathways, it could open up new exciting possibilities: with the growing availability of home FCP testing, these tests’ results combined with simple symptom questionnaires could feed into algorithms that allow patients to self-refer to secondary care services, reducing strain on primary care. This is something we’re going to explore in a large follow-up study we’re currently initiating.”

In a study conducted at the Faculty of Sport and Health Sciences and Gerontology Research Center, it was observed that health behaviors are interrelated in such a way that individuals who are the least physically active also consume the most alcohol, and a significant portion of them also smoke. Healthier behaviors were similarly interrelated.
“Smoking, alcohol consumption, and physical activity are often investigated separately in studies, but our study approach takes into account that each of us engages in multiple health behaviors simultaneously,” says doctoral researcher Johanna Ahola from the Gerontology Research Center and Faculty of Sport and Health Sciences.
The study followed the same individuals when they were 42 (2001), 50 (2009), and 61 years old (2020-2021). Health behavior patterns are relatively stable throughout middle adulthood, although particularly positive changes were observed during the 19-year follow-up period.
“The results are in line with previous studies. It was particularly encouraging to observe favorable behavior changes,” says Ahola. “Smoking decreased significantly during the follow-up period, which may be related not only to age but also to the prevailing societal circumstances. It can also be speculated that with the increased incidence of diseases in middle adulthood compared to earlier ages, general health precaution and health-related goals may become more important, leading to changes in behavior.”
Sociodemographic characteristics are reflected in health behavior patterns. Women, those who were married, held a degree, and were white-collar workers were more likely to engage in healthier behaviors. Similarly, those characterized by higher conscientiousness, openness, and agreeableness, as well as lower neuroticism and extraversion, were also more likely to adopt healthier behaviors.
“Examining personality traits in the health behavior patterns brought a new perspective compared to prior research,” says Ahola. “It has been previously observed that individuals characterized by high extraversion are more physically active than those scoring low in the trait. For a physical activity researcher, it was surprising that, in this study, low extraversion was associated with healthier behaviors.”
The research publication is based on the Jyväskylä Longitudinal Study of Personality and Social Development, where the development of the same individuals has been followed for over 50 years. From 1968 to 2012, the research was led by Professor Lea Pulkkinen, and from 2013 onwards, it has been led by Research Director Katja Kokko. The publication is part of the TRAILS project funded by the Research Council of Finland. The writing of the research article was also supported by the JYPE research grant awarded by the Rehabilitation Foundation Peurunka and the University of Jyväskylä.

New research from the University of Pittsburgh explains why metastatic uveal melanoma is resistant to conventional immunotherapies and how adoptive therapy, which involves growing a patient’s T cells outside the body before reinfusing them, can successfully treat this rare and aggressive cancer.
In a paper published today in Nature Communications, the Pitt researchers also explain how they developed a new clinical tool that predicts which patients will respond to adoptive therapy. The work, supported by UPMC Enterprises, is helping improve personalized therapies and avoid futile treatments for metastatic uveal melanoma.
“The dogma was that uveal melanoma is a ‘cold’ cancer, meaning that T cells can’t get into these tumors,” said senior author Udai Kammula, M.D., associate professor of surgery at Pitt and director of the Solid Tumor Cell Therapy Program at UPMC Hillman Cancer Center. “We show that T cells are in fact infiltrating metastases and they’re getting activated, but they’re just sitting there in a dormant state because something in the tumor is suppressing them. Adoptive therapy allows us to rescue these cells from the suppressive tumor microenvironment and successfully treat some patients.”
Uveal melanoma originates in the uveal tract of the eye but has a tendency to aggressively spread throughout the body, often to the liver. When metastasis occurs, this cancer is very difficult to treat and the prognosis for patients is almost always grim.
“Cutaneous melanoma, which affects the skin, is the poster child of immunotherapy. It responds incredibly well to immune checkpoint inhibitor drugs,” said Kammula. “None of these conventional immunotherapies work for uveal melanoma, but we hadn’t known why — until now.”
In a previous Lancet Oncologystudy, Kammula and his team used adoptive therapy to surgically extract metastatic tumors from 19 uveal melanoma patients and grow T cells from these tumors in the laboratory. When they infused the cells back, 35% of patients had either partial or complete regression of their cancer, evidence against the assumption that cancer-fighting cells called tumor-infiltrating lymphocytes (TILs) aren’t found in uveal melanoma. But it was still a mystery why immune checkpoint inhibitors, which rev up the activity of these T cells, are ineffective in treating this disease.
Kammula saw an opportunity to answer this question using a unique resource that he and his team have been building for the last decade: the largest known repository of uveal melanoma samples, corresponding tissues and clinical information.

When the researchers analyzed 100 metastases from 84 patients, they found that over half of these tumors were chock-full of T cells. Next, they performed single cell RNA sequencing to measure gene expression in almost 100,000 cells from six metastases. They found that the TILs in some of these tumors were activated and capable of attacking tumor cells in a dish, but they weren’t proliferating to high numbers in the tumor.
“We found that TILs from metastatic uveal melanoma have the potential to attack the tumor, but something in the tumor microenvironment is shutting them down, so they’re in a dormant, or quiescent, state,” explained Kammula. “By liberating these cells from the suppressive environment and growing them in the lab, we can rescue their tumor-fighting capacity when infused back into the patient.”
But TIL therapy doesn’t work for everyone, as the researchers found in their earlier study. To predict which patients will respond and which will not, Kammula and lead author Shravan Leonard-Murali, M.D., a post-doctoral fellow in the lab, developed a clinical tool called Uveal Melanoma Immunogenic Score (UMIS), a holistic measure of the tumor that reflects the activity of more than 2,000 genes expressed by tumor cells, immune cells and other cells that form the tumor microenvironment. UMIS ranged from 0.114 to 0.347 across 100 metastases, with higher values indicating tumors with more potent TILs.
When the researchers looked at patients who received adoptive therapy in the earlier study, they found that patients with higher UMIS scores had better tumor regression, suggesting that this biomarker could predict which patients are likely to respond.
They also found that patients with metastases scoring above 0.246 had significantly improved progression-free survival and overall survival than those with UMIS below this cutoff.
“If a patient’s UMIS level is below this threshold, we think that adoptive therapy is not appropriate. Using a biopsy to calculate a patient’s UMIS could help avoid futile therapies and unnecessarily subjecting patients to invasive operations,” said Kammula. “But the immune system is not static. UMIS offers a window into the tumor that could also help us find the optimal time to treat a patient with adoptive therapy, like picking a fruit when it’s at its ripest.”
Kammula is now evaluating the score prospectively in an ongoing TIL therapy clinical trial at Pitt for patients with metastatic uveal melanoma.

He and his team are also taking what they’ve learned from uveal melanoma to tackle other difficult-to-treat tumors such as pancreatic cancer, and they are developing a pan-cancer version of UMIS that will predict how well a patient with any type of cancer is likely to respond to adoptive therapy.
Additional authors on this research are Chetana Bhaskarla, Ph.D., Ghanshyam S. Yadav, Ph.D., Sudeep K. Maurya, Ph.D., Chenna R. Galivet, Ph.D., Joshua A. Tobin, Rachel J. Kann, Eishan Ashwat, Patrick S. Murphy, Ph.D., Anish B. Chakka, Ph.D., Vishal Soman, Paul G. Cantalupo, Ph.D., Xinming Zhuo, Ph.D., Gopi Vyas, M.S., Dara L. Kozak, Lindsey M. Kelly, Ph.D., Ed Smith, M.S., M.B.A., Uma R. Chandran, Ph.D., Yen-Michael S. Hsu, M.D., Ph.D., all of UPMC Hillman, Pitt or both.
In addition to support from UPMC Enterprises, the innovation, commercialization and venture capital arm of UPMC, this work was supported in part by the Pitt Center for Research Computing, the National Institutes of Health (S10OD028483), the UPMC Hillman Cancer Center Immunologic Monitoring and Cellular Products Laboratory (CCSG P30 CA047904), and a National Cancer Institute training grant (T32CA113263).

A new study led by the Harvard Pilgrim Health Care Institute has identified that a deficit in the placental expression of the gene insulin-like growth factor 1 (IGFBP1) and low IGFBP1 circulating levels are associated with insulin resistance during pregnancy, highlighting a potential risk factor for the development of gestational diabetes.
The study, “Placental IGFBP1 levels during early pregnancy and the risk of insulin resistance and gestational diabetes,” appears in the April 16, 2024 edition of Nature Medicine.
Gestational diabetes, a disease that can lead to multiple pregnancy and delivery complications, is the most common pregnancy metabolic complication, affecting 1 in 7 pregnancies. Existing research has shown that excess insulin resistance in pregnancy contributes to gestational diabetes, but the exact causes of this resistance remain unclear.
“The placenta — the major driver of changes in insulin physiology in pregnancy — is likely a key source of hormones involved in the development of gestational diabetes,” says Marie-France Hivert, Harvard Medical School associate professor of population medicine at the Harvard Pilgrim Health Care Institute and lead author of the study. “Our goal was to discover novel placental factors that are implicated in gestational diabetes, by studying all proteins expressed in placenta tissues, across the human genome. We identified placental insulin-like growth factor 1 (IGFBP1) as a secreted placental factor that is likely implicated in regulation of glucose in human pregnancy.”
The study builds on Dr. Hivert’s extensive research into the determinants of gestational diabetes using genetics and other omics approaches, and their interaction with lifestyle and environmental factors. The study team conducted genome-wide RNA sequencing on maternal-facing placental tissue samples, and measured identified proteins in blood collected in multiple pregnancy cohorts with diverse backgrounds.
The team identified 14 genes whose placental RNA expression levels were associated with insulin resistance, finding the strongest association with gene IGFBP1. By measuring the IGFBP1 protein levels in circulation, they found that IGFBP1 levels rise over the course of pregnancy and are 5 times higher in pregnant people compared to outside of pregnancy, arguing for the placenta being one of the major sources of this protein during pregnancy. Results also show that low levels of circulating IGFBP1 in early pregnancy could predict who is likely to develop gestational diabetes in late second trimester of pregnancy. Finally, the team found that the trajectory of IGFBP1 levels across pregnancy differs in people who have a subtype of gestational diabetes characterized by insulin resistance previously shown more likely to develop pregnancy complications.
“Identifying a novel protein that characterizes a subtype of gestational diabetes is one additional step towards developing precision medicine for gestational diabetes,” adds Dr. Hivert. “It’s possible that measuring IGFBP1 in the first trimester could help identify people at risk of developing gestational diabetes early in pregnancy, potentially offering a window for prevention. We hope to conduct future research to address whether this protein plays a causal role in gestational glycemic regulation.”

Actin is a highly abundant protein that controls the shape and movement of all our cells. Actin achieves this by assembling into filaments, one actin molecule at a time. The proteins of the formin family are pivotal partners in this process: positioned at the filament end, formins recruit new actin subunits and stay associated with the end by ‘stepping’ with the growing filament. There are as many as 15 different formins in our cells that drive actin filament growth at different speeds and for different purposes. Yet, the exact mechanism of action of formins and the basis for their different inherent speeds have remained elusive.
Now, for the first time, researchers from the groups of Stefan Raunser and Peter Bieling at the Max Planck Institute of Molecular Physiology in Dortmund have visualized at the molecular level how formins bind to the ends of actin filaments. This allowed them to uncover how formins mediate the addition of new actin molecules to a growing filament. Furthermore, they elucidated the reasons for the different speeds at which the different formins promote this process. The MPI researchers used a combination of biochemical strategies and electron cryo-microscopy (cryo-EM). The breakthrough, published in the journal Science, can help us explain why certain mutations in formins can lead to neurological, immune, and cardiovascular diseases. Max Plank researchers from Dortmund unveil at the molecular level how ring-like formin proteins promote actin filament growth in cells
Joining forces
“Our discovery allows us to interpret decades of biochemical studies on formins through new lenses, which answers many long-standing, open questions in this field,” says Peter Bieling. Previous structures from X-ray crystallization revealed that formins are made of two identical parts that encircle the actin filament in a ring-like conformation and step along it as it grows. In the speculative models suggested so far, formins interact through all their four binding domains with actin, while slow and fast-moving formin would adopt different shapes at the filament. “But those studies lacked high-resolution structures of formins bound to their relevant sites of activity, the barbed end of actin filaments,” says Wout Oosterheert, postdoc in the group of Stefan Raunser at the MPI Dortmund and co-first author of the publication.
Formins are highly dynamic proteins that assemble filaments rapidly, hence it is difficult to obtain enough filament ends for detailed structure determination. The MPI scientists analyzed not just one, but three distinct formins originating from fungi, mice, and humans, which all elongate actin filaments at highly different speeds. “One of the formins that we studied is very fast and can be considered the Ferrari among formins, while another formin behaves more like a tractor,” says Stefan Raunser. The scientists tested and optimized a wide variety of conditions that ultimately gave them a high number of formin-bound filaments. “We built on the experience that we gained from our previous studies. The iterative optimization of both the biochemistry and cryo-EM sample preparation was key for obtaining these structures,” says Micaela Boiero Sanders, the other co-first author of the study.
A new paradigm
The new structures, with resolutions around 3.5 Ångstrom, show that formins encircle actin like an asymmetric ring: One half of the ring is stably bound, while the other half is loosely associated with the filament and is free to capture a new subunit. “Analyzing the structures gave us a true ‘Eureka’ moment regarding the mechanism,” say Oosterheert and Boiero Sanders. When the new actin subunit arrives, its incorporation onto the filament destabilizes the formin arrangement and requires the stable half-ring to step onto the new subunit and become loose, while the other half-ring becomes stable. Thanks to this concerted mechanism, formins stay associated with the growing actin filament end over long distances. Contrary to previous hypotheses, the structures are similar for all three analyzed formins, with only three binding domains being engaged with actin at the same time.
By introducing mutations into formins, the MPI scientists also explained the speed differences among actin-formin complexes: if the formin ring is bound more tightly to the actin filament end, it is more difficult for the ring to let go and step onto a new, incoming actin subunit. As a result, filament growth is slower. “We now understand how a formin that behaves like a tractor can be made faster by giving it some Ferrari-like features,” says Peter Bieling. The MPI team expects that their results will be useful for the many scientists around the world that study the actin cytoskeleton. “Our new insights open up a large number of possibilities for elucidating the specific roles of the fifteen human formins at the cellular level, which can increase our understanding of how mutations in formin genes lead to severe diseases,” concludes Raunser.

Some of the world’s deadliest bacteria seek out and feed on human blood, a newly-discovered phenomenon researchers are calling “bacterial vampirism.”
A team led by Washington State University researchers have found the bacteria are attracted to the liquid part of blood, or serum, which contains nutrients the bacteria can use as food. One of the chemicals the bacteria seemed particularly drawn to was serine, an amino acid found in human blood that is also a common ingredient in protein drinks.
The research finding, published in the journal eLife, provides new insights into how bloodstream infections occur and could potentially be treated.
“Bacteria infecting the bloodstream can be lethal,” said Arden Baylink, a professor at WSU’s College of Veterinary Medicine and corresponding author for the research. “We learned some of the bacteria that most commonly cause bloodstream infections actually sense a chemical in human blood and swim toward it.”
Baylink and the lead author on the study, WSU Ph.D. student Siena Glenn, found at least three types of bacteria, Salmonella enterica, Escherichia coli and Citrobacter koseri, are attracted to human serum. These bacteria are a leading cause of death for people who have inflammatory bowel diseases (IBD), about 1% of the population. These patients often have intestinal bleeding that can be entry points for the bacteria into the bloodstream.
Using a high-powered microscope system designed by Baylink called the Chemosensory Injection Rig Assay, the researchers simulated intestinal bleeding by injecting microscopic amounts of human serum and watching as the bacteria navigated toward the source. The response is rapid — it takes less than a minute for the disease-causing bacteria to find the serum.
As part of the study, the researchers determined Salmonella has a special protein receptor called Tsr that enables bacteria to sense and swim toward serum. Using a technique called protein crystallography, they were able to view the atoms of the protein interacting with serine. The scientists believe serine is one of the chemicals from blood that the bacteria sense and consume.
“By learning how these bacteria are able to detect sources of blood, in the future we could develop new drugs that block this ability. These medicines could improve the lives and health of people with IBD who are at high risk for bloodstream infections,” Glenn said.
Scientists Zealon Gentry-Lear, Michael Shavlik, and Michael Harms of the University of Oregon, and Tom Asaki, a mathematician at WSU, contributed to the research. The study was funded by WSU and the National Institute of Allergy and Infectious Diseases.

In a new study, a Johns Hopkins Medicine-led research team reports that social stress during adolescence in female mice later results in prolonged elevation of the hormone cortisol after they give birth. The researchers say this corresponds to the equivalent hormonal changes in postpartum women who were exposed to adverse early life experiences — suggesting that early life stress may underlie a pathophysiological exacerbation of postpartum depression (PPD).
The team’s findings, first published online Apr. 11, 2024, in Nature Mental Health, also suggest that current drug treatments for PPD in people may, in some cases, be less effective at targeting the relevant chemical imbalances in the brain, and that alternative methods may be more beneficial.
According to previous studies, an estimated one-third of psychiatric conditions fail to respond to current therapies, and “PPD is difficult to treat,” says study senior author Akira Sawa, M.D., Ph.D., director of the Johns Hopkins Schizophrenia Center and professor of psychiatry, neuroscience, biomedical engineering, genetic medicine and pharmacology at the Johns Hopkins University School of Medicine. “The new study results add to evidence that patients with PPD are not all the same, and more individualized diagnosis and treatment — a precision medicine approach — is needed.”
PPD, states the federal government’s Office on Women’s Health, is estimated to occur in 7% to 20% of all women, most commonly within six weeks of giving birth. Symptoms include feelings of sadness, anxiety, and fatigue, and can make it difficult to complete basic self-care tasks and care for the new baby.
The current first-line treatment for PPD is the use of a class of anti-depressant pills called selective serotonin reuptake inhibitors (SSRIs), but these are only effective in approximately half of all patients. SSRIs boost the effects of the natural brain chemical serotonin, one of many hormone-like substances that help control mood. Some patients also are treated with IV infusions of a different class of drugs that target GABAA, a brain chemical linked to nerve hyperactivity.
However, the calming infusions are costly (more than $30,000 for a single course of one such drug) and often require hospitalization. They are generally reserved for the most severe and resistant cases of PPD.
In the new study, the Johns Hopkins-led research team aimed to build on evidence that adverse life events may affect the likelihood and severity of PPD. Previous studies have shown that PPD is more prevalent in teens, and in urban populations.

Working with mice, the researchers first created four test groups: unstressed virgins, stressed virgins, unstressed mothers and stressed mothers. The stressed mice were subjected to social isolation in their adolescence, and all groups were tested for stress. At seven days postpartum, the stressed mothers showed decreased mobility and a decrease in sugar preference, both of which are considered markers for depression. This persisted for at least three weeks after delivery.
As the second and most critical step, the researchers tested plasma levels of several hormones and found the level of cortisol was increased in mothers both with and without adverse early life experiences. However, cortisol levels in unstressed mothers decreased to normal levels after delivery, while the levels in mothers with adverse early life experiences remained high for one to three weeks after birth. This finding, Sawa says, suggests a correlation between prolonged post-delivery elevation of cortisol and behavioral changes in postpartum mice who experienced social isolation in adolescence.
If these findings translate to humans, it could mean that a different kind of antidepressant, a glucocorticoid receptor (GR) antagonist, which blocks the effects of elevated cortisol, could be a novel treatment option for PPD. Mifepristone may be one such drug.
“Unfortunately, everyone knows someone who has suffered or currently suffers from PPD, and it has such a huge impact on both mother and baby,” says Sawa. “The alternative line of treatment suggested by the mouse study — where the findings are consistent with those from our observational study in humans — might enable mothers to be treated at home and avoid separation from their babies, and target a different mechanism for depression that may be specific to PPD.”
Plans are underway, Sawa says, to collect precise data on cortisol levels in people with PPD to determine if GR antagonists would be more beneficial than current treatments for some, and later, to conduct clinical trials with alternatives to SSRIs.
Along with Sawa, members of the study team from Johns Hopkins Medicine are Sedona Lockhart, Jennifer Payne, Gary Wand, Daniel Wood and Kun Yang. Team members from the University of Alabama at Birmingham Heersink School of Medicine are study lead author Minae Niwa, Adeel Ahmed, Shin-ichi Kano, Kyohei Kin and Jose Francis-Oliveira.
Funding for this research was provided by National Institutes of Health grants MH-092443, MH-094268, K99MH-094408, MH-105660, MH-107730, DA-040127, and MH-116869; the Brain and Behavior Research Foundation (formerly the National Alliance for Research on Schizophrenia and Depression); and other sources.