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A clinical psychiatrist, she showed that suicide was often the result of mental illness, and that it could be avoided with the right treatment and public education.Early in her time as a medical student in the late 1950s, Paula J. Clayton watched a psychiatrist analyze a patient with clinical depression.The doctor, who had herself been analyzed by both Carl Jung and Sigmund Freud and now taught at Washington University, asked the patient to explain his dreams, and the two spent time discussing what they meant.But, when the session was over, the doctor did something that Freud would never do. She prescribed electroshock therapy.It was something of a revelation for Dr. Clayton: The old methods of psychiatry, steeped in Freudian theory, had their limits, and physiological treatments were needed too. She came to believe that a new approach was necessary, beyond analysis’s reliance on talk therapy, one based not in philosophy and speculation but empirical research and data and a conviction that mental illness, like any illness, can be diagnosed and treated.She was at the right place at the right time. Dr. Clayton was part of a generation of clinical psychiatrists who, in the decades after World War II, revolutionized their field by applying medical rigor to the diagnosis of mental illness — and nowhere was this revolution more apparent than Washington University. Her mentor, George Winokur, drilled into his students the commandment “Data Shall Be Your God.”Dr. Clayton joined the Washington University medical faculty in 1965, and in 1969 she and Dr. Winokur, along with their colleague Dr. Theodore Reich, published “Manic Depressive Illness,” one of the first books to study manic depression through a rigorous, outcome-based approach.“She was a very careful empirical researcher at a time when empirical research did not hold much sway,” Richard Friedman, a psychiatrist at Weill Cornell Medical College in New York, said in an interview.Dr. Clayton with colleagues at Washington University in the ‘70s. She and her colleagues were part of a generation of clinical psychiatrists who revolutionized their field by applying medical rigor to the diagnosis of mental illness.via Washington University in St. LouisDr. Clayton and her co-authors found, for example, that manic depression was likely hereditary, that it affected men and women differently, and that it had a high morbidity rate — that is, many patients, left untreated, died by suicide.The “untreated” part is important, because Dr. Clayton went on to become one of the leading voices for destigmatizing depression and suicide in America.She moved beyond the academy to become something of a public figure, adept at translating the latest research on mental illness for a broad audience at a time when issues like mania and suicide were still shrouded in mystery and myth.Dr. Clayton died on Sept. 4 in Pasadena, Calif., at 86. Her daughter, Clarissa Weirick, said the cause was complications from a non-Covid viral infection.First as a professor at the University of Minnesota — where she was the first woman to chair a psychiatry department in the country — and later as the medical director at the American Foundation for Suicide Prevention, Dr. Clayton worked tirelessly to show the public what medical researchers already knew: that suicide was almost always the result of an underlying mental illness.“When you’re feeling sick from cancer or heart disease, you certainly call your doctor first, and yet with suicide,” you don’t think of treatment as a solution, she said in a 2007 interview with a reporter for McClatchy. “I think it’s just that they don’t recognize it as a serious illness.”Dr. Clayton reveled in the role of mythbuster. Suicides do not peak around the holidays, she told reporters, audiences and congressional hearings — April and May see the highest numbers. Women attempt suicide twice as often as men, but men are four times as successful.“She was a pioneer and a force in suicide prevention in part because she believed people should know and understand that suicide can be prevented,” Dr. Jill Harkavy-Friedman, the vice president for research at the American Foundation for Suicide Prevention, said in an interview. “That didn’t happen before. People ran away from the topic.”Dr. Clayton in an undated photo. Even after she retired in 2015, she continued to write and speak, convinced that with enough public education, the country could start to lower its tragically high suicide rates. via Clayton familyPaula Jean Limberg was born on Dec. 1, 1934, in St. Louis. Her father, Oscar Limberg, worked for a clothing company. Her mother, Dorothea (Pflasterer) Limberg, was active in the women’s suffrage movement, something Dr. Clayton later cited as an inspiration for her own career.Her marriage to Charles Clayton ended in divorce. In addition to her daughter, she is survived by her sons, Matthew and Andrew, and seven grandchildren.She studied pre-med at the University of Michigan, graduating in 1956, and enrolled in medical school at Washington University, where she graduated in 1960. After joining the Washington University faculty, she moved to the University of Minnesota in 1980.Her work around bipolar disorder was especially groundbreaking. Though its broad contours were well understood, it was still seen as a mystery even by many psychiatrists. And too many people still saw manic outbursts of energy in somewhat romantic terms, as the seedbed for great art and ideas.“There was a bit of glamour attached to bipolar disorder, which was wholly inaccurate — there’s no glamour to that disease,” John Greden, a psychiatrist at the University of Michigan and the founder of the Eisenberg Family Depression Center, said in an interview.Dr. Clayton helped show that bipolar disorder and unipolar depression were two ends of a spectrum, a view that has led to breakthroughs in the diagnosis and treatment of both conditions.She also demonstrated that while bereavement and grief can trigger major depression, periods of grief, even ones lasting a year, were not in themselves depressive episodes. And she showed that grief, far from progressing along a neatly described five-stage process, was personal and idiosyncratic — an insight that changed the way doctors and the public understand how we deal with loss.Dr. Clayton stepped down as chairwoman at Minnesota in 1999, and after moving to Santa Fe, N.M., began teaching part time at the University of New Mexico.Just six years later, though, a recruiter contacted her: The American Foundation for Suicide Prevention needed a medical director, someone who could take the work of its network of researchers to the general public.Dr. Clayton jumped at the chance, leaving her life of semiretirement in New Mexico for New York. She created films for schools and parents and she became a constant presence at government hearings, from Congress to City Councils.She was especially vocal about suicide among members of the military and veterans, the rates of which spiked after the invasions of Afghanistan and Iraq, and among Native Americans. She urged insurance companies to improve mental health coverage. And even after she retired in 2015, she continued to write and speak, convinced that with enough public education, the country could start to lower its tragically high suicide rates.“Before her, people talked about suicide like it was this mystical, horrifying behavior,” Dr. Friedman said. “Her work destigmatized depression, and because of that, so many people owe their lives to her.”If you are having thoughts of suicide, call the National Suicide Prevention Lifeline at 1-800-273-8255 (TALK). You can find a list of additional resources at SpeakingOfSuicide.com/resources.

After infection with SARS-CoV-2, where does the immune system store the memory to provide long-term protection against reinfection?
Though numerous studies have examined blood to track immune responses to SARS-CoV-2, a new study of COVID survivors shows that the memory of the infection is primarily stored in T and B cells within the lung and the lymph nodes surrounding the lung.
The study, led by Donna Farber, PhD, the George H. Humphreys II Professor of Surgical Sciences and professor of microbiology & immunology at Columbia University Vagelos College of Physicians and Surgeons, was published online Oct. 7 ahead of print in Science Immunology.
Identifying the source of immunological memory to SARS-CoV-2 infection is important because it could lead to improved vaccines or boosters.
The study, which included collaborators Shane Crotty, PhD, and his team along with Alessandro Sette, PhD, at La Jolla Institute for Immunology, also found evidence that specialized sites, called germinal centers — where antibody-producing B cells and memory B cells are generated — were present within the lung-associated lymph nodes for up to six months after infection, even in elderly individuals. They found SARs-CoV-2-specific germinal center B cells and T-follicular-helper cells-the T cell population that promotes B cell differentiation — together in lung-associated lymph nodes.
This is the first direct evidence that such centers are established and persist after SARS-CoV-2 infection. This persistence of germinal center B cells can ensure long-term maintenance of antibodies in circulation and the continual maturation of the immune response.

Common gut bacteria can fuel the growth of prostate cancers and allow them to evade the effects of treatment, a new study finds.
Scientists revealed how gut bacteria contribute to the progression of advanced prostate cancers and their resistance to hormone therapy — by providing an alternative source of growth-promoting androgens, or male hormones.
Hormone therapy is the standard of care for advanced prostate cancer and works by lowering levels of androgens. But researchers found that low androgen levels in patients can drive the expansion of gut bacteria, which can become hormone factories to sustain prostate cancer growth.
Bacterial ‘fingerprints’ identified by scientists may help pick out patients at high risk of developing resistance to treatment who could benefit from strategies to manipulate their ‘microbiome’. For example, men could undergo a faecal transplant or take a yoghurt drink enriched with favourable bacteria.
A team of scientists from The Institute of Cancer Research, London, the Institute of Oncology Research in Bellinzona, Switzerland and the Swiss Federal Institute of Technology used mice and patient samples to investigate the role of gut bacteria in prostate cancer growth and progression.
The findings, once further validated in the clinic, could provide new opportunities for the treatment of prostate cancer through manipulation of the microbiome.

The hepatitis B virus (HBV) is a major health problem worldwide, causing close to one million deaths each year. Recent ancient DNA studies have shown that HBV has been infecting humans for millennia, but its past diversity and dispersal routes remain largely unknown. A new study conducted by a large team of researchers from all around the world provides major insights into the evolutionary history of HBV by examining the virus’ genomes from 137 ancient Eurasians and Native Americans dated to between ~10,500 and ~400 years ago. Their results highlight dissemination routes and shifts in viral diversity that mirror well-known human migrations and demographic events, as well as unexpected patterns and connections to the present.
HBV and the peopling of the Americas
Present-day HBV strains are classified into nine genotypes, two of which are found predominantly in populations of Native American ancestry. The study provides strong evidence that these strains descend from an HBV lineage that diverged around the end of the Pleistocene and was carried by some of the first inhabitants of the Americas.
“Our data suggest that all known HBV genotypes descend from a strain that was infecting the ancestors of the First Americans and their closest Eurasian relatives around the time these populations diverged,” says Denise Kühnert, leader of the tide research group and supervisor of the study.
HBV in prehistoric Europe
The study also shows that the virus was present in large parts of Europe as early as 10,000 years ago, before the spread of agriculture to the continent.
“Many human pathogens are thought to have emerged after the introduction of agriculture, but HBV was clearly already affecting prehistoric hunter-gatherer populations,” says Johannes Krause, director of the Department of Archaeogenetics at the Max Planck Institute for Evolutionary Anthropology and co-supervisor of the study.
After the Neolithic transition in Europe, the HBV strains carried by hunter-gatherers were replaced by new strains that were likely spread by the continent’s first farmers, mirroring the large genetic influx associated with the expansion of farming groups across the region. These new viral lineages continued to prevail throughout western Eurasia for close to 4,000 years. The dominance of these strains lasted through the expansion of Western Steppe Herders around 5,000 years ago, which dramatically altered the genetic profile of Europeans but remarkably was not associated with the spread of new HBV variants.
The collapse and re-emergence of pre-historic HBV
One of the most surprising findings of the study is a sudden decline of HBV diversity in western Eurasia during the second half of the 2nd millennium BCE, a time of major cultural shifts, including the collapse of large Bronze Age state societies in the eastern Mediterranean region.
“This could point to important changes in epidemiological dynamics over a very large region during this period, but we will need more research to understand what happened,” says Arthur Kocher, lead author and researcher in the tide group.
All ancient HBV strains recovered in western Eurasia after this period belonged to new viral lineages that still prevail in the region today. However, it appears that one variant related to the previous pre-historic diversity of the region has persisted to the present. This prehistoric variant has evolved into a rare genotype that seems to have emerged recently during the HIV pandemic, for reasons that remain to be understood.

Daily cycles in virtually every aspect of our physiology are driven by biological clocks (also called circadian clocks) in our cells. The cyclical interactions of clock proteins keep the biological rhythms of life in tune with the daily cycle of night and day, and this happens not only in humans and other complex animals but even in simple, single-celled organisms such as cyanobacteria.
A team of scientists has now reconstituted the circadian clock of cyanobacteria in a test tube, enabling them to study rhythmic interactions of the clock proteins in real time and understand how these interactions enable the clock to exert control over gene expression. Researchers in three labs at UC Santa Cruz, UC Merced, and UC San Diego collaborated on the study, published October 8 in Science.
“Reconstituting a complicated biological process like the circadian clock from the ground up has really helped us learn how the clock proteins work together and will enable a much deeper understanding of circadian rhythms,” said Carrie Partch, professor of chemistry and biochemistry at UC Santa Cruz and a corresponding author of the study.
Partch noted that the molecular details of circadian clocks are remarkably similar from cyanobacteria to humans. Having a functioning clock that can be studied in the test tube (“in vitro”) instead of in living cells (“in vivo”) provides a powerful platform for exploring the clock’s mechanisms and how it responds to changes. The team conducted experiments in living cells to confirm that their in vitro results are consistent with the way the clock operates in live cyanobacteria.
“These results were so surprising because it is common to have results in vitro that are somewhat inconsistent with what is observed in vivo. The interior of live cells is highly complex, in stark contrast to the much simpler conditions in vitro,” said Andy LiWang, professor of chemistry and biochemistry at UC Merced and a corresponding author of the paper.
The new study builds on previous work by Japanese researchers, who in 2005 reconstituted the cyanobacterial circadian oscillator, the basic 24-hour timekeeping loop of the clock. The oscillator consists of three related proteins: KaiA, KaiB, and KaiC. In living cells, signals from the oscillator are transmitted through other proteins to control the expression of genes in a circadian cycle.
The new in vitro clock includes, in addition to the oscillator proteins, two kinase proteins (SasA and CikA), whose activities are modified by interacting with the oscillator, as well as a DNA-binding protein (RpaA) and its DNA target.
“SasA and CikA respectively activate and deactivate RpaA such that it rhythmically binds and unbinds DNA,” LiWang explained. “In cyanobacteria, this rhythmic binding and unbinding at over 100 different sites in their genome activates and deactivates the expression of numerous genes important to health and survival.”
Using fluorescent labeling techniques, the researchers were able to track the interactions between all of these clock components as the whole system oscillates with a circadian rhythm for many days and even weeks. This system enabled the team to determine how SasA and CikA enhance the robustness of the oscillator, keeping it ticking under conditions in which the KaiABC proteins by themselves would stop oscillating.
The researchers also used the in vitro system to explore the genetic origins of clock disruption in an arrhythmic strain of cyanobacteria. They identified a single mutation in the gene for RpaA that reduces the protein’s DNA-binding efficiency.
“A single amino acid change in the transcription factor makes the cell lose the rhythm of gene expression, even though its clock is intact,” said coauthor Susan Golden, director of the Center for Circadian Biology at UC San Diego, of which Partch and LiWang are also members.
“The real beauty of this project is how the team drawn from three UC campuses came together to pool approaches toward answering how a cell can tell time,” she added. “The active collaboration extended well beyond the principal investigators, with the students and postdocs who were trained in different disciplines conferring among themselves to share genetics, structural biology, and biophysical data, explaining to one another the significance of their findings. The cross-discipline communication was as important to the success of the project as the impressive skills of the researchers.”
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Materials provided by University of California – Santa Cruz. Original written by Tim Stephens. Note: Content may be edited for style and length.

Researchers from Carnegie Mellon University have found a way to make deep brain stimulation (DBS) more precise, resulting in therapeutic effects that outlast what is currently available. The work, led by Aryn Gittis and colleagues in CMU’s Gittis Lab, will significantly advance the study of Parkinson’s disease.
DBS allows researchers and doctors to use thin electrodes implanted in the brain to send electrical signals to the part of the brain that controls movement. It is a proven way to help control unwanted movement in the body, but patients must receive continuous electrical stimulation to get relief from their symptoms. If the stimulator is turned off, the symptoms return immediately.
Gittis, an associate professor of biological sciences in the Mellon College of Science and faculty in theNeuroscience Institute, said that the new research could change that.
“By finding a way to intervene that has long-lasting effects, our hope is to greatly reduce stimulation time, therefore minimizing side effects and prolonging battery life of implants.”
Gittis set the foundation for this therapeutic approach in 2017, when her lab identified specific classes of neurons within the brain’s motor circuitry that could be targeted to provide long-lasting relief of motor symptoms in Parkinson’s models. In that work, the lab used optogenetics, a technique that uses light to control genetically modified neurons. Optogenetics, however, cannot currently be used on humans.
Since then, she has been trying to find a strategy that is more readily translated to patients suffering from Parkinson’s disease. Her team found success in mice with a new DBS protocol that uses short bursts of electrical stimulation.

Researchers at Johns Hopkins Medicine have found that a drug first developed to treat Alzheimer’s disease, schizophrenia and sickle cell disease reduces obesity and fatty liver in mice and improves their heart function — without changes in food intake or daily activity.
These findings, published online Oct. 7 in the Journal of Clinical Investigation, reveal that a chemical inhibitor of the enzyme PDE9 stimulates cells to burn more fat. This occurred in male mice and in female mice whose sex hormones were reduced by removing their ovaries, thus mimicking menopause. Postmenopausal women are well known to be at increased risk for obesity around their waist as well as at risk for cardiovascular and metabolic disease.
Inhibiting PDE9 did not cause these changes in female mice that had their ovaries, so female sex hormone status was important in the study.
“Currently, there isn’t a pill that has been proven effective for treating severe obesity, yet such obesity is a global health problem that increases the risk of many other diseases,” says senior investigator David Kass, M.D., Abraham and Virginia Weiss Professor of Cardiology at the Johns Hopkins University School of Medicine. “What makes our findings exciting is that we found an oral medication that activates fat-burning in mice to reduce obesity and fat buildup in organs like the liver and heart that contribute to disease; this is new.”
This study follows work reported by the same laboratory in 2015 that first showed the PDE9 enzyme is present in the heart and contributes to heart disease triggered by high blood pressure. Blocking PDE9 increases the amount of a small molecule known as cyclic GMP, which in turn controls many aspects of cell function throughout the body. PDE9 is the enzyme cousin of another protein called PDE5, which also controls cyclic GMP and is blocked by drugs such as Viagra. Inhibitors of PDE9 are experimental, so there is no drug name yet.
Based on these results, the investigators suspected PDE9 inhibition might improve cardiometabolic syndrome (CMS), a constellation of common conditions including high blood pressure; high blood sugar, cholesterol and triglycerides; and excess body fat, particularly around the waist. CMS is considered a pandemic by medical experts and a major risk factor for heart disease, stroke, type 2 diabetes, cancers and COVID-19.

In urban areas across the U.S., low-income neighborhoods and communities of color experience an average of 28% more nitrogen dioxide (NO2) pollution than higher-income and majority-white neighborhoods. The disparity is driven primarily by proximity to trucking routes on major roadways, where diesel trucks are emitters of NO2 and other air pollutants.
Nitrogen dioxide is a common air pollutant that can cause a range of health problems, such as chronic respiratory illness and asthma. But it can be difficult to trace.
A new study used high-resolution air pollution data measured with satellites to track NO2 for nearly two years in major cities across the U.S. The researchers then paired the pollution data with both demographic data and metrics that analyze the degree of racial segregation in a community.
Cities with bigger populations tended to have larger disparities in NO2 pollution between low-income neighborhoods of color and high-income white neighborhoods, according to the study. Phoenix, Los Angeles and Newark, N.J., have the highest NO2 inequalities, all with a discrepancy in NO2 exposure of over 40%.
Both commuter traffic and heavy-duty trucks contribute NO2 and other pollutants, but diesel trucks are the dominant source, contributing on average up to half of a city’s NO2 despite being at most 5% of traffic. Because diesel trucks also emit other harmful gases and particulates, changes in NO2 are also thought to reflect exposure to other pollutants as well.
The findings are detailed in the AGU journal Geophysical Research Letters, which publishes high-impact, short-format reports with immediate implications spanning all Earth and space sciences.

Multisystem inflammatory syndrome in children (MIS-C) is a serious condition associated with a recent COVID-19 infection. The syndrome is rare, and it remains unclear how the viral infection leads to MIS-C and why it only develops in some children.
One hypothesis was that children with MIS-C might mount an abnormal T cell response — immune cells that help the body fight viral infections — to the coronavirus, causing inflammation.
But abnormal T cell responses to the virus do not appear to be a cause of MIS-C, University of California San Diego School of Medicine researchers report in a study publishing October 2, 2021 in European Journal of Immunology.
All children with MIS-C who participated had normal T cell responses to the COVID-19 virus, comparable to children and adults who had recovered from COVID-19 without MIS-C. Children with a clinically similar but unrelated inflammatory condition called Kawasaki disease also served as a control group.
“Considering the rarity of MIS-C and Kawasaki disease, we were fortunate to have a relatively large group of patients participating in this study — one that’s only possible in this region, thanks to the early actions of UC San Diego, Rady Children’s Hospital and our Kawasaki Disease Research Center,” said senior author Alessandra Franco, MD, PhD, associate professor of pediatrics at UC San Diego School of Medicine. “This should be considered a preliminary observation, but we believe our study adds to the growing body of evidence regarding how kids respond to the COVID-19 virus.”
The team compared responses to bits of the COVID-19 virus by T cells isolated from 11 children with MIS-C to two control groups: 1) two children and five adults who had recovered from previous COVID-19 infections without MIS-C and 2) 10 children with Kawasaki disease.
They found that nine of the 11 children with MIS-C had T cells that specifically recognized the COVID-19 virus. But these T cell responses did not correlate with disease severity or age. Their T cells acted similarly to those of children and adults who had a previous COVID-19 infection but not MIS-C.
Examining additional children with MIS-C, the team found that these patients did have lower numbers of other immune cells, such as tolerogenic myeloid dendritic cells, compared to the children without MIS-C. These cells reduce inflammation and are particularly numerous in children. Fewer of these cells might help contribute to the development of MIS-C, Franco said.
Next Franco and team plan to study how T cell memory develops in children with MIS-C and how their immune systems restore to normal as they recover. They also hope to compare T cell dynamics in vaccinated and unvaccinated children.
MIS-C symptoms may include abdominal pain, bloodshot eyes, chest pain, headaches, rashes and vomiting. Parents should seek emergency medical care if their child experiences trouble breathing, confusion, inability to stay awake or blue-colored skin. MIS-C is treated with supportive care, such as fluids and anti-inflammatory medication. Some children with MIS-C may require treatment in an intensive care unit.
According to the Centers for Disease Control and Prevention, the best way parents can protect children from MIS-C is by taking actions to prevent the household from getting the virus that causes COVID 19, such as masking, avoiding crowded areas and vaccination for those who are eligible.
Co-authors include: Li-En Hsieh, Chisato Shimizu, Nanda Ramchandar, Elizabeth Moreno, Adriana H. Tremoulet, Jane C. Burns, UC San Diego; Alba Grifoni, John Sidney, La Jolla Institute for Immunology; Hiroko Shike, Penn State Milton S. Hershey Medical Center.
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Materials provided by University of California – San Diego. Original written by Heather Buschman, PhD. Note: Content may be edited for style and length.