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A new organoid model of the dopaminergic system sheds lights on its intricate functionality and potential implications for Parkinson’s disease. The model, developed by the group of Jürgen Knoblich at the Institute of Molecular Biotechnology (IMBA) of the Austrian Academy of Sciences, replicates the dopaminergic system’s structure, connectivity, and functionality. The study, published on December 5 in Nature Methods, also uncovers the enduring effects of chronic cocaine exposure on the dopaminergic circuit, even after withdrawal.
A completed run, the early morning hit of caffeine, the smell of cookies in the oven — these rewarding moments are all due to a hit of the neurotransmitter dopamine, released by neurons in a neural network in our brain, called the “dopaminergic reward pathway.” Apart from mediating the feeling of “reward,” dopaminergic neurons also play a crucial role in fine motor control, which is lost in diseases such as Parkinson’s disease. Despite dopamine’s importance, key features of the system are not yet understood, and no cure for Parkinson’s disease exists. In their new study, the group of Jürgen Knoblich at IMBA developed an organoid model of the dopaminergic system, which not only recapitulates the system’s morphology and nerve projections, but also its functionality.
A model of Parkinson’s disease
Tremor and a loss of motor control are characteristic symptoms of Parkinson’s disease and are due to a loss of neurons that release the neurotransmitter dopamine, called dopaminergic neurons. When dopaminergic neurons die, fine motor control is lost and patients develop tremors and uncontrollable movements. Although the loss of dopaminergic neurons is crucial in the development of Parkinson’s disease, the mechanisms how this happens, and how we can prevent — or even repair — the dopaminergic system is not yet understood.
Animal models for Parkinson’s disease have provided some insight into Parkinsons disease, however as rodents do not naturally develop Parkinson’s disease, animal studies proved unsatisfactory in recapitulating hallmark features of the disease. In addition, the human brain contains many more dopaminergic neurons, which also wire up differently within the human brain, sending projections to the striatum and the cortex. “We sought to develop an in vitro model that recapitulates these human features in so called brain organoids,” explains Daniel Reumann, previously a PhD student in the lab of Jürgen Knoblich at IMBA, and first author of the paper. “Brain organoids are human stem cell derived three-dimensional structures, which can be used to understand both human brain development, as well as function,” he explains further.
The team first developed organoid models of the so-called ventral midbrain, striatum and cortex — the regions linked by neurons in the dopaminergic system — and then developed a method for fusing these organoids together. As happens in the human brain, the dopaminergic neurons of the midbrain organoid send out projections to the striatum and the cortex organoids. “Somewhat surprisingly, we observed a high level of dopaminergic innervation, as well as synapses forming between dopaminergic neurons and neurons in striatum and cortex,” Reumann recalls.
To assess whether these neurons and synapses are functional, the team collaborated with Cedric Bardy’s group at SAHMRI and Flinders University, Australia, to investigate if neurons in this system would start to form functional neural networks. And indeed, when the researchers stimulated the midbrain which contains dopaminergic neurons, neurons in the striatum and cortex responded to the stimulation. “We successfully modelled the dopaminergic circuit in vitro, as the cells not only wire correctly, but also function together,” Reumann sums up.
The organoid model of the dopaminergic system could be used to improve cell therapies for Parkinson’s disease. In first clinical studies, researchers have injected precursors of dopaminergic neurons into the striatum, to try and make up for the lost natural innervation. However, these studies have had mixed success. In collaboration with the lab of Malin Parmar at Lund University, Sweden, the team demonstrated that dopaminergic progenitor cells injected into the dopaminergic organoid model mature into neurons and extend neuronal projections within the organoid. “Our organoid system could serve as a platform to test conditions for cell therapies, allowing us to observe how precursor cells behave in a three-dimensional human environment,” Jürgen Knoblich, the study’s corresponding author, explains. “This allows researchers to study how progenitors can be differentiated more efficiently and provides a platform which allows to study how to recruit dopaminergic axons to target regions, all in a high-throughput manner.”
Insights into the reward system
Dopaminergic neurons also fire whenever we feel rewarded, thus forming the basis of the “reward pathway” in our brains. But what happens when dopaminergic signaling is perturbed, such as in addiction? To investigate this question, the researchers made use of a well-known dopamine reuptake inhibitor, cocaine. When the organoids were exposed to cocaine chronically, over 80 days, the dopaminergic circuit changed functionally, morphologically and transcriptionally. These changes persisted, even when cocaine exposure was stopped 25 days before the end of the experiment, which simulated the withdrawal condition. “Even after almost a month after stopping cocaine exposure, the effects of cocaine on the dopaminergic circuit were still visible, which means that we can now investigate what the long-term effects of dopaminergic overstimulation are in a human-specific in vitro system,” Reumann summarizes.

A new study from researchers at UC San Diego’s Scripps Institution of Oceanography and UC San Francisco estimates 152,753 excess infant deaths were attributable to living in flood-prone areas in Bangladesh over the past 30 years. Additionally, across the study period, children born during rainy months faced higher risk of death than those born in dry months.
The paper was published Dec. 5 in the Proceedings of the National Academy of Sciences and supported by the National Institute of Allergy and Infectious Diseases.
The findings begin to unspool the long term public health impacts of recurring environmental hazards such as flooding, wildfires, or extreme heat, many of which are becoming more common or more severe under climate change, said study co-author Tarik Benmarhnia, an associate professor at Scripps Oceanography who studies climate change and health.
Benmarhnia and his co-authors were motivated to undertake the study as a way to move beyond cataloging the acute public health impacts of natural hazards linked to climate change.
“We wanted to document what happens when year after year some communities are exposed to these climate hazards,” said Benmarhnia.
Benmarhnia and his co-authors wanted to find a way to look at the long term public health burden of living in flood prone-areas on child mortality and Bangladesh seemed to offer an opportunity to quantify that burden over a long time period.
“Child mortality is a proxy for easily avoidable negative health outcomes,” said Benmarhnia. “If we can’t avoid child mortality there are also likely to be issues with malnutrition, mental health, and communicable diseases — from a public health perspective infant mortality is only the tip of the iceberg.”
Bangladesh sits in the Ganges-Brahmaputra-Meghna river basin, which also runs through Tibet, Nepal, Bhutan, and northern India and is home to more than 618 million people. Every year, monsoon season brings extensive flooding to Bangladesh, and those floods are predicted to become more frequent and extreme due to climate change.

To look at the long term health implications of repeated exposure to flooding, the study combined a well-established spatially-resolved flood-zone mapping tool and health data from 58,945 mothers and 150,081 births collected by U.S. AID’s Demographic and Health Surveys (DHS) program between 1988 and 2017. The study matched mothers that were nearly identical across other measurable characteristics that might impact infant mortality, such as wealth and education, and differed only in the flood-risk of their birthing location.
“We wanted to isolate as much as possible the effect of living in flood-prone areas from other factors that could alter the risk of child mortality,” said Benmarhnia.
The study estimated that living in flood prone areas was associated with an excess risk in infant mortality of 5.3 additional deaths per 1,000 births compared to living in non-flood prone areas over the 30-year period between 1988 and 2017, with children born during rainy months at higher risk of death than those born in dry months.
The researchers then used national population data, weighted statistical analysis, and the same flood-zone mapping tools to extrapolate their findings with this initial group to the entire country of Bangladesh. This national-scale analysis estimated that 152,753 excess infant deaths were attributable to living in flood-prone areas in Bangladesh over the past 30 years.
The study’s results don’t point to any particular mechanism for how flood exposure might drive increased infant mortality, and Benmarhnia said investigating potential causes will be a necessary step in developing effective interventions. That said, he suggested that flooding can impact food security and financial stability, especially for agricultural communities.
Benmarhnia said the findings suggest that focusing only on the immediate effects of flooding may underestimate their impact on population health, and that effects on infant mortality in particular appear to manifest over a longer time scale. The study also provides a template for measuring longer-term health impacts from floods and a generalizable example of how to study the long-term health effects of climate-related environmental hazards.

The role of climate change was not explicitly included in the analysis, said Benmarhnia, but he said there was a continuous increase in the overall risk of infant mortality across the study’s three decades.
“We didn’t quantify the role of climate change, but it’s the elephant in the room,” said Benmarhnia. “While our data can’t explicitly link our findings to climate change, they’re compatible with the notion that climate change is making flooding and the public health impacts that flow from it worse.”
In light of their findings, the study authors are now studying the potential of seasonally-timed nutritional interventions that can bolster food security when communities are at the greatest risk from flooding and other climate-sensitive exposures.
“We need to be thinking about and dealing with the long term consequences of other climate hazards and instances of so-called extreme weather,” said Benmarhnia. “We may also need to redefine our concept of extreme. The intensity is extreme but these environmental hazards like flooding are less and less rare. We may need to reframe these issues as recurring problems, and not just emergency situations.”
In addition to Benmarhnia, the study was co-authored by Francois Rerolle, who is a postdoctoral researcher at UC San Francisco and Scripps Oceanography, and Benjamin Arnold of UC San Francisco.

Most organ transplantations involve supply from older donors to younger recipients. Aging cells can become senescent, a condition in which they stop multiplying and secrete chemicals that negatively affect neighboring cells. Senescent cells accumulate in older donor organs, and have the potential to compromise transplant outcomes.
A study led by researchers from Brigham and Women’s Hospital, a founding member of the Mass General Brigham healthcare system, found that in preclinical models, transplanting older organs can trigger senescence in younger recipients. They observed that young and middle-aged mice that received heart transplants from older mice had impaired physical capacity, with reduced running times and grip strengths. Middle-aged mice who received older hearts also showed increased anxiety-related behavior, impaired memory and poorer learning performances.
The authors found that these accelerated aging-related effects in younger recipients were driven by the release of senescence-associated factors and mitochondrial DNA from older transplants. Treating older donor mice with senolytics, or senescence-inhibiting drugs, before organ extraction reduced symptoms of senescence in the recipient mice.
“Currently, due to insufficient supply in clinical organ transplantation, donor and recipient ages differ substantially,” said principal investigator Stefan G. Tullius, MD, PhD, of the Division of Transplant Surgery. “Our results suggest that senolytic treatments can be a potential therapeutic approach for improving the outcomes of older organs.”

Dr. Murphy’s safe, reliable container replaced breakable glass bottles used in transfusions in the Korean War. He also helped improve pacemakers and artificial kidneys.Dr. William P. Murphy Jr., a biomedical engineer who was an inventor of the vinyl blood bag that replaced breakable bottles in the Korean War and made transfusions safe and reliable on battlefields, in hospitals and at scenes of natural disasters and accidents, died on Thursday at his home in Coral Gables, Fla. He was 100.His death was confirmed on Monday by Mike Tomás, the president and chief executive of U.S. Stem Cell, a Florida company for which Dr. Murphy had long served as chairman. He became chairman emeritus last year.Dr. Murphy, the son of a Nobel Prize-winning Boston physician, was also widely credited with early advances in the development of pacemakers to stabilize erratic heart rhythms, of artificial kidneys to cleanse the blood of impurities, and of many sterile devices, including trays, scalpel blades, syringes, catheters and other surgical and patient-care items that are used once and thrown away.But Dr. Murphy was perhaps best known for his work on the modern blood bag: the sealed, flexible, durable and inexpensive container, made of polyvinyl chloride, that did away with fragile glass bottles and changed almost everything about the storage, portability and ease of delivering and transfusing blood supplies worldwide.Developed with a colleague, Dr. Carl W. Walter, in 1949-50, the bags are light, wrinkle-resistant and tear proof. They are easy to handle, preserve red blood cells and proteins, and ensure that the blood is not exposed to the air for at least six weeks. Blood banks, hospitals and other medical storage facilities depend on their longevity. Drones drop them safely into remote areas.In 1952, Dr. Murphy joined the United States Public Health Service as a consultant and, at the behest of the Army, went to Korea during the war there to demonstrate, with teams of medics, the use of the blood bags in transfusing wounded soldiers at aid stations near the front lines.“It was the first major test of the bags under battlefield conditions, and it was an unqualified success,” Dr. Murphy said in a telephone interview from his home for this obituary in 2019. In time, he noted, the bags became a mainstay of the blood-collection and storage networks of the American Red Cross and similar organizations abroad.The vinyl blood bag developed with a colleague by Dr. Murphy, for use in transfusions. It ensures that blood is not exposed to the air for at least six weeks. Blood banks, hospitals and other medical storage facilities depend on blood’s longevity. Andreas Feininger/The LIFE Picture Collection, via Shutterstock(For years, researchers have said an ingredient in polyvinyl chlorides, diethylhexyl phthalate, or DEHP — used in making building materials, clothing and many health care products — poses a cancer risk to humans. Since 2008, Congress has banned DEHP in children’s products in the U.S.; the European Union has required labels; and alternative chemicals have replaced DEHP in blood bags.)In Korea, Dr. Murphy recalled, he saw Army medics reusing needles to transfuse patients, and medical instruments were often inadequately sterilized. Alarmed at the dangers of infection, he designed a series of relatively inexpensive medical trays equipped with drugs and sterilized surgical tools that could be discarded after a single use, greatly reducing the risks of cross-contaminating patients.In 1957, he founded the Medical Development Corporation, a Miami company that two years later became Cordis Corporation, a developer and maker of devices for diagnosing and treating heart and vascular diseases. With Dr. Murphy as chief engineer, president, chief executive and chairman, Cordis produced what he called the first synchronous cardiac pacemaker.As the use of implanted pacemakers became more common in the 1960s and ’70s, Dr. Murphy said, he saw that the devices might be improved upon to respond not only to irregular heart rhythms — usually an abnormally slow beat — but also to signs of bleeding, tissue damage, blood-clot formation or problems with the pacemaker’s electrode leads into the heart muscle.These complications led him and his team to develop a new generation of pacemakers that could be programmed externally. Out of this effort came the first “dual demand” pacemaker of the 1980s, with probes into two of the heart’s chambers for a fuller picture of the organ’s activity and creeping flaws.The advanced Cordis pacemaker contained a tiny computer that could detect heart problems and, in effect, have two-way electronic conversations with a cardiologist. The cardiologist could, in turn, devise noninvasive solutions and program the computer to carry them out.In addition, Dr. Murphy said, his team devised better ways to virtually “see” inside the vascular system. His motorized-pressure device injected, with precision, a small dose of liquid, containing iodine for color, into a selected vessel. There, the liquid showed up on an X-ray image, called an angiogram, providing a window into nooks and crannies where blockages might be lurking.To remove blockages, Dr. Murphy and a colleague, Robert Stevens, devised sterile vascular catheters, or probes, that allowed access to obstructions in vessels. (Today’s angiographic injectors have a space-age robotic look, with tiny cameras and lights in the probes and a television screen outside to guide the doctor’s way through the tunnels.)Under Dr. Murphy, Cordis also ventured into artificial kidneys, which cleanse the blood of waste products that accumulate normally in the body. Vital to sustaining life, the cleansing occurs when blood flows on one side of a membrane while a bath of chemicals flows on the other side. Impurities in the blood pass through tiny pores in the membrane into the bath, and are carried away.Dr. Willem J. Kolff, a Dutch physician, made the first artificial kidney during World War II. It was a Rube Goldberg contraption: sausage casings wrapped around a wood drum rotating in a salt solution. Dr. Murphy’s device used densely packed hollow fibers of synthetic resins as filters. Despite its inefficiencies, it was widely used in wearable or implanted artificial kidneys.Later advancements in artificial kidneys and dialysis have given thousands of patients with failing kidneys access to treatment and prolonged lives. But the devices still do not measure up to the efficient human kidney; bioengineered kidneys are still a hope of the future.Dr. Murphy retired from Cordis in 1985 to pursue other commercial medical interests. By then, he held 17 patents, had written some 30 articles for professional journals and had received the Distinguished Service Award of the North American Society of Pacing and Electrophysiology. He received the Lemelson-MIT Lifetime Achievement Award in 2003 and was inducted into the National Inventors Hall of Fame in 2008.A wounded American soldier receiving a transfusion during the Korean War. Dr. Murphy’s vinyl blood bag was tested under battlefield conditions. Bettmann/Getty ImagesWilliam Parry Murphy Jr. was born on Nov. 11, 1923, in Boston. His father, a hematologist, shared the 1934 Nobel Prize in Physiology or Medicine for a study that showed that a diet of raw liver could ameliorate the effects of pernicious anemia. His mother, Harriett (Adams) Murphy, was the first woman to become a licensed dentist in Massachusetts.William Jr. and his older sister, Priscilla, grew up in Brookline, the Boston suburb. As a teenager Priscilla became the youngest qualified female pilot in the country but died shortly afterward in the crash of a small plane in a snowstorm near Syracuse, N.Y., on a nighttime medical-mercy flight from Boston.Fascinated as a boy with mechanics, William devised a gasoline-powered snow blower, whose design he sold to a company.After graduating from Milton Academy in Massachusetts, he studied pre-medicine at Harvard, where his father taught, and graduated in 1946. He earned his medical degree from the University of Illinois at Chicago in 1947. While studying mechanical engineering for a year at the Massachusetts Institute of Technology, he developed a film projector to display enlarged X-ray images to medical audiences.Dr. Murphy interned at St. Francis Hospital in Honolulu, then practiced medicine briefly at Peter Bent Brigham Hospital (now Brigham and Women’s Hospital) in Boston before taking up his career in biomedical engineering.In 1943, he married Barbara Eastham, an American linguist who had been born in China. They divorced in the early 1970s. In 1973, Dr. Murphy married Beverly Patterson. She survives him, along with three daughters from his first marriage, Wendy Sorakowski and Christine and Kathleen Murphy; two grandchildren; and one great-grandson.Dr. Murphy delivered the keynote address in 2016 at a conference held by the Academy of Regenerative Practices in Fort Lauderdale, Fla. Regenerative therapy using stem cells became a particular interest in his later years. via U.S. Stem CellAfter retiring from Cordis, Dr. Murphy and a colleague, John Sterner, in 1986 bought Hyperion Inc., which designed, manufactured and marketed medical laboratory and diagnostic devices. In 2003, he joined the board of Bioheart, which developed stem cell therapies. He became chairman of Bioheart in 2010 and later chairman of U.S. Stem Cell, a successor company. In 2019, a federal court empowered the Food and Drug Administration to stop U.S. Stem Cell from injecting patients with an extract made from their own belly fat. The action came after three patients suffered severe, permanent eye damage resulting from fat extracts injected into their eyes to treat macular degeneration. The company had maintained that the extract contained stem cells with healing and regenerative powers, but medical experts disputed that claim.Dr. Murphy had by then become enthusiastic about the promise of stem cell research. In 2014, he spoke to a Miami conference about the rapidly growing and controversial field of using stem cells derived from bone marrow and umbilical cord blood to treat neurodegenerative conditions, diabetes and heart disease. “That’s a whole new world of regenerative therapy that’s going to be critical to our future,” he said.Alex Traub

Researchers at the LKS Faculty of Medicine of the University of Hong Kong (HKUMed), and collaborators from the Zhongshan Ophthalmic Centre of Sun Yat-sen University, Guangzhou, have developed a light-activatable prodrug nanomedicine for age-related macular degeneration (AMD) therapy. Through the intravenous injection of the nanomedicine and application of light irradiation to diseased eyes, anti-angiogenic and photodynamic combination therapy can be activated, offering a minimally invasive alternative for the treatment of AMD and other ocular disorders characterised by abnormal blood vessel growth. The research has been published in Advanced Science and a Patent Cooperation Treaty application was filed based on the research.
According to the Hong Kong Eye Survey data published in 2019, the prevalence of early AMD among individuals aged 70 and older has reached 7.5% in Hong Kong1, making AMD the second most common cause of visual impairment and blindness in the adult population of Hong Kong. Currently, intravitreal injections of antibodies against vascular endothelial growth factor are the first-line treatment for wet AMD. However, this invasive procedure is uncomfortable for patients, and carries the risk of serious ocular complications, such as endophthalmitis and retinal detachment. Therefore, there is an urgent need for novel formulations that enable the delivery of anti-angiogenic agents into the eye without an intravitreal injection, such as intravenous injection.
Additionally, anti-angiogenic agents have limited efficacy in regressing existing neovascularisation. Photodynamic therapy (PDT) offers a clinical solution by utilising non-toxic photosensitisers activated by specific wavelengths of light to generate reactive oxygen species (ROS), which can damage and obliterate neovascularisation. PDT is widely used for the treatment of polypoidal choroidal vasculopathy, a common subtype of wet AMD in Asia. Therefore, combining anti-angiogenesis therapy with PDT may offer a more effective approach to treating wet AMD, thus helping slow down the progression of the disease and improve the vision outcome for patients.
Research methods and findings
The research team designed a novel photoactivatable prodrug nanosystem. After a single intravenous injection of the nanoparticles into a choroidal neovascularisation mouse model, red-light irradiation of the mouse’s eye activated the nanoparticles to generate ROS, which not only causes the regression of abnormal neovascularisation, but also triggers the release of anti-angiogenic drugs from the nanoparticles to inhibit the growth of new blood vessels. This combinational therapy demonstrated excellent therapeutic efficacy without any noticeable systemic or ocular side effects.
Research significance
The study represents the first attempt at integrating a photoactivatable anti-angiogenic agent with a photosensitiser into a single nanoformulation for AMD treatment. The treatment procedure is simple and safe, as the therapeutic effect of the anti-angiogenic agent and photosensitiser in ocular lesions can be achieved through the intravenous administration of nanoparticles and light irradiation to the eye. This pioneering research may open up new avenues for the development of minimally-invasive therapeutics for AMD and other neovascular ocular disorders. The formulation uses US FDA-approved therapeutic agents and excipients, making it promising for future clinical translation.
The study was led by Dr Wang Weiping, Associate Professor of Dr Li Dak-Sum Research Centre and Department of Pharmacology and Pharmacy, HKUMed, and Principal Investigator of the State Key Laboratory of Pharmaceutical Biotechnology, HKU. The other corresponding author was Professor Liang Xiaoling, Department of Ophthalmology, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, State Key Laboratory of Ophthalmology, Sun Yat-Sen University, and Zhongshan Ophthalmic Centre, Sun Yat-sen University; the co-first authors were Xu Shuting, PhD candidate, Department of Pharmacology and Pharmacy, HKUMed, and Dr Cui Kaixuan, Postdoctoral fellow, Department of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University. Other researchers included Long Kaiqi, PhD candidate, Department of Pharmacology and Pharmacy, HKUMed; Dr Li Jia and Dr Fan Ni, Postdoctoral fellows, Department of Pharmacology and Pharmacy; and Professor Lam Wai-ching, Head and Clinical Professor of the Department of Ophthalmology, Vancouver General Hospital and University of British Columbia, Canada, and Honorary Clinical Professor, Department of Ophthalmology, School of Clinical Medicine, HKUMed.
This work was supported by the National Natural Science Foundation of China Excellent Young Scientists Fund (No. 82222903) and the National Natural Science Foundation of China (No. 82271099).

Aggression is often associated as a negative emotion. Uncontrolled aggression can lead to conflict, violence and negative consequences for individuals and society. Yet that does not that mean that aggression serves no purpose. It is an instinctive behavior found in many species that may be necessary for survival. The key is managing and channeling aggression.
In a recent study using mice, researchers at Tohoku University have demonstrated that neuron-glial interactions in the cerebellum set the tone of aggression, suggesting that future therapeutic methods could rely on adjusting glial activity there to manage anger and aggression.
The findings were detailed in the journal Neuroscience Research on November 24, 2023.
Scientists have recently recognized the role of the cerebellum in non-motor functions such as social cognition. A malfunctioning cerebellum can occur in autism spectrum disorders and schizophrenia, leading to social interaction difficulties. In particular, it has been reported that a region of the cerebellum, known as the vermis, is associated with aggression in humans. Therefore, the researchers investigated the possibility that Bergmann glial cells in the cerebellar vermis regulate the volume of aggression in mice.
“Cells in the brain can be divided into neurons and glia, and although glia occupy approximately half of the brain, their participation in the brain’s information processing, plasticity, and health has long been an enigma,” says Professor Ko Matsui of the Super-network Brain Physiology lab at Tohoku University, who led the research. “Our newly created fiber photometry method provides a gateway for understanding the physiology of glia.”
Matsui and his colleagues employed the resident-intruder model, where one mouse (the intruder) goes into the territory of another mouse (the resident). When the unfamiliar male mouse enters the cage, quite commonly, a series of fights break out between the resident male mouse and the intruder. Each combat round lasted about 10 seconds, and these rounds were repeated at a frequency of approximately one per minute. The superiority and inferiority of the resident and intruder dynamically switched within each combat round.
The fiber photometry method revealed that intracellular Ca2+ levels in cerebellar glia decreased or increased in conjunction with the superiority or inferiority of the fight, respectively. When the combat broke up, the researchers observed 4 to 6 Hz theta band local field potentials in the cerebellum, along with a sustained increase in Ca2+ levels in the glia. Optogenetic stimulation of cerebellar glia induced the emergence of the theta band, causing an early breakup of the fighting.
Glia have been shown to control the local ionic and metabotropic environment in the brain and also to release transmitters that can affect neuronal activity in the vicinity. The results of this study suggest that the theta band cerebellar neuronal activity is regulated by the activity of Bergmann glial cells, thereby demonstrating that cerebellar glial cells play a role in regulating aggression in mice.
Lead study investigator, Yuki Asano, says that future anger management strategies and clinical control of excessive aggression and violent behavior may be realized by developing a therapeutic strategy that adjusts glial activity in the cerebellum. “Imagine a world without social conflict. By harnessing the innate ability of the cerebellar glia to control aggression, a peaceful future could be become reality.”

3D eye scans can reveal vital clues about kidney health that could help to track the progression of disease, research suggests.
The advance could revolutionise monitoring of kidney disease, which often progresses without symptoms in the early stages.
Experts say the technology has potential to support early diagnosis as current screening tests cannot detect the condition until half of the kidney function has been lost.
Researchers used highly-magnified images to detect changes to the retina — the layer of tissue at the back of the eye that senses light and sends signals to the brain. They found that the images offer a quick, non-invasive way to monitor kidney health.
The eye is the only part of the body where it is possible to view a key process called microvascular circulation — and this flow of blood through the body’s tiniest vessels is often affected in kidney disease.
Researchers at the University of Edinburgh investigated whether 3D images of the retina, taken using a technology called optical coherence tomography (OCT), could be used to identify and accurately predict the progression of kidney disease.
OCT scanners — used in most high street opticians — use light waves to create a cross-sectional picture of the retina, displaying each individual layer, within a few minutes.

The team looked at OCT images from 204 patients at different stages of kidney disease, including transplant patients, alongside 86 healthy volunteers.
They found that patients with chronic kidney disease had thinner retinas compared with healthy volunteers. The study also showed that thinning of the retina progressed as kidney function declined.
These changes were reversed when kidney function was restored following a successful transplant. Patients with the most severe form of the disease, who received a kidney transplant, experienced rapid thickening of their retinas after surgery.
More people than ever are at risk of kidney disease, which is often caused by other conditions that put a strain on the kidneys, including diabetes, high blood pressure and obesity.
With further research, regular eye checks could one day aid early detection and monitoring to prevent the disease from progressing. It could also allow patients to make lifestyle changes that reduce the risk of health complications, experts say.
The technology, supported by Heidelberg Engineering’s imaging platform, could also aid the development of new drugs, the research team says.

It could do so by measuring changes in the retina that indicate whether — and in what way — the kidney responds to potential new treatments.
The researchers say further studies — including longer-term clinical trials in larger groups of patients — are needed before the technology can be routinely used.
An estimated 7.2million people in the UK live with chronic kidney disease — more than 10% of the population. It costs the NHS around £7billion each year.
The study is published in Nature Communications. It was funded by Kidney Research UK, and supported by Edinburgh Innovations, the University’s commercialisation service.

There is no shortage of advice for women on what to eat, how to train, or what supplements to take during their menstrual cycles, but a new review by an international team of scientists has found little evidence to support such recommendations.
In fact, they found sparse research on women and exercise at all, and even less on the effect of their periods on sports performance, physiology, or physical fitness.
The authors of the paper, from McMaster University, Manchester Metropolitan University and the Australian Catholic University in Melbourne, are calling for much more high quality, standardized research on women.
A key finding from the review was that hormonal levels vary substantially between women during their menstrual periods and between the cycles of individual women. Virtually no woman has a standard version of a menstrual cycle, which is typically 28 days long, with ovulation consistently occurring on day 14.
“The data suggests that from woman to woman, there are significant variations in estrogen and progesterone, the primary hormones that characterize the phases of the menstrual cycle,” says co-lead author Alysha D’Souza, a graduate student in the Department of Kinesiology at McMaster University.
The findings are published in the most recent edition of the Journal of Applied Physiology.
“Hormone levels can vary substantially. Not just between two women, but within one woman from one cycle to the next,” says Mai Wageh, a PhD candidate in the Department of Kinesiology at McMaster and co-lead author of the article.

The findings prompted D’Souza and Wageh to dig deeper into physiological differences across the menstrual cycle, broadly categorized into follicular, ovulatory, and luteal phases. They found few or no differences when they looked at exercise results across the cycle phases and examined women’s use of fat versus carbohydrates, the potential for muscle growth, or blood-vessel function.
The review relied on various methods, including a systematic review and meta-analysis, narrative interpretation and a previous umbrella review.
“Many women are following advice and planning exercises and practices based on some ostensible benefit of menstrual cycle phase-based exercise. We saw no evidence that such practice is science-based,” said Stuart Phillips, a professor in the Department of Kinesiology at McMaster and senior author of the review.
“Women can feel better or worse, and some are even incapacitated during various phases of their cycle,” said Wageh. “You need an individualized approach to training. Track your cycle and your symptoms in each phase and adjust your exercise plan accordingly. There is no one-size-fits-all approach.”
The next steps for this work will be to determine whether symptoms often associated with menstruation are cycle-related or due to other stressors, including lack of sleep, poor nutrition, or work and relationship-related issues.

Lipids are the main constituents of our cell membranes, which are formed as lipid bilayers. The distribution of lipids is far from uniform; it is asymmetric, with different lipid compositions in the outside and inside layers. This asymmetry is essential for a variety of cellular functions, from maintaining membrane homeostasis to enabling cell signaling and numerous other physiological processes at or across membranes.
P4-ATPases, also known as flippases, are key players in creating and maintaining this lipid asymmetry. These enzymes actively transport lipids from the outside (exoplasmic) leaflet to the inside (cytosolic) leaflet coupled to ATP hydrolysis and ensure the proper distributions of lipids. The ATP8B1-CDC50A flippase complex in particular, has been the subject of the current study, leading to several new, groundbreaking discoveries.
The function of ATP8B1 lipid flippase is critical for the regulation of bile production, a vital substance in our digestive system, but the direct link within bile producing liver cells remains unknown. Additionally, recent studies have spotlighted the relevance of genetic variants in the regulatory segment of the ATP8B1 gene as a strong genetic marker for Alzheimer’s resilience. Interestingly, mutations that impair function of the closely related ATP8B4 lipid flippase are oppositely important risk factors of Alzheimer’s. It is therefore of strong interest to understand how ATP8B1 is linked to these processes and pathologies.
In the new study, the research team employed state-of-the-art cryo-electron microscopy techniques to capture nine different states associated with the lipid transport and determine structures at 2.4 to 3.1 Å resolution for these states. These structural insights, combined with functional and computational studies, reveal the inner workings of the human flippase ATP8B1-CDC50A complex and its fine regulation by specific regulatory lipids known as phosphoinositides, or PIPs.
These findings open doors to a deeper understanding of how lipid flippases operate and the intricate roles they play in cellular processes and are regulated. Importantly, the study also resolves earlier discrepancies about the ATP8B1 transport substrates.
Noteworthy, both up- or down-regulation of ATP8B1-CDC50 function could potentially be of interest in drug discovery, and the study also reveals critical information to such applications.

Published19 hours agoShareclose panelShare pageCopy linkAbout sharingImage source, Getty ImagesBy Nick TriggleHealth correspondentJunior doctors in England are to stage more strikes, in December and January, after rejecting a new pay offer put forward in talks with government.The British Medical Association (BMA) union said the proposal was worth an extra 3% on average this year. This is on top of an 8.8% rise already given.The strikes will be for three days from 07:00 on 20 December and six days from 07:00 on 3 January.The new-year walkout will be the longest in the NHS’s history.It coincides with what is traditionally one of the NHS’s busiest periods, with emergency services often under huge strain.The breakdown in talks comes after five weeks of negotiations during which industrial action had been suspended.The BMA wants a 35% pay uplift, to make up for what it says have been below-inflation rises since 2008.Fresh pay offer could end NHS consultant strikesWhy talk of a UK doctor exodus is prematureHow much do junior doctors really get paid? The government refused to comment on the detail of the offer, with sources saying there had still been room for movement if the talks had continued.Health Secretary Victoria Atkins said it was “disappointing” junior doctor leaders had walked away from negotiations.”The new strikes will result in more disruption for patients and extra pressure on NHS services and staff as we enter a busy winter period, risking patient safety,” she added.Image source, PA MediaDr Robert Laurenson and Dr Vivek Trivedi, who co-chair the BMA junior doctors committee, said: “We have been clear from the outset of these talks that we needed to move at pace – and if we did not have a credible offer, we would be forced to call strikes. “After five weeks of intense talks, the government was unable to present a credible offer on pay by the deadline. “Instead, we were offered an additional 3%, unevenly spread across doctors’ grades, which would still amount to pay cuts for many doctors this year.”Sir Julian Hartley, of NHS Providers, which represents health managers, said: “This is the outcome that NHS leaders were dreading.”Since industrial action started in the NHS, more than a million appointments and treatments have had to be cancelled.There have been walkouts by nurses, ambulance workers and physiotherapists, among others, but those by doctors have been the most disruptive.Pay dealThe rise given to junior doctors in April was weighted so those at the start of training – and therefore earning the least money – received the biggest rises.The BMA’s announcement of more strikes comes after the union reached a pay deal last week with the government on senior doctors, or consultants, who have also been taking strike action.Consultants will now vote on that deal, which involves an average pay rise of nearly 5% in January on top of the 6% rise they received in April.Other health workers, including nurses, accepted a pay offer of an extra 5% and a one-off sum of at least £1,655, in May.Are you a doctor with a view on the strike? Are you a patient affected? Share your experiences by emailing haveyoursay@bbc.co.uk.Please include a contact number if you are willing to speak to a BBC News journalist. You can also make contact in the following ways:WhatsApp: +44 7756 165803Tweet: @BBC_HaveYourSayUpload pictures or videoPlease read our terms and conditions and privacy policy

If you are reading this page but cannot see the form, visit the mobile version of the BBC website to submit your question or comment, or email haveyoursay@bbc.co.uk. Please include your name, age and location with any submission. More on this storyFresh pay offer could end NHS consultant strikesPublished27 NovemberNurses react with fury over doctor pay offerPublished28 NovemberWhat is the NHS pay offer?Published2 MayWhy talk of a UK doctor exodus is prematurePublished9 AugustNHS pay deal signed off for one million staffPublished2 MaySome NHS temporary staff miss out on full pay dealPublished21 JulyHow much do junior doctors really get paid?Published11 AugustRelated Internet LinksStatistics ? Consultant-led Referral to Treatment Waiting Times Data 2023-24.websiteThe BBC is not responsible for the content of external sites.