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Using a new model of brain activity, Indiana University computational neuroscientists Maria Pope, Richard Betzel and Olaf Sporns are exploring striking bursts of activity in the human brain that have not been examined before. These bursts may have potential to serve as biomarkers for brain disease and conditions such as depression, schizophrenia, dementia, and ADHD.
While analyzing human neuroimaging data, the IU research team discovered short bursts of activity that form ongoing “events” in the brain and are always taking place no matter the activity or state of the brain. In the course of a 10-minute brain scan, these events will occur roughly 10 to 20 times, each lasting for just a few seconds, the researchers found.
“What people had not seen is that how brain regions talk to each other is punctuated by these brief moments that are just a few seconds long during which there’s a lot happening,” said Olaf Sporns, who is Distinguished Professor and Robert H. Shaffer Chair in the College of Arts and Sciences Department of Psychological and Brain Sciences at IU Bloomington.
“Now that we see them, we’ve focused on those moments to get a picture of how specific brain regions link up and talk to each other during these events.”
To begin investigating the workings of these mysterious events, the team built a computational model. Led by Maria Pope, a graduate student in Sporns’ lab and a dual Ph.D. candidate in neuroscience and informatics, the group used neuroimaging data of a human brain to build a model replicating its connections. The model was then simulated in a state similar to the resting brain to create synthetic MRI signals, using mathematical equations that reenact neuronal activity.
The model showed burst-like events just like those seen in human brain recordings.

In a University of California, Irvine-led study, researchers revealed a striking pattern following a functional screen of extracts from plants collected in Muir Woods National Monument, in coastal redwood forest land in California. They found plants with a long history of use by Native Americans as topical analgesics, were often also used as gastrointestinal aids.
The study, published today in Frontiers in Physiology, found plants that activated the KCNQ2/3 potassium channel, a protein that passes electrical impulses in the brain and other tissues, showed a long history of use by Native Americans as topical analgesics, to treat conditions such as insect bites, stings, sores and burns. Less intuitively, the same plants that activated KCNQ2/3 and were used as folk analgesics, were often also used as gastrointestinal aids, especially for preventing diarrhea.
“Done in collaboration with the US National Parks Service, this study illustrates how much there is still to learn from the medicinal practices of Native Americans, and how, by applying molecular mechanistic approaches we can highlight their ingenuity, provide molecular rationalizations for their specific uses of plants, and potentially uncover new medicines from plants,” said Geoffrey Abbott, PhD, a professor in the Department of Physiology and Biophysics at the UCI School of Medicine.
KCNQ2/3 is present in nerve cells that sense pain, and its activation would be expected to soothe pain by disfavoring transmission of the pain signal. The breakthrough finding came when the team discovered that the same plant extracts that activate KCNQ2/3 have the opposite effect on the related intestinal potassium channel, KCNQ1-KCNE3. This finding was striking as previous studies on modern medicines showed that KCNQ1-KCNE3 inhibitors can prevent diarrhea.
The Abbott Lab is currently undertaking a much broader screen of native US plants toward these goals. Already they have shown that quercetin and tannic and gallic acids, present in several of the plants studied, explained many of the beneficial effects of the plants. The team also identified binding sites on the channel proteins that produce the effects.
With this knowledge at the molecular level of compounds that can activate versus inhibit closely related human ion channel proteins, future work can be directed at improving drug specificity and therefore safety, while retaining efficacy. More specifically, medicinal chemistry approaches can be applied to further optimize the plant compounds with the goal of treating pain and secretory diarrhea.
“I personally am very excited about the paper; it was my lab’s first published collaboration with the National Park Service, and it shines a light on the incredible ingenuity and medicinal wisdom of Californian Native American tribes,” said Abbott.
The public health implications for improved drugs in these areas are considerable. Novel, non-opioid analgesics are highly sought after as we battle the twin public health concerns of chronic pain and opioid addiction. In addition, according to the CDC, diarrheal diseases account for 1 in 9 child deaths worldwide; incredibly, diarrhea kills over 2000 children every day worldwide — more than AIDS, malaria and measles combined.
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Drinking coffee or tea may be associated with a lower risk of stroke and dementia, according to a study of healthy individuals aged 50-74 publishing Nov. 16 in the open-access journal PLOS Medicine. Drinking coffee was also associated with a lower risk of post-stroke dementia.
Strokes are life-threatening events which cause 10 percent of deaths globally. Dementia is a general term for symptoms related to decline in brain function and is a global health concern with a high economic and social burden. Post-stroke dementia is a condition where symptoms of dementia occur after a stroke.
Yuan Zhang and colleagues from Tianjin Medical University, Tianjin, China studied 365,682 participants from the UK Biobank, who were recruited between 2006 and 2010 and followed them until 2020. At the outset participants self-reported their coffee and tea intake. Over the study period, 5,079 participants developed dementia and 10,053 experienced at least one stroke.
People who drank 2-3 cups of coffee or 3-5 cups of tea per day, or a combination of 4-6 cups of coffee and tea had the lowest incidence of stroke or dementia. Individuals who drank 2-3 cups of coffee and 2-3 cups of tea daily had a 32% lower risk of stroke (HR, 0.68, 95% CI, 0.59-0.79; P

The most common pharmaceuticals on the market are made by chaining together rings of molecules to create the drugs that treat conditions including pain, depression and leukemia.
But creating those rings and forming them in a way that is tailored to each individual disease has always been a cumbersome and expensive process in medicinal chemistry.
New research, published today in the journal Chem, proposes a way to simplify that transformation. The discovery will likely make it easier to produce new drug candidates, the researchers say.
David Nagib, senior author of the study and associate professor of chemistry at The Ohio State University, likened the chain of molecules to a belt with no holes: With no way to fasten the circle and no measurements for where holes might go, the belt can’t be assembled in a way that keeps it closed.
“The problem we were trying to solve is how do you punch the hole so that it fits you perfectly, and get it right on the first try without measuring,” Nagib said. “The trick here was we had to put the holes in just the right place, but we had to figure out precisely where the holes should go, without any markings to tell us where that might be.”
The “belt” in this case is a string of carbon-hydrogen bonds, the most ubiquitous bonds in all of nature and medicines. Most drugs contain rings of carbon-hydrogen bonds, linked together by a “bridging” nitrogen atom, within complex structures that interact precisely with cellular components in the body — like a key fitting into a lock. The most common ring found in all medications are six-sided ones, called a piperidine.
But piperidines have long been difficult and expensive to produce, primarily because chemists could not quickly or cheaply replace a carbon-hydrogen bond with other chemical bonds.
Researchers in Nagib’s lab at Ohio State found a way to replace that bond — establishing the “hole” that allowed them to close the belt — by oxidizing two carbon-hydrogen bonds. Doing that allowed them to select hydrogen molecules and remove them from the molecule chain. Then, they used light and a copper catalyst to turn one of those bonds into the needed nitrogen ring. The light worked to excite catalysts in a chain process similar to photosynthesis, the way plants use light to create food for themselves.
The process solves a problem for making early-stage drug candidates still in development – it is still too expensive to be used to mass-produce medication. Nagib said future work will focus on using a cheaper starting material to scale up production.
“This discovery is something that can make it possible to more rapidly create a library of drug candidates for testing, so you can identify the right, most potent, most effective one more quickly,” Nagib said.
Ohio State researchers Leah M. Stateman, now at Merck and Co., Ross M. Dare and Alyson N. Paneque contributed to this work. The research was funded by the National Institutes of Health.
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Materials provided by Ohio State University. Original written by Laura Arenschield. Note: Content may be edited for style and length.

Immunotherapies, which harness the body’s natural defenses to combat disease, have revolutionized the treatment of aggressive and deadly cancers. But often, these therapies — especially those based on immune cells — must be tailored to the individual patient, costing valuable time and pushing their price into the hundreds of thousands of dollars.
Now, in a study published in the journal Cell Reports Medicine, UCLA researchers report a critical step forward in the development of an “off-the-shelf” cancer immunotherapy using rare but powerful immune cells that could potentially be produced in large quantities, stored for extended periods and safely used to treat a wide range of patients with various cancers.
“In order to reach the most patients, we want cell therapies that can be mass-produced, frozen and shipped to hospitals around the world,” said Lili Yang, a member of the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA and the study’s senior author. “That way, doses of these therapies can be ready and waiting for patients as soon as they are needed.”
For the study, Yang and her colleagues focused on invariant natural killer T cells, or iNKT cells, which are unique not only for their power and efficacy but also because they don’t carry the risk of graft-versus-host disease, which occurs when transplanted cells attack a recipient’s body and which is the reason most cell-based immunotherapies must be created on a patient-specific basis, Yang said.
The researchers developed a new method for producing large numbers of these iNKT cells using blood-forming stem cells, which can self-replicate and produce all kinds of blood and immune cells. The team used stem cells obtained from four donor cord-blood samples and eight donor peripheral blood samples.
“Our findings suggest that one cord blood donation could produce up to 5,000 doses of the therapy and one peripheral blood donation could produce up to 300,000 doses,” said Yang, who is also an associate professor of microbiology, immunology and molecular genetics and a member of the UCLA Jonsson Comprehensive Cancer Center. “At this yield, the cost of producing immune cell products could be dramatically reduced.”
The researchers first used genetic engineering to program the blood-forming stem cells to make them more likely to develop into iNKT cells. Next, these genetically engineered stem cells were placed into artificial thymic organoids, which mimic the environment of the thymus, a specialized organ in which T cells naturally mature in the body. After eight weeks in the organoids, each stem cell produced, on average, 100,000 iNKT cells.

Researchers at Georgia State University have created lightning-fast computer software that can help nations track and analyze pandemics, like the one caused by COVID-19, before they spread like wildfire around the globe.
The group of computer science and mathematics researchers says its new software is several orders of magnitude faster than existing computer programs and can process more than 200,000 novel virus genomes in less than two hours. The software then builds a clear visual tree of the strains and where they are spreading. This provides information that can be invaluable for countries making early decisions about lockdowns, quarantines, social distancing and testing during infectious disease outbreaks.
“The future of infectious outbreaks will no doubt be heavily data driven,” said Alexander Zelikovsky, a Georgia State computer science professor who worked on the project.
The new software was co-created with Pavel Skums, assistant professor of computer science, Mark Grinshpon, principal senior lecturer of mathematics and statistics, Daniel Novikov, a computer science Ph.D. student, and two former Georgia State Ph.D. students — Sergey Knyazev (now a postdoctoral scholar at the University of California at Los Angeles) and Pelin Icer (now a postdoctoral scholar at Swiss Federal Institute of Technology, ETH Zürich).
Their paper describing the new approach, “Scalable Reconstruction of SARS-CoV-2 Phylogeny with Recurrent Mutations,” was published in the Journal of Computational Biology.
“The COVID-19 pandemic has been an unprecedented challenge and opportunity for scientists,” said Skums, who noted that never before have researchers around the world sequenced so many complete genomes of any virus. The strains of SARS-CoV-2 are uploaded onto the free global GISAID database (https://www.gisaid.org/hcov19-variants/), where they can be data-mined and studied by any scientist. Zelikovsky, Skums and their colleagues analyzed more than 300,000 different GISAID strains for their new work.

SharecloseShare pageCopy linkAbout sharingImage source, Getty ImagesA woman from Argentina appears to have rid herself of HIV without drugs or treatment – the second documented case of its kind in the world.Doctors believe the patient’s immune system cleared the virus on its own.Tests on more than a billion of her cells found no viable trace of the infection, Archives of Internal Medicine reports.If this process could be harnessed, it might offer a way to wipe out or effectively cure HIV, experts say.Eliminating HIVThe findings are further proof a few people are born with natural resilience to HIV. Some have genes that prevent infection. Others – including “the Esperanza patient”, who wishes to remain anonymous – appear to catch but then eradicate the virus.But most people with HIV need life-long antiretroviral therapy (ART).And if they stop taking these drugs, the dormant virus can reawaken and cause problems again.In recent years, however, there have been reports of “elite controllers” who can suppress the virus, with help but no HIV medication. Adam Castillejo, from London, was able to stop taking his daily HIV pills after receiving a donor stem-cell treatment for a cancer he also had. London patient cured of HIV, say doctorsHis HIV-infected cells were wiped out and replaced during the cancer therapy.And fortuitously, his donor was one of the 1% of people born with genes that prevent HIV entering and infecting cells. It is unclear how long this advantage might last for Mr Castillejo, however. ‘Sterilising cure’But the Esperanza patient has had no detectable HIV for more than eight years. Loreen Willenberg, from San Francisco, also appears to be functionally cured of HIV by her own immune system. And this offers hope of a “sterilising cure” for other patients. Lead investigator Dr Xu Yu, from the Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard, said: “There may be an actionable path to a sterilising cure for people who are not able to do this on their own.”We are now looking toward the possibility of inducing this kind of immunity in persons on ART, through vaccination, with the goal of educating their immune systems to be able to control the virus without ART.”‘Abortive infection’Prof John Frater, from the University of Oxford, told BBC News while it was almost impossible to say if someone had been truly cured of HIV, the investigators had done “as much as could be asked of them with current technology” to prove it. “The key question is whether this patient has actually cured themselves or, alternatively, had some form of abortive infection, which tried to get going but the embers were snuffed out early,” he said. “Her immune system clearly shows a memory of having been infected, so there seems to be no question that she was. “Regardless, there may be similar patients out there, offering much to learn in the search for a HIV cure.” Prof Sarah Fidler, an expert in HIV medicine at Imperial College London, said the work would help inform immune therapies currently under development.But Dr Andrew Freedman, from Cardiff University Medical School, said current HIV drugs were extremely effective and while looking at future treatments was important, improving access to life-changing ART around the globe was an urgent priority. NatureAnnals of Internal MedicineThe BBC is not responsible for the content of external sites.

What to Know About Covid Boosters in N.Y.C.Sharon Otterman��Reporting from New York City“No one who feels they are at risk should be turned away,” Gov. Kathy Hochul said Monday. New York is not alone. Several states, like California, Colorado and Arkansas, have taken similarly liberal stances toward the C.D.C. guidelines. The idea, said Dr. Dave Chokshi, the city’s health commissioner, is to get as many people vaccinated and boosted as possible before the holiday season.

SharecloseShare pageCopy linkAbout sharingImage source, Getty ImagesUS drug company Pfizer has penned a deal to allow its experimental Covid-19 treatment pill to be made and sold in 95 developing nations. The deal with the UN-backed Medicines Patent Pool not-for-profit could make the treatment available to 53% of the world’s population. But it excludes several countries that have had large Covid-19 outbreaks, including Brazil.Pfizer says the pill lessens the risk of severe disease in vulnerable adults.In a statement on Tuesday, Pfizer said the agreement will allow local medicine manufacturers to produce the pill “with the goal of facilitating greater access to the global population”. Pfizer will not receive royalties on sales in lower income countries and said it would waive royalties in all nations included in the agreement while Covid remains a World Health Organization-designated public health emergency.In early November, Pfizer said clinical trials suggest that its Covid-19 pill, Paxlovid, cuts the risk of hospital admission or death by 89% for high-risk adult patients. Charles Gore, director of the Medicines Patent Pool, said in a statement the licence was important as “this oral drug is particularly well-suited for low- and middle-income countries and could play a critical role in saving lives”.Antiviral Covid pill 89% effective, Pfizer saysCovid map: Where are cases the highest? Most of the countries included are in Africa or Asia. However, nations like Brazil, China, Russia, Argentina and Thailand, which have experienced major outbreaks, are not part of the deal.Some experts say this is not enough to address inequalities in access to Covid-19 treatments and vaccines.Pfizer and other pharmaceutical companies have also pushed back against calls to lift patents on their Covid jabs.Could lifting patents mean Covid vaccines for all?Covid vaccines: How fast is worldwide progress?Doctors Without Borders said it was “disheartened” that the deal doesn’t make Pfizer’s Covid-19 pills available everywhere in the world in a statement to the Associated Press.”The world knows by now that access to Covid-19 medical tools need to be guaranteed for everyone, everywhere, if we really want to control this pandemic,” the group’s legal policy adviser Yuanqiong Hu said.In October, another drugmaker, Merck, announced a similar deal with the Medicines Patent Pool to allow manufacturers to produce its own Covid-19 pill, molnupiravir.

To navigate successfully in an environment, you need to continuously track the speed and direction of your head, even in the dark. Researchers at the Sainsbury Wellcome Centre at UCL have discovered how individual and networks of cells in an area of the brain called the retrosplenial cortex encode this angular head motion in mice to enable navigation both during the day and at night.
“When you sit on a moving train, the world passes your window at the speed of the motion of the carriage, but objects in the external world are also moving around relative to one another. One of the main aims of our lab is to understand how the brain uses external and internal information to tell the difference between allocentric and egocentric-based motion. This paper is the first step in helping us understand whether individual cells actually have access to both self-motion and, when available, the resultant external visual motion signals” said Troy Margrie, Associate Director of the Sainsbury Wellcome Centre and corresponding author on the paper.
In the study, published today in Neuron, the SWC researchers found that the retrosplenial cortex uses vestibular signals to encode the speed and direction of the head. However, when the lights are on, the coding of head motion is significantly more accurate.
“When the lights are on, visual landmarks are available to better estimate your own speed (at which your head is moving). If you can’t very reliably encode your head turning speed, then you very quickly lose your sense of direction. This might explain why, particularly in novel environments, we become much worse at navigating once the lights are turned out,” said Troy Margrie.
To understand how the brain enables navigation with and without visual cues, the researchers recorded from neurons across all layers in the retrosplenial cortex as the animals were free to roam around a large arena. This enabled the neuroscientists to identify neurons in the brain called angular head velocity (AHV) cells, which track the speed and direction of the head.
Sepiedeh Keshavarzi, Senior Research Fellow in the Margrie Lab, and lead author on the paper, also then recorded from these same AHV neurons during head-fixed conditions to allow the removal of specific sensory/motor information. By comparing very precise angular head rotations in the dark and in the presence of a visual cue (vertical gratings), with the results of the freely-moving condition, Sepiedeh was able to determine the while vestibular inputs alone can generate head angular velocity signals, their sensitivity to head motion speed is vastly improved when visual information is available.
“While it was already known that the retrosplenial cortex is involved in the encoding of spatial orientation and self-motion guided navigation, this study allowed us to look at integration at both a network and cellular level. We showed that a single cell can see both kinds of signals: vestibular and visual. What was also critically important was the development of a behavioural task that enabled us to determine that mice improve their estimation of their own head angular speed when a visual cue is present. It’s pretty compelling that both the coding of head motion and the mouse’s estimates of their motion speed both significantly improve when visual cues are available,” commented Troy Margrie.
The next steps will be to explore the pathways that bring vestibular and visual information to the retrosplenial cortex and where these signals might be relayed to. We now know there is, for example, a strong feedback loop with primary visual cortex that also receives motor signals relating to running speed. Future experiments designed to isolate and manipulate specific types of neural activity will inform us as to how the cortex disambiguates self-motion generated signals from allocentric ones, a process that is critical to how we navigate through a complex visual world.
This research was funded by the Sainsbury Wellcome Centre Core Grant from the Gatsby Charity Foundation (GAT3361) and Wellcome Trust (090843/F/09/Z and 214333/Z/18/Z).
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