Publisher Health

The eyes have been called the window to the brain. It turns out they also serve as an immunological barrier that protects the organ from pathogens and even tumors, Yale researchers have found.
In a new study, researchers showed that vaccines injected into the eyes of mice can help disable the herpes virus, a major cause of brain encephalitis. To their surprise, the vaccine activates an immune response through lymphatic vessels along the optic nerve.
The results were published Feb. 28 in the journal Nature.
“There is a shared immune response between the brain and the eye,” said Eric Song, an associate research scientist and resident physician in Yale School of Medicine’s Department of Immunobiology and corresponding author of the paper. “And the eyes provide easier access for drug therapies than the brain does.”
Wanting to explore immunological interactions between brain and eyes, the research team, which was led by Song, found that the eyes have two distinct lymphatic systems regulating immune responses in the front and rear of the eye. After they vaccinated mice with inactivated herpes virus, the researchers found that lymphatic vessels in the optic nerve sheath at the rear of the eye protected mice not only from active herpes infections, but from bacteria and even brain tumors.
Harnessing this new biology, Song’s team is currently testing newly created drugs from his lab delivered through eye injections that may help combat macular edema, or leaky blood vessels of the retina common in people with diabetes, and glaucoma.
“These results reveal a shared lymphatic circuit able to mount a unified immune response between posterior eye and the brain, highlighting an understudied immunological feature of the eyes and opening up the potential for new therapeutic strategies in ocular and central nervous system diseases,” the authors wrote.
Xiangyun Yin, an associate researcher in Yale’s Department of Immunobiology; Sophia Zhang, an undergraduate student at Yale College; and Ju Hyun Lee, a doctoral student in the Department of Biomedical Engineering, are co-lead authors of the study.

A microscopic battle rages in our bodies, as our cells constantly fend off invaders through our immune system, a complex system of cells and proteins designed to protect us from harmful pathogens. One of its central components is the enzyme cyclic GMP-AMP synthase (cGAS), which acts as a sentinel, detecting foreign DNA and initiating an immune response.
However, the immune system requires precise regulation to prevent cGAS from mistakenly attacking the body’s own tissues, leading to autoimmune disorders, which now affect about 10% of the global population.
Previous studies have revealed a little of how this happens. During cell division — mitosis — the membrane that protects the cell’s nucleus, the nuclear envelope, breaks down and cGAS quickly relocates into the nucleus. There, it attaches itself to nucleosomes — the basic structural unit of DNA packaging in the cell — and becomes covered by another protein called BAF.
All this ensures that cGAS stays inactive and fixed in place, and does not mistakenly interact with the cell’s own DNA. It represents a sophisticated balance between immune readiness and protecting the integrity of the cell’s genome. The question is, how does the cell coordinate this with its other everyday functions?
A new study from the group of Andrea Ablasser at EPFL sheds light on how cGAS is regulated, especially during the critical phase of cell division known as mitosis. The study is published in Nature.
The team used advanced imaging and molecular techniques to observe how cGAS is selectively broken down in the nucleus, preventing it from mistakenly responding to the cell’s own DNA. They found that the process is mediated by a protein complex known as CRL5-SPSB3, which recognizes a specific motif in cGAS and tags it in the nucleus for destruction. Using structural biology, biochemistry, and cell biology, the researchers visualized the interactions between cGAS and the protein complex at the atomic level.
Specifically, CRL5-SPSB3 adds a protein called ubiquitin to cGAS. Ubiquitin — as the name suggests — is found ubiquitously across eukaryotic cells and one of its functions is to mark other proteins for death. The ubiquitination of cGAS also marks it for destruction, effectively inactivating the sentinel once the threat of an invader has been neutralized.
By elucidating the structure of the cGAS-SPSB3 complex, the study maps out how cGAS is regulated within the nucleus of cells, highlighting the sophistication of the immune system`s regulatory networks.
The implications also extend beyond basic science, allowing scientists to explore new strategies for treating diseases where the immune system is either overactive, such as in autoimmune diseases, or underactive, as in cases of chronic infections or cancer. For example, modulating cGAS activity could potentially enhance the effectiveness of cancer immunotherapies or provide new approaches to preventing autoimmune conditions.

Scientists at UC San Francisco may have discovered a new way to test for autism by measuring how children’s eyes move when they turn their heads.
They found that kids who carry a variant of a gene that is associated with severe autism are hypersensitive to this motion.
The gene, SCN2A, makes an ion channel that is found throughout the brain, including the region that coordinates movement, called the cerebellum. Ion channels allow electrical charges in and out of cells and are fundamental to how they function. Several variants of this gene are also associated with severe epilepsy and intellectual disability.
The researchers found that children with these variants have an unusual form of the reflex that stabilizes the gaze while the head is moving, called the vestibulo-ocular reflex (VOR). In children with autism, it seems to go overboard, and this can be measured with a simple eye-tracking device.
The discovery could help to advance research on autism, which affects 1 out of every 36 children in the United States. And it could help to diagnose kids earlier and faster with a method that only requires them to don a helmet and sit in a chair.
“We can measure it in kids with autism who are non-verbal or can’t or don’t want to follow instructions,” said Kevin Bender, PhD, a professor in the UCSF Weill Institute for Neurosciences and co-senior author of the study, which appears Feb. 26 in Neuron. “This could be a game-changer in both the clinic and the lab.”
A telltale sign of autism in an eye reflex
Of the hundreds of gene mutations associated with autism, variants of the SCN2A gene are among the most common.

Since autism affects social communication, ion channel experts like Bender had focused on the frontal lobe of the brain, which governs language and social skills in people. But mice with an autism-associated variant of the SCN2A gene did not display marked behavioral differences associated with this brain region.
Chenyu Wang, a UCSF graduate student in Bender’s lab and first author of the study, decided to look at what the SCN2A variant was doing in the mouse cerebellum. Guy Bouvier, PhD, a cerebellum expert at UCSF and co-senior author of the paper, already had the equipment needed to test behaviors influenced by the cerebellum, like the VOR.
The VOR is easy to provoke. Shake your head and your eyes will stay roughly centered. In mice with the SCN2A variant, however, the researchers discovered that this reflex was unusually sensitive. When these mice were rotated in one direction, their eyes compensated perfectly, rotating in the opposite direction.
But this increased sensitivity came at a cost. Normally, neural circuits in the cerebellum can refine the reflex when needed, for example to enable the eyes to focus on a moving object while the head is also moving. In SCN2A mice, however, these circuits got stuck, making the reflex rigid.
A mouse result translates nearly perfectly to kids with autism
Wang and Bender had uncovered something rare: a behavior that arose from a variant to the SCN2A gene that was easy to measure in mice. But would it work in people?

They decided to test it with an eye-tracking camera mounted on a helmet. It was a “shot in the dark,” Wang said, given that the two scientists had never conducted a study in humans.
Bender asked several families from the FamilieSCN2A Foundation, the major family advocacy group for children with SCN2A variants in the US, to participate. Five children with SCN2A autism and eleven of their neurotypical siblings volunteered.
Wang and Bender took turns rotating the children to the left and right in an office chair to the beat of a metronome. The VOR was hypersensitive in the children with autism, but not in their neurotypical siblings.
The scientists could tell which children had autism just by measuring how much their eyes moved in response to their head rotation.
A CRISPR cure in mice
The scientists also wanted to see if they could restore the normal eye reflex in the mice with a CRISPR-based technology that restored SCN2A gene expression in the cerebellum.
When they treated 30-day-old SCN2A mice — equivalent to late adolescence in humans — their VOR became less rigid but was still unusually sensitive to body motion. But when they treated 3-day-old SCN2A mice — early childhood in humans — their eye reflexes were completely normal.
“These first results, using this reflex as our proxy for autism, point to an early window for future therapies that get the developing brain back on track,” Wang said.
It’s too early to say whether such an approach might someday be used to directly treat autism. But the eye reflex test, on its own, could clear the way to more expedient autism diagnosis for kids today, saving families from long diagnostic odysseys.
“If this sort of assessment works in our hands, with kids with profound, nonverbal autism, there really is hope it could be more widely adopted,” Bender said.
For funding and disclosures, see the paper.
Other UCSF authors are Kimberly D. Derderian, Elizabeth Hamada, Xujia Zhou, Andrew D. Nelson, Henry Kyoung, and Nadav Ahituv. Guy Bouvier is now a professor of neuroscience at the Université Paris-Saclay, France.

An analysis of 430,000 adults in the U.S. found that using cannabis, most commonly through smoking, eating or vaporizing it, was significantly associated with a higher risk of heart attack and stroke, even after controlling for tobacco use (combustible cigarettes and other tobacco products) and other cardiovascular risk factors, according to new research published today in the Journal of the American Heart Association, an open access, peer-reviewed journal of the American Heart Association.
Although cannabis, or marijuana, is illegal at the federal level, 24 states and Washington, D.C., have legalized the use of recreational cannabis. Additionally, the number of people in the U.S. who use cannabis has increased significantly in recent decades, according to the 2019 National Survey on Drug Use and Health from the Substance Abuse and Mental Health Services Administration of the U.S. Department of Health and Human Services. The annual survey found that in 2019, 48.2 million people ages 12 or older reported using cannabis at least once, compared to 25.8 million people ages 12 or older in 2002, an increase to 17% from 11%.
“Despite common use, little is known about the risks of cannabis use and, in particular, the cardiovascular disease risks,” said lead study author Abra Jeffers, Ph.D., a data analyst at Massachusetts General Hospital in Boston. “The perceptions of the harmfulness of smoking cannabis are decreasing, and people have not considered cannabis use dangerous to their health. However, previous research suggested that cannabis could be associated with cardiovascular disease. In addition, smoking cannabis — the predominant method of use — may pose additional risks because particulate matter is inhaled.”
In this study, researchers reviewed survey data collected for 430,000 adults from 2016 through 2020 to examine the association between cannabis use and adverse cardiovascular outcomes including heart disease, heart attack and stroke. The survey data was collected through the Behavioral Risk Factor Surveillance System, a national, cross-sectional survey performed annually by the U.S. Centers for Disease Control and Prevention.
The researchers specifically investigated whether cannabis use was associated with adverse cardiovascular outcomes among the general adult population, among people who had never smoked tobacco or used e-cigarettes, and among younger adults (defined as men under age 55 and women under age 65) at risk for heart disease. They also factored in the number of days per month that people used cannabis.
The analyses of found: Any cannabis use (smoked, eaten or vaporized) was independently associated with a higher number of adverse cardiovascular outcomes (coronary heart disease, myocardial infarction and stroke) and with more frequent use (more days per month), the odds of adverse outcomes were even higher. The results were similar after controlling for other cardiovascular risk factors, including tobacco and/or e-cigarette use, alcohol consumption, body mass index, Type 2 diabetes and physical activity. Both daily and non-daily cannabis users had an increased risk of heart attack compared to non-users; daily cannabis users had 25% higher odds of heart attack compared to non-users. The odds of stroke for daily cannabis users were 42% higher compared to non-users, with lower risk among those who used cannabis less than daily. Among younger adults at risk for premature cardiovascular disease (defined as men younger than 55 years old and women younger than 65 years old) cannabis use was significantly associated with 36% higher combined odds of coronary heart disease, heart attack and stroke, regardless of whether or not they also used traditional tobacco products. A separate analysis of a smaller subgroup of these adults who had never smoked tobacco cigarettes or used nicotine e-cigarettes also found a significant association between cannabis use and an increase in the combined odds of coronary heart disease, heart attack and stroke.”Our sample was large enough that we could investigate the association of cannabis use with cardiovascular outcomes among adults who had never used tobacco cigarettes or e-cigarettes,” Jeffers said. “Cannabis smoke is not all that different from tobacco smoke, except for the psychoactive drug: THC vs. nicotine. Our study shows that smoking cannabis has significant cardiovascular risk risks, just like smoking tobacco. This is particularly important because cannabis use is increasing, and conventional tobacco use is decreasing.”
Study background and details: Survey participants were ages 18-74, with an average age of 45 years. About half of the participants self-identified as female. 60.2% self-identified as white adults, 11.6 self-identified as Black adults, 19.3 self-identified as Hispanic adults and 8.9% self-identified as other. Nearly 90% of adults did not use cannabis at all; 7% used it less than daily; and 4% were daily users. Among current cannabis users, 73.8% reported smoking as the most common form of cannabis consumption. More than 60% of total respondents had never used tobacco cigarettes; 28.6% of daily cannabis users had never used tobacco cigarettes; 44.6% of non-daily cannabis users had never used tobacco cigarettes and 63.9% of participants who did not use cannabis had never used tobacco cigarettes.

The study had several limitations, including that cardiovascular conditions and cannabis use were self-reported, making them potentially subject to recall bias (potential errors in memory); that the authors did not have health data measuring participants’ baseline lipid profile or blood pressure; and the study captured data for only a single point in time for the participants. The authors note that there is a need for prospective cohort studies — studies that follow groups of individuals over time — to examine the association of cannabis use and cardiovascular outcomes while accounting for frequency of cannabis use.
“The findings of this study have very important implications for population health and should be a call to action for all practitioners, as this study adds to the growing literature that cannabis use and cardiovascular disease may be a potentially hazardous combination,” said Robert L. Page II, Pharm.D., M.S.P.H., FAHA, chair of the volunteer writing group for the 2020 American Heart Association Scientific Statement: Medical Marijuana, Recreational Cannabis, and Cardiovascular Health. Page is professor of clinical pharmacy, medicine and physical medicine at the Skaggs School of Pharmacy and Pharmaceutical Sciences at the University of Colorado School of Medicine in Aurora, Colorado. Page was not involved in this study.
“In the overall population, the study findings are consistent with other studies indicating that daily cannabis use was associated with an increase in heart attack, stroke and the combined endpoint of coronary heart disease, heart attack and stroke,” he said. “As cannabis use continues to grow in legality and access across the U.S., practitioners and clinicians need to remember to assess cannabis use at each patient encounter in order to have a non-judgmental, shared decision conversation about potential cardiovascular risks and ways to reduce those risks.”

Based on decades-long observations of centenarians, author Dan Buettner (Blue Zones) conjectures that people live longer when they get up and move around after sitting for twenty minutes. Now, a rigorous new study published in the Journal of the American Heart Association (JAHA) has data showing that older women who sat for 11.7 hours or more per day increased their risk of death by 30 percent, regardless of whether they exercised vigorously.
Study co-author Steve Nguyen, Ph.D., M.P.H., a postdoctoral fellow at the University of California San Diego Herbert Wertheim School of Public Health and Human Longevity Science, examined measurements of sitting and daily activity collected from hip devices worn for up to seven days by 6,489 women, aged 63 to 99, who were followed for eight years for mortality outcomes. This data was collected in a study led by Andrea LaCroix, Ph.D., M.P.H., Distinguished Professor at the Herbert Wertheim School of Public Health, as part of a long-term national project known as the Women’s Health Initiative (WHI), which began in 1991 and is ongoing.
Nguyen’s paper is the first to apply a novel and validated machine-learned algorithm called CHAP to examine total sitting time and length of sitting bouts in relation to the risk of death. “Sedentary behavior is defined as any waking behavior involving sitting or reclining with low energy expenditure,” explains Nguyen. “Previous techniques for calculating sedentary behavior used cut points that identified low or absent movement. The CHAP algorithm was developed using machine-learning, a type of artificial intelligence, that enhanced its ability to accurately distinguish between standing and sitting.” Fine-tuning “sitting” enabled Nguyen to parse total sitting time and usual sitting bout durations.
Sedentary behavior is a health risk because it reduces muscle contractions, blood flow and glucose metabolism. “When you’re sitting, the blood flow throughout your body slows down, decreasing glucose uptake. Your muscles aren’t contracting as much, so anything that requires oxygen consumption to move the muscles diminishes, and your pulse rate is low,” said LaCroix.
Unfortunately, exercise cannot undo these negative effects. According to the study, whether women participated in low or high amounts of moderate-to-vigorous intensity physical activity, they showed the same heightened risk if they sat for long hours.
“If I take a brisk long walk for an hour but sit the rest of the day, I’m still accruing all the negative effects on my metabolism,” said LaCroix.
Based on the research, LaCroix makes the following recommendation: “The risk starts climbing when you’re sitting about 11 hours per day, combined with the longer you sit in a single session. For example, sitting more than 30 minutes at a time is associated with higher risk than sitting only 10 minutes at a time. Most people aren’t going to get up six times an hour, but maybe people could get up once an hour, or every 20 minutes or so. They don’t have to go anywhere, they can just stand for a little while.”
However, Nguyen points out that not all sitting is the same. “Looking beyond conditions like cardiovascular disease, we start thinking about cognitive outcomes, including dementia,” he said. “There are cognitively stimulating activities that can result in sedentary behavior, like sitting while studying a new language. Is sedentary behavior in that context overall bad for a person? I think it’s hard to say.” Nguyen has recently received a National Institute of General Medical Sciences K99 award for 12 months of mentored research to look at protein signatures of physical activity and how they relate to dementia.

LaCroix is sympathetic to the challenges of modifying sedentary behavior, but she knows that the modifications are necessary, if not easy. “We’ve created this world in which it’s so fascinating to sit and do things. You can be engrossed by TV or scroll on your Instagram for hours. But sitting all the time isn’t the way we were meant to be as humans, and we could reverse all of that culturally just by not being so attracted to all the things that we do while sitting.”
Co-authors on the study include John Bellettiere, Blake Anuskiewicz and Loki Natarajan at UC San Diego, Chongzhi Di at Fred Hutchinson Cancer Center, Jordan Carlson at Children’s Mercy Kansas City and Michael J. LaMonte at University at Buffalo.
This study was funded, in part, by the National Institutes of Health (grants P01 AG052352, R01 HL105065, 75N92021D00001, 75N92021D00002, 75N92021D00003, 75N92021D00004, 75N92021D00005, 5T32AG058529?03, R01DK114945) and the Tobacco-Related Disease Research Program

Half a century ago, scientists Jim Watson and Alexey Olovnikov independently realized that there was a problem with how our DNA gets copied. A quirk of linear DNA replication dictated that telomeres that protect the ends of chromosomes should have been growing shorter with each round of replication, a phenomenon known as the end-replication problem.
But a solution was forthcoming: Liz Blackburn and Carol Greider discovered telomerase, an enzyme that adds the telomeric repeats to the ends of chromosomes. “Case closed, everybody thought,” says Rockefeller’s Titia de Lange.
Now, new research published in Nature suggests that there are two end-replication problems, not one. Further, telomerase is only part of the solution — cells also use the CST-Polα-primase complex, which has been extensively studied in de Lange’s laboratory. “For many decades we thought we knew what the end-replication problem was and how it was solved by telomerase,” says de Lange. “It turns out we had missed half the problem.”
The leading-strand problem
Since the description of the DNA double helix, it is known that DNA has two complementary strands running in opposite directions — one from 5′ to 3′; the other from 3′ to 5′. When DNA is replicated, the two strands are separated by the replication machinery, also called the replisome. The replisome copies the 3′ to 5′ strand without interruption, a process referred to as leading-strand synthesis. But the other strand is synthesized in short backward steps from many fragments (Okazaki fragments) that are later stitched together.
The process is fairly direct until the ends of the chromosomes. When copying the telomere, leading-strand DNA replication should copy the CCCTAA repeats to generate the TTAGGG repeat strand, while lagging-strand synthesis should do the opposite, making new CCCTAA repeats. The end-replication problem arises because leading strand synthesis fails to reproduce the last part of the telomere, leaving a blunt leading-end telomere without it characteristic and crucial 3′ overhang. Telomerase solves this problem by adding single-stranded TTAGGG repeats to the telomere end. As for the lagging-strand, DNA synthesis should not have a problem. It could start the last Okazaki fragment somewhere along the 3′ overhang.
“The DNA replication machinery cannot not fully duplicate the end of a linear DNA, much the same way that you can’t paint the floor under your feet” says Hiro Takai, senior staff scientist in the de Lange lab and lead author on the paper.

The lagging-strand problem
As descriptions of biological processes go, this model looked watertight. Until Takai made a surprising discovery while working on cells that lacked molecular machinery called the CST-Polα-primase complex. He and others had previously shown that CST-Polα-primase can replenish CCCTAA repeats at telomeres that had been attacked by DNA-degrading enzymes known as nucleases. This new data revealed something unexpected: not only was the leading strand in need of help — he found evidence that the end of the lagging strand could also not be synthesized by the replisome.
Takai’s work suggested that the end-replication problem was twice as serious as previously thought, impacting both strands of DNA. “The results just didn’t fit with the model for telomere replication,” de Lange says. “At that point, Hiro and I realized that either his results were not right or the model was wrong. As his results seemed very solid to me, we needed to revisit the model.”
De Lange contacted Joseph T. P. Yeeles, a biochemist who studies DNA replication at the Laboratory of Molecular Biology in Cambridge (the same lab where Watson and Crick worked on the structure of the DNA double helix). Yeeles agreed that it would be good to take a close look at how the replisome behaves at the end of a linear DNA template. Could the replisome use a 3′ overhang to make the last Okazaki fragment, as was proposed?
The results of Yeeles’ in vitro replication experiments were very clear. The replisome does not generate Okazaki fragments on the 3′ overhang; it actually stops lagging-strand synthesis long before the leading strand reaches the 5′ end. This second end-replication problem means that both strands of DNA will shorten with each division. Telomerase was only preventing this from happening at the leading strand and Hiro’s data suggested that CST-Polα-primase fixed the second end-replication problem, that of the lagging strand.
Takai spent the next four years designing new assays to confirm Yeeles’ findings in vivo. He was able to measure how much DNA is lost due to the lagging-strand end-replication problem, revealing how many CCCAAT repeats need to be added by CST-Polα-primase to keep telomeres intact.
The results change our understanding of telomere biology — requiring revision of the textbooks. But the findings may also have clinical implications. Individuals who inherit mutations in CST-Polα-primase suffer from telomere disorders, such as Coats plus syndrome, which is characterized by an eye disorder and abnormalities in the brain, bones, and GI tract. Through a better understanding of how we maintain our telomeres, strides could one day be made in addressing these devastating disorders.

Studies at MIT and elsewhere are producing mounting evidence that light flickering and sound clicking at the gamma brain rhythm frequency of 40 Hz can reduce Alzheimer’s disease (AD) progression and treat symptoms in human volunteers as well as lab mice. In a new study in Nature using a mouse model of the disease, researchers at The Picower Institute for Learning and Memory of MIT reveal a key mechanism that may contribute to these beneficial effects: clearance of amyloid proteins, a hallmark of AD pathology, via the brain’s glymphatic system, a recently discovered “plumbing” network parallel to the brain’s blood vessels.
“Ever since we published our first results in 2016, people have asked me how does it work? Why 40 Hz? Why not some other frequency?” said study senior author Li-Huei Tsai, Picower Professor of Neuroscience and director of The Picower Institute and MIT’s Aging Brain Initiative. “These are indeed very important questions we have worked very hard in the lab to address.”
The new paper describes a series of experiments, led by Mitch Murdock when he was a Brain and Cognitive Sciences doctoral student at MIT, showing that when sensory gamma stimulation increases 40 Hz power and synchrony in the brains of mice, that prompts a particular type of neuron to release peptides. The study results further suggest that those short protein signals then drive specific processes that promote increased amyloid clearance via the glymphatic system.
“We do not yet have a linear map of the exact sequence of events that occurs,” said Murdock, who was jointly supervised by Tsai and co-author and collaborator Ed Boyden, Y. Eva Tan Professor of Neurotechnology at MIT, a member of the McGovern Institute for Brain Research and an affiliate member of The Picower Institute. “But the findings in our experiments support this clearance pathway through the major glymphatic routes.”
From Gamma to Glymphatics
Because prior research has shown that the glymphatic system is a key conduit for brain waste clearance and may be regulated by brain rhythms, Tsai and Murdock’s team hypothesized that it might help explain the lab’s prior observations that gamma sensory stimulation reduces amyloid levels in Alzheimer’s model mice.
Working with “5XFAD” mice, which genentically model Alzheimer’s, Murdock and co-authors first replicated the lab’s prior results that 40 Hz sensory stimulation increases 40 Hz neuronal activity in the brain and reduces amyloid levels. Then they set out to measure whether there was any correlated change in the fluids that flow through the glymphatic system to carry away wastes. Indeed, they measured increases in cerebrospinal fluid in the brain tissue of mice treated with sensory gamma stimulation compared to untreated controls. They also measured an increase in the rate of interstitial fluid leaving the brain. Moreover, in the gamma-treated mice he measured increased diameter of the lymphatic vessels that drain away the fluids and measured increased accumulation of amyloid in cervical lymph nodes, which is the drainage site for that flow.

To investigate how this increased fluid flow might be happening, the team focused on the aquaporin 4 (AQP4) water channel of astrocyte cells, which enables the cells to facilitate glymphatic fluid exchange. When they blocked APQ4 function with a chemical, that prevented sensory gamma stimulation from reducing amyloid levels and prevented it from improving mouse learning and memory. And when, as an added test they used a genetic technique for disrupting AQP4, that also interfered with gamma-driven amyloid clearance.
In addition to the fluid exchange promoted by APQ4 activity in astrocytes, another mechanism by which gamma waves promote glymphatic flow is by increasing the pulsation of neighboring blood vessels. Several measurements showed stronger arterial pulsatility in mice subjected to sensory gamma stimulation compared to untreated controls.
One of the best new techniques for tracking how a condition, such as sensory gamma stimulation, affects different cell types is to sequence their RNA to track changes in how they express their genes. Using this method, Tsai and Murdock’s team saw that gamma sensory stimulation indeed promoted changes consistent with increased astrocyte AQP4 activity.
Prompted by peptides
The RNA sequencing data also revealed that upon gamma sensory stimulation a subset of neurons, called “interneurons,” experienced a notable uptick in the production of several peptides. This was not surprising in the sense that peptide release is known to be dependent on brain rhythm frequencies, but it was still notable because one peptide in particular, VIP, is associated with Alzheimer’s-fighting benefits and helps to regulate vascular cells, blood flow and glymphatic clearance.
Seizing on this intriguing result, the team ran tests that revealed increased VIP in the brains of gamma-treated mice. The researchers also used a sensor of peptide release and observed that sensory gamma stimulation resulted in an increase in peptide release from VIP-expressing interneurons.

But did this gamma-stimulated peptide release mediate the glymphatic clearance of amyloid? To find out, the team ran another experiment: they chemically shut down the VIP neurons. When they did so, and then exposed mice to sensory gamma stimulation, they found that there was no longer an increase in arterial pulsatility and there was no more gamma-stimulated amyloid clearance.
“We think that many neuropeptides are involved,” Murdock said. Tsai added that a major new direction for the lab’s research will be determining what other peptides or other molecular factors may be driven by sensory gamma stimulation.
Tsai and Murdock added that while this paper focuses on what is likely an important mechanism — glymphatic clearance of amyloid — by which sensory gamma stimulation helps the brain, it’s probably not the only underlying mechanism that matters. The clearance effects shown in this study occurred rather rapidly but in lab experiments and clinical studies weeks or months of chronic sensory gamma stimulation have been needed to have sustained effects on cognition.
With each new study, however, scientists learn more about how sensory stimulation of brain rhythms may help treat neurological disorders.
In addition to Tsai, Murdock and Boyden, the paper’s other authors are Cheng-Yi Yang, Na Sun, Ping-Chieh Pao, Cristina Blanco-Duque, Martin C. Kahn, Nicolas S. Lavoie, Matheus B. Victor, Md Rezaul Islam, Fabiola Galiana, Noelle Leary, Sidney Wang, Adele Bubnys, Emily Ma, Leyla A. Akay, TaeHyun Kim, Madison Sneve, Yong Qian, Cuixin Lai, Michelle M. McCarthy, Nancy Kopell, Manolis Kellis, Kiryl D. Piatkevich.
Support for the study came from Barbara J. Weedon, Henry E. Singleton, the Hubolow family, Robert A. and Renee E. Belfer, Eduardo Eurnekian, the Ko Hahn family, the Carol and Gene Ludwig Family Foundation, the Halis Family Foundation, Lester A. Gimpelson, the Dolby family, Jay L. and Carroll D. Miller, Lawrence and Debra Hilibrand, David B. Emmes, the Marc Haas Foundation, The Picower Institute for Learning and Memory, The JPB Foundation, and the National Institutes of Health.

The first nationwide count of telehealth abortions includes pills mailed to states with abortion bans by clinicians in states with shield laws.The NewsA growing share of abortions is now being administered through telemedicine, with clinicians prescribing mail-order abortion pills after online consultations, according to the first nationwide count of telehealth abortions in the U.S. medical system. At least one in six abortions, around 14,000 a month, was conducted via telehealth from July through September, the most recent months with available data.How It WorksPills are prescribed by virtual-only providers and by clinics that also offer in-person services. Patients fill out an online questionnaire or meet with a clinician via video or text chat. This method began nationwide in 2020, when the Food and Drug Administration began allowing abortion providers to mail pills without an in-clinic visit during the pandemic.Some of the prescriptions included in the new count were given to patients in states where abortion is banned, a new development made possible by shield laws. These laws protect clinicians in states where abortion is legal when they prescribe and mail pills to patients in states where it is not. Shield laws were in effect in Colorado, Massachusetts, New York, Vermont and Washington during the period covered by the new data, and California has since passed one.Why It MattersThe growth of telemedicine abortion has made it easier and often less expensive for women to get abortions, particularly if they live far from an abortion clinic or in one of the roughly one-third of states that have banned or substantially restricted abortions since the Supreme Court’s Dobbs decision in 2022.Activists, legislators and prosecutors in the states with bans are working to stem the flow of these mail-order pills. But they have so far proven hard to regulate.The new data, from WeCount, a research group that collects abortion numbers from providers nationwide and supports abortion rights, suggests that the overall number of abortions provided by clinicians in the United States is slightly higher now than it was before the Dobbs decision.We are having trouble retrieving the article content.Please enable JavaScript in your browser settings.Thank you for your patience while we verify access. If you are in Reader mode please exit and log into your Times account, or subscribe for all of The Times.Thank you for your patience while we verify access.Already a subscriber? Log in.Want all of The Times? Subscribe.

Published19 hours agoShareclose panelShare pageCopy linkAbout sharingImage source, GOSHGreat Ormond Street Hospital has written to the families of all children treated by one of its former surgeons after concerns were raised about his practice.Yaser Jabbar, a consultant orthopaedic surgeon, has not had a licence to practise medicine in the UK since 8 January, the medical register shows.Independent experts are now reviewing the concerns raised.The central London hospital apologised for any “worry and uncertainty” caused.The hospital trust said the Royal College of Surgeons (RCS) was asked to review its paediatric orthopaedic service following concerns raised by family members and staff.The RCS then raised concerns about Mr Jabbar, which the trust said were being taken “incredibly seriously” and would be reviewed by independent experts from other paediatric hospitals.A spokesman for the trust said: “We are sorry for the worry and uncertainty this may cause the families who are impacted.”We are committed to learning from every single patient that we treat, and to being open and transparent with our families when care falls below the high standards we strive for.”The spokesperson said Mr Jabbar, reported to be an expert in limb reconstruction, no longer worked at the hospital. Hospital failing intersex childrenGreat Ormond Street concerned over strike staffingGreat Ormond Street doctor suspended for dishonestyThe General Medical Council’s (GMC) website indicates the orthopaedic surgeon was made the subject of certain conditions on 4 January.Those conditions included having a clinical supervisor at all times and seeking approval from the GMC before beginning work in a non-NHS post or setting.Caroline Murgatroyd, a solicitor representing one of Mr Jabbar’s former patients, said while news of the review would be “worrying for many people”, she welcomed the steps being taken by the hospital.Her client has been told they will be updated in eight weeks on the review into Mr Jabbar’s practice.Listen to the best of BBC Radio London on Sounds and follow BBC London on Facebook, X and Instagram. Send your story ideas to hello.bbclondon@bbc.co.ukRelated Internet LinksGreat Ormond Street HospitalThe BBC is not responsible for the content of external sites.

A lack of federal regulation and a mishmash of state laws have made selling products featuring the cannabis-derived ingredient not worth the trouble.Just below rows of energy and kombucha drinks at Westside Market, a deli in the Chelsea neighborhood of Manhattan, sit a few glass bottles of Vybes. The drink, which comes in flavors like strawberry lavender and blood orange lime, is made with cannabidiol, more commonly known as CBD.But a lack of federal rules and a mishmash of state regulations have made it impossible for Vybes to be distributed by a national retailer, like Target or Walmart. That has hindered the potential growth for the drink, said Jonathan Eppers, who left the technology industry to create Vybes in 2018.“For the first two years, we were riding a rocket ship,” Mr. Eppers said. “But the patchwork of laws and regulations around the space has made it tough to grow our business.”A little more than six years ago, CBD, the nonintoxicating component that is derived from cannabis or hemp, was poised to be the next big “it” ingredient, part of a wave of beverages and foods that were promoted as having healthful benefits or providing relaxation. Start-ups flooded the market with products, many promising to soothe stressed-out and anxious consumers.At its apex around 2018, CBD was everywhere, appearing in water, chocolate bars, tinctures, gummies and skin serums. Consumers could buy athleisure apparel infused with CBD oil and feed their nervous pups CBD chews and snacks. Big corporations even jumped in. Molson Coors teamed up with a Canadian cannabis firm to create a line of CBD-infused drinks. Constellation Brands, the maker of Modelo beer, made a $4 billion investment in a publicly traded cannabis company. Ben & Jerry’s began looking into creating CBD-infused ice cream.In the last couple of years, however, the industry has stalled out. Molson Coors ended its joint venture, and Constellation has written down more than a $1 billion of its cannabis investments. Large companies have shelved plans for CBD products, and hundreds of start-ups have either shut down, shifted to other ingredients or simply tempered their growth projections.We are having trouble retrieving the article content.Please enable JavaScript in your browser settings.Thank you for your patience while we verify access. If you are in Reader mode please exit and log into your Times account, or subscribe for all of The Times.Thank you for your patience while we verify access.Already a subscriber? Log in.Want all of The Times? Subscribe.