Many People With Cancer Lack Protection Against Measles and Mumps

 In one of the first studies of its kind in recent decades, a team of researchers has discovered that a high percentage of people with cancer lack protection against measles and mumps. In an era when measles is resurfacing after being eradicated in the U.S. and the COVID-19 pandemic is delaying some children's vaccine schedules, this finding raises questions about the level of threat to cancer patients.

Measles is "hands-down one of the most infectious viruses” in today's world, said Dr. Steven Pergam, an infectious disease researcher at the Fred Hutchinson Cancer Research Center and a medical professor at the University of Washington. A person with measles can infect 12 to 18 unvaccinated people on average, whereas that range is 2 to 3.5 for the original strain of SARS-CoV-2 and 6 to 8 for the delta variant, Pergam said. A person with mumps can infect an average of 10 to 12 unvaccinated people.

The vaccine against measles, first tested in 1958, prevents disease circulation extremely well. It is often administered in combination with mumps and rubella vaccines in what is known as the MMR vaccine. Even though the MMR vaccine provides great protection against these serious illnesses, the vaccination rates have fallen, especially in certain communities, which has led to measles outbreaks in states such as New York, Minnesota and Washington in recent years.

To learn more about how these outbreaks could affect people with cancer, Pergam and his co-workers analyzed blood samples of the cancer patients who visited Seattle Cancer Care Alliance or Fred Hutch for appointments in a five-day period in August 2019. After analyzing 959 samples, the team discovered that 25% of the people with cancer lacked protective antibodies for measles and 38% lacked antibodies against mumps. These percentages are higher than the percentage for the general U.S. population, which was 4% for measles between 1999 and 2004, according to a study published in The Journal of Infectious Diseases.

Further analysis by the team revealed that younger patients between ages 30 and 59, patients with blood cancer, and cancer patients who received stem cell transplants were even less protected than the rest of the patient groups. The team published the results in the journal JAMA Network Open in July.

Pergam said the lower protection level for people with cancer is due to a combination of factors. Because blood cancers such as leukemia directly damage one's immune system, patients are less able to produce protective antibodies. Similarly, patients who receive bone marrow transplants lose their protective antibodies in the years after the transplant. 

Cancers in younger patients are more often blood cancer, which could explain the age trend, Pergam said. However, Elizabeth Krantz, a statistician at Fred Hutch and one of the authors of the paper, said that even after the relationships between the patients' ages and cancer types were detangled statistically, younger patients still showed lower protection.

One reason could be that older patients, who survived the era when measles and mumps were more common and routinely killed hundreds of people each year, may have caught the diseases and recovered. In the case of measles and mumps, the immunity that develops due to a real infection could be stronger than the immunity generated by the vaccine. 

Another reason could be that growing vaccine hesitancy resulted in some young people in the study lacking any protection that might be conferred either by a vaccine or a natural infection, Pergam said, although that's hard to prove.

"Measles is something that's sneaking around in the background," Pergam said, "and we need to be ready because we do think that rates of vaccine are dropping." A recent federal health report that studied 10 U.S. states said the MMR vaccination rates dropped about 22% for babies younger than 2 years old and about 63% for children between ages 2 and 8 early in the COVID-19 pandemic, compared to the same time periods between March and May in 2019 and 2018. 

It is not possible for a person with cancer to receive another MMR shot because it is a live-virus vaccine that could put their health at risk, Pergam said. To protect those who are vulnerable, our society needs to step up to reach the herd immunity level. "That means everyone needs to do their part," Pergam said. "Everyone needs to step forward, everyone needs to be caught up on their vaccines so that we don't have large outbreaks."

Source: Inside Science

Rare Human Syndrome May Explain Why Dogs are So Friendly

 Dogs and people with Williams syndrome may both owe their sociable personalities to changes in the same genes.

When it comes to sheer friendliness, few humans can match the average dog. But people with Williams syndrome may come close, their unusual genetics granting them a puppyish zeal for social interaction. Now, scientists have found that extreme friendliness in both species may share common genetic roots.

A friendly condition

Williams syndrome, also known as Williams-Beuren syndrome, occurs when people are missing of a chunk of DNA containing about 27 genes. The syndrome affects about one in 10,000 people, and it is associated with a suite of mental and physical traits, including bubbly, extroverted personalities, a broad forehead, full cheeks, heart defects, intellectual disability and an affinity for music.

The first hint of a link between dogs and Williams syndrome came in 2010, when evolutionary biologist Bridgett vonHoldt and her colleagues examined DNA from 225 wolves and 912 dogs from 85 breeds. They were looking for parts of the genome that have been shaped by selection since dogs diverged from wolves.

One gene that popped out was WBSCR17, suggesting that it or other genes near it were important in dog evolution. This region of the genome is similar in dogs and humans, and the human version of WBSCR17 is located near the sequence that is deleted in people with Williams syndrome.

Doggie DNA

In the new study, vonHoldt, now an evolutionary biologist at Princeton University in New Jersey, and her colleagues took a closer look at the region surrounding WBSCR17. First, they tested the friendliness of 18 dogs and 10 wolves, all raised with regular attention from human caretakers. They measured how much time each dog or wolf spent within a 1-meter radius of a human, as well as how hard the animal worked to solve a puzzle box.

As expected, wolves spent less time near humans, and most worked equally hard to solve their puzzle box regardless of whether a human was present. In contrast, dogs tended to look at the human instead of the puzzle box, focusing on the puzzle only when left alone.

While dogs were more sociable than wolves on average, individuals varied, with some wolves acting more friendly and some dogs acting more aloof. When the researchers analyzed DNA from 16 of the dogs and eight of the wolves, the behavioral differences turned out to be correlated with variations in three genes -- the WBSCR17 gene highlighted in the 2010 study, and two additional genes from within the canine equivalent of the Williams syndrome region.

For each of these three genes, the researchers found multiple variants that differed in structural ways, such as whether or not they contained an extra sequence of DNA. Some gene variants were found mostly in the friendly dogs and wolves, while others were found more often in unfriendly animals.

While personality traits like friendliness are probably shaped by hundreds or thousands of genes, these three genes appeared to play a surprisingly large role in controlling social behavior, said vonHoldt.

"Some of these structural variants could explain a huge shift in a behavioral profile -- that you go from being a wolf-like, aloof creature, to something that's obsessed with a human," she said.

When the researchers examined those same three genes in 201 dogs from 13 breeds, they found similar patterns of genetic variation between breeds traditionally associated with friendly behavior, and breeds generally considered to be more standoffish.

Source: InsideScience

Hair straightening chemicals associated with higher uterine cancer risk

 Women who used chemical hair straightening products were at higher risk for uterine cancer compared to women who did not report using these products, according to a new study from the National Institutes of Health. The researchers found no associations with uterine cancer for other hair products that the women reported using, including hair dyes, bleach, highlights, or perms.

The study data includes 33,497 U.S. women ages 35-74 participating in the Sister Study, a study led by the National Institute of Environmental Health Sciences (NIEHS), part of NIH, that seeks to identify risk factors for breast cancer and other health conditions. The women were followed for almost 11 years and during that time 378 uterine cancer cases were diagnosed.

The researchers found that women who reported frequent use of hair straightening products, defined as more than four times in the previous year, were more than twice as likely to go on to develop uterine cancer compared to those who did not use the products.

"We estimated that 1.64% of women who never used hair straighteners would go on to develop uterine cancer by the age of 70; but for frequent users, that risk goes up to 4.05%," said Alexandra White, Ph.D., head of the NIEHS Environment and Cancer Epidemiology group and lead author on the new study. "This doubling rate is concerning. However, it is important to put this information into context -- uterine cancer is a relatively rare type of cancer."

Uterine cancer accounts for about 3% of all new cancer cases but is the most common cancer of the female reproductive system, with 65,950 estimated new cases in 2022. Studies show that incidence rates of uterine cancer have been rising in the United States, particularly among Black women.

Approximately 60% of the participants who reported using straighteners in the previous year were self-identified Black women, according to the study published in the Journal of the National Cancer Institute. Although, the study did not find that the relationship between straightener use and uterine cancer incidence was different by race, the adverse health effects may be greater for Black women due to higher prevalence of use.

"Because Black women use hair straightening or relaxer products more frequently and tend to initiate use at earlier ages than other races and ethnicities, these findings may be even more relevant for them," said Che-Jung Chang, Ph.D., an author on the new study and a research fellow in the NIEHS Epidemiology Branch.

The findings are consistent with prior studies showing straighteners can increase the risk of hormone-related cancers in women.

The researchers did not collect information on brands or ingredients in the hair products the women used. However, in the paper they note that several chemicals that have been found in straighteners (such as parabens, bisphenol A, metals, and formaldehyde) could be contributing to the increased uterine cancer risk observed. Chemical exposure from hair product use, especially straighteners, could be more concerning than other personal care products due to increased absorption through the scalp which may be exacerbated by burns and lesions caused by straighteners.

"To our knowledge this is the first epidemiologic study that examined the relationship between straightener use and uterine cancer," said White. "More research is needed to confirm these findings in different populations, to determine if hair products contribute to health disparities in uterine cancer, and to identify the specific chemicals that may be increasing the risk of cancers in women."

This team previously found that permanent hair dye and straighteners may increase breast and ovarian cancer risk.

---

 Source: science daily

Pain relief without side effects and addiction

 New substances that activate adrenalin receptors instead of opioid receptors have a similar pain relieving effect to opiates, but without the negative aspects such as respiratory depression and addiction. This is the result of research carried out by an international team of researchers led by the Chair of Pharmaceutical Chemistry at Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU). Their findings, which have now been published in the  scientific journal Science, are a milestone in the development of non-opioid pain relief.

Opiates cause addiction, new substances do not

They are a blessing for patients suffering from severe pain, but they also have serious side effects: Opioids, and above all morphine, can cause nausea, dizziness and constipation and can also often cause slowed breathing that can even result in respiratory failure. In addition, opiates are addictive -- a high percentage of the drug problem in the USA is caused by pain medication, for example.

In order to tackle the unwanted medical and social effects of opioids, researchers all over the world are searching for alternative analgesics. Prof. Dr. Peter Gmeiner, Chair of Pharmaceutical Chemistry is one of these researchers. "We are focusing particularly on the molecular structures of the receptors that dock onto the pharmaceutical substances," says Gmeiner. "It is only when we understand these on the atomic level that we can develop effective and safe active substances." Collaborating with an international team of researchers, Prof. Gmeiner discovered an active substance in 2016 that bonds to known opioid receptors and that offers the same level of pain relief as morphine, even though it has no chemical similarity to opiates.

New approach: Adrenaline receptors instead of opioid receptors

Peter Gmeiner is currently following a lead that seems very promising: "Many non-opioid receptors are involved in pain processing, but only a small number of these alternatives have as yet been validated for use in therapies," he explains. Gmeiner and a team of researchers from Erlangen, China, Canada and the USA have now turned their attention to a new receptor that is responsible for binding adrenaline -- the alpha 2A adrenergic receptor. There are already some analgesics that target this receptor such as brimonidine, clonidine and dexmedetomidine. Gmeiner: "Dexmedetomidine relieves pain, but has a strong sedative effect, which means its use is restricted to intensive care in hospital settings and is not suitable for broader patient groups."

The aim of the research consortium is to find a chemical compound that activates the receptor in the central nervous system without a sedative effect. In a virtual library of more than 300 million different and easily accessible molecules, the researchers looked for compounds that physically match the receptor but are not chemically related to known medication. After a series of complex virtual docking simulations, around 50 molecules were selected for synthesis and testing and two of these fulfilled the desired criteria. They had good bonding characteristics, activated only certain protein sub-types and thus a very selective set of cellular signal pathways, whereas dexmedetomidine responds to a significantly wider range of proteins.

Pain relief without sedation in animal models

By further optimizing the identified molecules, for which extremely high-resolution cryo-electron microscopic imaging was used, the researchers were able to synthesize agonists that produced high concentrations in the brain and reduced the sensation of pain effectively in investigations with animal models. "Various tests confirmed that docking on the receptor was responsible for the analgesic effect," explains Gmeiner. "We are particularly pleased about the fact that none of the new compounds caused sedation, even at considerably higher doses than those that would be required for pain relief."

The successful separation of analgesic properties and sedation is a milestone in the development of non-opioid pain medication, especially as the newly-identified agonists are comparatively easy to manufacture and administer orally to patients. However, Prof. Gmeiner has to dampen any hopes of rapid widespread use in human medicine: "We are currently still talking about basic research. The development of medication is subject to strict controls and in addition to significant amounts of funding, it takes a long time. However, these results still make us very optimistic."

---

Source: science daily

Dogs can smell when we're stressed, study suggests

 The physiological processes associated with an acute psychological stress response produce changes in human breath and sweat that dogs can detect with an accuracy of 93.75%, according to a new study published this week in the open-access journal PLOS ONE by Clara Wilson of Queen's University Belfast, UK, and colleagues.

Odors emitted by the body constitute chemical signals that have evolved for communication, primarily within species. Given dogs' remarkable sense of smell, their close domestication history with humans, and their use to support human psychological conditions such as anxiety, panic attacks and post-traumatic stress disorder (PTSD), researchers wondered whether dogs could be sensing chemical signals to respond to their owners' psychological states.

In the new study, the researchers collected samples of breath and sweat from non-smokers who had not recently eaten or drank. Samples were collected both before and after a fast-paced arithmetic task, along with self-reported stress levels and objective physiological measures: heart rate (HR) and blood pressure (BP). Samples from 36 participants who reported an increase in stress because of the task, and experienced an increase in HR and BP during the task, were shown to trained dogs within three hours of being collected. Four dogs of different breeds and breed-mixes had been trained, using a clicker as well as kibble, to match odors in a discrimination task. At testing, dogs were asked to find the participant's stress sample (taken at the end of the task) while the same person's relaxed sample (taken only minutes before, prior to the task starting) was also in the sample line-up.

Overall, dogs could detect and perform their alert behavior on the sample taken during stress in 675 out of 720 trials, or 93.75% of the time, much greater than expected by chance (p<0.001). The first time they were exposed to a participant's stressed and relaxed samples, the dogs correctly alerted to the stress sample 94.44% of the time. Individual dogs ranged in performance from 90% to 96.88% accuracy.

The authors conclude that dogs can detect an odor associated with the change in Volatile Organic Compounds produced by humans in response to stress, a finding that tells us more about the human-dog relationship and could have applications to the training of anxiety and PTSD service dogs that are currently trained to respond predominantly to visual cues.

The authors add: "This study demonstrates that dogs can discriminate between the breath and sweat taken from humans before and after a stress-inducing task. This finding tells us that an acute, negative, psychological stress response alters the odor profile of our breath/sweat, and that dogs are able to detect this change in odor."

---

Source: science daily

Less than five hours' sleep a night linked to higher risk of multiple diseases

 Getting less than five hours of sleep in mid-to-late life could be linked to an increased risk of developing at least two chronic diseases, finds a new study led by UCL researchers.

The research, published in PLOS Medicine, analysed the impact of sleep duration on the health of more than 7,000 men and women at the ages of 50, 60 and 70, from the Whitehall II cohort study.

Researchers examined the relationship between how long each participant slept for, mortality and whether they had been diagnosed with two or more chronic diseases (multimorbidity) -- such as heart disease, cancer or diabetes -- over the course of 25 years.

People who reported getting five hours of sleep or less at age 50 were 20% more likely to have been diagnosed with a chronic disease and 40% more likely to be diagnosed with two or more chronic diseases over 25 years, compared to people who slept for up to seven hours.

Additionally, sleeping for five hours or less at the age of 50, 60, and 70 was linked to a 30% to 40% increased risk of multimorbidity when compared with those who slept for up to seven hours.

Researchers also found that sleep duration of five hours or less at age 50 was associated with 25% increased risk of mortality over the 25 years of follow-up -- which can mainly be explained by the fact that short sleep duration increases the risk of chronic disease(s) that in turn increase the risk of death.

Lead author, Dr Severine Sabia (UCL Institute of Epidemiology & Health, and Inserm, Université Paris Cité) said: "Multimorbidity is on the rise in high income countries and more than half of older adults now have at least two chronic diseases. This is proving to be a major challenge for public health, as multimorbidity is associated with high healthcare service use, hospitalisations and disability.

"As people get older, their sleep habits and sleep structure change. However, it is recommended to sleep for 7 to 8 hours a night -- as sleep durations above or below this have previously been associated with individual chronic diseases.

"Our findings show that short sleep duration is also associated with multimorbidity.

"To ensure a better night's sleep, it is important to promote good sleep hygiene, such as making sure the bedroom is quiet, dark and a comfortable temperature before sleeping. It's also advised to remove electronic devices and avoid large meals before bedtime. Physical activity and exposure to light during the day might also promote good sleep."

As part of the study, researchers also assessed whether sleeping for a long duration, of nine hours or more, affected health outcomes. There was no clear association between long sleep durations at age 50 and multimorbidity in healthy people.

However, if a participant had already been diagnosed with a chronic condition, then long sleep duration was associated with around a 35% increased risk of developing another illness. Researchers believe this could be due to underlying health conditions impacting sleep.

Jo Whitmore, senior cardiac nurse at the British Heart Foundation said: "Getting enough sleep allows your body to rest. There are a host of other ways that poor sleep could increase the risk of heart disease or stroke, including by increasing inflammation and increasing blood pressure.

"This research adds to a growing body of research that highlights the importance of getting a good night's sleep."

The research was funded by the National Institute on Aging, part of NIH, UK Medical Research Council, the British Heart Foundation and Wellcome.

Study limitations

Researchers used self-reported data on sleep, which is likely to be subject to reporting bias, although using data on 4,000 participants whose sleep was measured via an electronic device confirm the findings.

Meanwhile, data on sleep quality was only available for those aged 60 and 70.

The Whitehall II study only involves members of the civil service, who were all employed when recruited to the study and likely to be healthier than the general population.

---

 Source: science daily

Vast ice sheet facing climate fight on two fronts

 The Greenland ice sheet may be more vulnerable to climate change than previously thought, new research suggests.

Rising air temperatures amplify the effects of melting caused by ocean warming, leading to greater ice loss from the world's second largest ice sheet, a study reveals.

While previous studies have shown that rising air and ocean temperatures both cause the Greenland ice sheet to melt, the new study reveals how one intensifies the effects of the other.

Experts liken the effect to how ice cubes melt more quickly if they are in a drink that is being stirred -- the combination of warmer liquid and movement accelerates their demise.

In Greenland, amplification occurs when warm air temperatures melt the surface of the ice sheet, generating meltwater. Meltwater flowing into the ocean creates turbulence that results in more heat melting the edges of the ice sheet submerged in the ocean -- so-called submarine melting.

Researchers from the Universities of Edinburgh and California San Diego have evaluated submarine melting of the Greenland ice sheet -- which covers more than 650,000 square miles -- over a 40-year period from 1979 to 2018.

To determine the impact of both warming air and seas on ice sheet loss they used observational data and computer modelling to analyse the effect each had on submarine melting.

The team found that air temperature has had almost as much impact as ocean temperature on submarine melting, with some regional variations.

For example, ocean temperature is the main factor that controls submarine melting in south and central-west Greenland, while atmospheric warming is equally damaging in the island's northwest.

The findings suggest that if the atmosphere had not warmed since 1979, the retreat of Greenland's glaciers, driven by submarine melting, could have been reduced by a half in the northwest region, and by a third across Greenland as a whole.

The study, published in the journal Nature GeoScience, was supported by the UK Natural Environment Research Council and the US National Science Foundation.

Dr Donald Slater, of the University of Edinburgh's School of GeoSciences, who led the study, said: "The effect we investigated is a bit like ice cubes melting in a drink -- ice cubes will obviously melt faster in a warm drink than in a cold drink, hence the edges of the Greenland ice sheet melt faster if the ocean is warmer. But ice cubes in a drink will also melt faster if you stir the drink, and rising air temperatures in Greenland effectively result in a stirring of the ocean close to the ice sheet, causing faster melting of the ice sheet by the ocean.

"This unfortunately adds to the overwhelming body of evidence showing the sensitivity of the Greenland ice sheet to climate change, hence the need for urgent action to reduce greenhouse gas emissions 

Eating late increases hunger, decreases calories burned, and changes fat tissue

 Obesity afflicts approximately 42 percent of the U.S. adult population and contributes to the onset of chronic diseases, including diabetes, cancer, and other conditions. While popular healthy diet mantras advise against midnight snacking, few studies have comprehensively investigated the simultaneous effects of late eating on the three main players in body weight regulation and thus obesity risk: regulation of calorie intake, the number of calories you burn, and molecular changes in fat tissue. A new study by investigators from Brigham and Women's Hospital, a founding member of the Mass General Brigham healthcare system, found that when we eat significantly impacts our energy expenditure, appetite, and molecular pathways in adipose tissue. Their results are published in Cell Metabolism.

"We wanted to test the mechanisms that may explain why late eating increases obesity risk," explained senior author Frank A. J. L. Scheer, PhD, Director of the Medical Chronobiology Program in the Brigham's Division of Sleep and Circadian Disorders. "Previous research by us and others had shown that late eating is associated with increased obesity risk, increased body fat, and impaired weight loss success. We wanted to understand why."

"In this study, we asked, 'Does the time that we eat matter when everything else is kept consistent?'" said first author Nina Vujovic, PhD, a researcher in the Medical Chronobiology Program in the Brigham's Division of Sleep and Circadian Disorders. "And we found that eating four hours later makes a significant difference for our hunger levels, the way we burn calories after we eat, and the way we store fat."

Vujovic, Scheer and their team studied 16 patients with a body mass index (BMI) in the overweight or obese range. Each participant completed two laboratory protocols: one with a strictly scheduled early meal schedule, and the other with the exact same meals, each scheduled about four hours later in the day. In the last two to three weeks before starting each of the in-laboratory protocols, participants maintained fixed sleep and wake schedules, and in the final three days before entering the laboratory, they strictly followed identical diets and meal schedules at home. In the lab, participants regularly documented their hunger and appetite, provided frequent small blood samples throughout the day, and had their body temperature and energy expenditure measured. To measure how eating time affected molecular pathways involved in adipogenesis, or how the body stores fat, investigators collected biopsies of adipose tissue from a subset of participants during laboratory testing in both the early and late eating protocols, to enable comparison of gene expression patterns/levels between these two eating conditions.

Results revealed that eating later had profound effects on hunger and appetite-regulating hormones leptin and ghrelin, which influence our drive to eat. Specifically, levels of the hormone leptin, which signals satiety, were decreased across the 24 hours in the late eating condition compared to the early eating conditions. When participants ate later, they also burned calories at a slower rate and exhibited adipose tissue gene expression towards increased adipogenesis and decreased lipolysis, which promote fat growth. Notably, these findings convey converging physiological and molecular mechanisms underlying the correlation between late eating and increased obesity risk.

Vujovic explains that these findings are not only consistent with a large body of research suggesting that eating later may increase one's likelihood of developing obesity, but they shed new light on how this might occur. By using a randomized crossover study, and tightly controlling for behavioral and environmental factors such as physical activity, posture, sleep, and light exposure, investigators were able to detect changes the different control systems involved in energy balance, a marker of how our bodies use the food we consume.

In future studies, Scheer's team aims to recruit more women to increase the generalizability of their findings to a broader population. While this study cohort included only five female participants, the study was set up to control for menstrual phase, reducing confounding but making recruiting women more difficult. Going forward, Scheer and Vujovic are also interested in better understanding the effects of the relationship between meal time and bedtime on energy balance.

"This study shows the impact of late versus early eating. Here, we isolated these effects by controlling for confounding variables like caloric intake, physical activity, sleep, and light exposure, but in real life, many of these factors may themselves be influenced by meal timing," said Scheer. "In larger scale studies, where tight control of all these factors is not feasible, we must at least consider how other behavioral and environmental variables alter these biological pathways underlying obesity risk. "

Disclosures:

During the execution of this project, Scheer received lecture fees from Bayer HealthCare, Sentara HealthCare, Philips, Vanda Pharmaceuticals, and Pfizer Pharmaceuticals; received consulting fees from the University of Alabama at Birmingham; and served on the Board of Directors for the Sleep Research Society. Scheer's interests were reviewed and managed by Brigham and Women's Hospital and Partners HealthCare in accordance with their conflict of interest policies. None of these are related to the current work. Vujovic has been compensated for consulting services provided to the Novartis Institutes of Biomedical Research, also unrelated to the current work.

---

Source:science daily

Mechanism of hearing: Structure of key part of inner ear

 Scientists at Oregon Health & Science University have revealed, for the first time and in near-atomic detail, the structure of the key part of the inner ear responsible for hearing.

"This is the last sensory system in which that fundamental molecular machinery has remained unknown," said senior author Eric Gouaux, Ph.D., senior scientist with the OHSU Vollum Institute and a Howard Hughes Medical Institute investigator. "The molecular machinery that carries out this absolutely amazing process has been unresolved for decades."

Until now.

The researchers made the discovery by teasing out the structure through years of painstaking research to isolate the process that enables the inner ear to convert vibrations into sound, known as the mechanosensory transduction complex.

The study, which revealed the structure through cryo-electron microscopy, published today in the journal Nature. The findings could point the way toward developing new treatments for hearing impairments, which affect more than 460 million people worldwide.

The discovery reveals the architecture of the inner ear complex that converts vibrations into electrical impulses that the brain translates as sound. Known as mechanosensory transduction, the process is responsible for the sensations of balance and sound.

Scientists exploited the fact that the roundworm Caenorhabditis elegans harbors a mechanosensory complex very similar to that of humans.

Resolving the basic structure is the first step, according to Gouaux.

"It immediately suggests mechanisms by which one might be able to compensate for those deficits," Gouaux said. "If a mutation gives rise to a defect in the transduction channel that causes hearing loss, it's possible to design a molecule that fits into that space and rescues the defect. Or it may mean we can strengthen interactions that have been weakened."

Hearing loss can be inherited through gene mutations that alter the proteins comprising the science dailymechanosensory transduction complex. Or it can occur from damage, including sustained exposure to loud noise. In either case, OHSU researchers' discovery allows scientists to visualize the complex for the first time.

The finding is an extraordinary achievement, said one leading neuroscience researcher at OHSU who was not directly involved in the research.

"The auditory neuroscience field has been waiting for these results for decades, and now that they are right here -- we are ecstatic," said Peter Barr-Gillespie, Ph.D., an OHSU research scientist and national leader in hearing research. "The results from this paper immediately suggest new avenues of research, and so willsources:invigorscience dailyate the field for years to come."

Dust plumes observed being 'pushed' into interstellar space by intense starlight

 The results, made using infrared images of the binary star system WR140 taken over 16 years, are reported in the journal Nature.

In a complementary study of WR140, published in Nature Astronomy, NASA's James Webb Space Telescope (JWST) was able to see much deeper to snap an image of not just a single accelerating dust plume, but almost 20 of them, nested inside each other like a giant set of onion skins.

WR140 is comprised of a huge Wolf-Rayet star and an even bigger blue supergiant star, gravitationally bound in an eight-year orbit. This binary star, in the Cygnus constellation, has been monitored for two decades with one of the world's largest optical telescopes at the Keck Observatory in Hawaii.

WR140 episodically puffs out plumes of dust stretching thousands of times the distance from the Earth to the Sun. These dust plumes, produced every eight years, give astronomers a unique opportunity to observe how starlight can affect matter.

It's known that light carries momentum, exerting a push on matter known as radiation pressure. Astronomers often witness the outcome of this phenomenon in the form of matter coasting at high speed around the cosmos, but it's been a difficult process to catch in the act. Direct recording of acceleration due to forces other than gravity is rarely witnessed, and never in a stellar environment like this.

"It's hard to see starlight causing acceleration because the force fades with distance, and other forces quickly take over," said Yinuo Han from Cambridge's Institute of Astronomy, first author of the Nature paper. "To witness acceleration at the level that it becomes measurable, the material needs to be reasonably close to the star or the source of the radiation pressure needs to be extra strong. WR140 is a binary star whose ferocious radiation field supercharges these effects, placing them within reach of our high-precision data."

All stars generate stellar winds, but those from Wolf-Rayet stars can be more like a stellar hurricane. Elements such as carbon in the wind condense out as soot, which remains hot enough to glow bright in the infrared. Like smoke in the wind, this gives telescopes something that can be observed.

The team used an imaging technology known as interferometry which was able to act like a zoom lens for the 10-metre Keck telescope mirror, enabling the researchers to recover sufficiently sharp images of WR140 for the study.

Han and his team found that the dust does not stream out from the star with the wind in a hazy ball. Instead, the dust forms where the winds from the two stars collide, on the surface of a cone-shaped shock front between them.

Because the orbiting binary star is in constant motion, the shock front also rotates. The sooty plume gets wrapped into a spiral, in the same way that droplets form a spiral in a garden sprinkler.

The researchers found that WR140 has other tricks up its sleeve. The two stars are not on circular but rather elliptical orbits, and dust production turns on and off as the binary nears and departs the point of closest approach. By modelling these effects into the three-dimensional geometry of the dust plume, the astronomers were able to measure to location of dust features in three-dimensional space.

"Like clockwork, this star puffs out sculpted smoke rings every eight years, with all this wonderful physics written then inflated in the wind like a banner for us to read," said co-author Professor Peter Tuthill from the University of Sydney. "Eight years later as the binary returns in its orbit, another appears the same as the one before, streaming out into space inside the bubble of the previous one, like a set of giant nested Russian dolls."

Because the dust produced by this Wolf-Rayet is so predictable and expands to such large distances, it offered the astronomers a unique laboratory to examine the acceleration zone.

"In the absence of external forces, each dust spiral should expand at a constant speed," said Han, who is also a co-author on the JWST paper. "We were puzzled at first because we could not get our model to fit the observations, until we finally realised that we were seeing something new. The data did not fit because the expansion speed wasn't constant, but rather that it was accelerating. We'd caught that for the first time on camera."

"In one sense, we always knew this must be the reason for the outflow, but I never dreamed we'd be able to see the physics at work like this," said Tuthill. "When I look at the data now, I see WR140's plume unfurling a like giant sail made of dust. When it catches the photon wind streaming from the star, like a yacht catching a gust, it makes a sudden leap forward."

With JWST now in operation, researchers can learn much more about WR140 and similar systems. "The Webb telescope offers new extremes of stability and sensitivity," said Ryan Lau who led the JWST study. "We'll now be able to make observations like this much more easily than from the ground, opening a new window into the world of Wolf-Rayet physics."

Source: ScienceDaily

A new species of deep-sea fish discovered in the Atacama Trench

 A new small blue snailfish is changing our understanding of the world's deepest fishes.

In 2018, an international team of scientists studied the Atacama Trench, an expansive trench that runs along the west coast of South America as a deep underwater valley that mirrors the Andes Mountains. The team, including Newcastle University scientists, deployed free-falling landers to sample the sparse deep-sea creatures around cameras and traps with bait. Two lander systems from Newcastle University recorded three types of hadal snailfish and one of them was not like the others.

The small blue fish, seen from about 6,000 to 7,600 m deep, doesn't look like other hadal snailfish. With large eyes and striking colour, it resembles other species of snailfishes that are found living in much shallower waters. The team used a 3D x-ray technique called microcomputed tomography (micro-CT) and DNA barcoding to see where the new species fit within the snailfish family.

To the team's surprise, the new species appears to be a separate coloniser of the Atacama Trench. The new species belongs is a member of the genus Paraliparis. Species in this genus are particularly abundant in the Southern Ocean of the Antarctic and are rarely found deeper than 2,000 m. Significantly, this is the first time this genus has been found living in the hadal zone.

The team named the new species Paraliparis selti, meaning blue in the Kunza language of the indigenous peoples of the Atacama Desert. The description is published in the journal Marine Biodiversity.

Study lead author, Dr Thom Linley, a visiting researcher at Newcastle University said: "I find this family of fishes absolutely fascinating. They are not at all what we expect from a deep-sea fish and I love to show people that the world's deepest fishes are actually pretty cute.

"For me to get a camera down to where these animals live, it's made of inches thick stainless steel and sapphire glass. It then films these delicate and beautiful animals perfectly adapted to this extreme environment. With engineering-built force we can only clumsily visit these animals for a short time.

"We have been wondering for some time just what makes this type of fish so good at living deep. Maybe it was a series of lucky accidents, a chance fluke, that happened in one lineage. Finding this new species tells us that it's bigger than that. Lightning struck twice and there is something special about this Family.

"Paraliparis selti provides a fantastic opportunity to explore what allows fish to live so deep. If we only had a single lineage to study, we could never be sure which traits were just part of that lineage and which are the deep-sea secret sauce."

Source: ScienceDaily

'Smart plastic' material is step forward toward soft, flexible robotics and electronics

 Inspired by living things from trees to shellfish, researchers at The University of Texas at Austin set out to create a plastic much like many life forms that are hard and rigid in some places and soft and stretchy in others. Their success -- a first, using only light and a catalyst to change properties such as hardness and elasticity in molecules of the same type -- has brought about a new material that is 10 times as tough as natural rubber and could lead to more flexible electronics and robotics.

The findings are published today in the journal Science.

"This is the first material of its type," said Zachariah Page, assistant professor of chemistry and corresponding author on the paper. "The ability to control crystallization, and therefore the physical properties of the material, with the application of light is potentially transformative for wearable electronics or actuators in soft robotics."

Scientists have long sought to mimic the properties of living structures, like skin and muscle, with synthetic materials. In living organisms, structures often combine attributes such as strength and flexibility with ease. When using a mix of different synthetic materials to mimic these attributes, materials often fail, coming apart and ripping at the junctures between different materials.

Oftentimes, when bringing materials together, particularly if they have very different mechanical properties, they want to come apart," Page said. Page and his team were able to control and change the structure of a plastic-like material, using light to alter how firm or stretchy the material would be.

Chemists started with a monomer, a small molecule that binds with others like it to form the building blocks for larger structures called polymers that were similar to the polymer found in the most commonly used plastic. After testing a dozen catalysts, they found one that, when added to their monomer and shown visible light, resulted in a semicrystalline polymer similar to those found in existing synthetic rubber. A harder and more rigid material was formed in the areas the light touched, while the unlit areas retained their soft, stretchy properties.

Because the substance is made of one material with different properties, it was stronger and could be stretched farther than most mixed materials.

The reaction takes place at room temperature, the monomer and catalyst are commercially available, and researchers used inexpensive blue LEDs as the light source in the experiment. The reaction also takes less than an hour and minimizes use of any hazardous waste, which makes the process rapid, inexpensive, energy efficient and environmentally benign.

The researchers will next seek to develop more objects with the material to continue to test its usability.

"We are looking forward to exploring methods of applying this chemistry towards making 3D objects containing both hard and soft components," said first author Adrian Rylski, a doctoral student at UT Austin.

The team envisions the material could be used as a flexible foundation to anchor electronic components in medical devices or wearable tech. In robotics, strong and flexible materials are desirable to improve movement and durability.

Henry L. Cater, Keldy S. Mason, Marshall J. Allen, Anthony J. Arrowood, Benny D. Freeman and Gabriel E. Sanoja of The University of Texas at Austin also contributed to the research.

The research was funded by the National Science Foundation, the U.S. Department of Energy and the Robert A. Welch Foundation.

Source: ScienceDaily

World's first stem cell treatment for spina bifida delivered during fetal surgery

 Three babies have been born after receiving the world's first spina bifida treatment combining surgery with stem cells. This was made possible by a landmark clinical trial at UC Davis Health.

The one-of-a-kind treatment, delivered while a fetus is still developing in the mother's womb, could improve outcomes for children with this birth defect.

Launched in the spring of 2021, the clinical trial is known formally as the "CuRe Trial: Cellular Therapy for In Utero Repair of Myelomeningocele." Thirty-five patients will be treated in total.

The three babies from the trial that have been born so far will be monitored by the research team until 30 months of age to fully assess the procedure's safety and effectiveness.

The first phase of the trial is funded by a $9 million state grant from the state's stem cell agency, the California Institute for Regenerative Medicine (CIRM).

"This clinical trial could enhance the quality of life for so many patients to come," said Emily, the first clinical trial participant who traveled from Austin, Tex. to participate. Her daughter Robbie was born last October. "We didn't know about spina bifida until the diagnosis. We are so thankful that we got to be a part of this. We are giving our daughter the very best chance at a bright future."

Spina bifida, also known as myelomeningocele, occurs when spinal tissue fails to fuse properly during the early stages of pregnancy. The birth defect can lead to a range of lifelong cognitive, mobility, urinary and bowel disabilities. It affects 1,500 to 2,000 children in the U.S. every year. It is often diagnosed through ultrasound.

While surgery performed after birth can help reduce some of the effects, surgery before birth can prevent or lessen the severity of the fetus's spinal damage, which worsens over the course of pregnancy.

"I've been working toward this day for almost 25 years now," said Diana Farmer, the world's first woman fetal surgeon, professor and chair of surgery at UC Davis Health and principal investigator on the study.

The path to a future cure

As a leader of the Management of Myelomeningocele Study (MOMS) clinical trial in the early 2000s, Farmer had previously helped to prove that fetal surgery reduced neurological deficits from spina bifida. Many children in that study showed improvement but still required wheelchairs or leg braces.

Farmer recruited bioengineer Aijun Wang specifically to help take that work to the next level. Together, they launched the UC Davis Health Surgical Bioengineering Laboratory to find ways to use stem cells and bioengineering to advance surgical effectiveness and improve outcomes. Farmer also launched the UC Davis Fetal Care and Treatment Center with fetal surgeon Shinjiro Hirose and the UC Davis Children's Surgery Center several years ago.

Farmer, Wang and their research team have been working on their novel approach using stem cells in fetal surgery for more than 10 years. Over that time, animal modeling has shown it is capable of preventing the paralysis associated with spina bifida.

It's believed that the stem cells work to repair and restore damaged spinal tissue, beyond what surgery can accomplish alone.

Preliminary work by Farmer and Wang proved that prenatal surgery combined with human placenta-derived mesenchymal stromal cells, held in place with a biomaterial scaffold to form a "patch," helped lambs with spina bifida walk without noticeable disability.

"When the baby sheep who received stem cells were born, they were able to stand at birth and they were able to run around almost normally. It was amazing," Wang said.

When the team refined their surgery and stem cells technique for canines, the treatment also improved the mobility of dogs with naturally occurring spina bifida.

A pair of English bulldogs named Darla and Spanky were the world's first dogs to be successfully treated with surgery and stem cells. Spina bifida, a common birth defect in this breed, frequently leaves them with little function in their hindquarters.

By their post-surgery re-check at 4 months old, Darla and Spanky were able to walk, run and play.

The world's first human trial

When Emily and her husband Harry learned that they would be first-time parents, they never expected any pregnancy complications. But the day that Emily learned that her developing child had spina bifida was also the day she first heard about the CuRe trial.

For Emily, it was a lifeline that they couldn't refuse.

Participating in the trial would mean that she would need to temporarily move to Sacramento for the fetal surgery and then for weekly follow-up visits during her pregnancy.

After screenings, MRI scans and interviews, Emily received the life-changing news that she was accepted into the trial. Her fetal surgery was scheduled for July 12, 2021, at 25 weeks and five days gestation.

Farmer and Wang's team manufactures clinical grade stem cells -- mesenchymal stem cells -- from placental tissue in the UC Davis Health's CIRM-funded Institute for Regenerative Cures. The cells are known to be among the most promising type of cells in regenerative medicine.

The lab is a Good Manufacturing Practice (GMP) Laboratory for safe use in humans. It is here that they made the stem cell patch for Emily's fetal surgery.

"It's a four-day process to make the stem cell patch," said Priya Kumar, the scientist at the Center for Surgical Bioengineering in the Department of Surgery, who leads the team that creates the stem cell patches and delivers them to the operating room. "The time we pull out the cells, the time we seed on the scaffold, and the time we deliver, is all critical."

A first in medical history

During Emily's historic procedure, a 40-person operating and cell preparation team did the careful dance that they had been long preparing for.

After Emily was placed under general anesthetic, a small opening was made in her uterus and they floated the fetus up to that incision point so they could expose its spine and the spina bifida defect. The surgeons used a microscope to carefully begin the repair.

Then the moment of truth: The stem cell patch was placed directly over the exposed spinal cord of the fetus. The fetal surgeons then closed the incision to allow the tissue to regenerate.

"The placement of the stem cell patch went off without a hitch. Mother and fetus did great!" Farmer said.

The team declared the first-of-its-kind surgery a success.

Source: ScienceDaily

Study of over 5 million people's DNA reveals genetic links to height

 The study, published today (12 October) in Nature, is the largest ever genome-wide association study, using the DNA of over 5 million people from 281 contributing studies. It plugs a sizeable gap in our understanding of how our genetic differences account for differences in height. Over 1 million of the study's participants are of non-European -- African, East Asian, Hispanic or South Asian -- ancestry.

The 12,111 variants, which cluster around parts of the genome associated with skeletal growth, provide a powerful genetic predictor for height. The variants identified explain 40% of the variation in height for people of European ancestry, and around 10-20% for those of non-European ancestry.

Adult height is mostly determined by the information encoded in our DNA -- children from tall parents tend to be taller and those from short parents are shorter, but these estimates aren't perfect. Growth from a small baby into an adult, and the role genetics play in this, have traditionally been a complex and poorly understood area of human biology. Previously, the largest genome-wide association study looking at height used a sample size of up to 700,000 individuals, the current sample is about seven times more than previous studies.

The unprecedented scale of the research provides new levels of detail and biological insight as to why people are tall or short, with heritability being linked to various specific genomic regions. The findings show that genetic variants associated with height are concentrated in regions covering just over 20% of the genome.

The study's findings could help doctors to identify people who are not able to reach their genetically predicted height, which may then aid in the diagnosis of hidden diseases or conditions that may be stunting their growth or impacting their health. The research also provides a valuable blueprint on how it could be possible to use genome-wide studies to identify a disease's biology and subsequently its hereditary components.

Greater genomic diversity needed

While this study has a large number of participants from non-European ancestries compared to previous studies, the researchers emphasise the need for more diversity in genomic research.

Most of the genetic data available is from people of European ancestry, so genome-wide studies don't capture the wide range of ancestral diversity across the globe. Increasing the size of genome-wide studies in non-European ancestry populations is essential to achieve the same level of saturation and close the gap in prediction accuracy in different populations.

Dr Eirini Marouli, co-first author of the study and Senior Lecturer in Computational Biology at Queen Mary University of London, said:

"We have accomplished a feat in studying the DNA of over 5 million people that was broadly considered impossible until recently.

"Genomic studies are revolutionary and might hold the key to solving many global health challenges -- their potential is tremendously exciting. If we can get a clear picture of a trait such as height at a genomic level, we may then have the model to better diagnose and treat gene-influenced conditions like heart disease or schizophrenia, for example.

"If we can map specific parts of the genome to certain traits, it opens the door to widespread targeted, personalised treatments further down the line that could benefit people everywhere."

Source: ScienceDaily

Human brain cells in a dish learn to play Pong in real time

 Human and mouse neurons in a dish learned to play the video game Pong, researchers report October 12 in the journal Neuron. The experiments are evidence that even brain cells in a dish can exhibit inherent intelligence, modifying their behavior over time.

"From worms to flies to humans, neurons are the starting block for generalized intelligence," says first author Brett Kagan (@ANeuroExplorer), chief scientific officer at Cortical Labs in Melbourne, Australia. "So, the question was, can we interact with neurons in a way to harness that inherent intelligence?"

To start, the researchers connected the neurons to a computer in such a way where the neurons received feedback on whether their in-game paddle was hitting the ball. They monitored the neuron's activity and responses to this feedback using electric probes that recorded "spikes" on a grid.

The spikes got stronger the more a neuron moved its paddle and hit the ball. When neurons missed, their playstyle was critiqued by a software program created by Cortical Labs. This demonstrated that the neurons could adapt activity to a changing environment, in a goal-oriented way, in real time.

"We chose Pong due to its simplicity and familiarity, but, also, it was one of the first games used in machine learning, so we wanted to recognize that," says Kagan, who worked with collaborators from 10 other institutions on the project.

"An unpredictable stimulus was applied to the cells, and the system as a whole would reorganize its activity to better play the game and to minimize having a random response," he says. "You can also think that just playing the game, hitting the ball and getting predictable stimulation, is inherently creating more predictable environments."

The theory behind this learning is rooted in the free-energy principle. Simply put, the brain adapts to its environment by changing either its world view or its actions to better fit the world around it.

Pong wasn't the only game the research team tested. "You know when the Google Chrome browser crashes and you get that dinosaur that you can make jump over obstacles (Project Bolan). We've done that and we've seen some nice preliminary results, but we still have more work to do building new environments for custom purposes," says Kagan.

Future directions of this work have potential in disease modeling, drug discoveries, and expanding the current understanding of how the brain works and how intelligence arises.

Source: ScienceDaily

Clusters of genes help mice live longer

 Researchers from the National Institute on Aging (NIA)-funded Interventions Testing Program recently reported the discovery of multiple candidate genes that influence longevity. The three Interventions Testing Program sites -- The University of Texas Health Science Center at San Antonio, The University of Michigan at Ann Arbor and The Jackson Laboratory at Bar Harbor, Maine -- collaborated on the study with the labs of Robert W. Williams, PhD, of the University of Tennessee Health Science Center at Memphis and Johan Auwerx, MD, PhD, of the École Polytechnique Fédérale de Lausanne in Lausanne, Switzerland.

"Some candidate genes impacted female life span while others affected the male life span," said Randy Strong, PhD, of the Sam and Ann Barshop Institute for Longevity and Aging Studies at UT Health San Antonio. "One cluster of genes increased longevity of both sexes. In a rarity for these types of studies, the findings were made in a population of mice with genetic diversity comparable to human populations."

The high-impact journal Science published the findings Sept. 30. Strong directs the Interventions Testing Program site at the Barshop Institute, which first attracted National Institute on Aging (NIA) grant funding for the Interventions Testing Program in 2003 and is in its 19th year of the NIA funding.

Genetic smorgasbord

"The study models what happens in people," said research coauthor James Nelson, PhD, of the Barshop Institute. "Unlike mice in many other studies, mice in this newly reported research are not all the same. Each has different genetic variants, resulting in slightly different proteins that do slightly different things, which together can impact aging."

Even subtle differences can lead to different health outcomes as we age. Slight variations in the hemoglobin gene, for example, can cause the hemoglobin protein in red blood cells to be less effective at binding to oxygen and transferring it from the lungs to the body's tissues, Nelson noted. Anemia is one effect.

Female longevity

The discovery of genetic loci that influence longevity only in females is interesting and important, Strong said. Genetic loci are clusters of between 10 and 100 genes.

"Females and males differ in almost every aspect of aging you can explore," Strong said. "They each must be studied, both to understand aging in the two sexes and to develop effective treatments. If we offer the same drug therapies to females that we offer to males, and females' aging is caused by different genes, we are not going to be as effective in our treatments."

Confirmation in roundworms

The next steps are scrutinizing these candidate genes to find ones that are responsible for increased longevity. In the final part of the Science article, the team reported doing this. The researchers tested candidate genes in roundworms, which are often used in aging research because of their short life span. "A number of the candidate genes did affect longevity in the worms," Nelson said.

Source: ScienceDaily