Culture

Honey bee health has been on the decline for two decades, with U.S. and Canadian beekeepers now losing about 25 to 40% of their colonies annually. And queen bees are failing faster than they have in the past in their ability to reproduce. The reason has been a mystery, but researchers at North Carolina State University and the University of British Columbia are finding answers.

Their latest research, published Jan. 8 in the journal Communications Biology, offers clues about what's behind queen bee failure, finding that when sperm viability is low, the expression of a protein known to act against pathogens such as bacteria and viruses is high.

David Tarpy, a University Faculty Scholar and professor in NC State's Department of Entomology and Plant Pathology, says the study has important implications for beekeepers and their customers, the farmers who rely on honey bees to pollinate their crops.

"Beekeepers have identified problem queens as a top management concern, but what's causing the problem is largely invisible. Queens go bad, and we don't know why," Tarpy said.

Alison McAfee, a postdoctoral scientist at NC State and UBC, was the study's lead author. She explained that to have a healthy hive, honey bees depend on a healthy queen, the only female bee in a colony that can reproduce.

The queen mates with many males, but only early in life, storing all the sperm that she'll use in her lifetime in her spermatheca, an abdominal organ that looks like a tiny pearl. When the sperm begin to die, the queen can't produce as many fertilized eggs. That causes the colony's population to decline.

"Queens have the potential to live for five years, but these days, half the time queens (in managed honey bee colonies) are replaced within their first six months because they are failing," McAfee said. "If a beekeeper is really lucky, a queen might live two years. Beekeepers need answers about why their queens are failing.

"The more we can find out about what is actually happening within these failed queens, the closer we can get to understanding why this queen failure is happening in the first place."

In their research, McAfee, Tarpy and their colleagues found that queens that were failing reproductively had significantly fewer sperm than ones that were reproductively thriving. And a higher percentage of the sperm they did have were dead. The researchers also discovered that compared to reproductively healthy queen bees, the failed queens were more likely to have higher levels of two viruses - sacbrood virus and black queen cell virus.

"The high levels of these viruses and poor sperm viability made us interested in seeing if there was a trade-off happening in the honey bee queen," McAfee said. "There's a classical hypothesis in reproductive biology that you can't do everything well, so there's a trade-off between immunity and being able to reproduce. It's been found in quite a few other organisms, including insects, that there are such trade-offs."

To find out if the same would be true with the honeybee queen, the researchers used a tool known as a mass spectrometer to gain a better picture of what was going on in the spermatheca of the healthy and failed queens. They identified 2,000 different proteins and determined which ones were linked to sperm viability.

One of the most significant proteins linked to sperm viability, McAfee said, was lysozyme. Lysozyme is an enzyme that's part of animals' immune systems.

"The queens with the highest sperm viability had the lowest abundance of lysozyme, indicating that they weren't investing resources in this kind of immune response," McAfee added. "That supports this idea that there's a trade-off between the queens being able to fight off infections and being able to maintain their stored sperm."

Tarpy said that the research could begin allowing researchers to find the cause of queen failure and find molecular tools that could "help identify bad queens upstream in the process before beekeepers use them and before they realize they're bad."

Right now, the cause of queen failure isn't clear. "The underlying mechanisms could be disease. They could be pesticides. They could be improper nutrition," he said. "We don't know, so we are working our way backward to identify the causes."

Once the causes are clearly understood, Tarpy added, scientists can then work forward "to help beekeepers keep mortality levels down to sustainable levels and thus keep their colonies thriving."

Pulsed ultraviolet light can be an effective alternative to some of the antimicrobial technologies now used by the poultry industry to kill pathogens on eggshells, according to Penn State researchers, who simulated production conditions to test the technology.

Researcher Paul Patterson, professor of poultry science, College of Agricultural Sciences, suggests the technology has merit for commercial application in the egg industry.

"This study is unique because it scaled-up and applied components of standard egg processing to a conveyor and sanitizing eggs in a commercial setting," he said. "In the absence of water or other chemical sanitizers, this technology has the potential to achieve significant -- equal or greater -- microbial reductions than some currently available technologies."

Every year in the United States, an average of 287 eggs are consumed per person, and more than 14.1 billion eggs are set in hatchery incubators to produce chicks destined for the egg and meat bird industries. By reducing the microbial load on eggs, foodborne illness outbreaks associated with eggs and poultry meat can be reduced while chick health is maintained.

The egg industry currently uses sanitizers and detergents to decontaminate eggs and wash off any physical debris, while low-intensity ultraviolet light has been used as an additional antimicrobial step. However, pulsed ultraviolet light is more effective, explained lead researcher Josh Casser, doctoral candidate in animal science, because it delivers a higher intensity of ultraviolet light to the surface of the eggshell. That results in a greater microbial reduction in a shorter period of time than conventional ultraviolet light treatment.

In this study, the surfaces of shell eggs were inoculated with nonpathogenic bacteria strains used for research and were treated with pulsed ultraviolet light derived from a xenon flashlamp. Eggs were exposed on a modified egg-carrying conveyor that provided complete rotation of eggs under the flashlamp.

The novel conveyor devised for the experiment was instrumental in achieving acceptable decontamination, Casser noted, adding that the xenon flashlamps could be scaled up and customized for any commercial installation.

"As the egg rotates on its long axis along the way, the entire surface of the eggshell is exposed to the pulsed ultraviolet light energy, and the 27 seconds of exposure in our experiment resulted in an acceptable germicidal response," he said. "At three pulses per second, each egg is exposed to nearly 90 pulses, and each pulse has a duration of 360 microseconds -- an extremely short duration pulse."

The researchers, who recently published their results in Poultry Science, found that pulsed ultraviolet light treatment inactivated two different microbial strains, with greater energy resulting in a greater germicidal response.

The study also evaluated the effects of pulsed ultraviolet light treatment of hatching eggs on both embryo and chick growth. Using the same system, four batches of 125 fertile eggs were treated with the same and greater intensities of pulsed ultraviolet light. After processing, eggs were placed in a commercial incubator under normal incubation conditions.

There was no significant effect of the pulsed ultraviolet light treatment on percent fertility, hatchability or hatch. Also, there were no significant effects on post-hatch observations, including chick livability and average bird weight at hatch or at 42 days of age.

"Our research supports the application of pulsed ultraviolet light as an effective antimicrobial intervention for both table and hatching eggs," Cassar said. "If the egg industry embraces pulsed ultraviolet light technology and applies it in its processing operations, food safety would be improved because of the reduced pathogen presence on the surface of the eggs. And that matters because 9% of all foodborne illness in the U.S. is associated with eggs."

The technology is especially promising because it appears to have no negative consequences for the vital hatching-eggs component of the business, even at 10 times the UV-light intensity used in the table egg study, Patterson pointed out. Hatcheries produce the replacement stock for both the egg and broiler flocks of the poultry industry, including turkeys.

"Our research showed that there are no negative effects on hatching eggs and the embryos and chicks that are derived from those treated eggs," he said. "Using pulsed ultraviolet light before incubation in a hatchery setting would improve chick health, would avoid some of the financial constraints caused by poor chick quality resulting from chicks getting sick from early exposure to microbial pathogens, and potentially would improve the food safety of poultry meat."

Yale researchers have devised a way to peer into the brains of two people simultaneously while are engaged in discussion. What they found will not surprise anyone who has found themselves arguing about politics or social issues.

When two people agree, their brains exhibit a calm synchronicity of activity focused on sensory areas of the brain. When they disagree, however, many other regions of the brain involved in higher cognitive functions become mobilized as each individual combats the other's argument, a Yale-led research team reports Jan. 13 in the journal Frontiers of Human Neuroscience.

"Our entire brain is a social processing network," said senior author Joy Hirsch, the Elizabeth Mears and House Jameson Professor of Psychiatry and professor of comparative medicine and neuroscience. "However, it just takes a lot more brain real estate to disagree than to agree."

For the study, the researchers from Yale and the University College London recruited 38 adults who were asked to say whether they agreed or disagreed with a series of statements such as "same-sex marriage is a civil right" or "marijuana should be legalized." After matching up pairs based on their responses the researchers used an imaging technology called functional near-infrared spectroscopy to record their brain activity while they engaged in face-to-face discussions.

When the people were in agreement, brain activity was harmonious and tended to be concentrated on sensory areas of the brain such as the visual system, presumably in response to social cues from their partner. However, during disputes these areas of the brain were less active. Meanwhile, activity increased in the brain's frontal lobes, home of higher order executive functions.

"There is a synchronicity between the brains when we agree," Hirsch said. "But when we disagree, the neural coupling disconnects."

Understanding how our brains function while disagreeing or agreeing is particularly important in a polarized political environment, Hirsch noted.

In discord, she said, two brains engage many emotional and cognitive resources "like a symphony orchestra playing different music." In agreement, there "is less cognitive engagement and more social interaction between brains of the talkers, similar to a musical duet."

A pioneering study by University of Bristol researchers finds that the evolution of teeth in the giant prehistoric shark Megalodon and its relatives was a by-product of becoming huge, rather than an adaptation to new feeding habits.

The iconic extinct Megalodon was the largest shark to ever roam the seas. Its name translates to 'big tooth', making reference to its massive teeth, which represent the most abundant fossil remains of the species. They are broad and triangular, nothing like the curved, blade-like teeth of the closest relatives of Megalodon.

The differences in tooth shape seen in this group of giant sharks has been traditionally thought to reflect a shift in diet. While the oldest relatives probably used their teeth to pierce small and fast-moving prey like fish, Megalodon most likely used them to bite off big chunks of meat from marine mammals or dismember such prey with powerful lateral head shakes.

In the new study published today in the journal Scientific Reports, scientists used computational tools to understand how the dentitions of these megatooth sharks functioned during feeding.

Antonio Ballell, PhD student at the University of Bristol's School of Earth Sciences, said: "We applied engineering techniques to digitally simulate how different tooth shapes handled bite forces and loads resulting from lateral head movements.

"This method, called Finite Element Analysis, has been previously used to understand how resistant different biological structures are under specific forces.

"We expected to find that Megalodon teeth could resist forces better than those of its older and smaller relatives. Surprisingly, when we removed tooth size from the simulations, we recovered the opposite pattern: Megalodon teeth are relatively weaker than the most gracile teeth of other megatooth sharks."

Dr Humberto Ferrón, postdoctoral researcher and co-author of the study, said: "Our results might seem to be at odds with traditional functional interpretations of the dentitions of these group of giant sharks. We think that other biological processes might be responsible for the evolutionary change in their dentitions.

"For example, modifications in tooth shape that occurred from the older, smaller species to that of the more recent, larger forms like Megalodon are very similar to those observed along the growth of Megalodon.

"That is, juvenile Megalodon individuals have teeth that resemble those of older megatooth sharks. Thus, instead of feeding specialization, we think that the acquisition of its gigantic body size was responsible for the evolution of the peculiar teeth of Megalodon."

DURHAM, N.C. - Glioblastoma brain tumors are especially perplexing. Inevitably lethal, the tumors occasionally respond to new immunotherapies after they've grown back, enabling up to 20% of patients to live well beyond predicted survival times.

What causes this effect has long been the pursuit of researchers hoping to harness immunotherapies to extend more lives.

New insights from a team led by Duke's Preston Robert Tisch Brain Tumor Center provide potential answers. The team found that recurring glioblastoma tumors with very few mutations are far more vulnerable to immunotherapies than similar tumors with an abundance of mutations.

The finding, appearing online Jan. 13 in the journal Nature Communications, could serve as a predictive biomarker to help clinicians target immunotherapies to those tumors most likely to respond. It could also potentially lead to new approaches that create the conditions necessary for immunotherapies to be more effective.

"It's been frustrating that glioblastoma is incurable and we've had limited progress improving survival despite many promising approaches," said senior author David Ashley, M.D., Ph.D., professor in the departments of Neurosurgery, Medicine, Pediatrics and Pathology at Duke University School of Medicine.

"We've had some success with several different immunotherapies, including the poliovirus therapy developed at Duke," Ashley said. "And while it's encouraging that a subset of patients who do well when the therapies are used to treat recurrent tumors, about 80% of patients still die."

Ashley and colleagues performed genomic analyses of recurrent glioblastoma tumors from patients treated at Duke with the poliovirus therapy as well as others who received so-called checkpoint inhibitors, a form of therapy that releases the immune system to attack tumors.

In both treatment groups, patients with recurrent glioblastomas whose tumors had few mutations survived longer than the patients with highly mutated tumors. This was only true, however, for patients with recurrent tumors, not for patients with newly diagnosed disease who had not yet received treatment.

"This suggests that chemotherapy, which is the standard of care for newly diagnosed glioblastoma, might be altering the inflammatory response in these tumors," Ashley said, adding that chemotherapy could be serving an important role as a primer to trigger an evolution of the inflammation process in recurrent tumors.

Ashley said the finding in glioblastoma could also be relevant to other types of tumors, including kidney and pancreatic cancers, which have similarly shown a correlation between low tumor mutations and improved response to immunotherapies.

College campuses are at risk of becoming COVID-19 superspreaders for their entire county, according to a new vast study which shows the striking danger of the first two weeks of school in particular.

Looking at 30 campuses across the nation with the highest amount of reported cases, experts saw that over half of the institutions had spikes - at their peak - which were well above 1,000 coronavirus cases per 100,000 people per week within the first two weeks of class.

In some colleges, one in five students had been infected with the virus by the end of the fall term. Four institutions had over 5,000 cases.

In 17 of the campuses monitored, a new computer model developed by scientists at Stanford University shows outbreaks translated directly into peaks of infection within their home counties.

Out today, the team's research - published in the peer-reviewed journal Computer Methods in Biomechanics and Biomedical Engineering - crucially shows, however, that tight outbreak management, for example the immediate transition from in person to all online learning, can reduce the peaks within about two weeks.

Lead author Hannah Lu, from Stanford's Energy Resources Engineering program, says the incidence levels of 1,000 cases per 100,000 people per week - when compared to the first and second waves of the pandemic with peak incidences of 70 to 150 - means colleges are at real risk of developing an extreme incidence of COVID-19.

"Policy makers often use an incidence of 50 COVID-19 cases per 100,000 people per week as a threshold for high risk counties, states, or countries. All 30 institutions in our study exceeded this value, three even by two orders of that magnitude," she states.

"The number of students who had become infected just throughout the fall is more than twice of the national average since the beginning of the outbreak of 5.3%, with 17.3 million reported cases at a population of 328.2 million.

"At the University of Notre Dame, for instance, all 12,607 students were tested before the beginning of class and only nine had tested positive. Less than two weeks into the term, the seven-day incidence was 3083, with a reproduction number R0 of 3.29.

"However," she adds, "with around 90 reported deaths nationwide, mainly college employees and not students, the campus-related death rate of 0.02% remains well below the average death rate of COVID-19."

Members of the research team used advanced modelling, which assesses the real-time epidemiology of the COVID-19 outbreak using an SEIR (susceptible, exposed, infectious, and recovered) model to map how the disease spread across the campuses.

They drew COVID-19 case reports from 30 publicly available college dashboards across the United States throughout the fall of 2020. These institutions were either teaching in person, online or a hybrid of both. They selected colleges for which case numbers are reported on a daily basis and the total cumulative case number exceeded 100.

During this time window, the nationwide number of new cases had dropped below 50,000 per day.

A limitation of this study is that the true on-campus student population was often unreported and had to be approximated by the total fall quarter enrollment. "This likely underestimates of the real maximum incidence and the fraction of on-campus students that have been affected by the virus," the authors state.

Senior author, Ellen Kuhl, adds: "Strikingly, these local campus outbreaks rapidly spread across the entire county and triggered a peak in new infections in neighbouring communities in more than half of the cases.

"It is becoming increasingly clear that these initial college outbreaks are unrelated to the national outbreak dynamics. Instead, they are independent local events driven by campus reopening and inviting students back to campus.

"Our results confirm the widespread fear in early fall that colleges could become the new hot spots of COVID-19 transmission. But, at the same time, college administrators should be applauded for their rapid responses to successfully manage local outbreaks."

All reported campuses pursued regular surveillance testing, weekly or even twice per week, combined with aggressive test-trace-isolate strategies.

"The majority of colleges and universities were able to rapidly manage their outbreaks and suppress campus-wide infections, while the neighbouring communities were less successful in controlling the spread of the virus. As a result, for most institutions, the outbreak dynamics remained manageable throughout the entire fall of 2020 with narrow spikes of less than 300 cases per day," Lu states.

The team believes that this methodology, in combination with continuing online learning, is the best way to prevent college sites from becoming the major hub of the disease.

"Our study suggests that tight test-trace-isolate strategies, flexible transition to online instruction, and-most importantly-compliance with local regulations will be critical to ensure a safe campus reopening after the winter break," she added.

Professor Kuhl concludes: "We anticipate that the most important aspect upon campus reopening within the coming weeks will be the human factor. Unfortunately, the fall term has shown that the best of all strategies can become meaningless if people do not follow the recommendations."

Today, the largest study of genetic diversity in Ukraine was published in the open science journal GigaScience. The project was an international effort, bringing together researchers in Ukraine, the US and China and is the first fruits of this collaboration to set up a new Central Europe Center for Genomic Research in Ukraine. Led by researchers at Uzhhorod National University and Oakland University in the US, the work provides genetic understanding of the historic and pre-historic migration settlements in one of the key intersections of human trade and migration between the Eurasian peoples as well as the identification of genetic variants of medical interest in the Ukrainian population that differ from other European populations.

Two decades ago, after the publication of the draft of the human genome, one of the largest exploration projects in the genomics era began: The Human Genome Diversity Project (HGDP). This is an enormous international effort to map the entire pattern of human genetic variation across the world. To build this map, there have been numerous global surveys of individual genomes in a variety of geographic regions and populations, but crucial gaps still remain. One of the most notable is in Eastern-Europe and the Eurasian steppes.

Central to this is Ukraine, which is the largest country located fully in Europe. It is made up of a population formed via millennia of migration. This territory served as a key prehistoric and historic crossroads for the spread of humans across Europe and into Asia. Migration events here included modern human expansion into Neanderthal territory, the movement of nomads and early farmers just starting to domesticate plants and animals, the great human migrations during the Middle Ages, and the trade exchange routes of the Silk Road.

Lead investigator, Taras Oleksyk at Oakland University, says: "Our study shows there is significant genetic diversity in Ukraine, a country that had not been prioritized in genome surveys. We found more than 13 million genetic variants among the DNA samples -- nearly 500,000 of which were previously undocumented."

These variants, commonly known as mutations, are the result of evolutionary and demographic factors that have shaped Ukrainians' genetic makeup throughout history.

Oleksyk explains: "As humans moved across the world over millennia, they gained genetic mutations, often due to adaptation to their specific environments. These mutations have been passed down through generations, so when we look at genomes of Ukrainians and other populations, what we see is a reflection of their unique evolutionary histories."

The survey is an important part of understanding human diversity, as it shows the extensive breadth of genetic diversity in Ukraine -- a nation that was once thought to lack genetic relevance.

Oleksyk highlights this, saying their study shows that "Ukraine accounts for roughly a quarter of the genetic variation documented in Europe. It's a part of the world that cannot be ignored in future genetic and biomedical studies."

Investigation of genetic diversity, in addition to providing insight into human history, also plays an important role in identifying medically relevant mutations that differ between populations. In this study, the researchers looked for variants in the Ukraine population whose prevalence differed significantly compared to other European genome sequences openly available through the HGDP.

In particular, the study identified medically relevant mutations whose prevalence in the Ukrainian genomes differed significantly compared to other European genome sequences that are all openly available as part of the HGDP and 1000 genomes project. Some of the mutations identified have been linked to conditions such as breast cancer, autism and Leber Congenital Amaurosis (LCA), a rare inherited eye disease.

Compared to the other Europeans, the Ukrainians in the study had far fewer carriers of a mutation linked to breast cancer and LCA. However, they more often held a mutation associated with autism. Another mutation, known to inhibit a drug used to treat bone disorders, was less prevalent in the Ukrainians compared to the other Europeans. These findings contribute to a growing body of knowledge that could revolutionize modern medicine and provide more informed assessment of the medical requirements and resources needed in different areas, populations and peoples.

"With a deeper understanding of how mutations factor into disease, doctors can tailor treatments to people's genetic profile," said Oleksyk. "That's why it's important to have detailed descriptions of the world's genomes. This knowledge could profoundly impact human health, and even save lives."

In addition, Ukraine survey identified mutations that were prevalent in disease-associated genes, but whose precise effect is unknown. These mutations could be prime candidates for future research.

With these data now available, in addition to the findings in this work, researchers around the world can now access these data to carry out their own studies in areas from human biology and medicine to unraveling human history and prehistory.

CLEVELAND, Ohio (Jan. 13, 2021)--If you're a bit more forgetful or having more difficulty processing complex concepts than in the past, the problem may be your menopause stage. A new study claims that menopause stage is a key determinant of cognition and, contrary to previous studies, shows that certain cognitive declines may continue into the postmenopause period. Study results are published online today in Menopause, the journal of The North American Menopause Society (NAMS).

It's commonly assumed that people's memories decline with age, as does their ability to learn new things and grasp challenging concepts. But multiple large-scale studies have suggested that menopause is a sex-specific risk factor for cognitive dysfunction independent of aging and menopause symptoms such as depression, anxiety, and hot flashes.

Many of these previous studies, however, did not characterize the duration of cognitive changes taking place between premenopause and perimenopause but suggested that difficulties in memory and processing may resolve in the postmenopause period. A new study involving more than 440 primarily low-income women of color, including women with HIV, concluded that menopause stage is a key determinant of cognition but that clinically significant cognitive declines/cognitive impairment persist into postmenopause, affecting primarily learning and memory. Subtler declines in attention were additionally found to continue into the postmenopause period.

Researchers theorized that the difference in results relative to the duration of cognitive decline could be explained by the fact that this newer study included more low-income women with multiple risk factors for cognitive dysfunction, including the presence of HIV. Previous studies have confirmed that cognitive function is compromised by an array of risk factors, including HIV, poverty, low education, substance abuse, high levels of stress, limited access to quality healthcare, mental health problems, and medical comorbidities.

The new study is the first known study to assess changes in cognitive performance across menopause stages. It specifically showed cognitive declines over time in learning, memory, and attention from premenopause to early perimenopause and from premenopause to postmenopause. Many of these changes were documented to reach a clinically significant level of cognitive impairment.

Results are published in the article "Cognitive changes during the menopausal transition: a longitudinal study in women with and without HIV."

"This study, which included a racially diverse sample of low-income women and women with HIV, adds to existing literature on cognitive changes across the menopause transition and showed a significant cognitive decline in learning and memory that persisted into postmenopause. Additional research is needed to confirm these findings and to identify the factors responsible for individual differences in cognitive changes," says Dr. Stephanie Faubion, NAMS medical director.

The ability of our skin to protect us from chemicals is something we inherit. Some people are less well-protected which could imply an increased risk of being afflicted by skin disease or cancer. A new study from Karolinska Institutet in Sweden that has been published in Environmental Health Perspectives shows how the rate of uptake of common chemicals is faster in people with a genetically weakened skin barrier.

We are continually exposed to chemicals from many different sources, for example, food, hygiene products, cosmetics and textiles. Many people are also exposed to chemicals at their place of work which can constitute a work environment problem.

The protein filaggrin is important for the structure and moisture balance of the skin, properties that affect the skin's ability to function as a barrier against chemicals.

Earlier research has indicated that inherited variations of DNA sequences for filaggrin mean some people have less good "barrier protection" which leads to an increased uptake of chemicals. That could imply a greater risk of being afflicted by cancer or various skin diseases such as contact dermatitis.

This genetic variation is relatively common in northern Europe and occurs in a person when one of the parents has the genetic predisposition in question. About ten percent of Swedes have this variation.

Researchers at Karolinska Institutet and Lund University have shown in a new study that this genetic variation leads to a considerably faster uptake of three common chemicals through the skin.

The researchers screened 500 people in Sweden. The results are based on 23 people with the mutation that causes a deficit of filaggrin, and 31 people who do not have it. The participants in the study were exposed to a harmless dose of three chemicals on their skin for four hours.

The chemicals used for the study were a pesticide used in Sweden, a UV filter used in sunscreen, and a hydrocarbon found in, for example, smoke from firewood.

The researchers were able to calculate the speed of uptake and the dose in the body with the help of urine samples taken from the participants during a period of 48 hours.

"We found, for example, twice as high a dose of the pesticide in the people with a mutation compared with those without. The fact that the skin takes up a greater amount of certain chemicals as a result of a genetic variation could mean that people with this mutation get a higher internal dose and, in the long run, could be at greater risk of disease such as cancer or a hormonal disorder," says Karin Broberg, Professor at the Department of Environmental Medicine, Karolinska Institutet, and the study's last author. She continues:

"For the next step, we are planning to investigate whether the mutation affects the uptake of other chemicals in the skin. We also want to find out whether these mutations lead to disease caused by chemicals in the body and in the skin."

A thermoelectric device is an energy conversion device that utilizes the voltage generated by the temperature difference between both ends of a material; it is capable of converting heat energy, such as waste heat from industrial sites, into electricity that can be used in daily life. Existing thermoelectric devices are rigid because they are composed of hard metal-based electrodes and semiconductors, hindering the full absorption of heat sources from uneven surfaces. Therefore, recent studies were actively conducted on the development of flexible thermoelectric devices capable of generating energy in close contact with various heat sources such as human skins and hot water pipes.

The Korea Institute of Science and Technology (KIST) announced that a collaborative research team led by Dr. Seungjun Chung from the Soft Hybrid Materials Research Center and Professor Yongtaek Hong from the Department of Electrical and Computer Engineering at Seoul National University (SNU, President OH Se-Jung) developed flexible thermoelectric devices with high power generation performance by maximizing flexibility and heat transfer efficiency. The research team also presented a mass-production plan through an automated process including a printing process.

Concerning existing substrates used for research on flexible thermoelectric devices, their heat energy transfer efficiency is low as a result of very low thermal conductivity. Their heat absorption efficiency is also low due to lack of flexibility, forming a heat shield layer, e.g., air, when in contact with a heat source. To address this issue, organic-material-based thermoelectric devices with high flexibility have been under development, but their application on wearables is not easy because of its significantly lower performance compared to existing inorganic-material-based rigid thermoelectric devices.

The aforementioned research team improved the flexibility while lowering the resistance of the thermoelectric device by connecting an inorganic-material-based high-performance thermoelectric device to a stretchable substrate composed of silver nanowires. The developed thermoelectric device showed excellent flexibility, thereby allowing stable operation even when it is bent or stretched. In addition, metal particles with high thermal conductivity were inserted inside the stretchable substrate to increase the heat transfer capacity by 800% (1.4 W/mK) and power generation by a factor higher than three. (When the temperature difference was 40 ? or more between both ends of the developed thermoelectric device, 7 mW/cm2 of electricity was generated. When attached to human skin, 7 μW/cm2 of electricity was generated from the body temperature only.) Simultaneously, the researchers automated the entire complex process, from the soft-platform process to the development of the thermoelectric device, thus enabling mass-production of the device.

The developed device can be used as a high-temperature sensor in industrial sites or as a battery-free distance detection sensor for autonomous driving by using the temperature difference inside and outside of a car. Consequently, the device is expected to be able to solve the power-source issue for a battery-based sensor system, which has a risk of explosion in high-temperature environments.

Dr. Seungjun Chung, with KIST, said: "This research showed that it is possible to operate actual wearables such as high-temperature sensor gloves using external heat sources. Going forward, we will develop a flexible thermoelectric platform that can operate wearables with only body temperature." He went on to say: "Our research findings are significant in that the functional composite material, thermoelectric device platform, and high-yield automated process developed in this study will be able to contribute to the commercialization of battery-free wearables in the future."

WASHINGTON, January 12, 2021 -- A highly sensitive wearable sensor for cardiorespiratory monitoring could potentially be worn continuously by cardiac patients or others who require constant monitoring.

The small and inexpensive sensor, announced in Applied Physics Letters, by AIP Publishing, is based on an electrochemical system involving two ionic forms of iodine, I- and I3-. A solution containing these electrolyte substances is placed into a small circular cavity that is capped with a thin flexible diaphragm, allowing detection of subtle movements when placed on a patient's chest.

Small motions that arise from the heartbeat and breathing cause the flexible diaphragm to move the I-/I3- solution into a narrow channel in the device, where it is electrochemically detected by four platinum electrodes.

"The sensor body was fabricated using Ecoflex 00-20, which has proven to be a very soft, strong and stretchy silicone rubber that is widely used in medical simulation, orthotics, and prosthetics," said author Yong Xu.

The investigators created a mold for the circular chamber and the associated narrow channel using 3D printing. A solution to create Ecoflex 00-20 was poured into the mold to form the body of the sensor and was also spin-coated on a rapidly rotating disk to produce the thin diaphragm. After the diaphragm and chamber body were bonded together, the investigators used a syringe to fill the chamber with the electrolyte solution.

The resulting device is only 28 millimeters wide and is skin-safe, so it can be attached directly to the patient's body. The device was able to detect the heartbeat with high sensitivity. A signal-to-noise ratio of greater than 6:1 was achieved, which is considered good.

Respiration can be detected by this device in two different ways. Because of the sensor's stretchability, it deforms when the chest contracts and expands during breathing, functioning as a strain sensor. The other way the sensor detects respiration is due to the way the volume of the chest cavity changes during a breath, modulating the heartbeat signal. In this way, respiration is detected indirectly through changes in the heartbeat.

The authors suggest their sensor could potentially be used for diagnosis of respiratory diseases, such as COVID-19, which often leads to shortness of breath.

"Symptoms in the early stage of infection could be subtle," said Xu. "Wearable devices that are capable of accurate detection of subtle respiratory and cardiovascular variation are of great interest especially during the current pandemic."

PHILADELPHIA -- (Jan. 12, 2021) -- Scientists at The Wistar Institute have created an advanced humanized immune system mouse model that allows them to examine resistance to immune checkpoint blockade therapies in melanoma. It has revealed a central role for mast cells. These findings were published today in the journal Nature Communications.

Checkpoint inhibitors revolutionized therapeutic options for advanced melanoma. However, only a fraction of patients respond to this treatment and some relapse due to reemergence of therapy-resistant lesions.

"To better understand why some cancers do not respond or become resistant to checkpoint therapies, we need more preclinical models that mimic the human tumor immune environment," said Rajasekharan Somasundaram, Ph.D., a member of The Wistar Institute Melanoma Research Center, who is the first and corresponding author of the paper.

Due to critical differences in the murine and human immune systems, mouse models do not allow the study of immune mechanisms that are uniquely human. "Humanized" mouse models are widely used to mimic the human immune system in mice.

Wistar's new humanized mouse model relies upon transplanted human stem cells and tissues that have been uniquely engineered to produce combinations of human cytokines that result in a more physiologically relevant model system for evaluating new immuno-oncology therapies and effective treatments targeting the tumor microenvironment.

"Our novel humanized mouse model has a longer life span and allowed us to study treatment responses to immunotherapies after human tumor transplant," said Somasundaram, who was part of a Wistar team led by Meenhard Herlyn, D.V.M., D.Sc., professor in The Wistar Institute Cancer Center, director of The Wistar Institute Melanoma Research Center, and a co-senior author on the study.

Researchers transplanted human metastatic melanoma cell lines into their humanized mouse model and treated them with anti-PD-1 antibody therapy. By studying immune cell infiltration into the tumors, Somasundaram and colleagues observed an abundance of infiltrated mast cells in anti-PD-1-treated tumors. Mast cells are an immune cell found throughout the body, especially in the skin and mucosa, where they serve as a first line of defense against pathogens. In samples from melanoma patients receiving immune checkpoint therapies, the team saw the same higher abundance of mast cells in non-responding tumors.

The authors showed that combining anti-PD-1 therapy with small molecule inhibitors able to deplete mast cells caused complete regression of tumors in mice and prolonged survival in comparison with mice receiving either treatment. Importantly, mice that reached remission did not show any signs of recurrence for four weeks after cessation of therapy and developed memory T cell response against melanoma tumors.

"Our results suggest that mast cells are associated with resistance to anti-PD-1 therapy, and that depleting mast cells is beneficial to immune checkpoint therapy responses," said Herlyn. "This warrants further investigation into the development of new combined immunotherapy approaches with small molecule inhibitors for the treatment of melanoma patients."

What The Study Did: National register data from Denmark were used to examine if people with autism spectrum disorder (ASD) have higher rates of suicide attempts and suicide compared to those without ASD and to identify potential risk factors.

Author: Kairi Kõlves, Ph.D., of Griffith University in Brisbane, Australia, is the corresponding author.

To access the embargoed study: Visit our For The Media website at this link https://media.jamanetwork.com/

(doi:10.1001/jamanetworkopen.2020.33565)

Editor's Note: The article includes funding/support disclosures. Please see the article for additional information, including other authors, author contributions and affiliations, conflict of interest and financial disclosures, and funding and support.

A team of astronomers led by the University of Arizona has observed a luminous quasar 13.03 billion light-years from Earth - the most distant quasar discovered to date. Dating back to 670 million years after the Big Bang, when the universe was only 5% its current age, the quasar hosts a supermassive black hole equivalent to the combined mass of 1.6 billion suns.

In addition to being the most distant - and by extension, earliest - quasar known, the object is the first of its kind to show evidence of an outflowing wind of super-heated gas escaping from the surroundings of the black hole at a fifth of the speed of light. In addition to revealing a strong quasar-driven wind, the new observations also show intense star formation activity in the host galaxy where the quasar, formally designated J0313-1806, is located.

The researchers will present their findings, which have been accepted for publication in Astrophysical Journal Letters, during a press conference and a scientific talk at the 237th Meeting of the American Astronomical Society, which will be held virtually Jan. 11-15.

The previous record-holder among quasars in the infant universe was discovered three years ago. The UArizona team also contributed to that discovery. Quasars are thought to result from supermassive black holes gobbling up surrounding matter, such as gas or even entire stars, resulting in a maelstrom of superheated matter known as an accretion disk that swirls around the black hole. Because of the enormous energies involved, quasars are among the brightest sources in the cosmos, often outshining their host galaxies.

Although J0313-1806 is only 20 million light-years farther away than the previous record holder, the new quasar contains a supermassive black hole twice as heavy. This marks a significant advancement for cosmology, as it provides the strongest constraint yet on the formation of black holes in the early universe.

"This is the earliest evidence of how a supermassive black hole is affecting its host galaxy around it," said the paper's lead author Feige Wang, a Hubble Fellow at UArizona's Steward Observatory. "From observations of less distant galaxies, we know that this has to happen, but we have never seen it happening so early in the universe."

Quasars that already amassed millions, if not billions, of solar masses in their black holes at a time when the universe was very young pose a challenge to scientists trying to explain how they came into existence when they barely had the time to do so. A commonly accepted explanation of black hole formation involves a star exploding up as a supernova at the end of its life and collapsing into a black hole. When such black holes merge over time, they can - theoretically - grow into supermassive black holes. However, much like it would require many lifetimes to build a retirement fund by chipping in a dollar each year, quasars in the early universe are a little bit like toddler millionaires; they must have acquired their mass by other means.

The newly discovered quasar provides a new benchmark by ruling out two current models of how supermassive black holes form in such short timescales. In the first model, massive stars that consist largely of hydrogen and lack most other elements that make up later stars, including metals, form the first generation of stars in a young galaxy and provide the food for the nascent black hole. The second model involves dense star clusters, which collapse into a massive black hole right from the outset.

Quasar J0313-1806, however, boasts a black hole too massive to be explained by the aforementioned scenarios, according to the team that discovered it. The team calculated that if the black hole at its center formed as early as 100 million years after the Big Bang and grew as fast as possible, it still would have had to have at least 10,000 solar masses to begin with.

"This tells you that no matter what you do, the seed of this black hole must have formed by a different mechanism," said co-author Xiaohui Fan, Regents Professor and associate head of the UArizona Department of Astronomy. "In this case, one that involves vast quantities of primordial, cold hydrogen gas directly collapsing into a seed black hole."

Because this mechanism doesn't require full-fledged stars as raw material, it is the only one that would allow the supermassive black hole of quasar J0313-1806 to grow to 1.6 billion solar masses at such an early time in the universe. This is what makes the new record quasar so valuable, Fan explained.

"Once you go to lower redshifts, all the models could explain the existence of those less distant and less massive quasars," he said. "In order for the black hole to have grown to the size we see with J0313-1806, it would have to have started out with a seed black hole of at least 10,000 solar masses, and that would only be possible in the direct collapse scenario."

The newly discovered quasar appears to offer a rare glimpse into the life of a galaxy at the dawn of the universe when many of the galaxy-shaping processes that have since slowed or ceased in galaxies that have been around for much longer were still in full swing.

According to current models of galaxy evolution, supermassive black holes growing at their centers could be the main reason why galaxies ultimately stop making new stars. Acting like a blowtorch of cosmic proportions, quasars blast their surroundings fiercely, effectively sweeping their host galaxy clean of much of the cold gas that serves as the raw material from which stars form.

"We think those supermassive black holes were the reason why many of the big galaxies stopped forming stars at some point," Fan said. "We observe this 'quenching' at lower redshifts, but until now, we didn't know how early this process began in the history of the universe. This quasar is the earliest evidence that quenching may have been happening at very early times."

By measuring the quasar's luminosity, Wang's team calculated that the supermassive black hole at its center is ingesting the mass equivalent of 25 suns each year, on average, which is thought to be the main reason for its high-velocity hot plasma wind blowing into the galaxy around it at relativistic speed. For comparison, the black hole at the center of the Milky Way has become mostly dormant.

And while the Milky Way forms stars at the leisurely pace of about one solar mass each year, J0313-1806 churns out 200 solar masses in the same time period.

"This is a relatively high star formation rate, similar to that observed in other quasars of similar age, and it tells us the host galaxy is growing very fast," Wang said.

"These quasars presumably are still in the process of building their supermassive black holes" Fan added. "Over time, the quasar's outflow heats and pushes all the gas out of the galaxy, and then the black hole has nothing left to eat anymore and will stop growing. This is evidence about how these earliest massive galaxies and their quasars grow."

The researchers expect to find a few more quasars from the same time period, including potential new record breakers, said Jinyi Yang, the second author of the report, who is a Peter A. Strittmatter Fellow at the Steward Observatory. Yang and Fan were observing at the 6.5-meter Magellan Baade telescope
at the Las Campanas Observatory in Chile the night J0313-1806 was discovered.

"Our quasar survey covers a very wide field, allowing us to scan almost half of the sky," Yang said. "We have selected more candidates on which we will follow up with more detailed observations."

The researchers hope to uncover more about the quasar's secrets with future observations, especially with NASA's James Webb Space Telescope, currently slated for launch in 2021.

"With ground-based telescopes, we can only see a point source," Wang said. "Future observations could make it possible to resolve the quasar in more detail, show the structure of its outflow and how far the wind extends into its galaxy, and that would give us a much better idea of its evolutionary stage."

An international team of astronomers has discovered the most distant quasar yet found -- a cosmic monster more than 13 billion light-years from Earth powered by a supermassive black hole more than 1.6 billion times more massive than the Sun and more than 1,000 times brighter than our entire Milky Way Galaxy.

The quasar, called J0313-1806, is seen as it was when the Universe was only 670 million years old and is providing astronomers with valuable insight on how massive galaxies -- and the supermassive black holes at their cores -- formed in the early Universe. The scientists presented their findings to the American Astronomical Society's meeting, now underway virtually, and in a paper accepted to the Astrophysical Journal Letters.

The new discovery beats the previous distance record for a quasar set three years ago. Observations with the Atacama Large Millimeter/submillimeter Array (ALMA) in Chile confirmed the distance measurement to high precision.

Quasars occur when the powerful gravity of a supermassive black hole at a galaxy's core draws in surrounding material that forms an orbiting disk of superheated material around the black hole. The process releases tremendous amounts of energy, making the quasar extremely bright, often outshining the rest of the galaxy.

The black hole at the core of J0313-1806 is twice as massive as that of the previous record holder and that fact provides astronomers with a valuable clue about such black holes and their affect on their host galaxies.

"This is the earliest evidence of how a supermassive black hole is affecting the galaxy around it," said Feige Wang, a Hubble Fellow at the University of Arizona's Steward Observatory and leader of the research team. "From observations of less distant galaxies, we know that this has to happen, but we have never seen it happening so early in the Universe."

The huge mass of J0313-1806's black hole at such an early time in the Universe's history rules out two theoretical models for how such objects formed, the astronomers said. In the first of these models, individual massive stars explode as supernovae and collapse into black holes that then coalesce into larger black holes. In the second, dense clusters of stars collapse into a massive black hole. In both cases, however, the process takes too long to produce a black hole as massive as the one in J0313-1806 by the age at which we see it.

"This tells you that no matter what you do, the seed of this black hole must have formed by a different mechanism," said Xiaohui Fan, also of the University of Arizona. "In this case, it's a mechanism that involves vast quantities of primordial, cold hydrogen gas directly collapsing into a seed black hole."

The ALMA observations of J0313-1806 provided tantalizing details about the quasar host galaxy, which is forming new stars at a rate 200 times that of our Milky Way. "This is a relatively high star formation rate in galaxies of similar age, and it indicates that the quasar host galaxy is growing very fast," said Jinyi Yang, the second author of the report, who is a Peter A. Strittmatter Fellow at the University of Arizona.

The quasar's brightness indicates that the black hole is swallowing the equivalent of 25 Suns every year. The energy released by that rapid feeding, the astronomers said, probably is powering a powerful outflow of ionized gas seen moving at about 20 percent of the speed of light.

Such outflows are thought to be what ultimately stops star formation in the galaxy.

"We think those supermassive black holes were the reason why many of the big galaxies stopped forming stars at some point," Fan said. "We observe this 'quenching' at later times, but until now, we didn't know how early this process began in the history of the Universe. This quasar is the earliest evidence that quenching may have been happening at very early times."

This process also will leave the black hole with nothing left to eat and halt its growth, Fan pointed out.

In addition to ALMA, the astronomers used the 6.5-meter Magellan Baade telescope, the Gemini North telescope and W.M. Keck Observatory in Hawaii, and the Gemini South telescope in Chile.

The astronomers plan to continue studying J0313-1806 and other quasars with ground-based and space-based telescopes.

The National Radio Astronomy Observatory is a facility of the National Science Foundation, operated under cooperative agreement by Associated Universities, Inc.