Cancer doctors may soon have a new tool for treating melanoma and other types of cancer, thanks to work being done by researchers at the University of Colorado Cancer Center.
In a paper published in the journal PNAS last month, CU Cancer Center members Mayumi Fujita, MD, PhD, Angelo D’Alessandro, PhD, Morkos Henen, PhD, MS, Beat Vogeli, PhD, Eric Pietras, PhD, James DeGregori, PhD, Carlo Marchetti, PhD, and Charles Dinarello, MD, along with Isak Tengesdal, MS, a graduate student in the Division of Infectious Diseases at the University of Colorado School of Medicine, detail their work on NLRP3, an intracellular complex that has been found to participate in melanoma-mediated inflammation, leading to tumor growth and progression. By inhibiting NLRP3, the researchers found, they can reduce inflammation and the resultant tumor expansion.
Specifically, NLRP3 promotes inflammation by inducing the maturation and release of interleukin-1-beta, a cytokine that causes inflammation as part of the normal immune response to infection. In cancer, however, inflammation can cause tumors to grow and spread.
“NLRP3 is a member of a larger family that is involved in sensing danger signals,” Marchetti says. “It is a receptor that surveils the intercellular compartment of a cell, looking for danger molecules or pathogens. When NLRP3 recognizes these signals, it leads to the activation of caspase-1, a protein involved in the processing and maturation of interleukin-1-beta into its biological active form, causing an intense inflammatory response. We found that in melanoma, this process is dysregulated, resulting in tumor growth.”
The oral NLRP3 inhibitor used in their study (Dapansutrile) has already shown to be effective in clinical trials to treat gout and heart disease, and it is currently being tested in COVID-19 as well. The CU cancer researchers are now trying to find out if this NLRP3 inhibitor can be successfully used in melanoma patients who are resistant to checkpoint inhibitors.
“Checkpoint inhibitors increase the efficacy of the immune system to kill tumors, but sometimes tumors become resistant to this treatment,” Marchetti says. “A big part of cancer research now is to find therapies that can be combined with checkpoint inhibitors to improve their efficacy.”
With the hypothesis that an NLRP3 inhibitor is one of those therapies, CU Cancer Center researchers are studying the drug’s effects on melanoma, as well as breast cancer and pancreatic cancer. In addition to improving the immune response, the NLRP3 inhibitor can also help reduce the side effects of checkpoint inhibitors. Marchetti says this research can make a big difference for melanoma patients who don’t respond to checkpoint inhibitors alone.
“This was a very collaborative project that involved a lot of members of the university, and we are very excited about it,” he says. This project is important because it further shows that NLRP3-mediated inflammation plays a critical role in the progression of melanoma, and it opens new strategies to improve patient care.”
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Materials provided by University of Colorado Anschutz Medical Campus. Original written by Greg Glasgow. Note: Content may be edited for style and length.

Around the world, a huge amount of research and development work is currently being done on carbon-containing, or organic, molecules that emit coloured light after appropriate excitation. This research field is driven by the display industry and the development of biomedical imaging techniques. While precise colour tuning in organic fluorescent dyes has so far usually been achieved by mixing different molecules, ETH researchers have now developed an approach that can generate a broad palette of colours by way of chemical adjustments within the molecules themselves.
Yinyin Bao, a group leader in the group of ETH professor Jean-Christophe Leroux, and his team of scientists turned to fluorescent organic polymers for this work. These polymers can best be thought of as moving chains of varying lengths. “The chains have a symmetrical structure, and two components within them contribute to the fluorescence,” Bao explains. “One component, called the fluorophore, sits in the middle of the chain, while the other component occurs once at each of the chain’s two ends.” Joining the fluorophore in the middle of the chain with each end of the chain are links whose number and structure scientists can adjust. If the polymer chain is bent so that one of its ends comes to lie near the fluorophore and the chain is simultaneously irradiated with UV light, it fluoresces.
Distance affects the interaction
The scientists have now been able to show that the fluorescence colour depends not only on the structure of the chain links and ends, but also on the number of chain links. “It’s the interaction of the chain end and the fluorophore that’s responsible for the fluorescence of these polymers,” Bao says: “The distance between the two components affects how they interact and thus the colour that’s emitted.”
Using a method called living polymerisation, the researchers can regulate the number of chain links. First, they gradually grow the chain by a slow process of attaching building blocks to the fluorophore. Once the desired length is reached, the scientists can terminate the process and simultaneously generate the chain end molecule. This is how the researchers produced polymers with different colours: with fewer than 18 building blocks, the molecules fluoresce yellow; with 25 chain links, green; and with 44 or more links, blue. “What’s special about this is that these differently luminescent polymers are all composed of the exact same components. The only difference is the chain length,” Bao says.
Wide colour range OLEDs
The research team, including scientists from the group of ETH Professor Chih-Jen Shih and from the Royal Melbourne Institute of Technology in Australia, published their work in the journal Science Advances. Currently, the researchers can produce fluorescent polymers in yellow, green and blue, but they are working on extending the principle to include other colours, including red.
These new fluorescent polymers can’t be used directly as OLEDs (organic LEDs) in displays because their electrical conductivity is not sufficiently high, Bao explains. However, it ought to be possible to combine the polymers with semiconducting molecules in order to produce wide colour range OLEDs in a simple way. Used in concentrated solar power plants, they could also collect sunlight more efficiently and thus increase the plants’ efficiency. Bao sees their main areas of application in laboratory diagnostic procedures that use fluorescence, for example in PCR, as well as in microscopy and imaging procedures in cell biology and medicine. Other potential uses would be as security features on banknotes and certificates or in passports.
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Materials provided by ETH Zurich. Original written by Fabio Bergamin. Note: Content may be edited for style and length.

Tracking carbon dioxide levels indoors is an inexpensive and powerful way to monitor the risk of people getting COVID-19, according to new research from the Cooperative Institute for Research in Environmental Sciences (CIRES) and the University of Colorado Boulder. In any given indoor environment, when excess CO2 levels double, the risk of transmission also roughly doubles, two scientists reported this week in Environmental Science & Technology Letters.
The chemists relied on a simple fact already put to use by other researchers more than a decade ago: Infectious people exhale airborne viruses at the same time as they exhale carbon dioxide. That means CO2 can serve as a “proxy” for the number of viruses in the air.
“You’re never safe indoors sharing air with others, but you can reduce the risk,” said Jose-Luis Jimenez, co-author of the new assessment, a CIRES Fellow and professor of chemistry at the University of Colorado Boulder.
“And CO2 monitoring is really the only low-cost and practical option we have for monitoring,” said Zhe Peng, a CIRES and chemistry researcher, and lead author of the new paper. “There is nothing else.”
For many months, researchers around the world have been searching for a way to continually monitor COVID-19 infection risk indoors, whether in churches or bars, buses or hospitals. Some are developing instruments that can detect viruses in the air continually, to warn of a spike or to indicate relative safety. Others tested existing laboratory-grade equipment that costs tens of thousands of dollars.
Jimenez and colleagues turned to commercially available carbon dioxide monitors, which can cost just a few hundred dollars. First, they confirmed in the laboratory that the detectors were accurate. Then, they created a mathematical “box model” of how an infected person exhales viruses and CO2, how others in the room inhaled and exhaled, and how the viruses and gas accumulate in the air of a room or are removed by ventilation. The model takes into consideration infection numbers in the local community, but it does not detail air flow through rooms — that kind of modeling requires expensive, custom analysis for each room.
It’s important to understand that there is no single CO2 level at which a person can assume a shared indoor space is “safe,” Peng emphasized. That’s partly because activity matters: Are people in the room singing and talking loudly or exercising, or are they sitting quietly and reading or resting? A CO2 level of 1,000 ppm, which is well above outside levels of about 400 ppm, could be relatively safe in a quiet library with masks but not in an active gym without masks.
But in each indoor space, the model can illuminate “relative” risk: If CO2 levels in a gym drop from 2,800 to 1,000 ppm (~2,400 above background levels to 600), the risk of COVID-19 transmission drops, too, to one-quarter of the original risk. In the library, if an influx of people makes CO2 jump from 800 to 1,600 (400 to 1,200 above background), COVID transmission risk triples.
In the new paper, Peng and Jimenez also shared a set of mathematical formulae and tools that experts in building systems and public health can use to pin down actual, not just relative, risk. But the most important conclusion is that to minimize risk, keep the CO2 levels in all the spaces where we share air as low as practically possible.
“Wherever you are sharing air, the lower the CO2, the lower risk of infection,” Jimenez said.

A recent study finds that unhealthy eating behaviors at night can make people less helpful and more withdrawn the next day at work.
“For the first time, we have shown that healthy eating immediately affects our workplace behaviors and performance,” says Seonghee “Sophia” Cho, corresponding author of the study and an assistant professor of psychology at North Carolina State University. “It is relatively well established that other health-related behaviors, such as sleep and exercise, affect our work. But nobody had looked at the short-term effects of unhealthy eating.”
Fundamentally, the researchers had two questions: Does unhealthy eating behavior affect you at work the next day? And, if so, why?
For the study, researchers had 97 full-time employees in the United States answer a series of questions three times a day for 10 consecutive workdays. Before work on each day, study participants answered questions related to their physical and emotional well-being. At the end of each workday, participants answered questions about what they did at work. In the evening, before bed, participants answered questions about their eating and drinking behaviors after work.
In the context of the study, researchers defined “unhealthy eating” as instances when study participants felt they’d eaten too much junk food; when participants felt they’d had too much to eat or drink; or when participants reporting having too many late-night snacks.
The researchers found that, when people engaged in unhealthy eating behaviors, they were more likely to report having physical problems the next morning. Problems included headaches, stomachaches and diarrhea. In addition, when people reported unhealthy eating behaviors, they were also more likely to report emotional strains the next morning — such as feeling guilty or ashamed about their diet choices. Those physical and emotional strains associated with unhealthy eating were, in turn, related to changes in how people behaved at work throughout the day.

Cancer therapy in recent times relies on the use of several drugs derived from biological sources including different bacteria and viruses, among others. However, these bio-based drugs get easily degraded and therefore inactivated on administration into the body. Thus, effective delivery to and release of these drugs at target tumor sites are of paramount importance from the perspective of cancer therapy.
Recently, scientists have discovered unique three-dimensional, water-containing polymers, called hydrogels, as effective drug delivery systems (DDSs). Drugs loaded into these hydrogels remain relatively stable owing to the network-like structure and organic tissue-like consistency of these DDSs. Besides, drug release from hydrogels can be controlled by designing them to swell and shrink in response to certain stimuli, or minute changes in conditions, like temperature or pH (which determines the acidity of an environment). For instance, when conditions are just the right level of acidic in the tumor microenvironment, these DDSs either shrink or swell and release the drug.
However, there has been no method for the one-pot synthesis of hydrogels that respond to more than one such stimulus and degrade to release drugs at target tumor sites. Until now.
Now, a team of scientists, led by Professor Akihiko Kikuchi from Tokyo University of Science, reports the production of unique degradable hydrogels that respond to changes under multiple conditions in “reducing” environments mimicking the microenvironment of tumors. As Prof. Kikuchi observes, “In order to prepare degradable hydrogels that can release drugs in response to changes in the tumor microenvironment, we prepared hydrogels that respond to temperature, pH, and reducing environment, and analyzed their properties.”
In their study published in the Journal of Controlled Release, Prof. Kikuchi — along with his colleagues from Tokyo University of Science, Dr. Syuuhei Komatsu, Ms. Moeno Tago, and Ms. Yu Ando, and his collaborator on the study, Prof. Taka-Aki Asoh from Osaka University — details the steps of designing these novel hydrogels from the synthetic polymer poly(ethylene glycol) diglycidyl ether and the sulfur-containing organic compound cystamine. In response to low temperatures, these hydrogels swell up while they shrink at the physiological temperature. Additionally, the hydrogels respond to pH changes by virtue of possessing tertiary amino groups. It must be noted here that the pH of the tumor microenvironment fluctuates between 5.5 and 6.5 owing to glycolysis in the tumor cells. Under the reducing conditions of this environment, the hydrogels degrade because of the breakage of disulfide bonds and change into low molecular-weight water-soluble oligomers that are easily excreted from the body.
To further test their drug release properties, the scientists loaded these hydrogels with specific proteins by exploiting their temperature-dependent swelling-deswelling behavior and tested the controlled release of drugs under acidic or reducing conditions. It was found that the amount of drug loaded onto these hydrogels could be controlled by changing the mesh size of the hydrogel polymer network by changing temperature, suggesting the possibility of customizing these DDSs for specific drug delivery. Besides, the hydrogel network structure and electrostatic interactions in the network ensured that the proteins were preserved intact until delivery, unaffected by the swelling and shrinking of the hydrogels with pH changes in the surrounding environment. The scientists found that the loaded protein drugs were completely released only under reducing conditions.
Using these hydrogels and the tractability that they provide, doctors may soon be able to design “customized” hydrogels that are specific to patients, giving personalized medicine a big boost. In addition to that, this new DDS provides a way to kill cancer cells that are left behind after surgery. As Prof. Kikuchi states, “The implantation of this material in the affected area after cancer resection may eliminate residual cancer cells, making it a more powerful therapeutic tool.”
As cancer tightens its vise grip around the world, treatment options need to be varied and upgraded for customized and effective therapy. This unique and simple design technique to produce multi-stimuli-responsive hydrogels for effective drug delivery to target tumor sites may just be one among several such promising techniques to mount an answer to the challenge cancer poses to humanity.
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Materials provided by Tokyo University of Science. Note: Content may be edited for style and length.

Ants react to social isolation in a similar way as do humans and other social mammals. A study by an Israeli-German research team has revealed alterations to the social and hygienic behavior of ants that had been isolated from their group. The research team was particularly surprised by the fact that immune and stress genes were downregulated in the brains of the isolated ants. “This makes the immune system less efficient, a phenomenon that is also apparent in socially isolating humans — notably at present during the COVID-19 crisis,” said Professor Susanne Foitzik, who headed up the study at Johannes Gutenberg University Mainz (JGU). The study on a species of ant native to Germany has recently been published in Molecular Ecology.
Effects of isolation in social insects little studied so far
Humans and other social mammals experience isolation from their group as stressful, having a negative impact on their general well-being and physical health. “Isolated people become lonely, depressed, and anxious, develop addictions more easily, and suffer from a weakened immune system and impaired overall health,” added Professor Inon Scharf, lead author of the article and cooperation partner of the Mainz research group at Tel Aviv University in Israel. While the effects of isolation have been extensively studied in social mammals such as humans and mice, less is known about how social insects respond in comparable situations — even though they live in highly evolved social systems. Ants, for instance, live their entire lives as members of the same colony and are dependent on their colony mates. The worker ants relinquish their own reproductive potential and devote themselves to feeding the larvae, cleaning and defending the nest, and searching for food, while the queen does little more than just lay eggs.
The research team looked at the consequences of social isolation in the case of ants of the species Temnothorax nylanderi. These ants inhabit cavities in acorns and sticks on the ground in European forests, forming colonies of a few dozen workers. Young workers engaged in brood care were taken singly from 14 colonies and kept in isolation for varying lengths of time, from one hour to a maximum of 28 days. The study was conducted between January and March 2019 and highlighted three particular aspects in which changes were observed. After the end of their isolation, the workers were less interested in their adult colony mates, but the length of time they spent in brood contact increased; they also spent less time grooming themselves. “This reduction in hygienic behavior may make the ants more susceptible to parasites, but it is also a feature typical of social deprivation in other social organisms,” explained Professor Susanne Foitzik.
Stress due to isolation adversely affects the immune system
While the study revealed significant changes in the behaviors of the isolated insects, its findings with regard to gene activity were even more striking: Many genes related to immune system function and stress response were downregulated. In other words, these genes were less active. “This finding is consistent with studies on other social animals that demonstrated a weakening of the immune system after isolation,” said Professor Inon Scharf.
The discovery by the team of biologists led by Professor Susanne Foitzik is the first of its kind, combining behavioral and genetic analyses on the effects of isolation in social insects. “Our study shows that ants are as affected by isolation as social mammals are and suggests a general link between social well-being, stress tolerance, and immunocompetence in social animals,” concluded Foitzik, summarizing the results of the Israeli-German study. Foitzik is also collaborating with her Israeli partner Professor Inon Scharf and with co-author and group leader Dr. Romain Libbrecht of JGU on a new joint project on the fitness benefits and the molecular basis of spatial learning in ants, funded by the German Research Foundation (DFG).
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Materials provided by Johannes Gutenberg Universitaet Mainz. Note: Content may be edited for style and length.

An epigenetic study at the RIKEN Center for Integrative Medical Sciences shows that in mouse egg cells, modifications to histone H2A at lysine 119 lay the groundwork for inherited DNA functional modifications from the mother.
In books and the movies, a group of people on a special mission always sends out a scout to do reconnaissance before they proceed. Sometimes, the scouts leave signs or markers that allow the group to know where there should go. Researchers led by Azusa Inoue at the RIKEN Center for Integrative Medical Sciences in Japan have discovered a mark left behind in unfertilized egg cells that determine which DNA modifications will be inherited if the egg is fertilized. Specifically, they found that without initial modifications to histone H2A at lysine 119 — technically called H2AK119ub1 — later inheritable modifications would not occur. When allowed to develop, one consequence of this deficit was an enlarged placenta after embryo implantation. This study was published in Nature Genetics on April 5.
For many years we were taught in school that acquired traits were not inherited. In some sense this was correct; stretching your neck a lot to get food will not result in children with longer necks. However, your DNA function can be modified throughout your life. For example, DNA structure in chromosomes is supported by proteins called histones. When histones are modified, they can change how genes are expressed in the body. This is epigenetics, and a previous study by Inoue and colleagues showed that acquired tri-methylation of histone H3 at lysine 27 (thankfully abbreviate to H3K27me3) in mammalian egg cells can be inherited. In the new study, the team used technology called low-input CUT&RUN to begin answering the question of how this happens.
First, the researchers examined the timing of the two different histone modifications. They found that every gene exhibiting H3K27me3 also showed H2AK119ub1 in mouse egg cells. Suspecting its importance, the researchers knocked out two proteins that make up H2AK119ub1 in egg cells. Low-input CUT&RUN showed that the knock-out egg cells had much less H3K27me3 than controls at a subset of genes that normally bring H3K27me3 into the next generation. Thus, H2AK119ub1 acts like a kind of marker left by a scout, identifying where subsequent H3K27me3 should follow. “We discovered that H2AK119ub1 is necessary for maternal inheritance of H3K27me3, making the H2AK119ub1-H3K27me3 pathway a major player in transgenerational epigenetic inheritance in mammals,” says Inoue.
The researchers then found something they didn’t expect. Testing showed that the loss of H3K27me3 was itself inherited by fertilized embryos, and could not be reversed. Furthermore, this deficiency led increased lethality — miscarriages — and enlarged placentas. “It was surprising to find that defects in an egg’s histone modification are irreversibly inherited by embryos and cause long term consequences in development,” says Inoue.
The results thus showed that despite normal DNA in the mouse egg cell, if the proper instructions — first H2AK119ub1 and then H3K27me3 modifications — were missing, miscarriages and enlarged placentas could occur. These findings have clinical implications, especially for reproductive medicine and placental defects. “The next step,” says Inoue, “is to see whether any diseases or surrounding environments can affect the heritable histone modification.”
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Materials provided by RIKEN. Note: Content may be edited for style and length.

As states open vaccines and restaurants to all, wait staff and food service workers are often left behind. Some chefs have even opened pop-up spots to get their employees shots more quickly.Over the course of the pandemic, some of the most dangerous activities were those many Americans dearly missed: scarfing up nachos, canoodling with a date or yelling sports scores at a group of friends at a crowded, sticky bar inside a restaurant.Now, as more states loosen restrictions on indoor dining and expand access to vaccines, restaurant — who have morphed from cheerful facilitators of everyone’s fun to embattled frontline workers — are scrambling to protect themselves against the new slosh of business.“It’s been really stressful,” said Julia Piscioniere, a server at Butcher & Bee in Charleston. “People are OK with masks, but it is not like it was before. I think people take restaurants and their workers for granted. It’s taken a toll.”The return to economic vitality in the United States is led by places to eat and drink, which also suffered among the highest losses in the last year. Balancing the financial benefits of a return to regular hours with worker safety, particularly in states where theoretical vaccine access outstrips actual supply, is the industry’s latest hurdle.In many states, workers are still unable to get shots, especially in regions where they were not included in priority groups this spring. Immigrants, who make up a large segment of the restaurant work force, are often fearful of signing up, worrying that the process will legally entangle them.Some states have dropped mask mandates and capacity limits inside establishments — which the Centers for Disease Control and Prevention still deem a potentially risky setting — further endangering employees.“It is critical for food and beverage workers to have access to the vaccine, especially as patrons who come have no guarantee that they will be vaccinated and obviously will not be masked when eating or drinking,” said Dr. Alex Jahangir, the chairman of a coronavirus task force in Nashville. “This has been a major concern for me as we balance the competing interests of vaccinating everyone as soon as possible before more and more restrictions are lifted.”Servers in Texas are dealing with all of the above. The state strictly limited early eligibility for shots, but last week opened access to all residents 16 and over, creating an overwhelming demand for slots. The governor recently dropped the state’s loosely enforced mask mandate, and allowed restaurants to go forth and serve all comers, with zero limitations.“Texas is in a unique position because we have all these things going on,” said Anna Tauzin, the chief revenue and innovation officer of the Texas Restaurant Association.Michael Shemtov, owner of Butcher and Bee in Charleston, S.C., spoke to a television reporter during a vaccination drive at his restaurant. “If people can’t get appointments, let’s bring them to them,” he said.Ben ChrismanThe trade group is pairing with a health care provider to set aside days at mass vaccines sites in the state’s four biggest cities to target industry workers.The industry has taken matters in its own hands in other places, too.In Charleston, Michael Shemtov, who owns several spots, turned a food hall into a restaurant worker vaccine site on a recent Tuesday with the help of a local clinic. (The post-shot observation seating was at the sushi place; celebratory beers were tipped at an adjoining pizzeria.) Ms. Piscioniere and her partner eagerly availed themselves. “I am super relieved,” she said. “It’s been so hard to get appointments.”In Houston, Legacy Restaurants — which owns the Original Ninfa’s and Antone’s Famous Po’ Boys — is running two vaccine drives for all staff members and their spouses, moves the owners believe will protect workers and assure customers.Some cities and counties are also tackling the problem. Last month, Los Angeles County set aside the majority of appointments for five mass sites two days a week for the estimated 500,000 workers in the food and agriculture industries — half of whom are restaurant staff. In Nashville, the health department has opted to set aside 500 spots daily for the next week specifically for people in the food and hospitality industries. It is possible that restaurants will be able to require their workers be vaccinated in the future.Many business sectors were battered by the coronavirus pandemic, but there is broad agreement that hospitality was hardest hit and that low wage workers sustained some of the biggest blows. In February 2020, for instance, restaurant worker hours were up 2 percent over a previously strong period the year before; two months later those hours were cut by more than half.While hours and wages have recovered somewhat, the industry remains hobbled by rules that most other businesses — including airlines and retail stores — have not had to face. The reasons point to a sadly unfortunate reality that never changed: indoor dining, by nature of its actual existence, helped spread the virus.Tyler Cahill, 29, received his first Pfizer vaccine shot at Workshop, a food court in Charleston.Ben ChrismanA recent report by the C.D.C. found that after mask and other restrictions were lifted, on-premise restaurants led to daily increase in cases and death rates between 40 and 100 days later. Although other settings have turned into super-spreading events — funerals, wedding and large indoor events — many community outbreaks have found their roots in restaurants and bars.“Masks would normally help to protect people in indoor settings but because people remove masks when dining,” said Christine K. Johnson, professor of epidemiology and ecosystem health at the University of California, Davis, “there are no barriers to prevent transmission.”Not all governments have viewed restaurant workers as “essential,” even as restaurants have been a very active part of the American food chains — from half-open sites to takeout operations to cooking for those in need — during the entire pandemic. The National Restaurant Association helped push the C.D.C. to recommend that food service workers be included in priority groups of workers to get vaccines although not all states followed the guidelines.Almost every state in the nation has accelerated its vaccination program, targeting nearly all adult populations.“Most people in our government have considered restaurants nonessential luxuries,” said Rick Bayless, the well-known Chicago restaurateur, whose staff scoured all vaccines sites for weeks to get workers shots. “I think that’s shortsighted. The human race is at its core social and when we deny that aspect of our nature, we do harm to ourselves. Restaurants provide that very essential service. It can be done safely, but to minimize the risk for our staff, we should be prioritized for vaccination.”Texas did not designate as early vaccine recipients any workers beyond those in the health care and education sectors, but is now open to all.“The state leadership decided to ignore our industry as a whole as well as grocery workers,” said Michael Fojtasek, the owner of Olamaie in Austin. “Now because our state leadership has decided to lift a mask mandate while not giving us an opportunity to be vaccinated, it has created this really challenging access issue.” He has switched to a takeout sandwich business for now, and won’t reopen until every worker gets a shot, he said.Jade Fletcher, a server at the County Line in Austin. “I think it is important for them to be vaccinated,” Don Miller, the owner, said of his staff.Ilana Panich-Linsman for The New York TimesMany restaurant owners, however, said that they are going their own way with the rules, and customers often lead them there. “There is a lot of shaming that goes on if you open up and you don’t have your tables six feet apart,” said Don Miller, the owner of the County Line, a small chain in Texas and New Mexico.Moreover, his places continue to require masks and keep them at the hostess station for anyone who “forgets.” Most of his young work force, however, will likely wait a long time for a jab. “I think it is important for them to be vaccinated,” he said. “It hasn’t resonated with them as it hasn’t been available to that age group.”The restaurant industry has many more Latino immigrant workers than most other businesses, and some fear registration for the vaccine is complicating reopenings. Many workers at Danielle Leoni’s Phoenix restaurant, the Breadfruit and Rum Bar, declined unemployment insurance, and have shied from signing up for a shot. “Before you can even make an appointment you have to put in your name and date of birth and email,” Ms. Leoni said. “Those are questions that are deterrents for people trying to keep a low profile.”In Charleston, Mr. Shemtov was inspired by accounts of the immunization program in Israel, which was considered successful in part because the government took vaccines to job sites. “If people can’t get appointments, let’s bring them to them.”Other restaurants are devoting hours to making sure workers know how to sign up, locating leftover shots and networking with their peers. Some offer time off for a shot and the recovery period for side effects.“We don’t want them to have to choose between an hour or pay of a vaccine,” said Katie Button, the owner of Curate and La Bodega in Asheville, N.C.Still, some owners are not taking chances. “If we go out of business because we are one of the few restaurants in Arizona that won’t reopen, so be it,” Ms. Leoni said. “Nothing is more important than someone else’s health or safety.”

An international research team has sequenced the genomes of the oldest securely dated modern humans in Europe who lived around 45,000 years ago in Bacho Kiro Cave, Bulgaria. By comparing their genomes to the genomes of people who lived later in Europe and in Asia the researchers from the Max Planck Institute for Evolutionary Anthropology in Leipzig, Germany, show that this early human group in Europe contributed genes to later people, particularly present-day East Asians. The researchers also identified large stretches of Neanderthal DNA in the genomes of the Bacho Kiro Cave people, showing that they had Neanderthal ancestors about five to seven generations back in their family histories. This suggests that mixture with Neanderthals was the rule rather than the exception when the first modern humans arrived in Europe.
Last year, a research team led by researchers from the National Institute of Archaeology with Museum at the Bulgarian Academy of Sciences and the Max Planck Institute for Evolutionary Anthropology, Germany, reported the discovery of modern human remains found in direct association with the Initial Upper Palaeolithic stone tools at the site of Bacho Kiro Cave in Bulgaria. The oldest individuals found in the cave were directly radiocarbon dated to between 43,000 and 46,000 years ago. They are thus the earliest known dispersal of modern humans across the mid-latitudes of Eurasia.
Mateja Hajdinjak and colleagues have now sequenced the genomes of five individuals found at the Bacho Kiro Cave. Four individuals are between 43,000 to 46,000-years-old and were found together with stone tools belonging to the Initial Upper Palaeolithic, the earliest culture associated with modern humans in Eurasia. An additional individual found in the cave is around 35,000-years-old and found with stone tools of a later type. It was previously thought that bearers of the Initial Upper Palaeolithic died out without contributing genetically to modern humans arriving later. However, the researchers now show that the oldest Bacho Kiro Cave individuals, or groups closely related to them, contributed genes to present-day people. Surprisingly, this contribution is found particularly in East Asia and the Americas rather than in Europe where the Bacho Kiro Cave people lived. These genetic links to Asia mirror the links seen between the Initial Upper Palaeolithic stone tools and personal ornaments found in Bacho Kiro Cave and tools and ancient jewelry found across Eurasia to Mongolia.
Genetic differences between individuals
Importantly, the later 35,000-year-old individual found in Bacho Kiro Cave belonged to a group that was genetically distinct from the earlier inhabitants of the cave. This shows that the earliest history of modern humans in Europe may have been tumultuous and involved population replacements.
The earliest people at Bacho Kiro Cave lived at a time when Neanderthals were still around. The researchers therefore scanned their genomes for fragments of Neanderthal DNA. “We found that the Bacho Kiro Cave individuals had higher levels of Neanderthal ancestry than nearly all other early humans, with the exception of a 40,000-year-old individual from Romania. Crucially, most of this Neanderthal DNA comes in extremely long stretches. This shows that these individuals had Neanderthal ancestors some five to seven generations back in their family trees” says Mateja Hajdinjak.
Although only a handful of genomes from modern humans who lived at the same time in Eurasia as some of the last Neanderthals have been recovered, nearly all of them have recent Neanderthal ancestors. “The results suggest that the first modern humans that arrived in Eurasia mixed frequently with Neanderthals. They may even have become absorbed into resident Neanderthal populations. Only later on did larger modern human groups arrive and replace the Neanderthals” says Svante Pääbo, who coordinated the genetic research.
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Materials provided by Max-Planck-Gesellschaft. Note: Content may be edited for style and length.

Worldwide 39 percent of the adults were overweight in 2016, according to statistics of the World Health Organization. In the US the prevalence of obesity was 42.4 percent in 2017/2018, according to a survey of the National Center for Health Statistics (NCHS).
Concurrently millions of people want to lose weight. Physical exercise is an important option to achieve this. After all, more calories are consumed through sport than when sitting, standing or lying down.
But what influence does sport have on (direct) eating habits? Scientists at the Technical University of Munich (TUM) and the University of Nebraska (USA) have now investigated this question for the first time.
Randomized study
“In the sports context, we have the phenomenon of people overeating after physical activity,” said Prof. Köhler, Professor of Exercise, Nutrition and Health at the Technical University of Munich. “People want to reward themselves and their bodies for being active. So we use a hypothetical experiment to find out why people eat more after exercise compared to when they don’t exercise.”
The aim of a randomized crossover study was to investigate the influence of exercise on hypothetical decisions regarding the amount and timing of food intake. For this purpose, 41 healthy participants (23 women, 18 men) aged between 19 and 29 years with an average BMI of 23.7 were randomly assigned to either a 45-minute exercise session or a rest period of equal duration at the first visit and completed the other study condition at the second visit.