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People with type 2 diabetes tend to have poorer muscle function than others. Now a research team at Lund University in Sweden has discovered that in type 2 diabetes, a specific gene is of great importance for the ability of muscle stem cells to create new mature muscle cells. The findings are published in Nature Communications.

"In people with type 2 diabetes, the VPS39 gene is significantly less active in the muscle cells than it is in other people, and the stem cells with less activity of the gene do not form new muscle cells to the same degree. The gene is important when muscle cells absorb sugar from blood and build new muscle. Our study is the first ever to link this gene to type 2 diabetes", says Charlotte Ling, professor of epigenetics at Lund University who led the study.

In type 2 diabetes, the ability to produce insulin is impaired, and patients have chronically elevated blood sugar. Muscles are generally worse at absorbing sugar from food, and muscle function and strength are impaired in patients with type 2 diabetes.

A muscle consists of a mixture of fiber types with different properties. Throughout life, muscle tissue has the ability to form new muscle fibers. There are also immature muscle stem cells that are activated in connection with, for example, injury or exercise. In the current study, the researchers wanted to investigate whether epigenetic patterns in muscle stem cells can provide answers to why impaired muscle function occurs in type 2 diabetes.

Two groups were included in the study: 14 participants with type 2 diabetes and 14 healthy people in a control group. The participants in the groups were matched by age, gender and BMI (body mass index). The researchers studied epigenetic changes in the muscle stem cells in both groups, and under exactly the same conditions, they also extracted mature muscle cells and compared them. In total, they identified 20 genes , including VPS39, whose gene expression differed between the groups in both immature muscle stem cells and mature muscle cells. The researchers also compared the epigenetic patterns of muscle cells before and after cell differentiation in both groups.

"Despite the fact that both groups' muscle stem cells were grown under identical conditions, we saw more than twice as many epigenetic changes in the type 2 diabetes group during the differentiation from muscle stem cell to mature muscle cells. Muscle-specific genes were not regulated normally, and epigenetics did not function in the same way in cells from people with type 2 diabetes", says Charlotte Ling.

"The study clearly showed that muscle stem cells that lack the function of the gene VPS39, which is lower in type 2 diabetes, also lack the ability to form new mature muscle cells. This is because muscle stem cells that lack VPS39 due to altered epigenetic mechanisms cannot change their metabolism in the same way as muscle stem cells from controls - the cells therefore remain immature or break down and die", says Johanna Säll Sernevi, postdoc researcher at Lund University.

To confirm the findings, the researchers also used animal models with mice that had a reduced amount of the VPS39 gene, to mimic the disease. The mice subsequently had altered gene expression and reduced uptake of sugar from blood into the muscle tissue, just like the individuals with type 2 diabetes.

The comprehensive study is a collaboration between Swedish, Danish and German researchers, who believe that the findings open up new avenues for treating type 2 diabetes.

"The genome, our DNA, cannot be changed, although epigenetics in effect does. With this new knowledge, it is possible to change the dysfunctional epigenetics that occur in type 2 diabetes. For example, by regulating proteins, stimulating or increasing the amount of the VPS39 gene, it would be possible to affect the muscles' ability to regenerate and absorb sugar", concludes Charlotte Ling.

The giant star featured in this latest Hubble Space Telescope anniversary image is waging a tug-of-war between gravity and radiation to avoid self-destruction. The star, called AG Carinae, is surrounded by an expanding shell of gas and dust -- a nebula -- that is shaped by the powerful winds of the star. The nebula is about five light-years wide, which equals the distance from here to our nearest star, Alpha Centauri.

The huge structure was created from one or more giant eruptions several thousand years ago. The star's outer layers were blown into space, the expelled material amounting to roughly 10 times the mass of our Sun. These outbursts are typical in the life of a rare breed of star called a Luminous Blue Variable (LBV), a brief unstable phase in the short life of an ultra-bright, glamorous star that lives fast and dies young. These stars are among the most massive and brightest stars known. They live for only a few million years, compared to the roughly 10-billion-year lifetime of our own Sun. AG Carinae is a few million years old and resides 20 000 light-years away inside our Milky Way galaxy. The star's expected lifetime is between 5 million and 6 million years.

LBVs have a dual personality. They appear to spend years in semi-quiescent bliss and then they erupt in a petulant outburst, during which their luminosity increases -- sometimes by several orders of magnitude. These behemoths are stars in the extreme, far different from normal stars like our Sun. In fact AG Carinae is estimated to be up to 70 times more massive than our Sun and shines with the blinding brilliance of 1 million suns.

Major outbursts such as the one that produced the nebula featured in this image occur a few times during a LBV's lifetime. A LBV star only casts off material when it is in danger of self-destruction. Because of their massive forms and super-hot temperatures, luminous blue variable stars like AG Carinae are in a constant battle to maintain stability. It's an arm-wrestling contest between radiation pressure from within the star pushing outward and gravity pressing inward. This arm-wrestling match results in the star's expanding and contracting. The outward pressure occasionally wins the battle, and the star expands to such an immense size that it blows off its outer layers, like a volcano erupting. But this outburst only happens when the star is on the verge of coming apart. After the star ejects the material, it contracts to its normal (large) size, settles back down, and becomes stable again.

LBV stars are rare: fewer than 50 are known among the galaxies in our local group of neighbouring galaxies. These stars spend tens of thousands of years in this phase, a blink of an eye in cosmic time. Some are expected to end their lives in titanic supernova blasts, which enrich the Universe with the heavier elements beyond iron.

Like many other LBVs, AG Carinae remains unstable. It has experienced lesser outbursts that have not been as powerful as the one that created the present nebula. Although AG Carinae is semi-quiescient now, its searing radiation and powerful stellar wind (streams of charged particles) have been shaping the ancient nebula, sculpting intricate structures as outflowing gas slams into the slower-moving outer nebula. The wind is travelling at up to 1 million kilometres per hour, about 10 times faster than the expanding nebula. Over time, the hot wind catches up with the cooler expelled material, ploughs into it, and pushes it farther away from the star. This "snowplough" effect has cleared a cavity around the star.

The red material is glowing hydrogen gas laced with nitrogen gas. The diffuse red material at upper left pinpoints where the wind has broken through a tenuous region of material and swept it into space. The most prominent features, highlighted in blue, are filamentary structures shaped like tadpoles and lopsided bubbles. These structures are dust clumps illuminated by the star's light. The tadpole-shaped features, most prominent at left and bottom, are denser dust clumps that have been sculpted by the stellar wind. Hubble's sharp vision reveals these delicate-looking structures in great detail.

The image was taken in visible and ultraviolet light. Hubble is ideally suited for observations in ultraviolet light because this wavelength range can only be viewed from space.

How do the billions of cells communicate in order to perform tasks? The cells exert force on their environment through movement - and in doing so, they communicate. They work as a group in order to infiltrate their environment, perform wound healing and the like. They sense the stiffness or softness of their surroundings and this helps them connect and organize their collective effort. But when the connection between cells is distrubeddisturbed, a situation just like when cancer is initiated, can appear.

Assistant Professor Amin Doostmohammadi at the Niels Bohr Institute, University of Copenhagen has investigated the mechanics of cell movement and connection in an interdisciplinary project, collaborating with biophysicists in France, Australia, and Singapore, using both computer modelling and biological experiments. The result is now published in Nature Materials.

Amin Doostmohammadi explains: "We need to understand how cells translate this "knowledge from sensing" at the individual cell level and transform it into action on the collective level. This is still kind of a black box in biology - how do cell talk to their neighbors and act as a collective?"

The force of surrounding tissue dictates cell behavior

Individual cells have a contractile mode of motion: they pull on the surface they are located on to move themselves forward. However, cells lining up cavities and surfaces in our body, like the tubes of blood vessels or the cells at the surface of organs, are able to generate extensile forces. They do the opposite, they stretch instead of contract - and they form strong connections with their neighbors. Contractile cells are able to switch to becoming extensile cells, when coming into contact with their neighbors. If, for instance, when contractile cells sense a void or an empty space, like when a wound appears, they can loosen their cell - cell connection, become more individual, and when healing the wound, they form strong connections with their neighbors again, becoming extensile, closing the gap, so to speak.

Weakening cell connection can be the hallmark of cancer initiation

The cells connect to their neighbors by adherens junctions. They connect their internal cytoskeleton to one another and become able to transmit forces through the strong contacts. "So we asked ourselves what would happen if we prohibited the cells from making this strong connection - and it turned out that extensile, strongly connected cells turned into contractile cells with weaker connections. This is significant, because the loss of this contact is the hallmark of cancer initiation. The cells losing contact start behaving more as individuals and become able to infiltrate their surroundings. This process also happens when an embryo develops, but the key difference here is that when the healthy cells have achieved their goal, like forming an organ, they go back to their original form. Cancer cells do not. They are on a one way street", Amin Doostmohammadi says.

The basic action and reaction of cells are determined by surroundings and communication

How cells "decide" when to go from one form to another is a complicated mix of reacting to their environment, changes in the chemical composition of it, the mechanical stiffness or softness of the tissue - and many proteins in the cells are involved in the process. The key finding of this study is that this reaction to surroundings is constantly shifting: There is a constant cross-talk between cell - surroundings and cell - cell, and this is what determines the actions and reactions of the cells.

Are treatments for cancer within the scope of this new understanding in cell mechanics?

"We must always be careful, when talking about a serious and very complex disease like cancer", Amin Doostmohammadi says. "But what we can say is that this study brings us one step closer to understanding the basic mechanics of cell behavior, when the cells go from the normal behavior to the aggressive, cancer type cell behavior. So, one of the big questions this study raises is if we might be able to target the mechanics of the cells by some form of therapy or treatment, instead of targeting the DNA or chemical composition of the cells themselves? Could we target the environment instead of the cells? This is basic research, connecting physics and biology, into the mechanics of cell behavior, based on their sensing and responding to the surroundings and coordinating their effort - our improved understanding of this may well lead to new therapies, and there are trials going on at the moment at a preliminary stage".

New research provides evidence that people have transmitted SARS-CoV-2, the virus that causes COVID-19, to cats during the pandemic in the UK. The study, which is published in Veterinary Record, detected the virus last year in cats that developed mild or severe respiratory disease.

Investigators used a range of laboratory techniques to show that two domestic cats from households with suspected cases of COVID-19 were infected with SARS-CoV-2.

"These findings indicate that human-to-cat transmission of SARS-CoV-2 occurred during the COVID-19 pandemic in the UK, with the infected cats displaying mild or severe respiratory disease. Given the ability of the coronavirus to infect companion animals, it will be important to monitor for human-to-cat, cat-to-cat and cat-to-human transmission," said lead author Margaret Hosie, PhD, of the MRC-University of Glasgow Centre for Virus Research.

New research led by Curtin University has revealed how radar satellites can improve the ability to detect, monitor, prepare for and withstand natural disasters in Australia including bushfires, floods and earthquakes.

The research used Synthetic Aperture Radar data obtained by the European Space Agency Sentinel-1 satellite, amongst others, to evaluate Australia-specific case studies.

Lead researcher Dr Amy Parker, an ARC Research Fellow from Curtin's School of Earth and Planetary Sciences, said the Sentinel-1 satellite mission provided the first complete global Synthetic Aperture Radar (SAR) dataset and the first opportunity to use this type of data to assess hazards in new locations, including Australia.

"What makes SAR so valuable is that it provides all-weather and night-and-day capability to remotely monitor the Earth's surface, unlike traditional optical Earth Observation (EO) imagery which is at the mercy of cloud, fog, rainfall and smoke," Dr Parker said.

"SAR data can be used to precisely map topography, track movements of the ground surface, characterize land-use change, and map damage to infrastructure, all of which can significantly improve how we track and respond to natural disasters.

"But despite SAR satellites being well-documented as a hazard monitoring tool, the uptake of such data varies, and in Australia the use of SAR data has been limited."

The research applied SAR data to nine case studies covering critical issues such as bushfires, floods and earthquakes to assess the power of SAR as a disaster mitigation and prevention tool.

"For example we looked at the 2016 Wildman Coastal Plains Floods in the Northern Territory and found that SAR has added benefits in mapping flood patterns and floodplain dynamics."

Dr Parker said these benefits can also be applied to maintaining mine site safety and better understanding seismic hazards and activity.

"Globally, Australia is one of the largest users of Earth observation data derived from satellites, which contributes to national hazard monitoring and response and more than 100 state and federal government programs. Our research shows SAR data can effectively complement this." Dr Parker said.

"Previously SAR data has been considered too expensive to use as a tool for hazard mitigation, but our findings show, through Sentinel-1 we now have economically viable wall-to-wall, consistent sensor imaging of Australia.

"The uptake of SAR data for hazard applications globally will continue to benefit from validated case studies such as ours, the development of tools that support operational use, and the continued provision of open-access imagery by large-scale satellite missions."

Researchers from Nanjing University, National Sun Yat-sen University, and Northwestern University published a new paper in the Journal of Marketing that shows that the spatial distance between products and consumers can affect perceived value and willingness to pay.

The study, forthcoming in the Journal of Marketing, is titled "Values Created from Far and Near: Influence of Spatial Distance on Brand Evaluation" and is authored by Xing-Yu (Marcos) Chu, Chun-Tuan Chang, and Angela Y. Lee.

No one ever questions why some retail products are on display in cabinets behind the sales counter, where shoppers can only view them from a distance, while other displays take center stage to greet shoppers as they walk inside the store. Consumers likely reason that the former practice is to protect high-value products from potential damage or theft and that the latter practice is to entice shoppers to purchase these items. However, there are additional hidden advantages to these practices. This research team finds that keeping a distance between consumers and products enhances the perceived value and prestige of luxury items while proximity increases the perceived sincerity and closeness of popular products.

The researchers propose that the spatial distance between the product and the consumer, whether in real life or in ads or websites, may enhance or devalue consumers' perceptions of the product depending on whether the brand image reflects status or broad appeal. Specifically, distance signals prestige when status and luxury are relevant to the brand image, in which case a far distance should help enhance the brand image. On the other hand, distance signals social closeness when popularity and broad appeal are relevant to the brand image, in which case a close distance should help to enhance that brand image.

Across seven studies, they show that the distance between the product and the consumer, whether in real life or in ads, can have a profound influence on how consumers evaluate the product and make purchase decisions. The researchers observe the relationship between spatial distance and consumer perception and price judgments in a variety of contexts that include store display, window display, print ads, and websites. In the first study, participants designing a mock ad positioned the image of a product further away from the image of the model when the ad was for a prestigious brand than for a popular brand. In the next set of studies, participants estimated the same distance between the model and an expensive handbag to be further apart than for an inexpensive handbag; but they estimated the distance between the model and a popular brand to be closer than for an unpopular brand.

In the next two studies, participants evaluated an expensive leather backpack more favorably when they were standing five feet (versus three feet) away, but an everyday-use canvas backpack more favorably when they were standing three ft (versus five feet) away. Participants in the sixth study evaluated a coffeemaker with the tagline "Aromatic coffee, distinguished taste. Luxurious life, prestigious choice" more positively when it was positioned further away from the model in an ad, but the coffeemaker with the tagline "Aromatic coffee, trendy taste. Cozy life, popular choice" more positively when it was positioned closer to the model in the ad. Finally, in the last study, consumers receiving a text sent to their mobile phone were more likely to click on the ad with a "Luxurious lifestyle, Prestigious choice" tagline and visit the website to redeem a discount coupon when the product image is further away from the model in the ad. But they were more likely to click on the ad with a "Cozy lifestyle, Popular choice" tagline when the product image is closer to the model in the ad.

These findings offer useful insights to marketers about how to leverage visual cues in window and store displays and in advertising. By strategically matching the distance between the product and the consumer, marketers can effectively enhance value and increase consumers' willingness to pay a price premium for luxury brands by enhancing perceived prestige. Alternatively, they can enhance value and increase consumers' willingness to pay a price premium for brands with broad appeal by enhancing perceived social closeness. For luxury brands or products with an exclusive brand image, a distal distance signals prestige and exclusivity. In contrast, for popular brands or products that appeal to a wide customer base, a proximal distance signals connectedness and sincerity.

Images are powerful communication tools. Today's time-starved consumers are bombarded by information. Chu explains that "Vivid images can capture attention and convey meaning without words and lengthy messages. Marketers can easily incorporate the insights from our research into their communication strategy--whether it be window displays, store layouts, website designs, billboards, print ads, etc. Far distance can enhance perceived status for brands with a prestigious brand image whereas proximal distance can enhance social connectedness for brands with a popular brand image." Marketers should also be aware of the corresponding downsides--keeping a distance can dampen the perceived connectedness of popular products, while proximity can lower the perceived prestige of luxury products.

What The Study Did: This study assesses the association between COVID-19 and maternal and neonatal outcomes in pregnant women with COVID-19 diagnosis compared with pregnant women without COVID-19 diagnosis.

Authors: Aris T.Papageorghiou, M.D., of the University of Oxford in the United Kingdom, 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/jamapediatrics.2021.1050)

Editor's Note: The article includes conflict of interest and 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.

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What The Study Did: This cohort study examines viral dynamics and transmission of infection for NBA players, staff and vendors who had clinically recovered from SARS-CoV-2 infection but continued to have positive test results following discontinuation of isolation precautions.

Authors: Christina Mack, Ph.D., M.S.P.H., of IQVIA, Real World Solutions, in Durham, North Carolina, 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/jamainternmed.2021.2114)

Editor's Note: The article includes conflict of interest 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.

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Media advisory: The full study and editor's note are linked to this news release.

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As part of the Paris Agreement, nearly all countries agreed to take steps to limit the average increase in global surface temperature to less than 2 °C, or preferably 1.5 °C, compared with preindustrial levels. Since the Agreement was adopted, however, concerns about global warming suggest that countries should aim for the "preferable" warming limit of 1.5 °C.

What are the implications for China of trying to achieve this lower limit?

Prof. DUAN Hongbo from the University of Chinese Academy of Sciences and Prof. WANG Shouyang from the Academy of Mathematics and Systems Science of the Chinese Academy of Sciences, together with their collaborators, have attempted to answer this question.

Their results were published in an article entitled "Assessing China's efforts to pursue the 1.5°C warming limit," which was published in Science on April 22.

The authors used nine different integrated assessment models (IAMs) to make their evaluation of China's effort to achieve the warming limit of 1.5 °C.

The various models show different emission trajectories for carbon and noncarbon emissions. The majority of the IAMs will achieve near-zero or negative carbon emissions by around 2050, with a range from -0.13 billion tonnes of CO2 (GtCO2) to 2.34 GtCO2 across models. However, one highly consistent finding among all models is that the 1.5°C warming limit requires carbon emissions decrease sharply after 2020.

The researchers discovered that a steep and early drop in carbon emissions reduces dependency on negative emission technologies (NETs), i.e., technologies that capture and sequester carbon. One implication of this finding is that there is a trade-off between substantial early mitigation of carbon emissions and reliance on NETs, which may have uncertain performance. At the same time, the model showing the lowest carbon emissions by 2050 shows the greatest reliance on carbon capture and storage (CCS) technology--suggesting that NETs have an important role in reducing carbon emissions.

Although carbon emissions were an important focus of the study, the researchers also noted that reducing noncarbon emissions is necessary to stay under the warming limit. Specifically, carbon emissions must be reduced by 90%, CH4 emissions by about 71% and N2O emissions by about 52% to achieve the 1.5 °C goal.

The study showed that mitigation challenges differ across sectors, e.g., industry, residential and commercial, transportation, electricity and "other." Among these sectors, industry plays a big role in end-use energy consumption. Therefore, substantial changes in industrial energy use must occur to reach deep decarbonization of the entire economy and realization of the given climate goals. Indeed, a highly consistent finding across all models is that the largest proportion of emission reduction will come from a substantial decline in energy consumption.

The study also highlights the importance of replacing fossil fuels with renewables, a strategy that plays the next most important role in emission reduction behind reducing energy consumption. The study suggests that China needs to decrease its fossil energy consumption (as measured by standard coal equivalent, or Gtce) by about 74% in 2050 in comparison with the no policy scenario.

The researchers estimate that achieving the 1.5 °C goal will involve a loss of GDP in 2050 in the range of 2.3% to 10.9%, due to decreased energy consumption and other factors.

The study also noted that China's recently announced plan to become carbon neutral by 2060 largely accords with the 1.5 °C warming limit; however, achieving the latter goal is more challenging.

LA JOLLA--(April 22, 2021) Spinal cord nerve cells branching through the body resemble trees with limbs fanning out in every direction. But this image can also be used to tell the story of how these neurons, their jobs becoming more specialized over time, arose through developmental and evolutionary history. Salk researchers have, for the first time, traced the development of spinal cord neurons using genetic signatures and revealed how different subtypes of the cells may have evolved and ultimately function to regulate our body movements.

The findings, published in the journal Science on April 23, 2021, offer researchers new ways of classifying and tagging subsets of spinal cord cells for further study, using genetic markers that differentiate branches of the cells' family tree.

"A study like this provides the first molecular handles for scientists to go in and study the function of spinal cord neurons in a much more precise way than they ever have before," says senior author of the study Samuel Pfaff, Salk Professor and the Benjamin H. Lewis Chair. "This also has implications for treating spinal cord injuries."

Spinal neurons are responsible for transmitting messages between the spinal cord and the rest of the body. Researchers studying spinal neurons have typically classified the cells into "cardinal classes," which describe where in the spinal cord each type of neuron first appears during fetal development. But, in an adult, neurons within any one cardinal class have varied functions and molecular characteristics. Studying small subsets of these cells to tease apart their diversity has been difficult. However, understanding these subset distinctions is crucial to helping researchers understand how the spinal cord neurons control movements and what goes awry in neurogenerative diseases or spinal cord injury.

"It's been known for a long time that the cardinal classes, as useful as they are, are incomplete in describing the diversity of neurons in the spinal cord," says Peter Osseward, a graduate student in the Pfaff lab and co-first author of the new paper, along with former graduate student Marito Hayashi, now a postdoctoral fellow at Harvard University.

Pfaff, Osseward and Hayashi turned to single-cell RNA sequencing technologies to analyze differences in what genes were being activated in almost 7,000 different spinal neurons from mice. They used this data to group cells into closely related clusters in the same way that scientists might group related organisms into a family tree.

The first major gene expression pattern they saw divided spinal neurons into two branches: sensory-related neurons (which carry information about the environment through the spinal cord) and motor-related neurons (which carry motor commands through the spinal cord). This suggests that, in an ancient organism, one of the first steps in spinal cord evolution may have been a division of labor of spinal neurons into motor versus sensory roles, Pfaff says.

When the team analyzed the next branches in the family tree, they found that the sensory-related neurons then split into excitatory and inhibitory neurons--a division that describes how the neuron sends information. But when the researchers looked at motor-related neurons, they found a more surprising division: the cells clumped into two distinct groups based on a new genetic marker. When the team stained cells belonging to each group in the spinal cord, it became clear that the markers differentiated neurons based on whether they had long-range or short-range connections in the body. Further experiments revealed that the genetic patterns specific to long-range and short-range properties were common across all the cardinal classes tested.

"The assumption in the field was that the genetic rules of specifying long-range versus short-range neurons would be specific to each cardinal class," say Osseward and Hayashi. "So it was really interesting to see that it actually transcended cardinal class."

The observation was more than just interesting--it turned out to be useful as well. Previously, it might have taken many different genetic tags to narrow in on one particular neuron type that a researcher wanted to study. Using this many markers is technically challenging and largely prevented researchers from studying just one subtype of spinal cord neuron at a time.

With the new rules, just two tags--a previously known marker for cardinal class and the newly discovered genetic marker for long-range or short-range properties--can be used to flag very specific populations of neurons. This is useful, for instance, in studying which groups of neurons are affected by a spinal cord injury or neurodegenerative disease and, eventually, how to regrow those particular cells.

The evolutionary origin of the spinal neuron family tree studied in the new paper is likely very ancient because the genetic markers they discovered are conserved across many species, the researchers say. So, although they didn't study spinal neurons from animals other than mice, they predict that the same genetic patterns would be seen in most living animals with spinal cords.

"This is primordial stuff, relevant for everything from amphibians to humans," says Pfaff. "And in the context of evolution, these genetic patterns tell us what kind of neurons might have been found in some of the very earliest organisms."

BOSTON -- The foods people buy at a workplace cafeteria may not always be chosen to satisfy an individual craving or taste for a particular food. When co-workers are eating together, individuals are more likely to select foods that are as healthy--or unhealthy--as the food selections on their fellow employees' trays. "We found that individuals tend to mirror the food choices of others in their social circles, which may explain one way obesity spreads through social networks," says Douglas Levy, PhD, an investigator at the Mongan Institute Health Policy Research Center at Massachusetts General Hospital (MGH) and first author of new research published in Nature Human Behaviour. Levy and his co-investigators discovered that individuals' eating patterns can be shaped even by casual acquaintances, evidence that corroborates several multi-decade observational studies showing the influence of people's social ties on weight gain, alcohol consumption and eating behavior.

Previous research on social influence upon food choice had been primarily limited to highly controlled settings like studies of college students eating a single meal together, making it difficult to generalize findings to other age groups and to real-world environments. The study by Levy and his co-authors examined the cumulative social influence of food choices among approximately 6,000 MGH employees of diverse ages and socioeconomic status as they ate at the hospital system's seven cafeterias over two years. The healthfulness of employees' food purchases was determined using the hospital cafeterias' "traffic light" labeling system designating all food and beverages as green (healthy), yellow (less healthy) or red (unhealthy).

MGH employees may use their ID cards to pay at the hospitals' cafeterias, which allowed the researchers to collect data on individuals' specific food purchases, and when and where they purchased the food. The researchers inferred the participants' social networks by examining how many minutes apart two people made food purchases, how often those two people ate at the same time over many weeks, and whether two people visited a different cafeteria at the same time. "Two people who make purchases within two minutes of each other, for example, are more likely to know each other than those who make purchases 30 minutes apart," says Levy. And to validate the social network model, the researchers surveyed more than 1,000 employees, asking them to confirm the names of the people the investigators had identified as their dining partners.

"A novel aspect of our study was to combine complementary types of data and to borrow tools from social network analysis to examine how the eating behaviors of a large group of employees were socially connected over a long period of time," says co-author Mark Pachucki, PhD, associate professor of Sociology at the University of Massachusetts, Amherst.

Based on cross-sectional and longitudinal assessments of three million encounters between pairs of employees making cafeteria purchases together, the researchers found that food purchases by people who were connected to each other were consistently more alike than they were different. "The effect size was a bit stronger for healthy foods than for unhealthy foods," says Levy.

A key component of the research was to determine whether social networks truly influence eating behavior, or whether people with similar lifestyles and food preferences are more likely to become friends and eat together, a phenomenon known as homophily. "We controlled for characteristics that people had in common and analyzed the data from numerous perspectives, consistently finding results that supported social influence rather than homophily explanations," says Levy.

Why do people who are socially connected choose similar foods? Peer pressure is one explanation. "People may change their behavior to cement the relationship with someone in their social circle," says Levy. Co-workers may also implicitly or explicitly give each other license to choose unhealthy foods or exert pressure to make a healthier choice.

The study's findings have several broader implications for public health interventions to prevent obesity. One option may be to target pairs of people making food choices and offer two-for-one sales on salads and other healthful foods but no discounts on cheeseburgers. Another approach might be to have an influential person in a particular social circle model more healthful food choices, which will affect others in the network. The research also demonstrates to policymakers that an intervention that improves healthy eating in a particular group will also be of value to individuals socially connected to that group.

"As we emerge from the pandemic and transition back to in-person work, we have an opportunity to eat together in a more healthful way than we did before," says Pachucki. "If your eating habits shape how your co-workers eat--even just a little--then changing your food choices for the better might benefit your co-workers as well."

PHILADELPHIA--When researchers from Penn Medicine found that many patients with B-cell acute lymphoblastic leukemia (ALL) treated with the investigational chimeric antigen receptor (CAR) T cell therapy targeting the CD22 antigen didn't respond, they went back to the drawing board to determine why. They discovered that less is more when it comes to the length of what is known as the single-chain variable fragment -- the linker that bridges the two halves of the receptor that allows CAR T cells to latch onto tumor cells and attack them.

The findings are reported online today in Nature Medicine.

"A little difference of a few amino acids can make a huge difference for patients," said co-senior author Marco Ruella, MD, an assistant professor of Medicine in the division of Hematology-Oncology in the Perelman School of Medicine at the University of Pennsylvania and scientific director of the Lymphoma Program. "When we snipped 15 amino acids off the linker, the two halves of the CAR plastered together and pre-activated the CAR T cells."

Developed at Penn Medicine in collaboration with Novartis, the anti-CD19-CAR T cell (Kymriah™) is currently approved by the U.S. Food and Drug Administration for the treatment of pediatric and young adults with relapsed/refractory ALL; however, long-term follow up shows a significant fraction of patients who achieve remission ultimately relapse, often when the leukemia cells lose expression of the CD19 antigen and elude the new immune system. Researchers at Penn and elsewhere have developed a second approach for this group of patients: CAR T cells that target the CD22 antigen, also found on B cells.

Two clinical pilot studies conducted at Penn and Children's Hospital of Philadelphia with CAR-22 T cell therapy in six children and three adult patients with refractory/relapsed ALL showed overall poor clinical responses. Strikingly, those findings didn't align with the positive results from a similar trial at the National Cancer Institute (NCI). So, the team investigated further and found the only difference between the two treatments was the length of the single-chain variable fragment. The NCI CAR was five amino acids in length, while the Penn/CHOP trial CAR was 20 amino acids in length.

The Penn team in collaboration with Novartis then built a new 41BB-based CAR-22 T cell with a shorter linker and compared it to the previous CAR in both mouse and human cell studies. 41BB is a different co-stimulatory signal, along with CD28, needed for CAR T cell activation and survival. They showed that the shorter linker on the CAR construct was, in fact, more successful at pre-activating CAR T cells so that their response to B cells and subsequent anti-tumor activity improved. Researchers have generally assumed that when T cells are pre-activated prior to seeing their target they become easily exhausted.

"This finding really turns the current dogma on its head," said Saar I. Gill, MD, PhD, an assistant professor of Hematology-Oncology at Penn, who serves as co-senior author. "These days, most CARs come with one of two built-in turbo-charge systems: CD28 or 41BB. It turns out that the assumption was true only for CD28-stimulated CARs but not for the more commonly used 41BB-stimulated CARs. In fact, here we showed that the opposite is true."

Nathan Singh, MD, who conducted the study while at Penn and is now an assistant professor of Medicine in the Division of Oncology at Washington University School of Medicine in St. Louis, is the first author.

"These findings were rather unexpected, given what's been shown previously in the field," Singh said. "They highlight that even small molecular changes can have dramatic impact on the function of these synthetic molecules. Most exciting is that these data reveal a previously hidden path to improve CAR T cell function in a methodical manner."

The results from these studies have led to a new, ongoing clinical trial at Penn and CHOP in collaboration with Novartis for adult and pediatric patients with refractory/relapsed ALL investigating the shorter linker CAR. Additional studies are underway to determine if the length of linkers is important in other CAR T cells.

"Every CAR construct is different," Gill said. "But these findings suggest we need to modify the length of the linker when we test a new CAR to make sure we are generating the best version of it."

The citric acid cycle is an important metabolic pathway that enables living organisms to generate energy by degrading organic compounds into carbon dioxide (CO?). The first step in the cycle is usually performed by the enzyme citrate synthase, which builds citrate. But, in the absence of oxygen (under anaerobic conditions), some bacteria can perform the reverse cycle: They can build up biomass from CO?. In this so-called reversed citric acid cycle, citrate synthase is replaced by ATP-citrate lyase, which consumes cells' universal energy carrier ATP (adenosine triphosphate) to cleave citrate instead of forming it. However, a few years ago, a research team led by Ivan Berg (University of Münster) and Wolfgang Eisenreich (Technical University of Munich) discovered that instead of requiring ATP-citrate lyase for the reversed cycle, some anaerobic bacteria can use citrate synthase itself to catalyze citrate cleavage without consuming ATP. Now, the same team found that bacteria using this metabolic pathway (the reversed citric acid cycle through citrate synthase), depend on very high concentrations of both the enzyme and carbon dioxide.

As a comparison, the CO? concentration in air is around 0.04%, but bacteria using this pathway require at least 100 times more than that for their growth. The researchers assume that such CO? concentration-dependent pathways could have been widespread on the primordial earth, since the CO? concentration was high at the time. Therefore, this metabolic pathway may be a relic of early life. The results of the study have been published in the journal Nature (online in advance).

The team studied the anaerobic bacteria Hippea maritima and Desulfurella acetivorans. These organisms live without oxygen in hot springs, where the CO? concentration can be 90% and higher. "It is conceivable that many other organisms use this cycle to bind CO?," says Ivan Berg. "Our findings are in line with the results of several recent studies highlighting a potential widespread occurrence of this reversed oxidative citric acid cycle." Nevertheless, many bacteria use the energetically less efficient ATP-dependent reaction for citrate cleavage. "It was mysterious why this 'expensive' version of the pathway exists if an energetically much cheaper alternative through the backwards reaction of citrate synthase is feasible. Now we know that this is due to the low CO? concentrations in many environments. The cheap alternative doesn't work there." emphasizes Wolfgang Eisenreich.

These findings could also be of interest for biotechnology. With the knowledge that autotrophic organisms using this "backward cycle" depend on the CO? concentration, scientists can apply it to more efficiently convert substrates into value-added products.

The results in detail

The scientists wanted to understand what factor determines whether the citric acid cycle runs "forwards" or "backwards" in the bacteria. Cultivating the bacteria under different conditions, they noticed that the growth of these organisms was highly dependent on the CO? concentration in the gas phase. In detail, the high CO? concentration was needed to allow the function of another important enzyme, pyruvate synthase. This enzyme is responsible for assembling acetyl coenzyme A (acetyl-CoA), the product of the "reversed cycle". The high CO? concentration drives the pyruvate synthase reaction in the direction of carboxylation and the entire cycle backwards, enabling CO? to be converted into biomass. The studied Hippea maritima and Desulfurella acetivorans were able to grow very well at 20% and 40% CO? in the gas phase but only moderately at 5% CO?, and no growth was possible at 2% or 1% CO?. As a control, the scientists studied another autotrophic bacterium Desulfobacter hydrogenophilus, which uses the energetically more expensive ATP-citrate lyase version of the reversed citric acid cycle. In this bacterium, growth was not affected by the CO? concentration.

The "backward cycle" that uses citrate synthase for citrate cleavage cannot be bioinformatically predicted, as it does not have the key enzymes whose presence can be used as a marker for the functioning of the pathway. Therefore, as an identifying feature for bioinformatic analyzes, the scientists used the detected high levels of citrate synthase in these bacteria's protein cocktail. Using a special analysis tool, the researchers were able to predict the production levels of individual proteins. With this trick, it was possible to predict the functioning of the "backward cycle" for inorganic carbon fixation in many anaerobic bacteria.

The scientists also showed that no gene regulation was necessary for switching from the oxidative ("forward") to the reductive ("reverse") direction. "This means that the cells can react very quickly on the availability of the carbon source in the environment" says Ivan Berg. "They use either the reductive direction to fix CO?, if the concentration of CO? is high, or the oxidative direction, if another carbon source is available."

Methodological notes

The methods used in the study were mass spectrometry and 13C-isotope analyses, enzyme measurements, protein quantification as well as media and amino acid analyses using chromatographic and spectrometric methods (LC/MS or GC/MS). With bioinformatic methods, they examined the occurrence of certain nucleotide base combinations (codons) in order to make predictions about the production of individual proteins.

A new study from the University of Surrey has found that among people aged 55 to 75 more frequent use of the internet was beneficial for mental health and quality of life under lockdown. Those who used the internet more, particularly for staying in touch with friends and family, were at lower risk of depression and reported a higher quality of life.

Loneliness and social isolation have been major problems for many under lockdown, and for older people in particular. Loneliness raises risk of depression and other negative health outcomes. In a paper published in the journal Healthcare, researchers from Surrey investigated whether more frequent internet use in older people helped reduce this risk.

Researchers studied 3,491 individual participants drawn from the English Longitudinal Study of Ageing in Summer 2020, whilst social distancing measures were in place across the country. Participants were surveyed on the frequency and type of their internet usage - such as information searching or for communication purposes.

Those who reported using the internet frequently (once a day or more) had much lower levels of depression symptoms and reported higher quality of life compared to those who used the internet only once a week or less. Using the internet for communication was particularly linked to these beneficial effects, suggesting that going online to stay connected with friends and family helped combat the negative psychological effects of social distancing and lockdown in adults aged 55-75.

Conversely, the study found that people who mostly used the internet to search for health-related information reported higher levels of depression symptoms. This might be due to a greater degree of worry triggered by reading Covid-19 and other health-related internet sources.

Dr Simon Evans, Lecturer in Neuroscience at the University of Surrey, said: "As social restrictions continue during the Covid-19 pandemic, older people are at greater risk of loneliness and mental health issues. We found that older adults who used the internet more frequently under lockdown, particularly to communicate with others, had lower depression scores and an enhanced quality of life. As the Covid-19 situation evolves, more frequent internet use could benefit the mental health of older people by reducing loneliness and risk of depression, particularly if further lockdowns are imposed in the future."

Skeletal muscles enable voluntary movements and are controlled by a special type of neurons called motor neurons, which make direct contact with skeletal muscles through so-called neuromuscular junctions (NMJs). It is through NMJs that skeletal muscles receive signals making them contract or relax. In certain neurodegenerative diseases, such as amyotrophic lateral sclerosis (ALS), NMJs are destroyed, leading to progressive muscle weakness and ultimately death. Treatments for ALS mainly focus on alleviating symptoms but cannot stop or reverse its disease progression. To find more effective treatments, researchers require accurate and easily accessible lab-based models for ALS to understand its causes and to develop and test new therapies. One step in this direction was made by Ludo Van Den Bosch (ludo.vandenbosch@kuleuven.be) and colleagues in Belgium, who generated NMJs outside the human body in a so-called microfluidic device. In this sophisticated model, human motor neurons, which were derived from ALS patients, via induced pluripotent stem cells engineered from their own skin cells, and human skeletal muscle cells from healthy donors grew in separate mini-chambers on opposite sides of the device, whereby tiny channels connected the two chambers. Excitingly, with time, the neurons started to send connections, called axons, through the channels to form NMJs, which were able to transmit signals from the neurons to the muscle cells, similar to NMJs in the human body. However, when comparing motor neurons from ALS patients with healthy motor neurons in this setup, it was clear that ALS motor neurons sent less axons across the channels and formed less NMJs with the muscle cells. In addition, ALS motor neurons regenerated damaged axons less efficiently. Encouragingly, ALS motor neurons could be pushed to grow more axons, reaching levels similar to healthy motor neurons, by adding the chemical Tubastatin A to the cultures. Further studies will show how Tubastatin A, which inhibits a certain class of proteins in the cell, promotes axon growth in ALS motor neurons, and if similar effects can be achieved in animal models and ultimately in ALS patients. This new miniaturized model of NMJ formation, recently published in Stem Cell Reports, will find broad application in studying motor neuron pathology and the discovery of potential therapeutics in ALS.