Culture

CHAMPAIGN, Ill. -- If you want something done, ask a busy person - or so the saying goes. According to a new paper co-written by a University of Illinois scholar who studies attitudes and persuasion psychology, if you want to sell something quickly, it helps to try a busy consumer.

People on a tight deadline have stronger intentions to enact behaviors - whether it's redeeming a coupon or following through on receiving a flu shot - immediately after moving than after sitting, says research co-written by Dolores Albarracin, a professor of psychology and marketing at Illinois and the director of the Social Action Lab.

Movement - whether it's walking or running - is associated with action-oriented concepts and goals, whereas stasis - standing or sitting, for example - is associated with inaction-oriented concepts and goals.

Across one field experiment and three lab experiments, Albarracin and co-author Duo Jiang, a graduate student at Illinois, found that prior movement was associated with a higher probability of enacting behaviors while under a tight deadline.

Consider two people - one walking, the other sitting - who each face the decision of whether to go to a pharmacy for a flu shot.

"What we found is that walking involves activating action representations that in turn promote other actions outside of the context of walking," Albarracin said. "Likewise, sitting involves activating inaction representations that may promote inaction outside of the context of sitting. These general goals of action and inaction are likely to be broad enough to guide decisions about the flu shot: The person who's in motion will get the flu shot, and the person who's inactive won't."

The reason for this is that when you're in a hurry and you're under a close deadline, "both being in a hurry and having the deadline push in the same direction of completing the transaction as quickly as possible," Albarracin said.

"You're thinking, 'I can make this deadline,' and you can make it when you have thoughts about being active and energetic. Likewise, sitting involves rest and relaxation, which promotes more general inactivity and transfers to any behavior relevant in the moment."

The concepts and goals, whether they're action- or inaction-focused, can transfer to any task at hand, Albarracin said.

"If the task is a purchase, people are more willing to complete the purchase," she said. "But the goals elicited by movement affect decisions that need to be made immediately. So someone walking around a park is more likely to complete a deadline-driven purchase than someone sitting on a park bench contemplating life. But walking or sitting would not affect decisions about future purchases."

The research has implications for marketing and advertising, said Albarracin, also a professor of business administration with the Gies College of Business.
"If there's a deadline to buy a product or service and there's someone who's more action-oriented versus someone who's more static, you want to give the action people a tight deadline, because they'll respond really quickly, whereas the more sedentary people will just say, 'Eh, whatever,'" she said.

These findings also might extend to the types of products you're trying to sell, Albarracin said.

"If you're trying to sell a product with a very short shelf life, like food or coffee, you can use movement to your advantage," she said. "You give people a really tight window to purchase the product, and the more action-oriented people - who also are perhaps users of mobile technology - are going to snap it up. If you're selling something like athletic wear, for example, a close deadline would work better. But if you have a product that has a longer shelf life, like a car or a computer, whether your audience moves or uses mobile technology for consumer decisions may not matter."

Tel Aviv University and Sheba Medical Center researchers say they have discovered why more than half of patients with metastatic melanoma do not respond to immunotherapy cancer treatments.

Wielding proteomics, an innovative "protein mapping" approach, a team of researchers led by Prof. Tami Geiger, Prof. Gal Markel, and Dr. Michal Harel of TAU's Sackler School of Medicine and Sheba's Ella Lemelbaum Institute for Immuno-Oncology have answered the burning question: Why do immunotherapy treatments greatly help some patients with melanoma but not affect 60 percent of metastatic melanoma patients?

The researchers, whose findings were published on September 5 in Cell, compared the responses of 116 melanoma patients to immunotherapy -- one group in which immunotherapy was successful and a second in which immunotherapy was not successful. Harnessing proteomics, a powerful protein mapping technology, they discovered differences in the metabolism, or energy production process, of the cancer cells of the two groups.

"In recent years, a variety of cancer immunotherapy therapies have been used, therapies that strengthen the anti-cancer activity of the immune system," explains Prof. Markel, a senior oncologist and scientific director of the Ella Lemelbaum Institute. "These treatments have been shown to be highly effective for some patients and have revolutionized oncology. However, many patients do not respond to immunotherapy, and it is critical to understand why.

"Can we predict who will respond? Can we alter treatment in order to increase responses? In our research, we focused on metastatic melanoma, a devastating disease that until recently had no efficient treatments. It was clear to us that pre-treatment samples from responders and non-responders would be key."

To better understand treatment resistance mechanisms, the scientists examined tumors taken from 116 patients using proteomics.

"In the proteomic lab, we use an instrument called a mass-spectrometer, which enables global mapping of thousands of proteins," explains Prof. Geiger, head of TAU's Proteomics Lab. "We then followed up with extensive computational analysis to identify the proteins that differentiated between the response groups."

The proteomic comparison identified major differences between responders and non-responders to immunotherapy. "In the responders, we found higher levels of proteins associated with lipid metabolism, which led to better recognition by the immune system," says Prof. Geiger.

In collaboration with the Salk Institute in San Diego and Yale School of Medicine, researchers then examined their findings in melanoma tissue cultures and a mouse model of metastatic melanoma.

Using genetic engineering, they were able to silence the mechanism responsible for fatty acid metabolism.

"We found that upon silencing this metabolic pathway, the cancer cells manage to 'hide' from T-cells that are supposed to detect and destroy them," says Prof. Geiger. "As a result, cancer in these mice developed at a faster rate compared to the control group.

"In our study, we identified a significant difference between melanoma patients who live for years thanks to immunotherapy, and patients who are not at all affected by the treatment."

"These findings can also be relevant to many other malignancies," adds Prof. Markel. "Now, in subsequent studies, we are looking for ways to improve the response to immunotherapy and expand the circle of patients who benefit from it. In addition, we are looking for a method that will allow clinicians to anticipate which patients will respond to treatments."

Scientists from the School of Medicine, Trinity College Dublin, have, for the first time, discovered a family of proteins that are associated with lower blood sugar levels among obese patients with type 2 diabetes.

Their research is published today (Monday, September 9th, 2019) in the international journal Nature Communications here: https://rdcu.be/bQlWW. The study showed that patients with type 2 diabetes who have high levels of the protein, IL-36 cytokines, were found to have lower blood sugar levels, implying that those proteins are associated with better control of the patient's blood sugar levels and their disease.

IL-36 cytokines are members of a larger family of proteins known as the interleukin-1 family which have emerged as central players in the development of obesity related disease.

Researchers have linked the protective effects of these proteins with their ability to alter the make-up of the intestinal microbiome.

Obesity causes an increased level of fatty acids and inflammation leading to insulin resistance. When the body is resistant to the insulin it produces it causes a high build-up of glucose or blood sugar, ultimately leading to type 2 diabetes.

Obesity is now recognised as a global pandemic and has been definitively linked to a wide range of diseases including metabolic disorders such as diabetes, stroke and many types of cancer. The World Health Organisation state that global levels of obesity have more than doubled since 1980. In Ireland, according to the Healthy Ireland survey, 854,165 adults over 40 in the Republic of Ireland are at increased risk of developing (or have) type 2 diabetes. The economic burden of diabetes on the Irish health care system is becoming a major challenge for the government.

Given the scale and global reach of the problem, current approaches aimed at reversing the tide of obesity driven disease are insufficient. The Trinity research team believe that there is an urgent need to achieve a greater understanding of the mechanisms associated with obesity related diseases.

Lead scientist Dr Patrick Walsh from the School of Medicine, Trinity, said: "This study has added to a substantial body of work which has revealed the important function of the broader interleukin-1 family as mediators of metabolic health and disease. Our findings have opened the door to a deeper investigation of how IL-36 cytokines impact on the development of such diseases in humans and whether this can be exploited for the better treatment of patients."

The periodic table of elements was proposed in 1869, and thereafter became one of the cornerstones of the natural sciences. This table was designed to contain all the elements (atoms) found in nature in a special layout that groups them in rows and columns according to one of their most important characteristics, the number of electrons. Scientists have used the periodic table for decades to predict the characteristics of the then-unknown elements, which were added to the table over time.

Could there be such a periodic table for molecules? Although some researchers have thought about this possibility and proposed periodic rules for predicting the existence of certain molecules, these predictions were valid only for clusters of atoms with a quasi-spherical symmetry, because of the limitations of their own theory. However, there are many clusters of atoms with other shapes and other types of symmetries that should be accounted for with a better model. Thus, a research team from Tokyo Tech, including Dr. Takamasa Tsukamoto, Dr. Naoki Haruta, Prof. Kimihisa Yamamoto and colleagues, proposed a new approach to build a periodic table for molecules with multiple types of symmetries.

Their approach is based on a keen observation on the behavior of the valence electrons of atoms that form molecular clusters. The valence electrons can be regarded as "free" electrons in atoms with an outermost orbital, and thus they can interact with the electrons of other atoms to form compounds. When multiple atoms form a cluster with a symmetrical shape, their valence electrons tend to occupy specific molecular orbitals called as "super-atomic orbitals", in which they behave almost exactly as if they were the electrons of a huge atom.

By considering this fact and analyzing the effects of the structural symmetries for clusters (Fig. 1), the researchers proposed "symmetry-adapted orbital (SAO) models," which are in agreement with multiple known molecules as well as state-of-the-art quantum-mechanical calculations. The new periodic tables, which would be created for each symmetry type, would actually be four-dimensional, as shown in Fig. 2, because the molecules would be arranged according to four parameters: groups and periods (based on their "valence" electrons, similar to the normal periodic table), species (based on the constituting elements), and families (based on the number of atoms).

The SAO approach is very promising in the field of materials design. "Modern synthesis techniques enable us to produce many innovative materials based on the SAO model, such as lightweight magnetic materials," states Prof. Yamamoto. The road ahead for scientists lies in further expanding these tables to molecular clusters with other shapes and symmetries and predicting stable molecules that have yet to be developed. "Among the infinite combinations of constitutive elements, the proposed periodic table will be a significant contribution to the discovery of novel functional materials," concludes Prof. Yamamoto.

Washington, D.C. (September 9, 2019) - Food insecurity -- uncertainty about or a lack of consistent access to food that meets the needs of household members -- is a persistent social problem in the United States that affected roughly 14.3 million households in 2018 and nearly 14% of households with children, according to the U.S. Department of Agriculture. A new paper by researchers at the Boston University School of Social Work (BUSSW) and American University's School of Public Affairs (AU SPA) confirms the negative impact of food insecurity on child health, suggesting the urgent need for policies to combat this problem.

"Previous studies have pointed to a negative impact of food insecurity on child health, but our paper uses rich, nationally representative data to rule out other explanations for this relationship," says study lead author Margaret M.C. Thomas, MSW, doctoral candidate at BUSSW. "By comparing the outcomes of children in food-secure homes to those in food-insecure homes who were alike with respect to a large number of other factors, we have been able to more definitively characterize the serious negative health impacts of food insecurity."

Published in the journal Pediatrics, the research by Thomas and colleagues Associate Professor Daniel P. Miller, PhD (Boston University), and Associate Professor Taryn W. Morrissey, PhD (American University), points to a unique and negative effect of household food insecurity on children's health that is not due to the composition of their homes, the safety of their neighborhoods, or their household's income or receipt of public assistance. Instead, it shows the pervasive negative impacts of household food insecurity on children's health. "Household food insecurity was related to significantly worse general health, some acute and chronic health problems, worse health care access, and heightened emergency department use for children," says Morrissey.

The team of researchers used propensity scoring (PS) methods to investigate the effects of food insecurity on children's health by leveraging the inclusion of a measure of household food insecurity in the nationally representative National Health Interview Survey (NHIS). The NHIS data also include a rich set of background information about families including demographic characteristics, economic information, public program participation, and adult physical and mental health outcomes.

Thomas and her colleagues believe that their analytic approach is an important improvement over previous studies that use traditional regression methods. Using PS methods allowed them to better assess the causal impact of food insecurity on key domains of child health and health care use.

"Propensity scoring, a quasi-experimental family of methods, seeks to mimic the context of an experimental design by comparing outcomes among children who differ with respect to the household's food insecurity but who are alike in all other observable ways," Thomas says. "Because of the highly detailed information in the NHIS data, we were able to create a sample that is balanced with respect to known predictors of food insecurity."

Data on the independent impact of food insecurity on child health helps guide efforts to prevent food insecurity and ameliorate its consequences. The researchers suggest immediate policy responses, such as an increase in federal SNAP (Supplemental Nutrition Assistance Program) benefits for families.

"There are clear and consistent harmful impacts of food insecurity on children's general health, chronic health, acute health, and access to health care," Thomas says. "Without intervention, household food insecurity will continue to detrimentally impact children's health."

EVANSTON, Ill. -- The final chapter of the historic detection of the powerful merger of two neutron stars in 2017 officially has been written. After the extremely bright burst finally faded to black, an international team led by Northwestern University painstakingly constructed its afterglow -- the last bit of the famed event's life cycle.

Not only is the resulting image the deepest picture of the neutron star collision's afterglow to date, it also reveals secrets about the origins of the merger, the jet it created and the nature of shorter gamma ray bursts.

"This is the deepest exposure we have ever taken of this event in visible light," said Northwestern's Wen-fai Fong, who led the research. "The deeper the image, the more information we can obtain."

The study will be published this month in The Astrophysical Journal Letters. Fong is an assistant professor of physics and astronomy in Northwestern's Weinberg College of Arts and Sciences and a member of CIERA (Center for Interdisciplinary Exploration and Research in Astrophysics), an endowed research center at Northwestern focused on advancing studies with an emphasis on interdisciplinary connections.

Many scientists consider the 2017 neutron-star merger, dubbed GW170817, as LIGO's (Laser Interferometer Gravitational-Wave Observatory) most important discovery to date. It was the first time that astrophysicists captured two neutron stars colliding. Detected in both gravitational waves and electromagnetic light, it also was the first-ever multi-messenger observation between these two forms of radiation.

The light from GW170817 was detected, partly, because it was nearby, making it very bright and relatively easy to find. When the neutron stars collided, they emitted a kilonova -- light 1,000 times brighter than a classical nova, resulting from the formation of heavy elements after the merger. But it was exactly this brightness that made its afterglow -- formed from a jet travelling near light-speed, pummeling the surrounding environment -- so difficult to measure.

"For us to see the afterglow, the kilonova had to move out of the way," Fong said. "Surely enough, about 100 days after the merger, the kilonova had faded into oblivion, and the afterglow took over. The afterglow was so faint, however, leaving it to the most sensitive telescopes to capture it."

Hubble to the rescue

Starting in December 2017, NASA's Hubble Space Telescope detected the visible light afterglow from the merger and revisited the merger's location 10 more times over the course of a year and a half.

At the end of March 2019, Fong's team used the Hubble to obtain the final image and the deepest observation to date. Over the course of seven-and-a-half hours, the telescope recorded an image of the sky from where the neutron-star collision occurred. The resulting image showed -- 584 days after the neutron-star merger -- that the visible light emanating from the merger was finally gone.

Next, Fong's team needed to remove the brightness of the surrounding galaxy, in order to isolate the event's extremely faint afterglow.

"To accurately measure the light from the afterglow, you have to take all the other light away," said Peter Blanchard, a postdoctoral fellow in CIERA and the study's second author. "The biggest culprit is light contamination from the galaxy, which is extremely complicated in structure."

Fong, Blanchard and their collaborators approached the challenge by using all 10 images, in which the kilonova was gone and the afterglow remained as well as the final, deep Hubble image without traces of the collision. The team overlaid their deep Hubble image on each of the 10 afterglow images. Then, using an algorithm, they meticulously subtracted -- pixel by pixel -- all light from the Hubble image from the earlier afterglow images.

The result: a final time-series of images, showing the faint afterglow without light contamination from the background galaxy. Completely aligned with model predictions, it is the most accurate imaging time-series of GW170817's visible-light afterglow produced to date.

"The brightness evolution perfectly matches our theoretical models of jets," Fong said. "It also agrees perfectly with what the radio and X-rays are telling us."

Illuminating information

With the Hubble's deep space image, Fong and her collaborators gleaned new insights about GW170817's home galaxy. Perhaps most striking, they noticed that the area around the merger was not densely populated with star clusters.

"Previous studies have suggested that neutron star pairs can form and merge within the dense environment of a globular cluster," Fong said. "Our observations show that's definitely not the case for this neutron star merger."

According to the new image, Fong also believes that distant, cosmic explosions known as short gamma ray bursts are actually neutron star mergers -- just viewed from a different angle. Both produce relativistic jets, which are like a fire hose of material that travels near the speed of light. Astrophysicists typically see jets from gamma ray bursts when they are aimed directly, like staring directly into the fire hose. But GW170817 was viewed from a 30-degree angle, which had never before been done in the optical wavelength.

"GW170817 is the first time we have been able to see the jet 'off-axis,'" Fong said. "The new time-series indicates that the main difference between GW170817 and distant short gamma-ray bursts is the viewing angle."

Filial piety - the traditional value of caring for one's elders - is central to the Chinese concept of family and has long shaped intergenerational relationships, daily life, and well-being, for older Chinese adults. The intersection of Eastern values and Western norms, however, can alter cultural beliefs across generations and negatively impact aging Chinese immigrants' physical and mental health and the caregiving burdens faced by their children, according to two new Rutgers studies.

The studies, published in the Journal of the American Geriatrics Society, examine how adapting to Western culture affects Chinese-American immigrant families' filial values and the effect on intergenerational relationships.

The first study explored the role of intergenerational support on the health and well-being of a cohort of roughly 2,700 Chinese immigrants, aged 60 and older, with offspring. The data, taken from the Population Study of Chinese Elderly in Chicago, or PINE, the most extensive epidemiological cohort study of Chinese American older adults, indicated positive associations between participants' feeling of closeness with their children and self-reported health status and quality of life.

"For the aging Chinese, the intergenerational connection is inherently the key for many to age well," said Daniel Lai, the study's lead researcher and Chair Professor of Social Work and Gerontology in The Hong Kong Polytechnic University. "Promoting the use of interventions that involve an intergenerational component is the right direction for building health capacity of the aging Chinese Americans."

The second study measured the sense of filial obligation relative to caregiving burdens among 393 PINE Study participants' adult children, who were their parents' primary caregiver. The research, drawn from the Filial Piety Study - a study of the PINE Study participants' adult children - found children's sense of filial obligation towards their parents had a protective effect on their developmental, emotional, social, and physical caregiving burdens.

"It all comes down to expectations," said XinQi Dong, director of Rutgers University's Institute for Health, Health Care Policy and Aging Research and the lead researcher of the PINE and PIETY studies. "Although parent-child relationships remain important, older Chinese immigrants often adjust their filial expectations and learn to value independence after migrating. These two factors - closeness with children and the sense of control associated with increased independence - positively impact aging Chinese Americans' self-rated health and well-being.

"Conversely," Dong continued, "the adjustment to Western culture among the children of older Chinese immigrants' can affect their sense of filial obligations and, subsequently, their caregiving burdens."

Whether the effect is positive or negative depends on participants' acculturation levels and type of burden, according to May Guo, an associate professor at the University of Iowa, School of Social Work.

"For immigrant children with lower levels of acculturation, the protective effect of filial piety on their subjective burdens such as developmental and social burden is more salient," she said.

"However, among immigrant children with higher levels of acculturation, holding a strong sense of filial piety was actually associated with more objective burdens relating to time and physical burden "

Dong said both studies offer valuable practical and theoretical insight for healthcare professionals, psychosocial program administrators, and community leaders.

"To adequately and effectively treat older Chinese immigrants, healthcare professionals must be sensitive to the significance of emotional ties in this population," he said. "Providers should work to promote feelings of cohesion and intergenerational closeness among families while considering the importance of maintaining the feeling of control for aging Chinese Americans.

"Healthcare professionals should also be aware of the protective effect a sense of filial obligation has on the Chinese immigrant caregiving experience," Dong said. "Programs focused on celebrating the cultural heritage of immigrants and promoting the sense of filial obligation toward parental care can help improve the health of not only older Chinese Americans but also the well-being of their caregivers. Additional interventions could include helping caregivers find appropriate ways to balance traditional and new social norms."

WORCESTER -- Research from the lab of Mark Alkema, PhD, professor of neurobiology, sheds light on how the "flight-or-flight" response impairs long-term organism health. The study, conducted in the nematode worm, C. elegans, a common research model, was published in Nature.

When humans perceive a dangerous or stressful situation, the body releases stress hormones such as adrenalin. Adrenaline makes the heart beat faster, increases blood flow to the brain and muscles, and stimulates the body to make sugar to use for fuel. The rush of adrenaline triggers the "fight-or-flight" response which gives the person the ability to escape a predator or respond to a threat.

Dr. Alkema, working with the laboratory of Professor Diego Rayes at the National University of South in Argentina, studied the impact of the repeated activation of the "fight-or-flight" response on health in the nematode C. elegans. This small worm is a popular model organism that has helped resolve many fundamental questions in biology, ranging from development to brain function and disease.

Animals are exposed to different forms of stress. These can be abrupt, such as the appearance of a predator, or more progressive, like chronic food shortage, high temperatures, or oxidation.

"Much like in humans, repeated activation of the flight response in C. elegans drastically shortened lifespan," said Jeremy Florman, PhD candidate in the Alkema lab. "The flight response is crucial for the worm to escape from predators. But we find there is a cost; the repeated activation of the flight response reduces the worm's capacity to deal with other challenges it encounters in its environment."

In the study, investigators found that the flight response in C. elegans triggers the activation of a single pair of neurons that release tyramine, the invertebrate analog of adrenaline. In contrast, exposure to environmental challenges such as heat and oxidative stress reduces tyramine release. This stress hormone thus provides a switch that regulates the animal's response to either acute or long-term stressors.

Alkema and Rayes went on to show that tyramine stimulates the insulin pathway through the activation of an adrenergic-like receptor in the intestine. The activation of the insulin pathway can satisfy the animal's energy demands of the flight response. On the other hand, the down-regulation of the insulin pathway is needed help to protect cells from environmental stress and extend lifespan.

"This shows how a dynamic regulation of a stress neurohormone regulates the trade-off between acute and long-term stress responses," said Alkema. "The worm never ceases to amaze me; it keeps revealing fundamental molecular and neural mechanisms that may underlie even extremely complex human biology and disorders. Given the striking conservation of stress response mechanisms from worms to humans, it will be very interesting to see whether in humans the fight-or-flight response and stress neurohormones negatively impact health and aging through the activation of the insulin pathway."

Osaka, Japan - Tourette syndrome is a neurological disorder characterized by vocal and motor tics, which can contribute to anxiety, depression, and low self-esteem. Researchers in Japan have developed a removable dental appliance that can reduce these tics in both children and adults with Tourette syndrome. The ability to ameliorate tics could positively impact the everyday lives of individuals with Tourette syndrome.

While there is no cure for Tourette syndrome, there are several available options to treat severe tics. These include behavioral (e.g. psychotherapy and cognitive behavioral therapy), pharmacological (e.g. medications that block dopamine in the brain), and more intrusive surgical interventions (e.g. deep brain stimulation, whereby motor areas of the brain receive electrical stimulation). However, the efficacy of these treatments can vary, and patients still frequently suffer from physical, mental, and social disabilities. As an alternative treatment option, researchers at Osaka University have developed a custom-made oral splint. These are typically used for unconscious teeth clenching and grinding, and for temporomandibular disorders such as misalignment of the teeth or jaw. The oral splint is applied to the molars to increase the occlusal vertical dimension, which essentially means that the alignment of the nose, lips, and chin is altered. The study was recently published in Movement Disorders.

"Biting down on the device immediately improved both motor and vocal tics in 10 of the 14 children and 6 of the 8 adults that participated in the study," says Jumpei Murakami, joint first author of the study. "What's more, these effects were long lasting. Long-term improvements in motor tics after more than 100 days were especially evident in patients who were younger when their tics first started."

While it isn't yet clear how the oral splint exerts these effects, the action of biting down could serve as a sensory trick. Sensory tricks are voluntary maneuvers that usually involve touching parts of the face and head, and can alleviate involuntary movements. Sensory tricks have been well documented to temporarily improve dystonia, which is a movement disorder that is, like Tourette syndrome, characterized by uncontrollable tics.

"Considering previous findings on sensory tricks in patients with cervical dystonia, it seems possible that the oral splint modulates proprioceptive, or 'touch' signals," explains Yoshihisa Tachibana, co-first author of the study. "These 'touch' signals might be modified by the muscles involved in jaw-closing before being relayed to the brain."

While larger-scale studies are needed, the oral splint has clear therapeutic potential. As well as enhancing quality of life, ameliorating tics could improve psychosocial functioning in patients with Tourette syndrome.

The microorganisms living in the intestines could help with muscle growth and function, opening new doors to interventions for age-related skeletal muscle loss, an international research team led by Nanyang Technological University, Singapore (NTU Singapore) has found.

Through a series of strength and movement-related exercises conducted on mice, the team comprising researchers from Singapore, Sweden, Switzerland, France, UK, US, and Australia, found that mice with gut microbes had stronger skeletal muscles that can produce more energy when compared to mice without any gut microbes, known as germ-free mice.

All species, including humans, have a myriad of microbial species living inside them. Those that line the gut play a major role in body functions, from metabolism to the immune system.

Evidence for a link between gut microbes and skeletal muscle mass was strengthened when the international research team transplanted gut microbes from standard laboratory mice into germ-free mice. Muscle growth and function in the germ-free mice were partially restored following the transplant (See attached image).

The findings point to a new potential method for tackling age-related skeletal muscle loss by altering the gut microbe composition.

The study, published in Science Translational Medicine in July, could also pave the way for important studies relevant to muscle development, growth and formation of functional nerve-muscle communication.

Professor Sven Pettersson from the NTU Lee Kong Chian School of Medicine, who led the study, said, "These results further strengthen the growing evidence of gut microbes acting as crucial gatekeepers to human health, and provide new insight into muscle mass maintenance with respect to ageing. Given that healthy ageing is one of the main healthcare goals of Singapore's ageing population, these results are encouraging. They lay the foundation for future studies that evaluate how microbes and their metabolites may be potential targets of intervention to improve skeletal muscle strength in the elderly, especially in countries such as Singapore with rapidly ageing populations."

New insight on nerve-muscle communication

The study also shed light on the possible link between gut microbes and communication between nerves and muscles.

The researchers found that germ-free mice had reduced levels of key proteins essential for the assembly and function of a neuromuscular junction - a chemical structure that allows a motor nerve cell to communicate with a skeletal muscle fibre. These junctions allow signals to be transmitted to the muscle fibre, causing muscle contraction.

Transplanting gut microbes into germ-free mice partially restored the expression of these key proteins to the level observed in mice with gut bacteria.

Prof Pettersson said, "While additional experiments are needed to fully obtain the mechanisms underlying muscle atrophy and dysfunction in the nerve-muscle junction in germ-free mice, the results presented here allow for important and interesting future studies relevant to muscle development, growth and formation of functional nerve-muscle communication."

Understanding the mechanism of skeletal muscles

To study the impact of gut microbes on skeletal muscle mass and muscle atrophy, which is the wasting or loss of muscle tissue, Prof Pettersson and his team conducted three sets of exercise tests on both mice with gut microbes and germ-free mice with no trace of microbes in them.

In the weights test, each mouse was made to grasp a 26g weight to see if it could hold the weight for three seconds. Those who did so successfully then progressed to the next five weights, ranging from 33g to 100g.

The researchers also monitored the mice's movements for an hour in an open environment to measure the total distance they covered and the amount of time the mice spent standing on their hind legs.

The mice also ran on a treadmill set at a gradually increasing speed from 0 to 15 metres per minute, and then maintained at a constant speed.

Upon examination, the research team found that on top of reduced skeletal muscle mass and increased expression of genes linked to muscle atrophy, the skeletal muscles in germ-free mice also displayed problems with function and the generation of new mitochondria, whose role is to break down nutrients to form energy for cellular activity.

But when the researchers transplanted gut microbes from mice to germ-free mice, they found that these mice had their muscle growth and function partially restored, and showed reduced signs of muscle atrophy.

The study builds on Prof Pettersson's earlier studies on how gut microbes influence brain development, blood brain barrier integrity, and overall behaviour related to anxiety and fear.

Professor of microbiology Wang Yue from Singapore's Agency for Science, Technology and Research (A*STAR), who was not involved in the study, said the discovery will inspire scientists and clinicians to investigate the relationship between the microbial composition of the microbiota and the state of skeletal muscles in humans.

"This line of research will lead to novel ways to maintain or improve muscle mass, strength, and function by modulating the microbial composition in the gut. Such strategies are expected to have broad applications in tackling muscle-related health issues. One area with enormous potential is to delay or reverse age-related sarcopenia (the loss of skeletal muscle mass and strength as a result of ageing)," added the research director at A*STAR's Institute of Molecular and Cell Biology

Barcelona-- The largest stratified medicine dataset of non-small cell lung cancer patients indicates further molecular stratifications could benefit from targeted therapies, according to research presented today at the IASLC 2019 World Conference on Lung Cancer, hosted by the International Association for the Study of Lung Cancer.

The National Lung Matrix Trial is the largest precision medicine trial in NSCLC patients globally, testing a wide range of therapies tailored specifically to target key genetic changes in cancer cells. Data from this trial was reported today by Dr. Gary Middleton from the University of Birmingham, United Kingdom.

Oncogene-addicted NSCLC can achieve substantial clinical benefit with single agent targeted therapy. Seeking to extend this paradigm to other more genetically complex NSCLC, Dr. Middleton today reported first results of NLMT, an umbrella phase II trial that stratifies NSCLC patients to rationally selected targeted therapies. In an umbrella clinical trial, patients are assigned to a particular treatment arm of the trial based on their type of cancer and the specific molecular makeup of their cancer.

NLMT screens eight targeted drugs for signals of activity using a Bayesian adaptive design in 22 molecularly defined cohorts. For single agents, clinically relevant outcomes are either median progression-free survival for more than three months or objective response rate and/or durable clinical benefit rate (DCBR) at 24 weeks greater than 30 percent. This novel approach provides insight into the drug-biomarker combinations that have the strongest potential for further research.

Middleton and his colleagues recruited 315 patients from a screened population of more than 4,000 patients. Results were as follows:
Of the six palbociclib cohorts, the Bayesian estimate of the true median progression free survival in KRAS mutation was 5.4 months, KRAS mutation with concomitant STK11 loss 2.71 months, CDKN2A loss squamous 4.46 months and CDKN2A loss non-squamous 3.19 months. Data for crizotinib show greater than 99% predicted probability of success in ROS1 gene fusions and MET exon 14 skipping mutation but less than 1% for Met amplification with regards to objective response rate.

Middleton reported that responses to selumetinib/docetaxel in NF1 mutation in adenocarcinoma warrant continuation. Recruitment to vistusertib was halted at interim for LKB1 single mutation: the predicted probability of success for DCBR in those with KRAS mutation with concomitant STK11 loss is 32% with Bayesian estimate of the true DCBR of 27% and with no objective responses. Four cohorts received capivasertib including those with PIK3CA amplifications the Bayesian estimate for the true DCBR is less than 15% for all arms.

These first results from the largest stratified medicine dataset in NSCLC indicate further molecular stratifications could benefit from targeted therapies. Reporting interim outputs for all cohorts will allow reappraisal of the global stratified medicine strategy in cancer.

A future free of malaria, one of the world's oldest and deadliest diseases, can be achieved as early as 2050, according to a new report published today by The Lancet Commission on malaria eradication.

Authored by 41 of the world's leading malariologists, biomedical scientists, economists, and health policy experts, this seminal report synthesizes existing evidence with new epidemiological and financial analyses to demonstrate that - with the right tools, strategies, and sufficient funding - eradication of the disease is possible within a generation. The Commission's report is the first peer reviewed, academic document of its kind.

"For too long, malaria eradication has been a distant dream, but now we have evidence that malaria can and should be eradicated by 2050," said Sir Richard Feachem, Co-chair of The Lancet Commission on malaria eradication and Director of the Global Health Group at the University of California, San Francisco (UCSF). "This report shows that eradication is possible within a generation. But to achieve this common vision, we simply cannot continue with a business as usual approach. The world is at a tipping point, and we must instead challenge ourselves with ambitious targets and commit to the bold action needed to meet them."

Global malaria trends

Recent decades have seen unprecedented progress made against malaria, prompting discussions about the feasibility of eradicating the disease altogether. Since 2000, global malaria incidence and death rates declined by 36 and 60 percent, respectively, due to strong leadership, country-driven ambition, innovative new tools and strategies, and increased investments peaking at US$4.3 billion in 2016. Today, more than half of the world's countries are malaria-free.

However, this progress hangs in the balance. Despite global efforts, there are over 200 million cases of malaria reported around the world each year, claiming the lives of nearly half a million individuals. The achievements of the past two decades are threatened by recent plateaus in global funding, together with a rise of malaria cases in 55 countries across Africa, Asia and Latin America and increasing concern about parasite and vector resistance to currently available drugs and insecticides. Additionally, malaria continues to perpetuate cycles of inequity, with 29 countries accounting for the large majority of new cases and 85 percent of global deaths reported in 2017. All but two (Papua New Guinea and the Solomon Islands) of these countries are located in Africa. Just two countries (Nigeria and the Democratic Republic of the Congo) account for 36 percent of global cases alone.

"Despite unprecedented progress, malaria continues to strip communities around the world of promise and economic potential. This is particularly true in Africa, where just five countries account for nearly half of the global burden," said Dr. Winnie Mpanju-Shumbusho, Board Member of the RBM Partnership to End Malaria and Co-chair of The Lancet Commission on malaria eradication. "Malaria eradication is a public health and equity imperative of our generation."

Modeling a world free from malaria

The Lancet Commission on malaria eradication, a joint endeavor between The Lancet and UCSF, was convened in 2017 to consider the feasibility, affordability, and merit of malaria eradication, inform global opinion, and identify priority actions for the achievement of eradication.

In the report, the authors used new modelling to estimate plausible scenarios for the distribution and intensity of malaria in 2030 and 2050. Analyses indicate that socioeconomic and environmental trends, together with improved coverage of current malaria interventions, will create a world in 2050 with malaria persisting in pockets of low-level transmission across equatorial Africa.

Rather than continue efforts to gradually reduce malaria in most countries, hold the constant threat of resurgence at bay, and fight an ongoing and increasingly difficult struggle against drug and insecticide resistance, the report notes the malaria community can instead choose to commit to a time-bound eradication goal that will bring purpose, urgency, and dedication. The objective of these efforts is to convert the modelled future of persisting malaria into an engineered future of a world free of malaria in 2050.

Bending the malaria curve

To achieve eradication by 2050, the Commission urges that specific and deliberate actions at country, regional and global levels must be taken. This report identifies three ways to 'bend the curve' - or accelerate the decline in malaria cases worldwide.

First, the world must improve the management and implementation of current malaria control programs and make better use of existing tools - what the Commission refers to as the "software of eradication." Second, Commissioners highlight the need to improve the "hardware of eradication" by developing and rolling out innovative new tools to overcome the biological challenges to eradication. And lastly, malaria endemic countries and donors must provide the financial investment needed to ultimately rid the world of this disease. While the cost of malaria eradication is unknown--as it was for smallpox, polio, and Guinea worm when their respective eradication campaigns were launched, the Commission suggests that an annual increase of approximately US$2 billion will greatly accelerate progress. When combined with the increasing commitment and ambition by endemic countries and regions and strengthened leadership and accountability, these actions will propel us towards a world without malaria by 2050 or sooner.

Writing in a linked Comment, Dr. Tedros Adhanom Ghebreyesus, Director-General of the WHO, says: "The Lancet Commission makes a bold call for eradicating malaria by 2050. I would be thrilled to see this global scourge eradicated even earlier. But we will not achieve eradication within this time frame with the currently available tools and approaches...The good news is that we, the global malaria community, know what we need to do."

Dr. Tedros goes on to call for reinvigorated efforts in research and development, increased and more effective investment, and most importantly, stronger health systems based on primary health care and a commitment to achieving universal health coverage.

Speaking on the report, Dr. Fred Binka, a Commissioner and Foundation Vice-Chancellor, University of Health and Allied Sciences, Ghana, noted: "Malaria eradication is a goal of epic proportions, and it will require ambition, commitment and partnership like never before. But we know that its return is worth the investment, not only by saving lives in perpetuity, but also improving human welfare, strengthening economies and contributing to a healthier, safer and more equitable world. The time for action is now."]

As Rodolfo Martinez-Mota well knows, from the cactus spines in his clothes and skin, white-throated woodrats love to eat prickly pear cactus (from the Opuntia genus). They like the cactus so much that their gut microorganism community, or microbiome, is specially equipped to break down toxins in the cactus.

But Martinez-Mota and his colleagues in the University of Utah School of Biological Sciences also know that if the woodrat is in captivity and is eating an artificial diet, that finely tuned gut microbiome changes. In a paper published in the International Society for Microbial Ecology Journal, the research team reports that the native gut microbiome can be preserved in captivity by continuing to feed the animals their native foods instead of an artificial diet.

"We found that these changes can be avoided by providing wild diets to captive animals," Martinez-Mota says. "Our results also show that commercial diets are the main driver that induces microbial changes in captive rodents. We could hypothesize that the same applies to other captive animals."

Collection

The study was conducted in the lab of distinguished professor Denise Dearing, director of the School of Biological Sciences. Dearing has been studying several woodrat species for more than 20 years, learning about their adaptations to their harsh desert environment. Different woodrat species have adapted to detoxify the poisonous compounds in juniper, creosote and other desert plants.

When studying woodrats in her lab, Dearing and her students noticed that, after leaving their natural environment, the woodrats' gut microbiomes changed, becoming less diverse. There's a lot we still don't know about the connections between gut microbiology and health, but a less diverse microbiome is generally a bad thing. "However, we did not know what specific factors caused major microbial changes in previous experiments, which limited our conclusions," Dearing says. They suspected that diet may have been a primary factor.

Similar changes in gut microbiota have been seen in other mammals, with researchers offering various possible explanations, including diet. But so far, no other studies have isolated the effect of diet on mammals in captivity.

So, Dearing, postdoctoral fellows Martinez-Mota and Teri Orr and University of Pittsburgh collaborator Kevin Kohl designed an experiment to monitor woodrats' gut microbiomes in the lab, eating different diets. They found a population of woodrats near Castle Valley, Utah, with a diet that could be easily collected and transported to the lab: prickly pear cactus.

"This dietary specialization, and the feasibility to collect cacti in the natural habitat and recreate the wild diet in the laboratory, provided the conditions to have the perfect animal model system to test our hypothesis," Dearing says.

A prickly problem

Overall, they collected twelve woodrats. "The trapping of woodrats is always an adventure!" Martinez-Mota says. Woodrats are also often called packrats, he says. "They collect all sorts of things from railroad spikes, to bones, to paws of other animals. It's always interesting to see what they have collected," says Dearing.

The team collected cacti as well, feeding them to the woodrats en route to Salt Lake City. To prevent any injury to the rodents, the team despined the cacti. Martinez-Mota also despined the cacti in the lab, and still found spines in his clothes several weeks after the experiment had ended. In the wild, Dearing notes, the woodrats despine the cacti themselves and line their nests with the spines to deter predators. "It's ironic that the woodrats have co-opted the defense of their food, spines, to protect themselves," she adds.

In the lab, half of the woodrats received artificial diets (commercial high-fiber rabbit chow) while the other half received prickly pear collected from the wild.

A community's diversity

After three weeks, the research team looked at the results. On beginning the artificial diet, the chow-fed group lost more than a third of their bacterial gut species, including some in the Bifidobacterium and Lactobacillus genera (plural of genus).

"Both bacterial genera are associated with detoxification of the plant toxins ingested by the woodrat," Martinez-Mota says. "Thus, we could hypothesize that some functions of the woodrat core microbiome were compromised when animals fed on artificial diets."

Taking the place of the lost genera were already-established microbial communities such as Clostridiales, Ruminococcaceae and Lachnospiraceae, all involved in metabolizing nondigestible carbohydrates like the fiber in the chow. By the end of the three-week experiment, the chow-fed woodrats had gained back around 10% of their gut diversity.

In contrast, the cactus-fed group retained around 90% of their original microbiome diversity throughout the experiment. It's not always possible to know exactly what an animal is eating in the wild, the researchers say, but if that diet can be reasonably approximated in captivity, the animal's gut is likely to remain diverse--and healthy.

So, what does this mean for zoos and pet owners?

"People who maintain wild animals in captivity should supplement animal diets with food items that resemble food consumed in the wild," Martinez-Mota says.  "If supplementing a diet with wild food is not possible, then food items with similar nutritional/chemical composition should be provided."

Recent technological advancement has seen the development and utilization of photodetectors in different applications, including biological detection and image sensing. Polymer photodetectors (PPDs), in particular, have attracted significant attention owing to the numerous desirable properties and technological advantages of polymer semiconductors, i.e., adjustable energy levels, mechanical flexibility, large-area fabrication, solution process, and low cost. The photodiode type PPDs obeying photovoltaic effect exhibit external quantum efficiency (EQE) of less than 100%, which limits their applications in weak light detection. Thus researchers have been looking for better alternatives and have identified photomultiplication (PM) type PPDs as a promising direction. PM phenomenon is desirable for sensitive photodetectors with strong detection capability of weak light, which can avoid the use of complex pre-amplifier circuit, simplify the design of photo-detection systems and benefit the development of integrated optoelectronic products.

In 2015, Professor Fujun Zhang's group from Beijing Jiaotong University firstly reported the PM type PPDs with P3HT:PCBM (100:1, wt/wt) as active layers, processing single carrier transport property. This PM type PPDs exhibit EQE of >>100% and low dark current density. Subsequently, tremendous efforts on PM type PPDs were devoted in the performance improvement, response spectral range regulation, and function expansion. The reported PM type PPDs with single carrier transport property are primarily based on polymer donor P3HT system. It is urgent to explore new polymer material systems with PM phenomenon, which will further confirm the universality of PM type PPDs with single carrier transport property.

Recently, Professor Fujun Zhang's group developed the PM type PPDs with single carrier transport property, demonstrating the PM type all-polymer photodetectors (all-PPDs) with the sandwich structure of ITO/PEDOT:PSS/PBDB-T:PZ1 (100:x, wt/wt)/Al (Figure 1a).

The optimal all-PPDs with PBDB-T:PZ1 (100:1, wt/wt) as active layers exhibit EQE exceed 100% in the spectral range from 310 to 790 nm. Under 675 nm light illumination, the champion EQE value arrives to 1470%. The photogenerated electron distribution in active layer was simulated by using Transfer Matrix method.

The normalized response spectrum of PM type all-PPDs and normalized photogenerated electron distribution near the Al electrode are exhibited in Figure 1b, which further indicates that the working mechanism of PM type all-PPDs is hole tunneling injection assisted by interfacial band bending induced by trapped electrons in PZ1 near Al electrode. When the number of holes flowing through the all-PPDs is greater than the number of incident photons per unit time, the EQE values will be larger than 100%, leading to the PM phenomenon.

This work further confirms the universality of PM type PPDs with single carrier transport property, which would promote the exploration of new polymer semiconductors and the design of new device architectures to realize high performance PM type PPDs, meeting the need of versatility in integrated optoelectronic products.

The research team led by Dr. Daisuke Ono and Prof. Akihiro Yamanaka of the Graduate School of Medicine, Nagoya University, collaborating with Prof. Ken-ichi Honma and Prof. Sato Honma of Hokkaido University Graduate School of Medicine, and Prof. Yuchio Yanagawa of Gunma University Graduate School of Medicine revealed that inhibitory neurons (GABAergic neurons) of the central circadian clock in the suprachiasmatic nucleus (SCN) refine circadian output rhythms.

Physiology and behavior such as sleep/wakefulness, body temperature, and endocrine functions, exhibit 24-hour oscillations called circadian rhythms. The temporal order of physiology and behavior is regulated by the central circadian clock located in the SCN. Our findings can be developed to understand how the SCN regulates physiological phenomena. Furthermore, it might aid the development of new clinical approaches for a variety of diseases related to the circadian clock. These achievements were published online in Communications Biology on June 21, 2019.

This work was supported in part by The Uehara Memorial Foundation, The Nakajima Foundation, GSK Japan Research Grant 2015, Kowa Life Science Foundation, Takeda Science Foundation, Kato Memorial Bioscience Foundation, the Project for Developing Innovation Systems of the MEXT, and Creation of Innovation Centers for Advanced Interdisciplinary Research Areas Program, Ministry of Education, Culture, Sports, Science and Technology, Japan and JSPS KAKENHI (No. 15H04679, No. 26860156, No. 15K12763, No. 26290002, No. 15H05872, No. 17H05550, No. 18H02477).

Research Background

The temporal order of physiology and behavior in mammals is controlled by the master circadian clock located in the SCN. The SCN generates an endogenous circadian oscillation that entrains a day-night alternation. The SCN is composed of heterogeneous neurons with various neurotransmitters. Of these, an inhibitory neurotransmitter, γ-Amino-Butyric-Acid (GABA) is expressed in almost all SCN neurons; however, its role in circadian physiology is still unclear.

Research Results

In the present study, we examined GABA signaling in the SCN using mice lacking vesicular GABA transporter (VGAT-/-) or a GABA synthesizing enzyme, glutamate decarboxylase (GAD65-/-/67-/-). We simultaneously measured circadian rhythms with a bioluminescence reporter for the clock gene product PER2 (PER2::LUC), spontaneous firing, and intracellular calcium (Ca2+) levels for several circadian cycles in cultured SCN slices of perinatal mice. SCN lacking GABA exhibited burst firing throughout a day. The burst firing was associated with an abrupt increase in intracellular Ca2+, which was synchronous throughout the entire SCN slice. By contrast, the circadian PER2 rhythm was essentially kept intact. We also found that SCN-specific VGAT depletion in adult mice deteriorated the circadian behavioral rhythms.

Research Summary and Future Perspective

In conclusion, GABA is necessary for suppressing the burst firing of neuronal activity and abrupt increases of intracellular Ca2+ levels but not for the generation and stability of the molecular circadian oscillation in the SCN. The GABA network may refine the circadian firing rhythm to ensure noiseless communications with neurons outside the SCN.