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A group of researchers at Baylor College of Medicine, the Texas Heart Institute and the University of Texas Health Science Center at Houston reveals today in the journal Genes & Development new insights into the recently discovered healing capacity of the heart involving the Hippo cellular pathway. The group previously reported that inactivating the Hippo pathway in the adult murine heart promoted cardiac muscle regeneration after injury, opening the possibility of developing promising heart failure therapies.

In this study, the researchers discovered that inactivating the Hippo pathway in cardiac fibroblasts, non-muscle heart cells intertwined with cardiac muscle cells, promoted cardiac fibrosis and adversely effected cardiac function. These results highlight the need for targeting the Hippo pathway specifically in cardiac muscle cells, and not in cardiac fibroblasts, for safe and effective heart failure therapy.

"Heart failure remains the leading cause of mortality in the U.S., and one of the interests of my lab is to develop ways to heal heart muscle by studying cellular pathways involved in heart development and regeneration," said corresponding author Dr. James Martin, professor and Vivian L. Smith Chair in Regenerative Medicine at Baylor and director of the Cardiomyocyte Renewal Lab at the Texas Heart Institute.

During a heart attack, blood stops flowing into the heart; without oxygen, part of the heart muscle dies. The heart muscle does not regenerate; instead it replaces dead tissue with a scar, made from cells called fibroblasts. If there is too much scarring, the heart progressively weakens; a large proportion of people who had a severe heart attack will develop heat failure and scarring in the heart.

In previous studies, Martin and his colleagues discovered that inactivating the Hippo signaling pathway in adult murine hearts triggered cardiac muscle cell regeneration after heart attack. These findings raised hope for the development of promising heart failure therapies involving the Hippo pathway.

In the current study, Martin and his colleagues further investigated the Hippo pathway in the adult murine heart, this time focusing on its role in cardiac fibroblasts, non-muscle cells that are closely associated with cardiac muscle cells. The researchers conducted a number of basic studies, including single cell sequencing experiments that provided a high level of resolution to their analyses.

"We inactivated the Hippo pathway in resting adult hearts that did not have any injury and observed that the fibroblasts became activated; they proliferated and developed into myofibroblasts, a major cell type that appears in heart tissues after an injury," Martin said.

"Mouse hearts with a deficient Hippo pathway in cardiac fibroblasts spontaneously developed cardiac fibrosis, even without injury, which resulted in severe heart dysfunction," said co-first author Dr. Yang Xiao, who was a postdoctoral fellow in the Martin lab during this project. "This and other evidence indicated that the Hippo pathway is required to restrain cardiac fibrosis; Hippo is important for maintaining the fibroblasts in their resting state."

In addition, the researchers found that inactivating the Hippo pathway also triggered a molecular cascade resulting in an inflammatory response that was mediated by Yap, a molecule that regulates a number of molecular pathways.

"We know that Hippo and Yap work together. Hippo acts like a brake for Yap, so when we took away Hippo, Yap remained active and regulated the expression of important signaling molecules that 'talk' to macrophages and other immune cells luring them into the heart," Martin said.

The researchers believe they have identified important insights into heart function. Their findings inform about the genetic pathways that are important for maintaining the fibroblasts in their resting state.

What The Study Did: Data from the UK Biobank were used to examine whether genetic risk to psychotic experiences is shared with neuropsychiatric disorders.

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Authors: James T. R. Walters, M.R.C.Psych., Ph.D., and Stanley Zammit, M.R.C.Psych., Ph.D., of Cardiff University in Cardiff, United Kingdom, are the corresponding authors.

(doi:10.1001/jamapsychiatry.2019.2508)

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, financial disclosures, funding and support, etc.

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A research team has created CAR T cells that target an alternative B cell-specific surface marker, allowing them to effectively kill blood cancer cells that lack the prototypical target for CAR T therapy, CD19. The new T cells could help clinicians avoid the relapses that can occur in patients whose lymphoma cells lose CD19 - a prominent roadblock in standard CAR T cell therapy for B cell malignancies. CAR T cells are a highly effective therapy for blood cancers that have become resistant to standard treatments. However, up to 30% of patients with B cell malignancies such as lymphoma relapse after CAR T cell treatment, partly because their lymphoma cells stop expressing the target antigen. Seeking an alternative approach, Hong Qin and colleagues engineered CAR T cells that target a protein named BAFF-R, whose expression is also restricted to healthy and cancerous B cells. They tested their BAFF-R-directed CAR T cells in mice with human lymphoma cells, and found the treatment led to complete tumor regression and 100% long-term survival in the animals. The authors saw that the BAFF-R-directed CAR T cells could effectively target CRISPR-modified human leukemia cells that lacked CD19. Furthermore, the BAFF-R-CAR T cells also killed CD19-negative tumor cells isolated from four patients with leukemia who relapsed after being treated with a CD19-targeting antibody, and extended survival in mice that were implanted with cells from a fifth relapsed patient. The results show that BAFF-R is a viable target for CAR T cell treatments, although more experiments will be needed to confirm whether tumor cells could potentially evolve resistance by losing BAFF-R.

People are less motivated to take actions if its outcome is uncertain, and this could be true for climate-related issues. The uncertainty in climate response to the increase in greenhouse gas concentration, which is often believed to be substantially large, makes it difficult to believe the benefit of reducing emissions or the effectiveness of making society more resilient to climate-related hazards. This could be one of the reasons for inaction even though urgent action is called for. A new study published in Nature Climate Change, conducted by a Japanese research team (consisting of researchers at Ibaraki University, Kyoto University, National Agriculture and Food Research Organization, National Institute for Environmental Studies, Ritsumeikan University, Shibaura Institute of Technology, The University of Tokyo, and University of Tsukuba), might change such views. The study estimates economic impacts of climate change and suggests that mankind's decisions and actions can overwhelm the uncertainty in climate response in terms of reducing the impact of climate change.

Estimation of the economic impacts of climate change is itself extremely challenging because it can affect society in many ways. Collaboration between researchers in a diverse range of fields enabled the research team to conduct a global-scale assessment covering the economic impacts associated with climate change for nine impact sectors: the economic impacts arising from changes in agricultural productivity, undernourishment, heat-related excess mortality, cooling/heating demand, occupational health costs, capacity of hydroelectric power generation, capacity of thermal power generation, fluvial flooding, and coastal inundation.

Describing the novelty and significance of the study, Dr. Hijioka, the research managing director of Center for Climate Change Adaptation, National Institute for Environmental Studies states, "This is very special research, with no equivalent in the world."

The estimated value of the aggregated economic impacts had a large divergence depending on three assumptions: socioeconomic conditions, amount of greenhouse gas emissions, and climate responses to the increased greenhouse gas concentration. Under the most pessimistic combination of assumptions, the estimated economic impact will be equivalent to 8.6% of the global total GDP at the end of the 21st century, while it will be limited to around or less than 1% if the 2-degree target, which was adopted in the Paris Agreement, is achieved and societal resilience to climate-related hazards improves. More importantly, the results also indicated that the contribution of the uncertainty in the climate response to the divergence -- or variance -- of the estimates was minor compared to the contribution of the differences in the anthropogenically directed societal pathways (i.e., greenhouse gas emissions and socioeconomic developments). "This means that mankind has the potential to determine the scale of the economic impacts of climate change," explains Dr. Takakura, a researcher at National Institute for Environmental Studies.

According to the results of this study, the future is uncertain mainly because how we behave is uncertain, rather than because how the climate behaves is uncertain in terms of the economic impacts of climate change. "In other words, we can choose the future by taking or not taking actions,and have responsibility for the outcome," he added.

Originally from Africa, chikungunya is aptly named. It derives from a word in the Kimakonde language, meaning "to become contorted", because the severe muscle and joint pains endured by the patients prevent them from moving normally or performing their daily activities.

While the clinical manifestations of the disease are well understood, the mechanisms by which the virus infects human cells and multiplies remain poorly elucidated. Several studies had already identified certain host cell factors implicated in the replication of the virus. However, none had succeeded in explaining why the virus preferentially targets the muscle and joint cells, causing these clinical signs.

Researchers from Inserm, CNRS and Université de Paris led by Dr. Ali Amara at the AP-HP Saint-Louis Hospital Research Institute in Paris, in collaboration with Marc Lecuit's team from Institut Pasteur, Inserm and Université de Paris, have identified that the FHL1 protein is a key cellular factor for the replication and pathogenesis of chikungunya. FHL1 is a molecule present mainly in the muscle cells and fibroblasts, the preferred targets of the virus. Usually, FHL1 contributes to healthy muscle physiology and it is now thought to be diverted from that function by the virus to ensure its replication in the target cells.

To conduct this study, Amara's team used the CRISPR-Cas9 technology to systematically screen the genome of human cells in order to identify the host factors necessary for viral replication. In doing so, it isolated the gene coding for the FHL1 protein. The team then conducted a series of experiments showing the incapacity of the virus to infect cells whose FHL1 expression had been abolished.

In addition, the researchers have shown that the virus was incapable of multiplying within cells derived from patients suffering Emery-Dreifuss muscular dystrophy - a rare genetic disease. This muscle disease is the result of mutations of the FHL1 gene responsible for the breakdown of the FHL1 protein. The researchers have shown that the cells of these patients are resistant to the virus.

Finally, the researchers performed in vivo experiments in mice whose Fhl1 gene was invalidated. They have shown that these animals are totally resistant to infection and do not develop the disease, whereas the virus multiplies and causes major muscle lesions in mice expressing a functional FHL1 protein. These observations demonstrate that the FHL1 protein plays a key role in chikungunya virus replication and pathogenesis.

The precise role played by FHL1 in the viral infection is not fully understood. The researchers have discovered that FHL1 interacts with a viral protein known as nsP3. It is when binding to this that FHL1 participates in the replication of the virus.

"We now want to understand this interaction in molecular detail. The next step is to define why FHL1 is so specific to the chikungunya virus, and to decipher its mechanism of action at the molecular level. Elucidating the molecular structure of the FHL1-nsP3 complex could represent a major step forward in the development of antivirals that block the replication of the virus", emphasize Ali Amara and Laurent Meertens, the Inserm researchers in charge of the study.

At present, only symptomatic treatments are available for patients infected with chikungunya.

A new study of African Americans with poorly controlled asthma, found differences in patients' responses to commonly used treatments. Contrary to what researchers had expected, almost half of young children in the study responded differently than older children and adults, and than white children in prior studies.

"We shouldn't assume that current treatment strategies for asthma are ideal for all African Americans since for many years that population was not adequately represented in research," said Elliot Israel, M.D., senior study author and director of clinical research in the Pulmonary and Critical Care Medicine Division at Brigham and Women's Hospital. "We found that almost half of the African American children studied responded better to increasing the dose of inhaled corticosteroids than adding a long-acting bronchodilator. Thus, adding a long-acting bronchodilator may not be the right answer for nearly half of African American children."

The National Heart, Lung, and Blood Institute (NHLBI), part of the National Institutes of Health, funded this research to assess the best approach to asthma management in African Americans, who suffer much higher rates of serious asthma attacks, hospitalizations, and asthma-related deaths than whites. The findings appear today in the New England Journal of Medicine.

The researchers examined how to escalate or "step-up" asthma treatments for African Americans whose asthma had not been treated adequately with low doses of inhaled corticosteroids, the standard starting treatment. The treatment choices in the trial included increasing the dose of inhaled steroid, adding a long-lasting bronchodilator (used to help open airways), or both.

Based on prior studies, investigators expected that increasing the inhaled corticosteroid dose would lead to improvement in most African American children needing treatment for asthma.

The researchers found that in children under 12 years of age, either approach was effective: nearly half (46%) responded better to increasing the inhaled corticosteroid dose alone and just as many (46%) responded better to increasing the inhaled corticosteroid dose and adding a long-lasting bronchodilator.

"This study suggests that we cannot look at results from one population and extrapolate the findings to African Americans or any other group," said Michael Wechsler, M.D., principal investigator for the NHLBI-funded Best African American Response to Asthma Drugs (BARD) study and professor of medicine at National Jewish Health in Denver. "If children do not respond to one treatment, parents and providers could consider another option because there is almost a 50% chance of having a better response."

The multicenter study included 574 participants--about half of whom were ages 5-11 and half 12 years and older. All participants in this study had at least one self-identified African American grandparent, with an average of approximately 80% African ancestry, based on genetic testing.

Of the adolescents over 11 years old and adults, most (49%) responded better to adding a long-lasting bronchodilator than to increasing the inhaled corticosteroid dose, though 20-25% in this group showed no difference in their responses to these approaches.

Investigators also examined whether patient characteristics, including genetic ancestry, could be used to predict the response to the "step-up" treatments in the study participants. But they were unable to use genes indicative of African ancestry, or any of the other patient characteristics they measured in this group of patients, to predict treatment response.

"Although we cannot attribute the study's findings to genetic markers of African ancestry, there could be as-yet unknown genetic variants specific to people of African descent that affect how severe a patient's asthma is," said Wechsler. Before the trial began, the researchers did not expect the participants to have a better response to treatment regimens that included long-lasting bronchodilators, despite the inclusion of these agents in treatment recommendations. They said they were surprised that many (46% of the young children and 49% of the older children and adults) improved with long-lasting bronchodilators.

"These results provide new data about the management of asthma patients who self-identify as African American regardless of genetic ancestry," said James Kiley, Ph.D., director of the Division of Lung Diseases at NHLBI. "Every person and their provider should explore all of their management choices to achieve maximum asthma control, based on their response to specific medications."

Myelodysplastic syndrome (MDS), one of the most common blood cancers, has very few treatment options. Now, researchers at Cold Spring Harbor Laboratory (CSHL) have discovered a new and promising drug target for this deadly condition.

"At the moment, only a small portion of patients benefit from the standard therapy for MDS," said CSHL Fellow and cancer researcher Lingbo Zhang. "Therefore, there is a very important medical need for a new and novel therapy for this disease."

Zhang's lab working with experts from Memorial Sloan Kettering Cancer Center and National Institute of Diabetes and Digestive and Kidney Diseases discovered the new drug target that could meet this need. Their research was recently published in Science Translational Medicine.

"We have been working with a multidisciplinary team that consists of physicians and medicinal chemists to translate our basic discovery into novel therapeutics which can be tested in clinical trials for the benefit of patients," Zhang said.

The ultimate goal, Zhang said, is to create a drug that will adequately restore blood cell production in MDS patients who are resistant to existing treatments.

To understand exactly how the new drug target works, it's important to first know why MDS is so difficult to treat. Unlike many other cancers, MDS is not characterized by a tumor. Instead, this blood cancer is sometimes referred to as "bone marrow failure disorder."

Bone marrow is designed to produce enough blood for everyday survival. When blood cells are lost via bleeding or when they grow too old to do their job, replacement cells are made and begin to mature. MDS results from those replacements being too few, defective or both.

Traditional treatment options for MDS symptoms, such as anemia, rely on the body's natural ability to make more mature red blood cells, which is driven by a hormone called erythropoietin (EPO).

Immature red blood cells developing in the bone marrow, called progenitor cells, must be exposed to EPO to trigger their final change into fully mature red blood cells ready to aid the body. It would then stand to reason that delivering lots of EPO to the bone marrow would fix most MDS cases. But this is simply not the case.

The reason that only a small portion of patients respond to common EPO-based treatments is because many MDS patients don't have enough functional progenitor cells within their bone marrow to begin with. In some cases, what functional cells are available will indeed become mature red blood cells. However, once that supply runs out, EPO treatments stop working, causing drug resistance. That's why Zhang and his colleagues decided to take a different approach.

"So to treat this," Zhang explained, "you can't target the late progenitor. Their capacity to make new cells is very limited. But with the earlier cells, we have a chance."

Instead of relying on EPO and its target progenitor cells, they chose to target an even younger stage of the progenitor cells. The researchers discovered that when these cells are defective, activating a specific protein receptor called CHRM4 significantly hampers their ability to divide into those crucial EPO-responsive progenitor cells. By blocking this receptor, Zhang and his colleagues could restore healthy blood cell production.

In mice genetically designed to mirror the pathological features of human MDS, this strategy significantly improved survival rates.

"More importantly, these preclinical tests have shown that the treatment exhibited a sustained and long-term therapeutic efficacy," Zhang said. "We're now translating this discovery into clinical development, and we hope our progress will benefit patients in the near-future."

Kanazawa, Japan - Contrary to popular belief, there may be more than one mechanism involved in microbial airway protection. Researchers from Japan and China have found an alternative mechanism that may be involved in fighting microbial infections.

The inflammation pathway in response to microbial infections involves multiprotein complexes known as inflammasomes. It is known that inflammasomes induce inflammation by activating caspase-1, an enzyme that cleaves other proteins. In turn, caspase-1 converts the precursors of interleukin-1β and interleukin-18 known as pro-inflammatory cytokines to their active forms. In addition, caspase-1 processes gasdermin D, leading to pyroptosis, a necrotic form of inflammatory cell death.

In a study published in July of this year in Mucosal Immunology, the researchers found that caspase-1 is unnecessary in maintaining innate immune homeostasis in the airway. Instead, two protein components of the inflammasome, ASC and NLRP3, have found to be key players in this process.

"Based on previous reports, we understood that the protein NLRP3, plays a protective role against Streptococus pneumonia," says study author Kohsuke Tsuchiya. "Hence, we decided to further investigate the role of NLRP3 in microbial protection. Using mice models, we found that NLRP3, along with ASC, may play a protective role against S. pneumoniae."

The research team also found that ASC and NLRP3 protect the mice from S. pneumonia through a mechanism that is independent of caspase-1. Therefore, the researchers set out to elucidate this caspase-1-independent mechanism.

The results revealed that ASC and NLRP3 positively controlled the expression of the protein SPDEF during infection with S. pneumonia. SPDEF is a transcription factor involved with the expression of the mucosal defense factor genes. The study also showed that ASC and NLRP3 was key in activating STAT6, a regulator of the Spdef gene.

"Our results suggest that ASC and NLRP3 protect against microbial infections possibly through the STAT6-SPDEF pathway, which is independent of the caspase-1-dependent mechanism. This also means that both ASC and NLRP3 are acting independent of the inflammasome mechanism," says author Rendong Fang.

The group's findings may allow for new understanding of different possible mechanisms involved in maintaining innate immunity in the airway. However, further experiments are required, such as investigation into the mechanism linking S. pneumonia infection to STAT6 activation and whether both ASC and NLRP3 will maintain the expression of mucosal defense genes when infected by other microbial agents.

Millions of people across the globe are suffering from malnutrition despite some of the most nutritious fish species in the world being caught near their homes, according to new research published in Nature today.

Scientists from the ARC Centre of Excellence for Coral Reef Studies at James Cook University (Coral CoE at JCU) are part of an international team that found children in many tropical coastal areas could see significant health improvements if just a fraction of the fish caught nearby was diverted into their diets.

Co-author Dr David Mills from Coral CoE at JCU is a senior scientist with WorldFish. He says fish is an important source of protein, omega-3 fatty acids, and micronutrients such as iron, zinc, and calcium.

"Yet, more than two billion people worldwide suffer from micronutrient deficiencies," he said.

For some nations these deficiencies--linked to maternal mortality and stunted growth through childhood--are estimated to reduce GDP by up to 11 percent.

Lead author Prof Christina Hicks started the project when she was a research fellow at Coral CoE at JCU. The study suggests enough nutrients are already being fished from the oceans to substantially reduce malnutrition--but in some countries they are not reaching local populations, who are often those most in need.

"Our research shows that the nutrients currently fished from their waters exceed the dietary requirements for all under five-year olds living along their coasts," Prof Hicks said.

"If these catches were more accessible locally, they could have a huge impact on global food security and combat malnutrition-related disease in millions of people."

The team of 11 researchers recorded the concentration of seven nutrients in more than 350 species of marine fish and developed a statistical model to predict how much nutrition any given species of fish contains. This was based on their diet, sea water temperature and energy expenditure.

The predictive modelling allowed researchers to accurately calculate the likely nutrient composition of thousands of fish species that were never nutritionally analysed before.

They used this model to quantify the global distribution of nutrients available from existing marine fisheries. This information was then compared with the prevalence of nutrient deficiencies around the world.

Parts of Africa, Asia, the Pacific and the Caribbean were some of the regions with high malnutrition despite sufficient fish nutrients in the national catches.

Researchers say that a complex picture of international and illegal fishing and trade in seafood is standing between malnourished people and the more-than-adequate fish nutrients caught on their doorstep.

"It's time that food security policymakers acknowledge the nutrient-rich food swimming right under their noses and think about what can be done to increase access to fish by those populations," Dr Mills said.

Co-author Dr Philippa Cohen, a WorldFish partner investigator of Coral CoE at JCU, said the research clearly shows that the way fish are distributed needs to be carefully examined.

"Currently many of the world's fisheries are managed to get the most revenue, often by directing efforts towards catching the highest-priced species and shovelling fish landings towards the mouths of the rich in cities or feeding pets and livestock in wealthier countries," Dr Cohen said.

"By contrast, where collaborative management or co-management is in place, fisheries catches and value chains are in the hands, and reaching the mouths, of local populations."

Dr Mills said this highlights the need for fisheries policies focused on improving nutrition rather than simply increasing volumes of fish harvested or produced or the revenues generated from fish exports.

"As the demand for ocean resources increases up to the limit of what can be harvested sustainably in many instances, research initiatives like this show that there are opportunities to fish and distribute fish strategically to address fundamental challenges to human health and wellbeing," he said.

People today constantly encounter claims such as "Advil kills pain," "coffee prevents depression," or "Hilary promises amnesty" as brands, news outlets and social media sites vie for our attention--yet few people take the time to investigate whether these statements are true. Researchers have now uncovered one of the subtle psychological variables that influences whether people deem a claim to be true or false: the sequence of the letters.

Based on previous literature, the researchers knew that the brain attempts to organize information in ways that follow familiar patterns and sequences. One of the most universal, well-known patterns is the alphabet, and the investigators suspected that claims with first letters conforming to the arbitrary "ABCD" sequence--such as Andrenogel Increases Testosterone--would be perceived as more truthful. The study is available online in the Journal of Consumer Psychology.

"We go about our lives looking for natural sequences, and when we find a match to one of these patterns, it feels right," says study author Dan King, PhD, an assistant professor at the University of Texas Rio Grande Valley. "An embedded alphabetic sequence, even if unconsciously perceived, feels like a safe haven, and our brains can make unconscious judgments that cause-and-effect statements following this pattern are true."

To test this "symbolic sequence effect," the researchers conducted an experiment in which one group of participants read 10 claims that followed the natural alphabetic sequence, such as "Befferil Eases Pain" or "Aspen Moisturizes Skin," and the control group read statements that did not conform to alphabetical order, such as "Vufferil Eases Pain" or "Vaspen Moisturizes Skin." Then both groups rated their estimation of the truthfulness of the claims. The truthfulness ratings were significantly higher for the claims that followed an alphabetical order, even if participants could not attribute the source of the feeling of truthfulness.

Then the researchers tested whether they could temporarily alter the brain's pattern recognition process and consequently influence an individual's perception of a claim's truthfulness. In this experiment, one group of participants watched a short video clip of the alphabet sung normally while another group saw the clip with the ABC song sung in reverse order. Later, the groups rated the truthfulness of 10 claims.

The truthfulness ratings for claims following the reversed alphabetical sequence--such as "Uccuprin Strengthens Heart"--were higher for participants who had heard the alphabet sung in reverse.

The finding suggests that companies may be more likely to convince consumers that a slogan or claim is true if the causal statement follows an alphabetical order, King says. The more frightening implication, though, relates to fake news. Headlines with cause-effect statements that are in alphabetical order may feel more true, even if they are not.

"Consumers need to make evaluations based on fact or experimental evidence rather than whether something feels right," says King. "The alphabet is a random, arbitrary sequence we have learned, and it can play tricks on the brain when it comes to making judgments."

Scientists at the Center for Advancing Electronics Dresden (cfaed) at TU Dresden have succeeded in synthesizing sheet-like 2D polymers by a bottom-up process for the first time. A novel synthetic reaction route was developed for this purpose. The 2D polymers consist of only a few single atomic layers and, due to their very special properties, are a promising material for use in electronic components and systems of a new generation. The research result is a collaborative work of several groups at TU Dresden and Ulm University and was published this week in two related articles in the scientific journals "Nature Chemistry" and "Nature Communications".

Ever since Hermann Staudinger discovered the linear polymers in 1920, it has been a dream of synthetic scientists to extend the polymerization into the second dimension. A two-dimensional (2D) polymer is a sheet-like monomolecular macromolecule consisting of laterally connected repeat units with end groups along all edges. Given the enormous chemical and structural diversity of the building blocks (i.e., monomers), 2D polymers hold great promise in the rational material design tailored for next-generation applications, such as membrane separation, electronics, optical devices, energy storage and conversion, etc. However, despite the tremendous developments in synthetic chemistry over the last century, the bottom-up synthesis of 2D polymers with defined structures remains a formidable task.

Since 2014, a group of scientists from Technische Universität Dresden and Universität Ulm joined forces to pursue this intriguing yet challenging goal. The research team led by Prof. Dr. Xinliang Feng (TU Dresden) innovatively developed a novel synthetic route: using surfactant monolayer as a soft template to guide the supramolecular organization of monomers and the subsequent 2D polymerization at an air-water interface. This synthetic methodology is now termed as surfactant-monolayer-assistant interfacial synthesis (SMAIS). By using the SMAIS method, Dr. Tao Zhang synthesized crystalline quasi-2D polyaniline films with lateral size ~50 cm2 and tunable thickness (2.6 - 30 nm). The superior charge transport properties and chemiresistivity toward ammonia and volatile organic compounds render the quasi-2D polyaniline films as promising electroactive materials for thin-film organic electronics. To further explore the potential of SMAIS, Mr. Kejun Liu, Dr. Tao Zhang, Dr. Zhikun Zheng and Dr. Renhao Dong achieved controlled synthesis of highly-crystalline few-layer 2D polyimide and polyamide for the first time. The 2D polymers have a thickness of only a few nanometers and can be readily transferred onto arbitrary substrates, opening up exciting opportunity for the integration of 2D polymers into next-generation devices and systems.

Along with the pivotal developments on the synthesis front, the transmission electron microscopy group led by Prof. Dr. Ute Kaiser (Uni Ulm) provided another indispensable pillar of the joint research. Since the development of aberration correction, high-resolution TEM imaging has been a powerful technique in structural characterization down to the atomic scale. Yet, hydrogen-containing organic materials are extremely prone to structural disintegration under the electron beam, rendering HRTEM imaging of 2D polymers a highly demanding mission. By utilizing the spherical-aberration-corrected HRTEM, Dr. Haoyuan Qi has successfully unraveled the micro-morphology, molecular structures, grain boundary and edge structures, of the synthetic 2D polymers: an achievement which is rarely reported in literature.

The molecular structures and overall crystallinity have been further elucidated via synchrotron grazing-incidence X-ray scattering (cfaed Chair for Organic Devices, Prof. Dr. Stefan Mannsfeld, TU Dresden). The group of Prof. Dr. Thomas Heine (TU Dresden) provided density-functional tight-binding calculations which offers significant insights into the atomistic structures of the synthetic 2D polymers.

Bacteria have no mouth. They eat by absorbing substances from their environment via their cell wall. However, there are natural physical limits to this way of "eating". To bypass these limits, some bacteria enlarge their cell surface. For example, they form tubular extensions or small bubbles, so called vesicles. A group of researchers led by Jens Harder from the Max Planck Institute for Marine Microbiology in Bremen, Germany, has now observed for the first time that bacteria initially form tubes and then vesicles.

North Sea bacteria with pearl chains

„We have investigated a flavobacterium that is widespread in the North Sea," says Harder. These bacteria live in a nutrient-poor, so-called oligotrophic, environment. It is therefore advantageous for them to enlarge their cell surface and thus have more space to hold and absorb sugar and other food with enzymes on the surface. „Bacteria that have vesicles or tubes for this purpose have already been observed," Harder continues. "The flavobacteria we studied have one after the other: First we observed tubes, then regular strings of pearls. The formation of pearls probably results from a twisting of the fatty acid molecules in the cell wall."

Ecologically successful strategy

The flavobacteria examined in this study appear in large numbers in so-called bacterial blooms in the North Sea, which occur after the annual algae spring blooms. They have a special set of enzymes to use laminarin, the storage sugar of the algae. Harder and his colleagues fed the bacteria coloured laminarin to check whether there was an exchange between the pearl chains and the „main cell". And indeed, the dye also appeared in the pearl chains. „We think that enzymes on the surface of the pearl chains capture, hold and break up the laminarin sugar and then deliver it to the cell," Harder explains. It seems to pay. „The mass occurrence of flavobacteria after algal blooms clearly reveals their ecological success."

LAWRENCE -- Courses in introductory physics are required for nearly all university STEM degree programs not only because physics is considered foundational to those disciplines, but also because it provides students practical experience in applied mathematics. The latter is especially true for calculus-based physics courses, which typically provide students their first exposure to using calculus outside of their math classes.

Now, a team of physicists and educators at the University of Kansas has developed a curriculum for college-level students that shows promise in helping students in introductory physics classes further practice and develop their calculus skills, especially those who test lower in core math abilities. They term the approach "energy-first."

Their findings appear in the peer-reviewed journal Physical Review Physics Education Research.

"It's almost always the case that in introductory physics courses students are first taught mechanics in the context of forces. Later in the course, they are shown that they can also apply the concept of energy to solve most of the problems they already learned to solve with forces," said co-author Christopher Fischer, engineering physics director and associate chair of physics & astronomy at KU. "We decided instead we want to teach energy first -- because, number one, we think it's a more generally applicable way of thinking about physics. Number two, it also allows us to achieve our secondary goal of providing the students with more opportunities to use and practice their calculus skills."

From fall 2015 to spring of this year, Fischer and his KU colleagues monitored students and performed testing in two introductory physics classes at KU taken mostly by students pursuing degrees in the physical sciences and engineering. For one, they devised an "energy-first" curriculum. For the other, they kept to a more traditional approach that taught students about forces before teaching them about energy.

The presence of two different physics courses using different curricula naturally provided an opportunity for the researchers to compare the outcomes of students in the two courses.

"We sought to compare, as best we could, apples to apples," Fischer said. "In other words, we compared students who had the same ACT math scores but who took different physics courses to determine what effect our new physics curriculum had on student outcomes."

The researchers worked with the KU Center for Teaching Excellence and the KU Office of Institutional Research & Planning to obtain the students' ACT math scores.

Fischer and his colleagues found engineering students taking the new "energy-first" physics curriculum tended to earn higher grades in subsequent engineering classes (for instance, in a mechanical engineering class for which either of the two introductory physics classes was a prerequisite).

"What we saw was the engineering students who were taking our new physics curriculum did better in their engineering classes," he said.

Furthermore, the biggest benefits to student performance in downstream engineering classes were seen in students who had lower math ACT scores but took the "energy-first" physics class.

"The benefits were even larger the lower your initial math abilities were," Fischer said. "So, engineering students who had lower ACT math scores had larger benefits from taking this new curriculum, which got us thinking maybe tasking students with solving more problems using calculus in this physics class is helping them with their applied math skills in general, as well as their physics skills."

Fischer's KU colleagues on the project from the KU physics & astronomy department were lead author Sarah LeGresley, assistant teaching professor of physics & astronomy; Jennifer Delgado, associate teaching professor; Christopher Bruner, a doctoral student; and Michael Murray, professor of physics & astronomy.

The KU researchers examined how well students had picked up on the physics content by performing more assessments, again finding those in the "energy-first" cohort had the edge over those in the old-style introductory physics class.

"Separately, we did a side-by-side comparison of student performance on a standardized physics conceptual test that many different universities use," Fischer said. "And we saw that all the students in the new physics curriculum are doing better than the students from the traditional physics curriculum."

While these results certainly argue for the adoption of an "energy-first" approach, Fischer stressed because of the small sample size and limited demographics of students at only a single, large Midwestern university, the "energy-first" curriculum would need to be tried out on a broader level before concluding it was a superior method for teaching introductory physics to college-age students.

"We didn't have tens of thousands of students in our study," Fischer said. "We looked at only a few thousand. Thus, it's important that other universities try this new curriculum to see if our results can be replicated. Indeed, we would happily welcome other institutions to collaborate with us to test if our results are robust -- that's essential."

Additionally, the KU researchers hope to develop and implement an assessment to use in physics classes to understand math transference better.

"Is this new way of teaching physics helping students improve their applied calculus skills?" Fischer said. "To our knowledge, no one has built an assessment targeting that specific question. So, we're trying to figure out how to design such an instrument."

Finally, Fischer said the team would like to build off the lessons learned from the implementation of the "energy-first" physics approach to modify the curriculum of other classes in the department.

"Is there a way we could design something similar, or at least take advantage of this sort of design methodology for our department's algebra-based physics classes?" he said. "This naturally also motivates us to reach out to high schools to find collaborators to help us develop new and improved ways of teaching physics in a way that would be more useful for high school students."

The almond tree and the peach tree are two well-known species, since human beings have been eating their fruit (peach) or seed (almond) for thousands of years. Although at first sight the products of these trees may seem to be very different, both species are part of the Prunus genus and are genetically very similar, so much so that they can be crossed and fertile hybrids can be obtained from them. Now, an international team led by researchers of the Centre for Research in Agricultural Genomics (CRAG) has sequenced the genome of one almond tree variety and compared it to the peach tree genome. The detailed comparison of both genomes provides insights into their evolutionary history and reveals the key role played by the genome's mobile elements (also known as transposable elements, or transposons) in the diversification of both species. According to the authors of the paper, the movement of the transposons could lie at the origin of the differences between the fruit of both species or the flavour of the almond.

The knowledge of the almond tree's genome will be a very important tool in the improvement of the species. "For example, this information will enable us to look for more productive and more disease-resistant varieties and also rule out those that bear bitter almonds more easily," explains Pere Arús, an IRTA researcher at CRAG. Arús led the study that is now published in The Plant Journal, and also took part in the international consortium that ultimately sequenced the peach tree genome in 2013.

A common ancestor in the centre of Asia

The comparison of the genome of the 'Texas' almond tree variety ? the sequencing of which involved the team of Tyler Alioto of the Centro Nacional de Análisis Genòmico (CNAG-CRG), part of the Centre for Genomic Regulation (CRG) ? and the peach tree genome places the divergence of both species six million years in the past. The results are consistent with the existing hypothesis that places the existence of a common ancestor of these Prunus species in the centre of Asia and the subsequent separation of both populations that was brought about when the Himalayas massif was lifted. This geological phenomenon would have left both populations of Prunus exposed to totally different climates in which both species would evolve: the almond tree in the arid steppe of the centre and west of Asia and the peach tree in the subtropical climates of the East, in the area that is now South China.

The differentiation: mobile genetic elements

The authors of the paper found, as was to be expected, that the genomes of the almond tree and the peach tree have a high degree of conservation, and they investigated the extent of the differences between them and whether they could be accounted for by the action of the transposons.

Transposons are pieces of DNA with the capacity to change position within a genome and proliferate, jumping from one chromosome to another, and taking up a major part of the genome. In this transposition process, these mobile genetic elements may create mutations or change the genome's local properties, thus affecting gene regulation. There has been a great deal of discussion regarding the utility of these mobile genetic elements since Barbara McClinktock predicted their existence almost 70 years ago and for which she received the Nobel Prize in Medicine and Physiology in 1983.

The results of the analysis of the almond tree and peach tree genomes show that approximately 37% of their genome is comprised of mobile elements and that some of the genes that play a key role in the differentiation of both species are affected by the presence of these elements. "In this study, we discovered that the recent history of the transposons of the almond tree and the peach tree could lie at the basis of many of the important differences between both species," explains Josep M. Casacuberta, a CSIC investigator at CRAG expert in mobile genetic elements and study co-leader. "Although increasingly more studies have demonstrated the key role of the mobile elements in evolution, the comparison of the almond tree and the peach tree, both species with distinct characteristics but with very closely-related genomes, provides unique insights into the impact of the transposons on the initial steps in the separation of the species", continuous Casacuberta.

Key in the eradication of bitter almonds

Most of the Prunus species have a bitter and toxic seed, although there is a group of almond tree varieties that bear a sweet almond, an aspect that has been key in their domestication and their agricultural and economic interest. Previous studies identified certain genes involved in the synthesis of the compound that confers bitterness and toxicity upon these seeds: amygdalin. Now, the CRAG team has discovered that in sweet almond tree crops at least one of these genes involved in the synthesis of amygdalin is affected by transposon insertions, suggesting a key role not only in the diversification of the almond tree and the peach tree, but also in variations within the same species (bitter almond and sweet almond).

26 September 2019 - Seville, Spain The Non-Alcoholic Fatty Liver Disease prevalence in Europe is a preventable epidemic, leading researchers will report at the EASL Non-Alcoholic Fatty Liver Disease (NAFLD) Summit 2019 taking place this week in Seville, Spain.

More than half of adults and one third of children in Europe are classified as overweight or obese, with the highest proportion coming from lower socio-economic groups where NAFLD is prevalent.

NAFLD is the accumulation of excess fat in the liver and is now the most common cause of liver disease in Western countries due to the rapid rise in levels of obesity and type 2 diabetes. It is a major European health burden resulting in liver cirrhosis and liver cancer, as well as big increases in cardiovascular disease and non-liver cancers.

Lack of physical activity and excess calorie intake leads to weight gain and fat deposition, which plays a major role in the development and progression of NAFLD.

"We have reached a tipping point with obesity and NAFLD and swift action is urgently needed by policy makers to reverse the growing epidemic. Obesity is the normal response to an abnormal environment and can only be tackled by addressing the multiple physical, social and economic obesogenic drivers in society." said Philip N. Newsome, Secretary General of the European Association for the Study of Liver Disease (EASL) and also Director of the Centre for Liver and Gastrointestinal Research & Professor of Hepatology at the University of Birmingham.

There is an acute need to improve the diagnostic tools for NAFLD, and EASL is actively supporting several such research projects.

"Meanwhile we need to educate healthcare professionals how to make early diagnoses and implement interventions that can prevent progression to a more advanced disease. We also need to empower patients so they know what steps they can take to reduce their own risk."

"It is clear that many of the causes of NAFLD - sedentary behaviour, excessive energy intake and a poor diet are avoidable. If we are to reduce the incidence of obesity and NAFLD we need to have a significant re-think about the regulations regarding the sale and marketing of sugar products," concludes Newsome.

Sugar-sweetened beverages (SSBs) are one of the largest sources of added sugar with little, if any, nutritional value. Consequently, consumption of SSBs is now one of the leading causes of childhood and adult obesity and is associated with NAFLD and increased liver damage.

EASL has been strongly advocating for the introduction of fiscal measures to discourage the consumption of SSBs and for legislation to ensure that the food industry improves the labelling and composition of processed foods.

Helena Cortez-Pinto, EASL EU Policy Councillor and Professor at the Faculty of Medicine in Lisbon:

"Across the WHO European Region children are regularly exposed to marketing that promotes foods and drinks high in energy, saturated fats, trans-fatty acids, added sugar or salt. Food and beverage advertisements, and in particular those embedded in children's TV programmes, electronic and social media, have been shown to drive consumption of high-calorie and low-nutrient beverages and foods. EASL has argued that public health policy needs to include restrictions on the advertising and marketing to children of SSBs and industrially processed foods high in saturated fat, sugar and salt."

Researchers at the NAFLD Summit will also hear about solutions that include promoting a better diet and physical activity. EASL´s annual International Liver CongressTM taking place in London 15-19 April 2020 will have as its theme "A healthy liver for a healthy you".

"Healthy eating is an important step in the right direction, but this needs to be supported by fiscal measures from governments to encourage behavioural change."

"The Mediterranean Diet, characterised by a high intake of olive oil, nuts, fruits, vegetables and fish, and a low intake of red and processed meat and added sugar, is an effective solution and one that is beneficial in the treatment and also in the prevention of NAFLD," concludes Prof. Cortez-Pinto.