Culture

Trial participants who received a multinutrient formulation over an extended period of time showed a significantly less rapid deterioration in cognitive performance than the patients in a control group, who received only a placebo. These findings are from an ongoing European study LipiDiDiet in which 311 patients in eleven hospitals have been monitored for three years. The research results have been published in the highly ranked international journal 'Alzheimer's & Dementia. The Journal of the Alzheimer's Association' .

The early stages of Alzheimer's disease are characterized by a decline in brain and memory function, with short-term memory loss particularly affected. Patients and their families recognize these symptoms long before dementia occurs. 'By examining the cerebrospinal fluid and by using magnetic resonance brain imaging techniques that can show the hippocampal shrinkage that is so typical of Alzheimer's disease, we are able to identify patients who are at this early (prodromal) stage,' explains Tobias Hartmann, Professor of Experimental Neurology at Saarland University, who coordinates the European LipiDiDiet project. LipiDiDiet is a broad-based, long-term study of over three hundred participants who originally showed initial symptoms of memory impairment. The study was designed to investigate the effects of treating patients with a specially formulated medical food.

The previously published preliminary results showed that this nutrition-based intervention has a positive impact on the progression of the disease. 'But it is only now, after three years of treatment, that we are seeing how extensive the significant differences between trial participants who received the active nutrient drink and those in the control group really are,' explains Hartmann. Participants in the control group were given a placebo drink that was identical in terms of taste, texture and appearance. Neither the patients, nor the doctors and researchers knew who had been given the placebo and who had received the multinutrient drink. 'We found that there was 20 percent less brain shrinkage in patients with Alzheimer's disease who received the nutrient cocktail than in those in the control group, which represents a significant slowing in the rate of brain atrophy. More importantly, we have demonstrated that over the three years of treatment, patients who were given the multinutrient drink suffered between 40 and 70 percent less cognitive impairment than those who received the placebo,' says Hartmann.

'The positive effects of the treatment were most pronounced in those patients who began taking the multinutrient formulation at the earliest prodromal stage of Alzheimer's disease. We were particularly surprised to discover that these positive effects increased the longer treatment continued and that this finding was observed not only with respect to memory, but also with other cognitive abilities,' explains Professor Hartmann. Compared with those in the control group, the subjects who received the multinutrient drink were better able to master typical day-to-day challenges, such as paying a bill, remembering a route or dealing with emergencies.

The multinutrient formulation given to the Alzheimer's patients in the LipiDiDiet study was the commercially available medical food 'Fortasyn Connect', which contains a specific combination of essential fatty acids, vitamins and other nutrients. Specifically, Fortasyn Connect contains docosahexaenoic acid, eicosapentaenoic acid, uridine monophosphate, choline, vitamins B12, B6, C, E, and folic acid, phospholipids and selenium. Earlier preclinical research by the LipiDiDiet consortium and other laboratories, such as the Massachusetts Institute of Technology (MIT), has shown that these nutrients can reduce a number of the changes typically seen in the brains of Alzheimer's disease patients. Subsequent clinical studies demonstrated positive results from memory and EEG measurements that indicate increased brain activity in the trial participants that were given the nutrient drink.

Globally, around 47 million people are currently suffering from Alzheimer's disease or a similar neurodegenerative dementia, for which there is at present no known cure. Over the next 20 years, scientists expect this number to double, with forecasts suggesting that there will be around 130 million sufferers in 2050. 'Despite significant research efforts, we still do not have any medications that can cure early-stage Alzheimer's disease. Some of these drugs are able to provide temporary relief for certain symptoms, but after a while the patients usually return to their earlier pre-treatment state. In light of this, the positive effects that we have been able to achieve with our special multinutrient drink are a major success. Our hope is that the significantly slower progression that we see in our patients will continue so that they can maintain their independence well into old age,' says Tobias Hartmann.

CABI scientists have led new research which reveals strong evidence that a natural enemy of the prolific Asian fruit fly Drosphila suzukii - previously believed to be one species - is in fact two with only one of the parasitoid proving suitable as a biological control agent against the pest.

The scientists from CABI's Swiss Centre Delémont, as well as colleagues from INRAE in France, used a combination of molecular analysis and crossing experiments to gather evidence that Ganaspis brasiliensis is a complex of at least two cryptic species.

The study published in the journal Scientific Reports demonstrates with complimentary behavioural experiments that individuals from one genetic group readily parasitized several drosophila species regardless of their food source while individuals from the other one was almost exclusively specific to larvae feeding in ripening fruits.

Dr Lukas Seehausen, lead author of the study said, "Because only D. suzukii attacks ripening fruits in its area of invasion, parasitoids from this second group appear to be well suited as a biological control agent. Our study demonstrates the need for a combination of biosystematics with biological and ecological investigations for the development of safe and efficient biological control programs."

Drosophila suzukii is a frugivorous insect native to Eastern Asia that was accidentally introduced to the Americas and Europe in the 2000s, where it rapidly spread. Unlike sympatric Drosophila species in invaded areas, D. suzukii females are able to lay eggs inside unwounded ripening fruits due to their sclerotized serrated ovipositor, providing it with a unique niche virtually free from competition.

Other biological factors that facilitated the invasion are its broad host range that includes many crops and non-crop fruits as well as the absence of coevolved natural enemies able to control the fly in its invasive range.

The resulting high abundance of D. suzukii is leading to extensive damage, making it a major problem for fruit growers, especially in the soft fruit industry where it favours over 150 wild and cultivated fruits including cherries, blueberries and strawberries, as well as the fruits of ornamental plants.

Due to the high abundance of G. cf. brasiliensis and importance as a mortality factor of D. suzukii in Asia, this wasp has been repeatedly suggested as a biological control agent against D. suzukii. However, uncertainties concerning its taxonomic status and degree of specificity have so far cast doubt on its suitability for classical biological control.

Dr Seehausen added, "The discovery that G. cf. brasiliensis might be a species complex of at least two congeneric species and that one of them can clearly be associated with a higher habitat specificity to fresh fruits, shows the suitability of G. cf. brasiliensis for importation as a biological control agent and allows us to focus on that group for efforts to develop a classical biological control program against D. suzukii."

As part of the research the scientists recommend that the distribution of G. cf. brasiliensis in Asia should be assessed accurately to find out if this parasitoid is well adapted to temperate climates and can therefore successfully establish as a biological control agent against D. suzukii in temperate regions of Europe and the Americas.

"Integrated biosystematic studies play a crucial role in matching natural enemies with their hosts and are thus important to increase the efficacy in finding suitable candidates for classical biological control against invasive pests," Dr Seehausen said.

Nurses and other healthcare providers should talk to patients about their cannabis use the same way they talk about other habits like smoking and drinking: routinely and without judgment.

That should happen, but too often doesn't, said Marian Wilson, registered nurse and associate professor at the Washington State University College of Nursing. She is the lead author on a paper published recently in the journal Pain Management Nursing about
shared decision-making in talking about cannabis use.

"We want this paper to guide providers in how they can start opening up this conversation and normalizing it," Wilson said.

The shared decision-making model starts with either the patient or the provider bringing up the topic of cannabis use, then moving on to specifics about that patient's situation, benefits, and risks of cannabis use based on research and evidence, and finally formulating a plan.

"Central to patient-centered conversations is understanding the top priorities of patients," Wilson writes. "Researchers have suggested that clinicians should ask 'What matters to you?' as well as 'What is the matter?'"

Some studies have suggested cannabis use is beneficial to patients with chronic pain who are also using opioids, so many in that patient population are using cannabis or considering it, Wilson said. That's why it's especially important for providers working in pain management to discuss the subject, though patients may be reluctant to disclose cannabis use because they might have been penalized in the past.

Wilson says providers face real challenges in obtaining current, evidence-based information on the benefits and risks of cannabis use. The paper calls for the creation of a centralized, noncommercial, scientific repository of information, research, and best practices on cannabis use. Such a resource will become more important as cannabis legalization spreads nationwide.

"We want providers to ask people about their cannabis use and we want patients to feel comfortable talking about it, but right now many don't," Wilson said.

Tsukuba, Japan - Social rewards such as praise are known to enhance various stages of the learning process. Now, researchers from Japan have found that praise delivered by artificial beings such as robots and virtual graphics-based agents can have effects similar to praise delivered by humans, with important practical applications as social services such as education increasingly move to virtual and online platforms.

In a study published this month in PLOS ONE, researchers from the University of Tsukuba have shown that motor task performance in participants was significantly enhanced by praise from either one or two robots or virtual agents.

Although praise from robots and virtual agents has been found to enhance human motivation and performance during a task, whether these interactions have similar effects on offline skill consolidation, which is an essential component of the learning process, has not been investigated. Further, the various conditions associated with the delivery of praise by robot and virtual agents have not been thoroughly explored previously. The researchers at the University of Tsukuba aimed to address these questions in the present study.

"Previous studies have shown that praise from others can positively affect offline improvements in human motor skills," says first author Masahiro Shiomi. "However, whether praise from artificial beings can have similar effects on offline improvements has not been explored previously."

To examine these questions, the researchers asked participants to learn a finger-tapping task under several different conditions, which varied in terms of the timing and frequency of praise, the number of agents, and whether the agents were physically present or presented on a screen. The participants were then asked to repeat the task on the following day, and task performance was compared between the two days.

"We found that praise led to a measurable increase in task performance, indicating increased offline consolidation of the task," explains Professor Takamasa Iio. "Further, two agents led to significantly greater participant performance than one agent, even when the amount of praise was identical."

However, whether the praise was delivered by physical robots or by virtual agents did not influence the effects.

"Our study showed that praise from artificial beings improved skill consolidation in a manner that resembled praise delivered by humans," says first author Masahiro Shiomi. "Such findings may be useful for facilitating learning in children, for instance, or for exercise and rehabilitation applications."

Future work could consider the effects of praise delivered in different environments, for instance, in a VR environment, as well as the effects of greater numbers of agents. A greater understanding of the factors that influence the social effects of robot behavior is essential for improving the quality of human-robot interactions, which are increasingly an important element of education, services, and entertainment applications.

A simple COVID-19 test kit combines virus amplification with a CRISPR-Cas system for effective SARS-CoV-2 detection. The kit, called iSCAN, uses reagents that can be locally manufactured.

"Our whole iSCAN procedure can be completed in less than an hour and can be easily adopted as a point-of-care detection system at airports and borders," says KAUST Ph.D. student Ahmed Mahas.

The current gold standard in SARS-CoV-2 testing is the PCR test, in which DNA primers recognize specific RNA sequences in the viral genome that are then copied using a specific enzyme. This "amplification" process makes it easier to detect the originally small amounts of viral RNA present in the nasopharyngeal swabs taken from patients. This test can reliably detect if a person really has the virus without providing too many false positive or negative results. But it needs highly skilled personnel to conduct the test, which is done in multiple steps in central laboratories with sophisticated equipment.

iSCAN, developed by a team led by KAUST bioengineer Magdy Mahfouz overcomes many of the disadvantages of the PCR test while providing relatively trustworthy results.

Significantly, the test's reagents were manufactured at KAUST. This includes the enzymes needed for amplification and another enzyme that specifically detects viral sequences within the copied material. The availability of reagents and equipment has been a huge obstacle since the start of the COVID-19 pandemic.

To use iSCAN, the contents from a patient's sample, collected with a nasopharyngeal swab, are placed in a small test tube containing the DNA primers and enzymes that can amplify SARS-CoV-2 genetic material. The contents are incubated at a temperature of 62 degrees Celsius for half an hour. This process is referred to as RT-LAMP. Once enough viral RNA is amplified, a droplet containing the enzyme Cas12 is added to the mix and left for another 15 minutes. This enzyme only recognizes viral RNA belonging to SARS-CoV-2, overcoming an issue with RT-LAMP, where false amplification and cross-contamination can be a problem.

Finally, one of two methods can be used to visualize the result. One involves shining ultraviolet light on the sample, with a detector analyzing the light coming out from it to report the amount of viral RNA. The other approach involves inserting specially designed strips into the tubes, similar to those used in pregnancy tests. Both approaches work well, although the ultraviolet light method provided more accurate results.

The scientists tested their kit on synthesized viral RNA and on real patient samples. "We are now improving and simplifying our system for users in order to commercialize our iSCAN detection kit," says KAUST research scientist Zahir Ali.

University of Adelaide wine researchers are developing a fast and simple method of authenticating wine - a potential solution against the estimated billions of dollars' worth of wine fraud globally, but also offering a possible means of building regional branding.

The team of scientists were able to identify the geographical origins of wines originating from three wine regions of Australia and from Bordeaux in France with 100% accuracy with a novel technique of molecular fingerprinting using 'fluorescence spectroscopy', a technology that analyses fluorescence of molecules.

"Wine fraud is a significant problem for the global wine industry, given a yearly economic impact within Australia alone estimated at several hundred million dollars, and globally thought to be in the billions of dollars," says Ruchira Ranaweera, PhD student in the University's Waite Research Institute, who conducted the research.

"Wine authentication can help to avoid any uncertainty around wine labeling according to origin, variety, or vintage. The application of a relatively simple technique like this could be adapted for use in the supply chain as a robust method for authentication or detection of adulterated wines."

The researchers looked at Cabernet Sauvignon ¬- a globally important grape variety and the second most planted in Australia - from three different wine regions of Australia and Bordeaux in France, the birthplace of Cabernet Sauvignon.

The research has been published in the journal Food Chemistry and was supported by Wine Australia and the Australian Government, the Waite Research Institute and industry partners through the ARC Training Centre for Innovative Wine Production.

The researchers compared an existing approach for authentication, which involves measuring elements in wine samples using 'inductively coupled plasma-mass spectrometry' (ICP-MS), with the more simple, rapid and cost-effective fluorescence spectroscopy technique.

"This method provides a 'fingerprint' of the samples according to the presence of fluorophoric or light-emitting compounds," says Ms Ranaweera. "When used in combination with a robust data analysis using a particular machine learning algorithm, it is proving to be a powerful technique for authentication."

In every wine they tested using the novel combination of fluorescence spectroscopy with machine learning-driven data analysis, they were able to correctly allocate the wine to region with the fluorescence data but not with elements determined by ICP-MS.

There are other useful applications of this technology for the wine industry that are available now or in the pipeline, such as phenolic and wine colour analysis, and smoke taint detection.

Project leader Associate Professor David Jeffery, from the Waite Research Institute and the ARC Training Centre for Innovative Wine Production, says they hope ultimately to identify specific chemical markers that help discriminate between wine regions.

"Other than coming up with a robust method for authenticity testing, we are hoping to use the chemical information obtained from fluorescence data to identify the molecules that are differentiating the wines from the different regions," Associate Professor Jeffery says.

"This may help with regional branding, by understanding how their wines' characteristics are influenced by the region and how they differ from other regions."

Tokyo - Why did Japan largely contain COVID-19 despite famously jam-packed Tokyo and despite the country's proximity to China? With no penalties and only requests for cooperation, Japan's state of emergency somehow averted the large-scale outbreaks seen elsewhere. At least one viable answer has now emerged.

A new comparative analysis of people's mobility during the virus' first wave illustrates how drastically the Tokyo masses slowed. That slowdown may have throttled the spread of infections.

In a study from The University of Tokyo Institute of Industrial Science, researchers examined location data from more than 200,000 mobile phone users. Using these data, the researchers calculated the human movement in Tokyo before and during the state of emergency. The striking findings were published in Scientific Reports.

"Using anonymized data that represented about 2% of the population, we could compute human movement and contact rates at a 100-meter grid-cell scale," study first author Takahiro Yabe says. "We found that 1 week into the state of emergency, human mobility reduced by 50%, which led to a 70% drop in social contacts."

Less contact implies less disease spread.

Japan declared its state of emergency on April 7, followed by a gradual series of requests to close businesses and work from home, along with aggressive travel entry restrictions. However, under Japanese law, a mandatory lockdown could not be implemented or enforced.

The data spanned from January to April. A look at the major hub train stations around central Tokyo, including Shinjuku Station, the world's busiest, finds April 14 in Tokyo had 76%-87% fewer visits compared with pre-crisis January.

The researchers also analyzed how much and how far people in greater Tokyo traveled, with both showing around a 50% reduction. In other words, people moved less and stayed nearer to home. Social contact could also be computed based on people's spatial proximity. That, too, was substantially reduced, nearly to the 80% reduction level the government had targeted. The decline trends generally corresponded with governmental requests for people to do remote work, for school closures, and the actual state of emergency.

Going a step further, the study paired socioeconomic data with the mobility results. This showed those with higher income were more capable of reducing social contact and, consequently, lower the chance of COVID-19 transmission. Finally, the study put the mobility data against the estimated effective reproduction number, a key statistic estimating how many cases one infection can cause. This validated how the reduced contact also was likely to reduce infections.

"With a noncompulsory and nonpharmaceutical intervention, Tokyo had to rely on citizens' cooperation. Our study shows they cooperated by limiting their movement and contact, subsequently limiting infections," study co-author Yoshihide Sekimoto explains. "These findings offer insights that policymakers can apply when estimating necessary movement restrictions."

Amid the complex human and environmental dynamics behind fighting the spread of COVID-19, there is now stronger evidence that staying home and maintaining distance really work.

HANOVER, N.H. - November 5, 2020 - The biological clock of a popular food crop controls close to three-quarters of its genes, according to research from Dartmouth College.

The genetic research shows how the crop uses internal responses to the day-night cycle—known as circadian rhythms—to regulate processes such as reproduction, photosynthesis and reactions to stressful conditions.

The study, published in the journal eLife, can help researchers target genes to improve growth and stress resilience when a plant is moved to a new region or encounters changing climate conditions.

"As plants are cultivated in new geographic zones they must select traits that enable them to survive in different conditions," said C. Robertson McClung, a professor of biology at Dartmouth and senior researcher on the study. "Many of these traits are in circadian clock genes."

Like animals, plants have biological clocks that allow them to adapt to predictable changes, such as day-night cycles or the shift in seasons. While animals can relocate to adapt to such environmental changes, plants are stuck in place. To survive, plants need to activate and deactivate genes to alter their biological functions.

The research team used RNA-sequencing to identify how genes in the popular crop Brassica rapa are controlled by the plant's internal time-keeping mechanism. The B. rapa species includes varieties such as turnips, oilseed, Chinese cabbage and leafy vegetables.

In the study, plants were exposed to normal conditions featuring warm days and cool nights. They were then removed from this environment and sampled over a two-day period to reveal which genes were active in response to signals from the plant's internal clock.

The research found that over 16,000 genes, about three-quarters of all of the plant's genes, are regulated by circadian rhythms in the absence of light and temperature changes.

"We were surprised to find that such a high number of genes are regulated by the biological clock. This emphasizes the importance of circadian clock control of many functions within the plant," said McClung.

Many crop plants, such as wheat, potatoes and Brassica, have doubled or tripled their complete complements of genes. This led researchers to question what effect the additional gene pairs have on the plant's biological clock, or on survival processes such as resilience to drought.

The research team found that the extra gene copies are often active at different times of day from their gene pairs.

In addition, the researchers found that often only one member of a pair of duplicated genes responded to drought. In both these cases, the differences in timing of gene activation, or in drought-responsiveness, must have occurred after the genes had duplicated.

The findings lead to the conclusion that the same gene duplication that is responsible for a more sensitive biological clock also creates more drought resistance.

"During the evolution of land plants, the number of gene pairs expanded," said Kathleen Greenham, an assistant professor of plant and microbial biology at the University of Minnesota who co-led the study as a postdoctoral researcher at Dartmouth. "One set of copies can maintain critical growth processes while the others are free to evolve new functions that researchers can use to produce stress-resilient crops."

Identifying the differences within gene pairs that cause them to be responsive or non-responsive to drought conditions could give researchers a way of helping plants increase resilience to climate-induced changes.

"Time of day matters for gene expression when it comes to dealing with drought," said Ryan Sartor, a postdoctoral researcher at North Carolina State University who co-led the study. "This is an early step to help understand basic relationships. A more complete understanding of this complex system could lead toward the development of more stress-resistant crops."

According to the research team, the circadian rhythms that regulate much of plant biology are likely to be influenced by climate change since environmental cues become less reliable. This makes it harder for plants to adapt and survive, but it also serves as a clue for researchers searching for ways to build plant resilience.

Researchers at the Hong Kong University of Science and Technology (HKUST) have identified new therapeutic targets for Alzheimer's disease (AD) by studying the patients' brain with a newly-developed methodology. This novel approach also enables researchers to measure the effects of potential drugs on AD patients, opening new directions for AD research and drug development.

Although the pathological mechanisms of AD have been studied for decades, the disease remains incurable. One reason is that conventional research approaches have limited capability to identify molecular targets for drug development. Molecular and pathological pathway analysis generally examines AD patients' brain as a single unit, which usually underestimates the contributions of different brain cell types to AD and any abnormalities in them. This is especially the case with less-common cell types such as microglia (the brain's resident immune cells) and neurovascular cells (specifically endothelial cells), which only account for less than 5% and 1% of the total brain cell population, respectively.

However, a team led by Prof. Nancy Ip, Vice-President for Research and Development, Director of the State Key Laboratory of Molecular Neuroscience, and Morningside Professor of Life Science at HKUST, has more than circumvented this problem--they have also identified several new potential molecular targets in endothelial cells and microglia for AD drug development.

The team examined the functions of specific cell types in the postmortem brains of AD patients, which is typically impossible with conventional approaches, by using cutting-edge, single-cell transcriptome analysis, which can be used to characterize of the molecular changes in single cells. This yielded a comprehensive profile of the cell-type-specific changes in the transcriptome in the brains of AD patients. Subsequent analysis identified cell subtypes and pathological pathways associated with AD, highlighting a specific subpopulation of endothelial cells found in the brains' blood vessels. Accordingly, the team discovered that increased angiogenesis (the formation of new blood vessels from current ones) and immune system activation in a subpopulation of endothelial cells are associated with the pathogenesis of AD, suggesting a link between the dysregulation of blood vessels and AD. The researchers also identified novel targets for restoring neural homeostasis (the ability to maintain a relatively stable internal state despite external changes) in AD patients.

The team also leveraged their single-cell transcriptome analysis to study the mechanism by which the cytokine interleukin-33 (IL-33), an important protein for immune signaling, exerts beneficial actions, making it a possible AD therapeutic intervention. The researchers found that IL-33 reduces AD-like pathology by stimulating the development of a specific subtype of microglia that helps clear amyloid-beta, a neurotoxic protein found in AD brains. The team is also the first to capture data on the mechanisms by which microglia transform into an amyloid-beta-consuming phagocytic state, which is a major cellular mechanism for the removal of pathogens.

"The complex and heterogeneous cell composition within the brain makes it difficult to study disease mechanisms," Prof. Ip explained. "The advancement of single-cell technology has enabled us to identify specific cell subtypes and molecular targets, which is critical for developing new interventions for Alzheimer's disease."

The team has recently published their work in the prestigious scientific journals Proceedings of the National Academy of Sciences U S A (PNAS) and Cell Reports.

AD, the predominant form of dementia, currently affects over 50 million individuals worldwide and is projected to afflict 150 million people by 2050. Its pathological hallmarks include the accumulation of extracellular amyloid-beta depositions and neurofibrillary tangles. Over time, ineffective clearance of these pathological hallmarks leads to cellular dysfunction in AD, resulting in memory loss, communication problems, reduced physical abilities, and eventually death.

A new study from the University of Eastern Finland shows that individualised and family-based physical activity and dietary counselling considerably slows down the development of insulin resistance, which is a precursor of type 2 diabetes, in 6-9-year-old children. Published in Diabetologia, the study focused on predominantly normal-weight children.

Insulin resistance refers to the body's weakened metabolic response to insulin in the target tissues, i.e. in skeletal muscles, adipose tissue and the liver. Insulin resistance is usually the first sign of disturbed glucose metabolism, developing much earlier than abnormalities in pancreatic insulin secretion, elevated glucose levels and, eventually, type 2 diabetes. Earlier studies have shown that physical activity and dietary counselling reduces insulin resistance in overweight and obese children. This new study from the University of Eastern Finland is significant not only scientifically, but also in terms of public health and clinical practice, because it is the first to show that a combination of physical activity and dietary counselling can be used to slow down the long-term development of insulin resistance in children who were predominantly normal-weight at baseline.

More than 500 Finnish children aged between 6 and 9 years at baseline participated in the Physical Activity and Nutrition in Children (PANIC) study ongoing at the University of Eastern Finland. Children and their caregivers in the intervention group were given individualised and family-based physical activity and dietary counselling over a period of two years. Children and their caregivers in the control group, on the other hand, were given instructions on physical exercise and nutrition as per the national guidelines, but no actual lifestyle counselling. At baseline and two years later, the researchers analysed children's physical activity and sedentary behaviour using the Actiheart sensor that measures heart rate and body movements. Physical activity was also assessed by the PANIC Physical Activity Questionnaire, and dietary factors were assessed by a 4-day food record over four days. Children's body fat percentage and lean body mass were measured by dual-energy x-ray absorptiometry, DXA. Fasting serum insulin and HOMA-IR were used as indicators of insulin resistance.

The study showed that during the two-year follow-up, increase of insulin resistance was roughly 35% lower in the group that was given individualised and family-based physical activity and dietary counselling than in the control group. The attenuating effect of counselling on insulin resistance was explained especially by changes in physical activity and sedentary behaviour, and slightly less by changes in overall dietary quality and in the consumption of high-fat spreads. Counselling did not have an effect on body fat percentage or lean body mass, i.e. changes in body composition did not mediate the beneficial effect of intervention on insulin resistance.

"This is an interesting finding. The attenuating effect of physical activity and dietary counselling on insulin resistance in children is likely caused by the fact that physical activity and a healthy diet boost metabolism in skeletal muscles, adipose tissue and in the liver, and not so much by a lower body fat percentage or lean body mass," Professor Timo Lakka, the lead author of the study, says.

Although type 2 diabetes usually develops in adulthood, research suggests that its prevention is best begun already in childhood.

"Increasing physical activity, reducing sedentary behaviour and eating food of better quality should be a priority for all children, not just for those who are overweight," Professor Lakka points out.

Professor Lakka points out that in addition to body composition measurements, all children should also be asked about their physical activity, sedentary behaviour and diet when they visit a child health clinic or a school nurse.
"Identifying children who have unhealthy lifestyle habits and who are at an increased risk of type 2 diabetes in adulthood would allow a better targeting of measures that are geared towards preventing type 2 diabetes. The best way to collect lifestyle-related data is to use scientifically validated, well-proven digital applications. This would allow the data to be optimally used for promoting children's health and well-being, and for making scientifically informed decisions," Professor Lakka says.

For the first time, researchers have compared air pollution in urban and suburban areas across all of China. Using data from the China National Environmental Monitoring Center (CNEMC), the researchers found that one air pollutant, called particulate matter (PM2.5), may be overestimated in winter, while another pollutant, called ozone (O3), is significantly underestimated.

They published their results in the peer-reviewed journal Advances in Atmospheric Sciences (https://doi.org/10.1007/s00376-020-0054-2).

"Since the urban region accounts for only 2% of the whole country's area, the urban-dominant air quality data from the CNEMC network may overestimate winter PM2.5 but underestimate winter O3 over the vast domain of China," said paper author Xu Yue, professor at Nanjing University of Information Science & Technology. "The study suggests that the CNEMC monitoring data should be used with caution for evaluating chemical models and assessing ecosystem health, which require more data outside urban areas."

Both PM2.5 and Ozone are respiratory hazards and can be detrimental to human and animal health, as well as ecosystems.

"The differences between urban and non-urban areas, such as the intensity of human and plant activities, can lead to differences of ozone and PM2.5 concentrations between land types," Yue said. "Our study tries to answer the question: How different is the air pollution between urban and non-urban areas in China?"

The researchers examined air quality data from 1,171 urban and 110 suburban sites built by the CNEMC during an observational period from 2015 to 2018. "The pattern whereby the non-urban ozone concentrations and the urban PM2.5 level are higher dominates across time and space," Yue said. "Such contrast is significant in winter but insignificant in summer."

Since most of the data is available from urban sites, it does not likely apply uniformly across the rest of the country, according to Yue. This can be problematic when it comes to designing efforts to improve pollution and conserve plant life in suburban or rural areas.

"We suggest that more nonurban sites are necessary to build for better representation of air pollution level over the vast domain in China," Yue said. Ultimately, the researchers plan to improve their analysis model to achieve the most accurate estimation of air pollution impacts on ecosystem functions in China.

Plants can be infected by multiple viruses at once. However, the composition of the pathogen community varies, even if individuals belong to the same species and the same population. Ecologists at the University of Zurich have now shown that these differences are primarily due to genetic variation among the hosts. The loss of genetic diversity could thus render species more vulnerable to infections and extinction.

Viruses are ubiquitous across the plant and animal kingdoms - but most of them are still unknown to science. Researchers have only recently developed improved analysis techniques and statistical tools to tackle one of the key questions: Why are some individuals more susceptible to viruses, while others remain unharmed?

Combination of pathogens is important

It is already known that genetic differences can make animals or plants more resistant to a specific virus. However, it is becoming increasingly clear that most organisms do not only harbor one kind of pathogen but complex communities made up of different microbes. "Accounting for this diversity of infection is necessary to understand and predict disease dynamics and costs of infection for the host," says Professor Anna-Liisa Laine from the Department of Evolutionary Biology and Environmental Studies at the University of Zurich. For example, the first arriving pathogen could confer resistance to a second pathogen. But so far, little is known about the factors that shape the composition of virus communities.

With her research team at the Universities of Zurich and Helsinki, Laine has now shown that genetic differences have a major impact on the diversity of the virus community each individual supports. "This suggests that depletion of genetic diversity within a species can have significant consequences for the risk of virus infection," says Laine.

Identical plants in different environments

For their study, the team used the common weed Plantago lanceolata, also known as ribwort plantain. Individuals of this plant can be cloned by propagation of the roots - resulting in genetically identical offspring. With this method, the researchers generated 80 clones from each of four different genetic variants of ribwort plantain and placed them among populations of naturally occurring ribwort plantain at four locations in the Åland archipelago in the Baltic Sea. The cloned plants were thus exposed to virus attacks under natural conditions. "By placing identical plants in different environments and keeping everything else constant, we could rigorously test the role of genetics," explains Laine.

After two and seven weeks respectively, the researchers collected leaves and determined which of five frequently occurring plant viruses had infected the clones. They found that about two thirds of the plants were infected with at least one virus, while almost a quarter of those carried multiple viruses. Altogether, they found 17 different combinations, ranging from two to five viruses per plant.

Hereditary factors most significant

Sophisticated statistical modelling then allowed the researchers to discern how strongly the various factors ? genetics, location, plant size, damage by herbivores and interaction among the viruses - influenced the composition of the virus communities. The results revealed that host genetic differences explained most of the observed variation. "Although we had suspected that genotype would play a role, we were very surprised that it turned out to be the most important determinant," says Laine. Another important factor was the local environment, whereas others such as plant size and herbivores showed only minor effects.

"This demonstrates for the first time that genetic differences, most likely in immunity genes, are critical for how these diverse pathogen communities assemble inside hosts," says Laine. "One of the next steps will now be the identification of the underlying genes."

Genetic diversity makes species stronger

The results highlight the importance of genetic diversity within species. The loss of diversity makes species much more susceptible to virus infections, with far-reaching consequences for biodiversity. The genetic diversity of natural populations is already being increasingly depleted due to human destruction of natural habitats.

According to Laine, these findings could also be applied in agriculture to improve pathogen resistance in crop plants: "Incorporating genetic diversity to crop systems should be embraced as a sustainable means of controlling disease in agriculture. Not only individual pests, but entire communities of pathogens."

An analysis of aging in Down syndrome and hypercholesterolemia mouse models has suggested that a Down syndrome-associated gene, DSCR-1, protects against abnormal vascularization of the cornea and associated corneal opacity (blindness) by suppressing oxidized LDL cholesterol production and new downstream angiogenic signaling in patients with chronic high cholesterol. Epidemiological data suggests that, while the neurological pathology of Down syndrome patients worsens with age, they are also less susceptible to age-related vascular diseases. The responsible genes and mechanisms have not yet been clarified, but DSCR-1 appears to be a strong candidate for a wide range of vascular diseases, such as atherosclerosis and hypertension.

Down syndrome, the most common congenital disease in human genetics, has seen dramatic increases in longevity with advances in modern medicine. Unfortunately, new problems associated with this increased longevity have emerged, such early Alzheimer's, reduced vision, and muscle weakness. However, unlike the nervous system, the vascular system in Down syndrome patients is very resistant to aging pathologies like solid cancers (as opposed to blood cancers such as leukemia), atherosclerosis, hypertension, and Kawasaki disease--a systemic vasculitis that some researchers say has a connection to SARS-CoV-2, the virus that causes COVID-19. It has therefore become important to conduct comprehensive genomic and pathological analyses, including secondary analyses of gene expression on Down syndrome chromosomes and changes due to different chromosome numbers, to determine its cause.

Down syndrome occurs when there is an extra chromosome 21 instead of the usual two. DSCR-1 is located on chromosome 21 and suppresses signals related to angiogenesis. A research group based in Kumamoto University (Japan) crossed hypercholesterolemia (ApoE-deficient) mice with those that highly expressed DSCR-1 and those that were DSCR-1-deficient to analyze the effects of aging. By examining the pathological signals produced by high cholesterol, they hoped to determine why corneal opacity (prominent in ApoE deficiency) is protected against by high DSCR-1 expression and exacerbated by DSCR-1 deficiency.

DSCR-1-deficient mice showed slight age-related corneal opacity, which was dramatically exacerbated when crossed with ApoE-deficient mice, and increased corneal inflammation. DSCR-1 protects postnatal homeostasis based on its inhibitory and antioxidant effects on the NFAT transcription factor--a major factor in the development of Down syndrome. DSCR-1 deficiency results in the abnormal activation of NFAT and the signal transduction function of SDF-1 and its receptor CXCR4, which has an angiogenic effect in peripheral blood vessels. This results in increased angiogenesis and lymphangiogenesis in the corneal area.

Researchers further clarified that DSCR-1 deficiency increases oxidized LDL cholesterol which, in turn, increases SDF-1 production in the endothelium and the production of the angiogenesis-promoting factor VEGF in infiltrating macrophages, thus resulting in pathological angiogenesis (and clouding) in the cornea. This condition was greatly alleviated by the administration of antibodies that neutralize the function of SDF-1.

"This study shows that, in addition to suppressing cancer growth and cytokine storms in sepsis, DSCR-1 may have a protective effect on pathological angiogenesis under high cholesterol conditions," said study leader, Professor Takashi Minami. "We have also obtained data on NFAT/DSCR-1 signaling in patients with human corneal lesions, suggesting that drugs that block NFAT and its downstream SDF-1 function may be effective in protecting against age-related vascular disease."

Researchers from the Universities of Melbourne, York, Warwick and Oxford have shed light on how encapsulated viruses like hepatitis B, dengue and SARS-CoV-2 hijack the protein manufacturing and distribution pathways in the cell - they have also identified a potential broad spectrum anti-viral drug target to stop them in their tracks.

The findings have been published in PNAS today and are important to efforts to develop broad-spectrum antiviral agents.

Professor Spencer Williams from the School of Chemistry at Bio21 said the research will help define a new 'host-directed' approach for treating infections by encapsulated viruses.

"One approach to treating viral infections is to make a new drug for each virus that comes along. But it is slow. An alternative and attractive approach is to make a drug against a human target that viruses need to replicate. The same drug can then be used and reused against many different viruses, even ones that have yet to emerge," he said.

The findings result from work by Professor Gideon Davies and his UK team who clarified how the structure of the catalytic domain of human enzyme that trims sugar molecules from proteins during their production and Professor Williams' and his Bio21 team, who developed a series of inhibitors to block the enzyme.

When tested in human cell lines, these inhibitors where shown to reduce infection in dengue viruses.

"Encapsulated viruses tend to harness the 'glycosylation' step of protein production, whereby glycans, or sugar molecules coat newly assembled proteins," said Professor Williams.

"The sugar molecules provide instructions for proteins to fold into their correct 3D structure as well as transport instructions for the protein to be brought to its next destination within the cell. Glycosylation is facilitated by various enzymes that synthesize, trim, check and modify these sugar molecules."

Our body's cells contain around 42 million protein molecules. Protein production is a complex, multi-step process within the cell. Like products on a factory assembly-line, all proteins pass through 'quality control' check points where they are inspected before they are transported to their destination, to carry out their functions.

Viruses are not living organisms, but biological programs encoded in ribonucleic acid (RNA) or deoxyribonucleic acid (DNA).

They come to life when they enter a living cell and hijack the protein production systems. Viruses use the cell's machinery to copy their DNA or RNA (in the case of SARS-CoV2, it's RNA) and to produce the proteins they need to make copies of themselves.

The viral proteins produced in an infected cell undergo the 'glycosylation' and then pass through the quality control steps, which involves 'trimming' by an enzyme called 'MANEA'.

"Trimming is a crucial quality control step and when it does not occur, client proteins are marked for degradation. MANEA represents a key target for broad spectrum drug development against encapsulated viruses, as inhibitors will trigger destruction of their proteins," said Professor Davies.

Because viruses hijack this unusual biosynthetic pathway, it makes it a good potential drug target.

Researchers at the University of Warwick and University of Oxford studied the effect of the best inhibitors on viral replication.

Musculoskeletal disorders--which affect muscles, tendons, ligaments, bones, and joints--can severely affect individuals' physical and mental health, and they're especially prevalent among aging adults. Although many researchers are studying these conditions and their rates in different regions of the world, no study to date has provided an overview of the burden of all musculoskeletal disorders. Investigators have now done so in Arthritis & Rheumatology, an official journal of the American College of Rheumatology.

For the analysis, researchers examined data from the Global Burden of Disease Study 2017, which assessed the extent of diseases and injuries across 21 regions and 195 countries and territories from 1990 to 2017. Musculoskeletal disorders included rheumatoid arthritis, osteoarthritis, low back pain, neck pain, gout, and related conditions.

The team found that there were approximately 1.3 billion prevalent cases and 121,300 deaths due to musculoskeletal disorders in 2017, as wells as 138.7 million disability-adjusted life years, or the number of years lost due to ill-health, disability, or early death. The burden of these diseases generally increased with age for both sexes, was more prevalent among females, and was higher in developed countries.

"Our study describes the enormous global burden of disability from musculoskeletal conditions in a single paper," said senior author Rachelle Buchbinder, MD, of the Cabrini Institute and Monash University, in Australia. "These conditions are under-recognized despite their enormous costs to individuals, the economy, and the health system. Also, there has been a lack of any significant decline in the burden from these conditions over time, which means that there is still insufficient emphasis on addressing the problem."

Dr. Buchbinder noted that policy makers must be made aware of the size of this growing problem, especially in light of rapidly aging populations around the world. "A global response is needed, and this should be integrated with other strategies that can address some of the modifiable and important risk factors of musculoskeletal disorders, including obesity, poor nutrition, smoking, and sedentary lifestyles," she said. "As well, there should be an emphasis on reducing low-value care for some of the most burdensome conditions such as low back pain and osteoarthritis that is contributing to the problem."

The authors also stressed the need for standardized methods for collecting data on the prevalence and impact of musculoskeletal disorders across the world.