Culture

New research from the University of Virginia School of Medicine is shedding light on the development of the brain's immune defenses - and how those defenses respond to strokes that strike one in 4,000 babies in the first month of life.

The brain's frontline defenders are immune cells known as microglia. These cells make up 10%-15% of all cells found in the brain. But their origins have been hotly debated. UVA's Chia-Yi "Alex" Kuan, MD, PhD, has discovered that many were previously white blood cells known as monocytes. During brain development - and in response to infant strokes - the monocytes undergo an amazing conversion into troops to defend the brain.

"Most people believe that blood monocytes only come into the brain after injury to provoke damage, and then they either die or leave the brain. Some even say monocytes and microglia live in parallel universes," said Kuan, of UVA's Department of Neuroscience and its Center for Brain Immunology and Glia (BIG). "But our results showed that many microglial cells actually come from the blood monocytes, both in normal development and after newborn brain injury."

The Brain's Immune Defenders

The finding is the latest from UVA's Department of Neuroscience and BIG center, which have in recent years revolutionized our understanding of the brain's relationship with the immune system. To explore the origins of the brain's immune defenses, Kuan and his colleagues developed an innovative new lab model that should greatly benefit future research. That model allowed his team to trace the origins of microglia in the brains of lab mice.

The researchers found that many monocytes transform into microglia over the course of brain development. This was a surprise - prior to UVA's discovery, scientists widely believed that microglia do not come from the blood monocytes. But Kuan's team used a process called "fate mapping" to reveal the microglia's secret origins.

In addition, Kuan's team found that monocytes rush to the rescue during neonatal stroke. Neonatal strokes are interruptions of blood flow to the baby's brain in the first 28 days after birth. Such strokes have a wide variety of causes, from blood clots to developmental abnormalities. Common symptoms include seizures and extreme sleepiness, though in some cases there are no symptoms until much later in life, when children can develop speech difficulties and balance problems.

In such strokes, Kuan found, there is an initial rush of monocytes, which then gradually become more like microglia. This lasts at least 62 days after the brain injury. Some of these monocytes are ultimately reprogrammed to join the brain's defense forces, the UVA researchers determined.

"But do monocyte-descended microglia continue to impair brain development in infants that suffered from newborn stroke, leading to neurological deficits? Can we target these disguised monocytes to improve the outcomes of newborn brain injury?" said researcher Hong-Ru Chen, PhD, the first author of the new study. "These are fascinating questions that beg for more research."

"Food systems have the potential to nurture human health and support environmental sustainability; however, they are currently threatening both." This sentence, the opening statement of the EAT-Lancet Report published last year, reflects a growing consensus among global experts on food, nutrition and the environment: Our food system is broken and we need to fix it, fast.

To do so, the EAT-Lancet authors propose a "universal healthy reference diet" that is rich in fruits, vegetables, whole grains, legumes and nuts; and low on red meat, sugar, and highly processed foods. Undertaken at a global scale, this diet would be both good for the planet and the 10 billion people predicted to live on it by 2050.

The good news is this massive food systems transformation is possible.

The bad news is that putting it into action will require an unprecedented level of global cooperation.

Operationalizing the EAT-Lancet diet will require research and bold action on at least five broad themes: economics, politics, cultural norms, equity and governance, according to a group of authors that includes members of the EAT-Lancet commission.

Their analysis was published in Nature Food in August and was led by Christophe Béné of the Alliance of Bioversity International and CIAT. The article will be open-access until early September.

"If we really want to enact this change we need to look beyond the technological advances that will contribute to food system transformation," said Béné. "There is a whole series of tricky and challenging changes that come along with it."

In outlining the five priorities, the authors not only point to knowledge gaps but also emphasize real-world actions, some of which are already happening, that will be integral to systemic change.

"To fully realize the recommendations laid out in the EAT Lancet report, policymakers will need to prioritize food systems as a top development agenda. Researchers have an important role in providing the evidence of what works and potential trade-offs to policymakers so they can adapt and prioritize to their own local context," said Jessica Fanzo, Professor at Johns Hopkins University, EAT-Lancet co-author and the Lead of the 2017 High Level Panel of Experts Report on Nutrition and Food System.

Co-authors included Lawrence Haddad, the Executive Director of the Global Alliance for Improved Nutrition (GAIN) and recipient of the 2018 World Food Prize.

Economics

EAT-Lancet's reference diet works for people with access to, the money to buy, and the time to prepare healthier meals. But an estimated 1.6 billion people today do not have the money needed for a healthier diet, according to one study.

The costs of the transformation are unknown: changing land use and food production practices, and reducing food waste (which makes up about 30 percent of all food produced), and research is needed to estimate these costs.

For poor consumers, an already productive strategy has been the provision of discounts for healthy foods, perhaps rerouting production subsidies to the demand side of the economy. Land tenure rights, which incentivize productivity and are critical to conservation goals, could be guided by international technical guides.

Policy

The "global syndemic" of obesity, undernutrition and other health risks caused by poor diets - which together are the leading cause of poor health globally - require a thorough shakeup of the food system's status quo. This will require a complex combination of regulation and incentives to guide industrial food production toward healthier food products.

Often overlooked players in the food system, such as the world's 500 million smallholders, can contribute if there is scaled-up support to produce and consume a greater variety of healthy food.

More public research and development funding should be invested in non-staple, nutritious foods that can benefit small producers, the authors argue.

Other trends that must continue include increased public sentiment in favor of buying local and holding multinational food producers accountable for their role in unhealthy diets.

"The difficulties in implementing the required food transformations may therefore not be so much about the technicalities of the change, as they may be about the realpolitik of that change," the authors write.

Cultural norms

Consumers will be a key driver of the food system transformation. But increased wealth in middle-income countries is already driving transformation in the wrong direction - toward higher meat consumption and away from traditional, healthier foods that are deemed "foods of the poor."

"Unhealthy norms emerge all the time, as foods high in fat, sugar and salt become more widely available and marketed at lower prices throughout the world," write the authors. "Guiding cultural norms towards sustainability may also be challenging, more so because of the infinite diversity of diets from place to place, and the weak or incomplete evidence base on which to encourage these changes."

Equity

A 50 percent reduction in global red meat consumption is core to the EAT-Lancet diet. Such a dramatic shift would improve health and help conserve land that would be otherwise cleared for meat production.

But rural poor in many parts of the world would see their diets improved by consuming more animal-sourced protein, showing that any policies related to meat consumption need to be adapted to local contexts. Poorly nourished women and young children in low-income countries should increase their meat consumption, according to numerous studies.

"Beyond this specific example, the food transformation debate also needs to consider issues of social justice while averting promoting the message that changes involve only high-income countries," write the authors.

Women tend to represent a higher proportion of food system workers. They need additional protections, as do migrant laborers who are vital to harvest seasons worldwide. Child labor and slavery are not uncommon in the seafood industry.

Governance

Finally, the paper says that building the capacities of societies and decision-makers to navigate these different challenges may not be easy but it will be necessary. Grabbing the attention of governments that already need to focus on numerous, often competing priorities - including poverty, migration, security, natural disasters and pandemics - will not be easy.

"There is an urgent need to equip decision-makers at all levels with knowledge and skills to operate in this space," writes Béné.

The authors conclude: "The EAT-Lancet report did an excellent job of waking the world up to the interlinked issues of health and environment and showed that diets are the common denominator. But, at the crux of the great food transformation is the critical issue of science-policy interactions."

Osaka, Japan - As countries around the world race to develop a vaccine for SARS-CoV-2, the virus responsible for COVID-19, researchers are working to understand exactly how it causes the myriad of symptoms that seem to linger long after active viral infection. In a study published in scientific journal PNAS, researchers led by Osaka University identified an effective treatment for the deadly over-activation of the inflammatory response seen in many severe COVID-19 patients.

Cytokines are a group of small proteins that can either enhance or inhibit our body's immune response to infection, trauma, and diseases such as cancer. One of their main roles is to stimulate inflammation, which initiates the healing process. The problem is, overstimulation of the inflammatory response has an array of harmful complications, ranging from asthma to severe autoimmune diseases. One such complication, called cytokine release syndrome (CRS), is seen in patients suffering a hyperimmune response to microbial infection or trauma and can lead to multiple organ failure and even death.

"Despite knowing which cytokines are involved, there is still no specific immunotherapy for CRS and treatment is limited to supportive care," says study lead author Sujin Kang. "To better understand the molecular mechanisms of CRS pathogenesis, we first studied the cytokine profiles of 91 patients diagnosed with CRS associated with bacterial sepsis, acute respiratory distress syndrome, or burns."

Strikingly, patients from all three groups had elevated levels of proinflammatory cytokines IL-6, IL-8, IL-10, and MCP-10, as well as a protein called PAI-1, which causes small blood clots in vessels throughout the body, including the lungs. Importantly, increased PAI-1 levels are associated with more severe cases of pneumonia, a common cause of death among COVID-19 patients.

Because IL-6 was positively associated with the levels of the other cytokines and PAI-1, the researchers concluded that IL-6 signaling is crucial for the development of CRS following infection or trauma, and may play a role in the pathogenesis of COVID-19.

"Examination of cytokine profiles in severe COVID-19 patients revealed an increase in IL-6 early in the disease process, causing release of PAI-1 from blood vessels," says study senior author Tadamitsu Kishimoto. "Interestingly, PAI-1 levels were significantly higher in COVID-19 patients with severe respiratory impediment."

Most significantly though, when severe COVID-19 patients were treated with a human monoclonal antibody-based drug called Actemra®, which blocks IL-6 signaling, PAI-1 levels rapidly declined and severe disease symptoms were alleviated. IL-6 signaling blockade could therefore prove useful for the treatment of both CRS and the severe respiratory complications of COVID-19.

About half of the individuals of cowslip (Primula veris) have flowers with a short style, while the other half of individuals produce flowers with a long style. Recent discoveries have suggested that the loss and fragmentation of habitats may shake this optimal balance of morphologically different plants. This, in turn, decreases the reproductive success of plants and jeopardizes their future viability.

As the primary habitat, cowslips prefer semi-natural grasslands, which have experienced a dramatic area loss over the last hundred years throughout Europe. The study coordinated by the ecologists of the University of Tartu and the Estonian Fund for Nature aimed to examine whether this drastic landscape change has led to deviations in morph balance. To collect data across Estonia, they decided to implement a citizen science approach. A specifically designed web platform http://www.cowslips.eu facilitated an easy upload of data. "In addition, the task and importance of the cowslip observation campaign were explained in detailed guidelines, numerous videos, social media, and other communication platforms," commented Tsipe Aavik, the lead researcher of the heterostyly project.

Novel insight into fundamental research

Nearly 1,700 observations obtained during the campaign led to unexpected discoveries, is now published in the Journal of Ecology. First, data revealed a systematic dominance of short-styled morphs over long-styled morphs. Second, morph frequencies were more likely to deviate in smaller populations and deviations increased in landscapes with higher human population density.

"We are very thankful to all participants who helped to collect heterostyly data at such an unprecedented scale," commented Tsipe Aavik. "Although the first discoveries on heterostyly were made already by Darwin more than 150 years ago, data obtained in the citizen science campaign has helped us to add novel aspects into this fascinating topic with a long history of research."

The findings brought novel insights into fundamental research: the systematic dominance of the short-styled morphs is an intriguing but previously undescribed aspect in this otherwise well-studied plant mating system. However, perhaps even more important are the implications of these findings for conservation because deviating morph frequencies are likely to jeopardize the viability of heterostylous plants. The findings thus describe another threat in the list of negative consequences of habitat loss.

Perhaps Europe could be looking for cowslips one day

The surprising findings of the study have seeded an idea to widen the geographic scope of the study to examine whether the observed patterns are confirmed in other European countries. Furthermore, the discovery about the role of human population density altering morph balance encourages to look at the patterns of heterostyly in landscapes with more intense human impact than Estonia with its relatively low human population density. "In the spring of 2020, when we repeated the campaign, Latvian citizen scientists warmly welcomed the opportunity to contribute to heterostyly observations. But perhaps one day we all can participate in a project 'Europe is looking for cowslips'," adds Aavik with a hope that there still are places in Europe where one can find this beautiful and intriguing plant, cowslip.

'Dead' coral rubble can support more animals than live coral, according to University of Queensland researchers trialling a high-tech sampling method.

UQ's Dr Kenny Wolfe said that reef rubble habitat was often overlooked as desolate, unattractive and 'dead', however reef rubble was very much alive.

"When people think of coral reefs they often think of larger invertebrates that are easily found, such as sea cucumbers, starfish and giant clams," Dr Wolfe said.

"But interestingly, dead coral rubble supports more of what we call 'cryptic' animals than live coral.

"Cryptic animals are simply hidden creatures, that include tiny crabs, fishes, snails and worms - all of which hide in the nooks and crannies of the reef to avoid predation.

"And just like on land with small insects and bugs, biodiversity in the sea can be dominated by these tiny invertebrates."

As these creatures try to remain hidden, finding and surveying them requires particular care and attention.

Dr Wolfe teamed up with UQ Innovate to design 3D-printed coral stacks called RUBS (RUbble Biodiversity Samplers), to survey cryptic animals on coral reefs.

The 3D-printed 'coral' mimics the surrounding reef rubble, seamlessly inviting hidden reef organisms to be unknowingly monitored.

"Every piece of coral or rubble is different," Dr Wolfe said.

"RUBS provide a uniform method to survey the hidden majority on coral reefs.

"By sampling the RUBS' structures over time, the team were able to identify changes in the cryptic population, adding pieces to the puzzle and filling in the unknowns of coral reef food webs.

"This data fills important knowledge gaps, such as how small cryptic animals support coral reefs from the bottom of the food chain, all the way up to bigger predators."

Dr Wolfe believes that the new technique is another step in better understanding our precious reefs - whether considered 'alive' or 'dead'.

"We're really pulling back the curtain on just how alive these 'degraded' reefs are," he said.

"These are important habitats, which support coral reef biodiversity and important food webs.

"This new technology is a new opportunity for reef management, particularly for reef education and awareness.

"We're excited to learn about and celebrate the diversity of life in this misunderstood habitat."

A new study has shed light on the link between the consumption of ultra-processed foods (UPF) and the shortening of telomeres; sections of chromosomes that can be used as a marker of biological age. The work was conducted by Lucia Alonso-Pedrero and colleagues with the supervision of Professor Maira Bes-Rastrollo and Professor Amelia Marti, University of Navarra, Pamplona, Spain.

The research, being presented at this year's European and International Conference on Obesity (ECOICO 2020), held online this year (1-4 September), indicates that telomeres were twice as likely to be short in individuals who had a high consumption (more than 3 servings per day) of UPFs. Short telomeres are a marker of biological ageing at the cellular level, and the study suggests that diet may be causing the cells to age faster.

Telomeres are structures formed from a strand of DNA together with specialised proteins, and which are located at the ends of the chromosomes. Each human cell has 23 pairs of chromosomes that contain our genetic code, and while the telomeres do not contain genetic information themselves, they are vital for preserving the stability and integrity of chromosomes and by extension, the DNA that every cell in our body relies on to function. As we get older, our telomeres get shorter since each time a cell divides, part of the telomere is lost, thus telomere length (TL) is considered to be a marker of biological age.

Worldwide, fresh food consumption is decreasing while UPF intake is rising. UPFs are industrial formulations of food-derived substances (oils, fats, sugars, starch, protein isolates) that contain little or no whole food and often include flavourings, colourings, emulsifiers, and other cosmetic additives. The processes and ingredients used in the manufacturing of UPFs make them highly convenient (ready-to-consume, almost imperishable), highly attractive for consumers, and highly profitable (low cost ingredients, long shelf-life) for their manufacturers. These properties also result in them being nutritionally poor or unbalanced, and liable to be over-consumed, often at the expense of less processed and more nutritious alternatives.

Research has associated UPFs with serious diseases including hypertension, obesity, metabolic syndrome, depression, type 2 diabetes, and various cancers. These conditions are often age-related and are linked to oxidative stress, inflammation, and cellular ageing which can also influence TL. Despite this, there have been few studies into the effects of UPF consumption on TL, but those that have been conducted found associations between the intake of sugar-sweetened beverages (SSBs), alcohol, processed meats and other foods rich in saturated fats and sugar with having shorter telomeres. These studies are far from conclusive however, as other research has not shown a link between UPF and TL.

The authors objective was to evaluate the association between UPF consumption and the risk of TL within an elderly study population using the NOVA system method for classifying the degree of processing of different foods.

Data were obtained from participants in the SUN Project: an open prospective cohort of graduates from the University of Navarra and other Spanish universities. Recruitment began in 1999 and is permanently open to any graduate age 20 years old or more, with data collection being done via self-reported questionnaires mailed out every 2 years. This research is based on the analysis of a genetic study performed in May 2008 which all SUN Project participants over the age of 55 were invited to take part. In total, 886 individuals provided saliva samples for DNA analysis as well as accurate records of their daily food intake.

In total 645 men and 241 women with an average age of 67.7 years were included in the analysis and were grouped into 4 groups of equal size (quartiles) from 'low' to 'high' based on their UPF consumption: less than 2 servings/day, 2 to 2.5 servings/day, more than 2.5 to 3 servings/day, and more than 3 servings/day.

Those in the 'high' quartile were more likely to have family history of cardiovascular disease (CVD), diabetes, and abnormal blood fats, and to snack more in between meals. They also consumed more fats, saturated fats, polyunsaturated fats, sodium, cholesterol, SSBs, fast food, and processed meats while consuming less carbohydrates, protein, fibre, olive oil, fruits, vegetables, and other micronutrients. Participants who ate more UPFs were observed to be less likely to adhere to the 'Mediterranean diet' which has been linked to improved general health, and in particular a reduced risk of CVD.

The team found that as UPF consumption increased, the likelihood of having shortened telomeres rose dramatically with each quartile above the lowest having a risk increase of 29%, 40%, and 82% for the 'medium-low', 'medium-high', and 'high' UPF consumption groups respectively. The authors also found that UPF intake was associated with the risk of depression (especially in patients with low levels of physical activity), hypertension, overweight/obesity, and all-cause mortality.

The authors conclude: "In this cross-sectional study of elderly Spanish subjects we showed a robust strong association between ultra-processed food consumption and telomere length. Further research in larger longitudinal studies with baseline and repeated measures of TL is needed to confirm these observations."

From October 2022, the European Union (EU) will impose new nutritional requirements for total diet replacement (TDR) products which could make them unviable to produce and sell, according to new research being presented at The European and International Congress on Obesity (ECOICO 2020), held online this year from 1-4 September.

The study examining the feasibility of manufacturing TDR products according to these new dietary compositional criteria, reveals substantial challenges including reduced shelf-life, a worsening in organoleptic properties such as mouth feel and taste, and higher production costs.

"The mandatory nutrient values are markedly different to those which currently apply", explains Dr Kelly Johnston from King's College London and LighterLife UK Ltd, who led the research. "The sensory properties of the new formulation are likely to cause major compliance issues for consumers, and the diminished shelf life of some products would simply make them unviable to produce and sell."

The Foods for Specific Groups (FSG) Regulation--the nutritional criteria of which was decided by the European Food Safety Authority (EFSA)--will apply to formula-based TDR products for weight control, which consists of both very low and low calorie diet (VLCD and LCD) programmes [1]. These programmes are an established weight loss solution and have been available for more than 30 years throughout the EU.

The first controls on these specifically formulated types of foods were introduced in 1977, by the concept of Foods for Particular Nutritional Uses (PARNUTS). The PARNUTs legislation (2009/39/EC) allowed the food industry to market specific products indicating their suitability for nutritional use. However, because of no specific rules, different interpretation of product types across the EU led to similar foods being marketed as PARNUTs in some countries and as foods for normal consumption in others. So the new FSG Regulation was introduced to ensure application of uniform rules across the EU.

The new FSG Regulation stipulates that for TDR, the daily minimum protein content should increase from 50g to 75g per day (50% increase), while the values of essential fatty acids (linoleic and alpha linolenic) should more than double from 3g to 11g and 0.5g to 1.4g, respectively per day. There is also a new daily requirement for an extra 400mg of choline (an essential nutrient vital for many body functions including nerve signalling, and liver and muscle functioning).

In this study, researchers formulated 10 different VLCD TDR products (ie, bars, shakes, textured meals) to both the current formulation guidance and the new EU regulation, as well as a range of other "in-between" macronutrient versions. A team of trained sensory panellists working for an independent manufacturer were asked to compare organoleptic properties (ie, mouth feel, texture, appearance, aroma, and taste) and to examine the extent of quality changes between the different formulations, weekly, during storage over 10 weeks. The researchers also assessed production costs.

For the textured meal, the panel found that the increase in essential fatty acids negatively affected the organoleptic properties of the meal product--creating a "fatty mouthfeel" and an "unpalatable/unpleasant taste" [2]. This was not noted in either the current formulation or the 'in-between' test products.

In accelerated shelf-life tests, the panel reported unsatisfactory organoleptic profiles in 100% of new formulation samples compared with 20% in both the current formulation and 'in-between' samples. Additionally, rancidity was noted in new formulation samples from 4 weeks, whereas no rancidity was detected across the 10-week period for any other samples (see poster table 2).

Whilst the new recommended minimum protein content of 75g per day for TDR products was not reported to have any major adverse effects on sensory properties, the researchers estimate that the associated increase in raw material costs could increase the price to consumers by as much as 38%.

"We would like to see alternate compositional criteria, based on the currently available evidence", says Dr Johnston. "Specifically, because of the lack of evidence for the new additional requirements of so much fat."

According to co-author Dr Anthony Leeds from Frederiksburg Hospital, Denmark, "At a time when total diet replacement has been shown to have a potential role in delivering type 2 diabetes remission with improved quality of life and reduced drug costs across Europe, these legislative changes will challenge the commercial viability of existing total diet replacement, and deprive consumers of the freedom to choose this safe, cost-effective option."

AURORA, Colo. (Aug. 31, 2020) - A little understood region of the cerebellum plays a critical role in making split-second `go-no go' decisions, according to a new study from researchers at the University of Colorado Anschutz Medical Campus.

"We wanted to know how this kind of decision making takes place," said the study's senior author Diego Restrepo, PhD, professor of cell and developmental biology at the University of Colorado School of Medicine. "How, for example, do you decide to swing or not swing at a fast ball in baseball?"

The study was published online today in Nature Communications.

Employing mice rather than ball players, Restrepo and his team used a multiphoton microscope that peered into the brains of the free-moving rodents as they decided whether or not to lick a water solution.

The researchers focused specifically on the molecular layer interneurons (MLIs) in the cerebellum. The mice were given a sugar water reward if they licked a water spout in the presence of a specific, pleasant odor and they avoided a timeout when they refrained from licking in the presence of unscented mineral oil.

At first, the MLI responses did not differ between odors. But with learning, the reward odor prompted a large increase in MLI calcium responses. When the stimuli were reversed, the MLI switched responses to the odors.

When the scientists intervened with chemogenetic agents to inhibit MLI activity, the mice floundered and became less effective in making `go-no go' decisions.

"Our data indicate that the MLIs have a role in learning valence," Restrepo said. "That is, it helps determine whether something is good for me or not."

The findings further illuminate the function of the cerebellum, long associated primarily with movement. But it also plays a key role in cognition and emotion and is associated with non-motor conditions such as autism spectrum disorders.

"A lot of learning goes on inside the cerebellum," Restrepo said. "The cerebellum may also be the place where quick choice arises."

This study shows that it also coordinates both motion and decision making, when to go or not to go.

"We found an entire subset of brain cells that change after learning," Restrepo said. "It sheds further light on how the cerebellum functions and the complex web of connections that go into quick decision making."

CHAMPAIGN, Ill. — As COVID-19 continues to spread, bottlenecks in supplies and laboratory personnel have led to long waiting times for results in some areas. In a new study, University of Illinois, Urbana-Champaign researchers have demonstrated a prototype of a rapid COVID-19 molecular test and a simple-to-use, portable instrument for reading the results with a smartphone in 30 minutes, which could enable point-of-care diagnosis without needing to send samples to a lab.

“If such a device and test were available, we could test for COVID-19 at public events, auditoriums, large gatherings and potentially even at home for self-testing. The results could be sent back to the appropriate public health system for coordination,” said Rashid Bashir, a professor of bioengineering and the dean of the Grainger College of Engineering at Illinois. Bashir co-led the study with electrical and computer engineering professor Brian Cunningham and mechanical science and engineering professor Bill King.

Typical tests for SARS-CoV-2, the virus that causes COVID-19, take a sample from a patient with a long nasopharyngeal swab, put that swab into a substance called viral transport media, and send it to a lab for a multistep process of extracting, isolating and multiplying the telltale RNA inside the virus. This RNA multiplication process, called RT-PCR, requires several temperature fluctuation cycles, specialized equipment and trained personnel, Cunningham said.

As reported in the Proceedings of the National Academy of Sciences, the Illinois team used a simpler process to analyze the viral transport media, called LAMP, which bypasses the RNA extraction and purification steps.

“LAMP only needs one temperature – 65 C – so it is much easier to control,” said graduate student Anurup Ganguli, the first author of the study. “Also, LAMP works more robustly than PCR, especially when there are contaminants in the test sample. We can just briefly heat the sample, break open the virus and detect the genetic sequence that specifically identifies SARS-CoV-2.”

The researchers compared the LAMP assay with PCR, first using synthetic nasal fluid spiked with the virus and then with clinical samples. They found the results were in agreement with PCR results, and they documented the sensitivity and specificity of the LAMP test.

Then, the researchers incorporated the LAMP assay onto a small 3D-printed microfluidic cartridge that has two input slots for syringes: one for the sample-containing viral transport media, one for the LAMP chemicals. Once the two are injected, they react within the cartridge.

“We use modern, high speed additive manufacturing to make these cartridges.  The entire thing can be quickly scaled up to hundreds of thousands of tests,” King said. “Production scale-up is typically the biggest obstacle for commercial applications of microfluidic cartridges, and we can overcome that obstacle using this new approach. Modern additive manufacturing is elastic and scalable, and it can be ramped up very quickly compared with legacy manufacturing technologies.”

The team is working with Fast Radius Inc., a Chicago-based technology company King co-founded, to manufacture the microfluidic cartridges.

The cartridge can be inserted into a hand-held portable instrument with a heating chamber, which heats the cartridge to 65 degrees Celsius for the duration of the reaction, and a smartphone cradle for reading the results. In approximately 30 minutes, a positive result will emit fluorescent light.

“The reader illuminates the liquid compartments with light from blue LEDs, while the phone’s rear-facing camera records a movie of the green fluorescent light being generated,” Cunningham said. 

See a video of the cartridge, hand-held device and process on YouTube.

The researchers demonstrated the portable device with additional clinical samples, and found the results matched those of the standard PCR lab procedure.

The researchers are exploring whether the assay would work with saliva samples to eliminate the need for nasopharyngeal swabs, and collecting more patient data as they consider next steps for regulatory approvals, Bashir said.

Cognitive flexibility refers to the ability to readily switch between mental processes in response to external stimuli and different task demands. For example, when our brains are processing one task, an external stimulus is present, requiring us to switch our mental processes to attend to this external stimulus. This ability of switching from one to another mental task is the cognitive flexibility. Such flexibility can predict reading ability, academic success, resilience to stress, creativity, and lower risk of various neurological and psychiatric disorders. To shed light on the development of this critical cognitive process during early infancy, researchers at the UNC Biomedical Research Imaging Center (BRIC) at the UNC School of Medicine conducted a brain imaging study in infants to examine the emergence of neural flexibility, which refers to the frequency with which a brain region changes its role (or allegiance to one functional network to another). Neural flexibility is thought to underlie cognitive flexibility.

Publishing their work in the Proceedings of the National Academy of Sciences (PNAS), the researchers show that brain regions with high neural flexibility appear consistent with the core brain regions that support cognitive flexibility processing in adults, whereas brain regions governing basic brain functions, such as motor skills, exhibit lower neural flexibility in adults, demonstrating the emergence of functionally flexible brains during early infancy.

For this study, the authors used magnetic resonance imaging to examine brain activity up to seven times in 52 typically developing infants under the age of two during natural sleep. The researchers, led by Weili Lin, PhD, director of BRIC, the Dixie Lee Boney Soo Distinguished Professor of Neurological Medicine, and Vice Chair of Basic Research in the UNC Department of Radiology, found that neural flexibility increased with age across the whole brain, and specifically in brain regions that control movement, potentially enabling infants to learn new motor skills. Neural flexibility also increased with age in brain regions involved in higher-level cognitive processes, such as attention, memory, and response inhibition, indicating continuing development of these functional networks as babies become toddlers.

The age-related increase in neural flexibility was highest in brain regions already implicated in cognitive flexibility in adults, suggesting that cognitive flexibility may start to develop during the first two years of life.

"Neural flexibility in these brain regions may reflect early developmental processes that support the later emergence of cognitive flexibility," Lin said. "What we've imaged, in essence, is the brain's flexibility setting the stage for later maturity of higher cognitive brain functions."

Additional analysis of brain regions with especially high neural flexibility revealed the presence of relatively weak and unstable connections from these regions to other parts of the brain, potentially showing how these regions can rapidly switch their allegiances between different functional networks. By contrast, neural flexibility in brain regions involved in visual functions remained relatively low throughout the first two years of life, suggesting that these regions had already matured.

Lower levels of neural flexibility (i.e., greater established brain maturity) of visual brain regions at three and 18 months of age were associated with better performance on cognitive and behavioral assessments at the age of five or six years.

These findings provide insights into the development of higher-level brain functions, and could be used to predict cognitive outcomes later in life. The developed approach of assessing neural flexibility non-invasively could also provide a new means to assess subjects with neurodevelopmental disorders.

A team led by a biomedical scientist at the University of California, Riverside has found a new mechanism responsible for the abnormal development of neuronal connections in the mouse brain that leads to seizures and abnormal social behaviors.

The researchers focused on the area of the brain called hippocampus, which plays an important role in learning and social interactions; and synapses, which are specialized contacts between neurons.

Each neuron in the brain receives numerous excitatory and inhibitory synaptic inputs. The balance between excitation and inhibition in neuronal circuits, known as E/I balance and thought to be essential for circuit function and stability and important for information processing in the central nervous system, can play a role in causing many neurological disorders, including epilepsy, autism spectrum disorder, and schizophrenia.

The researchers also focused on a protein called ephrin-B1, which spans the membrane surrounding the cell and plays a role in maintaining the nervous system. The goal of their study was to determine if the deletion or over-production of ephrin-B1 in astrocytes -- glial cells in the brain that regulate synaptic connections between neurons -- affects synapse formation and maturation in the developing hippocampus and alters the E/I balance, leading to behavioral deficits.

"We found the changes in the E/I balance are regulated by astrocytes in the developing brain through the ephrin protein," said Iryna Ethell, a professor of biomedical sciences in the UCR School of Medicine who led the mouse study. "Further, astrocytic ephrin-B1 is linked to the development of inhibitory networks in the hippocampus during a critical developmental period, which is a new and unexpected discovery. Specifically, we show the loss of astrocytic ephrin-B1 tilts the E/I balance in favor of excitation by reducing inhibition, which then hyperactivates the neuronal circuits. This hyperactivity manifests as reduced sociability in the mice and suggests they can serve as a new model to study autism spectrum disorder."

The findings, published in the Journal of Neuroscience, can further scientists' understanding of the mechanisms that lead to neurodevelopmental disorders, allowing researchers to discover novel interventions for treating these disorders by targeting astrocytes during a specific developmental period.

Ethell explained that astrocyte dysfunctions are also linked to synapse pathologies associated with neurodevelopmental disorders and neurodegenerative diseases such as Alzheimer's disease where early dysfunction in synaptic connections can also lead to neuron loss.

"How exactly astrocytes use the ephrin protein to control the development of neuronal networks remains to be explored in future studies," she said. "Our findings open a new inquiry into future clinical applications as impaired inhibition has been linked to several developmental disorders, including autism and epilepsy."

The report is first to establish a link between astrocytes and the development of E/I balance in the mouse hippocampus during early postnatal development.

"We provide new evidence that different ephrin-B1 levels in astrocytes influence both excitatory and inhibitory synapses during development and contribute to the formation of neuronal networks in the brain and associated behaviors," Ethell said.

She explained that synapses are building blocks of neural networks and function as fundamental information-processing units in the brain. Excitatory synapses are cell-cell connections that facilitate neuronal activity, she said, whereas inhibitory connections negatively regulate brain activity to coordinate brain responses, their timing, and specificity.

"Hyperactivity of neuronal networks resulting from the loss or impaired function of inhibitory synapses can lead to neural dysfunctions and seizures," she added. "Like a car without brakes, the brain without inhibitory neurons cannot function properly and becomes overactive, resulting in loss of body control."

Ethell acknowledged further investigation is needed to determine how exactly ephrin signaling in astrocytes alters inhibitory synapses, and specifically how astrocytes may contribute to these mechanisms.

"Given the widespread and growing research interest in the astrocyte-mediated mechanisms that regulate E/I balance in neurodevelopmental disorders, our findings establish a foundation for future studies of astrocytes in clinically relevant conditions," she said.

According to a linguist from RUDN University, the number of COVID-19 cases in a country might be related to the existence of aspirated consonants in its main language of communication. This data can help create more accurate models to describe the spread of COVID-19. The results of the study were published in the Medical Hypotheses journal.

COVID-19 is mainly spread through droplets of liquid coming from the respiratory passages of an infected person. The disease spreads faster through coughing or sneezing, as in these cases the speed of the droplets increases. However, a regular conversation can also lead to infection, and the amount of produced droplets depends on the sounds pronounced by an infected speaker. The exact sounds that add the most to the spread of COVID-19 and other viruses haven't been identified yet. A RUDN linguist suggested that they might include aspirated consonants, i.e. the sounds that are accompanied by exhalation.

The issue of a correlation between the spread of infections and the language of the infected people was first brought up in 2003, after the outbreak of SARS-CoV-1in South China when over 8,000 cases were registered in 26 countries. The USA accounted for 70 of them, but Japan did not have a single patient, in spite of the fact that the number of Japanese tourists in China at that time was much higher than that of US travelers (3.2 mln vs 2.3 mln, respectively). Some scientists suggested a linguistic explanation: the staff of Chinese stores spoke to US tourists in English, and to Japanese guests in Japanese. Georgios Georgiou from RUDN University found the same correlation for COVID-19.

Unlike in Japanese, in the English language the consonants [p], [t], and [k] are aspirated. When they are pronounced, numerous small droplets are released from the respiratory passages of a speaker into the air. Such droplets may contain viral particles. Japanese has fewer aspirational consonants, and therefore Japanese speakers produce less airborne droplets during a conversation. To confirm whether the speakers of the languages that are rich in aspirated consonants are more prone to the COVID-19 infection, the RUDN linguist used the official data of 26 countries with 1,000+ registered COVID-19 cases as of March 23, 2020.

"Our study did not include Switzerland because it has several official languages. We also excluded countries with too many or too few cases per 1 mln residents (e.g. Italy and Japan, respectively) to avoid extreme values," said Georgios Georgiou, PhD, a postdoctoral researcher at the Department of General and Russian Linguistics, Philological Faculty of RUDN University.

The languages in the study were divided into two groups by the presence or absence of aspirated consonants. According to the scientists, although the groups did not show statistically significant differences, the countries that predominantly spoke the languages of the first group had more cases of COVID-19: 255 per 1 million residents (as opposed to 206 cases in the second group).

"Although no clear relationship was observed, we do not rule out that the spread of COVID-19 can be partially due to the presence of aspirated consonants in a country's main language of communication. This can be a valuable insight for epidemiologists,' added Georgios Georgiou.

However, the researchers of this paper recognize that it is difficult to determine such a relationship due to experimental limitations. For example, the different social distance measures taken in each country and the fact that we do not know exactly the linguistic background of the speakers in each country, render the paper's initial assumption just a hypothesis. However, this hypothesis has strong fundaments and can be studied in a future large-scale study.

The Covid-19 outbreak has caused immense problems at a macro socioeconomic level throughout the world. Not only has it affected the Covid-19 patients but has also taken a toll on the caregivers, physicians, paramedics and all others who have been engaged in the combat against the pandemic.

The current pandemic is feared to affect the physical and mental health and the well-being of people world over. The physicians, nurses and others directly dealing with the Covid-19 sufferers can be likely going through trauma consequences and burnout syndrome. Also, the impact of the quarantine lockdown on mental health has to be accounted for. It is, therefore, essential to include mental health as part of national public health response to the COVID-19 pandemic in assisting all those in need.

To view the letter please visit: https://benthamopen.com/ABSTRACT/TOPHJ-13-411

The spread of Covid-19 pandemic has been unprecedented considering the speed and severity with which it has affected most of the countries in the world. Viewing the magnitude and urgency required in handling the remedial measures, Dr. Allam proposes that we need a scoring system to help us classify the suspected patients in order to determine who would require a follow-up, home isolation, quarantine or further investigations. A scoring system is essential because the teams involved in finding and treating patients have found much difficulty in collecting nasopharyngeal swab specimen from all suspected patients. Also, the costs are very high for RT-PCR and CT Scans, if the doctors go on testing entire populations.

The proposed scoring system, that can prove a viable diagnostic tool for suspected patients, takes into account the Epidemiological Evidence of Exposure, Clinical Symptoms and Signs, and Investigations (if available). This simple scoring system for Covid-19 can be calculated in mere minutes, based on the data for the patients.

To find out the details for the proposed Scoring System for Covid-19, please view the letter here: https://benthamopen.com/ABSTRACT/TOPHJ-13-413

Aqueous zinc-based batteries (ZBBs) are widely used for portable and grid-scale applications due to their high safety, low cost and high energy density.

However, the inhomogeneous zinc deposition on anode during charging and the zinc dendrite formation decrease the cycling stability of ZBBs. Moreover, the traditional aqueous electrolytes are not capable of working at low temperature due to the suddenly dropped ionic conductivities, limiting the applicable temperature range of aqueous ZBBs.

Recently a research group led by Prof. LI Xianfeng from the Dalian Institute of Chemical Physics (DICP) of the Chinese Academy of Sciences (CAS) developed a low-temperature resisting, cost-effective, safe and eco-friendly hybrid electrolyte for aqueous ZBBs.

This work was published in Energy & Environmental Science.

The developed electrolyte, consisting of water (H2O), ethylene glycol (EG) and zinc sulfate (ZnSO4), exhibited high zinc-ion conductivity at low temperature.

"We demonstrated the unique solvation interaction of Zn2+ with EG through experiments together with theoretical calculation," said Prof. LI.

This interaction could not only enhance the hydrogen bonding between EG and H2O, providing the hybrid electrolyte with lower freezing point, but also weaken the solvation interaction of Zn2+ with H2O, achieving highly reversible Zn/Zn2+ chemistry and uniform zinc deposition.

Both the Zn-ion hybrid supercapacitors (ZHSCs) and Zn-ion batteries (ZIBs) with the hybrid electrolytes showed high energy densities, high power densities and long-cycle life at -20 °C. This series of hybrid electrolytes with tunable EG-to-H2O ratios provided good balance between performance and cost, which enabled promising application in various regions.

This work offers enlightenment for designing electrolytes for low-temperature energy storage devices. It was supported by the Natural Science Foundation of China and CAS Engineering Laboratory for Electrochemical Energy Storage.