Culture

A new study led by the Centre for Nutraceuticals in the University of Westminster shows that pink drinks can help to make you run faster and further compared to clear drinks.

The researchers found that a pink drink can increase exercise performance by 4.4 per cent and can also increase a 'feel good' effect which can make exercise seem easier.

The study, published in the journal Frontiers in Nutrition, is the first investigation to assess the effect of drink colour on exercise performance and provides the potential to open a new avenue of future research in the field of sports drinks and exercise.

During the study participants were asked to run on a treadmill for 30 minutes at a self-selected speed ensuring their rate of exertion remained consistent. Throughout the exercise they rinsed their mouths with either a pink artificially sweetened drink that was low in calories or a clear drink which was also artificially sweetened and low in calories.

Both drinks were exactly the same and only differed in appearance - the researchers added food dye to the pink drink to change the colour.

The researchers chose pink as it is associated with perceived sweetness and therefore increases expectations of sugar and carbohydrate intake.

Previous studies have also shown that rinsing the mouth with carbohydrates can improve exercise performance by reducing the perceived intensity of the exercise, so the researchers wanted to assess whether rinsing with a pink drink that had no carbohydrate stimulus could elicit similar benefits through a potential placebo effect.

The results show that the participants ran an average 212 metres further with the pink drink while their mean speed during the exercise test also increased by 4.4 per cent. Feelings of pleasure were also enhanced meaning participants found running more enjoyable.

Future exploratory research is necessary to find out whether the proposed placebo effect causes a similar activation to the reward areas of the brain that are commonly reported when rinsing the mouth with carbohydrates.

Talking about the study, Dr Sanjoy Deb, corresponding author on the paper from the University of Westminster, said: "The influence of colour on athletic performance has received interest previously, from its effect on a sportsperson's kit to its impact on testosterone and muscular power. Similarly, the role of colour in gastronomy has received widespread interest, with research published on how visual cues or colour can affect subsequent flavour perception when eating and drinking.

"The findings from our study combine the art of gastronomy with performance nutrition, as adding a pink colourant to an artificially sweetened solution not only enhanced the perception of sweetness, but also enhanced feelings of pleasure, self-selected running speed and distance covered during a run."

For college students under pressure, a dog may be the best stress fighter around.

Programs exclusively focused on petting therapy dogs improved stressed-out students' thinking and planning skills more effectively than programs that included traditional stress-management information, according to new Washington State University research.

The study was published today in the journal AERA Open, a peer-reviewed journal of the American Educational Research Association. The paper demonstrated that stressed students still exhibited these cognitive skills improvements up to six weeks after completion of the four-week-long program.

"It's a really powerful finding," said Patricia Pendry, associate professor in WSU's Department of Human Development. "Universities are doing a lot of great work trying to help students succeed academically, especially those who may be at risk due to a history of mental health issues or academic and learning issues. This study shows that traditional stress management approaches aren't as effective for this population compared with programs that focus on providing opportunities to interact with therapy dogs."

The researchers measured executive functioning in the 309 students involved in the study. Executive function is a term for the skills one needs to plan, organize, motivate, concentrate, memorize: "all the big cognitive skills that are needed to succeed in college," Pendry said.

Pendry conducted this study as a follow up to previous work, which found that petting animals for just 10 minutes had physiological impacts, reducing students' stress in the short-term.

In the three-year study, students were randomly assigned to one of three academic stress-management programs featuring varying combinations of human-animal interaction and evidenced-based academic stress management. The dogs and volunteer handlers were provided through Palouse Paws, a local affiliate of Pet Partners, a national organization with over 10,000 therapy teams.

"The results were very strong," Pendry said. "We saw that students who were most at risk ended up having most improvements in executive functioning in the human-animal interaction condition. These results remained when we followed up six weeks later."

Many universities, including WSU, have provided academic stress management programs and workshops for many years. These are traditionally very similar to college classes, where students listen to an expert, watch slideshows and take notes. They're often evidence-based courses that talk about ways to get more sleep, set goals, or manage stress or anxiety.

"These are really important topics, and these workshops are helping typical students succeed by teaching them how to manage stress," Pendry said. "Interestingly though, our findings suggest that these types of educational workshops are less effective for students that are struggling. It seems that students may experience these programs as another lecture, which is exactly what causes the students to feel stressed."

Human-animal interaction programs help by letting struggling students relax as they talk and think about their stressors. Through petting animals, they are more likely to relax and cope with these stressors rather than become overwhelmed. This enhances students' ability to think, set goals, get motivated, concentrate and remember what they are learning, Pendry said.

"If you're stressed, you can't think or take up information; learning about stress is stressful!" she said.

Animal sessions aren't just about changing behavior; they help students engage in positive thoughts and actions.

"You can't learn math just by being chill," Pendry said. "But when you are looking at the ability to study, engage, concentrate and take a test, then having the animal aspect is very powerful. Being calm is helpful for learning especially for those who struggle with stress and learning."

INDIANAPOLIS -- Artificial intelligence (AI)-driven healthcare has the potential to transform medical decision-making and treatment, but these algorithms must be thoroughly tested and continuously monitored to avoid unintended consequences to patients.

In a JAMA Network Open Invited Commentary, Regenstrief Institute President and Chief Executive Officer and Indiana University School of Medicine Associate Dean for Informatics and Health Services Research Peter Embí, M.D., M.S., strongly stated the importance of algorithmovigilance to address inherent biases in healthcare algorithms and their deployment. Algorithmovigilance, a term coined by Dr. Embí, can be defined as the scientific methods and activities relating to the evaluation, monitoring, understanding, and prevention of adverse effects of algorithms in healthcare.

"We wouldn't think of treating patients with a new pharmaceutical or device without first ensuring its efficacy and safety," said Dr. Embí. "In the same way, we must recognize that algorithms have the potential for both great benefit and harm and, therefore, require study. Also, compared with drugs or devices, algorithms often have additional complexities and variations, such as how they are deployed, who interacts with them, and the clinical workflows where interactions with algorithms take place."

The commentary was in response to a study from IBM scientists evaluating different approaches to debiasing healthcare algorithms developed to predict postpartum depression. Dr. Embí stated the study suggests that debiasing methods can help address underlying disparities represented in the data used to develop and deploy the AI approaches. He also said the study demonstrates that the evaluation and monitoring of these algorithms for effectiveness and equity is necessary and even ethically required.

"Algorithmic performance changes as it is deployed with different data, different settings and different human-computer interactions. These factors could turn a beneficial tool into one that causes unintended harm, so these algorithms must continually be evaluated to eliminate the inherent and systemic inequities that exist in our healthcare system," Dr. Embí continued. "Therefore, it's imperative that we continue to develop tools and capabilities to enable systematic surveillance and vigilance in the development and use of algorithms in healthcare."

ROCHESTER, Minn. ­­­-- Patients diagnosed with post-COVID-19 syndrome, also known as "PCS," "COVID-19 long-haul syndrome" and "Post-Acute Sequelae of SARS COV-2," experience symptoms such as mood disorders, fatigue and perceived cognitive impairment that can negatively affect returning to work and resuming normal activities, according to a Mayo Clinic study published in Mayo Clinic Proceedings.

The study reports on the first 100 patients to participate in Mayo Clinic's COVID-19 Activity Rehabilitation program (CARP), one of the first multidisciplinary programs established to evaluate and treat patients with post-COVID-19 syndrome. The patients were evaluated and treated between June 1 and Dec. 31, 2020. They had a mean age of 45, and 68% were female. They were evaluated a mean of 93 days after infection.

The most common symptom of patients seeking evaluation for post-COVID-19 syndrome was fatigue. Of the patients in the study, 80% reported unusual fatigue, while 59% had respiratory complaints and a similar percentage had neurologic complaints. More than one-third of patients reported difficulties performing basic activities of daily living, and only 1 in 3 patients had returned to unrestricted work activity.

"Most patients in the study had no preexisting comorbidities prior to COVID-19 infection, and many did not experience symptoms related to COVID-19 that were severe enough to require hospitalization," says Greg Vanichkachorn, M.D., medical director of Mayo Clinic's COVID-19 Activity Rehabilitation program and first author of the study. "Most of the patients had normal or nondiagnostic lab and imaging results, despite having debilitating symptoms. That's among the challenges of diagnosing PCS in a timely way and then responding effectively."

Nonetheless, the symptoms often resulted in significant negative effects as patients tried to return to normal daily activities, including work. "Most patients with whom we worked required physical therapy, occupational therapy or brain rehabilitation to address the perceived cognitive impairment," says Dr. Vanichkachorn. "While many patients had fatigue, more than half also reported troubles with thinking, commonly known as 'brain fog.' And more than one-third of patients had trouble with basic activities of life. Many could not resume their normal work life for at least several months."

Mayo Clinic developed the COVID-19 Activity Rehabilitation program at Mayo Clinic in Rochester in June 2020 to care for patients experiencing persistent symptoms after COVID-19 infection. In addition to Dr. Vanichkachorn, Mayo Clinic staff from many specialty fields are involved in diagnostics and treatment. Among services provided are psychosocial support for patients who frequently report feelings of abandonment, guilt and frustration during initial evaluation.

Mayo Clinic is conducting intensive research on post-COVID-19 syndrome, in part to better define how the condition presents across different socioeconomic groups and ethnicities. Prolonged symptoms, such as those experienced with post-COVID-19 syndrome, have been reported in prior epidemics.

"As the pandemic continues, we expect to see more patients who experience symptoms long after infection, and health care providers need to prepare for this, know what to look for, and know how to best provide for their patients' needs," says Dr. Vanichkachorn.

Patients who have recovered from acute infection shouldn't wait to be evaluated if they are experiencing prolonged symptoms, though Dr. Vanichkachorn says providers should be judicious in recommending expensive diagnostic tests, which often aren't covered by insurance and don't reveal significant information.

Environmental enrichment -- with infrastructure, unfamiliar odors and tastes, and toys and puzzles -- is often used in zoos, laboratories, and farms to stimulate animals and increase their wellbeing. Stimulating environments are better for mental health and cognition because they boost the growth and function of neurons and their connections, the glia cells that support and feed neurons, and blood vessels within the brain. But what are the deeper molecular mechanisms that first set in motion these large changes in neurophysiology? That's the subject of a recent study in Frontiers in Molecular Neuroscience.

Here, a multinational team of scientists used a large molecular toolbox to map, in unprecedented detail, how environmental enrichment leads to changes in the 3D organization of chromosomes in neurons and glia cells of the mouse brain, resulting in the activation or deactivation of a minority of genes within the genome. They show that genes which in humans are important for cognitive mental health are especially affected. This finding could inspire the search for novel therapies.

Enrichment first causes the 3D structure of chromosomes to 'open up'

"Here we show for the first time, with large-scale data from many state-of-the-art methods, that young adolescent mice that grew up in an extra stimulating environment have highly specific 'epigenetic' changes -- that is, molecular changes other than in DNA sequence -- to the chromosomes within the cells of the brain cortex," says corresponding author Dr Sergio Espeso-Gil from the Center for Genomic Regulation in Barcelona, Spain.

He continues: "These increase the local 'openness' and 'loopiness' of the chromosomes, especially around DNA stretches called enhancers and insulators, which then finetune more 'downstream' genes. This happens not only in neurons but also in the supportive glia cells, too often ignored in studies about learning."

Espeso-Gil and colleagues raised laboratory mice for the first month after birth in social groups inside housing with Lego blocks, ladders, balls, and tunnels that were frequently changed and moved around. As a control, mice were raised in smaller groups inside standard housing. The authors then used a swathe of complementary tools to look for molecular changes in neurons and glia cells within the brain cortex. These included changes in the 3D structure of chromosomes, in particular the local 'chromatin accessibility' (openness) and 'chromatin interactions' (where distant genes are brought together through loops, to coordinate activity).

Epigenetic 'master' switches

They show that one 'master' switch operational after environmental enrichment is a locally increased activity of the protein CTCF, which stimulates chromatin interactions within and between chromosomes. A second master switch works by locally increasing chromatin accessibility, especially within the pyramidal neurons that are important for cognition. A third is the highly localized adding of CH3- (methyl) groups to the important chromosomal protein histone H3, a change which activates nearby genes.

These switches mainly occur around genomic regions that contain enhancers, regulatory DNA that (when bound to proteins called transcription factors) can activate neighboring genes. Also affected were genomic regions with insulators, regulatory DNA that can override the gene-activating effect of neighboring enhancers.

The authors conclude that growing up in an enriched environment causes highly local and specific epigenetic changes in neurons and glia cells. These then change the activity -- predominantly by activation rather than inhibition -- of a minority of genes within the genome. Overall, 0.2-0.4% of all enhancers and 2-5% of all promoters (i.e. start sites for the first step of gene expression, where DNA is transcribed into protein-coding or regulatory RNA) are affected.

Link to mental health in humans

"Our results show that many of the genes involved are known to play a role in the growth and differentiation of neurons, the development of blood vessels, the formation and patterning of new synaptic connections on neurons, and molecular pathways implicated in memory and learning in mice," says Espeso-Gil.

"And when we look for parallel regions in the human genome, we find many regions that are statistically associated with differences in complex traits such as insomnia, schizophrenia, and Alzheimer's in humans, which means that our study could inform future research on these disorders. This points to the potential of environmental enrichment in therapies for mental health. Our research could also help to guide future research on chromatin interactions and the poorly known importance of glial cells for cognitive mental health."

Researchers used genetic engineering tools to create a virus that can enter specific neurons and insert into the prefrontal cortex a new genetic code that induces the production of modified proteins. In tests with mice, the alteration of these proteins was sufficient to modify brain activity, indicating a potential biomarker for the diagnosis of psychiatric disorders such as schizophrenia and autism.

Sometimes referred to as the “executive brain”, the prefrontal cortex is the region that governs higher-level cognitive functions and decision making. Studies of tissue from this brain region in patients with schizophrenia have detected alterations in two proteins: BDNF (brain-derived neurotrophic factor) and trkB (tyrosine receptor kinase B).

The relationship between BDNF and trkB is important during brain development. When these proteins bind to each other, they trigger a cascade of intracellular signals that are essential to neuronal maturation and growth. Imbalances in this kind of signaling may be associated with the manifestation of certain disorders.

A group of researchers affiliated with the Federal University of Minas Gerais (UFMG) and the University of São Paulo’s Ribeirão Preto Medical School (FMRP-USP) in Brazil, and with Sweden’s Karolinska Institute, have created a virus capable of carrying the genetic code for a mutant form of trkB. When the modified trkB binds to BDNF, the intracellular signaling cascade is blocked, reproducing characteristics observed in brain tissue from schizophrenia patients.

The research, conducted with funding from FAPESP and the Ministry of Education’s Coordination for the Improvement of Higher Education Personel (CAPES), involved parvalbumin-expressing inhibitory interneurons, or PV interneurons for short. Interneurons connect spinal motor and sensory neurons, and can also communicate with each other, forming circuits of various complexity. Firing at relatively high frequencies in the gamma range (30-80 Hertz), they resemble the conductor of an orchestra, regulating excitation and inhibition in the central nervous system. 

PV is a protein that plays a role in many processes, such as cell-cycle regulation and muscle contraction, among others. PV interneurons are the most common interneurons in the cortex, and are involved in attention, social memory, and more. Dysfunction of PV interneurons disrupting cortical information processing and cognitive behavior has been detected in psychiatric patients.

The neurons and interneurons in the human brain communicate via electrical and chemical signals to activate or inhibit nearby neurons as well as circuits in distant brain regions. The organized activity of these different circuits gives rise to consciousness, feelings and behavior.

“Using a novel viral strategy for cell-type-specific and spatially restricted expression of a dominant-negative trkB (trkB.DN), we show that BDNF/trkB signaling is essential to the integrity and maintenance of prefrontal PV interneurons in adult male and female mice,” the researchers write in an article published in February in the Journal of Neuroscience.

In the study, the genetically modified virus was introduced into the brain tissue of adult transgenic mice using Cre-Lox recombination, a site-specific recombinase technology for inserting or deleting target DNA sequences. The researchers then recorded electrical activity in the prefrontal cortex and found alterations in the excitation-inhibition balance, as well as changes in brain waves and neuronal activity resulting in more aggressive behavior and anxiety.

Specific circuits in the cortex were manipulated in an innovative manner using the technique, explained Cleiton Lopes Aguiar, a professor at UFMG’s Institute of Biological Sciences and co-principal investigator for the study alongside Marie Carlén, a professor at Karolinska Institute.

“The results show that manipulating BDNF/trkB in adults can alter not only brain activity but also complex behaviors that depend on the prefrontal cortex,” Aguiar said. “It can be inferred that BDNF/trkB signaling is necessary to development, and to maintain mature neural networks.”

According to Leonardo Rakauskas Zacharias, a co-author of the article and a researcher at FMRP-USP’s Epilepsy Research Laboratory, the new technique enhances the study of the developed adult brain.

The role of interneurons

In the same issue of the Journal of Neuroscience, the group published another article on synchronous activity of cortical inhibitory interneurons expressing parvalbumin. “Brain oscillations are fundamental to the coordination of neuronal activity across neurons and structures. Gamma oscillations (30-80 Hz) have received particular attention through their association with perceptual and cognitive processes. (...) [Here we] show how deficient PV inhibition can lead to increased and asynchronous excitatory firing, contaminating the local field potential and manifesting as increased gamma power. Thus, increased gamma power does not always reflect a genuine rhythm. Further, we show that ketamine-induced gamma increases are caused by separate network mechanisms,” the authors explain.

According to Nicolas Gustavo Guyon, a member of the group and a researcher at Karolinska Institute, their analysis of brain oscillations in genetically modified mice detected asynchronous activity due to the inability of PV interneurons to respond to all excitatory stimuli generated by other neurons.

For Aguiar, what both articles have in common is the search for a deeper understanding of the role played by interneurons in the prefrontal cortex and how the brain organizes the excitation-inhibition balance. “We’re exploring the normal brain in order to achieve a deeper understanding of psychiatric disorders such as schizophrenia,” he said. “We show that if there are alterations in certain specific aspects of these normal animals, they display symptoms that could be initial clues to the mechanisms underlying the disorders.”

According to the Pan American Health Organization (PAHO-WHO), mental illness accounts for more than a third of total disability in the Americas, yet investment in mental health programs falls well short of what is required to address the needs of psychiatric patients. The term covers mental disorders such as dementia and schizophrenia, as well as depression. Over 300 million people live with depression, 60 million with bipolar disorders, and 23 million with schizophrenia-related disorders (including 1.5 million Brazilians), the WHO estimates.

Zacharias points out that the group’s research projects have been in progress for more than seven years and their results could contribute to the development of potential treatments. “We work with basic science to understand the mechanisms of the brain, and our findings can help all those concerned understand psychiatric disorders a little better,” he said.

A new study by the University of Georgia revealed that more college students change majors within the STEM pipeline than leave the career path of science, technology, engineering and mathematics altogether.

Funded by a National Institutes of Health grant and a National Science Foundation Postdoctoral Fellowship and done in collaboration with the University of Wisconsin, the study examined interviews, surveys and institutional data from 1,193 students at a U.S. midwestern university for more than six years to observe a single area of the STEM pipeline: biomedical fields of study.

Out of 921 students who stayed in the biomedical pipeline through graduation, almost half changed their career plans within the biomedical fields.

"This was almost double the number of students who left biomedical fields altogether," said Emily Rosenzweig, co-author of the study and assistant professor in the Mary Frances Early College of Education's department of educational psychology. "This suggests that if we want to fully understand why there are shortages in certain STEM careers, we need to look at those who change plans within the pipeline, not just those who leave it."

Rosenzweig examined students' motivations for changing career plans and found that students were more often inspired to make a change because a new field seemed more attractive.

This finding pointed to an underexplored research area that educators, policymakers and administrators should devote more attention to in the future. Rather than focusing only on what makes students disenchanted with a particular career, factors that make alternative career paths seem valuable to students need to be considered.

"The sheer number of changes made by students who remained in the biomedical pipeline highlights the divergence of paths students take in their career decision-making," Rosenzweig said. "We should not simply assume that students are staying on course and progressing smoothly toward intended careers just because they have not left the [STEM] pipeline."

Ultimately, the research provides new insights about students' motivations for choosing various careers inside the STEM pipeline and demonstrates the importance of understanding this group if schools are to promote retention in particular STEM careers.

UCLA life scientists have identified six "words" that specific immune cells use to call up immune defense genes -- an important step toward understanding the language the body uses to marshal responses to threats.

In addition, they discovered that the incorrect use of two of these words can activate the wrong genes, resulting in the autoimmune disease known as Sjögren's syndrome. The research, conducted in mice, is published this week in the peer-reviewed journal Immunity (Cell Press).

"Cells have evolved an immune response code, or language," said senior author Alexander Hoffmann, the Thomas M. Asher Professor of Microbiology and director of the Institute for Quantitative and Computational Biosciences at UCLA. "We have identified some words in that language, and we know these words are important because of what happens when they are misused. Now we need to understand the meaning of the words, and we are making rapid progress. It's as exciting as when archaeologists discovered the Rosetta stone and could begin to read Egyptian hieroglyphs."

Immune cells in the body constantly assess their environment and coordinate their defense functions by using words -- or signaling codons, in scientific parlance -- to tell the cell's nucleus which genes to turn on in response to invaders like pathogenic bacteria and viruses. Each signaling codon consists of several successive actions of a DNA binding protein that, when combined, elicit the proper gene activation, in much the same way that successive electrical signals through a telephone wire combine to produce the words of a conversation.

The researchers focused on words used by macrophages, specialized immune cells that rid the body of potentially harmful particles, bacteria and dead cells. Using advanced microscopy techniques, they "listened" to macrophages in healthy mice and identified six specific codon-words that correlated to immune threats. They then did the same with macrophages from mice that contained a mutation akin to Sjögren's syndrome in humans to determine whether this disease results from the defective use of these words.

"Indeed, we found defects in the use of two of these words," Hoffmann said. "It's as if instead of saying, 'Respond to attacker down the street,' the cells are incorrectly saying, 'Respond to attacker in the house.'"

The findings, the researchers say, suggest that Sjögren's doesn't result from chronic inflammation, as long thought, but from a codon-word confusion that leads to inappropriate gene activation, causing the body to attack itself. The next step will be to find ways of correcting the confused word choices.

Many diseases are related to miscommunication in cells, but this study, the scientists say, is the first to recognize that immune cells employ a language, to identify words in that language and to demonstrate what can happen when word choice goes awry. Hoffman hopes the team's discovery will serve as a guide to the discovery of words related to other diseases.

The immune system at war: Words and codes

How are immune cells so effective at mounting a response that is specific and appropriate to each pathogen? The answer, Hoffman says, lies in "signaling pathways," the communication channels that link immune cells' receptor molecules -- which sense the presence of pathogens -- with different kinds of defense genes. The transcription factor NFκB is one of these signaling pathways and is recognized as a central regulator of immune cell responses to pathogen threats.

"The macrophage is capable of responding to different types of pathogens and mounting different kinds of defenses. The defense units -- army, navy, air force, special operations -- are mediated by groups of genes," he said. "For each immune threat, the right groups of genes must be mobilized. That requires precise and reliable communication with those units about the nature of the threat. NFκB dynamics provide the communication code. We identified the words in this code, but we don't yet fully understand how each defense unit interprets the various combinations of the codon-words."

And of course, calling up the wrong unit is not only ineffective, Hoffmann notes, but may do damage, as vehicles destroy roads, accidents happen and worse, as in the case of Sjogren's and, possibly, other diseases.

Algorithms, computers and calculus: Identifying the six words

For the study, the scientists analyzed how more than 12,000 cells communicate in response to 27 immune threat conditions. Based on the possible arrangement of temporal NFκB dynamics, they generated a list of more than 900 potential "words" -- analogous to all combinations of three-letter words with a vowel for the second letter.

Then, using an algorithm originally developed in the 1940s for the telecommunications industry, they monitored which of the potential words tended to show up when macrophages responded to a stimulus, such as a pathogen-derived substance. They discovered that six specific dynamical features, or "words," were most frequently correlated with that response.

An analogy would be listening to someone in a conversation and finding that certain three-letter words tend to be used, such as "the," "boy," "toy," and "get," but not "biy" or "bey," said lead author Adewunmi Adelaja, who earned his Ph.D. in Hoffmann's laboratory and is now working toward his M.D. at UCLA.

The team then used a machine learning algorithm to model the immune response of macrophages. If they taught a computer the six words, they asked, would it be able to recognize the stimulus when computerized versions of cells were "talking?" They confirmed that it could. Drilling down further, they explored what would happen if the computer only had five words available. They found that the computer made more mistakes in recognizing the stimulus, leading the team to conclude that all six words are required for reliable cellular communication.

The scientists also used calculus to study the biochemical molecular interactions inside the immune cells that produce the words.

Hoffmann and his colleagues revealed in the journal Science in 2014 how and why the immune system's B cells respond only to true threats. In a study published in Cell in 2013, his team showed for the first time that it was possible to correct a cellular miscommunication involving the connection of receptors to genes during inflammation without severe side effects.

The immune system's main job is identifying things that can make us sick. In the language of immunology, this means distinguishing "self" from "non-self": The cells of our organs are self, while disease-causing bacteria and viruses are non-self.

But what about the billions of bacteria that live in our guts and provide us with benefits like digesting food and making vitamins? Are they friend or foe?

This isn't only a philosophical question. An immune system that mistakes our good gut bacteria for an enemy can cause a dangerous type of inflammation in the intestines called colitis. An immune system that looks the other way while gut microbes spill past their assigned borders is equally dangerous. Understanding how the immune system learns to make a brokered peace with its microbial residents, called the microbiota, is therefore an important area of research.

"Right now, each of us has immune cells in our body that can recognize and attack specific members of our gut microbiota," says Gretchen Diehl, an immunologist in the Sloan Kettering Institute. "So, it's a puzzle why more of us don't have colitis caused by these cells attacking our gut microbes."

To try to solve that puzzle, Dr. Diehl and her colleagues, including SKI postdoctoral researcher Daniel Zegarra-Ruiz and immunologist Matthew Bettini at the University of Utah, recently conducted a study using lab mice to explore what happens to microbe-specific T cells (a type of immune cell) when mice are exposed as young pups to a common gut microbe.

"We thought that maybe T cells specific for this microbe would be eliminated from the mice, or perhaps the mice would develop anti-inflammatory T cells that would protect them from developing colitis," Dr. Diehl says. In other words, they hypothesized the bacteria would be seen as self.

Surprisingly, that wasn't the case. Not only were the microbe-specific T cells not deleted, they actually grew in number. The results, which were published May 12, 2021, in Nature, document a previously unknown way that gut microbes interact with the immune system and raise yet more questions about what goes awry in autoimmune disease.

Hidden Highway

The scientists focused their attention on an immune system organ called the thymus, which is located in the upper chest behind the breastbone. The thymus's main role is "educating" T cells about which markers, or antigens, in the body are self versus non-self. T cells that recognize self are actively culled while those that do not recognize self are spared. The non-self-recognizing T cells are then released into the circulation where they patrol for viruses, bacteria, and other invaders.

The education process is thought to be primarily about protecting the body from self-attacking T cells that could cause trouble in the form of autoimmunity. Dr. Diehl and her colleagues were taken aback to find that rather than eliminating T cells that recognize gut bacteria, the thymus was giving them the green light.

"We were very, very surprised that when we colonized mice with gut bacteria, instead of seeing the development of regulatory T cells that calm immune reactions or loss of microbe-specific T cells, we saw an expansion of them," she says. "As far as we are aware, this is the first time anyone has shown the thymus playing this role in the expansion of microbe-specific T cells."

Next they asked: How is information about gut bacteria making its way to the thymus?

Using standard gut microbiota detection techniques, they could see that bacterial DNA was showing up in the thymus, suggesting that the gut is somehow in communication with this organ via DNA. But that only raised the further question of how this DNA was getting there.

One possible explanation is that bacterial DNA is carried there by immune cells called dendritic cells, whose main job is, in fact, to carry suspicious antigens from tissues to lymph nodes. Traveling from the gut to the thymus hadn't been seen, but the scientists couldn't rule out that possibility.

To track the movement of dendritic cells, Dr. Diehl and her colleagues took advantage of a hi-tech lab mouse developed by Kat Hadjantonakis's lab at MSK. The mouse had been engineered to make a fluorescent marker called green fluorescent protein (GFP) in its cells. When GFP-containing cells are hit with light from a laser, they change from emitting green fluorescence to emitting red. By shining the laser in the intestine of the mouse, the scientists could turn gut dendritic cells red and then watch and see if red cells turned up in the mouse thymus. Sure enough, they did.

"The dendritic cells are clearly migrating that whole way, which is kind of crazy," Dr. Diehl says.

A Temporary Window

The gut-to-thymus journey only happens in very young animals. When the scientists looked at older animals, they didn't see the red cells turning up. Nor did they find any gut microbe DNA in the thymus or expansion of gut-specific T cells.

What might be the purpose of this gut-to-thymus traffic that only happens during a specific developmental window in the mice?

"What we think is happening is a kind of templating on the immune system," Dr. Diehl says. "In that timeframe, the mouse immune system is very underdeveloped and the most relevant thing for it to recognize is microbes. So, it brings gut antigens to the thymus to educate the T cells about these and related dangers."

As evidence for this possibility, they showed that the T cells that recognize the introduced bacteria also afford protection against pathogens the mice hadn't yet seen. But because they recognize gut microbes, these T cells can also cause inflammation that can lead to colitis.

What the scientists next want to understand is whether this process differs in people who are more susceptible to colitis.

Dr. Diehl wonders: "Do you have this happening for a more extended period of time in people with colitis? Do you have it happening for less? Does it restart in someone with colitis? These are all questions we want to explore."

Our body's relationship with bacteria is complex. While infectious bacteria can cause illness, our gut is also teaming with "good" bacteria that aids nutrition and helps keep us healthy. But even the "good" can have bad effects if these bacteria end up in tissues and organs where they're not supposed to be.

Now, research published in Nature reveals insights into how the body maintains this balance. Investigations with mice demonstrate that early life is a critical time when the immune system learns to recognize gut bacteria and sets up surveillance that keeps them in check. Defects in these mechanisms could help explain why the immune system sometimes attacks good bacteria in the wrong place, causing the chronic inflammation that's responsible for inflammatory bowel disease, the study's authors say.

"From the time we are born, our immune system is set up so that it can learn as much as it can to distinguish the good from the bad," says Matthew Bettini, Ph.D., associate professor of pathology at U of U Health and co-corresponding author with Sloan Kettering Institute immunologist Gretchen Diehl, Ph.D. "Our studies make clear that there is a window in which gut microbiota have access to the immune education process. This opens up possibilities for designing therapeutics that can influence the trajectory of the immune system during this early time point."

Setting Boundaries

In seeking to understand how the body maintains a healthy relationship with bacteria, Bettini, Diehl, and colleagues discovered ways in which the resident gut microbiota shape the developing immune system. They found that specialized immune cells capture pieces of bacteria and carry them over long distances, from the gut to the thymus. Located in the chest, above the heart, the thymus is a gland responsible for "educating" immune T cells. Delivery of the cargo prompts the thymus to produce T cells that are targeted to the microbiota. Then, the T cells exit the thymus to surveil lymph nodes, the gut, and other sites in order to keep the bacteria under control.

The scientists identified these steps by seeding the intestines of mice with a certain type of bacteria. In response, the thymus produced T cells that specifically recognized those bacteria. However, the scientist didn't know how this occurred.

Finding DNA from the bacteria in the thymus and lymph nodes was the first clue that microbiota migrated to those sites. To trace their journey, the researchers used specially engineered mice whose cells fluoresced red after being exposed to a laser. In the two days following photoactivation, red gut cells eventually made their way to the thymus, lymph nodes, and spleen.

These processes were robust within the first weeks of life but waned significantly by the time the mice reached adulthood.

"Our study challenges previous assumptions that potential pathogens have no influence on immune cells that are developing in the thymus," Bettini explains. "Instead, we see that there is a window of opportunity for the thymus to learn from these bacteria. Even though these events that shape which T cells are present happen early in life, they can have a greater impact later in life."

Bad Education

This notion was made apparent by the finding that T cells programmed to target beneficial bacteria could double as defense against closely related "bad" bacteria. Mice populated with E.coli at a young age were more than six times as likely to survive a lethal dose of Salmonella later in life. The results suggest that building immunity to microbiota also builds protection against harmful bacteria the body has yet to encounter.

Delving into these early communications between the body and microbiota demonstrates just how important it is to prime the immune system right from the start, Bettini says. "This early education of immune T cells is absolutely necessary to quickly develop a broad repertoire of cells to protect us."

"We believe that our findings may be extended to areas of research where certain bacteria have been found to be either protective or pathogenic for other conditions, such as Type 1 and Type 2 diabetes," Bettini says. "Now we're wondering, will this window of bacterial exposure and T cell development also be important in initiating these diseases?"

If you did not catch the flu this year — and there is an overwhelming chance that you did not — you have COVID-19 to thank.

It’s a small consolation, given the enormously disruptive scope of the pandemic. But it’s the focus of a new paper published in the journal Frontiers in Public Health by two Concordia researchers and their colleagues that studies the 2020 influenza figures from Canada, the United States, Australia and Brazil. The authors show there is a clear relationship between the implementation of COVID-mitigation measures such as hand-washing, masking and social distancing and the spread of the annual flu.

They write that these preventive measures all but eliminated the flu in countries where it can kill tens of thousands of people a year, even as cases of COVID-19 soared.

“With the introduction of COVID-19 mitigation measures, we saw a steep decline in influenza cases in the northern hemisphere,” says Jovana Stojanovic, a postdoctoral fellow in the Department of Health, Kinesiology and Applied Physiology and the lead author of the paper.

“Then we also observed that as COVID-19 cases went up and down in different ways, influenza was basically annulled across both the north and south hemispheres. That speaks volumes about how contagious COVID-19 is compared to influenza.”

Simon Bacon, a professor of health, kinesiology and applied physiology, co-authored the paper, along with Vincent Boucher and Kim Lavoie at UQAM as well as Jacqueline Boyle and Joanne Enticott of Monash University in Australia.

No peaks, all valleys

The researchers initially had two objectives. The first involved using data from FluNet, the World Health Organization’s influenza virological surveillance tool. They wanted to see how the epidemiological pattern of the 2019-20 influenza tracked onto the evolution of the COVID-19 pandemic after the introduction of public mitigation measures were introduced in Canada, the United States, Australia and Brazil.

The second was to combat the misleading statements and disinformation being circulated worldwide that COVID-19 was similar to influenza. Their graphs below clearly show the stark differences in transmissibility between the influenza and novel coronavirus.

“In the northern hemisphere, we initially had overlapping flu and COVID-19 cases,” Bacon says. “When we introduced basic measures like hand-washing, social distancing and wearing masks, the flu was almost totally obliterated while COVID kept going.”

The researchers note that the first two graphs, looking at Canada and the United States, show significant reduction of influenza cases compared with the averages of the four previous years after mitigation efforts were introduced (indicated by the solid black line). Flu season, which usually runs from October to May, effectively ended a month earlier in Canada and almost two months earlier in the United States. Cases remained close to nil at the start of the 2020 flu season in both countries, which roughly coincided with the second COVID-19 wave.

The next set of graphs, showing figures from Brazil and Australia, reveal similar figures. Flu season in the southern hemisphere lasts from May to November but in these cases, there was no traditional mid-year spike for flu, though COVID-19 was nearing its second-wave high. Flu cases remained near zero through the end of the year.

Easy steps

These findings offer lessons for public health authorities as we eye a post-COVID future, Bacon explains.

“We know the flu is particularly problematic for older individuals and those with respiratory conditions and so on,” he says. “When we interact with people in those high-risk brackets, we should maintain some measures like handwashing, mask-wearing and social distancing. We’re used to them now, so maintaining them moving forward is probably a good idea.”

DURHAM, N.H.-- A national report from the University of New Hampshire shows close to one and a half million children each year visit a doctor, emergency room or medical facility as a result of an assault, abuse, crime or other form of violence. This is four times higher than previous estimates based only on data from U.S. emergency rooms for violence-related treatment.

In their study, recently published on JAMA Network Open, researchers from UNH's Crimes against Children Research Center (CCRC) used survey information from a representative sample of 8,503 children and youth from across the country, ages two to 17 years, as part of a series of nationwide studies in 2011 and 2014. They found that while the majority of those needing medical attention for violence exposure were teens, one third were under the age of 10. The rate of past-year medical visits due to violence exposure was 1.9% which is equivalent to a national estimate of 1.4 million children and teens. Previous estimates based on data obtained only from emergency rooms were 340,000 visits, which reflects a severe undercount of violence related medical treatment for children.

"This flood of visits to medical authorities each year by young crime victims means that our medical professionals need to know more about how to help, not only treating the injuries but how to counsel children and their families about how to stay safe and how to get appropriate help from schools, therapists and child protection agencies," said David Finkelhor, director of the CCRC and lead author.

Most of the medical visits were to treat injuries but some were to document harms and others to seek supportive help for problems like bullying and sibling victimization. The violence responsible for these visits included gang violence, aggravated assault by peers, dating violence, sexual assault and parental abuse with the largest category being simple assault by other peers. Researchers say that children are the most crime exposed segment of the population, experiencing serious assaults at twice the rate as adults.

"We should not be treating assaults as just a rite of passage for children," said Finkelhor. "We need to build interpersonal safety into our education systems, our environments and prepare practitioners to provide resources on prevention and safety skills."

The 1949 letter by the physicist and Nobel laureate discusses bees, birds and whether new physics principles could come from studying animal senses.

It's a position still being realised within physics to this day, with a growing body of research and understanding of how animals such as birds and bees find their way around.

Now a study led by RMIT University in Melbourne, Australia, discusses how recent discoveries in migratory birds back up Einstein's thinking 72 years ago.

The previously unpublished letter was shared with researchers by Judith Davys - Einstein had addressed it to her late husband, radar researcher Glyn Davys.

RMIT's Associate Professor Adrian Dyer has published significant studies into bees and is the lead author of the new paper on Einstein's letter, published in the Journal of Comparative Physiology A.

Dyer said the letter shows how Einstein envisaged new discoveries could come from studying animals.

"Seven decades after Einstein proposed new physics might come from animal sensory perception, we're seeing discoveries that push our understanding about navigation and the fundamental principles of physics," he said.

The letter also proves Einstein met with Nobel laurate Karl von Frisch, who was a leading bee and animal sensory researcher.

In April 1949, von Frisch presented his research on how honeybees navigate more effectively using the polarisation patterns of light scattered from the sky.

The day after Einstein attended von Frisch's lecture, the two researchers shared a private meeting.

Although this meeting wasn't formally documented, the recently discovered letter from Einstein provides insight into what they might have talked about.

"It is thinkable that the investigation of the behaviour of migratory birds and carrier pigeons may someday lead to the understanding of some physical process which is not yet known," Einstein wrote.

Professor Andrew Greentree, a theoretical physicist at RMIT, said Einstein also suggested that for bees to extend our knowledge of physics, new types of behaviour would need to be observed.

"Remarkably, it is clear through his writing that Einstein envisaged new discoveries could come from studying animals' behaviours," Greentree said.

More than 70 years since Einstein sent his letter, research is revealing the secrets of how migratory birds navigate while flying thousands of kilometres to arrive at a precise destination.

In 2008, research on thrushes fitted with radio transmitters showed, for the first time, that these birds use a form of magnetic compass as their primary orientation guide during flight.

One theory for the origin of magnetic sense in birds is the use of quantum randomness and entanglement. Both of these physics concepts were first proposed by Einstein.

PROVIDENCE, R.I. [Brown University] -- Researchers with the BrainGate collaboration have, for the first time, used an implanted sensor to record the brain signals associated with handwriting, and used those signals to create text on a computer in real time.

In a study published in the journal Nature, a clinical trial participant with cervical spinal cord injury used the system to "type" words on a computer at a rate of 90 characters per minute, more than double the previous record for typing with a brain-computer interface. This was done by the participant merely thinking about the hand motions involved in creating written letters.

The research team is hopeful that such a system could one day help to restore people's ability to communicate following paralysis caused by injury or illness.

The new study is part of the BrainGate clinical trial, directed by Dr. Leigh Hochberg. Hochberg is a critical care neurologist and a professor at Brown University's School of Engineering and Carney Institute for Brain Science. Frank Willett, a research scientist at Stanford University and the Howard Hughes Medical Institute (HHMI), led the study, which was supervised by Krishna Shenoy, a Stanford professor and HHMI investigator, and Dr. Jaimie Henderson, a professor of neurosurgery at Stanford.

"An important mission of our BrainGate consortium research is to restore rapid, intuitive communication for people with severe speech or motor impairments," said Hochberg, who also directs the Center for Neurotechnology and Neurorecovery at Massachusetts General Hospital and the VA RR&D Center for Neurorestoration and Neurotechnology at the Dept. of Veterans Affairs Providence Healthcare System. "Frank's demonstration of fast, accurate neural decoding of handwriting marks an exciting new chapter in the development of clinically useful neurotechnologies."

The BrainGate collaboration has been working for several years on systems that enable people to generate text through direct brain control. Previous incarnations have involved trial participants thinking about the motions involved in pointing to and clicking letters on a virtual keyboard. That system enabled one participant to type 40 characters per minute, which was the previous record speed.

For this latest study, the team wanted to find out if asking a participant to think about motions involved in writing letters and words by hand would be faster.

"We want to find new ways of letting people communicate faster," Willett said. "This new system uses both the rich neural activity recorded by intracortical electrodes and the power of language models that, when applied to the neurally decoded letters, can create rapid and accurate text."

The trial participant, a 65-year-old (at the time of the study) man, was paralyzed from the neck down by a spinal cord injury. As part of the clinical trial, Henderson placed two tiny electrodes about the size of a baby aspirin in a part of his brain associated with the movement of his right arm and hand. Using signals the sensors picked up from individual neurons when the man imagined writing, a machine learning algorithm recognized the patterns his brain produced with each letter. With this system, the man could copy sentences and answer questions at a rate similar to that of someone the same age typing on a smartphone.

The system is so fast because each letter elicits a highly distinctive activity pattern, making it relatively easy for the algorithm to distinguish one from another, Willett says.

The new research is the latest in a series of advances in brain-computer interfaces (BCIs) made by the BrainGate collaboration, which includes researchers from Brown University, Massachusetts General Hospital, Harvard Medical School, the Providence VA Medical Center, Stanford University, and Case Western Reserve University.

In 2012, the team published landmark research in which clinical trial participants were able, for the first time, to operate multidimensional robotic prosthetics using a BCI. That work has been followed by a steady stream of refinements to the system, as well as new clinical breakthroughs that have enabled people to directly control tablet apps and even move their own paralyzed limbs. Most recently, the team demonstrated the first human use of a wireless intracortical BCI that can transmit neural data at full bandwidth.

Hochberg said he's grateful to clinical trial participants for making these breakthroughs and future ones possible.

"The people who enroll in the BrainGate trial are amazing," Hochberg said. "It's their pioneering spirit that not only allows us to gain new insights into human brain function, but that leads to the creation of systems that will help other people with paralysis."

Scientists have for the first time revealed the structure surrounding important receptors in the brain's hippocampus, the seat of memory and learning.

The study, carried out at Oregon Health & Science University, published today in the journal Nature.

The new study focuses on the organization and function of glutamate receptors, a type of neurotransmitter receptor involved in sensing signals between nerve cells in the hippocampus region of the brain. The study reveals the molecular structure of three major complexes of glutamate receptors in the hippocampus.

The findings may be immediately useful in drug development for conditions such as epilepsy, said senior author Eric Gouaux, Ph.D., senior scientist in the OHSU Vollum Institute, Jennifer and Bernard Lacroute Endowed Chair in Neuroscience Research and an Investigator with the Howard Hughes Medical Institute.

"Epilepsy or seizure disorders can have many causes," he said. "If one knows the underlying cause for a particular person's seizure activity, then you may be able to develop small molecules to modulate that activity."

Working with a mouse model, the OHSU researchers made the breakthrough by developing a chemical reagent based on monoclonal antibodies to isolate the receptor and the complex of subunits surrounding it. They then imaged the assemblage using state-of-the-art cryo-electron microscopy at the Pacific Northwest Cryo-EM Center, housed in OHSU's South Waterfront campus in Portland.

Gouaux anticipates the technique will transform structural biology.

"It really opens the door to specifically target the molecules that need to be targeted in order to treat a particular condition," he said. "A great deal of drug development is structure-based, where you see what the lock looks like and then you develop a key. If you don't know what the lock looks like, then it's much harder to develop a key."

Previously, scientists had to rely on mimicking the actual receptors by artificially engineering receptors by combining DNA segments in tissue culture. However, that technique has obvious shortcomings.

"It doesn't work perfectly because the real receptors are surrounded by a constellation of additional, sometimes previously unknown, subunits," Gouaux said.

The new monoclonal antibody reagents, also developed at OHSU, enabled scientists to isolate actual glutamate receptors from the brain tissue of mice. They then were able to image those samples in near-atomic detail using cryo-EM, which allowed them to capture the entire assemblage of three types of glutamate receptors along with their auxiliary subunits.

"Previously, it's been impossible to do this because we had no good way to isolate molecules and no way to see what they looked like," Gouaux said. "So this is a super exciting development."