Culture

Quick flashes of light in the night sky have been linked to the growing mass of satellites and debris zipping around Earth's orbit.

The orbital flashes, often mistaken for stars, are extremely common, occurring 1,000 times an hour, according to new research led by the University of North Carolina at Chapel Hill that may improve the accuracy of astronomical data.

Stargazers have long been tantalized by the inexplicable glimmers and the study published Nov. 5 in The Astrophysical Journal Letters provides a potential explanation for those mysterious flashes.

Most of the flashes require powerful telescopes for viewing, but up to 100 of them are bright enough to see with the naked eye in a suburban community.

"Astronomical surveys have seen occasional reflected light glints from satellites; those flashes can cause false alarms in surveys looking for new events in the sky," said lead study author Hank Corbett, graduate student at the UNC-Chapel Hill Department of Physics and Astronomy.

"For the first time, we have studied the flashes in a systematic way that will help reduce their impact on astronomical discoveries."

The team at UNC-Chapel Hill, along with collaborators from San Diego State University and the University of Barcelona, reported more than 100,000 flashes over a six-month period.

The flashes were observed with the Evryscopes, telescopes in California and Chile constructed and funded by the National Science Foundation. The pair of robotic, gigapixel-camera telescopes observe the entire sky above their observatories every two minutes.

"These measurements allow us to predict the impact of reflected-light flashes on both current and future professional observatories and develop techniques to mitigate their effects on data," Corbett said.

The orbital flashes are reflected not only from the satellites relied on for navigation, communication, weather forecasting, and more, but also from space trash such as dead satellites, paint chips and errant nuts and bolts that has accumulated since space exploration began six decades ago.

These short duration flashes can be indistinguishable from stars in images from professional observatories and are typically visible for only a fraction of a second.

"Millions of stargazers have likely observed these quick glimmers of light in the night sky," Corbett said. "Reflected-light flashes happen so fast that observers may dismiss them as visual noise, but this research provides a potential explanation for those mysterious flashes.

Rogue reflections from Earth satellites take two forms: short duration flashes that can lead to mistaken astrophysical events and streaks associated with fast-moving or slowly rotating satellites like SpaceX Starlink.

Companies are competing to launch thousands of satellites capable of beaming internet coverage to Earth. However, in the new study, researchers conclude that the upcoming satellite internet constellations, like SpaceX Starlink, are unlikely to contribute significantly to the appearance of flashes, though there are other potential impacts of satellite constellations on astronomers.

Bright streaks caused by sun-illuminated satellites moving across an image are a separate class of events that needs to be studied.

CAMBRIDGE, MA -- Dealing with a global pandemic has taken a toll on the mental health of millions of people. A team of MIT and Harvard University researchers has shown that they can measure those effects by analyzing the language that people use to express their anxiety online.

Using machine learning to analyze the text of more than 800,000 Reddit posts, the researchers were able to identify changes in the tone and content of language that people used as the first wave of the Covid-19 pandemic progressed, from January to April of 2020. Their analysis revealed several key changes in conversations about mental health, including an overall increase in discussion about anxiety and suicide.

"We found that there were these natural clusters that emerged related to suicidality and loneliness, and the amount of posts in these clusters more than doubled during the pandemic as compared to the same months of the preceding year, which is a grave concern," says Daniel Low, a graduate student in the Program in Speech and Hearing Bioscience and Technology at Harvard and MIT and the lead author of the study.

The analysis also revealed varying impacts on people who already suffer from different types of mental illness. The findings could help psychiatrists, or potentially moderators of the Reddit forums that were studied, to better identify and help people whose mental health is suffering, the researchers say.

"When the mental health needs of so many in our society are inadequately met, even at baseline, we wanted to bring attention to the ways that many people are suffering during this time, in order to amplify and inform the allocation of resources to support them," says Laurie Rumker, a graduate student in the Bioinformatics and Integrative Genomics PhD Program at Harvard and one of the authors of the study.

Satrajit Ghosh, a principal research scientist at MIT's McGovern Institute for Brain Research, is the senior author of the study, which was published last month in the Journal of Internet Medical Research. Other authors of the paper include Tanya Talkar, a graduate student in the Program in Speech and Hearing Bioscience and Technology at Harvard and MIT; John Torous, director of the digital psychiatry division at Beth Israel Deaconess Medical Center; and Guillermo Cecchi, a principal research staff member at the IBM Thomas J. Watson Research Center.

A wave of anxiety

The new study grew out of the MIT class 6.897/HST.956 (Machine Learning for Healthcare), in MIT's Department of Electrical Engineering and Computer Science. Low, Rumker, and Talkar, who were all taking the course last spring, had done some previous research on using machine learning to detect mental health disorders based on how people speak and what they say. After the Covid-19 pandemic began, they decided to focus their class project on analyzing Reddit forums devoted to different types of mental illness.

"When Covid hit, we were all curious whether it was affecting certain communities more than others," Low says. "Reddit gives us the opportunity to look at all these subreddits that are specialized support groups. It's a really unique opportunity to see how these different communities were affected differently as the wave was happening, in real-time."

The researchers analyzed posts from 15 subreddit groups devoted to a variety of mental illnesses, including schizophrenia, depression, and bipolar disorder. They also included a handful of groups devoted to topics not specifically related to mental health, such as personal finance, fitness, and parenting.

Using several types of natural language processing algorithms, the researchers measured the frequency of words associated with topics such as anxiety, death, isolation, and substance abuse, and grouped posts together based on similarities in the language used. These approaches allowed the researchers to identify similarities between each group's posts after the onset of the pandemic, as well as distinctive differences between groups.

The researchers found that while people in most of the support groups began posting about Covid-19 in March, the group devoted to health anxiety started much earlier, in January. However, as the pandemic progressed, the other mental health groups began to closely resemble the health anxiety group, in terms of the language that was most often used. At the same time, the group devoted to personal finance showed the most negative semantic change from January to April 2020, and significantly increased the use of words related to economic stress and negative sentiment.

They also discovered that the mental health groups affected the most negatively early in the pandemic were those related to ADHD and eating disorders. The researchers hypothesize that without their usual social support systems in place, due to lockdowns, people suffering from those disorders found it much more difficult to manage their conditions. In those groups, the researchers found posts about hyperfocusing on the news and relapsing back into anorexia-type behaviors since meals were not being monitored by others due to quarantine.

Using another algorithm, the researchers grouped posts into clusters such as loneliness or substance use, and then tracked how those groups changed as the pandemic progressed. Posts related to suicide more than doubled from pre-pandemic levels, and the groups that became significantly associated with the suicidality cluster during the pandemic were the support groups for borderline personality disorder and post-traumatic stress disorder.

The researchers also found the introduction of new topics specifically seeking mental health help or social interaction. "The topics within these subreddit support groups were shifting a bit, as people were trying to adapt to a new life and focus on how they can go about getting more help if needed," Talkar says.

While the authors emphasize that they cannot implicate the pandemic as the sole cause of the observed linguistic changes, they note that there was much more significant change during the period from January to April in 2020 than in the same months in 2019 and 2018, indicating the changes cannot be explained by normal annual trends.

Mental health resources

This type of analysis could help mental health care providers identify segments of the population that are most vulnerable to declines in mental health caused by not only the Covid-19 pandemic but other mental health stressors such as controversial elections or natural disasters, the researchers say.

Additionally, if applied to Reddit or other social media posts in real-time, this analysis could be used to offer users additional resources, such as guidance to a different support group, information on how to find mental health treatment, or the number for a suicide hotline.

"Reddit is a very valuable source of support for a lot of people who are suffering from mental health challenges, many of whom may not have formal access to other kinds of mental health support, so there are implications of this work for ways that support within Reddit could be provided," Rumker says.

The researchers now plan to apply this approach to study whether posts on Reddit and other social media sites can be used to detect mental health disorders. One current project involves screening posts in a social media site for veterans for suicide risk and post-traumatic stress disorder.

PITTSBURGH, Nov. 5, 2020 - Today in Science, researchers at the University of Pittsburgh School of Medicine describe a new method to extract tiny but extremely powerful SARS-CoV-2 antibody fragments from llamas, which could be fashioned into inhalable therapeutics with the potential to prevent and treat COVID-19.

These special llama antibodies, called "nanobodies," are much smaller than human antibodies and many times more effective at neutralizing the SARS-CoV-2 virus. They're also much more stable.

"Nature is our best inventor," said senior author Yi Shi, Ph.D., assistant professor of cell biology at Pitt. "The technology we developed surveys SARS-CoV-2 neutralizing nanobodies at an unprecedented scale, which allowed us to quickly discover thousands of nanobodies with unrivaled affinity and specificity."

To generate these nanobodies, Shi turned to a black llama named Wally--who resembles and therefore shares his moniker with Shi's black Labrador.

Shi and colleagues immunized the llama with a piece of the SARS-CoV-2 spike protein and, after about two months, the animal's immune system produced mature nanobodies against the virus.

Using a mass spectrometry-based technique that Shi has been perfecting for the past three years, lead author Yufei Xiang, a research assistant in Shi's lab, identified the nanobodies in Wally's blood that bind to SARS-CoV-2 most strongly.

Then, with the help of Pitt's Center for Vaccine Research (CVR), the scientists exposed their nanobodies to live SARS-CoV-2 virus and found that just a fraction of a nanogram could neutralize enough virus to spare a million cells from being infected.

These nanobodies represent some of the most effective therapeutic antibody candidates for SARS-CoV-2, hundreds to thousands of times more effective than other llama nanobodies discovered through the same phage display methods used for decades to fish for human monoclonal antibodies.

Shi's nanobodies can sit at room temperature for six weeks and tolerate being fashioned into an inhalable mist to deliver antiviral therapy directly into the lungs where they're most needed. Since SARS-CoV-2 is a respiratory virus, the nanobodies could find and latch onto it in the respiratory system, before it even has a chance to do damage.

In contrast, traditional SARS-CoV-2 antibodies require an IV, which dilutes the product throughout the body, necessitating a much larger dose and costing patients and insurers around $100,000 per treatment course.

"Nanobodies could potentially cost much less," said Shi. "They're ideal for addressing the urgency and magnitude of the current crisis."

In collaboration with Cheng Zhang, Ph.D., at Pitt, and Dina Schneidman-Duhovny, Ph.D., at the Hebrew University of Jerusalem, the team found that their nanobodies use a variety of mechanisms to block SARS-CoV-2 infection. This makes nanobodies ripe for bioengineering. For instance, nanobodies that bind to different regions on the SARS-CoV-2 virus can be linked together, like a Swiss army knife, in case one part of the virus mutates and becomes drug-resistant.

"As a virologist, it's incredible to see how harnessing the quirkiness of llama antibody generation can be translated into the creation of a potent nanoweapon against clinical isolates of SARS-CoV-2," said study coauthor and CVR Director Paul Duprex, Ph.D.

LOS ANGELES (Nov. 5, 2020) -- An enzyme that helps COVID-19 (coronavirus) infect the body also plays a role in inflammation and patient outcomes in inflammatory bowel disease (IBD), according to a new study led by Cedars-Sinai. The findings raise the possibility that anti-inflammatory drug therapies for IBD may aid recovery from coronavirus.

The multisite study, led by Cedars-Sinai and published today in the journal Gastroenterology, focused on angiotensin-converting enzyme 2 (ACE2), which normally plays a crucial health role by activating a hormone that helps regulate blood pressure. But in COVID-19 infections, the SARS-CoV-2 virus binds to ACE2 and uses it to invade and infect cells, "hijacking" them to spread the virus.

To learn more about how ACE2 affects the body, investigators examined its role in Crohn's disease and ulcerative colitis - two types of IBD that can cause inflammation and scarring (fibrosis) in the digestive tract along with diarrhea, cramping and loss of appetite.

"We chose these disorders because COVID-19, while known for attacking the lungs, frequently causes gastrointestinal symptoms," said Dermot P. McGovern, MD, PhD, the Joshua L. and Lisa Z. Greer Chair in Inflammatory Bowel Disease Genetics and senior author of the new study. "It was important for us to understand how COVID-19 might affect IBD patients who are treated with anti-inflammatory medications. Also, there is increasing evidence that the GI tract may serve as an alternate route for uptake of SARS-COV-2 in general."

By examining records of nearly 1,000 patients at Cedars-Sinai, Washington University in St. Louis, Missouri, and multiple other centers across North America, the team found that levels of ACE2 in the small bowel were lower in Crohn's patients and higher in the colons of ulcerative colitis patients than they were in patients without IBD. The differing ACE2 levels were associated with poorer outcomes and more severe disease in the IBD patients.

"We saw that the effect of ACE2 depended on both its specific location in the gastrointestinal tract and the specific disease involved," said McGovern, professor of Medicine and Biomedical Sciences. "So, this enzyme was a double-edged sword."

In both types of IBD, treatment with infliximab, an anti-inflammatory drug, normalized the levels of ACE2 and was associated with improved disease outcomes in patients. This finding suggests these drugs, commonly used in autoimmune diseases, also might improve outcomes in COVID-19, the investigators said, "Overall, our study supports the potential paradoxical function of ACE2 in inflammation and COVID-19," McGovern explained. "Individuals with higher ACE2 expression may be at increased risk of infection with SARS-CoV-2. But judging from our discoveries of how ACE2 works in IBD, this enzyme likely has anti-inflammatory and anti-fibrotic functions that also could help certain COVID-19 patients recover from the virus."

Further research is needed to delineate the processes involving ACE2 and what they might mean for treating COVID-19 patients, he said. In support of that effort, the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health recently awarded a two-year grant of $677,036 to McGovern to examine overlaps in the mechanisms that drive inflammation in IBD and COVID-19.

NEW YORK, NY (Nov. 5, 2020)--Children and adults produce different types and amounts of antibodies in response to infection with the new coronavirus, SARS-CoV-2, a new study from researchers at Columbia University Vagelos College of Physicians and Surgeons has found.

The differences in antibodies suggest the course of the infection and immune response is distinct in children and most children easily clear the virus from their bodies. 

"Our study provides an in-depth examination of SARS-CoV-2 antibodies in kids, revealing a stark contrast with adults," says Columbia University immunologist Donna Farber, PhD, the George H. Humphreys II Professor of Surgical Sciences in the Department of Surgery, who led the study with Matteo Porotto, PhD, associate professor of viral molecular pathogenesis in Columbia's Department of Pediatrics. The first authors, Stuart Weisberg, MD, PhD, assistant professor of pathology & cell biology, and Thomas Connors, MD, assistant professor of pediatrics, enrolled patients into the study and conducted the data analysis.

"In kids, the infectious course is much shorter and probably not as disseminated as in adults," Porotto adds. "Kids may clear this virus more efficiently than adults and they may not need a strong antibody immune response to get rid of it."

Children Less Affected by SARS-CoV-2

One of the striking manifestations of the COVID-19 pandemic is that the majority of children cope well with the virus while older people struggle.

"This is a new infection for everybody," Farber says, "but children are uniquely adapted to see pathogens for the first time. That's what their immune system is designed to do. Children have a lot of naive T cells that are able to recognize all sorts of new pathogens, whereas older people depend more on our immunological memories. We're not as able to respond to a new pathogen like children can."

Children Make Fewer SARS-CoV-2 Neutralizing Antibodies

Among the 47 children in the study, 16 were treated at Columbia University Irving Medical Center for MIS-C and 31 children of similar ages had tested positive for the virus after visiting the medical center for the treatment of other conditions. Half of the children without MIS-C had no COVID-19 symptoms. The 32 adults in the study ranged from severely affected patients admitted to the hospital to those with milder disease who recovered at home.

Both groups of children produced the same antibody profile, the study found, which differed from that of adults. 

Compared with adults, children produced fewer antibodies against the virus's spike protein--which the virus uses to infect human cells. The children's antibodies had the least neutralizing activity, while all adults, including young adults in their 20s, produced neutralizing antibodies. The sickest adults had the most neutralizing activity.

Though it may seem counterintuitive that the sickest patients produce antibodies with the greatest neutralizing activity, Farber says that likely reflects the amount of time the virus is present in the sickest patients. 

"There is a connection between the magnitude of your immune response and the magnitude of the infection: The more severe the infection, the more robust the immune response, because you need to have more immune cells and immune reactions to clear a higher dose of a pathogen." 

Other Antibody Differences Show Children's Infections Are Limited

In contrast to adults, children also produced very few antibodies against a viral protein that is only visible to the immune system after the virus infects human cells.

"That suggests that in kids, the infection doesn't really spread a lot and doesn't kill a lot of their cells," Farber says.

"Because children clear the natural virus rapidly, they do not have a widespread infection and they do not need a strong antibody response," Porotto says. 

The reduced course of infection in children may signify that they are infectious for a shorter period of time compared with adults and therefore less likely to spread the virus, although the researchers did not measure viral load in the children.

"Current studies in other countries indicate that younger school-age children are not vectors for the new coronavirus, so our data are consistent with those findings," Farber says.

Children Should Respond Well to Vaccine

The antibody responses found in children do not suggest that children will have a weaker response to a vaccine, the researchers say. 

Vaccines under development for SARS-CoV-2 contain pieces of the virus and do not mimic the normal route of infection.

"Even though children don't produce neutralizing antibodies in response to a natural infection with SARS-CoV-2, vaccines are designed to generate a protective immune response in the absence of an infection," Farber says. "Children respond very well to vaccines, and I think they will develop good neutralizing antibody responses to a SARS-CoV-2 vaccine, and they'll probably be better protected than the adults.

"That said, very few vaccine studies are currently enrolling children and we will need this data to really understand how well the vaccines work in children."

What Does the Adult Immune System Lack?

Though the findings suggest the course of infection in children and adults is different, it's still not known how the children are able to clear the virus more easily--and what the adult immune system lacks.

Farber, Porotto, and their colleagues at Columbia are now looking for differences in T-cell response (antibodies are produced by the immune system's B cells), especially T cells that reside in the lung. [Previous research from Farber's lab has shown these "stay-at-home" T cells are more important in fighting lung infections than T cells that travel through the body via the bloodstream].

Children infected with SARS-CoV-2 also may generate a stronger response from the innate immune system, which deploys interferon and cells called macrophages to indiscriminately attack cells infected by pathogens. Earlier studies suggest that the innate immune response may be delayed in adults infected with SARS-CoV-2.

"If the innate response is really strong, that can reduce the viral load in the lungs, and the antibodies and T cells of the adaptive response have less to clear up," Farber says. 

It's also possible that the virus is less able to infect children's cells, possibly because children's cells express fewer proteins the virus needs to infect human cells.

The Columbia researchers are now testing these possibilities with cells from children versus adults.

"There are still all these issues that we have very little information about," Porotto says. "The interaction between the virus and the host is the reason why we see so much diversity in responses to this virus, but we don't understand enough about this virus yet to really determine what leads to severe disease and what leads to mild disease."

November 5, 2020 - Studies using repetitive transcranial magnetic stimulation (rTMS), a noninvasive technique, to help veterans and active-duty service members living with depression, post-traumatic stress disorder (PTSD), and other lasting consequences of concussion have shown promise. However, there's an urgent need for studies designed to address the unique patterns of post-concussion symptoms seen in military populations, concludes a review in the November/December issue of the Journal of Head Trauma Rehabilitation (JHTR). The official journal of the Brain Injury Association of America, JHTR is published in the Lippincott portfolio by Wolters Kluwer.

"rTMS represents a novel innovative, and possibly transformative approach to the treatment of chronic neuropsychiatric and neurocognitive symptoms associated with military concussion," write David L. Brody, MD, PhD, of the Center for Neuroscience and Regenerative Medicine at the Uniformed Services University of the Health Sciences, Bethesda, Md., and colleagues. They highlight the need for higher-quality evidence to guide the use of rTMS for service members and veterans with post-concussion symptoms.

rTMS for post-concussive symptoms in veterans: 'Smarter trials' needed

More than 342,000 US service members have experienced concussion over the past two decades. Many of them are living with post-concussive symptoms - especially depression, PTSD, and cognitive issues, often in combination. Despite the high impact of these chronic neuropsychiatric and neurocognitive symptoms, there is a lack of effective, evidence-based treatments.

One potentially useful approach is rTMS, consisting of repeated sessions of noninvasive magnetic stimulation, targeted to specific areas of the brain. Specific rTMS protocols are approved for the treatment of selected patients with major depressive disorder. A growing body of evidence suggests that rTMS may be effective for PTSD and cognitive issues as well.

However, the effectiveness of rTMS for post-concussion symptoms remains unclear; many studies have specifically excluded patients with brain injury or head trauma. In addition, the nature of military concussions and post-concussion symptoms may be very different than in civilian populations.

To assess the current state of knowledge, Dr. Brody and colleagues reviewed the research literature on rTMS for post-concussion symptoms. They identified a total of nine clinical trials, mainly small-scale pilot studies. Evidence for the effectiveness of rTMS for specific types of symptoms was mixed, at best:

Depression. Of six studies evaluating the effects of rTMS for depression, three reported positive results but three found no improvement. Three of the studies did not assess veterans or service members.

PTSD. Three of the depression studies did include patients with military concussions, and all of them also included data on PTSD. However, just one study reported improvement in PTSD symptoms with rTMS.

Cognitive issues. Five studies included data on cognitive outcomes of rTMS; none found significant improvement. One recent trial designed for veterans with mild to moderate traumatic brain injury reported no improvement in executive functioning: a key aspect of cognitive performance.

Based on the results, "there is simply insufficient data" to support the effectiveness of any specific rTMS protocol, Dr. Brody and coauthors write. They do note that rTMS appears safe, and that the negative results in preliminary trials don't necessarily mean that rTMS is ineffective. Key questions remain as to the best stimulation settings and number of sessions, as well as the optimal approach to military and other patients with multiple clinical issues.

"The importance of optimizing feasibility and efficacy of rTMS to treat service members and veterans with chronic neuropsychiatric and neurocognitive symptoms associated with concussion cannot be overstated," Dr. Brody and colleagues conclude. "We need to begin to design smarter trials that are powered to answer research questions to confidently assess and recommend rTMS as a treatment option for this population."

Scientists have found that insulin has met an evolutionary cul-de-sac, limiting its ability to adapt to obesity and thereby rendering most people vulnerable to Type 2 diabetes.

A recent study from scientists at Indiana University School of Medicine, the University of Michigan and Case Western Reserve University has determined that the sequence of insulin has become entrenched at the edge of impaired production, an intrinsic vulnerability unmasked by rare mutations in the insulin gene causing diabetes in childhood. The study exploits biophysical concepts and methods to relate protein chemistry to the emerging field of evolutionary medicine.

Insulin is produced by a series of highly specific processes that occur in specialized cells, called beta cells. A key step is the folding of a biosynthetic precursor, called proinsulin, to achieve the hormone's functional three-dimensional structure. Past studies from this and other groups have suggested that impaired biosynthesis could be the result of diverse mutations that hinder the foldability of proinsulin.

This group sought to determine if the evolution of insulin in vertebrates--including humans--has encountered a roadblock. Has a complex series of steps imposed constraints that have frozen the sequence of insulin at a precipice of non-foldability? And if so, has this left humankind vulnerable to Type 2 diabetes as a pandemic disease of civilization?

According to the study published in the Proceedings of the National Academy of Sciences, the answers are yes and yes.

"Biological processes ordinarily evolve to be robust, and this protects us in the majority of cases from birth defects and diseases," said Michael Weiss, MD, PhD, Distinguished Professor at IU School of Medicine and lead investigator of the study. "Yet diabetes seems to be an exception."

Weiss and team looked at a subtle mutation in human insulin in relation to the insulins of other animals, such as cows and porcupines. The mutant human insulin functions within the range of natural variation among animal insulins, and yet this mutation has been excluded by evolution. The answer to this seeming paradox is that the forbidden mutation selectively blocks the folding of proinsulin and stresses beta cells.

The group discovered that even the slightest variation of the insulin-sequencing process not only impairs insulin folding (and eventual insulin secretion) but also induces cellular stress that leads to beta cell dysfunction and eventually permanent damage.

Weiss, who is also Chair of the Department of Biochemistry and Molecular Biology and a Precision Health Initiative Professor, said that the study highlights the importance of folding efficiency as a critical but hidden factor in the evolution of insulin over the past 540 million years. Humans have evolved to be vulnerable to diverse mutations in the insulin gene and that this vulnerability underlies a rare monogenic form of diabetes and provides an evolutionary backdrop to the present obesity-related diabetes pandemic.

National experts agree that this discovery provides key insight to better understanding the development of Type 2 diabetes in adults and children--which both are rising at alarming rates in Indiana and around the world.

"This study is a tour de force unraveling key elements of the structural biology of insulin that affect its synthesis and function," said Barbara Kahn, MD, George R. Minot Professor of Medicine at Harvard Medical School. "The authors highlight the fact that the insulin gene has been susceptible throughout evolution to mutations that impair insulin's function or stress beta cells. As we approach the 100th anniversary of the discovery of insulin, these elegant observations might lead to a better understanding of the pathogenesis of Type 2 diabetes."

Director of the University of Chicago Kolver Diabetes Center Louis Philipson, MD, agreed, adding that findings will shape future approaches to research in this area.

"The present findings define a major question for the future: whether harmful misfolding of proinsulin seen in patients bearing INS gene variants may also occur, at lower levels perhaps, but more broadly in the population of human Type 2 diabetes patients around the world," Philipson said.

Next, the group will work to fully define the sequence determinants that make proinsulin foldable in beta cells. Their hope is that this work will eventually lead to a new category of drugs that mitigate the cellular stress caused by proinsulin's precarious foldability and target cellular stress in beta cells, thereby preserving insulin-production for high-risk patients.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Less contact implies less disease spread.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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