Culture

Too little sleep can mean more asthma attacks in adults

ARLINGTON HEIGHTS, IL - (MAY 12, 2020) - A good night's sleep is crucial to good health. A new article in Annals of Allergy, Asthma and Immunology, the scientific journal of the American College of Allergy, Asthma and Immunology (ACAAI) reveals that too little sleep, and occasionally too much sleep, can negatively impact adults with asthma.

"Previous research revealed that poor sleep quality has a negative effect on asthma symptoms in adolescents," says Faith Luyster, PhD, lead author of the study. "Our study shows that adults with asthma are equally affected by too little (or sometimes too much) sleep. Compared to normal sleepers, short and long sleepers had a higher proportion of people who reported having an asthma attack in the past year (45 percent vs. 59 percent and 51 percent respectively) and had more days with impaired health-related quality of life. Impaired quality of life was characterized by more days of poor physical and mental health.

The study surveyed 1,389 adults who were 20 years and older who self-identified as having asthma. Of the group, 25.9 percent slept 5 hours or less, 65.9 percent slept 6-8 hours and 8.2 percent slept 9 or more hours. Sleep duration was measured by a single question, "How much sleep do you usually get at night on weekdays or workdays?" "Short sleepers" were more likely to be younger and non-White, while "long sleepers" were more likely to be older, female and a smoker.

Short sleepers, as compared to normal sleepers, had a greater likelihood of an asthma attack, dry cough, and an overnight hospitalization during the past year. Short sleepers also had significantly worse health related quality of life -- including days of poor physical and mental health and inactive days due to poor health -- and more frequent general healthcare use during the past year as compared to normal sleepers. The odds for long sleepers to have some activity limitation due to wheezing was higher when compared to normal sleepers. No significant differences in other patient-reported outcomes and healthcare use were observed between the long and normal sleepers.

"Disturbed sleep in an asthma patient can be a red flag indicating their asthma isn't well-controlled," says allergist Gailen D. Marshall, MD, PhD, ACAAI member and Editor-in-Chief of Annals. "This study adds solid evidence to the practice of asthma patients discussing sleep issues with their allergist to help determine if they need to change their asthma plan to achieve adequate sleep as a component of overall good asthma management. It also warns that consequences can be expected when sleep patterns are chronically inadequate."

Allergists are specially trained to diagnose and treat asthma. To find an allergist near you who can help create a personal plan to deal with your asthma and help you live your best life, use the ACAAI allergist locator.

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American College of Allergy, Asthma, and Immunology

SwRI scientist modeled Mars climate to understand habitability

image: An SwRI scientist modeled the climate of Mars to understand if hydrated salts or brines on the surface of the Red Planet could harbor life. The results suggest that hydrated salts and brines on Mars are not supportive of life. For example, if the dark streaks shown here are formed by the flow of briny water, then that briny water would be too cold to support life.

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NASA/JPL-Caltech/University of Arizona

SAN ANTONIO -- May 11, 2020 -- A Southwest Research Institute scientist modeled the atmosphere of Mars to help determine that salty pockets of water present on the Red Planet are likely not habitable by life as we know it on Earth. A team that also included scientists from Universities Space Research Association (USRA) and the University of Arkansas helped allay planetary protection concerns about contaminating potential Martian ecosystems. These results were published this month in Nature Astronomy.

Due to Mars' low temperatures and extremely dry conditions, a droplet of liquid water on its surface would instantly freeze, boil or evaporate, unless the droplet had dissolved salts in it. This brine would have a lower freezing temperature and would evaporate more slowly than pure liquid water. Salts are found across Mars, so brines could form there.

"Our team looked at specific regions on Mars -- areas where liquid water temperature and accessibility limits could possibly allow known terrestrial organisms to replicate -- to understand if they could be habitable," said SwRI's Dr. Alejandro Soto, a senior research scientist and co-author of the study. "We used Martian climate information from both atmospheric models and spacecraft measurements. We developed a model to predict where, when and for how long brines are stable on the surface and shallow subsurface of Mars."

Mars' hyper-arid conditions require lower temperatures to reach high relative humidities and tolerable water activities, which are measures of how easily the water content may be utilized for hydration. The maximum brine temperature expected is -55 F -- at the boundary of the theoretical low temperature limit for life.

"Even extreme life on Earth has its limits, and we found that brine formation from some salts can lead to liquid water over 40% of the Martian surface but only seasonally, during 2% of the Martian year," Soto continued. "This would preclude life as we know it."

While pure liquid water is unstable on the Martian surface, models showed that stable brines can form and persist from the equator to high latitudes on the surface of Mars for a few percent of the year for up to six consecutive hours, a broader range than previously thought. However, the temperatures are well below the lowest temperatures to support life.

"These new results reduce some of the risk of exploring the Red Planet while also contributing to future work on the potential for habitable conditions on Mars," Soto said.

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Southwest Research Institute

New Massachusetts poll: COVID-19 dominates views on politics, daily life

The COVID-19 pandemic dominates views of government, politics and virtually all aspects of daily life, according to a new poll of Massachusetts voters.

The poll by the UMass Lowell Center for Public Opinion of 1,000 Massachusetts registered voters found that a majority like the state's response to the pandemic and dislike how the federal government is handling it. Eighty-one percent said they approve of Gov. Charlie Baker's job performance and although he is a Republican, his approval is highest among Democrats (89 percent), compared to independents (77 percent) and Republicans (67 percent). His net favorability rating with voters is +57 (72 percent favorable, 15 percent unfavorable).

"One of the persistent threads in this survey is that many of the results about the current pandemic have been captured by what has become an all-too-predictable pattern of partisan-motivated reasoning. And yet, here we have Republican Gov. Charlie Baker, who seems to exist on a different plane when it comes to partisanship. The state is given high marks for its response to coronavirus and for Baker's job performance, but most remarkably, his approval rating with Democrats is higher than it is among Republicans," said Joshua Dyck, director of the Center for Public Opinion and associate professor of political science.

Eighty percent of voters said they are satisfied with the Commonwealth's response to COVID-19, compared to 37 percent who expressed satisfaction with the federal government's response. However, 82 percent of Republicans polled said they are satisfied with the federal response, compared to 18 percent of Democrats.

Only 32 percent of registered voters approve of President Donald Trump's job performance while 68 percent disapprove. Seventy-three percent of registered voters polled said they think the country is on the wrong track, compared to 27 percent who said it is on the right track. Seventy-four percent of Republicans said the country is headed in the right direction, compared with 6 percent of Democrats and 30 percent of independents surveyed.

The poll also found that 4 in 10 Massachusetts registered voters said they know someone who has tested positive for COVID-19 and 1 in 5 said they know someone who has died from the virus. Less than half of those polled (40 percent) said they are confident they could get a coronavirus test if they want one and those that are not confident are more likely to be from lower income brackets: 31 percent of those from families that earn less than $50,000 a year said they have no confidence they could get a test compared to 22 percent among those earning $100,000 or more annually. Sixty-one percent of voters said they are confident they could get a ventilator if needed, but 23 percent of non-white poll respondents said they have no confidence they could get a ventilator compared to 9 percent of white respondents.

"The effects of the COVID-19 pandemic appear to have exacerbated structural inequalities in ways that should concern public officials. Those at the lowest income levels are more likely to express no confidence that they will be able to access a test if needed, while people of color and those younger than 45 are more likely to say that they have lost income since the closure of non-essential businesses in Massachusetts. Furthermore, people of color are more than twice as likely to believe they will not have access to vital medical services like ventilators if hospitalized, reflecting realized anxiety over a history of unequal health service delivery," said Dyck.

Fifty percent of Massachusetts registered voters believe the state's social distancing measures - closing non-essential businesses, limiting gatherings of people and recommending people stay at home - will be lifted no later than July 4. Thirty-three percent said between July 4 and Labor Day, 11 percent said between Labor Day and New Year's 2021, and 5 percent said the order would stay in place into 2021.

"Despite repeated warnings from health officials that the return to our pre-pandemic lives will take years, not months, Bay Staters remain confident that social distancing orders will be lifted in time for them to enjoy the summer. Massachusetts voters have a good idea of what's going on now, but are in for a shock about what's to come. The question is, will voters lose faith in the officials they view favorably as the pandemic and the pain that comes with it drags on?" said John Cluverius, associate director of the UMass Lowell Center for Public Opinion and assistant professor of political science.

The economic impact of COVID-19 is being felt in Massachusetts, with 23 percent of those polled saying they have lost their job since the start of the pandemic. Of those who lost jobs, a majority said they are furloughed and believe they will be able to return. Thirty-one percent said their income has decreased.

The survey also asked registered voters several other questions about how COVID-19 is affecting their daily lives. Findings include:

55 percent have conducted social activities via video chat, but some said they have made exceptions to social distancing practices, such as visiting a family member (22 percent) and attending gatherings with neighbors (8 percent);

36 percent have changed spending habits in response to how employers have treated their employees during the pandemic;

83 percent have increased/improved their handwashing;

63 percent have stocked up on food and 51 percent on consumer products like toilet paper;

25 percent have learned a new skill at home.

Detailed poll results - including analysis, topline and methodology - are available at http://www.uml.edu/polls. The independent, nonpartisan poll was conducted by the University of Massachusetts Lowell's Center for Public Opinion using the latest technology and highest standards. The center is a member of the American Association for Public Opinion Research's Transparency Initiative and presents events and polls on political and social issues that provide unique opportunities for civic engagement, experiential learning and research.

Looking at the presidential race, 58 percent of Massachusetts registered voters said they would vote for former Vice President Joe Biden, the Democratic challenger to Trump, who has the support of 30 percent of registered voters. Seven percent of those polled said they will vote for another candidate and 4 percent said they are undecided.

Biden has a +17 net positive favorability rating (52 percent favorable, 35 percent unfavorable) with registered Massachusetts voters, compared with -34 negative favorability rating (30 percent favorable, 64 percent unfavorable) for Trump. Dr. Anthony Fauci of the White House coronavirus task force has a +57 net positive favorability rating (67 percent favorable, 10 percent unfavorable). Former President Barack Obama has a +42 net positive favorability rating. Vice President Mike Pence has a -29 net negative favorability rating and presidential adviser and son-in-law Jared Kushner is at a -44 net negative rating. More on public figures' favorability ratings from the poll is available at http://www.uml.edu/polls.

The poll also asked 531 likely voters in the Massachusetts Democratic primary, set for September, who they would vote for in the race for the party's nomination for U.S. Senate. The survey found a close race, with challenger Joe Kennedy III with 44 percent of support among likely voters and 42 percent supporting incumbent U.S. Sen. Ed Markey, while 10 percent are undecided. A poll by the Center for Public Opinion conducted in February of likely Massachusetts Democratic presidential primary voters found a similarly close race, with only 1 percentage point separating the candidates, but at that time, 23 percent of voters said they were undecided.

In the poll released today, Markey leads among likely voters who identify themselves as liberals (54 percent to 39 percent), while Kennedy is ahead among moderates (55 percent to 25 percent).

"It seems like so far, undecided voters are flipping a coin between the two candidates. It's a trench fight and both sides are dug in and holding their own," said Cluverius.

A majority of registered voters surveyed (72 percent) said they would vote in person if the election was held now and no remote option was available. Seventy-four percent said they support allowing voting by mail in any future Massachusetts election.

Massachusetts registered voters were also surveyed on a range of other topics and findings include:

Dunkin' has a +63 net positive favorability rating (73 percent favorable, 10 percent favorable) with Massachusetts registered voters from all parties, which is even higher than the +52 it received in a poll of likely Massachusetts Democratic primary voters in February;

Market Basket is even more popular than Dunkin', with a +64 positive net favorability rating;

Despite leaving New England for Tampa Bay, Tom Brady has a +35 positive net favorability rating (56 percent favorable and 21 percent unfavorable) and Rob Gronkowski, who is coming out of retirement to play with Brady, has a +41 net positive favorability rating;

Boston Mayor Marty Walsh has a +36 net positive favorability rating;

MassHealth also has a strong positive rating at +48 (59 percent favorable and 11 percent unfavorable).

The poll surveyed 1,000 Massachusetts registered voters and 531 likely voters in the Massachusetts Democratic Senate primary. The poll was designed and analyzed by the Center for Public Opinion and fielded by YouGov from April 27 through May 1. The adjusted margin of error for registered voters is plus or minus 3.6 percent and for likely voters, plus or minus 7.8 percent. Full poll methodology is available at http://www.uml.edu/polls.

UMass Lowell is a national research university located on a high-energy campus in the heart of a global community. The university offers its more than 18,000 students bachelor's, master's and doctoral degrees in business, education, engineering, fine arts, health, humanities, sciences and social sciences. UMass Lowell delivers high-quality educational programs, vigorous hands-on learning and personal attention from leading faculty and staff, all of which prepare graduates to be leaders in their communities and around the globe. http://www.uml.edu

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University of Massachusetts Lowell

Emotional well-being while home gardening similar to other popular activities, study finds

image: Research led by Princeton's Anu Ramaswami, the Sanjay Swani '87 Professor of India Studies, professor of civil and environmental engineering and the Princeton Environmental Institute (PEI), and research specialist Graham Ambrose is the first to quantify the emotional well-being (happiness) that people experience while gardening at home. Their results -- published in the journal Landscape and Urban Planning -- suggest that household gardens could be key to providing food security in urban areas and making cities more sustainable and livable. This infographic breaks down the key findings of the study.

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Mae-Yung Tang, Princeton Environmental Institute

As civic leaders and urban planners work to make cities more sustainable and livable by investing in outdoor spaces and recreational activities such as biking and walking, Princeton researchers have identified the benefit of an activity largely overlooked by policymakers -- home gardening.

The researchers found that, across the study's population, the level of emotional well-being, or happiness, reported while gardening was similar to what people reported while biking, walking or dining out, according to a study published in the journal Landscape and Urban Planning. Home gardening was the only activity out of the 15 studied for which women and people with low incomes reported higher emotional well-being than men and medium- and high-income participants, respectively.

"This has implications for equity in food action planning considering that people with lower incomes tend to have less access to healthy food options," said corresponding author Anu Ramaswami, Princeton's Sanjay Swani '87 Professor of India Studies, professor of civil and environmental engineering and the Princeton Environmental Institute (PEI). "Gardening could provide the health benefits of fresh fruits and vegetables, promote physical activity, and support emotional well-being, which can reinforce this healthy behavior."

The benefits of gardening on happiness were similar across racial boundaries and between urban and suburban areas, said first author Graham Ambrose, a research specialist in Princeton's Department of Civil and Environmental Engineering. In addition, whether people gardened alone or with others made no difference, and people who kept vegetable gardens reported a higher level of average emotional well-being than people who worked in ornamental gardens.

The findings came from a study of 370 people in the Minneapolis-St. Paul metropolitan area for which people used a cellphone app called Daynamica to report their emotional well-being while engaged in any of 15 daily activities. The app was developed by study co-author Yingling Fan, a professor of urban and regional planning at the University of Minnesota, who led a larger emotional well-being study as a part of the National Science Foundation-funded Sustainable Healthy Cities Network led by Ramaswami. Co-author Kirti Das, a postdoctoral research associate in civil and environmental engineering at Princeton, was instrumental in recruiting participants from a range of communities and in implementing the survey.

As part of ongoing research into urban food systems in Ramaswami's Sustainable Urban Infrastructure Systems Lab, she and Ambrose contributed questions to the survey that specifically related to household vegetable gardening. While the social and environmental benefits of community gardens are hot topics in urban research, available data seem to fall short when it comes to gardening in individual households, Ambrose said.

"People know where community gardeners garden, but it is hard to know who is gardening at home, which our group uniquely identified," Ambrose said. For example, study authors found that 31% of participants engaged in home gardening for about 90 minutes per week on average, compared to 19% who engaging in biking (an average of 30 minutes each week) and 85% who walked (an average of one hour and 40 minutes each week).

"Many more people garden than we think and it appears that it associates with higher levels of happiness similar to walking and biking," Ramaswami said. "In the movement to make cities more livable, gardening might be a big part of improving quality-of-life."

The researchers found that home gardening was among the top five activities in terms of how meaningful an activity felt to people while engaging in it.

"The high levels of meaningfulness that respondents reported while gardening might be associated with producing one's own food," Ambrose said. "The boost to emotional well-being is comparable to other leisure activities that currently get the lion's share of infrastructure investment. These finding suggest that, when choosing future well-being projects to fund, we should pay just as much attention to household gardening."

A few cities have conducted pilot household gardening projects with promising results. For example, a project operated by the Phipps Conservatory and Botanical Gardens in Pittsburgh provided participants with materials and training to start a garden at home. In 2017, three years after the project began, 70% of participants were still actively gardening.

The researchers of the current study plan to replicate this work among community gardeners in order to compare the emotional benefit of household gardens versus community gardens, Ramaswami said. These results will be important for food action planning in cities such as Minneapolis where Ramaswami has an ongoing project with community members and organizations, as well as the City of Minneapolis, to develop a food action plan.

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Princeton University

COPD and smoking associated with higher COVID-19 mortality

Current smokers and people with chronic obstructive pulmonary disease (COPD) have an increased risk of severe complications and higher mortality with COVID-19 infection, according to a new study published May 11, 2020 in the open-access journal PLOS ONE by Jaber Alqahtani of University College London, UK, and colleagues.

 

COPD is a common, persistent dysfunction of the lung associated with a limitation in airflow. An estimated 251 million people worldwide are affected by COPD. Given the effects of the SARS-CoV-2 coronavirus on respiratory function, the authors of the present study sought to understand the prevalence and the effects of COPD in COVID-19 patients.

 

In the new study, researchers systematically searched databases of scientific literature to find existing publications on the epidemiological, clinical characteristics and features of COVID-19 and the prevalence of COPD in COVID-19 patients. 123 potentially relevant papers were narrowed to 15 that met all quality and inclusion guidelines. The included studies had a total of 2473 confirmed COVID-19 patients. 58 (2.3%) of those patients also had COPD while 221 (9%) were smokers.

 

Critically ill COVID-19 patients with COPD had a 63% risk of severe disease and a 60% risk of mortality while critically ill patients without COPD had only a 33.4% risk of severe disease (RR 1.88, 95% CI 1.4-2.4) and 55% risk of mortality (RR 1.1, 95% CI 0.6-1.8). In addition, current smokers were 1.45 times more likely to have severe complications compared to former and never smokers (95% CI 1.03-2.04). The study was not able to examine whether there was an association between the frequency of COPD exacerbations, or severity of COPD, with COVID-19 outcomes or complications. The results are limited by the fact that few studies were available to review, as well as the diverse locations, settings, and designs of the included studies.

The authors add: "Despite the low prevalence of COPD and smoking in COVID-19 cases, COPD and current smokers were associated with greater COVID-19 severity and mortality."

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PLOS

Telehealth during COVID-19 may lead to better outcomes for diabetes patients

image: Journal that covers new technology and new products for the treatment, monitoring, diagnosis, and prevention of diabetes and its complications.

Image: 
Mary Ann Liebert, Inc., publishers

New Rochelle, NY, May 11, 2020--A new study has shown that for some patients with type 1 diabetes the close monitoring of their condition using telehealth protocols combined with appropriate technology may lead to better care during the COVID-19 pandemic, when patients are avoiding in-person visits. The study, which found that telehealth monitoring could help avoid admissions for diabetic ketoacidosis, is published in Diabetes Technology & Therapeutics (DTT), a peer-reviewed journal from Mary Ann Liebert, Inc., publishers. Click here to read the full-text article free on the Diabetes Technology & Therapeutics (DTT) website.

Entitled "The Silver Lining to COVID-19: Avoiding Diabetic Ketoacidosis Admissions with Telehealth," the article is coauthored by Anne Peters, MD, Keck School of Medicine of the University of Southern California (Los Angeles) and Satish Garg, MD, DTT Editor-in-Chief, University of Colorado Denver (Aurora).

The authors present two case studies of patients with type 1 diabetes who were treated from home using telehealth. The first was a 21-year-old male who had symptoms of COVID-19, was self-quarantining, and had rising blood glucose levels and strongly positive urinary ketones. Shared glucose data through a continuous glucose monitor (CGM) made it possible to make frequent insulin dose adjustments. He was able to recover without the need for physical interaction with the healthcare system.

The second case involved a 26-year-old woman with new-onset type 1 diabetes who was seen on day 1 briefly in the clinic for diabetes education and to obtain the necessary technology. She had very high glucose levels with ketosis. Ongoing management was via telehealth, and her glucose values improved significantly by day 6. She, too, avoided admission for hyperglycemia associated with diabetic ketosis.

"The COVID-19 pandemic has forced dramatic changes in the delivery of healthcare even in acute situations like diabetic ketoacidosis via telehealth," says DTT Editor-in-Chief Satish Garg, MD, Professor of Medicine and Pediatrics at the University of Colorado Denver (Aurora). "The clinical outcomes are similar without any hospital admissions, thus saving significant cost. This was made possible in part by the availability of CGM data through Clarity or the Share feature of the Dexcom G6."

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Mary Ann Liebert, Inc./Genetic Engineering News

How to tune out common odors and focus on important ones

"Imagine a dog playing in a garden and smelling all of these different flowery smells, and then somewhere in the distance a predator appears, like a fox. The raw input coming into the dog's nose is a smell that consists of something like 90% flowers and only five or 10% of this predator," CSHL Associate Professor Saket Navlakha explained.

"The question that we sought out to study here is, 'how does this dog suppress this uninformative signal of all these flowers... and amplify the significant part, which is the predator, so that it then reacts appropriately?'"

Dogs have complex brains, so researchers at Cold Spring Harbor Laboratory (CSHL) turned to fruit flies to figure it out. How does the simple fly brain learn to ignore prevalent odors to focus on newer but rarer odorants? These findings may apply to dogs or humans, and could be used to train artificially intelligent machines.

In the May 11 issue of the scientific journal PNAS, postdoctoral researcher Yang Shen and Navlakha outline how this surprisingly complex neural task, called odor habituation, happens in the fly brain and can be translated into computer code.

According to Shen, fruit flies are frequently in situations where their tiny brains need to distinguish between many many 'usual' smells and something potentially more important.

A fruit fly "has about 100,000 neurons in its brain and the actual connectivity of many of these neurons has now been mapped out," Navlakha added.

"This allows us to understand what are the mechanisms that the brain uses to solve this habituation problem from an algorithmic perspective," he said. "So that became the launching point for this project."

The researchers found that odor habituation is driven by an important signal filtering process. When a fly detects an odor, a few select neurons (called Kenyon cells) respond to it. The pattern of firing in these responding neurons make up what's called the "tag" for the odor. If an odor is constantly present but conveys no urgent information to the fly, the neurons that make up the odor's tag will start to decrease their activity over time. This is the brain habituating to a background smell. An odor tag with fewer active neurons is less likely to elicit a response in an organism than an odor with lots of neuron activity. As a result, smells that are around all the time can be ignored in favor of a new odor that is faint but important.

A fly brain suppresses responses to repeated odors, but the process can also be reversed if the odor becomes more rare or more important to the fly.

"By framing this computationally, we can better our understanding of the whole process of how signals are being processed in the brain," Shen said.

Navlakha is on a mission to bridge the divide between computational research and neuroscience.

"One of the goals of this entire research direction is to try and understand the brain as a kind of library of algorithms that has been evolved to solve basic information processing problems," he said. "This odor habituation process is something that has not been extensively used in, for example, robotics applications where you have a lot of streaming data and you want to filter unnecessary data."

"It wasn't our goal to say that this algorithm from neuroscience is better than anything else that anyone has developed," he added, "but it has been an opportunity to understand how biology solves this problem and how habituation affects our ability to perceive and discriminate odors."

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Cold Spring Harbor Laboratory

University of Toledo scientists discover new targets for preventing damage from viral infections

image: Dr. Malathi Krishnamurthy, associate professor in The University of Toledo Department of Biological Sciences

Image: 
Daniel Miller, The University of Toledo

When the body faces stressful conditions such as high temperatures or lack of nutrients, cells produce the same large structures they make to combat virus infections.

Scientists at The University of Toledo discovered the connection that could be an attractive bulls-eye to aim for when identifying new antiviral targets and immune modulators to fight diverse viruses.

"In light of the ongoing COVID-19 pandemic, this is a promising avenue to protect people by enhancing immune response and stop the spread of deadly viral infections," Dr. Malathi Krishnamurthy, associate professor in the UToledo Department of Biological Sciences, said. "There is an urgent need to identify new drugs and new drug targets."

Research published in the Journal of Virology shows how cells in our body use a unique platform that is normally made during stress to combat virus infection. These new targets have potential to lead to new drug therapies to prevent serious damage to human health by harmful viruses.

"Understanding the molecular mechanisms of how the body defends itself is critical for the development of new treatment strategies against viruses," Krishnamurthy said. "Currently available antiviral therapies target viral replication or viral proteins, but high mutation rates of viruses often lead to drug resistance. Therefore, identification of host response pathways identified in these studies that are common to many viruses can be used to combat a broad range of viral infections, including SARS-CoV2, and improve human health."

In this study, the researchers demonstrated how a combination of proteins and RNAs called stress granules produced in response to different types of environmental stress also is produced when an enzyme present in all our cells called Ribonuclease L (RNase L) is "turned on" in virus-infected cells.

During virus infection, double-stranded RNA (dsRNA) molecules are produced that alert the host cells of an infection to activate immune pathways.

Specialized cells in our body sense these dsRNAs, which are unique to a virus-infected cell, and produce a chemical called interferon to protect the body and clear the virus infection.

These interferons activate RNase L, which is "turned on" by a small molecule that is produced only during virus infection, and its activity produces more dsRNA to produce more interferon to clear the virus.

"In addition to RNase L, several other proteins in our cells orchestrate response to virus infection, and timely expression and coordination of response is critical to fight viral infections," Krishnamurthy said.

Unlike the body's response to conventional stress, these stress granules produced during virus infection orchestrate a more effective and rapid response to increase interferon production to clear viruses.

"Many viruses adapt and evade these host response pathways, and knowledge gained from these studies may help scientists find targets that can prevent serious damage to human health by harmful viruses," Krishnamurthy said.

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University of Toledo

A close relative of SARS-CoV-2 found in bats offers more evidence it evolved naturally

There is ongoing debate among policymakers and the general public about where SARS-CoV-2, the virus that causes COVID-19, came from. While researchers consider bats the most likely natural hosts for SARS-CoV-2, the origins of the virus are still unclear. On May 10 in the journal Current Biology, researchers describe a recently identified bat coronavirus that is SARS-CoV-2's closest relative in some regions of the genome and which contains insertions of amino acids at the junction of the S1 and S2 subunits of the virus's spike protein in a manner similar to SAR-CoV-2. While it's not a direct evolutionary precursor of SARS-CoV-2, this new virus, RmYN02, suggests that these types of seemingly unusual insertion events can occur naturally in coronavirus evolution, the researchers say.

"Since the discovery of SARS-CoV-2 there have been a number of unfounded suggestions that the virus has a laboratory origin," says senior author Weifeng Shi, director and professor at the Institute of Pathogen Biology at Shandong First Medical University in China. "In particular, it has been proposed the S1/S2 insertion is highly unusual and perhaps indicative of laboratory manipulation. Our paper shows very clearly that these events occur naturally in wildlife. This provides strong evidence against SARS-CoV-2 being a laboratory escape."

The researchers identified RmYN02 from an analysis of 227 bat samples collected in Yunnan province, China, between May and October of 2019. "Since the discovery that bats were the reservoir of SARS coronavirus in 2005, there has been great interest in bats as reservoir species for infectious diseases, particularly as they carry a very high diversity of RNA viruses, including coronaviruses," Shi says. RNA from the samples was sent for metagenomic next-generation sequencing in early January 2020, soon after the discovery of SARS-CoV-2.

Across the whole genome, the closest relative to SARS-CoV-2 is another virus, called RaTG13, which was previously identified from bats in Yunnan province. But RmYN02, the virus newly discovered here, is even more closely related to SARS-CoV-2 in some parts of the genome, including in the longest encoding section of the genome called 1ab, where they share 97.2% of their RNA. The researchers note that RmYN02 does not closely resemble SAR-CoV-2 in the region of the genome that encodes the key receptor binding domain that binds to the human ACE2 receptor that SARS-CoV-2 uses to infect host cells. This means it's not likely to infect human cells.

The key similarity between SARS-CoV-2 and RmYN02, is the finding that RmYN02 also contains amino acid insertions at the point where the two subunits of its spike protein meet. SARS-CoV-2 is characterized by a four-amino-acid insertion at the junction of S1 and S2; this insertion is unique to the virus and has been present in all SARS-CoV-2 sequenced so far. The insertions in RmYN02 are not the same as those in SARS-CoV-2, which indicates that they occurred through independent insertion events. But a similar insertion event happening in a virus identified in bats strongly suggests that these kinds of insertions are of natural origin. "Our findings suggest that these insertion events that initially appeared to be very unusual can, in fact, occur naturally in animal betacoronaviruses," Shi says.

"Our work sheds more light on the evolutionary ancestry of SARS-CoV-2," he adds. "Neither RaTG13 nor RmYN02 is the direct ancestor of SARS-CoV-2, because there is still an evolutionary gap between these viruses. But our study strongly suggests that sampling of more wildlife species will reveal viruses that are even more closely related to SARS-CoV-2 and perhaps even its direct ancestors, which will tell us a great deal about how this virus emerged in humans."

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Cell Press

Medicinal plants thrive in biodiversity hotspots

image: Species-rich tropical forest at Mount Halimun Salak National Park at the island of Java, Indonesia.

Image: 
Leipzig University / Alexandra Muellner-Riehl

With their rich repertoire of anti-infective substances, medicinal plants have always been key in the human fight to survive pathogens and parasites. This is why the search for herbal drugs with novel structures and effects is still one of the great challenges of natural product research today. Scientists from Leipzig University (UL), the Leibniz Institute of Plant Biochemistry (IPB) and the German Centre for Integrative Biodiversity Research (iDiv) have now shown a way to considerably simplify this search for bioactive natural compounds using data analyses on the phylogenetic relationships, spatial distribution and secondary metabolites of plants. Their new approach makes it possible to predict which groups of plants and which geographical areas are likely to have a particularly high density of species with medicinal effects. This could pave the way for a more targeted search for new medicinal plants in the future.

Over 70 per cent of all antibiotics currently in use originate from natural substances obtained from plants, fungi, bacteria and marine organisms. In the battle against infectious diseases, humans are particularly dependent on new drugs from natural sources, as pathogens are constantly changing and producing new dangerous strains. At the same time, we have not exhausted our natural resources. In the plant kingdom alone, only about ten per cent of all vascular plants have so far been screened for suitable active compounds. There are currently about 250,000 structures of natural products stored in scientific databases, with an estimated total of ca. 500,000 in plants alone. So far, however, researchers have not systematically tested the entire plant kingdom; instead, they have conducted isolated searches for drugs, partly in plants with known medicinal properties, and partly in preferred species or geographical regions, or depending on the type and sensitivity of the detection methods used.

Moreover, the knowledge of medicinal plants and their active compounds so far has not been documented consistently. Plants are named differently from region to region, while the metabolites isolated from them are given different trivial names in the literature. The scientists from Leipzig and Halle have now taken a first step towards collecting and standardising this knowledge. To this end, they collected information on the known secondary metabolites, phylogenetic relationships and distribution of the plants on the Indonesian island of Java. They recorded around 7,500 seed plant species, which contained some 16,500 metabolites listed in substance databases. Based on existing knowledge, almost 2,900 of these metabolites were identified as substances with anti-infective effects against viruses, bacteria, fungi or parasites. These 2,900 active compounds are produced by a total of 1,600 of the 7,500 plant species examined.

This shows that not all plant species produce bioactive compounds in the same way. "Rather, there tends to be a concentration of species that produce active compounds in individual plant families, with those species being usually closely related," says Professor Alexandra Muellner-Riehl from the Institute of Biology at Leipzig University, who is also a member of iDiv. In order to better narrow down these groups of plants rich in active compounds, the scientists combined the genetic data and the metabolite information. This made it possible to identify those groups of plants in which anti-infective substances occur with significant overrepresentation - and those where only few anti-infective activities have been documented so far. "This information allows us to identify specific plant groups that very likely possess anti-infective substances but have not yet been examined for them," says Dr Jan Schnitzler (Leipzig University and iDiv). At the same time, the study facilitates the identification of species for which little information on the presence of bioactive compounds has been reported so far. As Professor Ludger Wessjohann of the IPB points out, it is nevertheless important not to ignore these species in the search for new drugs, "because there is a high probability of finding new active substances with as yet completely unknown structures".

The approach can also be used to identify promising regions rich in bioactive compounds. In this case, the highest diversity of plant species can be found in Java's mountainous regions, where the greatest density of plants with anti-infective compounds can also be expected. So the search for new drugs will be more likely to succeed in species-rich areas than in the less biodiverse, agricultural lowlands of central and western Java. If adapted accordingly, Wessjohann and Muellner-Riehl say that this approach could easily be transferred to other geographical areas or other groups of bioactive compounds.

Credit: 
German Centre for Integrative Biodiversity Research (iDiv) Halle-Jena-Leipzig

New dataset helps tomato growers reduce spread of bacterial canker

image: Stem canker and unilateral leaf wilt caused by Clavibacter michiganensis on tomato

Image: 
Shree Thapa

Bacterial canker of tomato is a disease that can lead to significant losses in greenhouse and field production systems. This disease is caused by the bacterial pathogen Clavibacter michiganensis. The best way to control bacterial canker is by securing clean tomato seed and enforcing good sanitation practices.

A group of plant pathologists, primarily based at the University of California, Davis, became interested in studying Clavibacter when extension agents brought in diseased samples. In particular, they wanted to develop a diagnostic platform that could specifically detect the tomato pathogen, as some strains of Clavibacter do not cause disease.

Taking advantage of the huge advances in DNA sequencing over the last 10 years, these plant pathologists were able to identify genetic regions that can specifically detect the pathogen causing bacterial canker of tomato without giving false positives with nonpathogenic bacteria. They analyzed the genomes of 37 different Clavibacter strains in order to identify genetic regions only present in Clavibacter michiganensis. Using this information, they were able to develop a diagnostic platform.

"This diagnostic platform was based on amplification of three targets: two specific for Clavibacter michiganensis and one positive control," explained plant pathologist Gitta Coaker. "This platform is available for use without restriction and should facilitate the distribution of clean tomato seed to growers."

In an article in Phytopathology, Coaker and her team published large genomic datasets enabling other organizations to develop Clavibacter michiganensis-specific detection assay. The adoption of this assay in the field will help tomato growers reduce the spread of bacterial canker of tomato through easier screening of infected plant and seed materials.

Credit: 
American Phytopathological Society

Exploring why some COVID-19 patients lose their sense of smell

Doctors have reported that partial or total loss of the sense of smell is often an early symptom of infection with SARS-CoV-2, the virus that causes COVID-19. Now, researchers reporting in ACS Chemical Neuroscience have shown that in mice, two proteins required for SARS-CoV-2 entry are produced by cells of the nasal cavity that contribute to odor detection. Moreover, larger amounts of the proteins are made in older animals than in younger ones.

The new coronavirus still holds many secrets, one of which is how it can cause loss of smell -- even in infected people who have no other COVID-19 symptoms. SARS-CoV-2 hijacks two proteins to invade human cells: the cell surface receptor ACE2 and the protease TMPRSS2. However, scientists still aren't sure which cells in the olfactory epithelium (the tissue lining the nasal cavity) express these proteins and could potentially be infected by the virus. Finding out could help explain symptoms and aid in the development of more accurate diagnostic tests. So Rafal Butowt and colleagues studied the proteins' expression in mice and how their levels change with age.

Using several methods, the researchers found that ACE2 and TMPRSS2 are expressed in sustentacular cells -- cells of the nose that help transfer odors from the air to neurons. Older mice made more of the two proteins in nasal cells than younger mice. If also true in humans, this result could explain why older people are more susceptible to SARS-CoV-2, the researchers say. They also note that future studies should examine whether sustentacular cells can pass the virus to neurons, which could provide SARS-CoV-2 a route to infect the brain.

Credit: 
American Chemical Society

The microbiome controls immune system fitness

image: Microbiota-induced type I interferons control the functionality of dendritic cells.

Image: 
Image: Schaupp/ Charité.

Working alongside colleagues in Mainz, Bern, Hannover and Bonn, researchers from Charité - Universitätsmedizin Berlin, the Berlin Institute of Health (BIH) and the German Rheumatism Research Center Berlin (DRFZ) were able to show how the microbiome helps to render the immune system capable of responding to pathogens. If absent, relevant mediators are not released, resulting in a failure to activate metabolic processes in certain immune cells. According to the researchers' report, which has been published in Cell*, this leaves the relevant cells without the necessary fuel to mount an immune response.

Residing in environmental interfaces, the body's epithelial tissues represent potential gateways for pathogens. These tissues are also naturally colonized by a complex community of bacteria, viruses, fungi and parasites, and this is known as the microbiome. It is likely that, during the course of evolution, permanent interactions with these microorganisms resulted in the development of robust signaling pathways which help to protect the body. A team of researchers led by Prof. Dr. Andreas Diefenbach, Director of Charité's Institute of Microbiology, Infectious Diseases and Immunology, have been studying the microbiome's role in the body's immune response against harmful pathogens and the resulting effects on signaling pathways.

Presence of an infection triggers the body's immune response. A key role in this process is played by 'conventional dendritic cells' (cDCs). These form part of the body's innate immune system and carry a range of pattern recognition receptors, which enable them to quickly detect invading pathogens. The cells' initial response involves the release of cytokines, signaling proteins which attract immune cells to the site of infection. At the same time, these cells also use phagocytosis to engulf and digest invasive pathogens, after which they present individual particles as antigens on their cell surface. This, in turn, leads to the activation of T cells (which form part of the adaptive immune system) and results in a targeted immune response. In contrast, when T cell activation is triggered by cDCs presenting endogenous antigens, this leads to a faulty and undesirable immune response and results in autoimmune diseases.

The team of researchers led by Prof. Diefenbach found that cDCs are incapable of triggering immune responses in sterile conditions (i.e., in germ-free mice). The researchers concluded that cDCs must receive information while the cell is in its 'basal state' (which is characterized by the absence of infection) and that this information must derive from the microbiome. These microbiome-derived signals prime cDCs for a future response against pathogens. "We want to understand the nature of the microbiome's continuous effects on cDC function," says Prof. Diefenbach, who also holds an Einstein Professorship in Microbiology and leads the DRFZ's Mucosal Immunology Research Group. "In this study, we were able to show that, in their basal state, these specialist immune cells are subject to the uninterrupted microbiome-controlled signaling of type I interferons (IFN-I)." Interferons are cytokines, i.e. special signaling molecules which are known to play a role in antiviral activity. "Until now, we had known only little about the role of IFN-I in the basal state. cDCs, which do not receive this IFN-I signaling during the basal state, cannot fulfill the physiological functions which they perform as part of the body's fight against pathogens," explains the microbiologist. Study results suggest that the microbiome controls our immune system's fitness. It exerts this control by bringing the immune system to a state of 'readiness' in order to speed up its response to pathogens. ?

The researchers used various animal models in order to gain insight into the manner in which the microbiome-controlled IFN-I primes basal-state cDCs for future combat. Using sequencing technology, the researchers were able to compare the epigenomes and transcriptomes of cDCs from germ-free animals with those of control animals and animals deficient in IFN-I receptors. The researchers wanted to know what happens at the molecular level in cDCs when they are no longer exposed to IFN-I. Describing the researchers' observations, the study's first author, Laura Schaupp, says: "Interestingly, when we looked at cDCs from germ-free animals and those without IFN-I signaling, we were able to observe low levels of expression among genes involved in the mitochondrial respiratory chain." The Charité researcher adds: "Further analyses revealed that the cellular metabolism of cDCs from germ-free animals is dysfunctional, making them unable to initiate an immune response. The cells effectively lack the fuel needed to respond to pathogens." This suggests that the microbiome is of crucial importance to the functioning of cDCs. It appears essential to the ability of cDCs to mount an effective response to bacterial or viral infections, including responses mediated by T cells.??

The researchers' findings may contribute to the development of new therapeutic approaches. Many autoimmune diseases, such as systemic lupus erythematosus, are caused by an increased production of IFN-I. Other studies have shown that the microbiome influences the effectiveness of checkpoint inhibitors in cancer immunotherapies. "These phenomena will continue to be of great interest to us," says Prof. Diefenbach. "For instance, is it possible to change the composition of the microbiome in such a way as to reduce the availability of IFN-I, thereby exerting a positive influence on autoimmune diseases? Or might it be possible to improve responses to cancer immunotherapies by exerting a positive influence on the underlying IFN-I production?" The team of researchers now plan to conduct further studies which will explore these questions.

Credit: 
Charité - Universitätsmedizin Berlin

ACR releases gout management guideline

ATLANTA – Today, the American College of Rheumatology (ACR) released the 2020 Guideline for the Management of Gout. The updated guideline reflects new clinical evidence that became available since the ACR last released a treatment guideline for the condition in 2012, Among the 42 recommendations offered, addressing standard treat-to-target urate lowering therapy (ULT) was a key focus for the authors due to its benefit for all patients with gout that are on ULT.

“With this update, we sought to look at new and emerging clinical evidence that would be beneficial for treating patients with gout ,” said John FitzGerald, MD, PhD, a rheumatologist and one of the guideline’s co-principal investigators. “The guideline now includes expanded indications for starting ULT, a greater emphasis to use allopurinol as the first line agent for all patients with gout that require urate lowering therapy including those patients with chronic kidney disease, and broadened recommendations about who needs HLA-B*5801 testing prior to starting allopurinol.”

A highlight of the updated guideline is a strong recommendation to use a treat-to-target strategy with ULT for all patients with gout, based on data from newer clinical trials. The guideline suggests a management strategy of starting with a low-dose of a ULT medication and escalating the dosage to achieve and maintain a serum urate level of less than 6 mg/dL to optimize patient outcomes over a fixed-dose strategy. This strategy mitigates the risk of treatment-related adverse effects (i.e., hypersensitivity), as well as flare risk accompanying ULT initiation. Other recommendations include:

Indications for starting ULT have been expanded to conditionally consider patients with infrequent gout flares or after their first gout flare if they also have moderate to severe chronic kidney disease (CKD stage ≥ 3), marked hyperuricemia (serum urate > 9 mg/dl) or kidney stones.
A conditional recommendation against initiating ULT for patients experiencing their first gout flare without above comorbidities.
A strong recommendation to use allopurinol as the first-line ULT, including in patients with chronic kidney disease.
A strong recommendation to use an anti-inflammatory prophylaxis (e.g., colchicine, NSAIDs, prednisone/prednisolone) when starting ULT for at least 3-6 months rather than less than 3 months, with ongoing evaluation and continued prophylaxis as needed if the patient continues to experience flares.
A conditional recommendation for HLA-B*5801 testing prior to starting allopurinol for patients of Southeast Asian descent (e.g., Han Chinese, Korean, Thai) and African American descent who have a higher prevalence of HLA-B*5801 and against HLA-B*5801 testing in patients of other ethnic or racial backgrounds. 

Gout is the most common form of inflammatory arthritis, affecting about 9.2 million adults in the United States. This condition is painful and potentially disabling, can affect anyone, and its risk factors vary. Symptoms are usually intense episodes of painful swelling in single joints, most often in the feet, especially the big toe, but any joint can be involved.

ACR guidelines are currently developed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology, which creates rigorous standards for judging the quality of the literature available and assigns strengths to the recommendations. The updated and expanded recommendations can be viewed at Clinical Practice Guidelines Gout.

Media Contact:
Monica McDonaldmmcdonald@rheumatology.org404-633-3777, ext. 332

Credit: 
American College of Rheumatology

Multitasking in the workplace can lead to negative emotions

image: Participant engaged in essay writing under frequent email interruptions.
Top: Characteristic facial snapshots of the participant, annotated with the probabilistic estimates of the method for the presence of mixed emotions.
Bottom: Emotional co-occurrence results for the hour-long monitoring period. The matrix diagonal quantifies the presence of single emotions, while the off-diagonal elements of the matrix quantify the presence of mixed emotions.

Image: 
Ioannis Pavlidis, Computational Physiology Laboratory at the University of Houston

From writing papers to answering emails, it's common for office workers to juggle multiple tasks at once. But those constant interruptions can actually create sadness and fear and eventually, a tense working environment, according to a new study aimed at understanding what shapes the emotional culture of a workplace.

"Not only do people experience stress with multitasking, but their faces may also express unpleasant emotions and that can have negative consequences for the entire office culture," said study senior author Ioannis Pavlidis, director of the Computational Physiology Laboratory at the University of Houston.

Pavlidis, along with Gloria Mark at the University of California Irvine and Ricardo Gutierrez-Osuna at Texas A&M University, used a novel algorithm, based on co-occurrence matrices, to analyze mixed emotions manifested on the faces of so-called knowledge workers amidst an essay writing task. One group answered a single batch of emails before they began writing, thus limiting the amount of distraction, while the other group was frequently interrupted to answer emails as they came in.

The findings are published in the Proceedings of the 2020 CHI Conference on Human Factors in Computing Systems.

"Individuals who engaged in multitasking appeared significantly sadder than those who did not. Interestingly, sadness tended to mix with a touch of fear in the multitasking cohort," Pavlidis said. "Multitasking imposes an onerous mental load and is associated with elevated stress, which appears to trigger the displayed sadness. The simultaneous onset of fear is intriguing and is likely rooted to subconscious anticipation of the next disruption," he added. Because multitasking is a widespread practice, the display of these negative emotions can persist throughout the workday for many people. It is this ubiquitous, continuous and persistent character of the phenomenon that renders it such a dangerous `climate maker', the researchers emphasized.

The facial expressions of the workers who answered emails in one batch remained mostly neutral during the course of their uninterrupted writing task. However, there was an element of anger during the separate email task, perhaps attributed to the realization of the amount of work needed to process all the emails in one session, the researchers theorize. The good news is that email batching is localized in time and thus its emotional effects don't last long. Solutions are possible in this case; the team suggests addressing the email batch at a later time when responding to emails is the only task, recognizing that won't always be possible due to office pressure.

Negative displayed emotions - especially in open office settings - can have significant consequences on company culture, according to the paper. "Emotional contagion can spread in a group or workplace through the influence of conscious or unconscious processes involving emotional states or physiological responses."

Upon return to normalcy following the COVID-19 crisis, the results suggest organizations should pay attention to multi-tasking practices to ensure a cohesive working environment. "Currently, an intriguing question is what the emotional effect of multitasking at home would be, where knowledge workers moved their operation during the COVID 19 pandemic," said Pavlidis.

The study was made possible by a $1.2 million grant from the National Science Foundation and is part of a series that examines multitasking behavior among knowledge workers.

Credit: 
University of Houston