Culture

Promotional vaping Instagram posts outnumber anti-vaping content 10,000 to 1, according to a new study published in Frontiers in Communication.

Despite "The Real Cost" awareness campaign launched by the FDA in 2018, nearly one third of American teenagers are estimated to use e-cigarettes. The current study highlights the limited impact of the FDA campaign, while also using deep learning - an artificial intelligence method - to better understand the marketing tactics used by vaping companies.

"U.S. public health officials have been calling vaping among youth an epidemic and have been putting a lot of effort into trying to stop this epidemic by introducing #TheRealCost anti-vaping campaign," says Julia Vassey of the University of California, Berkeley, in the United States. "But this stark imbalance in the volume of posts has caused the FDA message to be overwhelmed by marketing from the vaping brands."

Many teenagers continue to view e-cigarettes as healthier than conventional cigarettes, but vaping is associated with inflammation, reduced immune responses and breathing troubles. To further understand how vaping is perceived on social media, Vassey and her collaborators at the UC Berkeley Center for Integrative Research on Childhood Leukemia and the Environment (CIRCLE) collected 245,894 Instagram posts spanning from before and after the #TheRealCost campaign launch. The team also conducted interviews with five vaping influencers and eight college-age social media users.

"We focused on Instagram because the vaping influencers we interviewed for this study identified Instagram as their most important social media marketing platform," explains Vassey. "Based on the results, the FDA anti-vaping campaign is not very popular and we saw Instagram user comments disputing the FDA claims of damaging health effects from nicotine and calling the campaign propaganda."

In contrast to the FDA's intentions, Vassey and her colleagues found that vaping posts received nearly three times more "likes" after the campaign launch. They also found that there were six times as many posts that had greater than 100 likes. Importantly, participants in the focus groups additionally suggested that the anti-vaping campaign promoted scare tactics rather than offering guidance on how to quit vaping.

By analyzing common themes across the Instagram images, the researchers found that over 70% contained e-juices and devices, which contain higher nicotine concentrations and are often popular among e-cigarette novices. The analytics data shared by the vaping influencers also showed that many of their followers were underage (13 to 17 years old).

The results of this study were limited to Instagram content (as opposed to other social media outlets) and the researchers plan to investigate how content translates to actual vaping use next.

"We're hoping the findings will inform public health regulators about the most popular channels used by vaping influencers to promote vaping content among underage population in order to help counter e-cigarette marketing and slow vaping proliferation among youth," says Vassey. "This study could also contribute to providing direction for future federal and local public health anti-vaping intervention campaigns."

In the Pacific Northwest, the range expansion of Barred Owls has contributed to a conservation crisis for Northern Spotted Owls, which are being displaced from their old-growth forest habitat. How will this interaction between species play out in the Sierra Nevada, where Barred Owls are just starting to move into the range of the California Spotted Owl? New research published in The Condor: Ornithological Applications suggests that wildlife managers may still be able to head off similar problems in critical areas of the Golden State -- if they act now.

The University of Wisconsin's Connor Wood and his colleagues used passive acoustic monitoring to survey Barred Owl populations over two years, deploying audio recorders over an area spanning more than 6,000 square kilometers across two national forests in northern California. Locating owl calls in the audio data allowed them to determine which sites were and were not occupied by owls. They found a 2.6-fold increase in the amount of territory occupied by Barred Owls between 2017 and 2018, and the old forest habitat preferred by Spotted Owls was the most likely to be colonized.

Populations of invasive species typically remain at low densities for several generations before growing rapidly. Because intervening to control a potentially damaging invasive species requires many resources, land managers often wait for strong evidence that a species will pose a threat before taking action. But, by the time the "growth phase" has started, it's often too late. Wood and his colleagues believe their results show that the growth phase of the Barred Owl population in the region is just beginning, meaning wildlife managers still have time to act. Only a narrow band of fairly unsuitable habitat connects the existing Pacific Northwest population of Barred Owls to the Sierra Nevada stronghold of California Spotted Owls, and the researchers recommend experimentally removing Barred Owls from the Sierra Nevada side of this pinch point to see if this can prevent them from becoming established further south.

"We suggested that managers act according to the Precautionary Principle: when there is a serious threat to human health or the environment, proactive responses are justified even if there is some uncertainty," says Wood. "We feel that experimental Barred Owl removals in the Sierra Nevada are an important step in determining the best long-term management strategy. This is not something that anyone takes lightly, but we feel that it is warranted because of the very real possibility that continued Barred Owl population growth could seriously endanger the California Spotted Owl. By catching this invasion in the early stages, we have a unique but potentially fleeting opportunity to inform policies that could prevent the California Spotted Owl from being driven extinct in the core of its range."

Mathematicians, physicists, and materials experts might not spring to mind as the first people to consult about whether you are brewing your coffee right. But a team of such researchers from around the globe--the United States, the United Kingdom, Ireland, Australia, and Switzerland--are challenging common espresso wisdom, finding that fewer coffee beans, ground more coarsely, are the key to a drink that is cheaper to make, more consistent from shot to shot, and just as strong. Their work appears January 22 in the journal Matter.

"Most people in the coffee industry are using fine-grind settings and lots of coffee beans to get a mix of bitterness and sour acidity that is unpredictable and irreproducible," says co-senior author Christopher Hendon (@chhendon), a computational chemist at the University of Oregon. "It sounds counterintuitive, but experiments and modeling suggest that efficient, reproducible shots can be accessed by simply using less coffee and grinding it more coarsely."

Though lots of factors are involved, the norm for brewing an espresso shot is to grind a relatively large amount of coffee beans (~20 grams) almost as finely as possible. The fine grind, common sense goes, means more surface area exposed to the brewing liquid, which ought to boost extraction yield--the fraction of the ground coffee that actually dissolves and ends up in the final drink.

But when the researchers put together a mathematical model to explain the extraction yield based on the factors under a barista's control--options such as the masses of water and dry coffee, the fineness or coarseness of the grounds, and the water pressure--and compared its predictions to brewing experiments, it became clear that the real relationship was more complicated. Grinding as finely as the industry standard clogged the coffee bed, reducing extraction yield, wasting raw material, and introducing variation in taste by sampling some grounds and missing others entirely.

Much number crunching and thousands of shots later, the team reached a recipe to simultaneously maximize extraction and produce espresso that would taste similar from one cup to the next. "One way to optimize extraction and achieve reproducibility is to grind coarser and use a little less water, while another is to simply reduce the mass of coffee," Hendon says.

Developing a model representative of espresso brewing was not a straightforward task. At a basic level, extraction yield depends on how water flows under pressure through a mass of coffee grounds. But that mass is made up of millions of individual grains of different shapes and sizes, jammed irregularly into a single filter bed. "You would need more computing power than Google has to accurately solve the physics and transport equations of brewing on a geometry as intricate as a coffee bed," says co-senior author Jamie M. Foster, a mathematician at the University of Portsmouth (UK).

To get past this hurdle, the researchers drew on an unlikely source--electrochemistry--likening how caffeine and other molecules dissolve out of coffee grounds to how lithium ions move through the electrodes of a battery. Borrowing modeling methodologies from battery work led to a rigorous coffee extraction model capable of making powerful and testable predictions.

Boosting the extraction yield through one or more of the routes illustrated by the model could also lead to economic gains for cafes and to sustainability benefits for the coffee industry as a whole. For example, at the current price of roasted coffee beans, dropping the mass of dry coffee from 20 grams to 15 grams per drink would add up to savings of a few thousand dollars per year for a small cafe, and $1.1 billion per year if scaled up to the whole US coffee industry. Being more efficient with coffee bean usage would also reduce waste at a time when coffee supply is under threat from changing climate in historic production areas.

The researchers stress, however, that their results do not purport to reduce all of espresso making down to a single set of brewing conditions or to a lone flavor profile. "Though there are clear strategies to reduce waste and improve reproducibility, there is no obvious optimal espresso point," says Hendon. "There is a tremendous dependency on the preferences of the person producing the coffee; we are elucidating the variables that they need to consider if they want to better navigate the parameter space of brewing espresso."

Washington, DC - January 22, 2020 - Candida auris is capable of forming high burden biofilms, which may help explain why this fungal pathogen is spreading in hospitals worldwide, according to a study published this week in mSphere, an open-access journal of the American Society for Microbiology. The research also establishes a new model to investigate the spread of this emerging fungal pathogen that causes invasive infections and is an emerging problem in hospitals worldwide.

"With these findings, we are able to have new tools to examine how Candida auris forms biofilms and spreads in this setting. Understanding more about this process could help us develop new strategies to prevent biofilm formation," said Jeniel Nett, MD, PhD, the study's principal investigator and assistant professor in the Departments of Medicine and Medical Microbiology & Immunology at the University of Wisconsin School of Medicine and Public Health. "Our tools can be used to determine how the biofilms are formed, which may lead to new strategies to prevent the transmission of or pharmaceutically target Candida auris."

Unlike many other Candida species, Candida auris spreads rapidly among patients and is efficient at colonizing skin. Because many of the patients infected with Candida auris have indwelling medical devices such as vascular catheters and endotracheal tubes, the researchers hypothesized that biofilms may be forming on these devices and on skin, facilitating transmission of Candida auris. "Candida species, similar to other fungal species and bacteria, can form communities that are adherent to a substrate, either on an artificial device or other surface," said Dr. Nett. "These biofilms communities are multilayered, and they often resist medical treatment, including antifungals, and host responses."

In the new study, Dr. Nett and colleagues developed a synthetic sweat media to represent skin conditions and using this model, they evaluated the growth of Candida auris and Candida albicans, one of the most common Candida species. They also examined the growth of these Candida species using a pig skin model to represent human skin conditions.

The researchers found that Candida auris exhibited a heightened capacity to both grow in the skin niche condition and to colonize pig skin and that Candida auris grew and colonized pig skin by forming multilayer biofilms. "Candida auris can grow approximately tenfold greater as a biofilm in this setting when compared to Candida albicans, one of the more common Candida species that does not seem to spread in hospital settings in this way," said Dr. Nett. "We think that this mode of growth is how Candida auris propagates in healthcare settings. Candida auris appears to colonize skin exceptionally well, growing particularly well in skin niche conditions."

The researchers said the formation of the biofilms is one of the reasons why Candida auris is difficult to clean in hospital settings. "These biofilms are likely on a lot of medical equipment used in healthcare settings," said Dr. Nett.

The researchers said their next steps are to further develop their model and examine Candida auris growth to determine some of the triggers for how Candida forms biofilms. "I was surprised that Candida auris formed such a condensed biofilm in this skin setting, as other species did not," said Dr. Nett. "We hypothesized that Candida auris may have a capacity to replicate in this environment, but we didn't expect it would be tenfold greater than the other Candida species."

It's a leading research strategy for eliminating HIV from the body: "shock and kill." The idea is to activate the dormant virus from within the immune cells where it hides, then eliminate it. One obstacle has been finding a safe way to wake up the virus.

In two complementary Nature papers, researchers now report that they have come closer to that goal. The papers are from researchers at the Yerkes National Primate Research Center of Emory University and the University of North Carolina at Chapel Hill, funded by the National Institutes of Health.

The papers rely on studies involving two animal models of HIV infection. Each study took a different approach. But both yielded promising results, disrupting viral latency at levels not seen before.

That means that the virus came out of its hiding places, even in the presence of antiretroviral drugs that had stopped it from replicating for months.

The findings do not represent a cure and follow-up studies in animals, as well as clinical studies in humans, are needed and planned. But the results represent an advance because they could potentially be combined with other approaches directed against the virus, the scientists say.

"If our goal is to cure HIV/AIDS, then we have to disrupt viral latency," says Guido Silvestri, MD, senior author of one of the Nature papers. "What we're doing now is a new combination approach that provides unprecedented levels of virus reactivation."

Silvestri is interim chair of pathology and laboratory medicine at Emory University School of Medicine, chief of microbiology and immunology at Yerkes National Primate Research Center, and a Georgia Eminent Research Scholar.

Past results of latency reversal experiments were not as sustained and extensive, says co-senior author J. Victor Garcia, PhD, director of the International Center for the Advancement of Translational Science and professor at the University of North Carolina School of Medicine.

"Previously, no one had successfully demonstrated systemic HIV induction in humans or an animal model with human cells, and then replicated this success in a completely different species infected with a different virus," Garcia says.

Ann Chahroudi, MD, PhD, co-senior author on both papers, says the studies described in the two papers take different approaches. She is associate professor of pediatrics and director of the Center for Childhood Infections & Vaccines at Emory and Children's Healthcare of Atlanta.

Both approaches were tested at Yerkes in monkeys infected with SIV, a close relative of HIV, and treated with antiretroviral drugs. At UNC, tests were also conducted in mice transplanted with human immune cells.

One paper describes a drug called AZD5582, which activates an intracellular pathway that leads to HIV and SIV reactivation. AZD5582 appears to be safe and relatively non-toxic in non-human primates. In 12 monkeys treated with the drug, just one experienced a temporary fever and loss of appetite. With the aim of beginning clinical trials, researchers at UNC and Qura Therapeutics -- a partnership between UNC and ViiV Healthcare -- are investigating compounds related to AZD5582.

"AZD5582 was remarkable in its ability to reactivate latent SIV from resting CD4+ T cells, and to induce continued virus production in the blood when monkeys were still receiving daily antiretroviral therapy," says Chahroudi.

In the study described in the second paper, researchers stimulated the cells that are the main viral hosts (CD4+ T cells) while also depleting another kind of immune cell (CD8+ T cells), which normally keeps the virus in check.

The combination of immune interventions was especially potent; both the stimulation and depletion components were necessary to see SIV re-emerge, Silvestri says. His lab had previously observed a similar but smaller effect with CD8 depletion alone. That means that CD8 T cells must have a role in keeping the virus inactive, which needs to be understood better, he says.

"The old paradigm is that you need CD8 cells to clear other infected cells," Silvestri says. "We're showing that CD8 cells are also involved in repressing latency reversal."

The main obstacle to a cure for HIV infection is the reservoir: immune cells that harbor the inactive virus when someone is being treated with antiretroviral drugs. Neither intervention - drug or immune stimulation/depletions - reduced the size of the reservoir, because once the animals were taken off antiretroviral drugs, viral levels did rebound. The scientists think the initial viral reactivation needs to be combined with other modes of treatment, such as antibodies directed against the virus itself.

"The exciting thing about these papers being published together are the concordance of the results in two animal models with both approaches, and the opening up of new avenues for research towards the goal of an HIV cure," says Chahroudi.

When Marie Antoinette was captured during the French Revolution, her hair reportedly turned white overnight. In more recent history, John McCain experienced severe injuries as a prisoner of war during the Vietnam War -- and lost color in his hair.

For a long time, anecdotes have connected stressful experiences with the phenomenon of hair graying. Now, for the first time, Harvard University scientists have discovered exactly how the process plays out: stress activates nerves that are part of the fight-or-flight response, which in turn cause permanent damage to pigment-regenerating stem cells in hair follicles.

The study, published in Nature, advances scientists' knowledge of how stress can impact the body.

"Everyone has an anecdote to share about how stress affects their body, particularly in their skin and hair -- the only tissues we can see from the outside," said senior author Ya-Chieh Hsu, the Alvin and Esta Star Associate Professor of Stem Cell and Regenerative Biology at Harvard. "We wanted to understand if this connection is true, and if so, how stress leads to changes in diverse tissues. Hair pigmentation is such an accessible and tractable system to start with -- and besides, we were genuinely curious to see if stress indeed leads to hair graying. "

Narrowing down the culprit

Because stress affects the whole body, researchers first had to narrow down which body system was responsible for connecting stress to hair color. The team first hypothesized that stress causes an immune attack on pigment-producing cells. However, when mice lacking immune cells still showed hair graying, researchers turned to the hormone cortisol. But once more, it was a dead end.

"Stress always elevates levels of the hormone cortisol in the body, so we thought that cortisol might play a role," Hsu said. "But surprisingly, when we removed the adrenal gland from the mice so that they couldn't produce cortisol-like hormones, their hair still turned gray under stress."

After systematically eliminating different possibilities, researchers honed in on the sympathetic nerve system, which is responsible for the body's fight-or-flight response.

Sympathetic nerves branch out into each hair follicle on the skin. The researchers found that stress causes these nerves to release the chemical norepinephrine, which gets taken up by nearby pigment-regenerating stem cells.

Permanent damage

In the hair follicle, certain stem cells act as a reservoir of pigment-producing cells. When hair regenerates, some of the stem cells convert into pigment-producing cells that color the hair.

Researchers found that the norepinephrine from sympathetic nerves causes the stem cells to activate excessively. The stem cells all convert into pigment-producing cells, prematurely depleting the reservoir.

"When we started to study this, I expected that stress was bad for the body -- but the detrimental impact of stress that we discovered was beyond what I imagined," Hsu said. "After just a few days, all of the pigment-regenerating stem cells were lost. Once they're gone, you can't regenerate pigment anymore. The damage is permanent."

The finding underscores the negative side effects of an otherwise protective evolutionary response, the researchers said.

"Acute stress, particularly the fight-or-flight response, has been traditionally viewed to be beneficial for an animal's survival. But in this case, acute stress causes permanent depletion of stem cells," said postdoctoral fellow Bing Zhang, the lead author of the study.

Answering a fundamental question

To connect stress with hair graying, the researchers started with a whole-body response and progressively zoomed into individual organ systems, cell-to-cell interaction and, eventually, all the way down to molecular dynamics. The process required a variety of research tools along the way, including methods to manipulate organs, nerves, and cell receptors.

"To go from the highest level to the smallest detail, we collaborated with many scientists across a wide range of disciplines, using a combination of different approaches to solve a very fundamental biological question," Zhang said.

The collaborators included Isaac Chiu, assistant professor of immunology at Harvard Medical School who studies the interplay between nervous and immune systems.

"We know that peripheral neurons powerfully regulate organ function, blood vessels, and immunity, but less is known about how they regulate stem cells," Chiu said.

"With this study, we now know that neurons can control stem cells and their function, and can explain how they interact at the cellular and molecular level to link stress with hair graying."

The findings can help illuminate the broader effects of stress on various organs and tissues. This understanding will pave the way for new studies that seek to modify or block the damaging effects of stress.

"By understanding precisely how stress affects stem cells that regenerate pigment, we've laid the groundwork for understanding how stress affects other tissues and organs in the body," Hsu said. "Understanding how our tissues change under stress is the first critical step towards eventual treatment that can halt or revert the detrimental impact of stress. We still have a lot to learn in this area."

Researchers have found how an antibiotic used to treat a debilitating gut infection stays put inside the body giving it time to effectively treat the problem, a discovery that will pave the way for the development of more effective antibiotic treatments to fight superbugs.

PE (pseudomembranous colitis) is a debilitating inflammation of the colon caused by infection with the microbe Clostridium difficile (and sometimes Staphylococcus aureus). The sugar- or carbohydrate-containing antibiotic known as vancomycin is taken by mouth to kill the infecting microbe.

To be effective, vancomycin needs to stay in the GI tract (gut) close to where it is needed and not be diluted away or lost through the lining of the gut and into the bloodstream. A multi-disciplinary team of scientists at the Universities of Nottingham and Leeds have now shown this 'staying put' mechanism is precisely what happens and that it can occur in an unexpected way.

Forming a formidable barrier

The research, published today in Scientific Reports shows that protein-carbohydrate molecules of the gut called mucins provide a formidable barrier helping to prevent the drug escaping using a unique mechanism of formation of large molecular complexes or clumps. The antibiotic and mucins join together to form a mucoadhesive complex, likely trapping the antibiotic within large complexes. It is the trapped vancomycin which the scientists believe may lead to delayed transit of the antibiotic leading to prolonged exposure of the antibiotic to the infectious C. difficile.

Dr Mary Phillips-Jones, Associate Professor in Polymer & Microbial Biophysics at the University of Nottingham led the research, she said: "Vancomycin is a precious 'last-line' antibiotic in the clinician's arsenal of therapies to fight several important pathogens including MRSA, pneumonia, as well as C. difficile. The clumping effect with gut mucins revealed in our study not only gives new information about what may happen when the antibiotic is given orally, but might also provide new insights into its behaviour when infused into patients suffering from other life-threatening infections."

The findings also fit with other studies which show that oral vancomycin produces high levels of vancomycin resistance amongst some gut bacteria (VRE), contributing to the generation of antimicrobial resistance (a serious concern); the clumping/ complexation phenomenon may therefore provide the first explanation of a mechanism by which this VRE generation occurs. But the benefits of taking oral vancomycin at the right time and when appropriate still outweigh any negative generation of antimicrobial resistance, and the study highlights that it is wise to take vancomycin when your GP advises it is good to do so.

Dr Stephen Harding, Professor of Applied Biochemistry at the University of Nottingham added: "The antibiotic vancomycin is a truly remarkable molecule - a drug with its own mucoadhesive or sticky property which slows its transit through the gut right down giving maximum therapeutic effect and minimizing unused vancomycin being returned to the environment. If scientists are going to win the fight against anti-microbial resistance, joint institutional and interdisciplinary approaches like this successful one are going to prove crucial."

EUGENE, Ore. - Jan. 22, 2020 - Espresso delivers a desired jolt of caffeine but getting a consistent good-taste is difficult. New research is offering a roadmap to reproducibility and a potential savings of $3.1 million a day for coffee shops across the United States.

In a new study, now online ahead of print in the journal Matter, a 10-member international team of researchers performed mathematical modeling and brewed hundreds of espresso shots to discover the key variables required to make consistently tasty coffee.

The general conclusions: Use less coffee at a courser grind than traditionally recommended, and brew it faster using less water than current practices.

That approach, the team concluded, reduces the amount of coffee used in espresso by 25 percent, saves coffee shops 13 cents per espresso-based drink and could make the industry more sustainable by reducing waste.

In the United States, alone, 124 million espresso-based drinks are consumed daily. From each bag of beans, a buyer realizes only about 18 to 22 percent of the mass getting into their coffee.

The approached gleaned from the research would allow extraction yields above that 22 percent level, said co-author Christopher H. Hendon, a chemist at the University of Oregon.

"We want to extract more from the coffee to save money, and be sustainable, but we also want it to taste delicious, not burnt or bitter," he said. "Our method allows us to push extractions and have the shots taste great, while being more sustainable and saving money."

And that, he said, would benefit the industry.

"For the local shop owner, this is an opportunity to save a lot of money without sacrificing quality," he said. "For the roaster, this is an opportunity to reflect on the approach to roasting and how people are brewing their coffee. For the producer, this should encourage them continue to produce high-quality coffee that can earn them the most money, knowing that more people will have access to it."

The research team - chemists, mathematicians and coffee professionals from five countries - analyzed grind size, water pressure, flow rate, amount of coffee and extraction kinetics to seek an optimum extraction yield - the percentage of coffee that gets into a shot of espresso. The recipe that emerged from the experiments, done in Brisbane, Australia, were tested in a Eugene coffee shop.

"The real impact of this paper is that the most reproducible thing you can do is use less coffee," Hendon said. "If you use 15 grams instead of 20 grams of coffee and grind your beans coarser, you end up with a shot that runs really fast but tastes great. Instead of taking 25 seconds, it could run in 7 to 14 seconds. But you end up extracting more positive flavors from the beans, so the strength of the cup is not dramatically reduced. Bitter, off-tasting flavors never have a chance to make their way into the cup."

The key to improving espresso reproducibility, Hendon said, is to determine which grind setting enables a maximum extraction from the coffee, and still tastes good.

In practice though, Hendon said, baristas typically find a grind setting on their equipment that produces the most concentrated, reproducible coffee, then modify the mass of water being used. That usually involves a reduction in shot volume to get a desired flavor. However, if the volume is too small, he said, an operator should grind coarser and repeat the volume-reduction process to reach a bigger drink of lower concentration but reproducibly tasty.

"Our model lets us take the leap from a very small particle size, less than the size of a hair, and solve a series of equations that tell us how much mass can be transported out of these little particles," said co-author Jamie M. Foster of the School of Mathematics and Physics at the University of Portsmouth in the United Kingdom.

In their modeling, the researchers drew on electrochemistry, likening how caffeine and other molecules dissolve out of coffee grounds to how lithium ions move through the electrodes of a battery. Borrowing modeling methodologies from battery work led to a rigorous coffee extraction model capable of making powerful and testable predictions.

Fine-tuning that formula for consumers, including those who brew their own espresso at home, however, requires human taste preferences to identify a sweet spot of consistent taste, which can vary from person to person and coffee to coffee, Hendon said. Baristas and home connoisseurs will need to use their judgment and experiment with their grinder and coffee-shop recipes to obtain consistent results.

"A good espresso beverage can be made in a multitude of ways," he said. "The point of this paper was to give people a map for making an espresso beverage that they like and then be able to make it 100 times in a row."

NMDARs (N-methyl-D-aspartate receptors) serve as valves on nerve cells, controlling the flow of electrical signals in the brain. This special group of receptors is suspect in many neurological diseases, including Alzheimer's, epilepsy, stroke, and Parkinson's. Biologists from Cold Spring Harbor Laboratory (CSHL) and chemists from the University of Bristol have joined forces, creating a chemical compound to enable more precise investigation of NMDAR activity.

In the latest issue of Nature Communications, CSHL Professor Hiro Furukawa and colleagues detailed how they identified and perfected a chemical compound that inhibits, or stops the activity of certain NMDARs. By inhibiting some NMDARs while letting others function, researchers can now identify the roles different types of NMDA receptors play in both healthy and diseased brains.

Jue Xiang Wang, a graduate of CSHL's Ph.D. program who helped lead the research, explained that the CSHL-Bristol team investigated how the novel compound UBP791 targets a pair of NMDAR subunits called GluN2C and GluN2D.

"There is evidence that GluN2C and GluN2D are relevant in the same brain regions where motor functions are affected by Parkinson's disease," she said. "Without good inhibitors, we could only speculate on what the 2C and 2D receptors do."

By inhibiting the activity of GluN2C and GluN2D receptors with higher efficiency and specificity than before, scientists can better study the role that they play in Parkinson's.

Video: https://www.youtube.com/watch?v=HQb2VczogL8

Furukawa's lab worked with Professor David Jane's chemistry lab at the University of Bristol to improve the NMDAR-targeting compound. The CSHL lab specializes in visualizing the physical structure of NMDARs using a technique called X-ray crystallography. Knowing the structure of the receptor was critical for the chemists, who were then able to design UBP791 to connect specifically with the GluN2C and GluN2D receptors much like how a key is made to fit into specific locks. Studying what makes UBP791 fit particularly well further allowed the scientists to improve the compound, creating its latest version, UBP1700.

The UBP1700 compound is more precise than any of its predecessors and "it's also more potent," said Wang. "That's important because researchers will only need small amounts of the compound to shut down the targeted receptors. This limits the potential for side-effects that the compound might produce."

Moving forward, Furukawa's lab and their Bristol collaborators will be working on further refining the new compound for use in research.

A new study from researchers at Columbia University Vagelos College of Physicians and Surgeons found that non-medical cannabis use--including frequent or problematic use--is significantly more common in adults with pain than in those without pain.

The findings were published in the American Journal of Psychiatry.

Since 1996, 34 states have passed medical marijuana laws and 11 states have legalized recreational cannabis use.

Studies indicate that heavy cannabis use increases the risk of vehicle accidents, respiratory and psychiatric symptoms, and cannabis use disorder.

"Despite this evidence, many people view cannabis use as harmless, and non-medical use of cannabis on a daily or near-daily basis has increased," says Deborah Hasin, PhD, a professor of epidemiology in the Department of Psychiatry at Columbia University Vagelos College of Physicians and Surgeons who led the current study. "In our study, we hoped to identify factors--such as pain--that may increase the risk of cannabis use disorder."

Hasin and colleagues analyzed data on marijuana use from the National Epidemiologic Surveys on Alcohol and Related Conditions in 2001-2002 and 2012-2013. The researchers compared non-medical cannabis use patterns in adults with and without pain (approximately 20% of participants in both surveys had moderate to severe pain).

Overall, non-medical marijuana use increased from about 4% in 2002 to 9.5% in 2013. In addition, in the most recent survey, those with pain were significantly more likely to engage in frequent non-medical cannabis use than those without pain (5.0% vs. 3.5%). The risk of cannabis use disorder was also significantly higher in those with pain (4.2% vs. 2.7%).

"Although meta-analyses of cannabis for treating pain show only mixed efficacy, particularly for plant marijuana, 66% of adults now view marijuana as beneficial for pain management. Given that about 20% of the adult population experienced moderate to severe pain, this puts a large group of U.S. adults at risk for frequent non-medical use and cannabis use disorder. Greater balance is needed in media reporting of marijuana issues, including messages that convey credible information about the nature and magnitude of health risks from non-medical cannabis use, including among the large group of US adults with pain," says Hasin. "Psychiatrists and other mental health professionals treating patients with pain should monitor their patients for signs and symptoms of cannabis use disorder."

The paper is titled "US adults with pain, an increasingly vulnerable group for non-medical cannabis use and cannabis use disorder: 2001-2002 and 2012-2013."

Mathematicians, physicists and materials experts might not spring to mind as the first people to consult about whether you are brewing your coffee right.

But a team of such researchers including Dr Jamie Foster, a mathematician at the University of Portsmouth, are challenging common espresso wisdom.

They have found, that fewer coffee beans, ground more coarsely, are the key to a drink that is cheaper to make, more consistent from shot to shot, and just as strong.

The study is published in the journal Matter.

Dr Foster and colleagues set out wanting to understand why sometimes two shots of espresso, made in seemingly the same way, can sometimes taste rather different.

They began by creating a new mathematical theory to describe extraction from a single grain, many millions of which comprise a coffee 'bed' which you would find in the basket of an espresso machine.

Dr Foster said: "In order to solve the equations on a realistic coffee bed you would need an army of super computers, so we needed to find a way of simplifying the equations.

"The hard mathematical work was in making these simplifications systematically, in such a way that none of the important detail was lost.

"The conventional wisdom is that if you want a stronger cup of coffee, you should grind your coffee finer. This makes sense because the finer the grounds mean that more surface area of coffee bean is exposed to water, which should mean a stronger coffee."

When the researchers began to look at this in detail, it turned out to be not so simple. They found coffee was more reliable from cup to cup when using fewer beans ground coarsely.

"When beans were ground finely, the particles were so small that in some regions of the bed they clogged up the space where the water should be flowing," Dr Foster said.

"These clogged sections of the bed are wasted because the water cannot flow through them and access that tasty coffee that you want in your cup. If we grind a bit coarser, we can access the whole bed and have a more efficient extraction.

"It's also cheaper, because when the grind setting is changed, we can use fewer beans and be kinder to the environment.

"Once we found a way to make shots efficiently, we realised that as well as making coffee shots that stayed reliably the same, we were using less coffee."

The new recipes have been trialled in a small US coffee shop over a period of one year and they have reported saving thousands of dollars. Estimates indicates that scaling this up to encompass the whole US coffee market could save over $US1.1bn dollar per year.

Previous studies have looked at drip filter coffee. This is the first time mathematicians have used theoretical modelling to study the science of the perfect espresso - a more complicated process due to the additional pressure.

CHAPEL HILL, NC - January 22, 2020 - Approximately 38 million people are infected with HIV worldwide, about 1.1 million people in the United States. Currently, people with HIV take antiretroviral therapy (ART), which can suppress HIV to undetectable levels in blood, but the virus persists throughout the body in latently infected resting CD4+ T cells. The immune system cannot recognize these cells and no current therapies can eliminate them. When ART is stopped, viral loads spike in blood. This is why people with HIV must take ART continuously, and this latent reservoir is considered the greatest obstacle to a cure.

Now, scientists from the University of North Carolina at Chapel Hill and Emory University used a compound called AZD5582 to activate latently infected CD4+ T cells at impressive levels in blood and many different tissues with no or very little toxicity.

Published in Nature, this seminal work was accomplished at the UNC School of Medicine in ART-suppressed mouse models with fully functioning human immune cells, the kind typically infected with HIV in humans. Importantly, this research was then extended in a longitudinal, multi-dose study at Emory University in ART-suppressed rhesus macaques infected with Simian Immunodeficiency Virus (SIV). Qura Therapeutics, a partnership between scientists at UNC-Chapel Hill and ViiV Healthcare, conducted the basic science investigations that expedited the work in animal models. More research is needed before testing could begin in humans, but this work is considered a significant scientific step toward developing curative therapies.

"Previously, no one had successfully tested a latency reversal molecule in humans or in an animal model with human cells demonstrating systemic HIV induction in peripheral blood, in resting CD4+ T cells from multiple tissues, and then replicated this success in a completely different species infected with a different virus," said co-senior author J. Victor Garcia, PhD, director of the International Center for the Advancement of Translational Science, professor of medicine and microbiology & immunology at the UNC School of Medicine.

Ann Chahroudi, MD, PhD, associate professor of pediatrics at Emory and director of the Center for Childhood Infections & Vaccines at Emory and Children's Healthcare of Atlanta, is co-senior author. "AZD5582 was remarkable in its ability to reactivate latent SIV from resting CD4+ T cells, and to induce continued virus production in the blood when monkeys were still receiving daily antiretroviral therapy," she said. "This is an exciting scientific achievement, and we hope this will be an important step toward one day eradicating the virus in people living with HIV."

This work was made possible by the Collaboratory of AIDS Researchers for Eradication (CARE) housed at UNC-Chapel Hill and part of the Martin Delaney Collaboratories for HIV Cure Research - the flagship HIV cure research program supported by the National Institutes of Health (NIH) - the Emory Consortium for Innovative AIDS Research (E-CIAR) in Nonhuman Primates, also supported by NIH, Qura Therapeutics, and ViiV Healthcare.

For several years, scientists have been trying various latency reversal agents to induce HIV out of latency so it becomes visible to the immune system, allowing an antiviral immune response to kill the virus-infected cells. Some agents focused on activating the canonical NF-kB pathway in CD4+ T cells to drive infected cells out of latency. But triggering that pathway involved many hundreds of genes, making such an aggressive approach too toxic.

Scientists at Qura Therapeutics - a partnership between UNC-Chapel Hill and ViiV Healthcare - turned their attention to the non-canonical NF-kB pathway in CD4+ T cells.

Co-senior author Richard Dunham, PhD, lead investigator at Qura Therapeutics, led studies with patients' cells necessary to show that AZD5582, a mimetic of the Second Mitochondrial Activator of Caspases (SMACm), could serve as an effective latency reversal agent. AZD5582 provides a gradual but persistent activation of the non-canonical NF-kB pathway while triggering fewer human genes than other latency reversal agents, potentially making it much less toxic.

"We are excited that we now, for the first time, have a simple, tractable tool to test the long-standing hypothesis that activating latent HIV can expose the viral reservoir to clearance," said Dunham, Director of HIV Cure at ViiV Healthcare.

UNC scientists led by Garcia, an Oliver Smithies Investigator and member of the UNC Center for AIDS Research, then tested AZD5582 in vivo using ART-suppressed mouse models that contain human CD4+ T cells in tissues throughout the body. Garcia and colleagues documented increases in viral RNA expressed in blood and nearly all tissues, including lymph nodes, thymus, bone marrow, liver, lung, and brain. In some cases, the viral RNA increase was more than 20 fold.

At Emory, Chahroudi and colleagues tested AZD5582 in ART-suppressed, SIV-infected macaques and found similar results, this time with multiple, weekly doses. They observed a spike in RNA expression in lymph nodes and blood of the primates, marking the first time a latency reversal agent accomplished this feat with little toxicity in both animal models used to study HIV.

In a second paper in the same issue of Nature, Emory researchers led by Guido Silvestri, MD and Chahroudi in collaboration with UNC researchers, accomplished latency reversal in a different way. They injected an antibody into nonhuman primates with ART-suppressed SIV infection to deplete CD8+ T cells, which are very important for controlling the infection. Then the researchers administered an altered version of the cytokine IL-15 to show that this combination pushed viral RNA to appear in blood and tissue where it previously had not been seen. Garcia and UNC colleagues confirmed these results for HIV in the same type of mouse model in which AZD5582 was tested.

While it is not yet clear if the strategy of depleting CD8 cells could be translated into humans, this result opens new ways to understand how HIV is controlled, and how its expression might be manipulated. .

Taken together, these findings demonstrate the power of science conducted across teams, across institutions, and between industry and academic partners. The Nature studies show that HIV can be pushed out of hiding - confirmed across different model systems - and the studies open a range of possibilities for the development of new therapies that might one day lead to a cure for HIV.

This release has been removed upon request of the submitting institution. Please contact Heloisa Helena Reinert here: Hreinert@fapesp.br, 55 11 3838-4151.

Everyone hates road construction, even the soils and bodies of water around the roads. Paved roads can't absorb water, so that responsibility falls to the soil next to the road. Unfortunately, those soils are often damaged during construction.

Water that runs off roads can contain harmful contaminants. If that water doesn't infiltrate into nearby soil, those contaminants can make their way into bodies of water and be harmful. Rich McLaughlin and his research team at North Carolina State University have been working on how to help soil be healthy and happy after road construction.

Over the years, McLaughlin's team noticed contractors were trying to grow grass on soils near roads after construction. They noticed this didn't seem to be working well. So, they began to test the soils. Results showed the soils were very compacted and little water was getting down into the soil.

"Not only did this compaction prevent grass from growing, much of the unpaved area beside the road was shedding water as quickly as paved roads and roofs," McLaughlin explains. "Over the past decade, we have worked to help grass become better established after construction. This also means that water can better infiltrate into these soils."

Most recently, the team has been studying the benefits of tilling and adding things, called amendments, to the soil. They want to see if this can help reduce the amount of runoff. This runoff can contain heavy metals, petroleum products, sediment, and excess nutrients. These would normally run into the stormwater system.

In a recent study, they established plots next to roads where they could try different treatments and collect runoff from the soil. Researchers inserted barriers into the soil around each plot to send the runoff into a pipe, connected to a collection tub.

They found that tilling the soil and sometimes adding compost could greatly improve the infiltration for years after it was applied. On soils that had vegetation for many years, the improvements were less dramatic (but still considerable).

"Previous studies indicated that a good stand of vegetation helps maintain the high infiltration rates generated by tillage, and that's the main benefit," McLaughlin says. "Water and contaminant uptake by the plants is helpful, but the effects on soil's physical properties is the most important."

Part of their recent work tested two different kinds of vegetation: grasses and wildflowers. Grasses are cheaper and quicker to establish but need to be mowed three or four times per year. The wildflowers seemed to help improve infiltration a bit more than grasses.

Wildflowers can also provide food and habitat for important pollinators like butterflies, which are in decline worldwide. They are also mowed less, cutting down on compaction from mower wheels. The researchers think the added benefit might be coming from the roots of the wildflower plants but haven't tested this thoroughly.

McLaughlin adds that as the human population grows and more roads are constructed, it's becoming important to manage this runoff. Helping runoff trickle down into soils where possible is one of the easiest ways to tackle the problem. The next step in the research is trying different wildflower types and mixes to test their effects.

"Improving soil physical conditions through tillage and amendments is what a typical gardener might do," he says. "The key factor, however, is that vigorous plant growth immediately after tillage is needed to maintain that condition, and no further tillage or amendments are needed. I'm always looking for ways to improve water quality in our lakes, streams, and estuaries because I enjoy all kinds of water-oriented activities, none of which are enjoyable in polluted waters."

McLaughlin presented his research at the 2019 International Annual Meeting of the American Society of Agronomy, Crop Science Society of America and Soil Science Society of America. This research was supported by the North Carolina Department of Transportation Roadside Environmental Unit.

New research from Cass Business School has found that business sustainability strategies can succeed alongside mainstream competitive strategies when managers believe in them.

In 'Toward a Process Theory of Making Sustainability Strategies Legitimate in Action', published in the Academy of Management Journal, the researchers found that although managers support sustainability strategies, there can be tensions in goals, values, and in product features. This can occur when implementing them alongside the mainstream strategy, creating the potential for 'decoupling' - where organisations adopt policies symbolically, without implementing them substantially.

However, they found that working through these tensions on specific tasks helps to overcome them. Resolving tensions reinforces the organisational-level legitimacy of the strategy and its integration within the mainstream strategy.

The three-year qualitative study focused on the implementation of a new sustainability strategy alongside a mainstream strategy at TechPro, a market-leading global manufacturer with 20,000 full-time employees and an annual revenue of $3.5 billion (USD). While the company had no existing sustainability strategy, it had a long history of placing a high premium on corporate values such as 'trustworthiness' and 'truthfulness' which guided the firm's environmental and social standards. The new sustainability strategy was popular with staff, who were keen to demonstrate their own values through its implementation.

While the new strategy focused on addressing TechPro's social and environmental responsibilities in product policy and staff behaviour, their existing mainstream strategy focused on the competitive objectives and targets associated with defending their market position. For example, improving operational efficiency to ensure competitive pricing and maintaining, and growing, market share.

Tensions arose when managers tried to implement the sustainability strategy alongside the mainstream strategy, in their day-to-day operations. Tensions were in three areas:

Between strategic goals when there was incompatibility between tasks involving both organisational environmental compliance and organisational profit.

Between product features where there was incompatibility in incorporating the sustainability and mainstream strategy features in the technical design of a product or in production process. For example, by choosing materials that were cost friendly versus environmentally friendly.

Between organisational values, defined as between competitive orientation versus social orientation and competitive products versus trustworthy products.

The researchers found that workers could resolve these tensions to carry out the two strategies in three ways:

Mutually adjusting by compromising and reinterpreting or splitting between the strategies, when they could not physically incorporate both into a product or product development process.

Prioritising the sustainability strategy over the mainstream strategy on values-driven tasks, so enabling differentiation between the tasks, while not inhibiting wider integration of the strategies within the organisation.

Combining them within a common purpose and by including the new sustainability strategy within their existing procedures.

Sustainability has become a strategic priority for companies worldwide as consumers, shareholders and employees become more environmentally and socially aware, said report co-author, Professor Paula Jarzabkowski of Cass Business School.

"Prioritising sustainability strategies can simultaneously enhance an organisation's competitiveness and its social agenda," she said.

"However, although the sustainability strategy was seen as the right thing to do, the company was also faced with rising cost pressures and a battle to maintain market leadership so it was difficult to implement both strategies at the same time."

Professor Jarzabkowski said the research was particularly interesting as TechPro is a leading global manufacturer of the kind of high-end goods that many of us have in our homes, rather than a traditional social enterprise which tend to already have an inbuilt sustainability strategy within their business.

"Surprisingly, we found that rather than suppress the sustainability strategy, or do only the minimum, sometimes TechPro managers prioritized it over competitive actions they could have taken," she said.

"This research gives us hope. If a mainstream global business with a huge market share and presence in households around the world can develop, and implement, a successful sustainability strategy alongside their mainstream strategy, then other businesses can do the same. This means that more firms are more environmentally and socially aware and this understanding will have positive benefits for people, planet and profit."

Professor Jarzabkowski said the support that managers and workers gave the sustainability strategy was also crucial to its success.

"Their belief in, and commitment to, incorporating sustainability within the business played a significant part in the success of both strategies."