Culture

Anxiety disorders and obsessive-compulsive disorder (OCD) are disabling psychiatric conditions and the major contributors to global burden of nonfatal illness. The lifetime prevalence of anxiety disorders in adults under 60 years ranged from approximately 30-35%, whereas the lifetime prevalence of in the general population is estimated at 2-3% for full OCD but over 25% for OCD symptoms. OCD is characterized by uncontrollable, reoccurring thoughts (called obsessions) and/or ritualized, repetitive behaviors (compulsions) that are aimed at getting rid of the obsessions and seeking relief from the anxiety caused by obsessions, indicating a close correlation between anxiety and OCD. Indeed, anxiety disorders have been reported epidemiologically as the most frequent comorbid conditions with OCD. Therefore, common pathologies may be present in anxiety disorders and OCD, and elucidation of the shared neural substrates will lead to greater insight into their pathophysiology and treatment.

In a study recently published in PNAS, Dr. Jing-Ning Zhu's group in Nanjing University reports that a glutamatergic neuronal circuitry from the prelimbic prefrontal cortex (PrL) to the nucleus accumbens (NAc) core is responsible for co-occurrence of anxiety- and obsessive-compulsive-like behaviors. Notably, activation of the histamine presynaptic H3 heteroreceptor localized in the PrL-NAc glutamatergic terminals ameliorates stress-induced anxiety and obsessive-compulsive-like behaviors.

The nucleus accumbens (NAc) is a well-known brain structure in the basal ganglia limbic loop, which is critical for the emotional and motivational regulation. Deep brain stimulation (DBS) targeting the NAc core has been found to improve obsessive-compulsive symptoms and decrease ratings of anxiety in patients suffering from treatment-resistant OCD or depression. In previous studies, Jing-Ning Zhu's group has reported that DBS can induce an increase in histamine release in the subthalamic nucleus to alleviate Parkinsonian motor deficits. Here, they create a new transgenic rat strain expressing Cre recombinase in the histamine-producing neurons, restrictedly localized in the tuberomammillary nucleus of the hypothalamus, and find that selective optogenetic activation of histaminergic afferent inputs in the NAc core remarkably improves anxiety as well as obsessive-compulsive-like behaviors induced by restraint stress. The amelioration effects of histamine on anxiety and obsessive-compulsive-like behaviors are mediated by the suppression of glutamatergic rather than GABAercigc transmission in the NAc core via presynaptic H3 heteroreceptors. Although the authors reveal that histamine H3 presynaptic receptor is expressed and localized in the glutamatergic terminals in NAc core from the PrL, basolateral amygdala, and ventral hippocampus, only the PrL-NAc pathway is the circuit mediating the co-occurrence of anxiety- and obsessive-compulsive-like behaviors. Chemogenetic inhibition of the PrL-NAc glutamatergic circuit significantly prevents the anxiogenic and obsessive-compulsive-like behaviors induced by acute restraint stress. Interestingly, microinjection of histamine or selective H3 receptor agonist RAMH locally into the NAc core alleviates both anxiety- and obsessive-compulsive-like phenotypes induced by optogenetic activation of PrL-NAc glutamatergic circuit.

Effective pharmacological interventions for the comorbidity of anxiety and OCD are still lacking. Presynaptic histamine H3 receptor, selectively acting on glutamatergic neurotransmission, may provide a potential target for the treatment of anxiety and OCD. Notably, several agonists for H3 receptor, including RAMH and its prodrugs, have entered clinical trials and been proved safe. Therefore, developing strategies, such as pharmacological and/or DBS therapy, for targeting H3 receptor/histaminergic afferents in the NAc core or PrL-NAc glutamatergic circuit may pave a new path for clinical treatment of anxiety disorders and OCD.

New class of living plant-based sensor interfaces wild-type plants with engineered optical nanosensors, able to detect arsenic levels as low as 0.2 parts per billion

Arsenic is a heavy metal highly toxic to humans and the ecosystem - inorganic arsenic in rice is estimated by some to lead to 50,000 premature deaths a year

This novel approach can be used to monitor arsenic uptake in any plant, as well as to convert any non-genetically modified plant to an environmental sensor to monitor soil arsenic levels, enabling applications in agricultural research and environmental monitoring

Readouts from these new nanosensors can be obtained quickly via portable, inexpensive electronics such as Raspberry Pi-based platforms

Singapore, 2 December 2020 - Scientists from Disruptive & Sustainable Technologies for Agricultural Precision (DiSTAP), an Interdisciplinary Research Group (IRG) at the Singapore-MIT Alliance for Research and Technology (SMART), MIT's research enterprise in Singapore, have engineered a novel type of plant nanobionic optical sensor that can detect and monitor, in real-time, levels of the highly toxic heavy metal arsenic in the belowground environment. This development provides significant advantages over conventional methods used to measure arsenic in the environment and will be important for both environmental monitoring and agricultural applications to safeguard food safety, as arsenic is a contaminant in many common agricultural products such as rice, vegetables, and tea leaves.

This new approach is described in a paper titled, "Plant Nanobionic Sensors for Arsenic Detection", published recently in Advanced Materials. The paper was led by Dr Tedrick Thomas Salim Lew, a recent graduate student of the Massachusetts Institute of Technology (MIT) and co-authored by Michael Strano, co-lead principal investigator of DiSTAP and Carbon P. Dubbs Professor at MIT, as well as Minkyung Park and Jianqiao Cui, both Graduate Students at MIT.

Arsenic and its compounds are a serious threat to humans and ecosystems. Long-term exposure to arsenic in humans can cause a wide range of detrimental health effects, including cardiovascular disease such as heart attack, diabetes, birth defects, severe skin lesions, and numerous cancers including those of the skin, bladder, and lung. Elevated levels of arsenic in soil as a result of anthropogenic activities such as mining and smelting is also harmful to plants, inhibiting growth and resulting in substantial crop losses. More troublingly, food crops can absorb arsenic from the soil, leading to contamination of food and produce consumed by humans. Arsenic in belowground environments can also contaminate groundwater and other underground water sources, the long-term consumption of which can cause severe health issues. As such, developing accurate, effective, and easy-to-deploy arsenic sensors is important to protect both the agriculture industry and wider environmental safety.

These novel optical nanosensors developed by SMART DiSTAP exhibit changes in their fluorescence intensity upon the detection of arsenic. Embedded in plant tissues with no detrimental effects on the plant, these sensors provide a non-destructive way to monitor the internal dynamics of arsenic taken up by plants from the soil. This integration of optical nanosensors within living plants enables the conversion of plants into self-powered detectors of arsenic from their natural environment, marking a significant upgrade from the time- and equipment-intensive arsenic sampling methods of current conventional methods.

Lead author Dr Tedrick Thomas Salim Lew said, "Our plant-based nanosensor is notable not only for being the first of its kind, but also for the significant advantages it confers over conventional methods of measuring arsenic levels in the belowground environment, requiring less time, equipment, and manpower. We envisage that this innovation will eventually see wide use in the agriculture industry and beyond. I am grateful to SMART DiSTAP and Temasek Life Sciences Laboratory (TLL), both of which were instrumental in idea generation, scientific discussion as well as research funding for this work."

Besides detecting arsenic in rice and spinach, the team also used a species of fern, Pteris cretica, which can hyperaccumulate arsenic. This species of fern can absorb and tolerate high levels of arsenic with no detrimental effect - engineering an ultrasensitive plant-based arsenic detector, capable of detecting very low concentrations of arsenic, as low as 0.2 parts per billion (ppb). In contrast, the regulatory limit for arsenic detectors is 10 parts per billion. Notably, the novel nanosensors can also be integrated into other species of plants. This is the first successful demonstration of living plant-based sensors for arsenic and represents a groundbreaking advancement which could prove highly useful in both agricultural research (e.g. to monitor arsenic taken up by edible crops for food safety), as well as in general environmental monitoring.

Previously, conventional methods of measuring arsenic levels included regular field sampling, plant tissue digestion, extraction and analysis using mass spectrometry. These methods are time-consuming, require extensive sample treatment, and often involve the use of bulky and expensive instrumentation. SMART DiSTAP's novel method of coupling nanoparticle sensors with plants' natural ability to efficiently extract analytes via the roots and transport them allows for the detection of arsenic uptake in living plants in real-time with portable, inexpensive electronics, such as a portable Raspberry Pi platform equipped with a charge-coupled device (CCD) camera, akin to a smartphone camera.

Co-author, DiSTAP co-lead Principal Investigator, and MIT Professor Michael Strano added, "This is a hugely exciting development, as, for the first time, we have developed a nanobionic sensor that can detect arsenic - a serious environmental contaminant and potential public health threat. With its myriad advantages over older methods of arsenic detection, this novel sensor could be a game-changer, as it is not only more time-efficient but also more accurate and easier to deploy than older methods. It will also help plant scientists in organizations such as TLL to further produce crops that resist uptake of toxic elements. Inspired by TLL's recent efforts to create rice crops which take up less arsenic, this work is a parallel effort to further support SMART DiSTAP's efforts in food security research, constantly innovating and developing new technological capabilities to improve Singapore's food quality and safety."

The research is carried out by SMART and supported by the National Research Foundation (NRF) Singapore under its Campus for Research Excellence And Technological Enterprise (CREATE) programme.

A Machine Learning Solution for Designing Materials with Desired Optical Properties
Berkeley Lab researchers' method can also quickly calculate optical properties of most materials
By Julie Chao

Understanding how matter interacts with light - its optical properties - is critical in a myriad of energy and biomedical technologies, such as targeted drug delivery, quantum dots, fuel combustion, and cracking of biomass. But calculating these properties is computationally intensive, and the inverse problem - designing a structure with desired optical properties - is even harder.

Now Berkeley Lab scientists have developed a machine learning model that can be used for both problems - calculating optical properties of a known structure and, inversely, designing a structure with desired optical properties. Their study was published in Cell Reports Physical Science.

"Our model performs bi-directionally with high accuracy and its interpretation qualitatively recovers physics of how metal and dielectric materials interact with light," said corresponding author Sean Lubner.

Lubner notes that understanding radiative properties (which includes optical properties) is equally important in the natural world for calculating the impact of aerosols such as black carbon on climate change.

The machine learning model proposed in this study was trained on spectral emissivity data from nearly 16,000 particles of various shapes and materials that can be experimentally fabricated.

"Our machine learning model speeds up the inverse design process by at least two to three orders of magnitude as compared to the traditional method of inverse design," said co-author Ravi Prasher, who is also Berkeley Lab's Associate Director for Energy Technologies.

Mahmoud Elzouka, Charles Yang, and Adrian Albert, all scientists in Berkeley Lab's Energy Technologies Area, were also co-authors.

A New Data Milestone for CUORE Experiment in Italy
CUORE collects a record volume of data for an experiment using solid crystals to search for an ultrarare process
By Glenn Roberts Jr.

Surrounded by lead and also shielded by nearly a mile of rock from the natural bombardment of particles at the Earth's surface, the CUORE experiment has amassed the largest dataset yet for a project of its kind, which is using solid crystals to detect a theorized event that would answer a big question about how matter won out over antimatter in our universe. It would also tell us whether ghostly particles called neutrinos, which pass through most matter uninterrupted, are essentially their own antiparticles.

The data collected by CUORE, the Cryogenic Underground Observatory for Rare Events, now represents more than a "ton-year" of data (equivalent to a year's worth of data if the crystals weighed one ton) collected by a solid-state (crystal vs. liquid or gas) detector for an experiment of its kind, based on the weight of its detector crystals. CUORE has an array of 988 detector crystals. Its crystals each weigh about 1.6 pounds, and in total they weigh about 0.8 ton.

Located at Gran Sasso National Laboratory (Laboratori Nazionali del Gran Sasso, or LNGS, operated by the Italian Nuclear Physics Institute, INFN) in central Italy, CUORE has reached a milestone in surpassing the data collected for comparable experiments by about 10 times, said Yury Kolomensky, U.S. spokesperson for the CUORE collaboration and senior faculty scientist at the U.S. Department of Energy's Lawrence Berkeley National Laboratory (Berkeley Lab).

The experiment is designed to detect a theorized, never-before-seen nuclear decay process known as neutrinoless double-beta decay, occurring in atoms of tellurium-130, a radioactive isotope in the detector crystals. An isotope is a form of an element with more or fewer neutrons (uncharged particles) in its nucleus than is standard.

CUORE has carried out its ultrasensitive search without interruption since March 19. It operates near absolute zero, the coldest temperature in the known universe. The CUORE collaboration plans to operate the experiment for another few years, and then upgrade it to CUPID - a new, even more sensitive detector. Berkeley Lab will lead the U.S. participation in the international CUPID project.

Thanks to this work, as the journal Trends in Plant Science recently noted, it is now known that functional amyloids serve biological functions in representatives of almost all large groups of living organisms: bacteria, archaea, animals, fungi, and plants.

This fundamental finding could help improve the nutritional value of plant seeds and even reduce allergenicity of legume seeds in the future.

On the packaging of more than a half of snacks and sweets, which may not contain nuts at all, a warning phrase is often found: 'It may contain traces of peanuts.' Some people are so allergic to this product that the smallest particles of the peanut or even its powder causes an unpleasant and sometimes dangerous reaction: from a simple rash to severe swelling. Peanut seeds contain many proteins, some of which can cause allergies. One of the most potent allergens is vicilin, which is found in various legumes, including peanuts and peas.

The study was conducted by the team of researchers from: St Petersburg University; the All-Russian Research Institute for Agricultural Microbiology; the Institute of Cytology of the Russian Academy of Sciences; the Institute of Theoretical and Experimental Biophysics of the Russian Academy of Sciences; Kazan Federal University; and the University of Burgundy (France). The research findings are published in the journal PLOS Biology. The scientists managed to show by experiments for the first time (previously they managed to predict this using bioinformatic algorithms) that the seeds of garden pea contain
amyloid-like aggregates of storage proteins - amyloid fibrils. They were previously found in bacteria, archaea, animals and fungi, but were first found in plants. Interestingly, most of the amyloids in pea seeds are formed by the aforementioned protein vicilin.

'Vicilin is one of the most important food allergens found in legumes. The mechanism of its allergenicity can potentially be associated with the amyloid properties of this protein that we have discovered. We have shown that storage proteins, which are the main reservoir of nutrients for the embryo, accumulate in seeds as amyloids. In the future, studying these mechanisms could help create less allergenic varieties of peas, peanuts, and other legumes,' said Anton Nizhnikov, the corresponding author of the research, Associate Professor at the Department of Genetics and Biotechnology at St Petersburg University, Laboratory Head at the All-Russian Research Institute of Agricultural Meteorology

'Interestingly, according to our bioinformatic data, the storage proteins of seeds not only of peas, but of a number of plants that do not belong to legumes, turned out to be abundant in sites that are prone to the formation of amyloids, that is, compact and stable fibrillar aggregates. This explains the ability of seeds to survive various unfavourable conditions and germinate after many years,' noted Kirill Antonets, the first author of the research, Associate Professor at the Department of Cytology and Histology at St Petersburg University, Senior Research Associate at the All-Russian Research Institute of Agricultural Meteorology.

Another possible applied value of this work is the creation of plant cultures with super nourishing seeds in the future. The in vitro experiments performed by the scientists have shown that mammals cannot completely digest plant amyloids: they cannot be broken down by digestive enzymes. As Anton Nizhnikov explains, amyloids significantly impair the nutritional value of seeds. It is therefore important to understand how the formation of amyloids in plant seeds can be reduced in order to obtain varieties with a larger amount of common proteins. Such crops can become particularly useful and nutritious for humans.

'Today we are also studying the amyloids of root nodule bacteria. These are the microorganisms that can enter into symbiosis with legumes and bind atmospheric nitrogen so that plants can receive more nutrients,' said Anton Nizhnikov. 'There is an assumption that amyloids can also play an important role in a mutually beneficial symbiotic process. At least root nodule bacteria, as we have shown, also have amyloids. We hope that our findings will be of benefit to the development of plant biology and microbiology, as well as for agriculture.'

For reference: a special fibrillar aggregate of proteins - amyloids - has become known for its association with a number of diseases caused by abnormal protein aggregation, known as amyloidosis. In these severe diseases, monomeric soluble proteins are converted into polymeric fibrillar deposits that form amyloid 'plaques' in various tissues and organs. In total, there are more than 40 human diseases associated with amyloids, and they are very
difficult to treat or are completely incurable.

However, as this research also confirms, in recent decades, scientists around the world have been finding more and more evidence that amyloids function in healthy organisms. This form of protein makes it possible to 'conserve' and stabilise various substances. Moreover, it acts as a kind of structural 'template'. This happens not only in plants. For example, in humans and animals, some of the hormones are stored precisely in the form of amyloids,
while other functional amyloids are involved in melanin biosynthesis and the formation of long-term memory.

Researchers led by Josef Lazar of the Institute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences (IOCB Prague) have demonstrated that molecules of fluorescent proteins act as antennas with optical properties (i.e. the ability to absorb and emit light) dependent on their spatial orientation. First discovered in jellyfish, fluorescent proteins are nowadays widely used in studies of molecular processes in living cells and organisms. The newly described properties of these molecules will find applications in basic biological research as well as in novel drug discovery. A team of researchers from IOCB Prague, the Institute of Microbiology, and the Institute of Molecular Genetics of the Czech Academy of Sciences has published its findings in the journal Proceedings of the National Academy of Sciences of the United States of America.

To achieve these results, the researchers produced sufficient amounts of fluorescent proteins by using genetically modified bacteria, identified the conditions under which the proteins form crystals, and determined the atomic structure of the crystals. Employing a unique microscope developed within the group, they then measured how these crystals absorb and emit light, and from the data they calculated the directional properties of the individual molecules. This allowed them to verify that the fluorescent protein molecules do not behave as tiny luminescent dots, as they are often mistakenly assumed, but rather as miniature antennas. Much like antennas for radio, WiFi, and television transmission, these molecules only absorb light from certain directions. Likewise, they only emit light in certain directions. The researchers also succeeded in precisely establishing these directions.

See the animation: https://youtu.be/cyB7z8UCUSk

The possibility of fluorescent protein molecules behaving as antennas capable of absorbing extraneous light had been assumed, but it long proved difficult to confirm, and that limited its applications. The obstacles have been overcome by Josef Lazar of IOCB Prague and his team, which specializes in the development and use of advanced optical microscopy methods.

"Based on the findings of other laboratories and our own, we suspected that fluorescent protein molecules likely behaved as antennas. Nonetheless, we were surprised to see just how true that analogy is and how accurately we were able to establish the directions from which these molecules absorb light and emit it," says Josef Lazar.

The fact that fluorescent protein molecules function as miniature antennas is interesting not only as a curiosity of physics - it can also have important practical applications. Attaching a fluorescent protein to some other protein of interest means attaching a miniature antenna to it that can then be used to establish, in detail, changes in the shape of the molecules of the protein of interest, directly in a living cell. Such changes in molecular shape can be induced by a drug, for instance. The present discovery will thus find applications in the study of important physiological processes at the molecular level as well as in novel drug discovery.

"The significance of our finding lies in the fact that even though fluorescent protein molecules are widely used in biological research, their ability to behave like antennas isn't fully appreciated yet, nor is it really being put to use. Knowledge of the directional properties of fluorescent proteins can lead to new ways of using these useful molecules," explains Lazar.

In collaboration with other groups at IOCB Prague, Josef Lazar's team is already attempting to apply the present findings in, for example, the study of the physiological effects of insulin and the development of insulin substitutes for peroral use. Another example of a possible application of the present discovery is the tracing of electrical signals in nerve cells, which could prove beneficial in the study of the brain and neurological diseases.

(Boston)-- In a multi-group collaborative involving the National Emerging Infectious Disease Laboratories (NEIDL), the Center for Regenerative Medicine (CReM), and the Center for Network Systems Biology (CNSB), scientists have reported the first map of the molecular responses of human lung cells to infection by SARS-CoV-2. By combining bioengineered human alveolar cells with sophisticated, highly precise mass spectrometry technology, Boston University School of Medicine (BUSM) researchers have identified host proteins and pathways in lung cells whose levels change upon infection by the SARS-CoV-2, providing insights into disease pathology and new therapeutic targets to block COVID-19.

They found a crucial type of protein modification called "phosphorylation" becomes aberrant in these infected lung cells. Phosphorylation of proteins play a major role in regulating protein function inside the cells of an organism and both protein abundance and protein phosphorylation are typically highly controlled processes in the case of normal/healthy cells. However, they discovered that SARS-CoV-2 throws the lung cells into disarray, causing abnormal changes in protein amounts and frequency of protein phosphorylation inside these cells. These abnormal changes help the virus to multiply eventually destroy the cells. The destruction of infected cells may result in widespread lung injury.

According to the researchers, as soon as the SARS-CoV-2 enters the lung cells, it rapidly begins to exploit the cell's core resources, which are otherwise required for the cell's normal growth and function. "The virus uses these resources to proliferate while evading attack by the body's immune system. In this way new viruses form which subsequently exit the exhausted and brutally damaged lung cell, leaving them to self-destruct. These new viruses then infect other cells, where the same cycle is repeated," explains corresponding author Andrew Emili, PhD, professor of biochemistry at BUSM.

The researchers examined lung alveolar cells from one to 24 hours after infection with SARS-CoV-2 to understand what changes occur in lung cells immediately (at one, three and six hours after infection by SARS-CoV-2) and what changes occur later (at 24 hours after infection). These changes were then compared to uninfected cells. All proteins from infected and uninfected alveolar cells, corresponding to the different time-points were extracted and labelled with unique barcoding tags called "tandem mass tag." These tags, which can be accurately detected only by a mass spectrometer, permit robust quantification of protein and phosphorylation abundance in cells.

"Our results showed that in comparison to normal/uninfected lung cells, SARS-CoV-2 infected lung cells showed dramatic changes in the abundance of thousands of proteins and phosphorylation events," said Darrell Kotton, MD, professor of pathology & laboratory medicine at BUSM and director of the CReM.

"Moreover, our data also showed that the SARS-CoV-2 virus induces a significant number of these changes as early as one hour post infection and lays the foundation for a complete hijack of the host lung cells," adds Elke M?hlberger, PhD, associate professor of microbiology and principal investigator at the NEIDL.

"There are important biological features specific to lung cells that are not reproduced by other cell types commonly used to study viral infection," said Andrew Wilson, MD, associate professor of medicine at BUSM and CReM investigator. "Studying the virus in the context of the cell type that is most damaged in patients is likely to yield insights that we wouldn't be able to see in other model systems."

The researchers also analyzed their data to identify prospective opportunities for COVID-19 treatment and found that at least 18 pre-existing clinically approved drugs (developed originally for other medical conditions/diseases) can be potentially re-purposed for use towards COVID-19 therapy. These drugs have shown exceptional promise to block the proliferation of the SARS-CoV-2 in lung cells.

Sophia Antipolis, 2 December 2020: Fourteen drinks a week is linked with a higher risk of health problems including stroke and embolism in patients with atrial fibrillation, according to research published in EP Europace, a journal of the European Society of Cardiology (ESC).1

"Our study suggests that atrial fibrillation patients should avoid heavy alcohol consumption to prevent stroke and other complications," said author Dr. Boyoung Joung of Yonsei University College of Medicine, Seoul, Republic of Korea.

The study included 9,411 patients with atrial fibrillation from 18 tertiary hospitals covering all geographical regions of South Korea. Patients were categorised into four groups according to their weekly alcohol consumption (one drink contains 14 grams of alcohol): abstainer/rare (0 grams/less than one drink), light (less than 100 grams/7 drinks), moderate (100-200 grams/7-14 drinks), and heavy (200 grams/14 drinks or more).

A total of 7,455 (79.2%) patients were classified as abstainer/rare, 795 (8.4%) as light, 345 (3.7%) as moderate, and 816 (8.7%) as heavy alcohol consumption.

Patients were followed-up for a median of 17.4 months for adverse events, which included stroke, transient ischaemic attack, systemic embolism (a blood clot in a limb or organ), and hospitalisation for rate or rhythm control of atrial fibrillation or for heart failure management. The researchers recorded how many patients experienced any of these events and calculated the incident rate (number of events per 100 person-years). Incident rates were 6.73, 5.77, 6.44, and 9.65 in the abstainer/rare, light, moderate, and heavy drinkers, respectively.

The researchers compared the risk of adverse events in the light, moderate, and heavy drinkers to the abstainer/rare group. Heavy drinking was associated with a 32% increased risk compared with the abstainers and rare drinkers. No significant association was observed for light or moderate alcohol consumption.

Dr. Joung said: "Our study did not find any significant association between light or moderate drinking and complications. A significant deleterious relationship with heavy drinking was identified, suggesting that heavy alcohol consumption should be avoided."

Subgroup analyses showed that the impact of heavy drinking was more pronounced in patients with low stroke risk2 compared to those at moderate or high stroke risk. Similarly, heavy drinking was associated with a greater likelihood of unfavourable outcomes in patients without high blood pressure compared to those with high blood pressure. Higher risks were also observed in patients not using beta-blockers or antiplatelet medications compared to those taking the drugs.

Dr. Joung said: "The findings indicate that heavy drinking is particularly detrimental for atrial fibrillation patients who are considered less vulnerable to complications. Clinicians should ask patients about their alcohol consumption and take it into account when calculating their stroke risk."

He concluded: "While heavy drinking should be strongly discouraged among atrial fibrillation patients, moderate drinking seems to be safe."

Autonomous systems are affecting virtually all aspects of society, so future designs must be guided by a broad range of societal stakeholders. That’s according to a new report led by scientists in the Oden Institute for Computational Engineering and Sciences at The University of Texas at Austin.

Ufuk Topcu of the Department of Aerospace Engineering and Engineering Mechanics led a yearlong effort involving more than 100 autonomy experts nationwide in the completion of a report titled “Assured Autonomy: Path Toward Living With Autonomous Systems We Can Trust.”

From spacecraft design to health care, vehicles to smart-cities planning, autonomous systems help us determine how society should run as a matter of routine. Yet the safety, security and regulation of these systems are still not prioritized.

“The management of autonomous systems needs to be at the crossing of science, technology, society, policy and governance,” Topcu said.

Commissioned by The Computing Community Consortium (CCC) — enabling high-impact research through state, industry and academic engagement within the computing community — the report begins by listing technologies that have disrupted society in the past. From the printing press “democratizing knowledge” to the industrial revolution “replacing man with machine” to more recently, the internet making instant global communications a given.

We are now witnessing the age of autonomous systems, where both humans and human intelligence can live harmoniously with machines and machine intelligence, assuming the right approach is taken now.

“Science and technology have always disrupted the status quo,” the report said. “But these systems are different from earlier technologies. Replacing humans and human intelligence with machines and machine intelligence is replacing within existing frameworks of laws, ethics, morality, norms, as well as an existing technology.”

With autonomy, a technical flaw in the software of a system, for example, can’t be seen as merely a bug. “That bug could be a potential violation of law and/or morality,” Topcu said.

The challenges faced require interdisciplinary approaches. “Autonomous systems are not just engineering marvels. They have an influence on individuals, groups, and even the culture as a whole,” said Art Markman of UT’s College of Liberal Arts and director of the IC2 Institute. “Engaging experts from a range of disciplines, including the humanities and the social and behavioral sciences, will be a crucial step to avoid unintended consequences of the deployment of new technologies.”

The direction taken by autonomous technologies is currently guided almost exclusively by scientists and engineers. According to Karen Willcox, director of the Oden Institute, it is time to “stretch our interdisciplinary thinking beyond the STEM fields.”

“Autonomy is a prime example of a domain where the interdisciplinary approaches of computational science - weaving together rigorous mathematical modeling with advanced computing and domain expertise - will play a critical role in developing better, safer systems,” Willcox said.

“But there is an urgent need to build deep collaborations in research and education with humanists and social scientists. This is a challenging but exciting future prospect.”

The core recommendation of the report is the creation of a network of institutes that can easily share ideas, concerns and, ultimately, develop a regulatory and quality assurance framework that underpins future advancements. The CCC calls for the implementation of a national research strategy for assurance with stakeholders in government, academia, industry and society all playing their part.

“Autonomy is a socioeconomic opportunity as well as a challenge, and the public will both perceive and be affected by it unevenly,” Topcu said.

The broader impact of autonomous technologies is a growing priority for researchers at UT Austin.

“Both basic and applied research in autonomous and AI technologies, particularly at UT, is increasingly focused on values-based designs,” said interim Vice President for Research Alison R. Preston. “Outlining the potential value of new technologies at the earliest design stages can limit the potential for unintended, negative consequences once a new technology is deployed. Understanding how to design autonomous systems that provide value to multiple stakeholders requires true collaboration, not just within any one university but among them. I’m proud that the Oden Institute is helping lead that charge.”

“Assured Autonomy: Path Toward Living With Autonomous Systems We Can Trust” is the product of several workshops facilitated by Ufuk Topcu and participating members of the CCC organizing committee: Nadya Bliss and Nancy Cooke (Arizona State University), Missy Cummings (Duke University), Ashley Llorens (Johns Hopkins University), Howard Shrobe (MIT), and Lenore Zuck (University of Illinois at Chicago).

December 2, 2020 -- The first U.S. Executive Order of the 2017 travel ban targeting individuals from Muslim majority countries may be associated with preterm births for women from those countries residing in the U.S., according to a new study conducted at Columbia University Mailman School of Public Health. The research also showed that structurally xenophobic and racist policies in the U.S. may have a harmful effect on early life indicators of life-long health outcomes. The findings are published on line in the journal Social Science and Medicine.

This is the first national study to consider the impact of a policy that is both xenophobic and Islamophobic (anti-immigrant and anti-Muslim) on birth outcomes of women from Muslim countries impacted by the 2017 travel ban.

"Our study provides new evidence about the importance of social characteristics of host countries and structurally stigmatizing contexts and reveals the potential public health implications of the global rise in xenophobia and populism," said Goleen Samari, PhD, assistant professor of population and family health at Columbia Mailman School, and principal investigator. "Even for populations that historically experience positive birth outcomes, anti-immigrant and Islamophobic policies are associated with abrupt and detrimental shifts in health outcomes."

The researchers conducted a national-level examination of women from Middle Eastern and North African (MENA) countries included in the 2017 travel ban, many of which include a Muslim majority. These populations are typically overlooked and understudied because of how religion and race and ethnicity are defined in health survey research.

Women from countries impacted by the 2017 travel ban experienced a nearly 7% increase in the odds of delivering a preterm infant between September 2017 and August 2018--a period that began approximately eight months after the executive order travel ban was enacted. Trends in preterm birth remain unchanged for native-born non-Hispanic White women.

The data controlled for seasonality, other forms of autocorrelation, and population-level shifts in preterm birth among all women giving birth.

"As many countries continue to shut down migration systems because of the COVID-19 pandemic, it is important to understand the secondary and tertiary effects of such restrictions. This study, therefore, is an important contribution to the literature on xenophobia, structural racism, and health and perinatal demography for an often overlooked and understudied immigrant population."

Plants get bacterial infections, just as humans do. When food crops and trees are infected, their yield and quality can suffer. Although some compounds have been developed to protect plants, few of them work on a wide variety of crops, and bacteria are developing resistance. Now, researchers reporting in ACS' Journal of Agricultural and Food Chemistry have modified natural plant alkaloids into new compounds that kill bacteria responsible for diseases in rice, kiwi and citrus.

Currently, no effective prevention or treatment exists for some plant bacterial diseases, including rice leaf blight, kiwifruit canker and citrus canker, which result in substantial agricultural losses every year. Scientists are trying to find new compounds that attack bacteria in different ways, reducing the chances that the microbes will develop resistance. Plant compounds called tetrahydro-β-carboline (THC) alkaloids are known to have antitumor, anti-inflammatory, antifungal, antioxidant and antiviral activities. So, Pei-Yi Wang, Song Yang and colleagues wondered whether derivatives of THC alkaloids could help fight plant bacterial diseases.

The researchers used a THC alkaloid called eleagnine, which is produced by Russian olive trees and some other plants, as a scaffold. To this framework, they added different chemical groups to make a series of new compounds, two of which efficiently killed three strains of plant pathogenic bacteria in liquid cultures. The team then tested the two compounds on rice, kiwi and citrus plant twigs and leaves and found that the new alkaloids could both prevent and treat bacterial infections. The researchers determined that the compounds worked by increasing levels of reactive oxygen species in the bacteria, which caused the bacterial cells to die.

Declines in blue-collar jobs may have left some working-class men frustrated by unmet job expectations and more likely to suffer an early death by suicide or drug poisoning, according to a study led by sociologists at The University of Texas at Austin.

In the study, the researchers compared life outcomes of 11,680 men to the job expectations they held as high school seniors in the early 1980s. The study showed that men who expected to work in jobs that did not require a college degree but later faced declines in the job market were nearly three times as likely to suffer early deaths by suicide and drug poisoning as men who sought work that required a bachelor's degree.

The study, published in JAMA Network Open, is the first to link the rise in suicide and drug-poisoning deaths among men without a college degree to declines in working-class jobs.

"Work plays a major role in how individuals experience their communities, derive a sense of purpose, and thus develop a sense of psychological well-being," said lead author Chandra Muller, a sociology professor and researcher at the Population Research Center at UT Austin. "It's possible that occupational expectations developed in adolescence serve as a benchmark for perceptions of adult success and, when unmet, pose a risk of self-injury."

Early death from self-injury has risen dramatically in recent decades, especially among middle-age white men whose deaths by suicide and drug poisoning increased by 9 and 31 per 100,000 (respectively) between 1980 and 2013. At the same time, the labor market also experienced a discerning trend: the decline of well-paying jobs that do not require a college degree.

Researchers from UT Austin, the University of Minnesota and the University of Wisconsin-Madison investigated the relationship between the two trends using data from the High School and Beyond cohort, a nationally representative sample of 11,680 men who were surveyed throughout high school in the early 1980s, again in 1992 (when they were 28-30 years old), and again in 2015.

Between 1992 and 2015, less than 6% of the sample had died. The researchers compared suicide and drug poisoning deaths, which are forms of self-injury, to other causes of early adult deaths, such as heart attacks and cancer. They found that the men most likely to suffer a death by suicide or drug poisoning were those who as adolescents expected to earn enough to support a family through some type of semi-skilled labor that later declined when they reached adulthood, such as manufacturing, mechanics and carpentry.

The study showed that neither educational attainment nor the actual job worked increased risk for death by self-injury. Furthermore, unmet occupational expectations were not associated with a higher risk of an early death by natural or other causes. This comparison further strengthened their conclusions about a link between a decline of working-class jobs and deaths of despair.

"Our findings suggest closed pathways to sustaining working-class jobs may contribute to men's increasing rates of suicide and drug-poisoning mortality," Muller said. "The social, psychological and cultural ideals associated with certain occupations are important considerations in labor policy, such as minimum wage policies or job retraining programs, as strategies for suicide prevention."

Second- and thirdhand tobacco smoke have received lots of attention, but much less is known about the compounds deposited on surfaces from cannabis smoke. Now, researchers reporting in ACS' Environmental Science & Technology have discovered that ozone --a component of outdoor and indoor air -- can react with tetrahydrocannabinol (THC), the psychoactive component of cannabis, on glass or cotton surfaces to produce new compounds, which they characterized for the first time.

Smoking emits reactive chemicals that remain in the air (so-called secondhand smoke) or deposit onto surfaces, including walls, windows, clothing and upholstery (thirdhand smoke). Unlike the secondhand variety, thirdhand smoke lingers long after a person stops smoking. Nicotine is semi-volatile and reacts with other chemicals on surfaces, producing new compounds that, if volatile, can also become airborne. Because cannabis smoke is chemically distinct from tobacco smoke, Aaron Wylie and Jonathan Abbatt wanted to characterize the compounds formed when THC, by itself or in cannabis smoke, on surfaces reacts with ozone in the air.

The researchers coated glass and cotton cloth, to simulate windows and clothing, with a THC solution. Then, they exposed the surfaces to concentrations of ozone that could exist in indoor air. In their analysis, they found that over time, the amount of THC on glass and cotton decreased, while the quantities of three THC oxidation products increased. In other experiments, the team used a smoking machine to deposit cannabis smoke onto cotton. Upon exposure to ozone, the same three compounds formed at roughly the same rate as observed for the THC-coated cloth. Because of the low volatility of THC and its oxidation products, the compounds are unlikely to be emitted to the air where they could be inhaled in as large amounts as nicotine, the researchers say. They say that somebody could still be exposed to THC and its derivatives, whose health effects are unknown, if they, for example, lick their fingers after touching a surface contaminated by cannabis smoke.

Lacking vaccines, countries have relied on multiple non-pharmaceutical interventions to control COVID-19 transmission. Despite the urging of the World Health Organization (WHO) in March to "test, test, and test," policy makers disagree on on how much testing is optimal. A new study, by Ravindra Prasan Rannan-Eliya and coauthors from the Institute for Health Policy in Colombo, Sri Lanka, uses data from multiple online sources to quantify testing impact on COVID-19 transmissibility in 173 countries and territories (accounting for 99 percent of the world's cases) between March and June 2020. The authors found that among interventions, testing intensity had the greatest influence: a tenfold increase in the ratio of tests to new cases reported reduced average COVID-19 transmission by 9 percent. The authors note that this helps explain why countries such as China, Australia, and New Zealand achieved near elimination of COVID-19 and why lockdowns and other interventions failed to slow spread of the virus in others, such as India and Peru. "Even the wealthiest countries, such as the US, UK, and Qatar, cannot expand testing and tracing fast enough to achieve epidemic control," the authors conclude. "Early and continuous aggressive testing to keep incidence within capacity to test, trace and isolate may be the best implementation of flattening the curve."

The tree of life describes the evolution of life and seeks to define the relationships between species. Likewise, the tree of cell types aims to organize cells in the brain into groups and describe their relationships to each other.

Scientists have long pondered just what the brain's tree of cell types looks like. Now, an international collaboration led by Dr. Andreas Tolias from Baylor College of Medicine, Dr. Philipp Berens from the University of Tübingen in Germany and Dr. Rickard Sandberg from the Karolinska Institute in Stockholm, Sweden, has published an article in Nature that provides one of the most detailed and complete characterizations of the diversity of neural types in the brain so far.

Uncovering the shape of the tree of cortical cell types with Patch-seq

Neuroscientists mostly use three fundamental features to describe neurons: their anatomy, or how they look under a microscope; their physiology, or how they respond when stimulated; and, more recently, the genes they express, which are known as their transcriptome.

For this study, the research team used an experimentally challenging technique that they developed several years ago, called Patch-seq. This technique allowed them to collect a large multimodal database including genetic, anatomical and physiological information from single cells in the mouse motor cortex.

"Gathering all these three fundamental features from the same set of neurons was the key that enabled us to get a much deeper understanding of how neurons in the motor cortex are related to each other and a clearer view of how the tree of cell types looks like," said co-first author Dr. Federico Scala, postdoctoral associate in Tolias lab at Baylor.

Dr. Dmitry Kobak, also co-first author and a research scientist in Berens lab, described that while the broad genetic families of neurons had distinct anatomical and physiological properties, within each family the neurons exhibited extensive anatomical and physiological diversity. Importantly, all the three basic neuronal characteristics (anatomy, physiology and transcriptome) were correlated, which enabled the team to find interesting links between them.

"Our data supports the view that the tree of cortical cell types may look more like a banana tree with few big leaves rather than an olive tree with many small ones. This view provides a simpler model to describe the diversity of neurons we find in the brain. We believe that this simpler view will lead to a more principled understanding of why we have so many cell types in the brain to begin with and what they are used for," said Tolias, Brown Foundation Endowed Chair of Neuroscience and director of the Center for Neuroscience and Artificial Intelligence at Baylor.

In this metaphor, neurons follow a hierarchy consisting of distinct, non-overlapping branches at the level of families, the large leaves of the banana tree. Within each family, neurons show continuous changes in their genetic, anatomical and physiological features, and all three features within a family are correlated. In parallel, work published simultaneously in Cell, scientists from the Allen Institute of Brain Science in Seattle obtained very similar results from mouse visual cortex underscoring that this view of cell types may be a general building principle of brain circuits.

WASHINGTON--Roly poly bugs may be a source of fun for kids and adults but these little bugs that form into balls at the slightest touch are causing problems for some threatened fish.

New research finds steelhead trout in a stream on the California coast accumulate mercury in their bodies when the fish eat roly polies and similar terrestrial bugs that fall into local waterways. The new study corroborates earlier findings that mercury can make its way to the top of the food chain in coastal California.

The results show for the first time that roly polies and other bugs are transferring high levels of the toxic metal to fish in an otherwise pristine watershed where environmental contaminants are not known to be a concern, according to the researchers.

"Our research is the first step in identifying [mercury] as a potential stressor on these populations," said Dave Rundio, a research fishery biologist at NOAA's Southwest Fisheries Science Center and co-leader of the study that will be presented 8 December at AGU's Fall Meeting 2020.

It is unclear whether mercury accumulation in steelhead and other species would affect humans, but the findings suggest mercury can move between connected ecosystems and affect threatened or endangered species in unsuspecting ways, according to the researchers.

Tracing mercury's path

Mercury is a toxic metal that can cause neurological and developmental problems in humans. Some mercury occurs naturally and is not harmful to living things, but certain bacteria convert elemental mercury into an active form that can become concentrated in the tissues of living organisms and accumulate in larger and larger amounts up through the food web.

A 2019 study by Peter Weiss-Penzias, an atmospheric chemist at the University of California Santa Cruz, found mercury from coastal California fog can make its way to the top of the terrestrial food chain and reach nearly toxic levels in the bodies of pumas.

In the new study, Rundio wanted to see if mercury can accumulate in top predators in aquatic ecosystems as well as on land. Rundio, Weiss-Penzias and other colleagues looked specifically at mercury levels in steelhead trout, a kind of rainbow trout that are one of the top sport fish in North America and culturally important to some Native American tribes.

The researchers took samples of steelhead trout and their prey from a stream in the Big Sur region of central California to see if they had elevated mercury concentrations in their tissues and to determine where that mercury came from.

Steelhead are predators with a varied diet in freshwater, eating anything from small fish and crustaceans to insects and even salamanders that fall into streams. Interestingly, terrestrial bugs like roly polies make up nearly half of a steelhead's diet in streams in coastal California.

The researchers found steelhead had elevated mercury levels in their tissues, and the older, more mature fish had more mercury than juveniles. Some of the mature stream trout they sampled had mercury concentrations that met or exceeded water quality and food consumption advisory levels.

From fog to fish

The researchers also found the terrestrial bugs the fish eat - most notable roly polies, which are a non-native species from Europe - had higher mercury concentrations than their aquatic counterparts. The findings suggest mercury rolls into coastal California through fog, is consumed by roly polies eating leaf detritus and water droplets, and moves up the food chain to the fish - similar to Weiss-Penzias's findings of how mercury makes it up the terrestrial food chain to pumas.

The new findings came as a surprise to Rundio because the steelhead they sampled live in a nearly pristine environment scientists thought to be free of environmental contaminants.

It is important to know where mercury accumulates in the environment and food webs because it a difficult toxin to get rid of, said Weiss-Penzias, who will present the work. Some toxins can be diluted enough in the environment that they become essentially harmless, but mercury becomes more concentrated as it moved up the food chain.

"We have to think of mercury in that sense and be extremely concerned about it because of the continual releases of coal combustion, gold mining, and other industrial processes," Weiss-Penzias said.