The Structure of a \u3cem\u3eLactobacillus helveticus\u3c/em\u3e Chlorogenic Acid Esterase and the Dynamics of Its Insertion Domain Provide Insights into Substrate Binding

Chlorogenic acid esterases (ChlEs) are a useful class of enzymes that hydrolyze chlorogenic acid (CGA) into caffeic and quinic acid. ChlEs can break down CGA in foods to improve their sensory properties and release caffeic acid in the digestive system to improve the absorption of bioactive compounds. This work presents the structure, molecular dynamics, and biochemical characterization of a ChlE from Lactobacillus helveticus (Lh). Molecular dynamics simulations suggest that substrate access to the active site of LhChlE is modulated by two hairpin loops above the active site. Docking simulations and mutational analysis suggest that two residues within the loops, Gln145 and Lys164, are important for CGA binding. Lys164 provides a slight substrate preference for CGA, whereas Gln145 is required for efficient turnover. This work is the first to examine the dynamics of a bacterial ChlE and provides insights on the substrate binding preference and turnover in this type of enzyme

New chondritic bodies identified in eight oxygen-bearing white dwarfs

We present observations and analyses of eight white dwarf stars that have accreted rocky material from their surrounding planetary systems. The spectra of these helium-atmosphere white dwarfs contain detectable optical lines of all four major rock-forming elements (O, Mg, Si, Fe). This work increases the sample of oxygen-bearing white dwarfs with parent body composition analyses by roughly thirty-three percent. To first order, the parent bodies that have been accreted by the eight white dwarfs are similar to those of chondritic meteorites in relative elemental abundances and oxidation states. Seventy-five percent of the white dwarfs in this study have observed oxygen excesses implying volatiles in the parent bodies with abundances similar to those of chondritic meteorites. Three white dwarfs have oxidation states that imply more reduced material than found in CI chondrites, indicating the possible detection of Mercury-like parent bodies, but are less constrained. These results contribute to the recurring conclusion that extrasolar rocky bodies closely resemble those in our solar system, and do not, as a whole, yield unusual or unique compositions.Comment: Accepted for publication in ApJ. 7 Figures, 7 Table

ECOSTRESS: NASA's next generation mission to measure evapotranspiration from the International Space Station

The ECOsystem Spaceborne Thermal Radiometer Experiment on Space Station ECOSTRESS) was launched to the International Space Station on June 29, 2018. The primary science focus of ECOSTRESS is centered on evapotranspiration (ET), which is produced as level‐3 (L3) latent heat flux (LE) data products. These data are generated from the level‐2 land surface temperature and emissivity product (L2_LSTE), in conjunction with ancillary surface and atmospheric data. Here, we provide the first validation (Stage 1, preliminary) of the global ECOSTRESS clear‐sky ET product (L3_ET_PT‐JPL, version 6.0) against LE measurements at 82 eddy covariance sites around the world. Overall, the ECOSTRESS ET product performs well against the site measurements (clear‐sky instantaneous/time of overpass: r2 = 0.88; overall bias = 8%; normalized RMSE = 6%). ET uncertainty was generally consistent across climate zones, biome types, and times of day (ECOSTRESS samples the diurnal cycle), though temperate sites are over‐represented. The 70 m high spatial resolution of ECOSTRESS improved correlations by 85%, and RMSE by 62%, relative to 1 km pixels. This paper serves as a reference for the ECOSTRESS L3 ET accuracy and Stage 1 validation status for subsequent science that follows using these data

COVID-19 reopening strategies at the county level in the face of uncertainty: Multiple Models for Outbreak Decision Support

Policymakers make decisions about COVID-19 management in the face of considerable uncertainty. We convened multiple modeling teams to evaluate reopening strategies for a mid- sized county in the United States, in a novel process designed to fully express scientific uncertainty while reducing linguistic uncertainty and cognitive biases. For the scenarios considered, the consensus from 17 distinct models was that a second outbreak will occur within 6 months of reopening, unless schools and non-essential workplaces remain closed. Up to half the population could be infected with full workplace reopening; non-essential business closures reduced median cumulative infections by 82%. Intermediate reopening interventions identified no win-win situations; there was a trade-off between public health outcomes and duration of workplace closures. Aggregate results captured twice the uncertainty of individual models, providing a more complete expression of risk for decision-making purposes.Integrative Biolog

Research design considerations for clinical studies of abuse-deterrent opioid analgesics: IMMPACT recommendations

Opioids are essential to the management of pain in many patients, but they also are associated with potential risks for abuse, overdose, and diversion. A number of efforts have been devoted to the development of abuse-deterrent formulations of opioids to reduce these risks. This article summarizes a consensus meeting that was organized to propose recommendations for the types of clinical studies that can be used to assess the abuse deterrence of different opioid formulations. Due to the many types of individuals who may be exposed to opioids, an opioid formulation will need to be studied in several populations using various study designs in order to determine its abuse-deterrent capabilities. It is recommended that the research conducted to evaluate abuse deterrence should include studies assessing: (1) abuse liability; (2) the likelihood that opioid abusers will find methods to circumvent the deterrent properties of the formulation; (3) measures of misuse and abuse in randomized clinical trials involving pain patients with both low risk and high risk of abuse; and (4) post-marketing epidemiological studies

The NANOGrav 15-year Data Set: Bayesian Limits on Gravitational Waves from Individual Supermassive Black Hole Binaries

Evidence for a low-frequency stochastic gravitational wave background has recently been reported based on analyses of pulsar timing array data. The most likely source of such a background is a population of supermassive black hole binaries, the loudest of which may be individually detected in these datasets. Here we present the search for individual supermassive black hole binaries in the NANOGrav 15-year dataset. We introduce several new techniques, which enhance the efficiency and modeling accuracy of the analysis. The search uncovered weak evidence for two candidate signals, one with a gravitational-wave frequency of $\sim$4 nHz, and another at $\sim$170 nHz. The significance of the low-frequency candidate was greatly diminished when Hellings-Downs correlations were included in the background model. The high-frequency candidate was discounted due to the lack of a plausible host galaxy, the unlikely astrophysical prior odds of finding such a source, and since most of its support comes from a single pulsar with a commensurate binary period. Finding no compelling evidence for signals from individual binary systems, we place upper limits on the strain amplitude of gravitational waves emitted by such systems.Comment: 23 pages, 13 figures, 2 tables. Accepted for publication in Astrophysical Journal Letters as part of Focus on NANOGrav's 15-year Data Set and the Gravitational Wave Background. For questions or comments, please email [email protected]

Plasticity in the Human Gut Microbiome Defies Evolutionary Constraints

The gut microbiome of primates, including humans, is reported to closely follow host evolutionary history, with gut microbiome composition being specific to the genetic background of its primate host. However, the comparative models used to date have mainly included a limited set of closely related primates. To further understand the forces that shape the primate gut microbiome, with reference to human populations, we expanded the comparative analysis of variation among gut microbiome compositions and their primate hosts, including 9 different primate species and 4 human groups characterized by a diverse set of subsistence patterns (n = 448 samples). The results show that the taxonomic composition of the human gut microbiome, at the genus level, exhibits increased compositional plasticity. Specifically, we show unexpected similarities between African Old World monkeys that rely on eclectic foraging and human populations engaging in nonindustrial subsistence patterns; these similarities transcend host phylogenetic constraints. Thus, instead of following evolutionary trends that would make their microbiomes more similar to that of conspecifics or more phylogenetically similar apes, gut microbiome composition in humans from nonindustrial populations resembles that of generalist cercopithecine monkeys. We also document that wild cercopithecine monkeys with eclectic diets and humans following nonindustrial subsistence patterns harbor high gut microbiome diversity that is not only higher than that seen in humans engaging in industrialized lifestyles but also higher compared to wild primates that typically consume fiber-rich diets

Global injury morbidity and mortality from 1990 to 2017: Results from the global burden of disease study 2017

Background Past research in population health trends has shown that injuries form a substantial burden of population health loss. Regular updates to injury burden assessments are critical. We report Global Burden of Disease (GBD) 2017 Study estimates on morbidity and mortality for all injuries. methods We reviewed results for injuries from the GBD 2017 study. GBD 2017 measured injury-specific mortality and years of life lost (YLLs) using the Cause of Death Ensemble model. To measure non-fatal injuries, GBD 2017 modelled injury-specific incidence and converted this to prevalence and years lived with disability (YLDs). YLLs and YLDs were summed to calculate disability-adjusted life years (DALYs). Findings In 1990, there were 4 260 493 (4 085 700 to 4 396 138) injury deaths, which increased to 4 484 722 (4 332 010 to 4 585 554) deaths in 2017, while age-standardised mortality decreased from 1079 (1073 to 1086) to 738 (730 to 745) per 100 000. In 1990, there were 354 064 302 (95% uncertainty interval: 338 174 876 to 371 610 802) new cases of injury globally, which increased to 520 710 288 (493 430 247 to 547 988 635) new cases in 2017. During this time, age-standardised incidence decreased non-significantly from 6824 (6534 to 7147) to 6763 (6412 to 7118) per 100 000. Between 1990 and 2017, age-standardised DALYs decreased from 4947 (4655 to 5233) per 100 000 to 3267 (3058 to 3505). Interpretation Injuries are an important cause of health loss globally, though mortality has declined between 1990 and 2017. Future research in injury burden should focus on prevention in high-burden populations, improving data collection and ensuring access to medical care