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bstract This review aimed to determine the most popular physical activities performed by children, adolescents, and adults globally. Statistic bureau websites and article databases Scopus, ...ProQuest, SPORTDiscus, and Science Direct were searched between November 17th, 2014 and April 31st, 2015. Eligible studies were published in the last 10 years with participation rates for specific physical activities among individuals five years or older. Data extraction for included articles (n = 64) was assessed independently and agreed upon by two authors. A random-effects model was used to calculate participation rates in specific activities for each age group and region. In total 73,304 articles were retrieved and 64 articles representing 47 countries were included in the final meta-analysis. Among adults, walking was the most popular activity in the Americas (18.9%; 95% CI 10.2 to 32.5), Eastern Mediterranean (15.0%; 95% CI 5.8 to 33.6), Southeast Asia (39.3%; 95% CI 0.9 to 98.0) and Western Pacific (41.8%; 95% CI 25.2 to 60.6). In Europe and Africa, soccer (10.0%; 95% CI 6.5 to 15.1) and running (9.3%; 95% CI 0.9 to 53.9), respectively, were top activities. Child and adolescent participation results were highly dependent upon region. American youth team sport participation was high, while youth from the Eastern Mediterranean and Western Pacific were more likely to report participation in lifelong physical activities. Global data for adults reflects a consistent pattern of participation in running and walking. Among all age groups and regions soccer was popular. In children and adolescents, preferences were variable between regions.
Vulnerability to relapse during periods of attempted abstinence from cocaine use is hypothesized to result from the rewiring of brain reward circuitries, particularly ventral tegmental area (VTA) ...dopamine neurons. How cocaine exposures act on midbrain dopamine neurons to precipitate addiction-relevant changes in gene expression is unclear. We found that histone H3 glutamine 5 dopaminylation (H3Q5dop) plays a critical role in cocaine-induced transcriptional plasticity in the midbrain. Rats undergoing withdrawal from cocaine showed an accumulation of H3Q5dop in the VTA. By reducing H3Q5dop in the VTA during withdrawal, we reversed cocaine-mediated gene expression changes, attenuated dopamine release in the nucleus accumbens, and reduced cocaine-seeking behavior. These findings establish a neurotransmission-independent role for nuclear dopamine in relapse-related transcriptional plasticity in the VTA.
We present the genome-wide chromatin accessibility profiles of 410 tumor samples spanning 23 cancer types from The Cancer Genome Atlas (TCGA). We identify 562,709 transposase-accessible DNA elements ...that substantially extend the compendium of known cis-regulatory elements. Integration of ATAC-seq (the assay for transposase-accessible chromatin using sequencing) with TCGA multi-omic data identifies a large number of putative distal enhancers that distinguish molecular subtypes of cancers, uncovers specific driving transcription factors via protein-DNA footprints, and nominates long-range gene-regulatory interactions in cancer. These data reveal genetic risk loci of cancer predisposition as active DNA regulatory elements in cancer, identify gene-regulatory interactions underlying cancer immune evasion, and pinpoint noncoding mutations that drive enhancer activation and may affect patient survival. These results suggest a systematic approach to understanding the noncoding genome in cancer to advance diagnosis and therapy.
Psi4 is an ab initio electronic structure program providing methods such as Hartree–Fock, density functional theory, configuration interaction, and coupled-cluster theory. The 1.1 release represents ...a major update meant to automate complex tasks, such as geometry optimization using complete-basis-set extrapolation or focal-point methods. Conversion of the top-level code to a Python module means that Psi4 can now be used in complex workflows alongside other Python tools. Several new features have been added with the aid of libraries providing easy access to techniques such as density fitting, Cholesky decomposition, and Laplace denominators. The build system has been completely rewritten to simplify interoperability with independent, reusable software components for quantum chemistry. Finally, a wide range of new theoretical methods and analyses have been added to the code base, including functional-group and open-shell symmetry adapted perturbation theory, density-fitted coupled cluster with frozen natural orbitals, orbital-optimized perturbation and coupled-cluster methods (e.g., OO-MP2 and OO-LCCD), density-fitted multiconfigurational self-consistent field, density cumulant functional theory, algebraic-diagrammatic construction excited states, improvements to the geometry optimizer, and the “X2C” approach to relativistic corrections, among many other improvements.
Optogenetic and chemogenetic actuators are critical for deconstructing the neural correlates of behavior. However, these tools have several limitations, including invasive modes of stimulation or ...slow on/off kinetics. We have overcome these disadvantages by synthesizing a single-component, magnetically sensitive actuator, "Magneto," comprising the cation channel TRPV4 fused to the paramagnetic protein ferritin. We validated noninvasive magnetic control over neuronal activity by demonstrating remote stimulation of cells using in vitro calcium imaging assays, electrophysiological recordings in brain slices, in vivo electrophysiological recordings in the brains of freely moving mice, and behavioral outputs in zebrafish and mice. As proof of concept, we used Magneto to delineate a causal role of striatal dopamine receptor 1 neurons in mediating reward behavior in mice. Together our results present Magneto as an actuator capable of remotely controlling circuits associated with complex animal behaviors.
•A string shortened by one module results in a 1.29 module equivalent power loss when connected to healthy string(s).•At VOC, shortened strings experience reverse current, which increases with the ...level of mismatch.•Reverse current may exceed the series fuse or reverse current rating of modules when paralleled.•Simple simulations effectively reproduce experimental results, expanding opportunities to model other modules or higher complexity arrays.
Numerous events may require intentional removal of one or more photovoltaic modules from a string, shortening the length of the string relative to others within the array, resulting in a str ing length mismatch. The impact of such a mismatch is not well understood either in measurable operational effects (voltage, current, power) or in the potential effects on long-term module health. It is impractical to solely approach this problem experimentally due to the size and complexity of arrays that may experience string length shortening. This work presents simulations, validated through limited field experiments on a two string array, providing a basis from which more complex arrays and scenarios may be explored. Refinement of the simulation achieves an overall error in IMPP for the nominal (S1) and test strings (S2) between the simulation and experimental values, through all test conditions, of +0.35±1.46% and -0.36±1.58% respectively. Shortening one of two strings by one module results in a power loss greater than the power contribution of the module alone (1.29 module equivalents); the impact increases through the maximum test case of a six module mismatch with a power loss equivalent to more than 11 modules. The impact of using string-end blocking diodes is presented with an emphasis at the array maximum power point and at open circuit. Implications are discussed for arrays of higher complexity.
Despite more than 2 million American cocaine users monthly, there is no approved drug for treating cocaine use disorder. Cocaine use disorder has a multifactorial aetiology, including both genetic ...and environmental factors. Both cocaine use and genetic variations demonstrably alter DNA methylation and gene expression in the brain in a complex manner. How these factors interact in the context of cocaine abuse in humans is unknown. We propose that we can identify potential drug targets for treating cocaine use disorders by examining genetic, epigenetic, and expression changes in the brains of individuals that abused cocaine. In this study, we identified the interaction between the epigenetics changes (DNA CpG methylation) and genetic variants (SNPs) in the HTR2A gene in the context of cocaine addiction by using brain tissue collected from individuals that overdosed on cocaine (N = 14) and healthy matched controls (N = 16). We generated DNA CpG methylation profiles in eight regions of HTR2A harbouring frequent SNPs, measuring both allelic and total methylation, and compared these methylation profiles with HTR2A mRNA expression. Furthermore, we examined the influence of common variants rs6311 and rs6313 on cocaine abuse, methylation, and gene expression. We found evidence that rs6311 regulates HTR2A methylation, consistent with earlier studies. Furthermore, the minor alleles for rs6311 and rs6313 are associated with significantly increased expression of a splice isoform in which exon 2 is truncated in both cocaine and control samples. These results reveal specific roles for HTR2A in the context of cocaine abuse, highlighting opportunities to modulate this target for treating cocaine use disorder.
Parasitic helminth infections, while a major cause of neglected tropical disease burden, negatively correlate with the incidence of immune-mediated inflammatory diseases such as inflammatory bowel ...diseases (IBD). To evade expulsion, helminths have developed sophisticated mechanisms to regulate their host's immune responses. Controlled experimental human helminth infections have been assessed clinically for treating inflammatory conditions; however, such a radical therapeutic modality has challenges. An alternative approach is to harness the immunomodulatory properties within the worm's excretory-secretory (ES) complement, its secretome. Here, we report a biologics discovery and validation pipeline to generate and screen in vivo a recombinant cell-free secretome library of helminth-derived immunomodulatory proteins. We successfully expressed 78 recombinant ES proteins from gastrointestinal hookworms and screened the crude in vitro translation reactions for anti-IBD properties in a mouse model of acute colitis. After statistical filtering and ranking, 20 proteins conferred significant protection against various parameters of colitis. Lead candidates from distinct protein families, including annexins, transthyretins, nematode-specific retinol-binding proteins, and SCP/TAPS were identified. Representative proteins were produced in mammalian cells and further validated, including ex vivo suppression of inflammatory cytokine secretion by T cells from IBD patient colon biopsies. Proteins identified herein offer promise as novel, safe, and mechanistically differentiated biologics for treating the globally increasing burden of inflammatory diseases.
Selenium (Se) is a redox-active environmental mineral that is converted to only a small number of metabolites and required for a relatively small number of mammalian enzymes. Despite this, dietary ...and environmental Se has extensive impact on every layer of omics space. This highlights a need for global network response structures to provide reference for targeted, hypothesis-driven Se research. In this review, we survey the Se research literature from the perspective of the responsive physical and chemical barrier between an organism (functional genome) and its environment (exposome), which we have previously termed the redox interface. Recent advances in metabolomics allow molecular phenotyping of the integrated genome-metabolome-exposome structure. Use of metabolomics with transcriptomics to map functional network responses to supplemental Se in mice revealed complex network responses linked to dyslipidemia and weight gain. Central metabolic hubs in the network structure in liver were not directly linked to transcripts for selenoproteins but were, instead, linked to transcripts for glucose transport and fatty acid β-oxidation. The experimental results confirm the survey of research literature in showing that Se interacts with the functional genome through a complex network response structure. The results imply that systematic application of data-driven integrated omics methods to models with controlled Se exposure could disentangle health benefits and risks from Se exposures and also serve more broadly as an experimental paradigm for exposome research.
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•Selenium (Se) is required for a small number of enzymes but dietary and environmental Se impacts every layer of omics space.•Metabolome and transcriptome interactions in mice reveal complex network responses linked to dyslipidemia and weight gain.•Central metabolic hubs in the network structure were linked to transcripts for glucose transport and fatty acid β-oxidation.•Global network response structures are needed to provide focus for targeted, hypothesis-driven Se research.
We present a new data set of annual historical (1750–2014) anthropogenic chemically reactive gases (CO, CH4, NH3, NOx, SO2, NMVOCs), carbonaceous aerosols (black carbon – BC, and organic carbon – ...OC), and CO2 developed with the Community Emissions Data System (CEDS). We improve upon existing inventories with a more consistent and reproducible methodology applied to all emission species, updated emission factors, and recent estimates through 2014. The data system relies on existing energy consumption data sets and regional and country-specific inventories to produce trends over recent decades. All emission species are consistently estimated using the same activity data over all time periods. Emissions are provided on an annual basis at the level of country and sector and gridded with monthly seasonality. These estimates are comparable to, but generally slightly higher than, existing global inventories. Emissions over the most recent years are more uncertain, particularly in low- and middle-income regions where country-specific emission inventories are less available. Future work will involve refining and updating these emission estimates, estimating emissions' uncertainty, and publication of the system as open-source software.
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