This review examines the effect of a dual task on the gait parameters of older adults with a mean gait speed of 1.0 m/s or greater, and the effect of type and complexity of task. A systematic review ...of Web of Science, PubMed, SCOPUS, Embase, and PsycINFO was performed in July 2016. Twenty-three studies (28 data sets) were reviewed and pooled for meta-analysis. The effect size on seven gait parameters was measured as the raw mean difference between single- and dual-task performance. Gait speed significantly reduced with the addition of a dual task, with increasing complexity showing greater decrements. Cadence, stride time, and measures of gait variability were all negatively affected under the dual-task condition. In older adults, the addition of a dual task significantly reduces gait speed and cadence, with possible implications for the assessment of older people, as the addition of a dual task may expose deficits not observed under single-task assessment.
A key goal of biology is to construct networks that predict complex system behavior. We combine multiple types of molecular data, including genotypic, expression, transcription factor binding site ...(TFBS), and protein-protein interaction (PPI) data previously generated from a number of yeast experiments, in order to reconstruct causal gene networks. Networks based on different types of data are compared using metrics devised to assess the predictive power of a network. We show that a network reconstructed by integrating genotypic, TFBS and PPI data is the most predictive. This network is used to predict causal regulators responsible for hot spots of gene expression activity in a segregating yeast population. We also show that the network can elucidate the mechanisms by which causal regulators give rise to larger-scale changes in gene expression activity. We then prospectively validate predictions, providing direct experimental evidence that predictive networks can be constructed by integrating multiple, appropriate data types.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Remodeling of host cellular membrane transport pathways is a common pathogenic trait of many intracellular microbes that is essential to their intravacuolar life cycle and proliferation. The ...bacterium Brucella abortus generates a host endoplasmic reticulum‐derived vacuole (rBCV) that supports its intracellular growth, via VirB Type IV secretion system‐mediated delivery of effector proteins, whose functions and mode of action are mostly unknown. Here, we show that the effector BspF specifically promotes Brucella replication within rBCVs by interfering with vesicular transport between the trans‐Golgi network (TGN) and recycling endocytic compartment. BspF targeted the recycling endosome, inhibited retrograde traffic to the TGN, and interacted with the Arf6 GTPase‐activating Protein (GAP) ACAP1 to dysregulate Arf6‐/Rab8a‐dependent transport within the recycling endosome, which resulted in accretion of TGN‐associated vesicles by rBCVs and enhanced bacterial growth. Altogether, these findings provide mechanistic insight into bacterial modulation of membrane transport used to promote their own proliferation within intracellular vacuoles.
SYNOPSIS
Host membrane transport remodeling via secreted effector proteins promotes proliferation of Brucella abortus bacteria within host cell vacuoles. Here, the effector BspF delivered by the Type IV secretion system is found to facilitate secretory vesicle rerouting by modulating Arf6/Rab8a GTPase signaling.
BspF interferes with host cell retrograde membrane transport through the tubular recycling endosome.
BspF binding to GTPase‐activating protein ACAP1 decreases Arf6/Rab8a‐dependent retrograde transport to the trans‐Golgi network (TGN).
BspF modulation of retrograde transport facilitates Syntaxin‐6‐dependent recruitment of TGN‐associated vesicles to Brucella‐containing vacuoles, and facilitates bacterial growth.
Brucella abortus effector protein BspF binding to host GTPase‐activating protein ACAP1 facilitates intracellular bacterial growth by decreasing retrograde vesicular transport to the trans‐Golgi network.
Within the framework of theological anthropology, a robust answer to the question "what is a human being?" necessarily requires more than a detailed explication of physical, biological parts. (1) ...Yet, theological treatments should engage empirical evidence about these constituent parts to anchor models of persons around what is empirically observable. (2) To facilitate the necessary interdisciplinary dialogue for such a robust treatment of persons, this article provides a brief overview of select neuroscience literature on self. Specifically, I provide an initial introduction to measuring neural activity and the brain's default mode network (DMN), a region of the brain associated with internal, self-related thoughts dissociated from external input. Some researchers have suggested that the DMN is what makes the "self" special; rather than the self being a higher-order composite construct, it may be foundational to the brain's operations. (3 )Although the role of the DMN in understanding self has not reached scientific consensus, a consideration of the DMN and the results of its dysfunction may stimulate interdisciplinary dialogue in at least two ways related to questions of selves. First, given the ongoing discussion about the proper interpretation of DMN data, this area may benefit from non-empirical, interdisciplinary contributions toward understanding selves. Second, the centrality of the DMN to selves suggests a healthy DMN is necessary (though not sufficient) for a healthy self. Practices for healthy DMN functioning can contribute to and be enriched by philosophical and theological perspectives about telos and Christian practice.
Structural variants (SVs) and short tandem repeats (STRs) comprise a broad group of diverse DNA variants which vastly differ in their sizes and distributions across the genome. Here, we identify ...genomic features of SV classes and STRs that are associated with gene expression and complex traits, including their locations relative to eGenes, likelihood of being associated with multiple eGenes, associated eGene types (e.g., coding, noncoding, level of evolutionary constraint), effect sizes, linkage disequilibrium with tagging single nucleotide variants used in GWAS, and likelihood of being associated with GWAS traits. We identify a set of high-impact SVs/STRs associated with the expression of three or more eGenes via chromatin loops and show that they are highly enriched for being associated with GWAS traits. Our study provides insights into the genomic properties of structural variant classes and short tandem repeats that are associated with gene expression and human traits.
Objective
Cerebrovascular deposition of β‐amyloid (cerebral amyloid angiopathy CAA) is a major cause of hemorrhagic stroke and a likely contributor to vascular cognitive impairment. We evaluated ...positron emission tomographic imaging with the β‐amyloid–binding compound Pittsburgh Compound B (PiB) as a potential noninvasive method for detection of CAA. We hypothesized that amyloid deposition would be observed with PiB in CAA, and based on the occipital predilection of CAA pathology and associated hemorrhages, that specific PiB retention would be disproportionately greater in occipital lobes.
Methods
We compared specific cortical PiB retention in 6 nondemented subjects diagnosed with probable CAA with 15 healthy control subjects and 9 patients with probable Alzheimer's disease (AD).
Results
All CAA and AD subjects were PiB‐positive, both by distribution volume ratio measurements and by visual inspection of positron emission tomographic images. Global cortical PiB retention was significantly increased in CAA (distribution volume ratio 1.18 ± 0.06) relative to healthy control subjects (1.04 ± 0.10; p = 0.0009), but was lower in CAA than in AD subjects (1.41 ± 0.17; p = 0.002). The occipital‐to‐global PiB ratio, however, was significantly greater in CAA than in AD subjects (0.99 ± 0.07 vs 0.86 ± 0.05; p = 0.003).
Interpretation
We conclude that PiB‐positron emission tomography can detect cerebrovascular β‐amyloid and may serve as a method for identifying the extent of CAA in living subjects. Ann Neurol 2007
Abstract
Objective
The COVID-19 pandemic dramatically altered social determinants of health including work, education, social connections, movement, and perceived control; and loneliness was commonly ...experienced. This longitudinal study examined how social determinants at the personal (micro), community (meso), and societal (macro) levels predicted loneliness during the pandemic.
Methods
Participants were 2056 Australian adults surveyed up to three times over 18 months in 2020 and 2021. Multi-level mixed-effect regressions were conducted predicting loneliness from social determinants at baseline and two follow-ups.
Results
Loneliness was associated with numerous micro determinants: male gender, lifetime diagnosis of a mental health disorder, experience of recent stressful event(s), low income, living alone or couples with children, living in housing with low natural light, noise, and major building defects. Lower resilience and perceived control over health and life were also associated with greater loneliness. At the meso level, reduced engagement with social groups, living in inner regional areas, and living in neighbourhoods with low levels of belongingness and collective resilience was associated with increased loneliness. At the macro level, increased loneliness was associated with State/Territory of residence.
Conclusions
Therapeutic initiatives must go beyond psychological intervention, and must recognise the social determinants of loneliness at the meso and macro levels.
Genotypes generated in next generation sequencing studies contain errors which can significantly impact the power to detect signals in common and rare variant association tests. These genotyping ...errors are not explicitly filtered by the standard GATK Variant Quality Score Recalibration (VQSR) tool and thus remain a source of errors in whole exome sequencing (WES) projects that follow GATK's recommended best practices. Therefore, additional data filtering methods are required to effectively remove these errors before performing association analyses with complex phenotypes. Here we empirically derive thresholds for genotype and variant filters that, when used in conjunction with the VQSR tool, achieve higher data quality than when using VQSR alone.
The detailed filtering strategies improve the concordance of sequenced genotypes with array genotypes from 99.33% to 99.77%; improve the percent of discordant genotypes removed from 10.5% to 69.5%; and improve the Ti/Tv ratio from 2.63 to 2.75. We also demonstrate that managing batch effects by separating samples based on different target capture and sequencing chemistry protocols results in a final data set containing 40.9% more high-quality variants. In addition, imputation is an important component of WES studies and is used to estimate common variant genotypes to generate additional markers for association analyses. As such, we demonstrate filtering methods for imputed data that improve genotype concordance from 79.3% to 99.8% while removing 99.5% of discordant genotypes.
The described filtering methods are advantageous for large population-based WES studies designed to identify common and rare variation associated with complex diseases. Compared to data processed through standard practices, these strategies result in substantially higher quality data for common and rare association analyses.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Television has become a nearly ubiquitous feature in children's cultural landscape. A review of the research into young children's learning from television indicates that the likelihood that children ...will learn from screen media is influenced by their developing social relationships with on-screen characters, as much as by their developing perception of the screen and their symbolic understanding and comprehension of information presented on screen. Considering the circumstances in which children under 6 years learn from screen media can inform teachers, parents, and researchers about the important nature of social interaction in early learning and development. The findings reviewed in this article suggest the social nature of learning, even learning from screen media.
The Pharma Proteomics Project is a precompetitive biopharmaceutical consortium characterizing the plasma proteomic profiles of 54,219 UK Biobank participants. Here we provide a detailed summary of ...this initiative, including technical and biological validations, insights into proteomic disease signatures, and prediction modelling for various demographic and health indicators. We present comprehensive protein quantitative trait locus (pQTL) mapping of 2,923 proteins that identifies 14,287 primary genetic associations, of which 81% are previously undescribed, alongside ancestry-specific pQTL mapping in non-European individuals. The study provides an updated characterization of the genetic architecture of the plasma proteome, contextualized with projected pQTL discovery rates as sample sizes and proteomic assay coverages increase over time. We offer extensive insights into trans pQTLs across multiple biological domains, highlight genetic influences on ligand-receptor interactions and pathway perturbations across a diverse collection of cytokines and complement networks, and illustrate long-range epistatic effects of ABO blood group and FUT2 secretor status on proteins with gastrointestinal tissue-enriched expression. We demonstrate the utility of these data for drug discovery by extending the genetic proxied effects of protein targets, such as PCSK9, on additional endpoints, and disentangle specific genes and proteins perturbed at loci associated with COVID-19 susceptibility. This public-private partnership provides the scientific community with an open-access proteomics resource of considerable breadth and depth to help to elucidate the biological mechanisms underlying proteo-genomic discoveries and accelerate the development of biomarkers, predictive models and therapeutics
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