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931.
David Bann Don Hire Todd Manini Rachel Cooper Anda Botoseneanu Mary M. McDermott Marco Pahor Nancy W. Glynn Roger Fielding Abby C. King Timothy Church Walter T. Ambrosius Thomas Gill for the LIFE Study Group 《PloS one》2015,10(2)
BackgroundIdentifying modifiable determinants of fat mass and muscle strength in older adults is important given their impact on physical functioning and health. Light intensity physical activity and sedentary behavior are potential determinants, but their relations to these outcomes are poorly understood. We evaluated associations of light intensity physical activity and sedentary time—assessed both objectively and by self-report—with body mass index (BMI) and grip strength in a large sample of older adults.MethodsWe used cross-sectional baseline data from 1130 participants of the Lifestyle Interventions and Independence for Elders (LIFE) study, a community-dwelling sample of relatively sedentary older adults (70-89 years) at heightened risk of mobility disability. Time spent sedentary and in light intensity activity were assessed using an accelerometer worn for 3–7 days (Actigraph GT3X) and by self-report. Associations between these exposures and measured BMI and grip strength were evaluated using linear regression.ResultsGreater time spent in light intensity activity and lower sedentary times were both associated with lower BMI. This was evident using objective measures of lower-light intensity, and both objective and self-reported measures of higher-light intensity activity. Time spent watching television was positively associated with BMI, while reading and computer use were not. Greater time spent in higher but not lower intensities of light activity (assessed objectively) was associated with greater grip strength in men but not women, while neither objectively assessed nor self-reported sedentary time was associated with grip strength.ConclusionsIn this cross-sectional study, greater time spent in light intensity activity and lower sedentary times were associated with lower BMI. These results are consistent with the hypothesis that replacing sedentary activities with light intensity activities could lead to lower BMI levels and obesity prevalence among the population of older adults. However, longitudinal and experimental studies are needed to strengthen causal inferences. 相似文献
932.
933.
The development of diabetic cardiomyopathy is a key contributor to heart failure and mortality in obesity and type 2 diabetes (T2D). Current therapeutic interventions for T2D have limited impact on the development of diabetic cardiomyopathy. Clearly, new therapies are urgently needed. A potential therapeutic target is protein kinase D (PKD), which is activated by metabolic insults and implicated in the regulation of cardiac metabolism, contractility and hypertrophy. We therefore hypothesised that PKD inhibition would enhance cardiac function in T2D mice. We first validated the obese and T2D db/db mouse as a model of early stage diabetic cardiomyopathy, which was characterised by both diastolic and systolic dysfunction, without overt alterations in left ventricular morphology. These functional characteristics were also associated with increased PKD2 phosphorylation in the fed state and a gene expression signature characteristic of PKD activation. Acute administration of the PKD inhibitor CID755673 to normal mice reduced both PKD1 and 2 phosphorylation in a time and dose-dependent manner. Chronic CID755673 administration to T2D db/db mice for two weeks reduced expression of the gene expression signature of PKD activation, enhanced indices of both diastolic and systolic left ventricular function and was associated with reduced heart weight. These alterations in cardiac function were independent of changes in glucose homeostasis, insulin action and body composition. These findings suggest that PKD inhibition could be an effective strategy to enhance heart function in obese and diabetic patients and provide an impetus for further mechanistic investigations into the role of PKD in diabetic cardiomyopathy. 相似文献
934.
Monica Siddalls Timothy A Currier Jassia Pang Kvin Lertpiriyapong Mary M Patterson 《Comparative medicine》2015,65(1):51-53
A zebra finch (Taeniopygia guttata) housed in a neuroscience laboratory was observed to have numerous feather mites. Subsequently, similar mites were found on other birds in the animal facility and research space. The most abundant mite was a novel, undescribed species in the genus Neocheyletiella. Whereas known Neocheyletiella mites have previously been characterized as skin parasites of various birds worldwide, the species on the zebra finches is unique because it lives and builds nests in the feathers. Infrequent specimens of a ‘true’ feather mite, a new species of Megninialges, were present also. Although multiple treatments using a pyrethrin spray were effective in eradicating the mites, topical ivermectin later was found to be more efficacious, better tolerated by the birds, and less labor intensive. This case highlights the general dearth of information regarding ectoparasites in zebra finches, even though these are the most frequently used songbirds in biomedical research. The mite epizootic also underscores the diverse pathogens possible in zebra finches that arrive from outside sources and why ongoing health monitoring of finch colonies is warranted.Zebra finches (Taeniopygia guttata) are increasingly popular as animal models in biomedical research, especially in the fields of neurobiology and behavior.2,7 Many investigators using these birds maintain inhouse, closed breeding colonies. When birds need to be imported, they are provided by colleagues or are obtained from a limited number of pet-bird dealers that often buy zebra finches from ‘backyard’ breeders. A primary concern about any outside supplier, as has been noted by other authors,1 is that little (if any) health monitoring of the birds might be done prior to shipment. Birds can arrive at research institutions infected with various parasites and potentially pathogenic bacteria, among other agents. Depending on many factors, such as parasite burden, infections can cause immediate morbidity and mortality or can be clinically silent. This report describes an epizootic of feather mites that presumably went undetected for some time. The 2 mite species observed in the finches had not previously been described by entomologists, and the most prevalent mite was sufficiently novel to justify the assignment of a scientific name. The infestation reinforces why vigilant diagnostic testing, and perhaps prophylactic treatment, of newly arrived zebra finches should occur before their release into the regular colony and why continued health surveillance of an established group of zebra finches is invaluable. 相似文献
935.
Davod Alizadehrad Timothy Krüger Markus Engstler Holger Stark 《PLoS computational biology》2015,11(1)
The flagellate Trypanosoma brucei, which causes the sleeping sickness when infecting a mammalian host, goes through an intricate life cycle. It has a rather complex propulsion mechanism and swims in diverse microenvironments. These continuously exert selective pressure, to which the trypanosome adjusts with its architecture and behavior. As a result, the trypanosome assumes a diversity of complex morphotypes during its life cycle. However, although cell biology has detailed form and function of most of them, experimental data on the dynamic behavior and development of most morphotypes is lacking. Here we show that simulation science can predict intermediate cell designs by conducting specific and controlled modifications of an accurate, nature-inspired cell model, which we developed using information from live cell analyses. The cell models account for several important characteristics of the real trypanosomal morphotypes, such as the geometry and elastic properties of the cell body, and their swimming mechanism using an eukaryotic flagellum. We introduce an elastic network model for the cell body, including bending rigidity and simulate swimming in a fluid environment, using the mesoscale simulation technique called multi-particle collision dynamics. The in silico trypanosome of the bloodstream form displays the characteristic in vivo rotational and translational motility pattern that is crucial for survival and virulence in the vertebrate host. Moreover, our model accurately simulates the trypanosome''s tumbling and backward motion. We show that the distinctive course of the attached flagellum around the cell body is one important aspect to produce the observed swimming behavior in a viscous fluid, and also required to reach the maximal swimming velocity. Changing details of the flagellar attachment generates less efficient swimmers. We also simulate different morphotypes that occur during the parasite''s development in the tsetse fly, and predict a flagellar course we have not been able to measure in experiments so far. 相似文献
936.
Why are mitochondria almost always inherited from one parent during sexual reproduction? Current explanations for this evolutionary mystery include conflict avoidance between the nuclear and mitochondrial genomes, clearing of deleterious mutations, and optimization of mitochondrial-nuclear coadaptation. Mathematical models, however, fail to show that uniparental inheritance can replace biparental inheritance under any existing hypothesis. Recent empirical evidence indicates that mixing two different but normal mitochondrial haplotypes within a cell (heteroplasmy) can cause cell and organism dysfunction. Using a mathematical model, we test if selection against heteroplasmy can lead to the evolution of uniparental inheritance. When we assume selection against heteroplasmy and mutations are neither advantageous nor deleterious (neutral mutations), uniparental inheritance replaces biparental inheritance for all tested parameter values. When heteroplasmy involves mutations that are advantageous or deleterious (non-neutral mutations), uniparental inheritance can still replace biparental inheritance. We show that uniparental inheritance can evolve with or without pre-existing mating types. Finally, we show that selection against heteroplasmy can explain why some organisms deviate from strict uniparental inheritance. Thus, we suggest that selection against heteroplasmy explains the evolution of uniparental inheritance. 相似文献
937.
Nitya Ramkumar Beth M. Harvey Jeffrey D. Lee Heather L. Alcorn Nancy F. Silva-Gagliardi C. Jane McGlade Timothy H. Bestor Jan Wijnholds Robert S. Haltiwanger Kathryn V. Anderson 《PLoS genetics》2015,11(10)
Crumbs family proteins are apical transmembrane proteins with ancient roles in cell polarity. Mouse Crumbs2 mutants arrest at midgestation with abnormal neural plate morphology and a deficit of mesoderm caused by defects in gastrulation. We identified an ENU-induced mutation, wsnp, that phenocopies the Crumbs2 null phenotype. We show that wsnp is a null allele of Protein O-glucosyltransferase 1 (Poglut1), which encodes an enzyme previously shown to add O-glucose to EGF repeats in the extracellular domain of Drosophila and mammalian Notch, but the role of POGLUT1 in mammalian gastrulation has not been investigated. As predicted, we find that POGLUT1 is essential for Notch signaling in the early mouse embryo. However, the loss of mouse POGLUT1 causes an earlier and more dramatic phenotype than does the loss of activity of the Notch pathway, indicating that POGLUT1 has additional biologically relevant substrates. Using mass spectrometry, we show that POGLUT1 modifies EGF repeats in the extracellular domain of full-length mouse CRUMBS2. CRUMBS2 that lacks the O-glucose modification fails to be enriched on the apical plasma membrane and instead accumulates in the endoplasmic reticulum. The data demonstrate that CRUMBS2 is the target of POGLUT1 for the gastrulation epithelial-to-mesenchymal transitions (EMT) and that all activity of CRUMBS2 depends on modification by POGLUT1. Mutations in human POGLUT1 cause Dowling-Degos Disease, POGLUT1 is overexpressed in a variety of tumor cells, and mutations in the EGF repeats of human CRUMBS proteins are associated with human congenital nephrosis, retinitis pigmentosa and retinal degeneration, suggesting that O-glucosylation of CRUMBS proteins has broad roles in human health. 相似文献
938.
939.
Lucia B. Carreon-Martinez Ryan P. Walter Timothy B. Johnson Stuart A. Ludsin Daniel D. Heath 《PloS one》2015,10(5)
Nutrient-rich, turbid river plumes that are common to large lakes and coastal marine ecosystems have been hypothesized to benefit survival of fish during early life stages by increasing food availability and (or) reducing vulnerability to visual predators. However, evidence that river plumes truly benefit the recruitment process remains meager for both freshwater and marine fishes. Here, we use genotype assignment between juvenile and larval yellow perch (Perca flavescens) from western Lake Erie to estimate and compare recruitment to the age-0 juvenile stage for larvae residing inside the highly turbid, south-shore Maumee River plume versus those occupying the less turbid, more northerly Detroit River plume. Bayesian genotype assignment of a mixed assemblage of juvenile (age-0) yellow perch to putative larval source populations established that recruitment of larvae was higher from the turbid Maumee River plume than for the less turbid Detroit River plume during 2006 and 2007, but not in 2008. Our findings add to the growing evidence that turbid river plumes can indeed enhance survival of fish larvae to recruited life stages, and also demonstrate how novel population genetic analyses of early life stages can contribute to determining critical early life stage processes in the fish recruitment process. 相似文献
940.
Marc Y. R. Henrion Mark P. Purdue Ghislaine Scelo Peter Broderick Matthew Frampton Alastair Ritchie Angela Meade Peng Li James McKay Mattias Johansson Mark Lathrop James Larkin Nathaniel Rothman Zhaoming Wang Wong-Ho Chow Victoria L. Stevens W. Ryan Diver Demetrius Albanes Jarmo Virtamo Paul Brennan Timothy Eisen Stephen Chanock Richard S. Houlston 《PloS one》2015,10(3)
So far six susceptibility loci for renal cell carcinoma (RCC) have been discovered by genome-wide association studies (GWAS). To identify additional RCC common risk loci, we performed a meta-analysis of published GWAS (totalling 2,215 cases and 8,566 controls of Western-European background) with imputation using 1000 Genomes Project and UK10K Project data as reference panels and followed up the most significant association signals [22 single nucleotide polymorphisms (SNPs) and 3 indels in eight genomic regions] in 383 cases and 2,189 controls from The Cancer Genome Atlas (TCGA). A combined analysis identified a promising susceptibility locus mapping to 1q24.1 marked by the imputed SNP rs3845536 (P
combined =2.30x10-8). Specifically, the signal maps to intron 4 of the ALDH9A1 gene (aldehyde dehydrogenase 9 family, member A1). We further evaluated this potential signal in 2,461 cases and 5,081 controls from the International Agency for Research on Cancer (IARC) GWAS of RCC cases and controls from multiple European regions. In contrast to earlier findings no association was shown in the IARC series (P=0.94; P
combined =2.73x10-5). While variation at 1q24.1 represents a potential risk locus for RCC, future replication analyses are required to substantiate our observation. 相似文献