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To clarify the mechanisms of Nosema ceranae parasitism, we deep-sequenced both honey bee host and parasite mRNAs throughout a complete 6-day infection cycle. By time-series analysis, 1122 parasite genes were significantly differently expressed during the reproduction cycle, clustering into 4 expression patterns. We found reactive mitochondrial oxygen species modulator 1 of the host to be significantly down regulated during the entire infection period. Our data support the hypothesis that apoptosis of honey bee cells was suppressed during infection. We further analyzed genome-wide genetic diversity of this parasite by comparing samples collected from the same site in 2007 and 2013. The number of SNP positions per gene and the proportion of non-synonymous substitutions per gene were significantly reduced over this time period, suggesting purifying selection on the parasite genome and supporting the hypothesis that a subset of N. ceranae strains might be dominating infection. 相似文献
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Shreaya Chakroborty Clark Briggs Megan B. Miller Ivan Goussakov Corinne Schneider Joyce Kim Jaime Wicks Jill C. Richardson Vincent Conklin Benjamin G. Cameransi Grace E. Stutzmann 《PloS one》2012,7(12)
Alzheimer’s disease (AD) is a devastating neurodegenerative condition with no known cure. While current therapies target late-stage amyloid formation and cholinergic tone, to date, these strategies have proven ineffective at preventing disease progression. The reasons for this may be varied, and could reflect late intervention, or, that earlier pathogenic mechanisms have been overlooked and permitted to accelerate the disease process. One such example would include synaptic pathology, the disease component strongly associated with cognitive impairment. Dysregulated Ca2+ homeostasis may be one of the critical factors driving synaptic dysfunction. One of the earliest pathophysiological indicators in mutant presenilin (PS) AD mice is increased intracellular Ca2+ signaling, predominantly through the ER-localized inositol triphosphate (IP3) and ryanodine receptors (RyR). In particular, the RyR-mediated Ca2+ upregulation within synaptic compartments is associated with altered synaptic homeostasis and network depression at early (presymptomatic) AD stages. Here, we offer an alternative approach to AD therapeutics by stabilizing early pathogenic mechanisms associated with synaptic abnormalities. We targeted the RyR as a means to prevent disease progression, and sub-chronically treated AD mouse models (4-weeks) with a novel formulation of the RyR inhibitor, dantrolene. Using 2-photon Ca2+ imaging and patch clamp recordings, we demonstrate that dantrolene treatment fully normalizes ER Ca2+ signaling within somatic and dendritic compartments in early and later-stage AD mice in hippocampal slices. Additionally, the elevated RyR2 levels in AD mice are restored to control levels with dantrolene treatment, as are synaptic transmission and synaptic plasticity. Aβ deposition within the cortex and hippocampus is also reduced in dantrolene-treated AD mice. In this study, we highlight the pivotal role of Ca2+ aberrations in AD, and propose a novel strategy to preserve synaptic function, and thereby cognitive function, in early AD patients. 相似文献
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Robert A. Montgomery Gary J. Roloff Jay M. Ver Hoef Joshua J. Millspaugh 《The Journal of wildlife management》2010,74(8):1917-1925
ABSTRACT Telemetry data have been widely used to quantify wildlife habitat relationships despite the fact that these data are inherently imprecise. All telemetry data have positional error, and failure to account for that error can lead to incorrect predictions of wildlife resource use. Several techniques have been used to account for positional error in wildlife studies. These techniques have been described in the literature, but their ability to accurately characterize wildlife resource use has never been tested. We evaluated the performance of techniques commonly used for incorporating telemetry error into studies of wildlife resource use. Our evaluation was based on imprecise telemetry data (mean telemetry error = 174 m, SD = 130 m) typical of field-based studies. We tested 5 techniques in 10 virtual environments and in one real-world environment for categorical (i.e., habitat types) and continuous (i.e., distances or elevations) rasters. Technique accuracy varied by patch size for the categorical rasters, with higher accuracy as patch size increased. At the smallest patch size (1 ha), the technique that ignores error performed best on categorical data (0.31 and 0.30 accuracy for virtual and real data, respectively); however, as patch size increased the bivariate-weighted technique performed better (0.56 accuracy at patch sizes >31 ha) and achieved complete accuracy (i.e., 1.00 accuracy) at smaller patch sizes (472 ha and 1,522 ha for virtual and real data, respectively) than any other technique. We quantified the accuracy of the continuous covariates using the mean absolute difference (MAD) in covariate value between true and estimated locations. We found that average MAD varied between 104 m (ignore telemetry error) and 140 m (rescale the covariate data) for our continuous covariate surfaces across virtual and real data sets. Techniques that rescale continuous covariate data or use a zonal mean on values within a telemetry error polygon were significantly less accurate than other techniques. Although the technique that ignored telemetry error performed best on categorical rasters with smaller average patch sizes (i.e., ≤31 ha) and on continuous rasters in our study, accuracy was so low that the utility of using point-based approaches for quantifying resource use is questionable when telemetry data are imprecise, particularly for small-patch habitat relationships. 相似文献
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Localization of the glucose phosphotransferase to a cytoplasmically accessible site on intracellular membranes 总被引:5,自引:0,他引:5
C Srisomsap K L Richardson J C Jay R B Marchase 《The Journal of biological chemistry》1988,263(33):17792-17797
UDP-glucose:glycoprotein glucose-1-phosphotransferase (Glc-phosphotransferase) catalyzes the transfer of alpha Glc-1-P from UDP-Glc to mannose residues on acceptor glycoproteins. The predominant acceptor for this transfer in rat liver is a glycoprotein of 62 kDa. This acceptor was labeled in liver homogenates through incubation with the 35S-labeled phosphorothioate analogue of UDP-Glc, and its distribution following differential centrifugation was compared to that of the glycoproteins labeled by CMP-[3H]N-acetylneuraminic acid. Whereas 94% of the 3H-labeled macromolecules fractionated to the microsomal pellet, 85% of the 35S-labeled 62-kDa glycoprotein was found in the high-speed supernatant. The distribution of the Glc-phosphotransferase was also examined following differential centrifugation, and the bulk of the activity was found in the 100,000 x g pellet. In contrast to results obtained with the lumenal microsomal markers 4 beta-galactosyltransferase and mannose-6-phosphatase, however, optimal activity of the Glc-phosphotransferase was not dependent on the disruption of microsomal vesicles by detergent. In addition, Glc-phosphotransferase was degraded by exogenous proteases in the absence of detergent, whereas the lumenal markers were not. We conclude, therefore, that the 62-kDa acceptor glycoprotein is cytoplasmic and is glycosylated by the Glc-phosphotransferase at a site accessible to the cytoplasm. This may prove to be a model for the topography of glycosylation of other cytoplasmic glycoproteins as well. 相似文献
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A systematic study of Lycopodium s.l. shows that only flavones occur in the four genera Huperzia, Lepidotis, Lycopodium s.s. and Diphasium. The arrangement of these taxa is discussed on the basis of the distribution of tricin, selgin, chrysoeriol, luteolin and apigenin. The evolutionary significance of these results and the uniqueness of Lycopodium phenolic metabolism are outlined. 相似文献