35 research outputs found

    Coronary-Heart-Disease-Associated Genetic Variant at the COL4A1/COL4A2 Locus Affects COL4A1/COL4A2 Expression, Vascular Cell Survival, Atherosclerotic Plaque Stability and Risk of Myocardial Infarction.

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    Genome-wide association studies have revealed an association between coronary heart disease (CHD) and genetic variation on chromosome 13q34, with the lead single nucleotide polymorphism rs4773144 residing in the COL4A2 gene in this genomic region. We investigated the functional effects of this genetic variant. Analyses of primary cultures of vascular smooth muscle cells (SMCs) and endothelial cells (ECs) from different individuals showed a difference between rs4773144 genotypes in COL4A2 and COL4A1 expression levels, being lowest in the G/G genotype, intermediate in A/G and highest in A/A. Chromatin immunoprecipitation followed by allelic imbalance assays of primary cultures of SMCs and ECs that were of the A/G genotype revealed that the G allele had lower transcriptional activity than the A allele. Electrophoretic mobility shift assays and luciferase reporter gene assays showed that a short DNA sequence encompassing the rs4773144 site interacted with a nuclear protein, with lower efficiency for the G allele, and that the G allele sequence had lower activity in driving reporter gene expression. Analyses of cultured SMCs from different individuals demonstrated that cells of the G/G genotype had higher apoptosis rates. Immunohistochemical and histological examinations of ex vivo atherosclerotic coronary arteries from different individuals disclosed that atherosclerotic plaques with the G/G genotype had lower collagen IV abundance and thinner fibrous cap, a hallmark of unstable, rupture-prone plaques. A study of a cohort of patients with angiographically documented coronary artery disease showed that patients of the G/G genotype had higher rates of myocardial infarction, a phenotype often caused by plaque rupture. These results indicate that the CHD-related genetic variant at the COL4A2 locus affects COL4A2/COL4A1 expression, SMC survival, and atherosclerotic plaque stability, providing a mechanistic explanation for the association between the genetic variant and CHD risk

    For-backward LSTM-based missing data reconstruction for time-series Landsat images

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    Reconstructing the missing data for cloud/shadow-covered optical satellite images has great significance for enhancing the data availability and multi-temporal analysis. In this study, we proposed a deep-learning-based method for cloud/shadow-covered missing data reconstruction for time-series Landsat images. Central to this method is the combined use of autoencoder, long-short-term memory (AE-LSTM)-based similar pixel clustering and for backward LSTM-based time-series prediction. First, manually delineated cloud/shadow-covered masks were overlaid onto multi-temporal satellite images to produce pixel-wise time-series data with masking values. Second, these pixel-wise time series were clustered by an AE-LSTM-based unsupervised method into multiple clusters, for searching similar pixels. Third, for each cluster of target images, a for-backward-LSTM-based model was established to restore missing values in time series data. Finally, reconstructed data were merged with cloud-free (image) regions to produce cloud-free time-series images. The proposed method was applied onto three datasets of multi-temporal Landsat-8 OLI images to restore cloud/shadow-covered images. The reconstruction results, showing an improvement of greater than 10% in normalized mean-square error compared to the state-of-the-art methods, demonstrated the effectiveness of the proposed method in time-series reconstruction for satellite images

    Prospective memory performance in patients with drug-naive, first-episode psychosis

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    Schizophrenia is associated with an impairment of prospective memory (PM) which refers to the ability to remember to carry out an intended action in the future. However, most of these studies were limited to chronic samples. The current study examined the event-based PM and time-based PM using a dual-task paradigm in 22 drug-naive, first-episode psychosis (FEP) patients and 23 healthy controls. Results indicated that FEP patients performed significantly poorer than healthy controls in both event-based and time-based PM. However, the significant difference in time-based PM disappeared after controlling for working memory. Correlation analysis indicated that both types of PM did not correlate with positive symptoms or negative symptoms, duration of illness, or duration of untreated psychosis. However, time-based PM was correlated with the general psychopathology subscale of the PANSS. Taken together, these findings suggest that PM deficits are present in drug-naive FEP patients; impairment of event-based PM appears to occur independently, whereas time-based PM impairment may be, in part, a secondary consequence of a working memory deficit. (C) 2012 Elsevier B. V. All rights reserved

    A Short Shaker Channel Mediates K+ Loading to Root Conducting Tissues and Contributes to Rice Grain Yield under Field Conditions

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    Abstract K + uptake to root conducting cells is a prerequisite for its release to the xylem vessels and long-distance delivery to the aerial parts, though the molecular mechanism underpinning such process remains insufficiently understood. Here we report the discovery in rice root of an essential component involved in loading of K + to the stelar tissues encoded by an unusual short Shaker K + channel OsK2.2. OsK2.2 represents a novel type of short Shaker channels lacking the sequences immediately downstream of the putative cyclic nucleotide binding domain that present to the C-termini of all plant Shaker channels reported to date. In silico analysis suggests that such short Shaker channels are monocot-specific and especially found in the Poaceae species. Functional assessment in Xenopus oocytes reveals that OsK2.2 uses such innate C-terminal shortness as an intrinsic strategy for maintaining large capacity of K + uptake to the cells. OsK2.2 predominantly localizes to the phloem and xylem peripheral cells of rice root vasculature. Disruption of OsK2.2 function causes approximately 30% lower K + in both phloem and xylem sap and reduces K + accumulation to the shoots. OsK2.2 strongly contributes to the grain yield of rice under field conditions. The essential contribution of such particular type of inward Shaker channel, operating in stelar tissues, to K + transport between roots and shoots and to grain yield, here evidenced in rice, may be a common trait amongst Poaceae species
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