A Genome-Wide Association Study of Diabetic Kidney Disease in Subjects With Type 2 Diabetes

dentification of sequence variants robustly associated with predisposition to diabetic kidney disease (DKD) has the potential to provide insights into the pathophysiological mechanisms responsible. We conducted a genome-wide association study (GWAS) of DKD in type 2 diabetes (T2D) using eight complementary dichotomous and quantitative DKD phenotypes: the principal dichotomous analysis involved 5,717 T2D subjects, 3,345 with DKD. Promising association signals were evaluated in up to 26,827 subjects with T2D (12,710 with DKD). A combined T1D+T2D GWAS was performed using complementary data available for subjects with T1D, which, with replication samples, involved up to 40,340 subjects with diabetes (18,582 with DKD). Analysis of specific DKD phenotypes identified a novel signal near GABRR1 (rs9942471, P = 4.5 x 10(-8)) associated with microalbuminuria in European T2D case subjects. However, no replication of this signal was observed in Asian subjects with T2D or in the equivalent T1D analysis. There was only limited support, in this substantially enlarged analysis, for association at previously reported DKD signals, except for those at UMOD and PRKAG2, both associated with estimated glomerular filtration rate. We conclude that, despite challenges in addressing phenotypic heterogeneity, access to increased sample sizes will continue to provide more robust inference regarding risk variant discovery for DKD.Peer reviewe

Validation of the Chinese version of underwood's daily spiritual experience scale-transcending cultural boundaries?

Background: Daily spiritual experience (DSE) refers to one's interaction with the transcendent in day-to-day life. Underwood's Daily Spiritual Experience Scale mic(DSES) was developed to measure this experiential component of religiousness and spirituality. Addressing ordinary daily experiences rather than particular beliefs, DSES has transcultural applicability potential. Purpose: The current study aimed to develop and evaluate the Chinese version of DSES (DSES-C). Method: The 16-item scale was translated faithfully through standard translation/back-translation procedures. The term "God" required an extended definition embracing both a humanized and a philosophical higher power in Chinese culture. The translated scale plus a battery of validation scales were administered to staff of a large rehabilitation service complex, resulting in 245 completed questionnaires. Results: Exploratory factor analysis revealed a similar factor structure as the original English version and similar problems with items 13 (compassion) and 14 (mercy). After carefully deliberating on the Chinese conceptualization of spirituality and balancing psychometric properties, the one-factor 16-item structure of the English version was supported. DSES-C showed high internal consistency (Cronbach's alpha=0.97). Construct validity was supported by correlations with validation scales in expected directions. Conclusion: The psychometric properties of DSES were similar to the English version in factor structure, internal consistency, and convergence/divergence construct validity. © 2009 International Society of Behavioral Medicine.link_to_subscribed_fulltex

Assignment of the human 14-3-3 epsilon isoform (YWHAE) to human chromosome 17p13 by in situ hybridization

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Mapping of the human cysteine-rich intestinal protein gene CRIP1 to the human chromosomal segment 7q11.23

We report here on the mapping of a cDNA encoding for human cysteine- rich heart protein (HCRHP), a counterpart of the murine cysteine-rich intestinal protein CRIP. By somatic cell hybrid analysis and radiation hybrid mapping, we have located the gene CRIP1 (HGMW-approved symbol) on the subcentromeric region of the q arm of human chromosome 7, flanking a deletion associated with Williams syndrome.link_to_subscribed_fulltex

Mapping of the human ribosomal large subunit protein gene RPL29 to human chromosome 3q29-qter

The human ribosomal protein L29, which we reported previously, was subsequently shown to have the same nucleotide sequence as that of cell surface heparin/heparan sulfate-binding protein, designated HP/HS interacting protein. A polymerase chain reaction-based strategy was used to distinguish the functional intron-containing gene RPL29 (HGMW-approved symbol) from multiple pseudogenes. By somatic cell hybrid analysis, radiation hybrid mapping, and fluorescence in situ hybridization, we have located RPL29 on the telomeric region of the q arm of chromosome 3. RPL29 is the most distal marker of the long arm of chromosome 3. Of the human ribosomal protein genes mapped, RPL29 is the shortest distance from another ribosomal protein gene marker, RPL35a which has also been mapped to the 3q29-qter region.link_to_subscribed_fulltex

LIM domain protein FHL1B interacts with PP2A catalytic β subunit - A novel cell cycle regulatory pathway

Four-and-a-half LIM domain protein 1B (FHL1B) is an alternatively-spliced isoform of FHL1. In this study, FHL1B was demonstrated to interact with the β catalytic subunit (Cβ) of a type 2A protein phosphatase (PP2A) by yeast two-hybrid screening. Domain studies using a small-scale yeast two-hybrid interaction assay revealed the mediation of protein-protein interaction by FHL1B's C-terminus. Interaction between FHL1B and PP2A was further verified by co-immunoprecipitation. FHL1B was also shown to shuttle between nucleus and cytoplasm at different phases of the cell cycle. These data suggest that the FHL1B/PP2A Cβ interaction may illustrate a novel cell-cycle regulatory pathway. Structured summary: MINT- 8044739: FHL1B (uniprotkb: Q13642-2) physically interacts (MI: 0915) with PP2Acbeta (uniprotkb: P62714) by two hybrid (MI: 0018). MINT- 8044769, MINT- 8044778: FHL1B (uniprotkb: Q13642-2) physically interacts (MI: 0915) with PP2Acbeta (uniprotkb: P62714) by anti bait coimmunoprecipitation (MI: 0006). © 2010 Federation of European Biochemical Societies.link_to_subscribed_fulltex

cDNA microarray analysis of early gene expression profiles associated with hepatitis B virus X protein-mediated hepatocarcinogenesis

Chronic hepatitis B virus (HBV) infection is one of the major causes of hepatocellular carcinoma. HBV encodes an oncogenic hepatitis B virus X protein (HBx), which can transactivate host cell transcriptional machinery and mediate cellular transformation. To disclose the early genetic response in HBx-mediated transformation process, we constructed a conditional HBx-expressing hepatocyte cell line, which allows us to compare the gene expression profiles under controllable HBx induction. A cDNA microarray containing more than 8700 mouse genes and ESTs was utilized to examine the gene expression profiles. We identified 260 candidate genes and 259 ESTs which have shown aberrant expression under HBx induction. Most of them are involved in signal transduction pathway, cell cycle control, metastasis, transcriptional regulation, immune response, and metabolism. These results provide additional insight into early cellular targets of HBx, which could give us a better understanding of the function of HBx and their progressive changes during HBx-mediated hepatocarcinogenesis. © 2004 Elsevier Inc. All rights reserved.link_to_subscribed_fulltex

Characterization of the human 36-kDa carboxyl terminal LIM domain protein (hCLIM1)

We characterized a human cDNA clone encoding a 36-kDa carboxyl terminal LIM domain protein with a PDZ domain at the amino terminal. This full-length cDNA clone has a predicted open reading frame (ORF) of 329 amino-acid residues. The ORF of this cDNA encodes the human homolog of rat CLP36, and the putative protein is named human 36-kDa carboxyl terminal LIM domain protein (hCLIM1, nomenclature approved by the HUGO/GDB Nomenclature Committee). The hCLIM1 probe was used to hybridize with poly(A)+ RNA of various human tissues. Strong signals were detected in heart and skeletal muscle; moderate signals were detected in spleen, small intestine, colon, placenta, and lung; weaker levels were detected in liver, thymus, kidney, prostate, and pancreas; and no observable signals were detected in brain, testis, ovary, and peripheral blood leukocytes. The hCLIM1 gene was studied by fluorescence in situ hybridization (FISH), somatic cell hybrid analysis, and radiation hybrid mapping, and it is located at the human chromosome 10q26.link_to_subscribed_fulltex

Single-cell transcriptomics reveals the landscape of intra-tumoral heterogeneity and stemness-related subpopulations in liver cancer

202308 bckwAccepted ManuscriptRGCOthersInnovation and Technology Commission grant for State Key Laboratory of Liver Research; University Development Fund of The University of Hong KongPublishe

Inferring protein-protein interactions based on sequences and interologs in Mycobacterium tuberculosis

Mycobacterium tuberculosis is a pathogenic bacterium that poses serious threat to human health. Inference of the protein interactions of M. tuberculosis will provide cues to understand the biological processes in this pathogen. In this paper, we constructed an integrated M. tuberculosis H37Rv protein interaction network by machine learning and ortholog-based methods. Firstly, we developed a support vector machine (SVM) method to infer the protein interactions by gene sequence information. We tested our predictors in Escherichia coli and mapped the genetic codon features underlying protein interactions to M. tuberculosis. Moreover, the documented interactions of other 14 species were mapped to the proteome of M. tuberculosis by the interolog method. The ensemble protein interactions were then validated by various functional linkages i.e., gene coexpression, evolutionary relationship and functional similarity, extracted from heterogeneous data sources. © 2012 Springer-Verlag.Link_to_subscribed_fulltex