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Articles by B Zhu
Total Records ( 4 ) for B Zhu
  L Griffith , P Raina , H Wu , B Zhu and L. Stathokostas

Objectives: to investigate the population impact on functional disability of chronic conditions individually and in combination.

Methods: data from 9,008 community-dwelling individuals aged 65 and older from the Canadian Study of Health and Aging (CSHA) were used to estimate the population attributable risk (PAR) for chronic conditions after adjusting for confounding variables. Functional disability was measured using activity of daily living (ADL) and instrumental activity of daily living (IADL).

Results: five chronic conditions (foot problems, arthritis, cognitive impairment, heart problems and vision) made the largest contribution to ADL- and IADL-related functional disabilities. There was variation in magnitude and ranking of population attributable risk (PAR) by age, sex and definition of disability. All chronic conditions taken simultaneously accounted for about 66% of the ADL-related disability and almost 50% of the IADL-related disability.

Conclusions: in community-dwelling older adults, foot problems, arthritis, cognitive impairment, heart problems and vision were the major determinants of disability. Attempts to reduce disability burden in older Canadians should target these chronic conditions; however, preventive interventions will be most efficient if they recognize the differences in the drivers of PAR by sex, age group and type of functional disability being targeted.

  M Spencer , A Yao Borengasser , R Unal , N Rasouli , C. M Gurley , B Zhu , C. A Peterson and P. A. Kern

Adipose tissue macrophages are associated with insulin resistance and are linked to changes in the extracellular matrix. To better characterize adipose macrophages, the extracellular matrix, and adipocyte-macrophage interactions, gene expression from adipose tissue and the stromal vascular fraction was assessed for markers of inflammation and fibrosis, and macrophages from obese and lean subjects were counted and characterized immunohistochemically. Coculture experiments examined the effects of adipocyte-macrophage interaction. Collagen VI gene expression was associated with insulin sensitivity and CD68 (r = –0.56 and 0.60, P < 0.0001) and with other markers of inflammation and fibrosis. Compared with adipose tissue from lean subjects, adipose tissue from obese subjects contained increased areas of fibrosis, which correlated inversely with insulin sensitivity (r = –0.58, P < 0.02) and positively with macrophage number (r = 0.70, P < 0.01). Although macrophages in crownlike structures (CLS) were more abundant in obese adipose tissue, the majority of macrophages were associated with fibrosis and were not organized in CLS. Macrophages in CLS were predominantly M1, but most other macrophages, particularly those in fibrotic areas, were M2 and also expressed CD150, a marker of M2c macrophages. Coculture of THP-1 macrophages with adipocytes promoted the M2 phenotype, with a lower level of IL-1 expression and a higher ratio of IL-10 to IL-12. Transforming growth factor-β (TGF-β) was more abundant in M2 macrophages and was further increased by coculture with adipocytes. Downstream effectors of TGF-β, such as plasminogen activator inhibitor-1, collagen VI, and phosphorylated Smad, were increased in macrophages and adipocytes. Thus adipose tissue of insulin-resistant humans demonstrated increased fibrosis, M2 macrophage abundance, and TGF-β activity.

  G. E Liu , Y Hou , B Zhu , M. F Cardone , L Jiang , A Cellamare , A Mitra , L. J Alexander , L. L Coutinho , M. E Dell'Aquila , L. C Gasbarre , G Lacalandra , R. W Li , L. K Matukumalli , D Nonneman , L. C. d. A Regitano , T. P. L Smith , J Song , T. S Sonstegard , C. P Van Tassell , M Ventura , E. E Eichler , T. G McDaneld and J. W. Keele

Genomic structural variation is an important and abundant source of genetic and phenotypic variation. Here, we describe the first systematic and genome-wide analysis of copy number variations (CNVs) in modern domesticated cattle using array comparative genomic hybridization (array CGH), quantitative PCR (qPCR), and fluorescent in situ hybridization (FISH). The array CGH panel included 90 animals from 11 Bos taurus, three Bos indicus, and three composite breeds for beef, dairy, or dual purpose. We identified over 200 candidate CNV regions (CNVRs) in total and 177 within known chromosomes, which harbor or are adjacent to gains or losses. These 177 high-confidence CNVRs cover 28.1 megabases or ~1.07% of the genome. Over 50% of the CNVRs (89/177) were found in multiple animals or breeds and analysis revealed breed-specific frequency differences and reflected aspects of the known ancestry of these cattle breeds. Selected CNVs were further validated by independent methods using qPCR and FISH. Approximately 67% of the CNVRs (119/177) completely or partially span cattle genes and 61% of the CNVRs (108/177) directly overlap with segmental duplications. The CNVRs span about 400 annotated cattle genes that are significantly enriched for specific biological functions, such as immunity, lactation, reproduction, and rumination. Multiple gene families, including ULBP, have gone through ruminant lineage-specific gene amplification. We detected and confirmed marked differences in their CNV frequencies across diverse breeds, indicating that some cattle CNVs are likely to arise independently in breeds and contribute to breed differences. Our results provide a valuable resource beyond microsatellites and single nucleotide polymorphisms to explore the full dimension of genetic variability for future cattle genomic research.

  W Yuan , J Xie , C Long , H Erdjument Bromage , X Ding , Y Zheng , P Tempst , S Chen , B Zhu and D. Reinberg

The presence of histone H3 lysine 36 methylation (H3K36me) correlates with actively transcribed genes. In yeast, histone H3K36me mediated by KMT3 (also known as Set2) recruits a histone deacetylase complex, Rpd3s, to ensure the fidelity of transcription initiation. We report the purification of human KMT3a (also known as HYPB or hSet2) complex and the identification of a novel, higher eukaryotic specific subunit, heterogeneous nuclear ribonucleoprotein L (HnRNP-L). Interestingly, although KMT3a has intrinsic activity in vitro, HnRNP-L is essential in vivo. Moreover, KMT3a generates mono-, di-, and trimethylated products in vitro, but RNA interference against KMT3a or HnRNP-L down-regulates exclusively the H3K36me3 mark in vivo.

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