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  • 1
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    MethHC: a database of DNA methylation and gene expression in human cancer (2015)
    Oxford University Press
    Details
    Publication Date: 2015-01-16
    Description: We present MethHC ( http://MethHC.mbc.nctu.edu.tw ), a database comprising a systematic integration of a large collection of DNA methylation data and mRNA/microRNA expression profiles in human cancer. DNA methylation is an important epigenetic regulator of gene transcription, and genes with high levels of DNA methylation in their promoter regions are transcriptionally silent. Increasing numbers of DNA methylation and mRNA/microRNA expression profiles are being published in different public repositories. These data can help researchers to identify epigenetic patterns that are important for carcinogenesis. MethHC integrates data such as DNA methylation, mRNA expression, DNA methylation of microRNA gene and microRNA expression to identify correlations between DNA methylation and mRNA/microRNA expression from TCGA (The Cancer Genome Atlas), which includes 18 human cancers in more than 6000 samples, 6548 microarrays and 12 567 RNA sequencing data.
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
    Published by Oxford University Press
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  • 2
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    Association Between Changes in Exposure to Air Pollution and Biomarkers of Oxidative Stress in Children Before and During the Beijing Olympics (2015)
    Oxford University Press
    Details
    Publication Date: 2015-04-08
    Description: It is not known whether exposure to air pollutants causes systemic oxidative stress in children. We investigated the association between exposure to air pollution and biomarkers of oxidative stress in relation to a governmental air quality intervention implemented during the 2008 Beijing Olympic Games. We studied 36 schoolchildren during 5 time periods before and during the Olympic Games in Beijing (June 2007–September 2008). The oxidative stress biomarkers 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) and malondialdehyde were measured in urine samples collected daily during each period. Generalized estimating equations were used to examine the relationship between repeated biomarker measurements and ambient air pollutant levels. During the Olympic intervention period, substantial reductions in air pollution (–19% to –72%), urinary 8-oxodG concentrations (–37.4%; 95% confidence interval: –53.5, –15.7), and urinary malondialdehyde concentrations (–25.3%; 95% confidence interval: –34.3, –15.1) were found. Malondialdehyde and 8-oxodG were significantly associated with concentrations of black carbon, fine particulate matter with an aerodynamic with diameter less than 2.5 μm, sulfur dioxide, nitrogen dioxide, and carbon monoxide. Biomarker changes per each interquartile-range increase in pollutants were largest at lag 0 or lag 1. In a 2-pollutant model, the most robust associations were for black carbon. These findings suggest that exposure to black carbon leads to systemic oxidative stress in children.
    Print ISSN: 0002-9262
    Electronic ISSN: 1476-6256
    Topics: Medicine
    Published by Oxford University Press
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  • 3
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    Quantitative HER2 and p95HER2 levels in primary breast cancers and matched brain metastases (2015)
    Oxford University Press
    Details
    Publication Date: 2015-08-21
    Description: Background Patients with advanced breast cancer positive for human epidermal growth factor receptor 2 (HER2) are at high risk for brain metastasis (BM). The prevalence and significance of expression of HER2 and its truncated form p95HER2 (p95) in BM is unknown. Methods Seventy-five pairs of formalin-fixed paraffin-embedded samples from matched primary breast cancers (PBCs) and BM were assayed for quantitative p95 and HER2-total (H2T) protein expression using the p95 VeraTag and HERmark assays, respectively. Results There was a net increase in p95 and H2T expression in BM relative to the matched PBC (median 1.5-fold, P = .0007 and 2.1-fold, P 〈 .0001, respectively). Cases with H2T-positive tumors were more likely to have the largest (≥5-fold) increase in p95 (odds ratio = 6.3, P = .018). P95 positivity in PBC correlated with progression-free survival (hazard ratio [HR] = 2.2, P = .013), trended with shorter time to BM (HR = 1.8, P = .070), and correlated with overall survival (HR = 2.1, P = .042). P95 positivity in BM correlated with time to BM (HR = 2.0, P = .016) but did not correlate with overall survival from the time of BM diagnosis (HR = 1.2, P = .61). Conclusions This is the first study of quantitative p95 and HER2 expression in matched PBC and BM. BM of breast cancer shows significant increases in expression of both biomarkers compared with matched PBC. These data provide a rationale for future correlative studies on p95 and HER2 levels in BM.
    Print ISSN: 1522-8517
    Electronic ISSN: 1523-5866
    Topics: Medicine
    Published by Oxford University Press on behalf of The Society for Neuro-Oncology (SNO).
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  • 4
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    ASD v3.0: unraveling allosteric regulation with structural mechanisms and biological networks (2016)
    Oxford University Press
    Details
    Publication Date: 2016-01-07
    Description: Allosteric regulation, the most direct and efficient way of regulating protein function, is induced by the binding of a ligand at one site that is topographically distinct from an orthosteric site. Allosteric Database (ASD, available online at http://mdl.shsmu.edu.cn/ASD ) has been developed to provide comprehensive information featuring allosteric regulation. With increasing data, fundamental questions pertaining to allostery are currently receiving more attention from the mechanism of allosteric changes in an individual protein to the entire effect of the changes in the interconnected network in the cell. Thus, the following novel features were added to this updated version: (i) structural mechanisms of more than 1600 allosteric actions were elucidated by a comparison of site structures before and after the binding of an modulator; (ii) 261 allosteric networks were identified to unveil how the allosteric action in a single protein would propagate to affect downstream proteins; (iii) two of the largest human allosteromes, protein kinases and GPCRs, were thoroughly constructed; and (iv) web interface and data organization were completely redesigned for efficient access. In addition, allosteric data have largely expanded in this update. These updates are useful for facilitating the investigation of allosteric mechanisms, dynamic networks and drug discoveries.
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
    Published by Oxford University Press
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  • 5
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    ASBench: benchmarking sets for allosteric discovery (2015)
    Oxford University Press
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    Publication Date: 2015-07-26
    Description: : Allostery allows for the fine-tuning of protein function. Targeting allosteric sites is gaining increasing recognition as a novel strategy in drug design. The key challenge in the discovery of allosteric sites has strongly motivated the development of computational methods and thus high-quality, publicly accessible standard data have become indispensable. Here, we report benchmarking data for experimentally determined allosteric sites through a complex process, including a ‘Core set’ with 235 unique allosteric sites and a ‘Core-Diversity set’ with 147 structurally diverse allosteric sites. These benchmarking sets can be exploited to develop efficient computational methods to predict unknown allosteric sites in proteins and reveal unique allosteric ligand–protein interactions to guide allosteric drug design. Availability and implementation: The benchmarking sets are freely available at http://mdl.shsmu.edu.cn/asbench . Contact: jian.zhang@sjtu.edu.cn Supplementary information: Supplementary data are available at Bioinformatics online
    Print ISSN: 1367-4803
    Electronic ISSN: 1460-2059
    Topics: Biology , Computer Science , Medicine
    Published by Oxford University Press
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  • 6
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    Variant Near FGF5 Has Stronger Effects on Blood Pressure in Chinese With a Higher Body Mass Index (2015)
    Oxford University Press
    Details
    Publication Date: 2015-07-10
    Description: BACKGROUND The objective of this study was to investigate the genetic association of 4 candidate variants with blood pressure and test the modifying effects of environmental factors including age, sex, and body mass index (BMI). METHODS We used a linear mixed-effects model to test for variant main effects and variant interactions with age, sex, and BMI on systolic (SBP) and diastolic (DBP) blood pressure in 7,319 Chinese adults from the China Health and Nutrition Survey (CHNS). We attempted to replicate our significant interaction findings in 1,996 Chinese men from the Fangchenggang Area Male Health and Examination Survey (FAMHES). RESULTS Two variants (rs11105378 near ATP2B1 and rs1458038 near FGF5 ) were significantly associated ( P 〈 0.00625 = 0.05/8) with both SBP and DBP in CHNS. Variant rs1378942 near CSK was nominally associated with SBP ( P = 0.01). The signal at rs1458038 exhibited a genotype-by-BMI interaction affecting blood pressure ( P interaction = 0.0018 for SBP; P interaction = 0.049 for DBP), with the strongest variant effects in those with the highest BMI. In FAMHES, rs1458038 also showed stronger effects on SBP and DBP among men with the highest BMI. CONCLUSIONS Our findings suggest high BMI increases the effect of the blood pressure-increasing allele at rs1458038 near FGF5 , further highlighting the importance of obesity prevention in reducing hypertension risk.
    Print ISSN: 0895-7061
    Electronic ISSN: 1879-1905
    Topics: Medicine
    Published by Oxford University Press
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  • 7
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    Water-use efficiency of four native trees under CO2 enrichment and N addition in subtropical model forest ecosystems (2015)
    Oxford University Press
    Details
    Publication Date: 2015-07-24
    Description: Aims We aimed to evaluate the changes in water-use efficiency (WUE) in native tree species in forests of subtropical China, and determine how coexisting species would be responding to increases in atmospheric carbon dioxide (CO 2 ) concentrations and nitrogen (N) deposition. Methods We used model forest ecosystems in open-top chambers to study the effects of elevated CO 2 ( ca . 700 µmol mol –1 ) alone and together with N addition (NH 4 NO 3 applied at 100kg N ha –1 year –1 ) on WUE of four native tree species ( Schima superba , Ormosia pinnata , Castanopsis hystrix and Acmena acuminatissima ) from 2006 to 2010. Important findings Our result indicated that all species increased their WUE when they were exposed to elevated CO 2 . Although higher WUE was shown in faster-growing species ( S. superba and O. pinnata ) than that of slower-growing species ( C. hystrix and Acmena acuminatissima ), the increased extent of WUE induced by elevated CO 2 was higher in the slower-growing species than that of the faster-growing species ( P 〈 0.01). The N treatment decreased WUE of S. superba, while the effects on other species were not significant. The interactions between elevated CO 2 and N addition increased intrinsic WUE of S. superba significantly ( P 〈 0.001), however, it did not affect WUE of the other tree species significantly. We conclude that the responses of native tree species to elevated CO 2 and N addition are different in subtropical China. The species-specific effects of elevated CO 2 and N addition on WUE would have important implications on species composition in China’s subtropics in response to global change.
    Print ISSN: 1752-993X
    Electronic ISSN: 1752-9921
    Topics: Biology
    Published by Oxford University Press
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  • 8
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    Simultaneous denoising and reconstruction of 5-D seismic data via damped rank-reduction method (2016)
    Oxford University Press
    Details
    Publication Date: 2016-07-20
    Description: The Cadzow rank-reduction method can be effectively utilized in simultaneously denoising and reconstructing 5-D seismic data that depend on four spatial dimensions. The classic version of Cadzow rank-reduction method arranges the 4-D spatial data into a level-four block Hankel/Toeplitz matrix and then applies truncated singular value decomposition (TSVD) for rank reduction. When the observed data are extremely noisy, which is often the feature of real seismic data, traditional TSVD cannot be adequate for attenuating the noise and reconstructing the signals. The reconstructed data tend to contain a significant amount of residual noise using the traditional TSVD method, which can be explained by the fact that the reconstructed data space is a mixture of both signal subspace and noise subspace. In order to better decompose the block Hankel matrix into signal and noise components, we introduced a damping operator into the traditional TSVD formula, which we call the damped rank-reduction method. The damped rank-reduction method can obtain a perfect reconstruction performance even when the observed data have extremely low signal-to-noise ratio. The feasibility of the improved 5-D seismic data reconstruction method was validated via both 5-D synthetic and field data examples. We presented comprehensive analysis of the data examples and obtained valuable experience and guidelines in better utilizing the proposed method in practice. Since the proposed method is convenient to implement and can achieve immediate improvement, we suggest its wide application in the industry.
    Keywords: Seismology
    Print ISSN: 0956-540X
    Electronic ISSN: 1365-246X
    Topics: Geosciences
    Published by Oxford University Press on behalf of The Deutsche Geophysikalische Gesellschaft (DGG) and the Royal Astronomical Society (RAS).
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  • 9
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    Molecular signatures associated with ZIKV exposure in human cortical neural progenitors (2016)
    Oxford University Press
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    Publication Date: 2016-10-14
    Description: Zika virus (ZIKV) infection causes microcephaly and has been linked to other brain abnormalities. How ZIKV impairs brain development and function is unclear. Here we systematically profiled transcriptomes of human neural progenitor cells exposed to Asian ZIKV C , African ZIKV M , and dengue virus (DENV). In contrast to the robust global transcriptome changes induced by DENV, ZIKV has a more selective and larger impact on expression of genes involved in DNA replication and repair. While overall expression profiles are similar, ZIKV C , but not ZIKV M , induces upregulation of viral response genes and TP53. P53 inhibitors can block the apoptosis induced by both ZIKV C and ZIKV M in hNPCs, with higher potency against ZIKV C -induced apoptosis. Our analyses reveal virus- and strain-specific molecular signatures associated with ZIKV infection. These datasets will help to investigate ZIKV-host interactions and identify neurovirulence determinants of ZIKV.
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
    Published by Oxford University Press
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  • 10
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    Pacing and sensing optimization of permanent His-bundle pacing in cardiac resynchronization therapy/implantable cardioverter defibrillators patients: value of integrated bipolar configuration (2016)
    Oxford University Press
    In: Europace
    Details
    Publication Date: 2016-09-01
    Description: Aims The clinical implementation of His-bundle pacing (HBP) has been limited by concern over higher capture thresholds (CTs) and lower R-wave amplitudes (RWAs), when compared with right ventricular (RV) pacing. The aim of this study was to assess the optimal pacing configuration for HBP lead when incorporated with cardiac resynchronization therapy/implantable cardioverter defibrillators (CRT-D/ICD) by testing of an integrated bipolar configuration. Methods and results HBP was achieved in 25 CRT-D and 13 ICD patients at implantation. Their RWA, CT@0.5 ms and impedance with His-bundle (HB) tip-RV coil, and HB unipolar and bipolar (tip-ring) configurations were measured acutely. Capture threshold in CRT-D patients was that needed to ‘correct’ complete left bundle block. Among all 16 CRT-D patients with permanent HBP, their RWA, CT@0.5 ms, and pacing impedance with HBP tip-RV coil and HBP tip-ring were measured at 1 month and 3 months follow-up. Higher RWA and lower CT were achieved with HB tip-RV coil configuration than either of the other two configurations at implantation ( n = 38, P 〈 0.05, respectively). At 1 and 3 months follow-up for patients receiving permanent HBP, RWA and CT with HB tip-RV coil configuration remained stable and better than those with HB tip-ring configuration ( n = 16, P 〈 0.05, respectively). Furthermore, HB lead pulse energy delivered with HB tip-RV coil configuration was also less than with HB tip-ring at 3 months ( n = 16, P = 0.017). Conclusion Incorporation of HBP into a CRT-D/ICD system is feasible, and pacing thresholds/sensing can be optimized using a novel integrated bipolar configuration with the RV lead.
    Print ISSN: 1099-5129
    Electronic ISSN: 1532-2092
    Topics: Medicine
    Published by Oxford University Press
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