| 1. |
- Ganesh, Santhi K., et al.
(författare)
-
Loci influencing blood pressure identified using a cardiovascular gene-centric array
- 2013
-
Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 22:8, s. 1663-1678
-
Tidskriftsartikel (refereegranskat)abstract
- Blood pressure (BP) is a heritable determinant of risk for cardiovascular disease (CVD). To investigate genetic associations with systolic BP (SBP), diastolic BP (DBP), mean arterial pressure (MAP) and pulse pressure (PP), we genotyped 50 000 single-nucleotide polymorphisms (SNPs) that capture variation in 2100 candidate genes for cardiovascular phenotypes in 61 619 individuals of European ancestry from cohort studies in the USA and Europe. We identified novel associations between rs347591 and SBP (chromosome 3p25.3, in an intron of HRH1) and between rs2169137 and DBP (chromosome1q32.1 in an intron of MDM4) and between rs2014408 and SBP (chromosome 11p15 in an intron of SOX6), previously reported to be associated with MAP. We also confirmed 10 previously known loci associated with SBP, DBP, MAP or PP (ADRB1, ATP2B1, SH2B3/ATXN2, CSK, CYP17A1, FURIN, HFE, LSP1, MTHFR, SOX6) at array-wide significance (P 2.4 10(6)). We then replicated these associations in an independent set of 65 886 individuals of European ancestry. The findings from expression QTL (eQTL) analysis showed associations of SNPs in the MDM4 region with MDM4 expression. We did not find any evidence of association of the two novel SNPs in MDM4 and HRH1 with sequelae of high BP including coronary artery disease (CAD), left ventricular hypertrophy (LVH) or stroke. In summary, we identified two novel loci associated with BP and confirmed multiple previously reported associations. Our findings extend our understanding of genes involved in BP regulation, some of which may eventually provide new targets for therapeutic intervention.
|
|
| 2. |
- Tragante, Vinicius, et al.
(författare)
-
Gene-centric Meta-analysis in 87,736 Individuals of European Ancestry Identifies Multiple Blood-Pressure-Related Loci.
- 2014
-
Ingår i: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297. ; 94:3, s. 349-360
-
Tidskriftsartikel (refereegranskat)abstract
- Blood pressure (BP) is a heritable risk factor for cardiovascular disease. To investigate genetic associations with systolic BP (SBP), diastolic BP (DBP), mean arterial pressure (MAP), and pulse pressure (PP), we genotyped ∼50,000 SNPs in up to 87,736 individuals of European ancestry and combined these in a meta-analysis. We replicated findings in an independent set of 68,368 individuals of European ancestry. Our analyses identified 11 previously undescribed associations in independent loci containing 31 genes including PDE1A, HLA-DQB1, CDK6, PRKAG2, VCL, H19, NUCB2, RELA, HOXC@ complex, FBN1, and NFAT5 at the Bonferroni-corrected array-wide significance threshold (p < 6 × 10(-7)) and confirmed 27 previously reported associations. Bioinformatic analysis of the 11 loci provided support for a putative role in hypertension of several genes, such as CDK6 and NUCB2. Analysis of potential pharmacological targets in databases of small molecules showed that ten of the genes are predicted to be a target for small molecules. In summary, we identified previously unknown loci associated with BP. Our findings extend our understanding of genes involved in BP regulation, which may provide new targets for therapeutic intervention or drug response stratification.
|
|
| 3. |
- Deepak, K G, et al.
(författare)
-
Smokeless tobacco use among patients with tuberculosis in Karnataka : the need for cessation services.
- 2012
-
Ingår i: National Medical Journal of India. - 0970-258X. ; 25:3, s. 142-5
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: India is home to the largest population of patients with tuberculosis and tobacco users in the world. Smokeless tobacco use exceeds smoking and is increasing. There is no study to date that reports smokeless tobacco use before and after the diagnosis and treatment of tuberculosis. We assessed smokeless tobacco use among former patients of tuberculosis in Karnataka, India.METHODS: We conducted a community-based, cross sectional study among 202 men, who had been diagnosed and treated for tuberculosis (mean age 48 years), selected by multistage, random sampling. Using a semi-structured interview schedule, retrospective smoking and smokeless tobacco use were captured at eight time-points before and after the diagnosis and treatment of tuberculosis.RESULTS: Most patients suspended tobacco use during treatment. A high 44% prevalence of smokeless tobacco use 6 months before diagnosis was reduced to just 8% during the intensive phase of treatment and climbed to 27% 6 months after treatment. The tobacco use relapse rate 6 months after completion of treatment was higher for smokeless tobacco use (52%, 95% CI 41%-62%) than for smoking (36%, 95% CI 26%-45%). We also found that many patients who were advised to quit smoking continued using smokeless tobacco after completion of treatment. Additionally, new smokeless tobacco use was documented. Of the 11 new exclusive smokeless tobacco users, 10 shifted from smoking to smokeless tobacco use as a form of harm reduction.CONCLUSION: Patients with tuberculosis are advised by their doctors, at the time of diagnosis, to quit smoking. Several patients shift from smoking to smokeless tobacco use, which needs to be addressed while providing tobacco cessation services.
|
|
| 4. |
- Maska, Martin, et al.
(författare)
-
A benchmark for comparison of cell tracking algorithms
- 2014
-
Ingår i: Bioinformatics. - : Oxford University Press (OUP). - 1367-4803 .- 1367-4811. ; 30:11, s. 1609-1617
-
Tidskriftsartikel (refereegranskat)abstract
- Motivation: Automatic tracking of cells in multidimensional time-lapse fluorescence microscopy is an important task in many biomedical applications. A novel framework for objective evaluation of cell tracking algorithms has been established under the auspices of the IEEE International Symposium on Biomedical Imaging 2013 Cell Tracking Challenge. In this article, we present the logistics, datasets, methods and results of the challenge and lay down the principles for future uses of this benchmark. Results: The main contributions of the challenge include the creation of a comprehensive video dataset repository and the definition of objective measures for comparison and ranking of the algorithms. With this benchmark, six algorithms covering a variety of segmentation and tracking paradigms have been compared and ranked based on their performance on both synthetic and real datasets. Given the diversity of the datasets, we do not declare a single winner of the challenge. Instead, we present and discuss the results for each individual dataset separately.
|
|
| 5. |
- Mefford, Heather C, et al.
(författare)
-
Rare copy number variants are an important cause of epileptic encephalopathies
- 2011
-
Ingår i: Annals of Neurology. - : Wiley. - 0364-5134 .- 1531-8249. ; 70:6, s. 974-985
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE:Rare copy number variants (CNVs)-deletions and duplications-have recently been established as important risk factors for both generalized and focal epilepsies. A systematic assessment of the role of CNVs in epileptic encephalopathies, the most devastating and often etiologically obscure group of epilepsies, has not been performed.METHODS:We evaluated 315 patients with epileptic encephalopathies characterized by epilepsy and progressive cognitive impairment for rare CNVs using a high-density, exon-focused, whole-genome oligonucleotide array.RESULTS:We found that 25 of 315 (7.9%) of our patients carried rare CNVs that may contribute to their phenotype, with at least one-half being clearly or likely pathogenic. We identified 2 patients with overlapping deletions at 7q21 and 2 patients with identical duplications of 16p11.2. In our cohort, large deletions were enriched in affected individuals compared to controls, and 4 patients harbored 2 rare CNVs. We screened 2 novel candidate genes found within the rare CNVs in our cohort but found no mutations in our patients with epileptic encephalopathies. We highlight several additional novel candidate genes located in CNV regions.INTERPRETATION:Our data highlight the significance of rare CNVs in the epileptic encephalopathies, and we suggest that CNV analysis should be considered in the genetic evaluation of these patients. Our findings also highlight novel candidate genes for further study.
|
|
| 6. |
- Rambabu, D., et al.
(författare)
-
Pd/C-mediated synthesis of (Z)-3-alkylidenephthalides of potential pharmacological interest
- 2013
-
Ingår i: Tetrahedron Letters. - Oxford, England : PERGAMON-ELSEVIER SCIENCE LTD. - 0040-4039 .- 1359-8562. ; 54:23, s. 2989-2995
-
Tidskriftsartikel (refereegranskat)abstract
- The coupling of o-bromobenzoic acid with terminal alkynes using 10% Pd/C-Et3N-CuI-PPh3 as a catalyst system leads to the synthesis of (Z)-3-alkylidenephthalides as the major product along with the traces of isocoumarin when the reaction was performed in 1,4-dioxane. The methodology afforded a range of compounds including (Z)-3-(4-(methylsulfonyl)benzylidene)isobenzofuran-1(3H)-one of potential pharmacological interest. (C) 2013 Elsevier Ltd. All rights reserved.
|
|
