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Search Results: 1 - 10 of 28422 matches for " Guangyun Sun "
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Quality assessment of buccal versus blood genomic DNA using the Affymetrix 500 K GeneChip
Jessica G Woo, Guangyun Sun, Mary Haverbusch, Subbarao Indugula, Lisa J Martin, Joseph P Broderick, Ranjan Deka, Daniel Woo
BMC Genetics , 2007, DOI: 10.1186/1471-2156-8-79
Abstract: Buccal cytobrushes stored for ~7 years at -80°C prior to extraction yielded sufficient double stranded DNA (dsDNA) to be successfully genotyped on the Affymetrix ~262 K NspI chip, with yields between 536 and 1047 ng dsDNA. Using the BRLMM algorithm, genotyping call rates for blood samples averaged 98.4%, and for buccal samples averaged 97.8%. Matched blood samples exhibited 99.2% concordance, while matched blood and buccal samples exhibited 98.8% concordance.Buccal cytobrushes stored long-term result in sufficient dsDNA concentrations to achieve high genotyping call rates and concordance with stored blood samples in the context of Affymetrix 500 K SNP genotyping. Thus, given high-quality collection and storage protocols, it is possible to use stored buccal cytobrush samples for genome-wide association studies.While blood is considered the optimal source for DNA, inclusion of a blood draw may deter study participation [1]. Buccal cytobrush collection is a simple, painless procedure that allows for effective DNA sampling from a large population, and has been used in several large epidemiologic studies [2,3]. However, concerns regarding the use of buccal brushes have included the lower quantity of genomic DNA isolated [4], lower quality of DNA [4,5], and the fidelity of results from buccal brushes compared with blood samples [5-7]. In addition, there is a concern that older buccal brush samples may not yield as high-quality results as fresh samples [8].The advent of large scale genotyping platforms has also resulted in a reduction in the amount of DNA required. The Affymetrix 500 K GeneChip requires only 250 ng of total genomic DNA per chip, 500 ng total, and this DNA quantity has not changed with the recent release of the Affymetrix 5.0 and 6.0 chips, which enable genotyping up to 1.8 million genetic markers [9-11]. Thus, the DNA requirements of the Affymetrix chips are well below the expected yield of total DNA for buccal samples. As the Affymetrix system uses restri
Common SNPs in FTO Gene Are Associated with Obesity Related Anthropometric Traits in an Island Population from the Eastern Adriatic Coast of Croatia
Ge Zhang,Rebekah Karns,Nina Smolej Narancic,Guangyun Sun,Hong Cheng,Sasa Missoni,Zijad Durakovic,Pavao Rudan,Ranajit Chakraborty,Ranjan Deka
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0010375
Abstract: Multiple studies have provided compelling evidence that the FTO gene variants are associated with obesity measures. The objective of the study was to investigate whether FTO variants are associated with a broad range of obesity related anthropometric traits in an island population.
Suggestive linkage detected for blood pressure related traits on 2q and 22q in the population on the Samoan islands
Karolina ?berg, Feng Dai, Satupaitea Viali, John Tuitele, Guangyun Sun, Subba R Indugula, Ranjan Deka, Daniel E Weeks, Stephen T McGarvey
BMC Medical Genetics , 2009, DOI: 10.1186/1471-2350-10-107
Abstract: We found suggestive univariate linkage for SBP on chromosome 2q35-q37 (LOD 2.4) and for PP on chromosome 22q13 (LOD 2.2), two chromosomal regions that recently have been associated with SBP and PP, respectively.We have detected additional evidence for a recently reported locus associated with SBP on chromosome 2q and a susceptibility locus for PP on chromosome 22q. However, differences observed between the results from our three partly overlapping genetically homogenous study samples from the Samoan islands suggest that additional studies should be performed in order to verify these results.High blood pressure or hypertension is a major risk factor involved in the development of cardiovascular diseases (CVD) [1], which today are primary causes of death in most industrial countries. We have previously searched for genetic susceptibility to two other common CVD risk factors, adiposity-related phenotypes [2-4] and lipid-related phenotypes [5] in our sample from the Samoan islands. Here we continued the search for genetic susceptibility to CVD risk factors in this population by investigating blood pressure related traits. We performed genome-wide linkage investigation for a dichotomous trait for hypertension (HT) where the study subjects were divided into two categories, non-hypertensive and hypertensive as well as for three quantitative traits including systolic blood pressure (SBP), diastolic blood pressure (DBP) and pulse pressure (PP). In addition we studied the simultaneous variation of SBP and DBP (SBP-DBP) by performing a genome-wide bivariate quantitative analysis.The population on the Samoan islands, including both American Samoa and Samoa, has a common evolutionary history of approximately 3,000 years with homogeneity of allele frequencies and linkage disequilibrium (LD) structure [6]. However, during the last century, and especially since World War II, the two polities have been differently influenced by political economic development [7-9], which has caused
Distribution of genome-wide linkage disequilibrium based on microsatellite loci in the Samoan population
Hui-Ju Tsai, Guangyun Sun, Diane Smelser, Satupaitea Viali, Joseph Tufa, Li Jin, Daniel E Weeks, Stephen T McGarvey, Ranjan Deka
Human Genomics , 2004, DOI: 10.1186/1479-7364-1-5-327
Finding Missing Heritability in Less Significant Loci and Allelic Heterogeneity: Genetic Variation in Human Height
Ge Zhang, Rebekah Karns, Guangyun Sun, Subba Rao Indugula, Hong Cheng, Dubravka Havas-Augustin, Natalija Novokmet, Zijad Durakovic, Sasa Missoni, Ranajit Chakraborty, Pavao Rudan, Ranjan Deka
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0051211
Abstract: Genome-wide association studies (GWAS) have identified many common variants associated with complex traits in human populations. Thus far, most reported variants have relatively small effects and explain only a small proportion of phenotypic variance, leading to the issues of ‘missing’ heritability and its explanation. Using height as an example, we examined two possible sources of missing heritability: first, variants with smaller effects whose associations with height failed to reach genome-wide significance and second, allelic heterogeneity due to the effects of multiple variants at a single locus. Using a novel analytical approach we examined allelic heterogeneity of height-associated loci selected from SNPs of different significance levels based on the summary data of the GIANT (stage 1) studies. In a sample of 1,304 individuals collected from an island population of the Adriatic coast of Croatia, we assessed the extent of height variance explained by incorporating the effects of less significant height loci and multiple effective SNPs at the same loci. Our results indicate that approximately half of the 118 loci that achieved stringent genome-wide significance (p-value<5×10?8) showed evidence of allelic heterogeneity. Additionally, including less significant loci (i.e., p-value<5×10?4) and accounting for effects of allelic heterogeneity substantially improved the variance explained in height.
Extent of Height Variability Explained by Known Height-Associated Genetic Variants in an Isolated Population of the Adriatic Coast of Croatia
Ge Zhang, Rebekah Karns, Guangyun Sun, Subba Rao Indugula, Hong Cheng, Dubravka Havas-Augustin, Natalija Novokmet, Dusko Rudan, Zijad Durakovic, Sasa Missoni, Ranajit Chakraborty, Pavao Rudan, Ranjan Deka
PLOS ONE , 2011, DOI: 10.1371/journal.pone.0029475
Abstract: Background Human height is a classical example of a polygenic quantitative trait. Recent large-scale genome-wide association studies (GWAS) have identified more than 200 height-associated loci, though these variants explain only 2~10% of overall variability of normal height. The objective of this study was to investigate the variance explained by these loci in a relatively isolated population of European descent with limited admixture and homogeneous genetic background from the Adriatic coast of Croatia. Methodology/Principal Findings In a sample of 1304 individuals from the island population of Hvar, Croatia, we performed genome-wide SNP typing and assessed the variance explained by genetic scores constructed from different panels of height-associated SNPs extracted from five published studies. The combined information of the 180 SNPs reported by Lango Allen el al. explained 7.94% of phenotypic variation in our sample. Genetic scores based on 20~50 SNPs reported by the remaining individual GWA studies explained 3~5% of height variance. These percentages of variance explained were within ranges comparable to the original studies and heterogeneity tests did not detect significant differences in effect size estimates between our study and the original reports, if the estimates were obtained from populations of European descent. Conclusions/Significance We have evaluated the portability of height-associated loci and the overall fitting of estimated effect sizes reported in large cohorts to an isolated population. We found proportions of explained height variability were comparable to multiple reference GWAS in cohorts of European descent. These results indicate similar genetic architecture and comparable effect sizes of height loci among populations of European descent.
A Combination of 3D-QSAR, Molecular Docking and Molecular Dynamics Simulation Studies of Benzimidazole-Quinolinone Derivatives as iNOS Inhibitors
Hao Zhang,Jinhang Zan,Guangyun Yu,Ming Jiang,Peixun Liu
International Journal of Molecular Sciences , 2012, DOI: 10.3390/ijms130911210
Abstract: Inducible Nitric Oxide Synthase (iNOS) has been involved in a variety of diseases, and thus it is interesting to discover and optimize new iNOS inhibitors. In previous studies, a series of benzimidazole-quinolinone derivatives with high inhibitory activity against human iNOS were discovered. In this work, three-dimensional quantitative structure-activity relationships (3D-QSAR), molecular docking and molecular dynamics (MD) simulation approaches were applied to investigate the functionalities of active molecular interaction between these active ligands and iNOS. A QSAR model with R 2 of 0.9356, Q 2 of 0.8373 and Pearson- R value of 0.9406 was constructed, which presents a good predictive ability in both internal and external validation. Furthermore, a combined analysis incorporating the obtained model and the MD results indicates: (1) compounds with the proper-size hydrophobic substituents at position 3 in ring-C (R 3 substituent), hydrophilic substituents near the X 6 of ring-D and hydrophilic or H-bond acceptor groups at position 2 in ring-B show enhanced biological activities; (2) Met368, Trp366, Gly365, Tyr367, Phe363, Pro344, Gln257, Val346, Asn364, Met349, Thr370, Glu371 and Tyr485 are key amino acids in the active pocket, and activities of iNOS inhibitors are consistent with their capability to alter the position of these important residues, especially Glu371 and Thr370. The results provide a set of useful guidelines for the rational design of novel iNOS inhibitors.
Hydroxyethyl starch 130/0.4 and sodium chloride injection as adjunctive therapy in patients with cerebral hypoperfusion
Han Junliang,Yang Fang,Jiang Wenrui,Zhang Guangyun
BMC Neurology , 2012, DOI: 10.1186/1471-2377-12-127
Abstract: Background Both severe stenosis and completed occlusion in internal carotid artery or its distal branches have been considered the main reasons of cerebral hypoperfusion, which contributes to the washout disturbances of embolism in low perfusion territories distal to stenosis. An aggravated hypoperfusion state in certain brain region may induce ischemic stroke and further cognitive decline. However, the effective medication for cerebral hypoperfusion is largely unsettled. Methods/design By using computed tomography perfusion (CTP) imaging, the trial will evaluate the effectiveness, safety and tolerability of hydroxyethyl starch (HES) 130/0.4 for patients with extra-/intra-cranial artery stenosis and cerebral hypoperfusion. From 5 neurological inpatient wards, 300 patients will be randomly recruited for administered routine medications plus intravascular volume therapies using the equal volume of HES 130/0.4 or 0.9% sodium chloride solution. Cerebral hypoperfusion state after 7-day intervention is the primary outcome measure. The secondary outcome measures includes, impaired renal function, abnormal heart function, hematological changes, neurological dysfunctions and cerebrovascular events in peri-intervention period and/or 3-month follow-up. The sample size will allow the detection of a two-sided 5% significance level between groups in the endpoint with a power of 80%. Discussion The trial would provide important efficacy and safety data on the intravascular administration of HES 130/0.4 in patients with unilateral cerebral hypoperfusion. The effects on kidney function, heart function, coagulation, neurological function and cerebralvascular events will be assessed. Trial registration ClinicalTrials.gov (Identifier: NCT01192581)
Identification of Amino Acids Essential for Estrone-3-Sulfate Transport within Transmembrane Domain 2 of Organic Anion Transporting Polypeptide 1B1
Nan Li, Weifang Hong, Hong Huang, Hanping Lu, Guangyun Lin, Mei Hong
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0036647
Abstract: As an important structure in membrane proteins, transmembrane domains have been found to be crucial for properly targeting the protein to cell membrane as well as carrying out transport functions in transporters. Computer analysis of OATP sequences revealed transmembrane domain 2 (TM2) is among those transmembrane domains that have high amino acid identities within different family members. In the present study, we identify four amino acids (Asp70, Phe73, Glu74, and Gly76) that are essential for the transport function of OATP1B1, an OATP member that is specifically expressed in the human liver. A substitution of these four amino acids with alanine resulted in significantly reduced transport activity. Further mutagenesis showed the charged property of Asp70 and Glu74 is critical for proper function of the transporter protein. Comparison of the kinetic parameters indicated that Asp70 is likely to interact with the substrate while Glu74 may be involved in stabilizing the binding site through formation of a salt-bridge. The aromatic ring structure of Phe73 seems to play an important role because substitution of Phe73 with tyrosine, another amino acid with a similar structure, led to partially restored transport function. On the other hand, replacement of Gly76 with either alanine or valine could not recover the function of the transporter. Considering the nature of a transmembrane helix, we proposed that Gly76 may be important for maintaining the proper structure of the protein. Interestingly, when subjected to transport function analysis of higher concentration of esteone-3-sulfate (50 μM) that corresponds to the low affinity binding site of OATP1B1, mutants of Phe73, Glu74, and Gly76 all showed a transport function that is comparable to that of the wild-type, suggesting these amino acids may have less impact on the low affinity component of esteone-3-sulfate within OATP1B1, while Asp 70 seems to be involved in the interaction of both sites.
Response Surface Optimized Ultrasonic-Assisted Extraction of Flavonoids from Sparganii Rhizoma and Evaluation of Their in Vitro Antioxidant Activities
Xinsheng Wang,Qinan Wu,Yanfang Wu,Guangyun Chen,Wei Yue,Qiaoli Liang
Molecules , 2012, DOI: 10.3390/molecules17066769
Abstract: An efficient ultrasound-assisted extraction technique was employed to extract total flavonoids from Sparganii rhizoma. The optimum extraction conditions for the highest yield of total flavonoids were ethanol concentration 53.62%, ultrasonication time 29.41 min and ultrasound power 300 W, which were determined using response surface methodology. The extraction yields of the optimal ultrasound-assisted extraction were higher than using conventional extraction. The crude extract was then purified on a polyamide resin, whereby the flavonoids content in the purified extract increased to 94.62%. The antioxidant activities of the purified flavonoids including DPPH radical scavenging activity, ABTS+ radical scavenging activity, reducing power, hydroxyl radical scavenging activity and superoxide anion scavenging activity, were evaluated in vitro, which suggested that the flavonoids showed significant antioxidant activities. Rutin, kaempferol and formononetin were identified in the extract by comparing relative retention times and UV-Vis spectra with those of reference standards.
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