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Biomedical subjects

Xin Xu

Publications and source records attributed to Xin Xu.

At least 109 records · Page 6Linked to original sources
PubMed2004

Initiation sites for human DNA replication at a putative ribulose-5-phosphate 3-epimerase gene.

Replication of the human genome requires the activation of thousands of replicons distributed along each one of the chromosomes. Each replicon contains an initiation, or origin, site, at which DNA synthesis begins. However, very little information is known about the nature and positioning of these initiation sites along human chromosomes. We have recently focused our attention to a 1.1 kb region of human chromosome 2 which functioned as an episomal origin in the yeast Saccharomyces cerevisiae. This region corresponded to the largest exon of a putative ribulose-5-phosphate-3-epimerase gene (RPE). In the present study we have used a real-time PCR-based nascent strand DNA abundance assay to map initiation sites for DNA replication in in vivo human chromosomes around a 13.4 kb region encompassing the putative RPE gene. By applying this analysis to a 1-1.4 kb nascent strand DNA fraction isolated from both normal skin fibroblasts, and the breast cell line MCF10; we have identified five initiation sites within the 13.4 kb region of chromosome 2. The initiation sites appear to map to similar positions in both cell lines and occur outside the coding regions of the putative RPE gene.

Breast Neoplasms↗
PubMed2004

Probe-induced native oxide decomposition and localized oxidation on 6H-SiC (0001) surface: an atomic force microscopy investigation.

We report, for the first time, the native oxide decomposition/etching and direct local oxide growth on 6H-SiC (0001) surface induced by atomic force microscopy (AFM). Surface native oxide was decomposed and assembled into protruded lines when the negatively biased AFM tip was scanned over surface areas. The mechanism of decomposition was found to be governed by the Fowler-Nordheim emission current enhanced by the negatively biased AFM tip. Direct oxide growth on the SiC surface was achieved when the AFM tip was immobilized and longer bias duration applied. In particular, the aspect ratio of oxide grown on SiC was found to be several times higher than that on the Si surface. The improved aspect ratio on SiC was attributed to the anisotropic OH(-) diffusion involved in vertical and lateral oxidation along the polar and nonpolar directions such as [0001] and [110] axis in SiC crystal. The electron transport in the above AFM grown oxide on SiC was further investigated by I-V characteristics. The dielectrical strength of AFM oxide against degradation and breakdown under electrical stressing was evaluated.

Journal Article↗
PubMed2004

A common haplotype of the nicotine acetylcholine receptor alpha 4 subunit gene is associated with vulnerability to nicotine addiction in men.

Nicotine is the major addictive substance in cigarettes, and genes involved in sensing nicotine are logical candidates for vulnerability to nicotine addiction. We studied six single-nucleotide polymorphisms (SNPs) in the CHRNA4 gene and four SNPs in the CHRNB2 gene with respect to nicotine dependence in a collection of 901 subjects (815 siblings and 86 parents) from 222 nuclear families with multiple nicotine-addicted siblings. The subjects were assessed for addiction by both the Fagerstrom Test for Nicotine Dependence (FTND) and the Revised Tolerance Questionnaire (RTQ). Because only 5.8% of female offspring were smokers, only male subjects were included in the final analyses (621 men from 206 families). Univariate (single-marker) family-based association tests (FBATs) demonstrated that variant alleles at two SNPs, rs1044396 and rs1044397, in exon 5 of the CHRNA4 gene were significantly associated with a protective effect against nicotine addiction as either a dichotomized trait or a quantitative phenotype (i.e., age-adjusted FTND and RTQ scores), which was consistent with the results of the global haplotype FBAT. Furthermore, the haplotype-specific FBAT showed a common (22.5%) CHRNA4 haplotype, GCTATA, which was significantly associated with both a protective effect against nicotine addiction as a dichotomized trait (Z=-3.04, P<.005) and significant decreases of age-adjusted FTND (Z=-3.31, P<.005) or RTQ scores (Z=-2.73, P=.006). Our findings provide strong evidence suggesting a common CHRNA4 haplotype might be protective against vulnerability to nicotine addiction in men.

Adult↗
PubMed2004

D919G polymorphism of methionine synthase gene is associated with blood pressure response to benazepril in Chinese hypertensive patients.

Individual variation in drug response is considered to have multiple origins arising from interactions among susceptible genes and environmental factors. A total of 726 hypertensive patients who took benazepril 10 mg once a day for 15 days and their families from Huoqiu county of Anhui Province, China, were used to study the association between D919G polymorphism of methionine synthase (MTR) gene and the antihypertensive effect of this angiotensin-converting enzyme inhibitor. Compared to the 919D allele, both population-based ( P=0.010) and family-based association tests (additive model P=0.018, dominant model P=0.025) demonstrated that the 919G allele was associated with a significantly less diastolic blood pressure reduction. No significant association was found between the extent of systolic blood pressure reduction and benazepril therapy. Our finding suggests that the D919G polymorphism of the MTR gene may be a useful genetic marker to predict the antihypertensive effect of short-term benazepril therapy in hypertensive patients of Anhui Province, China.

5-Methyltetrahydrofolate-Homocysteine S-Methyltran↗
PubMed2004

New alkali doped pillared carbon materials designed to achieve practical reversible hydrogen storage for transportation.

We propose a new generation of materials to maximize reversible H2 storage at room temperature and modest pressures (<20 bars). We test these materials using grand canonical Monte Carlo simulations with a first-principles-derived force field and find that the Li pillared graphene sheet system can take up 6.5 mass% of H2 (a density of 62.9 kg/m(3) at 20 bars and room temperature. This satisfies the DOE (Department of Energy) target of hydrogen-storage materials for transportation. We also suggest ways to synthesize these systems. In addition we show that Li-doped pillared single-wall nanotubes can lead to a hydrogen-storage capacity of 6.0 mass% and 61.7 kg/m(3) at 50 bars and room temperature storage, which is close to the DOE target.

Journal Article↗
PubMed2004

Self-assembly of normal alkanes on the Au (111) surfaces.

The self-assembled monolayers (SAMs) of normal alkanes (n-C(n)H(2n+2)) with different carbon chain lengths (n=14-38) in the interfaces between alkane solutions (or liquids), and the reconstructed Au (111) surfaces have been systematically studied by means of scanning tunneling microscopy (STM). In contrast to previous studies, which concluded that some n-alkanes (n=18-26) can not form well-ordered structures on Au (111) surfaces, we observed SAM formations for all these n-alkanes without any exceptions. We find that gold reconstruction plays a critical role in the SAM formation. The alkane monolayers adopt a lamellar structure in which the alkane molecules are packed side-by-side, to form commensurate structures with respect to the reconstructed Au (111) surfaces. The carbon skeletons are found to lie flat on the surfaces, which is consistent with the infrared spectroscopic studies. Interestingly, we find that two-dimensional chiral lamellar structures form for alkanes with an even carbon number due to the specific packing of alkane molecules in a tilted lamella. Furthermore, we find that the orientation of alkane molecules deviates from the exact [011] direction, because of the intermolecular interactions among the terminal methyl groups of neighboring lamellae; this results in differences of molecular orientation between mirror structures of adjacent zigzag alkane lamellae. Structural models have been proposed, that shed new light on monolayer formation.

Journal Article↗
PubMed2004

From The Cover: The X3LYP extended density functional for accurate descriptions of nonbond interactions, spin states, and thermochemical properties.

We derive the form for an exact exchange energy density for a density decaying with Gaussian-like behavior at long range. Based on this, we develop the X3LYP (extended hybrid functional combined with Lee-Yang-Parr correlation functional) extended functional for density functional theory to significantly improve the accuracy for hydrogen-bonded and van der Waals complexes while also improving the accuracy in heats of formation, ionization potentials, electron affinities, and total atomic energies [over the most popular and accurate method, B3LYP (Becke three-parameter hybrid functional combined with Lee-Yang-Parr correlation functional)]. X3LYP also leads to a good description of dipole moments, polarizabilities, and accurate excitation energies from s to d orbitals for transition metal atoms and ions. We suggest that X3LYP will be useful for predicting ligand binding in proteins and DNA.

Models, Theoretical↗
PubMed2004

A candidate gene association study on preterm delivery: application of high-throughput genotyping technology and advanced statistical methods.

Preterm delivery (PTD) is the leading cause of infant mortality and morbidity worldwide. The etiology of PTD is largely unknown but is believed to be complex, encompassing multiple genetic and environmental determinants. To date, reports of genetic studies on PTD are sparse. We conducted a large-scale case-control study exploring the associations of 426 single-nucleotide polymorphisms with PTD in 300 mothers with PTD and 458 mothers with term deliveries at the Boston Medical Center. Twenty-five candidate genes were included in the final haplotype analysis, and a significant association of F5 gene haplotype with PTD was revealed and remained significant after Bonferroni correction for multiple testing (P=0.025). We applied different statistical algorithms (both Gibbs sampling and expectation-maximization) in reconstructing haplotype phases and different tests (both likelihood ratio test and permutation test) in association analyses, and all yielded similar results. We also performed exploratory ethnicity-specific analyses, which confirmed the consistent findings of the F5 gene across the ethnic groups. Moreover, IL1R2 (P=0.002 in Blacks), NOS2A (P<0.001 in Whites) and OPRM1 (P=0.004 in Hispanics) gene haplotypes were associated with PTD in specific ethnic groups but not at global significance level. In summary, our results underscore the potentially important role of F5 gene variants in the pathogenesis of PTD, and demonstrate the utility of high-throughput genotyping and a haplotype-based approach in dissecting genetic basis of complex traits.

Algorithms↗
PubMed2004

Peroxisome proliferator-activated receptor alpha agonists increase nitric oxide synthase expression in vascular endothelial cells.

OBJECTIVE: There has been accumulating evidence demonstrating that activators for peroxisome proliferator-activated receptor alpha (PPARalpha) have antiinflammatory, antiatherogenic, and vasodilatory effects. We hypothesized that PPARalpha activators can modulate endothelial nitric oxide synthase (eNOS) expression and its activity in cultured vascular endothelial cells. METHODS AND RESULTS: Bovine aortic endothelial cells were treated with the PPARalpha activator fenofibrate. The amount of eNOS activity and the expression of eNOS protein and its mRNA were determined. Our data show that treatment with fenofibrate for 48 hours resulted in an increase in eNOS activity. Fenofibrate failed to increase eNOS activity within 1 hour. Fenofibrate also increased eNOS protein as well as its mRNA levels. RU486, which has been shown to antagonize PPARalpha action, inhibited the fenofibrate-induced upregulation of eNOS protein expression. WY14643 and bezafibrate also increased eNOS protein levels, whereas rosiglitazone did not. Transient transfection experiments using human eNOS promoter construct showed that fenofibrate failed to enhance eNOS promoter activity. Actinomycin D studies demonstrated that the half-life of eNOS mRNA increased with fenofibrate treatment. CONCLUSIONS: PPARalpha activators upregulate eNOS expression, mainly through mechanisms of stabilizing eNOS mRNA. This is a new observation to explain one of the mechanisms of PPARalpha-mediated cardiovascular protection.

Animals↗
PubMed2004

Identification of novel initiation sites for human DNA replication around ARSH1, a previously characterized yeast replicator.

Replication of mammalian chromosomes depends on the activation of a large number of origins of DNA replication distributed along the chromosomes. We have focused our attention on a human DNA region, named ARSH1, localized to chromosome 2, that had been previously shown to act as an episomal origin in the yeast Saccharomyces cerevisiae. In the present study we have used a nascent strand DNA abundance assay to map initiation sites for DNA replication in in vivo human chromosomes around a 5 kb region encompassing ARSH1. This analysis applied to a 1-1.4 kb nascent DNA strand fraction isolated from normal skin fibroblasts revealed the presence of two major initiations sites surrounding the ARSH1 region. With an equivalent DNA fraction obtained from HeLa cells, in addition to these sites, a broad initiation profile was observed which included the ARSH1 region. This DNA region however was not sufficient to support episomal replication of an ARSH1-containing plasmid transfected into HeLa cells.

Base Sequence↗
PubMed2004

Power estimation of multiple SNP association test of case-control study and application.

At the current stage, a large number of single nucleotide polymorphisms (SNPs) have been deployed in searching for genes underlying complex diseases. A powerful method is desirable for efficient analysis of SNP data. Recently, a novel method for multiple SNP association test using a combination of allelic association (AA) and Hardy-Weinberg disequilibrium (HWD) has been proposed. However, the power of this test has not been systematically examined. In this study, we conducted a simulation study to further evaluate the statistical power of the new procedure, as well as of the influence of the HWD on its performance. The simulation examined the scenarios of multiple disease SNPs among a candidate pool, assuming different parameters including allele frequencies and risk ratios, dominant, additive, and recessive genetic models, and the existence of gene-gene interactions and linkage disequilibrium (LD). We also evaluated the performance of this test in capturing real disease associated SNPs, when a significant global P value is detected. Our results suggest that this new procedure is more powerful than conventional single-point analyses with correction of multiple testing. However, inclusion of HWD reduces the power under most circumstances. We applied the novel association test procedure to a case-control study of preterm delivery (PTD), examining the effects of 96 candidate gene SNPs concurrently, and detected a global P value of 0.0250 by using Cochran-Armitage chi(2)s as "starting" statistics in the procedure. In the following single point analysis, SNPs on IL1RN, IL1R2, ESR1, Factor 5, and OPRM1 genes were identified as possible risk factors in PTD.

Algorithms↗
PubMed2004

Family-based tests for associating haplotypes with general phenotype data: application to asthma genetics.

We provide a general purpose family-based testing strategy for associating disease phenotypes with haplotypes when phase may be ambiguous and parental genotype data may be missing. These tests for linkage and association can be used in candidate gene studies with tightly linked markers. Our proposed weighted conditional approach extends the method described in Rabinowitz and Laird to multiple markers. It is attractive because it provides haplotype tests for family-based studies that are efficient and robust to population admixture, phenotype distribution specification, and ascertainment based on phenotypes. It can handle missing parental genotypes and/or missing phase in both offspring and parents. It yields either haplotype-specific (univariate) tests or multi-haplotype (global) tests. This extension has been implemented in the freely available software haplotype FBAT. We used the haplotype FBAT program to test for associations between asthma phenotypes and single nucleotide polymorphisms (SNPs) in the beta-2 adrenergic receptor gene. Whereas no single SNP showed significant association with asthma diagnosis or bronchodilator responsiveness (quantitative trait), a haplotype-based global test found a highly significant association with asthma diagnosis (P value <0.00005) and the measure of bronchodilator responsiveness (P value =0.016).

Algorithms↗
PubMed2004

Histone acetyltransferase activity of p300 enhances the activation of IL-12 p40 promoter.

Interleukin-12 (IL-12) is a heterodimeric cytokine produced by macrophages in response to intracellular pathogens and provides an obligatory signal for the differentiation of T-helper-1 cells. p300 is an important histone acetyltransferase (HAT) and has been implicated in the regulation of gene expression. Whether p300 plays a role in the IL-12 expression has not been investigated before. In this study, we analyzed the roles of p300 in the regulation of human IL-12 p40. By using RT-PCR and a series of co-transfection studies, we found that p300 had a stimulating effect on the expression of endogenous IL-12 p40 mRNA and on the activity of IL-12 p40 promoter. We also showed that the HAT activity of p300 was essential to its function in regulating IL-12 promoter, since the mutant p300 with the HAT domain deleted did not have such a stimulation effect. In addition, the adenovirus E1A protein suppressed the p300 function, whereas the mutant E1A lacking the p300 interaction domain did not. Furthermore, p300 was able to reinforce the c-Rel-mediated activation of IL-12 p40. Results presented in this paper implicate that p300 is involved in the transcriptional regulation of IL-12 p40, and IL-12 p40 is one of the target genes of p300.

Acetyltransferases↗
PubMed2004

The C677T polymorphism of the methylenetetrahydrofolate reductase gene is associated with the level of decrease on diastolic blood pressure in essential hypertension patients treated by angiotensin-converting enzyme inhibitor.

OBJECTIVES: Elevated plasma homocysteine has been implicated as a risk factor for hypertension. C677T polymorphism in methylenetetrahydrofolate reductase gene (MTHFR) is a major determinant of hyperhomocysteinemia, which results in endothelial dysfunction. Angiotensin-converting enzyme (ACE) inhibitors appear to remedy the endothelial dysfunction and restore endothelium-dependent vasodilatation. The co-existence of genetic polymorphisms in drug metabolizing enzymes, targets, receptors, and transporters may influence the drug efficacy. The purpose of this study was to investigate whether short-term blood pressure control by benazepril, an ACE inhibitor, was modulated by C677T MTHFR gene polymorphism. METHODS AND RESULTS: A total of 444 hypertensive patients, aged 27 to 65 years, without any anti hypertensive therapy within 2 weeks were included. All of them were treated orally with benazepril at a single daily fixed dosage of 10 mg for 15 consecutive days. Blood pressures were measured at baseline and on the 16th day of treatment. Among them, the frequency of MTHFR C677T genotype CC, CT and TT was 24.3%, 51.8%, and 23.9%, respectively. In a recessive model (CC+CT versus TT genotype), both baseline diastolic blood pressure (DBP) and diastolic blood pressure response (DeltaDBP) were significantly higher in patients with the TT genotype than in those with the CT or CC genotype (P value=0.0076 for DBP, and P value=0.0005 for DeltaDBP). We further divided all patients into three groups based on the tertiles of the DeltaBP distribution. Compared to subjects in the lowest tertile of DeltaDBP, the adjusted relative odds of having the TT genotype among subjects in the highest tertile was 2.6 (95% CI, 1.4 to 4.9). However, baseline systolic blood pressure (SBP) and SBP response did not significantly associate with MTHFR C677T polymorphism. CONCLUSIONS: Our finding suggests that MTHFR C667T polymorphism modulated baseline DBP and DBP responsiveness by short-term treatment of ACE inhibitor in Chinese essential hypertensive patients.

Adult↗
PubMed2004

Recurrent immature teratoma of the ovary: a case report of radical secondary cytoreduction with replacement of the aortic bifurcation.

BACKGROUND: Composing of less than 1% of all ovarian cancers, immature teratoma is a malignancy that mainly affects the young. Although standard treatment protocol for primary disease has improved over the past decades, the role of secondary cytoreduction in the setting of recurrence remains controversial. CASE: A 20-year-old Chinese female presented with recurrent immature teratoma at the level of the aortic bifurcation. Patient was status post a right salpingo-oophorectomy at time of her initial diagnosis 8 years ago, and subsequent exploratory laparotomies and chemotherapy when recurrence that developed at the before-mentioned site. She ultimately underwent a radical cytoreduction with en-block excision of the aortic mass and simultaneous artificial aortic bifurcation graft. CONCLUSION: There may be a beneficial role of radical secondary cytoreduction in the setting of recurrent immature teratoma.

Adult↗
PubMed2004

Expression of MRP14 gene is frequently down-regulated in Chinese human esophageal cancer.

Migration inhibitory factor-related protein 14 (MRP14) is one of calcium-binding proteins, referred as S100A9. The heterodimeric molecule formed by MRP14 with its partner MRP8 (S100A8) is the major fatty acid carrier in neutrophils. The MRP8/14 complex has been also implicated in the intracellular transport of arachidonic acid and its precursors in keratinocytes. We show here the involvement of MRP14 in human esophageal cancer. In an initial study, mRNA differential display-reverse transcription polymerase chain reaction (DD-PCR) was performed with two esophageal carcinomas, one esophageal adenocarcinoma and matched normal adjacent mucosa. DD-PCR with the arbitrary primer OPA3 showed that one cDNA band was highly expressed in normal tissues, but disappeared or substantially decreased in tumor counterparts. It was later identified to be the 3'-end of migration inhibitory factor-related protein 14 (MRP14). Northern blotting, RT-PCR and Western blotting corroborated the down-regulation of MRP14 in 58/64 squamous cell carcinomas and 2/2 adenocarcinomas as compared with adjacent normal epithelia of the esophagus. MRP14 was undetectable in 3/3 esophageal-carcinoma cell lines. Immunochemistry demonstrated that expression of MRP14 was restricted to normal esophageal epithelia. No mutation was found in the genomic DNA of the MRP14 gene by PCR and directed DNA sequencing. Our finding suggested that the reduction of MRP14 expression is a frequent event in Chinese human esophageal cancer.

ATP-Binding Cassette Transporters↗
PubMed2004

Beta2 adrenergic receptor gene Arg16Gly polymorphism is associated with therapeutic efficacy of benazepril on essential hypertension in Chinese.

BACKGROUND: There is considerable variability in individual response to antihypertensive agents. The reason for this is not known, but may be related to individual genetic variability. This study examined whether the therapeutic efficacy of benazepril on essential hypertension is modified by beta2 adrenergic receptor gene (ADRB2) Arg16Gly (R16G) polymorphism. METHODS AND RESULTS: We conducted a family-based study of 321 and 610 hypertensive subjects from Yuexi and Huoqiu Counties of Anhui, China, respectively. Both systolic and diastolic blood pressures (SBP and DBP) before and after a 15-day benazepril treatment were measured. ADRB2 R16G genotypes were determined for all subjects. ADRB2 G16 allele frequency was found to be 41.0% and. 47.4% in Huoqiu and Yuexi, respectively. In Yuexi family-based association test (FBAT) revealed that the G16 allele was associated with a greater DBP decrease in response to a 15-day benazepril treatment (Z = 2.12, P = 0.03), and the data were consistent with a dominant inheritance model. A similar trend was observed in Huoqiu Chinese, but the magnitudes of effects were smaller and did not reach statistical significance. The FBAT results were further confirmed by using a generalized estimating equation model. CONCLUSION: Our family-based study provided the first evidence that ADRB2 R16G polymorphism may play an important role in DBP response to benazepril treatment, although the magnitude of the effect appears to be modified by other risk factors such as plasma lipid and glucose profiles.

Adult↗