137 research outputs found

    Genome-wide analysis of the cis-regulatory modules of divergent gene pairs in yeast

    Get PDF
    AbstractIn budding yeast, approximately a quarter of adjacent genes are divergently transcribed (divergent gene pairs). Whether genes in a divergent pair share the same regulatory system is still unknown. By examining transcription factor (TF) knockout experiments, we found that most TF knockout only altered the expression of one gene in a divergent pair. This prompted us to conduct a comprehensive analysis in silico to estimate how many divergent pairs are regulated by common sets of TFs (cis-regulatory modules, CRMs) using TF binding sites and expression data. Analyses of ten expression datasets show that only a limited number of divergent gene pairs share CRMs in any single dataset. However, around half of divergent pairs do share a regulatory system in at least one dataset. Our analysis suggests that genes in a divergent pair tend to be co-regulated in at least one condition; however, in most conditions, they may not be co-regulated

    Association between chronic viral hepatitis infection and breast cancer risk: a nationwide population-based case-control study

    Get PDF
    <p>Abstract</p> <p>Background</p> <p>In Taiwan, there is a high incidence of breast cancer and a high prevalence of viral hepatitis. In this case-control study, we used a population-based insurance dataset to evaluate whether breast cancer in women is associated with chronic viral hepatitis infection.</p> <p>Methods</p> <p>From the claims data, we identified 1,958 patients with newly diagnosed breast cancer during the period 2000-2008. A randomly selected, age-matched cohort of 7,832 subjects without cancer was selected for comparison. Multivariable logistic regression models were constructed to calculate odds ratios of breast cancer associated with viral hepatitis after adjustment for age, residential area, occupation, urbanization, and income. The age-specific (<50 years and ≥50 years) risk of breast cancer was also evaluated.</p> <p>Results</p> <p>There were no significant differences in the prevalence of hepatitis C virus (HCV) infection, hepatitis B virus (HBV), or the prevalence of combined HBC/HBV infection between breast cancer patients and control subjects (<it>p </it>= 0.48). Multivariable logistic regression analysis, however, revealed that age <50 years was associated with a 2-fold greater risk of developing breast cancer (OR = 2.03, 95% CI = 1.23-3.34).</p> <p>Conclusions</p> <p>HCV infection, but not HBV infection, appears to be associated with early onset risk of breast cancer in areas endemic for HCV and HBV. This finding needs to be replicated in further studies.</p

    Undiagnosed diabetes mellitus among residents in Taiwanese long-term care facilities: A comparison of fasting glucose, postprandial plasma glucose, and hemoglobin A1c

    Get PDF
    AbstractBackgroundThe prevalence of diabetes mellitus (DM) is escalating with an aging population, and the chances of diabetic older patients admitted to long-term care facilities (LTCFs) are increased because of DM-related complications. However, undiagnosed DM among LTCF residents is a recognized hidden problem in this setting and may result in adverse outcomes.MethodsIn May 2011, 10 private LTCFs in northern Taipei participated in this study. Trained research nurses reviewed the medical records and performed physical examinations and blood sampling for all participants. Diabetes mellitus was diagnosed, based on the levels of fasting glucose, 2-hour postprandial plasma glucose, and hemoglobin A1c (HbA1c). Patients were categorized as having DM if they met the diagnostic cut-offs of the aforementioned criteria.ResultsOne hundred and ninety-nine residents (mean age, 79.6 ± 10.5 years; 52.3% males) participated in this study. They were all moderately/severely disabled (Karnofsky Performance Scale mean score was 50 ± 13). Forty-six (23.1%) residents were diabetic, based on their medical records, or were current users of antidiabetic agents. The prevalence was 29.6% after testing with a mean HbA1c level of 6.9% ± 0.9%. The overall undiagnosed DM rate was 4%, 3.5%, and 4.5%, based on fasting glucose, 2-hour postprandial plasma glucose, and HbA1c criteria, respectively. Diabetic patients had significantly higher serum levels of prealbumin, compared to nondiabetic patients (220.8 ± 45.9 vs. 201.1 ± 62.2 mg/L; p = 0.03), but there were no differences in the levels of hemoglobin, serum albumin, or total cholesterol. Diabetic patients had a significantly higher serum triglyceride level, compared to the nondiabetic patients (1.6 ± 0.7 vs. 1.1 ± 0.5 mmol/L; p < 0.01) and a lower high-density lipoprotein level (1.0 ± 0.3 vs. 1.2 ± 0.3 mmol/L; p < 0.01). Among 43 pharmacologically treated diabetic patients, 65.1% (28/43) of patients were using oral antidiabetic agents and 41.9% (18/43) of patients had been prescribed insulin, whereas 32.6% of the patients were managed by combination therapy.ConclusionThe prevalence of DM among LTCF residents in Taipei was 29.6%, and the undiagnosed rate was no more than 5%, based on fasting glucose, 2-hour postprandial plasma glucose, or HbA1c. Further study is needed for the optimal treatment strategy of DM in LTCFs

    Prenatal diagnosis of a de novo 9p terminal chromosomal deletion in a fetus with major congenital anomalies

    Get PDF
    AbstractObjectiveWe describe a prenatal ultrasonography diagnosis of omphalocele and symbrachydactyly in a fetus and review the literature on prenatal diagnosis of 9p terminal chromosomal deletions.Case reportA 31-year-old woman (gravida 3, para 1) was referred for genetic counseling because a fetal omphalocele had been detected. Prenatal ultrasonography at 17+ weeks of gestational age revealed a singleton female fetus with biometry equivalent to 18 weeks with an omphalocele. In addition, symbrachydactyly was also noted in the right arm; the wrist bones as well as the metacarpals were missing. A chromosomal study was arranged for a congenital anomaly involving omphalocele. We obtained Giemsa-banded chromosomes from fetal tissue cells, and an abnormal male karyotype with a terminal deletion of the short arm of chromosome 9 at band 9p13 was noted. After delivery, the fetus showed omphalocele, symbrachydactyly, trigonocephaly, sex reversal, a long philtrum, low-set ears, telecanthus, and a frontal prominence.ConclusionPrenatal diagnosis of abnormal ultrasound findings with omphalocele and symbrachydactyly should include the differential diagnosis of a chromosome 9p deletion

    Carotid Artery Intima-Media Thickness, Carotid Plaque and Coronary Heart Disease and Stroke in Chinese

    Get PDF
    Background: Our aim was to prospectively investigate the association between carotid artery intima-media thickness (IMT) as well as carotid plaque and incidence of coronary heart disease (CHD) and stroke in Chinese, among whom data are limited. Methods and Findings: We conducted a community-based cohort study composed of 2190 participants free of cardiovascular disease at baseline in one community. During a median 10.5-year follow up, we documented 68 new cases of coronary heart disease and 94 cases of stroke. The multivariate relative risks (RRs) associated with a change of 1 standard deviation of maximal common carotid IMT were 1.38 (95% confidence interval [CI], 1.12–1.70) for CHD and 1.47 (95% CI, 1.28–1.69) for stroke. The corresponding RRs with internal carotid IMT were 1.47 (95% CI, 1.21–1.79) for CHD and 1.52 (95% CI, 1.31–1.76) for stroke. Carotid plaque measured by the degree of diameter stenosis was also significantly associated with increased risk of CHD (p for trend<0.0001) and stroke (p for trend<0.0001). However, these associations were largely attenuated when adjusting for IMT measurements. Conclusions: This prospective study indicates a significant association between carotid IMT and incidence of CHD and stroke in Chinese adults. These measurements may be useful for cardiovascular risk assessment and stratification in Chinese

    The Affinity of Elongated Membrane-Tethered Ligands Determines Potency of T Cell Receptor Triggering

    Get PDF
    T lymphocytes are important mediators of adoptive immunity but the mechanism of T cell receptor (TCR) triggering remains uncertain. The interspatial distance between engaged T cells and antigen-presenting cells (APCs) is believed to be important for topological rearrangement of membrane tyrosine phosphatases and initiation of TCR signaling. We investigated the relationship between ligand topology and affinity by generating a series of artificial APCs that express membrane-tethered anti-CD3 scFv with different affinities (OKT3, BC3, and 2C11) in addition to recombinant class I and II pMHC molecules. The dimensions of membrane-tethered anti-CD3 and pMHC molecules were progressively increased by insertion of different extracellular domains. In agreement with previous studies, elongation of pMHC molecules or low-affinity anti-CD3 scFv caused progressive loss of T cell activation. However, elongation of high-affinity ligands (BC3 and OKT3 scFv) did not abolish TCR phosphorylation and T cell activation. Mutation of key amino acids in OKT3 to reduce binding affinity to CD3 resulted in restoration of topological dependence on T cell activation. Our results show that high-affinity TCR ligands can effectively induce TCR triggering even at large interspatial distances between T cells and APCs

    Comprehensive Genotyping in Two Homogeneous Graves' Disease Samples Reveals Major and Novel HLA Association Alleles

    Get PDF
    BACKGROUND: Graves' disease (GD) is the leading cause of hyperthyroidism and thyroid eye disease inherited as a complex trait. Although geoepidemiology studies showed relatively higher prevalence of GD in Asians than in Caucasians, previous genetic studies were contradictory concerning whether and/or which human leukocyte antigen (HLA) alleles are associated with GD in Asians. METHODOLOGY/PRINCIPAL FINDINGS: We conducted a case-control association study (499 unrelated GD cases and 504 controls) and a replication in an independent family sample (419 GD individuals and their 282 relatives in 165 families). To minimize genetic and phenotypic heterogeneity, we included only ethnic Chinese Han population in Taiwan and excluded subjects with hypothyroidism. We performed direct and comprehensive genotyping of six classical HLA loci (HLA-A, -B, -C, -DPB1, -DQB1 and -DRB1) to 4-digit resolution. Combining the data of two sample populations, we found that B*46:01 (odds ratio under dominant model [OR]  = 1.33, Bonferroni corrected combined P [P(Bc)]  = 1.17 x 10⁻²), DPB1*05:01 (OR  = 2.34, P(Bc) = 2.58 x 10⁻¹⁰), DQB1*03:02 (OR  = 0.62, P(Bc)  = 1.97 x 10⁻²), DRB1*15:01 (OR  = 1.68, P(Bc) = 1.22 x 10⁻²) and DRB1*16:02 (OR  = 2.63, P(Bc)  = 1.46 x 10⁻⁵) were associated with GD. HLA-DPB1*05:01 is the major gene of GD in our population and singly accounts for 48.4% of population-attributable risk. CONCLUSIONS/SIGNIFICANCE: These GD-associated alleles we identified in ethnic Chinese Hans, and those identified in other Asian studies, are totally distinct from the known associated alleles in Caucasians. Identification of population-specific association alleles is the critical first step for individualized medicine. Furthermore, comparison between different susceptibility/protective alleles across populations could facilitate generation of novel hypothesis about GD pathophysiology and indicate a new direction for future investigation
    corecore