The Chromatin Remodelling Factor dATRX Is Involved in Heterochromatin Formation

Despite extensive study of heterochromatin, relatively little is known about the mechanisms by which such a structure forms. We show that the Drosophila homologue of the human α-thalassemia and mental retardation X-linked protein (dATRX), is important in the formation or maintenance of heterochromatin through modification of position effect variegation. We further show that there are two isoforms of the dATRX protein, the longer of which interacts directly with heterochromatin protein 1 (dHP-1) through a CxVxL motif both in vitro and in vivo. These two proteins co-localise at heterochromatin in a manner dependent on this motif. Consistent with this observation, the long isoform of the dATRX protein localises primarily to the heterochromatin at the chromocentre on salivary gland polytene chromosomes, whereas the short isoform binds to many sites along the chromosome arms. We suggest that the establishment of a regular nucleosomal organisation may be common to heterochromatin and transcriptionally repressed chromatin in other locations, and may require the action of ATP dependent chromatin remodelling factors

A Novel Universal Primer-Multiplex-PCR Method with Sequencing Gel Electrophoresis Analysis

In this study, a novel universal primer-multiplex-PCR (UP-M-PCR) method adding a universal primer (UP) in the multiplex PCR reaction system was described. A universal adapter was designed in the 5′-end of each specific primer pairs which matched with the specific DNA sequences for each template and also used as the universal primer (UP). PCR products were analyzed on sequencing gel electrophoresis (SGE) which had the advantage of exhibiting extraordinary resolution. This method overcame the disadvantages rooted deeply in conventional multiplex PCR such as complex manipulation, lower sensitivity, self-inhibition and amplification disparity resulting from different primers, and it got a high specificity and had a low detection limit of 0.1 ng for single kind of crops when screening the presence of genetically modified (GM) crops in mixture samples. The novel developed multiplex PCR assay with sequencing gel electrophoresis analysis will be useful in many fields, such as verifying the GM status of a sample irrespective of the crop and GM trait and so on

Drosophila as a Model for MECP2 Gain of Function in Neurons

Methyl-CpG-binding protein 2 (MECP2) is a multi-functional regulator of gene expression. In humans loss of MECP2 function causes classic Rett syndrome, but gain of MECP2 function also causes mental retardation. Although mouse models provide valuable insight into Mecp2 gain and loss of function, the identification of MECP2 genetic targets and interactors remains time intensive and complicated. This study takes a step toward utilizing Drosophila as a model to identify genetic targets and cellular consequences of MECP2 gain-of function mutations in neurons, the principle cell type affected in patients with Rett-related mental retardation. We show that heterologous expression of human MECP2 in Drosophila motoneurons causes distinct defects in dendritic structure and motor behavior, as reported with MECP2 gain of function in humans and mice. Multiple lines of evidence suggest that these defects arise from specific MECP2 function. First, neurons with MECP2-induced dendrite loss show normal membrane currents. Second, dendritic phenotypes require an intact methyl-CpG-binding domain. Third, dendritic defects are amended by reducing the dose of the chromatin remodeling protein, osa, indicating that MECP2 may act via chromatin remodeling in Drosophila. MECP2-induced motoneuron dendritic defects cause specific motor behavior defects that are easy to score in genetic screening. In sum, our data show that some aspects of MECP2 function can be studied in the Drosophila model, thus expanding the repertoire of genetic reagents that can be used to unravel specific neural functions of MECP2. However, additional genes and signaling pathways identified through such approaches in Drosophila will require careful validation in the mouse model

Expression of ezrin is associated with invasion and dedifferentiation of hepatitis B related hepatocellular carcinoma

<p>Abstract</p> <p>Background</p> <p>Hepatocellular carcinoma (HCC) is the fifth most common malignancy in the world and constitutes the leading cause of cancer-related death among men, and second among women in Taiwan. Liver cirrhosis and HCC are relatively prevalent, and 80% to 85% of the patients with these conditions have positive results for hepatitis B surface antigen in Taiwan. Only 5% of the general population is seronegative for all hepatititis B virus (HBV) markers. This is the first study to determine the role of ezrin upon HBV HCC cell and patients with HBV HCC undergoing hepatectomy</p> <p>Methods</p> <p>Immunohistochemical study with ezrin in 104 human HBV-HCC cases were carried out to investigate its association with the clinicopathological features and the outcomes of 104 HBV-HCC patients undergoing hepatetomy. In addition, DNA constructs including the wild type ezrin (wt-ezrin) and mutant ezrin Tyr353 (Y353) were transfected into Hep3B cell to study its role in tumor invasion and differentiation.</p> <p>Results</p> <p>HBV HCC patients with ezrin over-expression independently have smaller tumor size, cirrhotic liver background, poor tumor differentiation, and more vascular invasion. Ezrin expression status has no impact on survival for HBV-HCC patients undergoing hepatectomy. The in vitro assay showed that wt-ezrin Hep3B cells have a significant higher level of AFP secretion and higher invasion ability as compared with the control and Y353- ezrin Hep3B cells.</p> <p>Conclusion</p> <p>Ezrin over-expression contributed to de-differentiation and invasion of HBV-HCC cell. HBV-HCC patients with ezrin over-expression were independently associated with tumor with smaller size, cirrhotic liver background, poor differentiation, and vascular invasion.</p

The prevalence of hypertension, obesity and dyslipidemia in individuals of over 30 years of age belonging to minorities from the pasture area of Xinjiang

<p>Abstract</p> <p>Background</p> <p>The prevalence of population-wide hypertension, obesity and dyslipidemia has not been well studied in the pasture area of Xinjiang. The present epidemiological study was performed to determine the prevalence of hypertension, obesity and dyslipidemia in minority populations from the pasture area of Xinjiang and to discuss the potential risk factors for hypertension.</p> <p>Methods</p> <p>A population-based, cross-sectional study in the Xinjiang pasture area was performed which included 2251 participants aged over 30 years (90.33% participation rate) of whom 71.26% were Kazaks. Several risk factors were considered: hypertension (defined as systolic or diastolic blood pressure or both of at least 140/90 mmHg measured on one occasion or treatment for hypertension) overweight/obesity (body mass index ≥ 25 kg/m²) alcohol intake, smoking/tobacco use and dyslipidemia. Outcomes were prevalence of hypertension, obesity and dyslipidemia and the associated risk factors of hypertension detected by multivariate logistic regression analysis taking into account various metabolic and lifestyle characteristics.</p> <p>Results</p> <p>The prevalence of hypertension, overweight/obesity and dyslipidemia in all participants from the pasture area of Xinjiang was 51.9%, 47.9% and 49.2% respectively. Independently, the prevalence and awareness of hypertension was 52.6% and 15.3% among Kazaks (n = 1604), 54.6% and 14.1% among Uygurs (n = 418), 39.5% and 16.1% among Mongolians (n = 81) and 43.9% and 18.2% among non-Xinjiang-born Han immigrants (n = 148). The prevalence of overweight/obesity in Kazaks, Uygurs, Mongolians and Han immigrants was 46.7%, 48.9%, 62.5% and 50.3%, respectively. The prevalence of dyslipidemia in the four ethnic groups mentioned was 53.5%, 34.8%, 49.3% and 47.3%, respectively. The mean blood pressure in all participants was 136/86 mmHg (pre-hypertensive), the mean BMI was 24.7 kg/m². Based on multiple logistic regression analysis, the significant risk factors for hypertension were age [1.07(1.06-1.09), P < 0.0001], overweight/obesity [overweight: 1.61(1.22-2.13), p = 0.0007; obesity: 1.95 (1.33-2.87), p = 0.0007], hypercholesterolemia [1.30(1.15-1.47), p < 0.0001] and an alcohol intake of over 30 g/day [2.22(1.43-3.45), p = 0.0004].</p> <p>Conclusions</p> <p>The considerably high prevalence of hypertension, overweight/obesity and dyslipidemia among the minority population aged over 30 from the pasture area of Xinjiang calls for effective preventive measures. Age, increased body mass index, hypercholesterolemia and ≥30 g/d alcohol intake can be counted as risk factors for hypertension, but further genetic or environmental clarification would be desirable to explain the unusually high prevalence of the conditions mentioned above.</p

Cost-effectiveness of human papillomavirus vaccination for prevention of cervical cancer in Taiwan

<p>Abstract</p> <p>Background</p> <p>Human papillomavirus (HPV) infection has been shown to be a major risk factor for cervical cancer. Vaccines against HPV-16 and HPV-18 are highly effective in preventing type-specific HPV infections and related cervical lesions. There is, however, limited data available describing the health and economic impacts of HPV vaccination in Taiwan. The objective of this study was to assess the cost-effectiveness of prophylactic HPV vaccination for the prevention of cervical cancer in Taiwan.</p> <p>Methods</p> <p>We developed a Markov model to compare the health and economic outcomes of vaccinating preadolescent girls (at the age of 12 years) for the prevention of cervical cancer with current practice, including cervical cytological screening. Data were synthesized from published papers or reports, and whenever possible, those specific to Taiwan were used. Sensitivity analyses were performed to account for important uncertainties and different vaccination scenarios.</p> <p>Results</p> <p>Under the assumption that the HPV vaccine could provide lifelong protection, the massive vaccination among preadolescent girls in Taiwan would lead to reduction in 73.3% of the total incident cervical cancer cases and would result in a life expectancy gain of 4.9 days or 8.7 quality-adjusted life days at a cost of US$324 as compared to the current practice. The incremental cost-effectiveness ratio (ICER) was US$23,939 per life year gained or US$13,674 per quality-adjusted life year (QALY) gained given the discount rate of 3$30,000 per QALY under most conditions, even when vaccine efficacy was suboptimal or when vaccine-induced immunity required booster shots every 13 years.</p> <p>Conclusions</p> <p>Although gains in life expectancy may be modest at the individual level, the results indicate that prophylactic HPV vaccination of preadolescent girls in Taiwan would result in substantial population benefits with a favorable cost-effectiveness ratio. Nevertheless, we should not overlook the urgency to improve the compliance rate of cervical screening, particularly for older individuals.</p

Crosstalk between Medulloblastoma Cells and Endothelium Triggers a Strong Chemotactic Signal Recruiting T Lymphocytes to the Tumor Microenvironment

Cancer cells can live and grow if they succeed in creating a favorable niche that often includes elements from the immune system. While T lymphocytes play an important role in the host response to tumor growth, the mechanism of their trafficking to the tumor remains poorly understood. We show here that T lymphocytes consistently infiltrate the primary brain cancer, medulloblastoma. We demonstrate, both in vitro and in vivo, that these T lymphocytes are attracted to tumor deposits only after the tumor cells have interacted with tumor vascular endothelium. Macrophage Migration Inhibitory Factor (MIF)” is the key chemokine molecule secreted by tumor cells which induces the tumor vascular endothelial cells to secrete the potent T lymphocyte attractant “Regulated upon Activation, Normal T-cell Expressed, and Secreted (RANTES).” This in turn creates a chemotactic gradient for RANTES-receptor bearing T lymphocytes. Manipulation of this pathway could have important therapeutic implications

Electron shuttle-mediated microbial Fe(III) reduction under alkaline conditions

Purpose: Extracellular Fe(III) reduction plays an important role in a variety of biogeochemical processes. Several mechanisms for microbial Fe(III) reduction in pH-neutral environments have been proposed, but pathways of microbial Fe(III) reduction within alkaline conditions have not been clearly identified. Alkaline soils are vastly distributed; thus, a better understanding of microbial Fe(III) reduction under alkaline conditions is of significance. The purpose of this study is to explore the dominant mechanism of bacterial iron reduction in alkaline environments. Materials and methods: We used antraquinone-2,6-disulfonate (AQDS) as a representative of quinone moities of humic substances and elemental sulfur and sulfate as sulfur species to investigate the potential role of humic substances and sulfur species in mediating microbial Fe(III) reduction in alkaline environments. We carried out thermodynamic calculations to predict the ability of bacteria to reduce Fe(III) (oxyhydr)oxides under alkaline conditions and the ability of AQDS and sulfur species to serve as electron acceptors for microbial anaerobic respiration in an assumed alkaline soil environments. A series of incubation experiments with two model dissimilatory metal reducing bacteria, Shewanella oneidensis MR-1 and Geobacter sulfurreducens PCA as well as mixed bacteria enriched from a soil were performed to confirm the contribution of AQDS and sulfur species to Fe(III) reduction under alkaline conditions. Results and discussion: Based on thermodynamic calculations, we predicted that, under alkaline conditions, the enzymatic reduction of Fe(III) (oxyhydr)oxides would be thermodynamically feasible but very weak. In our incubation experiments, the reduction of ferrihydrite by anaerobic cultures of Shewanella oneidensis MR-1, Geobacter sulfurreducens PCA or microbes enriched from a soil was significantly increased in the presence of S0 or AQDS. Notably, AQDS contributed more to promoting Fe(III) reduction as a soluble electron shuttle than S0 did under the alkaline conditions probably because of different mechanisms of microbial utilization of AQDS and S0. Conclusions: These results suggest that microbial reduction of Fe(III) (oxyhydr)oxides under alkaline conditions may proceed via a pathway mediated by electron shuttles such as AQDS and S0. Considering the high ability of electron shuttling and vast distribution of humic substances, we suggest that humic substance-mediated Fe(III) reduction may potentially be the dominant mechanism for Fe(III) reduction in alkaline environments