Expanding genotype/phenotype of neuromuscular diseases by comprehensive target capture/NGS

published_or_final_versio

A Transfer Matrix Method for Resonances in Randall-Sundrum Models

In this paper we discuss in detail a numerical method to study resonances in membranes generated by domain walls in Randall-Sundrum-like scenarios. It is based on similar works to understand the quantum mechanics of electrons subject to the potential barriers that exist in heterostructures in semiconductors. This method was used recently to study resonances of a three form field and lately generalized to arbitrary forms. We apply it to a lot of important models, namely those that contain the Gauge, Gravity and Spinor fields. In many cases we find a rich structure of resonances which depends on the parameters involved.Comment: 25 pages, 17 figure

Establishment of a viable cell detection system for microorganisms in wine based on ethidium monoazide and quantitative PCR

Fermentability and contamination level of wine can be assessed through the detection of viable fermentation-related and spoilage-related microorganisms. Ethidium monoazide in combination with quantitative PCR (EMA-qPCR) has been considered as a promising method to enumerate viable cells. Milling for 80 s by O 500-mu m glass beads is demonstrated to be optimal for DNA extraction from yeasts, lactic acid bacteria (LAB) and acetic acid bacteria (AAB) in wine to be used as a template for PCR. EMA-qPCR results from experiments using DNA extracted by this method correlate well with the results of a plating assay (R-2 > 0.99), and a PCR efficiency between 96% and 105% was obtained. Moreover, for all of these microorganisms, EMA treatment of pure cultures at a low concentration (10 mu g/mL) for 20 min photoactivation resulted in effective differentiation between viable and non-viable cells and had no effect on viable cells. Due to sublethal injury to some cells, underestimation of cell counts was found in most of the wine samples tested using the EMA-qPCR method, and a 40-min incubation in recovery medium could completely offset this error. Our results suggest an optimal glass-bead DNA extraction method and EMA treatment suitable for all of the main microorganisms in wine. The EMA-qPCR method was successfully applied to quantify yeasts. Saccharomyces cerevisiae (S. cerevisiae), LAB, non-Oenococcus oeni LAB (non-O. oeni LAB) and AAB in wine samples. (C) 2012 Elsevier Ltd. All rights reserved

Gender-Related Differences in the Prevalence of Cardiovascular Disease Risk Factors and their Correlates in Urban Tanzania.

\ud Urban areas in Africa suffer a serious problem with dual burden of infectious diseases and emerging chronic diseases such as cardiovascular diseases (CVD) and diabetes which pose a serious threat to population health and health care resources. However in East Africa, there is limited literature in this research area. The objective of this study was to examine the prevalence of cardiovascular disease risk factors and their correlates among adults in Temeke, Dar es Salaam, Tanzania. Results of this study will help inform future research and potential preventive and therapeutic interventions against such chronic diseases. The study design was a cross sectional epidemiological study. A total of 209 participants aged between 44 and 66 years were included in the study. A structured questionnaire was used to evaluate socioeconomic and lifestyle characteristics. Blood samples were collected and analyzed to measure lipid profile and fasting glucose levels. Cardiovascular risk factors were defined using World Health Organization criteria. The age-adjusted prevalence of obesity (BMI > or = 30) was 13% and 35%, among men and women (p = 0.0003), respectively. The prevalence of abdominal obesity was 11% and 58% (p < 0.0001), and high WHR (men: >0.9, women: >0.85) was 51% and 73% (p = 0.002) for men and women respectively. Women had 4.3 times greater odds of obesity (95% CI: 1.9-10.1), 14.2-fold increased odds for abdominal adiposity (95% CI: 5.8-34.6), and 2.8 times greater odds of high waist-hip-ratio (95% CI: 1.4-5.7), compared to men. Women had more than three-fold greater odds of having metabolic syndrome (p = 0.001) compared to male counterparts, including abdominal obesity, low HDL-cholesterol, and high fasting blood glucose components. In contrast, female participants had 50% lower odds of having hypertension, compared to men (95%CI: 0.3-1.0). Among men, BMI and waist circumference were significantly correlated with blood pressure, triglycerides, total, LDL-, and HDL-cholesterol (BMI only), and fasting glucose; in contrast, only blood pressure was positively associated with BMI and waist circumference in women. The prevalence of CVD risk factors was high in this population, particularly among women. Health promotion, primary prevention, and health screening strategies are needed to reduce the burden of cardiovascular disease in Tanzania.\u

Epidemiological survey of orthopedic joint dislocations based on nationwide insurance data in Taiwan, 2000-2005

<p>Abstract</p> <p>Background</p> <p>The epidemiology of acute orthopedic dislocations is poorly understood. A nationwide database provides a valuable resource for examining this issue in the Taiwanese population.</p> <p>Methods</p> <p>A 6-year retrospective cohort study of 1,000,000 randomly-sampled beneficiaries from the year 2005 was used as the original population. Based on the hospitalized and ambulatory data, the concomitant ICD9-CM diagnosis codes and treatment codes were evaluated and classified into 8 and 3 major categories, respectively. The cases matching both inclusive criteria of dislocation-related diagnosis codes and treatment codes were defined as incident cases.</p> <p>Results</p> <p>During 2000-2005, the estimated annual incidence (per 100,000 population) of total orthopedic dislocations in Taiwan was 42.1 (95%CI: 38.1-46.1). The major cause of these orthopedic dislocations was traffic accidents (57.4%), followed by accident falls (27.5%). The annual incidence dislocation by location was shoulder, 15.3; elbow, 7.7; wrist, 3.5; finger, 4.6; hip, 5.2; knee, 1.4; ankle, 2.0; and foot, 2.4. Approximately 16% of shoulder dislocations occurred with other concomitant fractures, compared with 17%, 53%, 16%, 76% and 52%, respectively, of dislocated elbow, wrist, hip, knee, and ankle cases. Including both simple and complex dislocated cases, the mean medical cost was US$612 for treatment of a shoulder dislocation,$504 for the elbow, $1,232 for the wrist,$1,103 for the hip, $1,888 for the knee, and$1,248 for the ankle.</p> <p>Conclusions</p> <p>In Taiwan, three-quarters of all orthopedic dislocations were of the upper limbs. The most common complex fracture-dislocation was of the knee, followed by the wrist and the ankle. Those usually needed a treatment combined with open reduction of fractures and resulted in a higher direct medical expenditure.</p

Cement leakage causes potential thermal injury in vertebroplasty

<p>Abstract</p> <p>Background</p> <p>Percutaneous vertebroplasty by injecting PMMA bone cement into the fractured vertebrae has been widely accepted in treatment of spinal compression fracture. However, the exothermic polymerization of bone cement may cause osseous or neural tissue injury. This study is thus designed to evaluate the potential risk of thermal damage in percutaneous vertebroplasty.</p> <p>Method</p> <p>Twelve porcine vertebrae were immersed in 37°C saline for the experiment. In the first stage of the study, vertebroplasty without cement leakage (control group, n = 6) was simulated. The anterior cortex, foramen, posterior cortex and the center of the vertebral body were selected for temperature measurement. Parameters including peak temperature and duration above 45°C were recorded. In the second stage, a model (n = 6) simulating bone cement leaking into the spinal canal was designed. The methods for temperature measurement were identical to those used in the first stage.</p> <p>Results</p> <p>In Stage 1 of the study (vertebroplasty of the porcine vertebral body in the absence of cement leakage), the average maximal temperature at the anterior cortex was 42.4 ± 2.2°C; at the neural foramen 39.5 ± 2.1°C; at the posterior cortex 40.0 ± 2.5°C and at the vertebral center, 68.1 ± 3.4°C. The average time interval above 45°C was 0 seconds at the anterior cortex; at the neural foramen, 0 seconds; at the posterior cortex, 0 seconds and at the vertebral center, 223 seconds. Thus, except at the core of the bone cement, temperatures around the vertebral body did not exceed 45°C. In Stage 2 of the study (cement leakage model), the average maximal temperature at the anterior cortex was 42.7 ± 2.4°C; at the neural foramen, 41.1 ± 0.4°C; at the posterior cortex, 59.1 ± 7.6°C and at the vertebral center, 77.3 ± 5.7°C. The average time interval above 45°C at the anterior cortex was 0 seconds; at the neural foramen, 0 seconds; at the posterior cortex, 329.3 seconds and at the vertebral center, 393.2 seconds. Based on these results, temperatures exceeded 45°C at the posterior cortex and at the vertebral center.</p> <p>Conclusions</p> <p>The results indicated that, for bone cement confined within the vertebra, curing temperatures do not directly cause thermal injury to the nearby soft tissue. If bone cement leaks into the spinal canal, the exothermic reaction at the posterior cortex might result in thermal injury to the neural tissue.</p

Transcriptome Fingerprinting Analysis: An Approach to Explore Gene Expression Patterns in Marine Microbial Communities

Microbial transcriptomics are providing new insights into the functional processes of microbial communities. However, analysis of each sample is still expensive and time consuming. A rapid and low cost method that would allow the identification of the most interesting samples for posterior in-depth metatranscriptomics analysis would be extremely useful. Here we present Transcriptome Fingerprinting Analysis (TFA) as an approach to fulfill this objective in microbial ecology studies. We have adapted the differential display technique for mRNA fingerprinting based on the PCR amplification of expressed transcripts to interrogate natural microbial eukaryotic communities. Unlike other techniques, TFA does not require prior knowledge of the mRNA sequences to be detected. We have used a set of arbitrary primers coupled with a fluorescence labeled primer targeting the poly(A) tail of the eukaryotic mRNA, with further detection of the resulting labeled cDNA products in an automated genetic analyzer. The output represented by electropherogram peak patterns allowed the comparison of a set of genes expressed at the time of sampling. TFA has been optimized by testing the sensitivity of the method for different initial RNA amounts, and the repeatability of the gene expression patterns with increasing time after sampling both with cultures and environmental samples. Results show that TFA is a promising approach to explore the dynamics of gene expression patterns in microbial communities

A Link between Prompt Optical and Prompt Gamma-Ray Emission in Gamma-Ray Bursts

The prompt optical emission that arrives with gamma-rays from a cosmic gamma-ray burst (GRB) is a signature of the engine powering the burst, the properties of the ultra-relativistic ejecta of the explosion, and the ejecta's interactions with the surroundings. Until now, only GRB 990123 had been detected at optical wavelengths during the burst phase. Its prompt optical emission was variable and uncorrelated with the prompt gamma-ray emission, suggesting that the optical emission was generated by a reverse shock arising from the ejecta's collision with the surrounding material. Here we report prompt optical emission from GRB 041219a. It is variable and correlated with the prompt gamma-rays, indicating a common origin for the optical light and the gamma-rays. Within the context of the standard fireball model of GRBs, we attribute this new optical component to internal shocks driven into the burst ejecta by variations of the inner engine. The correlated optical emission is a direct probe of the jet isolated from the medium. The timing of the uncorrelated optical emission is strongly dependent on the nature of the medium.Comment: 9 pages, 4 figures. Note: This paper has been accepted for publication in Nature, but is embargoed for discussion in the popular press until formal publication in Nature. Resubmit - Added table comparing Swift and RAPTOR dat

Membrane transport of camptothecin: facilitation by human P-glycoprotein (ABCB1) and multidrug resistance protein 2 (ABCC2)

BACKGROUND: The purpose of the present study was to continue the investigation of the membrane transport mechanisms of 20-(S)-camptothecin (CPT) in order to understand the possible role of membrane transporters on its oral bioavailability and disposition. METHODS: The intestinal transport kinetics of CPT were characterized using Caco-2 cells, MDCKII wild-type cells and MDCKII cells transfected with human P-glycoprotein (PGP) (ABCB1) or human multidrug resistance protein 2 (MRP2) (ABCC2). The effects of drug concentration, inhibitors and temperature on CPT directional permeability were determined. RESULTS: The absorptive (apical to basolateral) and secretory (basolateral to apical) permeabilities of CPT were found to be saturable. Reduced secretory CPT permeabilities with decreasing temperatures suggests the involvement of an active, transporter-mediated secretory pathway. In the presence of etoposide, the CPT secretory permeability decreased 25.6%. However, inhibition was greater in the presence of PGP and of the breast cancer resistant protein inhibitor, GF120918 (52.5%). The involvement of additional secretory transporters was suggested since the basolateral to apical permeability of CPT was not further reduced in the presence of increasing concentrations of GF120918. To investigate the involvement of specific apically-located secretory membrane transporters, CPT transport studies were conducted using MDCKII/PGP cells and MDCKII/MRP2 cells. CPT carrier-mediated permeability was approximately twofold greater in MDCKII/PGP cells and MDCKII/MRP2 cells than in MDCKII/wild-type cells, while the apparent K(m )values were comparable in all three cell lines. The efflux ratio of CPT in MDCKII/PGP in the presence of 0.2 μM GF120918 was not completely reversed (3.36 to 1.49). However, the decrease in the efflux ratio of CPT in MDCKII/MRP2 cells (2.31 to 1.03) suggests that CPT efflux was completely inhibited by MK571, a potent inhibitor of the Multidrug Resistance Protein transporter family. CONCLUSIONS: The current results provide evidence that PGP and MRP2 mediate the secretory transport of CPT in vitro. However, the involvement of other transporters cannot be ruled out based on these studies. Since these transporters are expressed in the intestine, liver and kidney variations in their expression levels and/or regulation may be responsible for the erratic oral absorption and biliary excretion of CPT observed in human subjects