Multi-ancestry genome-wide association meta-analysis of Parkinson?s disease

Although over 90 independent risk variants have been identified for Parkinson’s disease using genome-wide association studies, most studies have been performed in just one population at a time. Here we performed a large-scale multi-ancestry meta-analysis of Parkinson’s disease with 49,049 cases, 18,785 proxy cases and 2,458,063 controls including individuals of European, East Asian, Latin American and African ancestry. In a meta-analysis, we identified 78 independent genome-wide significant loci, including 12 potentially novel loci (MTF2, PIK3CA, ADD1, SYBU, IRS2, USP8, PIGL, FASN, MYLK2, USP25, EP300 and PPP6R2) and fine-mapped 6 putative causal variants at 6 known PD loci. By combining our results with publicly available eQTL data, we identified 25 putative risk genes in these novel loci whose expression is associated with PD risk. This work lays the groundwork for future efforts aimed at identifying PD loci in non-European populations

Dietary supplementation of N-carbamylglutamate promotes growth performance by modulating the homeostasis of gut microbiota in tilapia (Oreochromis niloticus)

N-carbamylglutamate (NCG) supplementation promotes the synthesis of arginine, improves physiological parameters and modulates gut function in fish. However, its beneficial effect on the fish gut microbiota remains unclear. Thus, we investigated the beneficial effect of NCG on homeostasis of gut microbiota in tilapia. Tilapia were fed with diets supplemented with different levels of dietary NCG (Ctrl, NCGI and NCGII) for 8 weeks. The weight gain and the specific growth rate were significantly higher (p < 0.05) in NCG-supplemented groups compared to the group Ctrl. Moreover, the V3-V4 region of 16S rDNA was sequenced, and the bioinformatic analysis suggested that dietary NCG supplementation had a limited impact on the α-diversity of gut microbiota, while Non-metric multidimensional scaling analysis (NMDS) showed that dietary NCG leads to a clear separation on gut microbiota among the three groups. Furthermore, NCG supplementation reshaped the tilapia gut microbiota community, according to co-occurrence analysis and metabolic pathways prediction via PICRUSt analysis, leading to an enrichment of nutritional metabolism related functions, such as amino acid and lipid metabolisms (p < 0.05). Subsequently, the redundancy analysis (RDA) demonstrated that the structural changes of gut microbiota were determined by NCG concentration. In addition, the linear discriminant analysis effect size (LEfSe) analysis revealed 65 differentially abundant taxonomic clades were dominant in tilapia supplemented with NCG. The cross-validation and Random Forest model identified 12 key bacterial taxa in response to the NCG supplementation. Among them, four key bacterial taxa played a fundamental role in nitrogen-fixing, which may indicate that NCG increases the amino acid biosynthesis of gut microbiota and contributes to the growth promotion of tilapia

Breast Cancer: Early Prediction of Response to Neoadjuvant Chemotherapy Using Parametric Response Maps for MR Imaging

Purpose: To prospectively compare the performance of dynamic contrast material-enhanced (DCE) magnetic resonance (MR) imaging using parametric response map (PRM) analysis with that using pharmacokinetic parameters (transfer constant [K-trans], rate constant [k(ep)], and relative extravascular extracellular space [v(e)]) in the early prediction of pathologic responses to neoadjuvant chemotherapy (NAC) in breast cancer patients. Materials and Methods: The institutional review board approved this study; informed consent was obtained. Between August 2010 and December 2012, 48 women (mean age, 46.4 years; range, 29-65 years) with breast cancer were enrolled and treated with an anthracycline-taxane regimen. DCE MR imaging was performed before and after the first cycle of chemotherapy, and the pathologic response was assessed after surgery. Tumor size and volume, PRM characteristics, and pharmacokinetic parameters (K-trans, k(ep), and v(e)) on MR images were assessed and compared according to the pathologic responses by using the Fisher exact test or the independent-sample t test. Results: Six of 48 (12%) patients showed pathologic complete response (CR) (pCR) and 42 (88%) showed nonpathologic CR (npCR). Thirty-eight (79%) patients showed a good response (Miller-Payne score of 3, 4, or 5), and 10 (21%) showed a minor response (Miller-Payne score of 1 or 2). The mean proportion of voxels with increased signal intensity (PRMSI+) in the pCR or good response group was significantly lower than that in the npCR or minor response group (14.0% +/- 6.5 vs 40.7% +/- 27.2, P < .001; 34.3% +/- 26.4 vs 52.8% +/- 24.9, P =.041). Area under the receiver operating characteristic curve for PRMSI+ in the pCR group was 0.770 (95% confidence interval: 0.626, 0.879), and that for the good response group was 0.716 (95% confidence interval: 0.567, 0.837). No difference in tumor size, tumor volume, or pharmacokinetic parameters was found between groups. Conclusion: PRM analysis of DCE MR images may enable the early identification of the pathologic response to NAC after the first cycle of chemotherapy, whereas pharmacokinetic parameters (K-trans, k(ep), and v(e)) do not. (C) RSNA, 201

Shape stabilised phase change materials based on a high melt viscosity HDPE and paraffin waxes

Shape stabilised phase change materials (SSPCMs) based on a high density poly(ethylene)(hv-HDPE) with high (H-PW, Tm = 56–58 °C) and low (L-PW, Tm = 18–23 °C) melting point paraffin waxes were readily prepared using twin-screw extrusion. The thermo-physical properties of these materials were assessed using a combination of techniques and their suitability for latent heat thermal energy storage (LHTES) assessed. The melt processing temperature (160 °C) of the HDPE used was well below the onset of thermal decomposition of H-PW (220 °C), but above that for L-PW (130 °C), although the decomposition process extended over a range of 120 °C and the residence time of L-PW in the extruder was <30 s. The SSPCMs prepared had latent heats up to 89 J/g and the enthalpy values for H-PW in the respective blends decreased with increasing H-PW loading, as a consequence of co-crystallisation of H-PW and hv-HDPE. Static and dynamic mechanical analysis confirmed both waxes have a plasticisation effect on this HDPE. Irrespective of the mode of deformation (tension, flexural, compression) modulus and stress decreased with increased wax loading in the blend, but the H-PW blends were mechanically superior to those with L-PW