High MIG (CXCL9) plasma levels favours response to peginterferon and ribavirin in HCV-infected patients regardless of DPP4 activity

Sustained virological response (SVR) following peginterferon (pegIFN) and ribavirin (RBV) treatment in hepatitis C virus (HCV) infected patients has been linked with the IL28B genotype and lower peripheral levels of the CXCR3-binding chemokine IP-10 (CXCL10). To further improve the understanding of these biomarkers we investigated plasma levels of the other CXCR3-binding chemokines and activity of the dipeptidyl peptidase IV (DPP4, CD26) protease, which cleaves IP-10, in relation to treatment response

Sustained synchronized neuronal network activity in a human astrocyte co-culture system

Impaired neuronal network function is a hallmark of neurodevelopmental and neurodegenerative disorders such as autism, schizophrenia, and Alzheimer's disease and is typically studied using genetically modified cellular and animal models. Weak predictive capacity and poor translational value of these models urge for better human derived in vitro models. The implementation of human induced pluripotent stem cells (hiPSCs) allows studying pathologies in differentiated disease-relevant and patient-derived neuronal cells. However, the differentiation process and growth conditions of hiPSC-derived neurons are non-trivial. In order to study neuronal network formation and (mal) function in a fully humanized system, we have established an in vitro co-culture model of hiPSC-derived cortical neurons and human primary astrocytes that recapitulates neuronal network synchronization and connectivity within three to four weeks after final plating. Live cell calcium imaging, electrophysiology and high content image analyses revealed an increased maturation of network functionality and synchronicity over time for co-cultures compared to neuronal monocultures. The cells express GABAergic and glutamatergic markers and respond to inhibitors of both neurotransmitter pathways in a functional assay. The combination of this co-culture model with quantitative imaging of network morphofunction is amenable to high throughput screening for lead discovery and drug optimization for neurological diseases

HER2 Status in Ovarian Carcinomas: A Multicenter GINECO Study of 320 Patients

BACKGROUND: Despite a typically good response to first-line combination chemotherapy, the prognosis for patients with advanced ovarian cancer remains poor because of acquired chemoresistance. The use of targeted therapies such as trastuzumab may potentially improve outcomes for patients with ovarian cancer. HER2 overexpression/amplification has been reported in ovarian cancer, but the exact percentage of HER2-positive tumors varies widely in the literature. In this study, HER2 gene status was evaluated in a large, multicentric series of 320 patients with advanced ovarian cancer, including 243 patients enrolled in a multicenter prospective clinical trial of paclitaxel/carboplatin-based chemotherapy. METHODOLOGY/PRINCIPAL FINDINGS: The HER2 status of primary tumors and metastases was evaluated by both immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) analysis of paraffin-embedded tissue on conventional slides. The prognostic impact of HER2 expression was analyzed. HER2 gene was overexpressed and amplified in 6.6% of analyzed tumors. Despite frequent intratumoral heterogeneity, no statistically significant difference was detected between primary tumors and corresponding metastases. CONCLUSIONS/SIGNIFICANCE: Our results show that the decision algorithm usually used in breast cancer (IHC as a screening test, with equivocal results confirmed by FISH) is appropriate in ovarian cancer. In contrast to previous series, HER2-positive status did not influence outcome in the present study, possibly due to the fact that patients in our study received paclitaxel/carboplatin-based chemotherapy. This raises the question of whether HER2 status and paclitaxel sensitively are linked

Application de la génomique en recherche clinique ( Etude des altérations quantitatives du génome tumoral à partir de tissus fixés et inclus en paraffineparaffine)

LE KREMLIN-B.- PARIS 11-BU Méd (940432101) / SudocSudocFranceF

cn.FARMS: a probabilistic model to detect DNA copy numbers

Motivation: Existing pre-processing methods for DNA microarrays designed to detect copy number variations (CNVs) lead to high false discovery rates (FDRs). High FDRs misguide researchers especially in the medical context where CNVs are wrongly associated with diseases. We propose a probabilistic latent variable model, cn.FARMS, for array-based CNV analysis which controls the FDR without loss of sensitivity. At a DNA region, cn.FARMS constructs a model by a Bayesian maximum a posteriori estimation where the unobserved, latent variable represents the copy number that is measured by observed genetic markers (probes). The latent variable’s prior prefers parameters which represent the null hypothesis, (same copy number for all samples), from which the posterior can only deviate by a high information content in the data. The more probes agree on the region’s copy number, the less is the uncertainty about the latent variable’s value, the higher is the information content. 
Results: We compared cn.FARMS on a HapMap Mapping250K_Nsp and SNP6.0 benchmark data set to CRMAv2 and dChip. The comparison is based on the sex determination based on the data from the X chromosome, where males possess one copy and females two. The ROC curve serves to compare the FDR for different true positive rates. In both experiments cn.FARMS yielded the best classification results.
Availability: This approach is publicly available in R at http://www.bioinf.jku.at/softwar

Percentage of mapped reads to the HCMV transcriptome in primary cell types.

<p>Six different blood donors (A-F) were processed to obtain monocytes which were differentiated to DCs, MΦ1 and MΦ2. Subsequently, these primary cell types were infected with TB40/E at MOI5. As a comparison, we infected NHDF cells (n = 3) at MOI 0.16, MOI 0.5 and MOI 5. Given in the top panel are the percentages of mapped reads on the HCMV genome for each cell type.</p