An Assessment of the Role of DNA Adenine Methyltransferase on Gene Expression Regulation in E coli

N6-Adenine methylation is an important epigenetic signal, which regulates various processes, such as DNA replication and repair and transcription. In γ-proteobacteria, Dam is a stand-alone enzyme that methylates GATC sites, which are non-randomly distributed in the genome. Some of these overlap with transcription factor binding sites. This work describes a global computational analysis of a published Dam knockout microarray alongside other publicly available data to throw insights into the extent to which Dam regulates transcription by interfering with protein binding. The results indicate that DNA methylation by DAM may not globally affect gene transcription by physically blocking access of transcription factors to binding sites. Down-regulation of Dam during stationary phase correlates with the activity of TFs whose binding sites are enriched for GATC sites

Technology transfer model for Austrian higher education institutions

The aim of this paper is to present the findings of a PhD research (Heinzl 2007, Unpublished PhD Thesis) conducted on the Universities of Applied Sciences in Austria. Four of the models that emerge from this research are: Generic Technology Transfer Model (Sect. 5.1); Idiosyncrasies Model for the Austrian Universities of Applied Sciences (Sect. 5.2); Idiosyncrasies-Technology Transfer Effects Model (Sect. 5.3); Idiosyncrasies-Technology Transfer Cumulated Effects Model (Sect. 5.3). The primary and secondary research methods employed for this study are: literature survey, focus groups, participant observation, and interviews. The findings of the research contribute to a conceptual design of a technology transfer system which aims to enhance the higher education institutions' technology transfer performance. © 2012 Springer Science+Business Media, LLC

A Differentiation-Based Phylogeny of Cancer Subtypes

Histopathological classification of human tumors relies in part on the degree of differentiation of the tumor sample. To date, there is no objective systematic method to categorize tumor subtypes by maturation. In this paper, we introduce a novel computational algorithm to rank tumor subtypes according to the dissimilarity of their gene expression from that of stem cells and fully differentiated tissue, and thereby construct a phylogenetic tree of cancer. We validate our methodology with expression data of leukemia, breast cancer and liposarcoma subtypes and then apply it to a broader group of sarcomas. This ranking of tumor subtypes resulting from the application of our methodology allows the identification of genes correlated with differentiation and may help to identify novel therapeutic targets. Our algorithm represents the first phylogeny-based tool to analyze the differentiation status of human tumors

Global Gene Expression Profiling Of Human Pleural Mesotheliomas: Identification of Matrix Metalloproteinase 14 (MMP-14) as Potential Tumour Target

BACKGROUND:The goal of our study was to molecularly dissect mesothelioma tumour pathways by mean of microarray technologies in order to identify new tumour biomarkers that could be used as early diagnostic markers and possibly as specific molecular therapeutic targets. METHODOLOGY:We performed Affymetrix HGU133A plus 2.0 microarray analysis, containing probes for about 39,000 human transcripts, comparing 9 human pleural mesotheliomas with 4 normal pleural specimens. Stringent statistical feature selection detected a set of differentially expressed genes that have been further evaluated to identify potential biomarkers to be used in early diagnostics. Selected genes were confirmed by RT-PCR. As reported by other mesothelioma profiling studies, most of genes are involved in G2/M transition. Our list contains several genes previously described as prognostic classifier. Furthermore, we found novel genes, never associated before to mesotheliom that could be involved in tumour progression. Notable is the identification of MMP-14, a member of matrix metalloproteinase family. In a cohort of 70 mesothelioma patients, we found by a multivariate Cox regression analysis, that the only parameter influencing overall survival was expression of MMP14. The calculated relative risk of death in MM patients with low MMP14 expression was significantly lower than patients with high MMp14 expression (P = 0.002). CONCLUSIONS:Based on the results provided, this molecule could be viewed as a new and effective therapeutic target to test for the cure of mesothelioma

Individualized markers optimize class prediction of microarray data

BACKGROUND: Identification of molecular markers for the classification of microarray data is a challenging task. Despite the evident dissimilarity in various characteristics of biological samples belonging to the same category, most of the marker – selection and classification methods do not consider this variability. In general, feature selection methods aim at identifying a common set of genes whose combined expression profiles can accurately predict the category of all samples. Here, we argue that this simplified approach is often unable to capture the complexity of a disease phenotype and we propose an alternative method that takes into account the individuality of each patient-sample. RESULTS: Instead of using the same features for the classification of all samples, the proposed technique starts by creating a pool of informative gene-features. For each sample, the method selects a subset of these features whose expression profiles are most likely to accurately predict the sample's category. Different subsets are utilized for different samples and the outcomes are combined in a hierarchical framework for the classification of all samples. Moreover, this approach can innately identify subgroups of samples within a given class which share common feature sets thus highlighting the effect of individuality on gene expression. CONCLUSION: In addition to high classification accuracy, the proposed method offers a more individualized approach for the identification of biological markers, which may help in better understanding the molecular background of a disease and emphasize the need for more flexible medical interventions

Effect of Synthetic Dietary Triglycerides: A Novel Research Paradigm for Nutrigenomics

The effect of dietary fats on human health and disease are likely mediated by changes in gene expression. Several transcription factors have been shown to respond to fatty acids, including SREBP-1c, NF-kappaB, RXRs, LXRs, FXR, HNF4alpha, and PPARs. However, it is unclear to what extent these transcription factors play a role in gene regulation by dietary fatty acids in vivo

Avelumab, an anti-PD-L1 antibody, in patients with locally advanced or metastatic breast cancer: a phase 1b JAVELIN Solid Tumor study

PURPOSE: Agents targeting programmed death receptor 1 (PD-1) or its ligand (PD-L1) have shown antitumor activity in the treatment of metastatic breast cancer (MBC). The aim of this study was to assess the activity of avelumab, a PD-L1 inhibitor, in patients with MBC. METHODS: In a phase 1 trial (JAVELIN Solid Tumor; NCT01772004), patients with MBC refractory to or progressing after standard-of-care therapy received avelumab intravenously 10 mg/kg every 2 weeks. Tumors were assessed every 6 weeks by RECIST v1.1. Adverse events (AEs) were graded by NCI-CTCAE v4.0. Membrane PD-L1 expression was assessed by immunohistochemistry (Dako PD-L1 IHC 73-10 pharmDx). RESULTS: A total of 168 patients with MBC, including 58 patients with triple-negative breast cancer (TNBC), were treated with avelumab for 2-50 weeks and followed for 6-15 months. Patients were heavily pretreated with a median of three prior therapies for metastatic or locally advanced disease. Grade >/= 3 treatment-related AEs occurred in 13.7% of patients, including two treatment-related deaths. The confirmed objective response rate (ORR) was 3.0% overall (one complete response and four partial responses) and 5.2% in patients with TNBC. A trend toward a higher ORR was seen in patients with PD-L1+ versus PD-L1- tumor-associated immune cells in the overall population (16.7% vs. 1.6%) and in the TNBC subgroup (22.2% vs. 2.6%). CONCLUSION: Avelumab showed an acceptable safety profile and clinical activity in a subset of patients with MBC. PD-L1 expression in tumor-associated immune cells may be associated with a higher probability of clinical response to avelumab in MBC

Valeur prédictive du dosage sérique de la FSH au 3ème jour d'un cycle "semi-naturel" en fécondation in vitro

PARIS-BIUM (751062103) / SudocCentre Technique Livre Ens. Sup. (774682301) / SudocSudocFranceF

Alternative and Legacy Perfluoroalkyl Substances: Differences between European and Chinese River/Estuary Systems

The production and use of long-chain perfluoroalkyl substances (PFASs) must comply with national and international regulations. Driven by increasingly stringent regulations, their production has been outsourced to less regulated countries in Asia: In addition, the fluoropolymer industry started to use fluorinated alternatives, such as 2,3,3,3-tetrafluoro-2-(1,1,2,2,3,3,3-heptafluoropropoxy)propanoic acid (HFPO-DA). Between August 2013 and September 2014, we investigated the occurrence and distribution of HFPO-DA and legacy PFASs in surface waters of the following river/estuary systems: the Elbe and Rhine Rivers in Germany, the Rhine-Meuse delta in The Netherlands, and the Xiaoqing River in China. Distinct differences were revealed among the study areas; notably, the Chinese samples were highly polluted by an industrial point source discharging mainly perfluorooctanoic acid (PFOA). This particular point solute resulted in concentrations more than 6000 times higher than an industrial point source observed in the Scheur River, where HFPO-DA was the dominant compound with a concentration of 73.1 ng/L. Moreover, HFPO-DA was detected in all Samples along the coastline of the North Sea, indicating that the compound may be transported from the Rhine-Meuse delta into the German Bight via the water current. To the best of our knowledge, the fluorinated alternative, HFPO-DA, was detected for the first time in surface Waters of Germany and China