398 research outputs found
An Urbanism oriented towards rail in Germany and France: selected findings of the Bahn.Ville project
Transit oriented development has become in the recent years a topic of high interest both for researchers and for practitioners. The French-German project Bahn.Ville 2 has the objective of testing the principles of an urbanism orientated towards rail by implementation on two regional railway lines (St. Etienne â Firminy, Lyon metropolitan region as well as Taunusbahn, Frankfurt/Rhein-Main region). This paper is presenting selected results on - innovations in regional planning instruments in France (SchĂ©ma de CohĂ©rence Territorial) and Germany (Regionaler FlĂ€chennutzungsplan) and their respective for a better integration of land-use and transport, - specific observations on neighborhood mobility in the station surrounding and propositions for high quality walking environments as well as - the potential of an observation tool designed to support public intervention on land-use and transport around stations. The results constitute three original contributions of the Bahn.Ville 2 project in the sense of the support sustainable mobility by an urbanism orientated towards rail
Altered Serum IgG Levels to a-Synuclein in Dementia with Lewy Bodies and Alzheimerâs Disease.
Natural self-reactive antibodies in the peripheral blood may play a considerable role in the control of potentially toxic proteins that may otherwise accumulate in the aging brain. The significance of serum antibodies reactive against asynuclein is not well known. We explored serum IgG levels to monomeric a-synuclein in dementia with Lewy bodies (DLB) and Alzheimerâs disease (AD) with a novel and validated highly sensitive ELISA assay. Antibody levels revealed stark differences in patients compared to healthy subjects and were dependent on diagnosis, disease duration and age. Anti-asynuclein IgG levels were increased in both patient groups, but in early DLB to a much greater extent than in AD. Increased antibody levels were most evident in younger patients, while with advanced age relatively low levels were observed, similar to healthy individuals, exhibiting stable antibody levels independent of age. Our data show the presence of differentially altered IgG levels against a-synuclein in DLB and AD, which may relate to a disturbed a-synuclein homeostasis triggered by the disease process. These observations may foster the development of novel, possibly preclinical biomarkers and immunotherapeutic strategies that target a-synuclein in neurodegenerative disease.Fil: Koehler, Niklas. Department of Psychiatry and Psychotherapy. EBERHARD-KARLS-UNIVERSITY;Fil: Stransky, Elke. Department of Psychiatry and Psychotherapy. EBERHARD-KARLS-UNIVERSITY;Fil: Shing, Mona. Department of Psychiatry and Psychotherapy. EBERHARD-KARLS-UNIVERSITY;Fil: Gaertner, Susanne. Department of Psychiatry and Psychotherapy, EBERHARD-KARLS-UNIVERSITY;Fil: Meyer, Mirjam. Department of Psychiatry and Psychotherapy. EBERHARD-KARLS-UNIVERSITY;Fil: Schreitmueller, Brigitte. Department of Psychiatry and Psychotherapy. EBERHARD-KARLS-UNIVERSITY;Fil: Leyhe, Thomas. Department of Psychiatry and Psychotherapy. EBERHARD-KARLS-UNIVERSITY;Fil: Laske, Cristoph. Department of Psychiatry and Psychotherapy. EBERHARD-KARLS-UNIVERSITY;Fil: Maetzler, Walter. Department of Neurodegeneration. HERTIE INSTITUTE FOR CLINICAL BRAIN RESEARCH;Fil: Kahle, Philipp. FUNCTIONAL NEUROGENETICS. HERTIE INSTITUTE FOR CLINICAL;Fil: Celej, Maria Soleda. MAX-PLANCK-INSTITUTE FOR BIOPHYSICAL CHEMISTRY; Consejo Nacional de Invest.cientif.y Tecnicas. Centro Cientifico Tecnol.conicet - Cordoba. Centro de Invest.en Qca.biol.de Cordoba (p);Fil: Jovin, Thomas M.. MAX-PLANCK-INSTITUTE FOR BIOPHYSICAL CHEMISTRY;Fil: Fallgatter, Andreas. Department of Psychiatry and Psychotherapy. EBERHARD-KARLS-UNIVERSITY;Fil: Batra, Anil. Department of Psychiatry and Psychotherapy. EBERHARD-KARLS-UNIVERSITY;Fil: Buchkremer, Gherard. Department of Psychiatry and Psychotherapy. EBERHARD-KARLS-UNIVERSITY;Fil: Schott, Klauss. Department of Psychiatry and Psychotherapy. EBERHARD-KARLS-UNIVERSITY;Fil: Richartz-Salzburger, Elke. Department of Psychiatry and Psychotherapy. EBERHARD-KARLS-UNIVERSITY
STAR-Fusion: Fast and Accurate Fusion Transcript Detection from RNA-Seq
Motivation Fusion genes created by genomic rearrangements can be potent drivers of tumorigenesis. However, accurate identification of functionally fusion genes from genomic sequencing requires whole genome sequencing, since exonic sequencing alone is often insufficient. Transcriptome sequencing provides a direct, highly effective alternative for capturing molecular evidence of expressed fusions in the precision medicine pipeline, but current methods tend to be inefficient or insufficiently accurate, lacking in sensitivity or predicting large numbers of false positives. Here, we describe STAR-Fusion, a method that is both fast and accurate in identifying fusion transcripts from RNA-Seq data.
Results We benchmarked STAR-Fusionâs fusion detection accuracy using both simulated and genuine Illumina paired-end RNA-Seq data, and show that it has superior performance compared to popular alternative fusion detection methods.
Availability and implementation STAR-Fusion is implemented in Perl, freely available as open source software at http://star-fusion.github.io, and supported on Linux
Scientific, Technical and Economic Committee for Fisheries (STECF) : 64th Plenary Report (PLEN-20-02)
The Scientific, Technical and Economic Committee for Fisheries (STECF) held its 64th plenary as a virtual meeting from 6-10 July 2020.-- 128 pagesCommission Decision of 25 February 2016 setting up a Scientific, Technical and Economic Committee for Fisheries, C(2016) 1084, OJ C 74, 26.2.2016, p. 4â10. The Commission may consult the group on any matter relating to marine and fisheries biology, fishing gear technology, fisheries economics, fisheries governance, ecosystem effects of fisheries, aquaculture or similar discipline
Scientific, technical and economic committee for fisheries â 64th plenary report (PLEN-20-02)
Commission Decision of 25 February 2016 setting up a Scientific, Technical and Economic Committee for Fisheries, C(2016) 1084, OJ C 74, 26.2.2016, p. 4â10. The Commission may consult the group on any matter relating to marine and fisheries biology, fishing gear technology, fisheries economics, fisheries governance, ecosystem effects of fisheries, aquaculture or similar disciplines. The Scientific, Technical and Economic Committee for Fisheries held its 64th plenary as a virtual meeting from 6 to 10 July 2020
FRA2 is a STAT5 target gene regulated by IL-2 in human CD4 T cells
Signal transducers and activators of transcription 5(STAT5) are cytokine induced signaling proteins, which regulate key immunological processes, such as tolerance induction, maintenance of homeostasis, and CD4 T-effector cell differentiation. In this study, transcriptional targets of STAT5 in CD4 T cells were studied by Chromatin Immunoprecipitation (ChIP). Genomic mapping of the sites cloned and identified in this study revealed the striking observation that the majority of STAT5-binding sites mapped to intergenic (>50 kb upstream) or intronic, rather than promoter proximal regions. Of the 105 STAT5 responsive binding sites identified, 94% contained the canonical (IFN-Îł activation site) GAS motifs. A number of putative target genes identified here are associated with tumor biology. Here, we identified Fos-related antigen 2 (FRA2) as a transcriptional target of IL-2 regulated STAT5. FRA2 is a basic -leucine zipper (bZIP) motif 'Fos' family transcription factor that is part of the AP-1 transcription factor complex and is also known to play a critical role in the progression of human tumours and more recently as a determinant of T cell plasticity. The binding site mapped to an internal intron within the FRA2 gene. The epigenetic architecture of FRA2, characterizes a transcriptionally active promoter as indicated by enrichment for histone methylation marks H3K4me1, H3K4me2, H3K4me3, and transcription/elongation associated marks H2BK5me1 and H4K20me1. FRA2 is regulated by IL-2 in activated CD4 T cells. Consistently, STAT5 bound to GAS sequence in the internal intron of FRA2 and reporter gene assays confirmed IL-2 induced STAT5 binding and transcriptional activation. Furthermore, addition of JAK3 inhibitor (R333) or Daclizumab inhibited the induction in TCR stimulated cells. Taken together, our data suggest that FRA2 is a novel STAT5 target gene, regulated by IL-2 in activated CD4 T cells
Medulloblastoma Exome Sequencing Uncovers Subtype-Specific Somatic Mutations
Medulloblastomas are the most common malignant brain tumors in children1. Identifying and understanding the genetic events that drive these tumors is critical for the development of more effective diagnostic, prognostic and therapeutic strategies. Recently, our group and others described distinct molecular subtypes of medulloblastoma based on transcriptional and copy number profiles2â5. Here, we utilized whole exome hybrid capture and deep sequencing to identify somatic mutations across the coding regions of 92 primary medulloblastoma/normal pairs. Overall, medulloblastomas exhibit low mutation rates consistent with other pediatric tumors, with a median of 0.35 non-silent mutations per megabase. We identified twelve genes mutated at statistically significant frequencies, including previously known mutated genes in medulloblastoma such as CTNNB1, PTCH1, MLL2, SMARCA4 and TP53. Recurrent somatic mutations were identified in an RNA helicase gene, DDX3X, often concurrent with CTNNB1 mutations, and in the nuclear co-repressor (N-CoR) complex genes GPS2, BCOR, and LDB1, novel findings in medulloblastoma. We show that mutant DDX3X potentiates transactivation of a TCF promoter and enhances cell viability in combination with mutant but not wild type beta-catenin. Together, our study reveals the alteration of Wnt, Hedgehog, histone methyltransferase and now N-CoR pathways across medulloblastomas and within specific subtypes of this disease, and nominates the RNA helicase DDX3X as a component of pathogenic beta-catenin signaling in medulloblastoma
Concevoir la ville à partir des gares, Rapport final du Projet Bahn.Ville 2 sur un urbanisme orienté vers le rail
ExpĂ©rimenter de nouvelles façons de faire de l'amĂ©nagement et du dĂ©veloppement urbain autour des gares ? C'est l'objectif du projet franco-allemand Bahn.Ville 2, recherche-action qui vise Ă promouvoir « un urbanisme orientĂ© vers le rail ». Valoriser les investissements faits sur les lignes ferroviaires rĂ©gionales pĂ©riurbaines par des mesures d'accompagnement dans le domaine de l'urbanisme, optimiser les conditions d'accessibilitĂ© aux gares de ces lignes, amĂ©liorer la qualitĂ© du service rendu aux usagers dans les lieux d'Ă©changes autour de ces gare telles sont les ambitions de ce projet rĂ©alisĂ© sur la pĂ©riode 2007-2009. Il s'agit de tester les conditions de la mise en Ćuvre d'un urbanisme orientĂ© vers le rail
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