03413nas a2200793 4500008004100000022001400041245009300055210006900148260001600217300000900233490000600242520096600248653001201214653001401226653002301240653001801263653003601281653003001317653001101347653003101358653001101389653002401400653002101424653001201445653002801457653002501485653004101510653001601551653000901567653000901576653002301585653001501608653003901623653001701662653003001679653003401709100002801743700002201771700003201793700002901825700002601854700002601880700003101906700003301937700002201970700003101992700001902023700002002042700002002062700002202082700002002104700002302124700001602147700002302163700002302186700002302209700001902232700002502251700002902276700002102305700002502326700003202351700001602383700001802399700003802417700001702455700002402472856012302496 2018 eng d a2041-172300aLRH-1 agonism favours an immune-islet dialogue which protects against diabetes mellitus.0 aLRH1 agonism favours an immuneislet dialogue which protects agai c2018 Apr 16 a14880 v93 a

Type 1 diabetes mellitus (T1DM) is due to the selective destruction of islet beta cells by immune cells. Current therapies focused on repressing the immune attack or stimulating beta cell regeneration still have limited clinical efficacy. Therefore, it is timely to identify innovative targets to dampen the immune process, while promoting beta cell survival and function. Liver receptor homologue-1 (LRH-1) is a nuclear receptor that represses inflammation in digestive organs, and protects pancreatic islets against apoptosis. Here, we show that BL001, a small LRH-1 agonist, impedes hyperglycemia progression and the immune-dependent inflammation of pancreas in murine models of T1DM, and beta cell apoptosis in islets of type 2 diabetic patients, while increasing beta cell mass and insulin secretion. Thus, we suggest that LRH-1 agonism favors a dialogue between immune and islet cells, which could be druggable to protect against diabetes mellitus.

10aAnimals10aApoptosis10aCell Communication10aCell Survival10aDiabetes Mellitus, Experimental10aDiabetes Mellitus, Type 210aFemale10aGene Expression Regulation10aHumans10aHypoglycemic Agents10aImmunity, Innate10ainsulin10aInsulin-Secreting Cells10aIslets of Langerhans10aIslets of Langerhans Transplantation10aMacrophages10aMale10aMice10aMice, Inbred C57BL10aPhenalenes10aReceptors, Cytoplasmic and Nuclear10aStreptozocin10aT-Lymphocytes, Regulatory10aTransplantation, Heterologous1 aCobo-Vuilleumier, Nadia1 aLorenzo, Petra, I1 aRodríguez, Noelia, García1 aGómez, Irene, de Gracia1 aFuente-Martin, Esther1 aLópez-Noriega, Livia1 aMellado-Gil, José, Manuel1 aRomero-Zerbo, Silvana-Yanina1 aBaquié, Mathurin1 aLachaud, Christian, Claude1 aStifter, Katja1 aPerdomo, German1 aBugliani, Marco1 aDe Tata, Vincenzo1 aBosco, Domenico1 aParnaud, Geraldine1 aPozo, David1 aHmadcha, Abdelkrim1 aFlorido, Javier, P1 aToscano, Miguel, G1 ade Haan, Peter1 aSchoonjans, Kristina1 aPalazón, Luis, Sánchez1 aMarchetti, Piero1 aSchirmbeck, Reinhold1 aMartín-Montalvo, Alejandro1 aMeda, Paolo1 aSoria, Bernat1 aBermúdez-Silva, Francisco-Javier1 aSt-Onge, Luc1 aGauthier, Benoit, R uhttp://clinbioinfosspa.es/content/lrh-1-agonism-favours-immune-islet-dialogue-which-protects-against-diabetes-mellitus01909nas a2200265 4500008004100000022001400041245007900055210006900134260001600203300001100219490000700230520106400237653001001301653001801311653004201329653001101371653002701382653001301409100003301422700002301455700001901478700002001497700002701517856009901544 2014 eng d a1367-481100angsCAT: a tool to assess the efficiency of targeted enrichment sequencing.0 angsCAT a tool to assess the efficiency of targeted enrichment se c2014 Jun 15 a1767-80 v303 a

MOTIVATION: Targeted enrichment sequencing by next-generation sequencing is a common approach to interrogate specific loci or the whole exome in the human genome. The efficiency and the lack of bias in the enrichment process need to be assessed as a quality control step before performing downstream analysis of the sequence data. Tools that can report on the sensitivity, specificity, uniformity and other enrichment-specific features are needed.

RESULTS: We have implemented the next-generation sequencing data Capture Assessment Tool (ngsCAT), a tool that takes the information of the mapped reads and the coordinates of the targeted regions as input files, and generates a report with metrics and figures that allows the evaluation of the efficiency of the enrichment process. The tool can also take as input the information of two samples allowing the comparison of two different experiments.

AVAILABILITY AND IMPLEMENTATION: Documentation and downloads for ngsCAT can be found at http://www.bioinfomgp.org/ngscat.

10aExome10aGenome, Human10aHigh-Throughput Nucleotide Sequencing10aHumans10aSequence Analysis, DNA10aSoftware1 aLópez-Domingo, Francisco, J1 aFlorido, Javier, P1 aRueda, Antonio1 aDopazo, Joaquin1 aSantoyo-López, Javier uhttp://clinbioinfosspa.es/content/ngscat-tool-assess-efficiency-targeted-enrichment-sequencing