20 research outputs found
Synergistic binding of transcription factors to cell-specific enhancers programs motor neuron identity
Efficient transcriptional programming promises to open new frontiers in regenerative medicine. However, mechanisms by which programming factors transform cell fate are unknown, preventing more rational selection of factors to generate desirable cell types. Three transcription factors, Ngn2, Isl1 and Lhx3, were sufficient to program rapidly and efficiently spinal motor neuron identity when expressed in differentiating mouse embryonic stem cells. Replacement of Lhx3 by Phox2a led to specification of cranial, rather than spinal, motor neurons. Chromatin immunoprecipitationâsequencing analysis of Isl1, Lhx3 and Phox2a binding sites revealed that the two cell fates were programmed by the recruitment of Isl1-Lhx3 and Isl1-Phox2a complexes to distinct genomic locations characterized by a unique grammar of homeodomain binding motifs. Our findings suggest that synergistic interactions among transcription factors determine the specificity of their recruitment to cell typeâspecific binding sites and illustrate how a single transcription factor can be repurposed to program different cell types.Project ALS FoundationNational Institutes of Health (U.S.) (Grant P01 NS055923
Genetically-Modified Human Pluripotent Stem Cells: New Hopes for the Understanding and the Treatment of Neurological Diseases?
International audienc
DGT : EQS adaptation for Nickel, Cadmium and Lead
As DGT results cannot be directly compared to marine water AA-EQS, the general objective of this document is to propose a methodology so that DGT results can be applied in a regulatory context for waterbody quality assessment. Using a pragmatic approach applied to the context of the WFD, this methodology is based on the study of European reports, European technical and scientific guidance documents, publications of network of experts and processing of MONITOOL dataset. For this purpose, the document is organised in two parts: - a bibliographic part with a review of the derivation process of EQSs, a description of the differences between DGT and spot sampling based measurements, the proposed methodology for the use of DGT results in a regulatory framework, by comparing DGT results to EQS ; - a data processing part carried out using MONITOOL datasets in order to adapt EQS marine water in EQSDGT for Cd, Ni and Pb. Moreover, another methodology is proposed, which is to predict the concentrations measured by DGT into its corresponding dissolved concentrations, so they can be directly compared to EQSmarine water
Preparation of functionalized aryl- and heteroarylpyridazines by nickel-catalyzed electrochemical cross-coupling reactions
0022-3263International audienceA general efficient electrochemical method for the preparation of aryl- and heteroarylpyridazines in a nickel-catalyzed cross-coupling reaction of 3-chloro-6-methoxypyridazine and 3-chloro-6-methylpyridazine with a range of functionalized aryl or heteroaryl halides is reported
Substances prioritaires DCE : Etude de détermination de facteurs de bioaccumulation (BAF) sur les mollusques en milieu marin
Pour permettre dâĂ©valuer la qualitĂ© chimique des masses dâeau en utilisant les rĂ©sultats de la surveillance opĂ©rĂ©e sur les bivalves via le ROCCH ou le RINBIO, il est nĂ©cessaire de transposer les seuils existants applicables dans les eaux marines en seuils « mollusques » et ainsi dâadapter les NQE eau marine (Normes de QualitĂ© Environnementale) en VGE mollusques (Valeur Guide Environnementale). Cette adaptation nĂ©cessite dâutiliser des facteurs de conversion eau-biote : les facteurs de bioconcentration (BCF) ou les facteurs de bioaccumulation (BAF) spĂ©cifiques de couples substance-espĂšce. Les BAF sont les facteurs Ă privilĂ©gier autant que possible car plus reprĂ©sentatifs de ce qui se passe dans le milieu avec notamment la prise en compte des diffĂ©rentes voies dâexposition des organismes aquatiques aux contaminants, i.e. la voie directe (eau) et la voie trophique (ingestion de proies contaminĂ©es). Cette dĂ©marche de dĂ©termination de VGE mollusques est engagĂ©e par Ifremer - OFB depuis 2015, et plusieurs Ă©tapes ont Ă©tĂ© rĂ©alisĂ©es : proposition de VGE mollusques (1) sur la base de donnĂ©es existantes, Ă©laboration dâune mĂ©thodologie de dĂ©termination de BAF pour les mollusques en milieu marin afin dâacquĂ©rir des donnĂ©es BAF terrain. Cette Ă©tude de dĂ©termination des BAF sur les mollusques en milieu marin a Ă©tĂ© conduite entre 2016 et 2019, elle concerne 27 substances prioritaires : 3 composĂ©s mĂ©talliques et 24 substances organiques. Sept sites ont Ă©tĂ© Ă©chantillonnĂ©s en parallĂšle sur les matrices eau marine et mollusques. Suivant les points, les mollusques Ă©chantillonnĂ©s Ă©taient des moules sauvages (ou dâĂ©levage) et / ou des moules encagĂ©s, et deux sites disposaient en plus dâhuĂźtres encagĂ©es. Les concentrations dans lâeau marine ont Ă©tĂ© mesurĂ©es sur eau brute et / ou eau filtrĂ©e. En dĂ©pit des nombreuses difficultĂ©s logistiques rencontrĂ©es, cette Ă©tude souligne dâun point de vue technique, lâintĂ©rĂȘt de la SBSE (Stir Bar Sorptive Extraction), pour la recherche de certaines substances organiques dans lâeau marine, la pertinence de rechercher ces substances sur eau brute mais Ă©galement sur eau filtrĂ©e. Cette Ă©tude permet de disposer de rĂ©sultats acquis en parallĂšle Ă la fois sur moules encagĂ©es, sur moules sauvages ou dâĂ©levage et de mesurer des BAF pour 10 substances : Cd, Ni, Pb, anthracĂšne, PBDE, DDT total, HCH, naphtalĂšne, octylphĂ©nol, TBT, permettant dâaffiner les VGE mollusques
An Alternative Splicing Switch Regulates Embryonic Stem Cell Pluripotency and Reprogramming
International audienc