53 research outputs found
Alteraciones en proteÃnas mitocondriales de condrocitos articulares humanos descritas mediante técnicas Proteómicas
Cornelia-de Lange syndrome-associated mutations cause a DNA damage signalling and repair defect
Cornelia de Lange syndrome is a multisystem developmental disorder typically caused by mutations in the gene encoding the cohesin loader NIPBL. The associated phenotype is generally assumed to be the consequence of aberrant transcriptional regulation. Recently, we identified a missense mutation in BRD4 associated with a Cornelia de Lange-like syndrome that reduces BRD4 binding to acetylated histones. Here we show that, although this mutation reduces BRD4-occupancy at enhancers it does not affect transcription of the pluripotency network in mouse embryonic stem cells. Rather, it delays the cell cycle, increases DNA damage signalling, and perturbs regulation of DNA repair in mutant cells. This uncovers a role for BRD4 in DNA repair pathway choice. Furthermore, we find evidence of a similar increase in DNA damage signalling in cells derived from NIPBL-deficient individuals, suggesting that defective DNA damage signalling and repair is also a feature of typical Cornelia de Lange syndrome
Nuclear organization and 3D chromatin architecture in cognition and neuropsychiatric disorders
Automatic detection of defective crankshafts by image analysis and supervised classification
This work has been partially supported by the Xunta de Galicia (Centro Singular de Investigaciòn de Galicia ED431G/01). Additionally, the research of Ricardo Cao, Mario Francisco-Fernández, Salvador Naya and Javier TarrÃo Saavedra has been partially supported by MINECO grants MTM2014-52876-R and MTM2017-82724-R, and by the Xunta de Galicia (Grupos de Referencia Competitiva ED431C-2016-015); whilst the research of Manuel G. Penedo has been partially supported by grants Xunta de Galicia (Grupos de Referencia Competitiva ED431C-2016-047), all the previous grants through the ERDF. This work has been also supported by FORJACEMIC project (Research into new processes and microalloyed steels for hot forging of automotive crankshafts)
A27 DECREASED LEVELS OF MITOCHONDRIAL SUPEROXIDE DISMUTASE IN OSTEOARTHRITIC HUMAN ARTICULAR CHONDROCYTES REVEALED BY MITOCHONDRIAL PROTEOMIC ANALYSIS
A Novel Mouse Model for the Hyper-IgM Syndrome: A Spontaneous Activation-Induced Cytidine Deaminase Mutation Leading to Complete Loss of Ig Class Switching and Reduced Somatic Hypermutation
We describe a spontaneously derived mouse line that completely failed to induce Ig class switching in vitro and in vivo. The mice inherited abolished IgG serum titers in a recessive manner caused by a spontaneous G→A transition mutation in codon 112 of the aicda gene, leading to an arginine to histidine replacement (AID(R112H)). Ig class switching was completely reconstituted by expressing wild-type AID. Mice homozygous for AID(R112H) had peripheral B cell hyperplasia and large germinal centers in the absence of Ag challenge. Immunization with SRBCs elicited an Ag-specific IgG1 response in wild-type mice, whereas AID(R112H) mice failed to produce IgG1 and had reduced somatic hypermutation. The phenotype recapitulates the human hyper-IgM (HIGM) syndrome that is caused by point mutations in the orthologous gene in humans, and the AID(R112H) mutation is frequently found in HIGM patients. The AID(R112H) mouse model for HIGM provides a powerful and more precise tool than conventional knockout strategies
NIPBL+/− haploinsufficiency reveals a constellation of transcriptome disruptions in the pluripotent and cardiac states
Adaptive recognition of intelligent inspection system for cable brackets in multiple assembly scenes
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