24 research outputs found
Limit cycles for cubic systems with a symmetry of order 4 and without in nite critical points
"Vegeu el resum a l'inici del document del fitxer adjunt"
ToponĂmia de la Ribagorça. CrĂČnica d'un projecte
Aquest projecte es va començar a dissenyar a finals dels anys 70 del segle passat. La primera pedra va ser un fitxer de toponĂmia de la Ribagorça que el doctor Francisco MarsĂĄ va encarregar a qui aleshores era el seu ajudant de cĂ tedra, Xavier Terrado. El professor Enric Moreu-Rei va assabentarse dâaquest treball i en va donar notĂcia en un dâaquells fulls ciclostilats que van acabar per convertir-se en el ButlletĂ Interior de la Societat dâOnomĂ stica. En la dĂšcada segĂŒent Joan Coromines va associar en Xavier Terrado a lâobra de lâOnomasticon Cataloniae i li va encomanar la revisiĂł de les cĂšdules que contenien la informaciĂł toponĂmica de la zona del Pirineu. TambĂ© va deixar en les seves mans les comprovacions sobre el terreny, lâaportaciĂł de noves dades documentals i fins i tot la redacciĂł dâun bon nombre dâarticles. Un cop finalitzat el compromĂs amb lâOnomasticon, Xavier Terrado va decidir dâaprofundir en lâestudi del territori ribagorçà i va proposar al professor JesĂșs VĂĄzquez Obrador, expert aragonesista de la Universitat de Saragossa, de codirigir un equip i un projecte. Lâobjectiu era la recopilaciĂł i lâestudi de tota la toponĂmia de lâantic comtat de Ribagorça (...
Genome-wide association analysis of dementia and its clinical endophenotypes reveal novel loci associated with Alzheimer's disease and three causality networks : The GR@ACE project
Introduction: Large variability among Alzheimer's disease (AD) cases might impact genetic discoveries and complicate dissection of underlying biological pathways. Methods: Genome Research at Fundacio ACE (GR@ACE) is a genome-wide study of dementia and its clinical endophenotypes, defined based on AD's clinical certainty and vascular burden. We assessed the impact of known AD loci across endophenotypes to generate loci categories. We incorporated gene coexpression data and conducted pathway analysis per category. Finally, to evaluate the effect of heterogeneity in genetic studies, GR@ACE series were meta-analyzed with additional genome-wide association study data sets. Results: We classified known AD loci into three categories, which might reflect the disease clinical heterogeneity. Vascular processes were only detected as a causal mechanism in probable AD. The meta-analysis strategy revealed the ANKRD31-rs4704171 and NDUFAF6-rs10098778 and confirmed SCIMP-rs7225151 and CD33-rs3865444. Discussion: The regulation of vasculature is a prominent causal component of probable AD. GR@ACE meta-analysis revealed novel AD genetic signals, strongly driven by the presence of clinical heterogeneity in the AD series
New insights into the genetic etiology of Alzheimer's disease and related dementias
Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE Δ4 allele
Multiancestry analysis of the HLA locus in Alzheimerâs and Parkinsonâs diseases uncovers a shared adaptive immune response mediated by HLA-DRB1*04 subtypes
Across multiancestry groups, we analyzed Human Leukocyte Antigen (HLA) associations in over 176,000 individuals with Parkinsonâs disease (PD) and Alzheimerâs disease (AD) versus controls. We demonstrate that the two diseases share the same protective association at the HLA locus. HLA-specific fine-mapping showed that hierarchical protective effects of HLA-DRB1*04 subtypes best accounted for the association, strongest with HLA-DRB1*04:04 and HLA-DRB1*04:07, and intermediary with HLA-DRB1*04:01 and HLA-DRB1*04:03. The same signal was associated with decreased neurofibrillary tangles in postmortem brains and was associated with reduced tau levels in cerebrospinal fluid and to a lower extent with increased AÎČ42. Protective HLA-DRB1*04 subtypes strongly bound the aggregation-prone tau PHF6 sequence, however only when acetylated at a lysine (K311), a common posttranslational modification central to tau aggregation. An HLA-DRB1*04-mediated adaptive immune response decreases PD and AD risks, potentially by acting against tau, offering the possibility of therapeutic avenues
Limit cycles for cubic systems with a symmetry of order 4 and without in nite critical points
"Vegeu el resum a l'inici del document del fitxer adjunt"