11 research outputs found

    Multiancestry analysis of the HLA locus in Alzheimer’s and Parkinson’s diseases uncovers a shared adaptive immune response mediated by HLA-DRB1*04 subtypes

    Get PDF
    Across multiancestry groups, we analyzed Human Leukocyte Antigen (HLA) associations in over 176,000 individuals with Parkinson’s disease (PD) and Alzheimer’s 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

    Amares: de la idea al tratamiento de un guiĂłn cinematogrĂĄfico

    Full text link
    ANÁLISIS DEL PROCESO DE ESCRITURA CINEMATOGRÁFICA A PARTIR DE UN PROYECTO DE LARGOMETRAJEPastor Campos, MDM. (2011). Amares: de la idea al tratamiento de un guión cinematogråfico. http://hdl.handle.net/10251/15261.Archivo delegad

    Estudio de marcadores predictivos en la enfermedad de graves : repercusion clĂ­nica e inmunolĂłgica a largo plazo de la terapĂ©utica mĂ©dica y/o quirĂșrgica

    Get PDF
    Reducción altaSe ha valorado la evolución de paråmetros bioquímicos e inmunológicos, en pacientes con enfermedad de graves en fase activa sometidos a terapia con antitiroideos yodo radiactivo o cirugía y evaluado que paråmetros pueden discriminar pacientes que se reactivan de los que permanecen en remisión tras la retirada del tratamiento antitiroideo. Observamos que cualquier terapia (antitiroideos, i131 o cirugía), adecuadamente prescrita y a corto plazo es efectiva para controlar el hipertiroidismo. A los dos años tras la terapia con antitiroideos, obtenemos el måximo porcentaje de reactivaciones (42,3%), con diferencia estadísticamente significativa frente a los tratados con i131 (16%) y cirugía (6,6%). La tiroglobulina sérica no es un buen índice de actividad tiroidea, no se modifica tras los distintos tratamientos, ni discrimina pacientes remitidos y reactivados. Los niveles de inmunoglulinas inhibidoras de la unión de tsh (tbii) aparecen elevados pretratamiento y tienden a declinar a largo plazo tras las distintas terapias destacando que un 40% de pacientes permanecen con títulos elevados de tbii a los 2 años de la tiroidectomia subtotal. Solamente los niveles de tbii y los antígenos hla dr3 y dr4, discriminan pacientes que se reactivan de los que permanecen en remisión después de la retirada de la medicación.Univ. de Granada, Departamento de Medicina. Leída el 01-03-9

    Control of post-harvest gray mold (Botrytis cinerea) on grape (Vitis vinifera) and tomato (Solanum lycopersicum) using volatile organic compounds produced by Xenorhabdus nematophila and Photorhabdus laumondii subsp. laumondii [Dataset]

    No full text
    Experiment performed in the lab, following details described in the publication https://doi.org/10.1007/s10526-023-10212-7Grant PID2019-104112RB I00 from Ministry of Science and Innovation (MCIN/AEI/10.13039/50110001103). Grant RYC-2016-19939 funded by Ministry of Science and Innovation (MCIN/ AEI/ 10.13039/501100011033) and “ESF Investing in your future”. The predoctoral contract FPI-UR 2021 (University of La Rioja) support IVDPeer reviewe

    Comparing the catch composition, profitability and discard survival from different trammel net designs targeting common spiny lobster (Palinurus elephas) in a Mediterranean fishery

    Get PDF
    In the Balearic Islands, different trammel net designs have been adopted to promote fisheries sustainability and reduce discards. Here, we compare the catch performance of three trammel net designs targeting the spiny lobster Palinurus elephas in terms of biomass, species composition and revenue from commercial catches and discards. Designs differ in the netting fiber type (standard polyfilament, PMF, or a new polyethylene multi-monofilament, MMF) and the use of a guarding net or greca, a mesh piece intended to reduce discards. Catches were surveyed by an on-board observer from 1,550 netting walls corresponding to 70 nets. The number of marketable species captured indicated that the lobster trammel net fishery has multiple targets, which contribute significantly to the total revenue. The discarded species ranged from habitat-forming species to elasmobranches, but the magnitude of gear-habitat interactions on the long term dynamics of benthos remains unclear. No relevant differences in revenue and weight of discards were detected after Bayesian analyses. However, the species composition of discards was different when using greca. Interestingly, high immediate survival was found for discarded undersized lobsters, while a seven day survival assessment, using captive observation, gave an asymptotic estimate of survival probability as 0.64 (95% CI [0.54–0.76]). Therefore, it is recommended that it would be beneficial for this stock if an exemption from the EU landing obligation regulation was sought for undersized lobsters in the Balearic trammel net fishery.This research received funding from the European Commission’s Horizon 2020 Research and Innovation Programme under Grant Agreement No. 634495 for the project Science, Technology, and Society Initiative to minimize Unwanted Catches in European Fisheries (MINOUW). Gaetano Catanese was supported by a research contract from DOC INIA-CCAA program. Hilmar Hinz was supported by the RamĂłn y Cajal Fellowship (grant by the Ministerio de EconomĂ­a y Competitividad de España and the Conselleria d’EducaciĂł, Cultura i Universitats Comunidad AutĂłnoma de las Islas Baleares). Andrea Campos-Candela was supported by a FPU pre-doctoral fellowship (ref. FPU13/01440) from the Spanish Ministry of Education, Culture and Sports (MECD).Peer reviewe

    Stimulation of ALK by the growth factor midkine renders glioma cells resistant to autophagy-mediated cell death

    No full text
    Δ9-tetrahydrocannabinol (THC), the main active component of marijuana, promotes cancer cell death via autophagy stimulation. We find that activation of the tyrosine kinase receptor ALK by its ligand midkine interferes with the signaling mechanism by which THC promotes autophagy-mediated glioma cell death.Depto. de Bioquímica y Biología MolecularFac. de Ciencias BiológicasTRUEpu

    Stimulation of the midkine/ALK axis renders glioma cells resistant to cannabinoid antitumoral action

    No full text
    Acknowledgements This work was supported by grants from Spanish Ministry of Science and Innovation (MICINN) (PS09/01401; HF2005/0021, FR2009-0052 and IT2009-0053 to GV; SAF2006/00918 to MG), Santander-Complutense (PR34/07-15856 to GV), Comunidad de Madrid (S-SAL/0261/2006 to MG). ML was sequentially the recipient of a ‘Juan de la Cierva’ contract, a postdoctoral contract from Spanish Ministry of Education and Science (MEC) and a postdoctoral contract from Comunidad de Madrid. ST was recipient of a research formation contract from Comunidad de Madrid, MS was recipient of a fellowship from MEC and of a research formation contract from Comunidad de Madrid, AC was recipient of fellowships from Gobierno Vasco, FEBS and EMBO. SH-T has a technician contract from MICINN and Fondo Social Europeo. We thank Horacio Zimman and Carmen Moreno from Hospital ClĂ­nico San Carlos as well as Leyre UrigĂŒen from Universidad del Pais Vasco for their kind collaboration in the processing and delivery of glioma samples; Miguel Ángel Piris, Raquel Villuendas, Paloma Cueva and Rosa PĂ©rez for technical advice in the gene expression experiments and other members of our lab for their continuous support.Identifying the molecular mechanisms responsible for the resistance of gliomas to anticancer treatments is an issue of great therapeutic interest. Δ9-Tetrahydrocannabinol (THC), the major active ingredient of marijuana, and other cannabinoids inhibit tumor growth in animal models of cancer, including glioma, an effect that relies, at least in part, on the stimulation of autophagy-mediated apoptosis in tumor cells. Here, by analyzing the gene expression profile of a large series of human glioma cells with different sensitivity to cannabinoid action, we have identified a subset of genes specifically associated to THC resistance. One of these genes, namely that encoding the growth factor midkine (Mdk), is directly involved in the resistance of glioma cells to cannabinoid treatment. We also show that Mdk mediates its protective effect via the anaplastic lymphoma kinase (ALK) receptor and that Mdk signaling through ALK interferes with cannabinoid-induced autophagic cell death. Furthermore, in vivo Mdk silencing or ALK pharmacological inhibition sensitizes cannabinod-resistant tumors to THC antitumoral action. Altogether, our findings identify Mdk as a pivotal factor involved in the resistance of glioma cells to THC pro-autophagic and antitumoral action, and suggest that selective targeting of the Mdk/ALK axis could help to improve the efficacy of antitumoral therapies for gliomas.Depto. de BioquĂ­mica y BiologĂ­a MolecularFac. de Ciencias BiolĂłgicasTRUEpu

    Intraoperative positive end-expiratory pressure and postoperative pulmonary complications: a patient-level meta-analysis of three randomised clinical trials.

    No full text

    New insights into the genetic etiology of Alzheimer’s disease and related dementias

    Get PDF
    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
    corecore