Seroprevalencia frente a borrelia burgdorferi sensu lato en la población canina de Catalunya

En este artículo, estudiamos la seroprevalencia frente a B. burgdorferi sensu lato en perros de Cataluña. Para ello analizamos 155 sueros mediante una inmunofluorescencia indirecta (Il-I).La seroprevalencia detectada fue del 3,2%. Esta prevalencia, junto al hecho de que la garrapata vectora se halla confinada a áreas muy concretas, sugieren la escasa importancia de la enfermedad de Lyme (EL)en nuestra zona. Por otro lado, la existencia de reacciones serológicas cruzadas ponen de manifiesto la necesidad de aplicar técnicas de diagnóstico más específicas.In this article, we report the seroprevalence of Borrelia burgdorferi sensu lata in dogs in Catalonia. 155 serum samples were analized by IFA. The seroprevalence was 3.2%. This prevalence showed a limited importance of Lyme disease in dogs in Catalonia since the tick vector is confined to very restricted areas. On the other hand, serological crossreactions suggested to use more specifíc diagnostic techniques

Study of the transport of substances across the blood-brain barrier with the 8D3 anti-transferrin receptor antibody

Podeu consultar el llibre complet a: http://hdl.handle.net/2445/128014Numerous strategies have been proposed to overcome the blood-brain barrier (BBB) and efficiently deliver therapeutic agents to the brain. One of these strategies consists of linking the pharmacologically active substance to a molecular vector that acts as a molecular Trojan Horse and is capable of crossing the BBB using a receptor-mediated transcellular transport system of the brain capillary endothelial cells (BCECs). The transferrin receptor (TfR) is related to a transcytosis process in these cells, and the 8D3 monoclonal antibody (mAb), directed against the mouse TfR, is able to induce a receptor response. Thus, the 8D3 antibody could be a potential molecular Trojan Horse to transport pharmacologically active substances across the BBB. On these bases, a series of experiments were performed where the 8D3 antibody was conjugated to different cargoes, the resulting constructs were administered in vivo to mice, and the distribution and intracellular mechanisms that these constructs undergo at the BBB were studied. Our results indicated a TfR-mediated and clathrin-dependent internalization process by which the 8D3-cargo constructs enters the BCEC. The resulting endocytic vesicles follow at least two different routes. On one hand, most vesicles enter intracellular processes of vesicular fusion and rearrangement in which the cargo is guided to late endosomes, multivesicular bodies or lysosomes. On the other hand, a small but not negligible percentage of the vesicles follow a different route in which they fuse with the abluminal membrane and open towards the basal lamina, indicating a potential route for the delivery of therapeutic substances. In this route, however, the 8D3−cargo remain fixed to the abluminal membrane, indicating that the 8D3 is maintained linked to the TfR, and the cargo does not go beyond the basal membrane. Altogether, different optimization approaches need to be developed for efficient drug delivery, but receptor-mediated transport (RMT) continues to be one of the most promising strategies to overcome the BBB

Design and optimization of oestrogen receptor PROTACs based on 4-hydroxytamoxifen.

In the last four decades, treatment of oestrogen receptor positive (ER+) breast cancer (BCa), has focused on targeting the estrogenic receptor signaling pathway. This signaling function is pivotal to sustain cell proliferation. Tamoxifen, a competitive inhibitor of oestrogen, has played a major role in therapeutics. However, primary and acquired resistance to hormone blockade occurs in a large subset of these cancers, and new approaches are urgently needed. Aromatase inhibitors and receptor degraders were approved and alternatively used. Yet, resistance appears in the metastatic setting. Here we report the design and synthesis of a series of proteolysis targeting chimeras (PROTACs) that induce the degradation of estrogen receptor alpha in breast cancer MCF-7 (ER+) cells at nanomolar concentration. Using a warhead based on 4-hydroxytamoxifen, bifunctional degraders recruiting either cereblon or the Von Hippel Lindau E3 ligases were synthesized. Our efforts resulted in the discovery of TVHL-1, a potent ERα degrader (DC50: 4.5 nM) that we envisage as a useful tool for biological study and a platform for potential therapeutics

Ullals de Baltasar -Delta de l'Ebre : proposta de pla de gestió i ús social

Les zones humides han sofert durant anys les velles concepcions de gestió de l'aigua, promovent la seva dessecació fins els anys 60. Com a resposta han sorgit un seguit de directives europees i lleis estatals i autonòmiques per intentar recuperar i restaurar aquests hàbitats amenaçats.Los humedades han sufrido durante años las viejas concepciones de gestión del agua, promoviendo su desecación hasta los años 60. Como respuesta han aparecido unas directivas y leyes para intentar recuperar y restaurar estos ecosistemas amenazados.The wetlands had suffered during years the old conceptions about water's management. It has been promoted to keep water from the lagoons because they were seen like unhealthy places, until the sixty's. It had appeared laws about the conservation and restauration of wetlands

Trafficking of Gold Nanoparticles Coated with the 8D3 Anti-Transferrin Receptor Antibody at the Mouse Blood-Brain Barrier

Receptor-mediated transcytosis has been widely studied as a possible strategy to transport neurotherapeutics across the blood-brain barrier (BBB). Monoclonal antibodies directed against the transferrin receptor (TfR) have been proposed as potential carrier candidates. A better understanding of the mechanisms involved in their cellular uptake and intracellular trafficking is required and could critically contribute to the improvement of delivery methods. Accordingly, we studied here the trafficking of gold nanoparticles (AuNPs) coated with the 8D3 anti-transferrin receptor antibody at the mouse BBB. 8D3-AuNPs were intravenously administered to mice and allowed to recirculate for a range of times, from 10 min to 24 h, before brain extraction and analysis by transmission electron microscope techniques. Our results indicated a TfR-mediated and clathrin-dependent internalization process by which 8D3-AuNPs internalize individually in vesicles. These vesicles then follow at least two different routes. On one hand, most vesicles enter intracellular processes of vesicular fusion and rearrangement in which the AuNPs end up accumulating in late endosomes, multivesicular bodies or lysosomes, which present a high AuNP content. On the other hand, a small percentage of the vesicles follow a different route in which they fuse with the abluminal membrane and open to the basal membrane. In these cases, the 8D3-AuNPs remain attached to the abluminal membrane, which suggests an endosomal escape, but not dissociation from TfR. Altogether, although receptor-mediated transport continues to be one of the most promising strategies to overcome the BBB, different optimization approaches need to be developed for efficient drug delivery. Keywords: blood−brain barrier; drug delivery; electron microscopy; monoclonal antibodies; receptor-mediated transport; transferrin receptor

Les interrogatives al tortosí i al lleidatà. Un element diferenciador de subdialectes

Aquest article forma part del projecte AMPER (Atles Multimèdia de la Prosodia de l’Espai Romànic) i se centra en el domini occidental del català. Concretament, s’hi analitza la producció de frases interrogatives absolutes de dues informants considerades representatives de dos subdialectes: el lleidatà i el tortosí. S’observa que les produccions obtingudes, tot i tractar-se d’informants del mateix diasistema dialectal, són força diferents. Aquestes diferències també es veuen avalades pels resultats obtinguts en les prospeccions de la percepció d’oracions interrogatives per part d’oients lleidatans i tortosins.This article is part of the AMPER project, which aims at creating a multimedia prosody atlas of the romance space, and focuses on Western Catalan. In particular, we analyse the production of absolute interrogative sentences by two informants representative of two subdialects: lleidatà and tortosí. We can appreciate that the data obtained are quite different between speakers, even though they belong to the same dialectal system. These differences are also supported by the results of perceptual tests in which interrogative sentences were played to listeners from Lleida and Tortosa

Neuroprotective role of trans-resveratrol in a murine model of familial Alzheimer's disease

The amyloid-β protein precursor/presenilin 1 (AβPP/PS1) mouse model of Alzheimer's disease (AD) has provided robust neuropathological hallmarks of familial AD-like pattern. AD is a neurodegenerative process that causes severe cognitive impairment; it is characterized by the accumulation of amyloid-β (Aβ) and hyperphosphorylated tau forms and by oxidative and inflammatory processes in brain. Currently, efforts are made to understand biochemical pathways because there is no effective therapy for AD. Resveratrol is a polyphenol that induces expression and activation of several neuroprotective pathways involving Sirtuin1 and AMPK. The objective of this work was to assess the effect of oral resveratrol administration on AβPP/PS1 mice. Long-term resveratrol treatment significantly prevented memory loss as measured by the object recognition test. Moreover, resveratrol reduced the amyloid burden and increased mitochondrial complex IV protein levels in mouse brain. These protective effects of resveratrol were mainly mediated by increased activation of Sirtuin 1 and AMPK pathways in mice. However, an increase has been observed in IL1β and TNF gene expression, indicating that resveratrol promoted changes in inflammatory processes, although no changes were detected in other key actors of the oxidative stress pathway. Taken together, our findings suggest that resveratrol is able to reduce the harmful process that occurs in AβPP/PS1 mouse hippocampus, preventing memory loss