Study of protein O-mannosylation in the context of endoplasmic reticulum protein homeostasis

Protein O-mannosylation is an essential, conserved and abundant post-translational modification in the eukaryotic secretory pathway. Protein O-mannosylation is initiated at the endoplasmic reticulum (ER) by the covalent addition of single mannoses to serine and threonine residues of target polypeptides. This reaction is catalyzed by members of the evolutionarily conserved protein mannosyltransferase family (PMT). In the model organism Saccaromyces Cerevisiae, among its different biological roles, protein O-mannosylation has been described to target both unfolded and irreversibly misfolded proteins. The recently named unfolded protein O-mannosylation (UPOM) pathway is hypothesized to function as a fail-safe mechanism to prevent ineffective folding attempts for polypeptides that did not achieve the native conformation within certain time window. However, although UPOM has been described to target multiple misfolded model proteins, the mechanism by which the PMT machinery discriminates misfolded polypeptides is unknown. In fact, the question of whether UPOM is a physiologically relevant mechanism contributing to maintain homeostasis in the ER remains unanswered. In this current work, it is shown: I) The relevance of the Pmt1-Pmt2 complex as necessary to maintain ER homeostasis being integrated in the unfolded protein response (UPR). II) Aiming to unravel the UPOM machinery, the genes PGI1 (phosphoglucose isomerase) and BFR1 (Brefeldin A resistance) were found as necessary for efficient UPOM. On one hand, the characterization of PGI1 highlighted a direct link between O-mannosylation, cytosolic sugar metabolism, and ER stress. On the other hand, the RNA binding protein (RBP) Bfr1 was found to modulate the translational state of PMT mRNAs among many other ORFs, mainly coding for proteins localizing to the secretory pathway, suggesting a role as a local translational control factor. III) Aiming to address the physiological relevance of UPOM in the ER protein quality control system, the impact of O-mannosylation on the stability of a subset of PMT target proteins was investigated. Both, protein stabilization and de-stabilization effects were presented. The prevalence of either effect was largely dependent on the nature of the O mannosylation substrate. In line with this, Pmt1 is shown to be necessary for the degradation of the beta-1,6 synthase Kre6 when mislocalized in the vacuole

Heat-related mortality trends under recent climate warming in Spain : a 36-year observational study

Altres ajuts: B00391(FI-2018)Anthropogenic greenhouse gas emissions have increased summer temperatures in Spain by nearly one degree Celsius on average between 1980 and 2015. However, little is known about the extent to which the association between heat and human mortality has been modified. We here investigate whether the observed warming has been associated with an upward trend in excess mortality attributable to heat or, on the contrary, a decrease in the vulnerability to heat has contributed to a reduction of the mortality burden. We analysed a dataset from 47 major cities in Spain for the summer months between 1980 and 2015, which included daily temperatures and 554,491 deaths from circulatory and respiratory causes, by sex. We applied standard quasi-Poisson regression models, controlling for seasonality and long-term trends, and estimated the temporal variation in heat-related mortality with time-varying distributed lag nonlinear models (DLNMs). Results pointed to a reduction in the relative risks of cause-specific and cause-sex mortality across the whole range of summer temperatures. These reductions in turn explained the observed downward trends in heat-attributable deaths, with the only exceptions of respiratory diseases for women and both sexes together. The heat-attributable deaths were consistently higher in women than in men for both circulatory and respiratory causes. The main limitation of our study is that we were not able to account for air pollution in the models because of data unavailability. Despite the summer warming observed in Spain between 1980 and 2015, the decline in the vulnerability of the population has contributed to a general downward trend in overall heat-attributable mortality. This reduction occurred in parallel with a decline in the vulnerability difference between men and women for circulatory and cardiorespiratory mortality. Despite these advances, the risk of death remained high for respiratory diseases, and particularly in women. Joan Ballester and colleagues reveal a general decline in heat-attributable deaths over the last 30 years in Spain, despite increasing temperatures, with the exception of respiratory disease, which is increasing, especially in women

Quan el Montseny és florit... Representacio paremiològica de la comarca d'Osona a l'enquesta Els refranys més usuals de la llengua catalana

Un cop analitzats els resultats de les enquestes obtingudes del projecte Els refranys més usuals de la llengua catalana, s'observa que, en termes relatius, Osona és la comarca amb més representació (88 enquestes). Contextualitzem aquest tresor paremiològic osonenc amb els resultats generals i, alhora, ens centrem en les peculiaritats i aportacions parèmiques dels participants de la comarca

On the dynamical mechanisms explaining the western Pacific subsurface temperature buildup leading to ENSO events

Despite steady progress in the understanding of El Niño–Southern Oscillation (ENSO) in the past decades, questions remain on the exact mechanisms explaining the heat buildup leading to the onset of El Niño (EN) events. Here we use an ensemble of ocean and atmosphere assimilation products to identify mechanisms that are consistently identified by all the data sets and that contribute to the heat buildup in the western Pacific 18 to 24 months before the onset of EN events. Meridional and eastward heat advection due to equatorward subsurface mass convergence and transport along the equatorial undercurrent are found to contribute to the subsurface warming at 170°E–150°W. In the warm pool, instead, surface horizontal convergence and downwelling motion have a leading role in subsurface warming. The picture emerging from our results highlights a sharp dynamical transition at 170°E near the level of the thermocline

Análisis de los factores que influyen en el consumo de alcohol en el botellón, en jóvenes entre 18 y 25 años de Alcoy, mediante técnicas estadísticas

[ES] Se realizará una encuesta dirigida a jóvenes entre 18-25 años de Alcoy, donde se tratarán de encontrar los factores que provocan mayor o menor consumo de alcohol en la calle, es decir, que hagan el conocido "botellón". Entre otras cosas se buscará si este fenómeno tiene que ver con el nivel de estudios, la remuneración por empleo o por paga etc. Los resultados de las encuestas se analizarán mediante distintas técnicas estadísticas, desde análisis univariante hasta multivariante, para conseguir sacar el máximo partido a los datos obtenidos.Roca Ballester, J. (2016). Análisis de los factores que influyen en el consumo de alcohol en el botellón, en jóvenes entre 18 y 25 años de Alcoy, mediante técnicas estadísticas. http://hdl.handle.net/10251/68940.TFG

Ús d’un qüestionari de resposta forçada com a ferramenta per avaluar l’estil d’afrontament en pacients amb dolor crònic: Desenvolupament i estudi de propietats psicomètriques

Treball Final de Màster Universitari en Psicologia General Sanitària. Codi: SBF018. Curs acadèmic: 2020/2021Introducció. Els estils d’afrontament són fonamentals per entendre l’adaptació de les persones al dolor crònic. Les mesures d’afrontament han utilitzat fins ara escales de resposta tipus Likert. Per evitar que una persona indique altes puntuacions tant en afrontament adaptatiu com desadaptatiu (un problema comú en escales Likert), es va crear una versió de resposta forçada del Social Problem Solving Inventory (SPSI), anomenat Forced-Choice SPSI (FC-SPSI). L’objectiu d’aquest treball és valorar-ne les propietats psicomètriques. Mètode. Els participants han estat 273 persones amb dolor crònic de dues Unitats de Dolor. Junt al FC-SPSI, se’ls va administrar mesures de salut (física i mental) i interferència del dolor (validesa de criteri concorrent) i d’afrontament (validesa de constructe). Les dades han estat processades amb l’SPSS 21. Resultats. Els factors evitació i afrontament racional del FC-SPSI correlacionaren de manera significativa (p<0.05) i en la direcció esperada amb els seus anàlegs de l’escala original SPSI. Això no va succeir amb el factor d’impulsivitat. La impulsivitat i, en menor mesura, l’afrontament racional es van relacionar amb millor salut física i mental i menys dolor. El contrari va succeir amb l’evitació. Conclusions. El constructe impulsivitat del FC-SPSI sembla no valorar el mateix que el seu homònim del SPSI. El FC-SPSI entén l’estil impulsiu com una “persistència centrada en la tasca” (estratègia adaptativa front el dolor); aquest qüestionari sembla ser una alternativa adient –i possiblement més conductual que el SPSI– pel fet d’utilitzar respostes forçades per avaluar els estils d’afrontament del dolor.Introduction. Coping styles are key to understand how people adapt to chronic pain. Coping measures so far have used Likert-type response scales. To prevent a person from indicating high scores on both adaptive and maladaptive coping (a common problem on Likert scales), a forced-choice version of the Social Problem Solving Inventory (SPSI) was created, named Forced-Choice SPSI (FC-SPSI). The aim of this work is to evaluate its psychometric properties. Methods. A clinical sample of 273 subjects with chronic pain belonging to the Pain Units of several Catalan hospitals was used for the study. Along with FC-SPSI, they were administered measures of health (physical and mental) and interference of pain (concurrent criterion validity) and coping (construct validity). Data was processed with SPSS 21. Results. The avoidance and rational coping factors of FC-SPSI correlated significantly (p <0.05) and in the expected direction with its analogues of the original SPSI scale. This did not happen with the impulsivity factor. Impulsiveness and, to a lesser extent, rational coping were associated with better physical and mental health and less pain. The opposite happened with avoidance. Conclusions. The FC-SPSI impulsivity construct does not seem to value the same as its SPSI namesake. FC-SPSI understands impulsive style as “taskcentered persistence” (adaptive strategy against pain); this questionnaire appears to be a suitable alternative -and more behavioral than the SPSI- for using forced choice to assess pain coping styles