Pompeu Fabra University

About: Pompeu Fabra University is a education organization based out in Barcelona, Spain. It is known for research contribution in the topics: Population & Gene. The organization has 8093 authors who have published 23570 publications receiving 858431 citations. The organization is also known as: Universitat Pompeu Fabra & UPF.

The sequential activation of the yeast HOG and SLT2 pathways is required for cell survival to cell wall stress.

Abstract: Yeast mitogen-activated protein kinase (MAPK) signaling pathways transduce external stimuli into cellular responses very precisely. The MAPKs Slt2/Mpk1 and Hog1 regulate transcriptional responses of adaptation to cell wall and osmotic stresses, respectively. Unexpectedly, we observe that the activation of a cell wall integrity (CWI) response to the cell wall damage caused by zymolyase (beta-1,3 glucanase) requires both the HOG and SLT2 pathways. Zymolyase activates both MAPKs and Slt2 activation depends on the Sho1 branch of the HOG pathway under these conditions. Moreover, adaptation to zymolyase requires essential components of the CWI pathway, namely the redundant MAPKKs Mkk1/Mkk2, the MAPKKK Bck1, and Pkc1, but it does not require upstream elements, including the sensors and the guanine nucleotide exchange factors of this pathway. In addition, the transcriptional activation of genes involved in adaptation to cell wall stress, like CRH1, depends on the transcriptional factor Rlm1 regulated by Slt2, but not on the transcription factors regulated by Hog1. Consistent with these findings, both MAPK pathways are essential for cell survival under these circumstances because mutant strains deficient in different components of both pathways are hypersensitive to zymolyase. Thus, a sequential activation of two MAPK pathways is required for cellular adaptation to cell wall damage.

Are Social Value Orientations Expressed Automatically? Decision Making in the Dictator Game

Abstract: Drawing on the social intuitionist model, the authors studied the hypothesis that social value orientations are expressed automatically in behavior. They compared spontaneous and more deliberated decisions in the dictator game and confirmed that social values determine behavior when responses are based on the automatic system. By means of both mediation and experimental analyses, the authors further demonstrate that the automatic expression of social value orientations is mediated by perceptions of interpersonal closeness. A reasoning process can subsequently override these automatic responses and disconnect decisions from perceptions of interpersonal closeness. This results in lower levels of other-regarding behavior, at least for prosocials.

The mutational footprints of cancer therapies.

Abstract: Some cancer therapies damage DNA and cause mutations in both cancerous and healthy cells. Therapy-induced mutations may underlie some of the long-term and late side effects of treatments, such as mental disabilities, organ toxicity and secondary neoplasms. Nevertheless, the burden of mutation contributed by different chemotherapies has not been explored. Here we identify the mutational signatures or footprints of six widely used anticancer therapies across more than 3,500 metastatic tumors originating from different organs. These include previously known and new mutational signatures generated by platinum-based drugs as well as a previously unknown signature of nucleoside metabolic inhibitors. Exploiting these mutational footprints, we estimate the contribution of different treatments to the mutation burden of tumors and their risk of contributing coding and potential driver mutations in the genome. The mutational footprints identified here allow for precise assessment of the mutational risk of different cancer therapies to understand their long-term side effects.

Inversion of a large-scale circuit model reveals a cortical hierarchy in the dynamic resting human brain

Abstract: We considered a large-scale dynamical circuit model of human cerebral cortex with region-specific microscale properties. The model was inverted using a stochastic optimization approach, yielding markedly better fit to new, out-of-sample resting functional magnetic resonance imaging (fMRI) data. Without assuming the existence of a hierarchy, the estimated model parameters revealed a large-scale cortical gradient. At one end, sensorimotor regions had strong recurrent connections and excitatory subcortical inputs, consistent with localized processing of external stimuli. At the opposing end, default network regions had weak recurrent connections and excitatory subcortical inputs, consistent with their role in internal thought. Furthermore, recurrent connection strength and subcortical inputs provided complementary information for differentiating the levels of the hierarchy, with only the former showing strong associations with other macroscale and microscale proxies of cortical hierarchies (meta-analysis of cognitive functions, principal resting fMRI gradient, myelin, and laminar-specific neuronal density). Overall, this study provides microscale insights into a macroscale cortical hierarchy in the dynamic resting brain.

Technical aspects of Muthén's LISCOMP approach to estimation of latent variable relations with a comprehensive measurement model.

Abstract: Muthen (1984) formulated a general model and estimation procedure for structural equation modeling with a mixture of dichotomous, ordered categorical, and continuous measures of latent variables. A general three-stage procedure was developed to obtain estimates, standard errors, and a chi-square measure of fit for a given structural model. While the last step uses generalized least-squares estimation to fit a structural model, the first two steps involve the computation of the statistics used in this model fitting. A key component in the procedure was the development of a GLS weight matrix corresponding to the asymptotic covariance matrix of the sample statistics computed in the first two stages. This paper extends the description of the asymptotics involved and shows how the Muthen formulas can be derived. The emphasis is placed on showing the asymptotic normality of the estimates obtained in the first and second stage and the validity of the weight matrix used in the GLS estimation of the third stage.