Institution
Pompeu Fabra University
Education•Barcelona, Spain•
About: Pompeu Fabra University is a education organization based out in Barcelona, Spain. It is known for research contribution in the topics: Population & Context (language use). The organization has 8093 authors who have published 23570 publications receiving 858431 citations. The organization is also known as: Universitat Pompeu Fabra & UPF.
Topics: Population, Context (language use), Gene, Computer science, Politics
Papers published on a yearly basis
Papers
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TL;DR: Findings establish a link between memory and behavioural deficits and antibody-mediated reduction of NMDAR, provide the biological basis by which removal of antibodies and antibodies-producing cells improve neurological function, and offer a model for testing experimental therapies in this and similar disorders.
Abstract: Anti-N-methyl D-aspartate receptor (NMDAR) encephalitis is a severe neuropsychiatric disorder that associates with prominent memory and behavioural deficits. Patients’ antibodies react with the N-terminal domain of the GluN1 (previously known as NR1) subunit of NMDAR causing in cultured neurons a selective and reversible internalization of cell-surface receptors. These effects and the frequent response to immunotherapy have suggested an antibody-mediated pathogenesis, but to date there is no animal model showing that patients’ antibodies cause memory and behavioural deficits. To develop such a model, C57BL6/J mice underwent placement of ventricular catheters connected to osmotic pumps that delivered a continuous infusion of patients’ or control cerebrospinal fluid (flow rate 0.25 µl/h, 14 days). During and after the infusion period standardized tests were applied, including tasks to assess memory (novel object recognition in open field and V-maze paradigms), anhedonic behaviours (sucrose preference test), depressive-like behaviours (tail suspension, forced swimming tests), anxiety (black and white, elevated plus maze tests), aggressiveness (resident-intruder test), and locomotor activity (horizontal and vertical). Animals sacrificed at Days 5, 13, 18, 26 and 46 were examined for brain-bound antibodies and the antibody effects on total and synaptic NMDAR clusters and protein concentration using confocal microscopy and immunoblot analysis. These experiments showed that animals infused with patients’ cerebrospinal fluid, but not control cerebrospinal fluid, developed progressive memory deficits, and anhedonic and depressive-like behaviours, without affecting other behavioural or locomotor tasks. Memory deficits gradually worsened until Day 18 (4 days after the infusion stopped) and all symptoms resolved over the next week. Accompanying brain tissue studies showed progressive increase of brain-bound human antibodies, predominantly in the hippocampus (maximal on Days 13–18), that after acid extraction and characterization with GluN1-expressing human embryonic kidney cells were confirmed to be against the NMDAR. Confocal microscopy and immunoblot analysis of the hippocampus showed progressive decrease of the density of total and synaptic NMDAR clusters and total NMDAR protein concentration (maximal on Day 18), without affecting the post-synaptic density protein 95 (PSD95) and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors. These effects occurred in parallel with memory and other behavioural deficits and gradually improved after Day 18, with reversibility of symptoms accompanied by a decrease of brain-bound antibodies and restoration of NMDAR levels. Overall, these findings establish a link between memory and behavioural deficits and antibody-mediated reduction of NMDAR, provide the biological basis by which removal of antibodies and antibody-producing cells improve neurological function, and offer a model for testing experimental therapies in this and similar disorders.
357 citations
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TL;DR: The balance of evidence suggested a positive association between greater exposure to outdoor blue spaces and both benefits to mental health and well-being and levels of physical activity, making synthesis difficult.
357 citations
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TL;DR: It is reported that the activity of glycogen synthase kinase-3 is necessary for the maintenance of the epithelial architecture and NFκB is identified as a transcription factor inhibited by GSK-3 in epithelial cells that is relevant for Snail expression.
Abstract: We report that the activity of glycogen synthase kinase-3 (GSK-3) is necessary for the maintenance of the epithelial architecture. Pharmacological inhibition of its activity or reducing its expression using small interfering RNAs in normal breast and skin epithelial cells results in a reduction of E-cadherin expression and a more mesenchymal morphology, both of which are features associated with an epithelial–mesenchymal transition (EMT). Importantly, GSK-3 inhibition also stimulates the transcription of Snail, a repressor of E-cadherin and an inducer of the EMT. We identify NFκB as a transcription factor inhibited by GSK-3 in epithelial cells that is relevant for Snail expression. These findings indicate that epithelial cells must sustain activation of a specific kinase to impede a mesenchymal transition.
357 citations
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TL;DR: A model of judgment under uncertainty is presented, in which an agent combines data received from the external world with information retrieved from memory to evaluate a hypothesis, which can account for some of the evidence on heuristics and biases presented by Kahneman and Tversky.
Abstract: We present a model of intuitive inference, called “local thinking,” in which an agent combines data received from the external world with information retrieved from memory to evaluate a hypothesis. In this model, selected and limited recall of information follows a version of the respresentativeness heuristic. The model can account for some of the evidence on judgment biases, including conjunction and disjunction fallacies, but also for several anomalies related to demand for insurance.
357 citations
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Harvard University1, Radcliffe Institute for Advanced Study2, Broad Institute3, University of California, Berkeley4, Howard Hughes Medical Institute5, Massachusetts Institute of Technology6, Sapienza University of Rome7, University of Padua8, Queen's University Belfast9, Russian Academy of Sciences10, Al-Farabi University11, University of Pennsylvania12, University College Dublin13, University of Vienna14, Pennsylvania State University15, Max Planck Society16, Birbal Sahni Institute of Palaeobotany17, Centre for Cellular and Molecular Biology18, Emory University19, Centre national de la recherche scientifique20, Kyrgyz National University21, Altai State University22, Academy of Sciences of the Czech Republic23, University of Oxford24, South Ural State University25, Kemerovo State University26, University College London27, Northwest University (China)28, University of Pittsburgh29, Samara State University30, Chelyabinsk State University31, University of Bologna32, Academy of Sciences of Uzbekistan33, University of Winnipeg34, Simon Fraser University35, National Museum of Natural History36, Tomsk State University37, Naturhistorisches Museum38, Národní muzeum39, Hazara University40, Deccan College Post-Graduate and Research Institute41, Pompeu Fabra University42, Hartwick College43, University of California, Santa Barbara44, Washington University in St. Louis45
TL;DR: It is shown that Steppe ancestry then integrated further south in the first half of the second millennium BCE, contributing up to 30% of the ancestry of modern groups in South Asia, supporting the idea that the archaeologically documented dispersal of domesticates was accompanied by the spread of people from multiple centers of domestication.
Abstract: By sequencing 523 ancient humans, we show that the primary source of ancestry in modern South Asians is a prehistoric genetic gradient between people related to early hunter-gatherers of Iran and Southeast Asia. After the Indus Valley Civilization's decline, its people mixed with individuals in the southeast to form one of the two main ancestral populations of South Asia, whose direct descendants live in southern India. Simultaneously, they mixed with descendants of Steppe pastoralists who, starting around 4000 years ago, spread via Central Asia to form the other main ancestral population. The Steppe ancestry in South Asia has the same profile as that in Bronze Age Eastern Europe, tracking a movement of people that affected both regions and that likely spread the distinctive features shared between Indo-Iranian and Balto-Slavic languages.
354 citations
Authors
Showing all 8248 results
Name | H-index | Papers | Citations |
---|---|---|---|
Andrei Shleifer | 171 | 514 | 271880 |
Paul Elliott | 153 | 773 | 103839 |
Bert Brunekreef | 124 | 806 | 81938 |
Philippe Aghion | 122 | 507 | 73438 |
Anjana Rao | 118 | 337 | 61395 |
Jordi Sunyer | 115 | 798 | 57211 |
Kenneth J. Arrow | 113 | 411 | 111221 |
Xavier Estivill | 110 | 673 | 59568 |
Roderic Guigó | 108 | 304 | 106914 |
Mark J. Nieuwenhuijsen | 107 | 647 | 49080 |
Jordi Alonso | 107 | 523 | 64058 |
Alfonso Valencia | 106 | 542 | 55192 |
Luis Serrano | 105 | 452 | 42515 |
Vadim N. Gladyshev | 102 | 490 | 34148 |
Josep M. Antó | 100 | 493 | 38663 |