Cuando nos quedamos solos : resistir en la incertidumbre Prácticas de emancipación y autonomía

Ante la incertidumbre que nos rodea se plantea la necesidad de resistir en la universidad sin ningún diagnóstico del presente. Sin embargo, podemos partir de las críticas a dos de los rasgos de la universidad moderna que la han caracterizado : autonomía y emancipación. Trataremos de vislumbrar qué prácticas de resistencia puedan tener lugar aquí y ahora, reelaborando críticamente ambos principios a partir de las reflexiones de Jacques Rancière y Michel Foucault.In view of the uncertainty that surrounds us, there appears the need to resist in the university without any diagnosis of the present. For it, we can depart from the critiques to two of the features that have been characterized the modern university : autonomy and emancipation. We will to try to glimpse what practices of resistance could take place here and now, re-elaborating critically both principles using the reflections of Jacques Rancière and Michel Foucault

La gubernamentalidad socialista “hay que inventarla”:: Biopolítica, seguridad y neoliberalismo

Los análisis que Foucault realiza en torno a los mecanismos de seguridad, la biopolítica y el neoliberalismo distan de establecer una elaboración cerrada. Constituyen, más bien, una serie de investigaciones entrelazadas en que se ponían en juego distintas hipótesis y modos de aproximación a esas problemáticas. Sin embargo, el curso de El nacimiento de la biopolítica constituye una tentativa de articular esos vínculos en torno a las transformaciones de la gubernamentalidad contemporánea. Lejos de una defensa del neoliberalismo, lo que Foucault trata de mostrar es que éste constituye una nueva forma de gubernamentalidad que se estaba gestando en el presente y que, por tanto, era necesario analizar en su diferencia

Crítica de la economía biopolítica : dimensiones políticas del pensamiento médico / Criticism of the biopolitical Economics: political dimensions of medical thinking

The present article carries out a re-examination of several of the interlaced axes that Foucauldian research develops across the history of medicine and the configuration of the biopolitical governmentality. When the management of the population in terms of security is intersected with a ?medical thought? that, beyond the limits of the discipline, constitutes a reasoning on the basis of the normal and the pathological, a set of policies appear that - from the constitution and crisis of the Welfare State to the problematic relations with the juridical sciences and the question of the health - place health, the body and the disease at the center of the management of life. By extending such analyses to some recent phenomena we will try to explore the challenges that contemporary neoliberalism leads us to face up to. Keywords: biopolitics, history of medicine, governmentality, liberalism, neoliberalis

Heterogeneous Infectivity and Pathogenesis of SARS-CoV-2 Variants Beta, Delta and Omicron in Transgenic K18-hACE2 and Wildtype Mice

The emerging SARS-CoV-2 variants of concern (VOCs) may display enhanced transmissibility, more severity and/or immune evasion; however, the pathogenesis of these new VOCs in experimental SARS-CoV-2 models or the potential infection of other animal species is not completely understood. Here we infected K18-hACE2 transgenic mice with B.1, B.1.351/Beta, B.1.617.2/Delta and BA.1.1/Omicron isolates and demonstrated heterogeneous infectivity and pathogenesis. B.1.351/Beta variant was the most pathogenic, while BA.1.1/Omicron led to lower viral RNA in the absence of major visible clinical signs. In parallel, we infected wildtype (WT) mice and confirmed that, contrary to B.1 and B.1.617.2/Delta, B.1.351/Beta and BA.1.1/Omicron can infect them. Infection in WT mice coursed without major clinical signs and viral RNA was transient and undetectable in the lungs by day 7 post-infection. In silico modeling supported these findings by predicting B.1.351/Beta receptor binding domain (RBD) mutations result in an increased affinity for both human and murine ACE2 receptors, while BA.1/Omicron RBD mutations only show increased affinity for murine ACE2.info:eu-repo/semantics/publishedVersio

Exome sequencing study in patients with multiple sclerosis reveals variants associated with disease course

BACKGROUND: It remains unclear whether disease course in multiple sclerosis (MS) is influenced by genetic polymorphisms. Here, we aimed to identify genetic variants associated with benign and aggressive disease courses in MS patients. METHODS: MS patients were classified into benign and aggressive phenotypes according to clinical criteria. We performed exome sequencing in a discovery cohort, which included 20 MS patients, 10 with benign and 10 with aggressive disease course, and genotyping in 2 independent validation cohorts. The first validation cohort encompassed 194 MS patients, 107 with benign and 87 with aggressive phenotypes. The second validation cohort comprised 257 patients, of whom 224 patients had benign phenotypes and 33 aggressive disease courses. Brain immunohistochemistries were performed using disease course associated genes antibodies. RESULTS: By means of single-nucleotide polymorphism (SNP) detection and comparison of allele frequencies between patients with benign and aggressive phenotypes, a total of 16 SNPs were selected for validation from the exome sequencing data in the discovery cohort. Meta-analysis of genotyping results in two validation cohorts revealed two polymorphisms, rs28469012 and rs10894768, significantly associated with disease course. SNP rs28469012 is located in CPXM2 (carboxypeptidase X, M14 family, member 2) and was associated with aggressive disease course (uncorrected p value < 0.05). SNP rs10894768, which is positioned in IGSF9B (immunoglobulin superfamily member 9B) was associated with benign phenotype (uncorrected p value < 0.05). In addition, a trend for association with benign phenotype was observed for a third SNP, rs10423927, in NLRP9 (NLR family pyrin domain containing 9). Brain immunohistochemistries in chronic active lesions from MS patients revealed expression of IGSF9B in astrocytes and macrophages/microglial cells, and expression of CPXM2 and NLRP9 restricted to brain macrophages/microglia. CONCLUSIONS: Genetic variants located in CPXM2, IGSF9B, and NLRP9 have the potential to modulate disease course in MS patients and may be used as disease activity biomarkers to identify patients with divergent disease courses. Altogether, the reported results from this study support the influence of genetic factors in MS disease course and may help to better understand the complex molecular mechanisms underlying disease pathogenesis

Heterogeneous Infectivity and Pathogenesis of SARS-CoV-2 Variants Beta, Delta and Omicron in Transgenic K18-hACE2 and Wildtype Mice

Altres ajuts: Fundació La Marató de TV3 202126-30-21The emerging SARS-CoV-2 variants of concern (VOCs) may display enhanced transmissibility, more severity and/or immune evasion; however, the pathogenesis of these new VOCs in experimental SARS-CoV-2 models or the potential infection of other animal species is not completely understood. Here we infected K18-hACE2 transgenic mice with B.1, B.1.351/Beta, B.1.617.2/Delta and BA.1.1/Omicron isolates and demonstrated heterogeneous infectivity and pathogenesis. B.1.351/Beta variant was the most pathogenic, while BA.1.1/Omicron led to lower viral RNA in the absence of major visible clinical signs. In parallel, we infected wildtype (WT) mice and confirmed that, contrary to B.1 and B.1.617.2/Delta, B.1.351/Beta and BA.1.1/Omicron can infect them. Infection in WT mice coursed without major clinical signs and viral RNA was transient and undetectable in the lungs by day 7 post-infection. In silico modeling supported these findings by predicting B.1.351/Beta receptor binding domain (RBD) mutations result in an increased affinity for both human and murine ACE2 receptors, while BA.1/Omicron RBD mutations only show increased affinity for murine ACE2

Novel Spike-stabilized trimers with improved production protect K18-hACE2 mice and golden Syrian hamsters from the highly pathogenic SARS-CoV-2 Beta variant

Most COVID-19 vaccines are based on the SARS-CoV-2 Spike glycoprotein (S) or their subunits. However, S shows some structural instability that limits its immunogenicity and production, hampering the development of recombinant S-based vaccines. The introduction of the K986P and V987P (S-2P) mutations increases the production and immunogenicity of the recombinant S trimer, suggesting that these two parameters are related. Nevertheless, S-2P still shows some molecular instability and it is produced with low yield. Here we described a novel set of mutations identified by molecular modeling and located in the S2 region of the S-2P that increase its production up to five-fold. Besides their immunogenicity, the efficacy of two representative S-2P-based mutants, S-29 and S-21, protecting from a heterologous SARS-CoV-2 Beta variant challenge was assayed in K18-hACE2 mice (an animal model of severe SARS-CoV-2 disease) and golden Syrian hamsters (GSH) (a moderate disease model). S-21 induced higher level of WH1 and Delta variants neutralizing antibodies than S-2P in K18-hACE2 mice three days after challenge. Viral load in nasal turbinate and oropharyngeal samples were reduced in S-21 and S-29 vaccinated mice. Despite that, only the S-29 protein protected 100% of K18-hACE2 mice from severe disease. When GSH were analyzed, all immunized animals were protected from disease development irrespectively of the immunogen they received. Therefore, the higher yield of S-29, as well as its improved immunogenicity and efficacy protecting from the highly pathogenic SARS-CoV-2 Beta variant, pinpoint the S-29 mutant as an alternative to the S-2P protein for future SARS-CoV-2 vaccine development

Author Correction to: SARS-CoV-2 interaction with Siglec-1 mediates trans-infection by dendritic cells

Correction to: https://doi.org/10.1038/s41423-021-00794-6; http://hdl.handle.net/10261/257710In the version of this correspondence initially published, one of the SARS-CoV-2 variants used in Fig. 1B, which was originally described in the article as the SARS-CoV-2 variant ‘B.1.1.248.2 Gamma’, is actually the ‘P.2 Zeta’ SARS-CoV-2 variant of interest. The GISAID accession ID EPI_ISL_1831696 provided is correct, but it belongs to the Zeta variant. The results and conclusions are not affected by this unintentional inaccuracy.Peer reviewe

Siglec-1 on dendritic cells mediates SARS-CoV-2 trans-infection of target cells while on macrophages triggers proinflammatory responses

COVID-19 pandemic is not yet under control by vaccination, and effective antivirals are critical for preparedness. Here we report that macrophages and dendritic cells, key antigen presenting myeloid cells (APCs), are largely resistant to SARS-CoV-2 infection. APCs effectively captured viruses within cellular compartments that lead to antigen degradation. Macrophages sense SARS-CoV-2 and released higher levels of cytokines, including those related to cytokine storm in severe COVID-19. The sialic acid-binding Ig-like lectin 1 (Siglec-1/CD169) present on APCs, which interacts with sialylated gangliosides on membranes of retroviruses or filoviruses, also binds SARS-CoV-2 via GM1. Blockage of Siglec-1 receptors by monoclonal antibodies reduces SARS-CoV-2 uptake and transfer to susceptible target cells. APCs expressing Siglec-1 and carrying SARS-CoV-2 are found in pulmonary tissues of non-human primates. Single cell analysis reveals the in vivo induction of cytokines in those macrophages. Targeting Siglec-1 could offer cross-protection against SARS-CoV-2 and other enveloped viruses that exploit APCs for viral dissemination, including those yet to come in future outbreaks.The research of CBIG consortium (constituted by IRTA-CReSA, BSC, & IrsiCaixa) is supported by Grifols pharmaceutical. The authors also acknowledge the crowdfunding initiative #Yomecorono (https://www.yomecorono.com). J.M-P. is supported by grant PID2019-109870RB-I00 from the Spanish Ministry of Science and Innovation and in part also by Grifols. CR lab is funded by RTI2018-094445-B100 (MCIU/AEI/FEDER, UE). The authors also acknowledge the crowdfunding initiative #Yomecorono (https://www.yomecorono.com). The NHP study was primarily supported by YNPRC Coronavirus Pilot Research Project Program grant to M.Pa. under award P51 OD11132, Emergent Venture Fast grant program to MPa under awards #2206 and #2144, and William and Lula Pitts Foundation (to MPa).N