18 research outputs found

    Integration of transcriptomics and proteomics Improves the characterization of the role of mussel gills in a bacterial waterborne infection

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    In recent years, the immune response of mussels (Mytilus galloprovincialis) has been studied at the transcriptomic level against several bacterial infections. As a result, different immune mechanisms have been revealed, including both conserved essential innate pathways and particularities of the mussel immune response according to its nature and environment. However, there is often a lack of functional verification because mussels are a non-model species and because transcriptomic and proteomic information is not always well correlated. In the current study, a high-throughput quantitative proteomics study coupled to LC-MS/MS analysis using isobaric tandem mass tags (TMTs) for protein labeling was employed to study the mussel gill immune response to a Vibrio splendidus bath (waterborne) infection at a functional protein level. A total of 4,242 proteins were identified and quantified, of which 226 were differentially expressed (DEPs) after infection, giving to the study a depth that was lacking in previous proteomic studies of the bivalve immune response. Modulated proteins evidenced an important cytoskeletal disruption caused by bacterial infection. A conserved network of associated proteins was modulated, regulating oxidative stress and NF-kB inflammatory responses and leading to innate immunity effectors. Proteomic results were submitted to an integrated analysis with those obtained in a previous transcriptomic approach with the same infection. Half of all the quantified proteins had a concordant transcriptomic expression trend, but this concordance increased when focusing on the DEPs. The correlation was higher within the immune-related DEPs, and the activation of the conserved NF-kB pro-inflammatory pathway was the main response in both approaches. The results of both techniques could be integrated to obtain a more complete vision of the response.Agencia Estatal de Investigación | Ref. RTI2018-095997-B-I00Xunta de Galicia | Ref. IN607B 2019/01Xunta de Galicia | Ref. ED431C 2020/05Agencia Estatal de Investigación | Ref. PRE2019-09076

    Outcomes from elective colorectal cancer surgery during the SARS-CoV-2 pandemic

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    This study aimed to describe the change in surgical practice and the impact of SARS-CoV-2 on mortality after surgical resection of colorectal cancer during the initial phases of the SARS-CoV-2 pandemic

    Hepatic levels of S-adenosylmethionine regulate the adaptive response to fasting

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    26 p.-6 fig.-1 tab.-1 graph. abst.There has been an intense focus to uncover the molecular mechanisms by which fasting triggers the adaptive cellular responses in the major organs of the body. Here, we show that in mice, hepatic S-adenosylmethionine (SAMe)—the principal methyl donor—acts as a metabolic sensor of nutrition to fine-tune the catabolic-fasting response by modulating phosphatidylethanolamine N-methyltransferase (PEMT) activity, endoplasmic reticulum-mitochondria contacts, β-oxidation, and ATP production in the liver, together with FGF21-mediated lipolysis and thermogenesis in adipose tissues. Notably, we show that glucagon induces the expression of the hepatic SAMe-synthesizing enzyme methionine adenosyltransferase α1 (MAT1A), which translocates to mitochondria-associated membranes. This leads to the production of this metabolite at these sites, which acts as a brake to prevent excessive β-oxidation and mitochondrial ATP synthesis and thereby endoplasmic reticulum stress and liver injury. This work provides important insights into the previously undescribed function of SAMe as a new arm of the metabolic adaptation to fasting.M.V.-R. is supported by Proyecto PID2020-119486RB-100 (funded by MCIN/AEI/10.13039/501100011033), Gilead Sciences International Research Scholars Program in Liver Disease, Acción Estratégica Ciberehd Emergentes 2018 (ISCIII), Fundación BBVA, HORIZON-TMA-MSCA-Doctoral Networks 2021 (101073094), and Redes de Investigación 2022 (RED2022-134485-T). M.L.M.-C. is supported by La CAIXA Foundation (LCF/PR/HP17/52190004), Proyecto PID2020-117116RB-I00 (funded by MCIN/AEI/10.13039/501100011033), Ayudas Fundación BBVA a equipos de investigación científica (Umbrella 2018), and AECC Scientific Foundation (Rare Cancers 2017). A.W. is supported by RTI2018-097503-B-I00 and PID2021-127169OB-I00, (funded by MCIN/AEI/10.13039/501100011033) and by “ERDF A way of making Europe,” Xunta de Galicia (Ayudas PRO-ERC), Fundación Mutua Madrileña, and European Community’s H2020 Framework Programme (ERC Consolidator grant no. 865157 and MSCA Doctoral Networks 2021 no. 101073094). C.M. is supported by CIBERNED. P.A. is supported by Ayudas para apoyar grupos de investigación del sistema Universitario Vasco (IT1476-22), PID2021-124425OB-I00 (funded by MCIN/AEI/10.13039/501100011033 and “ERDF A way of making Europe,” MCI/UE/ISCiii [PMP21/00080], and UPV/EHU [COLAB20/01]). M.F. and M.G.B. are supported by PID2019-105739GB-I00 and PID2020-115472GB-I00, respectively (funded by MCIN/AEI/10.13039/501100011033). M.G.B. is supported by Xunta de Galicia (ED431C 2019/013). C.A., T.L.-D., and J.B.-V. are recipients of pre-doctoral fellowships from Xunta de Galicia (ED481A-2020/046, ED481A-2018/042, and ED481A 2021/244, respectively). T.C.D. is supported by Fundación Científica AECC. A.T.-R. is a recipient of a pre-doctoral fellowship from Fundación Científica AECC. S.V.A. and C.R. are recipients of Margarita Salas postdoc grants under the “Plan de Recuperación Transformación” program funded by the Spanish Ministry of Universities with European Union’s NextGeneration EU funds (2021/PER/00020 and MU-21-UP2021-03071902373A, respectively). T.C.D., A.S.-R., and M.T.-C. are recipients of Ayuda RYC2020-029316-I, PRE2019/088960, and BES-2016/078493, respectively, supported by MCIN/AEI/10.13039/501100011033 and by El FSE invierte en tu futuro. S.L.-O. is a recipient of a pre-doctoral fellowship from the Departamento de Educación del Gobierno Vasco (PRE_2018_1_0372). P.A.-G. is recipient of a FPU pre-doctoral fellowship from the Ministry of Education (FPU19/02704). CIC bioGUNE is supported by Ayuda CEX2021-001136-S financiada por MCIN/AEI/10.13039/501100011033. A.B.-C. was funded by predoctoral contract PFIS (FI19/00240) from Instituto de Salud Carlos III (ISCIII) co-funded by Fondo Social Europeo (FSE), and A.D.-L. was funded by contract Juan Rodés (JR17/00016) from ISCIII. A.B.-C. is a Miguel Servet researcher (CPII22/00008) from ISCIII.Peer reviewe

    COVID-19 symptoms at hospital admission vary with age and sex: results from the ISARIC prospective multinational observational study

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    Background: The ISARIC prospective multinational observational study is the largest cohort of hospitalized patients with COVID-19. We present relationships of age, sex, and nationality to presenting symptoms. Methods: International, prospective observational study of 60 109 hospitalized symptomatic patients with laboratory-confirmed COVID-19 recruited from 43 countries between 30 January and 3 August 2020. Logistic regression was performed to evaluate relationships of age and sex to published COVID-19 case definitions and the most commonly reported symptoms. Results: ‘Typical’ symptoms of fever (69%), cough (68%) and shortness of breath (66%) were the most commonly reported. 92% of patients experienced at least one of these. Prevalence of typical symptoms was greatest in 30- to 60-year-olds (respectively 80, 79, 69%; at least one 95%). They were reported less frequently in children (≤ 18 years: 69, 48, 23; 85%), older adults (≥ 70 years: 61, 62, 65; 90%), and women (66, 66, 64; 90%; vs. men 71, 70, 67; 93%, each P < 0.001). The most common atypical presentations under 60 years of age were nausea and vomiting and abdominal pain, and over 60 years was confusion. Regression models showed significant differences in symptoms with sex, age and country. Interpretation: This international collaboration has allowed us to report reliable symptom data from the largest cohort of patients admitted to hospital with COVID-19. Adults over 60 and children admitted to hospital with COVID-19 are less likely to present with typical symptoms. Nausea and vomiting are common atypical presentations under 30 years. Confusion is a frequent atypical presentation of COVID-19 in adults over 60 years. Women are less likely to experience typical symptoms than men

    Discovering HIV related information by means of association rules and machine learning

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    Acquired immunodeficiency syndrome (AIDS) is still one of the main health problems worldwide. It is therefore essential to keep making progress in improving the prognosis and quality of life of affected patients. One way to advance along this pathway is to uncover connections between other disorders associated with HIV/AIDS-so that they can be anticipated and possibly mitigated. We propose to achieve this by using Association Rules (ARs). They allow us to represent the dependencies between a number of diseases and other specific diseases. However, classical techniques systematically generate every AR meeting some minimal conditions on data frequency, hence generating a vast amount of uninteresting ARs, which need to be filtered out. The lack of manually annotated ARs has favored unsupervised filtering, even though they produce limited results. In this paper, we propose a semi-supervised system, able to identify relevant ARs among HIV-related diseases with a minimal amount of annotated training data. Our system has been able to extract a good number of relationships between HIV-related diseases that have been previously detected in the literature but are scattered and are often little known. Furthermore, a number of plausible new relationships have shown up which deserve further investigation by qualified medical experts

    XV International Congress of Control Electronics and Telecommunications: "The role of technology in times of pandemic and post-pandemic: innovation and development for strategic social and productive sectors"

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    La anterior selección, motivados por la aseveración de Manuel Castells -hace casi 20 años ya- que la innovación y la difusión de la tecnología parecía ser la herramienta apropiada para el desarrollo en la era de la información. Este 2020, sin embargo, ante la situación disruptiva que aquejó y aqueja a la sociedad red como una estructura social emergente de la Era de la Información basada en redes de producción, energizadas por el poder y la experiencia; falló y debe reencontrar su rumbo. Es así que los problemas acuciantes, ahora, fueron: la atención sanitaria y la superación de la epidemia de Sars Cov 2; tomó forma la, hasta entonces, visión irrealista de Castells que … no podemos avanzar con nuestros modelos de desarrollo actual, destruyendo nuestro entorno y excluyendo a la mayor parte de la humanidad de los beneficios de la revolución tecnológica más extraordinaria de la historia, sin sufrir una devastadora reacción por parte de la sociedad y la naturaleza. Fue así que el Cuarto Mundo, específicamente, donde la suficiencia de recurso humano, de capital, trabajo, información y mercado -vinculados todos a través de la tecnología- supuso que atendería eficazmente a través de la población que podía por su capacidad hacer uso racional y profesional del conocimiento, las necesidades de la mayoritaria población vulnerable y vulnerada. Por lo anterior, poner en el centro a las personas, en entornos de tarea y trabajo globales hiperconectados combinando espacios físicos, corrientes de información con canales de conexión expeditos, y formando profesionales del conocimiento que asuman y afronten los retos derivados de la transformación digital de empresas, universidades, y organizaciones, pero en condiciones de equidad y sujetos de prosperidad, será el desafío en los escenarios presentes y futuros inmediatos.The previous selection, motivated by the assertion of Manuel Castells -almost 20 years ago- that innovation and diffusion of technology seemed to be the appropriate tool for development in the information age. This 2020, however, in the face of the disruptive situation that afflicted and continues to afflict the network society as an emerging social structure of the Information Age based on production networks, energized by power and experience; He failed and must find his way again. Thus, the pressing problems now were: health care and overcoming the Sars Cov 2 epidemic; Castells' until then unrealistic vision took shape that... we cannot advance with our current development models, destroying our environment and excluding the majority of humanity from the benefits of the most extraordinary technological revolution in history, without suffering a devastating reaction from society and nature. It was thus that the Fourth World, specifically, where the sufficiency of human resources, capital, work, information and market - all linked through technology - meant that it would serve effectively through the population that could, due to its capacity, make rational use. and knowledge professional, the needs of the majority vulnerable and vulnerable population. Therefore, putting people at the center, in hyperconnected global task and work environments, combining physical spaces, information flows with expedited connection channels, and training knowledge professionals who assume and face the challenges derived from the digital transformation of companies, universities, and organizations, but in conditions of equality and subject to prosperity, will be the challenge in the present and immediate future scenarios.Bogot

    Subcutaneous anti-COVID-19 hyperimmune immunoglobulin for prevention of disease in asymptomatic individuals with SARS-CoV-2 infection: a double-blind, placebo-controlled, randomised clinical trialResearch in context

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    Summary: Background: Anti-COVID-19 hyperimmune immunoglobulin (hIG) can provide standardized and controlled antibody content. Data from controlled clinical trials using hIG for the prevention or treatment of COVID-19 outpatients have not been reported. We assessed the safety and efficacy of subcutaneous anti-COVID-19 hyperimmune immunoglobulin 20% (C19-IG20%) compared to placebo in preventing development of symptomatic COVID-19 in asymptomatic individuals with SARS-CoV-2 infection. Methods: We did a multicentre, randomized, double-blind, placebo-controlled trial, in asymptomatic unvaccinated adults (≥18 years of age) with confirmed SARS-CoV-2 infection within 5 days between April 28 and December 27, 2021. Participants were randomly assigned (1:1:1) to receive a blinded subcutaneous infusion of 10 mL with 1 g or 2 g of C19-IG20%, or an equivalent volume of saline as placebo. The primary endpoint was the proportion of participants who remained asymptomatic through day 14 after infusion. Secondary endpoints included the proportion of individuals who required oxygen supplementation, any medically attended visit, hospitalisation, or ICU, and viral load reduction and viral clearance in nasopharyngeal swabs. Safety was assessed as the proportion of patients with adverse events. The trial was terminated early due to a lack of potential benefit in the target population in a planned interim analysis conducted in December 2021. ClinicalTrials.gov registry: NCT04847141. Findings: 461 individuals (mean age 39.6 years [SD 12.8]) were randomized and received the intervention within a mean of 3.1 (SD 1.27) days from a positive SARS-CoV-2 test. In the prespecified modified intention-to-treat analysis that included only participants who received a subcutaneous infusion, the primary outcome occurred in 59.9% (91/152) of participants receiving 1 g C19-IG20%, 64.7% (99/153) receiving 2 g, and 63.5% (99/156) receiving placebo (difference in proportions 1 g C19-IG20% vs. placebo, −3.6%; 95% CI -14.6% to 7.3%, p = 0.53; 2 g C19-IG20% vs placebo, 1.1%; −9.6% to 11.9%, p = 0.85). None of the secondary clinical efficacy endpoints or virological endpoints were significantly different between study groups. Adverse event rate was similar between groups, and no severe or life-threatening adverse events related to investigational product infusion were reported. Interpretation: Our findings suggested that administration of subcutaneous human hyperimmune immunoglobulin C19-IG20% to asymptomatic individuals with SARS-CoV-2 infection was safe but did not prevent development of symptomatic COVID-19. Funding: Grifols
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