Spatiotemporal Characteristics of the Largest HIV-1 CRF02_AG Outbreak in Spain: Evidence for Onward Transmissions

Background and Aim: The circulating recombinant form 02_AG (CRF02_AG) is the predominant clade among the human immunodeficiency virus type-1 (HIV-1) non-Bs with a prevalence of 5.97% (95% Confidence Interval-CI: 5.41–6.57%) across Spain. Our aim was to estimate the levels of regional clustering for CRF02_AG and the spatiotemporal characteristics of the largest CRF02_AG subepidemic in Spain.Methods: We studied 396 CRF02_AG sequences obtained from HIV-1 diagnosed patients during 2000–2014 from 10 autonomous communities of Spain. Phylogenetic analysis was performed on the 391 CRF02_AG sequences along with all globally sampled CRF02_AG sequences (N = 3,302) as references. Phylodynamic and phylogeographic analysis was performed to the largest CRF02_AG monophyletic cluster by a Bayesian method in BEAST v1.8.0 and by reconstructing ancestral states using the criterion of parsimony in Mesquite v3.4, respectively.Results: The HIV-1 CRF02_AG prevalence differed across Spanish autonomous communities we sampled from (p < 0.001). Phylogenetic analysis revealed that 52.7% of the CRF02_AG sequences formed 56 monophyletic clusters, with a range of 2–79 sequences. The CRF02_AG regional dispersal differed across Spain (p = 0.003), as suggested by monophyletic clustering. For the largest monophyletic cluster (subepidemic) (N = 79), 49.4% of the clustered sequences originated from Madrid, while most sequences (51.9%) had been obtained from men having sex with men (MSM). Molecular clock analysis suggested that the origin (tMRCA) of the CRF02_AG subepidemic was in 2002 (median estimate; 95% Highest Posterior Density-HPD interval: 1999–2004). Additionally, we found significant clustering within the CRF02_AG subepidemic according to the ethnic origin.Conclusion: CRF02_AG has been introduced as a result of multiple introductions in Spain, following regional dispersal in several cases. We showed that CRF02_AG transmissions were mostly due to regional dispersal in Spain. The hot-spot for the largest CRF02_AG regional subepidemic in Spain was in Madrid associated with MSM transmission risk group. The existence of subepidemics suggest that several spillovers occurred from Madrid to other areas. CRF02_AG sequences from Hispanics were clustered in a separate subclade suggesting no linkage between the local and Hispanic subepidemics

La biosíntesis de CoA y su papel esencial en el establecimiento de la plántula, en respuesta al estrés osmótico/salino y en el almacenamiento de lípidos en Arabidopsis thaliana

Tesis doctoral del Departamento de Biotecnología de la Universidad Politécnica de Valencia, realizada en el Instituto de Biología Molecular y Celular de Plantas (IBMCP-CSIC-UPV)El Coenzima A (CoA) es un cofactor en multitud de reacciones enzimáticas, entre ellas la oxidación de ácidos grasos, carbohidratos y aminoácidos y muchas otras reacciones de biosíntesis. En el mundo vegetal, el acetil-CoA (AcCoA) es un metabolito clave en el ciclo de Krebs, en ciclo del glioxilato y gluconeogénesis, en la biosíntesis de isoprenoides (en la ruta citosólica del mevalonato), de ácidos grasos y de derivados de la ruta de fenilpropanoides, así como en la acetilación de histonas. El profundo impacto del CoA en el metabolismo celular se traduce también en un importante papel en la respuesta de la planta ante situaciones de estrés salino/osmótico, por ejemplo mediante la síntesis de osmolitos. Con el objeto de estudiar las consecuencias fisiológicas que tiene sobre la planta la manipulación de la biosíntesis de CoA, hemos llevado a cabo abordajes de pérdida y ganancia de función en tres genes de la ruta, i.e. HAL3A, HAL3B y PPAT. HAL3A codifica una descarboxilasa de fosfopantotenoilcisteína que genera fosfopanteteína, el antepenúltimo intermediario en la biosíntesis de CoA. El genoma de Arabidopsis contiene un segundo gen, HAL3B, homólogo a HAL3A, aunque con un papel secundario, demostrado por el fenotipo en establecimiento del doble mutante heterozigoto aaBb y que no muestra Aabb. La fosfopanteteína generada en la reacción catalizada por HAL3A/HAL3B es el sustrato de PPAT, un enzima que transfiere adenilato a este sustrato para generar defosfoCoA, el penúltimo intermediario en la biosíntesis de CoA. Como se presumía del papel crucial de CoA en el metabolismo celular, un doble mutante hal3ahal3b fue letal durante el desarrollo embrionario. Plántulas con una sola copia funcional de HAL3B y nulas para HAL3A (aaBb) fueron viables y completaban el ciclo vital, no obstante mostraban un fenotipo de dependencia de sacarosa en el establecimiento de plántula, el cual es un atributo común con mutantes afectados en la - oxidación de los ácidos grasos. Medidas del contenido en ácidos grasos y acil-CoAs de plántulas de 5 días en medio carente de sacarosa mostraban una detención en el catabolismo de los lípidos de reserva y una reducción en la biosíntesis de CoA, con una disminución de ~80% en los niveles de acetil-CoA. Adicionalmente, los individuos aaBb mostraban una reducción severa en la producción de semillas y en la tolerancia a estrés salino. Similares efectos fenotípicos fueron obtenidos con un mutante de reducción de función del gen PPAT, i.e. ppat-1. En el mutante ppat-1 hay una reducción de ~90% en la expresión de PPAT, lo cual conduce a un severo retraso en el crecimiento. En cambio, plantas 35S:PPAT mostraban mayor crecimiento, resistencia a estrés salino/osmótico y mayor acumulación de ácidos grasos en semillas que plantas tipo silvestre. Estos resultados sugieren que la manipulación en plantas de cosecha de los niveles de CoA podría conducir a una mejora de la resistencia al estrés abiótico y del contenido lipídico en semillas oleaginosas y en general, en una mayor producción de biomasa.Peer reviewe

Utilización del enzima fosfopanteteina adeniltransferasa, implicado en la biosíntesis del coenzyma A, en la mejora del crecimiento vegetal, resistencia al estrés salino/osmótico, incremento de lípidos de reserva y modificación del contenido aminoacídico

Fecha de solicitud: 19-11-2009.- Titular: Consejo Superior de Investigaciones Científicas (CSIC)The invention relates to the use of the gene encoding phosphopantetheine adenylyltransferase (PPAT) as a regulator of CoA biosynthesis for the generation of new plant varieties having improved growth, resistance to osmotic and saline stress, increased lipid content in the seeds thereof and an altered amino acid composition. Specifically, the invention relates to the use of said gene as a regulator of CoA biosynthesis in plants in order to modify the phenotype of the plant, and to the genetically modified plants obtained, which have improved growth, resistance to osmotic and saline stress and seed lipid content over non-modified plants and which have an altered amino acid composition.La invención relaciona al uso del adenylyltransferase de codificación del phosphopantetheine del gen (PPAT) como regulador de la biosintesis de CoA para la generación de variedades nuevas de la planta que mejoran crecimiento, resistencia al esfuerzo osmótico y de la solución salina, el contenido creciente del lípido en las semillas de eso y una composición de aminoácidos alterada. Específicamente, la invención relaciona al uso del gen dicho como regulador de la biosintesis de CoA en plantas para modificar el fenotipo de la planta, y a las plantas genético modificadas obtenidas, que han mejorado el crecimiento, resistencia al esfuerzo osmótico y de la solución salina y a las plantas no-modificadas excedente del contenido del lípido de la semilla y que tienen una composición de aminoácidos alterada.Peer reviewe

Biointeractomic scaffold hovering over apoptotic cytrochrome c

1 página.The role of cytochrome c in apoptosis is well-established, but its participation in signaling pathways in vivo remains still poorly understood due to its essential role in mitochondrial respiration.Peer reviewe

COVID-19 in hospitalized HIV-positive and HIV-negative patients : A matched study

CatedresObjectives: We compared the characteristics and clinical outcomes of hospitalized individuals with COVID-19 with [people with HIV (PWH)] and without (non-PWH) HIV co-infection in Spain during the first wave of the pandemic. Methods: This was a retrospective matched cohort study. People with HIV were identified by reviewing clinical records and laboratory registries of 10 922 patients in active-follow-up within the Spanish HIV Research Network (CoRIS) up to 30 June 2020. Each hospitalized PWH was matched with five non-PWH of the same age and sex randomly selected from COVID-19@Spain, a multicentre cohort of 4035 patients hospitalized with confirmed COVID-19. The main outcome was all-cause in-hospital mortality. Results: Forty-five PWH with PCR-confirmed COVID-19 were identified in CoRIS, 21 of whom were hospitalized. A total of 105 age/sex-matched controls were selected from the COVID-19@Spain cohort. The median age in both groups was 53 (Q1-Q3, 46-56) years, and 90.5% were men. In PWH, 19.1% were injecting drug users, 95.2% were on antiretroviral therapy, 94.4% had HIV-RNA < 50 copies/mL, and the median (Q1-Q3) CD4 count was 595 (349-798) cells/μL. No statistically significant differences were found between PWH and non-PWH in number of comorbidities, presenting signs and symptoms, laboratory parameters, radiology findings and severity scores on admission. Corticosteroids were administered to 33.3% and 27.4% of PWH and non-PWH, respectively (P = 0.580). Deaths during admission were documented in two (9.5%) PWH and 12 (11.4%) non-PWH (P = 0.800). Conclusions: Our findings suggest that well-controlled HIV infection does not modify the clinical presentation or worsen clinical outcomes of COVID-19 hospitalization

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

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

How do women living with HIV experience menopause? Menopausal symptoms, anxiety and depression according to reproductive age in a multicenter cohort

CatedresBackground: To estimate the prevalence and severity of menopausal symptoms and anxiety/depression and to assess the differences according to menopausal status among women living with HIV aged 45-60 years from the cohort of Spanish HIV/AIDS Research Network (CoRIS). Methods: Women were interviewed by phone between September 2017 and December 2018 to determine whether they had experienced menopausal symptoms and anxiety/depression. The Menopause Rating Scale was used to evaluate the prevalence and severity of symptoms related to menopause in three subscales: somatic, psychologic and urogenital; and the 4-item Patient Health Questionnaire was used for anxiety/depression. Logistic regression models were used to estimate odds ratios (ORs) of association between menopausal status, and other potential risk factors, the presence and severity of somatic, psychological and urogenital symptoms and of anxiety/depression. Results: Of 251 women included, 137 (54.6%) were post-, 70 (27.9%) peri- and 44 (17.5%) pre-menopausal, respectively. Median age of onset menopause was 48 years (IQR 45-50). The proportions of pre-, peri- and post-menopausal women who had experienced any menopausal symptoms were 45.5%, 60.0% and 66.4%, respectively. Both peri- and post-menopause were associated with a higher likelihood of having somatic symptoms (aOR 3.01; 95% CI 1.38-6.55 and 2.63; 1.44-4.81, respectively), while post-menopause increased the likelihood of having psychological (2.16; 1.13-4.14) and urogenital symptoms (2.54; 1.42-4.85). By other hand, post-menopausal women had a statistically significant five-fold increase in the likelihood of presenting severe urogenital symptoms than pre-menopausal women (4.90; 1.74-13.84). No significant differences by menopausal status were found for anxiety/depression. Joint/muscle problems, exhaustion and sleeping disorders were the most commonly reported symptoms among all women. Differences in the prevalences of vaginal dryness (p = 0.002), joint/muscle complaints (p = 0.032), and sweating/flush (p = 0.032) were found among the three groups. Conclusions: Women living with HIV experienced a wide variety of menopausal symptoms, some of them initiated before women had any menstrual irregularity. We found a higher likelihood of somatic symptoms in peri- and post-menopausal women, while a higher likelihood of psychological and urogenital symptoms was found in post-menopausal women. Most somatic symptoms were of low or moderate severity, probably due to the good clinical and immunological situation of these women

Deep Underground Neutrino Experiment (DUNE) Near Detector Conceptual Design Report

International audienceThe Deep Underground Neutrino Experiment (DUNE) is an international, world-class experiment aimed at exploring fundamental questions about the universe that are at the forefront of astrophysics and particle physics research. DUNE will study questions pertaining to the preponderance of matter over antimatter in the early universe, the dynamics of supernovae, the subtleties of neutrino interaction physics, and a number of beyond the Standard Model topics accessible in a powerful neutrino beam. A critical component of the DUNE physics program involves the study of changes in a powerful beam of neutrinos, i.e., neutrino oscillations, as the neutrinos propagate a long distance. The experiment consists of a near detector, sited close to the source of the beam, and a far detector, sited along the beam at a large distance. This document, the DUNE Near Detector Conceptual Design Report (CDR), describes the design of the DUNE near detector and the science program that drives the design and technology choices. The goals and requirements underlying the design, along with projected performance are given. It serves as a starting point for a more detailed design that will be described in future documents