A dialectometric approach to Romanian intonation

[eng] This paper presents the first dialectometric analysis of intonational variation of standard spo-ken Romanian. The data analysed (26,680 sentences) were gathered within the AMPER-ROM project and the dialectometrical analysis has been carried out with ProDis. The results are consistent with the geolinguistic descriptions of Romanian varieties. ProDis identified two major areas for yes-no questions: a central-eastern one (Moldo-Walachian), with rising con-tours, and a central-western one (Transylvanian, discontinuously continuing over Bukovina to Bessarabia—the Republic of Moldova—), which presents also falling contours. The study suggests that intonational areas are somehow more conservative of and (relatively) independent from segmental dialectal areas

Prosodic distances between different survey sites in Romance-speaking Europe

[eng] The aim of this paper is to classify Romanian dialects from a prosodic point of view within the European Romance-speaking area. The data is part of the Multimedia Atlas of Romance Prosody - AMPER (Contini, 1992) and is analysed dialectometrically by means of ProDis (Elvira-García et al., 2015; Fernández Planas, 2016). The database includes more than 17,000 utterances produced by 48 speakers from 26 survey sites of 15 varieties of 6 Romance languages (Catalan, Spanish, Italian, Sardinian, Friulian and Romanian). The results show that the two main prosodic areas of Romanian (see Roseano, 2016b) remain separate when they are dialectometrized with data from other Romance languages. In addition, if one analyses questions and statements separately, it can be seen that questions allow us to distinguish geoprosodic areas more effectively than statements do (as suggested by previous studies such as Fernández Planas et al., 2015)

Identification of HIV-reservoir cells with reduced susceptibility to antibody-dependent immune response

HIV; Infectious disease; ReservoirVIH; Malalties infeccioses; ReservoriVIH; Enfermedades infecciosas; ReservorioHuman immunodeficiency virus (HIV) establishes a persistent infection in heterogeneous cell reservoirs, which can be maintained by different mechanisms including cellular proliferation, and represent the main obstacle to curing the infection. The expression of the Fcγ receptor CD32 has been identified as a marker of the active cell reservoirs in people on antiretroviral therapy (ART), but if its expression has any role in conferring advantage for viral persistence is unknown. Here, we report that HIV-infected cells expressing CD32 have reduced susceptibility to natural killer (NK) antibody-dependent cell cytotoxicity (ADCC) by a mechanism compatible with the suboptimal binding of HIV-specific antibodies. Infected CD32 cells have increased proliferative capacity in the presence of immune complexes, and are more resistant to strategies directed to potentiate NK function. Remarkably, reactivation of the latent reservoir from antiretroviral-treated people living with HIV increases the pool of infected CD32 cells, which are largely resistant to the ADCC immune mechanism. Thus, we report the existence of reservoir cells that evade part of the NK immune response through the expression of CD32.This study was supported by the Spanish Secretariat of Science and Innovation and FEDER funds (grants SAF2015-67334-R and RTI2018-101082-B-I00 [MINECO/FEDER]), the Spanish “Ministerio de Economia y Competitividad, Instituto de Salud Carlos III” (ISCIII, PI17/01470), GeSIDA and the Spanish AIDS network Red Temática Cooperativa de Investigación en SIDA (RD16/0025/0007), the Fundació La Marató TV3 (grants 201805-10FMTV3 and 201814-10FMTV3) and the Gilead fellowships GLD19/00084 and GLD18/00008. M.B is supported by the Miguel Servet program funded by the Spanish Health Institute Carlos III (CP17/00179). A.A-G is supported by the Spanish Secretariat of Science and Innovation Ph.D. fellowship (BES-2016–076382). The funders had no role in study design, data collection, and analysis, the decision to publish, or preparation of the manuscript

Procesamiento de consultas métrico-temporales

Las bases de datos actuales permiten almacenar datos no estructurados tales como imágenes, sonido, video, datos geométricos, etc. Las tecnologías tradicionales de bases de datos no son aplicables en este ámbito. El modelo de bases de datos métrico-temporal permite abordar aquellas situaciones en las que resulta necesario realizar búsquedas por similitud sobre datos no estructurados pero teniendo en cuenta también la componente temporal. En este modelo se combinan los espacios métricos con las bases de datos temporales, permitiendo así procesar consultas por similitud restringidas a un intervalo o a un instante de tiempo. Nuestra área de investigación es el diseño de índices eficientes para este tipo de bases de datos.Eje: Bases de datos y minería de datosRed de Universidades con Carreras en Informática (RedUNCI

Procesamiento de consultas y aplicaciones del modelo métrico temporal

Las bases de datos actuales permiten almacenar datos no estructurados tales como imágenes, sonido, video, datos geométricos, etc. Las tecnologías tradicionales de bases de datos no son aplicables en este ámbito. Nuevos modelos de bases de datos surgen para cubrir las necesidades de almacenamiento y búsqueda en estas bases de datos. Entre estos nuevos modelos podemos nombrar el espacial, el temporal, el de espacios métricos y el métricotemporal, entre otros. Nuestro área de investigación es el diseño de índices eficientes para estos nuevos modelos de bases de datos.Eje: Base de datos y minería de datosRed de Universidades con Carreras en Informática (RedUNCI

Latency reversal agents affect differently the latent reservoir present in distinct CD4+ t subpopulations

Latency reversal agents (LRAs) have proven to induce HIV-1 transcription in vivo but are ineffective at decreasing the size of the latent reservoir in antiretroviral treated patients. The capacity of the LRAs to perturb the viral reservoir present in distinct subpopulations of cells is currently unknown. Here, using a new RNA FISH/flow ex vivo viral reactivation assay, we performed a comprehensive assessment of the viral reactivation capacity of different families of LRAs, and their combinations, in different CD4 T cell subsets. We observed that a median of 16.28% of the whole HIV-reservoir induced HIV-1 transcripts after viral reactivation, but only 10.10% of these HIV-1 RNA cells produced the viral protein p24. Moreover, none of the LRAs were powerful enough to reactivate HIV-1 transcription in all CD4 T cell subpopulations. For instance, the combination of Romidepsin and Ingenol was identified as the best combination of drugs at increasing the proportion of HIV-1 RNA cells, in most, but not all, CD4 T cell subsets. Importantly, memory stem cells were identified as highly resistant to HIV-1 reactivation, and only the combination of Panobinostat and Bryostatin-1 significantly increased the number of cells transcribing HIV within this subset. Overall, our results validate the use of the RNA FISH/flow technique to assess the potency of LRAs among different CD4 T cell subsets, manifest the intrinsic differences between cells that encompass the latent HIV reservoir, and highlight the difficulty to significantly impact the latent infection with the currently available drugs. Thus, our results have important implications for the rational design of therapies aimed at reversing HIV latency from diverse cellular reservoirs

Inferring causal molecular networks: empirical assessment through a community-based effort

Inferring molecular networks is a central challenge in computational biology. However, it has remained unclear whether causal, rather than merely correlational, relationships can be effectively inferred in complex biological settings. Here we describe the HPN-DREAM network inference challenge that focused on learning causal influences in signaling networks. We used phosphoprotein data from cancer cell lines as well as in silico data from a nonlinear dynamical model. Using the phosphoprotein data, we scored more than 2,000 networks submitted by challenge participants. The networks spanned 32 biological contexts and were scored in terms of causal validity with respect to unseen interventional data. A number of approaches were effective and incorporating known biology was generally advantageous. Additional sub-challenges considered time-course prediction and visualization. Our results constitute the most comprehensive assessment of causal network inference in a mammalian setting carried out to date and suggest that learning causal relationships may be feasible in complex settings such as disease states. Furthermore, our scoring approach provides a practical way to empirically assess the causal validity of inferred molecular networks

Inferring causal molecular networks: empirical assessment through a community-based effort

It remains unclear whether causal, rather than merely correlational, relationships in molecular networks can be inferred in complex biological settings. Here we describe the HPN-DREAM network inference challenge, which focused on learning causal influences in signaling networks. We used phosphoprotein data from cancer cell lines as well as in silico data from a nonlinear dynamical model. Using the phosphoprotein data, we scored more than 2,000 networks submitted by challenge participants. The networks spanned 32 biological contexts and were scored in terms of causal validity with respect to unseen interventional data. A number of approaches were effective, and incorporating known biology was generally advantageous. Additional sub-challenges considered time-course prediction and visualization. Our results suggest that learning causal relationships may be feasible in complex settings such as disease states. Furthermore, our scoring approach provides a practical way to empirically assess inferred molecular networks in a causal sense

Autoantibodies neutralizing type I IFNs are present in ~4% of uninfected individuals over 70 years old and account for ~20% of COVID-19 deaths

Publisher Copyright: © 2021 The Authors, some rights reserved.Circulating autoantibodies (auto-Abs) neutralizing high concentrations (10 ng/ml; in plasma diluted 1:10) of IFN-alpha and/or IFN-omega are found in about 10% of patients with critical COVID-19 (coronavirus disease 2019) pneumonia but not in individuals with asymptomatic infections. We detect auto-Abs neutralizing 100-fold lower, more physiological, concentrations of IFN-alpha and/or IFN-omega (100 pg/ml; in 1:10 dilutions of plasma) in 13.6% of 3595 patients with critical COVID-19, including 21% of 374 patients >80 years, and 6.5% of 522 patients with severe COVID-19. These antibodies are also detected in 18% of the 1124 deceased patients (aged 20 days to 99 years; mean: 70 years). Moreover, another 1.3% of patients with critical COVID-19 and 0.9% of the deceased patients have auto-Abs neutralizing high concentrations of IFN-beta. We also show, in a sample of 34,159 uninfected individuals from the general population, that auto-Abs neutralizing high concentrations of IFN-alpha and/or IFN-omega are present in 0.18% of individuals between 18 and 69 years, 1.1% between 70 and 79 years, and 3.4% >80 years. Moreover, the proportion of individuals carrying auto-Abs neutralizing lower concentrations is greater in a subsample of 10,778 uninfected individuals: 1% of individuals 80 years. By contrast, auto-Abs neutralizing IFN-beta do not become more frequent with age. Auto-Abs neutralizing type I IFNs predate SARS-CoV-2 infection and sharply increase in prevalence after the age of 70 years. They account for about 20% of both critical COVID-19 cases in the over 80s and total fatal COVID-19 cases.Peer reviewe

Autoantibodies against type I IFNs in patients with critical influenza pneumonia

In an international cohort of 279 patients with hypoxemic influenza pneumonia, we identified 13 patients (4.6%) with autoantibodies neutralizing IFN-alpha and/or -omega, which were previously reported to underlie 15% cases of life-threatening COVID-19 pneumonia and one third of severe adverse reactions to live-attenuated yellow fever vaccine. Autoantibodies neutralizing type I interferons (IFNs) can underlie critical COVID-19 pneumonia and yellow fever vaccine disease. We report here on 13 patients harboring autoantibodies neutralizing IFN-alpha 2 alone (five patients) or with IFN-omega (eight patients) from a cohort of 279 patients (4.7%) aged 6-73 yr with critical influenza pneumonia. Nine and four patients had antibodies neutralizing high and low concentrations, respectively, of IFN-alpha 2, and six and two patients had antibodies neutralizing high and low concentrations, respectively, of IFN-omega. The patients' autoantibodies increased influenza A virus replication in both A549 cells and reconstituted human airway epithelia. The prevalence of these antibodies was significantly higher than that in the general population for patients 70 yr of age (3.1 vs. 4.4%, P = 0.68). The risk of critical influenza was highest in patients with antibodies neutralizing high concentrations of both IFN-alpha 2 and IFN-omega (OR = 11.7, P = 1.3 x 10(-5)), especially those <70 yr old (OR = 139.9, P = 3.1 x 10(-10)). We also identified 10 patients in additional influenza patient cohorts. Autoantibodies neutralizing type I IFNs account for similar to 5% of cases of life-threatening influenza pneumonia in patients <70 yr old