Construcción refleja como procedimiento semiatributivo

El interés del trabajo es doble: por un lado, trata de poner de relieve, en el conjunto de las oraciones reflejas, un modelo construccional específico, la secuencia “sujeto-SE-verbo-predicado” (sujeto, verbo reflejo, predicativo); por otro lado, se ejemplifica lo que es una función general de la partícula refleja cuando ocupa el lugar correspondiente a un segundo actante oracional. The interest of this work is double: on one hand, it tries to highlight, in the compound of reflexive sentences in Spanish, a specific constructional model, the “subject-SE-verb-predicate” sequence; on the other hand, it exemplifies what a general function of the reflexive particle is when it occupies the place corresponding to a second actor in the sentence

On natural metalinguistic abilities in aphasia: a preliminary study

Natural metalinguistic abilities, which are put into play without explicit instructions, constitute the cognitive basis for a 'reflexive' use of language, a particular manifestation of the executive function when applied to language and verbal behaviour. This reflexive use entails a specific attentional activity by speakers and hearers with regard to linguistic outputs, and an intentional experience-based control over the language use. Putting into play natural metalinguistic abilities can be considered a significant factor for explaining different kinds of adaptive processes. Our results permit us to conclude that an impairment of metalinguistic abilities is involved in aphasia to different degrees. Moreover, the examination of preserved metalinguistic abilities provides an alternative way for assessing the degree of severity of impaired communicative behaviour by people with aphasia. Our procedure, presumably, will also be useful for suggesting new factors when designing therapeutic programmes

An optimized MNK1b aptamer, apMNKQ2, and its potential use as a therapeutic agent in breast cancer

16 pags., 8 figs.Breast cancer is the most commonly diagnosed and leading cause of cancer death among women worldwide. Mitogen-activated protein kinase-interacting kinases (MNKs) promote the expression of several oncogenic proteins and are overexpressed in several types of cancer. In human cells, there are four isoforms of MNKs. The truncated isoform MNK1b, first described in our laboratory, has a higher basal activity and is constitutively active. Aptamers are emerging in recent years as potential therapeutic agents that show significant advantages over drugs of other nature. We have previously obtained and characterized a highly specific aptamer against MNK1b, named apMNK2F, with a dissociation constant in the nanomolar range, which produces significant inhibition of proliferation, migration, and colony formation in breast cancer cells. Furthermore, its sequence analysis predicted two G-quadruplex structures. In this work, we show the optimization process of the aptamer to reduce its size, improving its stability. The obtained aptamer, named apMNKQ2, is able to inhibit proliferation, colony formation, migration, and invasion in breast cancer cells. In murine models of breast cancer, apMNKQ2 has demonstrated its efficacy in reducing tumor volume and the number of metastases. In conclusion, apMNKQ2 could be used as an anti-tumor drug in the future.C.P.-D. was supported by grant RTC-2014-1986-1 from the Ministry of Economy and Competitiveness (Spain). R.F.-M... by predoctoral contract (PEJD-2018-BMD-4416) from the Community of Madrid (Spain) and FPU19/02929 from the Ministry of Science, Innovation and Universities (Spain). R.C.-B. for predoctoral contracts (PEJD 2016-BMD-2145 and 2018-BMD-9201) from the Community of Madrid and grant RTC2019-07227-1. M. EM., and V.M.G. are researchers at FIBio-HRC. Supported by grants RTC2019-07227-1, PID2020-116620GB-T.I.00, and PID2019-105417RB-I00, funded by MCIN/ AEI /10.13039/501100011033 (Ministry of Economy and Competitiveness, Spain).Peer reviewe

Costs and benefits of automation for astronomical facilities

The Observatorio Astrof\'isico de Javalambre (OAJ{\dag}1) in Spain is a young astronomical facility, conceived and developed from the beginning as a fully automated observatory with the main goal of optimizing the processes in the scientific and general operation of the Observatory. The OAJ has been particularly conceived for carrying out large sky surveys with two unprecedented telescopes of unusually large fields of view (FoV): the JST/T250, a 2.55m telescope of 3deg field of view, and the JAST/T80, an 83cm telescope of 2deg field of view. The most immediate objective of the two telescopes for the next years is carrying out two unique photometric surveys of several thousands square degrees, J-PAS{\dag}2 and J-PLUS{\dag}3, each of them with a wide range of scientific applications, like e.g. large structure cosmology and Dark Energy, galaxy evolution, supernovae, Milky Way structure, exoplanets, among many others. To do that, JST and JAST are equipped with panoramic cameras under development within the J-PAS collaboration, JPCam and T80Cam respectively, which make use of large format (~ 10k x 10k) CCDs covering the entire focal plane. This paper describes in detail, from operations point of view, a comparison between the detailed cost of the global automation of the Observatory and the standard automation cost for astronomical facilities, in reference to the total investment and highlighting all benefits obtained from this approach and difficulties encountered. The paper also describes the engineering development of the overall facilities and infrastructures for the fully automated observatory and a global overview of current status, pinpointing lessons learned in order to boost observatory operations performance, achieving scientific targets, maintaining quality requirements, but also minimizing operation cost and human resources.Comment: Global Observatory Control System GOC

Role of Neural NO Synthase (nNOS) Uncoupling in the Dysfunctional Nitrergic Vasorelaxation of Penile Arteries from Insulin-Resistant Obese Zucker Rats

Objective: Erectile dysfunction (ED) is considered as an early sign of vascular disease due to its high prevalence in patients with cardiovascular risk factors. Endothelial and neural dysfunction involving nitric oxide (NO) are usually implicated in the pathophysiology of the diabetic ED, but the underlying mechanisms are unclear. The present study assessed the role of oxidative stress in the dysfunctional neural vasodilator responses of penile arteries in the obese Zucker rat (OZR), an experimental model of metabolic syndrome/prediabetes. Methods and Results: Electrical field stimulation (EFS) under non-adrenergic non-cholinergic (NANC) conditions evoked relaxations that were significantly reduced in penile arteries of OZR compared with those of lean Zucker rats (LZR). Blockade of NO synthase (NOS) inhibited neural relaxations in both LZR and OZR, while saturating concentrations of the NOS substrate L-arginine reversed the inhibition and restored relaxations in OZR to levels in arteries from LZR. nNOS expression was unchanged in arteries from OZR compared to LZR and nNOS selective inhibition decreased the EFS relaxations in LZR but not in OZR, while endothelium removal did not alter these responses in either strain. Superoxide anion production and nitro-tyrosine immunostaining were elevated in the erectile tissue from OZR. Treatment with the NADPH oxidase inhibitor apocynin or acute incubation with the NOS cofactor tetrahydrobiopterin (BH4) restored neural relaxations in OZR to levels in control arteries, while inhibition of the enzyme of BH4 synthesis GTP-cyclohydrolase (GCH) reduced neural relaxations i

Imageability ratings across languages

Imageability is a psycholinguistic variable that indicates how well a word gives rise to a mental image or sensory experience. Imageability ratings are used extensively in psycholinguistic, neuropsychological, and aphasiological studies. However, little formal knowledge exists about whether and how these ratings are associated between and within languages. Fifteen imageability databases were cross-correlated using nonparametric statistics. Some of these corresponded to unpublished data collected within a European research network-the Collaboration of Aphasia Trialists (COST IS1208). All but four of the correlations were significant. The average strength of the correlations (rho = .68) and the variance explained (R (2) = 46%) were moderate. This implies that factors other than imageability may explain 54% of the results. Imageability ratings often correlate across languages. Different possibly interacting factors may explain the moderate strength and variance explained in the correlations: (1) linguistic and cultural factors; (2) intrinsic differences between the databases; (3) range effects; (4) small numbers of words in each database, equivalent words, and participants; and (5) mean age of the participants. The results suggest that imageability ratings may be used cross-linguistically. However, further understanding of the factors explaining the variance in the correlations will be needed before research and practical recommendations can be made

Deep-sequencing reveals broad subtype-specific HCV resistance mutations associated with treatment failure

A percentage of hepatitis C virus (HCV)-infected patients fail direct acting antiviral (DAA)-based treatment regimens, often because of drug resistance-associated substitutions (RAS). The aim of this study was to characterize the resistance profile of a large cohort of patients failing DAA-based treatments, and investigate the relationship between HCV subtype and failure, as an aid to optimizing management of these patients. A new, standardized HCV-RAS testing protocol based on deep sequencing was designed and applied to 220 previously subtyped samples from patients failing DAA treatment, collected in 39 Spanish hospitals. The majority had received DAA-based interferon (IFN) a-free regimens; 79% had failed sofosbuvir-containing therapy. Genomic regions encoding the nonstructural protein (NS) 3, NS5A, and NS5B (DAA target regions) were analyzed using subtype-specific primers. Viral subtype distribution was as follows: genotype (G) 1, 62.7%; G3a, 21.4%; G4d, 12.3%; G2, 1.8%; and mixed infections 1.8%. Overall, 88.6% of patients carried at least 1 RAS, and 19% carried RAS at frequencies below 20% in the mutant spectrum. There were no differences in RAS selection between treatments with and without ribavirin. Regardless of the treatment received, each HCV subtype showed specific types of RAS. Of note, no RAS were detected in the target proteins of 18.6% of patients failing treatment, and 30.4% of patients had RAS in proteins that were not targets of the inhibitors they received. HCV patients failing DAA therapy showed a high diversity of RAS. Ribavirin use did not influence the type or number of RAS at failure. The subtype-specific pattern of RAS emergence underscores the importance of accurate HCV subtyping. The frequency of “extra-target” RAS suggests the need for RAS screening in all three DAA target regions

Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality