Preliminary groundwater modelling by considering the interaction with superficial water: Aosta plain case (northern Italy)

The study is developed through scientific cooperation between the University of Milano-Bicocca and the Regional Agency for Environmental Protection (ARPA) of the Valle d'Aosta Region. Its aim is to produce a decision-support tool to help the Public Administration'manage groundwater and public water supply. The study area is the plain of Aosta, between the cities of Aymavilles and Brissogne; in this area groundwater represents the main source of public water supply. The valley is oriented east-west, along the Baltea for a length of 13.1 km and a width of 4.6 km. The textural and hydrogeological properties of the deposits are strictly connected to glacial deposition and to the subsequent sedimentary processes which took place in glacial, lacustrine and fluvial systems. The study is based on available well information in the Aosta plain - including water wells (133) and piezometers (121) - which have been coded and stored in the well database TANGRAM,. The database facilitates interpretation of the well data, and it allows three-dimensional mapping of subsurface hydrogeological characteristics through database codification and ordinary kriging interpolation. The study is designed to achieve two objectives. The first is to provide the Aosta Public Authorities with a well database in order to simplify groundwater management. The second is to provide Public Authorities with a groundwater flow model of the local aquifer. The model integrates surface and subsurface flows in order to fully account for all important stresses, both natural and anthropogenic, on the groundwater system. It provides a tool for testing hypotheses (such as the impact of new wells) and thereby allows science-based management of the aquifer resource

Avaliação de leitura: escala de fluência baseada em textos narrativos

El objetivo de este trabajo es aplicar una escala subjetiva de fluidez a fin de determinar si esta modalidad de evaluación configura una herramienta eficiente para valorar la fluidez lectora. Una muestra de niños y niñas argentinos de 5to grado de nivel primario fue evaluada con una tarea de comprensión lectora silente ad hoc (TCL), una tarea estandarizada de lectura de palabras (TL) y una tarea de lectura en voz alta para valorar la fluidez con la Escala de fluidez lectora para textos (EFT). Los datos obtenidos al aplicar la EFT fueron analizados y comparados con las puntuaciones de las tareas de CL y TL. Primero, se realizó un análisis de correlación que detectó que el puntaje total de la EFT y cada una de las categorías contempladas en su diseño se asociaron significativamente entre sí y con las puntuaciones alcanzadas por los participantes en la TL y en la TCL. Luego, para establecer si la EFT permite diferenciar entre sujetos con diferente nivel de comprensión se dividió a la muestra en dos grupos según su rendimiento en la TCL y se llevó adelante un análisis de contrastes para medias relacionadas que indicó diferencias en la puntuación global y en las distintas categorías de la EFT entre los grupos de alto y bajo nivel de comprensión. Estos resultados sugieren que la EFT es una herramienta fiable para la evaluación de la fluidez lectora en el ámbito educativo y clínico y es un instrumento sensible para detectar diferencias de rendimiento en comprensión lectora.The aim of this research is to apply a fluency scale in order to investigate if this way to assess is an efficient tool for measuring reading fluency. A sample of Argentinean primary school-aged children (5th grade) were assessed with an ad hoc silent reading comprehension task (RC), a standardized word reading task (WR), and an oral reading task (OR). Oral reading samples were analysed with the Text Reading Fluency Scale (TRFS) designed for this research. The results from the TRFS were analysed and compared with those from the RC and WR tasks. In first place, a correlation analysis was performed. Results showed that TRFS’ total score and each of the categories included in the rubric were significantly associated with each other as well as with participant´s rating achieved in RC and WR tasks. Then, further analysis was fulfilled to establish if TRFS can identify differences in reading comprehension level. The sample was divided according to their performance in the RC in two groups: high and low level of comprehension, and a contrast analysis was conducted. The results showed differences between high and low level of comprehension groups in TRFS´ total score and in the different categories of the rubric. These results suggest that TRFS is a reliable tool to evaluate reading fluency at school as well as in clinical practice and is a sensitive instrument for detecting reading comprehension performance level.O objetivo deste artigo é aplicar uma escala de fluência subjetiva a fim de determinar se esta modalidade de avaliação é uma ferramenta eficiente para avaliar a fluência da leitura. Uma amostra de crianças argentinas do 5º ano da escola primária foi avaliada com uma tarefa ad hoc de compreensão de leitura silenciosa (TCL), uma tarefa estandardizada de leitura de palavras (TL) e uma tarefa de leitura em voz alta para avaliar a fluência com a Escala de Fluência de Leitura para Textos (EFT). Os dados obtidos através da aplicação do EFT foram analisados e comparados com as pontuações das tarefas CL e TL. Primeiro, foi realizada uma análise de correlação que constatou que a pontuação total da EFT e cada uma das categorias no desenho da EFT estavam significativamente associadas umas às outras e às pontuações de TL e TCL dos participantes. Depois, para estabelecer se o EFT pode diferenciar entre sujeitos com diferentes níveis de compreensão, a amostra foi dividida em dois grupos de acordo com o seu desempenho no TCL e foi realizada uma análise de contrastes para meios relacionados, indicando diferenças na pontuação global e nas diferentes categorias de EFT entre os grupos de alta e baixa compreensão. Estes resultados sugerem que o EFT é uma ferramenta fiável para a avaliação da fluência da leitura em contextos educativos e clínicos e é um instrumento sensível para detectar diferenças no desempenho da compreensão da leitura.Fil: Fumagalli, Julieta Carolina. Universidad de Buenos Aires. Facultad de Filosofía y Letras. Instituto de Lingüística; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Ferroni, Marina Valeria. Universidad de Buenos Aires. Facultad de Filosofía y Letras. Instituto de Lingüística; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Jaichenco, Virginia Irene. Universidad de Buenos Aires. Facultad de Filosofía y Letras. Instituto de Lingüística; Argentina. Universidad Nacional de Hurlingham; Argentin

Correlation among different KRAS alterations, genetic co-mutations and PD-L1 expression in patients treated with immunotherapy in metastatic NSCLC

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Nirmatrelvir treatment of SARS-CoV-2-infected mice blunts antiviral adaptive immune responses

Alongside vaccines, antiviral drugs are becoming an integral part of our response to the SARS-CoV-2 pandemic. Nirmatrelvir-an orally available inhibitor of the 3-chymotrypsin-like cysteine protease-has been shown to reduce the risk of progression to severe COVID-19. However, the impact of nirmatrelvir treatment on the development of SARS-CoV-2-specific adaptive immune responses is unknown. Here, by using mouse models of SARS-CoV-2 infection, we show that nirmatrelvir administration blunts the development of SARS-CoV-2-specific antibody and T cell responses. Accordingly, upon secondary challenge, nirmatrelvir-treated mice recruited significantly fewer memory T and B cells to the infected lungs and mediastinal lymph nodes, respectively. Together, the data highlight a potential negative impact of nirmatrelvir treatment with important implications for clinical management and might help explain the virological and/or symptomatic relapse after treatment completion reported in some individuals

Sam68 regulates translation of target mRNAs in male germ cells, necessary for mouse spermatogenesis

Sam68 is a KH-type RNA-binding protein involved in several steps of RNA metabolism with potential implications in cell differentiation and cancer. However, its physiological roles are still poorly understood. Herein, we show that Sam68−/− male mice are infertile and display several defects in spermatogenesis, demonstrating an essential role for Sam68 in male fertility. Sam68−/− mice produce few spermatozoa, which display dramatic motility defects and are unable to fertilize eggs. Expression of a subset of messenger mRNAs (mRNAs) is affected in the testis of knockout mice. Interestingly, Sam68 is associated with polyadenylated mRNAs in the cytoplasm during the meiotic divisions and in round spermatids, when it interacts with the translational machinery. We show that Sam68 is required for polysomal recruitment of specific mRNAs and for accumulation of the corresponding proteins in germ cells and in a heterologous system. These observations demonstrate a novel role for Sam68 in mRNA translation and highlight its essential requirement for the development of a functional male gamete

Protective immune trajectories in early viral containment of non-pneumonic SARS-CoV-2 infection

The antiviral immune response to SARS-CoV-2 infection can limit viral spread and prevent development of pneumonic COVID-19. However, the protective immunological response associated with successful viral containment in the upper airways remains unclear. Here, we combine a multi-omics approach with longitudinal sampling to reveal temporally resolved protective immune signatures in non-pneumonic and ambulatory SARS-CoV-2 infected patients and associate specific immune trajectories with upper airway viral containment. We see a distinct systemic rather than local immune state associated with viral containment, characterized by interferon stimulated gene (ISG) upregulation across circulating immune cell subsets in non-pneumonic SARS-CoV2 infection. We report reduced cytotoxic potential of Natural Killer (NK) and T cells, and an immune-modulatory monocyte phenotype associated with protective immunity in COVID-19. Together, we show protective immune trajectories in SARS-CoV2 infection, which have important implications for patient prognosis and the development of immunomodulatory therapies

Genome-Wide Interrogation of Mammalian Stem Cell Fate Determinants by Nested Chromosome Deletions

Understanding the function of important DNA elements in mammalian stem cell genomes would be enhanced by the availability of deletion collections in which segmental haploidies are precisely characterized. Using a modified Cre-loxP–based system, we now report the creation and characterization of a collection of ∼1,300 independent embryonic stem cell (ESC) clones enriched for nested chromosomal deletions. Mapping experiments indicate that this collection spans over 25% of the mouse genome with good representative coverage of protein-coding genes, regulatory RNAs, and other non-coding sequences. This collection of clones was screened for in vitro defects in differentiation of ESC into embryoid bodies (EB). Several putative novel haploinsufficient regions, critical for EB development, were identified. Functional characterization of one of these regions, through BAC complementation, identified the ribosomal gene Rps14 as a novel haploinsufficient determinant of embryoid body formation. This new library of chromosomal deletions in ESC (DelES: http://bioinfo.iric.ca/deles) will serve as a unique resource for elucidation of novel protein-coding and non-coding regulators of ESC activity

Disentangling Signatures of Selection Before and After European Colonization in Latin Americans

Throughout human evolutionary history, large-scale migrations have led to intermixing (i.e., admixture) between previously separated human groups. Although classical and recent work have shown that studying admixture can yield novel historical insights, the extent to which this process contributed to adaptation remains underexplored. Here, we introduce a novel statistical model, specific to admixed populations, that identifies loci under selection while determining whether the selection likely occurred post-admixture or prior to admixture in one of the ancestral source populations. Through extensive simulations, we show that this method is able to detect selection, even in recently formed admixed populations, and to accurately differentiate between selection occurring in the ancestral or admixed population. We apply this method to genome-wide SNP data of ∼4,000 individuals in five admixed Latin American cohorts from Brazil, Chile, Colombia, Mexico, and Peru. Our approach replicates previous reports of selection in the human leukocyte antigen region that are consistent with selection post-admixture. We also report novel signals of selection in genomic regions spanning 47 genes, reinforcing many of these signals with an alternative, commonly used local-ancestry-inference approach. These signals include several genes involved in immunity, which may reflect responses to endemic pathogens of the Americas and to the challenge of infectious disease brought by European contact. In addition, some of the strongest signals inferred to be under selection in the Native American ancestral groups of modern Latin Americans overlap with genes implicated in energy metabolism phenotypes, plausibly reflecting adaptations to novel dietary sources available in the Americas