Translation of ABCE1 Is Tightly Regulated by Upstream Open Reading Frames in Human Colorectal Cells

This article belongs to the Special Issue mRNA Metabolism in Health and Disease.ATP-binding cassette subfamily E member 1 (ABCE1) belongs to the ABC protein family of transporters; however, it does not behave as a drug transporter. Instead, ABCE1 actively participates in different stages of translation and is also associated with oncogenic functions. Ribosome profiling analysis in colorectal cancer cells has revealed a high ribosome occupancy in the human ABCE1 mRNA 5'-leader sequence, indicating the presence of translatable upstream open reading frames (uORFs). These cis-acting translational regulatory elements usually act as repressors of translation of the main coding sequence. In the present study, we dissect the regulatory function of the five AUG and five non-AUG uORFs identified in the human ABCE1 mRNA 5'-leader sequence. We show that the expression of the main coding sequence is tightly regulated by the ABCE1 AUG uORFs in colorectal cells. Our results are consistent with a model wherein uORF1 is efficiently translated, behaving as a barrier to downstream uORF translation. The few ribosomes that can bypass uORF1 (and/or uORF2) must probably initiate at the inhibitory uORF3 or uORF5 that efficiently repress translation of the main ORF. This inhibitory property is slightly overcome in conditions of endoplasmic reticulum stress. In addition, we observed that these potent translation-inhibitory AUG uORFs function equally in cancer and in non-tumorigenic colorectal cells, which is consistent with a lack of oncogenic function. In conclusion, we establish human ABCE1 as an additional example of uORF-mediated translational regulation and that this tight regulation contributes to control ABCE1 protein levels in different cell environments.This research was partially funded by Fundação para a Ciência e a Tecnologia (UID/MULTI/04046/2013 to BioISI from FCT/MCTES/PIDDAC). Joana Silva was acknowledged with financial support from a fellowship from Fundação para a Ciência e a Tecnologia (SFRH/BD/106081/2015).info:eu-repo/semantics/publishedVersio

Complejidad sintáctica en narraciones de niños con desarrollo típico, trastorno específico del lenguaje y discapacidad intelectual

El desenvolupament tardà del llenguatge es defineix com la complexització de la llengua amb posterioritat a l’adquisició inicial i durant els primers anys d’escolarització. En aquest context, aquest treball cerca descriure com succeeix aquest procés en nens de tres poblacions diferents: desenvolupament típic (DT), trastorn específic del llenguatge (TEL) i discapacitat intel·lectual (DI). Per això, s’analitzen, des d’una perspectiva funcional-discursiva, les narracions orals de tres grups de nens xilens. La mostra la constituïren escolars amb DT=41, TEL=38 i DI=17, els quals van recontar una història presentada en format audiovisual. Dels resultats, en destaca que la diferència entre els tres grups no radica en la quantitat de vincles interclausulars utilitzats, sinó en els tipus de relacions interclausulars que prefereixen per a construir les seves narracions a l’interior dels paquets de clàusules.Later language development is defined as the increase in language complexity that occurs after the period of initial acquisition and during earlier years of schooling. In this context, this paper aims to describe how this process occurs in three different children populations: typical development (TD), specific language impairment (SLI) and intellectual disability (ID). To do this, the oral narratives of three groups of Chilean children are analyzed from a functional-discourse perspective. The sample consisted of TD=41, SLI=38 and ID=17 school-aged children, who retold a story presented in audiovisual format. The results show that the difference between the three groups is not based in the amount of interclause links used, but in the interclause relation types they prefer to build their stories into clause packages. The results indicate that the difference between the three groups is not based in the amount of interclause links used, but in the interclause relation types they prefer to build their stories into clauses packages

The impact of neutrino-nucleus interaction modeling on new physics searches

Accurate neutrino-nucleus interaction modeling is an essential requirement for the success of the accelerator-based neutrino program. As no satisfactory description of cross sections exists, experiments tune neutrino-nucleus interactions to data to mitigate mis-modeling. In this work, we study how the interplay between near detector tuning and cross section mis-modeling affects new physics searches. We perform a realistic simulation of neutrino events and closely follow NOvA's tuning, the first published of such procedures in a neutrino experiment. We analyze two illustrative new physics scenarios, sterile neutrinos and light neutrinophilic scalars, presenting the relevant experimental signatures and the sensitivity regions with and without tuning. While the tuning does not wash out sterile neutrino oscillation patterns, cross section mis-modeling can bias the experimental sensitivity. In the case of light neutrinophilic scalars, variations in cross section models completely dominate the sensitivity regardless of any tuning. Our findings reveal the critical need to improve our theoretical understanding of neutrino-nucleus interactions, and to estimate the impact of tuning on new physics searches. We urge neutrino experiments to follow NOvA's example and publish the details of their tuning procedure, and to develop strategies to more robustly account for cross section uncertainties, which will expand the scope of their physics program

A Model Framework to Estimate Impact and Cost of Genetics-Based Sterile Insect Methods for Dengue Vector Control

Vector-borne diseases impose enormous health and economic burdens and additional methods to control vector populations are clearly needed. The Sterile Insect Technique (SIT) has been successful against agricultural pests, but is not in large-scale use for suppressing or eliminating mosquito populations. Genetic RIDL technology (Release of Insects carrying a Dominant Lethal) is a proposed modification that involves releasing insects that are homozygous for a repressible dominant lethal genetic construct rather than being sterilized by irradiation, and could potentially overcome some technical difficulties with the conventional SIT technology. Using the arboviral disease dengue as an example, we combine vector population dynamics and epidemiological models to explore the effect of a program of RIDL releases on disease transmission. We use these to derive a preliminary estimate of the potential cost-effectiveness of vector control by applying estimates of the costs of SIT. We predict that this genetic control strategy could eliminate dengue rapidly from a human community, and at lower expense (approximately US$2∼30 per case averted) than the direct and indirect costs of disease (mean US$ 86–190 per case of dengue). The theoretical framework has wider potential use; by appropriately adapting or replacing each component of the framework (entomological, epidemiological, vector control bio-economics and health economics), it could be applied to other vector-borne diseases or vector control strategies and extended to include other health interventions

Calidad del servicio y la satisfacción de los usuarios de la Unidad de Gestión Educativa Local Andahuaylas, 2022

El presente estudio se desarrolló en la unidad de gestión educativa local de la región de Apurímac, entidad encargada de llevar a cabo la aplicación de las políticas públicas y administración del servicio educativo; se estableció como objetivo general: Determinar la relación entre la calidad del servicio y la satisfacción de los usuarios en la unidad de gestión educativa local, Andahuaylas, la investigación fue básica, enfoque cuantitativo, diseño no-experimental, con una muestra de 141 usuarios en la unidad de gestión educativa local de la región Apurímac; se aplicaron los cuestionarios sobre calidad del servicio y satisfacción de los usuarios a los usuarios de la mencionada entidad. Los resultados evidenciaron que la calidad del servicio obtuvo un nivel medio representado por el 51%, del mismo modo, prevaleció el nivel alto para la satisfacción de los usuarios el mismo que es representado por el 59%; se determinó que existe una relación significativa entre ambas variables ya que el grado de relación según Rho de Spearman fue de 0,747, obteniendo una relación positiva fuerte; siendo el p valor de 0.002 el cual es menor que 0.05, lo cual indica que existe una relación directa y significativa

Habitabilidad térmica en las viviendas básicas de la zona central de Chile, a la luz de los resultados preliminares del proyecto FONDEF D00I1039

First of all, we will introduce the thermal comfort conditions for the climatic zone where the study was carried on. Thermal Habitability will be defined in relation to the specified climatic conditions and the specific characteristics of the housing typology. To measure housing energy consumption Thermal Habitability indicator appears as a different concept of the criteria used in developed nations; climatic conditions and the way housing industry has developed in Chile can justify the use of Thermal Habitability criteria. We will present the methodology used for the measurements collected in the dataloggers and the analysis of the obtained results. We will show the preliminary values for Thermal Habitability for eight residential units taken during wintertime and we will discuss further application of it.En primer lugar se precisan las condiciones de bienestar térmico para la zona climática del país en la cual se realiza el estudio. Se define habitabilidad térmica en cuanto a las condiciones anteriores y a las características de uso de las viviendas. A diferencia de los criterios utilizados en países desarrollados se justifica dicho indicador debido, principalmente, a las condiciones climáticas y de utilización de la vivienda en nuestro país. Se utiliza como metodología la medición de registro de datos y se analizan sus resultados, dando a conocer valores preliminares de habitabilidad térmica de invierno de ocho viviendas y se discuten las perspectivas de su aplicación

Melodic expectations in 5- and 6-year-old children

It has been argued that children implicitly acquire the rules relating to the structure of music in their environment using domain-general mechanisms such as statistical learning. Closely linked to statistical learning is the ability to form expectations about future events. Whether children as young as 5 years can make use of such internalized regularities to form expectations about the next note in a melody is still unclear. The possible effect of the home musical environment on the strength of musical expectations has also been under-explored. Using a newly developed melodic priming task that included melodies with either “expected” or “unexpected” endings according to rules of Western music theory, we tested 5- and 6-year-old children (N = 46). The stimuli in this task were constructed using the information dynamics of music (IDyOM) system, a probabilistic model estimating the level of “unexpectedness” of a note given the preceding context. Results showed that responses to expected versus unexpected tones were faster and more accurate, indicating that children have already formed robust melodic expectations at 5 years of age. Aspects of the home musical environment significantly predicted the strength of melodic expectations, suggesting that implicit musical learning may be influenced by the quantity of informal exposure to the surrounding musical environment

Liderazgo directivo y gestión pedagógica en tiempos de pandemia en la institución educativa N° 40201 técnico agropecuario “La Colina” del distrito de Majes, Arequipa

El presente trabajo de investigación tiene como propósito establecer la relación que existe entre el liderazgo directivo y la gestión pedagógica en tiempos de pandemia en la Institución Educativa Nº 40201 Técnico Agropecuario “La Colina” del distrito de Majes, Arequipa y responde al enfoque cuantitativo. Dicho estudio es básico de nivel correlacional y un diseño no experimental; la población está formada por 32 docentes y la técnica de investigación es la encuesta. Los instrumentos administrados son dos cuestionarios; el primero denominado “Cuestionario de evaluación sobre el liderazgo del director” consta de 36 ítems y es de administración individual. El segundo instrumento lleva el nombre de “Cuestionario sobre gestión pedagógica” comprende 22 ítems y es de administración individual. El tratamiento estadístico se realizó en el programa SPSS versión 25 creado por la Universidad de Chicago y mediante la aplicación de la prueba rho de Spearman en la comprobación de hipótesis se obtuvo que entre la variable 1 “Liderazgo directivo” y la variable 2 “Gestión pedagógica” existe una correlación positiva media con un valor significativo de .554