Immature large ribosomal subunits containing the 7S pre-rRNA can engage in translation in Saccharomyces cerevisiae

Evolution has provided eukaryotes with mechanisms that impede immature and/or aberrant ribosomes to engage in translation. These mechanisms basically either prevent the nucleo-cytoplasmic export of these particles or, once in the cytoplasm, the release of associated assembly factors, which interfere with the binding of translation initiation factors and/or the ribosomal subunit joining. We have previously shown that aberrant yeast 40S ribosomal subunits containing the 20S pre-rRNA can engage in translation. In this study, we describe that cells harbouring the dob1–1 allele, encoding a mutated version of the exosome-assisting RNA helicase Mtr4, accumulate otherwise nuclear pre-60S ribosomal particles containing the 7S pre-rRNA in the cytoplasm. Polysome fractionation analyses revealed that these particles are competent for translation and do not induce elongation stalls. This phenomenon is rather specific since most mutations in other exosome components or co-factors, impairing the 3′ end processing of the mature 5.8S rRNA, accumulate 7S pre-rRNAs in the nucleus. In addition, we confirm that pre-60S ribosomal particles containing either 5.8S + 30 or 5.8S + 5 pre-rRNAs also engage in translation elongation. We propose that 7S pre-rRNA processing is not strictly required for pre-60S r-particle export and that, upon arrival in the cytoplasm, there is no specific mechanism to prevent translation by premature pre-60S r-particles containing 3′ extended forms of mature 5.8S rRNA

The dedicated chaperone Acl4 escorts ribosomal protein Rpl4 to its nuclear pre-60S assembly site

Ribosomes are the highly complex macromolecular assemblies dedicated to the synthesis of all cellular proteins from mRNA templates. The main principles underlying the making of ribosomes are conserved across eukaryotic organisms and this process has been studied in most detail in the yeast Saccharomyces cerevisiae. Yeast ribosomes are composed of four ribosomal RNAs (rRNAs) and 79 ribosomal proteins (r-proteins). Most r-proteins need to be transported from the cytoplasm to the nucleus where they get incorporated into the evolving pre-ribosomal particles. Due to the high abundance and difficult physicochemical properties of r-proteins, their correct folding and fail-safe targeting to the assembly site depends largely on general, as well as highly specialized, chaperone and transport systems. Many r-proteins contain universally conserved or eukaryote-specific internal loops and/or terminal extensions, which were shown to mediate their nuclear targeting and association with dedicated chaperones in a growing number of cases. The 60S r-protein Rpl4 is particularly interesting since it harbours a conserved long internal loop and a prominent C-terminal eukaryote-specific extension. Here we show that both the long internal loop and the C-terminal eukaryote-specific extension are strictly required for the functionality of Rpl4. While Rpl4 contains at least five distinct nuclear localization signals (NLS), the C-terminal part of the long internal loop associates with a specific binding partner, termed Acl4. Absence of Acl4 confers a severe slow-growth phenotype and a deficiency in the production of 60S subunits. Genetic and biochemical evidence indicates that Acl4 can be considered as a dedicated chaperone of Rpl4. Notably, Acl4 localizes to both the cytoplasm and nucleus and it has the capacity to capture nascent Rpl4 in a co-translational manner. Taken together, our findings indicate that the dedicated chaperone Acl4 accompanies Rpl4 from the cytoplasm to its pre-60S assembly site in the nucleus

Bicolour fluorescent molecular sensor for cations: design and experimental validation

Molecular entities whose fluorescence spectra are different when they bind metal cations are termed bicolour fluorescent molecular sensors. The basic design criteria of this kind of compound are presented and the different fluorescent responses are discussed in terms of their chemical behaviour and electronic features. These latter elements include intramolecular charge transfer (ICT), formation of intramolecular and intermolecular excimer/exciplex complexes and Fo ̈rster resonance energy transfer (FRET). Changes in the electronic properties of the fluorophore based on the decoupling between its constitutive units upon metal binding are also discussed. The possibility of generating fluorescent bicolour indicators that can capture metal cations in the gas phase and at solid–gas interfaces is also discussedThis work was supported by the Basque Government (Grants IT-1346-19 and IT1180-19), by the Spanish Ministry of Science and Innovation (MICINN-FEDER, Grants PID2019-104772GB-I00, PID2019-111281GB-I00, RED2018-102387-T, and RED2018-102471-T), and by the European Research Council (ERC) under the European's Union Horizon 2020 research and innovation programme (Grant agreement ERC-2020-SyG 951281)

Association between high and very high albuminuria and nighttime blood pressure: Influence of diabetes and chronic kidney disease

This is an author-created, uncopyedited electronic version of an article accepted for publication in Diabetes Care. The American Diabetes Association (ADA), publisher of Diabetes Care, is not responsible for any errors or omissions in this version of the manuscript or any version derived from it by third parties. The definitive publisher-authenticated version will be available in a future issue of Diabetes Care 39.10 (2016): 1729-1737 in print and online at http://care.diabetesjournals.orgNighttime blood pressure (BP) and albuminuria are two important and independent predictors of cardiovascularmorbidity andmortality. Here, we examined the quantitative differences in nighttime systolic BP (SBP) across albuminuria levels in patients with and without diabetes and chronic kidney disease. RESEARCH DESIGN AND METHODS A total of 16,546 patients from the Spanish Ambulatory Blood Pressure Monitoring Registry cohort (mean age 59.6 years, 54.9% men) were analyzed. Patients were classified according to estimated glomerular filtration rate (eGFR), as ≥60 or <60 mL/min/1.73 m2 (low eGFR), and urine albumin-to-creatinine ratio, as normoalbuminuria (<30 mg/g), high albuminuria (30-300 mg/g), or very high albuminuria (>300 mg/g). Office and 24-h BP were determined with standardized methods and conditions. RESULTS High albuminuria was associated with a statistically significant and clinically substantial higher nighttime SBP (6.8 mmHg higher than with normoalbuminuria, P < 0.001). This association was particularly striking at very high albuminuria among patients with diabetes and low eGFR (16.5 mmHg, P < 0.001). Generalized linear models showed that after full adjustment for demographic, lifestyles, and clinical characteristics, nighttime SBP was 4.8 mmHg higher in patients with high albuminuria than in those with normoalbuminuria (P < 0.001), and patients with very high albuminuria had a 6.1 mmHg greater nighttime SBP than those with high albuminuria (P < 0.001). These differences were 3.8 and 3.1 mmHg, respectively, among patients without diabetes, and 6.5 and 8 mmHg among patients with diabetes (P < 0.001). CONCLUSIONS Albuminuria in hypertensive patients is accompanied by quantitatively striking higher nighttime SBP, particularly in those with diabetes with very high albuminuria and low eGFRSpecific funding for this study analysis was obtained from FIS grants PI10/01011 PI11/02432, PI13/02321, PIE13/00045, PI14/01841, CP15/0129, and also from Fundación SENEFRO, Fondos FEDER, and by Cátedra UAM de Epidemiología y Control del Riesgo Cardiovascula

Memetic Evolutionary Multi-Objective Neural Network Classifier to Predict Graft Survival in Liver Transplant Patients

In liver transplantation, matching donor and recipient is a problem that can be solved using machine learning techniques. In this paper we consider a liver transplant dataset obtained from eleven Spanish hospitals, including the patient survival or the rejection in liver transplantation one year after the surgery. To tackle this problem, we use a multi-objective evolutionary algorithm for training generalized radial basis functions neural networks. The obtained models provided medical experts with a mathematical value to predict survival rates allowing them to come up with a right decision according to the principles of justice, efficiency and equit

ASIC para sistemas de medidas ambientales

El circuito integrado que aquí se describe ha sido diseñado con tecnología puramente digital, y tiene como función servir como centro concentrador de datos en estaciones meteorológicas, aunque por su diseño genérico puede ser usado en cualquier otro campo. Su objetivo principal es la adquisición de medidas (condiciones ambientales como velocidad y dirección del viento, tempera-turas, humedades relativas,...) y la generación de señales analógicas y digitales telemandadas procedentes de un canal de radio o de un canal SPI. Esta realización se enmarca dentro del programa GAME y ha sido desarrollada en colaboración con la empresa SAINCO

Distributed microprocessor controllers using optic fiber network

This work continues a previous project devoted to the supervision and control of electric motors in large industrial plants. This project consists in a set of microcontroller boards that communicate with a Global Control Card (GCC) The transmission of messages in the system is done using a optic fiber network. The GCC can be linked to a supervisory computer by a serial communication channel. A program processes the system schematics and authomatically generates the configuration files. This project has been realised in collaboration with INABBNSA (ABENGOA) and funded by the ATICA programme

Validación del sistema integral de análisis de las tareas en Educación Física

The purpose of this study was to develop and assess the validity of an instrument for analysing the tasks designed by the teacher of physical education. The instrument is organized into nine dimensions: contextual data, teacher data, learning unit data, session data, pedagogical variables, organizational variables, external load variables, communication variables, and task method. 15 expert judges who met the defined inclusion criteria participated in the validation process where assessed the univocity, relevance, and importance of each category quantitatively. Also, they provided qualitative contributions of each item. The content validity was calculated using Aiken's V coefficient and its confidence intervals. The exact critical value of Aiken's V at 99% CI was used for accepting the tasks (V>.78) and at 95% for revising them (V>.70). The mean values of Aiken's V for all items are above the cut-off point obtained at 99% confidence (Univocity: V=.89; Relevance: V=.91; Importance: V=.93). Two categories of the instrument had to be modified [V>.70 - <.78]. The reliability analysis showed excellent Cronbach's α coefficient values for Univocity (α=.94), Relevance (α=.89), and Importance (α=.92). The physical education task analysis instrument (SIATEF) showed high content validity and reliability and can be used in tasks analysis for physical education.El propósito de este estudio fue elaborar y evaluar la validez de un instrumento para analizar las tareas diseñadas por el profesor de educación física. El instrumento se organizó en nueve dimensiones: datos contextuales, datos del profesor, datos de la unidad didáctica, datos de la sesión, variables pedagógicas, variables de organización, variables de carga externa, variables de comunicación y método de la tarea. 15 jueces expertos que cumplían criterios de inclusión definidos participaron en el proceso de validación donde valoraron cuantitativamente la univocidad, pertinencia e importancia de cada categoría. Además, realizaron aportaciones cualitativas de cada ítem. La validez de contenido se calculó mediante el coeficiente de V de Aiken y sus intervalos de confianza. Se empleó el valor crítico exacto de la V de Aiken al 99% IC para aceptar las tareas (V>.78) y al 95% para su revisión (V>.70). Los valores medios de la V de Aiken de todos los apartados están por encima del punto de corte obtenido al 99% de confianza (Univocidad: V=.89); Pertinencia: V=.91; Importancia: V=.93). Dos categorías del instrumento tuvieron que ser modificadas [V>.70 - <.78]. El análisis de la fiabilidad mostró valores excelentes del coeficiente de α de Cronbach en Univocidad (α=.94), Pertinencia (α=.89), e Importancia (α=.92). El instrumento de análisis de las tareas de educación física (SIATEF) presentó una alta validez de contenido y fiabilidad y puede ser empleado para el análisis de las tareas en Educación Física

Drivers for spatial modelling of a critically endangered seabird on a dynamic ocean area: Balearic shearwaters are non-vegetarian

1. Spatial modelling is an important research tool to improve our knowledge about the distribution of wildlife in the ocean. Using different modelling techniques (MaxEnt and a generalized linear mixed model), a predictive habitat suitability model was developed for one of the most threatened seabirds in the world: the Balearic shearwater, Puffinus mauretanicus. 2. Models were developed using a 10-year dataset from the Gulf of Cádiz (on the south-western Iberian Peninsula), a key foraging area for Balearic shearwaters during migration and the non-breeding season. 3. Predictive habitat maps strongly matched the observed distribution patterns, pointing to bathymetric features as the main modelling drivers. The species was concentrated on shallow areas (up to approximately 100 m in depth) of the continental shelf, very close to the mouth of the Guadalquivir River. In contrast with previous studies, Balearic shearwater distribution in the highly dynamic Gulf of Cádiz was not correlated with areas of high chlorophyll a concentration. 4. This lack of spatial correlation probably arises from the delay between the phytoplankton bloom and the response of the zooplankton and small fish that are preyed upon by Balearic shearwaters, which may result in important displacements of this trophic chain across the Gulf of Cádiz. 5. The analysis presented contributes to a better understanding of the spatial distribution and ecology of the critically endangered top predator in the Gulf of Cádiz and offers important information to improve management plans.Versión del editor1,92