Adaptive changes in alphavirus mRNA translation allowed colonization of vertebrate hosts

Members of the Alphavirus genus are arboviruses that alternate replication in mosquitoes and vertebrate hosts. In vertebrate cells, the alphavirus resists the activation of antiviral RNA-activated protein kinase (PKR) by the presence of a prominent RNA structure (downstream loop [DLP]) located in viral 26S transcripts, which allows an eIF2-independent translation initiation of these mRNAs. This article shows that DLP structure is essential for replication of Sindbis virus (SINV) in vertebrate cell lines and animals but is dispensable for replication in insect cells, where no ortholog of the vertebrate PKR gene has been found. Sequence comparisons and structural RNA analysis revealed the evolutionary conservation of DLP in SINV and predicted the existence of equivalent DLP structures in many members of the Alphavirus genus. A mutant SINV lacking the DLP structure evolved in murine cells to recover a wild-type phenotype by creating an alternative structure in the RNA that restored the translational independence for eIF2. Genetic, phylogenetic, and biochemical data presented here support an evolutionary scenario for the natural history of alphaviruses, in which the acquisition of DLP structure in their mRNAs probably allowed the colonization of vertebrate host and the consequent geographic expansion of some of these viruses worldwideThis project was supported in part by the Fundación Mutua Madrileña (FMM 2008), the VIRUS-HOST Interaction Program (Comunidad de Madrid), and by a grant from the Ministerio de Ciencia e Innovación (BFU2010-17411). Institutional support from the Fundación Ramón Areces is also acknowledge

Simulating an Immune Response with a Combined Agent-Based Model of a Triple-Negative Breast Cancer Tumor and Vascular Network

Cytotoxic T-cells (CTLs) are one mechanism the immune system employs to eliminate cancer cells. In this study, I expand upon a previous 3-dimmensional agent-based model of triple-negative breast cancer to include a therapy simulating an immune response in the form of a CTL insertion into the tumor. The model consists of the tumor, comprised of progenitor cells, cancer stem cells, and tumor-associated macrophages, as well as an expanding vascular network. I investigate the effects of inserting different amounts of CTLs into the space, and their effect on tumor size in the short and longer terms. The results show that while CTLs decrease the size of the tumor they are ineffective at completely eliminating it, leading to continued tumor proliferation in the aftermat

Estudo fenomenolóxico na vivencia dunha ocupación: o marisqueo a pé

[Resumo] Introdución: na Comunidade Autónoma de Galicia as actividades profesionais relacionadas co mar, neste caso o marisqueo a pé, posúen unha especial transcendencia xa que representan en determinadas zonas costeiras un verdadeiro motor de desenvolvemento económico e social, ademais de constituír un importante soporte do noso acervo cultural. Polo tanto, a ocupación do marisqueo a pé outorga sentido e significado para a xente que desempeña este traballo. Así, este estudo fundaméntase en explorar como esta ocupación do mar vai en beneficio ou prexuízo do benestar dos seus traballadores. Obxectivo: ten como obxectivo xeral explorar a percepción das/os mariscadoras/es a pé sobre a súa ocupación laboral en relación co seu benestar. Metodoloxía: o estudo acometerase desde un enfoque cualitativo, baixo o deseño fenomenolóxico e adoptando como técnica conversacional a entrevista semiestruturada. As anteditas entrevistas realizaránselles ás/aos mariscadoras/es pertencentes á confraría de Noia, as/os cales traballan na Ría de Muros e Noia onde se asentan importantes bancos marisqueiros.[Resumen] Introducción: en la Comunidad Autónoma de Galicia las actividades profesionales relacionadas con el mar, en este caso el marisqueo a pie, poseen una especial trascendencia ya que representan en determinadas zonas costeras un verdadero motor de desarrollo económico y social, además de constituir un importante soporte de nuestra cultura. Por lo tanto, esta ocupación laboral otorga sentido y significado para la gente que desempeña este trabajo. Así, este estudio se fundamenta en explorar las vivencias de las/os mariscadoras/es y así conocer cómo esta ocupación del mar va en beneficio o prejuicio del bienestar de sus trabajadores. Objetivo: tiene como objetivo general explorar la percepción de las/los mariscadoras/es a pie sobre su ocupación laboral en relación a su bienestar. Metodología: el estudio se abordará desde un enfoque cualitativo, basado en el diseño fenomenológico y adoptando como técnica conversacional la entrevista semiestructurada. Dichas entrevistas se realizarán a las/los mariscadoras/es pertenecientes a la cofradía de Noia, las/los cuales trabajan en la Ría de Muros y Noia donde se asientan importantes bancos marisqueros.[Abstract] Introduction: In Galicia sea based professions, in this case shellfishing on foot, have a special transcendence as in some costal areas they are the driving force of the local social and economic development as well a being a cultural building block.Therefore this profession holds a vast significance and sentiment for those who work in this field. For this reason this study is based on the experiences of those who work in shellfishing and through this learn how this sea based occupation benefits or harms the welfare of its workers. Goal: The main goal is to explore how those who work in the shellfishing industry perceive the correlation between their work and their welfare. Method: The study has a qualitative focus based on a phenomenological design and adopting as a technique a semi structural conversational interview. Said interviews were carried out with those who work in shellfishing in Noia in the estuary of Muros and Noia where there is a vast concentration of shellfishing.Traballo fin de grao (UDC.FCS). Terapia ocupacional. Curso 2013/2014

Important hivernada i migració prenupcial d'aligot Buteo buteo a Mallorca, 2010-2011

Important common Buzzard Buteo buteo wintering and prenuptial migration in Mallorca, 2010–2011. The number of wintering common buzzards Buteo buteo detected in Mallorca in 2010–2011 was considerably higher than in other years and extended widely over the island. In Menorca higher than normal winter numbers were also recorded. In addition, the prenuptial migration study at the Albercutx watch tower on the Formentor peninsula (Pollença) recorded much stronger passage of this species than in any of the years 2003-2010, despite prenuptial migration being recorded annually between the beginning of March and the end of May since 2003 using a comparable sampling methodology and intensity

MicroRNAs in C. elegans Aging: Molecular Insurance for Robustness?

The last decade has witnessed a revolution in our appreciation of the extensive regulatory gene expression networks modulated by small untranslated RNAs. microRNAs (miRNAs), ~22 nt RNAs that bind imperfectly to partially homologous sites on target mRNAs to regulate transcript expression, are now known to influence a broad range of biological processes germane to development, homeostatic regulation and disease. It has been proposed that miRNAs ensure biological robustness, and aging has been described as a progressive loss of system and cellular robustness, but relatively little work to date has addressed roles of miRNAs in longevity and healthspan (the period of youthful vigor and disease resistance that precedes debilitating decline in basic functions). The C. elegans model is highly suitable for testing hypotheses regarding miRNA impact on aging biology: the lifespan of the animal is approximately three weeks, there exist a wealth of genetic mutations that alter lifespan through characterized pathways, biomarkers that report strong healthspan have been defined, and many miRNA genes have been identified, expression-profiled, and knocked out. 50/114 C. elegans miRNAs change in abundance during adult life, suggesting significant potential to modulate healthspan and lifespan. Indeed, miRNA lin-4 has been elegantly shown to influence lifespan and healthspan via its lin-14 mRNA target and the insulin signaling pathway. 27 of the C. elegans age-regulated miRNAs have sequence similarity with both fly and human miRNAs. We review current understanding of a field poised to reveal major insights into potentially conserved miRNA-regulated networks that modulate aging

La medición retrospectiva del bienestar mediante indicadores antropométricos: Zamora, 1840-1935

En este trabajo analizamos la altura de la población de una ciudad castellana, Zamora, en el largo plazo, con el propósito de estimar la evolución de su nivel de vida. Nuestro objetivo es probar que el capitalismo agrario como estrategia de crecimiento provocó un incremento del nivel de vida menor que el que indujo la industrialización plena. Por otra parte, constatamos la existencia de una "penalización" urbana en Castilla. Los niveles de vida de la población rural fueron más altos que los calculados para la urbana, al menos, hasta comienzos del siglo XX.In this paper we analyse the population height of a Castilian town, Zamora, in the long term in order to estimate the evolution of standard of living. Our aim is to prove that the agrarian capitalism a economic development strategy provoked and improvement of the standard of living smaller that the industrialization. On the other hand, we reveal the existence of an "urban penalty" in Castile. Rural inhabitants' standard of living, were higher than those calculated for the urban population, at least, until the beginnings of the 20 century

Study of extracellular matrix synthesis in C. elegans

The epithelial monolayer of cells surrounding the animal, the hypodermis, Synthesises five cuticles during the nematode life cycle. The first cuticle is formed within the egg, prior to hatching, and the remainder towards the end of each larval stage. Because of the structural role of the cuticle, mutations in genes involved in assembly of this ECM can cause a spectrum of effects from lethality late in embryogenesis to alterations in the nematode shape. The severity of phenotype correlates with the severity of cuticle synthesis defects. Accordingly, two distinct mutant alleles that cause death after embryonic elongation, possibly due to failure in synthesising an intact cuticle, were characterised . One mutant, ij15, was isolated from a forward genetic screen previously performed (I. Johnstone, Glasgow University, Glasgow, UK). ij15 defines mutationally the gene stc-1, which encodes a HSP70-like protein possibly localised in the secretory pathway. The other mutant, h402, defines mutationally the gene let-607. A second let-607 allele, h189, which results in larval lethaity at the L2 stage was also analysed in this study. let-607 corresponds to the predicted gene F57B10.1, which encodes a putative bZIP transcription factor. Both stc-1 and let-607 are expressed in the hypodermis at all developmental stages. Furthermore, disruption of the function of either stc-1 or let-607 by mutation or RNAi affects cuticle synthesis in different ways. Thus, stc-1 and let-607 encode for a HSP70-like protein and a putative bZIP transcription factor required for synthesis of the cuticular ECM in C. elegans. In addition, this study defines C. elegans mutant phenotypes that can be used as indicators for gene products with controlling roles in the synthesis of this ECM

Assessing the value of the information provision for enhancing the autonomy of mobility impaired users. Madrid pilot Site Study.

A City is the space where every person acquires the citizen condition, which demands access to multiple services and facilities, and develops social relations in a free and equal condition of options. A lack of accessibility limits independency and autonomy. Thus, the relationship between “sustainable development” and “accessibility for all” becomes clearer, and both goals reinforce each other. In this sense, information plays a key role in order to overcome existing barriers, specially for people who rarely use public transport, have impaired mobility, or make a particular journey for the first time. The impact and benefits is linked with public transport as a “facilitator” of mobility, and, in particular, for the aim of intermodality. The usefulness of information that should be provided (both the information itself and how is offered) to mobility impaired users (MI users) is discussed on this paper based on following of the ASK-IT project that has being carry out on Madrid. The work was done in close cooperation with representatives of all different types of MI user groups

Mapping mRNA-18S rRNA Contacts Within Translation Initation Complexby Means of Reverse Transcriptase Termination Sites and RNAseq

The nucleotides involved in RNA-RNA interaction can be tagged by chemical- or UV-induced crosslinking, and further identified by classical or modern high throughput techniques. The contacts of mRNA with 18S rRNA that occur along the mRNA channel of 40S subunit have been mapped by site-specific UV crosslinking followed by reverse transcriptase termination sites (RTTS) using radioactive or fluorescent oligonucleotides. However, the sensitivity of this technique is restricted to the detection of those fragments that resulted from the most frequent crosslinkings. Here, we combined RTTS with RNAseq to map the mRNA-18S rRNA contacts with a much deeper resolution. Although aimed to detect the interaction of mRNA with the ES6S region of 18S rRNA, this technique can also be applied to map the interaction of mRNA with other non-coding RNA molecules (e.g., snRNAs, microRNAs and lncRNAs) during transcription, splicing or RNA-mediated postranscriptional regulationThe technical support of Laura Barbado is acknowledged. This work was funded by Ministerio de Economía y Competitividad (BFU2017-84955-R) grant