The RNA-binding protein ELAV regulates Hox RNA processing, expression and function within the Drosophila nervous system

The regulated head-to-tail expression of Hox genes provides a coordinate system for the activation of specific programmes of cell differentiation according to axial level. Recent work indicates that Hox expression can be regulated via RNA processing but the underlying mechanisms and biological significance of this form of regulation remain poorly understood. Here we explore these issues within the developing Drosophila central nervous system (CNS). We show that the pan-neural RNA-binding protein (RBP) ELAV (Hu antigen) regulates the RNA processing patterns of the Hox gene Ultrabithorax (Ubx) within the embryonic CNS. Using a combination of biochemical, genetic and imaging approaches we demonstrate that ELAV binds to discrete elements within Ubx RNAs and that its genetic removal reduces Ubx protein expression in the CNS leading to the respecification of cellular subroutines under Ubx control, thus defining for the first time a specific cellular role of ELAV within the developing CNS. Artificial provision of ELAV in glial cells (a cell type that lacks ELAV) promotes Ubx expression, suggesting that ELAVdependent regulation might contribute to cell type-specific Hox expression patterns within the CNS. Finally, we note that expression of abdominal A and Abdominal B is reduced in elav mutant embryos, whereas other Hox genes (Antennapedia) are not affected. Based on these results and the evolutionary conservation of ELAV and Hox genes we propose that the modulation of Hox RNA processing by ELAV serves to adapt the morphogenesis of the CNS to axial level by regulating Hox expression and consequently activating local programmes of neural differentiation

AU-Rich Element-Mediated mRNA Decay Can Occur Independently of the miRNA Machinery in Mouse Embryonic Fibroblasts and Drosophila S2-Cells

AU-rich elements (AREs) are regulatory sequences located in the 3′ untranslated region of many short-lived mRNAs. AREs are recognized by ARE-binding proteins and cause rapid mRNA degradation. Recent reports claimed that the function of AREs may be – at least in part – relayed through the miRNA pathway. We have revisited this hypothesis using dicer knock-out mouse embryonic fibroblasts and cultured Drosophila cells. In contrast to the published results, we find no evidence for a general requirement of the miRNA pathway in the function of AREs. Endogenous ier3 mRNA, which is known to contain a functional ARE, was degraded rapidly at indistinguishable rates in wild type and dicer knock-out mouse embryonic fibroblasts. In cultured Drosophila cells, both ARE-containing GFP reporter mRNAs and the endogenous cecA1 mRNA were resistant to depletion of the mi/siRNA factors dcr-1, dcr-2, ago1 and ago2. Furthermore, the Drosophila miRNA originally proposed to recognize AU-rich elements, miR-289, is not detectably expressed in flies or cultured S2 cells. Even our attempts to overexpress this miRNA from its genomic hairpin sequence failed. Thus, this sequence cannot serve as link between the miRNA and the AU-rich element mediated silencing pathways. Taken together, our studies in mammalian and Drosophila cells strongly argue that AREs can function independently of miRNAs

Regulation of cytoplasmic RNA stability: lessons from drosophila

The process of RNA degradation is a critical level of regulation contributing to the control of gene expression. In the last two decades a number of studies have shown the specific and targeted nature of RNA decay and its importance in maintaining homeostasis. The key players within the pathways of RNA decay are well conserved with their mutation or disruption resulting in distinct phenotypes as well as human disease. Model organisms including Drosophila melanogaster have played a substantial role in elucidating the mechanisms conferring control over RNA stability. A particular advantage of this model organism is that the functions of ribonucleases can be assessed in the context of natural cells within tissues in addition to individual immortalised cells in culture. Drosophila RNA stability research has demonstrated how the cytoplasmic decay machines, such as the exosome, Dis3L2 and Xrn1, are responsible for regulating specific processes including apoptosis, proliferation, wound healing and fertility. The work discussed here has begun to identify specific mRNA transcripts that appear sensitive to specific decay pathways representing mechanisms through which the ribonucleases control mRNA stability. Drosophila research has also contributed to our knowledge of how specific RNAs are targeted to the ribonucleases including AU rich elements, miRNA targeting and 3’ tailing. Increased understanding of these mechanisms is critical to elucidating the control elicited by the cytoplasmic ribonucleases which is relevant to human disease

The global repressor FliZ antagonizes gene expression by σS-containing RNA polymerase due to overlapping DNA binding specificity

FliZ, a global regulatory protein under the control of the flagellar master regulator FlhDC, was shown to antagonize σS-dependent gene expression in Escherichia coli. Thereby it plays a pivotal role in the decision between alternative life-styles, i.e. FlhDC-controlled flagellum-based motility or σS-dependent curli fimbriae-mediated adhesion and biofilm formation. Here, we show that FliZ is an abundant DNA-binding protein that inhibits gene expression mediated by σS by recognizing operator sequences that resemble the −10 region of σS-dependent promoters. FliZ does so with a structural element that is similar to region 3.0 of σS. Within this element, R108 in FliZ corresponds to K173 in σS, which contacts a conserved cytosine at the −13 promoter position that is specific for σS-dependent promoters. R108 as well as C(−13) are also crucial for DNA binding by FliZ. However, while a number of FliZ binding sites correspond to known σS-dependent promoters, promoter activity is not a prerequisite for FliZ binding and repressor function. Thus, we demonstrate that FliZ also feedback-controls flagellar gene expression by binding to a site in the flhDC control region that shows similarity only to a −10 element of a σS-dependent promoter, but does not function as a promoter

Genome-Wide Assessment of AU-Rich Elements by the AREScore Algorithm

In mammalian cells, AU-rich elements (AREs) are well known regulatory sequences located in the 3′ untranslated region (UTR) of many short-lived mRNAs. AREs cause mRNAs to be degraded rapidly and thereby suppress gene expression at the posttranscriptional level. Based on the number of AUUUA pentamers, their proximity, and surrounding AU-rich regions, we generated an algorithm termed AREScore that identifies AREs and provides a numerical assessment of their strength. By analyzing the AREScore distribution in the transcriptomes of 14 metazoan species, we provide evidence that AREs were selected for in several vertebrates and Drosophila melanogaster. We then measured mRNA expression levels genome-wide to address the importance of AREs in SL2 cells derived from D. melanogaster hemocytes. Tis11, a zinc finger RNA–binding protein homologous to mammalian tristetraprolin, was found to target ARE–containing reporter mRNAs for rapid degradation in SL2 cells. Drosophila mRNAs whose expression is elevated upon knock down of Tis11 were found to have higher AREScores. Moreover high AREScores correlate with reduced mRNA expression levels on a genome-wide scale. The precise measurement of degradation rates for 26 Drosophila mRNAs revealed that the AREScore is a very good predictor of short-lived mRNAs. Taken together, this study introduces AREScore as a simple tool to identify ARE–containing mRNAs and provides compelling evidence that AREs are widespread regulatory elements in Drosophila

La manifestación de la experiencia en las unidades hoteleras. Un análisis de los comentarios a hoteles en Machu Picchu en la red TripAdvisor

This paper describes the image of hotels transmitted by customers on the social network TripAdvisor.es. It is a case study that breaks down and interprets the analysis of a set of comments in the Spanish language to 20 hotels in Machu Picchu (Peru). Moreover, we did a descriptive analysis, based on the inference of qualitative and quantitative data, to 177 comments of the aforementioned social network, distributed by the first 20 hotels listed in order of classification of the traveler, between the months October to December 2019. The comments were analyzed through a table composed of 14 categories and we observed that positive commentaries prevail in all categories, and that the experiences most appreciated by travelers and described in our sample were “Service”, “Food”, and “Location”.El presente artículo describe la imagen de los hoteles transmitida por los clientes en la red social TripAdvisor.es. Se trata de un estudio de caso que descompone e interpreta el análisis de un conjunto de comentarios, en la lengua castellana, acerca de 20 hoteles en Machu Picchu (Perú). Asimismo, se realizó un análisis descriptivo, basado en la inferencia de datos cualitativos y cuantitativos, a 177 comentarios de la red social mencionada, distribuidos en los primeros 20 hoteles de la lista de clasificación del viajero, entre los meses de octubre y diciembre de 2019. Los comentarios fueron analizados a través de una tabla compuesta por 14 categorías, observándose la prevalencia de comentarios positivos en todas las categorías y que las experiencias más apreciadas por los viajeros (y descritas en nuestra muestra) fueron “servicio”, “comida” y “ubicación”

Clinical Importance of the Human Umbilical Artery Potassium Channels

Potassium (K+) channels are usually predominant in the membranes of vascular smooth muscle cells (SMCs). These channels play an important role in regulating the membrane potential and vessel contractility—a role that depends on the vascular bed. Thus, the activity of K+ channels represents one of the main mechanisms regulating the vascular tone in physiological and pathophysiological conditions. Briefly, the activation of K+ channels in SMC leads to hyperpolarization and vasorelaxation, while its inhibition induces depolarization and consequent vascular contraction. Currently, there are four different types of K+ channels described in SMCs: voltage-dependent K+ (KV) channels, calcium-activated K+ (KCa) channels, inward rectifier K+ (Kir) channels, and 2-pore domain K+ (K2P) channels. Due to the fundamental role of K+ channels in excitable cells, these channels are promising therapeutic targets in clinical practice. Therefore, this review discusses the basic properties of the various types of K+ channels, including structure, cellular mechanisms that regulate their activity, and new advances in the development of activators and blockers of these channels. The vascular functions of these channels will be discussed with a focus on vascular SMCs of the human umbilical artery. Then, the clinical importance of K+ channels in the treatment and prevention of cardiovascular diseases during pregnancy, such as gestational hypertension and preeclampsia, will be explored

Desenvolvimento de uma estratégia de content marketing para redes sociais O caso da escola superior de ciências empresariais do instituto politécnico de viana do castelo: o caso da Escola Superior de Ciências Empresariais do Instituto Politécnico de Viana do Castelo

Social networks are increasingly being used by companies and brands as one of the main means of disseminating products and services, concerning to the exponential growth that these platforms have had in the last few years. Therefore, Higher Education Institutions aren’t exception and are also using the contents published on social networks as a way of advertising the institution itself and its training offer. Content marketing has increasingly become one of the most used strategies by companies and brands to increase engagement and attract new followers on their social networks. The main goal is to define and implement a content marketing strategy for social networks as Facebook and Instagram, through the development of a case study of Escola Superior de Ciências Empresariais (ESCE) of the Polytechnic Institute of Viana do Castelo, that can generate an increase in the school's awareness and following increase the number of new students. This project also aims to create greater identification from students, improve the engagement of the social networks with their followers and to get more interaction from users who don’t usually interact with ESCE's social network profiles. In order to achieve the proposed goals, the theoretical basis defines the bases for the definition of the strategy to be developed, as well as legitimizes its results, which, based on the case study, as a research strategy, is adequate when investigating the how and the why of a set of contemporary events, and therefore requires multiple methods and sources to explore, describe and explain the phenomenon in its own context. It is expected that the implementation of the content marketing strategy developed will have a significant increase in engagement in social networks as well as in the interaction by users who do not normally interact with ESCE's social network profiles.As redes sociais são cada vez mais utilizadas pelas empresas e marcas, como um dos principais meios de divulgação de produtos e serviços, devido ao crescimento que estas plataformas tiveram nos últimos anos. Como tal, as instituições de Ensino Superior não são exceção e utilizam os conteúdos publicados nas redes sociais como forma de divulgação da própria instituição e da sua oferta formativa. Especificamente, o content marketing tem vindo a tornar-se numa das estratégias mais utilizadas como forma de aumentar o engagement, e captar novos seguidores nas redes sociais. O objetivo principal consiste na definição e implementação de uma estratégia de content marketing para as redes sociais Facebook e Instagram, através do desenvolvimento de um caso de estudo na Escola Superior de Ciências Empresariais (ESCE) do Instituto Politécnico de Viana do Castelo, que consiga gerar um aumento da notoriedade da escola e um consequente aumento do número de alunos. Pretende-se ainda criar maior identificação dos alunos, melhorar o engagement das redes sociais com os seus seguidores e obter mais interação por parte de utilizadores que não interagem normalmente com os perfis das redes sociais da ESCE. Para alcançar os objetivos propostos, a fundamentação teórica determina as bases necessárias para a definição da estratégia a ser desenvolvida, bem como legitima os seus resultados que, sustentados no estudo de caso, enquanto estratégia de pesquisa, é adequado quando se pretende investigar o como e o porquê de um conjunto de eventos contemporâneos, e por isso requer múltiplos métodos e fontes para explorar, descrever e explicar o fenómeno no seu contexto. Espera-se que a aplicação da estratégia de content marketing desenvolvida, tenha um aumento significativo do engagement nas redes sociais, bem como na interação por parte de utilizadores que não interagem normalmente com os perfis das redes sociais da ESC

UV-B Filter Octylmethoxycinnamate Is a Modulator of the Serotonin and Histamine Receptors in Human Umbilical Arteries

Every day, people use personal care products containing UV filters. Although their use initially showed a protective role, toxicity is a concern for human health as several UV filters are endocrine-disrupting chemicals (EDCs). Exposure to EDCs may induce cardiovascular diseases and can affect the health of sensitive people, such as pregnant women. Currently, the world’s most widely used UV-B filter is octylmethoxycinnamate (OMC), an EDC. However, the disruptive effects on pregnant women are little known. The present work proposed to understand how long-term exposure to OMC affects vascular homeostasis. Endothelium-denuded human umbilical artery (HUA) rings were incubated in an organ bath system. Long-term effects of exposure to OMC (0.001–50 μmol/L) were evaluated on the contractile responses of HUA to the application of the contractile agents, serotonin (5-HT) and histamine (Hist). To investigate in more detail the vascular mode of action of OMC, through which it impairs the vascular homeostasis of HUA, the activity and expression of different 5-HT and Hist-receptors involved in contractility processes were studied. Our findings pointed out an increase in the reactivity of HUA to 5-HT and Hist due to OMC exposure. These alterations in reactivity may be precursors of preeclampsia development and/or gestational hypertension