Dscam1 in pancrustacean immunity: current status and a look to the future

The Down syndrome cell adhesion molecule 1 (Dscam1) gene is an extraordinary example of diversity: by combining alternatively spliced exons, thousands of isoforms can be produced from just one gene. So far, such diversity in this gene has only been found in insects and crustaceans, and its essential part in neural wiring has been well-characterized for Drosophila melanogaster. Ten years ago evidence from D. melanogaster showed that the Dscam1 gene is involved in insect immune defense and work on Anopheles gambiae indicated that it is a hypervariable immune receptor. These exciting findings showed that via processes of somatic diversification insects have the possibility to produce unexpected immune molecule diversity, and it was hypothesized that Dscam1 could provide the mechanistic underpinnings of specific immune responses. Since these first publications the quest to understand the function of this gene has uncovered fascinating insights from insects and crustaceans. However, we are still far from a complete understanding of how Dscam1 functions in relation to parasites and pathogens and its full relevance for the immune system. In this Hypothesis and Theory article, we first briefly introduce Dscam1 and what we know so far about how it might function in immunity. By focusing on seven questions, we then share our sometimes contrasting thoughts on what the evidence tells us so far, what essential experiments remain to be done, and the future prospects, with the aim to provide a multiangled view on what this fascinating gene has to do with immune defense

Desenvolvimento de competências linguísticas no 1.º CEB: ampliação do léxico a partir de textos tradicionais

Vários autores têm alertado para a existência de uma estreita relação entre o conhecimento lexical e as habilidades fonológicas e a aprendizagem da leitura e da escrita, destacando com particular ênfase a direta correspondência estabelecida entre o conhecimento lexical e a compreensão de um texto. É consensual, ainda, que tanto a fluência como a eficiência leitoras do indivíduo em qualquer faixa etária dependem do seu capital lexical. Quanto maior for o número de palavras conhecidas pela criança/jovem ou adulto, melhor será a sua compreensão textual/leitora e quanto melhor for a sua compreensão leitora maior será o seu conhecimento lexical. Ouvir ler textos/ler textos contribui para o aumento do capital lexical das crianças e para o seu desenvolvimento integral, sendo fundamental que desde cedo contactem com a literatura e que ouçam ler/recitar textos. À entrada para o 1º ano, momento em que muitas crianças iniciam a decifração/a cifração do código escrito da sua língua materna, muitas das palavras com que se deparam não têm qualquer significado no seu léxico mental. Cabe, pois, à escola criar estratégias que lhes permitam ampliar o léxico de forma lúdica, criativa e eficaz. No âmbito da investigação com vista à redação do Relatório Final, procurou evidenciar-se o contributo da literatura tradicional para a ampliação dos níveis de conhecimento linguístico, em particular do conhecimento lexical, dos alunos de uma turma do 1º ano de escolaridade, tendo-se, para a recolha de dados, recorrido à observação direta do grupo de crianças, às notas de campo, à recolha de produtos das atividades realizadas e à aplicação da Escala de Conhecimento de Vocabulário, desenvolvida por Paribakht & Wesche (1996)

As mulheres na construção civil: algumas notas a partir de um trabalho de campo

Este artigo tem por objetivo pensar os lugares das mulheres na construção civil, um mercado de trabalho visivelmente masculino, em que os homens ainda correspondem à maioria da mão de obra empregada. Partimos da dissertação de mestrado de Romcy (2013), intitulada: “Fala que nem homem”: gênero e poder em uma obra da construção civil, onde, a partir de pesquisa etnográfica, realizada em um canteiro de obras localizado em uma cidade do interior do Rio Grande do Sul, foram estudados os conflitos e hierarquias daquele espaço entre uma engenheira e pedreiros, para pensar a masculinidade.Em um universo com cerca de trinta homens, havia nove mulheres: duas engenheiras, uma arquiteta, quatro responsáveis pela limpeza e duas pela alimentação dos empregados. Procuro apresentar um pouco das interações destas mulheres na obra e em como elas foram importantes para pensar as relações de gênero naquele espaço. Esta discussão se torna relevante, na medida em que alguns dados vêm apontando um aumento das mulheres em todos os setores da construção civil

Mycobacterium tuberculosis lineage 4 comprises globally distributed and geographically restricted sublineages

Generalist and specialist species differ in the breadth of their ecological niches. Little is known about the niche width of obligate human pathogens. Here we analyzed a global collection of Mycobacterium tuberculosis lineage 4 clinical isolates, the most geographically widespread cause of human tuberculosis. We show that lineage 4 comprises globally distributed and geographically restricted sublineages, suggesting a distinction between generalists and specialists. Population genomic analyses showed that, whereas the majority of human T cell epitopes were conserved in all sublineages, the proportion of variable epitopes was higher in generalists. Our data further support a European origin for the most common generalist sublineage. Hence, the global success of lineage 4 reflects distinct strategies adopted by different sublineages and the influence of human migration

Pico, pico, saranico, quem te deu tamanho bico? : ampliar, no 1º CEB, o léxico a partir de textos tradicionais

info:eu-repo/semantics/publishedVersio

A new nomenclature for the livestock-associated Mycobacterium tuberculosis complex based on phylogenomics

Background: The bacteria that compose the Mycobacterium tuberculosis complex (MTBC) cause tuberculosis (TB) in humans and in different animals, including livestock. Much progress has been made in understanding the population structure of the human-adapted members of the MTBC by combining phylogenetics with genomics. Accompanying the discovery of new genetic diversity, a body of operational nomenclature has evolved to assist comparative and molecular epidemiological studies of human TB. By contrast, for the livestock-associated MTBC members, Mycobacterium bovis, M. caprae and M. orygis, there has been a lack of comprehensive nomenclature to accommodate new genetic diversity uncovered by emerging phylogenomic studies. We propose to fill this gap by putting forward a new nomenclature covering the main phylogenetic groups within M. bovis, M. caprae and M. orygis. Methods: We gathered a total of 8,747 whole-genome sequences (WGS) from public sources and 39 newly sequenced strains, and selected a subset of 839 WGS, representative of the worldwide diversity of M. bovis, M. caprae and M. orygis. We used phylogenetics and genetic diversity patterns inferred from WGS to define groups. Results: We propose to divide M. bovis, M. caprae and M. orygis, in three main phylogenetic lineages, which we named La1, La2 and La3, respectively. Within La1, we identified several monophyletic groups, which we propose to classify into eight sublineages (La1.1-La1.8). These differed in geographic distribution, with some being geographically restricted and others globally widespread, suggesting different expansion abilities. To ease molecular characterization of these MTBC groups by the community, we provide phylogenetically informed, single nucleotide polymorphisms that can be used as barcodes for genotyping. These makers were implemented in a new test suit in KvarQ, a platform-independent, open-source tool. Conclusions: Our results contribute to an improved classification of the genetic diversity within the livestock-associated MTBC, which will benefit future molecular epidemiological and evolutionary studies

Ultrasonography Reliability in the Detection of Inflammatory and Structural Abnormalities: An Exercise in Multiple Joints

Background Ultrasonography is an image technique that allows rheumatologists to visualize structural and inflammatory changes within a joint. The objective of this study was to assess the interobserver and intraobserver reliability of musculoskeletal ultrasound (US) in the detection of inflammatory and destructive joint changes in patients with polyarthritis. Methods A Delphi exercise was undertaken to standardize and adapt the EULAR-OMERACT elementary US definitions of inflammatory lesions (effusion, synovial hypertrophy, power Doppler, bone erosions, and synovitis) for each joint. Fifteen patients were analyzed, and video clips of 600 joints were collected. Each joint was scored for the presence of each elementary component, on 2 separate occasions, by 6 examiners. Interobserver and intraobserver agreement analysis was assessed through Fleiss κ coefficient (κ). Results Considering all patients and all joints, the interobserver values were highest for erosions and lowest for effusion (κ = 0.7314 and κ = 0.6044, respectively). When analyzing different regions, the highest interobserver agreement was for tibiotalar joint (κ = 0.8043) and the lowest for wrist (κ = 0.6767). Intraobserver reliability was excellent for each and all elementary components and anatomical region. Conclusions The present study showed either a good or excellent US interobserver and intraobserver reliability in elementary elements and anatomical region. This kind of US reliability exercises are important for standardization of exploration in everyday practice by reducing the variability associated with this imaging technique, and ensuring a greater degree of homogeneity and future comparability in the assessment of disease activity in polyarthritis patients.info:eu-repo/semantics/publishedVersio

An African origin for Mycobacterium bovis

Mycobacterium bovis; and; Mycobacterium caprae; are two of the most important agents of tuberculosis in livestock and the most important causes of zoonotic tuberculosis in humans. However, little is known about the global population structure, phylogeography and evolutionary history of these pathogens.; We compiled a global collection of 3364 whole-genome sequences from; M.bovis; and; M.caprae; originating from 35 countries and inferred their phylogenetic relationships, geographic origins and age.; Our results resolved the phylogenetic relationship among the four previously defined clonal complexes of; M.bovis; , and another eight newly described here. Our phylogeographic analysis showed that; M.bovis; likely originated in East Africa. While some groups remained restricted to East and West Africa, others have subsequently dispersed to different parts of the world.; Our results allow a better understanding of the global population structure of; M.bovis; and its evolutionary history. This knowledge can be used to define better molecular markers for epidemiological investigations of; M.bovis; in settings where whole-genome sequencing cannot easily be implemented.; During the last few years, analyses of large globally representative collections of whole-genome sequences (WGS) from the human-adapted Mycobacterium tuberculosis complex (MTBC) lineages have enhanced our understanding of the global population structure, phylogeography and evolutionary history of these pathogens. In contrast, little corresponding data exists for M. bovis, the most important agent of tuberculosis in livestock. Using whole-genome sequences of globally distributed M. bovis isolates, we inferred the genetic relationships among different M. bovis genotypes distributed around the world. The most likely origin of M. bovis is East Africa according to our inferences. While some M. bovis groups remained restricted to East and West Africa, others have subsequently dispersed to different parts of the world driven by cattle movements

Emerging Role of miR-21-5p in Neuron–Glia Dysregulation and Exosome Transfer Using Multiple Models of Alzheimer’s Disease

Alzheimer’s disease (AD) is a neurodegenerative disorder associated with neuron–glia dysfunction and dysregulated miRNAs. We previously reported upregulated miR-124/miR-21 in AD neurons and their exosomes. However, their glial distribution, phenotypic alterations and exosomal spread are scarcely documented. Here, we show glial cell activation and miR-21 overexpression in mouse organotypic hippocampal slices transplanted with SH-SY5Y cells expressing the human APP695 Swedish mutation. The upregulation of miR-21 only in the CSF from a small series of mild cognitive impairment (MCI) AD patients, but not in non-AD MCI individuals, supports its discriminatory potential. Microglia, neurons, and astrocytes differentiated from the same induced pluripotent stem cells from PSEN1ΔE9 AD patients all showed miR-21 elevation. In AD neurons, miR-124/miR-21 overexpression was recapitulated in their exosomes. In AD microglia, the upregulation of iNOS and miR-21/miR-146a supports their activation. AD astrocytes manifested a restrained inflammatory profile, with high miR-21 but low miR-155 and depleted exosomal miRNAs. Their immunostimulation with C1q + IL-1α + TNF-α induced morphological alterations and increased S100B, inflammatory transcripts, sAPPβ, cytokine release and exosomal miR-21. PPARα, a target of miR-21, was found to be repressed in all models, except in neurons, likely due to concomitant miR-125b elevation. The data from these AD models highlight miR-21 as a promising biomarker and a disease-modifying target to be further explored

A New Phylogenetic Framework for the Animal-Adapted Mycobacterium tuberculosis Complex

Tuberculosis (TB) affects humans and other animals and is caused by bacteria from the Mycobacterium tuberculosis complex (MTBC). Previous studies have shown that there are at least nine members of the MTBC infecting animals other than humans; these have also been referred to as ecotypes. However, the ecology and the evolution of these animal-adapted MTBC ecotypes are poorly understood. Here we screened 12,886 publicly available MTBC genomes and newly sequenced 17 animal-adapted MTBC strains, gathering a total of 529 genomes of animal-adapted MTBC strains. Phylogenomic and comparative analyses confirm that the animal-adapted MTBC members are paraphyletic with some members more closely related to the human-adapted Mycobacterium africanum Lineage 6 than to other animal-adapted strains. Furthermore, we identified four main animal-adapted MTBC clades that might correspond to four main host shifts; two of these clades are hypothesized to reflect independent cattle domestication events. Contrary to what would be expected from an obligate pathogen, MTBC nucleotide diversity was not positively correlated with host phylogenetic distances, suggesting that host tropism in the animal-adapted MTBC seems to be driven by contact rates and demographic aspects of the host population rather by than host relatedness. By combining phylogenomics with ecological data, we propose an evolutionary scenario in which the ancestor of Lineage 6 and all animal-adapted MTBC ecotypes was a generalist pathogen that subsequently adapted to different host species. This study provides a new phylogenetic framework to better understand the evolution of the different ecotypes of the MTBC and guide future work aimed at elucidating the molecular mechanisms underlying host range