Prostaglandin E2 Signals Through PTGER2 to Regulate Sclerostin Expression

The Wnt signaling pathway is a robust regulator of skeletal homeostasis. Gain-of-function mutations promote high bone mass, whereas loss of Lrp5 or Lrp6 co-receptors decrease bone mass. Similarly, mutations in antagonists of Wnt signaling influence skeletal integrity, in an inverse relation to Lrp receptor mutations. Loss of the Wnt antagonist Sclerostin (Sost) produces the generalized skeletal hyperostotic condition of sclerosteosis, which is characterized by increased bone mass and density due to hyperactive osteoblast function. Here we demonstrate that prostaglandin E2 (PGE2), a paracrine factor with pleiotropic effects on osteoblasts and osteoclasts, decreases Sclerostin expression in osteoblastic UMR106.01 cells. Decreased Sost expression correlates with increased expression of Wnt/TCF target genes Axin2 and Tcf3. We also show that the suppressive effect of PGE2 is mediated through a cyclic AMP/PKA pathway. Furthermore, selective agonists for the PGE2 receptor EP2 mimic the effect of PGE2 upon Sost, and siRNA reduction in Ptger2 prevents PGE2-induced Sost repression. These results indicate a functional relationship between prostaglandins and the Wnt/β-catenin signaling pathway in bone

Permanent education in health: a review

OBJECTIVE : To undertake a meta-synthesis of the literature on the main concepts and practices related to permanent education in health. METHODS : A bibliographical search was conducted for original articles in the PubMed, Web of Science, LILACS, IBECS and SciELO databases, using the following search terms: “public health professional education”, “permanent education”, “continuing education”, “permanent education health”. Of the 590 articles identified, after applying inclusion and exclusion criteria, 48 were selected for further analysis, grouped according to the criteria of key elements, and then underwent meta-synthesis. RESULTS : The 48 original publications were classified according to four thematic units of key elements: 1) concepts, 2) strategies and difficulties, 3) public policies and 4) educational institutions. Three main conceptions of permanent education in health were found: problem-focused and team work, directly related to continuing education and education that takes place throughout life. The main strategies for executing permanent education in health are discussion, maintaining an open space for permanent education, and permanent education clusters. The most limiting factor is mainly related to directly or indirect management. Another highlight is the requirement for implementation and maintenance of public policies, and the availability of financial and human resources. The educational institutions need to combine education and service aiming to form critical-reflexive graduates. CONCLUSIONS : The coordination between health and education is based as much on the actions of health services as on management and educational institutions. Thus, it becomes a challenge to implement the teaching-learning processes that are supported by critical-reflexive actions. It is necessary to carry out proposals for permanent education in health involving the participation of health professionals, teachers and educational institutions.OBJETIVO : Realizar metasíntesis de la literatura sobre los principales conceptos y prácticas relacionados con la educación permanente en salud. MÉTODOS : Se realizó búsqueda bibliográfica de artículos originales en las bases de datos PubMed, Web of Science, Lilacs, IBECS y SciELO, utilizando los siguientes descriptores: “ public health professional education”, “permanent education”, “continuing education”, “permanent education health ”. De un total de 590 artículos identificados, posterior a los criterios de inclusión y exclusión, fueron seleccionados 48 para análisis, los cuales fueron sometidos al análisis individual, análisis comparativo, análisis con criterios de agrupamiento de elementos-clave y sometidos a metasíntesis. RESULTADOS : Los 48 artículos originales fueron clasificados como elementos-clave en cuatro unidades temáticas: 1) Concepciones; 2) Estrategias y dificultades; 3) Políticas públicas e 4) Instituciones formadoras. Se encontraron tres concepciones principales de educación permanente en salud: ubicación del problema y enfocarlo en el trabajo en equipo, directamente relacionado con la educación continua y educación que se da a lo largo de la vida. Las principales estrategias para efectivar la educación permanente fueron la ubicación del problema, mantenimiento de espacios para la educación permanente y polos de educación permanente. El mayor factor limitante estuvo relacionado con la gerencia directa o indirecta. Fueron mencionadas la necesidad de implementación y mantenimiento de políticas públicas, así como la disponibilidad de recursos financieros y humanos. Las instituciones formadoras tendrían la necesidad de articular educación y servicio para la formación de egresados críticos-reflexivos. CONCLUSIONES : La articulación educación y salud se encuentra pautada tanto en las acciones de los servicios de salud, cuanto en la gestión y de instituciones formadoras. Así, se torna un desafío implementar procesos de educación-aprendizaje que sean respaldados por acciones crítico-reflexivas. Es necesario realizar propuestas de educación permanente en salud con la participación de profesionales de los servicios, profesores y profesionales de las instituciones de educación.OBJETIVO : Realizar metassíntese da literatura sobre os principais conceitos e práticas relacionados à educação permanente em saúde. MÉTODOS : Foi realizada busca bibliográfica de artigos originais nas bases de dados PubMed, Web of Science, Lilacs, IBECS e SciELO, utilizando os seguintes descritores: “ public health professional education ”, “ permanent education”, “continuing education ”, “ permanent education health ”. De um total de 590 artigos identificados, após os critérios de inclusão e exclusão, foram selecionados 48 para análise, os quais foram submetidos à análise individual, análise comparativa, análise com critérios de agrupamentos de elementos-chave e submetidos à metassíntese. RESULTADOS : Os 48 artigos originais foram classificados como elementos-chave em quatro unidades temáticas: 1) Concepções; 2) Estratégias e dificuldades; 3) Políticas públicas; e 4) Instituições formadoras. Foram encontradas três concepções principais de educação permanente em saúde: problematizadora e focada no trabalho em equipe, diretamente relacionada à educação continuada e educação que se dá ao longo da vida. As principais estratégias para efetivação da educação permanente foram a problematização, manutenção de espaços para a educação permanente e polos de educação permanente. O maior fator limitante foi relacionado à gerência direta ou indireta. Foram indicadas a necessidade de implementação e manutenção de políticas públicas, além de disponibilidade de recursos financeiros e de recursos humanos. As instituições formadoras teriam necessidade de articular ensino e serviço para a formação de egressos críticos-reflexivos. CONCLUSÕES : A articulação educação e saúde encontra-se pautada tanto nas ações dos serviços de saúde, quanto de gestão e de instituições formadoras. Assim, torna-se um desafio implementar processos de ensino-aprendizagem que sejam respaldados por ações crítico-reflexivas. É necessário realizar propostas de educação permanente em saúde com a participação de profissionais dos serviços, professores e profissionais das instituições de ensino

Identification of Conserved and HLA Promiscuous DENV3 T-Cell Epitopes

Anti-dengue T-cell responses have been implicated in both protection and immunopathology. However, most of the T-cell studies for dengue include few epitopes, with limited knowledge of their inter-serotype variation and the breadth of their human leukocyte antigen (HLA) affinity. In order to expand our knowledge of HLA-restricted dengue epitopes, we screened T-cell responses against 477 overlapping peptides derived from structural and non-structural proteins of the dengue virus serotype 3 (DENV3) by use of HLA class I and II transgenic mice (TgM): A2, A24, B7, DR2, DR3 and DR4. TgM were inoculated with peptides pools and the T-cell immunogenic peptides were identified by ELISPOT. Nine HLA class I and 97 HLA class II novel DENV3 epitopes were identified based on immunogenicity in TgM and their HLA affinity was further confirmed by binding assays analysis. A subset of these epitopes activated memory T-cells from DENV3 immune volunteers and was also capable of priming naïve T-cells, ex vivo, from dengue IgG negative individuals. Analysis of inter- and intra-serotype variation of such an epitope (A02-restricted) allowed us to identify altered peptide ligands not only in DENV3 but also in other DENV serotypes. These studies also characterized the HLA promiscuity of 23 HLA class II epitopes bearing highly conserved sequences, six of which could bind to more than 10 different HLA molecules representing a large percentage of the global population. These epitope data are invaluable to investigate the role of T-cells in dengue immunity/pathogenesis and vaccine design. © 2013 Nascimento et al

Genetic diversity in cultivated carioca common beans based on molecular marker analysis

A wide array of molecular markers has been used to investigate the genetic diversity among common bean species. However, the best combination of markers for studying such diversity among common bean cultivars has yet to be determined. Few reports have examined the genetic diversity of the carioca bean, commercially one of the most important common beans in Brazil. In this study, we examined the usefulness of two molecular marker systems (simple sequence repeats – SSRs and amplified fragment length polymorphisms – AFLPs) for assessing the genetic diversity of carioca beans. The amount of information provided by Roger’s modified genetic distance was used to analyze SSR data and Jaccards similarity coefficient was used for AFLP data. Seventy SSRs were polymorphic and 20 AFLP primer combinations produced 635 polymorphic bands. Molecular analysis showed that carioca genotypes were quite diverse. AFLPs revealed greater genetic differentiation and variation within the carioca genotypes (Gst = 98% and Fst = 0.83, respectively) than SSRs and provided better resolution for clustering the carioca genotypes. SSRs and AFLPs were both suitable for assessing the genetic diversity of Brazilian carioca genotypes since the number of markers used in each system provided a low coefficient of variation. However, fingerprint profiles were generated faster with AFLPs, making them a better choice for assessing genetic diversity in the carioca germplasm

Physical conditions and chemical abundances in photoionized nebulae from optical spectra

This chapter presents a review on the latest advances in the computation of physical conditions and chemical abundances of elements present in photoionized gas H II regions and planetary nebulae). The arrival of highly sensitive spectrographs attached to large telescopes and the development of more sophisticated and detailed atomic data calculations and ionization correction factors have helped to raise the number of ionic species studied in photoionized nebulae in the last years, as well as to reduce the uncertainties in the computed abundances. Special attention will be given to the detection of very faint lines such as heavy-element recombination lines of C, N and O in H II regions and planetary nebulae, and collisionally excited lines of neutron-capture elements (Z >30) in planetary nebulae.Comment: Book Chapter. 31 pages. 6 Figures. Accepted for publication in the book "Reviews in Frontiers of Modern Astrophysics: From Space Debris to Cosmology" (eds Kabath, Jones and Skarka; publisher Springer Nature) funded by the European Union Erasmus+ Strategic Partnership grant "Per Aspera Ad Astra Simul" 2017-1-CZ01-KA203-03556

Vampires in the village Žrnovo on the island of Korčula: following an archival document from the 18th century

Središnja tema rada usmjerena je na raščlambu spisa pohranjenog u Državnom arhivu u Mlecima (fond: Capi del Consiglio de’ Dieci: Lettere di Rettori e di altre cariche) koji se odnosi na događaj iz 1748. godine u korčulanskom selu Žrnovo, kada su mještani – vjerujući da su se pojavili vampiri – oskvrnuli nekoliko mjesnih grobova. U radu se podrobno iznose osnovni podaci iz spisa te rečeni događaj analizira u širem društvenom kontekstu i prate se lokalna vjerovanja.The main interest of this essay is the analysis of the document from the State Archive in Venice (file: Capi del Consiglio de’ Dieci: Lettere di Rettori e di altre cariche) which is connected with the episode from 1748 when the inhabitants of the village Žrnove on the island of Korčula in Croatia opened tombs on the local cemetery in the fear of the vampires treating. This essay try to show some social circumstances connected with this event as well as a local vernacular tradition concerning superstitions