Novel Pathogenic Mutations and Copy Number Variations in the VPS13A Gene in Patients With Chorea-Acanthocytosis

Chorea-acanthocytosis (ChAc) is a rare autosomal recessive neurodegenerative disorder caused by loss of function mutations in the vacuolar protein sorting 13 homolog A (VPS13A) gene that encodes chorein. It is characterized by adult-onset chorea, peripheral acanthocytes, and neuropsychiatric symptoms. In the present study, we performed a comprehensive mutation screen, including sequencing and copy number variation (CNV) analysis, of the VPS13A gene in ChAc patients. All 73 exons and flanking regions of VPS13A were sequenced in 35 patients diagnosed with ChAc. To detect CNVs, we also performed real-time quantitative PCR and long-range PCR analyses for the VPS13A gene on patients in whom only a single heterozygous mutation was detected. We identified 36 pathogenic mutations, 20 of which were previously unreported, including two novel CNVs. In addition, we investigated the expression of chorein in 16 patients by Western blotting of erythrocyte ghosts. This demonstrated the complete absence of chorein in patients with pathogenic mutations. This comprehensive screen provides an accurate and useful method for the molecular diagnosis of ChAc. (C) 2011 Wiley-Liss, Inc.

Ethanol and gene expression in brain

This article represents the proceedings of a symposium at the 2000 ISBRA Meeting in Yokohama, Japan. The chairs were Izuru Matusmoto and Peter A. Wilce. The presentations were (1) GABA receptor subunit expression in the human alcoholic brain, by Tracey Buckley and Peter Dodd; (2) NMDAR gene expression during ethanol addiction, by Jorg Puzke, Rainer Spanagel, Walther Zieglgansberger, and Gerald Wolf; (3) Differentially expressed gene in the nucleus accumbens from ethanol-administered rat, by Shuangying Leng; (4) Expression of a novel gene in the alcoholic brain, by Peter A. Wilce; and (5) Investigations of haplotypes of the dopamine Da-receptor gene in alcoholics, by Hans Rommelspacher, Ulrich Finckh, and Lutz G. Schmidt.

Antigenicity and immunogenicity of novel chimeric hepatitis B surface antigen particles with exposed hepatitis C virus epitopes

The small envelope protein of hepatitis B virus (HBsAg-S) can self-assemble into highly organized virus like particles (VLPs) and induce an effective immune response. In this study, a restriction enzyme site was engineered into the cDNA of HBsAg-S at a position corresponding to the exposed site within the hydrophilic a determinant region (amino acid [aa] 127-128) to create a novel HBsAg vaccine vector allowing surface orientation of the inserted sequence. We inserted sequences of various lengths from hypervariable region 1 (HVR1) of the hepatitis C virus (HCV) E2 protein containing immunodominant epitopes and demonstrated secretion of the recombinant HBsAg VLPs from transfected mammalian cells. A number of different recombinant proteins were synthesized, and HBsAg VLPs containing inserts up to 36 aa were secreted with an efficiency similar to that of wild-type HBsAg. The HVR1 region exposed on the particles retained an antigenic structure similar to that recognized immunologically during natural infection. VLPs containing epitopes from either HCV-1a or -1b strains were produced that induced strain-specific antibody responses in immunized mice. Injection of a combination of these VLPs induced antibodies against both HVR1 epitopes that resulted in higher titers than were achieved by vaccination with the individual VLPs, suggesting a synergistic effect. This may lead to the development of recombinant particles which are able to induce a broad anti-HCV immune response against the HCV quasispecies or other quasispecies-like infectious agents.

Duck hepatitis B virus expresses a regulatory HBx-like protein from a hidden open reading frame

Duck hepatitis B viruses (DHBV), unlike mammalian hepadnaviruses, are thought to lack X genes, which encode transcription-regulatory proteins believed to contribute to the development of hepatocellular carcinoma. A lack of association of chronic DHBV infection with hepatocellular carcinoma development supports this belief. Here, we demonstrate that DHBV genomes have a hidden open reading frame from which a transcription-regulatory protein, designated DHBx, is expressed both in vitro and in vivo. We show that DHBx enhances neither viral protein expression, intracellular DNA synthesis, nor virion production when assayed in the full-length genome context in LMH cells. However, similar to mammalian hepadnavirus X proteins, DHBx activates cellular and viral promoters via the Raf-mitogen-activated protein kinase signaling pathway and localizes primarily in the cytoplasm. The functional similarities as,well as the weak sequence homologies of DHBx and the X proteins of mammalian hepadnaviruses strongly suggest a common ancestry of ortho- and avihepadnavirus X genes. In addition, our data disclose similar intracellular localization and transcription regulatory functions of the corresponding proteins, raise new questions as to their presumed role in hepatocarcinogenesis, and imply unique opportunities for deciphering of their still-enigmatic in vivo functions.

Modern scientific methods and their potential in wastewater science and technology

Application of novel analytical and investigative methods such as fluorescence in situ hybridization, confocal laser scanning microscopy (CLSM), microelectrodes and advanced numerical simulation has led to new insights into micro-and macroscopic processes in bioreactors. However, the question is still open whether or not these new findings and the subsequent gain of knowledge are of significant practical relevance and if so, where and how. To find suitable answers it is necessary for engineers to know what can be expected by applying these modern analytical tools. Similarly, scientists could benefit significantly from an intensive dialogue with engineers in order to find out about practical problems and conditions existing in wastewater treatment systems. In this paper, an attempt is made to help bridge the gap between science and engineering in biological wastewater treatment. We provide an overview of recently developed methods in microbiology and in mathematical modeling and numerical simulation. A questionnaire is presented which may help generate a platform from which further technical and scientific developments can be accomplished. Both the paper and the questionnaire are aimed at encouraging scientists and engineers to enter into an intensive, mutually beneficial dialogue. (C) 2002 Elsevier Science Ltd. All rights reserved.

Adoption and maintenance of contour bunds and hedgerows in a dynamic environment - Experience in the Philippine uplands

The widespread adoption of soil conservation technologies by farmers (notably contour hedgerows) observed in Guba, Cebu City, Philippines, is not often observed elsewhere In the country. Adoption of these technologies was because of the interaction of such phenomena as site-specific factors, appropriate extension systems, and technologies. However, lack of hedgerow maintenance, decreasing hedgerow quality, and disappearance of hedgerows raised concerns about sustainability. The dynamic nature of upland farming systems suggests the need for a location-specific farming system development framework, which provides farmers with ongoing extension for continual promotion of appropriate conservation practices.

Nomenclature of the GLUT/SLC2A family of sugar/polyol transport facilitators

The recent identification of several additional members of the family of sugar transport facilitators (gene symbol SLC2A, protein symbol GLUT) has created a heterogeneous and, in part, confusing nomenclature. Therefore, this letter provides a summary of the family members and suggests a systematic nomenclature for SLC2A and GLUT symbols.

An optical flow-based sensing system for reactive mobile robot navigation

This work discusses the use of optical flow to generate the sensorial information a mobile robot needs to react to the presence of obstacles when navigating in a non-structured environment. A sensing system based on optical flow and time-to-collision calculation is here proposed and experimented, which accomplishes two important paradigms. The first one is that all computations are performed onboard the robot, in spite of the limited computational capability available. The second one is that the algorithms for optical flow and time-to-collision calculations are fast enough to give the mobile robot the capability of reacting to any environmental change in real-time. Results of real experiments in which the sensing system here proposed is used as the only source of sensorial data to guide a mobile robot to avoid obstacles while wandering around are presented, and the analysis of such results allows validating the proposed sensing system.

Aprendizagem por imitação através de mapeamento Visuomotor baseado em imagens omnidirecionais

Este trabalho propõe uma metodologia de aprendizagem que permite a um robô aprender uma tarefa adaptando-a e representando-a de acordo com a sua capacidade motora e sensorial. Primeiramente, um mapeamento sensoriomotor é criado e converte informação sensorial em informação motora. Depois, através de imitação, o robô aprende um conjunto de ações elementares formando um vocabulário motor. A imitação é baseada nas representações motoras obtidas com o mapeamento sensoriomotor. O vocabulário motor criado é então utilizado para aprender e realizar tarefas mais sofisticadas, compostas por seqüências ou combinações de ações elementares. Esta metodologia é ilustrada através de uma aplicação de mapeamento e navegação topológica com um robô móvel. O automovimento é utilizado como mapeamento visuomotor, convertendo o fluxo óptico em imagens omnidirecionais em informação motora (translação e rotação), a qual é usada para a criação de um vocabulário motor. A seguir, o vocabulário é utilizado para mapeamento e navegação topológica. Os resultados obtidos são interessantes e a abordagem proposta pode ser estendida a diferentes robôs e aplicações.

A recepção da obra de Paulo Coelho pela crítica literária e pelo leitor

Propõe-se um estudo acerca da recepção da obra de Paulo Coelho pela crítica literária e pelo leitor, envolvendo a indústria cultural, sob a perspectiva da Sociologia da Literatura. A pesquisa justifica-se pela grande proporção de leitores que a obra atinge: traduzida para 81 idiomas e lida em 168 países, tendo boa aceitação por diferentes perfis de leitores e por muitos críticos literários de outros países. No Brasil, a produção do escritor é recebida com uma certa reserva pela crítica literária. As intervenções da indústria cultural são discutidas por meio de um diálogo estabelecido entre Theodor W. Adorno, Max Horkheimer, Pierre Bourdieu, Umberto Eco, Luiz Costa Lima e Muniz Sodré. Em seguida, estabelece-se uma discussão sobre valor estético em relação à literatura contemporânea. Posteriormente, são mostradosos elementos temáticos recorrentes e a proximidade da narrativa coelhana com a oralidade, a partir da influência das canções compostas em parceria com Raul Seixas e da operação dos gêneros parábola e fábula.A recepção da crítica é analisada, baseando-se em estudos de Mário Maestri, Eloésio Paulo, teses e dissertações, artigos, entre outros. A recepção do leitor tem como aporte teórico Antonio Candido e Roger Chartier, dentre outros, apoiando-se na Estética da Recepção, especificamente nos estudos de Hans Robert Jauss e Regina Zilberman. É analisada a recepção da obra de Paulo Coelho pelos leitores da rede social Skoob, a fim de verificar o gênero, a idade,o nível de escolaridade, a condição socioeconômica e cultural e as impressões de leitura destes. Compreendendo esses sujeitos-leitores, historicamente, e valendo-se de outros aspectos (em vez dos estéticos) apontados pela Sociologia da Literatura, é possível estabelecer diálogos entre as preferências desses leitores com obras já legitimadas pela teoria e crítica literárias, ampliando o repertório destes e contribuindo para a mediação e a promoção da leitura, no Brasil.

A prática pedagógica como obra de arte : Gadamer e a estética do professor-artista

A partir de uma análise teórico-conceitual da obra do filósofo Hans-Georg Gadamer, este estudo deseja proporcionar um diálogo entre a arte e a educação. Na procura por abrir um caminho alternativo ao “dominante”, oferecido pela racionalidade técnico-instrumental, pensa-se em fundamentar a ideia do professor como artista que faz da sua prática pedagógica uma obra de arte. O texto começa com um capítulo introdutório que descreve o objeto e o método da pesquisa. Expõe também alguns pontos que a justificam. O primeiro deles discute as limitações de uma prática pedagógica fundamentada exclusivamente nos parâmetros da racionalidade técnico-instrumental. O segundo ponto enfoca as mobilizações pessoais que levaram à eleição do tema e o terceiro faz uma pequena descrição de alguns textos que discutem o conceito de professor-artista ou que relacionam a prática docente com a arte. O capítulo seguinte apresenta fundamentos teóricos do pensamento de Gadamer sobre a verdade, vivência, jogo, poesia, diálogo e linguagem, que são a base, em princípio, para a construção da ideia de obra de arte. Finalmente, um capítulo que mostra algumas possibilidades da racionalidade estética e traça as primeiras linhas sobre o que poderia ser o professor-artista baseado na teoria de Gadamer.

Tradutor das galáxias : questões de competência tradutória da cultura pop em webcomics

Dissertação (mestrado)—Universidade de Brasília, Instituto de Letras, Departamento de Línguas Estrangeiras e Tradução, Programa de Pós-Graduação em Estudos da Tradução, 2016.