Inhibitors of COP-mediated Transport and Cholera Toxin Action Inhibit Simian Virus 40 Infection

Simian virus 40 (SV40) is a nonenveloped virus that has been shown to pass from surface caveolae to the endoplasmic reticulum in an apparently novel infectious entry pathway. We now show that the initial entry step is blocked by brefeldin A and by incubation at 20degreesC. Subsequent to the entry step, the virus reaches a domain of the rough endoplasmic reticulum by an unknown pathway. This intracellular trafficking pathway is also brefeldin A sensitive. Infection is strongly inhibited by expression of GTP-restricted ADP-ribosylation factor 1 (Arf1) and Sar1 mutants and by microinjection of antibodies to betaCOP. In addition, we demonstrate a potent inhibition of SV40 infection by the dipeptide N-benzoyl-oxycarbonyl-Gly-Phe-amide, which also inhibits late events in cholera toxin action. Our results identify novel inhibitors of SV40 infection and show that SV40 requires COPI- and COPII-dependent transport steps for successful infection.

Perceptions of younger, middle-aged, and older adults in Australia and Japan: Stereotypes and age group vitality

This study investigated the perceptions of young adults in Japan and Australia about their own age group, as well as middle-aged and older adults. Using a self-administered questionnaire, 155 Japanese and 171 Australian students rated people in the three age groups on traits of personal vitality and benevolence, and also rated their age group vitalities. Results indicated that Australians perceived both middle-aged and older adults in more positive terms than did Japanese and also perceived the vitality of these age groups as higher. On the other hand, both Japanese and Australian young people judged the vitality of their own group as lower than that of middle-aged adults. These results suggest that norms of filial piety, especially its respect dimension, in Japan may be eroding, whereas older Australians may be gaining in social stature.

Adapting immunity with subunit vaccines: case studies with group A Streptococcus and malaria

Although vaccines have widely been regarded as the most cost-effective way to improve public health, for some organisms new technological advances in vaccine design and delivery, incurring additional developmental costs, will be essential. These organisms are typically those for which natural immunity is either slow to develop or does not develop at all. Clearly, such organisms have evolved strategies to evade immune responses and innovative approaches will be required to induce a type of immune response which is both different to that which develops naturally and is effective. This article describes some approaches to develop vaccines for two such organisms (malaria parasites and Streptococcus pyogenes (group A Streptococcus)) that are associated with widespread mortality and morbidity, mostly in the poorest countries of the world. At this stage, the challenges are primarily scientific, but if these hurdles are surmounted then the challenges will become financial ones - developing much needed vaccines for people least able to afford them. (C) 2002 Australian Society for Parasitology Inc. Published by Elsevier Science Ltd. All rights reserved.

Initiation of biological agents in patients with ankylosing spondylitis: results of a Delphi study by the ASAS Group

Background: There is ample evidence of important symptomatic efficacy of tumour necrosis factor alpha (TNFalpha) inhibition in ankylosing spondylitis (AS). Moreover, studies suggest that anti-TNF could be considered as the first disease controlling antirheumatic treatment (DC-ART) for AS. Objective: To determine precisely which patients with AS are most likely to benefit from anti-TNFalpha treatment because of the cost and possible long term side effects of such treatment. Methods: Assessment in Ankylosing Spondylitis (ASAS) members were asked to use a Delphi technique to name the characteristics of patients with AS for whom they would start DC-ART, in three different clinical presentations (isolated axial involvement, peripheral arthritis, enthesitis). Results: Among the 62 invited ASAS members, more than 50% actively participated in the four phases of definition according to the Delphi technique. For each of the three clinical presentations, a combination of five to six domains was proposed, with an evaluation instrument and a cut off point defining a minimum level of activity for each domain. Conclusion: This study provides a profile for a patient with AS for considering initiation of biological agents that reflects the opinion of the ASAS members, using a Delphi exercise. Further studies are required to assess their relevance and their consistency with clinical practice.

The VCAM-1 gene that encodes the vascular cell adhesion molecule is a target of the Sry-related high mobility group box gene, Sox18

VCAM-1 (vascular cell adhesion molecule-1) and Sox18 are involved in vascular development. VCAM-1 is an important adhesion molecule that is expressed on endothelial cells and has a critical role in endothelial activation, inflammation, lymphatic pathophysiology, and atherogenesis. The Sry-related high mobility group box factor Sox18 has previously been implicated in endothelial pathologies. Mutations in human and mouse Sox18 leads to hypotrichosis and lymphedema. Furthermore, both Sox18 and VCAM-1 have very similar spatio-temporal patterns of expression, which is suggestive of crosstalk. We use biochemical techniques, cell culture systems, and the ragged opossum (RaOP) mouse model with a naturally occurring mutation in Sox18 to demonstrate that VCAM-1 is an important target of Sox18. Transfection, site-specific mutagenesis, and gel shift analyses demonstrated that Sox18 directly targeted and trans-activated VCAM-1 expression. Importantly, the naturally occurring Sox18 mutant attenuates the expression and activation of VCAM-1 in vitro. Furthermore, in vivo quantitation of VCAM-1 mRNA levels in wild type and RaOP mice demonstrates that RaOP animals show a dramatic and significant reduction in VCAM-1 mRNA expression in lung, skin, and skeletal muscle. Our observation that the VCAM-1 gene is an important target of SOX18 provides the first molecular insights into the vascular abnormalities in the mouse mutant ragged and the human hypotrichosis-lymphedematelangiectasia disorder.

Caenorhabditis elegans mutants resistant to phosphine toxicity show increased longevity and cross-resistance to the synergistic action of oxygen

Phosphine (hydrogen phosphide, PH3) is the fumigant most widely used to protect stored products from pest infestation. Despite the importance of this chemical, little is known about its mode of action. We have created three phosphine-resistant lines (pre-1, pre-7, pre-33) in the model organism C. elegans, with LC50 values 2, 5, and 9 times greater than the fully susceptible parental strain. Molecular oxygen was shown to be an extremely effective synergist with phosphine as, under hyperoxic conditions, 100% mortality was observed in wild-type nematodes exposed to 0.1 mg/l phosphine, a nonlethal concentration in air. All three mutants were resistant to the synergistic effects of oxygen in proportion to their resistance to phosphine with one mutant, pre-33, showing complete resistance to this synergism. We take the proportionality of cross-resistance between phosphine and the synergistic effect of oxygen to imply that all three mutants circumvent a mechanism of phosphine toxicity that is directly coupled to oxygen metabolism. Compared with the wild-type strain, all three mutants have an extended average life expectancy of from 12.5 to 25.3%. This is consistent with the proposed involvement of oxidative stress in both phosphine toxicity and ageing. Because the wild-type and mutant nematodes develop at the same rate, the longevity is unlikely to be caused by a clk-type reduction in oxidative metabolism, a potential alternative mechanism of phosphine resistance.

Do expertise and the degree of perception-action coupling affect natural anticipatory performance?

Two experiments using a temporal occlusion paradigm (the first with expert and novice participants and the second with participants of intermediate skill) were conducted to examine the capability of tennis players to predict the direction of an opponent's service in situ. In both experiments two different response conditions, reflecting differing degrees of perception-action coupling, were employed. In a coupled condition players were required to make a movement-based response identical to that which they would use to hit a return of service in a game situation, whereas in an uncoupled condition a verbal prediction of service direction was required. Experiment 1 provided clear evidence of superior prediction accuracy under the coupled response condition when ball flight was available, plus some limited evidence to suggest that superior prediction accuracy under uncoupled response conditions might hold true if only advance (pre-contact) information was available. Experiment 2 showed the former finding to be a robust one, but was unable to reveal any support for the latter. Experiment 1 also revealed that expert superiority is more apparent for predictions made under natural (coupled) than uncoupled response-mode conditions. Collectively, these findings suggest that different perceptual processes may be in operation in anticipatory tasks which depend on skill level, the type of information presented, and degree of perception-action coupling inherent in the task requirements.

Evaluating plant breeding strategies by simulating gene action and dryland environment effects

Functional genomics is the systematic study of genome-wide effects of gene expression on organism growth and development with the ultimate aim of understanding how networks of genes influence traits. Here, we use a dynamic biophysical cropping systems model (APSIM-Sorg) to generate a state space of genotype performance based on 15 genes controlling four adaptive traits and then search this spice using a quantitative genetics model of a plant breeding program (QU-GENE) to simulate recurrent selection. Complex epistatic and gene X environment effects were generated for yield even though gene action at the trait level had been defined as simple additive effects. Given alternative breeding strategies that restricted either the cultivar maturity type or the drought environment type, the positive (+) alleles for 15 genes associated with the four adaptive traits were accumulated at different rates over cycles of selection. While early maturing genotypes were favored in the Severe-Terminal drought environment type, late genotypes were favored in the Mild-Terminal and Midseason drought environment types. In the Severe-Terminal environment, there was an interaction of the stay-green (SG) trait with other traits: Selection for + alleles of the SG genes was delayed until + alleles for genes associated with the transpiration efficiency and osmotic adjustment traits had been fixed. Given limitations in our current understanding of trait interaction and genetic control, the results are not conclusive. However, they demonstrate how the per se complexity of gene X gene X environment interactions will challenge the application of genomics and marker-assisted selection in crop improvement for dryland adaptation.

Translating policy: Power and action in Australia's country towns

Controversies In its present condition, rural Australia is characterised by a discourse of decline that sees country towns and regions as places of demoralisation and despair. From a Foucauldian governmentality perspective, those who live in these spaces are not so much 'powerless' to the demands of urban-based governments and global capital, as rendered governable according to the socio-political ambitions of late capitalism. While important insights have been derived from such analyses, it is argued in this paper that excessive attention is often paid to the power of the state with little concern for the various ways in which local people engage with, and transform the strategies and effects of state power. Rather than utilising the concept of resistance to make sense of these interactions, a sociology of translation is adopted from the Actor Network Theory literature. Applied to two case examples, it shows how governmental policies and programmes are frequently the outcome of the interactions and negotiations that take place between all those enrolled in the actor-network.

Organiza????o dos usu??rios, participa????o na gest??o e controle das organiza????es sociais

O artigo discute a participa????o dos usu??rios na gest??o das Organiza????es Sociais, prevista num projeto da reforma do aparelho de Estado atualmente em curso. A participa????o dos usu??rios na gest??o das institui????es p??blicas ?? um instrumento que pode resolver problemas da rela????o principal-agente, garantindo a implementa????o eficiente das pol??ticas. No projeto das Organiza????es Sociais, essa participa????o ?? viabilizada, entre outros meios, pela presen??a de entidades representativas da sociedade civil no Conselho de Administra????o da institui????o, pressupondo, portanto, a organiza????o dos usu??rios. Por essa raz??o, no artigo s??o analisadas as possibilidades de organiza????o dos usu??rios com base na abordagem da ???l??gica da a????o coletiva???.

A elaboração e instituição do currículo mínimo de matemática no Rio de Janeiro

O currículo traz subjacente a si, as ideias de seu tempo, o olhar de sua sociedade para questões humanas e outras tacitamente políticas. Traz em seu escopo toda uma trama de heranças históricas e a marca pessoal daqueles que se dedicaram a sua construção. E desta forma, analisar as tramas de um currículo de matemática é muito mais que olhar uma sequência de conteúdos linearmente organizados. É, sobretudo, entender, que aquela construção foi tecida de forma a sustentar um corpo de ideias que diz sobre seu tempo. Esta pesquisa evidenciou o processo de elaboração e instituição do currículo mínimo pela Seeduc/RJ e trouxe questionamentos e inquietações de naturezas cognitivas e sociais. Uma primeira inquietação concerne ao descarte de conteúdos do currículo anterior, que configura agora, este novo currículo. Esse processo de elaboração e instituição refletiu a inexistência de diálogo entre os diversos segmentos sociais e profissionais do campo educacional. Interesses governamentais interferiram diretamente nos educacionais, subtraindo a democracia das ações de políticas públicas implementadas. Ficou evidente que não houve clareza conceitual quando dessa e em contraste até mesmo com propostas nacionais e a legislação vigente. Através do Currículo Mínimo buscou-se unificar toda a rede de ensino da Seeduc/RJ, dentro de uma perspectiva academicista limitada, desconsiderando as especificidades locais e de cada grupo. Desta forma, foi desconsiderada a dialética educacional e a retórica da matemática enquanto disciplina acadêmica, que é uma forma particular da relação social. O processo instituído evidencia uma visão de professores passivos e alunos considerados mínimos.

Olhares acerca do processo de construção dos Projetos Políticos Pedagógicos dos cursos Técnicos Integrados ao Ensino Médio de Jovens e Adultos no contexto do Ifes campus Vitória

Este trabalho é resultado da investigação que teve como objetivo analisar o processo de construção dos Projetos Políticos Pedagógicos dos cursos do Proeja no contexto do Ifes campus Vitória. O problema de pesquisa buscou captar os movimentos e as experiências desencadeados nesse processo. No percurso metodológico, com ênfase na pesquisa qualitativa, foi necessário entrelaçar duas abordagens: a etnografia escolar e a pesquisa-ação em função da atuação profissional da pesquisadora no lócus de estudo. Variados instrumentos foram utilizados para levantamento e a produção dos dados, dentre os quais: questionários, entrevistas, diário de campo das observações, pesquisa bibliográfica e documental. Participaram da pesquisa aproximadamente 80 pessoas, entre docentes, alunos e gestores, abordados em contextos específicos: o grupo de formação continuada, a comissão dos projetos, o encontros dos alunos, a reunião intermediária dentre outros. O referencial teórico-metodológico pautado na perspectiva do materialismo histórico dialético embasou toda a trajetória investigativa, em coerência com a base da produção das pesquisas sobre trabalho e educação e por se constituir a referência que fundamenta os princípios estruturantes do currículo integrado na perspectiva da formação humana. Por meio da metáfora dos observatórios, focamos nossas lentes sobre as questões que desafiaram a construção dos projetos políticos pedagógicos e sua coerência com os princípios epistemológicos, políticos e pedagógicos do Proeja. Nesse movimento, diversos olhares foram captados, possibilitando-nos levantar os seguintes resultados: o percurso de construção dos projetos foi marcado por contradições que perpassam todo o processo e que constituíram um debate profícuo que tenciona a gestão pedagógica, administrativa e financeira do Ifes campus Vitória. O movimento se constituiu também em um processo de construção, partilha de saberes e experiências, impulsionado pela busca da apreensão dos sentidos da integração, que contraditoriamente não alcançou seus objetivos, embora não se possa negar os resultados positivos do processo no interior da Instituição. Dessa forma, os desafios para efetivação da formação integrada no Ifes persistem. Ganha centralidade nessa discussão os sujeitos a quem o programa se volta e suas demandas de formação, bem como as condições materiais de oferta dos cursos e de forma especial as condições de envolvimento dos professores com o programa e as reflexões sobre suas práticas.