Recent advances on the role of CD40 and dendritic cells in immunity and tolerance

CD40 is a key signaling pathway for the function of B cells, monocytes, and dendritic cells in the immune system, and plays an important role in inflammatory pathways of nonhemopoietic cells. The NFkappaB family of transcription factors is a critical mediator in inflammation. NFkappaB is involved both in the regulation of CD40 expression and in cell signaling after CD40 ligation. This positive feedback loop linking NFkappaB and CD40 plays an important role in the control of the adaptive immune response, with fundamental implications for immunity and tolerance in vivo.

Applied physiology and game analysis of rugby union

Increased professionalism in rugby has elicited rapid changes in the fitness profile of elite players. Recent research, focusing on the physiological and anthropometrical characteristics of rugby players, and the demands of competition are reviewed. The paucity of research on contemporary elite rugby players is highlighted, along with the need for standardised testing protocols. Recent data reinforce the pronounced differences in the anthropometric and physical characteristics of the forwards and backs. Forwards are typically heavier, taller, and have a greater proportion of body fat than backs. These characteristics are changing, with forwards developing greater total mass and higher muscularity. The forwards demonstrate superior absolute aerobic and anaerobic power, and Muscular strength. Results favour the backs when body mass is taken into account. The scaling of results to body mass can be problematic and future investigations should present results using power function ratios. Recommended tests for elite players include body mass and skinfolds, vertical jump, speed, and the multi-stage shuttle run. Repeat sprint testing is a possible avenue for more specific evaluation of players. During competition, high-intensity efforts are often followed by periods of incomplete recovery. The total work over the duration of a game is lower in the backs compared with the forwards; forwards spend greater time in physical contact with the opposition while the backs spend more time in free running, allowing them to cover greater distances. The intense efforts undertaken by rugby players place considerable stress on anaerobic energy sources, while the aerobic system provides energy during repeated efforts and for recovery. Training should focus on repeated brief high-intensity efforts with short rest intervals to condition players to the demands of the game. Training for the forwards should emphasise the higher work rates of the game, while extended rest periods can be provided to the backs. Players should not only be prepared for the demands of competition, but also the stress of travel and extreme environmental conditions. The greater professionalism of rugby union has increased scientific research in the sport; however, there is scope for significant refinement of investigations on the physiological demands of the game, and sports-specific testing procedures.

Structure of the HERG K+ channel S5P extracellular linker - Role of an amphipathic alpha-helix in C-type inactivation

The HERG K+ channel has very unusual kinetic behavior that includes slow activation but rapid inactivation. These features are critical for normal cardiac repolarization as well as in preventing lethal ventricular arrhythmias. Mutagenesis studies have shown that the extracellular peptide linker joining the fifth transmembrane domain to the pore helix is critical for rapid inactivation of the HERG K+ channel. This peptide linker is also considerably longer in HERG K+ channels, 40 amino acids, than in most other voltage-gated K+ channels. In this study we show that a synthetic 42-residue peptide corresponding to this linker region of the HERG K+ channel does not have defined structural elements in aqueous solution; however, it displays two well defined helical regions when in the presence of SDS micelles. The helices correspond to Trp(585)-Ile(593) and Gly(604)-Tyr(611) of the channel. The Trp(585)-Ile(593) helix has distinct hydrophilic and hydrophobic surfaces. The Gly(604)-Tyr(611) helix corresponds to an N-terminal extension of the pore helix. Electrophysiological studies of HERG currents following application of exogenous S5P peptides show that the amphipathic helix in the S5P linker interacts with the pore region of the channel in a voltage-dependent manner.

Ichthyotoxicity of Chattonella marina (Raphidophyceae) to damselfish (Acanthochromis polycanthus): the synergistic role of reactive oxygen species and free fatty acids

This investigation aimed to elucidate the relative roles of putative brevetoxins, reactive oxygen species and free fatty acids as the toxic principle of the raphidophyte Chattonella marina, using damselfish as the bioassay. Our investigations on Australian C. marina demonstrated an absence or only very low concentrations of brevetoxin-like compounds by radio-receptor binding assay and liquid chromatography-mass spectroscopy techniques. Chattonella is unique in its ability to produce levels of reactive oxygen species 100 times higher than most other algal species. However, high levels of superoxide on their own were found not to cause fish mortalities. Lipid analysis revealed this raphidophyte to contain high concentrations of the polyunsaturated fatty acid eicosapentaenoic acid (EPA; 18-23% of fatty acids), which has demonstrated toxic properties to marine organisms. Using damselfish as a model organism, we demonstrated that the free fatty acid (FFA) form of EPA produced a mortality and fish behavioural response similar to fish exposed to C. marina cells. This effect was not apparent when fish were exposed to other lipid fractions including a triglyceride containing fish oil, docosahexaenoate-enriched ethyl ester, or pure brevetoxin standards. The presence of superoxide together with low concentrations of EPA accelerated fish mortality rate threefold. We conclude that the enhancement of ichthyotoxicity of EPA in the presence of superoxide can account for the high C. marina fish killing potential. (C) 2003 Elsevier B.V All rights reserved.

Systematic review of the role of pre-oxygenation for tracheal suctioning in ventilated newborn infants

Pre-oxygenation for endotracheal suctioning for mechanically ventilated infants is routine practice in many neonatal intensive care units. In the present systematic review the evidence to support its use is discussed and the authors conclude that no confident recommendations can be made from the results of this review.

A role for pectin in the control of cell expansion

Uptake of nutrients and water depends on the growth of roots through elongation of individual cells near the. root tip. Many of the numerous components of Type I primary cell walls, those of dicotyledons and monocotyledons other than grasses (Poaceae), have been determined, and many hypotheses have been proposed for the control of cell expansion. This important aspect of plant growth still needs elucidation, however. A model is proposed in which pectin, which occurs as a calcium (Ca) pectate gel between the load-bearing cellulose microfibrils and xyloglucan (XG) chains, controls the rate at which cells expand. It is considered that the increasing tension generated by the expanding cell is transmitted to interlocked XG chains and cellulose microfibrils. The resulting deformation of the embedded Ca pectate gel elicits the excretion of protons from the cytoplasm, possibly via compounds such as cell wall-associated kinases, that weakens the Ca pectate gel, permitting slippage of XG molecules through the action of expansin. Further slippage is prevented by deformation of the pectic gel, proton diffusion, and the transfer of residual tension to adjacent XG chains. Evidence for this model is based on the effects of pH, Ca, and aluminum (Al) on root elongation and on the reactions of these cations with Ca pectate. This model allows for genetic selection of plants and adaptation of individual plants to root environmental conditions.

Model studies on the role of citrate, malate and pectin esterification on the enzymatic degradation of Al- and Ca-pectate gels: possible implications for Al-tolerance

Aluminium (At) tolerance in plants may be conferred by reduced binding of Al in the cell wall through low root cation exchange capacity (CEC) or by organic acid exudation. Root CEC is related to the degree of esterification (DE) of pectin in the cell wall, and pectin hydrolysis plays a role in cell expansion. Therefore, it was hypothesised that Al-tolerant plants with a low root CEC maintain pectin hydrolysis in the presence of Al, allowing cell expansion to continue. Irrespective of the DE, binding of Al to pectin reduced the enzymatic hydrolysis of Al-pectin gels by polygalacturonase (E.C. 3.2.1.15). Pectin gels with calcium (Ca) were slightly hydrolysed by polygalacturonase. It was concluded, therefore, that Al tolerance conferred by low root CEC is not mediated by the ability to maintain pectin hydrolysis. Citrate and malate, but not acetate, effectively dissolved Al-pectate gel and led to hydrolysis of the dissolved pectin by polygalacturonase. The organic acids did not dissolve Ca-pectate, nor did they increase pectin hydrolysis by polygalacturonase. It was concluded that exudation of some organic acids can remove Al bound to pectin and this could alleviate toxicity, constituting a tolerance mechanism. (C) 2003 Editions scientitiques et medicales Elsevier SAS. All rights reserved.

Role of HuR in skeletal myogenesis through coordinate regulation of muscle differentiation genes

In this report, we investigate the role of the RNA-binding protein HuR during skeletal myogenesis. At the onset of myogenesis in differentiating C2C12 myocytes and in vivo in regenerating mouse muscle, HuR cytoplasmic abundance increased dramatically, returning to a predominantly nuclear presence upon completion of myogenesis. mRNAs encoding key regulators of myogenesis-specific transcription (myogenin and MyoD) and cell cycle withdrawal (p21), bearing AU-rich regions, were found to be targets of HuR in a differentiation-dependent manner. Accordingly, mRNA half-lives were highest during differentiation, declining when differentiation was completed. Importantly, HuR-overexpressing C2C12 cells displayed increased target mRNA expression and half-life and underwent precocious differentiation. Our findings underscore a critical function for HuR during skeletal myogenesis linked to HuR's coordinate regulation of muscle differentiation genes.

A Sco homologue plays a role in defence against oxidative stress in pathogenic Neisseria

Sco proteins are found in mitochondria and in a variety of oxidase positive bacteria. Although Sco is required for the formation of the Cu-A centre in a cytochrome oxidase of the aa(3) type, it was observed that oxidases with a Cu-A centre are not present in many bacteria that contain a Sco homologue. Two bacteria of this type are the pathogens Neisseria meningitidis and Neisseria gonorrhoeae. The sco genes of N. gonorrhoeae strain 1291 and N. meningitidis strain MC58 were cloned, inactivated by inserting a kanamycin resistance cassette and used to make knockout mutants by allelic exchange. Both N. gonorrhoeae and N. meningitidis sco mutants were highly sensitive to oxidative killing by paraquat, indicating that Sco is involved in protection against oxidative stress in these bacteria. (C) 2003 Federation of European Biochemical Societies. Published by Elsevier Science B.V. All rights reserved.

Alunos com paralisia cerebral na escola : linguagem, comunicação alternativa e processos de comunicativos

O estudo assume como problema de investigação analisar as contribuições da Comunicação Alternativa e Ampliada (CAA) aos processos comunicativos de alunos sem fala articulada no contexto da escola, destacando nesses processos o papel potencializador dos interlocutores. Fundamenta-se na abordagem de linguagem e na noção de enunciado discutidas por Bakhtin e nas contribuições de Vigotski sobre a relação entre desenvolvimento e aprendizagem, postulando que a aquisição e o desenvolvimento da linguagem ocorrem no curso das aprendizagens, ao longo da vida. As análises e reflexões empreendidas evidenciam uma discussão acerca da linguagem que se desloca da dimensão orgânica para a dimensão da constituição do sujeito como humano. Sob essa visão, outros conceitos, como os de língua, fala, interação verbal, dialogia, enunciação, aprendizagem e desenvolvimento são problematizados e também considerados como elementos fundantes e presentes nas relações comunicativas entre os sujeitos sem fala articulada e seus interlocutores. Na primeira etapa, o estudo busca conhecer as formas organizativo-pedagógicas de cinco Secretarias Municipais de Educação da Região Metropolitana de Vitória e da Secretaria de Estado da Educação no que diz respeito à identificação dos alunos com Paralisia Cerebral, sem fala articulada, ao acompanhamento técnico-pedagógico e à formação de professores que atuam na Educação Especial. Na segunda etapa, objetiva conhecer a processualidade da organização do trabalho pedagógico instituída nos contextos escolares e investiga os processos comunicativos em/com dois alunos com severos comprometimentos motores e de fala em duas escolas de Ensino Fundamental, localizadas no município de Serra e de Vitória. Nesta etapa, opta pela pesquisa- ação colaborativo-crítica por contribuir, teórica e metodologicamente, para sustentar os fazeres individuais e coletivos nos lócus de investigação. Os resultados revelam que, institucionalmente, ainda não se conhece quem são e quantos são os alunos com Paralisia Cerebral sem fala articulada no contexto de suas reais necessidades. Esse desconhecimento é atribuído pelas gestoras das Secretarias Municipais de Educação investigadas ao considerarem que, via de regra, são tomadas apenas as informações do Educacenso-INEP. As identificações pontuais, quando ocorrem, são decorrentes de estratégias internas adotadas, sendo uma delas o assessoramento pedagógico das equipes às escolas. No que tange ao ensino, à aprendizagem e à avaliação, o estudo constata que são atravessados por concepções equivocadas sobre os sujeitos com Paralisia Cerebral sustentadas, sobretudo, pela baixa expectativa e pelo pouco “esforço” quanto à sua escolarização. Constata também que o uso dos recursos de CAA potencializa os processos comunicativos dos alunos investigados e, movimentados pela linguagem, possibilita-lhes enunciar e fixar posições, opiniões e decisões, assegurando-lhes mais autonomia e fluidez do processo comunicacional. As formas de mediação dos interlocutores assim como as dinâmicas dialógicas por eles utilizadas com os alunos se constituem como elementos importantes nos processos de comunicação e interação. A espera do outro, o apoio e o incentivo à reformulação daquilo que se quer expressar, as modificações e alterações no jogo dialógico são exemplos dessa mediação. Quanto às ações de reorganização do trabalho pedagógico, o estudo registra maior articulação e colaboração entre professores da classe, professora da Educação Especial e estagiária no planejamento das aulas, dos conteúdos, com a inserção no notebook para um dos alunos; o uso das pranchas de comunicação, por ambos os alunos e seus interlocutores, como ação inovadora nos contextos escolares; a realização de atividades pelos alunos, com gradativa autonomia, a partir da disponibilização de recursos de TA/CAA (pasta de conteúdos temáticos, figuras imantadas, quadro metálico, ponteira, plano inclinado, notebook); a proposição de ações intencionais de alfabetização, a partir da reorganização de espaços-tempos no cotidiano da escola. Conclui que as discussões teóricas e práticas das questões relacionadas com a linguagem, com os processos cognitivos e com o uso de recursos de TA/CAA alavancam mudanças na concepção dos profissionais das escolas pesquisadas que, ainda, sob uma visão reducionista quanto às formas de comunicação e de interação verbal, “impõem” limites à escolarização dos alunos com deficiência.

Sorte? Lógica? Modelos de significação e a noção de acaso de adultos alunos do Proeja

Esta tese se propôs investigar a lógica inferencial das ações e suas significações em situações que mobilizam as noções de composição probabilística e acaso, bem como o papel dos modelos de significação no funcionamento cognitivo de adultos. Participaram 12 estudantes adultos jovens da classe popular, voluntários, de ambos os sexos, de um curso técnico integrado ao Ensino Médio da Educação de Jovens e Adultos. Foram realizados três encontros, individualmente, com registro em áudio e planilha eletrônica, utilizando-se dois jogos, o Likid Gaz e o Lucky Cassino, do software Missão Cognição (Haddad-Zubel, Pinkas & Pécaut, 2006), e o jogo Soma dos Dados (Silva, Rossetti & Cristo, 2012). Os procedimentos da tarefa foram adaptados de Silva e Frezza (2011): 1) apresentação do jogo; 2) execução do jogo; 3) entrevista semiestruturada; 4) aplicação de três situações-problema com intervenção segundo o Método Clínico; 5) nova partida do jogo; e 6) realização de outras duas situações-problema sem intervenção do Método Clínico. Elaboraram-se níveis de análise heurística, compreensão dos jogos e modelos de significação a partir da identificação de particularidades de procedimentos e significações nos jogos. O primeiro estudo examinou as implicações dos modelos de significação e representações prévias no pensamento do adulto, considerando que o sujeito organiza suas representações ou esquemas prévios relativos a um objeto na forma de modelos de significação em função do grau de complexidade e novidade da tarefa e de sua estrutura lógico matemática, que evoluem por meio do processo de equilibração; para o que precisa da demanda a significar esse aspecto da 13 realidade. O segundo estudo investigou a noção de combinação deduzível evidenciada no jogo Likid Gaz, identificando o papel dos modelos de significação na escolha dos procedimentos, implicando na rejeição de condutas de sistematização ou enumeração. Houve predominância dos níveis iniciais de análise heurística do jogo. O terceiro estudo examinou a noção de probabilidade observada no jogo Lucky Cassino, no qual a maioria dos participantes teve um nível de compreensão do jogo intermediário, com maior diversidade de modelos de significação em relação aos outros jogos, embora com predominância dos mais elementares. A síntese das noções de combinação, probabilidade e acaso foi explorada no quarto estudo pelo jogo Soma dos Dados (Silva, Rossetti & Cristo, 2012), identificando-se que uma limitação para adequada compreensão das ligações imbricadas nessas noções é a implicação significante – se aleatório A, então indeterminado D (notação A  D), com construção de pseudonecessidades e pseudo-obrigações ou mesmo necessidades locais, generalizadas inapropriadamente. A resistência ou obstáculos do objeto deveria provocar perturbações, mas a estrutura cognitiva, o ambiente social e os modelos culturais, e a afetividade podem interferir nesse processo.

Climate governance in an international system under conservative hegemony: the role of major powers

In the last five years, climate change has been established as a central civilizational driver of our time. As a result of this development, the most diversified social processes - as well as the fields of science which study them - have had their dynamics altered. In International Relations, this double challenge could be explained as follows: 1) in empirical terms, climate change imposes a deepening of cooperation levels on the international community, considering the global common character of the atmosphere; and 2) to International Relations as a discipline, climate change demands from the scientific community a conceptual review of the categories designed to approach the development of global climate governance. The goal of this article is to discuss in both conceptual and empirical terms the structure of global climate change governance, through an exploratory research, aiming at identifying the key elements that allow understanding its dynamics. To do so, we rely on the concept of climate powers. This discussion is grounded in the following framework: we now live in an international system under conservative hegemony that is unable to properly respond to the problems of interdependence, among which - and mainly -, the climate issue.