Isolation and characterization of the full-length cDNA encoding a member of a novel cytochrome p450 family (CYP320A1) from the tropical freshwater snail, Biomphalaria glabrata, intermediate host for Schistosoma mansoni

Cytochrome p450s (cyp450s) are a family of structurally related proteins, with diverse functions, including steroid synthesis and breakdown of toxins. This paper reports the full-length sequence of a novel cyp450 gene, the first to be isolated from the tropical freshwater snail Biomphalaria glabrata, an important intermediate host of Schistosoma mansoni. The nucleotide sequence is 2291 bp with a predicted amino acid sequence of 584aa. The sequence demonstrates conserved cyp450 structural motifs, but is sufficiently different from previously reported cyp450 sequences to be given a new classification, CYP320A1. Initially identified as down-regulated in partially resistant snails in response to S. mansoni infection, amplification of this gene using RT-PCR in both totally resistant or susceptible snail lines when exposed to infection, and all tissues examined, suggests ubiquitous expression. Characterization of the first cyp450 from B. glabrata is significant in understanding the evolution of these metabolically important proteins.

Do dois ao múltiplo na terra do um: a experiência antropológica de David Maybury-Lewis

Este artigo busca uma compreensão da trajetória do antropólogo britânico, radicado nos EUA, David Maybury-Lewis. Aborda aspectos de sua formação intelectual, que envolveram uma longa pesquisa entre os Xavante e um estudo comparativo sobre os povos de língua jê e bororo do Brasil Central. Maybury-Lewis é um nome central para o desenvolvimento de um "americanismo tropical". Entre suas contribuições etnográficas e teóricas, pode-se citar a elaboração de um modelo analítico jê e bororo, a renovação dos estudos de parentesco e a reflexão sobre a relação entre povos indígenas e o Estado. Um tema parece, com efeito, permear a sua obra: o das organizações dualistas. Não por menos, esse foi o motivo de um longo debate com a obra de Lévi-Strauss, que será aqui destacado.

Hexachlorophene as a topically applied chemical for prophylaxis against Schistosoma mansoni infections in mice

Treatment of mouse tail skins with hexachlorophene (1.25% w/v) in absolute methanol or 70% isopropanol suppressed Schistosoma mansoni infections by more than 95% even when the application was performed up to three days prior to exposure to cercarial suspensions by tail immersion. Treatment with concentrations of 0.313% or higher one day prior to exposure provided at least 98% protection when the treated surface was not subjected to water washes of greater duration than 1/2 hour. Tail immersion application of 1.25% hexachlorophene one day prior to exposure still provided 87-92% protection after 3 hours water wash. Wipe application of 1.25% hexachlorophene three days prior to exposure still provided 93% protection following 3 hours water wash. High cercarial recoveries from exposure tubes at the end of exposure periods indicated high antipenetrant activity for hexachlorophene. Sufficient hexachlorophene leached from treated tail skins into the surrounding water to affect subsequently added cercariae so that they were no longer infective to untreated mice.

Prevalence of intestinal microsporidiosis in Human Immunodeficiency Virus-infected patients with diarrhea in major United States cities

To determine the prevalence of intestinal microsporidiosis in HIV-infected patients, we performed a prospective study of HIV-infected patients with diarrheal illnesses in three US hospitals and examined an observational database of HIV-infected patients in 10 US cities. Among 737 specimens from the three hospitals, results were positive for 11 (prevalence 1.5%); seven (64%) acquired HIV through male-to-male sexual contact, two (18%) through male-to-male sexual contact and injection drug use, and one (9%) through heterosexual contact; one (9%) had an undetermined mode of transmission. Median CD4 count within six months of diagnosis of microsporidiosis was 33 cells/µL (range 3 to 319 cells/µL). For the national observational database (n = 24,098), the overall prevalence of microsporidiosis was 0.16%. Prevalence of microsporidiosis among HIV-infected patients with diarrheal disease is low, and microsporidiosis is most often diagnosed in patients with very low CD4+ cell counts. Testing for microsporidia appears to be indicated, especially for patients with very low CD4+ cell counts.

Molecular characterisation of intermediate snail hosts and the search for resistance genes

The relationship between schistosomes and their intermediate hosts is an extremely intricate one with strains and species of the parasite depending on particular species of snail, which in turn may vary in their susceptibility to the parasites. In order to gain a better understanding of the epidemiology of the disease we have been investigating the use of molecular markers for snail identification and for studying host-parasite relationships. In this paper we will draw on examples concerning schistosomiasis in West and East Africa to illustrate how a molecular analysis can be used as part of a "total evidence" approach to characterisation of Bulinus species and provide insights into parasite transmission. Particular emphasis is given to ribosomal RNA genes (rRNA), random amplified polymorphic DNA (RAPDs) and the mitochondrial gene cytochrome oxidase I (COI). Snails resistant to infection occur naturally and there is a genetic basis for this resistance. In Biomphalaria glabrata resistance to Schistosoma mansoni is known to be a polygenic trait and we have initiated a preliminary search for snail genomic regions linked to, or involved in, resistance by using a RAPD based approach in conjunction with progeny pooling methods. We are currently characterising a variety of STSs (sequence tagged sites) associated with resistance. These can be used for local linkage and interval mapping to define genomic regions associated with the resistance trait. The development of such markers into simple dot-blot or specific PCR-based assays may have a direct and practical application for the identification of resistant snails in natural populations.

Ocorrência do fungo entomopatogênico Isaria javanica (Frieder. & Bally) Samson & Hywell-Jones (Fungi, Sordariomycetes) em lagartas de Lonomia obliqua Walker (Lepidoptera, Saturniidae, Hemileucinae)

Este fungo foi isolado pela primeira vez de lagartas de L. obliqua de uma agregação em plátano (Platanus acerifolia (Aiton) Wild - Platanaceae), em Bento Gonçalves, RS, Brasil. Após isolamento, purificação e caracterização, realizou-se um teste de patogenicidade com lagartas sadias de L. obliqua para corroborar, sua infectividade pelo postulado de Koch. Constatou-se correspondência morfológica e molecular entre o inóculo e o reisolado, comprovando sua patogenicidade a L. obliqua.

David Hume contra os contratualistas de seu tempo

O objetivo do texto é propor uma interpretação da obra de Hume que permita uma outra maneira de refutação ao contratualismo, diversa da refutação "oficial", baseada, aquela interpretação, no conceito de artifício, significativamente diferente do artifício criado pelos contratualistas, oposição esta a que a tradição de comentaristas da filosofia política humeana, de maneira geral, não faz referência, quando se trata da refutação ao contratualismo.

David Hume, o começo e o fim

O presente artigo analisa o uso abundante por Hume de ficções que relatam o que significaria para nós a ausência de experiência - ou porque esta ainda não existiria, ou porque, por algum motivo, ela não existira mais. Sugerimos que essas ficções, além de seu objetivo mais imediato de prestar o devido reconhecimento à experiência e ao hábito como únicos fundamentos possíveis de nossas inferências de causa e efeito, revelam a tensão permanente de nossa existência entre duas forças de atração: uma força que nos puxa em direção à regularidade e uniformidade das leis da natureza e da natureza humana, afastando-nos da singularidade, da pura diferença entre percepções atômicas e da indiferença original da imaginação; e uma outra, que apenas entrevemos, mas que se mantém como uma ameaça constante por trás de todas as associações, inferências, crenças e mecanismos de paixões: o reino da pura singularidade, a recaída na indiferença, a ruína da natureza humana.

A Educação Médica entre mapas e âncoras: a aprendizagem significativa de David Ausubel, em busca da Arca Perdida

O processo de aprendizagem tem motivado, desde a Antigüidade, intensos debates. Dentre as diferentes teorias propostas tem ganho relevância, nos séculos XX e XXI, a concepção cognitivista de David Ausubel, na qual se assume que os mecanismos do aprender são mais eficientes em situações nas quais o estudante consegue, utilizando conhecimentos prévios, agregar e incorporar significado aos novos conteúdos, evitando-se, assim, que esse conhecimento recém-incorporado seja armazenado, por meio de associações ineptas, à estrutura cognitiva. No âmbito da educação médica, diante das imperiosas mudanças necessárias para a formação de um profissional que aprenda a aprender, a aprendizagem significativa permite uma genuína contextualização dos conhecimentos necessários à prática médica, facultando, portanto, um aprendizado mais efetivo e permitindo a atuação em um contexto complexo e interdisciplinar. Em conformidade com o exposto, o presente manuscrito objetiva apresentar a teoria da aprendizagem significativa, discutindo elementos da incorporação deste conceito à educação médica.

David Trumbull, entre masonería y protestantismo: la conformación del frente anticlerial en Chile a fines del siglo XIX

El objetivo de este artículo es caracterizar la figura del Pastor Protestante David Trumbull en la configuración del Frente anticlerical chileno de fines del siglo XIX. Se analizan los planteamientos fundamentales de Trumbull, respecto a la vinculación Política-Religión en temáticas críticas de época, como lo fueron la búsqueda de la Libertad de Culto y la participación de lo protestante en la construcción del Chile republicano. Es considerada la interrelación entre Masonería y Protestantismo a través de la figura de Trumbull, como un articulador de perspectivas doctrinalmente contradictorias, pero instrumentalmente posibles de ser ensambladas por causa de un objetivo común, la implementación del ideario liberal.

The renal and hepatic distribution of Bence Jones proteins depends on glycosylation: a scintigraphic study in rats

The aim of the present study was to evaluate renal and liver distribution of two monoclonal immunoglobulin light chains. The chains were purified individually from the urine of patients with multiple myeloma and characterized as lambda light chains with a molecular mass of 28 kDa. They were named BJg (high amount of galactose residues exposed) and BJs (sialic acid residues exposed) on the basis of carbohydrate content. A scintigraphic study was performed on male Wistar rats weighing 250 g for 60 min after iv administration of 1 mg of each protein (7.4 MBq), as the intact proteins and also after carbohydrate oxidation. Images were obtained with a Siemens gamma camera with a high-resolution collimator and processed with a MicroDelta system. Hepatic and renal distribution were established and are reported as percent of injected dose. Liver uptake of BJg was significantly higher than liver uptake of BJs (94.3 vs 81.4%) (P<0.05). This contributed to its greater removal from the intravascular compartment, and consequently lower kidney accumulation of BJg in comparison to BJs (5.7 vs 18.6%) (P<0.05). After carbohydrate oxidation, there was a decrease in hepatic accumulation of both proteins and consequently a higher renal overload. The tissue distribution of periodate-treated BJg was similar to that of native BJs: 82.7 vs 81.4% in the liver and 17.3 vs 18.6% in the kidneys. These observations indicate the important role of sugar residues of Bence Jones proteins for their recognition by specific membrane receptors, which leads to differential tissue accumulation and possible toxicity

Nephrotoxicity of Bence-Jones proteins: interference in renal epithelial cell acidification

The aim of the present study was to evaluate the acidification of the endosome-lysosome system of renal epithelial cells after endocytosis of two human immunoglobulin lambda light chains (Bence-Jones proteins, BJP) obtained from patients with multiple myeloma. Renal epithelial cell handling of two BJP (neutral and acidic BJP) was evaluated by rhodamine fluorescence. Renal cells (MDCK) were maintained in culture and, when confluent, were incubated with rhodamine-labeled BJP for different periods of time. Photos were obtained with a fluorescence microscope (Axiolab-Zeiss). Labeling density was determined on slides with a densitometer (Shimadzu Dual-Wavelength Flying-Spot Scanner CS9000). Endocytosis of neutral and acidic BJP was correlated with acidic intracellular compartment distribution using acridine orange labeling. We compared the pattern of distribution after incubation of native neutral and acidic BJP and after complete deglycosylation of BJP by periodate oxidation. The subsequent alteration of pI converted neutral BJP to acidic BJP. There was a significant accumulation of neutral BJP in endocytic structures, reduced lysosomal acidification, and a diffuse pattern of acidification. This pattern was reversed after total deglycosylation and subsequent alteration of the pI to an acidic BJP. We conclude that the physicochemical characteristics of BJP interfere with intracellular acidification, possibly explaining the strong nephrotoxicity of neutral BJP. Lysosomal acidification is fundamental for adequate protein processing and catabolism.

As duas vias do princípio das vantagens comparativas de David Ricardo e o padrão-ouro: um ensaio crítico

This article critically resumes Ricardo's principle of comparative advantages pointing out internal coherence problems that have been neglected by the specialized literature. First, long-lasting disequilibria observed in the balance of trade seem incompatible with the idea that these disequilibria are caused by technical advances that change relative prices. Second, comparative advantages do not seem to work in an economy with a universally accepted commodity-money. Finally, the contradiction between the gold standard mechanisms, ruled by Smith's "Law of Reflux", and the quantitative theory of money, which is a necessary condition for the "second way" of the theory of comparative advantages.

David Hume e as finanças de James I

RESUMOEste artigo examina a análise de David Hume realizada em seu livro História da Inglaterra, da luta entre o parlamento e o rei James I sobre as finanças da coroa durante o primeiro trimestre do século XVII. Inicialmente, são apresentados os principais elementos políticos por trás da briga no coração do poder político da Inglaterra, seguidos por comentários do escritor escocês sobre as finanças reais, com ênfase nos seus pontos de vista sobre as receitas e despesas da Coroa durante o reinado de James I. No final são recuperados os fatores de longo prazo elencados como determinantes da nova postura parlamentar.