Pharmacogenetics of OATP Transporters Reveals That SLCO1B1 c.388A>G Variant Is Determinant of Increased Atorvastatin Response

Aims: The relationship between variants in SLCO1B1 and SLCO2B1 genes and lipid-lowering response to atorvastatin was investigated. Material and Methods: One-hundred-thirty-six unrelated individuals with hypercholesterolemia were selected and treated with atorvastatin (10 mg/day/4 weeks). They were genotyped with a panel of ancestry informative markers for individual African component of ancestry (ACA) estimation by SNaPshot® and SLCO1B1 (c.388A>G, c.463C>A and c.521T>C) and SLCO2B1 (−71T>C) gene polymorphisms were identified by TaqMan® Real-time PCR. Results: Subjects carrying SLCO1B1 c.388GG genotype exhibited significantly high low-density lipoprotein (LDL) cholesterol reduction relative to c.388AA+c.388AG carriers (41 vs. 37%, p = 0.034). Haplotype analysis revealed that homozygous of SLCO1B1*15 (c.521C and c.388G) variant had similar response to statin relative to heterozygous and non-carriers. A multivariate logistic regression analysis confirmed that c.388GG genotype was associated with higher LDL cholesterol reduction in the study population (OR: 3.2, CI95%:1.3–8.0, p < 0.05). Conclusion: SLCO1B1 c.388A>G polymorphism causes significant increase in atorvastatin response and may be an important marker for predicting efficacy of lipid-lowering therapy

The role of extracellular nucleic acids in the immune system modulation of Rhodnius prolixus (Hemiptera: Reduviidae)

Extracellular traps (ETs) are extracellular nucleic acids associated with cytoplasmic proteins that may aid in the capture and killing of pathogens. To date, only a few insects were shown to display this kind of immune response. Jaburetox, a peptide derived from jack bean urease, showed toxic effects in Rhodnius prolixus, affecting its immune response. The present study aims to evaluate the role of extracellular nucleic acids in R. prolixus' immune response, using Jaburetox as a model entomotoxin. The insects were treated with extracellular nucleic acids and/or Jaburetox, and the cellular and humoral responses were assessed. We also evaluated the release of extracellular nucleic acids induced by toxins, and performed immunocompetence assays using pathogenic bacteria. Our results demonstrated that extracellular nucleic acids can modulate the insect immune responses, either alone or associated with the toxin. Although RNA and DNA induced a cellular immune response, only DNA was able to neutralize the Jaburetox-induced aggregation of hemocytes. Likewise, the activation of the humoral response was different for RNA and DNA. Nevertheless, it was observed that both, extracellular DNA and RNA, immunocompensated the Jaburetox effects on insect defenses upon the challenge of a pathogenic bacterium. The toxin was not able to alter cellular viability, in spite of inducing an increase in the reactive species of oxygen formation. In conclusion, we have demonstrated a protective role for extracellular nucleic acids in R. prolixus´ immune response to toxins and pathogenic bacteria.Fil: Coste Grahl, Matheus V.. Universidade Federal do Rio Grande do Sul; BrasilFil: Perin, Ana Paula A.. Universidade Federal do Rio Grande do Sul; BrasilFil: Lopes, Fernanda C.. Universidade Federal do Rio Grande do Sul; BrasilFil: Porto, Bárbara N.. Pontificia Universidade Católica do Rio Grande do Sul; BrasilFil: Uberti, Augusto F.. Pontificia Universidade Católica do Rio Grande do Sul; BrasilFil: Canavoso, Lilian Etelvina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFil: Stanisçuaski, Fernanda. Universidade Federal do Rio Grande do Sul; BrasilFil: Fruttero, Leonardo Luis. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentin

Jaburetox-induced toxic effects on the hemocytes of Rhodnius prolixus (Hemiptera: Reduviidae)

Jaburetox is a recombinant peptide derived from a Canavalia ensiformis urease that presents toxic effects uponseveral species of insects, phytopathogenic fungi and yeasts of medical importance. So far, no toxicity of Jaburetoxto mammals has been shown. Previous reports have identified biochemical targets of this toxic peptide ininsect models, although its mechanism of action is not completely understood. In this work, we aimed to characterizethe effects of Jaburetox in hemolymphatic insect cells. For this purpose, the model insect and Chagas´disease vector Rhodnius prolixus was used. In vivo and in vitro experiments indicated that Jaburetox interacts witha subset of hemocytes and it can be found in various subcellular compartments. In insects injected with Jaburetoxthere was an increase in the gene expression of the enzymes UDP-N-acetylglucosamine pyrophosphorylase(UAP), chitin synthase and nitric oxide synthase (NOS). Nevertheless, the expression of NOS protein, the enzymeactivities of UAP and acid phosphatase (a possible link between UAP and NOS) as well as the phosphorylationstate of proteins remained unchanged upon the in vivo Jaburetox treatment. Nitric oxide (NO) imaging using fluorescentprobes showed that Jaburetox augmented NO production in the hemocyte aggregates when comparedto controls. Even though Jaburetox activated the hemocytes, as demonstrated by wheat germ agglutinin bindingassays, the peptide did not lead to an increase of their phagocytic behavior. Taken together, these findingscontribute to our understanding of toxic effects of Jaburetox, a peptide with biotechnological applications and aprospective tool for rational insect control.Fil: Moyetta, Natalia Rita. Pontificia Universidade Católica do Rio Grande do Sul; Brasil. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFil: Broll, Valquiria. Universidade Federal do Rio Grande do Sul; BrasilFil: Perin, Ana Paula A.. Universidade Federal do Rio Grande do Sul; BrasilFil: Uberti, Augusto F.. Universidade Federal do Rio Grande do Sul; BrasilFil: Coste Grahl, Matheus V.. Pontificia Universidade Católica do Rio Grande do Sul; BrasilFil: Staniscuaski, Fernanda. Universidade Federal do Rio Grande do Sul; BrasilFil: Carlini, Célia Regina R S. Pontificia Universidade Católica do Rio Grande do Sul; BrasilFil: Fruttero, Leonardo Luis. Pontificia Universidade Católica do Rio Grande do Sul; Brasil. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentin

Memoria docente, investigación y formación

El objetivo de este conjunto de trabajos es el de demarcar un campo de investigación -el de la investigación (auto)biográfica- que abarca, sin reservas, la multiplicidad de las escrituras de sí y la amplitud de sus cuatro dimensiones: la narrativa como fenómeno de lenguaje; como método y fuente de investigación, como práctica de (auto)formación y, finalmente, como un procedimiento de intervención educativa y social. La temática del libro congrega, entonces, a investigadores de distintos países con el propósito de problematizar los puntos de convergencia y buscar aproximaciones epistemológicas, teóricas y metodológicas que se expanden en múltiples direcciones, pero que encuentran puntos de intersección muy provechosos en el paradigma comprensivo de las Ciencias Humanas y Sociales, inaugurado por W. Dilthey (1833-1911), que hace de la autobiografía y la narrativa un modelo hermenéutico para la comprensión del mundo humano

Memoria docente, investigación y formación

El objetivo de este conjunto de trabajos es el de demarcar un campo de investigación -el de la investigación (auto)biográfica- que abarca, sin reservas, la multiplicidad de las escrituras de sí y la amplitud de sus cuatro dimensiones: la narrativa como fenómeno de lenguaje; como método y fuente de investigación, como práctica de (auto)formación y, finalmente, como un procedimiento de intervención educativa y social. La temática del libro congrega, entonces, a investigadores de distintos países con el propósito de problematizar los puntos de convergencia y buscar aproximaciones epistemológicas, teóricas y metodológicas que se expanden en múltiples direcciones, pero que encuentran puntos de intersección muy provechosos en el paradigma comprensivo de las Ciencias Humanas y Sociales, inaugurado por W. Dilthey (1833-1911), que hace de la autobiografía y la narrativa un modelo hermenéutico para la comprensión del mundo humano

Executive MBA programs: what do students perceive as value for their practices?

This paper explores MBA students’ perceptions about their learning process and the outcomes of development of capabilities and competences. A qualitative exploratory study was conducted between 2004 and 2008 with 160 students enrolled in 6 different MBA programs in Brazil. The data were collected at group activities using a questionnaire to lead the participants to identify the contents and experiences from their MBA’s that were associated with the development of capabilities and competences relevant to practice. Examining the current literature and its indications of a myriad of pedagogical approaches, we discuss the MBA educators’ pedagogical planning for developing capacities and competences without considering which knowledge is valued as relevant by students. Our results identified three aspects as the most relevant in MBA students’ learning experiences: (a) openness to exploit new ways of interpreting the world; (b) development of specific capabilities; and (c) development of relational competence. The main contribution of our study is to highlight the students’ active engagement in the learning opportunities created by MBA educators and their outcomes. Based on the evidence, we argue that the pedagogical planning developed by educators should consider MBA students as the protagonist of their management education process

Neotropical freshwater fisheries : A dataset of occurrence and abundance of freshwater fishes in the Neotropics

The Neotropical region hosts 4225 freshwater fish species, ranking first among the world's most diverse regions for freshwater fishes. Our NEOTROPICAL FRESHWATER FISHES data set is the first to produce a large-scale Neotropical freshwater fish inventory, covering the entire Neotropical region from Mexico and the Caribbean in the north to the southern limits in Argentina, Paraguay, Chile, and Uruguay. We compiled 185,787 distribution records, with unique georeferenced coordinates, for the 4225 species, represented by occurrence and abundance data. The number of species for the most numerous orders are as follows: Characiformes (1289), Siluriformes (1384), Cichliformes (354), Cyprinodontiformes (245), and Gymnotiformes (135). The most recorded species was the characid Astyanax fasciatus (4696 records). We registered 116,802 distribution records for native species, compared to 1802 distribution records for nonnative species. The main aim of the NEOTROPICAL FRESHWATER FISHES data set was to make these occurrence and abundance data accessible for international researchers to develop ecological and macroecological studies, from local to regional scales, with focal fish species, families, or orders. We anticipate that the NEOTROPICAL FRESHWATER FISHES data set will be valuable for studies on a wide range of ecological processes, such as trophic cascades, fishery pressure, the effects of habitat loss and fragmentation, and the impacts of species invasion and climate change. There are no copyright restrictions on the data, and please cite this data paper when using the data in publications