Pharmacogenetics of MicroRNAs and MicroRNAs Biogenesis Machinery in Pediatric Acute Lymphoblastic Leukemia

Despite the clinical success of acute lymphoblastic leukemia (ALL) therapy, toxicity is frequent. Therefore, it would be useful to identify predictors of adverse effects. In the last years, several studies have investigated the relationship between genetic variation and treatment-related toxicity. However, most of these studies are focused in coding regions. Nowadays, it is known that regions that do not codify proteins, such as microRNAs (miRNAs), may have an important regulatory function. MiRNAs can regulate the expression of genes affecting drug response. In fact, the expression of some of those miRNAs has been associated with drug response. Genetic variations affecting miRNAs can modify their function, which may lead to drug sensitivity. The aim of this study was to detect new toxicity markers in pediatric B-ALL, studying miRNA-related polymorphisms, which can affect miRNA levels and function. We analyzed 118 SNPs in pre-miRNAs and miRNA processing genes in association with toxicity in 152 pediatric B-ALL patients all treated with the same protocol (LAL/SHOP). Among the results found, we detected for the first time an association between rs639174 in DROSHA and vomits that remained statistically significant after FDR correction. DROSHA had been associated with alterations in miRNAs expression, which could affect genes involved in drug transport. This suggests that miRNA-related SNPs could be a useful tool for toxicity prediction in pediatric B-ALL.

Adenylate Cyclase Toxin promotes bacterial internalisation into non phagocytic cells

Bordetella pertussis causes whooping cough, a respiratory infectious disease that is the fifth largest cause of vaccine-preventable death in infants. Though historically considered an extracellular pathogen, this bacterium has been detected both in vitro and in vivo inside phagocytic and non-phagocytic cells. However the precise mechanism used by B. pertussis for cell entry, or the putative bacterial factors involved, are not fully elucidated. Here we find that adenylate cyclase toxin (ACT), one of the important toxins of B. pertussis, is sufficient to promote bacterial internalisation into non-phagocytic cells. After characterization of the entry route we show that uptake of "toxin-coated bacteria" proceeds via a clathrin-independent, caveolae-dependent entry pathway, allowing the internalised bacteria to survive within the cells. Intracellular bacteria were found inside non-acidic endosomes with high sphingomyelin and cholesterol content, or "free" in the cytosol of the invaded cells, suggesting that the ACT-induced bacterial uptake may not proceed through formation of late endolysosomes. Activation of Tyr kinases and toxin-induced Ca2+-influx are essential for the entry process. We hypothesize that B. pertussis might use ACT to activate the endocytic machinery of non-phagocytic cells and gain entry into these cells, in this way evading the host immune system.

Innovación, capacidad productiva, formación en el puesto de trabajo y productividad

[ES] Este estudio analiza la relación entre productividad laboral, innovación radical, innovación incremental, tecnología incorporada en maquinaria y equipos, utilización de la capacidad productiva y formación. Los datos utilizados son de empresas españolas, manufactureras y de servicios, procedentes de la Business Environment and enterprise Performance Survey (BEEPS). La técnica empleada para estimar los coeficientes del modelo es la regresión mínimo cuadrática ordinaria, ya que la variable dependiente (productividad laboral) es continua. Los resultados indican que la innovación radical y la formación influyen positiva y significativamente sobre la productividad laboral. La influencia de la tecnología incorporada también es significativa, pero de signo negativo. Finalmente, señalar que las empresas que más exportan y las de mayor tamaño alcanzan mayores niveles de productividad. Los hallazgos encontrados en este estudio tienen implicaciones para los responsables de la política económica. Los decisores políticos españoles deben promover y subsidiar la adquisición de maquinaria y equipos más eficientes para las empresas que alcanzan menores niveles de productividad, así como subsidiar la formación de trabajadores cualificados en el manejo de estos nuevos equipos. Además, también deben promover y subsidiar el desarrollo de actividades de elevado contenido en I+D para las empresas que consiguen elevados niveles de productividad, a fin de que incrementen su desempeño en innovación radical. La promoción y subsidiación de programas de formación relacionados con la I+D también resulta esencial en este tipo de empresas, máxime en un escenario caracterizado por un cambio tecnológico intenso y que se produce con gran rapidez.

O comércio intra-industrial brasileiro de 1990 a 2013: mensuração, decomposição e os determinantes

Em uma relação de bilateral,o comérciointra-industrial (CII)acontece quando os dois países exportam e importam produtos pertencentes a uma mesma indústria. Conforme apontam diversas pesquisas relacionadas a esse assunto, o intercâmbio intra-indústriade produtos tem aumentado sua participação nas transações bilaterais. Não obstante, os resultados mensurados para o comércio entre o Brasil e o resto do mundo revelam a predominância do engajamento inter-industrial em detrimento do intra-industrial. Observando dados de comércio que abrangem todos os produtos catalogados com seis dígitos no Sistema Harmonizado, esta dissertação investiga o comércio intra-industrial brasileiro entre o período de 1990 a 2013 sob suas duas formas: o intercâmbio de bens diferenciados horizontalmente e verticalmente. Ademais, a pesquisa de mensuração do CII vertical se dedica a definição dos lados superior e inferior, a fim de verificar se o Brasil é exportador ou importador líquido de bens verticalmente diferenciados de qualidade relativamente superior. Dentre a amostra de 57 países, as relações bilaterais em que o índice de Grubel e Lloyd (GL) se mostrou mais expressivo foram Argentina, Estados Unidos, México, Alemanha, Suécia, Uruguai, França, Itália, Reino Unido e Colômbia. Com relação aos setores que mais contribuíram para o índice que mensura o shareintra-industrial do comércio, destacam-se os ramos produtores de materiais de transporte e máquinas e materiais elétricos, também merecendo menção o setor de produtos químicos.Utilizando técnicas econométricas usuais da abordagem de dados em painel, a investigação dos determinantes do CII nos leva à aceitação da hipótese que relaciona o CII à presença de economias de escala. Além disso, os parâmetros estimados revelam que a distância geográfica que separa o Brasil de seu parceiro comercial prejudica mais o comércio intra-industrial vis-à-vis o inter-industrial. O processo de integração desencadeado pelo MERCOSUL, por sua vez, mostrou efeito positivo sobre o comércio intra-industrialvertical.

The development of the freezing and export of prawns in India

The paper deals with an overview on the preservation of fish by freezing process. Until a few years ago the surplus catches of fish, prawns were being dried, salted or pickled. The Kerala coast had always yielded large catches of prawns and about 5000 tons of dried prawns were annually exported to Burma and other Eastern countries. The Government of India looking at the great potential of this industry, has now, with a view to encourage exports, provided a series of incentives towards this end.