The Dimension of Npi in Mozambique: A Satellite Account Perspective

This study gives a first estimate of the economic and social dimension of the NPI sector in Mozambique in a satellite account perspective

El sexto continente - Por Alberto Luis Quaranla - Buenos Aires, Editorial Crespillo, 1950.

Fil: Yebara de Nahman, Saide. Universidad Nacional de Cuyo. Facultad de Filosofía y Letra

Mutilación genital femenina y matrimonio precoz en Kenia: la respuesta local ante normas globales

Cloward, Karisa. When Norms Collide. Local Responses to Activism against Female Genital Mutilation and Early Marriage. Oxford University Press, 2016314 págs.

Paracetamol-induced liver injury modelled in Xenopus laevis embryos

Introduction: Failure to predict drug-induced liver injury (DILI) remains a major contributing factor to lead compound drop-out during drug development. Xenopus embryos are amenable for early stage medium throughput small molecule screens and so have the potential to be used in pre-clinical screens. To begin to assess the usefulness and limitations of Xenopus embryos for safety assessment in the early phases of drug development, paracetamol was used as a model hepatotoxin. Paracetamol overdose is associated with acute liver injury. In mammals, the main mechanism of paracetamol-induced acute liver injury is an increased amount of the reactive metabolite N-acetyl-p-benzoquinone imine (NAPQI) combined with a reduction of free glutathione (GSH). Humans that have taken an overdose of paracetamol are often treated with N-acetyl cysteine (NAC). Method: Xenopus laevis embryos were treated with up to 5 mM paracetamol from stage 38 to stage 45 during development, when the liver is functional. The presence of paracetamol-induced liver injury was assessed by: (Dart et al., 2006) microRNA-122 (miR-122) expression (a hepatic marker), (Jaeschke, 2015) free GSH concentration (a marker of oxidative stress) and (Larson et al., 2005) NAC antioxidant intervention. Results: The amount of free GSH decreased significantly in embryos exposed to increasing paracetamol concentration. In embryos exposed to 5 mM paracetamol, 22.57 ± 4.25 nmol/mg GSH was detected compared to 47.11 ± 7.31 nmol/mg untreated embryos (mean ± SEM). In tail tissue, miRNA-122 expression increased 6.3-fold with 3 mM paracetamol concentration treatment compared to untreated embryos. NAC treatment altered the free GSH decline for embryos treated with up to 5 mM. Embryos exposed to 1 mM paracetamol and then exposed to 0.5 mM NAC 24 h prior to harvest, had an significantly higher amount GSH compared to embryos that were only exposed to 1 mM paracetamol (mean ± SEM; 97.1 ± 9.6 nmol/mg and 54.5 ± 6.6 nmol/mg respectively). Conclusion: Xenopus laevis embryos exhibit similar characteristics of paracetamol-induced liver injury observed in mammalian models. These data indicate that the Xenopus embryo could be a useful in vivo model to assess DILI and aid lead compound prioritisation during the early phase of drug development, in combination with pre-clinical in vitro studies. Consequently, the Xenopus embryo could contribute to the reduction principle as defined by the National Centre for the Replacement, Refinement and Reduction of Animals in Research

Pupal surveys for Aedes aegypti surveillance and potential targeted control in residential areas of Mérida, México.

A mosquito larval-pupal survey was conducted in 1,160 households of the Mexican city of Mérida during the rainy season of 2003 to determine their differential productivity for Aedes aegypti. Larvae and pupae were detected in 15 broad categories of container types. All breeding sites were found in the patios (backyards) and were potentially rain filled. Ae. aegypti pupae were produced from all categories of breeding site, and no single container type was predominately responsible for pupal production. The most productive buckets comprised 42% of the pupae-positive containers and provided 34% of the total pupae collected. Pupal production in buckets, together with plastic rubbish, pet dishes and basins, utensils for cooking and washing, tires, and flowerpots, accounted for almost 87% of pupal production. However, the most important pupal producers had low infestation indices for immature forms, illustrating that the use of positive-container indices can underestimate the importance of certain breeding sites. Overall, 40% of containers that were observed harboring Ae. aegypti pupae were classified as disposable. The remaining containers were considered useful, although some were seldom used. The discussion focuses on the potential utility of the pupal survey for targeting control, and its resulting pupae-per-person entomological indicator, both for comparison with a theoretical threshold for dengue transmission and for targeting vector control in this Mexican city

Role of uL3 in Multidrug Resistance in p53-Mutated Lung Cancer Cells

Cancer is one of the most common causes of death among adults. Chemotherapy is crucial in determining patient survival and quality of life. However, the development of multidrug resistance (MDR) continues to pose a significant challenge in the management of cancer. In this study, we analyzed the role of human ribosomal protein uL3 (formerly rpL3) in multidrug resistance. Our studies revealed that uL3 is a key determinant of multidrug resistance in p53-mutated lung cancer cells by controlling the cell redox status. We established and characterized a multidrug resistant Calu-6 cell line. We found that uL3 down-regulation correlates positively with multidrug resistance. Restoration of the uL3 protein level re-sensitized the resistant cells to the drug by regulating the reactive oxygen species (ROS) levels, glutathione content, glutamate release, and cystine uptake. Chromatin immunoprecipitation experiments and luciferase assays demonstrated that uL3 coordinated the expression of stress-response genes acting as transcriptional repressors of solute carrier family 7 member 11 (xCT) and glutathione S-transferase α1 (GST-α1), independently of Nuclear factor erythroid 2-related factor 2 (Nrf2). Altogether our results describe a new function of uL3 as a regulator of oxidative stress response genes and advance our understanding of the molecular mechanisms underlying multidrug resistance in cancers

RpL3 promotes the apoptosis of p53 mutated lung cancer cells by down-regulating CBS and NFκB upon 5-FU treatment

5-FU is a chemotherapy drug commonly used for the treatment of human cancers; however drug resistance represents a major challenge for its clinical application. In the present study, we reporte that rpL3 induced by 5-FU treatment in Calu-6 cells represses CBS transcription and reduces CBS protein stability leading to a decrease of CBS protein levels. rpL3 also regulates negatively the activation of NFκB by preventing NFκB nuclear translocation through IκB-α up-regulation. Furthermore, we demonstrate that rpL3 significantly enhances the apoptosis of 5-FU treated Calu-6 cells promoting the overexpression of the pro-apoptotic proteins Bax and the inhibition of the anti-apoptotic protein Bcl-2. We finally demonstrate that rpL3 potentiates 5-FU efficacy inhibiting cell migration and invasion. Our results suggest that combination of rpL3 and 5-FU is a promising strategy for chemotherapy of lung cancers lacking functional p53 that are resistant to 5-FU