In vitro and in vivo uptake studies of PAMAM G4.5 dendrimers in breast cancer

Background: Breast cancer is the second leading cause of cancer death worldwide. Nanotechnology approaches can overcome the side effects of chemotherapy as well as improve the efficacy of drugs. Dendrimers are nanometric size polymers which are suitable as drug delivery systems. To the best of our knowledge, studies on the application of PAMAM G4.5 (polyamidoamine half generation 4) dendrimers as potential drug delivery systems in breast cancer have not been reported. In this work we developed a PAMAM G4.5 dendrimer containing FITC (fluorescein isothiocyanate) dye to study their uptake by murine breast cancer cells and BALB/c mice breast tumors. Results: We performed a reaction between FITC and PAMAM G4.5 dendrimers which were previously derivatized with piperazine (linker molecule), characterized them by 1H NMR (proton nuclear magnetic resonance) spectroscopy and MALDI-TOF (matrix-assisted laser desorption/ionization- time-of-flight) mass spectrometry. The experimental data indicated that 2 FITC molecules could be bound covalently at the PAMAM G4.5 dendrimer surface, with 17 FITC molecules probably occluded in PAMAM dendrimers cavity. PAMAM-FITC dendrimer (PAMAM G4.5-piperazinyl-FITC dendrimer) size distribution was evaluated by DLS (dynamic light scattering) and TEM (transmission electron microscopy). The nanoparticle hydrodynamic size was 96.3 ± 1.4 nm with a PdI (polydispersion index) of 0.0296 ± 0.0171, and the size distribution measured by TEM was 44.2 ± 9.2 nm. PAMAM-FITC dendrimers were neither cytotoxic in 4T1 cells nor hemolytic up to 24 h of incubation. In addition, they were uptaken in vitro by 4T1 cells and in vivo by BALB/c mice breast tumors. PAMAM G4.5-piperazinyl-FITC dendrimer intracellular distribution was observed through histologic analysis of the tumor by laser confocal microscopy. Conclusion: These results indicate that PAMAM G4.5 dendrimers enter tumor tissue cells, being good candidates to be used as antitumor drug delivery systems for breast cancer treatment and diagnosis

Fotometría de Washington de cúmulos abiertos proyectados en dirección hacia el centro de la Galaxia

Resumen. Presentamos resultados preliminares obtenidos a partir del análisis fotométrico en las bandas C y T1 del sistema fotométrico de Washington de cuatro cúmulos abiertos (CAs) pobremente estudiados proyectados en la dirección del centro galáctico: Dias 6, NGC 5381, Ruprecht 128 y Czernik 37. A partir de los diagramas color-magnitud (C − T1, T1) y mediante el ajuste de isócronas teóricas calculadas para el sistema de Washington, derivamos sus parámetros fundamentales. Los presentes resultados constituyen parte de un proyecto mayor que prevé la caracterización de un centenar de CAs observados y analizados de manera homogénea.Abstract. We present preliminary results obtained from the photometric analysis in the C and T1 bands of the Washington photometric system of four poorly studied open clusters (OCs): Dias 6, NGC 5381, Ruprecht 128 and Czernik 37, projected in the Galactic center direction. We derived their fundamental parameters from their (C − T1, T1) colormagnitude diagrams, using theoretical isochrones computed for the Washington system. The present results are part of a major project which aims at characterizing almost a hundred OCs observed and analyzed in a homogeneous way.publishedVersionFil: Clariá Olmedo, Juan José. Universidad Nacional de Córdoba. Observatorio Astronómico de Córdoba; Argentina.Fil: Clariá Olmedi, Juan José. Conicet, Instituto de Ciencias Astronómicas, de la Tierra y del Espacio. Argentina.Fil: Parisi, María Celeste. Universidad Nacional de Córdoba. Observatorio Astronómico de Córdoba; Argentina.Fil: Parisi, María Celeste. Conicet, Instituto de Ciencias Astronómicas, de la Tierra y del Espacio. Argentina.Fil: Palma, Tali. Universidad Nacional de Córdoba. Observatorio Astronómico de Córdoba; Argentina.Fil: Palma, Tali. Conicet, Instituto de Ciencias Astronómicas, de la Tierra y del Espacio. Argentina.Fil: Oddone, Mónica Alejandra. Universidad Nacional de Córdoba. Observatorio Astronómico de Córdoba; Argentina.Fil: Ahumada, Andrea Verónica. Universidad Nacional de Córdoba. Observatorio Astronómico de Córdoba; Argentina.Fil: Ahumada, Andrea Verónica. Conicet, Instituto de Ciencias Astronómicas, de la Tierra y del Espacio. Argentina.Astronomía (incluye Astrofísica y Ciencias del Espacio

The actin cytoskeleton modulates the activation of iNKT cells by segregating CD1d nanoclusters on antigen-presenting cells

Invariant natural killer T (iNKT) cells recognize endogenous and exogenous lipid antigens presented in the context of CD1d molecules. The ability of iNKT cells to recognize endogenous antigens represents a distinct immune recognition strategy, which underscores the constitutive memory phenotype of iNKT cells and their activation during inflammatory conditions. However, the mechanisms regulating such “tonic” activation of iNKT cells remain unclear. Here, we show that the spatiotemporal distribution of CD1d molecules on the surface of antigen-presenting cells (APCs) modulates activation of iNKT cells. By using superresolution microscopy, we show that CD1d molecules form nanoclusters at the cell surface of APCs, and their size and density are constrained by the actin cytoskeleton. Dual-color single-particle tracking revealed that diffusing CD1d nanoclusters are actively arrested by the actin cytoskeleton, preventing their further coalescence. Formation of larger nanoclusters occurs in the absence of interactions between CD1d cytosolic tail and the actin cytoskeleton and correlates with enhanced iNKT cell activation. Importantly and consistently with iNKT cell activation during inflammatory conditions, exposure of APCs to the Toll-like receptor 7/8 agonist R848 increases nanocluster density and iNKT cell activation. Overall, these results define a previously unidentified mechanism that modulates iNKT cell autoreactivity based on the tight control by the APC cytoskeleton of the sizes and densities of endogenous antigen-loaded CD1d nanoclusters

Perspectivas psicossociais para o estudo do cotidiano de trabalho

Cette étude visait à analyser le débat et l'approfondissement théorique et méthodologique développé dans les études sur la vie quotidienne au travail. L'investigation a démarré à partir du dialogue interdisciplinaire entre l'anthropologie du travail, l'ergologie et la psychologie sociale du travail et il a systématisé les contributions mutuels entre ces domaines scientifiques, leurs approches et leurs départs de la thématisation et l'appropriation de l'activité humaine au travail sous la perspective du quotidien. L'analyse comparative a mis en évidence des axes qui différencient les manières pour approcher l'objet, qui se réfèrent aux relations établies entre savoirs pratiques et technico-scientifiques et aux manières d'intervention sur les situations de travail. Les approches comparatives partagent l'intérêt de connaître le vrai travail, la valeur attribuée à les savoirs des travailleurs et la sensibilité aux dimensions micropolitiques du quotidien. On en conclut que la localisation dans chacun de ces axes dépend d'une plus grande ou plus petite affiliation à les traditions d'anthropologie ou d'ergonomie.Este estudio tuvo como objetivo analizar el debate y la profundización teórica y metodológica desarrollada en los estudios acerca de la vida cotidiana en el trabajo. La investigación partió del diálogo interdisciplinario entre la antropología del trabajo, la ergología y la psicología social del trabajo y sistematizó las contribuciones mutuas entre eses campos científicos, sus aproximaciones y sus alejamientos de la tematización y la apropiación de la actividad humana en el trabajo bajo la perspectiva del cotidiano. El análisis comparativo destacó ejes que diferencian las formas de aproximación al objeto, que se refieren a las relaciones establecidas entre saberes prácticos y técnico-científicos y a los modos de intervención en las situaciones de trabajo. Los abordajes comparativos comparten el interés en conocer el trabajo real, el valor dado a los conocimientos de los trabajadores y la sensibilidad a las dimensiones micropolíticas del cotidiano. Se concluye que la localización en cada uno de eses ejes depende de la mayor o menor filiación a las tradiciones de la antropología o de la ergonomía.Este estudo teve por objetivo analisar o debate e o aprofundamento teórico e metodológico desenvolvido nos estudos sobre a vida cotidiana no trabalho. A investigação partiu do diálogo interdisciplinar entre a antropologia do trabalho, a ergologia e a psicologia social do trabalho e sistematizou as contribuições mútuas entre esses campos científicos, suas aproximações e seus afastamentos da tematização e da apropriação da atividade humana no trabalho sob a perspectiva do cotidiano. A análise comparativa destacou eixos que diferenciam as formas de aproximação ao objeto, que se referem às relações estabelecidas entre saberes práticos e técnico-científicos e aos modos de intervenção sobre as situações de trabalho. As abordagens comparativas compartilham o interesse em conhecer o trabalho real, o valor conferido aos conhecimentos dos trabalhadores e a sensibilidade às dimensões micropolíticas do cotidiano. Conclui-se que a localização em cada um desses eixos depende da maior ou menor filiação às tradições da antropologia ou da ergonomia.This study aimed to analyze the debate and the theoretical and methodological deepening of studies on daily life work. The investigation started from the interdisciplinary dialogue among anthropology of work, ergology, and social psychology of work and it systematized the mutual contributions among these scientific fields, their approximations and their departures from the thematization and appropriation of human activity at work from the perspective of daily life. The comparative analysis highlighted axes which differentiate the ways for approaching the object, that refer to the relations established between practical and technical-scientific kinds of knowledge and the modes of intervening on work situations. Comparative approaches share the interest in knowing the real work, the value attributed to workers' knowledge and sensitivity to the micropolitical dimensions of daily life. One concludes that the location in each of these axes depends on the greater or lesser affiliation to the traditions of anthropology or ergonomics

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Evaluación de los efectos del deterioro sobre el potencial fisiológico de semillas de poroto (Phaseolus vulgaris L.) por prueba de tetrazolio

Incidence of deterioration on the physiological potential of bean seeds has been analyzed by means of the tetrazolium test. With this purpose, samples of the Perla INTA (white) cultivar were submitted to artificial harm, by placing these in an accelerated aging chamber, at 41 °C and 100% RH, during 0; 1; 2; 3 and 4 days. Subsequently, each sublot was immersed during 25 minutes in a 0,5% tetrazolium solution at 40 °C, in the darkness. As references for this, germination power and seedling emergence of the treatment have been evaluated. For each level of deterioration being studied, the proportion of vigourous seed -estimated by the tetrazolium test- with the results of germination and seedlings emergence did'nt show significative differences (p< 0,05) between them; thus indicating that the study with tetrazolium results adequate in order to estimate vigour differences between seed lots of Perla INTA bean.Mediante pruebas de tetrazolio se evaluó la incidencia del deterioro sobre el potencial fisiológico de semillas de poroto. Para ello, muestras de Perla INTA (blanco) fueron sometidas a daño artificial, colocándolas en cámara de envejecimiento acelerado a 41 °C y 100% de humedad relativa, durante 0; 1; 2; 3 y 4 días. Posteriormente cada sublote fue sumergido durante 25 minutos en una solución de tetrazolio al 0,5% a 40 °C en oscuridad. Como referencias para este análisis se evaluaron además el poder germinativo y la emergencia de plántulas de cada tratamiento. Para cada nivel de deterioro en estudió la proporción de semillas vigorosas estimadas por el test de tetrazolio con los resultados de germinación y emergencia de plántulas, no evidenció diferencias significativas (p< 0,05) entre ellos. Esto indica que el estudio con tetrazolio resulta adecuado para estimar diferencias de vigor entre lotes de semillas de poroto Perla INTA