AZT exerts its antitumoral effect by telomeric and non-telomeric effects in a mammary adenocarcinoma model

Limitless replicative potential is one of the hallmarks of cancer that is mainly due to the activity of telomerase. This holoenzyme maintains telomere length, adding TTAGGG repetitions at the end of chromosomes in each cell division. In addition to this function, there are extratelomeric roles of telomerase that are involved in cancer promoting events. It has been demonstrated that TERT, the catalytic component of telomerase, acts as a transcriptional modulator in many signaling pathways. Taking into account this evidence and our experience on the study of azidothymidine (AZT) as an inhibitor of telomerase activity, the present study analyzes the effect of AZT on some telomeric and extratelomeric activities. To carry out the present study, we evaluated the transcription of genes that are modulated by the Wnt/β-catenin pathway, such as c-Myc and cyclin-D1 (Cyc-D1) and cell processes related with their expression, such as, proliferation, modifications of the actin cytoskeleton, cell migration and cell cycle in a mammary carcinoma cell line (F3II). Results obtained after treatment with AZT (600 µM) for 15 passages confirmed the inhibitory effect on telomerase. Regarding extratelomeric activities, our results showed a decrease of 64, 38 and 25% in the transcription of c-Myc, Cyc-D1 and TERT, respectively (p<0.05) after AZT treatment. Furthermore, we found an effect on cell migration, reaching an inhibition of 48% (p<0.05) and a significant passage-dependent increase on cell doubling time during treatment. Finally, we evaluated the effect on cell cycle, obtaining a decline in G0/G1 in AZT-treated cells. These results allow us to postulate that AZT is not only an inhibitor of telomerase activity, but also a potential modulator of extratelomeric processes involved in cancer promotion.Fil: Armando, Romina Gabriela. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Gomez, Daniel Eduardo. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Gomez, Daniel Eduardo. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

Space-Time Curvature Signatures in Bose-Einstein Condensates

We derive a generalized Gross-Pitaevski (GP) equation immersed on a electromagnetic and a weak gravitational field starting from the covariant Complex Klein-Gordon field in a curved space-time. We compare it with the GP equation where the gravitational field is added by hand as an external potential. We show that there is a small difference of order $g z/c^2$ between them that could be measured in the future using Bose-Einstein Condensates (BEC). This represents the next order correction to the Newtonian gravity in a curved space-time.Comment: 4 pages, no figure

Processes of MISS-formation in a modern siliciclastic tidal flat, Patagonia (Argentina)

The study focus on the description of several MISS as erosional pockets and remnants, flipped-over edges, and large microbial deformation structures as roll-ups, folds and gas domes, in the context of sediment composition, hydraulics, and geomorphology. The aim of the paper is to recognize the mechanisms of formation of MISS by analyses on hydrodynamics under the influence of the geomorphology. The study was conducted in an elongated inactive tidal channel colonized by microbial mats (2.5 × 0.3 km) in a progradation environment. To continuously record the water-level fluctuations, a HOBO water level logger was placed 40 cm below the flat surface for two years. The sea water enters several times a year, during storms, where the flood currents were characterized by faster velocity than ebb currents, reaching a water depth up to 0.70 m over the tidal flat. That coastal process creates MISS over the tidal flat. The most conspicuous microbial structures are the huge deformation roll-ups several m-scale, associated to elongated rip-off mats, folds and flipped over mats. The process of fluidization was postulated to explain the sand-infilling of gas domes and folds we observed. This process would result from the wave action on the water column that produces a temporal fluid behavior of the underlying sand.Fil: Maisano, Lucia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto Argentino de Oceanografía. Universidad Nacional del Sur. Instituto Argentino de Oceanografía; ArgentinaFil: Cuadrado, Diana Graciela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto Argentino de Oceanografía. Universidad Nacional del Sur. Instituto Argentino de Oceanografía; ArgentinaFil: Gomez, Eduardo Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto Argentino de Oceanografía. Universidad Nacional del Sur. Instituto Argentino de Oceanografía; Argentina. Universidad Tecnológica Nacional. Facultad Regional Bahía Blanca; Argentin

Sediment transport inferred by submarine bedforms

By means of bathymetric and side scan sonar records, the net circulation of sediments caused by tidal currents and waves in the outer Principal Channel of Bahía Blanca Estuary is inferred. On the northern coast of the studied area there are two harbours, Belgrano and Rosales, which are simultaneously affected by internal and external hydrosedimentological processes. Through this study, present and potential negative interactions between human activities and natural processes within the studied area are demonstrated.A través del análisis de registros batimétricos y de sonar de barrido lateral se infiere la circulación neta de sedimentos causada por olas y mareas en el sector externo del Canal Principal del estuario de Bahía Blanca. Sobre la costa norte del área de estudio se encuentran dos puertos, Puerto Belgrano y Puerto Rosales, los cuales son simultáneamente afectados por procesos hidrosedimentológicos internos y externos al estuario. Por medio de este estudio se evidencian las interacciones negativas, presentes y futuras, entre las actividades humanas y los procesos naturales.Fil: Cuadrado, Diana Graciela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto Argentino de Oceanografía. Universidad Nacional del Sur. Instituto Argentino de Oceanografía; ArgentinaFil: Gomez, Eduardo Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto Argentino de Oceanografía. Universidad Nacional del Sur. Instituto Argentino de Oceanografía; ArgentinaFil: Ginsberg, Silvia Susana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto Argentino de Oceanografía. Universidad Nacional del Sur. Instituto Argentino de Oceanografía; Argentin

Subaqueous landslides at the distal basin of Lago Nahuel Huapi (Argentina): Towards a tsunami hazard evaluation in Northern Patagonian lakes

The May 22nd, 1960 Valdivia earthquake, Chile (Mw 9.5) triggered a series of subaqueous mass-wasting processes (debris flows and slides) in Lago Nahuel Huapi (Argentina), generating a tsunami-like wave that hit the coasts of San Carlos de Bariloche. Aiming to provide a first preliminary insight into tsunami hazards for the lakeshore communities, in this paper we identify and characterize the subaqueous landslides at the populated distal basin of the lake. Swath bathymetric and seismic profiling surveys were carried out and high-resolution digital elevation models were derived from these data to perform a landslide inventory map. A series of morphometrical parameters (including the landslide area, the volume of displaced materials and the run-out distance, among others) were estimated upon selected events. The results indicated that landslide activity at the distal basin of Lago Nahuel Huapi has been concentrated in the vicinity of Bariloche (massive landslide triggered by the 1960 earthquake) and within steep delta fronts where the slope failures typically initiate at shallow waters (9–11 m depth). The sliding mass frequently travels basinward along a great distance (≥1000 m). At the delta fronts, the volume of material removed by landslides can reach ~40 × 104 m3 , leaving scar areas of up to 13 m thick. The periodic occurrence of rotational–translational mass movements initiating at the upper edge of the delta fronts, with vertical displacements of the mobilized materials reaching ~200 m, probably represents a potential tsunami hazard for the nearby populated coasts.Fil: Beigt, Debora. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte. Instituto Andino Patagónico de Tecnologías Biológicas y Geoambientales. Universidad Nacional del Comahue. Instituto Andino Patagónico de Tecnologías Biológicas y Geoambientales.; ArgentinaFil: Villarosa, Gustavo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte. Instituto Andino Patagónico de Tecnologías Biológicas y Geoambientales. Universidad Nacional del Comahue. Instituto Andino Patagónico de Tecnologías Biológicas y Geoambientales.; Argentina. Universidad Nacional del Comahue. Centro Regional Universitario Bariloche; ArgentinaFil: Gomez, Eduardo Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto Argentino de Oceanografía. Universidad Nacional del Sur. Instituto Argentino de Oceanografía; Argentina. Universidad Tecnológica Nacional; ArgentinaFil: Manzoni, Carolina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte. Instituto Andino Patagónico de Tecnologías Biológicas y Geoambientales. Universidad Nacional del Comahue. Instituto Andino Patagónico de Tecnologías Biológicas y Geoambientales.; Argentina. Universidad Nacional del Comahue. Centro Regional Universitario Bariloche; Argentin

Telomerase and telomere: their structure and dynamics in health and disease

La telomerasa es la enzima responsable del mantenimiento de la longitud de los telómeros mediante la adición de secuencias repetitivas ricas en guanina, y su actividad se observa principalmente en gametos, células madre y células tumorales. En las células somáticas humanas el potencial de proliferación es limitado, alcanzando la senescencia luego de 50-70 divisiones celulares, debido a que la ADN polimerasa no es capaz de copiar el ADN en los extremos de los cromosomas. Por el contrario, en la mayoría de las células tumorales el potencial de replicación es ilimitado debido al mantenimiento de la longitud telomérica dado por la telomerasa. Los telómeros tienen proteínas adicionales que regulan la unión de la telomerasa. De la misma manera la telomerasa también se asocia con un complejo de proteínas que regulan su actividad. Este trabajo se centra en la estructura y función del complejo telómero/telomerasa y a cómo las alteraciones en su comportamiento conducen al desarrollo de diversas enfermedades, principalmente cáncer. El desarrollo de inhibidores del sistema telómero / telomerasa podría ser un blanco con posibilidades prometedorasTelomerase is the enzyme responsible for the maintenance of telomere length by adding guanine-rich repetitive sequences. Its activity can be seen in gametes, stem cells and tumor cells. In human somatic cells the proliferative potential is limited, reaching senescence after 50-70 cell divisions, because the DNA polymerase is not able to copy the DNA at the ends of chromosomes. By contrast, in most tumor cells the replicative potential is unlimited due to the maintenance of the telomeric length given by telomerase. Telomeres have additional proteins that regulate the binding of telomerase, likewise telomerase associates, with a protein complex that regulates its activity. This work focuses on the structure and function of the telomere/telomerase complex and how changes in its behavior lead to the development of different diseases, mainly cancer. Development of inhibitors of the telomere/telomerase complex could be a target with promising possibilities.Fil: Gomez, Daniel Eduardo. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Armando, Romina Gabriela. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Farina, Hernán Gabriel. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Gomez, Daniel Eduardo. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

Cultivating sustainable cannabis in the Danish Medicinal Cannabis Pilot Programme : a case study at OC CARE ApS

In my research I explore the Danish Medicinal Cannabis Pilot Programme (Pilot Programme). The study was done with the case of OC Care ApS’ (OC Care) Envision Concept, a legislation-compliant growth facility with a controlled environment, designed to produce sustainable medicinal cannabis. OC Care was chosen as the single case for this study because they are the only licensed company with the aim to produce organic cannabis within the Pilot Programme. OC Care’s Envision Concept is analyzed through an agroecological perspective, by considering the economic, environmental, and social components that together make a system. To understand the context and set the boundaries for the study, the Pilot Programme is analyzed through system thinking methodology. To reach a holistic understanding of the case and its context, data was gathered through multiple sources: participant observation, informal conversations, and semi-structured interviews. Findings indicate that the Pilot Programme has a cautious approach towards legalization, and aims to produce scientific evidence to validate the benefits of medicinal cannabis and regulate its cultivation, processing, and distribution. Due to its pharmaceutical paradigm, hybrid framework, and Denmark’s competitive advantages, Denmark is becoming a leader in the European medicinal cannabis market. To produce organic and sustainable medicinal cannabis OC Care have developed the Envision Concept, a controlled environment cultivation and processing facility, compliant with the European Union’s (EU) Volume 4 EU Guidelines for Good Manufacturing Practice for Medicinal Products for Human and Veterinary Use. The Envision Concept is a system that integrates economic, environmental, and social interests to provide patients with an organic, standardized, and sustainable pharma-grade product.M-A

Radiocarbon reservoir ages and hardwater effect for the northeastern coastal waters of Argentina.

Accelerator mass spectrometry (AMS) radiocarbon dates were obtained for 18 mollusk shells collected alive along the Buenos Aires province coast, Argentina, over the period AD 1914–1935. Reservoir ages were estimated for all samples on the basis of the tree-ring calibration curve for the Southern Hemisphere (SHCal04, McCormac et al. 2004) and the marine ΔR values calculated as the difference between the conventional 14C age and the age deduced from the marine, mixedlayer model calculation (Marine04, Hughen et al. 2004). For most coastal locations, a great ΔR scatter was observed, ranging from 191 to 2482 yr, which is explained by the input of varying content of dissolved carbonate by rivers and groundwater (“hardwater effect”) and indicates a serious limitation for shell-based 14C chronologies. Within the interior of Bahía Blanca estuary, ΔR values ranged from –40 to 50 ± 46 as a consequence of the local geological particularities of the environment. This suggests that, with some restrictions, the marine calibration curve with standard parameters (ΔR = 0) could be used at this location.Fil: Gomez, Eduardo Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto Argentino de Oceanografía. Universidad Nacional del Sur. Instituto Argentino de Oceanografía; ArgentinaFil: Borel, Claudia Marcela. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Aguirre, Marina Laura. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Martinez, Daniel Emilio. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales. Instituto de Geología de Costas y del Cuaternario. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Instituto de Geología de Costas y del Cuaternario; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin