Cancer stem cells (CSCs) represent a subset of cells within tumours that exhibit self-renewal properties and the capacity to seed tumours. CSCs are typically refractory to conventional treatments and ...have been associated to metastasis and relapse. Salinomycin operates as a selective agent against CSCs through mechanisms that remain elusive. Here, we provide evidence that a synthetic derivative of salinomycin, which we named ironomycin (AM5), exhibits a more potent and selective activity against breast CSCs in vitro and in vivo, by accumulating and sequestering iron in lysosomes. In response to the ensuing cytoplasmic depletion of iron, cells triggered the degradation of ferritin in lysosomes, leading to further iron loading in this organelle. Iron-mediated production of reactive oxygen species promoted lysosomal membrane permeabilization, activating a cell death pathway consistent with ferroptosis. These findings reveal the prevalence of iron homeostasis in breast CSCs, pointing towards iron and iron-mediated processes as potential targets against these cells.
La aplicación y los cambios recurrentes de la tecnología digital se imponen a gran velocidad, interpelando a las disciplinas sociales que se ocupan del comportamiento humano. Esta disrupción digital ...refiere a un cambio de paradigma global, que supone romper con lo establecido y dar lugar a nuevas formas de hacer en las prácticas científicas, provocando que la información se mueva a un ritmo más veloz que el movimiento físico. La arqueología se está adaptando a estos cambios para aplicar las nuevas tecnologías en el ámbito del patrimonio virtual y la ciencia abierta, de manera versátil, flexible y expeditiva. Es así, que este nuevo paradigma digital, nos proporciona herramientas que se reflejan en estrategias que desafían nuestras estructuras del quehacer científico, así como nuestros antepasados homínidos se enfrentaron a los cambios tecnológicos culturales. La propuesta desde el proyecto ArqueoLab-UBA es presentar la implementación de herramientas digitales y virtuales, considerando aspectos teóricos y metodológicos en la práctica profesional. En este camino, es importante reflexionar acerca de la aplicación de las tecnologías en función de qué conocimiento construimos sobre el patrimonio y cuáles serán las estrategias de supervivencia en un mundo virtual futuro.
Objective
To investigate the presence and abundance of mosquito species in containers found in different types of cemeteries in Puerto Rico to assess their importance and make control ...recommendations.
Methods
We conducted surveys of containers with water in 16 cemeteries in southeastern Puerto Rico to detect the presence of larvae and pupae of Aedes aegypti and other mosquitoes; to identify the most common and productive containers and to study their variation in relation to the type of cemetery.
Results
The most common containers with water were flowerpots, followed in abundance by a variety of discarded containers and open tombs. We found a positive relationship between density of containers with water and rainfall. There was a rich community of mosquito species developing in containers of the inspected cemeteries: nine mosquito species belonging to four genera with Ae. aegypti and Ae. mediovittatus being the most frequent and abundant. We sampled 13 cement‐type cemeteries, 2 mixed and only 1 lawn cemetery, consequently, we could not draw any conclusion regarding container productivity and cemetery type.
Conclusions
Surveyed cemeteries were important sources of Ae. aegypti and other mosquitoes in flowerpots, discarded containers and open tombs. We recommend conducting further studies to establish how frequently inspections should occur; and mosquito control by emptying aquatic habitats and larviciding to reduce mosquito productivity and protect workers and visitors from mosquito bites and possible transmission of arboviruses.
The purpose of this research is to understand the conceptualizations and emotional responses produced by diversities in thirteen teacher trainers of the Primary Education Pedagogy degree, of a ...Chilean university with an important trajectory in teacher training in the Metropolitan Region, the national capital. A qualitative approach was used through semi-structured and projective interviews. The data were analyzed following the data analysis spiral proposed by Creswell (2013). It is concluded that the trainers have a descriptive representation of diversity that that does not consider inequalities, discriminations, or conflicts. Regarding their emotional responses about diversity, they positively value the possibility of new learning and an epistemic openness that generates multiple challenges. They also express not being prepared to deal with diversity in the pedagogical space, discomfort regarding certain diversities and an epistemic tension toward the concept of diversity and the classifications that may cause discrimination.
Topographical patterns are a powerful tool to study directional migration. Grooved substrates have been extensively used as in vitro models of aligned extracellular matrix fibers because they induce ...cell elongation, alignment, and migration through a phenomenon known as contact guidance. This process, which involves the orientation of focal adhesions, F-actin, and microtubule cytoskeleton along the direction of the grooves, has been primarily studied on hard materials of non-physiological stiffness. But how it unfolds when the stiffness of the grooves varies within the physiological range is less known. Here we show that substrate stiffness modulates the cellular response to topographical contact guidance. We find that for fibroblasts, while focal adhesions and actin respond to topography independently of the stiffness, microtubules show a stiffness-dependent response that regulates contact guidance. On the other hand, both clusters and single breast carcinoma epithelial cells display stiffness-dependent contact guidance, leading to more directional and efficient migration when increasing substrate stiffness. These results suggest that both matrix stiffening and alignment of extracellular matrix fibers cooperate during directional cell migration, and that the outcome differs between cell types depending on how they organize their cytoskeletons.
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Targeting Cancer Stem Cells with Small Molecules Müller, Sebastian; Cañeque, Tatiana; Acevedo, Verónica ...
Israel journal of chemistry,
April 2017, 2017-04-00, 20170401, 2017-04, Letnik:
57, Številka:
3-4
Journal Article
Recenzirano
Cancers arise as a result of physiological imbalances and subsequent uncontrolled cell division. Cancer initiation requires a set of biochemical alterations, including some occurring at the genetic ...and epigenetic levels. Thus, tumors are heterogeneous in nature making it challenging to selectively target different cancer cells by means of small molecule intervention. The paradigm of cancer stem cells (CSCs) describes subpopulations of cells with high self‐renewal and tumor‐seeding capacity. These cells, typically refractory to conventional therapies, can give rise to relapse after treatment. Combinatorial strategies, including drugs that selectively target this population of cells, have emerged in recent years. Here, we review how discovery‐based – unbiased – screening approaches have helped identify small molecules that specifically target CSCs. We also highlight biological pathways characteristic of CSCs that can potentially be selectively targeted in a hypothesis‐driven manner by small molecules. We describe molecules that effectively target CSCs and emphasize what is known about their biological modes of action. The diversity and complexity of biochemical processes that CSCs may be addicted to, raises the question of how selective targeting of these pathways can be achieved. This challenge may be addressed by the continuing production of structurally complex and diverse small molecules using target and diversity‐oriented synthesis approaches.
Dengue viruses cause hundreds of millions of infections every year in tropical and subtropical countries. Unfortunately, there is not a single universal vector control method capable of suppressing ...Aedes aegypti (L.) populations. Amongst novel control tools or approaches are various types of traps targeting gravid females or their eggs. Here, we provide details of the operational use of the Centers for Disease Control and Prevention autocidal gravid ovitrap (CDC-AGO trap) for the surveillance and control of Ae. aegypti. Adult mosquitoes were monitored every week in 2 isolated neighborhoods treated with 3 AGO traps per house in 85% of houses and in 2 reference neighborhoods without control traps. Between March 2013 and April 2015 we serviced the AGO traps 14 times in each community (every 2 months). Common trap problems were absent or broken trap tops (1-1.5%), flooded (0.1-0.7%) or dry (0.5-1.3%) traps, and missing (0.3-0.8%) or vandalized (0.5-1.4%) traps. Most traps kept a volume of infusion between 45% and 97% of their original volume (10 liters). Nontarget organisms captured in AGO traps were mostly small flies, and to a lesser extent ants, cockroaches, grasshoppers, butterflies, dragonflies, and lizards. Trap coverage ranged between 83% and 87% of houses in both communities throughout the study. We interpret such high levels of trap retention over time as an expression of acceptance by the community.
En los últimos años, la aplicación de los estudios arqueométricos se ha incrementado notablemente. Por un lado, porque se ha logrado expandir un campo interdisciplinario que ha permitido la ...capacitación de los profesionales. Por el otro, porque se han logrado desarrollar espacios de trabajo con acceso al uso de diferentes técnicas analíticas, así como el diálogo e intercambio en el análisis de los resultados entre especialistas. En cuanto al estudio de materiales cerámicos arqueológicos, los avances en el desarrollo de las técnicas y la tecnología vinculada al trabajo arqueométrico ha facilitado la revisión de resultados y datos que fueran obtenidos oportunamente durante las investigaciones, con el fin de continuar explorando problemáticas arqueológicas y resolver cuestiones pendientes relacionadas con procesos de producción y circulación de materiales cerámicos, prácticas sociales de intercambio, interacción e integración y sus rituales asociados, entre otros. Este trabajo tiene como objetivo mostrar la aplicación de nuevas tecnologías y metodologías adaptadas a materiales cerámicos para evaluar su potencial afín al alcance de la información obtenida y revisar e incorporar nuevos datos vinculados con el estudio de la procedencia de materias primas, caracterización de pastas y técnicas de manufactura usadas por los alfareros andinos. Para ello, se presentan dos casos de estudio de cerámicas arqueológicas de la Quebrada de Humahuaca, provincia de Jujuy (Argentina), a partir de análisis realizados con petrografía-QEMSCAN, Raman-IFT-IR, microscopio UV-IR y microestratrigrafías de pigmentos. Los resultados obtenidos han ofrecido información adicional y específica para interpretar las interacciones dentro y fuera del espacio de la Quebrada de Humahuaca en diferentes momentos cronológicos del pasado prehispánico, dando cuenta del uso del espacio circumpuneño por las comunidades que lo habitaron
El avance de las tecnologías digitales y la virtualización favoreció el uso de nuevas herramientas para el registro, representación, conservación y puesta en valor de materiales y yacimientos ...arqueológicos; además, ha facilitado la comunicación del conocimiento hacia el público en general. En este contexto, la arqueología virtual ha proporcionado un entorno profesional donde convergen especialistas de diferentes disciplinas. Según la definición de los Principios de Sevilla, la arqueología virtual tiene como objetivo investigar y desarrollar formas de aplicación de la visualización asistida por tecnologías para la gestión integral del patrimonio arqueológico, aunque aún se encuentra en construcción debido a la conjunción de enfoques, objetivos y limitaciones. El uso de estas tecnologías implica procedimientos en los que tiene lugar la creación de nuevas imágenes, que son concebidas como la construcción de un nuevo producto, al que llamamos patrimonio virtual. La imagen generada es entendida como una representación, es decir, como un producto con dos dimensiones articuladas: constituye una presencia en la ausencia de algo y además exhibe su propia presencia o materialidad como imagen. En este sentido, conforman un nuevo fenómeno anclado en un soporte digital/virtual y por lo tanto como un nuevo registro plausible para ser estudiado, preservado y comunicado. Este trabajo se constituye como un espacio interdisciplinario para reflexionar sobre el aporte de los métodos y técnicas digitales en la práctica de nuestra disciplina, tanto en la documentación, como en el análisis y reconstrucción virtual del material arqueológico, además de la gestión integral del patrimonio cultural. A tal efecto, se considera necesario establecer criterios de aplicación; también se prioriza generar un producto que pueda ser utilizado en la comunicación de la ciencia. La propuesta aquí explicada se basa en los tres ejes que guían el proyecto ArqueoLab-UBA: investigar, conservar y difundir el patrimonio cultural como medios para un abordaje integral y multidisciplinar de dicho patrimonio.
Lo más destacado:
Reflexionar sobre la construcción del patrimonio virtual en función de las tecnologías digitales aplicadas a la práctica arqueológica.
Plantear los desafíos y debates que dicha práctica conlleva en el contexto tecnológico actual y futuro.
Presentar una propuesta sobre arqueología digital pensada en función de los ejes temáticos que componen el proyecto ArqueoLab-UBA: investigar, conservar y difundir para la gestión integral del patrimonio cultural.
We have shown that the Centers for Disease Control and Prevention (CDC) autocidal gravid ovitraps (AGO trap) reduced the Aedes aegypti population and prevented mosquito outbreaks in southern Puerto ...Rico. After showing treatment efficacy for 1 year, we deployed three traps per home in an area that formerly did not have traps and in a site that served as the intervention area. Two new areas were selected as reference sites to compare the density of Ae. aegypti without traps. We monitored mosquitoes and weather every week in all four sites. The hypotheses were the density of Ae. aegypti in the former reference area converges to the low levels observed in the intervention area, and mosquito density in both areas having control traps is lower than in the new reference areas. Mosquito density in the former reference area decreased 79% and mosquito density in the new reference areas was 88% greater than in the intervention areas.
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