Hypoxia promotes chemoresistance in acute lymphoblastic leukemia cell lines by modulating death signaling pathways

International audienceBackground: Several studies show that bone marrow (BM) microenvironment and hypoxia condition can promote the survival of leukemic cells and induce resistance to anti-leukemic drugs. However, the molecular mechanism for chemoresistance by hypoxia is not fully understood.Methods: In the present study, we investigated the effect of hypoxia on resistance to two therapies, methotrexate (MTX) and prednisolone (PRD), in two cell models for acute lymphoblastic leukemia (ALL). To look for an implication of hypoxia in chemoresistance, cell viability, total cell density and cell proliferation were analyzed. Survival and death signaling pathways were also screened by "reverse phase protein array" (RPPA) and western blotting experiments conducted on selected proteins to confirm the results.Results: We found that hypoxia promotes chemoresistance in both ALL cell lines. The induction of drug-resistance by hypoxia was not associated with an increase in total cell density nor an increase in cell proliferation. Using RPPA, we show that chemoresistance induced by hypoxia was mediated through an alteration of cell death signaling pathways. This protective effect of hypoxia seems to occur via a decrease in pro-apoptotic proteins and an increase in anti-apoptotic proteins. The results were confirmed by immunoblotting. Indeed, hypoxia is able to modulate the expression of anti-apoptotic proteins independently of chemotherapy while a pro-apoptotic signal induced by a chemotherapy is not modulated by hypoxia.Conclusions: Hypoxia is a factor in leukemia cell resistance and for two conventional chemotherapies modulates cell death signaling pathways without affecting total cell density or cell proliferation

The Impact of Acceptance and Commitment Training and Multicultural Training on the stigmatizing attitudes and professional burnout of substance abuse counselors

Empirically validated methods for reducing stigma and prejudice toward recipients of behavioral healthcare services are badly needed. In the present study, two packages presented in one day workshops were compared to a biologically oriented Educational Control condition in the alleviation of stigmatizing attitudes in drug abuse counselors. One, Acceptance and Commitment Training (ACT), utilized acceptance, defusion, mindfulness, and values methods. The other, Multicultural Training, sensitized participants to group prejudices and biases. Measures of stigma and burnout were taken pre-training, post-training, and after a three month follow-up. Results showed that Multicultural Training had an impact on stigmatizing attitudes and burnout post-intervention but not at follow-up, but showed better gains in a sense of personal accomplishment as compared to the Educational Control at follow-up. ACT had a positive impact on stigma at follow-up and on burnout at post-treatment and follow-up and follow-up gains in burnout exceeded those of Multicultural Training. ACT also significantly changed the believability of stigmatizing attitudes. This process mediated the impact of ACT but not Multicultural Training on follow-up stigma and burnout. This preliminary study opens new avenues for reducing stigma and burnout in behavioral health counselors

The Implementation of Brazil Sustainable Urban Mobility Policy

Institute of Transport and Logistics Studies. Faculty of Economics and Business. The University of Sydne

Actuator Saturation in Individual Blade Control of Rotorcraft

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/97053/1/AIAA2012-1477.pd

A Survey of Volunteered Open Geo-Knowledge Bases in the Semantic Web

Over the past decade, rapid advances in web technologies, coupled with innovative models of spatial data collection and consumption, have generated a robust growth in geo-referenced information, resulting in spatial information overload. Increasing 'geographic intelligence' in traditional text-based information retrieval has become a prominent approach to respond to this issue and to fulfill users' spatial information needs. Numerous efforts in the Semantic Geospatial Web, Volunteered Geographic Information (VGI), and the Linking Open Data initiative have converged in a constellation of open knowledge bases, freely available online. In this article, we survey these open knowledge bases, focusing on their geospatial dimension. Particular attention is devoted to the crucial issue of the quality of geo-knowledge bases, as well as of crowdsourced data. A new knowledge base, the OpenStreetMap Semantic Network, is outlined as our contribution to this area. Research directions in information integration and Geographic Information Retrieval (GIR) are then reviewed, with a critical discussion of their current limitations and future prospects

Emerging Synergisms Between Drugs and Physiologically-Patterned Weak Magnetic Fields: Implications for Neuropharmacology and the Human Population in the Twenty-First Century

Synergisms between pharmacological agents and endogenous neurotransmitters are familiar and frequent. The present review describes the experimental evidence for interactions between neuropharmacological compounds and the classes of weak magnetic fields that might be encountered in our daily environments. Whereas drugs mediate their effects through specific spatial (molecular) structures, magnetic fields mediate their effects through specific temporal patterns. Very weak (microT range) physiologically-patterned magnetic fields synergistically interact with drugs to strongly potentiate effects that have classically involved opiate, cholinergic, dopaminergic, serotonergic, and nitric oxide pathways. The combinations of the appropriately patterned magnetic fields and specific drugs can evoke changes that are several times larger than those evoked by the drugs alone. These novel synergisms provide a challenge for a future within an electromagnetic, technological world. They may also reveal fundamental, common physical mechanisms by which magnetic fields and chemical reactions affect the organism from the level of fundamental particles to the entire living system

Dog Burials Associated with Human Burials in the West Indies during the Early Pre-Columbian Ceramic Age (500 BC-600 AD)

Across the Caribbean, the widespread presence of canine remains at archaeological sites from the Saladoid period raises questions about the role of “man’s best friend.” Dog (Canis familiaris) remains have been found located in both refuse middens and burials adjacent to human graves in a number of sites in the French Antilles and Barbuda, West Indies. This paper will critically examine dog remains and discuss the varied duality of the dog’s role in the Saladoid world: from food source to lifelong companion. The importance of dogs within Amerindian sites from Saint Martin, the Guadeloupe archipelago, Martinique and Barbuda will be explored from a zooarchaeological perspective, concluding with a critical discussion of changes in cultural patterns, as seen through the decline in dog remains during the Troumassoid and Suazoid period at the sites in the French Antilles. Résumé Sépultures de chiens associées à des sépultures humaines dans les Petites Antilles à l’Âge du Néoindien ancien (500 av. – 600 ap. J.-C.). Dans les Antilles, la présence généralisée de restes de chiens sur les sites de la période céramique ancienne Saladoïde soulève des questions sur le rôle de ce « meilleur ami de l’homme ». En effet, des chiens (Canis familiaris) ont été trouvés aussi bien dans des zones de rejets, qu’enterrés aux côtés de sépultures humaines dans un certain nombre de sites des Petites Antilles. Ce document examinera ces restes de chiens de façon critique et décrira les morphologies particulières des chiens des sites amérindiens de l’île de Saint-Martin, l\u27archipel de la Guadeloupe, la Martinique et de l’île de Barbuda, dans une perspective archéozoologique. Une discussion critique portera sur l\u27évolution des changements des modèles culturels, comme celui de la chute drastique des chiens enterrés pendant les périodes archéologiques plus tardives, Troumassoïde et Suazoïde, des sites des Antilles françaises. Enfin, la discussion portera sur la dualité du rôle du chien dans le monde Saladoïde, à la fois source de nourriture et compagnon de vie

The impact of the Fungus-Host-Microbiota interplay upon Candida albicans infections: current knowledge and new perspectives

This is the final version. Available on open access from Oxford University Press via the DOI in this recordCandida albicans is a major fungal pathogen of humans. It exists as a commensal in the oral cavity, gut or genital tract of most individuals, constrained by the local microbiota, epithelial barriers and immune defences. Their perturbation can lead to fungal outgrowth and the development of mucosal infections such as oropharyngeal or vulvovaginal candidiasis, and patients with compromised immunity are susceptible to life-threatening systemic infections. The importance of the interplay between fungus, host and microbiota in driving the transition from C. albicans commensalism to pathogenicity is widely appreciated. However, the complexity of these interactions, and the significant impact of fungal, host and microbiota variability upon disease severity and outcome, are less well understood. Therefore, we summarise the features of the fungus that promote infection, and how genetic variation between clinical isolates influences pathogenicity. We discuss antifungal immunity, how this differs between mucosae, and how individual variation influences a person's susceptibility to infection. Also, we describe factors that influence the composition of gut, oral and vaginal microbiotas, and how these affect fungal colonisation and antifungal immunity. We argue that a detailed understanding of these variables, which underlie fungal-host-microbiota interactions, will present opportunities for directed antifungal therapies that benefit vulnerable patients