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

Ebola virus VP35 induces high-level production of recombinant TPL-2–ABIN-2–NF-κB1 p105 complex in co-transfected HEK-293 cells

Activation of PKR (double-stranded-RNA-dependent protein kinase) by DNA plasmids decreases translation, and limits the amount of recombinant protein produced by transiently transfected HEK (human embryonic kidney)-293 cells. Co-expression with Ebola virus VP35 (virus protein 35), which blocked plasmid activation of PKR, substantially increased production of recombinant TPL-2 (tumour progression locus 2)–ABIN-2 [A20-binding inhibitor of NF-κB (nuclear factor κB) 2]–NF-κB1 p105 complex. VP35 also increased expression of other co-transfected proteins, suggesting that VP35 could be employed generally to boost recombinant protein production by HEK-293 cells

Long-term cropping system studies support intensive and responsive cropping systems in the low-rainfall Australian Mallee

Continuous-cropping systems based on no-till and crop residue retention have been widely adopted across the low-rainfall cereal belt in southern Australia in the last decade to manage climate risk and wind erosion. This paper reports on two long-term field experiments that were established in the late 1990s on texturally different soil types at a time of uncertainty about the profitability of continuous-cropping rotations in low-rainfall environments. Continuous-cereal systems significantly outyielded the traditional pasture–wheat systems in five of the 11 seasons at Waikerie (light-textured soil), resulting in a cumulative gross margin of AU$1600 ha–1 after the initial eight seasons, almost double that of the other treatments. All rotation systems at Kerribee (loam-textured soil) performed poorly, with only the 2003 season producing yields close to 3 t ha–1 and no profit achieved in the years 2004–08. For low-rainfall environments, the success of a higher input cropping system largely depends on the ability to offset the losses in poor seasons by capturing greater benefits from good seasons; therefore, strategies to manage climatic risk are paramount. Fallow efficiency, or the efficiency with which rainfall was stored during the period between crops, averaged 17% at Kerribee and 30% at Waikerie, also indicating that soil texture strongly influences soil evaporation. A ‘responsive’ strategy of continuous cereal with the occasional, high-value ‘break crop’ when seasonal conditions are optimal is considered superior to fixed or pasture–fallow rotations for controlling grass, disease or nutritional issues

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

Rapid injection of near-inertial shear into the stratified upper ocean at an Antarctic Circumpolar Current front

The impact on the upper ocean of the passage of a short, intense storm over a Southern Ocean site, in proximity to an Antarctic Circumpolar Current front, is characterized. The storm causes a wind-induced deepening of the mixed layer and generates an inertial current. Immediate post-storm observations indicate a mixed layer extending to approximately 50 m depth. Subsequent measurements show the upper-ocean to have re-stratified, injecting near-inertial shear in stratified waters within 1 day of the storm's passage. This time scale for the development of near-inertial shear is one order of magnitude shorter than that predicted by the ?-dispersion paradigm. The observed rapid changes in upper-ocean stratification point to the existence of an as yet undocumented, efficient mechanism for injection of near-inertial shear into the stratified ocean that is in turn associated with enhanced turbulence and mixing

Effectiveness, safety/tolerability of OBV/PTV/r ± DSV in patients with HCV genotype 1 or 4 with/without HIV-1 co-infection, chronic kidney disease (CKD) stage IIIb/V and dialysis in Spanish clinical practice – preliminary data Vie-KinD study

Poster presentatio

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

High Hepatitis B Prevalence and Vaccination Needs Among Transgender Women and Men Sex Workers in Barcelona, Spain

Background. Transgender women sex workers (TWSWs) and men sex workers (MSWs) are especially vulnerable to acquiring hepatitis B virus (HBV) infection. We aimed to describe HBV prevalence (hepatitis B surface antigen [HBsAg] and core antibody [HBcAb]) and associated risk factors for HBV exposure (HBcAb), to assess vaccination status and risk factors for no prior vaccination, and to compare HBV prevalence and vaccination status between TWSWs and MSWs. Methods. The SexCohort study was advertised to TWSWs and MSWs through several communication channels. At cohort entry through 2 community-based organizations in Barcelona, the study population was screened for HBV and other sexually transmitted infections, and an epidemiological questionnaire was administered (n = 271). Results. Overall, 93.0% of participants were migrants, mostly from South and Central American countries. HBsAg prevalence was 1.9% (TWSWs, 2.4%; vs MSWs, 0.9%; P = .42), and previous exposure to HBV was 31.8% (TWSWs, 38.5%; vs MSWs, 20.8%; P = .002). Over 5 years of sex work (adjusted odds ratio [aOR], 9.35), prior exposure to Treponema pallidum (aOR, 3.49), and treatment with anxiolytic drugs (aOR, 3.23) were associated with HBV exposure. Overall, 33.7% of participants exhibited immunity from vaccination (TWSWs, 30.8%; vs MSWs, 38.61%; P < .001), while 34.4% were candidates to HBV vaccination (TWSWs, 30.8%; vs MSWs, 40.6%; P < .001). Never having been on pre-exposure prophylaxis for HIV (odds ratio [OR], 4.23) and non-Spanish origin (OR, 5.00) were associated with no prior HBV vaccination. Conclusions. There is a need to reinforce screening and vaccination programs aimed at TWSWs and MSWs as integrated services offered at the community centers commonly accessed by these populations

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