251 research outputs found

    Phenethyl isothiocyanate exhibits antileukemic activity in vitro and in vivo by inactivation of Akt and activation of JNK pathways

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    Effects of phenethyl isothiocyanate (PEITC) have been investigated in human leukemia cells (U937, Jurkat, and HL-60) as well as in primary human acute myeloid leukemia (AML) cells in relation to apoptosis and cell signaling events. Exposure of cells to PEITC resulted in pronounced increase in the activation of caspase-3, -8, -9, cleavage/degradation of PARP, and apoptosis in dose- and time-dependent manners. These events were accompanied by the caspase-independent downregulation of Mcl-1, inactivation of Akt, as well as activation of Jun N-terminal kinase (JNK). Inhibition of PI3K/Akt by LY294002 significantly enhanced PEITC-induced apoptosis. Conversely, enforced activation of Akt by a constitutively active Akt construct markedly abrogated PEITC-mediated JNK activation, Mcl-1 downregulation, caspase activation, and apoptosis, and also interruption of the JNK pathway by pharmacological or genetically (e.g., siRNA) attenuated PEITC-induced apoptosis. Finally, administration of PEITC markedly inhibited tumor growth and induced apoptosis in U937 xenograft model in association with inactivation of Akt, activation of JNK, as well as downregulation of Mcl-1. Taken together, these findings represent a novel mechanism by which agents targeting Akt/JNK/Mcl-1 pathway potentiate PEITC lethality in transformed and primary human leukemia cells and inhibitory activity of tumor growth of U937 xenograft model

    Markedly Divergent Tree Assemblage Responses to Tropical Forest Loss and Fragmentation across a Strong Seasonality Gradient

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    We examine the effects of forest fragmentation on the structure and composition of tree assemblages within three seasonal and aseasonal forest types of southern Brazil, including evergreen, Araucaria, and deciduous forests. We sampled three southernmost Atlantic Forest landscapes, including the largest continuous forest protected areas within each forest type. Tree assemblages in each forest type were sampled within 10 plots of 0.1 ha in both continuous forests and 10 adjacent forest fragments. All trees within each plot were assigned to trait categories describing their regeneration strategy, vertical stratification, seed-dispersal mode, seed size, and wood density. We detected differences among both forest types and landscape contexts in terms of overall tree species richness, and the density and species richness of different functional groups in terms of regeneration strategy, seed dispersal mode and woody density. Overall, evergreen forest fragments exhibited the largest deviations from continuous forest plots in assemblage structure. Evergreen, Araucaria and deciduous forests diverge in the functional composition of tree floras, particularly in relation to regeneration strategy and stress tolerance. By supporting a more diversified light-demanding and stress-tolerant flora with reduced richness and abundance of shade-tolerant, old-growth species, both deciduous and Araucaria forest tree assemblages are more intrinsically resilient to contemporary human-disturbances, including fragmentation-induced edge effects, in terms of species erosion and functional shifts. We suggest that these intrinsic differences in the direction and magnitude of responses to changes in landscape structure between forest types should guide a wide range of conservation strategies in restoring fragmented tropical forest landscapes worldwide

    Switching of magnetization by non-linear resonance studied in single nanoparticles

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    Magnetization reversal in magnetic particles is one of the fundamental issues in magnetic data storage. Technological improvements require the understanding of dynamical magnetization reversal processes at nanosecond time scales. New strategies are needed to overcome current limitations. For example, the problem of thermal stability of the magnetization state (superparamagnetic limit) can be pushed down to smaller particle sizes by increasing the magnetic anisotropy. High fields are then needed to reverse the magnetization that are difficult to achieve in current devices. Here we propose a new method to overcome this limitation. A constant applied field, well below the switching field, combined with a radio-frequency (RF) field pulse can reverse the magnetization of a nanoparticle. The efficiency of this method is demonstrated on a 20 nm cobalt particle by using the micro-SQUID technique. Other applications of this method might be nucleation or depinning of domain walls.Comment: 11 pages, 5 figure

    The development and preliminary psychometric properties of two positive psychology outcome measures for people with dementia: the PPOM and the EID-Q.

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    Background: Positive psychology research in dementia care has largely been confined to the qualitative literature because of the lack of robust outcome measures. The aim of this study was to develop positive psychology outcome measures for people with dementia. Methods: Two measures were each developed in four stages. Firstly, literature reviews were conducted to identify and operationalise salient positive psychology themes in the qualitative literature and to examine existing measures of positive psychology. Secondly, themes were discussed within a qualitative study to add content validity for identified concepts (n = 17). Thirdly, draft measures were submitted to a panel of experts for feedback (n = 6). Finally, measures were used in a small-scale pilot study (n = 33) to establish psychometric properties. Results: Salient positive psychology themes were identified as hope, resilience, a sense of independence and social engagement. Existing measures of hope and resilience were adapted to form the Positive Psychology Outcome Measure (PPOM). Due to the inter-relatedness of independence and engagement for people with dementia, 28 items were developed for a new scale of Engagement and Independence in Dementia Questionnaire (EID-Q) following extensive qualitative work. Both measures demonstrated acceptable internal consistency (α = .849 and α = .907 respectively) and convergent validity. Conclusions: Two new positive psychology outcome measures were developed using a robust four-stage procedure. Preliminary psychometric data was adequate and the measures were easy to use, and acceptable for people with dementia

    A Phase 1 Randomized, Double Blind, Placebo Controlled Rectal Safety and Acceptability Study of Tenofovir 1% Gel (MTN-007)

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    Objective: Rectal microbicides are needed to reduce the risk of HIV acquisition associated with unprotected receptive anal intercourse. The MTN-007 study was designed to assess the safety (general and mucosal), adherence, and acceptability of a new reduced glycerin formulation of tenofovir 1% gel. Methods: Participants were randomized 1:1:1:1 to receive the reduced glycerin formulation of tenofovir 1% gel, a hydroxyethyl cellulose placebo gel, a 2% nonoxynol-9 gel, or no treatment. Each gel was administered as a single dose followed by 7 daily doses. Mucosal safety evaluation included histology, fecal calprotectin, epithelial sloughing, cytokine expression (mRNA and protein), microarrays, flow cytometry of mucosal T cell phenotype, and rectal microflora. Acceptability and adherence were determined by computer-administered questionnaires and interactive telephone response, respectively. Results: Sixty-five participants (45 men and 20 women) were recruited into the study. There were no significant differences between the numbers of ≥ Grade 2 adverse events across the arms of the study. Likelihood of future product use (acceptability) was 87% (reduced glycerin formulation of tenofovir 1% gel), 93% (hydroxyethyl cellulose placebo gel), and 63% (nonoxynol-9 gel). Fecal calprotectin, rectal microflora, and epithelial sloughing did not differ by treatment arms during the study. Suggestive evidence of differences was seen in histology, mucosal gene expression, protein expression, and T cell phenotype. These changes were mostly confined to comparisons between the nonoxynol-9 gel and other study arms. Conclusions: The reduced glycerin formulation of tenofovir 1% gel was safe and well tolerated rectally and should be advanced to Phase 2 development. Trial Registration: ClinicalTrials.gov NCT01232803

    The Prevalence and Psychopathological Correlates of Sibling Bullying in Children with and without Autism Spectrum Disorder

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    Using data from a prospective population based study, the prevalence and psychopathological correlates of sibling bullying in children with and without autism spectrum disorder (ASD) were estimated. There were 475 children with ASD and 13,702 children without ASD aged 11 years. Children with ASD were more likely to be bullied by their siblings compared to those without ASD. They were also more likely than those without ASD to both bully and be bullied by their siblings, which was associated with lower prosocial skills as well as more internalizing and externalizing problems compared to those not involved in any sibling bullying. Interventions to improve social and emotional outcomes in children with ASD should focus on both the affected and the unaffected sibling

    On the Role of Attention in Binocular Rivalry: Electrophysiological Evidence

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    During binocular rivalry visual consciousness fluctuates between two dissimilar monocular images. We investigated the role of attention in this phenomenon by comparing event-related potentials (ERPs) when binocular-rivalry stimuli were attended with when they were unattended. Stimuli were dichoptic, orthogonal gratings that yielded binocular rivalry and dioptic, identically oriented gratings that yielded binocular fusion. Events were all possible orthogonal changes in orientation of one or both gratings. We had two attention conditions: In the attend-to-grating condition, participants had to report changes in perceived orientation, focussing their attention on the gratings. In the attend-to-fixation condition participants had to report changes in a central fixation target, taking attention away from the gratings. We found, surprisingly, that attending to rival gratings yielded a smaller ERP component (the N1, from 160–210 ms) than attending to the fixation target. To explain this paradoxical effect of attention, we propose that rivalry occurs in the attend-to-fixation condition (we found an ERP signature of rivalry in the form of a sustained negativity from 210–300 ms) but that the mechanism processing the stimulus changes is more adapted in the attend-to-grating condition than in the attend-to-fixation condition. This is consistent with the theory that adaptation gives rise to changes of visual consciousness during binocular rivalry

    Hydrokinetic Turbine Effects on Fish Swimming Behaviour

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    Hydrokinetic turbines, targeting the kinetic energy of fast-flowing currents, are under development with some turbines already deployed at ocean sites around the world. It remains virtually unknown as to how these technologies affect fish, and rotor collisions have been postulated as a major concern. In this study the effects of a vertical axis hydrokinetic rotor with rotational speeds up to 70 rpm were tested on the swimming patterns of naturally occurring fish in a subtropical tidal channel. Fish movements were recorded with and without the rotor in place. Results showed that no fish collided with the rotor and only a few specimens passed through rotor blades. Overall, fish reduced their movements through the area when the rotor was present. This deterrent effect on fish increased with current speed. Fish that passed the rotor avoided the near-field, about 0.3 m from the rotor for benthic reef fish. Large predatory fish were particularly cautious of the rotor and never moved closer than 1.7 m in current speeds above 0.6 ms-1. The effects of the rotor differed among taxa and feeding guilds and it is suggested that fish boldness and body shape influenced responses. In conclusion, the tested hydrokinetic turbine rotor proved non-hazardous to fish during the investigated conditions. However, the results indicate that arrays comprising multiple turbines may restrict fish movements, particularly for large species, with possible effects on habitat connectivity if migration routes are exploited. Arrays of the investigated turbine type and comparable systems should therefore be designed with gaps of several metres width to allow large fish to pass through. In combination with further research the insights from this study can be used for guiding the design of hydrokinetic turbine arrays where needed, so preventing ecological impacts

    Neonicotinoid Insecticides and Their Impacts on Bees: A Systematic Review of Research Approaches and Identification of Knowledge Gaps

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    It has been suggested that the widespread use of neonicotinoid insecticides threatens bees, but research on this topic has been surrounded by controversy. In order to synthesize which research approaches have been used to examine the effect of neonicotinoids on bees and to identify knowledge gaps, we systematically reviewed research on this subject that was available on the Web of Science and PubMed in June 2015. Most of the 216 primary research studies were conducted in Europe or North America (82%), involved the neonicotinoid imidacloprid (78%), and concerned the western honey bee Apis mellifera (75%). Thus, little seems to be known about neonicotinoids and bees in areas outside Europe and North America. Furthermore, because there is considerable variation in ecological traits among bee taxa, studies on honey bees are not likely to fully predict impacts of neonicotinoids on other species. Studies on crops were dominated by seed-treated maize, oilseed rape (canola) and sunflower, whereas less is known about potential side effects on bees from the use of other application methods on insect pollinated fruit and vegetable crops, or on lawns and ornamental plants. Laboratory approaches were most common, and we suggest that their capability to infer real-world consequences are improved when combined with information from field studies about realistic exposures to neonicotinoids. Studies using field approaches often examined only bee exposure to neonicotinoids and more field studies are needed that measure impacts of exposure. Most studies measured effects on individual bees. We suggest that effects on the individual bee should be linked to both mechanisms at the sub-individual level and also to the consequences for the colony and wider bee populations. As bees are increasingly facing multiple interacting pressures future research needs to clarify the role of neonicotinoids in relative to other drivers of bee declines
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