Inhibition of IGF-I Receptor Signaling in Combination with Rapamycin or Temsirolimus Increases MYC-N Phosphorylation

BACKGROUND: It has been previously shown that blockade of the type 1 insulin-like growth factor receptor (IGF1R) signaling combined with mTOR inhibition decreased neuroblastoma proliferation in vitro. MYC-N inactivation occurs through phosphorylation by downstream elements of the IGF1R signaling pathway. It was hypothesized that inhibition of IGF1R signaling would increase the inactivation of MYC-N. MATERIALS AND METHODS: BE-2(c) and IMR-32 neuroblastoma cell lines were treated with varying concentrations of alphaIR3, rapamycin and temsirolimus either alone or in combination and the expression of MYC-N and phosphorylated MYC-N proteins were evaluated by Western blotting. The number of apoptotic cells was evaluated through cleaved caspase-3 expression. RESULTS: IGF1R signaling blockade in combination with mTOR inhibition decreased MYC-N protein expression, increased MYC-N phosphorylation and significantly increased cleaved caspase-3 expression in treated cells. CONCLUSION: The combination of rapamycin or temsirolimus with alphaIR3 decreases MYC-N expression, increases MYC-N phosphorylation and induces apoptosis in vitro which may have clinical relevance to children with neuroblastoma

Acute Ethanol Administration Rapidly Increases Phosphorylation of Conventional Protein Kinase C in Specific Mammalian Brain Regions in Vivo

Background Protein kinase C (PKC) is a family of isoenzymes that regulate a variety of functions in the central nervous system including neurotransmitter release, ion channel activity, and cell differentiation. Growing evidence suggests that specific isoforms of PKC influence a variety of behavioral, biochemical, and physiological effects of ethanol in mammals. The purpose of this study was to determine whether acute ethanol exposure alters phosphorylation of conventional PKC isoforms at a threonine 674 (p-cPKC) site in the hydrophobic domain of the kinase, which is required for its catalytic activity. Methods Male rats were administered a dose range of ethanol (0, 0.5, 1, or 2 g/kg, intragastric) and brain tissue was removed 10 minutes later for evaluation of changes in p-cPKC expression using immunohistochemistry and Western blot methods. Results Immunohistochemical data show that the highest dose of ethanol (2 g/kg) rapidly increases p-cPKC immunoreactivity specifically in the nucleus accumbens (core and shell), lateral septum, and hippocampus (CA3 and dentate gyrus). Western blot analysis further showed that ethanol (2 g/kg) increased p-cPKC expression in the P2 membrane fraction of tissue from the nucleus accumbens and hippocampus. Although p-cPKC was expressed in numerous other brain regions, including the caudate nucleus, amygdala, and cortex, no changes were observed in response to acute ethanol. Total PKC? immunoreactivity was surveyed throughout the brain and showed no change following acute ethanol injection

Ten Ways Remote Sensing Can Contribute to Conservation

In an effort to increase conservation effectiveness through the use of Earth observation technologies, a group of remote sensing scientists affiliated with government and academic institutions and conservation organizations identified 10 questions in conservation for which the potential to be answered would be greatly increased by use of remotely sensed data and analyses of those data. Our goals were to increase conservation practitioners’ use of remote sensing to support their work, increase collaboration between the conservation science and remote sensing communities, identify and develop new and innovative uses of remote sensing for advancing conservation science, provide guidance to space agencies on how future satellite missions can support conservation science, and generate support from the public and private sector in the use of remote sensing data to address the 10 conservation questions. We identified a broad initial list of questions on the basis of an email chain-referral survey. We then used a workshop-based iterative and collaborative approach to whittle the list down to these final questions (which represent 10 major themes in conservation): How can global Earth observation data be used to model species distributions and abundances? How can remote sensing improve the understanding of animal movements? How can remotely sensed ecosystem variables be used to understand, monitor, and predict ecosystem response and resilience to multiple stressors? How can remote sensing be used to monitor the effects of climate on ecosystems? How can near real-time ecosystem monitoring catalyze threat reduction, governance and regulation compliance, and resource management decisions? How can remote sensing inform configuration of protected area networks at spatial extents relevant to populations of target species and ecosystem services? How can remote sensing-derived products be used to value and monitor changes in ecosystem services? How can remote sensing be used to monitor and evaluate the effectiveness of conservation efforts? How does the expansion and intensification of agriculture and aquaculture alter ecosystems and the services they provide? How can remote sensing be used to determine the degree to which ecosystems are being disturbed or degraded and the effects of these changes on species and ecosystem functions