Insulin Production and Signaling in Renal Tubules of Drosophila Is under Control of Tachykinin-Related Peptide and Regulates Stress Resistance

The insulin-signaling pathway is evolutionarily conserved in animals and regulates growth, reproduction, metabolic homeostasis, stress resistance and life span. In Drosophila seven insulin-like peptides (DILP1-7) are known, some of which are produced in the brain, others in fat body or intestine. Here we show that DILP5 is expressed in principal cells of the renal tubules of Drosophila and affects survival at stress. Renal (Malpighian) tubules regulate water and ion homeostasis, but also play roles in immune responses and oxidative stress. We investigated the control of DILP5 signaling in the renal tubules by Drosophila tachykinin peptide (DTK) and its receptor DTKR during desiccative, nutritional and oxidative stress. The DILP5 levels in principal cells of the tubules are affected by stress and manipulations of DTKR expression in the same cells. Targeted knockdown of DTKR, DILP5 and the insulin receptor dInR in principal cells or mutation of Dilp5 resulted in increased survival at either stress, whereas over-expression of these components produced the opposite phenotype. Thus, stress seems to induce hormonal release of DTK that acts on the renal tubules to regulate DILP5 signaling. Manipulations of S6 kinase and superoxide dismutase (SOD2) in principal cells also affect survival at stress, suggesting that DILP5 acts locally on tubules, possibly in oxidative stress regulation. Our findings are the first to demonstrate DILP signaling originating in the renal tubules and that this signaling is under control of stress-induced release of peptide hormone

Effects of the September 2005 Solar Flares and Solar Proton Events on the Middle Atmosphere in WACCM

This work investigates middle atmosphere effects of the September 2005 solar flares and solar proton events (SPEs). X‐17 and X‐6.2 flares occurred on 7 and 9 September, respectively, while two moderate SPEs occurred on 10 and 15 September. Flare ionization and dissociation were calculated in the Whole Atmosphere Community Climate Model (WACCM) using the Flare Irradiance Spectral Model. Proton measurements from the Geostationary Operational Environmental Satellite system were used to compute solar proton ionization. SPEs are shown to have a larger impact than solar flares on the polar stratosphere and mesosphere; however, flares have a larger influence on the sunlit and equatorial lower thermosphere. The two flares differed significantly with respect to photon spectrum. The larger, X‐17 flare was stronger during the impulsive phase, while the X‐6.2 flare was stronger during the gradual phase. This resulted in the X‐17 flare causing more initial ionization but for a shorter duration. The simulated flare impacts also differed because specific wavelengths of the flares influenced the atmosphere above the model top. Model‐measurement comparisons show that WACCM captures the overall timing and spatial distribution of the observed electron enhancements, indicating a reasonable simulation of flare and SPE‐induced ionization. Both the SPEs and flares caused odd nitrogen increases in the mesosphere. Odd hydrogen produced in the lower mesosphere by the SPEs led to short‐lived ozone decreases of nearly 100%. The flares caused small temperature increases in the lower thermosphere but had no effect on the stratosphere

Immunizations with IFNgamma secreting tumor cells can eliminate fully established and invasive rat gliomas.

Immunotherapy of malignant primary brain tumors holds the potential to improve the dismal prognosis after current clinical therapy. Although immunotherapy of experimental gliomas has been demonstrated to have the capacity to cure intracerebral tumors no convincing effects of immunotherapy have been shown in clinical trials. One reason for this could be that some of the models used do not display full features of human glioblastomas. The N29 rat gliomas exhibited all the histologic features of human glioblastoma multiforme including nuclear atypia, mitotic figures, necrosis, and diffuse infiltration into the normal brain tissue. Surprisingly, immunotherapy with autologous interferon gamma producing tumor cells against preestablished intracerebral N29 tumors yielded a higher cure rate than immunotherapy against less invasive tumors. Furthermore, when immunizations were postponed until day 5 after tumor establishment 50% of the animals survived. When immunizations were postponed until day 11 after tumor establishment no glioma-bearing animals were cured but survival was significantly prolonged. The superior effect of immunotherapy in the invasive N29 model compared with the less invasive tumors could depend on combined effects of up-regulation of major histocompatibility complex I and induction of major histocompatibility complex II plus CD80 after transfection and irradiation of the tumor cells used for immunizations. This study demonstrates that immunotherapy against experimental brain tumors indeed is feasible even against highly invasive and established tumors. These results strengthen the translational potential of immunotherapy against malignant brain tumors