Chemotherapy-mediated p53-dependent DNA damage response in clear cell renal cell carcinoma: role of the mTORC1/2 and hypoxia-inducible factor pathways.

The DNA-damaging agent camptothecin (CPT) and its analogs demonstrate clinical utility for the treatment of advanced solid tumors, and CPT-based nanopharmaceuticals are currently in clinical trials for advanced kidney cancer; however, little is known regarding the effects of CPT on hypoxia-inducible factor-2α (HIF-2α) accumulation and activity in clear cell renal cell carcinoma (ccRCC). Here we assessed the effects of CPT on the HIF/p53 pathway. CPT demonstrated striking inhibition of both HIF-1α and HIF-2α accumulation in von Hippel-Lindau (VHL)-defective ccRCC cells, but surprisingly failed to inhibit protein levels of HIF-2α-dependent target genes (VEGF, PAI-1, ET-1, cyclin D1). Instead, CPT induced DNA damage-dependent apoptosis that was augmented in the presence of pVHL. Further analysis revealed CPT regulated endothelin-1 (ET-1) in a p53-dependent manner: CPT increased ET-1 mRNA abundance in VHL-defective ccRCC cell lines that was significantly augmented in their VHL-expressing counterparts that displayed increased phosphorylation and accumulation of p53; p53 siRNA suppressed CPT-induced increase in ET-1 mRNA, as did an inhibitor of ataxia telangiectasia mutated (ATM) signaling, suggesting a role for ATM-dependent phosphorylation of p53 in the induction of ET-1. Finally, we demonstrate that p53 phosphorylation and accumulation is partially dependent on mTOR activity in ccRCC. Consistent with this result, pharmacological inhibition of mTORC1/2 kinase inhibited CPT-mediated ET-1 upregulation, and p53-dependent responses in ccRCC. Collectively, these data provide mechanistic insight into the action of CPT in ccRCC, identify ET-1 as a p53-regulated gene and demonstrate a requirement of mTOR for p53-mediated responses in this tumor type

Space-charge limited conduction in epitaxial chromia films grown on elemental and oxide-based metallic substrates

We study temperature dependent (200 – 400 K) dielectric current leakage in high-quality, epitaxial chromia films, synthesized on various conductive substrates (Pd, Pt and V2O3). We find that trap-assisted space-charge limited conduction is the dominant source of electrical leakage in the films, and that the density and distribution of charge traps within them is strongly dependent upon the choice of the underlying substrate. Pd-based chromia is found to exhibit leakage consistent with the presence of deep, discrete traps, a characteristic that is related to the known properties of twinning defects in the material. The Pt- and V2O3-based films, in contrast, show behavior typical of insulators with shallow, exponentially-distributed traps. The highest resistivity is obtained for chromia fabricated on V2O3substrates, consistent with a lower total trap density in these films. Our studies suggest that chromia thin films formed on V2O3 substrates are a promising candidate for next-generation spintronics

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Edited lectures on Arid HorticultureEdited lectures on Arid HorticultureNot Availabl

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Not AvailableA four-year field experiment was conducted in order to assess the productivity and economic potential of five cropping systems, with two tillage (conventional and deep) and four nutrient management [no application, farm yard manure (FYM) at 5 t ha - 1, chemical fertilizer (CF), FYM at 5 t ha - 1 + CF] treatments in a hot, arid environment at Bikaner, India. Pearl millet [Pennisetum glaucum (L.) R. Br], cluster bean [Cyamopsis tetragonoloba (L.) Taub.] and moth bean [Vigna aconitifolia (Jacq.) Marechal] were grown in five rotations. The five rotations were: moth bean – pearl millet, cluster bean – pearl millet, moth bean – cluster bean, pearl millet – pearl millet and pearl millet + cluster bean – pearl millet + cluster bean. The moth bean – cluster bean cropping system recorded 21 – 148 %, 36 – 246 % and 33 – 178 % higher equivalent yields, return and water use efficiency, respectively than other cropping systems. Deep tillage increased equivalent yields by 20 % higher than conventional tillage. The combined application of CF and FYM recorded 15 and 32 % higher equivalent yields than their respective sole application. In this hot, arid ecosystem, a legume – legume system was more productive and profitable than other systems and higher crop yields could be achieved by combining deep tillage with the integrated use of CF and FYM.Not Availabl

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Edited lectures on Kitchen GardenEdited lectures on Kitchen GardenNot Availabl

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Not AvailableExperiment was conducted to assess the effect of temperature and salinity on germination and seedling growth of C. polygonoides and H. recurvum. Seeds were incubated at five temperatures (15, 20, 25, 30 and 35 °C) with six NaCl concentrations (0,100, 200, 300, 400 and 500 mM) for H. recurvum and with seven NaCl concentrations (0, 25, 50, 100, 200, 300, and 400 mM) for C. polygonoides. The 20–25 °C temperature seems to optimum for germination and seedling growth of C. polygonoides and H. recurvum. Germination and seedling growth were inhibited by either an increase or a decrease in temperature from the optimal temperature. The C. polygonoides germinated up to 100 mM NaCl concentration, whereas H. recurvum germinated up-to 400 mM NaCl concentration under optimal temperatures. The 50 % reduction in seedling growth of C. polygonoides and H. recurvum was recorded with > 50 mM and 300 mM NaCl, respectively. The interaction effect of temperature and salinity on all measured variables was significant. Salinity induced inhibition of germination and seedling growth was more at higher temperatures in both species. These results provide information pertaining to germination behaviour of species, and shows that in arid region, selection of suitable planting time and site must take into account both salinity and temperature.Not Availabl