ABSTRACT
The cellular adaptive response to hypoxia, mediated by high HIF1α levels includes metabolic reprogramming, restricted DNA replication and cell division. In contrast to healthy cells, the genome of cancer cells, and Kaposi's sarcoma associated herpesvirus (KSHV) infected cells maintains replication in hypoxia. We show that KSHV infection, despite promoting expression of HIF1α in normoxia, can also restrict transcriptional activity, and promoted its degradation in hypoxia. KSHV-encoded vCyclin, expressed in hypoxia, mediated HIF1α cytosolic translocation, and its degradation through a non-canonical lysosomal pathway. Attenuation of HIF1α levels by vCyclin allowed cells to bypass the block to DNA replication and cell proliferation in hypoxia. These results demonstrated that KSHV utilizes a unique strategy to balance HIF1α levels to overcome replication arrest and induction of the oncogenic phenotype, which are dependent on the levels of oxygen in the microenvironment.
Subject(s)
Cyclins/genetics , Cyclins/metabolism , DNA Replication , Herpesvirus 8, Human/genetics , Hypoxia-Inducible Factor 1, alpha Subunit/metabolism , Hypoxia/metabolism , Cell Proliferation , Gene Expression Regulation, Viral , HEK293 Cells , Herpesviridae Infections/metabolism , Humans , Oxygen/metabolism , Transcriptome , Virus Replication/physiologyABSTRACT
Critical analysis of thermogravimetric data, characterization of the biomass, and kinetic and thermodynamic analyses are crucial in the design of efficient biomass pyrolysis systems. In this study, characterization, kinetic and thermodynamic analysis was performed for pyrolysis of mustard oil residue (MOR). Thermogravimetric analysis (TGA) with differential thermal analysis (DTA) was applied to study thermal decomposition behaviour of MOR at 10, 20, and 30 °C/min. FTIR and XRD analyses were used to characterize MOR. Average activation energy estimated from employed isoconversional methods was ≈155 kJ/mol. Variation in activation energy was found to be statistically insignificant as suggested by p-value of 0.992 by one-way ANOVA method. The pyrolytic temperature for MOR ranged from 234 to 417 °C. Reaction mechanism predicted as R3 (third order) and D3 (three dimensional). Thermodynamic parameters (ΔHα, ΔGα, and ΔSα) showed that endothermicity increased from 0.2 to 0.8 conversion and product had highest energy at 0.8 conversion.
