High-risk human papillomaviruses (HPVs) are associated with carcinomas of the cervix and other genital tumors. The HPV oncoprotein E6 is essential for oncogenic transformation. We identify here hADA3, human homologue of the yeast transcriptional coactivator yADA3, as a novel E6-interacting protein and a target of E6-induced degradation. hADA3 binds selectively to the high-risk HPV E6 proteins and only to immortalization-competent E6 mutants. hADA3 functions as a coactivator for p53-mediated transactivation by stabilizing p53 protein. Notably, three immortalizing E6 mutants that do not induce direct p53 degradation but do interact with hADA3 induced the abrogation of p53-mediated transactivation and G 1 cell cycle arrest after DNA damage, comparable to wild-type E6. These findings reveal a novel strategy of HPV E6-induced loss of p53 function that is independent of direct p53 degradation. Given the likely role of the evolutionarily conserved hADA3 in multiple coactivator complexes, inactivation of its function may allow E6 to perturb numerous cellular pathways during HPV oncogenesis.
It is a well‐known fact that the pronounced photogenerated charge recombination and poor light absorption are the main bottlenecks of photocatalysis applications. The conventional approaches to address these problems involve bandgap engineering and suppression of charge recombination after light irradiation, which results in an enhancement in the photocatalytic performance of the materials. However, the most essential aspect of surface modification to engineer active sites on the catalyst surface is generally not given much importance. Contrary to this, defect engineering is another approach by which the optical, charge separation, and surface properties of the photocatalytic materials can be tuned. In this review article, the effect of the introduction of vacancies on the photocatalytic properties of selected semiconductor materials, viz., metal oxides, perovskite oxides, metal sulfides, oxyhalides, and nitrides is comprehensively summarized. The engineering of vacancies in these materials not only improves their optical and charge transfer properties but also affects the surface properties, which are helpful in the adsorption of the reactants on catalyst surface. Herein, photocatalytic hydrogen evolution and nitrogen fixation applications of vacancy engineered materials are discussed in detail along with the current trends, scalability requirements, and rigorous experimental protocols.
The Andhra Pradesh Children and Parents Study (APCAPS) was originally established to study the long-term effects of early-life undernutrition on risk of cardiovascular disease. Its aims were subsequently expanded to include trans-generational influences of other environmental and genetic factors on chronic diseases in rural India. It builds on the Hyderabad Nutrition Trial (HNT) conducted in 1987–90 to compare the effects on birthweight of a protein-calorie supplement for pregnant women and children. The index children of HNT and their mothers were retraced and examined in 2003–05, and the children re-examined as young adults aged 18–21 years in 2009–10. The cohort was expanded to include both parents and siblings of the index children in a recently completed follow-up conducted in 2010–12 (N = ∼6225 out of 10 213 participants). Recruitment of the remaining residents of these 29 villages (N = ∼55 000) in Ranga Reddy district of Andhra Pradesh is now under way. Extensive data on socio-demographic, lifestyle, medical, anthropometric, physiological, vascular and body composition measures, DNA, stored plasma, and assays of lipids and inflammatory markers on APCAPS participants are available. Details of how to access these data are available from the corresponding author.
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