Suchergebnisse

Vikas Bajpai and Anoop Saraya, Health Beyond Medicine: Some Reflections on the Politics and Sociology of Health in India. Delhi: Aakar Books, 2018, 310 pp., ₹995, ISBN: 9789350025277 (Hardbound).

This book seeks to encourage dialectical methods through the interaction of economic, political and social factors to approach social analysis. It examines various emerging issues in society in the era of globalization. The issues raised in the critique will benefit scholars in comprehending social reality with a new perspective and approach. This book will help policymakers look at more realistic conclusions for policy making. This title is co-published with Aakar Books. Print editions not for sale in South Asia (India, Sri Lanka, Nepal, Bangladesh, Pakistan and Bhutan).

This book seeks to encourage dialectical methods through the interaction of economic, political and social factors to approach social analysis. It examines various emerging issues in society in the era of globalization. The issues raised in the critique will benefit scholars in comprehending social reality with a new perspective and approach. This book will help policymakers look at more realistic conclusions for policy making. This title is co-published with Aakar Books. Print editions not for sale in South Asia (India, Sri Lanka, Nepal, Bangladesh, Pakistan and Bhutan).

15 pags., 6 figs., 3 tabs. -- Open Access funded by Creative Commons Atribution Licence 4.0 ; p53 is frequently mutated in human cancers. Its levels are tightly regulated by the E3 ubiquitin ligase MDM2. The complex between MDM2 and p53 is largely formed by the interaction between the N-terminal domain of MDM2 and the N-terminal transactivation (TA) domain of p53 (residues 15–29). We investigated the kinetic and thermodynamic basis of the MDM2/p53 interaction by using wild-type and mutant variants of the TA domain. We focus on the effects of phosphorylation at positions Thr18 and Ser20 including their substitution with phosphomimetics. Conformational propensities of the isolated peptides were investigated using in silico methods and experimentally by circular dichroism and H-NMR in aqueous solution. Both experimental and computational analyses indicate that the p53 peptides are mainly disordered in aqueous solution, with evidence of nascent helix around the Ser20-Leu25 region. Both phosphorylation and the phosphomimetics at Thr18 result in a decrease in the binding affinity by ten- to twenty-fold when compared to the wild-type. Phosphorylation and phosphomimetics at Ser20 result in a smaller decrease in the affinity. Mutation of Lys24 and Leu25 also disrupts the interaction. Our results may be useful for further development of peptide-based drugs targeting the MDM2/p53 interaction. ; This work was supported by Spanish Ministry of Economy and Competitiveness [CTQ 2015–64445-R (to JLN)]. JLN acknowledges the regional government Generalitat Valenciana for a BEST short-stay fellowship in the Department of Pharmacology, Cambridge, UK. LSI acknowledges support of a Senior Fellowship from the Medical Research Foundation (UK).