Isothermal titration calorimetry (ITC) is the only technique able to determine both the enthalpy and entropy of noncovalent association in a single experiment. The standard data analysis method based on nonlinear regression, however, provides unrealistically small uncertainty estimates due to its neglect of dominant sources of error. Here, we present a Bayesian framework for sampling from the posterior distribution of all thermodynamic parameters and other quantities of interest from one or more ITC experiments, allowing uncertainties and correlations to be quantitatively assessed. For a series of ITC measurements on metal:chelator and protein:ligand systems, the Bayesian approach yields uncertainties which represent the variability from experiment to experiment more accurately than the standard data analysis. In some datasets, the median enthalpy of binding is shifted by as much as 1.5 kcal/mol. A Python implementation suitable for analysis of data generated by MicroCal instruments (and adaptable to other calorimeters) is freely available online.
Pathological cardiac hypertrophy is the main determinant of the development of heart failure, for which there is often no effective therapy. The dysregulation of autophagy is implicated in hypertrophy, but the mechanism linking these processes is unclear. In this study, we characterized the regulatory role of miR-208a-3p in autophagy in H9c2 cardiomyoblasts induced by Angiotensin II (Ang II). We found that miR-208a-3p was up-regulated in Ang II-induced H9c2 cardiomyoblasts and in starvation-induced autophagy. The overexpression of miR-208a-3p increased Ang II-induced autophagy, and this was accompanied by the inhibition of programmed cell death protein (PDCD4) and upregulation of autophagy protein 5 (ATG5). A dual-luciferase report assay confirmed the direct binding between miR-208a-3p and PDCD4. PDCD4 knockdown up-regulated autophagy, and its overexpression down-regulated this process. Moreover, the PDCD4-mediated regulation of autophagy was modulated by ATG5. Taken together, these findings indicate that miR-208a-3p promotes autophagy during Ang II-induced hypertrophy and provide a basis for the development of therapies for hypertrophic-induced cardiac dysfunction.
About 40,000 inhabitants migrated from a high-risk area of esophageal squamous cell carcinoma (ESCC) to a low-risk area of esophageal cancer 40 years ago. Little is known about the change in the mortality in esophageal cancer among these immigrants. This study examined the impact of changing environments on esophageal cancer by comparing age-standardized mortality rates of immigrant group to the rates of native population (natives who live in high cancer location and have never moved) and host populations (hosts who live in low cancer location and have never moved people). All ESCC deaths taking place during 1999-2004 among the migrant, native, and host populations were identified by retrospective population-based screening. Direct age-adjusted mortality rates were calculated by using the China population of year 2000 as standard population. From 1999-2004, the average annual age-adjusted mortality of ESCC for the migrant, native, and host population was 61.6/100,000, 59.7/100,000, and 6.7/100,000, respectively. No decreasing tendency was found in mortality rate of ESCC in the population of young immigrants. The mortality rate of ESCC of migrants remained high even they had been living in the low endemic region for 40 years. This study strongly suggested that genetic susceptibility, rather than environment exposure, is responsible for the high risk of ESCC in the migrants.
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