Six models were devised for a hypothetical predator—prey system. The models differed in functional forms, but were calibrated to display similar output for a standard annual cycle. Parameters were assumed to be measured with error, and this uncertainty was propagated through the models by Monte Carlo simulation. Total uncertainty on model output was partitioned, for each model, into six component sums of squares, and components were examined as they changed over the simulated annual cycle. The results indicate that the models differ in their error propagation properties with more complex functions often generating greater uncertainty on output. The contribution of a specific model term to overall error is dependent on its mathematical form (especially, the partial derivative of the term with respect to the parameter) and also its position within the total model. No single model showed the smallest output uncertainty for all possible modeling objectives. The results indicate that the most useful data for testing a model should be gathered during periods of the year when the state variables are changing most rapidly.
In the present study, the gelatin from fresh croaker fish (Johnius sp) skin was obtained by rapid extraction and its properties were assessed. The gelling and melting temperature of croaker skin gelatin was 17.4 and 23.8°C as revealed by dynamic visco-elastic analysis using Controlled Stress Rheometer. Croaker skin gelatin (CSG) had the bloom value of 193.4 g. Scanning electron microscopic analysis of freeze dried gelatin showed the presence of voids surrounded by a loose network imitating a sponge or coral like structure. Texture profile parameters such as hardness, springiness, cohesiveness, gumminess, and chewiness of croaker fish skin gelatin gel were relatively lower than the porcine gelatin gel. The amino acid composition of gelatin revealed a higher proportion of glycine, alanine, and hydroxyl proline (30.25, 23.4, and 11.82 g/100 g protein, respectively) content. The electrophoretic analysis showed the presence of two peptide chains with the approximate molecular weight of 200 and 116 kDa corresponds to β and α peptide chain of collagen. The Fourier Transform Infrared (FT-IR) spectra of gelatin showed peaks correspond to the structures like α helix, β sheet, and random coil in the gelatin preparations.ARTICLE HISTORY
Dose-limiting cardiotoxicity remains a major limitation in the clinical use of cancer chemotherapeutics. Here, we describe a role for Regulator of G protein Signaling 7 (RGS7) in chemotherapy-dependent heart damage, the demonstration for a functional role of RGS7 outside of the nervous system and retina. Though expressed at low levels basally, we observed robust up-regulation of RGS7 in the human and murine myocardium following chemotherapy exposure. In ventricular cardiomyocytes (VCM), RGS7 forms a complex with Ca
2+
/calmodulin-dependent protein kinase (CaMKII) supported by key residues (K412 and P391) in the RGS domain of RGS7. In VCM treated with chemotherapeutic drugs, RGS7 facilitates CaMKII oxidation and phosphorylation and CaMKII-dependent oxidative stress, mitochondrial dysfunction, and apoptosis. Cardiac-specific RGS7 knockdown protected the heart against chemotherapy-dependent oxidative stress, fibrosis, and myocyte loss and improved left ventricular function in mice treated with doxorubicin. Conversely, RGS7 overexpression induced fibrosis, reactive oxygen species generation, and cell death in the murine myocardium that were mitigated following CaMKII inhibition. RGS7 also drives production and release of the cardiokine neuregulin-1, which facilitates paracrine communication between VCM and neighboring vascular endothelial cells (EC), a maladaptive mechanism contributing to VCM dysfunction in the failing heart. Importantly, while RGS7 was both necessary and sufficient to facilitate chemotherapy-dependent cytotoxicity in VCM, RGS7 is dispensable for the cancer-killing actions of these same drugs. These selective myocyte-intrinsic and myocyte-extrinsic actions of RGS7 in heart identify RGS7 as an attractive therapeutic target in the mitigation of chemotherapy-driven cardiotoxicity.
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