Genetic Dissection of Cardiac Remodeling in an Isoproterenol-Induced Heart Failure Mouse Model
PLOS GENETICS
Authors: Wang, Jessica Jen-Chu; Rau, Christoph; Avetisyan, Rozeta; Ren, Shuxun; Romay, Milagros C.; Stolin, Gabriel; Gong, Ke Wei; Wang, Yibin; Lusis, Aldons J.
Abstract
We aimed to understand the genetic control of cardiac remodeling using an isoproterenol-induced heart failure model in mice, which allowed control of confounding factors in an experimental setting. We characterized the changes in cardiac structure and function in response to chronic isoproterenol infusion using echocardiography in a panel of 104 inbred mouse strains. We showed that cardiac structure and function, whether under normal or stress conditions, has a strong genetic component, with heritability estimates of left ventricular mass between 61% and 81%. Association analyses of cardiac remodeling traits, corrected for population structure, body size and heart rate, revealed 17 genome-wide significant loci, including several loci containing previously implicated genes. Cardiac tissue gene expression profiling, expression quantitative trait loci, expression-phenotype correlation, and coding sequence variation analyses were performed to prioritize candidate genes and to generate hypotheses for downstream mechanistic studies. Using this approach, we have validated a novel gene, Myh14, as a negative regulator of ISO-induced left ventricular mass hypertrophy in an in vivo mouse model and demonstrated the up-regulation of immediate early gene Myc, fetal gene Nppb, and fibrosis gene Lgals3 in ISO-treated Myh14 deficient hearts compared to controls.
Spontaneous Microalgae Dewatering Directed by Retrievable, Recyclable, and Reusable Nanoparticle-Pinched Polymer Brushes
CHEMISTRY OF MATERIALS
Authors: Kuang, Liangju; Goins, Jason; Zheng, Wan; Eduafo, Patrick; Ma, Hairong; Posewitz, Matthew; Wu, David T.; Liang, Hongjun
Abstract
Selective capture and separation of solution borne planktonic cells is a ubiquitous challenge in diverse fields ranging from biofilm mitigation, cancer diagnostics, and water treatment to microalgae biofuels. Microalgae are promising feedstocks for carbon-neutral biofuels that will alleviate our repentant dependency on fossil fuels, but current technologies for dewatering microalgae add a prohibitive cost to the final products. We report here a nanoparticle-pinched polymer brush (NPPB) design that transforms ordinary polymer flocculants into supercoagulants by mimicking bacterial outer membrane vesicles in promoting bacteria coaggregation. Importantly, the NPPBs are retrievable via cost-effective magnetophoretic separation, recyclable after algae oil extraction and residual biomass removal, and reusable for repeated cycles of operations that significantly reduces the endless material cost of flocculants and their potential contamination of downstream processes and the environment. Using DLVO and self-consistent field theory to model the colloidal stability of microalgae and the dynamic response of polymer brushes, respectively, we reveal a fundamental transition from conventional chain-like polymer flocculants to NPPBs in modulating the interalgae pair potentials. Unlike the chain-like polymer flocculants that only induce slow microalgae dewatering with dose-sensitive flocculation dissociation equilibria, NPPBs direct rapid and irreversible microalgae coagulation. Although a minimum brush size on the NPPBs is predicted to initiate the coagulation, the benefit of increasing brush size quickly wanes and there is an optimal brush size beyond which the coagulation efficiency plateaus, which is consistent with our experimental observations. We anticipate that the concept of retrievable, recyclable, and reusable NPPBs is adaptable for capturing a broad range of live cells in solution.