Genome-wide association and Mendelian randomization study of NT-proBNP in patients with acute coronary syndrome
HUMAN MOLECULAR GENETICS
Authors: Johansson, Asa; Eriksson, Niclas; Lindholm, Daniel; Varenhorst, Christoph; James, Stefan; Syvanen, Ann-Christine; Axelsson, Tomas; Siegbahn, Agneta; Barratt, Bryan J.; Becker, Richard C.; Himmelmann, Anders; Katus, Hugo A.; Steg, Philippe Gabriel; Storey, Robert F.; Wallentin, Lars
Abstract
N-terminal pro-B-type natriuretic peptide (NT-proBNP) is a strong predictor of mortality in coronary artery disease and is widely employed as a prognostic biomarker. However, a causal relationship between NT-proBNP and clinical endpoints has not been established. We have performed a genome-wide association and Mendelian randomization study of NT-proBNP. We used a discovery set of 3740 patients from the PLATelet inhibition and patient Outcomes (PLATO) trial, which enrolled 18 624 patients with acute coronary syndrome (ACS). A further set of 5492 patients, from the same trial, was used for replication. Genetic variants at two novel loci (SLC39A8 and POC1B/GALNT4) were associated with NT-proBNP levels and replicated together with the previously known NPPB locus. The most significant SNP (rs198389, pooled P = 1.07 x 10(-15)) in NPPB interrupts an E-box consensus motif in the gene promoter. The association in SLC39A8 is driven by a deleterious variant (rs13107325, pooled P = 5.99 x 10(-10)), whereas the most significant SNP in POC1B/GALNT4 (rs11105306, pooled P = 1.02 x 10(-16)) is intronic. The SLC39A8 SNP was associated with higher risk of cardiovascular (CV) death (HR = 1.39, 95% CI: 1.08-1.79, P = 0.0095), but the other loci were not associated with clinical endpoints. We have identified two novel loci to be associated with NT-proBNP in patients with ACS. Only the SLC39A8 variant, but not the NPPB variant, was associated with a clinical endpoint. Due to pleotropic effects of SLC39A8, these results do not suggest that NT-proBNP levels have a direct effect on mortality in ACS patients. PLATO Clinical Trial Registration: ; NCT00391872.
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.