1.
Patient-specific mutations impair BESTROPHIN1's essential role in mediating Ca2+-dependent Cl- currents in human RPE.
Li, Y, Zhang, Y, Xu, Y, Kittredge, A, Ward, N, Chen, S, Tsang, SH, Yang, T
eLife. 2017
Abstract
Mutations in the human BEST1 gene lead to retinal degenerative diseases displaying progressive vision loss and even blindness. BESTROPHIN1, encoded by BEST1, is predominantly expressed in retinal pigment epithelium (RPE), but its physiological role has been a mystery for the last two decades. Using a patient-specific iPSC-based disease model and interdisciplinary approaches, we comprehensively analyzed two distinct BEST1 patient mutations, and discovered mechanistic correlations between patient clinical phenotypes, electrophysiology in their RPEs, and the structure and function of BESTROPHIN1 mutant channels. Our results revealed that the disease-causing mechanism of BEST1 mutations is centered on the indispensable role of BESTROPHIN1 in mediating the long speculated Ca2+-dependent Cl- current in RPE, and demonstrate that the pathological potential of BEST1 mutations can be evaluated and predicted with our iPSC-based 'disease-in-a-dish' approach. Moreover, we demonstrated that patient RPE is rescuable with viral gene supplementation, providing a proof-of-concept for curing BEST1-associated diseases.
2.
Coagulation behavior and floc characteristics of a novel composite poly-ferric aluminum chloride-polydimethyl diallylammonium chloride coagulant with different OH/(Fe3+ + Al3+) molar ratios.
Sun, C, Qiu, J, Zhang, Z, Marhaba, TF, Zhang, Y
Water science and technology : a journal of the International Association on Water Pollution Research. 2016;(7):1636-1643
Abstract
In this paper, flocculating performance and mechanisms of a new composite coagulant, poly-ferric aluminum chloride-polydimethyl diallylammonium chloride (PFAC-PD) with different OH-/(Fe3+ + Al3+) molar ratios, were investigated for humic acid (HA)-kaolin synthetic wastewater treatment. The impact of OH-/(Fe3+ + Al3+) molar ratios on the removal efficiencies of turbidity and dissolved organic carbon, specific UV absorbance, coagulation mechanisms and dynamics was explored during the coagulation process using composite coagulants. The coagulation experimental results revealed that the composite coagulants with lower OH-/(Fe3+ + Al3+) molar ratio exhibited better coagulation efficiency. When OH-/(Fe3+ + Al3+) molar ratio of the composite coagulant was 1.5, adsorption-bridging played a dominant role in coagulating HA-kaolin synthetic wastewater. The floc growth rate and floc size, increased with increasing OH-/(Fe3+ + Al3+) molar ratio and the highest peak height of the size distribution was obtained by PFAC-PD with OH-/(Fe3+ + Al3+) = 1.5. Also, the composite coagulants with higher OH-/(Fe3+ + Al3+) molar ratio formed more compact flocs, as reflected by the higher fractal dimension value. The flocs coagulated by PFAC-PD with basicity value of 1.0 gave strong strength and good recoverability.