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    Implication of transcription factor FOXD2 dysfunction in syndromic congenital anomalies of the kidney and urinary tract (CAKUT)
    (Elsevier B.V., 2024) Riedhammer, K.M.; Nguyen, T.-M.T.; Koşukcu, C.; Calzada-Wack, J.; Li, Y.; Assia, Batzir, N.; Saygılı S.
    Congenital anomalies of the kidney and urinary tract (CAKUT) are the predominant cause for chronic kidney disease below age 30 years. Many monogenic forms have been discovered due to comprehensive genetic testing like exome sequencing. However, disease-causing variants in known disease-associated genes only explain a proportion of cases. Here, we aim to unravel underlying molecular mechanisms of syndromic CAKUT in three unrelated multiplex families with presumed autosomal recessive inheritance. Exome sequencing in the index individuals revealed three different rare homozygous variants in FOXD2, encoding a transcription factor not previously implicated in CAKUT in humans: a frameshift in the Arabic and a missense variant each in the Turkish and the Israeli family with segregation patterns consistent with autosomal recessive inheritance. CRISPR/Cas9-derived Foxd2 knockout mice presented with a bilateral dilated kidney pelvis accompanied by atrophy of the kidney papilla and mandibular, ophthalmologic, and behavioral anomalies, recapitulating the human phenotype. In a complementary approach to study pathomechanisms of FOXD2-dysfunction–mediated developmental kidney defects, we generated CRISPR/Cas9-mediated knockout of Foxd2 in ureteric bud–induced mouse metanephric mesenchyme cells. Transcriptomic analyses revealed enrichment of numerous differentially expressed genes important for kidney/urogenital development, including Pax2 and Wnt4 as well as gene expression changes indicating a shift toward a stromal cell identity. Histology of Foxd2 knockout mouse kidneys confirmed increased fibrosis. Further, genome-wide association studies suggest that FOXD2 could play a role for maintenance of podocyte integrity during adulthood. Thus, our studies help in genetic diagnostics of monogenic CAKUT and in understanding of monogenic and multifactorial kidney diseases. © 2023 International Society of Nephrology
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    Trust exploration- and leadership incubation- based opinion dynamics model for social network group decision-making: A quantum theory perspective
    (Elsevier B.V., 2024) Wang, P.; Liu, P.; Li, Y.; Teng, F.; Pedrycz, W.
    Social network (SN) holds significant sway over the consciousness and behavior of involved individuals, serving as an evolutionary medium for opinion dynamics models. Consensus is a fundamental concept in group decision-making (GDM). How to effectively explore the opinion evolution during the consensus-reaching process through SN is of paramount significance for decision-making science. Therefore, a dual-mechanism containing trust exploration and leadership incubation is developed for modeling opinion dynamics, creating a favorable condition for achieving consensus. First, a novel mechanism for analyzing the completeness of SN is proposed, encompassing a trust propagation process that considers trust discount and stability, as well as a trust aggregation method grounded by quantum theory. Second, a trust screening rule is discussed to retain the valid indirect trust relationships (TRs), and then a leadership incubation mechanism is developed to promote the effective achievement of consensus opinions in group decision-making. Finally, a numerical study is presented to elucidate the superiority and rationality of the proposed methods, and some simulation experiments and comparative analyses demonstrating the effectiveness and advantages of which are covered. © 2024