Suchergebnisse

In existing studies on leader effectiveness, scholars have focused on the significance of the power distance orientation of followers for transformational leadership. In this study we identified middle-way thinking as a critical contingency for the effectiveness of leaders in China
that reflects idiosyncratic Chinese values. Participants were 304 Chinese employees and their supervisors. Multilevel modeling revealed that middle-way thinking of followers accentuated the positive effect of visionary leadership, the core component of transformational leadership, on the organizational
citizenship behavior of followers. The results also indicate that the power distance orientation of followers had a relatively limited moderating effect on the relationship between organizational citizenship behavior and visionary leadership. In the context of Chinese organizations, our findings
provide insight into the emic middle-way thinking of followers as a meaningful contingency that affects the effectiveness of leadership.

Abstract
Retinoblastoma (Rb) is a type of malignant tumor due to abnormal retinogenesis with biallelic mutations of the RB1 gene. Its pathogenesis has been proposed as a "two-mutation hypothesis" by Knudson since 1971; however, there remain some debates on disease onset sufficiency of the biallelic RB1 mutations. To obtain straightforward evidence for this hypothesis, we investigated whether two-hit mutations of the RB1 gene drive tumorigenesis in patient-induced pluripotent stem cell (hiPSC)-derived human retinal organoids (hROs) and whether single allelic mutation hiPSC-derived hROs exhibit molecular and cellular defects. We generated hiPSCs with a heterozygous germline mutation (RB1m1/wt) from a Rb patient. A second-allele RB1 gene mutation was knocked in to produce compound heterozygous mutations (RB1m1/m2) in the hiPSCs. These two hiPSC lines were independently developed into hROs through a stepwise differentiation. The hiPSC-RB1m1/m2 derived organoids demonstrated tumorigenesis in dishes, consistent with Rb profiles in spatiotemporal transcriptomes, in which developmentally photoreceptor fate-determining markers, CRX and OTX2, were highly expressed in hiPSC-RB1m1/m2 derived hROs. Additionally, ARR3+ maturing cone precursors were co-labeled with proliferative markers Ki67 or PCNA, in agreement with the consensus that human Rb is originated from maturing cone precursors. Finally, we demonstrated that retinal cells of hROs with monoallelic RB1 mutation were abnormal in molecular aspects due to its haploinsufficiency. In conclusion, this study provides straightforward supporting evidence in a way of reverse genetics for "two-hit hypothesis" in the Rb tumorigenesis and opens new avenues for development of early intervention and treatment of Rb.