Intergovernmental coordination, funding distribution, and performance evaluation must all be improved.

Translocation of the dense nucleus along a gravity vector initiates mechanical remodeling of a cell, but the underlying mechanisms of cytoskeletal network and focal adhesion complex (FAC) reorganization in a mammalian cell remain unclear. We quantified the remodeling of an MC3T3-E1 cell placed in upward-, downward-, or edgeon-orientated substrate. Nucleus longitudinal translocation presents a high value in downward orientation at 24 h or in edge-on orientation at 72 h, which is consistent with orientation-dependent distribution of perinuclear actin stress fibers and vimentin cords. Redistribution of total FAC area and fractionized super mature adhesion number coordinates this dependence at short duration. This orientation-dependent remodeling is associated with nucleus flattering and lamin A/C phosphorylation. Actin depolymerization or Rho-associated protein kinase signaling inhibition abolishes the orientation dependence of nucleus translocation, whereas tubulin polymerization inhibition or vimentin disruption reserves the dependence. A biomechanical model is therefore proposed for integrating the mechanosensing of nucleus translocation with cytoskeletal remodeling and FAC reorganization induced by a gravity vector.-Zhang, C., Zhou, L., Zhang, F., Lü, D., Li, N., Zheng, L., Xu, Y., Li, Z., Sun, S., Long, M. Mechanical remodeling of normally-sized mammalian cells under gravity vector. FASEB J. 31, 000-000 (2017). www.fasebj.org KEY WORDS: gravity-directed • mechanosensing • nucleus translocation • cytoskeletal remodeling • FAC reorganization Cells on Earth are subject to a variety of mechanical forces, including gravity. Statolith, or amyloplast, has long been assumed to be a gravity receptor for plant species to sense, transduce, and respond to altered gravity (1); however, little is known about mechanisms that underlie gravisensing and gravitransduction in mammalian cells, even though a body of evidence confirms the effect of gravity on their biological responses (2). Conceptual studies have indicated that the spreading and mitosis of normally sized (;10 1 mm) mammalian cells are sensitive to the change in gravity vector. For example, randomizing the direction of gravity has no effect on the division orientation of Chinese hamster ovary cells that are point-attached in a vertical plane (3). Inversion of culture substrate cannot alter the number and function of attached osteoblasts, even though an immediate response-diminished viable osteoblast number-is observed in sparse, early cultures (4). Cell area, nucleus translocation, cell cycle, and F-actin reorganization vary significantly in a duration-dependent manner when Ros 17/2.8 cells make up a monolayer and are spread on downward-or edge-on-orientated substrate compared with those on an upward orientation (5). More quantitative analysis is observed in large-sized Xenopus oocytes (;1 mm), where the nucleolus sedimentation is dominant compared with the thermal fluctuation at gravity potential . thermal energy scale (6), which implies that the sediment...

Osteosarcoma (OS) is the most common malignant primary bone tumor disease. HIF-1α was predicted to be the target gene of microRNA-20b (miR-20b). The present study was designed to illustrate the effect of miR-20b in regulating osteosarcoma via targeting HIF-1α. In this study, we found that the expression of HIF-1α was significantly increased, while miR-20b obviously decreased in OS patients and OS cell lines compared with healthy controls. Moreover, the luciferase report confirmed the targeting reaction between miR-20b and HIF-1α. Additionally, the overexpression of miR-20b suppressed the invasion and growth of both MG63 and U2OS cells, and inhibited the expressions of HIF-1α and VEGF pathway proteins, while the inhibition of miR-20b led to the reverse results. Furthermore, the overexpression of HIF-1α affected the suppression effect of miR-20b in MG63 cells, indicating that miR-20b suppresses the tumor cell process via inhibiting the expression of HIF-1α. Taken together, our results suggest that the upregulation of miR-20b affects the expression of HIF-1α, downregulates the VEGF pathway proteins, and suppresses cell invasion and proliferation rate. These results provide a potential therapeutic strategy for osteosarcoma.

Prior research has shown that humility in the workplace can provide many advantages. However, the literature has largely focused on leaders rather than employees. There is an important distinction between the two, because leaders have already achieved professional success that may or may not be due to humility (i.e., survivorship bias), whereas employees may feel pressure to focus on behaviors seemingly at odds with humility (i.e., getting ahead). Drawing on the social capital theory of career success, this study investigates whether and how humility helps employees achieve both short‐term (job performance) and long‐term (promotability) job success. We posit that, in the Chinese context, humility can promote employees’ objective job performance and promotability by accessing social resources from team leaders and coworkers. The beneficial effects can be explained by the mediating effects of leader–member exchange and employee advice network centrality. We conducted a path comparison on the relationship between the mediators and career success to further explain the mechanisms, and tested the model using a three‐wave survey with a sample of 689 employees and their leaders from 137 teams. Our findings largely support our theoretical predictions and extend our understanding of employee humility and career development.

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The purpose of the present study was to evaluate the effects of serum-starvation, contact-inhibition and roscovitine treatments on cell-cycle synchronization at the G0/G1 stage of ear skin fibroblasts isolated from transgenic cloned cattle. The developmental competence of re-cloned embryos was also examined. Our results showed that the proportion of G0/G1 cells from the serum-starved group at 3, 4 or 5 days was significantly higher compared with 1 or 2 days only (91.5, 91.7 and 93.5% versus 90.1 and 88.8%, respectively, p < 0.05); whilst there was no statistical difference among cells at 3, 4 or 5 days. For roscovitine-treated cells, the proportion of G0/G1 cells at 2, 3, 4 or 5 days was significantly higher than those treated for 1 day only (91.1, 90.1, 89.4 and 91.3% versus 86.51%, respectively, p < 0.05). The proportion of contact-inhibited G0/G1 cells rose significantly with treatment time, but was similar at 3, 4 and 5 days (89.4, 90.4, 91.4, 91.6 and 92.1%, respectively, p < 0.05). The efficiency of obtaining G0/G1 phase cells was lower when roscovitine treatment was employed to synchronize the cell cycle compared with the serum-starvation and contact-inhibition methods (89.7 versus 91.1% and 91.0%, p < 0.05). Moreover, obvious differences were observed in the rate of fused couplets and blastocysts (89.88 +/- 2.70 versus 87.40 +/- 5.13; 44.10 +/- 8.62 versus 58.38 +/- 13.28, respectively, p < 0.05), when nuclear transfer embryos were reconstructed using donors cells that had been serum starved or contact inhibited for 3 days. Our data indicate that 3 day treatment is feasible for harvesting sufficient G0/G1 cells to produce re-cloned transgenic bovine embryos, regardless of whether serum-starvation, contact-inhibition or roscovitine treatments are used as the synchronization methods.