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Oshima, H.

Publications and source records attributed to Oshima, H..

4 recordsLinked to original sources

Gait transition mechanism from quadrupedal to bipedal locomotion in the Japanese macaque based on inverted pendulum

The ability of non-human primates to transition from quadrupedal to bipedal locomotion offers critical insights into both the evolution of human bipedalism and the principles of complex motor control. While quadrupedal and bipedal gaits in non-human primates have been studied, the dynamic mechanisms underlying the transition between these gaits remain poorly understood. Japanese macaques trained to walk bipedally have been reported to utilize inverted pendulum dynamics to achieve efficient bipedal locomotion. Given the intrinsic instability of inverted pendulum systems, which can induce large changes in movement with minimal control input, we hypothesized that this mechanism also contributes to the gait transition. To test this, we developed a neuromusculoskeletal model of the Japanese macaque that integrates a detailed musculoskeletal structure with a physiologically inspired motor control system. Through forward dynamics simulations, we generated a variety of movement patterns by systematically parameterizing motor commands, including failed transitions that are difficult to capture experimentally. We then applied dynamical systems analysis using on an inverted pendulum model to examine the underlying principles of the transition process. Our results demonstrate that successful gait transitions depend on generating an inverted pendulum motion through appropriate control of the forward step length of one hindlimb. These findings provide mechanistic insights into how Japanese macaques coordinate their complex musculoskeletal systems to perform skilled, full-body movements in the gait transition, offering a deeper understanding of both advanced motor control and the evolution of human bipedalism.

neuroscience↗

Tumor-microvessel on-a-chip reveals sequential intravasation cascade of cancer cell clusters

Circulating tumor cell (CTC) clusters are often detected in blood samples of patients with high-grade tumor and are associated with tumor metastasis and poor prognosis. However, the underlying mechanisms by which CTC clusters are released from primary tumors beyond blood vessel barriers remain unclear. In this study, a three-dimensional (3D) in vitro culture system is developed to visualize tumor intravasation by positioning tumor organoids with distinct genetic backgrounds to surround microvessels. We visualized tumor intravasation in a cluster unit, including collective migration in the collagen gel, vessel co-option, and the release of CTC clusters as one of cluster invasion manners yet reported previously. In addition, our results show that both transforming growth factor-{beta} (TGF-{beta}) expression in tumor cells and subsequent induction of activin expression in endothelium are essential for tumor cell intravasation accompanied with endothelial-to-mesenchymal transition (EndoMT) in microvessels. Our 3D in vitro system can be used to develop therapeutic strategies for tumor metastasis by targeting CTC clusters.

cancer biology↗

Spatiotemporal observation reveals metastatic tumor-driven vascular remodeling as a potential route to polyclonal colonization

Polyclonal metastasis, which arises from clusters of circulating tumor cells, promotes metastasis development and has become a major target of metastasis inhibition. Mouse experiments have clearly verified that nonmetastatic and metastatic tumors coexist and form metastatic nests, but the detailed mechanism of extravasation remains unclear. We established a three-dimensional tumor microvessel model to investigate extravasation between nonmetastatic tumors, metastatic tumors, and mosaic tumor organoids in a mixed state by time-lapse imaging and to determine the sequential steps of the extravasation of tumor cells via vascular remodeling. This comparison revealed a new concept of extravascular invasion via vascular remodeling in metastatic carcinoma. Furthermore, the involvement of liver host cells, the hepatic stellate cells, demonstrated an interaction with metastatic cells to facilitate metastatic foci formation. Moreover, Adam28 was highly expressed exclusively in metastatic tumor cells, suggesting its involvement in vascular remodeling. These results demonstrate the ability of metastatic tumor cells for extravasation in polyclonal metastasis, which may lead to the development of new therapeutic targets.

cancer biology↗

APC mutant cells exploit compensatory chromosome alterations to restore tumour cell fitness

Cancer cells tolerate copy number alterations (CNAs) of genomic regions that are lethal to non-cancer cells. Certain CNAs are preferentially associated with specific cancer types and lineages, but the mechanisms underlying the emergence and selection of specific CNAs remain unclear. Adenomatous polyposis coli (APC) mutations induce mitotic errors, but their impact on tumor evolution remains elusive. We investigated APC function in cultured cells and tumors and found that its loss led to {beta}-catenin accumulation at centrosomes, suppressing its maturation through inhibition of key centrosome regulators, including Aurora kinase A (AURKA) that promotes tumor growth. These defects collectively reduced cellular fitness, leading to impaired mitotic fidelity and delayed cell cycle progression. However, in APC-mutant tumors, AURKA activity was maintained, at least in part, through the amplification of chromosomes harboring AURKA and its activator genes, yet this alone was insufficient to fully restore proliferation: aberrant chromosomal reorganization also emerged and contributed to the adaptive fitness of APC-mutant cells. Such a process of adaptive CNA selection provides a framework for understanding how specific CNAs are selected to counteract disadvantages imposed by genetic alterations during tumor progression, providing one key insight into how specific CNAs are selected in this context.

cell biology↗