Tug-of-war between actomyosin-driven antagonistic forces determines the positioning symmetry in cell-sized confinement

細胞内構造の配置対称性が決まる仕組みを解明 --人工細胞と物理学からメカニズムに迫る--. 京都大学プレスリリース. 2020-06-15.The tug-of-war at the heart of cellular symmetry. 京都大学プレスリリース. 2020-06-26.Symmetric or asymmetric positioning of intracellular structures including the nucleus and mitotic spindle steers various biological processes such as cell migration, division, and embryogenesis. In typical animal cells, both a sparse actomyosin meshwork in the cytoplasm and a dense actomyosin cortex underneath the cell membrane participate in the intracellular positioning. However, it remains unclear how these coexisting actomyosin structures regulate the positioning symmetry. To reveal the potential mechanism, we construct an in vitro model composed of cytoplasmic extracts and nucleus-like clusters confined in droplets. Here we find that periodic centripetal actomyosin waves contract from the droplet boundary push clusters to the center in large droplets, while network percolation of bulk actomyosin pulls clusters to the edge in small droplets. An active gel model quantitatively reproduces molecular perturbation experiments, which reveals that the tug-of-war between two distinct actomyosin networks with different maturation time-scales determines the positioning symmetry

Renoprotective Effects of DPP-4 Inhibitors

Diabetic kidney disease (DKD) is the leading cause of end-stage renal disease (ESRD) worldwide. Dipeptidyl peptidase (DPP)-4 inhibitors are widely used in the treatment of patients with type 2 diabetes (T2D). DPP-4 inhibitors reduce glucose levels by inhibiting degradation of incretins. DPP-4 is a ubiquitous protein with exopeptidase activity that exists in cell membrane-bound and soluble forms. It has been shown that an increased renal DPP-4 activity is associated with the development of DKD. A series of clinical and experimental studies showed that DPP-4 inhibitors have beneficial effects on DKD, independent of their glucose-lowering abilities, which are mediated by anti-fibrotic, anti-inflammatory, and anti-oxidative stress properties. In this review article, we highlight the current understanding of the clinical efficacy and the mechanisms underlying renoprotection by DPP-4 inhibitors under diabetic conditions

Additional file 1: of Reduced vascular events in type 2 diabetes by biguanide relative to sulfonylurea: study in a Japanese Hospital Database

Details of antihypertensive drugs andanti-dyslipidemia drugs used for subjects in study 1. (PPTX 70 kb