Animal cell cytokinesis results from patterned activation of the small GTPase Rho, which directs assembly of actomyosin in the equatorial cortex. Cytokinesis is restricted to a portion of the cell cycle following anaphase onset in which the cortex is responsive to signals from the spindle. We show that shortly after anaphase onset oocytes and embryonic cells of frogs and echinoderms exhibit cortical waves of Rho activity and F-actin polymerization. The waves are modulated by cyclin-dependent kinase 1 (Cdk1) activity and require the Rho GEF (guanine nucleotide exchange factor), Ect2. Surprisingly, during wave propagation, while Rho activity elicits F-actin assembly, F-actin subsequently inactivates Rho. Experimental and modeling results show that waves represent excitable dynamics of a reaction diffusion system with Rho as the activator and F-actin the inhibitor. We propose that cortical excitability explains fundamental features of cytokinesis including its cell cycle regulation.

Cell repair is attracting increasing attention due to its conservation, its importance to health, and its utility as a model for cell signaling and cell polarization. However, some of the most fundamental questions concerning cell repair have yet to be answered. Here we consider three such questions: 1) How are wound holes stopped? 2) How is cell regeneration achieved after wounding? 3) How is calcium inrush linked to wound stoppage and cell regeneration?

Rho GTPases such as Rho, Rac and Cdc42 are important regulators of the cortical cytoskeleton in processes including cell division, locomotion and repair. In these processes, Rho GTPases assume characteristic patterns wherein the active GTPases occupy mutually exclusive “zones” in the cell cortex. During cell wound repair, for example, a Rho zone encircles the wound edge and is in turn encircled by a Cdc42 zone. Here we evaluated the contributions of crosstalk between Rho and Cdc42 to the patterning of their respective zones in wounded Xenopus oocytes using experimental manipulations in combination with mathematical modeling. The results show that the position of the Cdc42 zone relative the Rho zone and relative to the wound edge is controlled by the level of Rho activity. In contrast, the outer boundary of the Rho zone is limited by the level of Cdc42 activity. Models based on positive feedback within zones and negative feedback from Rho to the GEF-GAP Abr to Cdc42 capture some, but not all, of the observed behaviors. We conclude that GTPase zone positioning is controlled at the level of Rho activity and we speculate that the Cdc42 zone or something associated with it limits the spread of Rho activity. [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text]

Early innate education of hematopoietic progenitors within the bone marrow (BM) stably primes them for either trained immunity or instead immunoregulatory functions. We herein demonstrate that in vivo or in vitro activation within the BM via Toll-like receptor-9 generates a population of plasmacytoid dendritic cell (pDC) precursors (CpG-pre-pDCs) that, unlike pDC precursors isolated from PBS-incubated BM (PBS-pre-pDCs), are endowed with the capacity to halt progression of ongoing experimental autoimmune encephalomyelitis. CpG activation enhances the selective migration of pDC precursors to the inflamed spinal cord, induces their immediate production of TGF-β, and after migration, of enhanced levels of IL-27. CpG-pre-pDC derived TGF-β and IL-27 ensure protection at early and late phases of the disease, respectively. Spinal cords of CpG-pre-pDC-protected recipient mice display enhanced percentages of host-derived pDCs expressing TGF-β as well as an accumulation of IL-10 producing B cells and of CD11c+ CD11b+ dendritic cells. These results reveal that pDC precursors are conferred stable therapeutic properties by early innate activation within the BM. They further extend to the pDC lineage promising perspectives for cell therapy of autoimmune diseases with innate activated hematopoietic precursor cells.

INTRODUCTION:This study sought to determine whether a decentralized, mobile-friendly, virtual model could achieve appropriate enrollment for a pregnancy health study after COVID-19 closed most clinical research. Preterm birth continues to be a significant and growing issue with 2021 rates exceeding 10%. There is urgent need for new research and technology to improve the ability to predict, prevent, and personalize treatment for complications such as preterm birth, preeclampsia, and gestational diabetes.METHODS:This was a prospective, observational study of a cell-free RNA platform utilizing direct-to-participant recruitment via targeted social media from July 2020 to December 2021. The IRB-approved study was open to patients aged 18–45 with a singleton pregnancy in the United States. Participants signed informed consent, provided record release forms, completed a short questionnaire, and scheduled mobile phlebotomy via a web-based platform.RESULTS:One thousand eight hundred ninety-four participants submitted samples in less than 18 months. Because of delays in shipping, insufficient volume, temperature stability, and hemolysis, 63 samples (3.3%) were not useable. Medical records were received for over 85% of participants. The cohort is geographically and ethnically diverse representing 1,220 zip codes across 30 states.CONCLUSION:This work demonstrates a decentralized, mobile-friendly, virtual study is feasible, efficient, scalable, and flexible, enabling clinical research during a global pandemic. The rate of medical records receipt is likely affected by the large quantity of unique providers and hospitals. This is a rapid, patient-accepted way to conduct clinical research as a supplement to traditional enrollment models.