Myosin-induced F-actin fragmentation facilitates contraction of actin networks.

Mechanical forces play a crucial role in diverse physiological processes, such as cell migration, cytokinesis, and morphogenesis. The actin cytoskeleton generates a large fraction of the mechanical forces via molecular interactions between actin filaments (F-actins) and myosin motors. Recent studies have shown that the common tendency of actomyosin networks to contract into a smaller structure deeply involves F-actin buckling induced by motor activities, fragmentation of F-actins, and the force-dependent unbinding of cross-linkers that inter-connect F-actins. The fragmentation of F-actins was shown to originate from either buckling or tensile force from previous single-molecule experiments. While the role of buckling in network contraction has been studied extensively, to date, the role of tension-induced F-actin fragmentation in network contraction has not been investigated. In this study, we employed in vitro experiments and an agent-based computational model to illuminate when and how the tension-induced F-actin fragmentation facilitates network contraction. Our experiments demonstrated that F-actins can be fragmented due to tensile forces, immediately followed by catastrophic rupture and contraction of networks. Using the agent-based model, we showed that F-actin fragmentation by tension results in distinct rupture dynamics different from that observed in networks only with cross-linker unbinding. Moreover, we found that tension-induced F-actin fragmentation is particularly important for the contraction of networks with high connectivity. Results from our study shed light on an important regulator of the contraction of actomyosin networks which has been neglected. In addition, our results provide insights into the rupture mechanisms of polymeric network structures and bio-inspired materials.

Impact of rehabilitation dose on body mass index change in older acute patients with stroke: a retrospective observational study.

Background: It is established that a low body mass index (BMI) correlates with a diminished home discharge rate and a decline in activities of daily living (ADL) capacity among elderly stroke patients. Nevertheless, there exists a paucity of knowledge regarding strategies to mitigate BMI reduction during the acute phase. This investigation seeks to elucidate the impact of rehabilitation dose, as determined by both physical and occupational therapy, on BMI alterations, positing that a heightened rehabilitation dose could thwart BMI decline. Methods: This retrospective, observational study was conducted in the stroke unit of a university hospital. Enrollees comprised individuals aged ≥65 years, hospitalized for stroke, and subsequently relocated to rehabilitation facilities between January 2019 and November 2020. The percentage change in BMI (%ΔBMI) was calculated based on BMI values at admission and discharge. Multivariate multiple regression analysis was employed to ascertain the influence of rehabilitation dose on %ΔBMI. Results: A total of 187 patients were included in the analysis, of whom 94% experienced a reduction in BMI during acute hospitalization. Following adjustment for sociodemographic and clinical factors, multivariable analyzes revealed a positive association between rehabilitation dose and %ΔBMI (ß = 0.338, p < 0.001). Conclusion: The findings of this study suggest that, in the context of acute stroke treatment, an augmented rehabilitation dose is associated with a diminished decrease in BMI.

Membrane-bound myosin IC drives the chiral rotation of the gliding actin filament around its longitudinal axis.

Myosin IC, a single-headed member of the myosin I family, specifically interacts with anionic phosphatidylinositol 4,5-bisphosphate (PI[4,5]P2) in the cell membrane via the pleckstrin homology domain located in the myosin IC tail. Myosin IC is widely expressed and physically links the cell membrane to the actin cytoskeleton; it plays various roles in membrane-associated physiological processes, including establishing cellular chirality, lipid transportation, and mechanosensing. In this study, we evaluated the motility of full-length myosin IC of Drosophila melanogaster via the three-dimensional tracking of quantum dots bound to actin filaments that glided over a membrane-bound myosin IC-coated surface. The results revealed that myosin IC drove a left-handed rotational motion in the gliding actin filament around its longitudinal axis, indicating that myosin IC generated a torque perpendicular to the gliding direction of the actin filament. The quantification of the rotational motion of actin filaments on fluid membranes containing different PI(4,5)P2 concentrations revealed that the rotational pitch was longer at lower PI(4,5)P2 concentrations. These results suggest that the torque generated by membrane-bound myosin IC molecules can be modulated based on the phospholipid composition of the cell membrane.

Urodynamic effect of vibegron on neurogenic lower urinary tract dysfunction in individuals with spinal cord injury: A retrospective study.

STUDY DESIGN: A Retrospective study. OBJECTIVES: To investigate the effects of vibegron on urodynamic parameters of individuals with spinal cord injury (SCI). SETTING: The National Hospital Organization, Murayama Medical Center, Japan. METHODS: We retrospectively analyzed the urodynamic parameters of 31 individuals with SCI within one year after injury, who were diagnosed with neurogenic lower urinary tract dysfunction (NLUTD) according to a urodynamic study (UDS), and prescribed vibegron between December 2018 and December 2020. Treatment criteria were as follows: cystometric capacity of <200 mL, bladder compliance of <20 mL/cmH2O, and/or presence of detrusor overactivity in the first UDS. We compared urodynamic data before and after vibegron treatment. RESULTS: Vibegron administration increased the maximum cystometric capacity (MCC) (median, from 185.0 to 340.0 mL, P = 0.001), bladder compliance (median, from 8.3 to 20.0 mL/cmH2O, P < 0.001). CONCLUSION: Vibegron therapy improved the bladder capacity and bladder compliance of individuals with NLUTD and SCI.

Visualizing dynamic actin cross-linking processes driven by the actin-binding protein anillin.

Anillin is a type of actin filament cross-linking protein that stabilizes the actin-based contractile ring during cytokinesis. To elucidate the underlying intermolecular interactions between actin filaments and anillin, we utilized total internal reflection fluorescence microscopy (TIRFM) and high-speed atomic force microscopy (Hs-AFM). Single-molecule imaging of anillin using TIRFM showed that anillin exists as monomers with relatively low binding affinity for actin filaments. Real-time imaging of actin filament cross-linking dynamics induced by anillin using Hs-AFM revealed that anillin monomers cross-link with actin filaments at a distance of 8 nm and that the polarity of those filaments is both parallel and antiparallel. These results are consistent with anillin playing a role in actin ring transition in vivo, where it might be responsible for thinning the ring-shaped apolar actin bundles.