An asymmetric junctional mechanoresponse coordinates mitotic rounding with epithelial integrity

Epithelia are continuously self-renewed, but how epithelial integrity is maintained during the morphological changes that cells undergo in mitosis is not well understood. Here, we show that as epithelial cells round up when they enter mitosis, they exert tensile forces on neighboring cells. We find that mitotic cell–cell junctions withstand these tensile forces through the mechanosensitive recruitment of the actin-binding protein vinculin to cadherin-based adhesions. Surprisingly, vinculin that is recruited to mitotic junctions originates selectively from the neighbors of mitotic cells, resulting in an asymmetric composition of cadherin junctions. Inhibition of junctional vinculin recruitment in neighbors of mitotic cells results in junctional breakage and weakened epithelial barrier. Conversely, the absence of vinculin from the cadherin complex in mitotic cells is necessary to successfully undergo mitotic rounding. Our data thus identify an asymmetric mechanoresponse at cadherin adhesions during mitosis, which is essential to maintain epithelial integrity while at the same time enable the shape changes of mitotic cells

How useful are prescribing indicators based on the DU90% method to distinguish the quality of prescribing between pharmacotherapy audit meetings with different levels of functioning?

Item does not contain fulltextOBJECTIVES: The objective of the study was to assess the association between the quality of drug prescribing based on three indicator types derived from the DU90% method and different levels of functioning in pharmacotherapy audit meetings (PTAMs). MATERIALS AND METHODS: The level of functioning in PTAMs in 2004 was assessed by a standard questionnaire. Data on prescriptions in 2004 by the GPs participating in the included PTAMs were extracted from the database of the Foundation for Pharmaceutical Statistics. Three types of DU90% indicators were computed for the seven mostly prescribed drug classes. With univariate and multivariate analyses of variance, differences in the results of three types of indicators for each of the seven drug classes were assessed according to the levels of PTAMs. RESULTS: For 84 PTAMs with varying levels of functioning, we found no association between the level of PTAM and the quality of prescribing for any of the indicators within the seven drug classes. In general, results gained of all PTAMs seemed to be high in quality for the aspects measured. CONCLUSIONS: It is difficult to define indicators based on the DU90% method, which can readily distinguish differences in the quality of drug prescribing between PTAMs with different levels of functioning. Indicators for prescribing should specifically meet relevant items in the quality of prescribing for certain drug classes. Items for classification of PTAM levels may need some reconsideration

A motor unit-based model of muscle fatigue

Muscle fatigue is a temporary decline in the force and power capacity of skeletal muscle resulting from muscle activity. Because control of muscle is realized at the level of the motor unit (MU), it seems important to consider the physiological properties of motor units when attempting to understand and predict muscle fatigue. Therefore, we developed a phenomenological model of motor unit fatigue as a tractable means to predict muscle fatigue for a variety of tasks and to illustrate the individual contractile responses of MUs whose collective action determines the trajectory of changes in muscle force capacity during prolonged activity. An existing MU population model was used to simulate MU firing rates and isometric muscle forces and, to that model, we added fatigue-related changes in MU force, contraction time, and firing rate associated with sustained voluntary contractions. The model accurately estimated endurance times for sustained isometric contractions across a wide range of target levels. In addition, simulations were run for situations that have little experimental precedent to demonstrate the potential utility of the model to predict motor unit fatigue for more complicated, real-world applications. Moreover, the model provided insight into the complex orchestration of MU force contributions during fatigue, that would be unattainable with current experimental approaches