Dynamics of Mechanical Signal Transmission through Prestressed Stress Fibers

Transmission of mechanical stimuli through the actin cytoskeleton has been proposed as a mechanism for rapid long-distance mechanotransduction in cells; however, a quantitative understanding of the dynamics of this transmission and the physical factors governing it remains lacking. Two key features of the actin cytoskeleton are its viscoelastic nature and the presence of prestress due to actomyosin motor activity. We develop a model of mechanical signal transmission through prestressed viscoelastic actin stress fibers that directly connect the cell surface to the nucleus. The analysis considers both temporally stationary and oscillatory mechanical signals and accounts for cytosolic drag on the stress fibers. To elucidate the physical parameters that govern mechanical signal transmission, we initially focus on the highly simplified case of a single stress fiber. The results demonstrate that the dynamics of mechanical signal transmission depend on whether the applied force leads to transverse or axial motion of the stress fiber. For transverse motion, mechanical signal transmission is dominated by prestress while fiber elasticity has a negligible effect. Conversely, signal transmission for axial motion is mediated uniquely by elasticity due to the absence of a prestress restoring force. Mechanical signal transmission is significantly delayed by stress fiber material viscosity, while cytosolic damping becomes important only for longer stress fibers. Only transverse motion yields the rapid and long-distance mechanical signal transmission dynamics observed experimentally. For simple networks of stress fibers, mechanical signals are transmitted rapidly to the nucleus when the fibers are oriented largely orthogonal to the applied force, whereas the presence of fibers parallel to the applied force slows down mechanical signal transmission significantly. The present results suggest that cytoskeletal prestress mediates rapid mechanical signal transmission and allows temporally oscillatory signals in the physiological frequency range to travel a long distance without significant decay due to material viscosity and/or cytosolic drag

Serum screening with Down's syndrome markers to predict pre-eclampsia and small for gestational age: Systematic review and meta-analysis

<p>Abstract</p> <p>Background</p> <p>Reliable antenatal identification of pre-eclampsia and small for gestational age is crucial to judicious allocation of monitoring resources and use of preventative treatment with the prospect of improving maternal/perinatal outcome. The purpose of this systematic review was to determine the accuracy of five serum analytes used in Down's serum screening for prediction of pre-eclampsia and/or small for gestational age.</p> <p>Methods</p> <p>The data sources included Medline, Embase, Cochrane library, Medion (inception to February 2007), hand searching of relevant journals, reference list checking of included articles, contact with experts. Two reviewers independently selected the articles in which the accuracy of an analyte used in Downs's serum screening before the 25^thgestational week was associated with the occurrence of pre-eclampsia and/or small for gestational age without language restrictions. Two authors independently extracted data on study characteristics, quality and results.</p> <p>Results</p> <p>Five serum screening markers were evaluated. 44 studies, testing 169,637 pregnant women (4376 pre-eclampsia cases) and 86 studies, testing 382,005 women (20,339 fetal growth restriction cases) met the selection criteria. The results showed low predictive accuracy overall. For pre-eclampsia the best predictor was inhibin A>2.79MoM positive likelihood ratio 19.52 (8.33,45.79) and negative likelihood ratio 0.30 (0.13,0.68) (single study). For small for gestational age it was AFP>2.0MoM to predict birth weight < 10^thcentile with birth < 37 weeks positive likelihood ratio 27.96 (8.02,97.48) and negative likelihood ratio 0.78 (0.55,1.11) (single study). A potential clinical application using aspirin as a treatment is given as an example.</p> <p>There were methodological and reporting limitations in the included studies thus studies were heterogeneous giving pooled results with wide confidence intervals.</p> <p>Conclusion</p> <p>Down's serum screening analytes have low predictive accuracy for pre-eclampsia and small for gestational age. They may be a useful means of risk assessment or of use in prediction when combined with other tests.</p

Dilemmas Of Downsizing During the Great Recession: Crisis Strategies of European Employers

Summary The present paper analyzes the choices faced by European employers when threatened with the prospect of the mass lay-off of their employees as a result of the Great Recession. By means of a representative survey among employers in Italy, Germany, Denmark, Poland, the Netherlands and Sweden in 2009, we show that employers mainly prefer to tackle such threats by offering short-time work, and by early retirement packages to older workers, in conjunction with buy-outs. The latter preference is particularly visible in countries where employers perceive the level of employment protection to be high. The only notable exception is Denmark, where employers prefer to reduce working hours. In general, a sense of generational fairness influences downsizing preferences, with those employers who favor younger workers particularly likely to use early retirement and buy-outs when downsizing, followed by working time reductions. Wage reductions and administrative dismissal are less favored by European employers. In particular, CEOs and owners are more inclined than lower-level managers to cut wages