Caveolin-1 Modulates Mechanotransduction Responses to Substrate Stiffness through Actin-Dependent Control of YAP

The transcriptional regulator YAP orchestrates many cellular functions, including tissue homeostasis, organ growth control, and tumorigenesis. Mechanical stimuli are a key input to YAP activity, but the mechanisms controlling this regulation remain largely uncharacterized. We show that CAV1 positively modulates the YAP mechanoresponse to substrate stiffness through actin-cytoskeleton-dependent and Hippo-kinase-independent mechanisms. RHO activity is necessary, but not sufficient, for CAV1-dependent mechanoregulation of YAP activity. Systematic quantitative interactomic studies and image-based small interfering RNA (siRNA) screens provide evidence that this actin-dependent regulation is determined by YAP interaction with the 14-3-3 protein YWHAH. Constitutive YAP activation rescued phenotypes associated with CAV1 loss, including defective extracellular matrix (ECM) remodeling. CAV1-mediated control of YAP activity was validated in vivo in a model of pancreatitis-driven acinar-to-ductal metaplasia. We propose that this CAV1-YAP mechanotransduction system controls a significant share of cell programs linked to these two pivotal regulators, with potentially broad physiological and pathological implications. Moreno-Vicente et al. report that CAV1, a key component of PM mechanosensing caveolae, mediates adaptation to ECM rigidity by modulating YAP activity through the control of actin dynamics and phosphorylation-dependent interaction of YAP with the 14-3-3-domain protein YWHAH. Cav1-dependent YAP regulation drives two pathophysiological processes: ECM remodeling and pancreatic ADM. © 2018 The Author

Optimal streaks in a Falkner-Skan boundary layer

This paper deals with the optimal streaky perturbations (which maximize the perturbed energy growth) in a wedge flow boundary layer. These three dimensional perturbations are governed by a system of linearized boundary layer equations around the Falkner-Skan base flow. Based on an asymptotic analysis of this system near the free stream and the leading edge singularity, we show that for acute wedge semi-angle, all solutions converge after a streamwise transient to a single streamwise-growing solution of the linearized equations, whose initial condition near the leading edge is given by an eigenvalue problem first formulated in this context by Tumin (2001). Such a solution may be regarded as a streamwise evolving most unstable streaky mode, in analogy with the usual eigenmodes in strictly parallel flows, and shows an approximate self-similarity, which was partially known and is completed in this paper. An important consequence of this result is that the optimization procedure based on the adjoint equations heretofore used to define optimal streaks is not necessary. Instead, a simple low-dimensional optimization process is proposed and used to obtain optimal streaks. Comparison with previous results by Tumin and Ashpis (2003) shows an excellent agreement. The unstable streaky mode exhibits transient growth if the wedge semi-angle is smaller than a critical value that is slightly larger than $\pi/6$, and decays otherwise. Thus the cases of right and obtuse wedge semi-angles exhibit less practical interest, but they show a qualitatively different behavior, which is briefly described to complete the analysis

Game species: extinction hidden by census numbers

Management of game species may involve a risk of alteration of their genetic properties. Local adaptations may be disrupted if artificially selected individuals from farms or those belonging to distant geographical areas are introduced to increase population density or trophy ‘quality’. In Spain, red deer (Cervus elaphus) from different European subspecies have been introduced to increase the size of trophies (antlers) of local populations. Legislation against these introductions is not effective for various reasons, and once the individuals are in the Iberian peninsula it is virtually impossible to prevent their spreading throughout the whole territory without a genetic tool to distinguish between autochthonous and foreign specimens. We have developed such a genetic test and propose a strategy to dissuade land-owners from importing foreign deer. Since deer are bred mainly for their antlers, our strategy is based on an agreement with the National Trophy Body in Spain which rejects trophies from foreign populations. Rejection decreases the value of the trophy so that it becomes more profitable to produce autochthonous deer. Using such a strategy at some critical step in the production or commercialisation process may be a good model to apply in protecting genetic properties of exploited species

Especies de caza: procesos de extinción ocultos tras elevados tamaños de censo

Management of game species may involve a risk of alteration of their genetic properties. Local adaptations may be disrupted if artificially selected individuals from farms or those belonging to distant geographical areas are introduced to increase population density or trophy “quality”. In Spain, red deer (Cervus elaphus) from different European subspecies have been introduced to increase the size of trophies (antlers) of local populations. Legislation against these introductions is not effective for various reasons, and once the individuals are in the Iberian peninsula it is virtually impossible to prevent their spreading throughout the whole territory without a genetic tool to distinguish between autochthonous and foreign specimens. We have developed such a genetic test and propose a strategy to dissuade land–owners from importing foreign deer. Since deer are bred mainly for their antlers, our strategy is based on an agreement with the National Trophy Body in Spain which rejects trophies from foreign populations. Rejection decreases the value of the trophy so that it becomes more profitable to produce autochthonous deer. Using such a strategy at some critical step in the production or commercialization process may be a good model to apply in protecting genetic properties of exploited species.La gestión de las especies de caza puede conllevar riesgos de alteración de sus propiedades genéticas. Las adaptaciones locales pueden deteriorarse si ejemplares producidos mediante selección artificial en granjas o procedentes de áreas geográficas distantes, son introducidos para aumentar la densidad poblacional o la "calidad" de los trofeos de caza. En España, se han introducido ejemplares de ciervo ibérico (Cervus elaphus) procedentes de distintas subespecies europeas para aumentar así el tamaño de las cuernas (trofeos de caza) de las poblaciones autóctonas. La legislación contra este tipo de introducciones no es eficaz por diversos motivos y, una vez introducidos los ejemplares en la península ibérica, es prácticamente imposible prevenir su dispersión por todo el territorio sin contar con herramientas genéticas que permitan diferenciar los ejemplares autóctonos de los foráneos. Nosotros hemos desarrollado un test genético para este fin, y hemos propuesto una estrategia para disuadir a lospropietarios de llevar a cabo la importación de ejemplares foráneos. Puesto que los ciervos se crían fundamentalmente por su cornamenta como trofeo de caza, nuestra estrategia se ha basado en un acuerdo con la Junta Nacional de Homologación de Trofeos de Caza, para que ésta rechace los trofeos pertenecientes a ejemplares foráneos. Este rechazo reduce el valor de los ejemplares procedentes de otras poblaciones y favorece la producción de ciervo autóctono. Sugerimos que la utilización de estrategias de este tipo en puntos clave de procesos de producción o comercialización, puede ser un buen modelo a aplicar para proteger las propiedades genéticas de las especies sujetas a explotación por el hombre

On balancedness and D-Completeness of the space of Semi-lipschitz functions

Let (X, d) be a quasi-metric space and (Y, q) be a quasi-normed linear space. We show that the normed cone of semi-Lipschitz functions from (X, d) to (Y, q) that vanish at a point x0 E X, is balanced. Moreover, it is complete in the sense of D. Doitchinov whenever (Y, q) is a biBanach spac

The direct boundary element method: 2D site effects assessment on laterally varying layered media (methodology)

The Direct Boundary Element Method (DBEM) is presented to solve the elastodynamic field equations in 2D, and a complete comprehensive implementation is given. The DBEM is a useful approach to obtain reliable numerical estimates of site effects on seismic ground motion due to irregular geological configurations, both of layering and topography. The method is based on the discretization of the classical Somigliana's elastodynamic representation equation which stems from the reciprocity theorem. This equation is given in terms of the Green's function which is the full-space harmonic steady-state fundamental solution. The formulation permits the treatment of viscoelastic media, therefore site models with intrinsic attenuation can be examined. By means of this approach, the calculation of 2D scattering of seismic waves, due to the incidence of P and SV waves on irregular topographical profiles is performed. Sites such as, canyons, mountains and valleys in irregular multilayered media are computed to test the technique. The obtained transfer functions show excellent agreement with already published results