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

Simulations of model magnetorheological fluids in squeeze flow mode

A particle-level simulation methodology is proposed to study the squeeze flow behavior of model magnetorheological (MR) fluids. The simulation algorithm takes into account Brownian motion and local field corrections to magnetic interactions of the particles. Simulation results obtained from using different initial configurations, including one single-particle-width chain per simulation box, random or lattice arrangements of preassembled single-particle-width chains as well as randomly dispersed particle suspensions, are compared with experimental data and predictions of a recently developed microscopic model. The assumption of single-particle-width chain structures in the systems has been shown to generate normal stresses larger than those found in experiments and the micromechanical model. However, much better agreement between the simulation and experimental results have been reached when using random initial configurations in the simulations

Magnetite mineralization inside cross-linked protein crystals

Crystallization in confined spaces is a widespread process in nature that also has important implications for the stability and durability of many man-made materials. It has been reported that confinement can alter essential crystallization events, such as nucleation and growth and, thus, have an impact on crystal size, polymorphism, morphology, and stability. Therefore, the study of nucleation in confined spaces can help us understand similar events that occur in nature, such as biomineralization, design new methods to control crystallization, and expand our knowledge in the field of crystallography. Although the fundamental interest is clear, basic models at the laboratory scale are scarce mainly due to the difficulty in obtaining well-defined confined spaces allowing a simultaneous study of the mineralization process outside and inside the cavities. Herein, we have studied magnetite precipitation in the channels of cross-linked protein crystals (CLPCs) with different channel pore sizes, as a model of crystallization in confined spaces. Our results show that nucleation of an Fe-rich phase occurs inside the protein channels in all cases, but, by a combination of chemical and physical effects, the channel diameter of CLPCs exerted a precise control on the size and stability of those Fe-rich nanoparticles. The small diameters of protein channels restrain the growth of metastable intermediates to around 2 nm and stabilize them over time. At larger pore diameters, recrystallization of the Fe-rich precursors into more stable phases was observed. This study highlights the impact that crystallization in confined spaces can have on the physicochemical properties of the resulting crystals and shows that CLPCs can be interesting substrates to study this process

Supporting autonomy in physical education: Perception versus reality.

Esta investigación se centró, por una parte en la percepción de apoyo a la autonomía en las clases de Educación física, que tienen tanto el alumnado como el profesorado, y por otra, en la coherencia entre percepción y la realidad observada en las clases. Se aplicaron dos escalas al profesorado y al alumnado con el objeto de conocer con qué frecuencia se producen comportamientos instructivos favorables al desarrollo de la autonomía, y se observaron y grabaron en video clases impartidas por el profesorado. Los resultados muestran que la frecuencia de los comportamientos instructivos de apoyo a la autonomía durante la intervención de enseñanza es significativamente menor que la percibida por el alumnado y el profesorado. La realidad observada muestra un perfil de profesorado con gran margen de mejora en comportamientos como: calidad de la comunicación, funcionalidad de las tareas, fomento del pensamiento del alumnado, situaciones en las que el alumnado pueda expresar su opinión sobre las tareas y motivación intrínsecaThis investigation, on the one hand it focuses on students´ and teachers´ perception about autonomy support during Physical Education instruction, and on the other hand, in the coherence between perception and reality observed in the classes. Two scales were administered to determine the frequency of instructional behaviors favoring the development of autonomy, and teacher´s classes were observed and videotaped. The results show that the observed frequency of instructional behavior favoring autonomy support during classes is significantly lower than that perceived by students and teachers. The observed reality reveals a teacher profile with room for improvement in behaviors such as: communication quality, task functionality, promotion of students’ thinking, creation of situations in which students can express their opinions of the tasks, and increasing intrinsic motivationEl presente artículo forma parte del estudio realizado con la financiación del proyecto SEJ2007-672687/EDU del Ministerio de Ciencia e Innovació

Hydrodynamic modelling and operational oceanography for oil-spill events in the andalusian coast: a real case study during the fedra accident (October 2008)

Peer Reviewe

Testing the goodness of fit of a hilbertian autoregressive model

The presented methodology for testing the goodness-of-fit of an Autoregressive Hilbertian model (ARH(1) model) provides an infinite-dimensional formulation of the approach proposed in Koul and Stute (1999), based on empirical process marked by residuals. Applying a central and functional central limit result for Hilbert-valued martingale difference sequences, the asymptotic behavior of the formulated H-valued empirical process, also indexed by H, is obtained under the null hypothesis. The limiting process is H-valued generalized (i.e., indexed by H) Wiener process, leading to an asymptotically distribution free test. Consistency is also analyzed. The case of misspecified autocorrelation operator of the ARH(1) process is addressed as well. Beyond the Euclidean setting, this approach allows to implement goodness of fit testing in the context of manifold and spherical functional autoregressive processes

Complicaciones torácicas en un paciente con luxación subclavicular del hombro

Se presenta una paciente de 88 años de edad con una luxación subclavicular de hombro derecho y un traumatismo torácico asociado que incluía fractura de las tres primeras costillas y hemotórax. El traumatismo torácico parecía estar muy estrechamente relacionado con la luxación glenohumeral. El tratamiento de la luxación se efectuó mediante reducción cerrada e inmovilización con vendaje de Gilchrist. El traumatismo del hemitórax derecho requirió toracocentesis en 2 ocasiones e ingreso en la unidad de cuidados intensivos por insuficiencia respiratoria. La evolución fue satisfactoria, estando la paciente asintomática a los 3 meses del traumatismo, con movilidad del hombro prácticamente completa.The case of a 88-year-old women with a subclavicular right shoulder dislocation and concomitant thoracic trauma involving fracture of the three first ribs and hemothorax is reported. The thoracic trauma appeared to be closely related to the shoulder dislocation. Close reduction and Gilchrist's immovilization was the treatment applied to the shoulder dislocation. Right thoracic trauma required evacuation of the hemothorax in two ocasions and inward in the Intensive Care Unit. Three months after trauma, the outcome was satisfactory with almost complete recovery of the shoulder range of motion

Forage allowances offered to pregnant ewes until middle and late gestation: Organ priorities on foetus development

Effect of forage allowance before conception and until mid or late gestation was evaluated for effects on foetal and neonatal weights, carcass, nervous systems, metabolic and reproductive organ weights, body dimensions, and variation in intensity of the effects among organs. Effects of two forage allowances, HFA: high forage allowance (2.9 - 3.8 kg of dry matter (DM)/kg bodyweight (BW)) and LFA: low forage allowance (1.4 - 2.6 kg DM/kg BW) were evaluated from 23 days before conception until 70 or 122 days postpartum. On gestation day 70, nine ewes per treatment, each carrying one male foetus, were euthanized and their foetuses were removed. The foetuses were weighed, their carcass and organ weights were recorded, and their external genitalia dimensions were measured. Nine additional lambs per treatment were euthanized 12 hours after birth and the same data were recorded. Hearts from day 70 LFA foetuses were lighter, their external genitalia were smaller, and their foetal weight tended to be less than in HFA. Newborn lambs from LFA ewes had lighter carcasses, livers, kidneys, adrenal glands and testes, shorter penises, but higher brain to liver weight ratios than in HFA. The cerebellum, brain, and heart weights of LFA and HFA newborn lambs did not differ. Low forage allowance until late gestation influenced both foetal and lamb weights and affected organ weights differentially. Thus, the treatments induced differences in prioritization of nutrients, with the central nervous system receiving the highest priority, and carcass and external genitalia the lowest. Keywords: foetal programming, intrauterine growth restriction, lambs, undernutritio