PTP1B triggers integrin-mediated repression of myosin activity and modulates cell contractility

Cell contractility and migration by integrins depends on precise regulation of protein tyrosine kinase and Rho-family GTPase activities in specific spatiotemporal patterns. Here we show that protein tyrosine phosphatase PTP1B cooperates with β3 integrin to activate the Src/FAK signalling pathway which represses RhoAmyosin- dependent contractility. Using PTP1B null (KO) cells and PTP1B reconstituted (WT) cells, we determined that some early steps following cell adhesion to fibronectin and vitronectin occurred robustly in WT cells, including aggregation of β3 integrins and adaptor proteins, and activation of Src/FAK-dependent signalling at small puncta in a lamellipodium. However, these events were significantly impaired in KO cells. We established that cytoskeletal strain and cell contractility was highly enhanced at the periphery of KO cells compared to WT cells. Inhibition of the Src/FAK signalling pathway or expression of constitutive active RhoA in WT cells induced a KO cell phenotype. Conversely, expression of constitutive active Src or myosin inhibition in KO cells restored the WT phenotype.We propose that this novel function of PTP1B stimulates permissive conditions for adhesion and lamellipodium assembly at the protruding edge during cell spreading and migration.Fil: González Sánchez Wusener, Ana Elena. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas; ArgentinaFil: González, Angela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas; ArgentinaFil: Nakamura, Fumihiko. Harvard Medical School. Department Of Medicine; Estados UnidosFil: Arregui, Carlos Oscar. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas; Argentin

Robo-advisors: la digitalización y automatización del asesoramiento financiero y la gestión de carteras. Una aproximación jurídica

El análisis de la los Robo-Advisors genera gran interés debido a su rápido desarrollo en los últimos años, la forma en la que se constituyen mediante startsups, su cambio en la cultura empresarial financiera, su innovadora idea de negocio así como la necesidad de un marco jurídico seguro para el desarrollo de su actividad. Los Robo-Advisors suponen una gran competencia para las entidades financieras tradicionales, las cuales se está viendo perjudicadas con la aparición de estas nuevas empresas. El negocio bancario tradicional se ha visto obligado a adoptar diferentes estrategias para poder hacer frente a las misma: desarrollar su propio Robo-advisors, invertir en los mismos o comprarlos. A lo largo del trabajo, se realiza un análisis del modelo de mercado que plantean los Robo-advisors en el sector financiero y de los problemas jurídicos que surgen de su operativa, al no tener expreso reconocimiento legal. Se analiza el estado actual de la cuestión en nuestro país, teniendo presente la reforma que para nuestro Derecho financiero ha supuesto la MiFID II/MiFIR así como el encaje del Robo-advisor en la gestión colectiva de patrimonios y el asesoramiento en materia de inversiones.<br /

Discussion of Energy Metrics for Water Distribution System Assessment: Case Study of the Toronto Network by Rebecca Dziedzic and Bryan W. Karney

[EN] The paper under discussion presents a metric that allows auditing the energy performance of pressurized water networks. This same metric (except for the period used to perform the audit) was already presented by the discussers in this journal (Cabrera et al. 2010). In the discussers opinion, this poses a minor difference from a conceptual point of view. While in the discussers proposal integration was extended to longer periods (days or years) to gain a general understanding of the issue, the paper under discussion uses shorter periods of time similar to those used to analyze network behavior with extended period simulation. The increased time resolution allows delving into greater depth in the assessment as well as developing and comparing different scenarios (e.g., winter versus summer).Cabrera Marcet, E.; Gomez Selles, E.; Cabrera Rochera, E.; Arregui De La Cruz, F. (2016). Discussion of Energy Metrics for Water Distribution System Assessment: Case Study of the Toronto Network by Rebecca Dziedzic and Bryan W. Karney. Journal of Water Resources Planning and Management. 142(11):07016003-1-07016003-3. doi:10.1061/(ASCE)WR.1943-5452.0000721S07016003-107016003-31421

Protocolo de detección de malos tratos a personas mayores

Elaboración de un protocolo de detección de situaciones de malos tratos a personas mayores en el ámbito de la localidad de Ejea de los Caballeros desde una perspectiva social y sanitari

Mapping smooth profile H-plane rectangular waveguide structures to substrate integrated waveguide technology

The guidelines for mapping rectangular waveguide structures to substrate integrated waveguide (SIW) technology are well understood for structures with straight walls. However, the mapping of a smooth profile structure from rectangular waveguide to SIW technology is not trivial and it needs to be carefully studied. A general procedure for mapping any smooth profile H-plane rectangular waveguide structure to SIW technology is proposed. A practical example is also provided and experimentally validated

Pathogenic LRRK2 regulates centrosome cohesion via Rab10/RILPL1-mediated CDK5RAP2 displacement

Mutations in LRRK2 increase its kinase activity and cause Parkinson's disease. LRRK2 phosphorylates a subset of Rab proteins which allows for their binding to RILPL1. The phospho-Rab/RILPL1 interaction causes deficits in ciliogenesis and interferes with the cohesion of duplicated centrosomes. We show here that centrosomal deficits mediated by pathogenic LRRK2 can also be observed in patient-derived iPS cells, and we have used transiently transfected cell lines to identify the underlying mechanism. The LRRK2-mediated centrosomal cohesion deficits are dependent on both the GTP conformation and phosphorylation status of the Rab proteins. Pathogenic LRRK2 does not displace proteinaceous linker proteins which hold duplicated centrosomes together, but causes the centrosomal displacement of CDK5RAP2, a protein critical for centrosome cohesion. The LRRK2-mediated centrosomal displacement of CDK5RAP2 requires RILPL1 and phospho-Rab proteins, which stably associate with centrosomes. These data provide fundamental information as to how pathogenic LRRK2 alters the normal physiology of a cell.We are grateful to Erich Nigg and Francis Barr for providing a variety of constructs and antibodies, and to Dario Alessi for providing various A549 cell lines and MEF cells. We thank LauraMontosa for excellent technical assistance with confocal microscopy. This work was supported by The Michael J. Fox Foundation for Parkinson's research (to S.H.), intramural funding from Rutgers University (to S.H.), the Spanish Ministry of Economy and Competitiveness (SAF2017-89402-R to S.H.), the BBVA Foundation (to S.H., S.A.C., and R.W. M.), the Spanish Ministry of Education, Culture and Sport (FPU12/04367 to J.M. P., FPU15/05233 to A.J. L.O.), and the Spanish Ministry of Science, Innovation and Universities (EST18/00412 to A.J.L. O.)

Fraccionamiento partidario y disciplina política en el gobierno del Partido Nacional

Artículo origina

Selección de árboles Plus de Pinus pinaster tolerantes a Armillaria ostoyae

1 página.-- Trabajo presentado en Vitoria (España) en septiembre-octubre de 2010.Peer reviewe