Mechanotransduction via endothelial adhesion molecule CD31 initiates transmigration and reveals a role for VEGFR2 in diapedesis.

Engagement of platelet endothelial cell adhesion molecule 1 (PECAM, PECAM-1, CD31) on the leukocyte pseudopod with PECAM at the endothelial cell border initiates transendothelial migration (TEM, diapedesis). We show, using fluorescence lifetime imaging microscopy (FLIM), that physical traction on endothelial PECAM during TEM initiated the endothelial signaling pathway. In this role, endothelial PECAM acted as part of a mechanotransduction complex with VE-cadherin and vascular endothelial growth factor receptor 2 (VEGFR2), and this predicted that VEGFR2 was required for efficient TEM. We show that TEM required both VEGFR2 and the ability of its Y1175 to be phosphorylated, but not VEGF or VEGFR2 endogenous kinase activity. Using inducible endothelial-specific VEGFR2-deficient mice, we show in three mouse models of inflammation that the absence of endothelial VEGFR2 significantly (by ≥75%) reduced neutrophil extravasation by selectively blocking diapedesis. These findings provide a more complete understanding of the process of transmigration and identify several potential anti-inflammatory targets.

Juegos pequeños con nociones de ajedrez para el desarrollo de las habilidades motrices básicas en la Educación Física

El juego es una forma natural de aprender, ya que incluye elementos de aprendizaje en interacción con lo lúdico. Específicamente el juego de ajedrez, se aplica en el sistema educativo de algunos países como un instrumento multidisciplinario, pues ayuda en el desarrollo del pensamiento cognitivo, la planificación, la imaginación, la anticipación, el autocontrol, la toma de decisiones, la creatividad y la inteligencia. En ese sentido, los profesores de Educación Física del 2do grado de la Escuela Primaria 1728, en el barrio Tchioco, en Lubango presentaron dificultades en la aplicación de métodos que permitan el desarrollo de las habilidades motrices básicas de manera atractiva a sus alumnos. De ahí que el objetivo de esta investigación consistió en proponer juegos pequeños con nociones de ajedrez para el mejoramiento de las habilidades motrices básicas, en los alumnos antes mencionados. Para ello, se efectuó un estudio descriptivo, no experimental, de corte transversal y se emplearon métodos científicos del nivel teórico como el analítico-sintético, inducción-deducción, histórico-lógico y funcional-sistémico-estructural y del nivel empírico como la revisión de documentos, la observación y la entrevista; así como el cálculo porcentual para el análisis de los datos arrojados. Los resultados obtenidos permitieron caracterizar el estado de desarrollo del objetivo propuesto y adecuar la propuesta de juegos elaborada.

SÍNTESE O jogo é uma forma natural de aprendizagem, pois inclui elementos de aprendizagem em interação com o jogo. Especificamente, o jogo de xadrez é aplicado no sistema educacional de alguns países como um instrumento multidisciplinar, pois ajuda no desenvolvimento do pensamento cognitivo, planejamento, imaginação, antecipação, autocontrole, tomada de decisões, criatividade e inteligência. Neste sentido, os professores de Educação Física da 2ª série do Ensino Fundamental 1728, no bairro de Tchioco, em Lubango, apresentaram dificuldades na aplicação de métodos que permitem o desenvolvimento de habilidades motoras básicas de forma atrativa para seus alunos. Assim, o objetivo desta pesquisa consistiu em propor pequenas partidas com noções de xadrez para a melhoria das habilidades motoras básicas dos alunos acima mencionados. Para este fim, foi realizado um estudo descritivo, não-experimental, transversal e descritivo e foram utilizados métodos científicos a nível teórico, tais como analítico-sintético, indução-dedução, histórico-lógico e funcional-sistêmico-estrutural, e a nível empírico, tais como revisão de documentos, observação e entrevista, bem como cálculo percentual para a análise dos dados obtidos. Os resultados obtidos tornaram possível caracterizar o estado de desenvolvimento do objetivo proposto e adaptar a proposta de jogo elaborada.

The game is a natural way of learning, since it includes elements of learning in interaction with play. Specifically, the game of chess is applied in the educational system of some countries as a multidisciplinary instrument, since it helps in the development of cognitive thinking, planning, imagination, anticipation, self-control, decision-making, creativity and intelligence. In this sense, the Physical Education teachers of the 2nd grade of the 1728 Elementary School, in the Tchioco neighborhood, in Lubango presented difficulties in the application of methods that allow the development of basic motor skills in an attractive way for their students. Hence, the objective of this research was to propose small games with notions of chess for the improvement of basic motor skills in the aforementioned students. For this, a descriptive, non-experimental, cross-sectional study was carried out and scientific methods were used at the theoretical level such as analytical-synthetic, induction-deduction, historical-logical and functional-systemic-structural and at the empirical level such as the review of documents, observation and interview; as well as the percentage calculation for the analysis of the data obtained. The results obtained allowed to characterize the state of development of the proposed objective and to adapt the proposal of games elaborated.

Circadian regulator CLOCK promotes tumor angiogenesis in glioblastoma.

Glioblastoma (GBM) is one of the most aggressive tumors in the adult central nervous system. We previously revealed that circadian regulation of glioma stem cells (GSCs) affects GBM hallmarks of immunosuppression and GSC maintenance in a paracrine and autocrine manner. Here, we expand the mechanism involved in angiogenesis, another critical GBM hallmark, as a potential basis underlying CLOCK's pro-tumor effect in GBM. Mechanistically, CLOCK-directed olfactomedin like 3 (OLFML3) expression results in hypoxia-inducible factor 1-alpha (HIF1α)-mediated transcriptional upregulation of periostin (POSTN). As a result, secreted POSTN promotes tumor angiogenesis via activation of the TANK-binding kinase 1 (TBK1) signaling in endothelial cells. In GBM mouse and patient-derived xenograft models, blockade of the CLOCK-directed POSTN-TBK1 axis inhibits tumor progression and angiogenesis. Thus, the CLOCK-POSTN-TBK1 circuit coordinates a key tumor-endothelial cell interaction and represents an actionable therapeutic target for GBM.

Los componentes de la condición física, su relación con el estado de salud en estudiantes universitarios / As componentes da aptidão física, a sua relação com o estado de saúde nos estudantes universitários / The components of physical fitness, its relationship to health status in universities students

RESUMEN El presente artículo pretende interiorizar la importancia y los beneficios de la práctica regular de actividad física. El objetivo de este trabajo consistió en realizar un estudio de los componentes de la condición física relacionada con la salud en los estudiantes de la carrera de Licenciatura en estudios Socio-Culturales de la Universidad de Pinar del Río "Hermanos Saíz Montes de Oca". Se seleccionaron aleatoriamente a 19 estudiantes de primer año de dicha carrera. Se utilizaron los métodos de investigación del nivel teórico y empírico como el análisis de documentos y la medición. Los valores obtenidos, en cuanto al porciento de grasa, indican que el factor de riesgo que conlleva la excesiva acumulación de grasas puede traer como consecuencia la aparición de varias enfermedades crónicas no transmisibles. Además, se evidencia que el 73 % de la muestra investigada presenta deficiencias en la potencia aeróbica máxima, o sea para suministrar el oxígeno necesario a los músculos durante un esfuerzo físico máximo. De manera general, la muestra alcanza un nivel aceptable que les permite mantener un esfuerzo a intensidad media o baja con suficiente aporte de oxígeno. Por ello es necesario el estricto cumplimiento de un plan de acciones que estén orientadas a la modificación de la composición corporal de los estudiantes objeto de estudio.

RESUMO Este artigo visa interiorizar a importância e os benefícios da prática regular da atividade física. O objetivo deste trabalho era realizar um estudo das componentes da condição física relacionadas com a saúde nos alunos do curso de licenciatura em Estudos Sócio-Culturais da Universidade de Pinar del Río "Hermanos Saíz Montes de Oca". Dezanove estudantes do primeiro ano desta carreira foram selecionados de forma aleatória. Foram utilizados métodos teóricos e empíricos de investigação, tais como análise e medição de documentos. Os valores obtidos em termos de percentagem de lípidos indicam que o factor de risco de acumulação excessiva de lípidos pode levar ao aparecimento de várias doenças crónicas não transmissíveis. Além disso, é evidente que 73 % da amostra investigada apresenta deficiências na potência aeróbica máxima, ou seja, para fornecer o oxigénio necessário aos músculos durante um esforço físico máximo. Em geral, a amostra atinge um nível aceitável que lhes permite manter um esforço a média ou baixa intensidade com suficiente fornecimento de oxigénio. Por conseguinte, é necessário o cumprimento rigoroso de um plano de ações orientadas para a modificação da composição corporal dos estudantes em estudo.

ABSTRACT This article aims to internalize the importance and benefits of the regular practice of physical activity. The objective of this work consisted in carrying out a study of the components of health-related physical fitness in students of the Bachelor's Degree in Socio-Cultural Studies of the University of Pinar del Río "Hermanos Saíz Montes de Oca". Nineteen first year students of this career were randomly selected. Theoretical and empirical research methods were used, such as document analysis and measurement. The values obtained, in terms of the percentage of fat, indicate that the risk factor of excessive fat accumulation can lead to the appearance of several chronic non-communicable diseases. In addition, it is evident that 73 % of the investigated sample presents deficiencies in the maximum aerobic power, that is, to supply the necessary oxygen to the muscles during a maximum physical effort. In general, the sample reaches an acceptable level that allows them to maintain an effort at medium or low intensity with sufficient oxygen supply. Therefore, it is necessary to strictly comply with a plan of actions aimed at modifying the body composition of the students under study.

Time-Variant SRC Kinase Activation Determines Endothelial Permeability Response.

In the current model of endothelial barrier regulation, the tyrosine kinase SRC is purported to induce disassembly of endothelial adherens junctions (AJs) via phosphorylation of VE cadherin, and thereby increase junctional permeability. Here, using a chemical biology approach to temporally control SRC activation, we show that SRC exerts distinct time-variant effects on the endothelial barrier. We discovered that the immediate effect of SRC activation was to transiently enhance endothelial barrier function as the result of accumulation of VE cadherin at AJs and formation of morphologically distinct reticular AJs. Endothelial barrier enhancement via SRC required phosphorylation of VE cadherin at Y731. In contrast, prolonged SRC activation induced VE cadherin phosphorylation at Y685, resulting in increased endothelial permeability. Thus, time-variant SRC activation differentially phosphorylates VE cadherin and shapes AJs to fine-tune endothelial barrier function. Our work demonstrates important advantages of synthetic biology tools in dissecting complex signaling systems.

El diagnóstico para el trabajo en equipo en la docencia en Cultura Física / The diagnosis for teamwork in teaching in Physical Culture

RESUMEN La formación integral y contextualizada a la altura de los niveles de desarrollo de la universidad contemporánea, reclama una revolución continua en la formación de su claustro docente, responsable de tan complejo proceso. Con esta investigación se intenta dar respuesta a la necesidad del profesorado de mejorar las estrategias educativas y desempeño profesional. El objetivo entonces fue determinar el nivel de desarrollo del trabajo en equipo en la actuación profesional de los docentes de la Universidad de Ciencias de la Cultura Física y el Deporte «Manuel Fajardo¼. Se inició con un diagnóstico psicopedagógico de los profesores; se aplicaron encuestas a 15 docentes de dicha institución, quienes imparten las asignaturas del ejercicio de la profesión y 111 estudiantes del primer año de la carrera. También se empleó la técnica de IADOV para conocer la satisfacción de los docentes con respecto al trabajo en equipo. Se utilizó la triangulación como método. Como resultado se corroboró la necesidad de la búsqueda de estrategias para la asimilación de la habilidad de trabajo en equipo.

ABSTRACTS Comprehensive and contextualized training at the level of the development levels of contemporary diversity, calls for a continuous revolution in the training of university professors, responsible for such a complex process. With this research we try to respond to the need of teachers to improve educational strategies and their professional performance. The objective of the same was to determine the level of development of teamwork in the professional performance of teachers of the University of Physical Culture and Sport Sciences (UCCFD) «Manuel Fajardo¼. It began with a psycho pedagogical diagnosis of the teachers; surveys were applied to 15 teachers of the UCCFD of the subject of the exercise of the profession and 111 students of the first year of the career, using also the technique of IADOV to know the satisfaction of the teachers with respect to the work in team besides the triangulation by method. As a result, the need to search for strategies for the assimilation of teamwork skills was corroborated.

Targeted Recycling of the Lateral Border Recycling Compartment Precedes Adherens Junction Dissociation during Transendothelial Migration.

Leukocyte transendothelial migration (TEM) requires two major events: local dissociation of adherens junctions manifested as gaps in vascular endothelial (VE)-cadherin staining at the site of TEM and targeted trafficking of the lateral border recycling compartment (LBRC) to the site of TEM. However, the association between LBRC recycling and VE-cadherin gaps remains unknown. We found that when targeting of the LBRC is selectively inhibited using established methods, such as a function blocking anti-platelet endothelial cell adhesion molecule 1 antibody, depolymerizing microtubules, or microinjection of an antibody that inhibits kinesin, VE-cadherin gaps do not form around the blocked leukocyte. This is the first time that the LBRC has been implicated in this process. We obtained similar results for neutrophils and monocytes and in studies using live cell imaging microscopy conducted under fluid shear conditions. Depolymerizing microtubules did not affect the ability of leukocytes to induce tyrosine phosphorylation of VE-cadherin. A VE-cadherin double mutant (Y658F, Y731F) expressed in endothelial cells acted as a dominant negative and inhibited VE-cadherin gap formation and TEM, yet targeting of the LBRC still occurred. These data suggest that targeting of the LBRC to the site of TEM precedes VE-cadherin clearance. Recruitment of the LBRC may play a role in clearing VE-cadherin from the site of TEM.

Factores predisponentes de embarazo en adolescentes de nuevo turumo. Venezuela. 2007- 2008 / Predisponent factors of pregnancy in adolescents of nuevo turumo. Venezuela. 2007-2008

Introducción: el embarazo en la adolescencia es un problema de salud mundial. En el mundo existen más de mil millones de adolescentes que aportan anualmente 15 millones de partos y de ellos 80% son pertenecientes a países en vías de desarrollo. Objetivo: identificar factores predisponentes de embarazo en adolescentes de Nuevo Turumo, Venezuela desde agosto de 2007 a agosto de 2008. Material y Métodos: se realizó un estudio descriptivo de corte transversal con 32 embarazadas adolescentes de Nuevo Turumo desde agosto de 2007 a agosto de 2008 seleccionadas según los criterios de inclusión y exclusión. Se utilizaron métodos teóricos (análisis, síntesis e histórico lógico) y empíricos (entrevista directa). Para el análisis de resultados se utilizó el paquete estadístico SPSS 11.5 y se calcularon frecuencias absolutas y relativas. Resultados: predominaron las embarazadas en la adolescencia tardía; las adolescentes casadas sobre las solteras; la escolaridad correspondió a la secundaria terminada y sin terminar; la menarquia en la adolescencia temprana, inicio de las relaciones sexuales en la adolescencia media; pocos conocimientos y utilización de los métodos anticonceptivos, no vinculación al trabajo. Acceso a los medios de comunicación y tiempo libre dedicado mayormente a la televisión e Internet. Conclusiones: los factores predisponentes de embarazo en las adolescentes de Nuevo Turumo fueron: predominio de secundaria básica terminada como nivel escolar; presencia de la menarquia en la adolescencia temprana; inicio de las relaciones sexuales en la adolescencia media; pocos conocimientos y utilización de los métodos anticonceptivos; no vinculación al trabajo y acceso a los medios de comunicación y tiempo libre, dedicado mayormente a la televisión e Internet.

Introduction: the pregnancy in the adolescence is a problem of worldwide health. In the world exists more than a thousand millions teen that contribute annually 15 millions of childbirths and of them 80% are from developing countries. Objective: to identify predisponent factors of pregnancy in adolescents of Nuevo Turumo, Venezuela since August 2007 to August 2008. Material and Methods: a descriptive cross section study was accomplished with 32 pregnant adolescents of Nuevo Turumo since August 2007 to August 2008, selected according to the criteria of inclusion and exclusion. Theory's methods (analysis, synthesis and historical logical) and empiric methods (direct interview) were used. To the analysis of the results the statistical package 11.5 was used and the statistic graphs owner to the descriptive statistic (absolute frequency) and measure of resume for qualities variable, in this case the percent. Results: predominate overdue adolescence, the married woman over single woman, scholarship corresponded to the secondary school finished and unfinished, the first menstruation in the premature adolescence, start of sexual relations in the halfway adolescence. Few knowledge and less utilization of contraceptive methods, no linkage to the work. The access to the means of communications and free time dedicated largely to the television and Internet. Conclusions: predisposition factors in Nuevo Turumo adolescent pregnant were: Basic College ended like educational level; menarche presented in the early adolescence; beginning of sexual relation in meddle adolescence; poor knowledge and use of contraceptive and most of the free time is used in internet and see television.

Transdominant regulation of integrin function: mechanisms of crosstalk.

Transdominant inhibition of integrins or integrin-integrin crosstalk is an important regulator of integrin ligand binding and subsequent signaling events that control a variety of cell functions in many tissues. Here we discuss examples of integrin crosstalk and detail our current understanding of the molecular mechanisms that are involved in this receptor phenomenon. The cytoskeleton associated protein talin is a key regulator of integrin crosstalk. We describe how the interaction of talin and the cytoplasmic tail of beta integrin is controlled and how competitive inhibitors of this binding play a role in integrin crosstalk. We conclude with a discussion of how integrin crosstalk impacts the interpretation of integrin inhibitor and knockdown studies in both the laboratory and clinical setting.

Recruitment of vimentin to the cell surface by beta3 integrin and plectin mediates adhesion strength.

Much effort has been expended on analyzing how microfilament and microtubule cytoskeletons dictate the interaction of cells with matrix at adhesive sites called focal adhesions (FAs). However, vimentin intermediate filaments (IFs) also associate with the cell surface at FAs in endothelial cells. Here, we show that IF recruitment to FAs in endothelial cells requires beta3 integrin, plectin and the microtubule cytoskeleton, and is dependent on microtubule motors. In CHO cells, which lack beta3 integrin but contain vimentin, IFs appear to be collapsed around the nucleus, whereas in CHO cells expressing beta3 integrin (CHOwtbeta3), vimentin IFs extend to FAs at the cell periphery. This recruitment is regulated by tyrosine residues in the beta3 integrin cytoplasmic tail. Moreover, CHOwtbeta3 cells exhibit significantly greater adhesive strength than CHO or CHO cells expressing mutated beta3 integrin proteins. These differences require an intact vimentin network. Therefore, vimentin IF recruitment to the cell surface is tightly regulated and modulates the strength of adhesion of cells to their substrate.

Integrin cross-talk in endothelial cells is regulated by protein kinase A and protein phosphatase 1.

In endothelial cells (ECs) beta1 integrin function-blocking antibodies inhibit alphavbeta3 integrin-mediated adhesion to a recombinant alpha4-laminin fragment (ralpha4LN fragment). beta1 integrin sequestration of talin is not the mechanism by which beta1 integrin modulates alphavbeta3 integrin ligand binding. Rather, treatment of the ECs with beta1 integrin function-blocking antibodies enhances cAMP-dependent protein kinase (PKA) activity and increases beta3 integrin serine phosphorylation. The PKA inhibitor H-89 abrogates the effect of beta1 integrin function-blocking antibodies on beta3 integrin serine phosphorylation and EC-ralpha4LN fragment binding. beta3 integrin contains a serine residue at position 752. To confirm the importance of this residue in alphavbeta3 integrin-ralpha4LN fragment binding, we mutated it to alanine (beta3S752A) or aspartic acid (beta3S752D). Chinese hamster ovary (CHO) cells expressing wild type or beta3S752A integrin attach robustly to ligand. CHO cells expressing beta3S752D integrin do not. Because the beta3 cytoplasmic tail lacks a PKA consensus site, it is unlikely that PKA acts directly on beta3 integrin. Instead, we have tested an hypothesis that PKA regulates beta3 integrin serine phosphorylation indirectly through phosphorylation of inhibitor-1, which, when phosphorylated, inhibits protein phosphatase 1 (PP1). Treatment of ECs with beta1 integrin function-blocking antibodies significantly increases phosphorylation of inhibitor-1. Furthermore, blocking PP1 activity pharmacologically inhibits alphavbeta3-mediated cell adhesion to the ralpha4LN fragment when both PKA and beta1 integrin function are inhibited. Concomitantly, there is an increase in serine phosphorylation of the beta3 integrin cytoplasmic tail. These results indicate a novel mechanism by which beta1 integrin negatively modulates alphavbeta3 integrin-ligand binding via activation of PKA and inhibition of PP1 activity.

Evaluation of routine depopulation, cleaning, and disinfection procedures in the live bird markets, New York.

During the past years surveillance for avian influenza has been conducted in the live bird markets (LBMs) in New York as well as other states along the east coast. Repeated attempts to eradicate H5 and H7 influenza from the New York markets have focused efforts on the LBMs themselves. Despite repeated mandatory market closures accompanied by cleaning and disinfecting (C/D) procedures, avian influenza virus continued to be isolated. In an effort to assess the adequacy of the C/D procedure, samples were collected in temporal proximity to the depopulation and C/D. Comparison of the pre-C/D (83% virus positive), at C/D approval (1.6% positive) and post-C/D testing (33% positive) indicate that the current procedures of C/D can be effective at eliminating these influenza viruses. However, reinfection via introduction of influenza-virus-positive birds can occur shortly after the market reopens.

Complex interactions between the laminin alpha 4 subunit and integrins regulate endothelial cell behavior in vitro and angiogenesis in vivo.

The alpha4 laminin subunit is a component of the basement membrane of blood vessels where it codistributes with the integrins alphavbeta3, alpha3beta1, and alpha6beta1. An antibody against the G domain (residues 919-1207; G(919-1207)) of the alpha4 laminin subunit inhibits angiogenesis in a mouse-human chimeric model, indicating the functional importance of this domain. Additional support for the latter derives from the ability of recombinant G(919-1207) to support endothelial cell adhesion. In particular, endothelial cell adhesion to G(919-1207) is half-maximal at 1.4 nM, whereas residues 919-1018 and 1016-1207 of the G domain are poor cellular ligands. Function blocking antibodies against integrins alphavbeta3 and beta1 and a combination of antibodies against alpha3 and alpha6 integrin subunits inhibit endothelial cell attachment to G(919-1207). Moreover, both alphavbeta3 and alpha3beta1 integrin bind with high affinity to G(919-1207). Together, our studies demonstrate that the G domain of laminin alpha4 chain is a specific, high affinity ligand for the alphavbeta3 and alpha3beta1 integrin heterodimers and that these integrins, together with alpha6beta1, function cooperatively to mediate endothelial cell-alpha4 laminin interaction and hence blood vessel development. We propose a model based on these data that reconcile apparent discrepancies in the recent literature with regard to the role of the alphavbeta3 integrin in angiogenesis.