WNT Signaling in Tumors: The Way to Evade Drugs and Immunity

©2019. This manuscript version is made available under the CC-BY 4.0 license http://creativecommons.org/licenses/by /4.0/ This document is the Published, version of a Published Work that appeared in final form in Frontiers in Immunology. To access the final edited and published work see https://doi.org/10.3389/fimmu.2019.02854WNT/β-catenin signaling is involved in many physiological processes. Its implication in embryonic development, cell migration, and polarization has been shown. Nevertheless, alterations in this signaling have also been related with pathological events such as sustaining and proliferating the cancer stem cell (CSC) subset present in the tumor bulk. Related with this, WNT signaling has been associated with the maintenance, expansion, and epithelial-mesenchymal transition of stem cells, and furthermore with two distinctive features of this tumor population: therapeutic resistance (MDR, multidrug resistance) and immune escape. These mechanisms are developed and maintained by WNT activation through the transcriptional control of the genes involved in such processes. This review focuses on the description of the best known WNT pathways and the molecules involved in them. Special attention is given to the WNT cascade proteins deregulated in tumors, which have a decisive role in tumor survival. Some of these proteins function as extrusion pumps that, in the course of chemotherapy, expel the drugs from the cells; others help the tumoral cells hide from the immune effector mechanisms. Among the WNT targets involved in drug resistance, the drug extrusion pump MDR-1 (P-GP, ABCB1) and the cell adhesion molecules from the CD44 family are highlighted. The chemokine CCL4 and the immune checkpoint proteins CD47 and PD-L1 are included in the list of WNT target molecules with a role in immunity escape. This pathway should be a main target in cancer therapy as WNT signaling activation is essential for tumor progression and survival, even in the presence of the anti-tumoral immune response and/or antineoplastic drugs. The appropriate design and combination of anti-tumoral strategies, based on the modulation of WNT mediators and/or protein targets, could negatively affect the growth of tumoral cells, improving the efficacy of these types of therapies

Control de legalidad en la formulación de la acusación en el sistema penal acusatorio colombiano

En el sistema procesal acusatorio colombiano al legislar el inicio formal de la etapa del juicio omitió darle un espacio para el control judicial al escrito de acusación, argumentándose que esa era precisamente una expresión de la división de funciones entre investigación y juzgamiento, empero cierto es que una ausencia absoluta de control de la acusación hace nugatoria la posibilidad de la tutela real efectiva que como principio dentro del marco del derecho al debido proceso constitucional se erige en una garantía propia del Estado Social y de Derecho fundado en el respeto irrestricto a la dignidad humana. La posición asumida por el máximo Tribunal de la jurisdicción ordinaria es que “Si el acto que concreta el resultado de las averiguaciones, como es la acusación, fuera corregido, cuestionado, o validado por el juez, actividad en la cual se comprometería inapropiadamente con su éxito reflejado en una segura condena; y no se podría pregonar la igualdad de las partes cuando la posición procesal de una de ellas es avalada por el juez llamado a dirimir la -hasta entonces- desequilibrada controversia; y qué no decir de la imparcialidad de un juez que ya ha cobijado con su aprobación una acusación que anuncia un debate que apenas comienza”. Afirmación anterior que si bien es respetable, también lo es que quien controla la acusación puede no ser el juez que ha de dirimir el debate probatorio en juicio, con lo cual se queda sin fundamento el criterio de la Corte, tal y como lo previó el legislador frente a quien ejerce funciones de control de garantías y su prohibición de conocer del juicio, o del juez de conocimiento que conoce y deniega la preclusión quedando impedido para continuar con la acción penal, es más no se compadece con la realidad procesal hoy día sobre ausencia de imparcialidad en juicio oral por el juez de conocimiento al controlar la acusación, ya que en la audiencia preparatoria se mina la convicción del tercero imparcial al valorar los argumentos de las partes (incluso de la víctimas y Ministerio Público) para resolver sobre la admisión, inadmisión, rechazo o exclusión de sus peticiones probatorias, conforme los criterios de pertinencia, admisibilidad legalidad, utilidad y necesidad de la prueba, y ello no implica necesariamente violación al debido proceso ni quiebre de imparcialidad, aunque no son pocos los escenarios judiciales donde se avista una decisión judicial desde dicha audiencia en detrimento de las garantías procesales que gobiernan el proceso penal y por su puesto la presunción de inocencia

Wnt signaling in tumors: The way to evade drugs and immunity

©2019. This manuscript version is made available under the CC-BY 4.0 license http://creativecommons.org/licenses/by /4.0/ This document is the Published, version of a Published Work that appeared in final form in Frontiers in Immunology. To access the final edited and published work see doi: 10.3389/fimmu.2019.02854WNT/b-catenin signaling is involved in many physiological processes. Its implication in embryonic development, cell migration, and polarization has been shown. Nevertheless, alterations in this signaling have also been related with pathological events such as sustaining and proliferating the cancer stem cell (CSC) subset present in the tumor bulk. Related with this, WNT signaling has been associated with the maintenance, expansion, and epithelial-mesenchymal transition of stem cells, and furthermore with two distinctive features of this tumor population: therapeutic resistance (MDR, multidrug resistance) and immune escape. These mechanisms are developed and maintained by WNT activation through the transcriptional control of the genes involved in such processes. This review focuses on the description of the best known WNT pathways and the molecules involved in them. Special attention is given to the WNT cascade proteins deregulated in tumors, which have a decisive role in tumor survival. Some of these proteins function as extrusion pumps that, in the course of chemotherapy, expel the drugs from the cells; others help the tumoral cells hide from the immune effector mechanisms. Among the WNT targets involved in drug resistance, the drug extrusion pump MDR-1 (P-GP, ABCB1) and the cell adhesion molecules from the CD44 family are highlighted. The chemokine CCL4 and the immune checkpoint proteins CD47 and PD-L1 are included in the list of WNT target molecules with a role in immunity escape. This pathway should be amain target in cancer therapy as WNT signaling activation is essential for tumor progression and survival, even in the presence of the anti-tumoral immune response and/or antineoplastic drugs. The appropriate design and combination of anti-tumoral strategies, based on the modulation of WNT mediators and/or protein targets, could negatively affect the growth of tumoral cells, improving the efficacy of these types of therapies

Meaning of Feedback in the Teaching Practice of the Physical Education, Recreation and Sports Practicing Student

El artículo presenta resultados del proyecto de investigación “sentidos de los modos corporales y saberes docentes del prácticum en Educación Física, Recreación y Deporte de la Universidad de Caldas”. Objetivo: comprender los sentidos del feedback en la interacción durante el prácticum. Método: se apoyó en el enfoque cualitativo, corte descriptivo-comprensivo y método hermenéutico. Resultados: durante el prácticum, la utilización de los modos corporales como la comunicación verbal y la no verbal en la clase de educación física, permite evidenciar la importancia de la utilización del feedback en los procesos didácticos como mecanismos de motivación, consolidación de los gestos motores y deportivos a través de la trasposición didáctica vivenciada en los contextos educativos. Conclusión: la utilización correcta del feedback, en el campo de la educación física, recreación y deporte, contribuye al desarrollo de diferentes competencias educativas, comunicativas y motrices, favoreciendo los procesos de enseñanza-aprendizaje entre el practicante-profesor, el profesor-titular, el profesor-asesor y los estudiantes, ya sea de forma teórico/práctica, individualizada y objetiva.This paper presents the results of the research project “Meanings of body modes and teaching knowledge of the teaching practice in the Physical Education, Recreation and Sports Program of Universidad de Caldas”. Objective: To understand the meanings of the feedback in the interaction during the teaching practice. Method: the project was based on the qualitative approach, it was a descriptive-comprehensive research using the hermeneutic method. Results: During the teaching practice the use of body modes such as verbal and non-verbal communication in the hysical Education class allows demonstrating the importance of the use of feedback in the learning processes as motivation mechanisms, consolidation of motion and sports gestures through the teaching transposition experienced in educational contexts. Conclusion: The correct use of feedback in the field of physical education, recreation and sports contributes to the evelopment of different educational, communicative and motor skills, favoring the teaching-learning processes between practicing student-teacher, teacher-homeroom teacher, homeroom teacher-practice advisor and the students either in a theoretical/practical, individualized and objective way

Sentidos del feedback en el prácticum de educación física, recreación y deporte

El artículo presenta resultados del proyecto de investigación “sentidos de los modos corporales y saberes docentes del prácticum en Educación Física, Recreación y Deporte de la Universidad de Caldas”. Objetivo: comprender los sentidos del feedback en la interacción durante el prácticum. Método: se apoyó en el enfoque cualitativo, corte descriptivo-comprensivo y método hermenéutico. Resultados: durante el prácticum, la utilización de los modos corporales como la comunicación verbal y la no verbal en la clase de educación física, permite evidenciar la importancia de la utilización del feedback en los procesos didácticos como mecanismos de motivación, consolidación de los gestos motores y deportivos a través de la trasposición didáctica vivenciada en los contextos educativos. Conclusión: la utilización correcta del feedback, en el campo de la educación física, recreación y deporte, contribuye al desarrollo de diferentes competencias educativas, comunicativas y motrices, favoreciendo los procesos de enseñanza-aprendizaje entre el practicante-profesor, el profesor-titular, el profesor-asesor y los estudiantes, ya sea de forma teórico/práctica, individualizada y objetiva

Hybrid, public and private environmental governance: The case of sustainable coastal zone management in Quintana Roo, Mexico

Coastal zones (CZ) are social-ecological systems where rapid forms of economic development are disrupting the existing patterns of relationships, raising challenges for governance. Institutional flexibility, broad participation, multilevel governance, and adaptability have been identified as critical conditions for the governance of social-ecological systems. While the importance of agency, through the substantive participation of private actors in rulemaking, has been researched, there is a need to examine the dynamics involved in, and consequence of, hybrid governance arrangements. An empirical study is presented of hybrid governance, involving federal and local government and locally based private actors from civil society organizations, environmental non-government organizations and local business interest associations, in the state of Quintana Roo, Mexico. The CZ of Quintana Roo is facing pressures from economic development, mainly tourism, with consequences for water pollution and fisheries. Through qualitative, mixed methods, we found that a thick network of private actors has mobilized to play an important role in environmental management and to act in collaboration with the State. Multiple rationales account for this development, including high levels of environmental awareness, particularly with respect to water pollution, while the lack of institutional capacity also motivates state actors to seek partnerships. While private governance is emerging, our data reveal a complex case, where private actor mobilization seeks to promote better regulations, to share data and resources, and to improve implementation capacity within the public administration. Hybrid governance contributes to effective environmental governance of the CZ. However, this can also risk state retreat from its public responsibilities

Visible-Light-Activated Molecular Nanomachines Kill Pancreatic Cancer Cells

Recently, synthetic molecular nanomachines (MNMs) that rotate unidirectionally in response to UV light excitation have been used to produce nanomechanical action on live cells to kill them through the drilling of holes in their cell membranes. In the work here, visible-light-absorbing MNMs are designed and synthesized to enable nanomechanical activation by 405 nm light, thereby using a wavelength of light that is less phototoxic than the previously employed UV wavelengths. Visible-light-absorbing MNMs that kill pancreatic cancer cells upon response to light activation are demonstrated. Evidence is presented to support the conclusion that MNMs do not kill cancer cells by the photothermal effect when used at low optical density. In addition, MNMs suppress the formation of reactive oxygen species, leaving nanomechanical action as the most plausible working mechanism for cell killing under the experimental conditions

Efficiency of two methods for eggplant ( Solanum Melongena L. Cv. Lila Criolla) pollen Viability evaluation

La viabilidad del polen influye en la producción y en la calidad de frutos de las especies cultivadas. Su estudio es necesario en los programas de mejoramiento, especialmente, cuando se pretende producir cultivares híbridos. La investigación, se realizó en Montería, Departamento de Córdoba, Colombia, con el propósito de comparar la eficiencia de dos métodos para evaluar la viabilidad del polen de berenjena (Solanum melongena L. cv. Lila criolla) —germinación in vitro y sal de tetrazolio-, bajo condiciones tropicales, y determinar su uso potencial, para la producción de semilla híbrida. La prueba de viabilidad con la sal de tetrazolio mostró que la concen-tración de 0,25% permite diferenciar, cualitativa y cuanti-tativamente, los granos de polen viables y, además, acusó disminución lineal significativa por cada unidad porcentual de la concentración de la sal. Con el método in vitro, el in-cremento lineal fue significativo por cada hora de incuba-ción. Ambos métodos resultaron confiables, para estimar la viabilidad del polen en el cultivar estudiado, con la salvedad de la concentración de tetrazolio.Pollen viability influences the production and fruit quality of cultivated species. Its study is necessary in breeding pro-grams, especially when trying to produce hybrid cultivars. The research was carried out at Monteria, Cordoba, Colom-bia, in order to compare the efficiency of two methods for assessing pollen viability of the eggplant (Solanum melon-gena L. cv. Lila criolla): in vitro germination and tetrazolium salt- under tropical conditions, and to determine its potential use in hybrid seed production. The viability test with the te-trazolium salt showed that the concentration of 0.25% allows differentiating, qualitatively and quantitatively, viable pollen grains, and it also presented significant linear decrease per unit of concentration of salt. In the in vitro method, the linear increase was significant for each hour of incubation. Both methods were reliable for estimating pollen viability in the cultivar studied.Incluye referencias bibliográfica