La Comunicación Participativa como Estrategia para Fortalecer los Lazos de la Comunicación Interna y Externa en Perspectiva de Red Social en la OSP Fundación Cambiando Estrellas de Yopal

La Fundación Cambiando Estrellas es una organización que tiene como misión llegar hasta el último rincón de la población más vulnerable, buscando espacios para poder generar una transformación cultural, social, recreativa y pedagógica, utilizando espacios públicos como los parques, las canchas de fútbol, bibliotecas y colegios. Su compromiso es con la primera infancia y el adulto mayor; de esta manera busca dignificar e inculcar en estas poblaciones los valores y cambios culturales, haciéndolos sentir útiles y menos vulnerables. Se realizó una investigación de tipo sociocrítico como fase final del Diplomado en Construcción de Redes Sociales de Comunicación, se analizó el estado de la comunicación participativa en la OSP Fundación Cambiando Estrellas, se realizó un trabajo a profundidad desde las diferentes actividades y referencias del Diplomado bajo la técnica de investigación acción. Se realizaron importantes hallazgos, uno de ellos y principal es la falta de comunicación interna y externa, y fue así como se pudo percibir la débil participación de casi todos los voluntarios creando dificultados en el equipo, que si bien, cuentan con los espacios, no cuentan con voz, eliminando de esta manera, cualquier posibilidad de que la fundación crezca y pueda evolucionar con satisfacción.The Fundación Cambiando Estrellas is an organization whose mission is to reach until the last corner of the most vulnerable population, seeking enough spaces to generate a cultural, social, recreational and pedagogical transformation, this in order to use public spaces such as parks, soccer fields, libraries and schools and at the same time committed to early childhood, the elderly, thereby dignifying and instilling in them values ​​and cultural changes. Making them feel useful and less vulnerable. A very strict investigation was carried out, presenting it as the final phase of the Diploma in Construction of Social Communication Networks, we analized carefully the status of the OSP in participatory communication at the Fundación Cambiando Estrellas , in-depth work was carried out from all the different activities and references of the Diploma under the research technique and participation mythologies, puzzling findings were found, one of them and the main one is the lack of internal and external communication. And this is how it was possible to perceive the weak participation of almost all the volunteers, leading them to a fragile teamwork of the volunteers, who, although they have the spaces, but do not have a voice, thus eliminating any possibility that the foundation grows and can evolve with satisfaction

Downregulation of NFAT2 promotes melanogenesis in B16 melanoma cells

Nuclear factor of activated T-cells (NFAT) proteins are, calcium-regulated transcription factors, key regulator of stimulation-dependent gene activation. In our microarray analysis for the genes expressed in human black and white hairs, NFAT2 was significantly upregulated in the white hair, compared to the black hair. The aim of this study was to investigate functional role of NFAT2 in melanogenesis. Western blot analysis was performed to investigate the expression of NFAT2 protein in B16 melanoma cells. Our data showed that NFAT2 expression was increased in the hypopigmented B16 cells, while tyrosinase and MITF expression was decreased. To investigate the potential role of NFAT2, the recombinant adenovirus expressing microRNA specific for NFAT2 was transduced into the cultured B16 melanoma cells. Consistently, inhibition of NFAT2 enhanced tyrosinase activity and melanin content. Moreover, cyclosporine A, which is known as a calcineurin inhibitor blocking NFAT activation, enhanced tyrosinase activity and melanin content. These data suggest that NFAT2 may play an important role in regulation of melanogenesis in melanocyte

Targeted calcium influx boosts cytotoxic T lymphocyte function in the tumour microenvironment

Adoptive cell transfer utilizing tumour-targeting cytotoxic T lymphocytes (CTLs) is one of the most effective immunotherapies against haematological malignancies, but significant clinical success has not yet been achieved in solid tumours due in part to the strong immunosuppressive tumour microenvironment. Here, we show that suppression of CTL killing by CD4+CD25+Foxp+ regulatory T cell (Treg) is in part mediated by TGFβ-induced inhibition of inositol trisphosphate (IP3) production, leading to a decrease in T cell receptor (TCR)-dependent intracellular Ca2+ response. Highly selective optical control of Ca2+ signalling in adoptively transferred CTLs enhances T cell activation and IFN-γ production in vitro, leading to a significant reduction in tumour growth in mice. Altogether, our findings indicate that the targeted optogenetic stimulation of intracellular Ca2+ signal allows for the remote control of cytotoxic effector functions of adoptively transferred T cells with outstanding spatial resolution by boosting T cell immune responses at the tumour sites

Renal Transplant Immunosuppression Impairs Natural Killer Cell Function In Vitro and In Vivo

Background: Despite an increasing awareness of the importance of innate immunity, the roles of natural killer (NK) cells in transplant rejection and antiviral and cancer immunity during immunosuppression have not been clearly defined. Methods: To address this issue we have developed a quantitative assay of NK cell function that can be used on clinical samples and have studied the influence of immunosuppression on NK cell function. NK cell degranulation and intracellular interferon (IFN)-c production were determined by flow cytometry of peripheral blood samples. Results: Overnight ex vivo treatment of peripheral blood cells from healthy controls with ciclosporin or tacrolimus inhibited NK cell degranulation and IFN-c production in a dose-dependent manner. A similar impairment of function was seen in NK cells from patients treated in vivo with calcineurin inhibitors. In the early post-transplant period, there was a variable reduction of NK cell counts after treatment with alemtuzumab and basiliximab. Conclusions: The functional inhibition of NK cells in early transplant patients coincides with the period of maximum susceptibility to viral infections. The ability to assay NK cell function in clinical samples allows assessment of the impact of immunosuppressio

Circulating NK cells and their subsets in Behçet's disease

Behçet's disease (BD) is an autoinflammatory, chronic relapsing/remitting disease of unknown aetiology with both innate and acquired immune cells implicated in disease pathogenesis. Peripheral blood natural killer (NK) cells and their CD56Dim /CD56Bright subsets were surface phenotyped using CD27 and CD16 surface markers in 60 BD patients compared to 60 healthy controls (HCs). Functional potential was assessed by production of interferon (IFN)-γ, granzyme B, perforin and the expression of degranulation marker CD107a. The effects of disease activity (BDActive versus BDQuiet ) and BD medication on NK cells were also investigated. Peripheral blood NK cells (P < 0·0001) and their constituent CD56Dim (P < 0·0001) and CD56Bright (P = 0·0015) subsets were depleted significantly in BD patients compared to HCs, and especially in those with active disease (BDActive ) (P < 0·0001). BD patients taking azathioprine also had significantly depleted NK cells compared to HCs (P < 0·0001). A stepwise multivariate linear regression model confirmed BD activity and azathioprine therapy as significant independent predictor variables of peripheral blood NK percentage (P < 0·001). In general, CD56Dim cells produced more perforin (P < 0·0001) and granzyme B (P < 0·01) expressed higher CD16 levels (P < 0·0001) compared to CD56Bright cells, confirming their increased cytotoxic potential with overall higher NK cell CD107a expression in BD compared to HCs (P < 0·01). Interestingly, IFN-γ production and CD27 expression were not significantly different between CD56Dim /CD56Bright subsets. In conclusion, both BD activity and azathioprine therapy have significant independent depletive effects on the peripheral blood NK cell compartment.Centre for Clinical and Diagnostic Oral Sciences, Institute of Dentistry, Barts and The London School of Medicine and Dentistry, Queen Mary University of London Wellcome Trust . Grant Number: 096954/Z/1

Can Non-lytic CD8+T Cells Drive HIV-1 Escape?

The CD8+ T cell effector mechanisms that mediate control of HIV-1 and SIV infections remain poorly understood. Recent work suggests that the mechanism may be primarily non-lytic. This is in apparent conflict with the observation that SIV and HIV-1 variants that escape CD8+ T cell surveillance are frequently selected. Whilst it is clear that a variant that has escaped a lytic response can have a fitness advantage compared to the wild-type, it is less obvious that this holds in the face of non-lytic control where both wild-type and variant infected cells would be affected by soluble factors. In particular, the high motility of T cells in lymphoid tissue would be expected to rapidly destroy local effects making selection of escape variants by non-lytic responses unlikely. The observation of frequent HIV-1 and SIV escape poses a number of questions. Most importantly, is the consistent observation of viral escape proof that HIV-1- and SIV-specific CD8+ T cells lyse infected cells or can this also be the result of non-lytic control? Additionally, the rate at which a variant strain escapes a lytic CD8+ T cell response is related to the strength of the response. Is the same relationship true for a non-lytic response? Finally, the potential anti-viral control mediated by non-lytic mechanisms compared to lytic mechanisms is unknown. These questions cannot be addressed with current experimental techniques nor with the standard mathematical models. Instead we have developed a 3D cellular automaton model of HIV-1 which captures spatial and temporal dynamics. The model reproduces in vivo HIV-1 dynamics at the cellular and population level. Using this model we demonstrate that non-lytic effector mechanisms can select for escape variants but that outgrowth of the variant is slower and less frequent than from a lytic response so that non-lytic responses can potentially offer more durable control

No Specific Subcellular Localization of Protein Kinase C Is Required for Cytotoxic T Cell Granule Exocytosis*

Cytotoxic T cells kill virus-infected cells and tumor cells by releasing lytic granules that contain cell-killing contents. Exocytosis requires calcium influx and protein kinase C (PKC) activation. Here, we extend our previous finding regarding the lack of isoform specificity of PKCs in the granule release step, showing that mutant constitutively active PKCδ can substitute for phorbol esters and support exocytosis. PKCδ, a novel PKC isoform, was recently shown to play a role in lytic granule reorientation. Surprisingly, however, our results suggested that mutant PKCδ did not localize to the plasma membrane (PM). To test directly whether PKC has to be in the PM to drive exocytosis, we generated mutants of various PKC isoforms that were tethered either to the outer mitochondrial membrane or to the PM. Tethered mutant PKCδs were able to promote exocytosis as effectively as the untethered version. The substrates of PKCs involved in lytic granule exocytosis are currently unknown, but subcellular localization is believed to be a critical factor in determining PKC accessibility to substrates. That there is no requirement for specific PKC localization in lytic granule exocytosis may have important implications for the identity of PKC substrates