Mesenchymal Stem Cells Prevent the Rejection of Fully Allogenic Islet Grafts by the Immunosuppressive Activity of Matrix Metalloproteinase-2 and -9

OBJECTIVE Mesenchymal stem cells (MSCs) are known to be capable of suppressing immune responses, but the molecular mechanisms involved and the therapeutic potential of MSCs remain to be clarified. RESEARCH DESIGN AND METHODS We investigated the molecular mechanisms underlying the immunosuppressive effects of MSCs in vitro and in vivo. RESULTS Our results demonstrate that matrix metalloproteinases (MMPs) secreted by MSCs, in particular MMP-2 and MMP-9, play an important role in the suppressive activity of MSCs by reducing surface expression of CD25 on responding T-cells. Blocking the activity of MMP-2 and MMP-9 in vitro completely abolished the suppression of T-cell proliferation by MSCs and restored T-cell expression of CD25 as well as responsiveness to interleukin-2. In vivo, administration of MSCs significantly reduced delayed-type hypersensitivity responses to allogeneic antigen and profoundly prolonged the survival of fully allogeneic islet grafts in transplant recipients. Significantly, these MSC-mediated protective effects were completely reversed by in vivo inhibition of MMP-2 and MMP-9. CONCLUSIONS We demonstrate that MSCs can prevent islet allograft rejection leading to stable, long-term normoglycemia. In addition, we provide a novel insight into the mechanism underlying the suppressive effects of MSCs on T-cell responses to alloantigen.</p

La gesti?n de la calidad en Per?: un estudio de la norma ISO 9001, sus beneficios y los principales cambios en la versi?n 2015

Considering the great importance of quality management at the present international juncture, this research reviews and analyzes the most important standard pertaining thereto, i.e. ISO 9001. In this paper, the origins of the term ?quality? are established, as well as its evolution over time. It is defined by using the description of the family of standards. In addition, its structure and also the principles on which it is based were identified. Following the above and as an additional result of this work, the qualitative and quantitative benefits with which the standard provides companies registered with it are detailed. Finally, the main changes that the new ISO 9001:2015 revision will include are established.Debido a la gran relevancia que tiene la gesti?n de calidad en la actual coyuntura internacional, el presente trabajo de investigaci?n revisa y analiza la m?s destacada norma en esta materia: la ISO 9001. En el documento, se establecen los or?genes y la evoluci?n del t?rmino calidad. Este se define mediante la descripci?n de la familia de normas. Se identifican tambi?n su estructura y los principios sobre los que se basa. A partir de lo anterior, como un resultado adicional del trabajo, se detallan los beneficios cualitativos y cuantitativos que la norma brinda a las empresas que se adscriben a la misma. Por ?ltimo, se establecen las principales modificaciones que incorporara la nueva ISO 9001 versi?n 2015

Evoluci?n del sistema financiero peruano y su reputaci?n bajo el ?ndice Merco. Per?odo: 2010-2014

The aim of this study is to analyse the evolution and performance of the Peruvian financial system in the last few years, as well as the role of the banking reputation in this, taking different bases such as the Merco Index and financial solvency. The study is both quantitative and qualitative, and is specifically focused on the 4 most representative banks of the system, and selected on the basis of investments, deposits, and assets. The analysis looks to establish an initial relationship between corporative reputation (through the value of the Merco Index) and financial solvency, with the analysis being able to be complemented with further studies with the other indicators that are shown in Annexes 1 to 3.El objetivo del presente estudio es analizar la evoluci?n y desempe?o del sistema financiero peruano en los ?ltimos a?os y el rol de la reputaci?n bancaria en ?l, tomando como base diversos indicadores tales como el valor de ?ndice Merco y la solvencia financiera. El estudio es tanto cuantitativo como cualitativo y se enfoca espec?ficamente en los 4 bancos m?s representativos del sistema, seleccionados con base en las colocaciones, captaciones y patrimonio. El an?lisis busca establecer una relaci?n inicial entre la reputaci?n corporativa (a trav?s del valor de ?ndice merco) y la solvencia financiera. En estudios posteriores se puede complementar el an?lisis con otros indicadores que se muestran en los anexos 1 al 3

Estudio hidrol?gico e hidr?ulico para el control de inundaciones en la cuenca del r?o Purires, valle del Guarco. Informe t?cnico

Ilus. Tab. 11 ref. Sum. (Es

Gesti?n integral de riesgos y antisoborno: un enfoque operacional desde la perspectiva iso 31000 e iso 37001

This paper seeks to explain how companies can apply risk management from an operational approach and the necessary guidelines to carry out an efficient management of it (Bromiley et al., 2015). Therefore, we first work out the risk in operations and explain the types of events, the factors that cause it, and details measurement tools such as severity. Then, the theory about management standards related to risk management, such as iso 37001, iso 31000 and COSO, in their latest versions, is reviewed. The research paper proposes an application in the area of risks, through a proposal of a general risk scheme and a structure of risk management for organizations. Finally, new aspects are developed to consider the case of cybernetic risk.El presente art?culo busca explicar de qu? manera las empresas pueden aplicar la gesti?n de riesgos desde un enfoque operacional y los lineamientos necesarios para llevar a cabo una eficiente gesti?n de los mismos (Bromiley et al., 2015). En primer lugar, se analiza el riesgo en las operaciones y se explican los tipos de p?rdidas y los factores que las puede originar; adem?s, se detallan herramientas de medici?n como la severidad. Luego, se revisa la teor?a de los est?ndares de gesti?n relacionados a los riesgos, tales como el iso 37001, iso 31000 y COSO, en sus ?ltimas versiones. El documento de investigaci?n propone una aplicaci?n en el ?rea de riesgos, mediante una propuesta de esquema general de riesgos y una estructura de gesti?n de riesgos para las organizaciones. Finalmente, se desarrollan nuevos aspectos a considerar como el caso del riesgo cibern?tico

Modelaci?n hidrol?gica e hidr?ulica para el control de inundaciones en Centroam?rica: casos r?o Purires y Turrialba

Ilus. 22 tab. 20 ref

Regulation of anxiety and initiation of sexual behavior by CREB in the nucleus accumbens

Sexual deficits and other behavioral disturbances such as anxiety-like behaviors can be observed in animals that have undergone social isolation, especially in species having important social interactions. Using a model of protracted social isolation in adult rats, we observed increased anxiety-like behavior and deficits in both the latency to initiate sexual behavior and the latency to ejaculate. We show, using transgenic cAMP response element (CRE)-LacZ reporter mice, that protracted social isolation also reduces CRE-dependent transcription within the nucleus accumbens. This decrease in CRE-dependent transcription can be mimicked in nonisolated animals by local viral gene transfer of a dominant negative mutant of CRE-binding protein (CREB). We previously showed that this manipulation increases anxiety-like behavior. We show here that it also impairs initiation of sexual behavior in nonisolated animals, a deficit that can be corrected by anxiolytic drug treatment. This local reduction in CREB activity, however, has no influence on ejaculation parameters. Reciprocally, we used the viral transgenic approach to overexpress CREB in the nucleus accumbens of isolated animals. We show that this local increase in CREB activity completely rescued the anxiety phenotype of the isolated animals, as well as their deficit in initiating sexual behavior, but failed to rescue the deficit in ejaculation. Our data suggest a role for the nucleus accumbens in anxiety responses and in specific aspects of sexual behavior. The results also provide insight into the molecular mechanisms by which social interactions affect brain plasticity and behavior