Nipah Virus Infection Generates Ordered Structures in Cellulo.

Nipah virus (NiV) is a zoonotic paramyxovirus with a fatality rate of up to 92% in humans. While several pathogenic mechanisms used by NiV to counteract host immune defense responses have been described, all of the processes that take place in cells during infection are not fully characterized. Here, we describe the formation of ordered intracellular structures during NiV infection. We observed that these structures are formed specifically during NiV infection, but not with other viruses from the same Mononegavirales order (namely Ebola virus) or from other orders such as Bunyavirales (Junín virus). We also determined the kinetics of the appearance of these structures and their cellular localization at the cellular periphery. Finally, we confirmed the presence of these NiV-specific ordered structures using structured illumination microscopy (SIM), as well as their localization by transmission electron microscopy (TEM), scanning electron microscopy (SEM), and correlative light and electron microscopy (CLEM). Herein, we describe a cytopathogenic mechanism that provides a new insight into NiV biology. These newly described ordered structures could provide a target for novel antiviral approaches.

New insights on the interaction mechanism of rhTNFα with its antagonists Adalimumab and Etanercept.

TNFα is a pro-inflammatory cytokine that is a therapeutic target for inflammatory autoimmune disorders. Thus, TNFα antagonists are successfully used for the treatment of these disorders. Here, new association patterns of rhTNFα and its antagonists Adalimumab and Etanercept are disclosed. Active rhTNFα was purified by IMAC from the soluble fraction of transformed Escherichia coli. Protein detection was assessed by SDS-PAGE and Western blot. The KD values for rhTNFα interactions with their antagonists were obtained by non-competitive ELISA and by microscale thermophoresis (MST). Molecular sizes of the complexes were evaluated by size-exclusion chromatography-high performance liquid chromatography (SEC-HPLC). Surprisingly, both antagonists recognized the monomeric form of rhTNFα under reducing and non-reducing conditions, indicating unexpected bindings of the antagonists to linear epitopes and to rhTNFα monomers. For the first time, the interactions of rhTNFα with Adalimumab and Etanercept were assessed by MST, which allows evaluating molecular interactions in solution with a wide range of concentrations. Biphasic binding curves with low and high KD values (<10-9 M and >10-8 M) were observed during thermophoresis experiments, suggesting the generation of complexes with different stoichiometry, which were confirmed by SEC-HPLC. Our results demonstrated the binding of TNFα-antagonists with rhTNFα monomers and linear epitopes. Also, complexes of high molecular mass were observed. This pioneer investigation constitutes valuable data for future approaches into the study of the interaction mechanism of TNFα and its antagonists.

Determinantes urbanos para el ejercicio del control social en salud en el Distrito Capital, 1986-1996 / Urban determinants for the exercise of social control in health in the Capital District, 1986-1996

El desarrollo de este estudio parte de la idea de que los determinantes urbanos de la ciudad de Santa Fe de Bogotá son características que además de darle una connotación propia al citadino, pueden estar caracterizando el ejercicio del control social en la prestación de los servicios de salud y desarrollo de la seguridad social en salud en el Distrito Capital. Se hace una aproximación exploratoria al tema a partir de las características de los líderes comunitarios, teniendo como referentes algunos determinantes que la teoría ha definido como propios de lo urbano, en aspectos económicos, culturales, poblacionales, institucionales y en la oferta de servicios públicos. El estudio tiene como marco de referencia las reformas de los sistemas de salud de los últimos diez años; en él se hace una reflexión del significado que tiene la Constitución de 1991 sobre la participación social y su relación con la posible construcción de un nuevo concepto de ciudadanía. Así, los determinantes urbanos se identifican tomando como base inicial los definidos en el marco de referencia a partir de los elementos generales que en teoría se han descrito como características de la ciudad, y posteriormente se buscan y se confrontan algunos de éstos en el contexto local, otros en el contexto nacional, y otros en el institucional y cultural de los líderes comunitarios. El control social se abordó en el contexto de la participación, y tanto el uno como la otra desde el Estado, por ser el generador de estos procesos. Las reformas de los sistemas y los aspectos normativos de la participación comunitaria se hicieron a partir de la revisión de los tres sistemas de salud que han existido en Colombia, plasmados en el decreto 056 de 1975, la ley 10 de 1990 y la ley 100 de 1993. Se presenta una caracterización por etapas y en los tres sistemas de salud sobre la participación comunitaria promovida por el Estado en los contextos nacional y local en la última década. Hace un recorrido de la forma como ha evolucionado el uso de los términos participación comunitaria y control social en salud y propone una definición de los mismos. Genera algunas recomendaciones para diferenciar el papel de cada organización comunitaria según el régimen o plan de beneficios en el SGSSS. Diseña alternativas para involucrar a la población de estratos altos en el control social. Identifica aspectos concretos sobre las relaciones de los sectores comunitarios con las instituciones de salud y con sus funcionarios, y que están afectando positiva y negativamente su quehacer como líderes en el SGSSS. Finalmente, se hace una propuesta metodológica en la cual se retoman las conclusiones del trabajo así como las principales debilidades manifestadas por los líderes.

The development of this study is based on the idea that the urban determinants of the city of Santa Fe de Bogotá are characteristics that, in addition to giving a connotation of the city-dweller, may be characterizing the exercise of social control in the provision of health services and the development of social security in health in the Capital District. An exploratory approach to the subject is made on the basis of the characteristics of community leaders, taking as a reference some determinants that theory has defined as typical of the urban, in economic, cultural, population, institutional aspects and in the supply of public services. The study has as a frame of reference the health system reforms of the last ten years; it reflects on the meaning of the 1991 Constitution on social participation and its relationship with the possible construction of a new concept of citizenship. Thus, the urban determinants are identified taking as an initial basis those defined in the frame of reference from the general elements that have been described in theory as characteristics of the city, and then some of these are sought and confronted in the local context, others in the national context, and others in the institutional and cultural context of community leaders. Social control was approached in the context of participation, and both the one and the other from the State, for being the generator of these processes. The reforms of the systems and the normative aspects of community participation were made from the review of the three health systems that have existed in Colombia, embodied in Decree 056 of 1975, Law 10 of 1990 and Law 100 of 1993. It presents a characterization by stages and in the three health systems of the community participation promoted by the State in the national and local contexts in the last decade. It reviews how the use of the terms community participation and social control in health has evolved and proposes a definition of these terms. It generates some recommendations to differentiate the role of each community organization according to the regime or benefit plan in the SGSSS. Designs alternatives to involve the population of high strata in the social control. It identifies specific aspects of the relationship between the community sectors and the health institutions and their officials that are positively and negatively affecting their work as leaders in the SGSSS. Finally, a methodological proposal is made in which the conclusions of the work as well as the main weaknesses expressed by the leaders are taken up.