Control of RelB during dendritic cell activation integrates canonical and noncanonical NF-κB pathways.

The NF-κB protein RelB controls dendritic cell (DC) maturation and may be targeted therapeutically to manipulate T cell responses in disease. Here we report that RelB promoted DC activation not as the expected RelB-p52 effector of the noncanonical NF-κB pathway, but as a RelB-p50 dimer regulated by canonical IκBs, IκBα and IκBɛ. IκB control of RelB minimized spontaneous maturation but enabled rapid pathogen-responsive maturation. Computational modeling of the NF-κB signaling module identified control points of this unexpected cell type-specific regulation. Fibroblasts that we engineered accordingly showed DC-like RelB control. Canonical pathway control of RelB regulated pathogen-responsive gene expression programs. This work illustrates the potential utility of systems analyses in guiding the development of combination therapeutics for modulating DC-dependent T cell responses

Valor predictivo de variables bioquímicas y diámetro del colédoco medido por ecografía en pacientes con coledocolitiasis.

El síndrome biliar obstructivo, consta con patologías que tienen manifestaciones comunes como el dolor abdominal, ictericia y colestasis(1). La colelitiasis es la presencia de litios en la vesícula biliar, siendo una entidad frecuentemente encontrada en la parte occidental del planeta y en las poblaciones nativas del continente americano, estudios epidemiológicos por autopsias una prevalencia tan alta de hasta el 50% para la población de los indios PIMA por ejemplo. Estudios han concluido que el origen de procedencia juega un papel dominante entre los varios factores de riesgo etiológicos(1). Objetivo. Determinar el valor predictivo del diámetro del colédoco y de las pruebas bioquímicas para el diagnóstico de Coledocolitiasis y la concordancia entre ambos abordajes. RESULTADOS. De los 120 casos de pacientes analizados, 89 pacientes presentaron coledocolitiasis y 31 pacientes correspondieron a otros diagnosticos de via biliar. Se analizaron mediante test de Mann Whitney, se correlacionaron atreves del test de Spearman y su concordanciaatravez de kappa de cohen. CONCLUSIONES. La probabilidad de tener coledocolitiasis no es proporcional al número de predictores positivos, comprobándose que ningún indicador único (bilirrubina total, directa e indirecta, fosfatasa alcalina, AST, ALT y diámetro de colédoco medido por USG) es capaz de predecir, con total exactitud, la presencia de coledocolitiasis. El diámetro del colédoco tiene una pobre correlación entre diámetro del colédoco y diagnóstico de coledocolitiasis, esto puede deberse a que los exámenes imagenológicos fueron realizados por diferentes profesionales lo que evidencia un sesgo de operador dependiente. Existe una relación moderada entre fosfatasa alcalina y el diagnóstico de coledocolitiasis.Tesis presentada para optar al título de Doctorado en Medicin

IL-27R signalling mediates early viral containment and impacts innate and adaptive immunity after chronic lymphocytic choriomeningitis virus infection

Chronic viral infections represent a major challenge to host's immune response and a unique network of immunological elements, including cytokines, are required for their containment. By using a model persistent infection with the natural murine pathogen lymphocytic choriomeningitis virus clone 13 (LCMV Cl13) we investigated the role of one such cytokine, interleukin 27 (IL-27), in the control of chronic infection. We found that IL-27R signalling promoted control of LCMV Cl13 as early as day 1 and 5 after infection and that il27p28 transcripts were rapidly elevated in multiple subsets of dendritic cells (DCs) and myeloid cells. In particular, plasmacytoid DCs (pDCs), the most potent type-1-interferon (IFN-I) producing cells, significantly increased il27p28 in a TLR7 dependent fashion. Notably, mice deficient in IL-27 specific receptor (R), WSX-1, exhibited a pleiotropy of innate and adaptive immune alterations after chronic LCMV infection, including compromised NK cell cytotoxicity and antibody responses. While, the majority of these immune alterations appeared cell-extrinsic, cell-intrinsic IL-27R was necessary to maintain early pDC numbers, which, alongside lower IFN-I transcription in CD11b+ DCs and myeloid cells, may explain the compromised IFN-I elevation that we observed early after LCMV Cl13 infection in IL-27R-deficient mice. Together these data highlight the critical role of IL-27 in enabling optimal anti-viral immunity early and late after infection with a systemic persistent virus and suggest that a previously unrecognized positive feedback-loop mediated by IL-27 in pDCs might be involved in this process

Capacidad a ductilidad de pilas, columnas o torres en puentes especiales: tipo pórtico y atirantado

El presente trabajo de tesis es pertinente para el desarrollo de nueva información técnica en materia de diseño sismo-resistente de puentes especiales, la cual actualmente es insuficiente a nivel local, nacional e incluso internacional. Por lo tanto, este trabajo proporcionará literatura técnica en el análisis sísmico de puentes especiales y su capacidad de incursionar en el rango inelástico. Con este trabajo se pretende aportar valores de demanda de ductilidad máxima de algunos puentes especiales, específicamente: tipo pórtico y atirantado. De manera que sirvan como referencia para futuros proyectos de estructuras similares. De esta forma, proporcionar información válida para que el diseñador de puentes especiales tenga mayores herramientas de diseño y mejores concepciones de estas estructuras. Finalmente, con los resultados obtenidos se desea aportar información que estimule a nivel nacional la creación de una normatividad para puentes especiales con estudios que representen el peligro sísmico de México.Investigación realizada con el apoyo del Programa Nacional de Posgrados de Calidad del Consejo Nacional de Ciencia y Tecnología (CONACYT)

Juxtaposition of system dynamics and agent-based simulation for a case study in immunosenescence

Advances in healthcare and in the quality of life significantly increase human life expectancy. With the aging of populations, new un-faced challenges are brought to science. The human body is naturally selected to be well-functioning until the age of reproduction to keep the species alive. However, as the lifespan extends, unseen problems due to the body deterioration emerge. There are several age-related diseases with no appropriate treatment; therefore, the complex aging phenomena needs further understanding. It is known that immunosenescence is highly correlated to the negative effects of aging. In this work we advocate the use of simulation as a tool to assist the understanding of immune aging phenomena. In particular, we are comparing system dynamics modelling and simulation (SDMS) and agent-based modelling and simulation (ABMS) for the case of age-related depletion of naive T cells in the organism. We address the following research questions: Which simulation approach is more suitable for this problem? Can these approaches be employed interchangeably? Is there any benefit of using one approach compared to the other? Results show that both simulation outcomes closely fit the observed data and existing mathematical model; and the likely contribution of each of the naive T cell repertoire maintenance method can therefore be estimated. The differences observed in the outcomes of both approaches are due to the probabilistic character of ABMS contrasted to SDMS. However, they do not interfere in the overall expected dynamics of the populations. In this case, therefore, they can be employed interchangeably, with SDMS being simpler to implement and taking less computational resources

The Equifinality of Archaeological Networks: an Agent-Based Exploratory Lab Approach

When we find an archaeological network, how can we explore the necessary versus contingent processes at play in the formation of that archaeological network? Given a set of circumstances or processes, what other possible network shapes could have emerged? This is the problem of equifinality, where many different means could potentially arrive at the same end result: the networks that we observe. This paper outlines how agent-based modelling can be used as a laboratory for exploring different processes of archaeological network formation. We begin by describing our best guess about how the (ancient) world worked, given our target materials (here, the networks of production and patronage surrounding the Roman brick industry in the hinterland of Rome). We then develop an agent-based model of the Roman extractive economy which generates different kinds of networks under various assumptions about how that economy works. The rules of the simulation are built upon the work of Bang (2006; 2008) who describes a model of the Roman economy which he calls the ‘imperial Bazaar’. The agents are allowed to interact, and the investigators compare the kinds of networks this description generates over an entire landscape of economic possibilities. By rigorously exploring this landscape, and comparing the resultant networks with those observed in the archaeological materials, the investigators will be able to employ the principle of equifinality to work out the representativeness of the archaeological network and thus the underlying processes

Ontogenetic differences in muscle fatty acid profile of white sharks Carcharodon carcharias off Guadalupe Island, México

Carcharodon carcharias is a protected species occupying the apex of most marine foodwebs where they are present. Aggregation areas, such as Guadalupe Island, México,  that have been related to feeding events, are of special interest for this species conservation. The aim of this study was to describe the fatty acid profile of C. carcharias' muscle for the first time on Guadalupe Island, using non-lethal biopsy methods to determine ontogenetic and sex differences in relation to diet and habitat use. Fatty acid profiles and biomarkers from different individuals are explored as a source of integrated information of their diet. Analysis of the fatty acid composition of individuals with varying total lengths (2.3-5.0 m) suggested a dietary shift between juveniles and adults occurring at aproximately 3 m. Fatty acid biomarkers indicated a higher degree of carnivorism in adults than in juveniles. Additionally, these ecological tracers suggested that juveniles feed in shallow waters close to the coast, while adults feed in deep waters along inshore and offshore areas. This study represents a first step towards using fatty acid composition as a relevant tool for further understanding dietary shifts and habitat use throughout the ontogeny of C. carcharias. However, to corroborate this, further studies with larger sample sizes are required