Susceptibility to COPD:Differential Proteomic Profiling after Acute Smoking

Cigarette smoking is the main risk factor for COPD (Chronic Obstructive Pulmonary Disease), yet only a subset of smokers develops COPD. Family members of patients with severe early-onset COPD have an increased risk to develop COPD and are therefore defined as "susceptible individuals". Here we perform unbiased analyses of proteomic profiles to assess how "susceptible individuals" differ from age-matched "non-susceptible individuals" in response to cigarette smoking. Epithelial lining fluid (ELF) was collected at baseline and 24 hours after smoking 3 cigarettes in young individuals susceptible or non-susceptible to develop COPD and older subjects with established COPD. Controls at baseline were older healthy smoking and non-smoking individuals. Five samples per group were pooled and analysed by stable isotope labelling (iTRAQ) in duplicate. Six proteins were selected and validated by ELISA or immunohistochemistry. After smoking, 23 proteins increased or decreased in young susceptible individuals, 7 in young non-susceptible individuals, and 13 in COPD in the first experiment; 23 proteins increased or decreased in young susceptible individuals, 32 in young non-susceptible individuals, and 11 in COPD in the second experiment. SerpinB3 and Uteroglobin decreased after acute smoke exposure in young non-susceptible individuals exclusively, whereas Peroxiredoxin I, S100A9, S100A8, ALDH3A1 (Aldehyde dehydrogenase 3A1) decreased both in young susceptible and non-susceptible individuals, changes being significantly different between groups for Uteroglobin with iTRAQ and for Serpin B3 with iTRAQ and ELISA measures. Peroxiredoxin I, SerpinB3 and ALDH3A1 increased in COPD patients after smoking. We conclude that smoking induces a differential protein response in ELF of susceptible and non-susceptible young individuals, which differs from patients with established COPD. This is the first study applying unbiased proteomic profiling to unravel the underlying mechanisms that induce COPD. Our data suggest that SerpinB3 and Uteroglobin could be interesting proteins in understanding the processes leading to COPD

Modeling the Spatial Distribution and Fruiting Pattern of a Key Tree Species in a Neotropical Forest: Methodology and Potential Applications

Damien Caillaud is with UT Austin and Max Planck Institute for Evolutionary Anthropology; Margaret C. Crofoot is with the Smithsonian Tropical Research Institute, Max Planck Institute for Ornithology, and Princeton University; Samuel V. Scarpino is with UT Austin; Patrick A. Jansen is with the Smithsonian Tropical Research Institute, Wageningen University, and University of Groningen; Carol X. Garzon-Lopez is with University of Groningen; Annemarie J. S. Winkelhagen is with Wageningen University; Stephanie A. Bohlman is with Princeton University; Peter D. Walsh is with VaccinApe.Background -- The movement patterns of wild animals depend crucially on the spatial and temporal availability of resources in their habitat. To date, most attempts to model this relationship were forced to rely on simplified assumptions about the spatiotemporal distribution of food resources. Here we demonstrate how advances in statistics permit the combination of sparse ground sampling with remote sensing imagery to generate biological relevant, spatially and temporally explicit distributions of food resources. We illustrate our procedure by creating a detailed simulation model of fruit production patterns for Dipteryx oleifera, a keystone tree species, on Barro Colorado Island (BCI), Panama. Methodology and Principal Findings -- Aerial photographs providing GPS positions for large, canopy trees, the complete census of a 50-ha and 25-ha area, diameter at breast height data from haphazardly sampled trees and long-term phenology data from six trees were used to fit 1) a point process model of tree spatial distribution and 2) a generalized linear mixed-effect model of temporal variation of fruit production. The fitted parameters from these models are then used to create a stochastic simulation model which incorporates spatio-temporal variations of D. oleifera fruit availability on BCI. Conclusions and Significance -- We present a framework that can provide a statistical characterization of the habitat that can be included in agent-based models of animal movements. When environmental heterogeneity cannot be exhaustively mapped, this approach can be a powerful alternative. The results of our model on the spatio-temporal variation in D. oleifera fruit availability will be used to understand behavioral and movement patterns of several species on BCI.The National Center For Ecological Analysis is supported by NSF Grant DEB-0553768, the University of California Santa Barbara and the State of California. The Forest Dynamics Plots were funded by NSF Grants to Stephen Hubbell DEB-0640386, DEB-0425651, DEB-0346488, DEB-0129874, DEB-00753102, DEB-9909347, DEB-9615226, DEB-9615226, DEB-9405933, DEB-9221033, DEB-9100058, DEB-8906869, DEB-8605042, DEB-8206992, DEB-7922197, and by the Center for Tropical Forest Science, the Smithsonian Tropical Forest Research Institute, The John D. and Catherine T. MacArthur Foundation, the Mellon Foundation and the Celera Foundation. DC is supported by NSF grant DEB-0749097 to L.A. Meyers. SS is supported by an NSF Graduate Research Fellowship. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Biological Sciences, School o

Terrestrialization, Miniaturization and Rates of Diversification in African Puddle Frogs (Anura: Phrynobatrachidae)

Terrestrialization, the evolution of non-aquatic oviposition, and miniaturization, the evolution of tiny adult body size, are recurring trends in amphibian evolution, but the relationships among the traits that characterize these phenomena are not well understood. Furthermore, these traits have been identified as possible “key innovations” that are predicted to increase rates of speciation in those lineages in which they evolve. We examine terrestrialization and miniaturization in sub-Saharan puddle frogs (Phrynobatrachidae) in a phylogenetic context to investigate the relationship between adaptation and diversification through time. We use relative dating techniques to ascertain if character trait shifts are associated with increased diversification rates, and we evaluate the likelihood that a single temporal event can explain the evolution of those traits. Results indicate alternate reproductive modes evolved independently in Phrynobatrachus at least seven times, including terrestrial deposition of eggs and terrestrial, non-feeding larvae. These shifts towards alternate reproductive modes are not linked to a common temporal event. Contrary to the “key innovations” hypothesis, clades that exhibit alternate reproductive modes have lower diversification rates than those that deposit eggs aquatically. Adult habitat, pedal webbing and body size have no effect on diversification rates. Though these traits putatively identified as key innovations for Phrynobatrachus do not seem to be associated with increased speciation rates, they may still provide opportunities to extend into new niches, thus increasing overall diversity

ICAR: endoscopic skull‐base surgery

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