Defective postsecretory maturation of MUC5B mucin in cystic fibrosis airways

In cystic fibrosis (CF), airway mucus becomes thick and viscous, and its clearance from the airways is impaired. The gel-forming mucins undergo an ordered "unpacking/maturation" process after granular release that requires an optimum postsecretory environment, including hydration and pH. We hypothesized that this unpacking process is compromised in the CF lung due to abnormal transepithelial fluid transport that reduces airway surface hydration and alters ionic composition. Using human tracheobronchial epithelial cells derived from non-CF and CF donors and mucus samples from human subjects and domestic pigs, we investigated the process of postsecretory mucin unfolding/maturation, how these processes are defective in CF airways, and the probable mechanism underlying defective unfolding. First, we found that mucins released into a normal lung environment transform from a compact granular form to a linear form. Second, we demonstrated that this maturation process is defective in the CF airway environment. Finally, we demonstrated that independent of HCO3- and pH levels, airway surface dehydration was the major determinant of this abnormal unfolding process. This defective unfolding/maturation process after granular release suggests that the CF extracellular environment is ion/water depleted and likely contributes to abnormal mucus properties in CF airways prior to infection and inflammation

Kepler-22b: A 2.4 Earth-radius Planet in the Habitable Zone of a Sun-like Star

A search of the time-series photometry from NASA's Kepler spacecraft reveals a transiting planet candidate orbiting the 11th magnitude G5 dwarf KIC 10593626 with a period of 290 days. The characteristics of the host star are well constrained by high-resolution spectroscopy combined with an asteroseismic analysis of the Kepler photometry, leading to an estimated mass and radius of 0.970 +/- 0.060 MSun and 0.979 +/- 0.020 RSun. The depth of 492 +/- 10ppm for the three observed transits yields a radius of 2.38 +/- 0.13 REarth for the planet. The system passes a battery of tests for false positives, including reconnaissance spectroscopy, high-resolution imaging, and centroid motion. A full BLENDER analysis provides further validation of the planet interpretation by showing that contamination of the target by an eclipsing system would rarely mimic the observed shape of the transits. The final validation of the planet is provided by 16 radial velocities obtained with HIRES on Keck 1 over a one year span. Although the velocities do not lead to a reliable orbit and mass determination, they are able to constrain the mass to a 3{\sigma} upper limit of 124 MEarth, safely in the regime of planetary masses, thus earning the designation Kepler-22b. The radiative equilibrium temperature is 262K for a planet in Kepler-22b's orbit. Although there is no evidence that Kepler-22b is a rocky planet, it is the first confirmed planet with a measured radius to orbit in the Habitable Zone of any star other than the Sun.Comment: Accepted to Ap

Curious bivalves: Systematic utility and unusual properties of anomalodesmatan mitochondrial genomes

publisher: Elsevier articletitle: Curious bivalves: Systematic utility and unusual properties of anomalodesmatan mitochondrial genomes journaltitle: Molecular Phylogenetics and Evolution articlelink: http://dx.doi.org/10.1016/j.ympev.2017.03.004 content_type: article copyright: Crown Copyright © 2017 Published by Elsevier Inc. All rights reserved.The file attached is the final draft version of the article

Expression of the chloride channel CLC-K in human airway epithelial cells

Airway submucosal gland function is severely disrupted in cystic fibrosis (CF), as a result of genetic mutation of the cystic fibrosis transmembrane conductance regulator (CFTR), an apical membrane Cl– channel. To identify other Cl– channel types that could potentially substitute for lost CFTR function in these cells, we investigated the functional and molecular expression of Cl– channels in Calu-3 cells, a human cell line model of the submucosal gland serous cell. Whole cell patch clamp recording from these cells identified outwardly rectified, pH- and calcium-sensitive Cl– currents that resemble those previously ascribed to ClC-K type chloride channels. Using reverse transcription – polymerase chain reaction, we identified expression of mRNA for ClC-2, ClC-3, ClC-4, ClC-5, ClC-6, ClC-7, ClC-Ka, and ClC-Kb, as well as the common ClC-K channel b subunit barttin. Western blotting confirmed that Calu-3 cells express both ClC-K and barttin protein. Thus, Calu-3 cells express multiple members of the ClC family of Cl– channels that, if also expressed in native submucosal gland serous cells within the CF lung, could perhaps act to partially substitute lost CFTR function. Furthermore, this work represents the first evidence for functional ClC-K chloride channel expression within the lung

Clustering of Document Images using Graph Summaries

International audienceDocument image classification is an important step in document image analysis. Based on classification results we can tackle other tasks such as indexation, understanding or navigation in document collections. Using a document representation and an unsupervized classification method, we can group documents that from the user point of view constitute valid clusters. The semantic gap between a domain independent document representation and the user implicit representation can lead to unsatisfactory results. In this paper we describe document images based on frequent occurring symbols. This document description is created in an unsupervised manner and can be related to the domain knowledge. Using data mining techniques applied to a graph based document representation we found frequent and maximal subgraphs. For each document image, we construct a bag containing the frequent subgraphs found in it. This bag of "symbols" represents the description of a document. We present results obtained on a corpus of graphical document images