The 6 minute walk in idiopathic pulmonary fibrosis: longitudinal changes and minimum important difference

The response characteristics of the 6 minute walk test (6MWT) in studies of idiopathic pulmonary fibrosis (IPF) are only poorly understood, and the change in walk distance that constitutes the minimum important difference (MID) over time is unknown

The Extreme Behavior of the Radio-loud Narrow-line Seyfert 1 Galaxy J0849+5108

Simultaneous radio, optical (both photometry and polarimetry), X-ray, and γ-ray observations of the radio-loud narrow-line Seyfert 1 (RL-NLSy1) galaxy J0849+5108 are presented. A massive three-magnitude optical flare across five nights in 2013 April is detected, along with associated flux increases in the γ-ray, infrared, and radio regimes; no comparable event was detected in the X-rays, though this may be due to poor coverage. A spectral energy distribution (SED) for the object using quasi-simultaneous data centered on the optical flare is compared to the previously published SEDs for the object by D'Ammando et al. The flare event coincided with a high degree of optical polarization. High amplitude optical microvariability is clearly detected, and is found to be of comparable amplitude when the object is observed in both faint and bright states. The object is also seen to undergo rapid shifts in polarization in both degree and electric vector position angle within a single night. J0849+5108 appears to show even more extreme variability than that previously reported for the similar object J0948+0022. These observations appear to support the growing claim that some RL-NLSy1 galaxies constitute a sub-class of blazar-like active galactic nuclei

High-throughput single cell arrays as a novel tool in biopreservation

Microwell array cytometry is a novel high-throughput experimental technique that makes it possible to correlate pre-stress cell phenotypes and post-stress outcomes with single cell resolution. Because the cells are seeded in a high density grid of cell-sized microwells, thousands of individual cells can be tracked and imaged through manipulations as extreme as freezing or drying. Unlike flow cytometry, measurements can be made at multiple time points for the same set of cells. Unlike conventional image cytometry, image analysis is greatly simplified by arranging the cells in a spatially defined pattern and physically separating them from one another. To demonstrate the utility of microwell array cytometry in the field of biopreservation, we have used it to investigate the role of mitochondrial membrane potential in the cryopreservation of primary hepatocytes. Even with optimized cryopreservation protocols, the stress of freezing almost always leads to dysfunction or death in part of the cell population. To a large extent, cell fate is dominated by the stochastic nature of ice crystal nucleation, membrane rupture, and other biophysical processes, but natural variation in the initial cell population almost certainly plays an important and under-studied role. Understanding why some cells in a population are more likely to survive preservation will be invaluable for the development of new approaches to improve preservation yields. For this paper, primary hepatocytes were seeded in microwell array devices, imaged using the mitochondrial dyes Rh123 or JC-1, cryopreserved for up to a week, rapidly thawed, and checked for viability after a short recovery period. Cells with a high mitochondrial membrane potential before freezing were significantly less likely to survive the freezing process, though the difference in short term viability was fairly small. The results demonstrate that intrinsic cell factors do play an important role in cryopreservation survival, even in the short term where extrinsic biophysical factors would be expected to dominate. We believe that microwell array cytometry will be an important tool for a wide range of studies in biopreservation and stress biology. © 2009 Elsevier Inc. All rights reserved

Maternal Choline Supplementation Alters Fetal Growth Patterns in a Mouse Model of Placental Insufficiency

Impairments in placental development can adversely affect pregnancy outcomes. The bioactive nutrient choline may mitigate some of these impairments, as suggested by data in humans, animals, and human trophoblasts. Herein, we investigated the effects of maternal choline supplementation (MCS) on parameters of fetal growth in a Dlx3+/− (distal-less homeobox 3) mouse model of placental insufficiency. Dlx3+/− female mice were assigned to 1X (control), 2X, or 4X choline intake levels during gestation. Dams were sacrificed at embryonic days E10.5, 12.5, 15.5, and 18.5. At E10.5, placental weight, embryo weight, and placental efficiency were higher in 4X versus 1X choline. Higher concentrations of hepatic and placental betaine were detected in 4X versus 1X choline, and placental betaine was positively associated with embryo weight. Placental mRNA expression of Igf1 was downregulated by 4X (versus 1X) choline at E10.5. No differences in fetal growth parameters were detected at E12.5 and 15.5, whereas a small but significant reduction in fetal weight was detected at E18.5 in 4X versus 1X choline. MCS improved fetal growth during early pregnancy in the Dlx3+/− mice with the compensatory downregulation of Igf1 to slow growth as gestation progressed. Placental betaine may be responsible for the growth-promoting effects of choline

Nanorobotic investigation identifies novel visual, structural and functional correlates of autoimmune pathology in a blistering skin disease model

Copyright © 2014 Seiffert-Sinha et al. There remain major gaps in our knowledge regarding the detailed mechanisms by which autoantibodies mediate damage at the tissue level. We have undertaken novel strategies at the interface of engineering and clinical medicine to integrate nanoscale visual and structural data using nanorobotic atomic force microscopy with cell functional analyses to reveal previously unattainable details of autoimmune processes in real-time. Pemphigus vulgaris is a life-threatening autoimmune blistering skin condition in which there is disruption of desmosomal cell-cell adhesion structures that are associated with the presence of antibodies directed against specific epithelial proteins including Desmoglein (Dsg) 3. We demonstrate that pathogenic (blister-forming) anti-Dsg3 antibodies, distinct from non-pathogenic (non-blister forming) anti-Dsg3 antibodies, alter the structural and functional properties of keratinocytes in two sequential steps - an initial loss of cell adhesion and a later induction of apoptosis-related signaling pathways, but not full apoptotic cell death. We propose a ''2-Hit'' model for autoimmune disruption associated with skin-specific pathogenic autoantibodies. These data provide unprecedented details of autoimmune processes at the tissue level and offer a novel conceptual framework for understanding the action of selfreactive antibodies.published_or_final_versio

Galaxy Zoo: Exploring the Motivations of Citizen Science Volunteers

The Galaxy Zoo citizen science website invites anyone with an Internet connection to participate in research by classifying galaxies from the Sloan Digital Sky Survey. As of April 2009, more than 200,000 volunteers had made more than 100 million galaxy classifications. In this paper, we present results of a pilot study into the motivations and demographics of Galaxy Zoo volunteers, and define a technique to determine motivations from free responses that can be used in larger multiple-choice surveys with similar populations. Our categories form the basis for a future survey, with the goal of determining the prevalence of each motivation.Comment: 15 pages, 3 figure