Identification of miRNA signatures associated with radiation-induced late lung injury in mice.

Acute radiation exposure of the thorax can lead to late serious, and even life-threatening, pulmonary and cardiac damage. Sporadic in nature, late complications tend to be difficult to predict, which prompted this investigation into identifying non-invasive, tissue-specific biomarkers for the early detection of late radiation injury. Levels of circulating microRNA (miRNA) were measured in C3H and C57Bl/6 mice after whole thorax irradiation at doses yielding approximately 70% mortality in 120 or 180 days, respectively (LD70/120 or 180). Within the first two weeks after exposure, weight gain slowed compared to sham treated mice along with a temporary drop in white blood cell counts. 52% of C3H (33 of 64) and 72% of C57Bl/6 (46 of 64) irradiated mice died due to late radiation injury. Lung and heart damage, as assessed by computed tomography (CT) and histology at 150 (C3H mice) and 180 (C57Bl/6 mice) days, correlated well with the appearance of a local, miRNA signature in the lung and heart tissue of irradiated animals, consistent with inherent differences in the C3H and C57Bl/6 strains in their propensity for developing radiation-induced pneumonitis or fibrosis, respectively. Radiation-induced changes in the circulating miRNA profile were most prominent within the first 30 days after exposure and included miRNA known to regulate inflammation and fibrosis. Importantly, early changes in plasma miRNA expression predicted survival with reasonable accuracy (88-92%). The miRNA signature that predicted survival in C3H mice, including miR-34a-5p, -100-5p, and -150-5p, were associated with pro-inflammatory NF-κB-mediated signaling pathways, whereas the signature identified in C57Bl/6 mice (miR-34b-3p, -96-5p, and -802-5p) was associated with TGF-β/SMAD signaling. This study supports the hypothesis that plasma miRNA profiles could be used to identify individuals at high risk of organ-specific late radiation damage, with applications for radiation oncology clinical practice or in the context of a radiological incident

Scaling in Late Stage Spinodal Decomposition with Quenched Disorder

We study the late stages of spinodal decomposition in a Ginzburg-Landau mean field model with quenched disorder. Random spatial dependence in the coupling constants is introduced to model the quenched disorder. The effect of the disorder on the scaling of the structure factor and on the domain growth is investigated in both the zero temperature limit and at finite temperature. In particular, we find that at zero temperature the domain size, $R(t)$, scales with the amplitude, $A$, of the quenched disorder as $R(t) = A^{-\beta} f(t/A^{-\gamma})$ with $\beta \simeq 1.0$ and $\gamma \simeq 3.0$ in two dimensions. We show that $\beta/\gamma = \alpha$, where $\alpha$ is the Lifshitz-Slyosov exponent. At finite temperature, this simple scaling is not observed and we suggest that the scaling also depends on temperature and $A$. We discuss these results in the context of Monte Carlo and cell dynamical models for phase separation in systems with quenched disorder, and propose that in a Monte Carlo simulation the concentration of impurities, $c$, is related to $A$ by $A \sim c^{1/d}$.Comment: RevTex manuscript 5 pages and 5 figures (obtained upon request via email [email protected]

RNA sequencing analysis of human podocytes reveals glucocorticoid regulated gene networks targeting non-immune pathways

Glucocorticoids are steroids that reduce inflammation and are used as immunosuppressive drugs for many diseases. They are also the mainstay for the treatment of minimal change nephropathy (MCN), which is characterised by an absence of inflammation. Their mechanisms of action remain elusive. Evidence suggests that immunomodulatory drugs can directly act on glomerular epithelial cells or ‘podocytes’, the cell type which is the main target of injury in MCN. To understand the nature of glucocorticoid effects on non-immune cell functions, we generated RNA sequencing data from human podocyte cell lines and identified the genes that are significantly regulated in dexamethasone-treated podocytes compared to vehicle-treated cells. The upregulated genes are of functional relevance to cytoskeleton-related processes, whereas the downregulated genes mostly encode pro-inflammatory cytokines and growth factors. We observed a tendency for dexamethasone-upregulated genes to be downregulated in MCN patients. Integrative analysis revealed gene networks composed of critical signaling pathways that are likely targeted by dexamethasone in podocytes

Novel translocation responses of cytosolic phospholipase A2α fluorescent proteins

AbstractCytosolic phospholipase A2 (cPLA2)α responds to the rise in cytosolic Ca2+ ([Ca2+]i) attending cell stimulation by moving to intracellular membranes, releasing arachidonic acid (AA) from these membranes, and thereby initiating the synthesis of various lipid mediators. Under some conditions, however, cPLA2α translocation occurs without any corresponding changes in [Ca2+]i. The signal for such responses has not been identified. Using confocal microscopy to track fluorescent proteins fused to cPLA2α or cPLA2α's C2 domain, we find that AA mimics Ca2+ ionophores in stimulating cPLA2α translocations to the perinuclear ER and to a novel site, the lipid body. Unlike the ionophores, AA acted independently of [Ca2+]i rises and did not translocate the proteins to the Golgi. AA's action did not involve its metabolism to eicosanoids or acylation into cellular lipids. Receptor agonists also stimulated translocations targeting lipid bodies. We propose that AA is a signal for Ca2+-independent cPLA2α translocation and that lipid bodies are common targets of cPLA2α and contributors to stimulus-induced lipid mediator synthesis

Impact of dialect use on a basic component of learning to read

Can some black-white differences in reading achievement be traced to differences in language background? Many African American children speak a dialect that differs from the mainstream dialect emphasized in school. We examined how use of alternative dialects affects decoding, an important component of early reading and marker of reading development. Behavioral data show that use of the alternative pronunciations of words in different dialects affects reading aloud in developing readers, with larger effects for children who use more African American English. Mechanisms underlying this effect were explored with a computational model, investigating factors affecting reading acquisition. The results indicate that the achievement gap may be due in part to differences in task complexity: children whose home and school dialects differ are at greater risk for reading difficulties because tasks such as learning to decode are more complex for them

Infinite factorization of multiple non-parametric views

Combined analysis of multiple data sources has increasing application interest, in particular for distinguishing shared and source-specific aspects. We extend this rationale of classical canonical correlation analysis into a flexible, generative and non-parametric clustering setting, by introducing a novel non-parametric hierarchical mixture model. The lower level of the model describes each source with a flexible non-parametric mixture, and the top level combines these to describe commonalities of the sources. The lower-level clusters arise from hierarchical Dirichlet Processes, inducing an infinite-dimensional contingency table between the views. The commonalities between the sources are modeled by an infinite block model of the contingency table, interpretable as non-negative factorization of infinite matrices, or as a prior for infinite contingency tables. With Gaussian mixture components plugged in for continuous measurements, the model is applied to two views of genes, mRNA expression and abundance of the produced proteins, to expose groups of genes that are co-regulated in either or both of the views. Cluster analysis of co-expression is a standard simple way of screening for co-regulation, and the two-view analysis extends the approach to distinguishing between pre- and post-translational regulation

New Interactions: The relationship between journalists and audiences mediated by Google Glass

From the first studies of wearables inside MIT’s Media Lab decades ago to the smartwatches and smartglasses sold these days as consumer devices, wearables provide clues to better understand new paths to record and distribute information. Google Glass was one of the first immersive products, allowing users to capture and stream information to the Web, creating screen-based micro-interactions displayed in front of the user’s eye or sent to their smartphone. The first-person perspective is not new, but network-enabled Glass creates a novel state of streamed information and images, potentially making the journalist an avatar of the audience. Possibilities also lay in the development of Glass-specific ambient or calm communications—providing users with seamless information updates. Our study explores how Glass, attached to the head of the journalist-broadcaster, creates alternative behaviours in those captured due to its almost-invisible camera. These and other aspects of Glass will be explored during this paper, recalling experiences made across multiple test beds in the United Kingdom, Porto Alegre, Brazil and the Sahara Desert. The lessons acquired from these experiences allow us to understand not only new ways to inform, but new relationships between journalists, newsrooms and the public

Message-Passing Methods for Complex Contagions

Message-passing methods provide a powerful approach for calculating the expected size of cascades either on random networks (e.g., drawn from a configuration-model ensemble or its generalizations) asymptotically as the number $N$ of nodes becomes infinite or on specific finite-size networks. We review the message-passing approach and show how to derive it for configuration-model networks using the methods of (Dhar et al., 1997) and (Gleeson, 2008). Using this approach, we explain for such networks how to determine an analytical expression for a "cascade condition", which determines whether a global cascade will occur. We extend this approach to the message-passing methods for specific finite-size networks (Shrestha and Moore, 2014; Lokhov et al., 2015), and we derive a generalized cascade condition. Throughout this chapter, we illustrate these ideas using the Watts threshold model.Comment: 14 pages, 3 figure

Ion flow in a zeolitic imidazolate framework results in ionic diode phenomena

Ionic transport (for applications in nanofluidics or membranes) and “ionic diode” phenomena in a zeolitic imidazolate framework (ZIF-8) are investigated by directly growing the framework from aqueous Zn2+ and 2-methylimidazole as an “asymmetric plug” into a 20 ?m diameter pore in a ca. 6 ?m thin poly-ethylene-terephthalate (PET) film

Ion flow in a zeolitic imidazolate framework results in ionic diode phenomena

Ionic transport (for applications in nanofluidics or membranes) and "ionic diode" phenomena in a zeolitic imidazolate framework (ZIF-8) are investigated by directly growing the framework from aqueous Zn2+ and 2-methylimidazole as an "asymmetric plug" into a 20 μm diameter pore in a ca. 6 μm thin poly-ethylene-terephthalate (PET) film.</p