A study of alterations in DNA epigenetic modifications (5mC and 5hmC) and gene expression influenced by simulated microgravity in human lymphoblastoid cells

Cells alter their gene expression in response to exposure to various environmental changes. Epigenetic mechanisms such as DNA methylation are believed to regulate the alterations in gene expression patterns. In vitro and in vivo studies have documented changes in cellular proliferation, cytoskeletal remodeling, signal transduction, bone mineralization and immune deficiency under the influence of microgravity conditions experienced in space. However microgravity induced changes in the epigenome have not been well characterized. In this study we have used Next-generation Sequencing (NGS) to profile ground-based “simulated” microgravity induced changes on DNA methylation (5-methylcytosine or 5mC), hydroxymethylation (5-hydroxymethylcytosine or 5hmC), and simultaneous gene expression in cultured human lymphoblastoid cells. Our results indicate that simulated microgravity induced alterations in the methylome (~60% of the differentially methylated regions or DMRs are hypomethylated and ~92% of the differentially hydroxymethylated regions or DHMRs are hyperhydroxymethylated). Simulated microgravity also induced differential expression in 370 transcripts that were associated with crucial biological processes such as oxidative stress response, carbohydrate metabolism and regulation of transcription. While we were not able to obtain any global trend correlating the changes of methylation/ hydroxylation with gene expression, we have been able to profile the simulated microgravity induced changes of 5mC over some of the differentially expressed genes that includes five genes undergoing differential methylation over their promoters and twenty five genes undergoing differential methylation over their gene-bodies. To the best of our knowledge, this is the first NGS-based study to profile epigenomic patterns induced by short time exposure of simulated microgravity and we believe that our findings can be a valuable resource for future explorations

Application developers’ product offering strategies in multi-platform markets

Mobile application (app) developers usually face challenges in product offering decisions. Our research develops an analytical framework to address a product offering problem that app developers face when introducing paid or free apps in a two-platform market. We provide optimal conditions and platform decisions for each strategy (in single and two platforms) by providing a framework for offering either a paid or a free app. When offering a paid app, we identify platforms’ willingness-to-pays, user densities, and platform-specific app-launching costs as key factors that determine platform selection strategy; if a free app is considered, users’ disutility sensitivity to advertisement is an extra factor for app developers to consider. The developer\u27s intrinsic capability and the app\u27s nature form the quality upper bound for the app. When the quality upper bound is low and users are less sensitive to advertisement, these apps are often offered free in the app market. We find that if users’ disutility sensitivities to advertisements are small, introducing a free app is preferable to a paid app

Research in Humanitarian Supply Chain Management and a New Framework

With the frequency and magnitude of disasters on the rise, millions of people suffer huge losses every year. Scholars have recently proposed various frameworks in disaster relief management in order to guide the research in this field. Although successful disaster relief requires the entire humanitarian supply chain to respond in harmony, it is surprising that there exists no humanitarian relief framework drawn from the perspective of supply chain management. In this article, we create a new research framework for Humanitarian Supply Chain Management (HSCM) that is complimentary but distinct from commercial supply chain management (CSCM) frameworks. The framework we developed offers a new lens for humanitarian researchers. We also conduct a systematic literature review in this field and identify some opportunities for future research. The results strongly suggest the need for additional empirical research to test the existing concepts and models. Second, there is evidence that research focusing on “upstream” relief chain has been neglected relative to “downstream”. Additionally, due to its rapid advancement, information technology related research opportunities in this field would always be there. Keywor

Microglia at sites of atrophy restrict the progression of retinal degeneration via galectin-3 and trem2 interactions

Degenerative diseases of the outer retina, including age-related macular degeneration (AMD), are characterized by atrophy of photoreceptors and retinal pigment epithelium (RPE). In these blinding diseases, macrophages are known to accumulate ectopically at sites of atrophy, but their ontogeny and functional specialization within this atrophic niche remain poorly understood, especially in the human context. Here, we uncovered a transcriptionally unique profile of microglia, marked by galectin-3 upregulation, at atrophic sites in mouse models of retinal degeneration and in human AMD. Using disease models, we found that conditional deletion of galectin-3 in microglia led to defects in phagocytosis and consequent augmented photoreceptor death, RPE damage and vision loss, suggestive of a protective role. Mechanistically, Trem2 signaling orchestrated the migration of microglial cells to sites of atrophy, and there, induced galectin-3 expression. Moreover, pharmacologic Trem2 agonization led to heightened protection, but only in a galectin-3-dependent manner, further signifying the functional interdependence of these two molecules. Likewise in elderly human subjects, we identified a highly conserved population of microglia at the transcriptomic, protein and spatial levels, and this population was enriched in the macular region of postmortem AMD subjects. Collectively, our findings reveal an atrophy-associated specialization of microglia that restricts the progression of retinal degeneration in mice and further suggest that these protective microglia are conserved in AMD