Biomedical Sciences Publications (UMKC)
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Items in this collection are the scholarly output of the Department of Biomedical Sciences faculty, staff, and students, either alone or as co-authors, and which may or may not have been published in an alternate format.
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Item RNA-seq analysis of synovial fibroblasts brings new insights into rheumatoid arthritis(2012-12-21) Heruth, Daniel P; Gibson, Margaret; Grigoryev, Dmitry N; Zhang, Li Qin; Ye, Shui QingAbstract Background Rheumatoid arthritis (RA) is a chronic autoimmune-disease of unknown origin that primarily affects the joints and ultimately leads to their destruction. Growing evidence suggests that synvovial fibroblasts play important roles in the initiation and the perpetuation of RA but underlying molecular mechanisms are not understood fully. In the present study, Illumina RNA sequencing was used to profile two human normal control and two rheumatoid arthritis synvovial fibroblasts (RASFs) transcriptomes to gain insights into the roles of synvovial fibroblasts in RA. Results We found that besides known inflammatory and immune responses, other novel dysregulated networks and pathways such as Cell Morphology, Cell-To-Cell Signaling and Interaction, Cellular Movement, Cellular Growth and Proliferation, and Cellular Development, may all contribute to the pathogenesis of RA. Our study identified several new genes and isoforms not previously associated with rheumatoid arthritis. 122 genes were up-regulated and 155 genes were down-regulated by at least two-fold in RASFs compared to controls. Of note, 343 known isoforms and 561 novel isoforms were up-regulated and 262 known isoforms and 520 novel isoforms were down-regulated by at least two-fold. The magnitude of difference and the number of differentially expressed known and novel gene isoforms were not detected previously by DNA microarray. Conclusions Since the activation and proliferation of RASFs has been implicated in the pathogenesis of rheumatoid arthritis, further in-depth follow-up analysis of the transcriptional regulation reported in this study may shed light on molecular pathogenic mechanisms underlying synovial fibroblasts in arthritis and provide new leads of potential therapeutic targets.Item Associations between the built environment and physical activity in public housing residents(2007-11-12) Heinrich, Katie M; Lee, Rebecca E; Suminski, Richard R; Regan, Gail R; Reese-Smith, Jacqueline Y; Howard, Hugh H; Haddock, C Keith; Poston, Walker SC; Ahluwalia, Jasjit SAbstract Background Environmental factors may influence the particularly low rates of physical activity in African American and low-income adults. This cross-sectional study investigated how measured environmental factors were related to self-reported walking and vigorous physical activity for residents of low-income public housing developments. Methods Physical activity data from 452 adult residents residing in 12 low-income housing developments were combined with measured environmental data that examined the neighborhood (800 m radius buffer) around each housing development. Aggregated ecological and multilevel regression models were used for analysis. Results Participants were predominately female (72.8%), African American (79.6%) and had a high school education or more (59.0%). Overall, physical activity rates were low, with only 21% of participants meeting moderate physical activity guidelines. Ecological models showed that fewer incivilities and greater street connectivity predicted 83% of the variance in days walked per week, p < 0.001, with both gender and connectivity predicting days walked per week in the multi-level analysis, p < 0.05. Greater connectivity and fewer physical activity resources predicted 90% of the variance in meeting moderate physical activity guidelines, p < 0.001, and gender and connectivity were the multi-level predictors, p < 0.05 and 0.01, respectively. Greater resource accessibility predicted 34% of the variance in days per week of vigorous physical activity in the ecological model, p < 0.05, but the multi-level analysis found no significant predictors. Conclusion These results indicate that the physical activity of low-income residents of public housing is related to modifiable aspects of the built environment. Individuals with greater access to more physical activity resources with fewincivilities, as well as, greater street connectivity, are more likely to be physically active.Item Gene selection for classification of microarray data based on the Bayes error(2007-10-03) Zhang, Ji-Gang; Deng, Hong-WenAbstract Background With DNA microarray data, selecting a compact subset of discriminative genes from thousands of genes is a critical step for accurate classification of phenotypes for, e.g., disease diagnosis. Several widely used gene selection methods often select top-ranked genes according to their individual discriminative power in classifying samples into distinct categories, without considering correlations among genes. A limitation of these gene selection methods is that they may result in gene sets with some redundancy and yield an unnecessary large number of candidate genes for classification analyses. Some latest studies show that incorporating gene to gene correlations into gene selection can remove redundant genes and improve classification accuracy. Results In this study, we propose a new method, Based Bayes error Filter (BBF), to select relevant genes and remove redundant genes in classification analyses of microarray data. The effectiveness and accuracy of this method is demonstrated through analyses of five publicly available microarray datasets. The results show that our gene selection method is capable of achieving better accuracies than previous studies, while being able to effectively select relevant genes, remove redundant genes and obtain efficient and small gene sets for sample classification purposes. Conclusion The proposed method can effectively identify a compact set of genes with high classification accuracy. This study also indicates that application of the Bayes error is a feasible and effective wayfor removing redundant genes in gene selection.Item HAPSIMU: a genetic simulation platform for population-based association studies(2008-08-05) Zhang, Feng; Liu, Jianfeng; Chen, Jie; Deng, Hong-WenAbstract Background Population structure is an important cause leading to inconsistent results in population-based association studies (PBAS) of human diseases. Various statistical methods have been proposed to reduce the negative impact of population structure on PBAS. Due to lack of structural information in real populations, it is difficult to evaluate the impact of population structure on PBAS in real populations. Results We developed a genetic simulation platform, HAPSIMU, based on real haplotype data from the HapMap ENCODE project. This platform can simulate heterogeneous populations with various known and controllable structures under the continuous migration model or the discrete model. Moreover, both qualitative and quantitative traits can be simulated using additive genetic model with various genetic parameters designated by users. Conclusion HAPSIMU provides a common genetic simulation platform to evaluate the impact of population structure on PBAS, and compare the relative performance of various population structure identification and PBAS methods.Item The neuroprotective properties of palmitoylethanolamine against oxidative stress in a neuronal cell line(2009-12-10) Duncan, R Scott; Chapman, Kent D; Koulen, PeterAbstract Background N-acylethanolamines (NAEs) are lipids upregulated in response to cell and tissue injury and are involved in cytoprotection. Arachidonylethanolamide (AEA) is a well characterized NAE that is an endogenous ligand at cannabinoid and vanilloid receptors, but it exists in small quantities relative to other NAE types. The abundance of other NAE species, such as palmitoylethanolamine (PEA), together with their largely unknown function and receptors, has prompted us to examine the neuroprotective properties and mechanism of action of PEA. We hypothesized that PEA protects HT22 cells from oxidative stress and activates neuroprotective kinase signaling pathways. Results Indeed PEA protected HT22 cells from oxidative stress in part by mediating an increase in phosphorylated Akt (pAkt) and ERK1/2 immunoreactivity as well as pAkt nuclear translocation. These changes take place within a time frame consistent with neuroprotection. Furthermore, we determined that changes in pAkt immunoreactivity elicited by PEA were not mediated by activation of cannabinoid receptor type 2 (CB2), thus indicating a novel mechanism of action. These results establish a role for PEA as a neuroprotectant against oxidative stress, which occurs in a variety of neurodegenerative diseases. Conclusions The results from this study reveal that PEA protects HT22 cells from oxidative stress and alters the localization and expression levels of kinases known to be involved in neuroprotection by a novel mechanism. Overall, these results identify PEA as a neuroprotectant with potential as a possible therapeutic agent in neurodegenerative diseases involving oxidative stress.