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Sleep deprivation (SD) plays a complex role in central nervous system (CNS) diseases. Recent studies indicate that short-term SD can affect the extent of ischemic damage. The aim of this study was to investigate whether short-term SD could stimulate hippocampal neurogenesis in a rat model of global cerebral ischemia/reperfusion (GCIR).One hundred Sprague-Dawley rats were randomly divided into Sham, GCIR and short-term SD groups based on different durations of SD; the short-term SD group was randomly divided into three subgroups: the GCIR+6hSD*3d-treated, GCIR+12hSD-treated and GCIR+12hSD*3d-treated groups. The GCIR rat model was induced via the bilateral occlusion of the common carotid arteries and hemorrhagic hypotension. The rats were sleep-deprived starting at 48 h following GCIR. A Morris water maze test was used to assess learning and memory ability; cell proliferation and differentiation were analyzed via 5-bromodeoxyuridine (BrdU) and neuron-specific enolase (NSE), respectively, at 14 and 28 d; the expression of hippocampal BDNF was measured after 7 d.The different durations of short-term SD designed in our experiment exhibited improvement in cognitive function as well as increased hippocampal BDNF expression. Additionally, the short-term SD groups also showed an increased number of BrdU- and BrdU/NSE-positive cells compared with the GCIR group. Of the three short-term SD groups, the GCIR+12hSD*3d-treated group experienced the most substantial beneficial effects.Short-term SD, especially the GCIR+12hSD*3d-treated method, stimulates neurogenesis in the hippocampal dentate gyrus (DG) of rats that undergo GCIR, and BDNF may be an underlying mechanism in this process.

Cross-linking immunoprecipitation coupled with high-throughput sequencing (CLIP-Seq) has made it possible to identify the targeting sites of RNA-binding proteins in various cell culture systems and tissue types on a genome-wide scale. Here we present a novel model-based approach (MiClip) to identify high-confidence protein-RNA binding sites from CLIP-seq datasets. This approach assigns a probability score for each potential binding site to help prioritize subsequent validation experiments. The MiClip algorithm has been tested in both HITS-CLIP and PAR-CLIP datasets. In the HITS-CLIP dataset, the signal/noise ratios of miRNA seed motif enrichment produced by the MiClip approach are between 17% and 301% higher than those by the ad hoc method for the top 10 most enriched miRNAs. In the PAR-CLIP dataset, the MiClip approach can identify ∼50% more validated binding targets than the original ad hoc method and two recently published methods. To facilitate the application of the algorithm, we have released an R package, MiClip (http://cran.r-project.org/web/packages/MiClip/index.html), and a public web-based graphical user interface software (http://galaxy.qbrc.org/tool_runner?tool_id=mi_clip) for customized analysis.

Many studies try to identify cancer diagnostic biomarkers by comparing peripheral whole blood (PWB) of cancer samples and healthy controls, explicitly or implicitly assuming that such biomarkers are potential candidate biomarkers for distinguishing cancer from nonmalignant inflammation-associated diseases.Multiple PWB gene expression profiles for lung cancer/inflammation-associated pulmonary diseases were used for differential mRNAs identification and comparison and for proportion estimation of PWB cell subtypes.The differentially expressed genes (DE genes) between lung cancer/inflammation-associated pulmonary patients and healthy controls were reproducibly identified in different datasets. For these DE genes observed in lung cancer/inflammation-associated pulmonary diseases, more than 90.2% were differentially expressed between myeloid cells and lymphoid cells, with at least 96.8% having consistent directions of regulation (up- or down-regulations) in myeloid cells compared to lymphoid cells, explainable by the shifted populations of PWB cell subtypes under the disease conditions. The comparison of DE genes for lung cancer and inflammation-associated pulmonary diseases showed that the overlapping genes were 100% consistent in the sense of direction of regulation.The differential blood mRNAs observed in lung cancer and in inflammation-associated pulmonary diseases were similar, both mainly reflecting the difference between myeloid cells and lymphoid cells predominantly determined by PWB cell population shifts. Thus, the strategy of comparing cancer with healthy controls may provide little information of the ability of the identified candidate biomarkers in discriminating cancer from inflammation-associated pulmonary diseases.

BACKGROUND: Patients with ulcerative colitis (UC) are predisposed to colitis-associated colorectal cancer (CAC). However, the transcriptional mechanism of the transformation from UC to CAC is not fully understood. METHODOLOGY: Firstly, we showed that CAC and non-UC-associated CRC were very similar in gene expression. Secondly, based on multiple datasets for UC and CRC, we extracted differentially expressed (DE) genes in UC and CRC versus normal controls, respectively. Thirdly, we compared the dysregulation directions (upregulation or downregulation) between DE genes of UC and CRC in CRC-related functions overrepresented with the DE genes of CRC, and proposed a regulatory model to explain the CRC-like dysregulation of genes in UC. A case study for "positive regulation of immune system process" was done to reveal the functional implication of DE genes with reversal dysregulations in these two diseases. PRINCIPAL FINDINGS: In all the 44 detected CRC-related functions except for "viral transcription", the dysregulation directions of DE genes in UC were significantly similar with their counterparts in CRC, and such CRC-like dysregulation in UC could be regulated by transcription factors affected by pro-inflammatory stimuli for colitis. A small portion of genes in each CRC-related function were dysregulated in opposite directions in the two diseases. The case study showed that genes related to humoral immunity specifically expressed in B cells tended to be upregulated in UC but downregulated in CRC. CONCLUSIONS: The CRC-like dysregulation of genes in CRC-related functions in UC patients provides hints for understanding the transcriptional basis for UC to CRC transition. A small portion of genes with distinct dysregulation directions in each of the CRC-related functions in the two diseases implicate that their reversal dysregulations might be critical for UC to CRC transition. The cases study indicates that the humoral immune response might be inhibited during the transformation from UC to CRC.

Somatic cells can be reprogrammed to a pluripotent state by over-expression of defined factors, and pluripotency has been confirmed by the tetraploid complementation assay. However, especially in human cells, estimating the quality of Induced Pluripotent Stem Cell(iPSC) is still difficult. Here, we present a novel supervised method for the assessment of the quality of iPSCs by estimating the gene expression profile using a 2-D "Differentiation-index coordinate", which consists of two "developing lines" that reflects the directions of ES cell differentiation and the changes of cell states during differentiation. By applying a novel liner model to describe the differentiation trajectory, we transformed the ES cell differentiation time-course expression profiles to linear "developing lines"; and use these lines to construct the 2-D "Differentiation-index coordinate" of mouse and human. We compared the published gene expression profiles of iPSCs, ESCs and fibroblasts in mouse and human "Differentiation-index coordinate". Moreover, we defined the Distance index to indicate the qualities of iPS cells, which based on the projection distance of iPSCs-ESCs and iPSCs-fibroblasts. The results indicated that the "Differentiation-index coordinate" can distinguish differentiation states of the different cells types. Furthermore, by applying this method to the analysis of expression profiles in the tetraploid complementation assay, we showed that the Distance index which reflected spatial distributions correlated the pluripotency of iPSCs. We also analyzed the significantly changed gene sets of "developing lines". The results suggest that the method presented here is not only suitable for the estimation of the quality of iPS cells based on expression profiles, but also is a new approach to analyze time-resolved experimental data.