A novel regulatory event-based gene set analysis method for exploring global functional changes in heterogeneous genomic data sets

<p>Abstract</p> <p>Background</p> <p>Analyzing gene expression data by assessing the significance of pre-defined gene sets, rather than individual genes, has become a main approach in microarray data analysis and this has promisingly derive new biological interpretations of microarray data. However, the detection power of conventional gene list or gene set-based approaches is limited on highly heterogeneous samples, such as tumors.</p> <p>Results</p> <p>We developed a novel method, the regulatory <b>e</b>vent-based <b>G</b>ene <b>S</b>et <b>A</b>nalysis (eGSA), which considers not only the consistently changed genes but also every gene regulation (event) of each sample to overcome the detection limit. In comparison with conventional methods, eGSA can detect functional changes in heterogeneous samples more precisely and robustly. Furthermore, by utilizing eGSA, we successfully revealed novel functional characteristics and potential mechanisms of very early hepatocellular carcinoma (HCC).</p> <p>Conclusion</p> <p>Our study creates a novel scheme to directly target the major cellular functional changes in heterogeneous samples. All potential regulatory routines of a functional change can be further analyzed by the regulatory event frequency. We also provide a case study on early HCCs and reveal a novel insight at the initial stage of hepatocarcinogenesis. eGSA therefore accelerates and refines the interpretation of heterogeneous genomic data sets in the absence of gene-phenotype correlations.</p

AGE-BSA down-regulates endothelial connexin43 gap junctions

<p>Abstract</p> <p>Background</p> <p>Advanced glycation end products generated in the circulation of diabetic patients were reported to affect the function of vascular wall. We examined the effects of advanced glycation end products-bovine serum albumin (AGE-BSA) on endothelial connexin43 (Cx43) expression and gap-junction communication.</p> <p>Results</p> <p>In human aortic endothelial cells (HAEC) treated with a series concentrations of AGE-BSA (0-500 μg/ml) for 24 and 48 hours, Cx43 transcript and Cx43 protein were reduced in a dose dependent manner. In addition, gap-junction communication was reduced. To clarify the mechanisms underlying the down-regulation, MAPKs pathways in HAEC were examined. Both a MEK1 inhibitor (PD98059) and a p38 MAPK inhibitor (SB203580) significantly reversed the reductions of Cx43 mRNA and protein induced by AGE-BSA. Consistently, phosphorylation of ERK and p38 MAPK was enhanced in response to exposure to AGE-BSA. However, all reversions of down-regulated Cx43 by inhibitors did not restore the functional gap-junction communication.</p> <p>Conclusions</p> <p>AGE-BSA down-regulated Cx43 expression in HAEC, mainly through reduced Cx43 transcription, and the process involved activation of ERK and p38 MAPK.</p

easyExon – A Java-based GUI tool for processing and visualization of Affymetrix exon array data

<p>Abstract</p> <p>Background</p> <p>Alternative RNA splicing greatly increases proteome diversity and thereby contribute to species- or tissue-specific functions. The possibility to study alternative splicing (AS) events on a genomic scale using splicing-sensitive microarrays, including the Affymetrix GeneChip Exon 1.0 ST microarray (exon array), has appeared very recently. However, the application of this new technology is hindered by the lack of free and user-friendly software devoted to these novel platforms.</p> <p>Results</p> <p>In this study we present a Java-based freeware, easyExon <url>http://microarray.ym.edu.tw/easyexon</url>, to process, filtrate and visualize exon array data with an analysis pipeline. This tool implements the most commonly used probeset summarization methods as well as AS-orientated filtration algorithms, e.g. MIDAS and PAC, for the detection of alternative splicing events. We include a biological filtration function according to GO terms, and provide a module to visualize and interpret the selected exons and transcripts. Furthermore, easyExon can integrate with other related programs, such as Integrate Genome Browser (IGB) and Affymetrix Power Tools (APT), to make the whole analysis more comprehensive. We applied easyExon on a public accessible colon cancer dataset as an example to illustrate the analysis pipeline of this tool.</p> <p>Conclusion</p> <p>EasyExon can efficiently process and analyze the Affymetrix exon array data. The simplicity, flexibility and brevity of easyExon make it a valuable tool for AS event identification in genomic research.</p

Exploring the heterogeneity of effects of corticosteroids on acute respiratory distress syndrome: a systematic review and meta-analysis

INTRODUCTION: The effectiveness of corticosteroid therapy on the mortality of acute respiratory distress syndrome (ARDS) remains under debate. We aimed to explore the grounds for the inconsistent results in previous studies and update the evidence. METHODS: We searched MEDLINE, Cochrane Central Register of Controlled Trials and Web of Science up to December 2013. Eligible studies included randomized clinical trials (RCTs) and cohort studies that reported mortality and that had corticosteroid nonusers for comparison. The effect of corticosteroids on ARDS mortality was assessed by relative risk (RR) and risk difference (RD) for ICU, hospital, and 60-day mortality using a random-effects model. RESULTS: Eight RCTs and 10 cohort studies were included for analysis. In RCTs, corticosteroids had a possible but statistically insignificant effect on ICU mortality (RD, −0.28; 95% confidence interval (CI), −0.53 to −0.03 and RR, 0.55; 95% CI, 0.24 to 1.25) but no effect on 60-day mortality (RD, −0.01; 95% CI, −0.12 to 0.10 and RR, 0.97; 95% CI, 0.75 to 1.26). In cohort studies, corticosteroids had no effect on ICU mortality (RR, 1.05; 95% CI, 0.74 to 1.49) but non-significantly increased 60-day mortality (RR, 1.30; 95% CI, 0.96 to 1.78). In the subgroup analysis by ARDS etiology, corticosteroids significantly increased mortality in influenza-related ARDS (three cohort studies, RR, 2.45, 95% CI, 1.40 to 4.27). CONCLUSIONS: The effects of corticosteroids on the mortality of ARDS differed by duration of outcome measures and etiologies. Corticosteroids did not improve longer-term outcomes and may cause harm in certain subgroups. Current data do not support routine use of corticosteroids in ARDS. More clinical trials are needed to specify the favorable and unfavorable subgroups for corticosteroid therapy

Ventricular divergence correlates with epicardial wavebreaks and predicts ventricular arrhythmia in isolated rabbit hearts during therapeutic hypothermia

INTRODUCTION: High beat-to-beat morphological variation (divergence) on the ventricular electrogram during programmed ventricular stimulation (PVS) is associated with increased risk of ventricular fibrillation (VF), with unclear mechanisms. We hypothesized that ventricular divergence is associated with epicardial wavebreaks during PVS, and that it predicts VF occurrence. METHOD AND RESULTS: Langendorff-perfused rabbit hearts (n = 10) underwent 30-min therapeutic hypothermia (TH, 30°C), followed by a 20-min treatment with rotigaptide (300 nM), a gap junction modifier. VF inducibility was tested using burst ventricular pacing at the shortest pacing cycle length achieving 1:1 ventricular capture. Pseudo-ECG (p-ECG) and epicardial activation maps were simultaneously recorded for divergence and wavebreaks analysis, respectively. A total of 112 optical and p-ECG recordings (62 at TH, 50 at TH treated with rotigaptide) were analyzed. Adding rotigaptide reduced ventricular divergence, from 0.13±0.10 at TH to 0.09±0.07 (p = 0.018). Similarly, rotigaptide reduced the number of epicardial wavebreaks, from 0.59±0.73 at TH to 0.30±0.49 (p = 0.036). VF inducibility decreased, from 48±31% at TH to 22±32% after rotigaptide infusion (p = 0.032). Linear regression models showed that ventricular divergence correlated with epicardial wavebreaks during TH (p<0.001). CONCLUSION: Ventricular divergence correlated with, and might be predictive of epicardial wavebreaks during PVS at TH. Rotigaptide decreased both the ventricular divergence and epicardial wavebreaks, and reduced the probability of pacing-induced VF during TH

Hyperbilirubinemia with urinary tract infection in infants younger than eight weeks old

AbstractBackgroundHyperbilirubinemia is one of the most common causes for hospital admission in neonatal infants. Previous studies have found that jaundice may be one of the initial symptoms related to urinary tract infection (UTI) in infants. This study is to evaluate the incidence and related factors of neonatal infants with the initial presentation of hyperbilirubinemia and final diagnosis of UTI in a tertiary teaching hospital.MethodsWe retrospectively investigated the medical records of admitted infants younger than 8 weeks old with hyperbilirubinemia between January and December 2008. The jaundiced infants having tests of urinalysis were enrolled into our study and grouped into UTI or no UTI group according to the findings of urinary culture.ResultsA total of 217 neonatal jaundiced infants were enrolled. Among them, 12 cases (5.5%) were grouped into the UTI group, and the most common cultured bacterium from their urine was Escherichia coli. There was no significant difference in the babies’ birth weight, maternal conditions, or total bilirubin levels between the two groups. There was also no significant difference between the two groups in their admission age (9.7 ± 13.5 days vs. 6.1 ± 6.7 days in UTI and no UTI groups, respectively) or the ratio of outpatients (50% vs. 25% in UTI and no UTI groups, respectively) (p > 0.05). The cases of UTI group had significantly lower hemoglobin (15.2 ± 2.7 g/dL vs. 17.2 ± 2.3 g/dL, respectively) and higher formula feeding rate (8.3% vs. 2.9%, respectively) than the no UTI group (p < 0.05).ConclusionThe incidence of UTI in the admitted infants with hyperbilirubinemia was as high as approximately 5.5%. The most common cultured bacterium in urine was E coli. Therefore, performing urinary tests to exclude the possibility of coincidental UTI may be necessary for admitted jaundiced infants younger than 8 weeks old

Protein tyrosine phosphatase receptor type O (Ptpro) regulates cerebellar formation during zebrafish development through modulating Fgf signaling

Protein activities controlled by receptor protein tyrosine phosphatases (RPTPs) play comparably important roles in transducing cell surface signals into the cytoplasm by protein tyrosine kinases. Previous studies showed that several RPTPs are involved in neuronal generation, migration, and axon guidance in Drosophila, and the vertebrate hippocampus, retina, and developing limbs. However, whether the protein tyrosine phosphatase type O (ptpro), one kind of RPTP, participates in regulating vertebrate brain development is largely unknown. We isolated the zebrafish ptpro gene and found that its transcripts are primarily expressed in the embryonic and adult central nervous system. Depletion of zebrafish embryonic Ptpro by antisense morpholino oligonucleotide knockdown resulted in prominent defects in the forebrain and cerebellum, and the injected larvae died on the 4th day post-fertilization (dpf). We further investigated the function of ptpro in cerebellar development and found that the expression of ephrin-A5b (efnA5b), a Fgf signaling induced cerebellum patterning factor, was decreased while the expression of dusp6, a negative-feedback gene of Fgf signaling in the midbrain-hindbrain boundary region, was notably induced in ptpro morphants. Further analyses demonstrated that cerebellar defects of ptpro morphants were partially rescued by inhibiting Fgf signaling. Moreover, Ptpro physically interacted with the Fgf receptor 1a (Fgfr1a) and dephosphorylated Fgfr1a in a dose-dependant manner. Therefore, our findings demonstrate that Ptpro activity is required for patterning the zebrafish embryonic brain. Specifically, Ptpro regulates cerebellar formation during zebrafish development through modulating Fgf signaling. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00018-013-1259-7) contains supplementary material, which is available to authorized users

SAMF: An SDN-Based Framework for Access Point Management in Large-scale Wi-Fi Networks

Large-scale Wi-Fi networks have encountered several critical issues of access point (AP) management such as manual configuration, channel interference, and unbalanced loads, which should be carefully addressed to ensure efficient system performance. Since most of the commercial Wi-Fi products are proprietary and hardware-dependent, some recent studies have aimed at introducing open and programmable solutions. Unfortunately, the studies demand additional protocols and software agents but cannot provide complete solutions. To this end, this experience paper presents the design, prototype implementation, and evaluation of SAMF, which is an open, programmable, and generic framework for access point management in large-scale Wi-Fi networks. By adopting the concept of SDN technology and OpenFlow protocol, SAMF can readily be deployed on low-cost commodity access point hardware and a cloud-based controller, while enabling new network services to be integrated rapidly. Furthermore, experimental results confirm that the framework can significantly reduce operational costs since it accelerates the AP configuration process by approximately 15 times. Besides, SAMF can increase system throughput up to 26.5% and improve the balanced degree of the system by about 40%

Konsep Demokrasi Politik Dalam Islam

Coexistence of chronic rhinosinusitis (CRS) with asthma appears to impair asthma control. Type-2 innate lymphoid cells (ILC2s) respond to the cytokines of thymic stromal lymphopoietin (TSLP), interleukin (IL)-25 and IL-33, thus contributing to airway diseases such as CRS and asthma. We investigate whether the augmented Th2-cytokines in CRS might be related to sinonasal tract ILC2s corresponding to enhanced IL-25, IL-33 and TSLP release in severe asthmatics, and be involved in asthma control. Twenty-eight asthmatics (12 non-severe and 16 severe) with CRS receiving nasal surgery were enrolled. The predicted FEV1 inversely associated with CRS severity of CT or endoscopy scores. Higher expression of Th2-driven cytokines (IL-4, IL-5, IL-9, and IL-13), TSLP, IL-25 and IL-33 in nasal tissues was observed in severe asthma. Severe asthmatics had higher ILC2 cell counts in their nasal tissues. ILC2 counts were positively correlated with Th2-cytokines. Nasal surgery significantly improved asthma control and lung function decline in severe asthma and CRS. The higher expression of IL-33/ILC2 axis-directed type 2 immune responses in nasal tissue of CRS brought the greater decline of lung function in severe asthma. ILC2-induced the upregulated activity of Th2-related cytokines in asthmatics with CRS may contribute to a recalcitrant status of asthma control