GEM-TREND: a web tool for gene expression data mining toward relevant network discovery

<p>Abstract</p> <p>Background</p> <p>DNA microarray technology provides us with a first step toward the goal of uncovering gene functions on a genomic scale. In recent years, vast amounts of gene expression data have been collected, much of which are available in public databases, such as the Gene Expression Omnibus (GEO). To date, most researchers have been manually retrieving data from databases through web browsers using accession numbers (IDs) or keywords, but gene-expression patterns are not considered when retrieving such data. The Connectivity Map was recently introduced to compare gene expression data by introducing gene-expression signatures (represented by a set of genes with up- or down-regulated labels according to their biological states) and is available as a web tool for detecting similar gene-expression signatures from a limited data set (approximately 7,000 expression profiles representing 1,309 compounds). In order to support researchers to utilize the public gene expression data more effectively, we developed a web tool for finding similar gene expression data and generating its co-expression networks from a publicly available database.</p> <p>Results</p> <p>GEM-TREND, a web tool for searching gene expression data, allows users to search data from GEO using gene-expression signatures or gene expression ratio data as a query and retrieve gene expression data by comparing gene-expression pattern between the query and GEO gene expression data. The comparison methods are based on the nonparametric, rank-based pattern matching approach of Lamb et al. (Science 2006) with the additional calculation of statistical significance. The web tool was tested using gene expression ratio data randomly extracted from the GEO and with in-house microarray data, respectively. The results validated the ability of GEM-TREND to retrieve gene expression entries biologically related to a query from GEO. For further analysis, a network visualization interface is also provided, whereby genes and gene annotations are dynamically linked to external data repositories.</p> <p>Conclusion</p> <p>GEM-TREND was developed to retrieve gene expression data by comparing query gene-expression pattern with those of GEO gene expression data. It could be a very useful resource for finding similar gene expression profiles and constructing its gene co-expression networks from a publicly available database. GEM-TREND was designed to be user-friendly and is expected to support knowledge discovery. GEM-TREND is freely available at <url>http://cgs.pharm.kyoto-u.ac.jp/services/network</url>.</p

Exercise can improve sleep quality: a systematic review and meta-analysis

Background Insomnia is common. However, no systematic reviews have examined the effect of exercise on patients with primary and secondary insomnia, defined as both sleep disruption and daytime impairment. This systematic review and meta-analysis aimed to examine the effectiveness/efficacy of exercise in patients with insomnia. Methods We searched the Cochrane Central Register of Controlled Trials, MEDLINE, Embase, PsycINFO, World Health Organization International Clinical Trials Registry Platform, and ClinicalTrials.gov to identify all randomized controlled trials that examined the effects of exercise on various sleep parameters in patients with insomnia. All participants were diagnosed with insomnia, using standard diagnostic criteria or predetermined criteria and standard measures. Data on outcome measures were subjected to meta-analyses using random-effects models. The Cochrane Risk of Bias Tool and Grading of Recommendations, Assessment, Development, and Evaluation approach were used to assess the quality of the individual studies and the body of evidence, respectively. Results We included nine studies with a total of 557 participants. According to the Pittsburgh Sleep Quality Index (mean difference [MD], 2.87 points lower in the intervention group; 95% confidence interval [CI], 3.95 points lower to 1.79 points lower; low-quality evidence) and the Insomnia Severity Index (MD, 3.22 points lower in the intervention group; 95% CI, 5.36 points lower to 1.07 points lower; very low-quality evidence), exercise was beneficial. However, exercise interventions were not associated with improved sleep efficiency (MD, 0.56% lower in the intervention group; 95% CI, 3.42% lower to 2.31% higher; moderate-quality evidence). Only four studies noted adverse effects. Most studies had a high or unclear risk of selection bias. Discussion Our findings suggest that exercise can improve sleep quality without notable adverse effects. Most trials had a high risk of selection bias. Higher quality research is needed

Inhibitory effects of caffeine on allergic rhinitis symptoms in mice

We examined the effects of caffeine treatment on ovalbumin- and histamine-induced rhinitis mouse models and on corticosterone and catecholamine levels in mouse plasma. Treatment with caffeine decreased sneezing and nasal rubbing in both models, but direct nasal administration had no effect. Plasma levels of corticosterone and catecholamine, which have known anti-allergy effects, were increased by caffeine treatment. The increases in corticosterone and catecholamine may be associated with the suppression of rhinitis symptoms

Erythropoietin Receptor Signaling Mitigates Renal Dysfunction-Associated Heart Failure by Mechanisms Unrelated to Relief of Anemia

ObjectivesWe examined the effect of asialoerythropoietin (asialoEPO), a nonerythrogenic derivative of erythropoietin (EPO), on renal dysfunction-associated heart failure.BackgroundAlthough EPO is known to exert beneficial effects on cardiac function, the clinical benefits in patients with chronic kidney disease are controversial. It remains to be addressed whether previously reported outcomes were the result of relief of the anemia, adverse effects of EPO, or direct cardiovascular effects.MethodsMice underwent 5/6 nephrectomy to cause renal dysfunction. Eight weeks later, when renal dysfunction was established, anemia and cardiac dysfunction and remodeling were apparent. Mice were then assigned to receive saline (control), recombinant human erythropoietin (rhEPO) at 5,000 IU (714 pmol)/kg, or asialoEPO at 714 pmol/kg, twice/week for 4 weeks.ResultsAlthough only rhEPO relieved the nephrectomy-induced anemia, both rhEPO and asialoEPO significantly and similarly mitigated left ventricular dilation and dysfunction. The hearts of rhEPO- or asialoEPO-treated mice showed less hypertrophy, reflecting decreases in cardiomyocyte hypertrophy and degenerative subcellular changes, as well as significant attenuation of fibrosis, leukocyte infiltration, and oxidative deoxyribonucleic acid damage. These phenotypes were accompanied by restored expression of GATA-4, sarcomeric proteins, and vascular endothelial growth factor and decreased inflammatory cytokines and lipid peroxidation. Finally, myocardial activation was observed of extracellular signal-regulated protein kinase and signal transducer and activator of transcription pathways in the treated mice.ConclusionsEPO receptor signaling exerts direct cardioprotection in an animal model of renal dysfunction-associated heart failure, probably by mitigating degenerative, pro-fibrosis, inflammatory, and oxidative processes but not through relief of anemia

Super-hard X-Ray Emission from eta Carinae Observed with Suzaku

We present the Suzaku results of eta Carinae in the 5--50 keV range conducted twice around the apastron in 2005 August for 50 ks and in 2006 February for 20 ks. The X-ray Imaging Spectrometer (XIS) produced hard (5--12 keV) band spectra, resolving K shell lines from highly ionized Fe and Ni. The Hard X-ray Detector yielded a significant detection in the super-hard (15--50 keV) band, which is uncontaminated by near-by sources. We constrained the temperature of the optically-thin thermal plasma emission dominant in the hard band as 3--4 keV using the K-shell line features with the XIS. We found significant excess emission above the thermal emission in the super-hard band with the PIN, confirming the previous INTEGRAL ISGRI report. The entire 5--50 keV spectra were fitted by a combination of a thermal plasma model plus a flat power-law or a very hot thermal bremsstrahlung model for the excess emission. No significant change of the excess emission was found at different epochs within the systematic and statistical uncertainties and no flare-like flux amplification was seen in the hard band, indicating that the excess emission is a steady phenomenon. We argue that the super-hard emission is attributable to the inverse Compton of stellar UV photons by non-thermal electrons or to the thermal bremsstrahlung of very hot plasma, and not to the bremsstrahlung by non-thermal electrons colliding with cold ambient matter.Comment: Accepted for publication in PASJ (10 pages, 7 Postscript figures

Circadian regulation of intracellular G-protein signalling mediates intercellular synchrony and rhythmicity in the suprachiasmatic nucleus

Synchronous oscillations of thousands of cellular clocks in the suprachiasmatic nucleus (SCN), the circadian centre, are coordinated by precisely timed cell–cell communication, the principle of which is largely unknown. Here we show that the amount of RGS16 (regulator of G protein signalling 16), a protein known to inactivate Gαi, increases at a selective circadian time to allow time-dependent activation of intracellular cyclic AMP signalling in the SCN. Gene ablation of Rgs16 leads to the loss of circadian production of cAMP and as a result lengthens circadian period of behavioural rhythm. The temporally precise regulation of the cAMP signal by clock-controlled RGS16 is needed for the dorsomedial SCN to maintain a normal phase-relationship to the ventrolateral SCN. Thus, RGS16-dependent temporal regulation of intracellular G protein signalling coordinates the intercellular synchrony of SCN pacemaker neurons and thereby defines the 24 h rhythm in behaviour

Neural Network Development in Late Adolescents during Observation of Risk-Taking Action

Emotional maturity and social awareness are important for adolescents, particularly college students beginning to face the challenges and risks of the adult world. However, there has been relatively little research into personality maturation and psychological development during late adolescence and the neural changes underlying this development. We investigated the correlation between psychological properties (neuroticism, extraversion, anxiety, and depression) and age among late adolescents (n = 25, from 18 years and 1 month to 22 years and 8 months). The results revealed that late adolescents became less neurotic, less anxious, less depressive and more extraverted as they aged. Participants then observed video clips depicting hand movements with and without a risk of harm (risk-taking or safe actions) during functional magnetic resonance imaging (fMRI). The results revealed that risk-taking actions elicited significantly stronger activation in the bilateral inferior parietal lobule, temporal visual regions (superior/middle temporal areas), and parieto-occipital visual areas (cuneus, middle occipital gyri, precuneus). We found positive correlations of age and extraversion with neural activation in the insula, middle temporal gyrus, lingual gyrus, and precuneus. We also found a negative correlation of age and anxiety with activation in the angular gyrus, precentral gyrus, and red nucleus/substantia nigra. Moreover, we found that insula activation mediated the relationship between age and extraversion. Overall, our results indicate that late adolescents become less anxious and more extraverted with age, a process involving functional neural changes in brain networks related to social cognition and emotional processing. The possible neural mechanisms of psychological and social maturation during late adolescence are discussed

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead