Individual mRNA expression profiles reveal the effects of specific microRNAs

BACKGROUND: MicroRNAs (miRNAs) are oligoribonucleotides with an important role in regulation of gene expression at the level of translation. Despite imperfect target complementarity, they can also significantly reduce mRNA levels. The validity of miRNA target gene predictions is difficult to assess at the protein level. We sought, therefore, to determine whether a general lowering of predicted target gene mRNA expression by endogenous miRNAs was detectable within microarray gene expression profiles. RESULTS: The target gene sets predicted for each miRNA were mapped onto known gene expression data from a range of tissues. Whether considering mean absolute target gene expression, rank sum tests or 'ranked ratios', many miRNAs with significantly reduced target gene expression corresponded to those known to be expressed in the cognate tissue. Expression levels of miRNAs with reduced target mRNA levels were higher than those of miRNAs with no detectable effect on mRNA expression. Analysis of microarray data gathered after artificial perturbation of expression of a specific miRNA confirmed the predicted increase or decrease in influence of the altered miRNA upon mRNA levels. Strongest associations were observed with targets predicted by TargetScan. CONCLUSION: We have demonstrated that the effect of a miRNA on its target mRNAs' levels can be measured within a single gene expression profile. This emphasizes the extent of this mode of regulation in vivo and confirms that many of the predicted miRNA-mRNA interactions are correct. The success of this approach has revealed the vast potential for extracting information about miRNA function from gene expression profiles.

Analysing orchestrations with risk profiles and angel-daemon games

In this paper game theory is used to analyse the effect of a number of service failures during the execution of a grid orchestration. A service failure may be catastrophic in that it causes an entire orchestration to fail. Alternatively, a grid manager may utilise alternative services in the case of failure, allowing an orchestration to recover, A risk profile provides a means of modelling situations in a way that is neither overly optimistic nor overly pessimistic. Risk profiles are analysed using angel and daemon games. A risk profile can be assigned a valuation through an analysis of the structure of its associated Nash equilibria. Some structural properties of valuation functions, that show their validity as a measure for risk, are given. Two main cases are considered, the assessment of Orc expressions and the arrangement of a meeting using reputations.

Absolute atomic oxygen density profiles in the discharge core of a microscale atmospheric pressure plasma jet

The micro atmospheric pressure plasma jet is an rf driven (13.56 MHz, ~20 W) capacitively coupled discharge producing a homogeneous plasma at ambient pressure when fed with a gas flow of helium (1.4 slm) containing small admixtures of oxygen (~0.5%). The design provides excellent optical access to the plasma core. Ground state atomic oxygen densities up to 3x1016 cm-3 are measured spatially resolved in the discharge core by absolutely calibrated two-photon absorption laser-induced fluorescence spectroscopy. The atomic oxygen density builds up over the first 8 mm of the discharge channel before saturating at a maximum level. The absolute value increases linearly with applied power.

Cardiovascular disease risk profiles among 'healthy' siblings of patients with early-onset cardiovascular disease:Application of the new SCORE system

BACKGROUND: Cardiovascular disease (CVD) occurs more frequently in individuals with a family history of premature CVD. Within families the demographics of CVD are poorly described. DESIGN: We examined the risk estimation based on the Systematic Coronary Risk Evaluation (SCORE) system and the Joint British Guidelines (JBG) for older unaffected siblings of patients with premature CVD (onset ≤55 years for men and ≤60 years for women). METHODS: Between August 1999 and November 2003 laboratory and demographic details were collected on probands with early-onset CVD and their older unaffected siblings. Siblings were screened for clinically overt CVD by a standard questionnaire and 12-lead electrocardiogram (ECG). RESULTS: A total of 790 siblings was identified and full demographic details were available for 645. The following siblings were excluded: 41 with known diabetes mellitus; seven with random plasma glucose of 11.1 mmol/l or greater; and eight with ischaemic ECG. Data were analysed for 589 siblings from 405 families. The mean age was 55.0 years, 43.1% were men and 28.7% were smokers. The mean total serum cholesterol was 5.8 mmol/l and hypertension was present in 49.4%. Using the SCORE system, when projected to age 60 years, 181 men (71.3%) and 67 women (20.0%) would be eligible for risk factor modification. Using JBG with a 10-year risk of 20% or greater, 42 men (16.5%) and four women (1.2%) would be targeted. CONCLUSIONS: Large numbers of these asymptomatic individuals meet both European and British guidelines for the primary prevention of CVD and should be targeted for risk factor modification. The prevalence of individuals defined as eligible for treatment is much higher when using the SCORE system. © 2007 European Society of Cardiology.

Comparative analysis of dna methylation profiles in peripheral blood leukocytes versus lymphoblastoid cell lines

Previous reports have shown that DNA methylation profiles within primary human malignant tissues are altered when these cells are transformed into cancer cell lines. However, it is unclear if similar differences in DNA methylation profiles exist between DNA derived from peripheral blood leukocytes (PBLs) and corresponding Epstein-Barr Virus transformed lymphoblastoid cell lines (LCLs). To assess the utility of LCLs as a resource for methylation studies we have compared DNA methylation profiles in promoter and 5' regions of 318 genes in PBL and LCL sample pairs from patients with type 1 diabetes with or without nephropathy. We identified a total of 27 (similar to 8%) genes that revealed different DNA methylation profiles in PBL compared with LCL-derived DNA samples. In conclusion, although the profiles for most promoter regions were similar between PBL-LCL pairs, our results indicate that LCL-derived DNA may not be suitable for DNA methylation studies at least in diabetic nephropathy.

Sequential extracellular matrix-focused and baited-global cluster analysis of serial transcriptomic profiles identifies candidate modulators of renal tubulointerstitial fibrosis in murine adriamycin-induced nephropathy

Transcriptome analysis using microarray technology represents a powerful unbiased approach for delineating pathogenic mechanisms in disease. Here molecular mechanisms of renal tubulointerstitial fibrosis (TIF) were probed by monitoring changes in the renal transcriptome in a glomerular disease-dependent model of TIF ( adriamycin nephropathy) using Affymetrix (mu74av2) microarray coupled with sequential primary biological function-focused and secondary