The MicroArray Quality Control (MAQC) project shows inter- and intraplatform reproducibility of gene expression measurements

Over the last decade, the introduction of microarray technology has had a profound impact on gene expression research. The publication of studies with dissimilar or altogether contradictory results, obtained using different microarray platforms to analyze identical RNA samples, has raised concerns about the reliability of this technology. The MicroArray Quality Control (MAQC) project was initiated to address these concerns, as well as other performance and data analysis issues. Expression data on four titration pools from two distinct reference RNA samples were generated at multiple test sites using a variety of microarray-based and alternative technology platforms. Here we describe the experimental design and probe mapping efforts behind the MAQC project. We show intraplatform consistency across test sites as well as a high level of interplatform concordance in terms of genes identified as differentially expressed. This study provides a resource that represents an important first step toward establishing a framework for the use of microarrays in clinical and regulatory settings.     

Age-dependent characterization of pendrin gene expression in various tissues of deer mice

Pendrin is a membrane transport protein which functions as the transporter of chloride, bicarbonate, formate, and iodide. In this study, we characterized pendrin gene expression in various tissues of deer mice (Peromyscus maniculatus), a sentinel wildlife species. Deer mice were euthanized at post-natal day (PND) 21 (day of weaning) and PND 45 (24 days post-weaning) for tissue collection. A deer mouse-specific partial pendrin cDNA sequence was generated, from which Taqman-specific probe and primers were designed for quantification of mRNA equivalents of pendrin gene expression using real-time polymerase chain reaction (PCR). The expression profile was standardized to glyceraldehyde-3-phosphate dehydrogenase (GAPDH). Results indicate that the pendrin gene was expressed at different levels in the different tissues of developing deer mice relative to GAPDH expression. Expression in the tissues was determined to be age-dependent. Pendrin gene was highly expressed in the kidney, lungs and reproductive tissues. PND 21 expression in the kidney and testes was significantly lower than PND 45. This study represents the first identification of differential expression of pendrin gene in various deer mouse tissues.     

Metabolism of chlorpyrifos and chlorpyrifos oxon by human hepatocytes

The metabolism of chlorpyrifos (CPS) and chlorpyrifos oxon (CPO) by human hepatocytes and human liver S9 fractions was investigated using LC-MS/MS. Cytochrome P450 (CYP)-dependent and phase II-related products were determined following incubation with CPS and CPO. CYP-related products, 3,5,6-trichloro-2-pyridinol (TCP), diethyl thiophosphate, and dealkylated CPS, were found following CPS treatment and dealkylated CPO following CPO treatment. Diethyl phosphate was not identified because of its high polarity and lack of retention with the chromatographic conditions employed. Phase II-related conjugates, including O- and S-glucuronides as well as 11 GSH-derived metabolites, were identified in CPS-treated human hepatocytes, although the O-sulfate of TCP conjugate was found only when human liver S9 fractions were used as the enzyme source. O-Glucuronide of TCP was also identified in CPO-treated hepatocytes. CPS and CPO were identified using HPLC-UV after CPS metabolism by the human liver S9 fraction. However, CPO was not found following treatment of human hepatocytes with either CPS or CPO. These results suggest that human liver plays an important role in detoxification, rather than activation, of CPS.     

An experimental metagenome data management and analysis system

The application of shotgun sequencing to environmental samples has revealed a new universe of microbial community genomes (metagenomes) involving previously uncultured organisms. Metagenome analysis, which is expected to provide a comprehensive picture of the gene functions and metabolic capacity for microbial communities, needs to be conducted in the context of a comprehensive data management and analysis system. We present in this paper IMG/M, an experimental metagenome data management and analysis system that is based on the Integrated Microbial Genomes (IMG) system. IMG/M provides tools and viewers for analyzing both metagenomes and isolate genomes individually or in a comparative context. IMG/M is available at http://img.jgi.doe.gov/m.     

Appendix: A general regression model for analysis of independent maternal and paternal age effects for 47,+21 and other disorders that may arise from mutant gametes from either parent

Summary Biological considerations suggest that regression equations used to model the rate of mutational outcomes as a possible function of maternal age and paternal age (or other parental factors) are most appropriately additive models of the type: r=(h(x)+j(y) or r=(h(x)+(k(x)·j(y)), where r is the rate of the outcome event, x is maternal age, y is paternal age, and h, j and k are functions to be specified. The first, simpler model assumes that there is no independent maternal age effect upon formation of a gamete or zygote with a paternally derived mutation or upon survival of the consequent conceptus. The second more general model relaxes this assumption. These models appear preferable to those used previously, such as log r=(h(x)+j(y)) or equivalently r=exp (h(x)·j(y)), which posit complex relationships closer to a multiplicative interaction for which it is difficult to suggest obvious biological interpretations.     

Zur Taxonomie desGentianella crispata-Komplexes

Ohne Zusammenfassung     

Blood pressure, heart rate and motor activity in 6 inbred rat strains and wild rats (Rattus norvegicus): a comparative study.

Inbreeding for many generations under optimal environmental conditions may have favoured the survival of alleles for blood pressure increase in phenotypically normotensive rat strains. To prove this hypothesis we measured telemetrically systolic (SBP) and diastolic blood pressure (DBP), heart rate (HR) and motor activity (MA) in 6 inbred rat strains (BB, BN, LEW, DA, F344, WKY) and wild rats most probably possessing all of the alleles for normotension. For the first time it is shown that systolic blood pressure can significantly differ between normotensive inbred rat strains and that most probably some inbred rat strains will be characterised by a systolic blood pressure found in their progenitors, the wild rats. In addition, the typical night activity of rodents was not seen in 2 inbred rat strains. All findings together may be interpreted in the sense that most, if not all inbred rats strains have more or less disturbances in blood pressure, HR and/or MA and that there is most probably no "healthy" inbred rat strain available so that wild rats may be an alternative for crossing studies dissecting hypertension in particular and diseases in general.