CARMAweb (Comprehensive R-based Microarray Analysis web service) is a web application designed for the analysis of microarray data. CARMAweb performs data preprocessing (background correction, quality control and normalization), detection of differentially expressed genes, cluster analysis, dimension reduction and visualization, classification, and Gene Ontology-term analysis. This web application accepts raw data from a variety of imaging software tools for the most widely used microarray platforms: Affymetrix GeneChips, spotted two-color microarrays and Applied Biosystems (ABI) microarrays. R and packages from the Bioconductor project are used as an analytical engine in combination with the R function Sweave, which allows automatic generation of analysis reports. These report files contain all R commands used to perform the analysis and guarantee therefore a maximum transparency and reproducibility for each analysis. The web application is implemented in Java based on the latest J2EE (Java 2 Enterprise Edition) software technology. CARMAweb is freely available at .

Background & AimsDiseases of the human gastrointestinal (GI) tract are often accompanied by diarrhea with profound alterations in the GI microbiota termed dysbiosis. Whether dysbiosis is due to the disease itself or to the accompanying diarrhea remains elusive. With this study we characterized the net effects of osmotic diarrhea on the composition of the GI microbiota in the absence of disease.MethodsWe induced osmotic diarrhea in four healthy adults by oral administration of polyethylene glycol 4000 (PEG). Stool as well as mucosa specimens were collected before, during and after diarrhea and 16S rDNA-based microbial community profiling was used to assess the microbial community structure.ResultsStool and mucosal microbiotas were strikingly different, with Firmicutes dominating the mucosa and Bacteroidetes the stools. Osmotic diarrhea decreased phylotype richness and showed a strong tendency to equalize the otherwise individualized microbiotas on the mucosa. Moreover, diarrhea led to significant relative shifts in the phyla Bacteroidetes and Firmicutes and to a relative increase in the abundance of Proteobacteria on the mucosa, a phenomenon also noted in several inflammatory and diarrheal GI diseases.ConclusionsChanges in microbial community structure induced by osmotic diarrhea are profound and show similarities to changes observed in other GI diseases including IBD. These effects so must be considered when specimens from diarrheal diseases (i.e. obtained by stratification of samples according to diarrheal status) or conditions wherein bowel preparations like PEG (i.e. specimens obtained during endoscopy) are used.

Kohlschütter-Tönz syndrome (KTS) is an autosomal-recessive disease characterized by the combination of epilepsy, psychomotor regression, and amelogenesis imperfecta. The molecular basis has not yet been elucidated. Here, we report that KTS is caused by mutations in ROGDI. Using a combination of autozygosity mapping and exome sequencing, we identified a homozygous frameshift deletion, c.229_230del (p.Leu77Alafs(∗)64), in ROGDI in two affected individuals from a consanguineous family. Molecular studies in two additional KTS-affected individuals from two unrelated Austrian and Swiss families revealed homozygosity for nonsense mutation c.286C>T (p.Gln96(∗)) and compound heterozygosity for the splice-site mutations c.531+5G>C and c.532-2A>T in ROGDI, respectively. The latter mutation was also found to be heterozygous in the mother of the Swiss affected individual in whom KTS was reported for the first time in 1974. ROGDI is highly expressed throughout the brain and other organs, but its function is largely unknown. Possible interactions with DISC1, a protein involved in diverse cytoskeletal functions, have been suggested. Our finding that ROGDI mutations cause KTS indicates that the protein product of this gene plays an important role in neuronal development as well as amelogenesis.

Background: The advancements of proteomics technologies have led to a rapid increase in the number, size and rate at which datasets are generated. Managing and extracting valuable information from such datasets requires the use of data management platforms and computational approaches.

differentiation and concomitant gene expression, we found that co-expressed genes were closer together. In addition, we found that genes in the same 1-μm-diameter neighborhood associated with either the same splicing speckle or to a lesser extent with the same transcription factory. Dispersal of speckles by overexpression of the serine-arginine (SR) protein kinase cdc2-like kinase Clk2 led to a significant drop in the number of genes in shared neighborhoods. We demonstrate quantitatively that the frequencies of speckle and factory sharing can be explained by assuming stochastic selection of a nuclear body within a restricted sub-volume defined by the original global gene positioning present prior to gene expression. We conclude that the spatial organization of these genes is a two-step process in which transcription-induced association with nuclear bodies enhances and refines a pre-existing global organization.