We present the YEAst Search for Transcriptional Regulators And Consensus Tracking (YEASTRACT; ) database, a tool for the analysis of transcription regulatory associations in Saccharomyces cerevisiae. This database is a repository of 12 346 regulatory associations between transcription factors and target genes, based on experimental evidence which was spread throughout 861 bibliographic references. It also includes 257 specific DNA-binding sites for more than a hundred characterized transcription factors. Further information about each yeast gene included in the database was obtained from Saccharomyces Genome Database (SGD), Regulatory Sequences Analysis Tools and Gene Ontology (GO) Consortium. Computational tools are also provided to facilitate the exploitation of the gathered data when solving a number of biological questions as exemplified in the Tutorial also available on the system. YEASTRACT allows the identification of documented or potential transcription regulators of a given gene and of documented or potential regulons for each transcription factor. It also renders possible the comparison between DNA motifs, such as those found to be over-represented in the promoter regions of co-regulated genes, and the transcription factor-binding sites described in the literature. The system also provides an useful mechanism for grouping a list of genes (for instance a set of genes with similar expression profiles as revealed by microarray analysis) based on their regulatory associations with known transcription factors.

A critical question facing the field of metabolomics is whether data obtained from different centers can be effectively compared and combined. An important aspect of this is the interlaboratory precision (reproducibility) of the analytical protocols used. We analyzed human samples in six laboratories using different instrumentation but a common protocol (the AbsoluteIDQ p180 kit) for the measurement of 189 metabolites via liquid chromatography (LC) or flow injection analysis (FIA) coupled to tandem mass spectrometry (MS/MS). In spiked quality control (QC) samples 82% of metabolite measurements had an interlaboratory precision of <20%, while 83% of averaged individual laboratory measurements were accurate to within 20%. For 20 typical biological samples (serum and plasma from healthy individuals) the median interlaboratory coefficient of variation (CV) was 7.6%, with 85% of metabolites exhibiting a median interlaboratory CV of <20%. Precision was largely independent of the type of sample (serum or plasma) or the anticoagulant used but was reduced in a sample from a patient with dyslipidaemia. The median interlaboratory accuracy and precision of the assay for standard reference plasma (NIST SRM 1950) were 107% and 6.7%, respectively. Likely sources of irreproducibility were the near limit of detection (LOD) typical abundance of some metabolites and the degree of manual review and optimization of peak integration in the LC-MS/MS data after acquisition. Normalization to a reference material was crucial for the semi-quantitative FIA measurements. This is the first interlaboratory assessment of a widely used, targeted metabolomics assay illustrating the reproducibility of the protocol and how data generated on different instruments could be directly integrated in large-scale epidemiological studies.

Background: Extracellular exosomes contain various functional elements. Results: Exosomal Tax protein causes phenotypic changes in uninfected cells. Conclusion: Exosomes may play critical roles in extracellular delivery of oncogenic material derived from HTLV-1-infected cells. Significance: Exosomal delivery of Tax and other putative oncogenic components produced during HTLV-1 infection potentially contributes to pathogenesis of adult T-cell leukemia, myelopathy, or tropical spastic paraparesis.

Highlights d Ab and tau work together to cause behavioral and transcriptional deficits in mice d In mice with Ab and tau, glial gene expression increases and synaptic genes decrease d Tau is present in synaptic terminals in APP/PS1+Tau mice and human Alzheimer brain d In mice, lowering tau levels improves cognition and restores gene expression

Background: Nicotinic acid adenine dinucleotide phosphate (NAADP) regulates calcium release from internal acidic stores via two-pore channels (TPCs).Results: A novel photosensitive probe (5-azido-NAADP) identified high affinity NAADP binding sites that interact with, but are distinct from, TPCs.Conclusion: High affinity NAADP-binding proteins complex with TPCs.Significance: This work provides new mechanistic insights into how NAADP regulates calcium release via TPCs.