A search engine to identify pathway genes from expression data on multiple organisms

<p>Abstract</p> <p>Background</p> <p>The completion of several genome projects showed that most genes have not yet been characterized, especially in multicellular organisms. Although most genes have unknown functions, a large collection of data is available describing their transcriptional activities under many different experimental conditions. In many cases, the coregulatation of a set of genes across a set of conditions can be used to infer roles for genes of unknown function.</p> <p>Results</p> <p>We developed a search engine, the Multiple-Species Gene Recommender (MSGR), which scans gene expression datasets from multiple organisms to identify genes that participate in a genetic pathway. The MSGR takes a query consisting of a list of genes that function together in a genetic pathway from one of six organisms: <it>Homo sapiens</it>, <it>Drosophila melanogaster</it>, <it>Caenorhabditis elegans</it>, <it>Saccharomyces cerevisiae</it>, <it>Arabidopsis thaliana</it>, and <it>Helicobacter pylori</it>. Using a probabilistic method to merge searches, the MSGR identifies genes that are significantly coregulated with the query genes in one or more of those organisms. The MSGR achieves its highest accuracy for many human pathways when searches are combined across species. We describe specific examples in which new genes were identified to be involved in a neuromuscular signaling pathway and a cell-adhesion pathway.</p> <p>Conclusion</p> <p>The search engine can scan large collections of gene expression data for new genes that are significantly coregulated with a pathway of interest. By integrating searches across organisms, the MSGR can identify pathway members whose coregulation is either ancient or newly evolved.</p

Improvements to GALA and dbERGE II: databases featuring genomic sequence alignment, annotation and experimental results

We describe improvements to two databases that give access to information on genomic sequence similarities, functional elements in DNA and experimental results that demonstrate those functions. GALA, the database of Genome ALignments and Annotations, is now a set of interlinked relational databases for five vertebrate species, human, chimpanzee, mouse, rat and chicken. For each species, GALA records pairwise and multiple sequence alignments, scores derived from those alignments that reflect the likelihood of being under purifying selection or being a regulatory element, and extensive annotations such as genes, gene expression patterns and transcription factor binding sites. The user interface supports simple and complex queries, including operations such as subtraction and intersections as well as clustering and finding elements in proximity to features. dbERGE II, the database of Experimental Results on Gene Expression, contains experimental data from a variety of functional assays. Both databases are now run on the DB2 database management system. Improved hardware and tuning has reduced response times and increased querying capacity, while simplified query interfaces will help direct new users through the querying process. Links are available at http://www.bx.psu.edu/

Microcrystals coating the wing membranes of a living insect (Psocoptera: Psyllipsocidae) from a Brazilian cave

Two specimens of Psyllipsocus yucatan with black wings were found with normal individuals of this species on guano piles produced by the common vampire bat Desmodus rotundus. These specimens have both pairs of wings dorsally and ventrally covered by a black crystalline layer. They did not exhibit any signs of reduced vitality in the field and their morphology is completely normal. This ultrathin (1.5 µm) crystalline layer, naturally deposited on a biological membrane, is documented by photographs, SEM micrographs, energy dispersive spectroscopy (EDS) and X-ray diffractometry (XRD). The crystalline deposit contains iron, carbon and oxygen, but the mineral species could not be identified. Guano probably played a role in its formation; the presence of iron may be a consequence of the excretion of iron by the common vampire bat. This enigmatic phenomenon lacks obvious biological significance but may inspire bionic applications. Nothing similar has ever been observed in terrestrial arthropods

A FOXO1-induced oncogenic network defines the AML1-ETO preleukemic program

Key Points Increased FOXO1 is oncogenic in human CD34+ cells and promotes preleukemia transition. FOXO1 is required by AE preleukemia cells for the activation of a stem cell molecular program.</jats:p

Ganzheitliche Untersuchungsmethoden zur Erfassung und Prüfung der Qualität ökologischer Lebensmittel: Stand der Entwicklung und Validierung

In dem wachsenden Markt ökologischer Lebensmittel werden Methoden zur produktorientierten Qualitätserfassung gefordert. Dabei geht es u.a. um die Unterscheidung von Produkten aus unterschiedlichen Anbauverfahren. Die Ziele des Projektes waren daher: 1. ausgewählte ganzheitliche Methoden gemäß ISO 17025 zu validieren, d.h. Laborprozesse festzulegen, sowie Einflussgrößen und Verfahrensmerkmale zu bestimmen, 2. zu testen, ob diese Verfahren eine Differenzierung von definierten Proben statistisch abgesichert zeigen können. . Diese Ziele konnten erreicht werden. Es wurde bestätigt, dass einige der Methoden auf Grundlage dokumentierter Prozeduren Lebensmittel aus definierten Anbauversuchen (u.a. aus dem DOK-Versuch am FIBL/CH) reproduzierbar unterscheiden können. Die Koordination und die Validierung der Kupferchlorid-Kristallisation sowie die Messung der Polyphenole lag bei der Universität Kassel, FG Ökologische Lebensmittelqualität und Ernährungskultur. Die KWALIS GmbH, Dipperz, validierte die Fluoreszenz-Anregungsspektroskopie und die Bestimmung des Physiologischen Aminosäurestatus, die EQC GmbH, Weidenbach die elektrochemischen Messungen. Dr. Kromidas, Saarbrücken übernahm die Beratung der Validierungsprozeduren. . An Blindproben wurde untersucht, ob die Verfahren für Weizen- und Möhrenproben aus definierten Anbau- und Sortenversuchen geeignet sind (Fragestellung der Validierung). Die Proben wurden von unabhängiger Stelle (OEL-FAL, Trenthorst) codiert. Die Proben wurden gleichzeitig an alle Partner versandt; dadurch konnten die Methoden auch untereinander verglichen werden. Die Methoden Kupferchlorid-Kristallisation, Fluoreszenz-Anregungsspektroskopie und Physiologischer Aminosäurestatus sind für die Fragestellung geeignet. Mit allen drei Methoden konnten die Proben differenziert und gruppiert werden. Darüber hinaus konnten mit der Fluoreszenz-Anregungsspektroskopie und über den physiologischen Aminosäurestatus die Proben auch den Anbauweisen richtig zugeordnet werden. Allerdings ist damit noch keine Aussage über die Fähigkeit dieser Verfahren möglich, generell Proben aus ökologischer und konventioneller Herkunft zu unterscheiden. Dafür sind weitere Untersuchungen sowohl an Proben definierter Herkunft als auch an Marktproben notwendig

Epigenetic and transcriptional dysregulation in CD4+ T cells in patients with atopic dermatitis

Atopic dermatitis (AD) is one of the most common skin disorders among children. Disease etiology involves genetic and environmental factors, with 29 independent AD risk loci enriched for risk allele-dependent gene expression in the skin and CD4+ T cell compartments. We investigated the potential epigenetic mechanisms responsible for the genetic susceptibility of CD4+ T cells. To understand the differences in gene regulatory activity in peripheral blood T cells in AD, we measured chromatin accessibility (an assay based on transposase-accessible chromatin sequencing, ATAC-seq), nuclear factor kappa B subunit 1 (NFKB1) binding (chromatin immunoprecipitation with sequencing, ChIP-seq), and gene expression levels (RNA-seq) in stimulated CD4+ T cells from subjects with active moderate-to-severe AD, as well as in age-matched non-allergic controls. Open chromatin regions in stimulated CD4+ T cells were highly enriched for AD genetic risk variants, with almost half of the AD risk loci overlapping AD-dependent ATAC-seq peaks. AD-specific open chromatin regions were strongly enriched for NF-κB DNA-binding motifs. ChIP-seq identified hundreds of NFKB1-occupied genomic loci that were AD- or control-specific. As expected, the AD-specific ChIP-seq peaks were strongly enriched for NF-κB DNA-binding motifs. Surprisingly, control-specific NFKB1 ChIP-seq peaks were not enriched for NFKB1 motifs, but instead contained motifs for other classes of human transcription factors, suggesting a mechanism involving altered indirect NFKB1 binding. Using DNA sequencing data, we identified 63 instances of altered genotype-dependent chromatin accessibility at 36 AD risk variant loci (30% of AD risk loci) that might lead to genotype-dependent gene expression. Based on these findings, we propose that CD4+ T cells respond to stimulation in an AD-specific manner, resulting in disease- and genotype-dependent chromatin accessibility alterations involving NFKB1 binding

Analysis and prevention of dent defects formed during strip casting of twin-induced plasticity steels

Rapid-solidification experiments were conducted for understanding dent defects formed during strip casting of twin-induced plasticity (TWIP) steels. The rapid-solidification experiments reproduced the dent defects formed on these steels, which were generally located at valleys of the shot-blasted roughness on the substrate. The rapid-solidification experiment results reveal that the number of dips, the Mn content of the steel, and the surface roughness of the substrate affect the depth and size of dents formed on the solidified-shell surfaces, while the composition of the atmosphere gases and the carbon content of the steel are not factors. The formation of dents was attributed to the entrapment of gases inside the roughness valleys of the substrate surface and their volume expansion due to the temperature of the steel melt and the latent heat. The dents could be prevented when the thermal expansion of gases was suppressed by making longitudinal grooves on the substrate surface, which allowed the entrapped gases to escape. Sound solidified shells were obtained by optimizing the width and depth of the longitudinal grooves and by controlling the shot-blasting conditions.ope

Is Transcription Factor Binding Site Turnover a Sufficient Explanation for Cis-Regulatory Sequence Divergence?

The molecular evolution of cis-regulatory sequences is not well understood. Comparisons of closely related species show that cis-regulatory sequences contain a large number of sites constrained by purifying selection. In contrast, there are a number of examples from distantly related species where cis-regulatory sequences retain little to no sequence similarity but drive similar patterns of gene expression. Binding site turnover, whereby the gain of a redundant binding site enables loss of a previously functional site, is one model by which cis-regulatory sequences can diverge without a concurrent change in function. To determine whether cis-regulatory sequence divergence is consistent with binding site turnover, we examined binding site evolution within orthologous intergenic sequences from 14 yeast species defined by their syntenic relationships with adjacent coding sequences. Both local and global alignments show that nearly all distantly related orthologous cis-regulatory sequences have no significant level of sequence similarity but are enriched for experimentally identified binding sites. Yet, a significant proportion of experimentally identified binding sites that are conserved in closely related species are absent in distantly related species and so cannot be explained by binding site turnover. Depletion of binding sites depends on the transcription factor but is detectable for a quarter of all transcription factors examined. Our results imply that binding site turnover is not a sufficient explanation for cis-regulatory sequence evolution