Neuregulin signaling is dispensable for NMDA- and GABA(A)-receptor expression in the cerebellum in vivo.

Published versio

The Comprehensive Phytopathogen Genomics Resource: a web-based resource for data-mining plant pathogen genomes

The Comprehensive Phytopathogen Genomics Resource (CPGR) provides a web-based portal for plant pathologists and diagnosticians to view the genome and trancriptome sequence status of 806 bacterial, fungal, oomycete, nematode, viral and viroid plant pathogens. Tools are available to search and analyze annotated genome sequences of 74 bacterial, fungal and oomycete pathogens. Oomycete and fungal genomes are obtained directly from GenBank, whereas bacterial genome sequences are downloaded from the A Systematic Annotation Package (ASAP) database that provides curation of genomes using comparative approaches. Curated lists of bacterial genes relevant to pathogenicity and avirulence are also provided. The Plant Pathogen Transcript Assemblies Database provides annotated assemblies of the transcribed regions of 82 eukaryotic genomes from publicly available single pass Expressed Sequence Tags. Data-mining tools are provided along with tools to create candidate diagnostic markers, an emerging use for genomic sequence data in plant pathology. The Plant Pathogen Ribosomal DNA (rDNA) database is a resource for pathogens that lack genome or transcriptome data sets and contains 131 755 rDNA sequences from GenBank for 17 613 species identified as plant pathogens and related genera

GenCLiP: a software program for clustering gene lists by literature profiling and constructing gene co-occurrence networks related to custom keywords

<p>Abstract</p> <p>Background</p> <p>Biomedical researchers often want to explore pathogenesis and pathways regulated by abnormally expressed genes, such as those identified by microarray analyses. Literature mining is an important way to assist in this task. Many literature mining tools are now available. However, few of them allows the user to make manual adjustments to zero in on what he/she wants to know in particular.</p> <p>Results</p> <p>We present our software program, GenCLiP (Gene Cluster with Literature Profiles), which is based on the methods presented by Chaussabel and Sher (<it>Genome Biol </it>2002, 3(10):RESEARCH0055) that search gene lists to identify functional clusters of genes based on up-to-date literature profiling. Four features were added to this previously described method: the ability to 1) manually curate keywords extracted from the literature, 2) search genes and gene co-occurrence networks related to custom keywords, 3) compare analyzed gene results with negative and positive controls generated by GenCLiP, and 4) calculate probabilities that the resulting genes and gene networks are randomly related. In this paper, we show with a set of differentially expressed genes between keloids and normal control, how implementation of functions in GenCLiP successfully identified keywords related to the pathogenesis of keloids and unknown gene pathways involved in the pathogenesis of keloids.</p> <p>Conclusion</p> <p>With regard to the identification of disease-susceptibility genes, GenCLiP allows one to quickly acquire a primary pathogenesis profile and identify pathways involving abnormally expressed genes not previously associated with the disease.</p

Swift trust and commitment: the missing links for humanitarian supply chain coordination?

Coordination among actors in a humanitarian relief supply chain decides whether a relief operation can be or successful or not. In humanitarian supply chains, due to the urgency and importance of the situation combined with scarce resources, actors have to coordinate and trust each other in order to achieve joint goals. This paper investigated empirically the role of swift trust as mediating variable for achieving supply chain coordination. Based on commitment-trust theory we explore enablers of swift-trust and how swift trust translates into coordination through commitment. Based on a path analytic model we test data from the National Disaster Management Authority of India. Our study is the first testing commitment-trust theory (CTT) in the humanitarian context, highlighting the importance of swift trust and commitment for much thought after coordination. Furthermore, the study shows that information sharing and behavioral uncertainty reduction act as enablers for swift trust. The study findings offer practical guidance and suggest that swift trust is a missing link for the success of humanitarian supply chains

Transcriptome of Aphanomyces euteiches: New Oomycete Putative Pathogenicity Factors and Metabolic Pathways

Aphanomyces euteiches is an oomycete pathogen that causes seedling blight and root rot of legumes, such as alfalfa and pea. The genus Aphanomyces is phylogenically distinct from well-studied oomycetes such as Phytophthora sp., and contains species pathogenic on plants and aquatic animals. To provide the first foray into gene diversity of A. euteiches, two cDNA libraries were constructed using mRNA extracted from mycelium grown in an artificial liquid medium or in contact to plant roots. A unigene set of 7,977 sequences was obtained from 18,864 high-quality expressed sequenced tags (ESTs) and characterized for potential functions. Comparisons with oomycete proteomes revealed major differences between the gene content of A. euteiches and those of Phytophthora species, leading to the identification of biosynthetic pathways absent in Phytophthora, of new putative pathogenicity genes and of expansion of gene families encoding extracellular proteins, notably different classes of proteases. Among the genes specific of A. euteiches are members of a new family of extracellular proteins putatively involved in adhesion, containing up to four protein domains similar to fungal cellulose binding domains. Comparison of A. euteiches sequences with proteomes of fully sequenced eukaryotic pathogens, including fungi, apicomplexa and trypanosomatids, allowed the identification of A. euteiches genes with close orthologs in these microorganisms but absent in other oomycetes sequenced so far, notably transporters and non-ribosomal peptide synthetases, and suggests the presence of a defense mechanism against oxidative stress which was initially characterized in the pathogenic trypanosomatids

LRRK2 Biology from structure to dysfunction: research progresses, but the themes remain the same

Since the discovery of leucine-rich repeat kinase 2 (LRRK2) as a protein that is likely central to the aetiology of Parkinson's disease, a considerable amount of work has gone into uncovering its basic cellular function. This effort has led to the implication of LRRK2 in a bewildering range of cell biological processes and pathways, and probable roles in a number of seemingly unrelated medical conditions. In this review we summarise current knowledge of the basic biochemistry and cellular function of LRRK2. Topics covered include the identification of phosphorylation substrates of LRRK2 kinase activity, in particular Rab proteins, and advances in understanding the activation of LRRK2 kinase activity via dimerisation and association with membranes, especially via interaction with Rab29. We also discuss biochemical studies that shed light on the complex LRRK2 GTPase activity, evidence of roles for LRRK2 in a range of cell signalling pathways that are likely cell type specific, and studies linking LRRK2 to the cell biology of organelles. The latter includes the involvement of LRRK2 in autophagy, endocytosis, and processes at the trans-Golgi network, the endoplasmic reticulum and also key microtubule-based cellular structures. We further propose a mechanism linking LRRK2 dimerisation, GTPase function and membrane recruitment with LRRK2 kinase activation by Rab29. Together these data paint a picture of a research field that in many ways is moving forward with great momentum, but in other ways has not changed fundamentally. Many key advances have been made, but very often they seem to lead back to the same places

Knocking out alpha-synuclein in melanoma cells downregulates L1CAM and decreases motility

Abstract The Parkinson’s disease (PD) associated protein, alpha-synuclein (α-syn/SNCA), is highly expressed in aggressive melanomas. The goal of this study was to reveal possible mechanism(s) of α-syn involvement in melanoma pathogenesis. Herein, we asked whether α-syn modulates the expression of the pro-oncogenic adhesion molecules L1CAM and N-cadherin. We used two human melanoma cell lines (SK-MEL-28, SK-MEL-29), SNCA-knockout (KO) clones, and two human SH-SY5Y neuroblastoma cell lines. In the melanoma lines, loss of α-syn expression resulted in significant decreases in the expression of L1CAM and N-cadherin and concomitant significant decreases in motility. On average, there was a 75% reduction in motility in the four SNCA-KOs tested compared to control cells. Strikingly, comparing neuroblastoma SH-SY5Y cells that have no detectable α-syn to SH-SY5Y cells that stably express α-syn (SH/+αS), we found that expressing α-syn increased L1CAM and single-cell motility by 54% and 597%, respectively. The reduction in L1CAM level in SNCA-KO clones was not due to a transcriptional effect, rather we found that L1CAM is more efficiently degraded in the lysosome in SNCA-KO clones than in control cells. We propose that α-syn is pro-survival to melanoma (and possibly neuroblastoma) because it promotes the intracellular trafficking of L1CAM to the plasma membrane