A combination of 454 pyrosequencing and Sanger sequencing was used to sample and characterize the transcriptome of the entomopathogenic oomycete Lagenidium giganteum. More than 50,000 high-throughput reads were annotated through homology searches. Several selected reads served as seeds for the amplification and sequencing of full-length transcripts. Phylogenetic analyses inferred from full-length cellulose synthase alignments revealed that L giganteum is nested within the peronosporalean galaxy and as such appears to have evolved from a phytopathogenic ancestor. In agreement with the phylogeny reconstructions, full-length L. giganteum oomycete effector orthologs, corresponding to the cellulose-binding elicitor lectin (CBEL), crinkler (CRN), and elicitin proteins, were characterized by domain organizations similar to those of pathogenicity factors of plantpathogenic oomycetes. Importantly, the L. giganteum effectors provide a basis for detailing the roles of canonical CRN, CBEL, and elicitin proteins in the infectious process of an oomycete known principally as an animal pathogen. Finally, phylogenetic analyses and genome mining identified members of glycoside hydrolase family 5 subfamily 27 (GH5_27) as putative virulence factors active on the host insect cuticle, based in part on the fact that GH5_27 genes are shared by entomopathogenic oomycetes and fungi but are underrepresented in nonentomopathogenic genomes. The genomic resources gathered from the L. giganteum transcriptome analysis strongly suggest that filamentous entomopathogens (oomycetes and fungi) exhibit convergent evolution: they have evolved independently from plant-associated microbes, have retained genes indicative of plant associations, and may share similar cores of virulence factors, such as GH5_27 enzymes, that are absent from the genomes of their plant-pathogenic relatives.

No abstract

A large number of studies have emphasized the spatial proximity of economic activity and its relation to the spatiality of knowledge creation in various types of connections. Far less attention has been paid to the understanding of the determinants of ‘cultural’ and geographical proximity in international R&D cooperation projects involving SMEs and the role of the quality of the Regional Innovation System (RIS). Using a database of completed European Cooperative Research projects, we conclude that: 1) technologically more complex projects are more likely to involve ‘culturally’ and geographically distant partners; 2) RIS related variables determine ‘cultural’ proximity but not geographical proximity; 3) at first sight surprisingly, international cooperation projects involving the 1st promoters of innovation-led regions (high patent propensity and high human capital levels) are culturally more distant

The human genome contains thousands of novel and uncharacterized proteins. These unknown genes are difficult to mine due to lack of adequate information. Hence, they remain largely untapped. Reasoning that new druggable targets for cancer can be discovered from these uncharacterized proteins, we have developed a protocol to mine these proteins for cancer relevance. Using various cancer-related databases, we have developed a database of uncharacterized ORF proteins. Numerous ORFs from this database offer druggable targets. To develop a proof of concept for mining these targets, we have chosen one target, C1ORF87 for detailed characterization. The C1ORF87 was analyzed using bioinformatics approaches for mRNA and protein expression, SNPs, LOH, protein motifs and domains and for gene network interactions. We have identified the C1ORF87 gene as a calcium binding protein with an EF-Hand motif. The EF-hand motifs are present in numerous calcium binding proteins, which exert a complex function in tumor growth and suppression. We show that the C1ORF87 gene is down-regulated in the lung and breast carcinomas and up-regulated in the liver carcinomas. Hematopoietic and neuronal tumors were largely negative. Its expression in select normal tissues suggests that the C1ORF87 may be a putative druggable gene. Our results suggest that the C1ORF 87 gene may play a significant role in specific carcinomas. We further demonstrate that the dark matter of the human proteome can be readily mined to predict putative cancer targets. Detailed characterization of the C1ORF87 gene will be presented. Citation Format: Ana Paula Delgado, Pamela Brandao, Sheilin Hamid, Wim Van de Ven, Ramaswamy Narayanan. Discovery of a novel carcinoma-associated EF hand containing protein by mining the dark matter of the human proteome. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4189. doi:10.1158/1538-7445.AM2014-4189

No abstract