Topological Properties of Co-Occurrence Networks in Published Gene Expression Signatures

Meta-analysis of high-throughput gene expression data is often used for the interpretation of proprietary gene expression data sets. We have recently shown that co-occurrence patterns of gene expression in published cancer-related gene expression signatures are reminiscent of several cancer signaling pathways. Indeed, significant co-occurrence of up to ten genes in published gene expression signatures can be exploited to build a co-occurrence network from the sets of co-occurring genes (“co-occurrence modules”). Such co-occurrence network is represented by an undirected graph, where single genes are assigned to vertices and edges indicate that two genes are significantly co-occurring. Thus, graph-cut methods can be used to identify groups of highly interconnected vertices (“network communities”) that correspond to sets of genes that are significantly co-regulated in human cancer. Here, we investigate the topological properties of co-occurrence networks derived from published gene expression signatures and show that co-occurrence networks are characterized by scale-free topology and hierarchical modularity. Furthermore, we report that genes with a “promiscuous” or a “faithful” co-occurrence pattern can be distinguished. This behavior is reminiscent of date and party hubs that have been identified in protein-protein interaction networks

Mining published lists of cancer related microarray experiments: Identification of a gene expression signature having a critical role in cell-cycle control

BACKGROUND: Routine application of gene expression microarray technology is rapidly producing large amounts of data that necessitate new approaches of analysis. The analysis of a specific microarray experiment profits enormously from cross-comparing to other experiments. This process is generally performed by numerical meta-analysis of published data where the researcher chooses the datasets to be analyzed based on assumptions about the biological relations of published datasets to his own data, thus severely limiting the possibility of finding surprising connections. Here we propose using a repository of published gene lists for the identification of interesting datasets to be subjected to more detailed numerical analysis. RESULTS: We have compiled lists of genes that have been reported as differentially regulated in cancer related microarray studies. We searched these gene lists for statistically significant overlaps with lists of genes regulated by the tumor suppressors p16 and pRB. We identified a highly significant overlap of p16 and pRB target genes with genes regulated by the EWS/FLI fusion protein. Detailed numerical analysis of these data identified two sets of genes with clearly distinct roles in the G1/S and the G2/M phases of the cell cycle, as measured by enrichment of Gene Ontology categories. CONCLUSION: We show that mining of published gene lists in the absence of numerical detail about gene expression levels constitutes a fast, easy to perform, widely applicable, and unbiased route towards the identification of biologically related gene expression microarray datasets

Streptococcal cysteine proteinase releases kinins: a novel virulence mechanism

Previous work has indicated a crucial role for the extracellular cysteine proteinase of Streptococcus pyogenes in the pathogenicity and virulence of this important human pathogen. Here we find that the purified streptococcal cysteine proteinase releases biologically active kinins from their purified precursor protein, H-kininogen, in vitro, and from kininogens present in the human plasma, ex vivo. Kinin liberation in the plasma is due to the direct action of the streptococcal proteinase on the kininogens, and does not involve the previous activation of plasma prekallikrein, the physiological plasma kininogenase. Judged from the amount of released plasma kinins the bacterial proteinase is highly efficient in its action. This is also the case in vivo. Injection of the purified cysteine proteinase into the peritoneal cavity of mice resulted in a progressive cleavage of plasma kininogens and the concomitant release of kinins over a period of 5 h. No kininogen degradation was seen in mice when the cysteine proteinase was inactivated by the specific inhibitor, Z-Leu-Val-Gly-CHN2, before administration. Intraperitoneal administration into mice of living S. pyogenes bacteria producing the cysteine proteinase induced a rapid breakdown of endogenous plasma kininogens and release of kinins. Kinins are hypotensive, they increase vascular permeability, contract smooth muscle, and induce fever and pain. The release of kinins by the cysteine proteinase of S. pyogenes could therefore represent an important and previously unknown virulence mechanism in S. pyogenes infections

Production of compact plants by overexpression of AtSHI in the ornamental Kalanchoe

Growth retardation is an important breeding aim and an essential part of horticultural plant production Here, the potential of transferring the Arabidopsis short internode (shi) mutant phenotype was explored by expressing the AtSHI gene in the popular ornamental plant Kalanchoe A 35S-AtSHI construct was produced and transferred into eight genetically different cultivars of Kalanchoe by Agrobacterium tumefaciens The resulting transgenic plants showed dwarfing phenotypes like reduced plant height and diameter, and also more compact inflorescences, as a result of increased vegetative height The shi phenotype was stable over more than five vegetative subcultivations Compared with Arabidopsls, the ectopic expression of AtSHI in Kalanchoe showed several differences None of the Kalanchoe SHI-lines exhibited alterations in leaf colour or morphology, and most lines were not delayed in flowering Moreover, continuous treatment of lines delayed in flowering with low concentrations of gibberellins completely restored the time of flowering These features are very Important as a delay in flowering would increase plant production costs significantly. The effect of expression controlled by the native Arabidopsls SHI promoter was also investigated in transgenic Kalanchoe and resulted in plants with a longer flowering period Two AtSHI like genes were identified in Kalanchoe indicating a widespread presence of this transcription factor These findings are important because they suggest that transformation with the AtSHI gene could be applied to several species as a tool for growth retardation, and that this approach could substitute the use of conventional chemical growth regulation in plant productio

Marine Microalgae: Promising Source for New Bioactive Compounds

The study of marine natural products for their bioactive potential has gained strength in recent years. Oceans harbor a vast variety of organisms that offer a biological and chemical diversity with metabolic abilities unrivalled in terrestrial systems, which makes them an attractive target for bioprospecting as an almost untapped resource of biotechnological applications. Among them, there is no doubt that microalgae could become genuine cell factories for the biological synthesis of bioactive substances. Thus, in the course of inter-laboratory collaboration sponsored by the European Union (7th FP) into the MAREX Project focused on the discovery of novel bioactive compounds of marine origin for the European industry, a bioprospecting study on 33 microalgae strains was carried out. The strains were cultured at laboratory scale. Two extracts were prepared for each one (biomass and cell free culture medium) and, thus, screened to provide information on the antimicrobial, the anti-proliferative, and the apoptotic potential of the studied extracts. The outcome of this study provides additional scientific data for the selection of Alexandrium tamarensis WE, Gambierdiscus australes, Prorocentrum arenarium, Prorocentrum hoffmannianum, and Prorocentrum reticulatum (Pr-3) for further investigation and offers support for the continued research of new potential drugs for human therapeutics from cultured microalgae.Peer reviewe

A Common Variant of PNPLA3 (p.I148M) Is Not Associated with Alcoholic Chronic Pancreatitis

Contains fulltext : 110441.pdf (publisher's version ) (Open Access)BACKGROUND: Chronic pancreatitis (CP) is an inflammatory disease that in some patients leads to exocrine and endocrine dysfunction. In industrialized countries the most common aetiology is chronic alcohol abuse. Descriptions of associated genetic alterations in alcoholic CP are rare. However, a common PNPLA3 variant (p.I148M) is associated with the development of alcoholic liver cirrhosis (ALC). Since, alcoholic CP and ALC share the same aetiology PNPLA3 variant (p.I148M) possibly influences the development of alcoholic CP. METHODS: Using melting curve analysis we genotyped the variant in 1510 patients with pancreatitis or liver disease (961 German and Dutch alcoholic CP patients, 414 German patients with idiopathic or hereditary CP, and 135 patients with ALC). In addition, we included in total 2781 healthy controls in the study. RESULTS: The previously published overrepresentation of GG-genotype was replicated in our cohort of ALC (p-value <0.0001, OR 2.3, 95% CI 1.6-3.3). Distributions of genotype and allele frequencies of the p.I148M variant were comparable in patients with alcoholic CP, idiopathic and hereditary CP and in healthy controls. CONCLUSIONS: The absence of an association of PNPLA3 p.I148M with alcoholic CP seems not to point to a common pathway in the development of alcoholic CP and alcoholic liver cirrhosis