Zebrafish Hagoromo mutants upregulate fgf8 post-embryonically and develop neuroblastoma

We screened an existing collection of zebrafish insertional mutants for cancer susceptibility by histologic examination of heterozygotes at 2 years of age. As most mutants had no altered cancer predisposition, this provided the first comprehensive description of spontaneous tumor spectrum and frequency in adult zebrafish. Moreover, the screen identified four lines, each carrying a different dominant mutant allele of Hagoromo previously linked to adult pigmentation defects, which develop tumors with high penetrance and that histologically resemble neuroblastoma. These tumors are clearly neural in origin, although they do not express catecholaminergic neuronal markers characteristic of human neuroblastoma. The zebrafish tumors result from inappropriate maintenance of a cell population within the cranial ganglia that are likely neural precursors. These neoplasias typically remain small but they can become highly aggressive, initially traveling along cranial nerves, and ultimately filling the head. The developmental origin of these tumors is highly reminiscent of human neuroblastoma. The four mutant Hagoromo alleles all contain viral insertions in the fbxw4 gene, which encodes an F-box WD40 domain–containing protein. However, although one allele clearly reduced the levels of fbxw4 mRNA, the other three insertions had no detectable effect on fbw4 expression. Instead, we showed that all four mutations result in the postembryonic up-regulation of the neighboring gene, fibroblast growth factor 8 (fgf8). Moreover, fgf8 is highly expressed in the tumorigenic lesions. Although fgf8 overexpression is known to be associated with breast and prostate cancer in mammals, this study provides the first evidence that fgf8 misregulation can lead to neural tumors. (Mol Cancer Res 2009;7(6):841–50)National Cancer Institute (U.S.) (Grant CA106416

The salmon louse genome: Copepod features and parasitic adaptations

Copepods encompass numerous ecological roles including parasites, detrivores and phytoplankton grazers. Nonetheless, copepod genome assemblies remain scarce. Lepeophtheirus salmonis is an economically and ecologically important ectoparasitic copepod found on salmonid fish. We present the 695.4 Mbp L. salmonis genome assembly containing ≈60% repetitive regions and 13,081 annotated protein-coding genes. The genome comprises 14 autosomes and a ZZ-ZW sex chromosome system. Assembly assessment identified 92.4% of the expected arthropod genes. Transcriptomics supported annotation and indicated a marked shift in gene expression after host attachment, including apparent downregulation of genes related to circadian rhythm coinciding with abandoning diurnal migration. The genome shows evolutionary signatures including loss of genes needed for peroxisome biogenesis, presence of numerous FNII domains, and an incomplete heme homeostasis pathway suggesting heme proteins to be obtained from the host. Despite repeated development of resistance against chemical treatments L. salmonis exhibits low numbers of many genes involved in detoxification.publishedVersio

Dissecting the Transcriptional Regulatory Properties of Human Chromosome 16 Highly Conserved Non-Coding Regions

Non-coding DNA conservation across species has been often used as a predictor for transcriptional enhancer activity. However, only a few systematic analyses of the function of these highly conserved non-coding regions (HCNRs) have been performed. Here we use zebrafish transgenic assays to perform a systematic study of 113 HCNRs from human chromosome 16. By comparing transient and stable transgenesis, we show that the first method is highly inefficient, leading to 40% of false positives and 20% of false negatives. When analyzed in stable transgenic lines, a great majority of HCNRs were active in the central nervous system, although some of them drove expression in other organs such as the eye and the excretory system. Finally, by testing a fraction of the HCNRs lacking enhancer activity for in vivo insulator activity, we find that 20% of them may contain enhancer-blocking function. Altogether our data indicate that HCNRs may contain different types of cis-regulatory activity, including enhancer, insulators as well as other not yet discovered functions

In vitro study of the relationship between sulfur level and various parameters of rumen microbial activity

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Étude in vitro (RUSITEC) de la transformation de divers composés soufrés dans le rumen

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Using document-oriented GUIs in dynamic software product lines

Dynamic Software Product Line (DSPL) Engineering has gained interest through its promise of being able to unify software adaptation whereby software adaptation can be realised at compile time and runtime. While previous work has enabled program logic adaptation by the use of language extensions and platform support, little attention has been placed on Graphical User Interface (GUI) variability. Different design patterns including the Model View Controller are commonly used in GUI implementation, with GUI documents being used for declaring the GUI. To handle dynamic GUI variability currently, the developer needs to implement GUI refinements using multiple techniques. This paper proposes a solution for dealing with GUI document variability, statically and dynamically, in a unified way. In our approach, we currently use a compile time method for producing GUI variants, and code transformations to handle these variants within the application at runtime. To avoid GUI duplicates, only GUI variants that are unique, and related to a valid product configuration, are produced. To validate our approach, we implemented tool support to enable this for Android based applications

Context-aware content-centric collaborative workflow management for mobile devices

The paper examines mobile context-aware contentcentric workflows. With the proliferation of mobile devices, distributed collaborative teams can communicate, share content and remain productive while working out of the office. The collaboration process can be enhanced, more dynamic and efficient by using a workflow management technology that responds to collaborators’ requirements, supports coordination of a teamwork and is adapted for context-aware content manipulation. This paper discusses context awareness and proposes to extend the existing collaborative workflow approach by a context-aware content lifecycle in order to make workflow processes more adaptive to collaboration needs

Influence de la dose de soufre élémentaire sur l'activité fermentaire des microbes du rumen dans un système de fermentation semi-continu

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