The Human Splice Variant Δ16HER2 Induces Rapid Tumor Onset in a Reporter Transgenic Mouse

Several transgenic mice models solidly support the hypothesis that HER2 (ERBB2) overexpression or mutation promotes tumorigenesis. Recently, a HER2 splice variant lacking exon-16 (Δ16HER2) has been detected in human breast carcinomas. This alternative protein, a normal byproduct of HER2, has an increased transforming potency compared to wild-type (wt) HER2 receptors. To examine the ability of Δ16HER2 to transform mammary epithelium in vivo and to monitor Δ16HER2-driven tumorigenesis in live mice, we generated and characterized a mouse line that transgenically expresses both human Δ16HER2 and firefly luciferase under the transcriptional control of the MMTV promoter. All the transgenic females developed multifocal mammary tumors with a rapid onset and an average latency of 15.11 weeks. Immunohistochemical analysis revealed the concurrent expression of luciferase and the human Δ16HER2 oncogene only in the mammary gland and in strict correlation with tumor development. Transgenic Δ16HER2 expressed on the tumor cell plasma membrane from spontaneous mammary adenocarcinomas formed constitutively active homodimers able to activate the oncogenic signal transduction pathway mediated through Src kinase. These new transgenic animals demonstrate the ability of the human Δ16HER2 isoform to transform “per se” mammary epithelium in vivo. The high tumor incidence as well as the short latency strongly suggests that the Δ16HER2 splice variant represents the transforming form of the HER2 oncoprotein

Whole-genome genotyping of grape using a panel of microsatellite

The use of microsatellite markers in large-scale genetic studies is limited by its low throughput and high cost and labor requirements. Here, we provide a panel of 45 multiplex PCRs for fast and cost-efficient genome-wide fluorescence-based microsatellite analysis in grapevine. The developed multiplex PCRs panel (with up to 15-plex) enables the scoring of 270 loci covering all the grapevine genome (9 to 20 loci/chromosome) using only 45 PCRs and sequencer runs. The 45 multiplex PCRs were validated using a diverse grapevine collection of 207 accessions, selected to represent most of the cultivated Vitis vinifera genetic diversity. Particular attention was paid to quality control throughout the whole process (assay replication, null allele detection, ease of scoring). Genetic diversity summary statistics and features of electrophoretic profiles for each studied marker are provided, as are the genotypes of 25 common cultivars that could be used as references in other studies

(Table 1, page 215) Chemical composition Mn deposits from the Middle Jurassic part of the Austrian Kalkalpen

The X-ray diffraction analyzes of two ferromanganese crust samples found at the base of the Klaus red Jurassic limestone beds of the Unterberg formation indicate pyrolusite as the main mineral. The crusts contain also a range of trace elements in concentrations comparable of present day oceanic deposits. The low Fe/Mn ratio found in sample 06-32a is in agreement with the geochemical data from Pacific Ocean manganese nodules and crusts of hydrothermal genesis. However, the simultaneously high contents in cerium and yttrium (rare earth metals) are more likely to suggest a precipitation of the manganese from the free water column (hydrogenetic origin). In addition, there are no identified hydrothermal sources in the vicinity of the hosting limestone beds. Iron-rich manganese nodules have also been found in the Jurrasic limestones beds of the Ruhpolding formation. In these deposits, hematite is the dominant mineral phase. The high Fe/Mn ratio as well the detritic material they contain (quartz, mica) lead to a possible continental margin origin for these nodules

From CAQDAS to Text Mining : the domain ontology as a model of knowledge representation about qualitative research practices

The nature of qualitative research practices is multiparadigmaticity which creates coexistence of different research and analytical approaches. This paper is a methodological reflection on how the process of qualitative data analysis is developing, moving from traditional CAQDAS coding procedures through Content Analysis dictionary-based approach towards the textual data exploration for knowledge discovery in corpora using Natural Language Processing and Text Mining procedures. This change is described on the example of the process of analyzing and discovering the ways through which qualitative research practices are conceptualized and represented in the vivid language of scholarly articles. Taking into account the problem of a "curse of abundance" in the present-day field of qualitative research I try to organize and articulate these practices in a legible system of knowledge representation about contemporary qualitative research field

Pronuclear injection for the production of transgenic mice

Transgenic mice have been instrumental in dissecting the role of various neuronal proteins under both physiological and pathological conditions. Pronuclear injection is the most widely used protocol for the generation of transgenic mice. Here, we describe all steps involved from DNA purification to the set up of a mouse colony including vasectomy, injection of the DNA into a donor zygote, transfer of injected zygotes into recipient foster mice, screening of offspring and establishment of transgenic mouse lines. We discuss the use of neuron-specific promoters to express proteins with a role in Alzheimer disease. Transgenic expression of a truncated form of the microtubule-associated protein tau (Δtau) is used as an example for the anticipated results