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Selected AbstractsBeyond the High-Performance Paradigm?BRITISH JOURNAL OF INDUSTRIAL RELATIONS, Issue 1 2001An Analysis of Variation in Canadian Managerial Perceptions of Reform Programme Effectiveness Proponents of the high-performance paradigm often argue that the variable success of new forms of work organization is explained primarily by a failure to implement them comprehensively and to adopt complementary HRM practices. This paper argues that these explanations are inadequate and develops an alternative, political economy approach which accounts more fully for how conflicts embedded in the employment relation limit the effectiveness of reforms. It draws on a unique longitudinal data set representing 78 Canadian workplaces to analyse the extent to which reform programme content, pre-existing HRM conditions and workplace context variables are associated with reform programme effectiveness. [source] Systematic methods, fossils, and relationships within Heteroptera (Insecta)CLADISTICS, Issue 3 2010Gerasimos Cassis Three recent papers dealing with phylogenetic relationships within the Heteroptera are discussed and analysed. A character set representing 43 taxa and 78 characters is used to test theories presented in those papers. The conclusions of Grimaldi and Engel concerning the placement of the Cretaceous fossil taxon Cretopiesma in the Piesmatidae are rejected in favour of placement in the Aradidae. The placement by Nel et al. of Protodoris from Eocene amber of the Paris Basin in the Thaumastocoridae is considered ambiguous because it has none of the diagnostic characters of that family group and is therefore regarded as incertae sedis. The arguments of Sweet concerning the elevation of the Aradoidea to infraordinal status on the basis of autapomorphies are also treated as invalid. General arguments against the use of phenetic methods in palaeontology, and ad hoc approaches under the guise of cladistics, are offered, with the conclusion that rigorous cladistic analyses are a prerequisite to testable conclusions concerning the placement of fossil and Recent taxa. ,© The Willi Hennig Society 2009. [source] A role for the pregnane X receptor in flucloxacillin-induced liver injury,HEPATOLOGY, Issue 5 2010Elise Andrews Drug-induced liver injury (DILI) due to flucloxacillin is a rare but serious complication of treatment. There is some evidence that flucloxacillin is a human pregnane X receptor (PXR) agonist. This study was designed to investigate the relevance of PXR to flucloxacillin toxicity and to identify genes changing in expression in response to flucloxacillin. Changes in gene expression in human hepatocytes after treatment with 500 ,M flucloxacillin for 72 hours were examined by expression microarray analysis. The ability of flucloxacillin to act as a PXR agonist was investigated with reporter gene experiments. Flucloxacillin DILI cases (n = 51), drug-exposed controls without toxicity (n = 64), and community controls (n = 90) were genotyped for three common PXR polymorphisms. Luciferase reporter assays were used to assess the significance of a promoter region PXR polymorphism. Seventy-two probe sets representing 50 different genes showed significant changes in expression of 1.2-fold or higher. Most genes showing changes greater than 3-fold were known to be rifampicin-responsive, and this suggested a PXR-dependent mode of regulation. Using a luciferase-everted repeat separated by 6 base pairs element construct, we confirmed that flucloxacillin was a PXR agonist. We found a difference in the distribution of a PXR polymorphism (rs3814055; C-25385T) between flucloxacillin DILI cases and controls with the CC genotype associated with an increased risk of disease (odds ratio = 3.37, 95% confidence interval = 1.55-7.30, P = 0.0023). Reporter gene experiments showed lower promoter activity for the C allele than the T allele. Conclusion: Flucloxacillin is a PXR agonist at pharmacologically relevant concentrations, and a functionally significant upstream PXR polymorphism is a risk factor for flucloxacillin-induced DILI. Hepatology 2010 [source] ApcMin/+ mouse model of colon cancer: Gene expression profiling in tumorsJOURNAL OF CELLULAR BIOCHEMISTRY, Issue 6 2004Daniel Leclerc Abstract The ApcMin/+ mouse is a popular animal model for studies of human colon cancer, but the molecular changes associated with neoplasia in this system have only been partially characterized. Our aim was to identify novel genes involved in tumorigenesis in this model. RNA from intestinal adenomas and from pre-neoplastic small intestine were prepared from six ApcMin/+ mice. The tumor transcriptomes were analyzed with high-density oligonucleotide microarrays representing ,12,000 probe sets; we compared their profiles with those of matched pre-neoplastic intestine. Stringent analysis revealed reproducible changes for 98 probe sets representing 90 genes, including novel observations regarding 50 genes whose involvement in this mouse model has never been reported. In addition to the expected changes in growth regulatory genes, the altered gene products could be assigned to four functional groupings that should enhance tumorigenesis: metabolic changes that would result in a high rate of glycolysis, alterations in enzymes involved in reactive oxygen species or carcinogen metabolism, cytoskeletal elements, and proteins involved in tumor invasion or angiogenesis. A fifth group consisted of expression changes that might restrict tumor progression, suggesting that the adenomatous state reflects a balance of pro- and anti-tumorigenic factors. Since many of the altered genes had not previously been reported to be involved in any tumorigenic processes, our observations provide a host of new candidates for potential modulation to prevent or treat intestinal neoplasia. Supplementary material for this article can be found at http://www.mrw.interscience.wiley.com/suppmat/0730-2312/suppmat/v93.html. © 2004 Wiley-Liss, Inc. [source] |