Investigating the properties of cancer stem cells and epithelial to mesenchymal transition in human prostate cancer

In recent years, the cancer stem cell hypothesis has emerged as a compelling but controversial model of cancer progression. Contrary to the clonal evolution model, the cancer stem cell hypothesis postulates that, akin to normal tissues, tumours are hierarchical and only a rare subpopulation of cells, so-called “cancer stem cells” (CSCs), possess the unique biological properties required for tumourigenesis. In addition to tumour initiation, cancer stem cells are held solely accountable for tumour differentiation, tumour maintenance, tumour spread and tumour relapse following therapy. Of late, there has been much evidence to suggest that cancer cells reactivate the latent embryonic programme, epithelial to mesenchymal transition (EMT), in order to acquire the invasive and migratory properties necessary for the successful completion of the invasion-metastasis cascade. Intriguingly, the EMT programme was recently implicated in the generation of cells with the properties of stem cells in a breast cancer model, therefore, it is evident that multiple populations of CSCs may exist within a given tumour. Since metastasis is accountable for the vast majority of cancer-associated mortalities and CSCs are implicated in therapy failure and subsequent cancer relapse, it is apparent that epithelial to mesenchymal transition and cancer stem cells are of utmost clinical relevance

BeadArray Expression Analysis Using Bioconductor

Illumina whole-genome expression BeadArrays are a popular choice in gene profiling studies. Aside from the vendor-provided software tools for analyzing BeadArray expression data (GenomeStudio/BeadStudio), there exists a comprehensive set of open-source analysis tools in the Bioconductor project, many of which have been tailored to exploit the unique properties of this platform. In this article, we explore a number of these software packages and demonstrate how to perform a complete analysis of BeadArray data in various formats. The key steps of importing data, performing quality assessments, preprocessing, and annotation in the common setting of assessing differential expression in designed experiments will be covered

Local industrial systems and the location of FDI in Italy

This article investigates the determinants of foreign direct investment (FDI)location across Italian provinces. Specifically it examines the relationship between industry- specific local industrial systems and the location of inward FDI. This extends previous analysis beyond the mere density of activity, to illustrate the importance of the specific nature of agglomerations in attracting inward investment. The article develops a model of FDI location choice using a unique FDI database stratified by industry and province. The results also suggest that the importance of agglomeration differs between industries, and offers some explanation for this

Red clover-derived isoflavones and mammographic breast density: a double-blind, randomized, placebo-controlled trial [ISRCTN42940165]

INTRODUCTION: Isoflavones are hypothesized to protect against breast cancer, but it is not clear whether they act as oestrogens or anti-oestrogens in breast tissue. Our aim was to determine the effects of taking a red clover-derived isoflavone supplement daily for 1 year on mammographic breast density. Effects on oestradiol, follicle-stimulating hormone (FSH), luteinizing hormone (LH), lymphocyte tyrosine kinase activity and menopausal symptoms were also assessed. METHODS: A total of 205 women (age range 49–65 years) with Wolfe P2 or DY mammographic breast patterns were randomly assigned to receive either a red clover-derived isoflavone tablet (26 mg biochanin A, 16 mg formononetin, 1 mg genistein and 0.5 mg daidzein) or placebo. Change in mammographic breast density, serum oestradiol, FSH, LH, menopausal symptoms and lymphocyte tyrosine kinase activity from baseline to 12 months were assessed. RESULTS: A total of 177 women completed the trial. Mammographic breast density decreased in both groups but the difference between the treatment and placebo was not statistically significant. There was a significant interaction between treatment group and oestrogen receptor (ESR1) PvuII polymorphism for the change in estimated percentage breast density (mean ± standard deviation): TT isoflavone 1.4 ± 12.3% and TT placebo -9.6 ± 14.2%; CT isoflavone -5.2 ± 12.0% and CT placebo -2.8 ± 10.3%; and CC isoflavone -3.4 ± 9.7% and CC placebo -1.1 ± 9.5%. There were no statistically significant treatment effects on oestradiol, FSH, or LH (assessed only in postmenopausal women), or on lymphocyte tyrosine kinase activity. Baseline levels of menopausal symptoms were low, and there were no statistically significant treatment effects on frequency of hot flushes or other menopausal symptoms. CONCLUSION: In contrast to studies showing that conventional hormone replacement therapies increase mammographic breast density, the isoflavone supplement did not increase mammographic breast density in this population of women. Furthermore, there were no effects on oestradiol, gonadotrophins, lymphocyte tyrosine kinase activity, or menopausal symptoms

Characterization of the Dispersal of Non-Domiciliated Triatoma dimidiata through the Selection of Spatially Explicit Models

Chagas disease is one of the most important neglected diseases in Latin America. Although insecticides have been successfully sprayed to control domiciliated vector populations, this strategy has proven to be ineffective in areas where non-domiciliated vectors immigrating from peridomestic or sylvatic ecotopes can (re-)infest houses. The development of strategies for the control of non-domiciliated vectors has thus been identified by the World Health Organization as a major challenge. Such development primarily requires a description of the spatio-temporal dynamics of infestation by these vectors, and a good understanding of their dispersal. We combined for the first time extensive spatio-temporal data sets describing house infestation dynamics by Triatoma dimidiata inside one village, and spatially explicit population dynamics models. The models fitted and predicted remarkably the observed infestation dynamics. They thus provided both key insights into the dispersal of T. dimidiata in this area, and a suitable mathematical background to evaluate the efficacy of various control strategies. Interestingly, the observed and modelled patterns of infestation suggest that interventions could focus on the periphery of the village, where there is the highest risk of transmission. Such spatial optimization may allow for reducing the cost of control, compensating for repeated interventions necessary for non-domiciliated vectors

Structure and dynamics of the pan-genome of Streptococcus pneumoniae and closely related species

Background Streptococcus pneumoniae is one of the most important causes of microbial diseases in humans. The genomes of 44 diverse strains of S. pneumoniae were analyzed and compared with strains of non-pathogenic streptococci of the Mitis group. Results Despite evidence of extensive recombination, the S. pneumoniae phylogenetic tree revealed six major lineages. With the exception of serotype 1, the tree correlated poorly with capsular serotype, geographical site of isolation and disease outcome. The distribution of dispensable genes, genes present in not all, but more than one strain, was consistent with phylogeny, although horizontal gene transfer events attenuated this correlation in the case of ancient lineages. Homologous recombination, involving short stretches of DNA, was the dominant 13 evolutionary process of the core genome of S. pneumoniae. Genetic exchange occurred both within and across the borders of the species, and S. mitis was the main reservoir of genetic diversity of S. pneumoniae. The pan-genome size of S. pneumoniae increased logarithmically with the number of strains and linearly with the number of polymorphic sites of the sampled genomes, suggesting that acquired genes accumulate proportionately to the age of clones. Most genes associated with pathogenicity were shared by all S. pneumoniae strains, but were also present in S. mitis, S. oralis and S. infantis, indicating that these genes are not sufficient to determine virulence. Conclusion Genetic exchange with related species sharing the same ecological niche is the main mechanism of evolution of S. pneumoniae. The open pan genome guarantees the species a quick and economical response to diverse environments

FDI in hot labour markets: The implications of the war for talent

This paper highlights an inherent contradiction that exists within investment promotion activities in rich countries. Since the financial crisis, many inward investment agencies have shifted their activities from job creation per se to seeking to attract investment in high-tech activities. Such knowledge-intensive sectors are engaged in what has become referred to as “the war for talent”, so locations need to understand their value proposition to firms, especially where labour is tight. This paper explores the implications of this, in terms of the impact on employment and earnings of high skilled labour. We show that, because skill shortages already exist in many of these sectors, seeking to attract inward investment in these sectors simply causes the earnings of such workers to be bid up, and employment in the incumbent sector to fall. We highlight the over-riding importance that firms place on the availability of skilled labour when determining locations, and how policies which promote labour market flexibility, particularly through investment in skills to address skill shortages, can significantly mitigate the adverse effects, which tend to be more keenly felt in poorer regions of Europe where skilled labour is in even shorter supply

Cognitieve revalidatie voor kinderen en jongeren met niet-aangeboren hersenletsel:wat zijn de effectieve componenten?

Veel kinderen en jongeren met niet-aangeboren hersenletsel (nah) ervaren problemen met cognitief functioneren, zoals een verminderd geheugen of slechtere concentratie. Dit artikel is gebaseerd op bevindingen en inzichten uit het proefschrift ‘executive functions of children and adolescents: novel perspectives on assessment and intervention’. Een belangrijk doel van het promotietraject was beter inzicht te krijgen in hoe we cognitieve functies en bijbehorende problemen bij kinderen en jongeren met nah kunnen verbeteren. Cognitieve problemen bij kinderen en jongeren kunnen mogelijk worden behandeld met cognitieve revalidatie. Interventies voor cognitieve revalidatie kunnen worden gecategoriseerd op basis van hun hoofdcomponenten: 1) strategiegebruik en/of metacognitie, 2) herhaald oefenen, en 3) externe hulpmiddelen. Resultaten van een literatuurstudie naar cognitieve revalidatie laten zien dat door interventies die zijn gebaseerd op metacognitie en/of strategiegebruik vooral adaptief gedrag en sociaal functioneren verbeteren. Interventies op basis van herhaald oefenen verbeterden de prestaties op taken die vergelijkbaar zijn met de geoefende taken. Multi-componenten-interventies die deze twee componenten combineren, leken te leiden tot verbeteringen in zowel cognitief als adaptief gedrag en sociaal functioneren. Externe hulpmiddelen verbeterden het functioneren in het specifieke gebied waarop het hulpmiddel was gericht, bijvoorbeeld het geheugen. De beschikbare gegevens suggereren dat interventies bestaande uit meerdere componenten, zoals een combinatie van metacognitie- en/of strategiegebruik en herhaald oefenen, veelbelovend zijn, omdat deze kunnen leiden tot verbeteringen in zowel het cognitieve als psychosociale functioneren van kinderen en adolescenten met nah