GLI1 Confers Profound Phenotypic Changes upon LNCaP Prostate Cancer Cells That Include the Acquisition of a Hormone Independent State

The GLI (GLI1/GLI2) transcription factors have been implicated in the development and progression of prostate cancer although our understanding of how they actually contribute to the biology of these common tumours is limited. We observed that GLI reporter activity was higher in normal (PNT-2) and tumourigenic (DU145 and PC-3) androgen-independent cells compared to androgen-dependent LNCaP prostate cancer cells and, accordingly, GLI mRNA levels were also elevated. Ectopic expression of GLI1 or the constitutively active ΔNGLI2 mutant induced a distinct cobblestone-like morphology in LNCaP cells that, regarding the former, correlated with increased GLI2 as well as expression of the basal/stem-like markers CD44, β1-integrin, ΔNp63 and BMI1, and decreased expression of the luminal marker AR (androgen receptor). LNCaP-GLI1 cells were viable in the presence of the AR inhibitor bicalutamide and gene expression profiling revealed that the transcriptome of LNCaP-GLI1 cells was significantly closer to DU145 and PC-3 cells than to control LNCaP-pBP (empty vector) cells, as well as identifying LCN2/NGAL as a highly induced transcript which is associated with hormone independence in breast and prostate cancer. Functionally, LNCaP-GLI1 cells displayed greater clonal growth and were more invasive than control cells but they did not form colonies in soft agar or prostaspheres in suspension suggesting that they do not possess inherent stem cell properties. Moreover, targeted suppression of GLI1 or GLI2 with siRNA did not reverse the transformed phenotype of LNCaP-GLI1 cells nor did double GLI1/GLI2 knockdowns activate AR expression in DU145 or PC-3 cells. As such, early targeting of the GLI oncoproteins may hinder progression to a hormone independent state but a more detailed understanding of the mechanisms that maintain this phenotype is required to determine if their inhibition will enhance the efficacy of anti-hormonal therapy through the induction of a luminal phenotype and increased dependency upon AR function

A proxy record of winter temperatures since 1836 from ice freeze-up/breakup in lake Näsijärvi, Finland

One obstacle on the way to a comprehensive spatial reconstruction of regional temperature changes over the past centuries is the sparseness of long winter temperature records. This paper reconstructs a proxy record of April and November–December temperatures in south-central Finland for the interval from 1836 to 1872 from breakup and freeze-up dates and ice-cover duration of a lake. Emphasis is on detecting the suitable winter months and quantifying the calibrations with measured temperatures (1873–2002). The calibration slope for the breakup date (0.158°C/day) is larger than for freeze-up date (0.119°C/day) or duration (0.090°C/day). A comparison with results from other proxy records shows that the slope may depend also on the geographical site. Trend analyses of the full temperature records (1836–2002) indicate the existence of minor change-points at around 1867 (April temperature) and 1874 (November–December temperature), with warming rates thereafter of 1.67°C per century (April) and 1.16°C per century (November–December). Spectral analyses reveal peaks in the band between 2 and 5 year period, which may point to influences of the North Atlantic Oscillation, and less power in the decadal band (up to 42 year period)

Invasive Species Control and Resolution of Wildlife Damage Conflicts: A Framework for Chemical and Genetically Based Management Methods

Vertebrate wildlife damage management relates to developing and employing methods to mitigate against damage caused by wildlife in the areas of food production, property damage, and animal or human health and safety. Of the many management tools available, chemical methods (e.g., toxicants) draw the most attention owing to issues related to environmental burden, species specificity, and humaneness. Research and development focusing on RNA interference and gene drives may be able to address the technical aspects of performance goals. However, there remain many questions about regulation, environmental risk, and societal acceptance for these emerging biological technologies. Here we focus on the development and use of these biological technologies for use in vertebrate pest management and conservation (e.g., management of wildlife diseases). We then discuss the regulatory framework and challenges these technologies present and conclude with a discussion on factors to consider for enabling these technologies for pest management and conservation applications under a commercially applied framework