The androgen receptor and signal-transduction pathways in hormone-refractory prostate cancer. Part 1: modifications to the androgen receptor

Prostate cancer is the second most common male malignancy in the western world an increasing incidence in an ageing population. Treatment of advanced prostate cancer relies on androgen deprivation. Although the majority of patients initially respond favourably to androgen deprivation therapy, the mean time to relapse is 12-18 months. Currently there are few treatments available for men who have developed resistance to hormone therapy, due to the lack of understanding of the molecular mechanisms underlying development of this disease. Recently, however, major advances have been made in understanding both androgen receptor (AR) dependent and independent pathways which promote development of hormone resistant prostate cancer. This review will focus on modifications to the AR and associated pathways. Molecular modifications to the androgen receptor itself, e.g. mutations and/or amplification, although involved in the development of hormone resistance cannot explain all cases. Phosphorylation of AR, via either Ras/MAP kinase or PI3K/Akt signal transduction pathways, have been shown to activate AR in both a ligand (androgen) dependent and independent fashion. During this review we will discuss the clinical evidence to support AR dependent pathways as mediators of hormone resistance

Hollywood blockbusters and long-tailed distributions: An empirical study of the popularity of movies

Numerical data for all movies released in theaters in the USA during the period 1997-2003 are examined for the distribution of their popularity in terms of (i) the number of weeks they spent in the Top 60 according to the weekend earnings, and (ii) the box-office gross during the opening week, as well as, the total duration for which they were shown in theaters. These distributions show long tails where the most popular movies are located. Like the study of Redner [S. Redner, Eur. Phys. J. B 4, 131 (1998)] on the distribution of citations to individual papers, our results are consistent with a power-law dependence of the rank distribution of gross revenues for the most popular movies with a exponent close to -1/2.Comment: 4 pages, 4 figure

The growth hormone receptor gene deleted for exon three (GHRd3) polymorphism is associated with birth and placental weight.

Human growth hormone receptor (GHR) transcripts have two isoforms, full-length (GHRfl) or exon 3 deleted (GHRd3). An association of these isoforms has been found with small for gestational age (SGA) infants but does not influence adult height. The role of this polymorphism in the birth size spectrum in the general population is unclear

Beaver: Nature's ecosystem engineers

This is the final version. Available on open access from Wiley via the DOI in this record. Beavers have the ability to modify ecosystems profoundly to meet their ecological needs, with significant associated hydrological, geomorphological, ecological, and societal impacts. To bring together understanding of the role that beavers may play in the management of water resources, freshwater, and terrestrial ecosystems, this article reviews the state-of-the-art scientific understanding of the beaver as the quintessential ecosystem engineer. This review has a European focus but examines key research considering both Castor fiber—the Eurasian beaver and Castor canadensis—its North American counterpart. In recent decades species reintroductions across Europe, concurrent with natural expansion of refugia populations has led to the return of C. fiber to much of its European range with recent reviews estimating that the C. fiber population in Europe numbers over 1.5 million individuals. As such, there is an increasing need for understanding of the impacts of beaver in intensively populated and managed, contemporary European landscapes. This review summarizes how beaver impact: (a) ecosystem structure and geomorphology, (b) hydrology and water resources, (c) water quality, (d) freshwater ecology, and (e) humans and society. It concludes by examining future considerations that may need to be resolved as beavers further expand in the northern hemisphere with an emphasis upon the ecosystem services that they can provide and the associated management that will be necessary to maximize the benefits and minimize conflicts.Natural Environment Research Council (NERC)Wellcome TrustDevon Wildlife TrustPlymouth City CouncilCornwall Wildlife TrustUniversity of Exete

The costs of preventing and treating chagas disease in Colombia

Background: The objective of this study is to report the costs of Chagas disease in Colombia, in terms of vector disease control programmes and the costs of providing care to chronic Chagas disease patients with cardiomyopathy. Methods: Data were collected from Colombia in 2004. A retrospective review of costs for vector control programmes carried out in rural areas included 3,084 houses surveyed for infestation with triatomine bugs and 3,305 houses sprayed with insecticide. A total of 63 patient records from 3 different hospitals were selected for a retrospective review of resource use. Consensus methodology with local experts was used to estimate care seeking behaviour and to complement observed data on utilisation. Findings: The mean cost per house per entomological survey was $4.4 (in US$ of 2004), whereas the mean cost of spraying a house with insecticide was $27. The main cost driver of spraying was the price of the insecticide, which varied greatly. Treatment of a chronic Chagas disease patient costs between$46.4 and $7,981 per year in Colombia, depending on severity and the level of care used. Combining cost and utilisation estimates the expected cost of treatment per patient-year is$1,028, whereas lifetime costs averaged $11,619 per patient. Chronic Chagas disease patients have limited access to healthcare, with an estimated 22% of patients never seeking care. Conclusion: Chagas disease is a preventable condition that affects mostly poor populations living in rural areas. The mean costs of surveying houses for infestation and spraying infested houses were low in comparison to other studies and in line with treatment costs. Care seeking behaviour and the type of insurance affiliation seem to play a role in the facilities and type of care that patients use, thus raising concerns about equitable access to care. Preventing Chagas disease in Colombia would be cost-effective and could contribute to prevent inequalities in health and healthcare.Wellcome Trus

Using the theory of planned behaviour as a process evaluation tool in randomised trials of knowledge translation strategies : A case study from UK primary care

Peer reviewedPublisher PD

Suggested Improvements for the Allergenicity Assessment of Genetically Modified Plants Used in Foods

Genetically modified (GM) plants are increasingly used for food production and industrial applications. As the global population has surpassed 7 billion and per capita consumption rises, food production is challenged by loss of arable land, changing weather patterns, and evolving plant pests and disease. Previous gains in quantity and quality relied on natural or artificial breeding, random mutagenesis, increased pesticide and fertilizer use, and improved farming techniques, all without a formal safety evaluation. However, the direct introduction of novel genes raised questions regarding safety that are being addressed by an evaluation process that considers potential increases in the allergenicity, toxicity, and nutrient availability of foods derived from the GM plants. Opinions vary regarding the adequacy of the assessment, but there is no documented proof of an adverse effect resulting from foods produced from GM plants. This review and opinion discusses current practices and new regulatory demands related to food safety

ERK1/2 signaling dominates over RhoA signaling in regulating early changes in RNA expression induced by endothelin-1 in neonatal rat cardiomyocytes

Cardiomyocyte hypertrophy is associated with changes in gene expression. Extracellular signal-regulated kinases 1/2 (ERK1/2) and RhoA [activated by hypertrophic agonists (e.g. endothelin-1)] regulate gene expression and are implicated in the response, but their relative significance in regulating the cardiomyocyte transcriptome is unknown. Our aim was to establish the significance of ERK1/2 and/or RhoA in the early cardiomyocyte transcriptomic response to endothelin-1.Cardiomyocytes were exposed to endothelin-1 (1 h) with/without PD184352 (to inhibit ERK1/2) or C3 transferase (C3T, to inhibit RhoA). RNA expression was analyzed using microarrays and qPCR. ERK1/2 signaling positively regulated approximately 65% of the early gene expression response to ET-1 with a small (approximately 2%) negative effect, whereas RhoA signaling positively regulated approximately 10% of the early gene expression response to ET-1 with a greater (approximately 14%) negative contribution. Of RNAs non-responsive to endothelin-1, 66 or 448 were regulated by PD184352 or C3T, respectively, indicating that RhoA had a more significant effect on baseline RNA expression. mRNAs upregulated by endothelin-1 encoded a number of receptor ligands (e.g. Ereg, Areg, Hbegf) and transcription factors (e.g. Abra/Srf) that potentially propagate the response.ERK1/2 dominates over RhoA in the early transcriptomic response to endothelin-1. RhoA plays a major role in maintaining baseline RNA expression but, with upregulation of Abra/Srf by endothelin-1, RhoA may regulate changes in RNA expression over longer times. Our data identify ERK1/2 as a more significant node than RhoA in regulating the early stages of cardiomyocyte hypertrophy

The impact of trench defects in InGaN/GaN light emitting diodes and implications for the "green gap" problem

The impact of trench defects in blue InGaN/GaN light emitting diodes (LEDs) has been investigated. Two mechanisms responsible for the structural degradation of the multiple quantum well (MQW) active region were identified. It was found that during the growth of the p-type GaN capping layer, loss of part of the active region enclosed within a trench defect occurred, affecting the top-most QWs in the MQW stack. Indium platelets and voids were also found to form preferentially at the bottom of the MQW stack. The presence of high densities of trench defects in the LEDs was found to relate to a significant reduction in photoluminescence and electroluminescence emission efficiency, for a range of excitation power densities and drive currents. This reduction in emission efficiency was attributed to an increase in the density of non-radiative recombination centres within the MQW stack, believed to be associated with the stacking mismatch boundaries which form part of the sub-surface structure of the trench defects. Investigation of the surface of green-emitting QW structures found a two decade increase in the density of trench defects, compared to its blue-emitting counterpart, suggesting that the efficiency of green-emitting LEDs may be strongly affected by the presence of these defects. Our results are therefore consistent with a model that the “green gap” problem might relate to localized strain relaxation occurring through defects.This is the accepted manuscript version. The final version is available from AIP at http://scitation.aip.org/content/aip/journal/apl/105/11/10.1063/1.4896279?showFTTab=true&containerItemId=content/aip/journal/apl

Effect of thermal treatment and storage on bioactive compounds, organic acids and antioxidant activity of baobab fruit (Adansonia digitata) pulp from Malawi

Bioactive compounds of baobab (Adansonia digitata) pulp from Malawi were investigated. The effect of thermal treatment and storage on selected quality attributes of the juice was also evaluated. Organic compounds were analysed by HPLC; total phenol content (TPC) and total antioxidant activity (FRAP, ABTS and DPPH) were measured by spectrophotometry. Malawi baobab pulp contains high levels of procyanidin B2 (533 ± 22.6 mg/100 g FW), vitamin C (AA + DHA) (466 ± 2.5 mg/100 g FW), gallic acid (68.5 ± 12.4 mg/100 g FW) and (−)-epicatechin (43.0 ± 3.0 mg/100 g FW) and showed a maximum TPC of 1.89 × 103 ± 1.61 mg GAE/100 g FW. The maximum antioxidant activity was 2.81 × 103 ± 92.8 mg TEAC/100 g FW for FRAP, 1.52 × 103 ± 17.1 mg TEAC/100 g FW for ABTS and 50.9 ± 0.43% DPPH for DPPH. Thermal pasteurisation (72 °C, 15 s) retained vitamin C which further showed extended half-life under refrigeration temperature (6 °C). Procyanidin B2, (−)-epicatechin, TPC and antioxidant activity fluctuated during storage. Antioxidant activity was significantly correlated (p ≤ 0.05) with bioactive compounds and TPC