Androgen levels increase by intratumoral de novo steroidogenesis during progression of castration-resistant prostate cancer

Although systemic androgen deprivation prolongs life in advanced prostate cancer, remissions are temporary because patients almost uniformly progress to a state of a castration-resistant prostate cancer (CRPC) as indicated by recurring PSA. This complex process of progression does not seem to be stochastic as the timing and phenotype are highly predictable, including the observation that most androgen-regulated genes are reactivated despite castrate levels of serum androgens. Recent evidence indicates that intraprostatic levels of androgens remain moderately high following systemic androgen deprivation therapy, whereas the androgen receptor (AR) remains functional, and silencing the AR expression following castration suppresses tumor growth and blocks the expression of genes known to be regulated by androgens. From these observations, we hypothesized that CRPC progression is not independent of androgen-driven activity and that androgens may be synthesized de novo in CRPC tumors leading to AR activation. Using the LNCaP xenograft model, we showed that tumor androgens increase during CRPC progression in correlation to PSA up-regulation. We show here that all enzymes necessary for androgen synthesis are expressed in prostate cancer tumors and some seem to be up-regulated during CRPC progression. Using an ex vivo radiotracing assays coupled to high-performance liquid chromatography-radiometric/mass spectrometry detection, we show that tumor explants isolated from CRPC progression are capable of de novo conversion of [(14)C]acetic acid to dihydrotestosterone and uptake of [(3)H]progesterone allows detection of the production of six other steroids upstream of dihydrotestosterone. This evidence suggests that de novo androgen synthesis may be a driving mechanism leading to CRPC progression following castration.

An analysis of the effectiveness of parliamentary questions in the Uttar Pradesh State Legislative Assembly (India)

Parliamentary questions are the most popular and visible tool for making the executive accountable to the legislature. However, their use, purpose and effectiveness vary in different countries. In this study, 4023 parliamentary questions asked in the Uttar Pradesh State Legislative Assembly were analysed. The results show that half of the total members of the Assembly used this device. Contrary to findings in the Australian parliamentary system, there was no evidence of ‘Dorothy Dix’ and party influence on parliamentary questions. Furthermore, 30% of the questions were aimed at seeking information and 70% pressed for action. The government provided the required information in 95% of the questions in the former category but only took action in 37% in the latter category. The study concludes that parliamentary questions serve as an effective legislative tool in the Uttar Pradesh Legislature

BLAST Atlas : a function based multiple genome browser

BLAST Atlas is a visual analysis system for comparative genomics that supports genome-wide gene characterisation, functional assignment and function-based browsing of one or more chromosomes. Inspired by applications such as the WorldWide Telescope, Bing Maps 3D and Google Earth, BLAST Atlas uses novel three-dimensional gene and function views that provide a highly interactive and intuitive way for scientists to navigate, query and compare gene annotations. The system can be used for gene identification and functional assignment or as a function-based multiple genome comparison tool which complements existing position based comparison and alignment viewers.

An analysis of parliamentary questions raised by Opposition in the Uttar Pradesh (India) State Legislative Assembly

The use of parliamentary questions is the most popular and visible tool in the hands of the Opposition as a means to make government accountable. Their main purpose is to seek information or press for action. Contemporary parliamentary literature from the UK, Canada, and Australia, however, suggests that parliamentary questions have lost their effectiveness. The literature points out that Question Time in parliaments has become a battle ground between Ruling and Opposition parties in their fight to gain maximum political advantage. In this context, the effectiveness of parliamentary questions in the Indian state legislatures has not been investigated. The aim of this study, therefore, is to analyse the use, purpose and effectiveness of parliamentary questions in the State Legislative Assembly of Uttar Pradesh (India) to explore differences, if any, between Ruling and Opposition parties. In this study, 4023 parliamentary questions asked in the Uttar Pradesh State Legislative Assembly were analysed. The effectiveness of answers was also analysed qualitatively. The results show that half of the total members of the Assembly used this device, out of which 60% of the questions were asked by the Opposition party members. 31% of the questions from the Opposition were seeking information and 69% were pressing for action. The government provided the required information in 96% of the questions in the former category and took action in only 35% of the latter category. Furthermore, 60% of the questions raised by the Opposition were related to constituency matters and the remaining 40% were related to policy issues or public welfare. Comparing the data with the ruling party, the results indicate that the use,purpose and effectiveness of parliamentary questions were similar to that of the Opposition except some minor differences. Surprisingly, there was no evidence of any ‘Dorothy Dix’ questions. The study concludes parliamentary question is an effective device in the Indian state of Uttar Pradesh.