An androgen receptor mutation in the MDA-MB-453 cell line model of molecular apocrine breast cancer compromises receptor activity

Recent evidence indicates that the estrogen receptor-a-negative, androgen receptor (AR)- positive molecular apocrine subtype of breast cancer is driven by AR signaling. The MDA-MB-453 cell line is the prototypical model of this breast cancer subtype; its proliferation is stimulated by androgens such as 5a-dihydrotestosterone (DHT) but inhibited by the progestin medroxyprogesterone acetate (MPA) via AR-mediated mechanisms. We report here that the AR gene in MDAMB- 453 cells contains a G-T transversion in exon 7, resulting in a receptor variant with a glutamine to histidine substitution at amino acid 865 (Q865H) in the ligand binding domain. Compared with wild-type AR, the Q865H variant exhibited reduced sensitivity to DHT and MPA in transactivation assays in MDA-MB-453 and PC-3 cells but did not respond to non-androgenic ligands or receptor antagonists. Ligand binding, molecular modeling, mammalian two-hybrid and immunoblot assays revealed effects of the Q865H mutation on ligand dissociation, AR intramolecular interactions, and receptor stability. Microarray expression profiling demonstrated that DHT and MPA regulate distinct transcriptional programs in MDA-MB-453 cells. Gene Set Enrichment Analysis revealed that DHT- but not MPA-regulated genes were associated with estrogen-responsive transcriptomes from MCF-7 cells and the Wnt signaling pathway. These findings suggest that the divergent proliferative responses of MDA-MB-453 cells to DHT and MPA result from the different genetic programs elicited by these two ligands through the AR-Q865H variant. This work highlights the necessity to characterize additional models of molecular apocrine breast cancer to determine the precise role of AR signaling in this breast cancer subtype. Endocrine-Related Cancer (2012) 19 599–613

Sovereignty, song and 'The Sapphires' (Wayne Blair 2012)

With its foregrounding of the political issue of the denial of Aboriginal Australian sovereignty by British invaders in its big budget, mainstream narrative, 'The Sapphires' (Wayne Blair 2012) is shown to be another example of a "fourth formation" (Starrs 2012) in Moore and Muecke's 1985 model. Blair's feel-good movie features an all-Aboriginal Australian troupe of singers, The Sapphires, who undertake a journey of self-discovery whereby they learn the importance of choosing the protest songs of black Soul over the white coloniser's "whining" Country and Western songs and this is historically contextualised with a discussion of Aboriginal Australians and popular radio. Furthermore, this paper argues the iconic 'Welcome to Country' is twice subverted to reinforce this theme, firstly in the Cummeragunja pub and secondly in war-torn Vietnam. Finally, the prediction is made that a "fifth formation", in which seeking recognition of Aboriginal Australian sovereignty is no longer the goal because it has become the ongoing reality, will soon be the project of Australian film-makers as they celebrate this long overdue societal shift.

The nest and eggs of Wayne's warbler (Dendroica Virens Waynei) taken near Mount Pleasant, S.C.

This document contains information on the nest and eggs of the bird, Wayne’s Warbler, taken near Mount Pleasant, South Carolina.

Remesas y desarrollo económico. Un análisis empírico del caso mexicano

El objetivo de este trabajo es contribuir a identificar el efecto de las remesas que envían los emigrantes a sus comunidades de origen en México. Del mismo modo, se estudia el efecto que la participación de la mujer tiene en este proceso. La fuente de información es el Consejo Nacional de Población de México CONAPO y contiene variables a nivel estatal y municipal para el año 2000. La base de datos contiene índices de desarrollo humano, intensidad migratoria y remesas para los 2443 municipios mexicanos. La evidencia empírica sugiere que las remesas tienen un impacto positivo sobre los niveles de desarrollo de las comunidades receptoras. No obstante, la relación entre remesas y desarrollo es no lineal. Adicionalmente, se en contró que el efecto positivo que tienen las remesas sobre el desarrollo es más alto cuando la cabeza de familia de los hogares receptores es mujer.

Louise Hanson-Dyer : leading by example

The article provides an example of music patronage, which can be sustained and realized in challenging conditions and focuses on the contribution of music publisher Louise Hanson-Dyer (1884-1962) . Her example demonstrates how patronage inspires confidence in music, elevates standards, and generates more creativity.

Thinking with the body: Mind and movement in the work of Wayne McGregor | Random Dance

Thinking with the Body was an exhibition at London's Wellcome Collection, offering a glimpse into Wayne McGregor | Random Dance's interdisciplinary research and the impact it has in the rehearsal studio. Staged in the run-up to the first performances of Atomos at Sadler's Wells (Oct 2013), the exhibition featured the results of over a decade of interdisciplinary research into choreographic creativity which has been applied in the studio, in dance education, and to increase public understanding.

Wellcome Collection is a free visitor destination exploring the connections between medicine, life and art in the past, present and future. Wellcome Collection is part of the Wellcome Trust, a global charitable foundation dedicated to achieving improvements in human and animal health.

The exhibition finished on 27 October 2013, but the film exhibits are still available to view online.