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

SAP-Related Education - Status-Quo and Experience

Integrating Enterprise Systems solutions in the curriculum of not only universities but all types of institutes of higher learning has been a major challenge for nearly ten years. Enterprise Systems education is surprisingly well documented in a number of papers on Information Systems education. However, most publications in this area report on the individual experiences of an institution or an academic. This paper focuses on the most popular Enterprise System - SAP - and summarizes the outcomes of a global survey on the status quo of SAP-related education. Based on feedback of 305 lecturers and more than 700 students, it reports on the main factors of Enterprise Systems education including, critical success factors, alternative hosting models, and students’ perceptions. The results show among others an overall increasing interest in advanced SAP solutions and international collaboration, and a high satisfaction with the concept of using Application Hosting Centers.

Psychiatric disorder in HIV infection

Objective: This study aimed to investigate rates of psychiatric disorder in human immunodeficiency virus (HIV) infection, in an Australian sample of homosexual and bisexual men. Method: A cross-sectional study of a total of 65 HIV sero-negative (HIV-) and 164 HIV sero-positive men (HIVt) (79 CDC stage 1 1/1 11 and 85 CDC stage IV) was conducted in three centres. Lifetime and current prevalence rates of psychiatric disorder were evaluated using the Diagnostic Interview Schedule Version lllR (DIS-IIIR). Results: Elevated current and lifetime rates of major depression were detected in both HIV negative and HIV positive homosexual/bisexual men. Lifetime rates of alcohol abuseldependence were significantly elevated in HIV positive men (CDC group IV) when compared with HIV negative men. Among the HIV positive group the majority of psychiatric disorders detected were preceded by a pre-HIV diagnosis of psychiatric disorder. Major depression represented the disorder most likely to have first onset after HIV infection diagnosis. Conclusions: Lifetime rates of major depression were elevated in this sample of HIV-negative and HIV-positive men, In the HIV-positive men, psychiatric disorder was significantly associated with the presence of lifetime psychiatric disorder prior to HIV infection diagnosis, The findings indicate the importance of evaluation of psychiatric history prior to HIV infection and the clinical significance of depressive syndromes in this population.

Varieties of Asian capitalism : toward an institutional theory of Asian enterprise

In this paper we respond to calls for an institution-based perspective on strategy. With its emphasis upon mimetic, coercive, and normative isomorphism, institutional theory has earned a deterministic reputation and seems an unlikely foundation on which to construct a theory of strategy. However, a second movement in institutional theory is emerging that gives greater emphasis to creativity and agency. We develop this approach by highlighting co-evolutionary processes that are shaping the varieties of capitalism (VoC) in Asia. To do so, we examine the extent to which the VoC model can be fruitfully applied in the Asian context. In the spirit of the second movement of institutional theory, we describe three processes in which firm strategy collectively and intentionally feeds back to shape institutions: (1) filling institutional voids, (2) retarding institutional innovation, and (3) deploying institutional escape. We outline the key contributions contained in the articles of this Special Issue and discuss a research agenda generated by the VoC perspective.

United Arab Emirates

The United Arab Emirates (UAE) is part of the geographic region known as the Middle East. With a land mass of 82,000 square kilometres, predominantly desert and mountains it is bordered by Oman, Saudi Arabia and the Arabian Gulf. The UAE is strategically located due to its proximity to other oil rich Middle Eastern countries such as Kuwait, Iraq, Iran, and Saudi Arabia. The UAE was formed from a federation of seven emirates (Abu Dhabi, Dubai, Sharjah, Ras Al Khaimah, Ajman, Fujuriah, and Um Al Quain) in December 1971 (Ras Al Khaimah did not join the federation until 1972) (Heard-bey, 2004, 370). Abu Dhabi is the political capital, and the richest emirate; while Dubai is the commercial centre. The majority of the population of the various Emirates live along the coast line as sources of fresh water often heavily influenced the site of different settlements. Unlike some near neighbours (Iran and Iraq) the UAE has not undergone any significant political instability since it was formed in 1971. Due to this early British influences the UAE has had very strong political and economic ties with first Britain, and, more recently, the United States of America (Rugh, 2007). Until the economic production of oil in the early 1960’s the different Emirates had survived on a mixture of primary industry (dates), farming (goats and camels), pearling and subsidies from Britain (Davidson 2005, 3; Hvit, 2007, 565) Along with near neighbours Kuwait, Bahrain, Oman, Qatar and Saudi Arabia, the UAE is part of the Gulf Cooperation Council (GCC), a trading bloc. (Hellyer, 2001, 166-168).

Reasons for cannabis use in men with and without psychosis

Psychoses are relatively low prevalence disorders that have a disproportionately negative impact on individuals and society. Cannabis use is one factor that can exacerbate the negative consequences associated with psychotic disorders. Relatively few studies have examined the effects or reasons for using cannabis self-reported by individuals with psychosis. The present study is the first known to compare directly such factors in individuals with and without psychosis, within a single study. At baseline and follow-up participants with psychosis most commonly reported using cannabis for positive mood alteration (36% and 42%), coping with negative affect (27% and 29%) and for social activity reasons (38% and 29%). The control group most commonly reported using cannabis for relaxation (34% and 43%) and social activity reasons (49% and 51%). Participants with psychosis were less likely to report relaxation as the most important effect after use (27%) or expect it at follow-up (49%) compared to the control group (53% and 70%). In both groups, addiction and positive affect enhancement were the composite variable scores correlated most consistently with concurrent amount and frequency of use.

The foraging behaviour of the Black rat (Rattus rattus) within Australian macadamia orchards

The black rat (Rattus rattus) has been shown to be the primary species responsible for causing significant crop losses within the Australian macadamia industry. This species success within macadamia orchards is directly related to the flexibility expressed in its foraging behaviour. In this paper a conceptual foraging model is presented which proposes that the utilisation of resources by rodents within various components of the system is related not only to their relative abundance, but also to predator avoidance behaviour. Nut removal from high predation risk habitats during periods of low resource abundance in low risk compartments of the system is considered an essential behaviour that allows high rodent densities to be maintained throughout the year.

Being stoned : a review of self-reported cannabis effects.

Although there has been considerable research into the adverse effects of cannabis, less attention has been directed toward subjective effects that may be associated with ongoing cannabis use. Examination of self-reported cannabis effects is an important issue in understanding the widespread use of cannabis. While reviews have identified euphoria as a primary factor in maintaining cannabis use, relaxation is the effect reported most commonly in naturalistic studies of cannabis users, irrespective of the method used. Self-reported effects in 12 naturalistic and 18 laboratory studies were compared. Regardless of methodology there was considerable variation in the effects experienced. Variation has been reported in terms of opposite effects being experienced by different individuals, variation of effects by individuals within a single occasion and between occasions of use. Factors that might explain this variation are outlined. Limitations of the available literature and suggested directions for future research are discussed.