The application of Reporter Gene Assays for the detection of endocrine disruptors in sport supplements.

The increasing availability and use of sports supplements is of concern as highlighted by a number of studies reporting endocrine disruptor contamination in such products. The health food supplement market, including sport supplements, is growing across the Developed World. Therefore, the need to ensure the quality and safety of sport supplements for the consumer is essential. The development and validation of two reporter gene assays coupled with solid phase sample preparation enabling the detection of estrogenic and androgenic constituents in sport supplements is reported. Both assays were shown to be of high sensitivity with the estrogen and androgen reporter gene assays having an EC50 of 0.01 ng mL-1 and 0.16 ng mL-1 respectively. The developed assays were applied in a survey of 63 sport supplements samples obtained across the Island of Ireland with an additional seven reference samples previously investigated using LC–MS/MS. Androgen and estrogen bio-activity was found in 71% of the investigated samples. Bio-activity profiling was further broken down into agonists, partial agonists and antagonists. Supplements (13) with the strongest estrogenic bio-activity were chosen for further investigation. LC–MS/MS analysis of these samples determined the presence of phytoestrogens in seven of them. Supplements (38) with androgen bio-activity were also selected for further investigation. Androgen agonist bio-activity was detected in 12 supplements, antagonistic bio-activity was detected in 16 and partial antagonistic bio-activity was detected in 10. A further group of supplements (7) did not present androgenic bio-activity when tested alone but enhanced the androgenic agonist bio-activity of dihydrotestosterone when combined. The developed assays offer advantages in detection of known, unknown and low-level mixtures of endocrine disruptors over existing analytical screening techniques. For the detection and identification of constituent hormonally active compounds the combination of biological and physio-chemical techniques is optimal.

The Uncertainty of Experience: On George Brecht's Event Scores

George Brecht, an artist best known for his associations with Fluxus, is considered to have made significant contributions to emerging traditions of conceptual art and experimental music in the early 1960s. His Event scores, brief verbal scores that comprised lists of terms or open-ended instructions, provided a signature model for indeterminate composition and were ‘used extensively by virtually every Fluxus artist’. This article revisits Brecht’s early writings and research to argue that, while Event scores were adopted within Fluxus performance, they were intended as much more than performance devices. Specifically, Brecht conceived of his works as ‘structures of experience’ that, by revealing the underlying connections between chanced forms, could enable a kind of enlightenment rooted within an experience of a ‘unified reality’.

Advanced glycation: an important pathological event in diabetic and age related ocular disease

The formation of advanced glycation end products (AGEs) is a key pathophysiological event with links to a range of important human diseases. It is now clear that AGEs may act as mediators, not only of diabetic complications(1 2) but also of widespread age related pathology such as Alzheimer's disease,(3) decreased skin elasticity,(4) (5) male erectile dysfunction,(6) (7) pulmonary fibrosis,(8) and atherosclerosis.(9 10) Since many cells and tissues of the eye are profoundly influenced by both diabetes and ageing, it is fitting that advanced glycation is now receiving considerable attention as a possible modulator in important visual disorders. An increasing number of reports confirm widespread AGE accumulation at sites of known ocular pathology and demonstrate how these products mediate crosslinking of long lived molecules in the eye. Such studies also underscore the putative pathophysiological role of advanced glycation in ocular cell dysfunction in vitro and in vivo.

RUNX3 inactivation by frequent promoter hypermethylation and protein mislocalization constitute an early event in breast cancer progression

Background We had previously established that inactivation of RUNX3 occurs by frequent promoter hypermethylation and protein mislocalization in invasive ductal carcinomas (IDC) of breast. Here, we hypothesize that inactivation of RUNX3 occurring in ductal carcinoma in situ (DCIS) represent early event in breast carcinogenesis. Methods The study cohort of 40 patients included 17 pure DCIS cases and 23 cases of DCIS with associated IDC (DCIS-IDC). The DCIS and IDC components of mixed cases were manually microdissected to permit separate evaluation. All the 63 samples including 17 pure DCIS, 23 samples each of DCIS and IDC of DCIS-IDC cases were analyzed for RUNX3 protein expression using R3-6E9 monoclonal antibody as well as promoter methylation status by methylation specific PCR. Results Compared to matched normal breast samples (4 of 40, 10%), DCIS (35 of 40, 88%) and IDC (21 of 23, 91%) exhibited significant RUNX3 inactivation (P

Threshold In School – As Event And Place For The Autism Spectrum Disorder Pupil

As architects and designers we have a responsibility to provide an inclusive built environment. For the Autistic Spectrum Disorder (ASD) sufferer however, the built environment can be a frightening and confusing place, difficult to negotiate and tolerate. The challenge of integrating more fully into society is denied by an alienating built environment. This barrier can be magnified for ASD pupils in a poorly designed school, where their environment can further distance them from learning. Instead, if more at ease in their surroundings, in an ASD friendly environment, the ASD pupil stands a greater chance of doing better.

Whilst researchers have looked at the classroomenvironment, the transition of classroom to corridor andbeyond has so far been largely ignored. However, theneed for a well-considered threshold between class andcorridor needs to be considered. In this regard, threshold is much more than a doorway, but instead an event that demands a carefully considered place. The following paper firstly outlines why threshold as place andevent for the ASD pupil should be given consideration. It then goes onto highlight, through case studies in anIrish context, the opportunities for aiding the ASD pupil integrating in a mainstream school environment throughsensitive use of threshold. Finally it highlights inconclusion, some of the benefits for an enriched school environment for all pupils, if considering threshold as design generator.The objective is straightforward. By increasing awareness of the relationship between the ASD child and the built environment it will hopefully facilitate greater inclusion of the ASD pupil into mainstream education and society at large.

N1, P2 and T-complex of the auditory brain event-related potentials to tones with varying rise times in adults with and without dyslexia

Dyslexia is a learning difficulty affecting the acquisition of fluent reading and spelling skills due to poor phonological processing. Underlying deficits in processing sound rise time have also been found in children and adults with dyslexia. However, the neural basis for these deficits is unknown. In the present study event-related potentials were used to index neural processing and examine the effect of rise time manipulation on the obligatory N1. T-complex and P2 responses in English speaking adults with and without dyslexia. The Tb wave of the T-complex showed differences between groups, with the amplitudes for Tb becoming less negative with increased rise time for the participants with dyslexia only. Frontocentral N1 and P2 did not show group effects. Enhanced Tb amplitude that is modulated by rise time could indicate altered neural networks at the lateral surface of the superior temporal gyrus in adults with dyslexia. (C) 2011 Elsevier B.V. All rights reserved.

An Affordance Based Approach to Decision Making in Sport: Discussing a Novel Methodological Framework

Decision making is a fundamental clement of any sport, particularly open, fast, dynamic team sports such as football, basketball and rugby. At the elite level, athletes appear to consistently make good decisions in situations that are highly temporally constrained. To further understand how this is done has been the aim of researchers within the perception-action field for several decades. The purpose of this article is to present novel contributions, both theoretical and methodological, that are pushing the boundaries of this area of research. The theoretical framework (Ecological psychology) within which the work is posited will be described, followed by a description of Virtual Reality (VR) technology and how it relates to the theoretical aims. Finally, an applied example will be summarised in order to demonstrate how the theoretical approach and the methodological approach come together in practice.