Diverse roles of androgen receptor (AR) domains in AR-mediated signaling

Androgens control male sexual development and maintenance of the adult male phenotype. They have very divergent effects on their target organs like the reproductive organs, muscle, bone, brain and skin. This is explained in part by the fact that different cell types respond differently to androgen stimulus, even when all these responses are mediated by the same intracellular androgen receptor. To understand these tissue- and cell-specific readouts of androgens, we have to learn the many different steps in the transcription activation mechanisms of the androgen receptor (NR3C4). Like all nuclear receptors, the steroid receptors have a central DNA-binding domain connected to a ligand-binding domain by a hinge region. In addition, all steroid receptors have a relatively large amino-terminal domain. Despite the overall structural homology with other nuclear receptors, the androgen receptor has several specific characteristics which will be discussed here. This receptor can bind two types of androgen response elements (AREs): one type being similar to the classical GRE/PRE-type elements, the other type being the more divergent and more selective AREs. The hormone-binding domain has low intrinsic transactivation properties, a feature that correlates with the low affinity of this domain for the canonical LxxLL-bearing coactivators. For the androgen receptor, transcriptional activation involves the alternative recruitment of coactivators to different regions in the amino-terminal domain, as well as the hinge region. Finally, a very strong ligand-induced interaction between the amino-terminal domain and the ligand-binding domain of the androgen receptor seems to be involved in many aspects of its function as a transcription factor. This review describes the current knowledge on the structure-function relationships within the domains of the androgen receptor and tries to integrate the involvement of different domains, subdomains and motifs in the functioning of this receptor as a transcription factor with tissue- and cell-specific readouts

An awkward fishing expedition

We report the case of a patient, among a group of five, in a small outbreak of histamine fish poisoning (HFP). The epidemic character of the ailment led us to the correct diagnosis. In this case, the diagnosis was also associated with a Kounis syndrome (KS). Literature concerning this subject is reviewed, reporting recent physiopathological data

Building a Small Cinema: Resisting Neoliberal Colonization in Liverpool

In its stated aim of “creating cinemas not supermarkets,” the Small Cinema project voiced its alterity to the recent redevelopment of Liverpool’s city center and those of other former industrial cities throughout the Midlands and the north of the UK. These regeneration projects addressed the problem of a shrinking manufacturing base by replacing them with service industries, a move which has entailed the privatization of vast tracts of public space. Conversely, the building, functioning, and general praxis of the Small Cinema project suggests a mode of practice that more accurately fits within the paradigm of a collaborative commons than a capitalist marketplace. The project’s exemption from market criteria grants it the freedom to pursue public over private goods, thereby constituting a point of resistance to the ongoing neoliberalization of the city and changes to government policy that make it increasingly difficult for non-profit projects to exist. Historically speaking, cinemas have been accessible to the working class in a way that other artistic media have not. However, while the history of film as a tool for political subversion is well documented, less attention has been paid to the physical construction of independent cinematic space, its programming/running, and its potential as a node of resistance to neoliberal colonization. This paper uses the case study of the Small Cinema project in Liverpool as a means by which to understand how cinematic spaces can counteract the effects of policies that continue to have such a detrimental impact on the arts and education, as well as social health and well-being