A High Throughput Screen Identifies Chemical Modulators of the Laminin-Induced Clustering of Dystroglycan and Aquaporin-4 in Primary Astrocytes

Background: Aquaporin-4 (AQP4) constitutes the principal water channel in the brain and is clusteredat the perivascular astrocyte endfeet. This specific distribution of AQP4 plays a major role in maintaining water homeostasis in the brain. A growing body of evidence points to a role ofthe dystroglycan complex and its interaction with perivascular laminin in the clusteringof AQP4 atperivascular astrocyte endfeet. Indeed, mice lacking components of this complex or in which laminindystroglycan interaction is disrupted show a delayed onset of brain edema due to a redistribution of AQP4 away from astrocyte endfeet. It is therefore important to identify inhibitory drugs of laminin-dependent AQP4 clustering which may prevent or reduce brain edema. Methodolgy/Principal Findings: In the present study we used primary rat astrocyte cultures toscreen a library of.3,500 chemicals and identified 6 drugs that inhibit the laminin-induced clustering of dystroglycan and AQP4. Detailed analysis of the inhibitory drug, chloranil, revealed that its inhibition of the clustering is due to the metalloproteinase-2-mediated ß-dystroglycan shedding and subsequent loss of laminin interaction with dystroglycan. Furthermore, chemical variants of chloranil induced a similar effect on ß-dystroglycan and this was prevented by the antioxidant N-acetylcysteine. Conclusion/Significance: These findings reveal the mechanism of action of chloranil in preventing the laminin-induced clustering of dystroglycan and AQP4 and validate the use of high-throughput screening as a tool to identify drugs tha

the placental body in 4D : everyday practices of non-diagnostic sonography

Feminist scholars have long argued that the pregnant body is erased – both literally and discursively – from mainstream foetal representations. Janemaree Maher argues that the placenta, as point of distinction and connection between pregnant women and foetuses, has the radical potential to refigure understandings of pregnant embodiment and subjectivity, and offer ‘a way to begin thinking through the impasse of pregnant representation’. Drawing on Maher's notion of the ‘placental body’, this article will examine the place of the placenta in the practice of non-diagnostic 4D ultrasound scanning. The analysis seeks to connect Maher's theoretical perspective, and the rich feminist literature around foetal imaging, with observational data from my study of 4D scans. I will argue that the capacity of 3- and 4D sonography to image the placenta and umbilical cord in a way that is newly intelligible to lay viewers might present an opportunity for thinking differently about the interconnections – material and social – between pregnant women and foetuses and to relocate women as the subjects of their pregnancies