Background: Duchenne muscular dystrophy (DMD) is caused by the loss of dystrophin. Severe and ultimately lethal, DMD progresses relatively slowly in that patients become wheelchair bound only around age twelve with a survival expectancy reaching the third decade of life. Methods: The mildly-affected mdx mouse model of DMD, and transgenic DysDMTB-mdx and Fiona-mdx mice expressing dystrophin or utrophin, respectively, were exposed to either mild (scruffing) or severe (subordination stress) stress paradigms and profiled for their behavioral and physiological responses. A subgroup of mdx mice exposed to subordination stress were pretreated with the beta-blocker metoprolol. Findings: Subordination stress caused lethality in »30% of mdx mice within 24 h and »70% lethality within 48 h, which was not rescued by metoprolol. Lethality was associated with heart damage, waddling gait and hypo-locomotion, as well as marked up-regulation of the hypothalamus-pituitary-adrenocortical axis. A novel cardiovascular phenotype emerged in mdx mice, in that scruffing caused a transient drop in arterial pressure, while subordination stress caused severe and sustained hypotension with concurrent tachycardia. Transgenic expression of dystrophin or utrophin in skeletal muscle protected mdx mice from scruffing and social stress-induced responses including mortality. Interpretation: We have identified a robust new stress phenotype in the otherwise mildly affected mdx mouse that suggests relatively benign handling may impact the outcome of behavioural experiments, but which should also expedite the knowledge-based therapy development for DMD.

This paper presents details of instrumental development to extend synchrotron X-ray microtomography techniques to in situ studies under static compression (high pressure), shear stress or the both conditions at simultaneous high temperatures. To achieve this, a new rotating tomography Paris-Edinburgh cell has been developed. This ultra-compact portable device easily and successfully adapted to various multi-modal synchrotron experimental set-up at ESRF, SOLEIL and DIAMOND is explained in detail. An in-depth description of proof of concept first experiments performed on a high resolution imaging beamline is then given, which illustrate the efficiency of the set-up and the data quality that can be obtained. ARTICLE HISTORY

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Core formation has left a lasting geochemical signature on the Earth. In order to constrain the composition of the Earth we must fully understand the processes by which newly formed Earth, and the bodies which accreted to it, differentiated. Percolation of iron-rich melt through solid silicate has been invoked as a mechanism for differentiation and core formation in terrestrial bodies in the early solar system. However, to date the contribution of percolation to core formation cannot be assessed due to the absence of data on Fe-rich melt migration velocities. Here we use a novel experimental design to investigate textural changes in an analog system, Au melt in polycrystalline h-BN, at 3 GPa, relevant to core formation in the early solar system. Using a combination of high resolution, in-situ X-ray tomography and fast 2-D radiographic imaging, we obtain the first direct data on melt migration velocities at high PT. Melt migration is highly variable and episodic, driven by variations in differential pressure during melt migration and matrix compaction. Smaller scale melt processes, representing migration of melt along pre-existing melt networks, give comparatively fast velocities of 0.6-60 µms −1. Ex-situ experiments are used to compare melt networks in analog systems to Fe-rich melt in silicates. Two competing processes for melt migration are percolation of melt along grain boundaries, and hydraulic fracturing induced by melt injection. Typically, both processes are noted in experimental and natural systems, although the relative importance of each mechanism is variable. Using a simple model for melt flow through a porous media, migration velocities determined here account for full differentiation of Earth-sized bodies within 10 1-10 3 Myr, for submicron diameter melt bands, or within a few Myr or micron-sized melt bands. This is consistent with rapid timescales inferred from geochemistry for core formation in planetesimals, implying that percolation may have had an important contribution to core differentiation in the Earth.

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