Identification of exosomal muscle-specific miRNAs in serum of myotonic dystrophy patients relating to muscle disease progress

Myotonic dystrophy type 1 (DM1) is the most common form of adult-onset muscular dystrophy, which is characterised by progressive muscle wasting and the discovery of reliable blood-based biomarkers could be useful for the disease progress monitoring. There have been some reports showing that the presence of specific miRNAs in blood correlates with DM1. In one of these, our group identified four muscle-specific miRNAs, miR-1, miR-133a, miR-133b and miR-206, which correlated with the progression of muscle wasting observed in DM1 patients. The levels of the four muscle-specific miRNAs were elevated in the serum of DM1 patients compared to healthy participants and were also elevated in the serum of progressive muscle wasting DM1 patients compared to disease-stable DM1 patients. The aim of this work was to characterise the ontology of these four muscle-specific miRNAs in the blood circulation of DM1 patients. Here we show that the four muscle-specific miRNAs are encapsulated within exosomes isolated from DM1 patients. Our results show for the first time, the presence of miRNAs encapsulated within exosomes in blood circulation of DM1 patients. More interestingly, the levels of the four exosomal muscle-specific miRNAs are associated with the progression of muscle wasting in DM1 patients. We propose that exosomal muscle-specific miRNAs may be useful molecular biomarkers for monitoring the progress of muscle wasting in DM1 patients. There has been a growing interest regarding the clinical applications of exosomes and their role in prognosis and therapy of various diseases and the above results contribute towards this way

Identification of exosomal muscle-specific miRNAs in serum of myotonic dystrophy patients relating to muscle disease progress

Myotonic dystrophy type 1 (DM1) is the most common form of adult-onset muscular dystrophy, which is characterised by progressive muscle wasting and the discovery of reliable blood-based biomarkers could be useful for the disease progress monitoring. There have been some reports showing that the presence of specific miRNAs in blood correlates with DM1. In one of these, our group identified four muscle-specific miRNAs, miR-1, miR-133a, miR-133b and miR-206, which correlated with the progression of muscle wasting observed in DM1 patients. The levels of the four muscle-specific miRNAs were elevated in the serum of DM1 patients compared to healthy participants and were also elevated in the serum of progressive muscle wasting DM1 patients compared to disease-stable DM1 patients. The aim of this work was to characterise the ontology of these four muscle-specific miRNAs in the blood circulation of DM1 patients. Here we show that the four muscle-specific miRNAs are encapsulated within exosomes isolated from DM1 patients. Our results show for the first time, the presence of miRNAs encapsulated within exosomes in blood circulation of DM1 patients. More interestingly, the levels of the four exosomal muscle-specific miRNAs are associated with the progression of muscle wasting in DM1 patients. We propose that exosomal muscle-specific miRNAs may be useful molecular biomarkers for monitoring the progress of muscle wasting in DM1 patients. There has been a growing interest regarding the clinical applications of exosomes and their role in prognosis and therapy of various diseases and the above results contribute towards this way

Syn- to post-orogenic exhumation of metamorphic nappes: Structure and thermobarometry of the western Attic-Cycladic metamorphic complex (Lavrion, Greece)

International audienceThe Lavrion peninsula is located along the western boundary of the Attic-Cycladic metamorphic complex in the internal zone of the Hellenic orogenic belt. The nappe stack is well exposed and made, from top to bottom, of (i) a non-metamorphic upper unit composed of an ophiolitic melange, (ii) a middle unit mainly composed of the Lavrion schists in blueschist facies, (iii) and a basal unit mainly composed of the Kamariza schists affected by pervasive retrogression of the blueschist facies metamorphism in greenschist facies. The middle unit is characterized by a relatively steep-dipping foliation associated with isoclinal folds of weakly organized axial orientation. This foliation is transposed into a shallow-dipping foliation bearing a N-S trending lineation. The degree of transposition increases with structural depth and is particularly marked at the transition from the middle to the basal unit across a low-angle mylonitic to cataclastic detachment. The blueschist facies foliation of the Lavrion schists (middle unit) is underlined by high pressure phengite intergrown with chlorite. The Kamariza schists (basal unit) contains relics of the blueschist mineral paragenesis but is dominated by intermediate pressure phengite also intergrown with chlorite and locally with biotite. Electron probe micro-analyzer chemical mapping combined with inverse thermodynamic modeling (local multi-equilibrium) reveals distinct pressure–temperature conditions of crystallization of phengite and chlorite assemblages as a function of their structural, microstructural and microtextural positions. The middle unit is characterized by two metamorphic conditions grading from high pressure (M1, 9–13 kbar) to lower pressure (M2, 6–9 kbar) at a constant temperature of ca. 315 °C. The basal unit has preserved a first set of HP/LT conditions (M1–2, 8–11 kbar, 300 °C) partially to totally transposed-retrogressed into a lower pressure mineral assemblage (M3, 5–8.5 kbar) associated with a slight but significant increase in temperature (∼350 °C)