Induction of p38, tumour necrosis factor-α and RANTES by mechanical stretching of keratinocytes expressing mutant keratin 10R156H

Epidermolytic hyperkeratosis (bullous congenital ichthyosiform erythroderma), characterized by ichthyotic, rippled hyperkeratosis, erythroderma and skin blistering, is a rare autosomal dominant disease caused by mutations in keratin 1 or keratin 10 (K10) genes. A severe phenotype is caused by a missense mutation in a highly conserved arginine residue at position 156 (R156) in K10.

Stochastic amplitude-modulated stretching of Rabbit flexor digitorum profundus tendons reduces stiffness compared to Cyclic Loading but does not affect Tenocyte Metabolism

Background It has been demonstrated that frequency modulation of loading influences cellular response and metabolism in 3D tissues such as cartilage, bone and intervertebral disc. However, the mechano-sensitivity of cells in linear tissues such as tendons or ligaments might be more sensitive to changes in strain amplitude than frequency. Here, we hypothesized that tenocytes in situ are mechano-responsive to random amplitude modulation of strain. Methods We compared stochastic amplitude-modulated versus sinusoidal cyclic stretching. Rabbit tendon were kept in tissue-culture medium for twelve days and were loaded for 1h/day for six of the total twelve culture days. The tendons were randomly subjected to one of three different loading regimes: i) stochastic (2 – 7% random strain amplitudes), ii) cyclic_RMS (2–4.42% strain) and iii) cyclic_high (2 - 7% strain), all at 1 Hz and for 3,600 cycles, and one unloaded control. Results At the end of the culture period, the stiffness of the “stochastic” group was significantly lower than that of the cyclic_RMS and cyclic_high groups (both, p < 0.0001). Gene expression of eleven anabolic, catabolic and inflammatory genes revealed no significant differences between the loading groups. Conclusions We conclude that, despite an equivalent metabolic response, stochastically stretched tendons suffer most likely from increased mechanical microdamage, relative to cyclically loaded ones, which is relevant for tendon regeneration therapies in clinical practice.

Magmatic–hydrothermal molybdenum isotope fractionation and its relevance to the igneous crustal signature

We analysed the Mo isotope composition of a comprehensive series of molybdenite samples from the porphyry- type Questa deposit (NM, USA), as well as one rhyolite and one granite sample, directly associated with the Mo mineralization. The δ98Mo of the molybdenites ranges between −0.48‰ and +0.40‰, with a median at −0.05‰. The median Mo isotope composition increases from early magmatic (−0.29‰) to hydrothermal (−0.05‰) breccia mineralization (median bulk breccia = −0.17‰) to late stockwork veining (+0.22‰). Moreover, variations of up to 0.34‰ are found between different molybdenite crystals within an individual hand specimen. The rhyolite sample with 0.12 μg g−1 Mo has δ98Mo = −0.57‰ and is lighter than all molybde- nites from the Questa deposit, interpreted to represent the igneous leftover after aqueous ore fluid exsolution. We recognize three Mo isotope fractionation processes that occur between about 700 and 350 °C, affecting the Mo iso- tope composition of magmatic–hydrothermal molybdenites. Δ1Mo: Minerals preferentially incorporate light Mo isotopes during progressive fractional crystallization in subvolcanic magma reservoirs, leaving behind a melt enriched in heavy Mo isotopes. Δ2Mo: Magmatic–hydrothermal fluids preferentially incorporate heavy Mo iso- topes upon fluid exsolution. Δ3Mo: Light Mo isotopes get preferentially incorporated in molybdenite during crys- tallization from an aqueous fluid, leaving behind a hydrothermal fluid that gets heavier with progressive molybdenite crystallization. The sum of all three fractionation processes produces molybdenites that record heavier δ98Mo compositions than their source magmas. This implies that the mean δ98Mo of molybdenites published so far (~0.4‰) likely represents a maximum value for the Mo isotope composition of Phanerozoic igneous upper crust.

Seismic anisotropy in the Morcles nappe shear zone: Implications for seismic imaging of crustal scale shear zones

Microstructures and textures of calcite mylonites from the Morcles nappe large-scale shear zone in southwestern Switzerland develop principally as a function of 1) extrinsic physical parameters including temperature, stress, strain, strain rate and 2) intrinsic parameters, such as mineral composition. We collected rock samples at a single location from this shear zone, on which laboratory ultrasonic velocities, texture and microstructures were investigated and quantified. The samples had different concentration of secondary mineral phases (< 5 up to 40 vol.%). Measured seismic P wave anisotropy ranges from 6.5% for polyphase mylonites (~ 40 vol.%) to 18.4% in mylonites with < 5 vol.% secondary phases. Texture strength of calcite is the main factor governing the seismic P wave anisotropy. Measured S wave splitting is generally highest in the foliation plane, but its origin is more difficult to explain solely by calcite texture. Additional texture measurements were made on calcite mylonites with low concentration of secondary phases (≤ 10 vol.%) along the metamorphic gradient of the shear zone (15 km distance). A systematic increase in texture strength is observed moving from the frontal part of the shear zone (anchimetamorphism; 280 °C) to the higher temperature, basal part (greenschist facies; 350–400 °C). Calculated P wave velocities become increasingly anisotropic towards the high-strain part of the nappe, from an average of 5.8% in the frontal part to 13.2% in the root of the basal part. Secondary phases raise an additional complexity, and may act either to increase or decrease seismic anisotropy of shear zone mylonites. In light of our findings we reinterpret the origin of some seismically reflective layers in the Grône–Zweisimmen line in southwestern Switzerland (PNR20 Swiss National Research Program). We hypothesize that reflections originate in part from the lateral variation in textural and microstructural arrangement of calcite mylonites in shear zones.

Upper crustal deformation in continent-continent collision: A case study from the Bernard nappe complex (Valais, Switzerland)

The Penninic nappes in the Swiss Alps formed during continental collision between the Adriatic and European plates in Cenozoic times. Although intensely studied, the finite geometry of the basement-bearing Penninic nappes in western Switzerland has remained a matter of debate for decades (e.g., “Siviez-Mischabel dilemma”) and the paleogeographic origin of various nappes has been disputed. Here, we present new structural data for the central part of the Penninic Bernard nappe complex, which contains pre-Permian basement and Permo-Mesozoic metasedimentary units. Our lithological and structural observations indicate that the discrepancy between the different structural models proposed for the Bernard nappe complex can be explained by a lateral discontinuity. In the west, the presence of a Permian graben caused complex isoclinal folding, whereas in the east, the absence of such a graben resulted mainly in imbricate thrusting. The overall geometry of the Bernard nappe complex is the result of three main deformation phases: (1) detachment of Mesozoic cover sediments along Triassic evaporites (Evolène phase) during the early stages of collision, (2) Eocene top-to-the-N(NW) nappe stacking (Anniviers phase), and (3) subsequent backfolding and backshearing (Mischabel phase). The southward localized backshearing is key to understand the structural position and paleogeographic origin of units, such as the Frilihorn and Cimes Blanches “nappes” and the Antrona ophiolites. Based on these observations, we present a new tectonic model for the entire Penninic region of western Switzerland and discuss this model in terms of continental collision zone processes.