Lamin-Related Congenital Muscular Dystrophy Alters Mechanical Signaling and Skeletal Muscle Growth

Laminopathies are a clinically heterogeneous group of disorders caused by mutations in the LMNA gene, which encodes the nuclear envelope proteins lamins A and C. The most frequent diseases associated with LMNA mutations are characterized by skeletal and cardiac involvement, and include autosomal dominant Emery–Dreifuss muscular dystrophy (EDMD), limb-girdle muscular dystrophy type 1B, and LMNA-related congenital muscular dystrophy (LMNA-CMD). Although the exact pathophysiological mechanisms responsible for LMNA-CMD are not yet understood, severe contracture and muscle atrophy suggest that mutations may impair skeletal muscle growth. Using human muscle stem cells (MuSCs) carrying LMNA-CMD mutations, we observe impaired myogenic fusion with disorganized cadherin/β catenin adhesion complexes. We show that skeletal muscle from Lmna-CMD mice is unable to hypertrophy in response to functional overload, due to defective fusion of activated MuSCs, defective protein synthesis and defective remodeling of the neuromuscular junction. Moreover, stretched myotubes and overloaded muscle fibers with LMNA-CMD mutations display aberrant mechanical regulation of the yes-associated protein (YAP). We also observe defects in MuSC activation and YAP signaling in muscle biopsies from LMNA-CMD patients. These phenotypes are not recapitulated in closely related but less severe EDMD models. In conclusion, combining studies in vitro, in vivo, and patient samples, we find that LMNA-CMD mutations interfere with mechanosignaling pathways in skeletal muscle, implicating A-type lamins in the regulation of skeletal muscle growth.     

Nondegradative additive manufacturing of medical grade copolyesters of high molecular weight and with varied elastic response

Although additive manufacturing through melt extrusion has become increasingly popular as a route to design scaffolds with complex geometries the technique if often limited by the reduction in molecular weight and the viscoelastic response when degradable aliphatic polyesters of high molecular weight are used. Here we use a melt extruder and fused filament fabrication printer to produce a reliable nondegradative route for scaffold fabrication of medical grade copolymers of L-lactide, poly(ε-caprolactone-co-L-lactide), and poly(L-lactide-co-trimethylene carbonate). We show that degradation is avoided using filament extrusion and fused filament fabrication if the process parameters are deliberately chosen based upon the rheological behavior, mechanical properties, and polymer composition. Structural, mechanical, and thermal properties were assessed throughout the process to obtain comprehension of the relationship between the rheological properties and the behavior of the medical grade copolymers in the extruder and printer. Scaffolds with a controlled architecture were achieved using high-molecular-weight polyesters exhibiting a large range in the elastic response causing negligible degradation of the polymers. © 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2020 , 137, 48550.     

Argon: Systematic Review on Neuro- and Organoprotective Properties of an “Inert” Gas

Argon belongs to the group of noble gases, which are regarded as chemically inert. Astonishingly some of these gases exert biological properties and during the last decades more and more reports demonstrated neuroprotective and organoprotective effects. Recent studies predominately use in vivo or in vitro models for ischemic pathologies to investigate the effect of argon treatment. Promising data has been published concerning pathologies like cerebral ischemia, traumatic brain injury and hypoxic ischemic encephalopathy. However, models applied and administration of the therapeutic gas vary. Here we provide a systematic review to summarize the available data on argon’s neuro- and organoprotective effects and discuss its possible mechanism of action. We aim to provide a summary to allow further studies with a more homogeneous setting to investigate possible clinical applications of argon.     

Ultranarrow Bandwidth Organic Photodiodes by Exchange Narrowing in Merocyanine H‐ and J‐Aggregate Excitonic Systems

Ultranarrowband organic photodiodes (OPDs) are demonstrated for thin film solid state materials composed of tightly packed dipolar merocyanine dyes. For these dyes the packing arrangement can be controlled by the bulkiness of the donor substituent, leading to either strong H‐ or strong J‐type exciton coupling in the interesting blue (H‐aggregate) and NIR (J‐aggregate) spectral ranges. Both bands are shown to arise from one single exciton band according to fluorescence measurements and are not just a mere consequence of different polymorphs within the same thin film. By fabrication of organic thin‐film transistors, these dyes are demonstrated to exhibit hole transport behavior in spin‐coated thin films. Moreover, when used as organic photodiodes in planar heterojunctions with C₆₀ fullerene, they show wavelength‐selective photocurrents in the solid state with maximum external quantum efficiencies of up to 11% and ultranarrow bandwidths down to 30 nm. Thereby, narrowing the linewidths of optoelectronic functional materials by exciton coupling provides a powerful approach to produce ultranarrowband organic photodiodes.     

Hydrogenation behavior on 30 nm vanadium thin films with two different adhesion conditions

The influence of a thin polycarbonate de-adhesion layer on the hydrogen concentration is studied on 30 nm vanadium films deposited on glass substrates, using electrochemical hydrogenography in an optical microscopy and scanning tunneling microscopy. It is shown that the optical reflection provides information about the de-adhesion morphology (buckles) while the optical transmission signal gives information about concentration and film thickness changes. Artificially patterned samples allow simultaneous studying adhered and de-adhered film parts, for similar mean concentrations. The optical data clearly show a different hydrogen behavior of the two parts. Data interpretation suggests higher local hydrogen content in the adhered film parts than for the detached films parts. Strong changes in the optical transmission of the adhered film parts can be attributed to strong morphological changes at the film surface. These changes are mainly attributed to grain sliding processes in the vanadium film.     

可持续理念的体现——杭州来福士中心

正UNStudio由Ben van Berkel和Caroline Bos创立,是一个国际性的建筑设计网络。拥有三个全方位服务的国际事务所,分别位于阿姆斯特丹、香港和上海。专于建筑、室内建筑、产品设计、城市发展和基础设施项目。地址:浙江省杭州市钱江新城富春路业主方:凯德集团建筑面积:392526m~2项目年份:2017醒目的裙楼之上坐落着两座流线型的高楼,从中可以饱览钱塘江和西湖的迷人风光。     

Discontinuous Precipitation and Phase Stability In Re- and Ru-Containing Nickel-Base Superalloys

The phase stability of nickel-base superalloys has been investigated using a new in-house-designed alloy series with stepwise increased additions of Re and Ru at otherwise fixed atomic fractions of alloying elements. Results presented in this study are focused on the lesser-known topologically closed packed (TCP) formation of columnar colonies or so-called discontinuous precipitation. A detailed investigation of these colonies allowed for identifying compositional changes during the growth process and for providing a three-dimensional (3-D) illustration of the TCP phases within these colonies. The results were used to compare the colony growth process with existing growth models. Furthermore, the influence of Re and Ru on the appearance of discontinuous precipitation has been investigated by means of colony width and the effect on creep properties. Larson-Miller plots are given to illustrate the creep strength of directionally solidified samples with and without TCP colonies compared with single crystalline samples free from TCP colonies.     

FEM simulation supported evaluation of a hydrogen grain boundary diffusion coefficient in MgH2

The diffusion coefficient data of hydrogen in the Magnesium-hydrogen system shows a large scatter, their trends extrapolations vary at room temperature between 10^?12 m²/s and 10^?29 m²/s. At room temperature the hydrogen diffusion coefficient in MgH₂ is, thus, uncertain by about 17 orders of magnitude. This may be partially attributed to grain boundaries contributing to the measured diffusion coefficient. In this paper we use finite-element (FEM) simulations to evaluate the influence of the grain boundary diffusion on the measured total diffusion depending on the difference of the grain boundary (D_GB) and volume (D_V) diffusion coefficients, as well as on the grain size. These results will be compared to Harrisson's analytical solutions. When the diffusion coefficients differ by more than D_V < 10^?3·D_GB, Harrison's diffusion regime C becomes the best way to describe the total diffusion. The results are used to re-interpret literature data on hydrogen diffusion in MgH₂ from this grain boundary contribution point of view. At 300 K, a hydrogen grain boundary diffusion coefficient ranging from D_GB = 10^?17 m²/s to D_GB = 10^?20 m²/s, depending on the individual type of sample in MgH₂, results from the data evaluation.