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排序方式: 共有345条查询结果,搜索用时 31 毫秒
1.
Daniel J. Owens Julien Messant Sophie Moog Mark Viggars Arnaud Ferry Kamel Mamchaoui Emmanuelle Lacne Norma Romro Astrid Brull Gisle Bonne Gillian Butler-Browne Catherine Coirault 《International journal of molecular sciences》2021,22(1)
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. 相似文献
2.
Astrid Ahlinder Tiziana Fuoco Álvaro Morales-López Mohammed A. Yassin Kamal Mustafa Anna Finne-Wistrand 《应用聚合物科学杂志》2020,137(15):48550
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. 相似文献
3.
One Question,Multiple Answers: Biochemical and Biophysical Screening Methods Retrieve Deviating Fragment Hit Lists 下载免费PDF全文
Dr. Johannes Schiebel Nedyalka Radeva Dr. Helene Köster Dr. Alexander Metz Timo Krotzky Dr. Maren Kuhnert Prof. Wibke E. Diederich Prof. Andreas Heine Dr. Lars Neumann Dr. Cedric Atmanene Dominique Roecklin Dr. Valérie Vivat‐Hannah Dr. Jean‐Paul Renaud Dr. Robert Meinecke Dr. Nina Schlinck Dr. Astrid Sitte Franziska Popp Dr. Markus Zeeb Prof. Gerhard Klebe 《ChemMedChem》2015,10(9):1511-1521
Fragment‐based lead discovery is gaining momentum in drug development. Typically, a hierarchical cascade of several screening techniques is consulted to identify fragment hits which are then analyzed by crystallography. Because crystal structures with bound fragments are essential for the subsequent hit‐to‐lead‐to‐drug optimization, the screening process should distinguish reliably between binders and non‐binders. We therefore investigated whether different screening methods would reveal similar collections of putative binders. First we used a biochemical assay to identify fragments that bind to endothiapepsin, a surrogate for disease‐relevant aspartic proteases. In a comprehensive screening approach, we then evaluated our 361‐entry library by using a reporter‐displacement assay, saturation‐transfer difference NMR, native mass spectrometry, thermophoresis, and a thermal shift assay. While the combined results of these screening methods retrieve 10 of the 11 crystal structures originally predicted by the biochemical assay, the mutual overlap of individual hit lists is surprisingly low, highlighting that each technique operates on different biophysical principles and conditions. 相似文献
4.
Dirk Oliver Schmidt Susanne Hoffmann‐Eifert Hehe Zhang Camilla La Torre Astrid Besmehn Michael Noyong Rainer Waser Ulrich Simon 《Small (Weinheim an der Bergstrasse, Germany)》2015,11(48):6444-6456
Resistively switching devices are considered promising for next‐generation nonvolatile random‐access memories. Today, such memories are fabricated by means of “top–down approaches” applying thin films sandwiched between nanoscaled electrodes. In contrast, this work presents a “bottom–up approach” disclosing for the first time the resistive switching (RS) of individual TiO2 nanoparticles (NPs). The NPs, which have sizes of 80 and 350 nm, respectively, are obtained by wet chemical synthesis and thermally treated under oxidizing or vacuum conditions for crystallization, respectively. These NPs are deposited on a Pt/Ir bottom electrode and individual NPs are electrically characterized by means of a nanomanipulator system in situ, in a scanning electron microscope. While amorphous NPs and calcined NPs reveal no switching hysteresis, a very interesting behavior is found for the vacuum‐annealed, crystalline TiO2–x NPs. These NPs reveal forming‐free RS behavior, dominantly complementary switching (CS) and, to a small degree, bipolar switching (BS) characteristics. In contrast, similarly vacuum‐annealed TiO2 thin films grown by atomic layer deposition show standard BS behavior under the same conditions. The interesting CS behavior of the TiO2–x NPs is attributed to the formation of a core–shell‐like structure by re‐oxidation of the reduced NPs as a unique feature. 相似文献
5.
6.
UNStudio Ben van Berkel Hannes Pfau Astrid Piber Jin Xing Hufton+Crow Seth Powers 《中国建筑装饰装修》2018,(4)
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。 相似文献
7.
Andreas Liess Alhama Arjona‐Esteban Astrid Kudzus Julius Albert Ana‐Maria Krause Aifeng Lv Matthias Stolte Klaus Meerholz Frank Würthner 《Advanced functional materials》2019,29(21)
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. 相似文献
8.
Anshu Tyagi Florian Döring Hans-Ulrich Krebs Astrid Pundt 《International Journal of Hydrogen Energy》2017,42(35):22575-22582
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. 相似文献
9.
Anke H?llig Anita Schug Astrid V. Fahlenkamp Rolf Rossaint Mark Coburn Argon Organo-Protective Network 《International journal of molecular sciences》2014,15(10):18175-18196
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. 相似文献
10.