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排序方式: 共有473条查询结果,搜索用时 15 毫秒
461.
Frederik Braun Andreas Hentschel Albert Sickmann Theodore Marteau Swantje Hertel Fabian Frster Holger Prokisch Matias Wagner Saskia Wortmann Adela Della Marina Heike Klbel Andreas Roos Ulrike Schara-Schmidt 《International journal of molecular sciences》2021,22(15)
Mutations in the SPATA5 gene are associated with epilepsy, hearing loss and mental retardation syndrome (EHLMRS). While SPATA5 is ubiquitously expressed and is attributed a role within mitochondrial morphogenesis during spermatogenesis, there is only limited knowledge about the associated muscular and molecular pathology. This study reports on a comprehensive workup of muscular pathology, including proteomic profiling and microscopic studies, performed on an 8-year-old girl with typical clinical presentation of EHLMRS, where exome analysis revealed two clinically relevant, compound-heterozygous variants in SPATA5. Proteomic profiling of a quadriceps biopsy showed the dysregulation of 82 proteins, out of which 15 were localized in the mitochondrion, while 19 were associated with diseases presenting with phenotypical overlap to EHLMRS. Histological staining of our patient’s muscle biopsy hints towards mitochondrial pathology, while the identification of dysregulated proteins attested to the vulnerability of the cell beyond the mitochondria. Through our study we provide insights into the molecular etiology of EHLMRS and provide further evidence for a muscle pathology associated with SPATA5 deficiency, including a pathological histochemical pattern accompanied by dysregulated protein expression. 相似文献
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465.
Pahlow M Müller D Tesche M Eichler H Feingold G Eberhard WL Cheng YF 《Applied optics》2006,45(28):7429-7442
Simulation studies were carried out with regard to the feasibility of using combined observations from sunphotometer (SPM) and lidar for microphysical characterization of aerosol particles, i.e., the retrieval of effective radius, volume, and surface-area concentrations. It was shown that for single, homogeneous aerosol layers, the aerosol parameters can be retrieved with an average accuracy of 30% for a wide range of particle size distributions. Based on the simulations, an instrument combination consisting of a lidar that measures particle backscattering at 355 and 1574 nm, and a SPM that measures at three to four channels in the range from 340 to 1020 nm is a promising tool for aerosol characterization. The inversion algorithm has been tested for a set of experimental data. The comparison with the particle size distribution parameters, measured with in situ instrumentation at the lidar site, showed good agreement. 相似文献
466.
Chen Lyu Lili Wang Birgit Stadlbauer Alexander Buchner Heike Pohla 《International journal of molecular sciences》2022,23(24)
Emerging evidence from research or clinical studies reported that ABCG2 (ATP-binding cassette sub-family G member 2) interrelates with multidrug resistance (MDR) development in cancers. However, no comprehensive pan-cancer analysis is available at present. Therefore, we explore multiple databases, such as TCGA to investigate the potential therapeutic roles of ABCG2 across 33 different tumors. ABCG2 is expressed on a lower level in most cancers and shows a protective effect. For example, a lower expression level of ABCG2 was detrimental to the survival of adrenocortical carcinoma (TCGA-ACC), glioblastoma multiforme (GBM), and kidney renal clear cell carcinoma (KIRC) patients. Distinct associations exist between ABCG2 expression and stemness scores, microenvironmental scores, microsatellite instability (MSI), and tumor mutational burden (TMB) of tumor patients. We observed a significant positive correlation between the ABCG2 mutation site and prognosis in uterine corpus endometrial carcinoma (UCEC) patients. Moreover, transmembrane transporter activity and hormone biosynthetic-associated functions were found to be involved in the functionality of ABCG2 and its related genes. The cDNAs of cancer cell lines were collected to detect exon mutation sequences and to analyze ABCG2 mRNA expression. The mRNA expression level of ABCG2 showed a significant difference among spheres and drug-resistant cancer cell lines compared with their corresponding adherent cancer cell lines in six types of cancer. This pan-cancer study provides, for the first time, a comprehensive understanding of the multifunctionality of ABCG2 and unveils further details of the potential therapeutic role of ABCG2 in pan-cancer. 相似文献
467.
Dr. Simon J. A. Wiedemeyer Dr. Guojie Wu Dr. T. L. Phuong Pham Heike Lang-Henkel Benjamin Perez Urzua Prof. James C Whisstock Dr. Ruby H. P. Law Prof. Torsten Steinmetzer 《ChemMedChem》2023,18(6):e202200632
Two series of macrocyclic plasmin inhibitors with a C-terminal benzylamine group were synthesized. The substitution of the N-terminal phenylsulfonyl group of a previously described inhibitor provided two analogues with sub-nanomolar inhibition constants. Both compounds possess a high selectivity against all other tested trypsin-like serine proteases. Furthermore, a new approach was used to selectively introduce asymmetric linker segments. Two of these compounds inhibit plasmin with Ki values close to 2 nM. For the first time, four crystal structures of these macrocyclic inhibitors could be determined in complex with a Ser195Ala microplasmin mutant. The macrocyclic core segment of the inhibitors binds to the open active site of plasmin without any steric hindrance. This binding mode is incompatible with other trypsin-like serine proteases containing a sterically demanding 99-hairpin loop. The crystal structures obtained experimentally explain the excellent selectivity of this inhibitor type as previously hypothesized. 相似文献
468.
Ass. Prof. Tien Dinh Vu Associate Prof. Rangabhashiyam Selvasembian Dr.-Ing. Ivana Mutavdžin Dr.-Ing. Elena Horosanskaia Prof. Heike Lorenz Prof. Andreas Seidel-Morgenstern 《化学,工程师,技术》2023,95(11):1851-1857
The flavonoid rutin is present in significant amounts in the flower buds of Sophora japonica L. It offers numerous desired pharmacological effects. Under certain extraction conditions quercetin is found as a hydrolysis product which needs to be separated from rutin. This paper describes the application of liquid chromatography to solve this task. Based on the determination of adsorption equilibrium constants and column efficiencies, the productivity of the separation process is estimated, and scale-up considerations are presented. A comparison with alternatively directly crystallizing rutin from raw extracts is also reported. 相似文献
469.
Heike Lindauer Peter Czerney Ulrich-W. Grummt 《Advanced Synthesis \u0026amp; Catalysis》1995,337(1):216-221
A series of new acidochromic dyes absorbing in the NIR spectral region (up to 900 nm) has been synthesized with a systematic variation of the underlying nonsymmetric pyrylium trimethinium acridine structure. The dyes exhibit pKa-values between 5.7 and 6.7. Semiempirical MO-calculations were performed to elucidate the essentials of the chromophores. 相似文献
470.
Dr. Patrick Werner Dr. Patrick Schuenke Dr. Oxana Krylova Heike Nikolenko Prof. Dr. Matthias Taupitz Dr. Leif Schröder 《ChemMedChem》2022,17(13):e202100764
Glycosaminoglycans (GAGs) are highly negatively charged macromolecules with a large cation binding capacity, but their interaction potential with exogeneous Gd3+ ions is under-investigated. These might be released from chelates used as Gadolinium-based contrast agents (GBCAs) for clinical MR imaging due to transmetallation with endogenous cations like Zn2+. Recent studies have quantified how an endogenous GAG sequesters released Gd3+ ions and impacts the thermodynamic and kinetic stability of some GBCAs. In this study, we investigate and compare the chelation ability of two important GAGs (heparin and chondroitin sulfate), as well as the homopolysaccharides dextran and dextran sulfate that are used as models for alternative macromolecular chelators. Our combined approach of MRI-based relaxometry and isothermal titration calorimetry shows that the chelation process of Gd3+ into GAGs is not just a long-range electrostatic interaction as proposed for the Manning model, but presumably a site-specific binding. Furthermore, our results highlight the crucial role of sulfate groups in this process and indicate that the potential of a specific GAG to engage in this mechanism increases with its degree of sulfation. The transchelation of Gd3+ ions from GBCAs to sulfated GAGs should thus be considered as one possible explanation for the observed long-term deposition of Gd3+ in vivo and related observations of long-term signal enhancements on T1-weighted MR images. 相似文献