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排序方式: 共有4916条查询结果,搜索用时 62 毫秒
1.
Jens Mller Anne Busch Christian Berens Helmut Hotzel Andreas Burkovski 《International journal of molecular sciences》2021,22(7)
Corynebacterium silvaticum is a newly identified animal pathogen of forest animals such as roe deer and wild boars. The species is closely related to the emerging human pathogen Corynebacterium ulcerans and the widely distributed animal pathogen Corynebacterium pseudotuberculosis. In this study, Corynebacterium silvaticum strain W25 was characterized with respect to its interaction with human cell lines. Microscopy, measurement of transepithelial electric resistance and cytotoxicity assays revealed detrimental effects of C. silvaticum to different human epithelial cell lines and to an invertebrate animal model, Galleria mellonella larvae, comparable to diphtheria toxin-secreting C. ulcerans. Furthermore, the results obtained may indicate a considerable zoonotic potential of this newly identified species. 相似文献
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Dr. Blijke S. Kroezen Gabriele Conti Benedetta Girardi Dr. Jonathan Cramer Dr. Xiaohua Jiang Dr. Said Rabbani Jennifer Müller Maja Kokot Enrico Luisoni Prof. Daniel Ricklin Dr. Oliver Schwardt Prof. Beat Ernst 《ChemMedChem》2020,15(18):1706-1719
Siglecs are members of the immunoglobulin gene family containing sialic acid binding N-terminal domains. Among them, Siglec-8 is expressed on various cell types of the immune system such as eosinophils, mast cells and weakly on basophils. Cross-linking of Siglec-8 with monoclonal antibodies triggers apoptosis in eosinophils and inhibits degranulation of mast cells, making Siglec-8 a promising target for the treatment of eosinophil- and mast cell-associated diseases such as asthma. The tetrasaccharide 6’-sulfo-sialyl Lewisx has been identified as a specific Siglec-8 ligand in glycan array screening. Here, we describe an extended study enlightening the pharmacophores of 6’-sulfo-sialyl Lewisx and the successful development of a high-affinity mimetic. Retaining the neuraminic acid core, the introduction of a carbocyclic mimetic of the Gal moiety and a sulfonamide substituent in the 9-position gave a 20-fold improved binding affinity. Finally, the residence time, which usually is the Achilles tendon of carbohydrate/lectin interactions, could be improved. 相似文献
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Jasmin Kuhn Philipp M. Klein Nader Al Danaf Joel Z. Nordin Sren Reinhard Dominik M. Loy Miriam Hhn Samir El Andaloussi Don C. Lamb Ernst Wagner Yoshitsugu Aoki Taavi Lehto Ulrich Lchelt 《Advanced functional materials》2019,29(48)
Phosphorodiamidate morpholino oligomers (PMOs) are oligonucleotide analogs that can be used for therapeutic modulation of pre‐mRNA splicing. Similar to other classes of nucleic acid‐based therapeutics, PMOs require delivery systems for efficient transport to the intracellular target sites. Here, artificial peptides based on the oligo(ethylenamino) acid succinyl‐tetraethylenpentamine (Stp), hydrophobic modifications, and an azide group are presented, which are used for strain‐promoted azide‐alkyne cycloaddition conjugation with splice‐switching PMOs. By systematically varying the lead structure and formulation, it is determined that the type of contained fatty acid and supramolecular assembly have a critical impact on the delivery efficacy. A compound containing linolenic acid with three cis double bonds exhibits the highest splice‐switching activity and significantly increases functional protein expression in pLuc/705 reporter cells in vitro and after local administration in vivo. Structural and mechanistic studies reveal that the lipopeptide PMO conjugates form nanoparticles, which accelerate cellular uptake and that the content of unsaturated fatty acids enhances endosomal escape. In an in vitro Duchenne muscular dystrophy exon skipping model using H2K‐mdx52 dystrophic skeletal myotubes, the highly potent PMO conjugates mediate significant splice‐switching at very low nanomolar concentrations. The presented aminoethylene‐lipopeptides are thus a promising platform for the generation of PMO‐therapeutics with a favorable activity/toxicity profile. 相似文献
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BACKGROUND & AIMS: The molecular mechanisms underlying pancreatitis are largely unknown. The goal of this study was to identify an early genetic event that correlated with pancreatitis. METHODS: Differential display of messenger RNAs (mRNAs) was conducted on normal pancreas vs. those of animals with secretagogue-induced pancreatitis. Northern blots from normal animals and animals with experimental acute pancreatitis were probed with cloned complementary DNAs for chemokines. Pancreatitis was induced with cerulein and by retrograde injection of bile salts. Immunocytochemistry was used to identify the source of chemokine expression. Pyrrolidine dithiocarbamate was tested for effects on chemokine expression and pancreatitis. RESULTS: A differentially amplified band was consistently observed early after cerulein hyperstimulation. This band was identified as a portion of the mob-1 gene, an alpha-chemokine. Northern analysis indicated that mRNAs for mob-1 and another chemokine, mcp-1, were induced after cerulein hyperstimulation in vivo. mob-1 mRNA was also induced by retrograde injection of bile salts and by cerulein in acinar cells in vitro. mob-1 protein was localized to exocrine cells in pancreata of diseased animals. Pyrrolidine dithiocarbamate inhibited both chemokine gene expression and early inflammatory characteristics of pancreatitis. CONCLUSIONS: Chemokines are induced in acinar cells by treatments that induce pancreatitis and may play an important role in the early stages of the disease. 相似文献
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This article describes a study of delamination growth along 0 °/0 °, 0 °/ 5 °, ± 5 °, and 0 °/90 ° interfaces sandwiched between unidirectional carbon fibre/epoxy composite material. Relationships between damage criticality, growth rate and acoustic emission activity for delamination growth have been studied and the transferability of results from laboratory coupons to composite structural elements has been examined. Two types of coupon tests, conventional delamination beams and rigidly loaded single edge notched strips, have been compared for different mode ratios. Comparative tests have been made on buckling-induced delamination in plates. A graphite crack gauge has been used to measure delamination length and growth rate, ranging from 0.05–2000 m/s. Damage growth was also followed using visual, ultrasonic C-scan, X-ray radiography, macro-video and acoustic emission measurements. Empirical evaluations of interlaminar toughness for delamination beams are made using the Irwin-Kies relation. Unstable growth is analysed using elasto-dynamic moving finite elements. Bucklinginduced delamination is analysed using plate/shell FE methods with growth/remeshing algorithms. 相似文献
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Prof. Dr.-Ing. Thorsten Spitta Dipl. Ing. Helmut Schmidpeter 《WIRTSCHAFTSINFORMATIK》2002,44(2):141-150
This paper analyses the characteristics of software houses as service providers. The tasks of internal IT-services are determined from these characteristics and a reporting system for the IT-controlling is outlined. The concept results from the analysis of one of the 25 largest German software houses. The paper concludes with a case study of the fiscal year 2000 IT-controlling report of the above-mentioned firm. 相似文献