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51.
Sara Heidl Isabella Ellinger Verena Niederberger Eva E. Waltl Renate Fuchs 《Protoplasma》2016,253(6):1557-1564
The airway epithelium is a central player in the defense against pathogens including efficient mucociliary clearance and secretion of immunoglobulins, mainly polymeric IgA, but also IgG. Pulmonary administration of therapeutic antibodies on one hand, and intranasal immunization on the other, are powerful tools to treat airway infections. In either case, the airway epithelium is the primary site of antibody transfer. In various epithelia, bi-polar transcytosis of IgG and IgG immune complexes is mediated by the human neonatal Fc receptor, FcRn, but FcRn expression in the nasal epithelium had not been demonstrated, so far. We prepared affinity-purified antibodies against FcRn α-chain and confirmed their specificity by Western blotting and immunofluorescence microscopy. These antibodies were used to study the localization of FcRn α-chain in fixed nasal tissue. We here demonstrate for the first time that ciliated epithelial cells, basal cells, gland cells, and endothelial cells in the underlying connective tissue express the receptor. A predominant basolateral steady state distribution of the receptor was observed in ciliated epithelial as well as in gland cells. Co-localization of FcRn α-chain with IgG or with early sorting endosomes (EEA1-positive) but not with late endosomes/lysosomes (LAMP-2-positive) in ciliated cells was observed. This is indicative for the presence of the receptor in the recycling/transcytotic pathway but not in compartments involved in lysosomal degradation supporting the role of FcRn in IgG transcytosis in the nasal epithelium. 相似文献
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Zeynep Eroglu Sheri L. Holmen Qing Chen Nikhil I. Khushalani Ravi Amaravadi Reena Thomas Kamran A. Ahmed Hussein Tawbi Sunandana Chandra Joseph Markowitz Inna Smalley James K. C. Liu Yian Ann Chen Yana G. Najjar Florian A. Karreth Daniel Abate‐Daga Isabella C. Glitza Jeffrey A. Sosman Vernon K. Sondak Marcus Bosenberg Meenhard Herlyn Michael B. Atkins Harriet Kluger Kim Margolin Peter A. Forsyth Michael A. Davies Keiran S. M. Smalley 《Pigment cell & melanoma research》2019,32(3):458-469
In February 2018, the Melanoma Research Foundation and the Moffitt Cancer Center hosted the Second Summit on Melanoma Central Nervous System (CNS) Metastases in Tampa, Florida. In this white paper, we outline the current status of basic science, translational, and clinical research into melanoma brain metastasis development and therapeutic management. We further outline the important challenges that remain for the field and the critical barriers that need to be overcome for continued progress to be made in this clinically difficult area. 相似文献
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Ines Pires da Silva Isabella C. Glitza Lauren E. Haydu Romany Johnpulle Patricia D. Banks George D. Grass Simone M. A. Goldinger Jessica L. Smith Ashlyn S. Everett Peter Koelblinger Rachel Roberts‐Thomson Michael Millward Victoria G. Atkinson Alexander Guminski Rony Kapoor Robert M. Conry Matteo S. Carlino Wei Wang Mark J. Shackleton Zeynep Eroglu Serigne Lo Angela M. Hong Georgina V. Long Douglas B. Johnson Alexander M. Menzies 《Pigment cell & melanoma research》2019,32(4):553-563
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The influence of amino acids with contrasting conformational tendencies on the stereochemistry of oligopeptides has been investigated using an octapeptide Boc-Leu-Aib-Val-Gly-Gly-Leu-Aib-Val-OMe, which contains two helix-promoting Aib residues and a central helix-destabilizing Gly-Gly segment. Single crystal x-ray diffraction studies reveal that a 3 10-helix is formed up to the penultimate Aib residue, at which point there is a helix reversal in the backbone, reminiscent of a C-terminal 6 → I hydrogen bond. The curious feature in the crystal is the solvation of the possible 6 → 1 bond by a CH3OH molecule, where the OH is inserted between O(3) and N(8) and participates in hydrogen bonds with both. The cell parameters are as follows: space group P212121, a = 10.649(4) Å, b = 15.694(5) Å, c = 30.181(8) Å, R = 6.7% for 3427 data (| F0| > 3σF) observed to 0.9 Å. Nuclear magnetic resonance studies in CDCl3 using NH group solvent accessibility and nuclear Overhauser effects as probes are consistent with a 3 10-helical conformation. In contrast, in (CD3)2SO, unfolding of the central segment results in a multiple β-turn structure, with β-turn conformations populated at residues 1–2, 3–4, and 6–7. CD studies in methanol-2,2,2-trifluoroethanol (TFE) mixtures also provide evidence for a solvent-dependent structural transition. Helical conformations are populated in TFE, while type II β-turn structures are favored in methanol. © 1996 John Wiley & Sons, Inc. 相似文献
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Diana Szliov Jerneja tor Isabella Thiel Marcus Weinguny Michael Hanscho Gabriele Lhota Nicole Borth Jürgen Zanghellini David E. Ruckerbauer Isabel Rocha 《PLoS computational biology》2021,17(6)
Chinese hamster ovary (CHO) cells are the leading platform for the production of biopharmaceuticals with human-like glycosylation. The standard practice for cell line generation relies on trial and error approaches such as adaptive evolution and high-throughput screening, which typically take several months. Metabolic modeling could aid in designing better producer cell lines and thus shorten development times. The genome-scale metabolic model (GSMM) of CHO can accurately predict growth rates. However, in order to predict rational engineering strategies it also needs to accurately predict intracellular fluxes. In this work we evaluated the agreement between the fluxes predicted by parsimonious flux balance analysis (pFBA) using the CHO GSMM and a wide range of 13C metabolic flux data from literature. While glycolytic fluxes were predicted relatively well, the fluxes of tricarboxylic acid (TCA) cycle were vastly underestimated due to too low energy demand. Inclusion of computationally estimated maintenance energy significantly improved the overall accuracy of intracellular flux predictions. Maintenance energy was therefore determined experimentally by running continuous cultures at different growth rates and evaluating their respective energy consumption. The experimentally and computationally determined maintenance energy were in good agreement. Additionally, we compared alternative objective functions (minimization of uptake rates of seven nonessential metabolites) to the biomass objective. While the predictions of the uptake rates were quite inaccurate for most objectives, the predictions of the intracellular fluxes were comparable to the biomass objective function. 相似文献