المؤلفون: Zhen-Ning Zhang, Freitas, Beatriz C., Hao Qian, Lux, Jacques, Acab, Allan, Trujillo, Cleber A., Herai, Roberto H., Viet Anh Nguyen Huu, Wen, Jessica H., Joshi-Barr, Shivanjali, Karpiak, Jerome V., Engler, Adam J., Xiang-Dong Fu, Muotri, Alysson R., Almutairi, Adah

المصدر: Proceedings of the National Academy of Sciences of the United States of America; 3/22/2016, Vol. 113 Issue 12, p3185-3190, 6p

مصطلحات موضوعية: HYDROGELS, NEURAL stem cells, PROGENITOR cells, CELL migration inhibition, CELLULAR control mechanisms, CARRIER protein genetics

مستخلص: Probing a wide range of cellular phenotypes in neurodevelopmental disorders using patient-derived neural progenitor cells (NPCs) can be facilitated by 3D assays, as 2D systems cannot entirely recapitulate the arrangement of cells in the brain. Here, we developed a previously unidentified 3D migration and differentiation assay in layered hydrogels to examine how these processes are affected in neurodevelopmental disorders, such as Rett syndrome. Our soft 3D system mimics the brain environment and accelerates maturation of neurons from human induced pluripotent stem cell (iPSC)-derived NPCs, yielding electrophysiologically active neurons within just 3 wk. Using this platform, we revealed a genotype-specific effect of methyl-CpG-binding protein-2 (MeCP2) dysfunction on iPSC-derived neuronal migration and maturation (reduced neurite outgrowth and fewer synapses) in 3D layered hydrogels. Thus, this 3D system expands the range of neural phenotypes that can be studied in vitro to include those influenced by physical and mechanical stimuli or requiring specific arrangements of multiple cell types. [ABSTRACT FROM AUTHOR]

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المؤلفون: Sheng Hou, Jianping Ding, Baozhen Peng, Yajun Guo, Hao Wang, Daipong Zhang, Meilan Zhang, Sheng Li

مصطلحات موضوعية: Efalizumab, Intercellular Adhesion Molecule-1, chemical and pharmacologic phenomena, Plasma protein binding, CD11a, Biology, Antibodies, Monoclonal, Humanized, Epitope, Autoimmune Diseases, Epitopes, medicine, Humans, Lymphocyte function-associated antigen 1, Binding site, Multidisciplinary, Binding Sites, Antibodies, Monoclonal, Biological Sciences, Ligand (biochemistry), Molecular biology, Lymphocyte Function-Associated Antigen-1, Cell biology, Cell Migration Inhibition, medicine.drug, Protein Binding

الوصف: Lymphocyte function-associated antigen 1 (LFA-1) plays important roles in immune cell adhesion, trafficking, and activation and is a therapeutic target for the treatment of multiple autoimmune diseases. Efalizumab is one of the most efficacious antibody drugs for treating psoriasis, a very common skin disease, through inhibition of the binding of LFA-1 to the ligand intercellular adhesion molecule 1 (ICAM-1). We report here the crystal structures of the Efalizumab Fab alone and in complex with the LFA-1 αLI domain, which reveal the molecular mechanism of inhibition of LFA-1 by Efalizumab. The Fab binds with an epitope on the inserted (I) domain that is distinct from the ligand-binding site. Efalizumab binding blocks the binding of LFA-1 to ICAM-1 via steric hindrance between its light chain and ICAM-1 domain 2 and thus inhibits the activities of LFA-1. These results have important implications for the development of improved antibodies and new therapeutic strategies for the treatment of autoimmune diseases.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::d7bb5d93aa7095c0b4773e3daebdfac8Test
https://europepmc.org/articles/PMC2657446Test/