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4001
[ "In", "elderly", "healthy", "subjects", ",", "Type", "II", "receptors", "were", "also", "significantly", "decreased", "(", "from", "1796", "+/-", "671", "to", "720", "+/-", "345", ")", "." ]
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4002
[ "We", "suggest", "that", "in", "young", "subjects", "Type", "II", "receptors", "are", "initially", "up-regulated", "by", "dexamethasone", ",", "and", "then", "down-regulated", ",", "while", "in", "aged", "subjects", "an", "up-regulation", "can", "not", "be", "achieved", ",", "as", "suggested", "by", "the", "higher", "values", "of", "plasma", "cortisol", "usually", "found", "in", "aging", "subjects", "." ]
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4003
[ "Analysis", "of", "the", "ligand-binding", "domain", "of", "human", "retinoic", "acid", "receptor", "alpha", "by", "site-directed", "mutagenesis", "." ]
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4004
[ "Three", "subtypes", "of", "retinoic", "acid", "receptors", "(", "RAR", ")", ",", "termed", "RAR", "alpha", ",", "RAR", "beta", ",", "and", "RAR", "gamma", ",", "have", "been", "described", "." ]
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4005
[ "They", "are", "composed", "of", "different", "structural", "domains", ",", "including", "distinct", "domains", "for", "DNA", "and", "ligand", "binding", "." ]
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4006
[ "RARs", "specifically", "bind", "all-trans-retinoic", "acid", "(", "RA", ")", ",", "9-cis-RA", ",", "and", "retinoid", "analogs", "." ]
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4007
[ "In", "this", "study", ",", "we", "examined", "the", "functional", "role", "of", "cysteine", "and", "arginine", "residues", "in", "the", "ligand-binding", "domain", "of", "hRAR", "alpha", "(", "hRAR", "alpha-LBD", ",", "amino", "acids", "154", "to", "462", ")", "." ]
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4008
[ "All", "conserved", "cysteine", "and", "arginine", "residues", "in", "this", "domain", "were", "mutated", "by", "site-directed", "mutagenesis", ",", "and", "the", "mutant", "proteins", "were", "characterized", "by", "blocking", "reactions", ",", "ligand-binding", "experiments", ",", "transactivation", "assays", ",", "and", "protease", "mapping", "." ]
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4009
[ "Changes", "of", "any", "cysteine", "residue", "of", "the", "hRAR", "alpha-LBD", "had", "no", "significant", "influence", "on", "the", "binding", "of", "all-trans", "RA", "or", "9-cis", "RA", "." ]
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4010
[ "Interestingly", ",", "residue", "C-235", "is", "specifically", "important", "in", "antagonist", "binding", "." ]
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4011
[ "With", "respect", "to", "arginine", "residues", ",", "only", "the", "two", "single", "mutations", "of", "R-276", "and", "R-394", "to", "alanine", "showed", "a", "dramatic", "decrease", "of", "agonist", "and", "antagonist", "binding", "whereas", "the", "R272A", "mutation", "showed", "only", "a", "slight", "effect", "." ]
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4012
[ "For", "all", "other", "arginine", "mutations", ",", "no", "differences", "in", "affinity", "were", "detectable", "." ]
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4013
[ "The", "two", "mutations", "R217A", "and", "R294A", "caused", "an", "increased", "binding", "efficiency", "for", "antagonists", "but", "no", "change", "in", "agonist", "binding", "." ]
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4014
[ "From", "these", "results", ",", "we", "can", "conclude", "that", "electrostatic", "interactions", "of", "retinoids", "with", "the", "RAR", "alpha-LBD", "play", "a", "significant", "role", "in", "ligand", "binding", "." ]
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4015
[ "In", "addition", ",", "antagonists", "show", "distinctly", "different", "requirements", "for", "efficient", "binding", ",", "which", "may", "contribute", "to", "their", "interference", "in", "the", "ligand-inducible", "transactivation", "function", "of", "RAR", "alpha", "." ]
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4016
[ "IL4", "and", "IL13", "receptors", "share", "the", "gamma", "c", "chain", "and", "activate", "STAT6", ",", "STAT3", "and", "STAT5", "proteins", "in", "normal", "human", "B", "cells", "." ]
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4017
[ "IL13", "induces", "the", "same", "biological", "effects", "as", "IL4", "in", "normal", "human", "B", "cells", "." ]
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4018
[ "We", "show", "that", "as", "in", "the", "IL4R", "complex", ",", "both", "IL4R", "alpha", "and", "IL2R", "gamma", "c", "are", "components", "of", "the", "IL13R", "and", "that", "both", "cytokines", "induced", "STAT6", ",", "STAT3", "and", "STAT5", "activation", "in", "B", "cells", "." ]
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4019
[ "In", "spite", "of", "this", "similar", "downstream", "signalling", ",", "IL4", "and", "IL13", "used", "a", "different", "set", "of", "Janus", "kinases", ":", "IL13", "is", "unable", "to", "activate", "JAK1", "and", "JAK3", "." ]
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4020
[ "Calcineurin", "mutants", "render", "T", "lymphocytes", "resistant", "to", "cyclosporin", "A", "." ]
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4021
[ "The", "immunosuppressants", "cyclosporin", "A", "(", "CsA", ")", "and", "FK506", "have", "been", "widely", "used", "to", "prevent", "and", "treat", "graft", "rejection", "after", "human", "organ", "and", "tissue", "transplantations", "." ]
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4022
[ "CsA", "and", "FK506", "associate", "with", "intracellular", "binding", "proteins", "(", "i.e.", ",", "CsA", "with", "cyclophilin", "A", "and", "FK506", "with", "FKBP12", ")", "to", "form", "protein/drug", "complexes", "that", "suppress", "the", "immune", "system", "by", "preventing", "activation", "of", "T", "cells", "in", "response", "to", "antigen", "presentation", "." ]
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4023
[ "The", "common", "target", "of", "CsA", "and", "FK506", "is", "calcineurin", ",", "a", "Ca2+/calmodulin-regulated", ",", "serine/threonine-specific", "protein", "phosphatase", "that", "regulates", "the", "nuclear", "import", "of", "a", "transcription", "factor", ",", "NF-AT", ",", "required", "for", "expression", "of", "T", "cell", "activation", "genes", "." ]
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4024
[ "In", "previous", "studies", ",", "we", "identified", "calcineurin", "mutations", "that", "block", "binding", "by", "the", "cyclophilin", "A/CsA", "or", "FKBP12/FK506", "complexes", "and", "thereby", "render", "yeast", "cells", "resistant", "to", "the", "antifungal", "effects", "of", "CsA", "or", "FK506", "." ]
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4025
[ "In", "this", "report", ",", "we", "demonstrate", "that", "the", "corresponding", "mutations", "in", "murine", "calcineurin", "render", "the", "T", "cell", "receptor", "signal", "transduction", "cascade", "CsA", "resistant", "in", "human", "Jurkat", "T", "cells", "." ]
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4026
[ "Our", "findings", "support", "the", "recently", "determined", "calcineurin", "X-ray", "crystal", "structure", ",", "provide", "evidence", "that", "calcineurin", "is", "the", "only", "CsA-sensitive", "component", "limiting", "signaling", "from", "the", "T", "cell", "receptor", "to", "the", "nucleus", ",", "and", "suggest", "a", "means", "to", "render", "cells", "and", "tissues", "resistant", "to", "the", "toxic", "side", "effects", "of", "CsA", "and", "FK506", "." ]
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4027
[ "Epstein-Barr", "viral", "latency", "is", "disrupted", "by", "the", "immediate-early", "BRLF1", "protein", "through", "a", "cell-specific", "mechanism", "." ]
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4028
[ "Epstein-Barr", "virus", "(", "EBV", ")", ",", "the", "causative", "agent", "of", "infectious", "mononucleosis", ",", "is", "a", "human", "herpesvirus", "associated", "with", "epithelial", "cell", "malignancies", "(", "nasopharyngeal", "carcinoma", ")", "as", "well", "as", "B-cell", "malignancies", "." ]
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4029
[ "Understanding", "how", "viral", "latency", "is", "disrupted", "is", "a", "central", "issue", "in", "herpesvirus", "biology", "." ]
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4030
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4031
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4032
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4033
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4034
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4035
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4036
[ "Eosinophils", "play", "an", "important", "role", "in", "the", "effector", "phase", "of", "allergic", "inflammation", "." ]
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4037
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4038
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4039
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4040
[ "Implications", "for", "immunity", "and", "vaccine", "design", "." ]
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4041
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4042
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4043
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4044
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4045
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4046
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4051
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4053
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4054
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4055
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4056
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