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SotiriosKastanas

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[ "BMC", "Genetics", "Correspondence", "Minor", "differences", "in", "haplotype", "frequency", "estimates", "can", "produce", "very", "large", "differences", "in", "heterogeneity", "test", "statistics", "David", "Curtis*1", "and", "Ke", "Xu2", "BioMed", "Central", "Open", "Access", "Address:", "1Academic", "Department", "of", "Psychiatry,", "Queen", "Mary's", "School", "of", "Medicine", "and", "Dentistry,", "London", "E1", "1BB,", "UK", "and", "2Laboratory", "of", "Neurogenetics,", "National", "Institute", "on", "Alcohol", "Abuse", "and", "Alcoholism,", "5625", "Fishers", "Lane,", "Room", "3S32,", "Bethesda,", "MD", "20892-9412,", "USA", "Email:", "David", "Curtis*", "-", "david.curtis@qmul.ac.uk;", "Ke", "Xu", "-", "ke@mail.nih.gov", "*", "Corresponding", "author", "Published:", "27", "June", "2007", "BMC", "Genetics", "2007,", "8:38", "doi:10.1186/1471-2156-8-38", "This", "article", "is", "available", "from:", "http://www.biomedcentral.com/1471-2156/8/38", "Received:", "12", "November", "2006", "Accepted:", "27", "June", "2007", "©", "2007", "Curtis", "and", "Xu;", "licensee", "BioMed", "Central", "Ltd.", "This", "is", "an", "Open", "Access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "License", "(http://creativecommons.org/licenses/by/2.0),", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited.", "Abstract", "Background:", "Tests", "for", "association", "between", "a", "haplotype", "and", "disease", "are", "commonly", "performed", "using", "a", "likelihood", "ratio", "test", "for", "heterogeneity", "between", "case", "and", "control", "haplotype", "frequencies.", "Using", "data", "from", "a", "study", "of", "association", "between", "heroin", "dependence", "and", "the", "DRD2", "gene,", "we", "obtained", "estimated", "haplotype", "frequencies", "and", "the", "associated", "likelihood", "ratio", "statistic", "using", "two", "different", "computer", "programs,", "MLOCUS", "and", "GENECOUNTING.", "We", "also", "carried", "out", "permutation", "testing", "to", "assess", "the", "empirical", "significance", "of", "the", "results", "obtained.", "Results:", "Both", "programs", "yielded", "similar,", "though", "not", "identical,", "estimates", "for", "the", "haplotype", "frequencies.", "MLOCUS", "produced", "a", "p", "value", "of", "1.8*10-15", "and", "GENECOUNTING", "produced", "a", "p", "value", "of", "5.4*10-4.", "Permutation", "testing", "produced", "a", "p", "value", "2.8*10-4.", "Conclusion:", "The", "fact", "that", "very", "large", "differences", "occur", "between", "the", "likelihood", "ratio", "statistics", "from", "the", "two", "programs", "may", "reflect", "the", "fact", "that", "the", "haplotype", "frequencies", "for", "the", "combined", "group", "are", "not", "constrained", "to", "be", "equal", "to", "the", "weighted", "averages", "of", "the", "frequencies", "for", "the", "cases", "and", "controls,", "as", "they", "would", "be", "if", "they", "were", "directly", "observed", "rather", "than", "being", "estimated.", "Minor", "differences", "in", "haplotype", "frequency", "estimates", "can", "result", "in", "very", "large", "differences", "in", "the", "likelihood", "ratio", "statistic", "and", "associated", "p", "value.", "Background", "We", "wish", "to", "point", "out", "a", "serious", "and", "previously", "unde-", "scribed", "problem", "with", "using", "heterogeneity", "testing", "to", "test", "for", "differences", "in", "haplotype", "frequencies", "between", "cases", "and", "controls.", "As", "implemented", "in", "several", "applications", "[1-", "3]", "a", "likelihood", "ratio", "statistic", "(LRS)", "is", "calculated", "as", "2(LCASE+LCONTROL-LCOMBINED),", "where", "the", "relevant", "log", "like-", "lihoods", "are", "produced", "using", "maximum", "likelihood", "esti-", "mates", "of", "the", "haplotype", "frequencies.", "Although", "this", "approach", "is", "reasonable", "in", "theory,", "severe", "problems", "can", "arise", "in", "practice", "if", "the", "likelihood", "maximisation", "process", "is", "less", "than", "perfect.", "Although", "the", "estimation-maximisation", "(EM)", "method", "usually", "performs", "well,", "it", "is", "known", "that", "it", "is", "not", "guaranteed", "always", "to", "find", "a", "global", "maximum.", "In", "many", "circumstances", "small", "errors", "in", "numerical", "estimates", "do", "not", "have", "practical", "signficance.", "However", "we", "have", "dis-", "covered", "that", "in", "the", "context", "of", "heterogeneity", "testing", "appar-", "ently", "trivial", "differences", "in", "estimating", "the", "haplotype", "frequency", "parameters", "can", "have", "very", "large", "impacts", "on", "the", "associated", "likelihoods", "and", "LRS", "values.", "Results", "In", "Table", "1", "we", "present", "the", "haplotype", "frequency", "estimates", "and", "associated", "log", "likelihoods", "and", "LRS", "values", "obtained", "Page", "1", "of", "3", "(page", "number", "not", "for", "citation", "purposes)" ]

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[ "Extended", "report", "HSC70", "blockade", "by", "the", "therapeutic", "peptide", "P140", "affects", "autophagic", "processes", "and", "endogenous", "MHCII", "presentation", "in", "murine", "lupus", "Nicolas", "Page,1", "Frédéric", "Gros,1", "Nicolas", "Schall,1", "Marion", "Décossas,1", "Dominique", "Bagnard,2", "Jean-Paul", "Briand,1", "Sylviane", "Muller1", "▶", "Additional", "data", "(supplementary", "figures)", "are", "published", "online", "only.", "To", "view", "these", "files", "please", "visit", "the", "journal", "online", "at", "(http://ard.bmj.", "com).", "1", "CNRS", "UPR9021,", "Institut", "de", "Biologie", "Moléculaire", "et", "Cellulaire,", "Strasbourg,", "France", "2", "INSERM", "U682,", "Université", "de", "Strasbourg,", "Strasbourg,", "France", "Correspondence", "to", "Sylviane", "Muller,", "CNRS", "UPR9021,", "Institut", "de", "Biologie", "Moléculaire", "et", "Cellulaire,", "67000", "Strasbourg,", "France;", "s.muller@ibmc-cnrs.unistra.fr", "Accepted", "11", "November", "2010", "Published", "Online", "First", "20", "December", "2010", "This", "paper", "is", "freely", "available", "online", "under", "the", "BMJ", "Journals", "unlocked", "scheme,", "see", "http://", "ard.bmj.com/info/unlocked.dtl", "Ann", "Rheum", "Dis", "2011;70:837–843.", "doi:10.1136/ard.2010.139832", "ABSTRACT", "Background", "The", "P140", "phosphopeptide", "issued", "from", "the", "spliceosomal", "U1-70K", "small", "nuclear", "ribonucleoprotein", "protein", "displays", "protective", "properties", "in", "MRL/lpr", "lupus-", "prone", "mice.", "It", "binds", "both", "major", "histocompatibility", "class", "II", "(MHCII)", "and", "HSC70/Hsp73", "molecules.", "P140", "peptide", "increases", "MRL/lpr", "peripheral", "blood", "lymphocyte", "apoptosis", "and", "decreases", "autoepitope", "recognition", "by", "T", "cells.", "Objective", "To", "explore", "further", "the", "mode", "of", "action", "of", "P140", "peptide", "on", "HSC70+", "antigen-presenting", "cells.", "Methods", "P140", "biodistribution", "was", "monitored", "in", "real", "time", "using", "an", "imaging", "system", "and", "by", "fluorescence", "and", "electron", "microscopy.", "Fluorescence", "activated", "cell", "sorting", "and", "Western", "blotting", "experiments", "were", "used", "to", "evaluate", "the", "P140", "effects", "on", "autophagic", "flux", "markers.", "Results", "P140", "fluorescence", "accumulated", "especially", "in", "the", "lungs", "and", "spleen.", "P140", "peptide", "reduced", "the", "number", "of", "peripheral", "and", "splenic", "T", "and", "B", "cells", "without", "affecting", "these", "cells", "in", "normal", "mice.", "Remaining", "MRL/lpr", "B", "cells", "responded", "normally", "to", "mitogens.", "P140", "peptide", "decreased", "the", "expression", "levels", "of", "HSC70/Hsp73", "chaperone", "and", "stable", "MHCII", "dimers,", "which", "are", "both", "increased", "in", "MRL/", "lpr", "splenic", "B", "cells.", "It", "impaired", "refolding", "properties", "of", "chaperone", "HSC70.", "In", "MRL/lpr", "B", "cells,", "it", "increased", "the", "accumulation", "of", "the", "autophagy", "markers", "p62/SQSTM1", "and", "LC3-II,", "consistent", "with", "a", "downregulated", "lysosomal", "degradation", "during", "autophagic", "flux.", "Conclusion", "The", "study", "results", "suggest", "that", "after", "P140", "peptide", "binding", "to", "HSC70,", "the", "endogenous", "(auto)", "antigen", "processing", "might", "be", "greatly", "affected", "in", "MRL/", "lpr", "antigen-presenting", "B", "cells,", "leading", "to", "the", "observed", "decrease", "of", "autoreactive", "T-cell", "priming", "and", "signalling", "via", "a", "mechanism", "involving", "a", "lysosomal", "degradation", "pathway.", "This", "unexpected", "mechanism", "might", "explain", "the", "beneficial", "effect", "of", "P140", "peptide", "in", "treated", "MRL/lpr", "mice.", "INTRODUCTION", "Systemic", "lupus", "erythematosus", "is", "a", "multifacto-", "rial", "(multigenic)", "and", "highly", "polymorphic", "systemic", "autoimmune", "disorder.", "It", "affects", "multiple", "organs,", "including", "skin,", "muscle,", "joints", "and", "vital", "internal", "organs", "such", "as", "kidneys", "and", "heart.", "Current", "pharma-", "cological", "treatments", "are", "largely", "palliative", "and", "result", "in", "non-specific", "immunosuppression.", "The", "goal", "today", "is", "to", "design", "more", "specific", "and", "effective", "treatments.", "P140", "peptide", "is", "a", "21-mer", "fragment", "of", "the", "spli-", "ceosomal", "U1-70K", "small", "nuclear", "ribonucleoprotein", "protein", "that", "significantly", "ameliorates", "clinical", "and", "biological", "manifestations", "in", "autoimmune", "patients", "with", "systemic", "lupus", "erythematosus", "and", "enhances", "survival", "in", "lupus-prone", "mice.1", "2", "This", "peptide", "con-", "tains", "a", "phosphoserine", "residue", "at", "position", "140,", "a", "modification", "that", "specifically", "occurs", "at", "an", "early", "stage", "of", "apoptosis,", "before", "the", "cleavage", "of", "the", "C-terminal", "part", "of", "the", "protein", "by", "caspase-3", "and", "the", "dephosphorylation", "of", "other", "serine", "residues", "by", "a", "PP1", "phosphatase-mediated", "mechanism.3", "Originally", "thought", "to", "act", "solely", "via", "the", "modulation", "of", "intrac-", "ellular", "signalling", "induced", "by", "αβ", "autoreactive", "T-cell", "receptor", "(TCR)", "engagement,2", "4", "P140", "was", "unexpect-", "edly", "found", "to", "interact", "selectively", "with", "the", "consti-", "tutive", "heat-shock", "HSC70/Hsp73", "protein.5", "By", "a", "granzyme-B", "and", "caspase-dependent", "mechanism,", "it", "induces", "in", "Fas-deficient", "MRL/lpr", "lupus", "mice", "apopto-", "sis", "of", "B", "cells", "and", "CD4,", "CD8", "or", "double", "negative", "(DN)", "αβTCR+/CD4/CD8/B220+", "T", "lymphocytes", "through", "a", "regulatory", "circuit", "involving", "γδT", "cells.5", "Intravenous", "P140", "peptide", "administration", "into", "young", "MRL/lpr", "mice", "thus", "causes", "T-", "and", "B-cell", "egress", "from", "periph-", "eral", "blood", "but", "does", "not", "affect", "T-cell", "priming,", "and", "does", "not", "interfere", "with", "the", "ability", "of", "P140-treated", "mice", "to", "resist", "to", "an", "infectious", "viral", "challenge.6", "P140", "also", "downregulates", "the", "expression", "of", "programmed", "death", "1", "(PD-1/CD279)", "receptor,", "a", "molecule", "of", "the", "CD28", "family,", "which", "is", "overexpressed", "at", "the", "sur-", "face", "of", "MRL/lpr", "CD4", "T", "cells.5", "P140", "peptide", "thus", "displays", "various", "effects", "on", "the", "immune", "system", "that", "probably", "interfere", "with", "several,", "yet", "unidentified,", "molecular", "pathways", "leading", "finally", "to", "a", "decreased", "T-cell", "autoreactivity", "and", "to", "significantly", "lower", "levels", "of", "autoantibodies", "to", "native", "DNA.", "In", "the", "postulated", "P140", "mode", "of", "action,", "bind-", "ing", "to", "the", "chaperone", "HSC70", "protein", "seems", "to", "be", "central.", "The", "implication", "of", "or", "any", "defect", "of", "the", "HSC70", "pathway", "in", "regulating", "immune", "functions", "in", "lupus", "is", "not", "documented.", "It", "is", "not", "known", "either", "if", "HSC70-chaperoned", "molecules,", "such", "as", "other", "Hsps", "and", "major", "histocompatibility", "complex", "(MHC)", "molecules,", "are", "affected", "by", "P140–HSC70", "binding.", "To", "address", "these", "major", "questions,", "we", "evaluated", "the", "effect", "of", "P140", "administration", "on", "the", "expres-", "sion", "of", "HSC70", "and", "MHCII", "molecules,", "and", "studied", "the", "possible", "influence", "of", "P140", "on", "autophagosomal", "pathways", "implicated", "in", "the", "endogenous", "MHCII", "loading.", "Since", "HSC70", "is", "involved", "in", "certain", "phases", "of", "these", "pathways,", "we", "expected", "that", "binding", "of", "P140", "to", "HSC70", "might", "alter", "the", "delivery", "of", "intracel-", "lular", "material", "into", "the", "endosomal/lysosomal", "path-", "way", "and", "therefore", "thwart", "the", "final", "presentation", "of", "self-antigens", "to", "autoreactive", "T", "cells.", "METHODS", "Synthetic", "peptides", "and", "biochemical", "assays", "Peptides", "were", "assembled", "and", "purified", "as", "des-", "cribed.1", "5", "The", "P140", "peptide", "was", "also", "synthesised", "837" ]

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[ "Wang", "et", "al.", "BMC", "Developmental", "Biology", "2010,", "10:91", "http://www.biomedcentral.com/1471-213X/10/91", "R", "E", "S", "E", "A", "R", "C", "H", "A", "R", "T", "I", "C", "L", "E", "Open", "Access", "Commitment", "of", "chondrogenic", "precursors", "of", "the", "avian", "scapula", "takes", "place", "after", "epithelial-", "mesenchymal", "transition", "of", "the", "dermomyotome", "Baigang", "Wang1,2*,", "Qin", "Pu3,", "Raja", "De2,", "Ketan", "Patel4,", "Bodo", "Christ2,", "Jörg", "Wilting1,", "Ruijin", "Huang2,3*", "Abstract", "Background:", "Cells", "of", "the", "epithelially", "organised", "dermomyotome", "are", "traditionally", "believed", "to", "give", "rise", "to", "skeletal", "muscle", "and", "dermis.", "We", "have", "previously", "shown", "that", "the", "dermomyotome", "can", "undergo", "epithelial-mesenchymal", "transition", "(EMT)", "and", "give", "rise", "to", "chondrogenic", "cells,", "which", "go", "on", "to", "form", "the", "scapula", "blade", "in", "birds.", "At", "present", "we", "have", "little", "understanding", "regarding", "the", "issue", "of", "when", "the", "chondrogenic", "fate", "of", "dermomyotomal", "cells", "is", "determined.", "Using", "quail-chick", "grafting", "experiments,", "we", "investigated", "whether", "scapula", "precursor", "cells", "are", "committed", "to", "a", "chondrogenic", "fate", "while", "in", "an", "epithelial", "state", "or", "whether", "commitment", "is", "established", "after", "EMT.", "Results:", "We", "show", "that", "the", "hypaxial", "dermomyotome,", "which", "normally", "forms", "the", "scapula,", "does", "not", "generate", "cartilaginous", "tissue", "after", "it", "is", "grafted", "to", "the", "epaxial", "domain.", "In", "contrast", "engraftment", "of", "the", "epaxial", "dermomyotome", "to", "the", "hypaxial", "domain", "gives", "rise", "to", "scapula-like", "cartilage.", "However,", "the", "hypaxial", "sub-ectodermal", "mesenchyme", "(SEM),", "which", "originates", "from", "the", "hypaxial", "dermomyotome", "after", "EMT,", "generates", "cartilaginous", "elements", "in", "the", "epaxial", "domain,", "whereas", "in", "reciprocal", "grafting", "experiments,", "the", "epaxial", "SEM", "cannot", "form", "cartilage", "in", "the", "hypaxial", "domain.", "Conclusions:", "We", "suggest", "that", "the", "epithelial", "cells", "of", "the", "dermomyotome", "are", "not", "committed", "to", "the", "chondrogenic", "lineage.", "Commitment", "to", "this", "lineage", "occurs", "after", "it", "has", "undergone", "EMT", "to", "form", "the", "sub-ectodermal", "mesenchyme.", "Background", "Epithelial", "and", "mesenchymal", "cells", "differ", "from", "each", "other", "in", "several", "aspects.", "Epithelial", "cells", "are", "connected", "to", "each", "other", "by", "cell", "surface", "contacts", "such", "as", "desmosomes", "and", "gap", "junctions,", "form", "dense", "cell", "layers", "resting", "on", "a", "basal", "lamina", "and", "exhibiting", "apical-basal", "polarity.", "In", "contrast,", "mesenchymal", "cells", "have", "no", "association", "with", "the", "basal", "lamina", "and", "usually", "do", "not", "possess", "elaborated", "adhesion", "complexes", "with", "neighbouring", "cells,", "which", "increase", "their", "migratory", "potential.", "Under", "certain", "physiological", "or", "pathological", "conditions", "epithelial", "cells", "lose", "their", "charac-", "teristics", "and", "undergo", "morphological", "changes", "to", "convert", "into", "mesenchymal", "cells,", "a", "biological", "process", "known", "as", "epithelial-mesenchymal", "transition", "(EMT)", "[1].", "The", "*", "Correspondence:", "baigang.wang@medizin.uni-goettingen.de;", "ruijin.", "huang@uni-bonn.de", "1Department", "of", "Anatomy", "and", "Cell", "Biology,", "University", "of", "Goettingen,", "Kreuzbergring", "36,", "37075", "Goettingen,", "Germany", "2Institute", "of", "Anatomy", "and", "Cell", "Biology,", "University", "of", "Freiburg,", "Albertstrasse", "17,", "79104", "Freiburg,", "Germany", "Full", "list", "of", "author", "information", "is", "available", "at", "the", "end", "of", "the", "article", "process", "of", "EMT", "is", "reversible", "and", "the", "opposite", "mechan-", "ism", "converts", "mesenchymal", "cells", "into", "epithelia", "(mesench-", "ymal-to-epithelial", "transition,", "MET).", "EMT", "and", "MET", "play", "key", "roles", "not", "only", "during", "early", "embryonic", "development,", "for", "example", "during", "implantation", "of", "the", "embryo", "into", "the", "uterus,", "gastrulation", "and", "de-lamina-", "tion", "of", "neural", "crest", "cells,", "but", "also", "during", "later", "developmen-", "tal", "stages", "such", "as", "in", "somite", "development", "and", "organogenesis", "[2].", "Somites", "are", "balls", "of", "epithelial", "cells,", "which", "arise", "from", "the", "paraxial", "mesoderm", "(mesenchyme)", "by", "means", "of", "MET.", "Later,", "the", "ventral", "half", "of", "each", "somite", "undergoes", "EMT", "to", "give", "rise", "to", "the", "sclerotome", "[3],", "while", "the", "dorsal", "half", "remains", "epithe-", "lial", "and", "forms", "the", "dermomyotome,", "source", "of", "the", "skeletal", "muscle,", "dermis", "[4],", "scapula", "blade", "in", "birds", "[5]", "and", "medial", "scapula", "border", "in", "mammals", "[6].", "The", "avian", "dermomyotome", "in", "specific", "axial", "regions", "undergoes", "EMT", "to", "form", "sub-ectodermal", "mesenchyme", "which", "gives", "rise", "to", "scapula", "[7].", "This", "process", "is", "con-", "trolled", "by", "signals", "from", "the", "ectoderm", "and", "the", "lateral", "plate", "mesoderm", "[7,8].", "Furthermore", "only", "cells", "originating", "©", "2010", "Wang", "et", "al;", "licensee", "BioMed", "Central", "Ltd.", "This", "is", "an", "Open", "Access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "License", "(http://creativecommons.org/licenses/by/2.0),", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited." ]

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[ "International", "Scholarly", "Research", "Network", "ISRN", "Nursing", "Volume", "2012,", "Article", "ID", "676905,", "6", "pages", "doi:10.5402/2012/676905", "Research", "Article", "Mapping", "the", "Diagnosis", "Axis", "of", "an", "Interface", "Terminology", "to", "the", "NANDA", "International", "Taxonomy", "Maria-Eul", "a`lia", "Juve´", "Udina,1", "Maribel", "Gonzalez", "Samartino,2", "and", "Cristina", "Matud", "Calvo2", "1", "School", "of", "Nursing,", "University", "of", "Barcelona,", "Campus", "of", "Bellvitge,", "Feixa", "Llarga", "s/n,", "08907", "Hospitalet", "de", "Llobregat,", "Spain", "2", "Nursing", "Information", "Systems", "Department,", "University", "Hospital", "of", "Bellvitge,", "08907", "Hospitalet", "de", "Llobregat,", "Spain", "Correspondence", "should", "be", "addressed", "to", "Maria-Eula`lia", "Juve´", "Udina,", "ejuve@gencat.cat", "Received", "11", "March", "2012;", "Accepted", "8", "May", "2012", "Academic", "Editors:", "B.", "Mandleco", "and", "A.", "Williams", "Copyright", "©", "2012", "Maria-Eula`lia", "Juve´", "Udina", "et", "al.", "This", "is", "an", "open", "access", "article", "distributed", "under", "the", "Creative", "Commons", "Attribution", "License,", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited.", "Background.", "Nursing", "terminologies", "are", "designed", "to", "support", "nursing", "practice", "but,", "as", "with", "any", "other", "clinical", "tool,", "they", "should", "be", "evaluated.", "Cross-mapping", "is", "a", "formal", "method", "for", "examining", "the", "validity", "of", "the", "existing", "controlled", "vocabularies.", "Objectives.", "The", "study", "aims", "to", "assess", "the", "inclusiveness", "and", "expressiveness", "of", "the", "nursing", "diagnosis", "axis", "of", "a", "newly", "implemented", "interface", "terminology", "by", "cross-mapping", "with", "the", "NANDA-I", "taxonomy.", "Design/Methods.", "The", "study", "applied", "a", "descriptive", "design,", "using", "a", "cross-sectional,", "bidirectional", "mapping", "strategy.", "The", "sample", "included", "728", "concepts", "from", "both", "vocabularies.", "Concept", "cross-mapping", "was", "carried", "out", "to", "identify", "one-to-one,", "negative,", "and", "hierarchical", "connections.", "The", "analysis", "was", "conducted", "using", "descriptive", "statistics.", "Results.", "Agreement", "of", "the", "raters’", "mapping", "achieved", "97%.", "More", "than", "60%", "of", "the", "nursing", "diagnosis", "concepts", "in", "the", "NANDA-I", "taxonomy", "were", "mapped", "to", "concepts", "in", "the", "diagnosis", "axis", "of", "the", "new", "interface", "terminology;", "71.1%", "were", "reversely", "mapped.", "Conclusions.", "Main", "results", "for", "outcome", "measures", "suggest", "that", "the", "diagnosis", "axis", "of", "this", "interface", "terminology", "meets", "the", "validity", "criterion", "of", "cross-mapping", "when", "mapped", "from", "and", "to", "the", "NANDA-I", "taxonomy.", "1.", "Introduction", "Language", "plays", "an", "important", "role", "in", "defining", "what", "nurses", "do", "and", "why", "they", "do", "it.", "In", "recent", "decades,", "language", "systems", "have", "become", "a", "priority", "for", "international", "nursing", "agendas.", "Standardized", "controlled", "vocabularies", "are", "a", "means", "to", "develop,", "express,", "and", "understand", "nursing", "phenomena", "and", "actions", "through", "concepts;", "to", "quote", "Matney", "et", "al.", "“structured", "nursing", "terminologies", "are", "needed", "to", "drive,", "document", "and", "evaluate", "nursing", "practice”", "[1].", "The", "use", "of", "electronic", "health", "records", "and", "information", "sys-", "tems", "at", "all", "levels", "of", "the", "healthcare", "agencies", "is", "now", "widespread", "all", "over", "the", "world.", "In", "order", "to", "optimize", "the", "efficiency", "of", "these", "records", "and", "systems", "and", "to", "facilitate", "the", "exchange", "of", "infor-", "mation", "among", "professionals", "and", "institutions,", "they", "must", "be", "based", "on", "controlled", "vocabularies", "[2,", "3];", "as", "Mu¨", "ller-Staub", "et", "al.", "explain", "“standardized", "computer-compatible", "professional", "ter-", "minology", "is", "becoming", "a", "requirement,", "especially", "by", "institutions", "and", "healthcare", "systems", "that", "bear", "the", "costs", "of", "health", "care”", "[4].", "Controlled", "nursing", "vocabularies", "can", "be", "implemented", "as", "interface", "terminologies", "at", "the", "point", "of", "care", "and", "as", "administrative", "terminologies", "to", "retrieve", "nursing", "clinical", "data", "in", "order", "to", "support", "decision-making", "[4–6].", "To", "date,", "twelve", "nursing", "terminologies", "and", "data", "sets", "have", "been", "recognized", "by", "the", "American", "Nurses", "Association", "(ANA)", "for", "supporting", "nursing", "practice:", "the", "North", "American", "Nursing", "Diagnosis", "Association", "International", "Taxonomy", "(NANDA-I),", "the", "Nursing", "Interventions", "Classification", "(NIC),", "the", "Clinical", "Care", "Classification", "(CCC),", "the", "Omaha", "System,", "the", "Nursing", "Outcomes", "Classification", "(NOC),", "the", "Nursing", "Management", "Minimum", "Data", "Set", "(NMMDS),", "the", "Perioperative", "Nursing", "Data", "Set", "(PNDS),", "SNOMED", "Clinical", "Terms,", "the", "Nursing", "Minimum", "Data", "Set", "(NMDS),", "the", "International", "Classification", "for", "Nursing", "Practice", "(ICNP)", "from", "the", "International", "Council", "of", "Nurses,", "the", "ABCcodes,", "and", "the", "Logical", "Observation", "Identifiers", "Names", "and", "Codes", "(LOINC)", "[7].", "The", "North", "American", "Nursing", "Diagnosis", "Association", "International", "Taxonomy", "(NANDA-I)", "is", "considered", "the", "most" ]

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[ "Original", "Article", "The", "Prevalence", "of", "Human", "Papilloma", "Virus", "in", "Esophageal", "Squamous", "Cell", "Carcinoma", "IJMS", "Vol", "37,", "No", "2,", "June", "2012", "Sadat", "Noori1,", "Ahmad", "Monabati1,2,", "Abbasali", "Ghaderi3", "1Department", "of", "Pathology,", "School", "of", "Medicine,", "Shiraz", "University", "of", "Medical", "Sciences,", "Shiraz,", "Iran.", "2Hematology", "Research", "Center,", "Nemazee", "Hospital,", "Shiraz", "University", "of", "Medical", "Sciences,", "Shiraz,", "Iran.", "3Department", "of", "Immunology,", "School", "of", "Medicine,", "Shiraz", "University", "of", "Medical", "Sciences,", "Shiraz,", "Iran.", "Correspondence:", "Sadat", "Noori", "MD,", "Department", "of", "Pathology,", "School", "of", "Medicine,", "Shiraz", "University", "of", "Medical", "Sciences,", "Zand", "Avenue,", "Shiraz,", "Iran.", "Tel/Fax:", "+98", "711", "2349521", "Email:", "noorisadat@yahoo.com", "Received:", "13", "August", "2011", "Revised:", "29", "September", "2011", "Accepted:", "13", "November", "2011", "126", "Abstract", "Background:", "Carcinomas", "of", "esophagus,", "mostly", "squamous", "cell", "carcinomas,", "occur", "throughout", "the", "world.", "There", "are", "a", "number", "of", "suspected", "genetic", "or", "environmental", "etiologies.", "Human", "papilloma", "virus", "(HPV)", "is", "said", "to", "be", "a", "major", "etiology", "in", "areas", "with", "high", "incidence", "of", "esophageal", "carcinoma,", "while", "it", "is", "hardly", "detectable", "in", "low", "incidence", "regions.", "This", "study", "was", "designed", "to", "evaluate", "the", "prevalence", "of", "HPV", "in", "esophageal", "squamous", "cell", "carcinoma", "(ESCC)", "cases", "diagnosed", "in", "Pathology", "Department,", "Medical", "School,", "Shiraz", "University", "of", "Medical", "Sciences.", "Methods:", "DNA", "material", "for", "PCR", "amplification", "of", "HPV", "genome", "was", "extracted", "from", "formalin-fixed", "paraffin-embedded", "tissue", "blocks", "of", "92", "cases", "of", "ESCC,", "diagnosed", "during", "20", "years", "from", "1982", "to", "2002.", "Polymerase", "chain", "reaction", "was", "performed", "for", "amplification", "and", "detection", "of", "common", "HPV", "and", "type", "specific", "HPV-16", "and", "HPV-18", "genomic", "sequences", "in", "the", "presence", "of", "positive", "control", "(HPV-18", "and", "HPV", "positive", "biopsies", "of", "uterine", "exocervix)", "and", "additional", "internal", "controls", "i.e.", "beta-globin", "and", "cytotoxic", "T", "lymphocyte", "antigen", "4", "(CTLA4).", "Result:", "Good", "amplification", "of", "positive", "control", "and", "internal", "con-", "trols", "was", "observed.", "However,", "no", "amplification", "of", "HPV", "genome", "was", "observed.", "Conclusion:", "There", "is", "no", "association", "between", "HPV", "infection", "and", "the", "development", "of", "esophageal", "squamous", "cell", "carcinoma", "in", "the", "cases", "evaluated.", "Please", "cite", "this", "article", "as:", "Noori", "S,", "Monabati", "A,", "Ghaderi", "AA.", "The", "Prevalence", "of", "Human", "Papilloma", "Virus", "in", "Esophageal", "Squamous", "Cell", "Carcinoma.", "Iran", "J", "Med", "Sci.", "2012;37(2):126-133.", "Keywords", "●", "Squamous", "cell", "carcinoma", "●", "esophagus", "●", "human", "papilloma", "virus", "●", "polymerase", "chain", "reaction", "Introduction", "Malignant", "esophageal", "tumors", "usually", "arise", "from", "epithelial", "layer", "of", "the", "esophagus.", "Worldwide,", "squamous", "cell", "carcinomas", "(SCC)", "constitute", "90%", "of", "esophageal", "cancers", "although", "in", "some", "regions", "such", "as", "United", "States", "their", "incidence", "is", "comparable", "to", "that", "of", "adenocarcinomas.", "While", "esophageal", "SCC", "(ESCC)", "occurs", "throughout", "the", "world,", "its", "incidence", "varies", "widely", "among", "countries", "and", "within", "regions", "of", "the", "same", "country.", "The", "region", "extending", "from", "northern", "Iran", "across", "central", "Asia", "to", "northern", "China", "exhibits", "annual", "incidence", "rate", "exceeding", "100", "per", "100,000", "with", "deaths", "from", "cancer", "of", "the", "esophagus", "constituting", "more", "than", "20%", "of", "all", "cancer", "deaths.", "The", "death", "from", "cancer", "of", "the", "esophagus", "in", "this", "area", "constitutes", "more", "than", "20%", "of", "all", "cancer", "deaths.1", "Fars", "province", "in", "the", "south", "of", "Iran", "with", "an", "average", "annual", "Iran", "J", "Med", "Sci", "June", "2012;", "Vol", "37", "No", "2" ]

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[ "International", "Scholarly", "Research", "Network", "ISRN", "Dentistry", "Volume", "2012,", "Article", "ID", "695151,", "5", "pages", "doi:10.5402/2012/695151", "Research", "Article", "The", "Effect", "of", "Three", "Different", "Disinfection", "Materials", "on", "Alginate", "Impression", "by", "Spray", "Method", "Hamid", "Badrian,1", "Ehsan", "Ghasemi,2", "Navid", "Khalighinejad,1", "and", "Nafiseh", "Hosseini3", "1", "Dental", "Implant", "Research", "Center,", "School", "of", "Dentistry,", "Isfahan", "University", "of", "Medical", "sciences,", "81746-73461", "Isfahan,", "Iran", "2", "Department", "of", "Prosthodontic,", "Torabinezhad", "Center", "Research,", "Dental", "School,", "University", "of", "Medical", "Sciences,", "81746-73461", "Isfahan,", "Iran", "3", "Department", "of", "Microbiology,", "School", "of", "Medicine,", "Isfahan", "University", "of", "Medical", "Sciences,", "81746-73461", "Isfahan,", "Iran", "Correspondence", "should", "be", "addressed", "to", "Ehsan", "Ghasemi,", "e", "ghasemi@yahoo.com", "Received", "11", "April", "2012;", "Accepted", "6", "June", "2012", "Academic", "Editors:", "M.", "Behr,", "M.", "Del", "Fabbro,", "and", "D.", "Wray", "Copyright", "©", "2012", "Hamid", "Badrian", "et", "al.", "This", "is", "an", "open", "access", "article", "distributed", "under", "the", "Creative", "Commons", "Attribution", "License,", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited.", "Introduction.", "The", "aim", "of", "this", "study", "was", "to", "investigate", "the", "effect", "of", "three", "different", "types", "of", "disinfectant", "agents", "on", "alginate", "impression", "material", "after", "5", "and", "10", "minutes.", "Method", "and", "Materials.", "In", "this", "in", "vitro", "experimental", "study,", "66", "circular", "samples", "of", "alginate", "impression", "material", "were", "contaminated", "with", "Staphylococcus", "aureus,", "Pseudomonas", "aeruginosa,", "and", "Candida", "albicans", "fungus.", "Except", "for", "control", "samples,", "all", "of", "them", "were", "disinfected", "with", "sodium", "hypochlorite", "0.525,", "Deconex,", "and", "Epimax", "by", "way", "of", "spraying.", "Afterwards,", "they", "were", "kept", "in", "plastic", "bags", "with", "humid", "rolled", "cotton", "for", "5", "and", "10", "minutes.", "The", "number", "of", "colonies", "was", "counted", "after", "24", "and", "48", "hours", "for", "bacteria", "and", "after", "72", "hours", "for", "fungus.", "Statistical", "Mann-Whitney", "test", "was", "used", "for", "data", "analysis", "(α", "=", "0.05).", "Results.", "After", "5", "minutes,", "Epimax", "showed", "the", "highest", "disinfection", "action", "on", "Staphylococcus", "aureus", "as", "it", "completely", "eradicated", "the", "bacteria.", "The", "disinfection", "capacity", "of", "different", "agents", "can", "be", "increased", "as", "time", "elapses", "except", "for", "Pseudomonas", "aeruginosa", "which", "was", "eradicated", "completely", "in", "both", "5", "and", "10", "minutes.", "Conclusion.", "This", "study", "revealed", "that", "alginate", "can", "be", "effectively", "disinfected", "by", "three", "types", "of", "disinfecting", "agents", "by", "spraying", "method,", "although", "Epimax", "showed", "the", "highest", "disinfection", "action", "after", "10", "minutes", "compared", "to", "other", "agents.", "1.", "Introduction", "Dentists,", "dental", "materials,", "and", "dental", "laboratories", "are", "exposed", "to", "different", "types", "of", "pathogenic", "microorganisms.", "Impression", "materials,", "impression", "trays,", "and", "poured", "stone", "cast", "have", "been", "said", "to", "be", "the", "main", "source", "of", "cross", "infection", "between", "patients", "and", "dentists", "[1].", "New", "researches", "have", "shown", "that", "67%", "of", "materials", "sent", "to", "dental", "laboratories", "are", "infected", "by", "various", "microorganisms", "[2].", "The", "most", "frequently", "identified", "microorganisms", "are", "Streptococcus", "species,", "Staphylococcus", "species,", "Escherichia", "coli", "species,", "Actinomyces", "species,", "Antitratus", "species,", "Pseudomonas", "species,", "Enterobacter", "species,", "Klebsiella", "pneumonia,", "and", "Can-", "dida", "species", "[3].", "Taking", "this", "into", "account,", "we", "should", "make", "an", "effort", "to", "eliminate", "most", "of", "these", "microorganisms", "and", "reduce", "the", "rate", "of", "infection", "transmission", "in", "dental", "laboratories.", "The", "International", "Dental", "Federation", "(IDF)", "insists", "on", "disinfecting", "all", "impressions", "taken", "from", "patients", "before", "sending", "them", "to", "laboratories", "[4].", "Also", "the", "American", "Dental", "Association", "(ADA)", "has", "advised", "all", "dental", "stuffs", "to", "disinfect", "patients’", "impression", "trays", "[5].", "In", "some", "studies,", "it", "has", "been", "declared", "that", "washing", "the", "impression", "materials", "with", "tap", "water", "only", "removes", "40%", "of", "bacteria;", "however,", "some", "studies", "reported", "that", "it", "has", "the", "capacity", "to", "reduce", "90%,", "microorganisms", "[6].", "The", "most", "common", "chemical", "disinfectants", "which", "are", "used", "by", "dentists", "are", "alcohols,", "aldehydes,", "chlorine", "combination,", "phenols,", "biguanides,", "iodide", "combinations,", "and", "ammonium", "[7].", "There", "are", "two", "common", "methods", "to", "disinfect", "dental", "materials:", "(1)", "immersion", "and", "(2)", "spraying", "[6].", "Disinfection", "by", "soaking", "in", "chemical", "materials", "has", "been", "shown", "to", "cover", "all", "surfaces", "of", "impression", "materials", "in", "one", "time", "[8],", "while", "spraying", "is", "not", "capable", "of", "disinfecting", "all", "surfaces", "effectively", "and", "also", "cannot", "cover", "all", "undercuts.", "Contrary", "to", "immersing,", "spraying", "can", "significantly", "reduce", "the" ]

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[ "Implementation", "Science", "Research", "article", "Explaining", "the", "effects", "of", "an", "intervention", "designed", "to", "promote", "evidence-based", "diabetes", "care:", "a", "theory-based", "process", "evaluation", "of", "a", "pragmatic", "cluster", "randomised", "controlled", "trial", "Jillian", "J", "Francis*1,", "Martin", "P", "Eccles2,", "Marie", "Johnston3,", "Paula", "Whitty2,", "Jeremy", "M", "Grimshaw4,", "Eileen", "FS", "Kaner5,", "Liz", "Smith6", "and", "Anne", "Walker1", "BioMed", "Central", "Open", "Access", "Address:", "1Health", "Services", "Research", "Unit,", "University", "of", "Aberdeen,", "Aberdeen,", "UK,", "2Institute", "of", "Health", "and", "Society,", "Newcastle", "University,", "Newcastle", "upon", "Tyne,", "UK,", "3College", "of", "Life", "Sciences", "and", "Medicine,", "University", "of", "Aberdeen,", "Aberdeen,", "UK,", "4Clinical", "Epidemiology", "Program,", "Ottawa", "Health", "Research", "Institute", "and", "Department", "of", "Medicine,", "University", "of", "Ottawa,", "Ontario,", "Canada,", "5Faculty", "of", "Medical", "Sciences,", "Newcastle", "University,", "Newcastle", "upon", "Tyne,", "UK", "and", "6Manchester", "Business", "School,", "University", "of", "Manchester,", "Manchester,", "UK", "Email:", "Jillian", "J", "Francis*", "-", "j.francis@abdn.ac.uk;", "Martin", "P", "Eccles", "-", "Martin.Eccles@newcastle.ac.uk;", "Marie", "Johnston", "-", "m.johnston@abdn.ac.uk;", "Paula", "Whitty", "-", "p.m.whitty@ncl.ac.uk;", "Jeremy", "M", "Grimshaw", "-", "jgrimshaw@ohri.ca;", "Eileen", "FS", "Kaner", "-", "E.F.S.Kaner@newcastle.ac.uk;", "Liz", "Smith", "-", "liz.smith@mbs.ac.uk;", "Anne", "Walker", "-", "anne_walker@yahoo.co.uk", "*", "Corresponding", "author", "Published:", "19", "November", "2008", "Implementation", "Science", "2008,", "3:50", "doi:10.1186/1748-5908-3-50", "This", "article", "is", "available", "from:", "http://www.implementationscience.com/content/3/1/50", "Received:", "1", "May", "2006", "Accepted:", "19", "November", "2008", "©", "2008", "Francis", "et", "al;", "licensee", "BioMed", "Central", "Ltd.", "This", "is", "an", "Open", "Access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "License", "(http://creativecommons.org/licenses/by/2.0),", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited.", "Abstract", "Background:", "The", "results", "of", "randomised", "controlled", "trials", "can", "be", "usefully", "illuminated", "by", "studies", "of", "the", "processes", "by", "which", "they", "achieve", "their", "effects.", "The", "Theory", "of", "Planned", "Behaviour", "(TPB)", "offers", "a", "framework", "for", "conducting", "such", "studies.", "This", "study", "used", "TPB", "to", "explore", "the", "observed", "effects", "in", "a", "pragmatic", "cluster", "randomised", "controlled", "trial", "of", "a", "structured", "recall", "and", "prompting", "intervention", "to", "increase", "evidence-based", "diabetes", "care", "that", "was", "conducted", "in", "three", "Primary", "Care", "Trusts", "in", "England.", "Methods:", "All", "general", "practitioners", "and", "nurses", "in", "practices", "involved", "in", "the", "trial", "were", "sent", "a", "postal", "questionnaire", "at", "the", "end", "of", "the", "intervention", "period,", "based", "on", "the", "TPB", "(predictor", "variables:", "attitude;", "subjective", "norm;", "perceived", "behavioural", "control,", "or", "PBC).", "It", "focussed", "on", "three", "clinical", "behaviours", "recommended", "in", "diabetes", "care:", "measuring", "blood", "pressure;", "inspecting", "feet;", "and", "prescribing", "statins.", "Multivariate", "analyses", "of", "variance", "and", "multiple", "regression", "analyses", "were", "used", "to", "explore", "changes", "in", "cognitions", "and", "thereby", "better", "understand", "trial", "effects.", "Results:", "Fifty-nine", "general", "medical", "practitioners", "and", "53", "practice", "nurses", "(intervention:", "n", "=", "55,", "41.98%", "of", "trial", "participants;", "control:", "n", "=", "57,", "38.26%", "of", "trial", "participants)", "completed", "the", "questionnaire.", "There", "were", "no", "differences", "between", "groups", "in", "mean", "scores", "for", "attitudes,", "subjective", "norms,", "PBC", "or", "intentions.", "Control", "group", "clinicians", "had", "'normatively-driven'", "intentions", "(i.e.,", "related", "to", "subjective", "norm", "scores),", "whereas", "intervention", "group", "clinicians", "had", "'attitudinally-driven'", "intentions", "(i.e.,", "related", "to", "attitude", "scores)", "for", "foot", "inspection", "and", "statin", "prescription.", "After", "controlling", "for", "effects", "of", "the", "three", "predictor", "variables,", "this", "group", "difference", "was", "significant", "for", "foot", "inspection", "behaviour", "(trial", "group", "×", "attitude", "interaction,", "beta", "=", "0.72,", "p", "<", "0.05;", "trial", "group", "×", "subjective", "norm", "interaction,", "beta", "=", "-0.65,", "p", "<", "0.05).", "Conclusion:", "Attitudinally-driven", "intentions", "are", "proposed", "to", "be", "more", "consistently", "translated", "into", "action", "than", "normatively-driven", "intentions.", "This", "proposition", "was", "supported", "by", "the", "findings,", "thus", "offering", "an", "interpretation", "of", "the", "trial", "effects.", "This", "analytic", "approach", "demonstrates", "the", "potential", "of", "the", "TPB", "to", "explain", "trial", "effects", "in", "terms", "of", "different", "relationships", "between", "variables", "rather", "than", "differences", "in", "mean", "scores.", "This", "study", "illustrates", "the", "use", "of", "theory-based", "process", "evaluation", "to", "uncover", "processes", "underlying", "change", "in", "implementation", "trials.", "Page", "1", "of", "11", "(page", "number", "not", "for", "citation", "purposes)" ]

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[ "Dempfle", "et", "al.", "Critical", "Care", "2011,", "15:R23", "http://ccforum.com/content/15/1/R23", "R", "E", "S", "E", "A", "R", "C", "H", "Open", "Access", "Endogenous", "plasma", "activated", "protein", "C", "levels", "and", "the", "effect", "of", "enoxaparin", "and", "drotrecogin", "alfa", "(activated)", "on", "markers", "of", "coagulation", "activation", "and", "fibrinolysis", "in", "pulmonary", "embolism", "Carl-Erik", "H", "Dempfle1*,", "Elif", "Elmas1,", "Andreas", "Link2,", "Nenad", "Suvajac1,", "Volker", "Liebe1,", "Jonathan", "Janes3,", "Martin", "Borggrefe1", "Abstract", "Introduction:", "There", "are", "no", "published", "data", "on", "the", "status", "of", "endogenous", "activated", "protein", "C", "(APC)", "in", "pulmonary", "embolism", "(PE),", "and", "no", "data", "on", "the", "effect", "of", "drotrecogin", "alfa", "(activated)", "(DAA)", "given", "in", "addition", "to", "therapeutic", "dose", "enoxaparin.", "Methods:", "In", "this", "double-blind", "clinical", "trial,", "47", "patients", "with", "computed", "tomography", "(CT)-confirmed", "acute", "submassive", "PE", "treated", "with", "1", "mg/kg", "body", "weight", "of", "enoxaparin", "twice", "daily", "were", "randomized", "to", "groups", "receiving", "a", "12-hour", "intravenous", "infusion", "of", "6,", "12,", "18,", "or", "24", "μg/kg/hour", "of", "DAA", "or", "a", "placebo.", "Blood", "samples", "were", "drawn", "before", "starting", "DAA", "infusion,", "after", "4,", "8", "and", "12", "hours", "(at", "the", "end", "of", "the", "infusion", "period),", "and", "on", "treatment", "days", "2,", "3,", "4,", "5", "and", "6.", "Results:", "Initial", "endogenous", "plasma", "activated", "protein", "C", "(APC)", "levels", "were", "0.36", "±", "0.48", "ng/ml", "(<0.10", "to", "1.72", "ng/ml)", "and", "remained", "in", "the", "same", "range", "in", "the", "placebo", "group.", "APC", "levels", "in", "patients", "treated", "with", "DAA", "were", "13.67", "±", "3.57", "ng/ml,", "32.71", "±", "8.76", "ng/ml,", "36.13", "±", "7.60", "ng/ml,", "and", "51.79", "±", "15.84", "ng/ml", "in", "patients", "treated", "with", "6,", "12,", "18,", "and", "24", "μg/kg/hour", "DAA,", "respectively.", "In", "patients", "with", "a", "D-dimer", "level", ">4", "mg/L", "indicating", "a", "high", "level", "of", "acute", "fibrin", "formation", "and", "dissolution,", "DAA", "infusion", "resulted", "in", "a", "more", "rapid", "drop", "in", "soluble", "fibrin,", "D-dimer,", "and", "fibrinogen/", "fibrin", "degradation", "products", "(FDP)", "levels,", "compared", "to", "enoxaparin", "alone.", "There", "was", "a", "parallel", "decline", "of", "soluble", "fibrin,", "D-dimer,", "FDP,", "and", "plasmin-plasmin", "inhibitor", "complex", "(PPIC)", "in", "response", "to", "treatment", "with", "enoxaparin", "±", "DAA,", "with", "no", "evidence", "of", "a", "systemic", "profibrinolytic", "effect", "of", "the", "treatment.", "Conclusions:", "In", "patients", "with", "acute", "submassive", "PE", "endogenous", "APC", "levels", "are", "low.", "DAA", "infusion", "enhances", "the", "inhibition", "of", "fibrin", "formation.", "Trial", "registration:", "ClinicalTrials.gov:", "NCT00191724", "Introduction", "Activated", "protein", "C", "inhibits", "blood", "coagulation", "by", "inacti-", "vating", "factors", "Va", "and", "VIIIa", "[1].", "Inactivation", "of", "factor", "VIIIa", "reduces", "the", "activity", "of", "the", "tenase", "complex", "and", "the", "production", "of", "factor", "Xa.", "Inactivation", "of", "factor", "Va", "reduces", "the", "activity", "of", "the", "prothrombinase", "complex", "and", "the", "production", "of", "thrombin.", "Both", "mechanisms", "reduce", "*", "Correspondence:", "carl-erik.dempfle@umm.de", "1I.", "Department", "of", "Medicine,", "University", "Medical", "Center", "Mannheim,", "Theodor", "Kutzer", "Ufer,", "Mannheim,", "D-68167,", "Germany", "Full", "list", "of", "author", "information", "is", "available", "at", "the", "end", "of", "the", "article", "the", "amount", "of", "thrombin", "and", "fibrin", "generated.", "In", "vivo,", "protein", "C", "is", "activated", "by", "the", "thrombin-thrombomodulin", "complex,", "which", "forms", "when", "thrombin", "binds", "to", "throm-", "bomodulin", "on", "intact", "endothelium.", "Binding", "of", "thrombin", "to", "thrombomodulin", "also", "changes", "the", "specificity", "of", "thrombin", "from", "a", "procoagulant", "to", "an", "anticoagulant", "enzyme", "[2].", "In", "addition", "to", "its", "effects", "on", "blood", "coagula-", "tion", "activation,", "activated", "protein", "C", "when", "bound", "to", "the", "endothelial", "protein", "C", "receptor", "(EPCR),", "activa-", "tes", "protease-activated", "receptors", "(PARs),", "inducing", "a", "variety", "of", "cytoprotective", "cellular", "responses,", "including", "©", "2011", "Dempfle", "et", "al.;", "licensee", "BioMed", "Central", "Ltd.", "This", "is", "an", "open", "access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "License", "(http://creativecommons.org/licenses/by/2.0),", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited." ]

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[ "PSYCHIATRY", "Hepatitis", "A", "virus", "among", "drug", "users", "and", "the", "role", "of", "vaccination:", "a", "review", "Fabio", "Lugoboni", "*,", "Benedetta", "Pajusco,", "Anna", "Albiero", "and", "Gianluca", "Quaglio", "Addiction", "Unit,", "Department", "of", "Internal", "Medicine,", "Verona", "University", "Hospital,", "Verona,", "Italy", "REVIEW", "ARTICLE", "published:", "12", "January", "2012", "doi:", "10.3389/fpsyt.2011.00079", "Edited", "by:", "Lorenzo", "Leggio,", "Gemelli", "Hospital,", "Italy", "Reviewed", "by:", "Anna", "Ferrulli,", "Catholic", "University", "of", "Rome,", "Italy", "Giovanni", "Addolorato,", "Catholic", "University", "of", "Rome,", "Italy", "*Correspondence:", "Fabio", "Lugoboni", ",", "Addiction", "Unit,", "Department", "of", "Internal", "Medicine,", "Verona", "University", "Hospital,", "P.le", "L.A.", "Scuro", "10,", "37134", "Verona,", "Italy.", "e-mail:", "fabio.lugoboni@", "ospedaleuniverona.it", "In", "countries", "with", "advanced", "economies", "better", "health", "and", "hygiene", "conditions,", "along", "with", "the", "introduction,", "in", "some", "cases,", "of", "global", "vaccination,", "have", "relegated", "most", "viral", "hepatitis", "to", "marginal", "social", "groups", "and,", "in", "particular,", "drug", "users", "(DUs).", "The", "availability", "of", "safe", "and", "effective", "vaccines", "for", "hepatitis", "A", "virus", "(HAV)", "and", "B", "(HBV)", "may", "play", "a", "major", "role", "in", "combating", "this", "phenomenon.", "Despite", "the", "availability", "of", "a", "safe", "and", "effective", "vaccine", "for", "over", "a", "decade", "and", "the", "recommendations", "of", "international", "health", "organizations,", "vaccinations", "against", "HAV", "among", "DUs", "are", "not", "as", "widely", "known", "and", "available", "as", "are", "HBV", "vaccinations.", "The", "purpose", "of", "this", "review", "article", "is", "to", "present", "the", "most", "significant", "data", "in", "the", "literature", "on", "the", "preva-", "lence", "of", "HAV", "among", "DUs", "and", "the", "role", "of", "targeted", "vaccination.", "To", "our", "knowledge,", "the", "present", "article", "is", "the", "first", "to", "solely", "deal", "with", "vaccination", "against", "HAV", "in", "DUs.", "Immunization", "after", "the", "administration", "of", "anti-HAV", "vaccine", "has", "been", "demonstrated", "in", "DUs", "even", "if", "they", "have", "responded", "significantly", "less", "than", "either", "the", "general", "population", "or", "carriers", "of", "chronic", "liver", "disease.", "All", "the", "vaccines", "were", "well", "tolerated", "and", "adherence", "to", "the", "vaccine", "schedule", "was", "good.", "Further", "studies", "are", "needed", "to", "optimize", "the", "timing", "and", "doses", "of", "vaccine", "to", "be", "administered", "to", "DUs,", "especially", "to", "assess", "adherence", "and", "antibody", "persistence.", "Vaccination", "campaigns", "are", "feasible", "among", "DUs", "and", "have", "proven", "to", "be", "highly", "cost–effective.", "Keywords:", "adherence,", "drug", "users,", "hepatitis", "A", "vaccination,", "intravenous,", "immunization,", "HAV,", "vaccine,", "DUs", "INTRODUCTION", "Addiction", "and", "diffusion", "of", "viral", "hepatitis", "are", "two", "different", "phe-", "nomena", "but", "have", "long", "been", "closely", "correlated.", "Addiction", "is", "a", "global", "phenomenon,", "with", "geographic", "location", "having", "relatively", "little", "to", "do", "with", "its", "progress", "in", "a", "country,", "while", "there", "are", "large", "differences", "in", "the", "spread", "of", "viral", "hepatitis", "as", "related", "to", "its", "progression", "in", "dif-", "ferent", "countries.", "Such", "differences", "tend", "to", "decrease", "significantly", "among", "drug", "users", "(DUs;", "United", "Nations", "Office", "on", "Drug,", "and", "Crime,", "2006;", "Aceijas", "et", "al.,", "2004).", "In", "drug-addicted", "patients,", "in", "conjunction", "with", "the", "decrease", "of", "HIV-rate", "mortality,", "death", "from", "liver", "diseases", "have", "significantly", "increased", "(EMCDDA,", "2003;", "Schae-", "fer", "and", "Mauss,", "2008).", "Counteracting", "this", "spread", "is", "a", "priority", "task,", "which", "has", "to", "involve", "all", "the", "structures", "that", "can", "interact", "with", "drug", "abusers.", "Hepatitis", "C", "virus", "(HCV)", "is", "surely", "the", "most", "important", "hepatitis", "among", "DUs", "regarding", "both", "its", "diffusion", "and", "its", "high", "percentage", "of", "chronic", "disease.", "Currently,", "it", "is", "the", "most", "common", "cause", "of", "chronic", "hepatitis", "in", "developed", "countries", "(Centers", "for", "Diseases", "Control", "and", "Prevention,", "2002;", "Schaefer", "and", "Mauss,", "2008).", "Health", "education", "and", "harm", "reduction", "policies", "(i.e.,", "methadone", "or", "buprenorphine", "maintenance", "therapies", "and", "needle-exchange", "programs)", "are", "at", "the", "moment", "the", "only", "measure", "of", "prevention", "of", "HCV,", "since", "there", "is", "neither", "specific", "vaccination", "nor", "effective", "prophylaxis", "against", "exposure.", "Interventions", "using", "strategies", "that", "Abbreviations:", "CLD,", "chronic", "liver", "disease;", "DUs,", "drug", "users;", "GPOP,", "general", "popula-", "tion;", "HAV,", "hepatitis", "A", "virus;", "HBV,", "hepatitis", "B", "virus;", "HCV,", "hepatitis", "C", "virus;", "HDV,", "hepatitis", "D", "virus.", "combined", "substance-use", "treatment", "and", "support", "for", "safe", "injection", "were", "most", "effective", "at", "reducing", "HCV", "seroconversion", "(Hagan", "et", "al.,", "2011).", "Vaccination", "campaigns", "targeted", "at", "high-risk", "groups", "and", "the", "introduction", "of", "mass", "vaccination", "in", "almost", "all", "developed", "countries", "has", "significantly", "reduced", "HBV", "prevalence", "among", "the", "youngest", "DUs", "(Baral", "et", "al.,", "2007;", "Brim", "et", "al.,", "2007).", "HBV", "infection", "through", "sexual", "transmission", "has", "an", "important", "role", "among", "non-injective", "DUs", "(Gyarmath", "et", "al.,", "2002;", "Rich", "et", "al.,", "2006).", "Hepatitis", "D", "virus", "(HDV)", "is", "caused", "by", "a", "defective", "RNA-virus", "that", "requires", "the", "presence", "of", "the", "HBV", "Surface", "Antigen", "for", "transmission.", "HDV", "can", "be", "acquired", "both", "as", "a", "co-infection", "with", "HBV", "and", "as", "an", "overlap", "in", "a", "chronic", "HBV", "carrier.", "HDV", "infection", "can", "be", "effec-", "tively", "prevented", "with", "vaccination", "against", "HBV,", "while", "protection", "does", "not", "exist", "for", "chronic", "HBV", "carriers.", "In", "Europe", "and", "in", "the", "USA", "HDV", "infection", "has", "almost", "disappeared", "in", "the", "general", "population", "(GPOP),", "remaining", "confined", "almost", "entirely", "to", "DUs", "(Gaeta", "et", "al.,", "2000;", "Farci,", "2003).", "Hepatitis", "A", "virus", "(HAV),", "the", "causative", "agent", "of", "type", "A", "viral", "hepatitis,", "is", "an", "ancient", "picornavirus", "virus,", "which", "was", "identified", "almost", "40", "years", "ago.", "Each", "year", "HAV", "affects", "1.5", "million", "people", "worldwide.", "The", "geography", "of", "infection", "is", "tightly", "linked", "to", "the", "quality", "of", "sewage", "water", "depuration", "systems.", "Improved", "living", "conditions", "and", "subsequent", "changes", "in", "HAV", "epidemiology", "have", "decreased", "the", "disease", "burden", "of", "hepatitis", "A", "in", "most", "developed", "countries", "(Martin", "and", "Lemon,", "2006;", "Koslap-petraco", "et", "al.,", "2008;", "Jacobsen", "and", "Wiersma,", "2010).", "The", "clinical", "manifestations", "of", "HAV", "infection", "range", "from", "asymptomatic", "to", "fulminant", "hepatitis.", "The", "severity", "of", "the", "disease", "is", "strongly", "dependent", "on", "the", "age", "of", "the", "host,", "being", "the", "asymptomatic", "disease", "typical", "of", "childhood", "while,", "www.frontiersin.org", "January", "2012", "|", "Volume", "2", "|", "Article", "79", "|", "1" ]

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[ "JCB", "Article", "Dislocation", "and", "degradation", "from", "the", "ER", "are", "regulated", "by", "cytosolic", "stress", "Judy", "K.", "VanSlyke", "and", "Linda", "S.", "Musil", "Division", "of", "Molecular", "Medicine,", "Oregon", "Health", "Sciences", "University,", "Portland,", "OR", "97201", "A", "dislocation", "of", "the", "substrate", "protein", "from", "the", "ER", "into", "key", "step", "in", "ER-associated", "degradation", "(ERAD)", "is", "the", "cytosol", "to", "gain", "access", "to", "the", "proteasome.", "Very", "little", "is", "known", "about", "how", "this", "process", "is", "regulated,", "especially", "in", "the", "case", "of", "polytopic", "proteins.", "Using", "pulse-chase", "analysis", "combined", "with", "subcellular", "fractionation,", "we", "show", "that", "connexins,", "the", "four", "transmembrane", "structural", "components", "of", "gap", "junctions,", "can", "be", "chased", "in", "an", "intact", "form", "from", "the", "ER", "membrane", "into", "the", "cytosol", "of", "proteasome", "inhibitor–", "treated", "cells.", "Dislocation", "of", "endogenously", "expressed", "connexin", "from", "the", "ER", "was", "reduced", "50–80%", "when", "the", "cytosolic", "heat", "shock", "response", "was", "induced", "by", "mild", "oxidative", "or", "thermal", "stress,", "but", "not", "by", "treatments", "that", "instead", "upregulate", "the", "ER", "unfolded", "protein", "response.", "Cytosolic", "but", "not", "ER", "stresses", "slowed", "the", "normally", "rapid", "degradation", "of", "connexins,", "and", "led", "to", "a", "striking", "increase", "in", "gap", "junction", "formation", "and", "function", "in", "otherwise", "assembly-inefficient", "cell", "types.", "These", "treatments", "also", "inhibited", "the", "dislocation", "and", "turnover", "of", "a", "connexin-unrelated", "ERAD", "substrate,", "unassembled", "major", "histocompatibility", "complex", "class", "I", "heavy", "chain.", "Our", "findings", "demonstrate", "that", "dislocation", "is", "negatively", "regulated", "by", "physiologically", "relevant,", "nonlethal", "stress.", "They", "also", "reveal", "a", "previously", "unrecognized", "relationship", "between", "cytosolic", "stress", "and", "intercellular", "communication.", "Introduction", "After", "insertion", "into", "the", "ER,", "nascent", "secretory", "proteins", "can", "either", "be", "exported", "to", "the", "Golgi", "or", "destroyed", "by", "ER-associated", "degradation", "(ERAD)*", "(McCracken", "and", "Brodsky,", "1996).", "ERAD", "is", "carried", "out", "by", "the", "26S", "proteasome,", "the", "multicata-", "lytic", "protease", "complex", "that", "mediates", "the", "majority", "of", "protein", "degradation", "in", "the", "cytosol", "and", "nucleus", "(Plemper", "and", "Wolf,", "1999).", "It", "has", "been", "demonstrated", "that", "ERAD", "substrates", "(with", "certain", "possible", "exceptions;", "Walter", "et", "al.,", "2001)", "gain", "access", "to", "the", "proteasome", "by", "being", "extracted", "from", "the", "ER", "via", "the", "Sec61", "translocon", "in", "a", "process", "referred", "to", "as", "disloca-", "tion", "(Wiertz", "et", "al.,", "1996b;", "Pilon", "et", "al.,", "1997;", "Plemper", "et", "al.,", "1997;", "Zhou", "and", "Schekman,", "1999).", "Major", "substrates", "for", "ERAD", "include", "proteins", "that", "are", "conformationally", "abnormal", "as", "a", "result", "of", "mutation,", "lack", "of", "assembly", "partners,", "or", "imper-", "fect", "folding.", "To", "date,", "no", "mechanism", "has", "been", "described", "to", "regulate", "the", "dislocation", "of", "multiple", "unrelated", "proteins", "under", "physiologically", "relevant", "conditions.", "Address", "correspondence", "to", "Linda", "S.", "Musil,", "Division", "of", "Molecular", "Medicine", "NRC3,", "Oregon", "Health", "Sciences", "University,", "3181", "Southwest", "Sam", "Jackson", "Park", "Rd.,", "Portland,", "OR", "97201.", "Tel.:", "(503)", "494-1300.", "Fax:", "(503)", "494-7368.", "E-mail:", "Musill@OHSU.edu", "*Abbreviations", "used", "in", "this", "paper:", "ALLN,", "acetyl-leu-leu-norleucinal;", "BFA,", "brefeldin", "A;", "Cx32,", "connexin32;", "Cx43,", "connexin43;", "ERAD,", "ER-", "associated", "degradation;", "MHC1,", "major", "histocompatibility", "complex", "class", "I;", "NAC,", "N-acetyl", "cysteine.", "Key", "words:", "endoplasmic", "reticulum;", "proteasome;", "heat-shock", "response;", "connexins;", "gap", "junctions", "", "The", "Rockefeller", "University", "Press,", "0021-9525/2002/04/381/14", "$5.00", "The", "Journal", "of", "Cell", "Biology,", "Volume", "157,", "Number", "3,", "April", "29,", "2002", "381–394", "http://www.jcb.org/cgi/doi/10.1083/jcb.200111045", "Connexins", "form", "a", "family", "of", "nonglycosylated,", "tetra-spanning", "proteins", "with", "both", "amino", "and", "carboxyl", "termini", "facing", "the", "cytosol.", "Connexins", "are", "the", "structural", "components", "in", "verte-", "brates", "of", "gap", "junctions,", "which", "are", "collections", "of", "intercellular", "channels", "that", "mediate", "the", "regulatable", "cell-to-cell", "transfer", "of", "low", "molecular", "mass", "substances", "including", "ions", "and", "second", "messengers", "(for", "review", "see", "Goodenough", "et", "al.,", "1996).", "Cell", "types", "differ", "greatly", "in", "the", "efficiency", "with", "which", "they", "assem-", "ble", "connexins", "into", "gap", "junctions", "under", "basal", "conditions,", "and", "have", "been", "operationally", "categorized", "as", "either", "assembly", "in-", "competent", "(no", "gap", "junctions),", "assembly", "inefficient", "(few", "gap", "junctions", "relative", "to", "the", "level", "of", "connexin", "expressed", "on", "the", "cell", "surface),", "or", "assembly", "efficient", "(Musil", "et", "al.,", "2000).", "Pulse-chase", "analysis", "in", "tissue", "culture", "cells", "and", "in", "whole", "organs", "has", "revealed", "that", "both", "gap", "junction–assembled", "and", "–unassociated", "forms", "of", "connexins", "turn", "over", "remarkably", "quickly", "(t1/2", "1.5–5", "h),", "much", "faster", "than", "most", "other", "types", "of", "plasma", "membrane", "proteins", "(Fallon", "and", "Goodenough,", "1981;", "Musil", "et", "al.,", "1990;", "Beardslee", "et", "al.,", "1998).", "We", "have", "recently", "shown", "that", "40%", "or", "more", "of", "newly", "synthesized", "wild-type", "connexin43", "(Cx43)", "and", "connexin32", "(Cx32),", "and", "up", "to", "100%", "of", "some", "mutant", "forms", "of", "Cx32,", "are", "rapidly", "degraded", "in", "the", "cell", "types", "examined", "even", "if", "their", "exit", "from", "the", "ER", "is", "blocked", "(VanSlyke", "et", "al.,", "2000).", "This", "ER-associated", "turnover", "is", "sensitive", "to", "chemical", "inhibitors", "of", "the", "proteasome", "but", "not", "of", "the", "lysosome,", "thereby", "characterizing", "connexins", "as", "substrates", "for", "ERAD.", "It", "is", "likely,", "but", "has", "not", "yet", "been", "381" ]

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[ "Hariri", "and", "Shin", "Biology", "of", "Mood", "&", "Anxiety", "Disorders", "2011,", "1:1", "http://www.biolmoodanxietydisord.com/content/1/1/1", "E", "D", "I", "T", "O", "R", "I", "A", "L", "Biology", "of", "Mood", "&", "Anxiety", "Disorders", "Open", "Access", "Welcome", "to", "Biology", "of", "Mood", "&", "Anxiety", "Disorders", "Ahmad", "R", "Hariri1*", "and", "Lisa", "M", "Shin2,3", "We", "are", "witnessing", "dramatic", "and", "exciting", "shifts", "in", "the", "very", "foundations", "of", "mental", "health", "and", "psychiatry", "[1-3].", "At", "this", "time", "perhaps", "more", "than", "any", "other", "it", "is", "impera-", "tive", "that", "research", "into", "the", "biological", "underpinnings", "of", "psychopathology", "be", "given", "a", "proper", "outlet", "to", "inform,", "educate", "and", "advance", "these", "processes", "in", "the", "service", "of", "improving", "the", "human", "condition.", "Indeed,", "specialized", "out-", "lets", "have", "been", "created", "for", "biological", "research", "in", "a", "num-", "ber", "of", "disorders", "including", "autism,", "schizophrenia", "and", "bipolar", "disorder", "[4-6].", "Surprisingly,", "no", "such", "dedicated", "outlet", "has", "been", "available", "for", "mood", "and", "anxiety", "disor-", "ders,", "the", "most", "common", "forms", "of", "psychopathology,", "until", "now.", "Biology", "of", "Mood", "&", "Anxiety", "Disorders", "(BMAD)", "is", "a", "new", "open", "access", "peer-reviewed", "journal", "that", "publishes", "highly", "innovative", "basic,", "translational", "and", "clinical", "research", "that", "advances", "our", "understanding", "of", "mood", "and", "anxiety", "disor-", "ders.", "The", "journal", "welcomes", "research", "in", "all", "areas", "relevant", "to", "the", "disorders", "at", "the", "level", "of", "their", "underlying", "mechan-", "isms.", "Research", "areas", "of", "interest", "include", "but", "are", "not", "lim-", "ited", "to:", "pathophysiology,", "predictive", "risk", "markers,", "treatment", "predictors,", "individual", "differences", "and", "develop-", "mental", "trajectories", "of", "mood", "and", "anxiety", "disorders.", "Experimental", "approaches", "include", "but", "are", "not", "limited", "to:", "neuroimaging,", "psychophysiology,", "behavioral", "and", "mole-", "cular", "genetics,", "pharmacology,", "gene-environment", "interac-", "tions,", "and", "non-human", "animal", "models.", "Our", "idea", "behind", "BMAD", "is", "to", "create", "a", "venue", "for", "cut-", "ting-edge", "research", "that", "will", "become", "the", "destination", "of", "choice", "for", "the", "best", "work", "in", "the", "field.", "We", "are", "dedicated", "to", "providing", "an", "outlet", "for", "contributions", "that", "advance", "the", "field", "in", "any", "significant", "way.", "We", "believe", "that", "BMAD", "will", "be", "an", "important", "platform", "for", "presenting", "the", "findings", "of", "those", "interested", "in", "the", "biology", "of", "mood", "and", "anxiety", "dis-", "orders", "at", "any", "and", "all", "levels.", "The", "enthusiastic", "response", "from", "colleagues", "in", "neuroscience,", "psychology,", "psychiatry,", "psychophysiology,", "pharmacology", "and", "genetics", "who", "have", "graciously", "committed", "their", "time", "and", "expertise", "by", "joining", "*", "Correspondence:", "ahmad.hariri@duke.edu", "1Laboratory", "of", "NeuroGenetics,", "Department", "of", "Psychology", "&", "Neuroscience,", "Institute", "for", "Genome", "Sciences", "&", "Policy,", "Duke", "University,", "Durham,", "NC", "USA", "Full", "list", "of", "author", "information", "is", "available", "at", "the", "end", "of", "the", "article", "the", "Editorial", "Board", "of", "BMAD", "[7]", "is", "testament", "to", "the", "value", "of", "this", "novel", "venue.", "Continued", "progress", "in", "understanding", "the", "biology", "of", "mood", "and", "anxiety", "disorders", "is", "critically", "dependent", "on", "the", "integration", "of", "knowledge", "gained", "across", "many", "disci-", "plines,", "methodologies", "and", "model", "systems;", "currently", "such", "knowledge", "is", "divided", "across", "publications", "in", "many", "journals,", "none", "of", "which", "is", "focused", "entirely", "on", "the", "biol-", "ogy", "of", "mood", "and", "anxiety", "disorders.", "The", "Editors", "of", "BMAD", "thus", "believe", "that", "there", "is", "a", "need", "for", "a", "dedicated", "journal", "in", "this", "highly", "diverse", "field,", "and", "given", "the", "rising", "popularity", "of", "open", "access", "publication,", "we", "thought", "that", "a", "new", "open", "access", "journal", "in", "our", "field", "was", "particularly", "timely.", "The", "three", "publications", "in", "this", "inaugural", "issue", "highlight", "the", "diversity", "and", "breadth", "of", "relevant", "research", "we", "seek", "to", "encourage", "and", "promote", "at", "BMAD.", "Fisher", "and", "colleagues", "report", "on", "a", "multimodal", "PET/fMRI", "study", "demonstrating", "that", "the", "balance", "between", "excitatory", "5-HT2A", "and", "inhibi-", "tory", "5-HT1A", "receptors", "in", "the", "medial", "prefrontal", "cortex", "determines,", "at", "least", "in", "part,", "the", "functional", "responsive-", "ness", "of", "the", "amygdala.", "These", "data", "provide", "unique", "insight", "into", "specific", "molecular", "mechanisms", "through", "which", "a", "common", "treatment", "target,", "namely", "5-HT", "signaling,", "mod-", "ulates", "a", "corticolimbic", "circuitry", "heavily", "implicated", "in", "the", "pathophysiology", "of", "mood", "and", "anxiety", "disorders.", "Murphy", "and", "Frodl", "present", "findings", "of", "altered", "white", "matter", "path-", "ways", "in", "depression", "derived", "from", "a", "meta-analysis", "of", "dif-", "fusion", "tensor", "imaging", "studies.", "Their", "meta-analysis", "reveals", "specific", "decreases", "in", "the", "functional", "integrity", "of", "the", "superior", "longitudinal", "fasciculus", "in", "patients", "with", "major", "depressive", "disorder.", "Finally,", "Waters", "and", "McCor-", "mick", "describe", "the", "challenges", "involved", "in", "examining", "the", "effect", "of", "exogenous", "corticosterone", "on", "anxiety-like", "and", "depressive", "behavior", "in", "adolescent", "rats.", "Such", "diversity", "will", "continue", "to", "be", "featured", "in", "the", "forthcoming", "months,", "including", "reviews", "on", "facial", "emotion", "processing", "in", "major", "depressive", "disorder,", "evoked", "potential", "studies", "in", "post", "traumatic", "stress", "disorder", "(PTSD),", "and", "validation", "criteria", "in", "animal", "models", "of", "anxiety", "and", "depression,", "as", "well", "as", "original", "research", "on", "the", "involvement", "of", "the", "habenula", "in", "PTSD.", "©", "2011", "Hariri", "and", "Shin;", "licensee", "BioMed", "Central", "Ltd.", "This", "is", "an", "Open", "Access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "License", "(http://creativecommons.org/licenses/by/2.0),", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited." ]

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[ "e", "n", "i", "c", "i", "d", "e", "M", "l", "a", "t", "n", "e", "m", "i", "r", "e", "p", "x", "E", "f", "o", "l", "a", "n", "r", "u", "o", "J", "e", "h", "T", "CORRESPONDENCE", "Andrea", "L.", "Cox:", "acox@jhmi.edu", "Abbreviations", "used:", "E1,", "envelope", "glycoprotein", "1;", "E2,", "envelope", "glycoprotein", "2;", "HCV,", "hepatitis", "C", "virus;", "HVR1,", "hypervariable", "region", "1;", "SFC,", "spot-forming", "colony.", "JEM", "©", "The", "Rockefeller", "University", "Press", "$8.00", "Vol.", "201,", "No.", "11,", "June", "6,", "2005", "1741–1752", "www.jem.org/cgi/doi/10.1084/jem.20050121", "A", "R", "T", "I", "C", "L", "E", "Cellular", "immune", "selection", "with", "hepatitis", "C", "virus", "persistence", "in", "humans", "Andrea", "L.", "Cox,1,2", "Timothy", "Mosbruger,1", "Qing", "Mao,1", "Zhi", "Liu,1", "Xiao-Hong", "Wang,1", "Hung-Chih", "Yang,1", "John", "Sidney,6", "Alessandro", "Sette,6", "Drew", "Pardoll,1,2,3,4", "David", "L.", "Thomas,1,5", "and", "Stuart", "C.", "Ray1", "1Department", "of", "Medicine,", "2Department", "of", "Oncology,", "3Department", "of", "Molecular", "Biology", "and", "Genetics,", "4Department", "of", "Pathology,", "and", "5Department", "of", "Epidemiology,", "Johns", "Hopkins", "Medical", "Institutions,", "Baltimore,", "MD", "21231", "6La", "Jolla", "Institute", "for", "Allergy", "and", "Immunology,", "San", "Diego,", "CA", "92121", "Hepatitis", "C", "virus", "(HCV)", "infection", "frequently", "persists", "despite", "substantial", "virus-specific", "cellular", "immune", "responses.", "To", "determine", "if", "immunologically", "driven", "sequence", "variation", "occurs", "with", "HCV", "persistence,", "we", "coordinately", "analyzed", "sequence", "evolution", "and", "CD8", "T", "cell", "responses", "to", "epitopes", "covering", "the", "entire", "HCV", "polyprotein", "in", "subjects", "who", "were", "followed", "prospectively", "from", "before", "infection", "to", "beyond", "the", "first", "year.", "There", "were", "no", "substitutions", "in", "T", "cell", "epitopes", "for", "a", "year", "after", "infection", "in", "a", "subject", "who", "cleared", "viremia.", "In", "contrast,", "in", "subjects", "with", "persistent", "viremia", "and", "detectable", "T", "cell", "responses,", "we", "observed", "substitutions", "in", "69%", "of", "T", "cell", "epitopes,", "and", "every", "subject", "had", "a", "substitution", "in", "at", "least", "one", "epitope.", "In", "addition,", "amino", "acid", "substitutions", "occurred", "13-fold", "more", "often", "within", "than", "outside", "T", "cell", "epitopes", "(P", "0.001,", "range", "5–38).", "T", "lymphocyte", "recognition", "of", "8", "of", "10", "mutant", "peptides", "was", "markedly", "reduced", "compared", "with", "the", "initial", "sequence,", "indicating", "viral", "escape.", "Of", "16", "nonenvelope", "substitutions", "that", "occurred", "outside", "of", "known", "T", "cell", "epitopes,", "8", "represented", "conversion", "to", "consensus", "(P", "0.015).", "These", "findings", "reveal", "two", "distinct", "mechanisms", "of", "sequence", "evolution", "involved", "in", "HCV", "persistence:", "viral", "escape", "from", "CD8", "T", "cell", "responses", "and", "optimization", "of", "replicative", "capacity.", "The", "World", "Health", "Organization", "estimates", "there", "are", "170", "million", "persons", "with", "hepatitis", "C", "virus", "(HCV)", "infection", "worldwide,", "and", "an", "esti-", "mated", "4", "million", "persons", "are", "infected", "with", "HCV", "in", "the", "United", "States", "(1,", "2).", "In", "most", "countries,", "HCV", "infection", "is", "found", "in", "1–2%", "of", "the", "general", "population", "and", "may", "cause", "cirrhosis", "or", "hepatocellular", "cancer,", "but", "only", "when", "infec-", "tion", "persists", "(3–7).", "Patients", "in", "the", "acute", "phase", "of", "HCV", "infection", "are", "much", "more", "likely", "to", "respond", "to", "therapy", "that", "is", "designed", "to", "eradicate", "the", "virus", "than", "are", "patients", "after", "progression", "to", "chronicity", "(8–10).", "The", "features", "unique", "to", "acute", "infection", "that", "allow", "increased", "responsiveness", "to", "interferon", "therapy", "remain", "unknown.", "Spontaneous", "clearance", "of", "HCV", "infection", "occurs", "in", "20%", "of", "acutely", "infected", "individuals", "and", "is", "associated", "with", "a", "broadly", "specific", "and", "vigorous", "cellular", "immune", "response", "(11–14).", "Although", "the", "cellular", "immune", "response", "is", "often", "less", "vigorous", "and", "more", "nar-", "rowly", "directed", "in", "those", "who", "fail", "to", "clear", "the", "infection,", "nonetheless,", "a", "cellular", "immune", "re-", "sponse", "often", "is", "present", "in", "early", "infection", "and", "may", "persist", "into", "chronic", "infection.", "Why", "the", "early", "response", "fails", "to", "control", "viremia", "in", "those", "who", "progress", "to", "chronic", "infection", "is", "not", "clear,", "but", "responses", "generated", "in", "acute", "infection", "have", "been", "shown", "to", "decline", "in", "some", "sub-", "jects", "who", "remained", "persistently", "infected,", "and", "chronic", "infection", "is", "characterized", "by", "low", "fre-", "quencies", "of", "CD8", "T", "cells", "in", "peripheral", "blood", "(13,", "15–20).", "Although", "the", "liver", "has", "the", "poten-", "tial", "to", "delete", "antigen-specific", "T", "cell", "responses,", "HCV-specific", "CD8", "CTL", "lines", "have", "been", "generated", "from", "the", "liver", "of", "chronically", "in-", "fected", "humans", "and", "chimpanzees;", "this", "suggests", "that", "elimination", "of", "HCV-specific", "lymphocytes", "from", "the", "liver", "is", "neither", "universal", "nor", "neces-", "sary", "for", "HCV", "persistence", "(21–24).", "Survival", "of", "HCV,", "despite", "virus-specific", "CD8", "CTL,", "might", "be", "explained", "by", "impaired", "cellular", "effector", "functions", "(proliferation,", "cytokine", "secretion,", "cytolytic", "activity),", "T", "cell", "exhaustion,", "or", "den-", "dritic", "cell", "dysfunction", "(16,", "25–27).", "A", "final", "possibility", "is", "that", "persistence", "is", "facilitated", "by", "viral", "evolution", "over", "the", "course", "of", "infection,", "enabling", "escape", "by", "mutation", "of", "key", "epitopes", "targeted", "by", "T", "lymphocytes.", "Mutational", "escape", "from", "T", "cell", "responses", "has", "been", "noted", "in", "HIV,", "1741" ]

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[ "Available", "online", "at", "http://www.biij.org/2010/2/e12", "doi:", "10.2349/biij.6.2.e12", "biij", "Biomedical", "Imaging", "and", "Intervention", "Journal", "REVIEW", "ARTICLE", "Development", "and", "use", "of", "iron", "oxide", "nanoparticles", "(Part", "1):", "Synthesis", "of", "iron", "oxide", "nanoparticles", "for", "MRI", "J", "Lodhia*,1,", "BAppSci", "(MedRadSci),", "G", "Mandarano1,", "BAppSci", "(MedRad),", "GradCert", "(Higher", "Ed.),", "NJ", "Ferris2,", "MBBS,", "MMed,", "FRANZCR,", "P", "Eu", "2", ",", "BSci.,", "MSci,", "SF", "Cowell", "1", ",", "PhD,", "MEd,", "ANMT", "1", "Division", "of", "Medical", "Radiations,", "School", "of", "Medical", "Sciences,", "RMIT", "University,", "Victoria,", "Australia", "2", "Peter", "MacCallum", "Cancer", "Institute,", "Melbourne,", "Victoria,", "Australia", "Received", "5", "August", "2009;", "accepted", "24", "November", "2009", "ABSTRACT", "Contrast", "agents,", "such", "as", "iron", "oxide,", "enhance", "MR", "images", "by", "altering", "the", "relaxation", "times", "of", "tissues", "in", "which", "the", "agent", "is", "present.", "They", "can", "also", "be", "used", "to", "label", "targeted", "molecular", "imaging", "probes.", "Unfortunately,", "no", "molecular", "imaging", "probe", "is", "currently", "available", "on", "the", "clinical", "MRI", "market.", "A", "promising", "platform", "for", "MRI", "contrast", "agent", "development", "is", "nanotechnology,", "where", "superparamagnetic", "iron", "oxide", "nanoparticles", "(SPIONS)", "are", "tailored", "for", "MR", "contrast", "enhancement,", "and/or", "for", "molecular", "imaging.", "SPIONs", "can", "be", "produced", "using", "a", "range", "of", "methods", "and", "the", "choice", "of", "method", "will", "be", "influenced", "by", "the", "characteristics", "most", "important", "for", "a", "particular", "application.", "In", "addition,", "the", "ability", "to", "attach", "molecular", "markers", "to", "SPIONS", "heralds", "their", "application", "in", "molecular", "imaging.", "There", "are", "many", "reviews", "on", "SPION", "synthesis", "for", "MRI;", "however,", "these", "tend", "to", "be", "targeted", "to", "a", "chemistry", "audience.", "The", "development", "of", "MRI", "contrast", "agents", "attracts", "experienced", "researchers", "from", "many", "fields", "including", "some", "researchers", "with", "little", "knowledge", "of", "medical", "imaging", "or", "MRI.", "This", "situation", "presents", "medical", "radiation", "practitioners", "with", "opportunities", "for", "involvement,", "collaboration", "or", "leadership", "in", "research", "depending", "on", "their", "level", "of", "commitment", "and", "their", "ability", "to", "learn.", "Medical", "radiation", "practitioners", "already", "possess", "a", "large", "portion", "of", "the", "understanding,", "knowledge", "and", "skills", "necessary", "for", "involvement", "in", "MRI", "development", "and", "molecular", "imaging.", "Their", "expertise", "in", "imaging", "technology,", "patient", "care", "and", "radiation", "safety", "provides", "them", "with", "skills", "that", "are", "directly", "applicable", "to", "research", "on", "the", "development", "and", "application", "of", "SPIONs", "and", "MRI.", "In", "this", "paper", "we", "argue", "that", "MRI", "SPIONs,", "currently", "limited", "to", "major", "research", "centres,", "will", "have", "widespread", "clinical", "use", "in", "the", "future.", "We", "believe", "that", "knowledge", "about", "this", "growing", "area", "of", "research", "provides", "an", "opportunity", "for", "medical", "radiation", "practitioners", "to", "enhance", "their", "specialised", "expertise", "to", "ensure", "best", "practice", "in", "a", "truly", "multi-disciplinary", "environment.", "This", "review", "outlines", "how", "and", "why", "SPIONs", "can", "be", "synthesised", "and", "examines", "their", "characteristics", "and", "limitations", "in", "the", "context", "of", "MR", "imaging.", "©", "2010", "Biomedical", "Imaging", "and", "Intervention", "Journal.", "All", "rights", "reserved.", "Keywords:", "Magnetic", "resonance", "imaging", "(MRI),", "iron", "oxide,", "nanoparticles,", "synthesis", "*", "Corresponding", "author.", "Present", "address:", "Division", "of", "Medical", "Radiations,", "School", "of", "Medical", "Sciences,", "RMIT", "University,", "Bundoora", "West", "campus,", "PO", "Box", "71,", "Bundoora", "3083,", "Victoria", "Australia.", "Tel:", "+", "61", "3", "9925", "6660;", "Fax:", "+61", "3", "9925", "7466;", "E-mail:", "jyoti.lodhia@rmit.edu.au", "(Jyoti", "Lodhia)." ]

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[ "Glarne", "Cyra", "tnemo", "published:", "23", "April", "2012", "doi:", "10.3389/fneur.2012.00056", "The", "“brain–skin", "connection”", "in", "protein", "misfolding", "and", "amyloid", "deposits:", "embryological,", "pathophysiological,", "and", "therapeutic", "common", "grounds?", "Philip", "P.", "Foster1,2,3,4*", "1", "Division", "of", "Pulmonary", "and", "Critical", "Care", "Medicine,", "Department", "of", "Internal", "Medicine,", "University", "ofTexas", "Medical", "Branch,", "Galveston,TX,", "USA", "2", "Division", "of", "Cognitive", "and", "Behavioral", "Neurology,", "Department", "of", "Neurology,", "University", "ofTexas", "Medical", "Branch,", "Galveston,TX,", "USA", "3", "Encephalogistics,", "Inc.,", "Galveston,TX,", "USA", "4", "Brain-Mind", "Project,", "Inc.,", "Galveston,TX,", "USA", "*Correspondence:", "ppfoster@utmb.edu", "A", "commentary", "on", "Association", "of", "skin", "with", "the", "pathogen-", "esis", "and", "treatment", "of", "neurodegenerative", "amyloidosis", "by", "Clos,", "A.", "L.,", "Kayed,", "R.,", "and", "Lasagna-", "Reeves,", "C.", "A.", "(2012).", "Front.", "Neur.", "3:5.", "doi:", "10.3389/fneur.2012.00005", "A", "brief", "history", "of", "amyloidosis", "goes", "back", "to", "autopsies", "of", "the", "seventeenth", "century", "report-", "ing", "a", "waxing", "substance", "(Cordier,", "2008).", "Later,", "in", "the", "middle", "of", "the", "nineteenth", "cen-", "tury,", "Rudolph", "Virchow", "described", "an", "“amy-", "loid”(starch,", "amulon,", "Greek,", "amylum,", "Latin)", "degeneration", "and", "infiltration", "of", "the", "lungs", "within", "alveoli", "and", "small", "vessels", "in", "a", "patient", "who", "presented", "with", "systemic", "amyloidosis", "(heart,", "lungs,", "liver,", "and", "kidneys;", "Cordier,", "2008).", "What", "amyloid-related", "diseases", "share", "is", "a", "common", "molecular", "ternary", "structure", "which", "involves", "abnormal", "aggregation", "of", "numerous", "widespread", "copies", "of", "the", "same", "protein", "into", "well-ordered", "filamentous", "β-sheet", "rich", "structures", "(Friedman,", "2011)", "known", "as", "amyloid", "fibrils", "of", "10–12", "nm", "diam-", "eters", "(Plante-Bordeneuve", "and", "Said,", "2011).", "This", "abnormal", "accumulation", "of", "amyloid", "oligomers,", "protofibrils,", "or", "fibrils", "is", "con-", "sidered", "to", "be", "one", "of", "the", "major", "contributor", "to", "neurodegeneration", "and", "the", "hallmark", "of", "Alzheimer’s", "(AD)", "and", "Parkinson’s", "diseases", "(Arora", "et", "al.,", "2004).", "A", "primary", "cause", "under-", "lying", "these", "accumulations", "is", "the", "folding", "of", "polypeptide", "chains", "to", "specific", "three-dimen-", "sional", "proteins", "in", "abnormal", "ways", "(Selkoe,", "2003).", "The", "progressive", "misfolding", "of", "spe-", "cific", "proteins", "into", "aggregation", "may", "lead", "to", "cell", "alteration", "or", "death.", "Aggregated", "forms", "share", "many", "characteristics.", "One", "of", "them", "is", "that", "amyloid", "deposits", "show", "specific", "optical", "behavior", "such", "as", "birefringence", "on", "binding", "dyes", "(Congo", "red).", "The", "systemic", "distribu-", "www.frontiersin.org", "tion", "of", "amyloidoses", "may", "produce", "extracel-", "lular", "deposits", "in", "multiple", "organs", "(Joachim", "et", "al.,", "1989).", "In", "this", "paper,", "Clos,", "Kayed,", "and", "Lasagna-Reeves", "present", "a", "novel", "perspective", "about", "the", "relation", "of", "dermis–epidermis–", "brain", "and", "offer", "a", "review", "about", "amyloid", "deposits", "that", "are", "central", "to", "the", "strong“brain–", "skin”", "connection.", "This", "connection", "starts", "as", "early", "as", "the", "sharing", "a", "joint", "embryological", "origin.", "Common", "multipotent", "embryonic", "progenitor", "stem", "cells", "from", "the", "ectoderm", "on", "the", "surface", "of", "the", "post-gastrulation", "embryo", "receive", "specific", "signaling", "from", "their", "envi-", "ronment", "that", "instruct", "them", "to", "commit", "to", "a", "particular", "differentiation", "program", "which", "will", "give", "rise", "to", "the", "nervous", "system", "or", "skin", "epithelium", "(Quan", "and", "Hassan,", "2005;", "Fuchs,", "2007).", "Clos,", "Kayed,", "and", "Lasagna-Reeves", "highlight", "common", "“brain–skin”", "patho-", "physiological", "disorders", "such", "as", "the", "role", "of", "presenilin", "1", "(PS-1)", "for", "proteolytic", "process-", "ing", "of", "the", "amyloid", "precursor", "protein", "(APP)", "which", "is", "altered", "in", "AD;", "alteration", "also", "found", "in", "skin", "cancers", "(Xia", "et", "al.,", "2001;", "Kang", "et", "al.,", "2002).", "They", "also", "draw", "parallels", "between", "neurodegenerative", "disorders", "of", "Parkinson’s", "disease", "(Lewy", "bodies,", "α-synuclein,", "mela-", "nin)", "and", "amyotrophic", "lateral", "sclerosis", "(ALS", "inclusion", "bodies)", "which", "share", "common", "fea-", "tures", "with", "skin", "diseases", "(Hays", "et", "al.,", "2006).", "In", "addition,", "Clos,", "Kayed,", "and", "Lasagna-Reeves", "are", "describing", "transdermal", "route-of-entry", "as", "an", "elected", "administration", "route", "for", "potential", "medications", "to", "patients", "with", "neurodegen-", "erative", "diseases", "such", "as", "Rivastigmine", "(AD", "and", "Parkinson),", "Rotigotine", "(Parkinson).", "A", "favorable", "coefficient", "of", "partition", "(physi-", "ologically", "based", "pharmacokinetics,", "PBPK;", "Thrall", "et", "al.,", "2002)", "to", "the", "brain", "via", "the", "skin", "vector", "seems", "promising", "for", "potential", "drugs", "targeting", "the", "brain", "(Zhao", "et", "al.,", "2011).", "In", "PDAPP", "transgenic", "mice,", "the", "immunization", "with", "the", "42-amino-acid", "form", "of", "the", "peptide", "(Aβ42)", "prevents", "the", "development", "of", "cere-", "bral", "β-amyloid-plaque", "formation,", "neuritic", "dystrophy", "and", "astrogliosis", "(Schenk", "et", "al.,", "1999);", "the", "transdermal", "route", "has", "also", "been", "successfully", "used", "without", "detrimental", "side", "effects", "such", "as", "T", "cell", "infiltration", "and", "cere-", "bral", "microhemorrhage", "(Nikolic", "et", "al.,", "2007).", "Occurrence", "of", "the", "systemic", "deposition", "of", "β-amyloid", "protein", "in", "multiple", "tissues", "such", "as", "skin", "or", "brain", "infers", "that", "the", "initial", "amy-", "loid", "protein", "may", "be", "produced", "locally", "in", "all", "organs", "affected", "or", "may,", "as", "observed", "in", "other", "human", "amyloidoses,", "be", "derived", "from", "a", "com-", "mon", "circulating", "precursor", "(Joachim", "et", "al.,", "1989).", "Therefore", "the", "transdermal", "β-amyloid", "immunization", "also", "directly", "targeting", "skin", "β-amyloid", "deposits", "may", "further", "reduce", "a", 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[ "J", "Korean", "Med", "Sci", "2008;", "23:", "533-6", "ISSN", "1011-8934", "DOI:", "10.3346/jkms.2008.23.3.533", "Copyright", "The", "Korean", "Academy", "of", "Medical", "Sciences", "A", "Case", "of", "a", "Patient", "with", "Both", "Chorea", "and", "Restless", "Legs", "Syndrome", "The", "patient", "was", "a", "44-yr-old", "man", "with", "end-stage", "renal", "disease", "who", "had", "developed", "chorea", "as", "a", "result", "of", "hypoglycemic", "injury", "to", "the", "basal", "ganglia", "and", "thalamus", "and", "who", "was", "subsequently", "diagnosed", "with", "depression", "and", "restless", "legs", "syndrome", "(RLS).", "For", "proper", "management,", "the", "presence", "of", "a", "complex", "medical", "condition", "including", "two", "contrasting", "diseases,", "chorea", "and", "RLS,", "had", "to", "be", "considered.", "Tra-", "madol", "improved", "the", "pain", "and", "dysesthetic", "restlessness", "in", "his", "feet", "and", "legs,", "and", "this", "was", "gradually", "followed", "by", "improvements", "in", "his", "depressed", "mood,", "insomnia,", "lethar-", "gy,", "and", "feelings", "of", "hopelessness.", "This", "case", "suggests", "that", "the", "dopaminergic", "sys-", "tem", "participates", "intricately", "with", "the", "opioid,", "serotoninergic,", "and", "noradrenergic", "sys-", "tems", "in", "the", "pathophysiology", "of", "RLS", "and", "pain", "and", "indirectly", "of", "depression", "and", "insomnia.", "Key", "Words", ":", "Restless", "Legs", "Syndrome;", "Chorea;", "Sleep", "Initiation", "and", "Maintenance", "Disorde;", "Depression;", "Tra-", "madol", "Yoon-Kyung", "Shin,", "Seung-Chul", "Hong,", "Yon", "Kwon", "Ihn*,", "Jong-Hyun", "Jeong,", "Jin-Hee", "Han,", "and", "Sung-Pil", "Lee", "Departments", "of", "Psychiatry", "and", "Radiology*,", "St.", "Vincent’s", "Hospital,", "The", "Catholic", "University", "of", "Korea", "College", "of", "Medicine,", "Suwon,", "Korea", "Received", ":", "20", "April", "2007", "Accepted", ":", "20", "September", "2007", "Address", "for", "correspondence", "Seung-Chul", "Hong,", "M.D.", "Department", "of", "Psychiatry,", "St.", "Vincent", "Hospital,", "The", "Catholic", "University", "of", "Korea,", "93", "Ji-dong,", "Paldal-gu,", "Suwon", "442-723,", "Korea", "Tel", ":", "+82.31-249-7161,", "Fax", ":", "+82.31-248-6758", "E-mail", ":", "hscjohn@hotmail.com", "INTRODUCTION", "The", "patient", "in", "this", "report", "was", "suffering", "from", "diabetic", "neu-", "ropathy,", "end-stage", "renal", "disease,", "restless", "legs", "syndrome", "(RLS),", "and", "depression.", "He", "had", "injuries", "of", "both", "basal", "ganglia", "and", "the", "thalamus", "as", "a", "result", "of", "hypoglycemia,", "causing", "chorea", "and", "more", "severe", "leg", "pains", "and", "dysesthetic", "sensations.", "RLS", "is", "a", "sensorimotor", "disorder", "characterized", "by", "unpleasant", "leg", "sen-", "sations", "together", "with", "an", "irresistible", "inner", "urge", "to", "move.", "Chorea", "is", "a", "neurological", "syndrome", "characterized", "by", "abrupt", "involun-", "tary", "movements", "resulting", "from", "a", "continuous", "flow", "of", "random", "muscle", "contractions.", "The", "first-line", "pharmacological", "treat-", "ment", "for", "RLS", "is", "a", "dopaminergic", "agent,", "whereas", "anti-dopamin-", "ergic", "drugs", "are", "the", "main", "pharmacological", "treatment", "for", "chorea.", "In", "general,", "greater", "D2-receptor", "blocking", "action", "results", "in", "greater", "anti-choreic", "efficacy", "(1).", "Dopaminergic", "drugs", "for", "RLS", "would", "aggravate", "the", "choreic", "movements,", "while", "anti-", "dopaminergic", "agents", "for", "the", "treatment", "of", "chorea", "would", "exac-", "erbate", "the", "RLS.", "In", "this", "report,", "the", "association", "between", "the", "complex", "medical", "conditions", "and", "symptoms", "of", "a", "patient", "with", "two", "coexisting,", "opposing", "diseases", "is", "discussed.", "This", "report", "also", "introduces", "the", "process", "through", "which", "proper", "diagnoses", "and", "treatments", "were", "sought.", "CASE", "REPORT", "A", "44-yr-old", "man", "with", "insomnia", "and", "depression", "was", "referr-", "ed", "to", "the", "psychiatric", "department", "of", "our", "institution.", "He", "com-", "plained", "that", "he", "rarely", "fell", "asleep", "because", "of", "dysesthetic", "sen-", "533", "sations", "and", "pain", "in", "the", "lower", "legs", "and", "feet", "and", "that", "he", "was", "depressed", "and", "feeling", "hopeless.", "Although", "he", "was", "aware", "of", "having", "had", "a", "high", "blood", "sugar", "level", "for", "10", "yr,", "he", "never", "sought", "treatment.", "About", "3", "yr", "earlier,", "in", "summer", "2003,", "he", "began", "to", "experience", "cold,", "numbing,", "and", "pins-and-needles", "sensations", "on", "his", "toes", "that", "eventually", "spread", "throughout", "his", "feet.", "About", "a", "year", "later,", "he", "started", "taking", "hypoglycemic", "agents.", "Howev-", "er,", "the", "pain", "in", "his", "feet", "became", "severe,", "and", "restlessness", "as", "a", "result", "of", "creeping", "sensations", "in", "his", "lower", "legs", "gradually", "start-", "ed", "to", "occur", "when", "he", "was", "lying", "down", "or", "sitting", "awake.", "He", "tried", "massaging", "and", "beating", "his", "legs", "and", "walking", "around.", "The", "unpleasant", "sensations", "and", "restlessness", "were", "temporarily", "relieved", "by", "massage", "and", "walking,", "but", "the", "pain", "in", "his", "feet", "remained", "little", "changed.", "These", "dysesthetic", "sensations", "were", "most", "severe", "when", "he", "lay", "down", "to", "sleep,", "increasing", "his", "sleep", "latency", "to", "longer", "than", "one", "hour.", "He", "woke", "repeatedly", "and", "had", "a", "difficulty", "falling", "back", "asleep", "because", "of", "further", "dysesthetic", "sensations.", "In", "July", "2005,", "the", "patient", "received", "hemodialysis", "for", "end-stage", "renal", "disease.", "In", "those", "days", "his", "serum", "hemoglobin,", "iron,", "and", "ferritin", "levels", "were", "7.4", "g/dL,", "29", "μg/dL,", "and", "97", "ng/", "mL,", "respectively,", "so", "oral", "iron", "supplementation", "was", "adminis-", "tered.", "He", "gradually", "became", "depressed,", "experienced", "feelings", "of", "worthlessness,", "lost", "his", "appetite,", "and", "eventually", "stopped", "eating.", "His", "speech", "became", "slow,", "and", "his", "arms", "and", "legs", "trem-", "bled", "and", "twitched", "involuntarily.", "Subsequently,", "he", "showed", "irregular,", "spasmodic,", "involuntary", "movements", "in", "his", "limbs", "and", "on", "his", "face.", "He", "was", "taken", "to", "the", "emergency", "center", "of", "St.", "Vincent’s", "Hospital", "on", "26", "June", "2006", "by", "his", "son.", "His", "blood", "sugar", "level", "was", "very", "low", "(49", "mg/dL).", "T2-", "and", "fluid-attenuated", "inversion", "recovery", "(FLAIR)-weighted", "magnetic", "resonance" ]

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[ "JCB:", "ARTICLE", "Linking", "axonal", "degeneration", "to", "microtubule", "remodeling", "by", "Spastin-mediated", "microtubule", "severing", "Katia", "J.", "Evans,1,2", "Edgar", "R.", "Gomes,1,3", "Steven", "M.", "Reisenweber,1,2", "Gregg", "G.", "Gundersen,1,3", "and", "Brett", "P.", "Lauring1,2", "1Department", "of", "Pathology,", "2Taub", "Institute", "for", "Research", "on", "Alzheimer's", "Disease", "and", "the", "Aging", "Brain,", "and", "3Department", "of", "Anatomy", "and", "Cell", "Biology,", "College", "of", "Physicians", "and", "Surgeons,", "Columbia", "University,", "New", "York,", "NY", "10032", "Y", "G", "O", "L", "O", "I", "B", "L", "L", "E", "C", "F", "O", "L", "A", "N", "R", "U", "O", "J", "E", "H", "T", "utations", "in", "the", "AAA", "adenosine", "triphosphatase", "M", "(ATPase)", "Spastin", "(SPG4)", "cause", "an", "autosomal", "dominant", "form", "of", "hereditary", "spastic", "paraple-", "gia,", "which", "is", "a", "retrograde", "axonopathy", "primarily", "charac-", "terized", "pathologically", "by", "the", "degeneration", "of", "long", "spi-", "nal", "neurons", "in", "the", "corticospinal", "tracts", "and", "the", "dorsal", "columns.", "Using", "recombinant", "Spastin,", "we", "find", "that", "six", "mu-", "tant", "forms", "of", "Spastin,", "including", "three", "disease-associated", "forms,", "are", "severely", "impaired", "in", "ATPase", "activity.", "In", "contrast", "to", "a", "mutation", "designed", "to", "prevent", "adenosine", "triphosphate", "(ATP)", "binding,", "an", "ATP", "hydrolysis–deficient", "Spastin", "mutant", "predicted", "to", "remain", "kinetically", "trapped", "on", "target", "proteins", "Introduction", "Neurons", "expend", "considerable", "effort", "maintaining", "and", "some-", "times", "degrading", "axons", "in", "response", "to", "a", "variety", "of", "cues.", "Human", "genetic", "phenotypes", "afforded", "by", "diseases", "that", "are", "characterized", "by", "axonal", "degeneration", "and", "the", "study", "of", "the", "corresponding", "disease", "genes", "may", "shed", "light", "into", "the", "mechanisms", "responsible", "for", "axonal", "homeostasis", "and", "neurodegenerative", "disorders.", "Muta-", "tions", "in", "Spastin,", "an", "AAA", "ATPase", "that", "is", "widely", "expressed,", "are", "the", "most", "common", "cause", "of", "the", "autosomal", "dominant", "heredi-", "tary", "spastic", "paraplegia", "(Hazan", "et", "al.,", "1999),", "which", "is", "a", "retro-", "grade", "axonopathy", "that", "primarily", "affects", "the", "corticospinal", "tracts", "and", "the", "fasciculis", "gracilis", "characterized", "clinically", "primarily", "by", "spastic", "gait", "(Fink,", "2002).", "The", "function", "of", "Spastin", "is", "unclear.", "Neuronal", "suppres-", "sion", "of", "Drosophila", "melanogaster", "Spastin", "using", "RNAi", "results", "in", "undergrowth", "of", "the", "neuromuscular", "junction", "and", "increased", "synaptic", "currents,", "whereas", "overexpression", "results", "in", "decreased", "currents", "(Trotta", "et", "al.,", "2004).", "AAA", "proteins", "often", "function", "as", "oligomers,", "with", "each", "pro-", "tomer", "usually", "containing", "one", "or", "two", "AAA", "ATPase", "modules.", "Correspondence", "to", "Brett", "P.", "Lauring:", "bl320@columbia.edu", "The", "online", "version", "of", "this", "paper", "contains", "supplemental", "material.", "©", "The", "Rockefeller", "University", "Press", "$8.00", "The", "Journal", "of", "Cell", "Biology,", "Vol.", "168,", "No.", "4,", "February", "14,", "2005", "599–606", "http://www.jcb.org/cgi/doi/10.1083/jcb.200409058", "decorates", "microtubules", "in", "transfected", "cells.", "Analysis", "of", "disease-associated", "missense", "mutations", "shows", "that", "some", "more", "closely", "resemble", "the", "canonical", "hydrolysis", "mutant,", "whereas", "others", "resemble", "the", "ATP-binding", "mutant.", "Using", "real-time", "imaging,", "we", "show", "that", "Spastin", "severs", "microtu-", "bules", "when", "added", "to", "permeabilized,", "cytosol-depleted", "cells", "stably", "expressing", "GFP-tubulin.", "Using", "purified", "com-", "ponents,", "we", "also", "show", "that", "Spastin", "interacts", "directly", "with", "microtubules", "and", "is", "sufficient", "for", "severing.", "These", "studies", "suggest", "that", "defects", "in", "microtubule", "severing", "are", "a", "cause", "of", "axonal", "degeneration", "in", "human", "disease.", "These", "domains", "share", "several", "key", "structural", "motifs", "and", "are", "homologous", "to", "some", "degree", "among", "all", "AAA", "proteins.", "NH2-", "terminal", "domains", "of", "AAA", "family", "members", "that", "bind", "adaptors", "or", "directly", "to", "target", "proteins", "are", "usually", "highly", "divergent", "and,", "therefore,", "are", "determinant", "of", "specificity", "of", "cellular", "function.", "This", "portion", "of", "Spastin", "contains", "an", "MIT", "domain—a", "domain", "of", "unknown", "function", "(Ciccarelli", "et", "al.,", "2003)", "found", "in", "several", "proteins", "that", "function", "in", "the", "endosome,", "including", "VPS4/SKD1", "(an", "AAA", "ATPase", "involved", "in", "endosomal", "trafficking),", "and", "in", "sorting", "nexin", "15.", "Interestingly,", "another", "hereditary", "spastic", "para-", "plegia", "gene,", "Spartin,", "contains", "an", "MIT", "domain.", "Although", "the", "MIT", "domain", "mediated", "interaction", "of", "Spastin", "with", "the", "endosomal", "protein", "CHMP1B", "(Reid", "et", "al.,", "2005)", "raises", "the", "possibility", "an", "endosome-related", "function,", "Spastin’s", "AAA", "ATPase", "domain", "(Frohlich,", "2001;", "Frickey", "and", "Lupas,", "2004)", "is", "most", "homologous", "to", "those", "found", "in", "VPS4,", "Fidegtin,", "and", "Katanin,", "a", "microtubule-severing", "AAA", "ATPase", "(McNally", "and", "Vale,", "1993).", "First", "purified", "from", "mitotic", "sea", "urchin", "extracts,", "Katanin", "has", "been", "shown", "to", "play", "a", "role", "in", "microtubule", "reorganization", "at", "the", "onset", "of", "mitosis", "(McNally", "and", "Vale,", "1993;", "McNally", "and", "Thomas,", "1998).", "In", "neurons,", "Katanin", "appears", "to", "be", "a", "source", "of", "noncentrosomal", "microtubules", "(Ahmad", "et", "al.,", "1999).", "Katanin", "JCB", "599" ]

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[ "Comparing", "Transcription", "Rate", "and", "mRNA", "Abundance", "as", "Parameters", "for", "Biochemical", "Pathway", "and", "Network", "Analysis", "Brewster", "Hayles,", "Sailu", "Yellaboina¤,", "Degeng", "Wang*", "Department", "of", "Cell", "Biology,", "Microbiology,", "and", "Molecular", "Biology", "(CMMB),", "University", "of", "South", "Florida,", "Tampa,", "Florida,", "United", "States", "of", "America", "Abstract", "The", "cells", "adapt", "to", "extra-", "and", "intra-cellular", "signals", "by", "dynamic", "orchestration", "of", "activities", "of", "pathways", "in", "the", "biochemical", "networks.", "Dynamic", "control", "of", "the", "gene", "expression", "process", "represents", "a", "major", "mechanism", "for", "pathway", "activity", "regulation.", "Gene", "expression", "has", "thus", "been", "routinely", "measured,", "most", "frequently", "at", "steady-state", "mRNA", "abundance", "level", "using", "micro-", "array", "technology.", "The", "results", "are", "widely", "used", "in", "statistical", "inference", "of", "the", "structures", "of", "underlying", "biochemical", "networks,", "with", "the", "assumption", "that", "functionally", "related", "genes", "exhibit", "similar", "dynamic", "profiles.", "Steady-state", "mRNA", "abundance,", "however,", "is", "a", "composite", "of", "two", "factors:", "transcription", "rate", "and", "mRNA", "degradation", "rate.", "The", "question", "being", "asked", "here", "is", "therefore", "whether", "steady-state", "mRNA", "abundance", "or", "any", "of", "two", "factors", "is", "a", "more", "informative", "measurement", "target", "for", "studying", "network", "dynamics.", "The", "yeast", "S.", "cerevisiae", "was", "used", "as", "model", "organism", "and", "transcription", "rate", "was", "chosen", "out", "of", "the", "two", "factors", "in", "this", "study,", "because", "genome-wide", "determination", "of", "transcription", "rates", "has", "been", "reported", "for", "several", "physiological", "processes", "in", "this", "species.", "Our", "strategy", "is", "to", "test", "which", "one", "is", "a", "better", "measurement", "of", "functional", "relatedness", "between", "genes.", "The", "analysis", "was", "performed", "on", "those", "S.", "cerevisiae", "genes", "that", "have", "bacterial", "orthologs", "as", "identified", "by", "reciprocal", "BLAST", "analysis,", "so", "that", "functional", "relatedness", "of", "a", "gene", "pair", "can", "be", "measured", "by", "the", "frequency", "at", "which", "their", "bacterial", "orthologs", "co-occur", "in", "the", "same", "operon", "in", "the", "collection", "of", "bacterial", "genomes.", "It", "is", "found", "that", "transcription", "rate", "data", "is", "generally", "a", "better", "parameter", "for", "functional", "relatedness", "than", "steady", "state", "mRNA", "abundance,", "suggesting", "transcription", "rate", "data", "is", "more", "informative", "to", "use", "in", "deciphering", "the", "logics", "used", "by", "the", "cells", "in", "dynamic", "regulation", "of", "biochemical", "network", "behaviors.", "The", "significance", "of", "this", "finding", "for", "network", "and", "systems", "biology,", "as", "well", "as", "biomedical", "research", "in", "general,", "is", "discussed.", "Citation:", "Hayles", "B,", "Yellaboina", "S,", "Wang", "D", "(2010)", "Comparing", "Transcription", "Rate", "and", "mRNA", "Abundance", "as", "Parameters", "for", "Biochemical", "Pathway", "and", "Network", "Analysis.", "PLoS", "ONE", "5(3):", "e9908.", "doi:10.1371/journal.pone.0009908", "Editor:", "Timothy", "Ravasi,", "King", "Abdullah", "University", "of", "Science", "and", "Technology,", "Saudi", "Arabia", "Received", "January", "5,", "2010;", "Accepted", "February", "19,", "2010;", "Published", "March", "26,", "2010", "Copyright:", "2010", "Hayles", "et", "al.", "This", "is", "an", "open-access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "License,", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "author", "and", "source", "are", "credited.", "Funding:", "This", "work", "was", "supported", "by", "the", "University", "of", "South", "Florida", "(USF)", "Foundation", "and", "a", "USF", "New", "Researcher", "Grant", "to", "D.W.", "The", "funders", "had", "no", "role", "in", "study", "design,", "data", "collection", "and", "analysis,", "decision", "to", "publish,", "or", "preparation", "of", "the", "manuscript.", "Competing", "Interests:", "The", "authors", "have", "declared", "that", "no", "competing", "interests", "exist.", "*", "E-mail:", "dwang1@cas.usf.edu", "¤", "Current", "address:", "Biostatistics", "Branch,", "National", "Institute", "of", "Environmental", "Health", "Sciences", "(NIEHS),", "National", "Institutes", "of", "Health", "(NIH),", "Research", "Triangle", "Park,", "North", "Carolina,", "United", "States", "of", "America", "Introduction", "Biochemical", "networks", "underlie", "essentially", "all", "cellular", "functions.", "Proteins", "encoded", "in", "the", "genomic", "sequences", "form", "biochemical", "pathways", "and", "pathways", "join", "together", "to", "form", "networks.", "Cellular", "biochemical", "networks", "are", "highly", "modular", "in", "that", "they", "consist", "of", "a", "hierarchical", "organization", "of", "functional", "modules", "[1].", "For", "instance,", "metabolic", "enzymes", "form", "the", "metabolic", "network;", "protein", "kinases", "are", "backbones", "of", "the", "signaling", "network;", "and", "transcription", "factors", "are", "major", "components", "of", "the", "transcription", "regulation", "network.", "The", "cells", "constantly", "adapt", "to", "changes", "in", "their", "environment", "and", "internal", "conditions.", "Consequently,", "biochemical", "networks", "are", "never", "static.", "The", "cells", "respond", "to", "extra-", "and", "intra-cellular", "signals", "by", "dynamic", "orchestration", "of", "activities", "of", "pathways", "in", "the", "networks;", "activate", "pathways", "that", "are", "needed", "and", "inactivate", "the", "others", "[2].", "For", "example,", "during", "carbon", "source", "shift", "from", "glucose", "to", "galactose,", "the", "yeast", "cells", "activate", "galactose", "utilization", "pathways,", "while", "inactivating", "pathways", "required", "for", "glucose", "metabolism", "[3,4].", "Roughly", "two", "factors", "determine", "how", "active", "a", "pathway", "is:", "the", "abundance", "and", "the", "activity", "of", "its", "components.", "The", "activity", "of", "many", "proteins,", "the", "latter", "of", "the", "two", "factors,", "is", "under", "tight", "post-", "translational", "control.", "There", "are", "many", "forms", "of", "post-translational", "control:", "covalent", "chemical", "modification", "such", "as", "phosphorylation", "[5]", "and", "glycosylation", "[6],", "allosteric", "interaction", "with", "regulatory", "partners", "[7],", "etc.", "The", "other", "determining", "factor", "of", "biochemical", "pathway", "activity,", "the", "abundance", "of", "proteins,", "is", "also", "under", "tight", "cellular", "regulation.", "Gene", "expression", "regulation", "is", "one", "of", "the", "major", "regulatory", "mechanisms.", "Hence,", "gene", "expression", "has", "been,", "and", "will", "continue", "to", "be,", "extensively", "studied.", "Perhaps", "due", "to", "the", "availability", "of", "reliable", "and", "economical", "measurement", "methods", "such", "as", "the", "SAGE", "[8],", "the", "micro-array", "and", "the", "upcoming", "deep", "sequencing", "technologies", "[9],", "mRNA", "transcript", "levels", "have", "been", "the", "most", "frequently", "studied,", "even", "though", "gene", "expression", "process", "is", "a", "multi-stepped", "process.", "Measurement", "targets", "are", "usually", "steady", "state", "mRNA", "abundance.", "The", "results", "are", "widely", "used", "in", "statistical", "inference", "of", "the", "structures", "of", "underlying", "biochemical", "networks", "[10],", "as", "well", "as", "in", "regulatory", "sequence", "analysis", "to", "detect", "common", "sequence", "motifs", "that", "drive", "transcription", "of", "functionally", "related", "genes", "[11,12].", "The", "underlying", "assumption", "is", "that", "functionally", "related", "genes", "should", "exhibit", "similar", "PLoS", "ONE", "|", "www.plosone.org", "1", "March", "2010", "|", "Volume", "5", "|", "Issue", "3", "|", "e9908" ]

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[ "Hindawi", "Publishing", "Corporation", "Journal", "of", "Ophthalmology", "Volume", "2012,", "Article", "ID", "831502,", "7", "pages", "doi:10.1155/2012/831502", "Review", "Article", "New", "Treatments", "for", "Bacterial", "Keratitis", "Raymond", "L.", "M.", "Wong,1", "R.", "A.", "Gangwani,1", "Lester", "W.", "H.", "Yu,2", "and", "Jimmy", "S.", "M.", "Lai1", "1", "Eye", "Institute,", "The", "University", "of", "Hong", "Kong,", "Room", "301,", "Level", "3,", "Block", "B,", "100", "Cyberport", "Road,", "Cyberport", "4,", "Hong", "Kong", "2", "Department", "of", "Ophthalmology,", "Queen", "Mary", "Hospital,", "Hong", "Kong", "Correspondence", "should", "be", "addressed", "to", "Jimmy", "S.", "M.", "Lai,", "laism@hku.hk", "Received", "31", "May", "2012;", "Revised", "30", "July", "2012;", "Accepted", "19", "August", "2012", "Academic", "Editor:", "Rajesh", "Sinha", "Copyright", "©", "2012", "Raymond", "L.", "M.", "Wong", "et", "al.", "This", "is", "an", "open", "access", "article", "distributed", "under", "the", "Creative", "Commons", "Attribution", "License,", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited.", "Purpose.", "To", "review", "the", "newer", "treatments", "for", "bacterial", "keratitis.", "Data", "Sources.", "PubMed", "literature", "search", "up", "to", "April", "2012.", "Study", "Selection.", "Key", "words", "used", "for", "literature", "search:", "“infectious", "keratitis”,", "“microbial", "keratitis”,", "“infective", "keratitis”,", "“new", "treatments", "for", "infectious", "keratitis”,", "“fourth", "generation", "fluoroquinolones”,", "“moxifloxacin”,", "“gatifloxacin”,", "“collagen", "cross-linking”,", "and", "“photodynamic", "therapy”.", "Data", "Extraction.", "Over", "2400", "articles", "were", "retrieved.", "Large", "scale", "studies", "or", "publications", "at", "more", "recent", "dates", "were", "selected.", "Data", "Synthesis.", "Broad", "spectrum", "antibiotics", "have", "been", "the", "main", "stay", "of", "treatment", "for", "bacterial", "keratitis", "but", "with", "the", "emergence", "of", "bacterial", "resistance;", "there", "is", "a", "need", "for", "newer", "antimicrobial", "agents", "and", "treatment", "methods.", "Fourth-", "generation", "fluoroquinolones", "and", "corneal", "collagen", "cross-linking", "are", "amongst", "the", "new", "treatments.", "In", "vitro", "studies", "and", "prospective", "clinical", "trials", "have", "shown", "that", "fourth-generation", "fluoroquinolones", "are", "better", "than", "the", "older", "generation", "fluoroquinolones", "and", "are", "as", "potent", "as", "combined", "fortified", "antibiotics", "against", "common", "pathogens", "that", "cause", "bacterial", "keratitis.", "Collagen", "cross-linking", "was", "shown", "to", "improve", "healing", "of", "infectious", "corneal", "ulcer", "in", "treatment-resistant", "cases", "or", "as", "an", "adjunct", "to", "antibiotics", "treatment.", "Conclusion.", "Fourth-generation", "fluoroquinolones", "are", "good", "alternatives", "to", "standard", "treatment", "of", "bacterial", "keratitis", "using", "combined", "fortified", "topical", "antibiotics.", "Collagen", "cross-linking", "may", "be", "considered", "in", "treatment-resistant", "infectious", "keratitis", "or", "as", "an", "adjunct", "to", "antibiotics", "therapy.", "1.", "Introduction", "Infectious", "keratitis", "is", "a", "potentially", "blinding", "ocular", "condition", "of", "cornea", "which", "can", "cause", "severe", "visual", "loss", "if", "not", "treated", "at", "early", "stage.", "If", "the", "appropriate", "antimicrobial", "treatment", "is", "delayed,", "only", "50%", "of", "the", "eyes", "gain", "good", "visual", "recovery", "[1].", "It", "can", "be", "caused", "by", "bacteria,", "virus,", "fungus,", "protozoa,", "and", "parasites.", "The", "common", "risk", "factors", "for", "infectious", "keratitis", "include", "ocular", "trauma,", "contact", "lens", "wear,", "recent", "ocular", "surgery,", "preexisting", "ocular", "surface", "disease,", "dry", "eyes,", "lid", "deformity,", "corneal", "sensational", "impairment,", "chronic", "use", "of", "topical", "steroids,", "and", "systemic", "immunosuppression", "[2–", "5].", "The", "common", "pathogens", "include", "Staphylococcus", "aureus,", "coagulase-negative", "Staphylococcus,", "Pseudomonas", "aeruginosa,", "Streptococcus", "pneumonia,", "and", "Serratia", "species.", "The", "majority", "of", "community", "acquired", "cases", "of", "bacterial", "keratitis", "resolve", "with", "empiric", "treatment", "and", "do", "not", "require", "culture", "[6].", "Corneal", "scraping", "for", "culture", "and", "sensitivity", "is", "indicated", "for", "corneal", "ulcers", "that", "are", "large", "in", "size,", "central", "in", "location,", "extend", "from", "middle", "to", "deep", "stroma,", "associated", "with", "pain,", "simultaneous", "presence", "of", "anterior", "chamber", "reaction", "or", "hypopyon,", "poor", "vision,", "and", "presence", "of", "corneal", "abscess", "or", "unresponsive", "to", "broad", "spectrum", "antibiotic", "therapy", "[6].", "Recent", "studies", "have", "shown", "increasing", "evidence", "of", "resistance", "of", "microbes", "to", "antimicrobial", "agents", "[7–9].", "Microorganisms", "develop", "resistance", "due", "to", "chromosomal", "mutation,", "expression", "of", "latent", "chromosomal", "genes", "by", "induction", "or", "exchange", "of", "genetic", "material", "via", "transformation", "[9,", "10].", "This", "can", "cause", "continued", "progression", "of", "the", "disease", "process", "despite", "the", "use", "of", "broad", "spectrum", "antibiotics.", "The", "purpose", "of", "this", "study", "was", "to", "review", "the", "newer", "treatments", "available", "for", "treating", "the", "infectious", "keratitis", "including", "those", "which", "are", "resistant", "to", "the", "antimicrobial", "therapy.", "2.", "Methods", "A", "PubMed", "literature", "search", "was", "conducted", "up", "to", "April", "2012", "using", "the", "following", "key", "words:", "“infectious", "keratitis”,", "“microbial", "keratitis”,", "“infective", "keratitis”,", "“new", "treatments", "for" ]

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[ "ORIGINAL", "RESEARCH", "ARTICLE", "published:", "30", "August", "2011", "doi:", "10.3389/fgene.2011.00055", "Gender-specific", "hierarchy", "in", "nuage", "localization", "of", "PIWI-interacting", "RNA", "factors", "in", "Drosophila", "Akihiro", "Nagao1†,", "Kaoru", "Sato1†,", "Kazumichi", "M.", "Nishida1,", "Haruhiko", "Siomi", "1", "and", "Mikiko", "C.", "Siomi", "1,2*", "1", "Siomi", "Lab,", "Department", "of", "Molecular", "Biology,", "Keio", "University", "School", "of", "Medicine,", "Tokyo,", "Japan", "2", "Japan", "Science", "and", "Technology", "Agency,", "Core", "Research", "for", "Evolutional", "Science", "and", "Technology,", "Saitama,", "Japan", "Edited", "by:", "Muller", "Fabbri,", "The", "Ohio", "State", "University,", "USA", "Reviewed", "by:", "Patrick", "Provost,", "Université", "Laval,", "Canada", "Francesca", "Fanini,", "Istituto", "Scientifico", "Romagnolo", "per", "lo", "Studio", "e", "la", "Cura", "dei", "Tumori,", "Italy", "Michael", "Frohman,", "Stony", "Brook", "University,", "USA", "*Correspondence:", "Mikiko", "C.", "Siomi,", "Keio", "University", "School", "of", "Medicine,", "3", "Shinanomachi,", "Shinjuku-ku,", "Tokyo", "160-8582,", "Japan.", "e-mail:", "siomim@z6.keio.jp", "†Akihiro", "Nagao", "and", "Kaoru", "Sato", "have", "contributed", "equally", "to", "this", "work.", "PIWI-interacting", "RNAs", "(piRNAs)", "are", "germline-specific", "small", "non-coding", "RNAs", "that", "form", "piRNA-induced", "silencing", "complexes", "(piRISCs)", "by", "associating", "with", "PIWI", "proteins,", "a", "sub-", "clade", "of", "the", "Argonaute", "proteins", "predominantly", "expressed", "in", "the", "germline.", "piRISCs", "protect", "the", "integrity", "of", "the", "germline", "genome", "from", "invasive", "transposable", "DNA", "elements", "by", "silencing", "them.", "Multiple", "piRNA", "biogenesis", "factors", "have", "been", "identified", "in", "Drosophila.", "The", "majority", "of", "piRNA", "factors", "are", "localized", "in", "the", "nuage,", "electron-dense", "non-membranous", "cytoplas-", "mic", "structures", "located", "in", "the", "perinuclear", "regions", "of", "germ", "cells.", "Thus,", "piRNA", "biogenesis", "is", "thought", "to", "occur", "in", "the", "nuage", "in", "germ", "cells.", "Immunofluorescence", "analyses", "of", "ovaries", "from", "piRNA", "factor", "mutants", "have", "revealed", "a", "localization", "hierarchy", "of", "piRNA", "factors", "in", "female", "nuage.", "However,", "whether", "this", "hierarchy", "is", "female-specific", "or", "can", "also", "be", "applied", "in", "male", "gonads", "remains", "undetermined.", "Here,", "we", "show", "by", "immunostaining", "of", "both", "ovaries", "and", "testes", "from", "piRNA", "factor", "mutants", "that", "the", "molecular", "hierarchy", "of", "piRNA", "factors", "shows", "gender-specificity,", "especially", "for", "Krimper", "(Krimp),", "a", "Tudor-domain-containing", "protein", "of", "unknown", "function(s):", "Krimp", "is", "dispensable", "for", "PIWI", "protein", "Aubergine", "(Aub)", "nuage", "local-", "ization", "in", "ovaries", "but", "Krimp", "and", "Aub", "require", "each", "other", "for", "their", "proper", "nuage", "localization", "in", "testes.", "This", "suggests", "that", "the", "functional", "requirement", "of", "Krimp", "in", "piRNA", "biogenesis", "may", "be", "different", "in", "male", "and", "female", "gonads.", "Keywords:", "nuage,", "piRNA,", "PIWI,", "Drosophila,", "germline", "INTRODUCTION", "PIWI-interacting", "RNAs", "(piRNAs)", "are", "germline-specific", "small", "RNAs", "that", "function", "in", "RNA", "silencing.", "In", "Drosophila,", "piRNAs", "arise", "mostly", "from", "transposable", "elements", "and", "associate", "with", "germline-", "specific", "Argonaute", "proteins", "(PIWI", "proteins),", "Aubergine", "(Aub),", "Piwi,", "and", "Ago3,", "to", "guide", "PIWI", "proteins", "to", "their", "targets", "(Saito", "et", "al.,", "2006,", "2009;", "Vagin", "et", "al.,", "2006;", "Aravin", "et", "al.,", "2007;", "Brennecke", "et", "al.,", "2007;", "Gunawardane", "et", "al.,", "2007;", "Nishida", "et", "al.,", "2007).", "Mutations", "in", "the", "piwi", "genes", "lead", "to", "de-repression", "of", "transposable", "elements", "(Cox", "et", "al.,", "1998;", "Schmidt", "et", "al.,", "1999;", "Vagin", "et", "al.,", "2004;", "Kalmykova", "et", "al.,", "2005;", "Klattenhoff", "et", "al.,", "2007;", "Li", "et", "al.,", "2009).", "Mutations", "in", "the", "piRNA-producing", "genomic", "loci,", "the", "piRNA", "clusters,", "show", "a", "similar", "phenotype", "(Brennecke", "et", "al.,", "2007).", "Thus,", "both", "PIWI", "and", "piRNAs", "are", "necessary", "for", "transposon", "silencing", "in", "the", "germline.", "Through", "this", "mechanism,", "the", "PIWI–piRNA", "complex,", "also", "called", "the", "piRNA-", "induced", "silencing", "complex", "(piRISC),", "protects", "the", "integrity", "of", "the", "germline", "genome", "from", "invasive", "transposable", "DNA", "elements", "and", "ensures", "oogenesis", "and", "spermatogenesis.", "PIWI-interacting", "RNAs", "are", "produced", "through", "two", "mecha-", "nisms,", "the", "primary", "processing", "pathway", "and", "the", "amplification", "loop", "(or", "the", "Ping-Pong", "cycle;", "Aravin", "et", "al.,", "2007;", "Brennecke", "et", "al.,", "2007;", "Gunawardane", "et", "al.,", "2007;", "Li", "et", "al.,", "2009;", "Malone", "et", "al.,", "2009;", "Siomi", "et", "al.,", "2011).", "Primary", "piRNAs", "are", "first", "produced", "through", "the", "pri-", "mary", "processing", "pathway;", "then,", "the", "majority", "of", "primary", "piRNAs", "are", "amplified", "by", "the", "Ping-Pong", "cycle", "to", "maintain", "a", "high", "expres-", "sion", "level", "of", "piRNAs", "in", "the", "germline.", "Maternally", "deposited", "piRNAs", "also", "serve", "as", "primary", "piRNAs", "to", "induce", "the", "Ping-Pong", "cycle", "in", "embryos.", "Primary", "piRNAs", "are", "mostly", "antisense", "to", "transposon", "mRNAs,", "show", "a", "strong", "bias", "for", "uracil", "at", "the", "5", "end", "(1U", "bias)", "and", "are", "favor-", "ably", "loaded", "onto", "Aub", "and", "Piwi", "(Li", "et", "al.,", "2009;", "Malone", "et", "al.,", "2009).", "Primary", "piRNAs", "in", "ovarian", "somatic", "cells", "require", "the", "female", "ster-", "ile", "(1)", "Yb", "(Yb)", "gene", "for", "their", "accumulation", "(Olivieri", "et", "al.,", "2010;", "Saito", "et", "al.,", "2010;", "Qi", "et", "al.,", "2011).", "Yb", "is", "necessary", "for", "self-renewal", "of", "germline", "and", "somatic", "stem", "cells", "in", "ovaries", "(Szakmary", "et", "al.,", "2009).", "Germ", "cells", "do", "not", "express", "Yb", "and,", "therefore,", "Yb", "is", "unneces-", "sary", "for", "primary", "piRNA", "production", "in", "germ", "cells.", "Zucchini", "(zuc)", "and", "armitage", "(armi)", "are", "necessary", "for", "primary", "piRNA", "produc-", "tion", "in", "both", "ovarian", "somas", "(Haase", "et", "al.,", "2010;", "Olivieri", "et", "al.,", "2010;", "Saito", "et", "al.,", "2010)", "and", "germ", "cells", "(Malone", "et", "al.,", "2009).", "Vasa,", "maelstrom", "(mael),", "krimper", "(krimp),", "armi,", "and", "spindle-E", "(spn-E)", "are", "necessary", "for", "primary", "piRNA", "accumulation", "in", "testes", "(Nagao", "et", "al.,", "2010).", "Other", "genes", "necessary", "for", "primary", "piRNA", "production", "remain", "elusive.", "The", "Ping-Pong", "cycle", "performs", "piRNA", "amplification", "and", "transposon", "silencing,", "simultaneously;", "this", "is", "because", "transposon", "mRNAs", "serve", "as", "substrates", "for", "the", "Aub–piRNA", "complexes.", "The", "Aub-Slicer", "activity,", "the", "endonuclease", "activity", "required", "for", "cleav-", "ing", "the", "target", "mRNAs", "(Gunawardane", "et", "al.,", "2007;", "Nishida", "et", "al.,", "2007),", "determines", "the", "5", "end", "of", "mature", "piRNAs", "in", "the", "sense", "orientation.", "Mature", "piRNAs", "are", "then", "loaded", "onto", "Ago3.", "Thus,", "Ago3-associating", "piRNAs", "are", "mostly", "in", "the", "sense", "orientation.", "The", "www.frontiersin.org", "August", "2011", "|", "Volume", "2", "|", "Article", "55", "|", "1" ]

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[ "Journal", "of", "Carcinogenesis", "Short", "paper", "Comparative", "study", "of", "matrix", "metalloproteinase", "expression", "between", "African", "American", "and", "Caucasian", "Women", "Jacquline", "A", "Mason1,", "Haile", "F", "Yancy1,", "Kerrie", "Lashley2,", "Marty", "Jett3", "and", "Agnes", "A", "Day*1", "BioMed", "Central", "Open", "Access", "Address:", "1Department", "of", "Microbiology,", "College", "of", "Medicine", "Howard", "University,", "Washington,", "D.C.", "20059,", "USA,", "2Department", "of", "Biology", "Howard", "University,", "Washington,", "D.C.", "20059,", "USA", "and", "3Division", "of", "Pathology,", "Walter", "Reed", "Army", "Institute", "of", "Research,", "Washington,", "D.C.", "20021,", "USA", "Email:", "Jacquline", "A", "Mason", "-", "Jacquline.A.Mason@comcast.net;", "Haile", "F", "Yancy", "-", "Hyancy@aol.com;", "Kerrie", "Lashley", "-", "kerrielashley@hotmail.com;", "Marty", "Jett", "-", "marti.jett@na.amedd.army.mil;", "Agnes", "A", "Day*", "-", "aday@howard.edu", "*", "Corresponding", "author", "Published:", "29", "October", "2004", "Journal", "of", "Carcinogenesis", "2004,", "3:15", "doi:10.1186/1477-3163-3-15", "This", "article", "is", "available", "from:", "http://www.carcinogenesis.com/content/3/1/15", "Received:", "13", "September", "2004", "Accepted:", "29", "October", "2004", "©", "2004", "Mason", "et", "al;", "licensee", "BioMed", "Central", "Ltd.", "This", "is", "an", "Open", "Access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "License", "(http://creativecommons.org/licenses/by/2.0),", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited.", "Abstract", "To", "date", "there", "are", "26", "human", "matrix", "metalloproteinases", "(MMPs)", "which", "are", "classified", "according", "to", "their", "substrate", "specificity", "and", "structural", "similarities.", "The", "four", "major", "subgroups", "of", "MMPs", "are", "gelatinases,", "interstitial", "collagenases,", "stromelysins,", "and", "membrane-type", "matrix", "metalloproteinases", "(MT-MMPs).", "This", "study", "investigates", "the", "expression", "of", "26", "MMPs,", "which", "have", "been", "shown", "to", "play", "a", "role", "in", "cancer", "metastasis.", "Breast", "tissues", "and", "cell", "lines", "derived", "from", "African", "American", "patients", "and", "Caucasian", "patients", "were", "assayed", "to", "demonstrate", "alterations", "in", "the", "transcription", "of", "genes", "primarily", "responsible", "for", "degrading", "the", "extracellular", "matrix", "(ECM).", "The", "expression", "levels", "of", "the", "extracellular", "matrix", "and", "adhesion", "molecules", "were", "analyzed", "using", "the", "gene", "array", "technology.", "Steady", "state", "levels", "of", "mRNAs", "were", "validated", "by", "RT-PCR", "analysis.", "Total", "RNA", "was", "isolated", "from", "tissue", "and", "cell", "lines", "and", "used", "in", "the", "RT-PCR", "assays.", "From", "this", "data,", "differential", "expression", "of", "MMPs", "between", "6", "breast", "cancer", "cell", "lines", "and", "2", "non-cancer", "breast", "cell", "lines", "was", "demonstrated.", "We", "have", "performed", "an", "in", "vitro", "comparison", "of", "MMP", "expression", "and", "established", "differences", "in", "12", "MMPs", "(3,", "7,", "8,", "9,", "11–15,", "23B,", "26,", "and", "28)", "expression", "between", "African", "American", "and", "Caucasian", "breast", "cell", "lines.", "Thus,", "evidence", "indicates", "that", "altered", "expression", "of", "MMPs", "may", "play", "a", "role", "in", "the", "aggressive", "phenotype", "seen", "in", "African", "American", "women.", "Introduction", "In", "2003,", "it", "was", "estimated", "that", "approximately", "1.3", "million", "Americans", "would", "be", "diagnosed", "with", "invasive", "cancer.", "Of", "this", "group,", "racial/ethnic", "minorities", "account", "for", "a", "dispro-", "portionate", "number", "of", "these", "cancers", "[1,2].", "Invasive", "breast", "cancer", "usually", "begins", "in", "either", "the", "lobules", "or", "the", "ducts", "of", "the", "breast.", "These", "tumors", "then", "metastasize", "via", "the", "breast", "associated", "and", "thoracic", "lymphatic", "tissue", "[3].", "The", "inci-", "dence", "of", "breast", "cancer", "in", "Caucasian", "women", "(112", "out", "of", "100,000)", "is", "higher", "than", "in", "African", "American", "women", "(AA)", "(95", "out", "of", "100,000)", "after", "the", "age", "of", "40,", "however,", "the", "mor-", "tality", "suffered", "by", "(AA)(37", "out", "of", "100,000)", "is", "higher", "than", "Caucasian", "women", "(CAU)", "(31", "out", "of", "100,000)", "at", "every", "age", "[4].", "Thus", "a", "greater", "percentage", "of", "AA", "women", "die", "from", "breast", "cancer", "and", "resulting", "metastasis.", "In", "2004,", "an", "esti-", "mated", "215,990", "new", "cases", "of", "invasive", "breast", "cancer", "is", "expected", "to", "occur", "among", "women", "in", "the", "United", "States", "[5].", "Breast", "cancer", "is", "the", "most", "common", "cancer", "among", "AA", "women;", "however,", "the", "rate", "of", "newly", "diagnosed", "cases", "is", "about", "13%", "lower", "than", "CAU", "women", "[6].", "There", "is", "Page", "1", "of", "6", "(page", "number", "not", "for", "citation", "purposes)" ]

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[ "Lipid", "mediators", "in", "innate", "immunity", "against", "tuberculosis:", "opposing", "roles", "of", "PGE2", "and", "LXA4", "in", "the", "induction", "of", "macrophage", "death", "A", "RT", "I", "C", "L", "E", "e", "n", "i", "c", "i", "d", "e", "M", "l", "a", "t", "n", "e", "m", "i", "r", "e", "p", "x", "E", "f", "o", "l", "a", "n", "r", "u", "o", "J", "e", "h", "T", "CORRESPONDENCE", "Heinz", "G.", "Remold:", "hremold@rics.bwh.harvard.edu", "Abbreviations", "used:", "5-LO,", "5-lipoxygenase;", "AA,", "arachidonic", "acid;", "COX,", "cyclooxygenase;", "cPLA2,", "cytosolic", "PLA2;", "EP,", "E", "prostanoid;", "LC-MS-MS,", "liquid", "chromatography", "tandem", "mass", "spectrometry;", "MOI,", "multi-", "plicity", "of", "infection;", "mPGES,", "microsomal", "prostaglandin", "E", "synthase;", "MPT,", "mitochondrial", "permeability", "transition;", "PI,", "propidium", "iodide;", "PI3K,", "phos-", "phatidylinositol-3", "kinase;", "PKA,", "protein", "kinase", "A;", "siRNA,", "small", "interfering", "RNA.", "The", "Rockefeller", "University", "Press", "$30.00", "J.", "Exp.", "Med.", "Vol.", "205", "No.", "12", "2791-2801", "www.jem.org/cgi/doi/10.1084/jem.20080767", "Minjian", "Chen,1", "Maziar", "Divangahi,1", "Huixian", "Gan,1", "Daniel", "S.J.", "Shin,1", "Song", "Hong,2", "David", "M.", "Lee,1", "Charles", "N.", "Serhan,2", "Samuel", "M.", "Behar,1", "and", "Heinz", "G.", "Remold1", "1Department", "of", "Medicine", "and", "Division", "of", "Rheumatology,", "Immunology,", "and", "Allergy", "and", "2Center", "for", "Experimental", "Therapeutics", "and", "Reperfusion", "Injury,", "Department", "of", "Anesthesiology,", "Perioperative,", "and", "Pain", "Medicine,", "Brigham", "and", "Women’s", "Hospital", "and", "Harvard", "Medical", "School,", "Boston,", "MA", "02115", "Virulent", "Mycobacterium", "tuberculosis", "(Mtb)", "induces", "a", "maladaptive", "cytolytic", "death", "modality,", "necrosis,", "which", "is", "advantageous", "for", "the", "pathogen.", "We", "report", "that", "necrosis", "of", "macrophages", "infected", "with", "the", "virulent", "Mtb", "strains", "H37Rv", "and", "Erdmann", "depends", "on", "predominant", "LXA4", "production", "that", "is", "part", "of", "the", "antiinflammatory", "and", "inflammation-resolving", "action", "induced", "by", "Mtb.", "Infection", "of", "macrophages", "with", "the", "avirulent", "H37Ra", "triggers", "production", "of", "high", "levels", "of", "the", "prostanoid", "PGE2,", "which", "promotes", "protection", "against", "mitochondrial", "inner", "membrane", "perturbation", "and", "necrosis.", "In", "contrast", "to", "H37Ra", "infection,", "PGE2", "production", "is", "significantly", "reduced", "in", "H37Rv-infected", "macrophages.", "PGE2", "acts", "by", "engaging", "the", "PGE2", "receptor", "EP2,", "which", "induces", "cyclic", "AMP", "production", "and", "protein", "kinase", "A", "activation.", "To", "verify", "a", "role", "for", "PGE2", "in", "control", "of", "bacterial", "growth,", "we", "show", "that", "infection", "of", "prostaglan-", "din", "E", "synthase", "(PGES)", "/", "macrophages", "in", "vitro", "with", "H37Rv", "resulted", "in", "significantly", "higher", "bacterial", "burden", "compared", "with", "wild-type", "macrophages.", "More", "importantly,", "PGES", "/", "mice", "harbor", "significantly", "higher", "Mtb", "lung", "burden", "5", "wk", "after", "low-dose", "aerosol", "infection", "with", "virulent", "Mtb.", "These", "in", "vitro", "and", "in", "vivo", "data", "indicate", "that", "PGE2", "plays", "a", "critical", "role", "in", "inhibition", "of", "Mtb", "replication.", "Tuberculosis", "is", "the", "predominant", "cause", "for", "mortal-", "ity", "from", "chronic", "pulmonary", "bacterial", "infections", "worldwide", "causing", "nearly", "two", "million", "deaths", "yearly.", "Tuberculosis", "has", "become", "more", "serious", "as", "a", "consequence", "of", "the", "global", "AIDS", "epidemic", "and", "the", "emergence", "of", "multidrug-resistant", "Mycobacte-", "rium", "tuberculosis", "(Mtb),", "the", "causative", "agent", "of", "tu-", "berculosis", "(1).", "Natural", "transmission", "of", "Mtb", "occurs", "predominantly", "via", "inhalation", "of", "aerosols", "contain-", "ing", "small", "numbers", "of", "bacteria", "that", "are", "deposited", "in", "the", "distal", "airways", "of", "the", "lung", "(2).", "The", "pathogens", "are", "phagocytosed", "by", "pulmonary", "M", ",", "which", "serve", "as", "a", "sanctuary", "for", "Mtb", "(3).", "Virulent", "Mtb,", "which", "M.", "Divangahi", "and", "H.", "Gan", "contributed", "equally", "to", "this", "study.", "M.", "Chen’s", "present", "address", "is", "Clinical", "Research", "Center,", "The", "First", "Affiliated", "Hospital,", "Guangxi", "Medical", "University,", "Nanning,", "Guangxi", "530021,", "People’s", "Republic", "of", "China.", "S.", "Hong’s", "present", "address", "is", "Louisiana", "State", "University", "Neuro-", "science", "Center,", "New", "Orleans,", "LA", "70112.", "The", "online", "version", "of", "this", "article", "contains", "supplemental", "material.", "reside", "in", "M", ",", "initially", "evade", "elimination", "by", "the", "immune", "system", "via", "preventing", "apoptosis", "and", "in-", "hibiting", "maturation", "of", "the", "phagosome–lysosome", "organelle", "of", "the", "host", "M", "(4,", "5).", "The", "net", "effect", "is", "to", "diminish", "entry", "of", "bacterial", "proteins", "into", "the", "class", "II", "MHC", "antigen-processing", "pathway", "(4)", "and", "to", "create", "a", "protected", "intracellular", "milieu", "where", "ba-", "cilli", "remain", "metabolically", "active", "and", "replication", "competent", "(6).", "For", "M", "infected", "with", "virulent", "H37Rv,", "necrosis", "characterized", "by", "cytolysis", "is", "the", "dominant", "form", "of", "cell", "death,", "which", "affords", "a", "pro-", "tective", "milieu", "for", "Mtb", "(7,", "8).", "Thus,", "subversion", "of", "cell", "death", "toward", "necrosis", "is", "of", "considerable", "ad-", "vantage", "for", "the", "pathogen.", "©", "2008", "Chen", "et", "al.", "This", "article", "is", "distributed", "under", "the", "terms", "of", "an", "Attribu-", "tion–Noncommercial–Share", "Alike–No", "Mirror", "Sites", "license", "for", "the", "first", "six", "months", "after", "the", "publication", "date", "(see", "http://www.jem.org/misc/terms.shtml).", "After", "six", "months", "it", "is", "available", "under", "a", "Creative", "Commons", "License", "(Attribution–Noncom-", "mercial–Share", "Alike", "3.0", "Unported", "license,", "as", "described", "at", "http://creativecommons", ".org/licenses/by-nc-sa/3.0/).", "2791" ]

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[ "REVIEW", "ARTICLE", "published:", "22", "August", "2012", "doi:", "10.3389/fpls.2012.00203", "RNA", "trafficking", "in", "parasitic", "plant", "systems", "Megan", "LeBlanc,", "Gunjune", "Kim", "and", "James", "H.", "Westwood*", "Department", "of", "Plant", "Pathology,", "Physiology", "and", "Weed", "Science,", "Virginia", "Tech,", "Blacksburg,", "VA,", "USA", "Edited", "by:", "Yiguo", "Hong,", "College", "of", "Life", "and", "Environmental", "Sciences,", "Hangzhou", "Normal", "University,", "China", "Reviewed", "by:", "Ralf", "Kaldenhoff,", "Technische", "Universität", "Darmstadt,", "Germany", "Roberto", "Ruiz-Medrano,", "CINVESTAV-IPN,", "Maxico", "*Correspondence:", "James", "H.", "Westwood,", "Department", "of", "Plant", "Pathology,", "Physiology", "and", "Weed", "Science,", "Virginia", "Tech,", "401", "Latham", "Hall", "(0390),", "Blacksburg,", "VA", "24061,", "USA.", "e-mail:", "westwood@vt.edu", "RNA", "trafficking", "in", "plants", "contributes", "to", "local", "and", "long-distance", "coordination", "of", "plant", "devel-", "opment", "and", "response", "to", "the", "environment.", "However,", "investigations", "of", "mobile", "RNA", "identity", "and", "function", "are", "hindered", "by", "the", "inherent", "difficulty", "of", "tracing", "a", "given", "molecule", "of", "RNA", "from", "its", "cell", "of", "origin", "to", "its", "destination.", "Several", "methods", "have", "been", "used", "to", "address", "this", "prob-", "lem,", "but", "all", "are", "limited", "to", "some", "extent", "by", "constraints", "associated", "with", "accurately", "sampling", "phloem", "sap", "or", "detecting", "trafficked", "RNA.", "Certain", "parasitic", "plant", "species", "form", "symplastic", "connections", "to", "their", "hosts", "and", "thereby", "provide", "an", "additional", "system", "for", "studying", "RNA", "traf-", "ficking.", "The", "haustorial", "connections", "of", "Cuscuta", "and", "Phelipanche", "species", "are", "similar", "to", "graft", "junctions", "in", "that", "they", "are", "able", "to", "transmit", "mRNAs,", "viral", "RNAs,", "siRNAs,", "and", "proteins", "from", "the", "host", "plants", "to", "the", "parasite.", "In", "contrast", "to", "other", "graft", "systems,", "these", "parasites", "form", "con-", "nections", "with", "host", "species", "that", "span", "a", "wide", "phylogenetic", "range,", "such", "that", "a", "high", "degree", "of", "nucleotide", "sequence", "divergence", "may", "exist", "between", "host", "and", "parasites", "and", "allow", "con-", "fident", "identification", "of", "most", "host", "RNAs", "in", "the", "parasite", "system.", "The", "ability", "to", "identify", "host", "RNAs", "in", "parasites,", "and", "vice", "versa,", "will", "facilitate", "genomics", "approaches", "to", "understanding", "RNA", "trafficking.", "This", "review", "discusses", "the", "nature", "of", "host–parasite", "connections", "and", "the", "potential", "significance", "of", "host", "RNAs", "for", "the", "parasite.", "Additional", "research", "on", "host–parasite", "interactions", "is", "needed", "to", "interpret", "results", "of", "RNA", "trafficking", "studies,", "but", "parasitic", "plants", "may", "provide", "a", "fascinating", "new", "perspective", "on", "RNA", "trafficking.", "Keywords:", "Cuscuta,", "haustorium,", "host–parasite", "interactions,", "Orobanchaceae,", "Orobanche,", "Phelipanche,", "RNA", "trafficking", "INTRODUCTION", "RNA", "trafficking", "in", "plants", "has", "received", "increasing", "attention", "in", "recent", "years.", "It", "is", "an", "important", "phenomenon", "in", "that", "it", "suggests", "that", "plants", "operate", "at", "the", "level", "of", "supracellular", "organisms,", "meaning", "that", "mRNA", "is", "not", "restricted", "to", "the", "cell", "in", "which", "it", "was", "synthesized,", "but", "rather", "moves", "from", "cell-to-cell", "and", "even", "over", "long", "distances", "through", "the", "phloem", "(Lucas", "and", "Lee,", "2004).", "Under", "this", "model", "mRNAs", "function", "in", "cells", "distant", "from", "their", "point", "of", "origin", "by", "car-", "rying", "information", "throughout", "the", "plant", "and", "act", "as", "part", "of", "a", "system", "for", "coordinating", "plant", "development.", "However,", "the", "study", "of", "RNA", "movement", "between", "cells", "of", "a", "single", "organism", "presents", "tremendous", "challenges.", "It", "is", "difficult", "to", "confi-", "dently", "determine", "the", "cell", "of", "origin", "of", "an", "RNA", "molecule", "when", "the", "genotypes", "of", "source", "and", "destination", "cells", "are", "identical.", "This", "inabil-", "ity", "to", "distinguish", "mRNA", "origins", "hampers", "research,", "and", "while", "it", "is", "currently", "thought", "that", "there", "are", "about", "1,100", "proteins", "and", "hun-", "dreds", "of", "mRNAs", "that", "undergo", "long-distance", "movement", "(Atkins", "et", "al.,", "2011),", "the", "actual", "scope", "of", "RNA", "trafficking", "over", "short", "and", "long", "distances", "is", "unknown.", "Parasitic", "plants", "are", "relevant", "to", "the", "consideration", "of", "RNA", "traf-", "ficking", "because", "certain", "species", "have", "the", "ability", "to", "form", "symplastic", "unions", "with", "host", "species", "wherein", "the", "connections", "allow", "the", "trans-", "fer", "of", "RNA.", "In", "the", "case", "of", "lespedeza", "dodder", "(Cuscuta", "pentagona),", "the", "connections", "permit", "transfer", "of", "mRNA", "from", "host", "to", "parasite", "(Roney", "et", "al.,", "2007;", "David-Schwartz", "et", "al.,", "2008),", "and", "this", "raises", "exciting", "prospects", "for", "understanding", "RNA", "trafficking", "in", "plants.", "Because", "Cuscuta", "has", "a", "relatively", "wide", "host", "range", "and", "can", "effec-", "tively", "parasitize", "a", "number", "of", "species", "from", "a", "diverse", "range", "of", "plant", "families,", "this", "parasite", "can", "act", "as", "a", "sink", "for", "host", "mobile", "RNA", "from", "many", "different", "species.", "Furthermore,", "the", "evolution-", "ary", "distance", "between", "Cuscuta", "and", "most", "of", "its", "hosts", "means", "that", "the", "majority", "of", "mRNAs", "synthesized", "in", "a", "host", "have", "sequences", "that", "are", "divergent", "from", "those", "of", "Cuscuta,", "thus", "simplifying", "the", "process", "of", "bioinformatically", "recognizing", "host", "mRNA", "that", "has", "trafficked", "into", "the", "parasite.", "To", "the", "extent", "that", "Cuscuta", "connections", "to", "hosts", "approximate", "normal", "cell-to-cell", "connections", "within", "plants,", "Cus-", "cuta", "can", "serve", "as", "an", "exceptionally", "wide", "heterograft", "to", "facilitate", "studies", "of", "mobile", "RNA.", "This", "review", "will", "examine", "the", "nature", "of", "host–parasite", "connections", "and", "consider", "the", "advantages", "and", "dis-", "advantages", "of", "using", "parasites", "for", "studies", "of", "RNA", "trafficking", "in", "plants.", "PARASITIC", "PLANT", "CONNECTIONS:", "THE", "PERFECT", "GRAFT?", "The", "connection", "between", "parasitic", "plants", "and", "their", "hosts", "has", "been", "compared", "to", "“the", "perfect", "graft”", "(Kuijt,", "1983).", "The", "analogy", "of", "par-", "asitic", "plant", "connections", "to", "graft", "unions", "is", "appropriate", "in", "that", "both", "involve", "fusing", "together", "separate", "plants", "to", "forge", "new", "cellu-", "lar", "connections", "and", "vascular", "continuity.", "Both", "grafts", "and", "parasite", "connections", "establish", "symplastic", "connections", "(Although", "this", "is", "not", "true", "of", "all", "parasite", "species,", "it", "is", "accepted", "for", "Cuscuta", "and", "Phelipanche", "spp.),", "and", "have", "the", "ability", "to", "transmit", "RNA", "(West-", "wood", "et", "al.,", "2009;", "Harada,", "2010).", "However,", "whereas", "man-made", "grafts", "are", "the", "result", "of", "joining", "cut", "tissues,", "the", "parasitic", "connection", "involves", "a", "highly", "coordinated", "biological", "invasion", "(Joel", "and", "Losner-", "Goshen,", "1994;", "Lee,", "2007).", "Although", "parasitism", "may", "elicit", "defense", "responses", "from", "the", "host", "(Borsics", "and", "Lados,", "2002;", "Griffitts", "et", "al.,", "www.frontiersin.org", "August", "2012", "|", "Volume", "3", "|", "Article", "203", "|", "1", "“fpls-03-00203”", "—", "2012/8/20", "—", "19:45", "—", "page", "1", "—", "#1" ]

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[ "DIABETICMedicine", "P20BODA37licxMra4uficb2ogEtike-rn3wtdnaoi0,cexa7UlMi1drKPtaAeituacdrlbvietcliscnhlteriensg,Li2nt0dnhy6perglycaemciaY.Miyarzakietael.atic", "B-cell", "function", "is", "altered", "by", "oxidative", "stress", "induced", "by", "acute", "hyperglycaemia", "Y.", "Miyazaki,", "H.", "Kawano,", "T.", "Yoshida,", "S.", "Miyamoto,", "J.", "Hokamaki,", "Y.", "Nagayoshi,", "H.", "Yamabe,", "H.", "Nakamura*,", "J.", "Yodoi†", "and", "H.", "Ogawa", "Department", "of", "Cardiovascular", "Medicine,", "Graduate", "School", "of", "Medical", "Sciences,", "Kumamoto", "University,", "Kumamoto,", "*Thioredoxin", "Project,", "Department", "of", "Experimental", "Therapeutics,", "Translational", "Research", "Centre,", "Kyoto", "University", "Hospital", "and", "†Department", "of", "Biological", "Responses,", "Institute", "for", "Virus", "Research,", "Kyoto", "University,", "Kyoto,", "Japan", "Accepted", "29", "August", "2006", "Abstract", "Aims", "Type", "2", "diabetes", "is", "preceded", "by", "a", "symptom-free", "period", "of", "impaired", "glu-", "cose", "tolerance", "(IGT).", "Pancreatic", "B-cell", "function", "decreases", "as", "glucose", "intolerance", "develops.", "In", "many", "patients", "with", "IGT,", "fasting", "blood", "glucose", "is", "within", "normal", "limits", "and", "hyperglycaemia", "occurs", "only", "postprandially.", "We", "examined", "whether", "pancreatic", "B-cell", "function", "changes", "during", "acute", "hyperglycaemia", "induced", "by", "oral", "glucose", "loading.", "Methods", "We", "calculated", "the", "insulinogenic", "index", "(I.I.)", "as", "an", "indicator", "of", "pancreatic", "B-cell", "function", "and", "measured", "serum", "levels", "of", "thioredoxin,", "a", "marker", "of", "cellular", "redox", "state,", "and", "8-hydroxy-2′-deoxyguanosine", "(8-OHdG),", "a", "marker", "of", "oxidative", "stress,", "during", "a", "75-g", "oral", "glucose", "tolerance", "test", "(OGTT)", "in", "45", "subjects", "[24", "patients", "with", "normal", "glucose", "tolerance", "(NGT),", "14", "with", "IGT", "and", "seven", "with", "Type", "2", "diabetes].", "Results", "Thioredoxin", "levels", "decreased", "after", "glucose", "loading", "[66.1", "±", "23.7,", "*59.3", "±", "22.4,", "*49.3", "±", "21.2", "and", "*37.7", "±", "18.0", "ng/ml,", "fasting", "(0", "min)", "and", "at", "30,", "60", "and", "120", "min,", "respectively;", "*P", "<", "0.001", "vs.", "fasting].", "In", "contrast,", "concentrations", "of", "8-OHdG", "peaked", "at", "30", "min", "and", "then", "gradually", "decreased", "(0.402", "±", "0.123,", "*0.440", "±", "0.120,", "†0.362", "±", "0.119", "and", "†0.355", "±", "0.131", "ng/ml,", "*P", "<", "0.05", "vs.", "fasting,", "†P", "<", "0.01", "vs.", "30", "min).", "The", "insulinogenic", "index", "correlated", "with", "the", "change", "in", "thioredoxin", "levels", "(r", "=", "0.34,", "P", "<", "0.05).", "However,", "there", "was", "no", "relationship", "with", "the", "change", "in", "8-OHdG", "levels", "from", "0", "to", "30", "min.", "Conclusions", "Hyperglycaemia", "in", "response", "to", "oral", "glucose", "impairs", "pancreatic", "B-cell", "function", "with", "decreasing", "thioredoxin", "levels.", "The", "augmented", "oxidative", "stress", "induced", "by", "hyperglycaemia", "may", "affect", "the", "cellular", "redox", "state.", "These", "findings", "strongly", "suggest", "that", "repeated", "postprandial", "hyperglycaemia", "may", "play", "an", "important", "role", "in", "the", "development", "and", "progression", "of", "diabetes", "mellitus.", "Diabet.", "Med.", "24,", "154–160", "(2007)", "Keywords", "blood", "glucose,", "impaired", "glucose", "tolerance,", "oxidative", "stress,", "post-", "prandial", "hyperglycaemia", "Abbreviations", "8-OHdG,", "8-hydroxy-2′-deoxyguanosine;", "ANOVA,", "analysis", "of", "vari-", "ance;", "DM,", "diabetes", "mellitus;", "IGT,", "impaired", "glucose", "tolerance;", "I.I.,", "insulinogenic", "index;", "NGT,", "normal", "glucose", "tolerance;", "OGTT,", "oral", "glucose", "tolerance", "test;", "TRX,", "thioredoxin", "Correspondence", "to:", "Hiroaki", "Kawano", "MD,", "PhD,", "Department", "of", "Cardiovascular", "Medicine,", "Graduate", "School", "of", "Medical", "Sciences,", "Kumamoto", "University,", "1-1-1", "Honjo,", "Kumamoto", "City", "860–8556,", "Japan.", "E-mail:", "koumei@kumamoto-u.ac.jp", "Re-use", "of", "this", "article", "is", "permitted", "in", "accordance", "with", "the", "Creative", "Commons", "Deed,", "Attribution", "2.5,", "which", "does", "not", "permit", "commercial", "exploitation.", "154", "Introduction", "Diabetes", "mellitus", "is", "associated", "with", "the", "development", "of", "athero-", "sclerosis", "[1].", "Both", "macrovascular", "disease,", "such", "as", "acute", "coronary", "syndrome,", "stroke", "and", "claudication,", "and", "microvascular", "disease,", "such", "as", "diabetic", "nephropathy", "and", "retinopathy,", "are", "commoner", "in", "diabetic", "than", "in", "non-diabetic", "populations", "and", "contribute", "©", "2007", "The", "Authors.", "Journal", "compilation", "©", "2007", "Diabetes", "UK.", "Diabetic", "Medicine,", "24,", "154–160" ]

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[ "J", "Chem", "Ecol", "(2007)", "33:655–668", "DOI", "10.1007/s10886-006-9245-2", "Jasmonic", "Acid-Induced", "Changes", "in", "Brassica", "oleracea", "Affect", "Oviposition", "Preference", "of", "Two", "Specialist", "Herbivores", "Maaike", "Bruinsma", "&", "Nicole", "M.", "Van", "Dam", "&", "Joop", "J.", "A.", "Van", "Loon", "&", "Marcel", "Dicke", "Received:", "6", "September", "2006", "/", "Accepted:", "18", "December", "2006", "/", "Published", "online:", "2", "March", "2007", "#", "Springer", "Science", "+", "Business", "Media,", "LLC", "2007", "Abstract", "Jasmonic", "acid", "(JA)", "is", "a", "key", "hormone", "involved", "in", "plant", "defense", "responses.", "The", "effect", "of", "JA", "treatment", "of", "cabbage", "plants", "on", "their", "acceptability", "for", "oviposition", "by", "two", "species", "of", "cabbage", "white", "butterflies,", "Pieris", "rapae", "and", "P.", "brassicae,", "was", "investigated.", "Both", "butterfly", "species", "laid", "fewer", "eggs", "on", "leaves", "of", "JA-treated", "plants", "compared", "to", "control", "plants.", "We", "show", "that", "this", "is", "due", "to", "processes", "in", "the", "plant", "after", "JA", "treatment", "rather", "than", "an", "effect", "of", "JA", "itself.", "The", "oviposition", "preference", "for", "control", "plants", "is", "adaptive,", "as", "development", "time", "from", "larval", "hatch", "until", "pupation", "of", "P.", "rapae", "caterpillars", "was", "longer", "on", "JA-treated", "plants.", "Total", "glucosinolate", "content", "in", "leaf", "surface", "extracts", "was", "similar", "for", "control", "and", "treated", "plants;", "however,", "two", "of", "the", "five", "glucosinolates", "were", "present", "in", "lower", "amounts", "in", "leaf", "surface", "extracts", "of", "JA-treated", "plants.", "When", "the", "butterflies", "were", "offered", "a", "choice", "between", "the", "purified", "glucosinolate", "fraction", "isolated", "from", "leaf", "surface", "extracts", "of", "JA-treated", "plants", "and", "that", "from", "control", "plants,", "they", "did", "not", "discriminate.", "Changes", "in", "leaf", "surface", "glucosinolate", "profile,", "therefore,", "do", "not", "seem", "to", "explain", "the", "change", "in", "oviposition", "preference", "of", "the", "butterflies", "after", "JA", "treatment,", "suggesting", "that", "as", "yet", "unknown", "infochemicals", "are", "involved.", "Keywords", "Host", "plant", "selection", ".", "Glucosinolates", ".", "Pieris", "rapae", ".", "Pieris", "brassicae", ".", "Cabbage", ".", "Performance", ".", "Octadecanoid", "pathway", "Introduction", "Plants", "can", "be", "attacked", "by", "many", "herbivorous", "insects", "and", "have", "evolved", "a", "variety", "of", "defense", "strategies,", "including", "morphological", "barriers,", "synthesis", "of", "toxic", "or", "repellent", "secondary", "metabolites,", "and", "the", "release", "of", "synomones", "that", "attract", "natural", "enemies", "of", "the", "herbivores.", "M.", "Bruinsma", "(*)", ":", "J.", "J.", "A.", "Van", "Loon", ":", "M.", "Dicke", "Laboratory", "of", "Entomology,", "Wageningen", "University,", "P.O.", "Box", "8031,", "6700", "EH", "Wageningen,", "The", "Netherlands", "e-mail:", "maaike.bruinsma@wur.nl", "N.", "M.", "Van", "Dam", "Centre", "for", "Terrestrial", "Ecology,", "Netherlands", "Institute", "of", "Ecology", "(NIOO-KNAW),", "P.O.", "Box", "40,", "6666", "ZG", "Heteren,", "The", "Netherlands" ]

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[ "Kwon", "et", "al.", "BMC", "Cancer", "2010,", "10:392", "http://www.biomedcentral.com/1471-2407/10/392", "R", "E", "S", "E", "A", "R", "C", "H", "A", "R", "T", "I", "C", "L", "E", "Open", "Access", "Cinnamon", "extract", "induces", "tumor", "cell", "death", "through", "inhibition", "of", "NF", "B", "and", "AP1", "Ho-Keun", "Kwon1,", "Ji-Sun", "Hwang1,", "Jae-Seon", "So1,", "Choong-Gu", "Lee1,", "Anupama", "Sahoo1,", "Jae-Ha", "Ryu1,", "Won", "Kyung", "Jeon2,", "Byoung", "Seob", "Ko2,", "Chang-Rok", "Im3,", "Sung", "Haeng", "Lee4,", "Zee", "Yong", "Park1,", "Sin-Hyeog", "Im1*", "Abstract", "Background:", "Cinnamomum", "cassia", "bark", "is", "the", "outer", "skin", "of", "an", "evergreen", "tall", "tree", "belonging", "to", "the", "family", "Lauraceae", "containing", "several", "active", "components", "such", "as", "essential", "oils", "(cinnamic", "aldehyde", "and", "cinnamyl", "aldehyde),", "tannin,", "mucus", "and", "carbohydrate.", "They", "have", "various", "biological", "functions", "including", "anti-oxidant,", "anti-microbial,", "anti-", "inflammation,", "anti-diabetic", "and", "anti-tumor", "activity.", "Previously,", "we", "have", "reported", "that", "anti-cancer", "effect", "of", "cinnamon", "extracts", "is", "associated", "with", "modulation", "of", "angiogenesis", "and", "effector", "function", "of", "CD8+", "T", "cells.", "In", "this", "study,", "we", "further", "identified", "that", "anti-tumor", "effect", "of", "cinnamon", "extracts", "is", "also", "link", "with", "enhanced", "pro-apoptotic", "activity", "by", "inhibiting", "the", "activities", "NF", "B", "and", "AP1", "in", "mouse", "melanoma", "model.", "Methods:", "Water", "soluble", "cinnamon", "extract", "was", "obtained", "and", "quality", "of", "cinnamon", "extract", "was", "evaluated", "by", "HPLC", "(High", "Performance", "Liquid", "Chromatography)", "analysis.", "In", "this", "study,", "we", "tested", "anti-tumor", "activity", "and", "elucidated", "action", "mechanism", "of", "cinnamon", "extract", "using", "various", "types", "of", "tumor", "cell", "lines", "including", "lymphoma,", "melanoma,", "cervix", "cancer", "and", "colorectal", "cancer", "in", "vitro", "and", "in", "vivo", "mouse", "melanoma", "model.", "Results:", "Cinnamon", "extract", "strongly", "inhibited", "tumor", "cell", "proliferation", "in", "vitro", "and", "induced", "active", "cell", "death", "of", "tumor", "cells", "by", "up-regulating", "pro-apoptotic", "molecules", "while", "inhibiting", "NF", "B", "and", "AP1", "activity", "and", "their", "target", "genes", "such", "as", "Bcl-2,", "BcL-xL", "and", "survivin.", "Oral", "administration", "of", "cinnamon", "extract", "in", "melanoma", "transplantation", "model", "significantly", "inhibited", "tumor", "growth", "with", "the", "same", "mechanism", "of", "action", "observed", "in", "vitro.", "Conclusion:", "Our", "study", "suggests", "that", "anti-tumor", "effect", "of", "cinnamon", "extracts", "is", "directly", "linked", "with", "enhanced", "pro-apoptotic", "activity", "and", "inhibition", "of", "NF", "B", "and", "AP1", "activities", "and", "their", "target", "genes", "in", "vitro", "and", "in", "vivo", "mouse", "melanoma", "model.", "Hence,", "further", "elucidation", "of", "active", "components", "of", "cinnamon", "extract", "could", "lead", "to", "development", "of", "potent", "anti-tumor", "agent", "or", "complementary", "and", "alternative", "medicine", "for", "the", "treatment", "of", "diverse", "cancers.", "Background", "Herbal", "medicines", "are", "plant-derived", "products", "which", "have", "been", "used", "as", "traditional", "folk", "medicine", "and", "food", "addi-", "tives.", "Recently", "their", "medicinal", "properties", "are", "under", "extensive", "investigation", "and", "become", "a", "major", "part", "of", "com-", "plementary", "and", "alternative", "medicines", "(CAMs).", "Their", "potency", "for", "treating", "different", "diseases", "has", "been", "reported", "including", "cancer,", "allergy", "and", "diabetes", "[1-4].", "Cinnamomum", "cassia", "bark", "is", "the", "outer", "skin", "of", "an", "ever-", "green", "tall", "tree", "belonging", "to", "the", "family", "Lauraceae.", "Its", "extracts", "contain", "several", "active", "components", "such", "as", "*", "Correspondence:", "imsh@gist.ac.kr", "1School", "of", "Life", "Sciences", "and", "Immune", "Synapse", "Research", "Center,", "Gwangju", "Institute", "of", "Science", "and", "Technology", "(GIST),", "1", "Oryong-dong,", "Puk-ku,", "Gwangju", "500-712,", "Republic", "of", "Korea", "essential", "oils", "(cinnamic", "aldehyde", "and", "cinnamyl", "alde-", "hyde),", "tannin,", "mucus", "and", "carbohydrates", "[5,6].", "They", "have", "various", "biological", "functions", "including", "anti-oxidant,", "anti-", "microbial,", "anti-inflammation,", "anti-diabetic", "effects", "[7-12],", "and", "anti-tumor", "activity", "[11,13].", "However,", "for", "the", "devel-", "opment", "of", "cinnamon", "as", "CAMs", "for", "cancer", "treatment,", "further", "studies", "are", "necessary", "such", "as", "elucidation", "of", "working", "mechanisms", "and", "characterization", "of", "active", "compounds", "directly", "linked", "with", "anti-tumor", "activity.", "Cancers", "are", "the", "most", "life-threatening", "health", "problems", "in", "the", "world", "[14].", "There", "have", "been", "many", "trials", "to", "treat", "cancers", "through", "modulation", "of", "anti-tumor", "immune", "response,", "apoptosis", "and", "anti-tumor", "proteins", "[15-18].", "Tumor", "cells", "are", "generally", "resistant", "to", "apoptosis;", "hence", "selective", "killing", "of", "tumor", "cells", "by", "promoting", "apoptosis", "©", "2010", "Kwon", "et", "al;", "licensee", "BioMed", "Central", "Ltd.", "This", "is", "an", "Open", "Access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "License", "(http://creativecommons.org/licenses/by/2.0),", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited." ]

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[ "Furrer", "et", "al.", "BMC", "Ophthalmology", "2012,", "12:24", "http://www.biomedcentral.com/1471-2415/12/24", "R", "E", "S", "E", "A", "R", "C", "H", "A", "R", "T", "I", "C", "L", "E", "Open", "Access", "Evaluation", "of", "filtering", "blebs", "using", "the", "‘Wuerzburg", "bleb", "classification", "score’", "compared", "to", "clinical", "findings", "Sandra", "Furrer1,", "Marcel", "N", "Menke2,", "Jens", "Funk3", "and", "Marc", "Töteberg-Harms3,4*", "Abstract", "Background:", "To", "determine", "the", "agreement", "between", "intraocular", "pressure", "and", "the", "‘Wuerzburg", "bleb", "classification", "score’,", "as", "well", "as", "between", "single", "items", "of", "the", "score", "and", "intraocular", "pressure.", "Interobserver", "variability", "was", "analyzed.", "Methods:", "57", "post-trabeculectomy", "eyes", "were", "included.", "Colour", "photographs", "were", "used", "to", "score", "the", "filtering", "bleb", "in", "accordance", "to", "the", "Wuerzburg", "bleb", "classification", "score", "by", "two", "different", "examiners.", "At", "the", "same", "visit,", "clinical", "data", "such", "as", "intraocular", "pressure,", "best", "corrected", "visual", "acuity,", "slit", "lamp", "biomicroscopy", "and", "medical", "history", "were", "obtained", "by", "another", "examiner.", "Results:", "After", "trabeculectomy,", "42", "out", "of", "57", "eyes", "(73.7%)", "reached", "the", "target", "pressure", "(≤21mmHg,", "and", "intraocular", "pressure", "reduction", "of", "at", "least", "20%,", "without", "antiglaucoma", "medication,", "and", "without", "any", "additional", "intervention).", "Fair", "agreement", "was", "found", "between", "intraocular", "pressure", "and", "Wuerzburg", "bleb", "classification", "score", "≥8", "points", "and", "≥7", "points", "(kappa", "0.24", "and", "0.27,", "respectively).", "Analyzing", "the", "subgroups", "of", "the", "morphological", "criteria,", "best", "agreement", "was", "found", "between", "occurrence", "of", "microcysts", "and", "target", "intraocular", "pressure", "(к", "0.22", "–", "0.34).", "Conclusions:", "Evaluating", "filtering", "blebs", "after", "trabeculectomy", "by", "using", "the", "Wuerzburg", "bleb", "classification", "score", "is", "a", "good", "technique", "for", "predicting", "intraocular", "pressure", "control", "in", "eyes", "attaining", "a", "minimum", "score", "of", "seven", "points.", "The", "presence", "of", "microcysts", "on", "the", "filtering", "bleb", "predicts", "that", "the", "eye", "is", "likely", "to", "attain", "target", "pressure.", "Keywords:", "Filtering", "bleb,", "Glaucoma,", "Filtration", "surgery,", "Bleb", "grading,", "Trabeculectomy", "Background", "Since", "first", "described", "by", "Cairns", "in", "1968", "[1],", "trabeculect-", "omy", "(TE)", "has", "been", "widely", "used", "and", "remains", "the", "gold", "standard", "in", "surgical", "treatment", "of", "glaucoma.", "Long-term", "success", "depends", "on", "preoperative", "and", "intraoperative", "con-", "ditions,", "but", "long-term", "success", "also", "highly", "depends", "on", "the", "persistence", "of", "filtration", "efficiency", "at", "the", "bleb", "site.", "Therefore,", "postoperative", "observation", "and", "care", "of", "the", "developing", "filtering", "bleb", "in", "clinical", "practice", "is", "an", "import-", "ant", "tool", "in", "reaching", "the", "target", "pressure", "after", "filtration", "surgery", "in", "a", "higher", "percentage", "of", "the", "patients", "[2,3].", "Since", "1989,", "a", "number", "of", "observations", "and", "classifica-", "tions", "of", "filtering", "blebs", "using", "morphological", "criteria", "*", "Correspondence:", "MarcToeteberg@aol.com", "3Department", "of", "Ophthalmology,", "UniversityHospital", "of", "Zurich,", "Frauenklinikstrasse", "24,", "8091", "Zurich,", "Switzerland", "4Massachusetts", "Eye", "&", "Ear", "Infirmary,", "Harvard", "Medical", "School,", "Boston,", "MA,", "USA", "Full", "list", "of", "author", "information", "is", "available", "at", "the", "end", "of", "the", "article", "have", "been", "described", "[4-7].", "These", "early", "efforts", "included", "various", "assessments", "of", "filtering", "bleb", "morphology", "and", "emphasize", "a", "general", "consensus", "in", "the", "morphologic", "fea-", "tures", "that", "indicate", "favourable", "in", "contrast", "to", "unfavour-", "able", "filtering", "bleb", "development", "[8].", "The", "most", "frequent", "matter", "of", "failing", "filtering", "surgery", "is", "still", "subconjunctival", "scarring", "which", "needs", "intensified", "postoperative", "care", "of", "the", "filtering", "bleb", "even", "if", "intraocular", "pressure", "(IOP)", "remains", "well", "controlled", "[9].", "In", "order", "to", "allow", "a", "well-", "structured", "assessment", "of", "bleb", "morphology", "and", "to", "pre-", "dict", "potential", "signs", "of", "failure", "early", "enough", "(to", "initiate", "wound", "healing", "modulation", 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[ "BMC", "Genomics", "Research", "article", "Comparison", "of", "the", "transcriptomic", "\"stress", "response\"", "evoked", "by", "antimycin", "A", "and", "oxygen", "deprivation", "in", "saccharomyces", "cerevisiae", "Liang-Chuan", "Lai1,4,", "Matthew", "T", "Kissinger2,4,", "Patricia", "V", "Burke3,4", "and", "Kurt", "E", "Kwast*4", "BioMed", "Central", "Open", "Access", "Address:", "1Department", "of", "Physiology,", "National", "Taiwan", "University", "College", "of", "Medicine,", "Taipei,", "Taiwan", "(R.O.C.),", "2Coskata", "Inc.,", "4575", "Weaver", "Pkwy,", "Suite", "100,", "Warrenville,", "IL", "60555,", "USA,", "3Department", "of", "Microbiology,", "University", "of", "Illinois,", "Urbana,", "IL", "61801,", "USA", "and", "4Department", "of", "Molecular", "&", "Integrative", "Physiology,", "University", "ofIllinois,", "Urbana,", "IL", "61801,", "USA", "Email:", "Liang-Chuan", "Lai", "-", "llai@ntu.edu.tw;", "Matthew", "T", "Kissinger", "-", "mkissi@yahoo.com;", "Patricia", "V", "Burke", "-", "burke@life.uiuc.edu;", "Kurt", "E", "Kwast*", "-", "kwast@uiuc.edu", "*", "Corresponding", "author", "Published:", "23", "December", "2008", "BMC", "Genomics", "2008,", "9:627", "doi:10.1186/1471-2164-9-627", "This", "article", "is", "available", "from:", "http://www.biomedcentral.com/1471-2164/9/627", "Received:", "22", "October", "2007", "Accepted:", "23", "December", "2008", "©", "2008", "Lai", "et", "al;", "licensee", "BioMed", "Central", "Ltd.", "This", "is", "an", "Open", "Access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "License", "(http://creativecommons.org/licenses/by/2.0),", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited.", "Abstract", "Background:", "Acute", "changes", "in", "environmental", "parameters", "(e.g.,", "O2,", "pH,", "UV,", "osmolarity,", "nutrients,", "etc.)", "evoke", "a", "common", "transcriptomic", "response", "in", "yeast", "referred", "to", "as", "the", "\"environmental", "stress", "response\"", "(ESR)", "or", "\"common", "environmental", "response\"", "(CER).", "Why", "such", "a", "diverse", "array", "of", "insults", "should", "elicit", "a", "common", "transcriptional", "response", "remains", "enigmatic.", "Previous", "functional", "analyses", "of", "the", "networks", "involved", "have", "found", "that,", "in", "addition", "to", "up-regulating", "those", "for", "mitigating", "the", "specific", "stressor,", "the", "majority", "appear", "to", "be", "involved", "in", "balancing", "energetic", "supply", "and", "demand", "and", "modulating", "progression", "through", "the", "cell", "cycle.", "Here", "we", "compared", "functional", "and", "regulatory", "aspects", "of", "the", "stress", "responses", "elicited", "by", "the", "acute", "inhibition", "of", "respiration", "with", "antimycin", "A", "and", "oxygen", "deprivation", "under", "catabolite", "non-repressed", "(galactose)", "conditions.", "Results:", "Gene", "network", "analyses", "of", "the", "transcriptomic", "responses", "revealed", "both", "treatments", "result", "in", "the", "transient", "(10", "–", "60", "min)", "down-regulation", "of", "MBF-", "and", "SBF-regulated", "networks", "involved", "in", "the", "G1/S", "transition", "of", "the", "cell", "cycle", "as", "well", "as", "Fhl1", "and", "PAC/RRPE-associated", "networks", "involved", "in", "energetically", "costly", "programs", "of", "ribosomal", "biogenesis", "and", "protein", "synthesis.", "Simultaneously,", "Msn2/", "4", "networks", "involved", "in", "hexose", "import/dissimilation,", "reserve", "energy", "regulation,", "and", "autophagy", "were", "transiently", "up-regulated.", "Interestingly,", "when", "cells", "were", "treated", "with", "antimycin", "A", "well", "before", "experiencing", "anaerobiosis", "these", "networks", "subsequently", "failed", "to", "respond", "to", "oxygen", "deprivation.", "These", "results", "suggest", "the", "transient", "stress", "response", "is", "elicited", "by", "the", "acute", "inhibition", "of", "respiration", "and,", "we", "postulate,", "changes", "in", "cellular", "energetics", "and/or", "the", "instantaneous", "growth", "rate,", "not", "oxygen", "deprivation", "per", "se.", "After", "a", "considerable", "delay", "(≥", "1", "generation)", "under", "anoxia,", "predictable", "changes", "in", "heme-regulated", "gene", "networks", "(e.g.,", "Hap1,", "Hap2/3/4/5,", "Mot3,", "Rox1", "and", "Upc2)", "were", "observed", "both", "in", "the", "presence", "and", "absence", "of", "antimycin", "A.", "Conclusion:", "This", "study", "not", "only", "differentiates", "between", "the", "gene", "networks", "that", "respond", "to", "respiratory", "inhibition", "and", "those", "that", "respond", "to", "oxygen", "deprivation", "but", "suggests", "the", "function", "of", "the", "ESR", "or", "CER", "is", "to", "balance", "energetic", "supply/demand", "and", "coordinate", "growth", "with", "the", "cell", "cycle,", "whether", "in", "response", "to", "perturbations", "that", "disrupt", "catabolic", "pathways", "or", "those", "that", "require", "rapidly", "up-regulating", "energetically", "costly", "programs", "for", "combating", "specific", "stressors.", "Page", "1", "of", "14", "(page", "number", "not", "for", "citation", "purposes)" ]

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[ "CELLULAR", "AND", "INFECTION", "MICROBIOLOGY", "Shiga", "toxin", "2-induced", "intestinal", "pathology", "in", "infant", "rabbits", "is", "A-subunit", "dependent", "and", "responsive", "to", "the", "tyrosine", "kinase", "and", "potential", "ZAK", "inhibitor", "imatinib", "Samuel", "M.", "Stone", "1,", "Cheleste", "M.", "Thorpe", "1,", "Amrita", "Ahluwalia", "1,2,", "Arlin", "B.", "Rogers", "3,", "Fumiko", "Obata", "4,", "Aimee", "Vozenilek", "4,", "Glynis", "L.", "Kolling", "5,", "Anne", "V.", "Kane", "1,6,", "Bruce", "E.", "Magun", "7", "and", "Dakshina", "M.", "Jandhyala", "1*", "1", "Division", "of", "Geographic", "Medicine", "and", "Infectious", "Diseases,", "Tufts", "Medical", "Center,", "and", "Tufts", "University", "School", "of", "Medicine,", "Boston,", "MA,", "USA", "2", "VA", "Long", "Beach", "Healthcare", "System,", "Long", "Beach,", "CA,", "USA", "3", "Department", "of", "Pathology", "and", "Laboratory", "Medicine,", "The", "University", "of", "North", "Carolina", "School", "of", "Medicine,", "Chapel", "Hill,", "NC,", "USA", "4", "Department", "of", "Microbiology", "and", "Immunology,", "University", "of", "Maryland", "School", "of", "Medicine,", "Baltimore,", "MD,", "USA", "5", "Department", "of", "Internal", "Medicine/Nephrology,", "University", "of", "Virginia,", "Charlottesville,", "VA,", "USA", "6", "Phoenix", "Laboratory,", "Tufts", "Medical", "Center,", "Boston,", "MA,", "USA", "7", "Department", "of", "Cell", "and", "Developmental", "Biology,", "Oregon", "Health", "and", "Science", "University,", "Portland,", "OR,", "USA", "ORIGINAL", "RESEARCH", "ARTICLE", "published:", "08", "November", "2012", "doi:", "10.3389/fcimb.2012.00135", "Edited", "by:", "Alfredo", "G.", "Torres,", "University", "of", "Texas", "Medical", "Branch,", "USA", "Reviewed", "by:", "Vernon", "L.", "Tesh,", "Texas", "A&M", "University", "Health", "Science", "Center,", "USA", "Jennifer", "Ritchie,", "University", "of", "Surrey,", "UK", "*Correspondence:", "Dakshina", "M.", "Jandhyala,", "Division", "of", "Geographic", "Medicine", "and", "Infectious", "Disease,", "Tufts", "Medical", "Center,", "Box", "041,", "750", "Washington", "Street,", "Boston,", "MA", "02111,", "USA.", "e-mail:", "djandhyala@", "tuftsmedicalcenter.org", "Shiga", "toxin", "producing", "Escherichia", "coli", "(STEC)", "are", "a", "major", "cause", "of", "food-borne", "illness", "worldwide.", "However,", "a", "consensus", "regarding", "the", "role", "Shiga", "toxins", "play", "in", "the", "onset", "of", "diarrhea", "and", "hemorrhagic", "colitis", "(HC)", "is", "lacking.", "One", "of", "the", "obstacles", "to", "understanding", "the", "role", "of", "Shiga", "toxins", "to", "STEC-mediated", "intestinal", "pathology", "is", "a", "deficit", "in", "small", "animal", "models", "that", "perfectly", "mimic", "human", "disease.", "Infant", "rabbits", "have", "been", "previously", "used", "to", "study", "STEC", "and/or", "Shiga", "toxin-mediated", "intestinal", "inflammation", "and", "diarrhea.", "We", "demonstrate", "using", "infant", "rabbits", "that", "Shiga", "toxin-mediated", "intestinal", "damage", "requires", "A-subunit", "activity,", "and", "like", "the", "human", "colon,", "that", "of", "the", "infant", "rabbit", "expresses", "the", "Shiga", "toxin", "receptor", "Gb3.", "We", "also", "demonstrate", "that", "Shiga", "toxin", "treatment", "of", "the", "infant", "rabbit", "results", "in", "apoptosis", "and", "activation", "of", "p38", "within", "colonic", "tissues.", "Finally", "we", "demonstrate", "that", "the", "infant", "rabbit", "model", "may", "be", "used", "to", "test", "candidate", "therapeutics", "against", "Shiga", "toxin-mediated", "intestinal", "damage.", "While", "the", "p38", "inhibitor", "SB203580", "and", "the", "ZAK", "inhibitor", "DHP-2", "were", "ineffective", "at", "preventing", "Shiga", "toxin-mediated", "damage", "to", "the", "colon,", "pretreatment", "of", "infant", "rabbits", "with", "the", "drug", "imatinib", "resulted", "in", "a", "decrease", "of", "Shiga", "toxin-mediated", "heterophil", "infiltration", "of", "the", "colon.", "Therefore,", "we", "propose", "that", "this", "model", "may", "be", "useful", "in", "elucidating", "mechanisms", "by", "which", "Shiga", "toxins", "could", "contribute", "to", "intestinal", "damage", "in", "the", "human.", "Keywords:", "Shiga", "toxin,", "globotriaosylceramide,", "inflammation,", "colon,", "rabbit,", "p38,", "imatinib", "INTRODUCTION", "Shiga", "toxin-producing", "Escherichia", "coli", "(STEC)", "are", "a", "heterogenous", "group", "of", "E.", "coli", "strains", "responsible", "for", "food-", "and", "water-borne", "ill-", "ness", "worldwide.", "Depending", "on", "the", "strain,", "approximately", "5–22%", "of", "infected", "individuals", "will", "suffer", "severe", "illnesses", "that", "can", "result", "in", "permanent", "disability", "or", "death", "(Paton", "et", "al.,", "1998;", "Kulasekara", "et", "al.,", "2009;", "Frank", "et", "al.,", "2011).", "Severe", "illnesses", "attributed", "to", "STEC-associated", "sequelae", "include", "hemorrhagic", "colitis", "(HC)", "and", "the", "hemolytic", "uremic", "syndrome", "(HUS),", "the", "predominant", "cause", "of", "renal", "failure", "in", "US", "children", "(Siegler,", "2003).", "Other", "than", "vol-", "ume", "expansion", "during", "the", "diarrheal", "phase,", "no", "approved", "specific", "preventative", "treatments", "exist", "for", "STEC-associated", "HUS.", "Shiga", "toxins", "(Stxs)", "are", "the", "key", "virulence", "factors", "responsi-", "ble", "for", "promoting", "severe", "disease", "during", "STEC", "infection.", "Stxs", "are", "AB5", "toxins", "consisting", "of", "a", "single", "A-subunit", "non-covalently", "bound", "to", "5", "B-subunits.", "The", "B-subunits", "are", "necessary", "for", "bind-", "ing", "of", "the", "toxin", "to", "the", "surface", "of", "the", "host", "cells", "via", "interac-", "tion", "with", "neutral", "glycolipids", "with", "the", "glycosphingolipid", "receptor", "globotriaosylceramide", "(Gb3)", "being", "the", "major", "receptor", "(Lingwood", "et", "al.,", "2010).", "Once", "bound,", "the", "toxin", "undergoes", "receptor-mediated", "endocytosis", "and", "is", "transported", "retrograde", "through", "the", "early", "endosome,", "the", "Golgi", "apparatus,", "and", "to", "the", "endoplasmic", "retic-", "ulum", "(ER).", "Somewhere", "between", "the", "early", "endosome", "and", "the", "trans-Golgi", "network,", "the", "enzymatically", "active", "portion", "of", "the", "A-subunit", "is", "proteolytically", "cleaved", "possibly", "by", "furin", "into", "an", "A1", "fragment", "which", "remains", "bound", "to", "the", "A2", "fragment", "and", "non-covalently", "associated", "B-subunits", "via", "an", "intramolecular", "disul-", "fide", "bond", "(Garred", "et", "al.,", "1995a,b;", "Tam", "and", "Lingwood,", "2007).", "Eventually", "the", "disulfide", "bond", "is", "reduced,", "possibly", "in", "the", "ER", "(Spooner", "and", "Lord,", "2012),", "and", "the", "enzymatically", "active", "A1", "frag-", "ment", "is", "translocated", "to", "the", "cytoplasm,", "where", "its", "N-glycosidase", "activity", "results", "in", "the", "depurination", "of", "a", "single", "adenine", "residue", "located", "in", "the", "alpha-sarcin/ricin", "loop", "of", "the", "28S", "ribosomal", "RNA", "(Endo", "and", "Tsurugi,", "1987;", "Endo", "et", "al.,", "1987,", "1988).", "This", "depuri-", "nation", "event", "results", "in", "the", "cessation", "of", "protein", "synthesis", "in", "the", "translational", "elongation", "phase", "and", "activates", "a", "proinflammatory", "signaling", "cascade", "referred", "to", "as", "the", "ribotoxic", "stress", "response", "(RSR)", "(Iordanov", "et", "al.,", "1997).", "The", "RSR", "is", "defined", "as", "the", "activation", "of", "MAPKinases", "by", "cer-", "tain", "protein", "synthesis", "inhibitors", "including", "Shiga", "toxins,", "ricin,", "Frontiers", "in", "Cellular", "and", "Infection", "Microbiology", "www.frontiersin.org", "November", "2012", "|", "Volume", "2", "|", "Article", "135", "|", "1" ]

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[ "Bousios", "et", "al.", "BMC", "Genomics", "2010,", "11:89", "http://www.biomedcentral.com/1471-2164/11/89", "R", "E", "S", "E", "A", "R", "C", "H", "A", "R", "T", "I", "C", "L", "E", "Open", "Access", "Highly", "conserved", "motifs", "in", "non-coding", "regions", "of", "Sirevirus", "retrotransposons:", "the", "key", "for", "their", "pattern", "of", "distribution", "within", "and", "across", "plants?", "Alexandros", "Bousios1*,", "Nikos", "Darzentas2,", "Athanasios", "Tsaftaris2,3,", "Stephen", "R", "Pearce1", "Abstract", "Background:", "Retrotransposons", "are", "key", "players", "in", "the", "evolution", "of", "eukaryotic", "genomes.", "Moreover,", "it", "is", "now", "known", "that", "some", "retrotransposon", "classes,", "like", "the", "abundant", "and", "plant-specific", "Sireviruses,", "have", "intriguingly", "distinctive", "host", "preferences.", "Yet,", "it", "is", "largely", "unknown", "if", "this", "bias", "is", "supported", "by", "different", "genome", "structures.", "Results:", "We", "performed", "sensitive", "comparative", "analysis", "of", "the", "genomes", "of", "a", "large", "set", "of", "Ty1/copia", "retrotransposons.", "We", "discovered", "that", "Sireviruses", "are", "unique", "among", "Pseudoviridae", "in", "that", "they", "constitute", "an", "ancient", "genus", "characterized", "by", "vastly", "divergent", "members,", "which", "however", "contain", "highly", "conserved", "motifs", "in", "key", "non-coding", "regions:", "multiple", "polypurine", "tract", "(PPT)", "copies", "cluster", "upstream", "of", "the", "3’", "long", "terminal", "repeat", "(3’LTR),", "of", "which", "the", "terminal", "PPT", "tethers", "to", "a", "distinctive", "attachment", "site", "and", "is", "flanked", "by", "a", "precisely", "positioned", "inverted", "repeat.", "Their", "LTRs", "possess", "a", "novel", "type", "of", "repeated", "motif", "(RM)", "defined", "by", "its", "exceptionally", "high", "copy", "number,", "symmetry", "and", "core", "CGG-CCG", "signature.", "These", "RM", "boxes", "form", "CpG", "islands", "and", "lie", "a", "short", "distance", "upstream", "of", "a", "conserved", "promoter", "region", "thus", "hinting", "towards", "regulatory", "functions.", "Intriguingly,", "in", "the", "envelope-containing", "Sireviruses", "additional", "boxes", "cluster", "at", "the", "5’", "vicinity", "of", "the", "envelope.", "The", "5’LTR/internal", "domain", "junction", "and", "a", "polyC-rich", "integrase", "signal", "are", "also", "highly", "conserved", "domains", "of", "the", "Sirevirus", "genome.", "Conclusions:", "Our", "comparative", "analysis", "of", "retrotransposon", "genomes", "using", "advanced", "in", "silico", "methods", "highlighted", "the", "unique", "genome", "organization", "of", "Sireviruses.", "Their", "structure", "may", "dictate", "a", "life", "cycle", "with", "different", "regulation", "and", "transmission", "strategy", "compared", "to", "other", "Pseudoviridae,", "which", "may", "contribute", "towards", "their", "pattern", "of", "distribution", "within", "and", "across", "plants.", "Background", "Retrotransposons", "and", "retroviruses", "(collectively", "referred", "as", "retroelements)", "can", "replicate", "their", "genomes", "via", "an", "RNA", "intermediate", "and", "insert", "the", "copies", "into", "new", "chro-", "mosomal", "locations", "of", "the", "host", "organism", "[1,2].", "This", "‘copy", "and", "paste’", "process", "has", "the", "potential", "to", "greatly", "amplify", "their", "abundance,", "even", "over", "short", "evolutionary", "timescales,", "enabling", "them", "to", "become", "a", "major", "compo-", "nent", "of", "genomes", "[3-5].", "Unlike", "retrotransposons,", "retro-", "viruses", "have", "additional", "coding", "capacity", "in", "the", "form", "of", "an", "envelope", "(ENV)", "gene", "that", "allows", "them", "to", "enter", "the", "extracellular", "space", "and", "infect", "other", "individuals.", "Retro-", "transposons", "lack", "the", "ENV", "gene", "and", "cannot", "escape", "the", "cell,", "however", "they", "are", "free", "to", "reinfect", "their", "host", "genome.", "*", "Correspondence:", "alexandros.bousios@gmail.com", "1Department", "of", "Biology", "and", "Environmental", "Science,", "School", "of", "Life", "Sciences,", "University", "of", "Sussex,", "Brighton,", "UK", "Long", "Terminal", "Repeat", "(LTR)", "retrotransposons", "form", "the", "most", "abundant", "transposable", "element", "type", "in", "plants,", "lar-", "gely", "accounting", "for", "the", "vast", "differences", "in", "genome", "sizes", "[6].", "Small", "genome", "plants", "like", "Arabidopsis", "(121", "Mbp)", "and", "rice", "(389", "Mbp)", "are", "sparsely", "populated", "by", "LTR", "ret-", "rotransposons,", "5.6%", "[7]", "and", "17%", "[8]", "respectively.", "In", "con-", "trast,", "the", "LTR", "retrotransposon-derived", "fraction", "of", "medium/large", "genomes", "may", "reach", "up", "to", "75%", "in", "maize", "(2.300", "Mbp)", "[9,10]", "and", "70%", "in", "barley", "(5439", "Mbp)", "[11].", "The", "two", "main", "superfamilies", "of", "LTR", "retrotransposons", "are", "the", "Ty1/copia", "(Pseudoviridae)", "and", "Ty3/gypsy", "(Meta-", "viridae)", "[12],", "which", "differ", "in", "the", "order", "they", "package", "their", "genes", "in", "the", "coding", "domains.", "Both", "typically", "con-", "tain", "the", "gag", "gene", "and", "the", "pol", "gene", "region.", "gag", "encodes", "a", "capsid", "protein", "that", "forms", "the", "virus-like", "particle", "(VLP),", "which", "houses", "one", "or", "two", "RNA", "genomes", "and", "the", "enzymes", "for", "the", "cytoplasmic", "step", "of", "reverse", "©", "2010", "Bousios", "et", "al;", "licensee", "BioMed", "Central", "Ltd.", "This", "is", "an", "Open", "Access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "License", "(http://creativecommons.org/licenses/by/2.0),", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited." ]

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[ "Gue´", "ret1,2*", "Abstract", "Bloom’s", "Syndrome", "and", "PICH", "Helicases", "Cooperate", "with", "Topoisomerase", "IIa", "in", "Centromere", "Disjunction", "before", "Anaphase", "Se´", "bastien", "Rouzeau1,2,", "Fabrice", "P.", "Cordelie`", "res1,2,3,", "Ge´", "raldine", "Buhagiar-Labarche`", "de1,2,", "Ilse", "Hurbain4,5,6,", "Rosine", "Onclercq-Delic1,2,", "Simon", "Gemble1,2,", "Laura", "Magnaghi-Jaulin7,", "Christian", "Jaulin7,", "Mounira", "Amor-", "1", "Institut", "Curie,", "Centre", "de", "Recherche,", "Centre", "Universitaire,", "Baˆt", "Orsay,", "France,", "2", "CNRS", "UMR3348,", "Stress", "Ge´notoxiques", "et", "Cancer,", "Orsay,", "France,", "3", "Institut", "Curie,", "Centre", "de", "Recherche,", "Plateforme", "d’Imagerie", "Cellulaire", "et", "Tissulaire", "IBiSA,", "Centre", "Universitaire,", "Baˆt", "Orsay,", "France,", "4", "Institut", "Curie,", "Centre", "de", "Recherche,", "Paris,", "France,", "5", "Structure", "et", "Compartimentation", "membranaire,", "CNRS", "UMR144,", "Paris,", "France,", "6", "Plateforme", "d’Imagerie", "Cellulaire", "et", "Tissulaire", "IBiSA,", "CNRS", "UMR", "144,", "Paris,", "France,", "7", "Institut", "de", "Ge´ne´tique", "et", "De´veloppement,", "CNRS", "UMR", "6290,", "Universite´", "de", "Rennes", "1,", "Rennes,", "France", "Centromeres", "are", "specialized", "chromosome", "domains", "that", "control", "chromosome", "segregation", "during", "mitosis,", "but", "little", "is", "known", "about", "the", "mechanisms", "underlying", "the", "maintenance", "of", "their", "integrity.", "Centromeric", "ultrafine", "anaphase", "bridges", "are", "physiological", "DNA", "structures", "thought", "to", "contain", "unresolved", "DNA", "catenations", "between", "the", "centromeres", "separating", "during", "anaphase.", "BLM", "and", "PICH", "helicases", "colocalize", "at", "these", "ultrafine", "anaphase", "bridges", "and", "promote", "their", "resolution.", "As", "PICH", "is", "detectable", "at", "centromeres", "from", "prometaphase", "onwards,", "we", "hypothesized", "that", "BLM", "might", "also", "be", "located", "at", "centromeres", "and", "that", "the", "two", "proteins", "might", "cooperate", "to", "resolve", "DNA", "catenations", "before", "the", "onset", "of", "anaphase.", "Using", "immunofluorescence", "analyses,", "we", "demonstrated", "the", "recruitment", "of", "BLM", "to", "centromeres", "from", "G2", "phase", "to", "mitosis.", "With", "a", "combination", "of", "fluorescence", "in", "situ", "hybridization,", "electron", "microscopy,", "RNA", "interference,", "chromosome", "spreads", "and", "chromatin", "immunoprecipitation,", "we", "showed", "that", "both", "BLM-deficient", "and", "PICH-deficient", "prometaphase", "cells", "displayed", "changes", "in", "centromere", "structure.", "These", "cells", "also", "had", "a", "higher", "frequency", "of", "centromeric", "non", "disjunction", "in", "the", "absence", "of", "cohesin,", "suggesting", "the", "persistence", "of", "catenations.", "Both", "proteins", "were", "required", "for", "the", "correct", "recruitment", "to", "the", "centromere", "of", "active", "topoisomerase", "IIa,", "an", "enzyme", "specialized", "in", "the", "catenation/decatenation", "process.", "These", "observations", "reveal", "the", "existence", "of", "a", "functional", "relationship", "between", "BLM,", "PICH", "and", "topoisomerase", "IIa", "in", "the", "centromere", "decatenation", "process.", "They", "indicate", "that", "the", "higher", "frequency", "of", "centromeric", "ultrafine", "anaphase", "bridges", "in", "BLM-deficient", "cells", "and", "in", "cells", "treated", "with", "topoisomerase", "IIa", "inhibitors", "is", "probably", "due", "not", "only", "to", "unresolved", "physiological", "ultrafine", "anaphase", "bridges,", "but", "also", "to", "newly", "formed", "ultrafine", "anaphase", "bridges.", "We", "suggest", "that", "BLM", "and", "PICH", "cooperate", "in", "rendering", "centromeric", "catenates", "accessible", "to", "topoisomerase", "IIa,", "thereby", "facilitating", "correct", "centromere", "disjunction", "and", "preventing", "the", "formation", "of", "supernumerary", "centromeric", "ultrafine", "anaphase", "bridges.", "Citation:", "Rouzeau", "S,", "Cordelie`res", "FP,", "Buhagiar-Labarche`de", "G,", "Hurbain", "I,", "Onclercq-Delic", "R,", "et", "al.", "(2012)", "Bloom’s", "Syndrome", "and", "PICH", "Helicases", "Cooperate", "with", "Topoisomerase", "IIa", "in", "Centromere", "Disjunction", "before", "Anaphase.", "PLoS", "ONE", "7(4):", "e33905.", "doi:10.1371/journal.pone.0033905", "Editor:", "Beth", "A.", "Sullivan,", "Duke", "University,", "United", "States", "of", "America", "Received", "November", "4,", "2011;", "Accepted", "February", "19,", "2012;", "Published", "April", "26,", "2012", "Copyright:", "2012", "Rouzeau", "et", "al.", "This", "is", "an", "open-access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "License,", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "author", "and", "source", "are", "credited.", "Funding:", "This", "work", "was", "supported", "by", "grants", "from", "the", "Institut", "Curie", "(PIC),", "the", "Centre", "National", "de", "la", "Recherche", "Scientifique", "(CNRS),", "the", "Cance´ropoˆ", "le/Re´gion", "Ile-", "de-France,", "the", "Ligue", "contre", "le", "Cancer", "Grand-Ouest,", "the", "Association", "pour", "la", "Recherche", "sur", "le", "Cancer", "(1071),", "the", "Agence", "Nationale", "de", "la", "Recherche", "(EpiCentr)", "and", "by", "fellowships", "from", "the", "Ministe`re", "de´le´gue´", "de", "l’Enseignement", "Supe´rieur", "et", "de", "la", "Recherche", "and", "from", "the", "Ligue", "Nationale", "contre", "le", "Cancer.", "The", "funders", "had", "no", "role", "in", "study", "design,", "data", "collection", "and", "analysis,", "decision", "to", "publish,", "or", "preparation", "of", "the", "manuscript.", "Competing", "Interests:", "The", "authors", "have", "declared", "that", "no", "competing", "interests", "exist.", "*", "E-mail:", "mounira.amor@curie.fr", "Introduction", "The", "centromere", "is", "a", "highly", "differentiated", "chromosomal", "structure", "consisting,", "in", "human", "cells,", "of", "a-satellite", "DNA", "repeats", "[1].", "It", "plays", "an", "essential", "role", "in", "cell", "division,", "particularly", "in", "kinetochore", "assembly,", "and", "in", "ensuring", "the", "segregation", "of", "equal", "number", "of", "chromosomes", "to", "daughter", "cells", "during", "mitosis", "[2].", "The", "maintenance", "of", "centromere", "stability", "is", "thus", "essential", "to", "prevent", "chromosomal", "instability", "and", "cancer", "development", "[3].", "Our", "interest", "in", "centromere", "stability", "began", "with", "the", "unexpected", "discovery", "that", "a", "helicase-like", "protein,", "PICH", "(Plk1-interacting", "checkpoint", "‘‘heli-", "case’’)", "and", "the", "Bloom", "syndrome", "helicase", "(BLM)", "colocalized", "to", "centromeric", "ultrathin", "DNA", "threads", "that", "could", "not", "be", "counter-", "stained", "with", "conventional", "DNA", "dyes", "or", "antibodies", "against", "histones", "[4,5].", "These", "threads", "were", "found", "to", "be", "common", "in", "all", "cultured", "normal", "cells", "tested,", "and", "are", "therefore", "probably", "physiological", "structures.", "These", "PICH-", "and", "BLM-positive", "DNA", "threads,", "which", "are", "also", "called", "ultrafine", "anaphase", "bridges", "(UFBs),", "are", "thought", "to", "contain", "unresolved", "DNA", "catenations", "between", "the", "centromeres", "separating", "during", "anaphase", "or", "to", "originate", "from", "incompletely", "replicated", "DNA", "[4,5].", "Almost", "all", "the", "UFBs", "detected", "in", "untreated", "cells", "are", "of", "centromeric", "origin", "and", "have", "been", "proposed", "to", "prevent", "reactivation", "of", "the", "spindle", "assembly", "checkpoint", "(SAC)", "during", "early", "anaphase,", "by", "maintaining", "tension", "across", "centromeres", "[4,6].", "As", "cells", "progress", "through", "anaphase,", "UFBs", "become", "progressively", "longer", "and", "decrease", "in", "number.", "They", "are", "no", "longer", "detectable", "by", "telophase.", "The", "resolution", "of", "centromeric", "UFBs", "requires", "topo-", "PLoS", "ONE", "|", "www.plosone.org", "1", "April", "2012", "|", "Volume", "7", "|", "Issue", "4", "|", "e33905" ]

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[ "Published", "online", "11", "May", "2010", "Nucleic", "Acids", "Research,", "2010,", "Vol.", "38,", "Web", "Server", "issue", "W155–W160", "doi:10.1093/nar/gkq331", "The", "Ontology", "Lookup", "Service:", "bigger", "and", "better", "Richard", "C", "oˆte´", "1,*,", "Florian", "Reisinger1,", "Lennart", "Martens2,3,", "Harald", "Barsnes4,", "Juan", "Antonio", "Vizcaino1", "and", "Henning", "Hermjakob1", "1European", "Bioinformatics", "Institute,", "Wellcome", "Trust", "Genome", "Campus,", "Cambridge,", "CB10", "1SD,", "UK,", "2Department", "of", "Medical", "Protein", "Research,", "VIB,", "Ghent,", "Belgium,", "3Department", "of", "Biochemistry,", "Ghent", "University,", "Ghent,", "Belgium", "and", "4Department", "of", "Informatics,", "University", "of", "Bergen,", "Norway", "Received", "January", "29,", "2010;", "Revised", "April", "4,", "2010;", "Accepted", "April", "17,", "2010", "ABSTRACT", "The", "Ontology", "Lookup", "Service", "(OLS;", "http://www.ebi", ".ac.uk/ols)", "has", "been", "providing", "several", "means", "to", "query,", "browse", "and", "navigate", "biomedical", "ontologies", "and", "controlled", "vocabularies", "since", "it", "first", "went", "into", "production", "4", "years", "ago,", "and", "usage", "statistics", "indicate", "that", "it", "has", "become", "a", "heavily", "accessed", "service", "with", "millions", "of", "hits", "monthly.", "The", "volume", "of", "data", "available", "for", "querying", "has", "increased", "7-fold", "since", "its", "inception.", "OLS", "functionality", "has", "been", "integrated", "into", "several", "high-usage", "databases", "and", "data", "entry", "tools.", "Improvements", "in", "the", "data", "model", "and", "loaders,", "as", "well", "as", "interface", "enhancements", "have", "made", "the", "OLS", "easier", "to", "use", "and", "capture", "more", "annotations", "from", "the", "source", "data.", "In", "addition,", "newly", "released", "software", "packages", "now", "provide", "easy", "means", "to", "fully", "integrate", "OLS", "function-", "ality", "in", "external", "applications.", "INTRODUCTION", "Ontologies", "and", "controlled", "vocabularies", "(CVs)", "have", "more", "than", "demonstrated", "their", "essential", "function", "when", "dealing", "with", "large", "volumes", "of", "complex", "data", "currently", "being", "generated", "by", "high-throughput", "multi-domain", "analysis", "tech-", "niques", "(1).", "They", "provide", "a", "framework", "around", "which", "large", "data", "sets", "can", "be", "systematically", "annotated", "and", "queried.", "For", "this", "framework", "to", "function", "efficiently,", "however,", "the", "ontologies", "and", "CVs", "must", "be", "made", "available", "to", "the", "user", "community.", "The", "Ontology", "Lookup", "Service", "(OLS)", "has", "been", "in", "pro-", "duction", "since", "mid-2005", "and", "has", "quickly", "become", "one", "of", "the", "most", "accessed", "services", "in", "the", "Proteomics", "Services", "team", "at", "the", "EBI,", "with", "monthly", "usage", "figures", "in", "the", "millions", "of", "hits.", "This", "includes", "both", "the", "programmatic", "as", "well", "as", "the", "inter-", "active", "interfaces", "that", "the", "service", "offers.", "The", "OLS", "has", "been", "previously", "described", "and", "readers", "are", "invited", "to", "refer", "to", "the", "original", "publication", "for", "in-depth", "information", "on", "the", "tech-", "nical", "architecture", "and", "data", "models", "(2,3).", "The", "core", "functionality", "of", "the", "OLS", "has", "remained", "largely", "unchanged", "since", "its", "inception,", "allowing", "users", "to", "query", "ontologies", "and", "CVs", "by", "name", "or", "identifier", "as", "well", "as", "ob-", "taining", "metadata,", "such", "as", "synonyms,", "definitions,", "cross", "ref-", "erences", "and", "other", "annotations,", "for", "a", "given", "term.", "Users", "can", "also", "traverse", "the", "relationships", "between", "terms.", "The", "usabil-", "ity", "and", "volume", "of", "data", "captured,", "however,", "has", "been", "enhanced", "and", "this", "will", "be", "expanded", "below.", "The", "OLS", "has", "always", "been", "designed", "to", "be", "used", "in", "other", "projects", "as", "a", "means", "to", "integrate", "ontology", "and", "CV", "anno-", "tation", "and", "query", "functionality.", "A", "SOAP", "web", "service", "has", "been", "available", "since", "the", "OLS", "went", "into", "production.", "A", "full", "description", "of", "the", "web", "service", "has", "already", "been", "published", "(2,3)", "and", "users", "who", "wish", "to", "make", "use", "of", "it", "are", "encouraged", "to", "go", "to", "the", "OLS", "web", "service", "developer", "section", "for", "the", "most", "up-to-date", "documentation", "and", "code", "samples", "(http://www.ebi.ac.uk/ontology-lookup/WSDLDocument", "ation.do).", "AVAILABLE", "DATA", "The", "first", "OLS", "publication", "described", "it", "as", "containing", "42", "ontologies,", "accounting", "for", "roughly", "135", "000", "terms.", "Over", "a", "4-year", "period,", "the", "data", "loaded", "into", "the", "OLS", "has", "been", "expanded", "to", "79", "ontologies,", "representing", "over", "971", "000", "unique", "terms", "(Figure", "1).", "These", "cover", "far-ranging", "topics", "such", "as", "model", "organism", "anatomy", "and", "development,", "physi-", "ology", "and", "disease,", "instrumentation", "and", "methods", "and", "many", "others.", "In", "the", "2", "years", "since", "the", "OLS", "was", "previously", "published", "in", "NAR,", "25", "new", "ontologies", "have", "been", "added", "(Table", "1).", "Users", "are", "encouraged", "to", "go", "online", "at", "http://www.ebi.ac.uk/ontology-lookup/ontologyList.do", "to", "access", "a", "full", "listing", "of", "currently", "available", "ontologies", "and", "CVs.", "The", "ontologies", "and", "CVs", "loaded", "in", "the", "OLS", "are", "main-", "tained", "by", "various", "external", "groups", "that", "are", "domain", "experts", "in", "their", "fields.", "To", "maintain", "the", "OLS", "as", "up-to-date", "as", "possible", "with", "the", "current", "state", "of", "knowledge,", "the", "ontology", "providers", "are", "polled", "on", "a", "daily", "basis", "and", "updated", "files", "are", "downloaded", "and", "parsed", "to", "update", "the", "core", "OLS", "database.", "Currently,", "the", "OLS", "loaders", "poll", "six", "*To", "whom", "correspondence", "should", "be", "addressed.", "Tel:", "+44", "1223", "492", "610;", "Fax:", "+44", "1223", "494", "468;", "Email:", "rcote@ebi.ac.uk", "The", "Author(s)", "2010.", "Published", "by", "Oxford", "University", "Press.", "This", "is", "an", "Open", "Access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "Non-Commercial", "License", "(http://creativecommons.org/licenses/", "by-nc/2.5),", "which", "permits", "unrestricted", "non-commercial", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited." ]

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[ "Malaria", "Journal", "Research", "Analysis", "of", "von", "Willebrand", "factor", "A", "domain-related", "protein", "(WARP)", "polymorphism", "in", "temperate", "and", "tropical", "Plasmodium", "vivax", "field", "isolates", "Saber", "Gholizadeh1,2,", "Navid", "Dinparast", "Djadid*1,", "Hamid", "Reza", "Basseri2,", "Sedigheh", "Zakeri1", "and", "Hossein", "Ladoni2", "BioMed", "Central", "Open", "Access", "Address:", "1Malaria", "and", "Vector", "Research", "Group", "(MVRG),", "Biotechnology", "Research", "Center", "(BRC),", "Pasteur", "Institute", "of", "Iran", "(PII),", "Tehran,", "Iran,", "Pasteur", "Avenue,", "PO", "BOX", "1316943551,", "Tehran,", "Iran", "and", "2Department", "of", "Medical", "Entomology,", "School", "of", "Public", "Health,", "Tehran", "University", "of", "Medical", "Sciences,", "Tehran,", "Iran", "Email:", "Saber", "Gholizadeh", "-", "sabergholizadeh@yahoo.com;", "Navid", "Dinparast", "Djadid*", "-", "ndinparastdjadid@yahoo.com;", "Hamid", "Reza", "Basseri", "-", "basserih@sina.tums.ac.ir;", "Sedigheh", "Zakeri", "-", "zakeris@yahoo.com;", "Hossein", "Ladoni", "-", "laddonih@yahoo.com", "*", "Corresponding", "author", "Published:", "23", "June", "2009", "Malaria", "Journal", "2009,", "8:137", "doi:10.1186/1475-2875-8-137", "This", "article", "is", "available", "from:", "http://www.malariajournal.com/content/8/1/137", "Received:", "6", "March", "2009", "Accepted:", "23", "June", "2009", "©", "2009", "Gholizadeh", "et", "al;", "licensee", "BioMed", "Central", "Ltd.", "This", "is", "an", "Open", "Access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "License", "(http://creativecommons.org/licenses/by/2.0),", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited.", "Abstract", "Background:", "The", "identification", "of", "key", "molecules", "is", "crucial", "for", "designing", "transmission-blocking", "vaccines", "(TBVs),", "among", "those", "ookinete", "micronemal", "proteins", "are", "candidate", "as", "a", "general", "class", "of", "malaria", "transmission-blocking", "targets.", "Here,", "the", "sequence", "analysis", "of", "an", "extra-cellular", "malaria", "protein", "expressed", "in", "ookinetes,", "named", "von", "Willebrand", "factor", "A", "domain-related", "protein", "(WARP),", "is", "reported", "in", "91", "Plasmodium", "vivax", "isolates", "circulating", "in", "different", "regions", "of", "Iran.", "Methods:", "Clinical", "isolates", "were", "collected", "from", "north", "temperate", "and", "southern", "tropical", "regions", "in", "Iran.", "Primers", "have", "been", "designed", "based", "on", "P.", "vivax", "sequence", "(ctg_6991)", "which", "amplified", "a", "fragment", "of", "about", "1044", "bp", "with", "no", "size", "variation.", "Direct", "sequencing", "of", "PCR", "products", "was", "used", "to", "determine", "polymorphism", "and", "further", "bioinformatics", "analysis", "in", "P.", "vivax", "sexual", "stage", "antigen,", "pvwarp.", "Results:", "Amplified", "pvwarp", "gene", "showed", "886", "bp", "in", "size,", "with", "no", "intron.", "BLAST", "analysis", "showed", "a", "similarity", "of", "98–100%", "to", "P.", "vivax", "Sal-I", "strain;", "however,", "Iranian", "isolates", "had", "2", "bp", "mismatches", "in", "247", "and", "531", "positions", "that", "were", "non-synonymous", "substitution", "[T", "(ACT)", "to", "A", "(GCT)", "and", "R", "(AGA)", "to", "S", "(AGT)]", "in", "comparison", "with", "the", "Sal-I", "sequence.", "Conclusion:", "This", "study", "presents", "the", "first", "large-scale", "survey", "on", "pvwarp", "polymorphism", "in", "the", "world,", "which", "provides", "baseline", "data", "for", "developing", "WARP-based", "TBV", "against", "both", "temperate", "and", "tropical", "P.", "vivax", "isolates.", "Background", "Plasmodium", "vivax", "is", "one", "of", "the", "two", "most", "prevalent", "species", "of", "human", "malaria", "parasites", "that", "occurs", "throughout", "the", "tropics,", "except", "in", "western", "and", "central", "sub-Saharan", "Africa,", "where", "the", "absence", "of", "Duffy", "factor", "on", "the", "surface", "of", "red", "blood", "cells", "largely", "protects", "the", "local", "populations", "[1].", "In", "addition,", "recent", "studies", "have", "suggested", "that", "vivax", "malaria", "can", "become", "lethal", "in", "a", "similar", "way", "to", "severe", "falciparum", "malaria", "[2-5].", "To", "date,", "the", "anti-malarial", "treatment", "and", "the", "vector", "control", "measures", "have", "not", "had", "a", "significant", "impact", "on", "the", "transmission", "of", "malaria", "from", "humans", "to", "mosqui-", "toes.", "Therefore,", "vaccine-targeting", "antigens", "expressed", "on", "Page", "1", "of", "7", "(page", "number", "not", "for", "citation", "purposes)" ]

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[ "J.", "Cell", "Commun.", "Signal.", "(2009)", "3:89–94", "DOI", "10.1007/s12079-009-0037-7", "REVIEW", "Connective", "tissue", "growth", "factor", "(CTGF,", "CCN2)", "gene", "regulation:", "a", "potent", "clinical", "bio-marker", "of", "fibroproliferative", "disease?", "Andrew", "Leask", "&", "Sunil", "K.", "Parapuram", "&", "Xu", "Shi-wen", "&", "D.", "J.", "Abraham", "Received:", "25", "November", "2008", "/", "Accepted:", "9", "January", "2009", "/", "Published", "online:", "21", "January", "2009", "#", "The", "Author(s)", "2009.", "This", "article", "is", "published", "with", "open", "access", "at", "Springerlink.com", "Abstract", "The", "CCN", "(cyr61,", "ctgf,", "nov)", "family", "of", "modular", "proteins", "regulate", "diverse", "biological", "affects", "including", "cell", "adhesion,", "matrix", "production,", "tissue", "remodelling,", "prolifera-", "tion", "and", "differentiation.", "Recent", "targeted", "gene", "disruption", "studies", "have", "demonstrated", "the", "CCN", "family", "to", "be", "develop-", "mentally", "essential", "for", "chondrogenesis,", "osteogenesis", "and", "angiogenesis.", "CCN2", "is", "induced", "by", "agents", "such", "as", "angio-", "tensin", "II,", "endothelin-1,", "glucocorticoids,", "HGF,", "TGFβ,", "and", "VEGF,", "and", "by", "hypoxia", "and", "biomechanical", "and", "shear", "stress.", "Dysregulated", "expression", "of", "CCN2", "has", "also", "been", "widely", "documented", "in", "many", "fibroproliferative", "diseases.", "This", "mini-", "review", "will", "focus", "on", "CCN2,", "and", "the", "recent", "progress", "in", "understanding", "CCN2", "gene", "regulation", "in", "health", "and", "disease.", "That", "CCN2", "should", "be", "considered", "a", "novel", "and", "informative", "surrogate", "clinical", "bio-marker", "for", "fibroproliferative", "disease", "is", "discussed.", "Keywords", "CCN2", ".", "CTGF", ".", "Fibrosis", ".", "Biomarker", "This", "article", "also", "appears", "in", "the", "newsletter", "section", "of", "the", "CCN", "society", "website:", "www.ccnsociety.com/.", "A.", "Leask", "(*)", ":", "S.", "K.", "Parapuram", "CIHR", "Group", "in", "Skeletal", "Development", "and", "Remodeling,", "Division", "of", "Oral", "Biology", "and", "Department", "of", "Physiology", "and", "Pharmacology,", "Schulich", "School", "of", "Medicine", "and", "Dentistry,", "University", "of", "Western", "Ontario,", "Dental", "Sciences", "Building,", "London,", "ON", "N6A", "5C1,", "Canada", "e-mail:", "Andrew.leask@schulich.uwo.ca", "X.", "Shi-wen", ":", "D.", "J.", "Abraham", "Centre", "for", "Rheumatology,", "Royal", "Free", "and", "University", "College", "Medical", "School,", "University", "College", "London", "(Royal", "Free", "Campus),", "Rowland", "Hill", "Street,", "London", "NW3", "2PF,", "UK", "Introduction", "The", "CCN", "(cyr61,", "ctgf,", "nov)", "family", "comprises", "six", "members", "(CCN1–6).", "These", "proteins", "act", "through", "integrin-", "and", "heparan", "sulfate", "proteoglycan-mediated", "adhesive", "signaling", "to", "directly", "modulate", "adhesion", "and", "indirectly", "modulate", "the", "functional", "activities", "of", "other", "extracellular", "ligands", "such", "as", "cytokines,", "growth", "factors,", "morphogens", "and", "matrix", "compo-", "nents", "(Leask", "and", "Abraham", "2006).", "Of", "these,", "connective", "tissue", "growth", "factor", "(CTGF,", "CCN2)", "is", "perhaps", "the", "best", "studied", "family", "member.", "CCN2", "was", "initially", "identified", "as", "a", "protein", "secreted", "by", "cultured", "human", "endothelial", "cells", "(Bradham", "et", "al.", "1991).", "In", "adult", "mammals,", "CCN2", "exhibits", "a", "restricted", "expression,", "produced", "only", "by", "hepatic", "stellate", "cells", "(Paradis", "et", "al.", "1999;", "Chen", "et", "al.", "2001)", "and", "kidney", "mesangial", "cells", "(Ito", "et", "al.", "1998;", "Chen", "et", "al.", "2002).", "Although", "CCN2", "is", "not", "normally", "expressed", "by", "other", "mesenchymal", "cells,", "it", "is", "rapidly", "induced", "during", "the", "tissue", "repair", "process,", "for", "example", "upon", "injury", "(Igarashi", "et", "al.", "1993;", "Kapoor", "et", "al.", "2008).", "The", "most", "potent", "inducer", "of", "CCN2", "expression", "thus", "far", "identified", "is", "TGFβ.", "The", "induction", "of", "CCN2", "by", "TGFβ", "is", "restricted", "to", "the", "mesenchymal", "cell", "lineages", "(e.g.", "tissue", "fibroblasts,", "myofi-", "broblasts,", "pericytes)", "and", "generally", "not", "in", "epithelial", "cells", "(Leask", "et", "al.", "2001,", "2003;", "Kantarci", "et", "al.", "2006).", "However,", "CCN2", "is", "expressed", "in", "response", "to", "TGFβ", "in", "renal", "proximal", "tubule", "epithelial", "cells", "(Phanish", "et", "al.", "2005).", "These", "results", "indicate", "that", "CCN2", "gene", "regulation", "in", "response", "to", "TGFβ", "can", "differ", "based", "on", "the", "cell", "type", "examined.", "CCN2", "is", "over-expressed", "in", "connective", "tissue", "pathologies", "such", "as", "in", "excessive", "scarring", "and", "fibrosis", "and", "in", "stroma", "surrounding", "tumors", "(Blom", "et", "al.", "2002).", "Data", "examining", "the", "location", "of", "CCN2", "expression", "and", "the", "use", "of", "genetically", "modified", "cells", "has", "led", "to", "a", "hypothesis", "that", "CCN2", "selectively", "mediates", "or", "sustains", "the", "specific", "actions", "of", "DO00037;", "No", "of", "Pages" ]

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[ "Evaluation", "of", "Treatments", "in", "Patients", "with", "Nocturnal", "Bruxism", "on", "Bite", "Force", "and", "Occlusal", "Contact", "Area:", "A", "preliminary", "report", "Alper", "Alkana", "Emel", "Bulutb", "Selim", "Aricic", "Shuichi", "Satod", "Objectives:", "The", "purpose", "of", "this", "study", "was", "to", "investigate", "the", "short-term", "effects", "of", "occlusal", "splint", "therapy", "and", "tricyclic", "antidepressants", "on", "the", "bite", "force", "and", "occlusal", "contact", "area", "of", "patients", "presenting", "with", "nocturnal", "bruxism.", "Methods:", "A", "maxillary", "full-coverage", "hard", "acrylic", "splint", "was", "applied", "to", "the", "five", "patients", "(Group", "S).", "Five", "patients", "took", "a", "tricyclic", "antidepressant", "(Amitriptiline", "HCl,", "10", "mg/day)", "for", "3", "months", "(Group", "A)", "and", "a", "control", "group", "(Group", "C)", "comprising", "of", "10", "dental", "school", "students", "with", "normal", "occlusion", "was", "also", "formed.", "Using", "a", "Dental", "Prescale", "(Fuji", "Photo", "Film", "Corporation,", "Tokyo,", "Japan)", "and", "an", "Occluzer", "computer", "(FPD703,", "Fuji", "Photo", "Film", "Corporation,", "Tokyo,", "Japan)", "the", "bite", "force", "and", "occlusal", "contact", "area", "were", "measured.", "The", "evaluations", "were", "made", "just", "before", "the", "treatment", "and", "at", "1", "month", "and", "3", "months", "of", "treatment.", "Results:", "The", "bite", "force", "and", "occlusal", "contact", "area", "before", "treatment", "in", "study", "Groups", "A", "and", "S", "were", "found", "to", "be", "higher", "than", "those", "in", "the", "Group", "C.", "Furthermore,", "the", "bite", "force", "and", "occlusal", "contact", "area", "increased", "during", "treatment", "in", "Group", "A", "whilst", "they", "decreased", "in", "Group", "S.", "Bite", "force", "and", "occlusal", "contact", "area", "in", "Group", "S", "were", "lower", "at", "both", "1", "month", "and", "3", "months", "of", "treatment", "than", "in", "Group", "C.", "Conclusions:", "It", "could", "be", "tentatively", "suggested", "that", "occlusal", "splint", "therapy", "may", "be", "more", "effective", "than", "tricyclic", "antidepressant", "in", "the", "treatment", "of", "bruxism.", "Further", "investigations", "of", "this", "measurement", "method", "involving", "larger", "study", "populations", "and", "a", "longer", "follow-up", "period", "are", "needed.", "(Eur", "J", "Dent", "2008;2:276-282)", "Key", "words:", "Antidepressant;", "Bite", "force;", "Bruxism;", "Occlusal", "contact", "area;", "Splint.", "a", "Associate", "Professor", "and", "Chairman,", "DDS,", "PhD,", "Department", "of", "Oral", "and", "Maxillofacial", "Surgery,", "Faculty", "of", "Dentistry,", "Erciyes", "University,", "Kayseri,", "Turkey.", "b", "Assistant", "Professor,", "DDS,", "PhD,", "Department", "of", "Oral", "and", "Maxillofacial", "Surgery,", "Faculty", "of", "Dentistry,", "Ondokuz", "Mayis", "University,", "Samsun,", "Turkey.", "c", "Professor,", "DDS,", "MMedSci,", "PhD,", "Department", "of", "Orthodonthics,", "Faculty", "of", "Dentistry,", "Ondokuz", "Mayis", "University,", "Samsun,", "Turkey.", "d", "Lecturer,", "Division", "of", "Maxillofacial", "Surgery,", "Graduate", "School", "of", "Dentistry,", "Tohoku", "University,", "Sendai,", "Japan.", "Corresponding", "author:", "Dr.", "Emel", "Bulut", "Ondokuz", "Mayis", "Universitesi,", "Dis", "Hekimligi", "Fakultesi", "55139,", "Kurupelit,", "Samsun,", "Turkey.", "Phone:", "+90", "362", "3121919-3008", "Fax:", "+90", "362", "4576032", "E-mail:", "euzun@omu.edu.tr", "276", "European", "Journal", "of", "Dentistry" ]

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[ "Wang", "and", "Brown", "Molecular", "Neurodegeneration", "2010,", "5:52", "http://www.molecularneurodegeneration.com/content/5/1/52", "R", "E", "S", "E", "A", "R", "C", "H", "A", "R", "T", "I", "C", "L", "E", "Open", "Access", "A", "hereditary", "spastic", "paraplegia", "mutation", "in", "kinesin-1A/KIF5A", "disrupts", "neurofilament", "transport", "Lina", "Wang,", "Anthony", "Brown*", "Abstract", "Background:", "Hereditary", "spastic", "paraplegias", "are", "a", "group", "of", "neurological", "disorders", "characterized", "by", "progressive", "distal", "degeneration", "of", "the", "longest", "ascending", "and", "descending", "axons", "in", "the", "spinal", "cord,", "leading", "to", "lower", "limb", "spasticity", "and", "weakness.", "One", "of", "the", "dominantly", "inherited", "forms", "of", "this", "disease", "(spastic", "gait", "type", "10,", "or", "SPG10)", "is", "caused", "by", "point", "mutations", "in", "kinesin-1A", "(also", "known", "as", "KIF5A),", "which", "is", "thought", "to", "be", "an", "anterograde", "motor", "for", "neurofilaments.", "Results:", "We", "investigated", "the", "effect", "of", "an", "SPG10", "mutation", "in", "kinesin-1A", "(N256S-kinesin-1A)", "on", "neurofilament", "transport", "in", "cultured", "mouse", "cortical", "neurons", "using", "live-cell", "fluorescent", "imaging.", "N256S-kinesin-1A", "decreased", "both", "anterograde", "and", "retrograde", "neurofilament", "transport", "flux", "by", "decreasing", "the", "frequency", "of", "anterograde", "and", "retrograde", "movements.", "Anterograde", "velocity", "was", "not", "affected,", "whereas", "retrograde", "velocity", "actually", "increased.", "Conclusions:", "These", "data", "reveal", "subtle", "complexities", "to", "the", "functional", "interdependence", "of", "the", "anterograde", "and", "retrograde", "neurofilament", "motors", "and", "they", "also", "raise", "the", "possibility", "that", "anterograde", "and", "retrograde", "neurofilament", "transport", "may", "be", "disrupted", "in", "patients", "with", "SPG10.", "Background", "Hereditary", "spastic", "paraplegias", "are", "a", "group", "of", "neurologi-", "cal", "disorders", "characterized", "by", "progressively", "increasing", "lower-extremity", "weakness", "and", "spasticity", "[1].", "The", "pri-", "mary", "cause", "appears", "to", "be", "distal", "degeneration", "of", "the", "longest", "ascending", "and", "descending", "axons", "in", "the", "spinal", "cord,", "though", "the", "explanation", "for", "this", "selective", "vulner-", "ability", "is", "not", "known.", "To", "date,", "at", "least", "41", "spastic", "paraple-", "gia", "gene", "loci", "have", "been", "mapped", "(termed", "SPG1", "through", "SPG", "41)", "and", "17", "genes", "have", "been", "identified", "[2].", "The", "inheritance", "can", "be", "autosomal", "dominant,", "autosomal", "recessive,", "or", "X-linked.", "One", "of", "the", "autosomal", "dominant", "forms,", "SPG10,", "is", "caused", "by", "mutations", "in", "kinesin-1A,", "also", "known", "as", "KIF5A,", "which", "is", "a", "member", "of", "the", "kine-", "sin-1", "family", "of", "motor", "proteins.", "Kinesin-1", "motor", "proteins", "are", "heterotetramers", "com-", "posed", "of", "two", "heavy", "chains", "and", "two", "light", "chains", "[3].", "There", "are", "three", "kinesin-1", "heavy", "chain", "genes", "in", "mam-", "mals:", "kinesin-1A,", "B", "and", "C", "(also", "known", "as", "KIF5A,", "B", "and", "C)", "[4].", "Kinesin-1A", "and", "kinesin-1C", "are", "neuron", "specific,", "whereas", "kinesin-1B", "(\"conventional", "kinesin”)", "is", "expressed", "*", "Correspondence:", "brown.2302@osu.edu", "Center", "for", "Molecular", "Neurobiology", "and", "Department", "of", "Neuroscience,", "The", "Ohio", "State", "University,", "Columbus,", "OH", "43210,", "USA", "ubiquitously", "[5-7].", "Little", "is", "known", "about", "the", "cargoes", "of", "kinesin-1A,", "though", "potential", "cargoes", "and", "interactors", "include", "HAP-1", "(huntingtin", "associated", "protein-1)", "[8],", "DISC-1", "(disrupted", "in", "schizophrenia", "protein-1)", "and", "the", "NUDEL/LIS1/14-3-3ε", "complex", "[9],", "Grb2", "(growth", "factor", "receptor", "bound", "protein-2)", "[10],", "and", "b-dystrobrevin", "[11,12].", "Neurofilaments", "are", "the", "intermediate", "filaments", "of", "neu-", "rons.", "They", "are", "heteropolymers", "of", "variable", "composition", "and", "subunit", "stoichiometry,", "typically", "composed", "of", "the", "low,", "medium", "and", "high", "molecular", "weight", "neurofilament", "triplet", "proteins", "(NFL,", "M", "and", "H),", "as", "well", "as", "peripherin", "and/or", "alpha-internexin", "[13].", "Live-cell", "imaging", "of", "neuro-", "filament", "transport", "in", "cultured", "neurons", "and", "computa-", "tional", "modeling", "studies", "of", "neurofilament", "transport", "in", "vivo", "have", "demonstrated", "that", "neurofilaments", "move", "along", "axons", "in", "a", "rapid,", "intermittent", "and", "bidirectional", "manner", "[14-17].", "Studies", "on", "kinesin-1A", "knockout", "mice", "have", "suggested", "that", "kinesin-1A", "may", "be", "an", "anterograde", "motor", "for", "neu-", "rofilaments", "in", "axons", "[18].", "In", "support", "of", "this", "proposal,", "we", "observed", "a", "75%", "reduction", "in", "the", "frequency", "of", "neuro-", "filament", "movement", "in", "cultured", "neurons", "from", "kinesin-", "1A", "knockout", "mice", "[19].", "Interestingly,", "both", "anterograde", "©", "2010", "Wang", "and", "Brown;", "licensee", "BioMed", "Central", "Ltd.", "This", "is", "an", "Open", "Access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "License", "(http://creativecommons.org/licenses/by/2.0),", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited." ]

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[ "Byl", "Journal", "of", "Medical", "Case", "Reports", "2012,", "6:216", "http://www.jmedicalcasereports.com/content/6/1/216", "R", "E", "S", "E", "A", "R", "C", "H", "A", "R", "T", "I", "C", "L", "E", "JOURNAL", "OF", "MEDICAL", "CASE", "REPORTS", "Open", "Access", "Mobility", "training", "using", "a", "bionic", "knee", "orthosis", "in", "patients", "in", "a", "post-stroke", "chronic", "state:", "a", "case", "series", "Nancy", "N", "Byl", "Abstract", "Introduction:", "An", "emerging", "area", "of", "neurorehabilitation", "is", "the", "use", "of", "robotic", "devices", "to", "enhance", "the", "efficiency", "and", "effectiveness", "of", "lower", "extremity", "physical", "therapy", "post-stroke.", "Many", "of", "the", "robotic", "devices", "currently", "available", "rely", "on", "computer-driven", "locomotive", "algorithms", "combined", "with", "partial", "bodyweight-supported", "treadmill", "training", "that", "drive", "reflex", "stepping", "with", "minimal", "patient", "intention", "during", "therapy.", "In", "this", "case", "series,", "we", "examined", "the", "effect", "of", "task-oriented", "mobility", "training", "in", "patients", "in", "a", "post-stroke", "chronic", "state", "using", "a", "novel,", "wearable,", "mobile,", "intention-based", "robotic", "leg", "orthosis.", "Case", "presentation:", "Three", "individuals,", "all", "of", "whom", "had", "reached", "a", "plateau", "with", "conventional", "bodyweight-supported", "treadmill", "training,", "participated", "in", "task-oriented", "mobility", "therapy", "(1.5", "hours,", "two", "to", "four", "times", "per", "week", "for", "four", "weeks)", "with", "a", "robotic", "leg", "orthosis", "under", "supervision", "by", "a", "physical", "therapist.", "Participant", "1", "was", "a", "59-year-old", "Caucasian", "man,", "who", "had", "an", "ischemic", "left", "stroke", "six", "years", "previously", "with", "resultant", "right", "hemiparesis.", "Participant", "2", "was", "a", "42-year-old", "Caucasian", "woman", "with", "left", "hemiparesis", "after", "a", "right", "stroke", "15", "months", "previously.", "Participant", "3", "was", "a", "62-year-old", "Caucasian", "woman", "with", "a", "history", "of", "a", "right", "middle", "cerebral", "artery", "aneurysm", "with", "third", "degree", "sub-arachnoid", "hemorrhage", "10", "years", "ago.", "Immediately", "after", "training,", "all", "participants", "demonstrated", "improved", "gait", "speed", "(10", "meter", "walk),", "stride", "length", "and", "walking", "endurance", "(6", "minute", "walk)", "compared", "with", "baseline", "measurements.", "Improvements", "were", "maintained", "one", "month", "after", "training.", "Timed", "up", "and", "go", "and", "five", "times", "sit-to-stand", "were", "maintained", "for", "all", "three", "participants,", "with", "only", "one", "individual", "remaining", "outside", "the", "safety", "performance", "norm.", "Conclusions:", "Lower", "extremity", "training", "integrating", "an", "intention-based", "robotic", "leg", "orthosis", "may", "improve", "gait", "speed,", "endurance", "and", "community", "levels", "of", "participation", "in", "select", "patients", "in", "a", "post-stroke", "chronic", "state", "after", "plateauing", "within", "a", "bodyweight-supported", "treadmill", "training", "program.", "The", "wearable,", "mobile", "assistive", "robotic", "device", "safely", "supplemented", "supervised", "physical", "therapy", "including", "mobility", "and", "balance", "skill", "training.", "Introduction", "Individuals", "who", "receive", "coordinated", "rehabilitation", "ser-", "vices", "after", "stroke", "demonstrate", "reduced", "mortality", "and", "achieve", "greater", "independence", "than", "those", "who", "do", "not", "[1].", "Although", "early", "intervention", "and", "rehabilitation", "are", "pre-", "ferred", "in", "the", "recovery", "process,", "research", "indicates", "late", "re-", "covery", "may", "also", "occur", "for", "chronic", "stroke", "survivors.", "Late", "recovery", "mechanisms", "require", "patient", "effort", "and", "attention", "including", "progressive", "repetitive", "task-specific", "training", "to", "drive", "neural", "remodeling", "and", "reorganization", "[2].", "Correspondence:", "byln@ptrehab.ucsf.edu", "Department", "of", "Physical", "Therapy", "and", "Rehabilitation", "Science,", "School", "of", "Medicine,", "University", "of", "California", "San", "Francisco", "(UCSF),", "PT", "Health", "and", "Wellness", "Center,", "Bakar", "Community", "Center,", "1675", "Owens", "Street,", "Box", "0736,", "San", "Francisco", "94158-2332,", "USA", "An", "emerging", "area", "in", "neurorehabilitation", "is", "the", "use", "of", "robotic", "devices", "to", "enhance", "the", "efficiency", "and", "effective-", "ness", "of", "post-stroke", "therapy.", "A", "number", "of", "designs", "have", "been", "commercialized.", "These", "wearable,", "assistive", "robotic", "devices", "typically", "demand", "attention", "and", "repetition", "from", "the", "patient,", "while", "providing", "feedback", "through", "various", "modes", "to", "improve", "performance.", "Early", "studies", "of", "upper-", "limb", "robotic", "devices", "remain", "inconclusive", "when", "evaluating", "their", "benefit", "over", "conventional", "physical", "therapy", "[3].", "Robotic", "systems", "for", "lower", "extremity", "therapy", "on", "a", "bodyweight-", "supported", "treadmill", "are", "subject", "to", "many", "of", "the", "same", "limita-", "tions", "as", "conventional", "bodyweight-supported", "treadmill", "training", "(BWSTT)", "[4,5]", "as", "they", "do", "not", "compensate", "for", "the", "lack", "of", "visual", "flow,", "balance", "and", "intention", "requirements", "inherent", "to", "this", "kind", "of", "movement", "training.", "©", "2012", "Byl;", "licensee", "BioMed", "Central", "Ltd.", "This", "is", "an", "Open", "Access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "License", "(http://creativecommons.org/licenses/by/2.0),", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited." ]

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[ "Systems", "Analysis", "of", "Chaperone", "Networks", "in", "the", "Malarial", "Parasite", "Plasmodium", "falciparum", "Soundara", "Raghavan", "Pavithra[,", "Ranjit", "Kumar[,", "Utpal", "Tatu*", "Department", "of", "Biochemistry,", "Indian", "Institute", "of", "Science,", "Bangalore,", "Karnataka,", "India", "Molecular", "chaperones", "participate", "in", "the", "maintenance", "of", "cellular", "protein", "homeostasis,", "cell", "growth", "and", "differentiation,", "signal", "transduction,", "and", "development.", "Although", "a", "vast", "body", "of", "information", "is", "available", "regarding", "individual", "chaperones,", "few", "studies", "have", "attempted", "a", "systems", "level", "analysis", "of", "chaperone", "function.", "In", "this", "paper,", "we", "have", "constructed", "a", "chaperone", "interaction", "network", "for", "the", "malarial", "parasite,", "Plasmodium", "falciparum.", "P.", "falciparum", "is", "responsible", "for", "several", "million", "deaths", "every", "year,", "and", "understanding", "the", "biology", "of", "the", "parasite", "is", "a", "top", "priority.", "The", "parasite", "regularly", "experiences", "heat", "shock", "as", "part", "of", "its", "life", "cycle,", "and", "chaperones", "have", "often", "been", "implicated", "in", "parasite", "survival", "and", "growth.", "To", "better", "understand", "the", "participation", "of", "chaperones", "in", "cellular", "processes,", "we", "created", "a", "parasite", "chaperone", "network", "by", "combining", "experimental", "interactome", "data", "with", "in", "silico", "analysis.", "We", "used", "interolog", "mapping", "to", "predict", "protein–protein", "interactions", "for", "parasite", "chaperones", "based", "on", "the", "interactions", "of", "corresponding", "human", "chaperones.", "This", "data", "was", "then", "combined", "with", "information", "derived", "from", "existing", "high-throughput", "yeast", "two-", "hybrid", "assays.", "Analysis", "of", "the", "network", "reveals", "the", "broad", "range", "of", "functions", "regulated", "by", "chaperones.", "The", "network", "predicts", "involvement", "of", "chaperones", "in", "chromatin", "remodeling,", "protein", "trafficking,", "and", "cytoadherence.", "Importantly,", "it", "allows", "us", "to", "make", "predictions", "regarding", "the", "functions", "of", "hypothetical", "proteins", "based", "on", "their", "interactions.", "It", "allows", "us", "to", "make", "specific", "predictions", "about", "Hsp70–Hsp40", "interactions", "in", "the", "parasite", "and", "assign", "functions", "to", "members", "of", "the", "Hsp90", "and", "Hsp100", "families.", "Analysis", "of", "the", "network", "provides", "a", "rational", "basis", "for", "the", "anti-malarial", "activity", "of", "geldanamycin,", "a", "well-known", "Hsp90", "inhibitor.", "Finally,", "analysis", "of", "the", "network", "provides", "a", "theoretical", "basis", "for", "further", "experiments", "designed", "toward", "understanding", "the", "involvement", "of", "this", "important", "class", "of", "molecules", "in", "parasite", "biology.", "Citation:", "Pavithra", "SR,", "Kumar", "R,", "Tatu", "U", "(2007)", "Systems", "analysis", "of", "chaperone", "networks", "in", "the", "malarial", "parasite", "Plasmodium", "falciparum.", "PLoS", "Comput", "Biol", "3(9):", "e168.", "doi:10.1371/journal.pcbi.0030168", "Introduction", "Molecular", "chaperones", "have", "emerged", "in", "recent", "years", "as", "key", "players", "in", "several", "cellular", "processes.", "In", "addition", "to", "assisting", "in", "the", "folding", "of", "newly", "synthesized", "proteins,", "they", "play", "crucial", "roles", "in", "the", "translocation", "of", "proteins", "across", "organelle", "membranes,", "quality", "control", "in", "the", "endoplasmic", "reticulum", "(ER),", "turnover", "of", "misfolded", "proteins,", "as", "well", "as", "signal", "transduction", "[1–3].", "By", "chaperoning", "key", "signaling", "proteins", "such", "as", "protein", "kinases", "and", "transcription", "factors,", "chaperones", "such", "as", "Hsp90", "(heat", "shock", "protein", "90)", "also", "participate", "in", "cell", "growth,", "differentiation,", "apoptosis,", "and", "development", "[4,5].", "As", "such,", "many", "chaperones", "are", "also", "essential", "under", "non-stress", "conditions", "and", "are", "relatively", "abundant", "in", "the", "cell.", "There", "are", "different", "families", "of", "stress", "proteins,", "the", "major", "ones", "being", "the", "Hsp40,", "Hsp60,", "Hsp70,", "Hsp90,", "Hsp100,", "TCP-1/CCT,", "and", "the", "small", "Hsp", "families", "[6].", "These", "families", "of", "chaperones", "are", "ubiquitous", "and", "conserved", "in", "most", "organisms", "from", "bacteria", "to", "higher", "eukaryotes.", "In", "recent", "years,", "the", "importance", "of", "chaperones", "in", "developmental", "processes", "has", "been", "highlighted", "by", "the", "demonstration", "of", "a", "role", "for", "Hsp90", "in", "buffering", "genetic", "variation", "[7–9].", "Despite", "the", "important", "processes", "in", "which", "chaperones", "have", "been", "implicated,", "most", "studies", "have", "been", "restricted", "to", "the", "analysis", "of", "individual", "chaperones.", "There", "is", "growing", "realiza-", "tion", "that", "chaperones", "function", "in", "complexes", "with", "partner", "co-", "chaperones", "and", "other", "effectors", "[10,11].", "These", "modular", "complexes", "participate", "in", "multiple", "pathways", "in", "the", "cell,", "emphasizing", "the", "need", "to", "examine", "protein–protein", "interac-", "tion", "networks", "for", "a", "better", "understanding", "of", "cellular", "processes.", "Chaperone", "interaction", "networks,", "for", "example,", "may", "provide", "a", "theoretical", "framework", "to", "study", "the", "response", "of", "a", "cell", "to", "stressful", "conditions.", "Keeping", "in", "mind", "the", "central", "importance", "of", "chaperones", "in", "biological", "processes,", "we", "have", "made", "an", "effort", "at", "analyzing", "chaperone", "interaction", "networks", "in", "human", "beings,", "as", "well", "as", "one", "of", "the", "most", "important", "human", "pathogens,", "the", "malarial", "parasite", "P.", "falciparum.", "During", "its", "life", "cycle,", "the", "parasite", "continually", "cycles", "between", "a", "cold-blooded", "insect", "vector", "and", "a", "warm-blooded", "human", "host", "and", "experiences", "episodes", "of", "heat", "shock", "frequently", "[12].", "Within", "the", "human", "body,", "the", "parasite", "experiences", "heat", "shock", "periodically", "during", "the", "febrile", "episodes", "that", "are", "a", "clinical", "hallmark", "of", "malaria.", "It", "is", "therefore", "possible", "that", "heat", "shock", "proteins", "have", "a", "role", "to", "play", "in", "the", "adaptation", "to", "and", "survival", "of", "the", "parasite", "in", "the", "human", "host.", "The", "malarial", "parasite", "expresses", "several", "chaperones", "including", "proteins", "of", "the", "Hsp40,", "Hsp60,", "Hsp70,", "and", "Hsp90", "families", "[13–17].", "Parasite", "Hsp70,", "for", "example,", "has", "been", "shown", "to", "be", "capable", "of", "suppressing", "the", "thermosensitivity", "of", "a", "DnaK", "(Hsp70)", "mutant", "of", "E.", "coli,", "suggesting", "that", "PfHsp70", "may", "have", "a", "cytoprotective", "Editor:", "Philip", "E.", "Bourne,", "University", "of", "California", "San", "Diego,", "United", "States", "of", "America", "Received", "September", "5,", "2006;", "Accepted", "July", "11,", "2007;", "Published", "September", "14,", "2007", "Copyright:", "2007", "Pavithra", "et", "al.", "This", "is", "an", "open-access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "License,", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "author", "and", "source", "are", "credited.", "Abbreviations:", "ER,", "endoplasmic", "reticulum;", "GA,", "geldanamycin;", "HPRD,", "Human", "Protein", "Reference", "Database;", "Hsp/HSP,", "heat", "shock", "protein", "*", "To", "whom", "correspondence", "should", "be", "addressed.", "E-mail:", "tatu@biochem.iisc.ernet.in", "[", "These", "authors", "contributed", "equally", "to", "this", "work.", "PLoS", "Computational", "Biology", "|", "www.ploscompbiol.org", "1701", "September", "2007", "|", "Volume", "3", "|", "Issue", "9", "|", "e168" ]

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[ "BMC", "Cancer", "Research", "article", "BioMed", "Central", "Open", "Access", "Identification", "of", "a", "panel", "of", "tumor-associated", "antigens", "from", "breast", "carcinoma", "cell", "lines,", "solid", "tumors", "and", "testis", "cDNA", "libraries", "displayed", "on", "lambda", "phage", "Emiliano", "Pavoni1,", "Paola", "Vaccaro1,", "Andrea", "Pucci1,", "Giorgia", "Monteriù1,", "Elisa", "Beghetto1,", "Stefano", "Barca2,", "Maria", "Luisa", "Dupuis2,", "Adolfo", "De", "Pasquale", "Ceratti3,", "Antonio", "Lugini3,", "Maurizio", "Cianfriglia2,", "Enrico", "Cortesi3,", "Franco", "Felici1,4", "and", "Olga", "Minenkova*1", "Address:", "1Kenton", "Labs,", "c/o", "Sigma", "Tau,", "Pomezia", "(Rome),", "00040,", "Italy,", "2Laboratorio", "di", "Immunologia,", "Reparto", "Immunologia", "dei", "Tumori,", "Istituto", "Superiore", "di", "Sanità,", "Roma,", "00100,", "Italy,", "3Oncologia", "Medica,", "Dipartimento", "di", "Medicina", "Sperimentale", "e", "Patologia,", "Facoltà", "di", "Medicina", "e", "Chirurgia,", "Università", "di", "Roma", "\"La", "Sapienza\",", "Rome,", "00100,", "Italy", "and", "4Dipartimento", "di", "Scienze", "Microbiologiche,", "Genetiche", "e", "Molecolari,", "Università", "di", "Messina,", "98100,", "Italy", "Email:", "Emiliano", "Pavoni", "-", "pavoni@kenton.it;", "Paola", "Vaccaro", "-", "vaccaro@kenton.it;", "Andrea", "Pucci", "-", "pucci@kenton.it;", "Giorgia", "Monteriù", "-", "monteriu@kenton.it;", "Elisa", "Beghetto", "-", "beghetto@kenton.it;", "Stefano", "Barca", "-", "sbarca@iss.it;", "Maria", "Luisa", "Dupuis", "-", "mldupuis@iss.it;", "Adolfo", "De", "Pasquale", "Ceratti", "-", "adolfo.ceratti@tiscali.it;", "Antonio", "Lugini", "-", "antoniolugini@libero.it;", "Maurizio", "Cianfriglia", "-", "cianfri@iss.it;", "Enrico", "Cortesi", "-", "enrico.cortesi@uniroma1.it;", "Franco", "Felici", "-", "felici@kenton.it;", "Olga", "Minenkova*", "-", "minenkova@kenton.it", "*", "Corresponding", "author", "Published:", "12", "November", "2004", "BMC", "Cancer", "2004,", "4:78", "doi:10.1186/1471-2407-4-78", "This", "article", "is", "available", "from:", "http://www.biomedcentral.com/1471-2407/4/78", "Received:", "18", "June", "2004", "Accepted:", "12", "November", "2004", "©", "2004", "Pavoni", "et", "al;", "licensee", "BioMed", "Central", "Ltd.", "This", "is", "an", "Open", "Access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "License", "(http://creativecommons.org/licenses/by/2.0),", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited.", "Abstract", "Background:", "Tumor-associated", "antigens", "recognized", "by", "humoral", "effectors", "of", "the", "immune", "system", "are", "a", "very", "attractive", "target", "for", "human", "cancer", "diagnostics", "and", "therapy.", "Recent", "advances", "in", "molecular", "techniques", "have", "led", "to", "molecular", "definition", "of", "immunogenic", "tumor", "proteins", "based", "on", "their", "reactivity", "with", "autologous", "patient", "sera", "(SEREX).", "Methods:", "Several", "high", "complexity", "phage-displayed", "cDNA", "libraries", "from", "breast", "carcinomas,", "human", "testis", "and", "breast", "carcinoma", "cell", "lines", "MCF-7,", "MDA-MB-468", "were", "constructed.", "The", "cDNAs", "were", "expressed", "in", "the", "libraries", "as", "fusion", "to", "bacteriophage", "lambda", "protein", "D.", "Lambda-displayed", "libraries", "were", "efficiently", "screened", "with", "sera", "from", "patients", "with", "breast", "cancer.", "Results:", "A", "panel", "of", "21", "clones", "representing", "18", "different", "antigens,", "including", "eight", "proteins", "of", "unknown", "function,", "was", "identified.", "Three", "of", "these", "antigens", "(T7-1,", "T11-3", "and", "T11-9)", "were", "found", "to", "be", "overexpressed", "in", "tumors", "as", "compared", "to", "normal", "breast.", "A", "serological", "analysis", "of", "the", "21", "different", "antigens", "revealed", "a", "strong", "cancer-related", "profile", "for", "at", "least", "five", "clones", "(T6-2,", "T6-7,", "T7-", "1,", "T9-21", "and", "T9-27).", "Conclusions:", "Preliminary", "results", "indicate", "that", "patient", "serum", "reactivity", "against", "five", "of", "the", "antigens", "is", "associated", "with", "tumor", "disease.", "The", "novel", "T7-1", "antigen,", "which", "is", "overexpressed", "in", "breast", "tumors", "and", "recognized", "specifically", "by", "breast", "cancer", "patient", "sera,", "is", "potentially", "useful", "in", "cancer", "diagnosis.", "Page", "1", "of", "10", "(page", "number", "not", "for", "citation", "purposes)" ]

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[ "Tropical", "Plant", "Biol.", "(2010)", "3:123–135", "DOI", "10.1007/s12042-010-9046-1", "Lablab", "purpureus—A", "Crop", "Lost", "for", "Africa?", "Brigitte", "L.", "Maass", "&", "Maggie", "R.", "Knox", "&", "S.", "C.", "Venkatesha", "&", "Tefera", "Tolera", "Angessa", "&", "Stefan", "Ramme", "&", "Bruce", "C.", "Pengelly", "Received:", "11", "November", "2009", "/", "Accepted:", "18", "February", "2010", "/", "Published", "online:", "28", "March", "2010", "#", "The", "Author(s)", "2010.", "This", "article", "is", "published", "with", "open", "access", "at", "Springerlink.com", "Abstract", "In", "recent", "years,", "so-called", "‘lost", "crops’", "have", "been", "appraised", "in", "a", "number", "of", "reviews,", "among", "them", "Lablab", "purpureus", "in", "the", "context", "of", "African", "vegetable", "species.", "This", "crop", "cannot", "truly", "be", "considered", "‘lost’", "because", "worldwide", "more", "than", "150", "common", "names", "are", "applied", "to", "it.", "Based", "on", "a", "comprehensive", "literature", "review,", "this", "paper", "aims", "to", "put", "forward", "four", "theses,", "(i)", "Lablab", "is", "one", "of", "the", "most", "diverse", "domesticated", "legume", "species", "and", "has", "multiple", "uses.", "Although", "its", "largest", "agro-morphological", "diversity", "occurs", "in", "South", "Asia,", "its", "origin", "appears", "to", "be", "Africa.", "(ii)", "Crop", "improvement", "in", "South", "Asia", "is", "based", "on", "limited", "genetic", "diversity.", "(iii)", "The", "restricted", "research", "and", "development", "performed", "in", "Africa", "focuses", "either", "on", "improving", "forage", "or", "soil", "properties", "mostly", "through", "one", "popular", "cultivar,", "Rongai,", "Communicated", "by:", "Desiree", "M.", "Hautea", "Elaborated", "from", "a", "presentation", "at", "the", "International", "Symposium", "“Underutilized", "plants", "for", "food,", "nutrition,", "income", "and", "sustainable", "development”,", "3–7", "March", "2008,", "Arusha,", "Tanzania;", "organized", "by", "ICUC,", "GFU,", "AVRDC,", "GlobalHort,", "Bioversity", "International,", "PROTA,", "and", "ISHS.", "B.", "L.", "Maass", ":", "TT.eTf.erAanTg.esAs.a", ":", "S.", "Ramme", "Department", "of", "Crop", "Sciences:", "Agronomy", "in", "the", "Tropics,", "Georg-August-University", "Goettingen,", "Grisebachstr.", "6,", "D-37077", "Goettingen,", "Germany", "M.", "R.", "Knox", "John", "Innes", "Centre", "(JIC),", "Colney", "Lane,", "Norwich", "NR4", "7UH,", "UK", "S.", "C.", "Venkatesha", "University", "of", "Agricultural", "Sciences,", "GKVK", "Campus,", "Bangalore", "560065", "Karnataka,", "India", "while", "the", "available", "diversity", "of", "lablab", "in", "Africa", "might", "be", "under", "threat", "of", "genetic", "erosion.", "(iv)", "Lablab", "is", "better", "adapted", "to", "drought", "than", "common", "beans", "(Phaseolus", "vulgaris)", "or", "cowpea", "(Vigna", "unguiculata),", "both", "of", "which", "have", "been", "preferred", "to", "lablab", "in", "African", "agricultural", "production", "systems.", "Lablab", "might", "offer", "comparable", "opportunities", "for", "African", "agriculture", "in", "the", "view", "of", "global", "change.", "Its", "wide", "potential", "for", "adaptation", "throughout", "eastern", "and", "southern", "Africa", "is", "shown", "with", "a", "GIS", "(geographic", "information", "systems)", "approach.", "Keywords", "Cover", "crop", ".", "Dolichos", ".", "Forage", ".", "Genetic", "diversity", ".", "Genetic", "erosion", ".", "Homegarden", ".", "Hyacinth", "bean", ".", "Landrace", ".", "Pulse", ".", "Traditional", "vegetable", ".", "Underutilized", "crop", "B.", "C.", "Pengelly", "Commwealth", "Scientific", "and", "Industrial", "Research", "Organisation", "(CSIRO):", "Sustainable", "Ecosystems,", "306", "Carmody", "Road,", "St.", "Lucia,", "Qld.", "4067,", "Australia", "Present", "Address:", "B.", "L.", "Maass", "(*)", "CIAT-TSBF,", "ICRAF", "Campus,", "PO", "Box", "30677-00100,", "Nairobi,", "Kenya", "e-mail:", "b.maass@cgiar.org", "Present", "Address:", "T.efTe.raATn.geAs.sa", "The", "University", "of", "Western", "Australia", "(M703),", "35", "Stirling", "Highway,", "Crawley,", "WA", "6009,", "Australia" ]

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[ "Available", "online", "http://ccforum.com/content/11/3/R63", "Research", "Vol11No3", "Red", "blood", "cell", "transfusions", "and", "the", "risk", "of", "acute", "respiratory", "distress", "syndrome", "among", "the", "critically", "ill:", "a", "cohort", "study", "Marya", "D", "Zilberberg1,", "Chureen", "Carter2,", "Patrick", "Lefebvre3,", "Monika", "Raut2,", "Francis", "Vekeman3,", "Open", "Access", "Mei", "Sheng", "Duh4", "and", "Andrew", "F", "Shorr5", "1School", "of", "Public", "Health", "and", "Health", "Sciences,", "University", "of", "Massachusetts,", "Amherst,", "P.O.", "Box", "303,", "Goshen,", "MA", "01032,", "USA", "2Ortho", "Biotech", "Clinical", "Affairs,", "LLC,", "430", "Route", "22", "East,", "Bridgewater,", "NJ", "08807,", "USA", "3Groupe", "d'analyse,", "1080", "Beaver", "Hall", "Hill,", "Suite", "1810,", "Montreal,", "Quebec,", "H2Z", "1S8,", "Canada", "4Analysis", "Group,", "111", "Huntington", "Avenue,", "Tenth", "Floor,", "Boston,", "MA", "02199,", "USA", "5Washington", "Hospital", "Center,", "110", "Irving", "Street,", "NW,", "Washington,", "DC", "20010,", "USA", "Corresponding", "author:", "Marya", "D", "Zilberberg,", "mzilberb@schoolph.umass.edu", "Received:", "28", "Feb", "2007", "Revisions", "requested:", "29", "Mar", "2007", "Revisions", "received:", "11", "Apr", "2007", "Accepted:", "6", "Jun", "2007", "Published:", "6", "Jun", "2007", "Critical", "Care", "2007,", "11:R63", "(doi:10.1186/cc5934)", "This", "article", "is", "online", "at:", "http://ccforum.com/content/11/3/R63", "©", "2007", "Zilberberg", "et", "al.;", "licensee", "BioMed", "Central", "Ltd.", "This", "is", "an", "open", "access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "License", "(http://creativecommons.org/licenses/by/2.0),", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited.", "Abstract", "Introduction", "Recent", "data", "indicate", "that", "transfusion", "of", "packed", "red", "blood", "cells", "(pRBCs)", "may", "increase", "the", "risk", "for", "the", "development", "of", "acute", "respiratory", "distress", "syndrome", "(ARDS)", "in", "critically", "ill", "patients.", "Uncertainty", "remains", "regarding", "the", "strength", "of", "this", "relationship.", "Methods", "To", "quantify", "the", "association", "between", "transfusions", "and", "intensive", "care", "unit", "(ICU)-onset", "ARDS,", "we", "performed", "a", "cohort", "study", "within", "Crit,", "a", "multicenter,", "prospective,", "observational", "study", "of", "transfusion", "practice", "in", "the", "ICU", "which", "enrolled", "4,892", "critically", "ill", "patients", "in", "284", "ICUs", "in", "the", "United", "States.", "Diagnostic", "criteria", "for", "ARDS", "were", "prospectively", "defined,", "and", "we", "focused", "on", "subjects", "without", "ARDS", "at", "admission.", "The", "development", "of", "ARDS", "in", "the", "ICU", "served", "as", "the", "primary", "endpoint.", "Results", "Among", "the", "4,730", "patients", "without", "ARDS", "at", "admission,", "246", "(5.2%)", "developed", "ARDS", "in", "the", "ICU.", "At", "baseline,", "ARDS", "cases", "were", "younger,", "more", "likely", "to", "be", "in", "a", "surgical", "ICU,", "and", "more", "likely", "to", "be", "admitted", "with", "pneumonia", "or", "sepsis", "than", "controls", "without", "ARDS.", "Cases", "also", "were", "more", "likely", "to", "have", "a", "serum", "creatinine", "of", "greater", "than", "2.0", "mg/dl", "(23%", "versus", "18%)", "and", "a", "serum", "albumin", "of", "less", "than", "or", "equal", "to", "2.3", "g/dl", "(54%", "versus", "30%)", "and", "were", "more", "severely", "ill", "upon", "ICU", "admission", "as", "measured", "by", "either", "the", "APACHE", "II", "(Acute", "Physiology", "and", "Chronic", "Health", "Evaluation", "II)", "or", "SOFA", "(Sequential", "Organ", "Failure", "Assessment)", "score", "(p", "<", "0.05", "for", "all).", "Sixty-seven", "percent", "and", "42%", "of", "cases", "and", "controls,", "respectively,", "had", "exposure", "to", "pRBC", "transfusions", "(p", "<", "0.05),", "and", "the", "unadjusted", "odds", "ratio", "(OR)", "of", "developing", "ARDS", "in", "transfused", "patients", "was", "2.74", "(95%", "confidence", "interval", "[CI],", "2.09", "to", "3.59;", "p", "<", "0.0001)", "compared", "to", "those", "never", "transfused.", "After", "age,", "baseline", "severity", "of", "illness,", "admitting", "diagnosis,", "and", "process-of-care", "factors", "were", "adjusted", "for,", "the", "independent", "relationship", "between", "pRBC", "transfusions", "and", "ICU-onset", "ARDS", "remained", "significant", "(adjusted", "OR,", "2.80;", "95%", "CI,", "1.90", "to", "4.12;", "p", "<", "0.0001).", "Conclusion", "Development", "of", "ARDS", "after", "ICU", "admission", "is", "common,", "occurring", "in", "approximately", "5%", "of", "critically", "ill", "patients.", "Transfusion", "of", "pRBCs", "is", "independently", "associated", "with", "the", "development", "of", "ARDS", "in", "the", "ICU.", "Introduction", "Acute", "respiratory", "distress", "syndrome", "(ARDS)", "remains", "a", "fre-", "quent", "complication", "of", "critical", "illness", "and", "is", "associated", "with", "significant", "morbidity", "and", "mortality.", "Its", "age-adjusted", "incidence", "rate", "in", "the", "United", "States", "exceeds", "85", "cases", "per", "100,000", "per-", "son-years,", "and", "the", "case", "fatality", "rate", "is", "near", "40%", "[1].", "Illustrating", "its", "burden,", "Rubenfeld", "and", "colleagues", "[1]", "estimated", "that", "ARDS", "leads", "to", "200,000", "intensive", "care", "unit", "(ICU)", "admissions", "annu-", "ally", "and", "necessitates", "3.6", "million", "inpatient", "days", "of", "care.", "Multiple", "insults", "can", "lead", "to", "ARDS", "and", "range", "from", "sepsis", "to", "trauma", "[2-5].", "Because", "the", "manner", "in", "which", "care", "is", "delivered", "to", "at-risk", "patients", "may", "contribute", "to", "ARDS", "development,", "there", "is", "a", "need", "to", "better", "understand", "process-of-care", "variables", "in", "APACHE", "II", "=", "Acute", "Physiology", "and", "Chronic", "Health", "Evaluation", "II;", "ARDS", "=", "acute", "respiratory", "distress", "syndrome;", "CI", "=", "confidence", "interval;", "ICU", "=", "inten-", "sive", "care", "unit;", "OR", "=", "odds", "ratio;", "pRBC", "=", "packed", "red", "blood", "cell;", "SIRS", "=", "systemic", "inflammatory", "response", "syndrome;", "SOFA", "=", "Sequential", "Organ", "Failure", "Assessment;", "TRALI", "=", "transfusion-related", "acute", "lung", "injury.", "Page", "1", "of", "9", "(page", "number", "not", "for", "citation", "purposes)" ]

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[ "e", "n", "i", "c", "i", "d", "e", "M", "l", "a", "t", "n", "e", "m", "i", "r", "e", "p", "x", "E", "f", "o", "l", "a", "n", "r", "u", "o", "J", "e", "h", "T", "CORRESPONDENCE", "Tania", "H.", "Watts:", "tania.watts@utoronto.ca", "Abbreviations", "used:", "CHX,", "cycloheximide;", "LCMV,", "lympho-", "cytic", "choriomeningitis", "virus;", "PD-1,", "programmed", "death", "1;", "siRNA,", "small", "interfering", "RNA;", "TRAF,", "TNFR-associated", "factor", "1.", "A", "r", "t", "i", "c", "l", "e", "Loss", "of", "the", "signaling", "adaptor", "TRAF1", "causes", "CD8+", "T", "cell", "dysregulation", "during", "human", "and", "murine", "chronic", "infection", "Chao", "Wang,1", "Ann", "J.", "McPherson,1", "R.", "Brad", "Jones,1", "Kim", "S.", "Kawamura,5", "Gloria", "H.Y.", "Lin,1", "Philipp", "A.", "Lang,1,5", "Thanuja", "Ambagala,1", "Marc", "Pellegrini,5", "Thomas", "Calzascia,5", "Nasra", "Aidarus,1", "Alisha", "R.", "Elford,5", "Feng", "Yun", "Yue,2", "Elisabeth", "Kremmer,6", "Colin", "M.", "Kovacs,7", "Erika", "Benko,7", "Cecile", "Tremblay,8", "Jean-Pierre", "Routy,9", "Nicole", "F.", "Bernard,10", "Mario", "A.", "Ostrowski,1,2,4", "Pamela", "S.", "Ohashi,1,3,5", "and", "Tania", "H.", "Watts1", "1Department", "of", "Immunology,", "2Clinical", "Sciences", "Division,", "University", "of", "Toronto,", "Toronto,", "M5S", "1A8,", "Canada", "3Department", "of", "Medical", "Biophysics,", "University", "of", "Toronto,", "Toronto,", "M5G", "2M9,", "Canada", "4Li", "Ka", "Shing", "Knowledge", "Institute", "at", "St.", "Michael’s", "Hospital,", "University", "of", "Toronto,", "Toronto,", "M5B", "1W8,", "Canada", "5The", "Campbell", "Family", "Cancer", "Research", "Institute,", "Ontario", "Cancer", "Institute,", "University", "Health", "Network,", "Toronto,", "M5G", "2M9,", "Canada", "6Helmholtz", "Zentrum", "München,", "German", "Research", "Center", "for", "Environmental", "Health,", "Institute", "of", "Molecular", "Immunology,", "83177", "Munich,", "Germany", "7Maple", "Leaf", "Medical", "Clinic,", "Toronto,", "M5B", "1L6,", "Canada", "8Département", "de", "microbiologie", "et", "immunologie,", "Université", "de", "Montréal,", "Montréal,", "H3C", "3J7,", "Canada", "9Immunodeficiency", "Service", "and", "Division", "of", "Hematology,", "Royal", "Victoria", "Hospital,", "and", "10Research", "Institute", "of", "the", "McGill", "University", "Health", "Center,", "Montreal,", "H3A", "1A1,", "Canada", "The", "signaling", "adaptor", "TNFR-associated", "factor", "1", "(TRAF1)", "is", "specifically", "lost", "from", "virus-specific", "CD8", "T", "cells", "during", "the", "chronic", "phase", "of", "infection", "with", "HIV", "in", "humans", "or", "lymphocytic", "chorio-", "meningitis", "virus", "(LCMV)", "clone", "13", "in", "mice.", "In", "contrast,", "TRAF1", "is", "maintained", "at", "higher", "levels", "in", "virus-specific", "T", "cells", "of", "HIV", "controllers", "or", "after", "acute", "LCMV", "infection.", "TRAF1", "expression", "negatively", "correlates", "with", "programmed", "death", "1", "expression", "and", "HIV", "load", "and", "knockdown", "of", "TRAF1", "in", "CD8", "T", "cells", "from", "viral", "controllers", "results", "in", "decreased", "HIV", "suppression", "ex", "vivo.", "Consistent", "with", "the", "desensitization", "of", "the", "TRAF1-binding", "co-stimulatory", "receptor", "4-1BB,", "4-1BBL–deficient", "mice", "have", "defects", "in", "viral", "control", "early,", "but", "not", "late,", "in", "chronic", "infection.", "TGF", "induces", "the", "posttranslational", "loss", "of", "TRAF1,", "whereas", "IL-7", "restores", "TRAF1", "levels.", "A", "combination", "treatment", "with", "IL-7", "and", "agonist", "anti–4-1BB", "antibody", "at", "3", "wk", "after", "LCMV", "clone", "13", "infection", "expands", "T", "cells", "and", "reduces", "viral", "load", "in", "a", "TRAF1-dependent", "manner.", "Moreover,", "transfer", "of", "TRAF1+", "but", "not", "TRAF1", "memory", "T", "cells", "at", "the", "chronic", "stage", "of", "infection", "reduces", "viral", "load.", "These", "findings", "identify", "TRAF1", "as", "a", "potential", "biomarker", "of", "HIV-specific", "CD8", "T", "cell", "fitness", "during", "the", "chronic", "phase", "of", "disease", "and", "a", "target", "for", "therapy.", "Immune", "dysregulation", "is", "a", "hallmark", "of", "chronic", "viral", "infection", "(Virgin", "et", "al.,", "2009).", "Chronic", "infection", "with", "human", "immunodeficiency", "virus", "(HIV)", "or", "hepatitis", "C", "virus", "in", "humans,", "or", "with", "lymphocytic", "choriomeningitis", "virus", "(LCMV)", "clone", "13", "in", "mice,", "results", "in", "up-regulation", "of", "in-", "hibitory", "receptors", "such", "as", "programmed", "death", "1", "(PD-1)", "and", "TIM-3", "on", "effector", "T", "cells,", "as", "well", "as", "the", "sustained", "production", "of", "immune", "M.", "Pellegrini’s", "present", "address", "is", "Walter", "and", "Eliza", "Hall", "Insti-", "tute", "of", "Medical", "Research,", "Parkville,", "Australia.", "T.", "Calzascia’s", "present", "address", "is", "Novartis", "Institute", "for", "Bio-", "medical", "Research,", "Basel,", "Switzerland.", "regulatory", "cytokines", "such", "as", "TGF", "and", "IL-10", "(Barber", "et", "al.,", "2006;", "Day", "et", "al.,", "2006;", "Freeman", "et", "al.,", "2006;", "Petrovas", "et", "al.,", "2006;", "Trautmann", "et", "al.,", "2006;", "Urbani", "et", "al.,", "2006;", "Brooks", "et", "al.,", "2008;", "Jones", "et", "al.,", "2008;", "Tinoco", "et", "al.,", "2009;", "Jin", "et", "al.,", "2010).", "It", "is", "thought", "that", "these", "regu-", "latory", "mechanisms", "minimize", "immune", "pathol-", "ogy,", "but", "also", "contribute", "to", "the", "inability", "of", "the", "©", "2012", "Wang", "et", "al.", "This", "article", "is", "distributed", "under", "the", "terms", "of", "an", "Attribution–", "Noncommercial–Share", "Alike–No", "Mirror", "Sites", "license", "for", "the", "first", "six", "months", "after", "the", "publication", "date", "(see", "http://www.rupress.org/terms).", "After", "six", "months", "it", "is", "available", "under", "a", "Creative", "Commons", "License", "(Attribution–Noncommercial–Share", "Alike", "3.0", "Unported", "license,", "as", "described", "at", "http://creativecommons.org/licenses/", "by-nc-sa/3.0/).", "The", "Rockefeller", "University", "Press", "$30.00", "J.", "Exp.", "Med.", "Vol.", "209", "No.", "1", "77-91", "www.jem.org/cgi/doi/10.1084/jem.20110675", "77" ]

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[ "Hindawi", "Publishing", "Corporation", "Journal", "of", "Skin", "Cancer", "Volume", "2012,", "Article", "ID", "820474,", "5", "pages", "doi:10.1155/2012/820474", "Review", "Article", "New", "Trends", "in", "Dermoscopy", "to", "Minimize", "the", "Risk", "of", "Missing", "Melanoma", "Aimilios", "Lallas,1", "Zoe", "Apalla,1", "and", "Georgios", "Chaidemenos2", "1", "State", "Clinic", "of", "Dermatology,", "Hospital", "of", "Skin", "and", "Venereal", "Diseases,", "124", "Delfon", "Street,", "54643", "Thessaloniki,", "Greece", "2", "Private", "Practice,", "8", "Kosma", "Aitolou", "Street,", "54643", "Thessaloniki,", "Greece", "Correspondence", "should", "be", "addressed", "to", "Aimilios", "Lallas,", "emlallas@gmail.com", "Received", "9", "August", "2012;", "Accepted", "18", "September", "2012", "Academic", "Editor:", "Iris", "Zalaudek", "Copyright", "©", "2012", "Aimilios", "Lallas", "et", "al.", "This", "is", "an", "open", "access", "article", "distributed", "under", "the", "Creative", "Commons", "Attribution", "License,", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited.", "During", "the", "last", "decades,", "induction", "of", "dermoscopy", "in", "the", "clinical", "setting", "resulted", "in", "significant", "modifications", "in", "the", "management", "of", "melanocytic", "lesions.", "Indeed,", "the", "dermatoscope", "reveals", "a", "fascinating", "world", "of", "morphologic", "structures", "invisible", "to", "the", "naked", "eye,", "adding", "valuable", "information", "to", "a", "clinician", "evaluating", "a", "mole.", "However,", "since", "the", "technique", "counts", "only", "a", "couple", "of", "decades,", "new", "research", "data", "are", "continuously", "gathering", "and", "modify", "the", "“optimal”", "management", "of", "melanocytic", "lesions.", "In", "the", "present", "paper,", "we", "summarize", "the", "latest", "trends", "in", "dermoscopy", "concerning", "early", "melanoma", "diagnosis,", "management", "of", "nodular", "lesions,", "diagnosis", "of", "mucosal", "melanoma,", "and", "digital", "followup.", "1.", "Introduction", "During", "the", "last", "decades,", "induction", "of", "dermoscopy", "in", "the", "clin-", "ical", "setting", "resulted", "in", "significant", "modifications", "in", "the", "man-", "agement", "of", "melanocytic", "lesions", "[1].", "Incidence", "of", "melanoma", "increases", "more", "rapidly", "than", "any", "other", "cancer,", "and", "this", "has", "partially", "been", "attributed", "to", "the", "development", "of", "highly", "sen-", "sitive", "diagnostic", "techniques—mainly", "dermoscopy—,", "which", "allowed", "the", "detection", "of", "clinically", "not", "identifiable", "tumors", "[2].", "Indeed,", "the", "dermatoscope", "reveals", "a", "fascinating", "world", "of", "morphologic", "structures", "invisible", "to", "the", "naked", "eye,", "adding", "valuable", "information", "to", "a", "clinician", "evaluating", "a", "mole.", "The", "controversy", "whether", "dermoscopy", "improves", "diagnos-", "tic", "accuracy", "when", "assessing", "melanocytic", "lesions", "belongs", "to", "the", "history,", "since", "several", "lines", "of", "evidence", "clearly", "demonstrate", "that", "use", "of", "dermoscopy", "both", "enhances", "melanoma", "detection", "and", "decreases", "the", "number", "of", "unnecessary", "excisions", "[3].", "Addi-", "tionally", "to", "its", "use", "for", "diagnostic", "purposes,", "dermoscopy,", "by", "revealing", "unknown", "information", "on", "morphology,", "enhanced", "the", "understanding", "of", "nevogenesis", "and", "generated", "new", "con-", "cepts", "and", "theories", "[4].", "However,", "since", "the", "technique", "counts", "only", "a", "couple", "of", "decades,", "new", "research", "data", "are", "continu-", "ously", "gathering", "and", "modify", "the", "“optimal”", "management", "of", "melanocytic", "lesions.", "The", "aim", "of", "this", "paper", "was", "to", "summarize", "the", "latest", "trends", "in", "dermoscopy", "for", "minimizing", "the", "risk", "to", "miss", "melanoma.", "2.", "New", "Trends", "in", "Early", "Melanoma", "Detection", "With", "the", "introduction", "of", "dermoscopy,", "the", "new", "morphologic", "world", "of", "features", "and", "structures", "had", "to", "be", "explored.", "In", "order", "to", "enhance", "the", "utility", "of", "the", "method", "in", "the", "clinical", "setting,", "various", "diagnostic", "models", "and", "algorithms", "have", "been", "developed", "[5–7].", "Indeed,", "application", "of", "these", "algo-", "rithms", "resulted", "in", "significant", "improvement", "of", "the", "diagnostic", "accuracy", "of", "clinicians", "evaluating", "melanocytic", "lesions", "[8–", "10].", "Simplified", "diagnostic", "approaches", "were", "also", "proposed,", "aiming", "to", "facilitate", "the", "use", "of", "dermoscopy", "from", "less", "experi-", "enced", "clinicians", "and", "nondermatologists", "and", "thus", "widen", "the", "application", "field", "of", "the", "method", "[11].", "Additionally", "to", "their", "applicability", "in", "daily", "routine,", "algorithms", "are", "also", "considered", "of", "value", "for", "educational", "purposes,", "providing", "a", "mathematic", "and", "comprehensive", "model", "and", "guiding", "the", "inexperienced", "clinician", "on", "how", "to", "deal", "with", "the", "various", "dermoscopic", "features.", "Several", "lines", "of", "evidence,", "including", "meta-analyses", "and", "randomized", "trials,", "have", "validated", "the", "value", "of", "dermoscopy" ]

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[ "Predictors", "of", "Safe", "Delivery", "Service", "Mulumebet", "A.", "et", "al", "95", "ORIGINAL", "ARTICLE", "PREDICTORS", "OF", "SAFE", "DELIVERY", "SERVICE", "UTILIZATION", "IN", "ARSI", "ZONE,", "SOUTH-EAST", "ETHIOPIA", "Mulumebet", "Abera1,", "Abebe", "G/mariam1,", "Tefera", "Belachew1", "ABSTRACT", "BACKGROUND:", "Evidence", "show", "that", "lack", "of", "access", "to", "and", "use", "of,", "essential", "obstetric", "care", "services", "to", "be", "a", "crucial", "factor", "that", "contributes", "to", "the", "high", "maternal", "morbidity", "and", "mortality.", "Skilled", "attendance", "during", "labor,", "delivery", "and", "early", "post-partum", "period", "could", "reduce", "deaths", "due", "to", "obstructed", "labor,", "hemorrhage,", "sepsis", "and", "eclampsia.", "There", "is", "limited", "information", "on", "the", "mothers’", "use", "of", "skilled", "delivery", "services", "in", "the", "study", "area.", "This", "study", "assessed", "the", "predictors", "of", "safe", "delivery", "service", "utilization", "in", "Arsi", "Zone,", "Southeast", "Ethiopia.", "METHODS:", "A", "cross-", "sectional", "community", "based", "study", "using", "quantitative", "and", "qualitative", "methods", "was", "conducted", "from", "February", "15th", "to", "March", "15th", "2006.", "A", "total", "of", "1089", "women", "who", "had", "at", "least", "one", "birth", "one", "year", "prior", "to", "the", "study", "were", "involved", "in", "the", "study", "from", "nine", "rural", "and", "four", "urban", "kebeles", "in", "three", "Woredas", "(Districts)", "selected", "using", "a", "systematic", "sampling", "method", "from", "all", "households", "in", "the", "study", "area.", "A", "pre-tested", "structured", "interviewer", "administered", "questionnaire", "was", "used", "to", "collect", "data.", "Information", "on", "the", "utilization", "of", "safe", "delivery", "service", "and", "socio-demographic,", "individual", "and", "institutional", "factors", "and", "past", "obstetric", "history", "were", "collected.", "Focus", "Group", "Discussion", "guide", "was", "used", "for", "qualitative", "data", "collection.", "The", "data", "were", "edited,", "cleaned,", "and", "entered", "into", "a", "computer", "and", "analyzed", "using", "SPSS", "for", "windows", "version", "12.0.", "RESULT:", "One", "thousand", "seventy", "four", "women", "who", "had", "at", "least", "one", "birth", "were", "interviewed", "making", "a", "response", "rate", "98.6%.", "Two", "hundred", "seventy", "one", "(75.0%)", "of", "urban", "and", "373(52.0%)", "rural", "women", "received", "antenatal", "care", "from", "skilled", "health", "professional", "at", "least", "once", "during", "their", "last", "pregnancy.", "Thirty-one", "(4.3%)", "of", "rural", "and", "145", "(40.4%)", "of", "urban", "women", "delivered", "in", "health", "institution.", "In", "multivariate", "analysis", "showed", "that", "residential", "area", "OR=", "8.5,", "95%CI;", "(5.1,13.9),", "parity", "OR=0.18,", "95%CI;", "(0.08,", "0.42),", "and", "ANC", "service", "use", "OR=", "4.5,", "95%CI;", "(2.2,8.9),", "and", "maternal", "education", "OR=4.6,", "95%CI;", "(1.7,12.8),", "were", "most", "significant", "predictors", "of", "safe", "delivery", "service", "use", "by", "mothers", "(P<", "0.01).", "CONCLUSION:", "Birth", "attended", "by", "skilled", "personnel", "was", "low", "in", "the", "study", "area.", "Maternal", "education,", "her", "birth", "experience", "and", "her", "use", "of", "prenatal", "services", "are", "important", "predictors.", "Promoting", "information,", "education", "and", "communication", "on", "safe", "delivery", "service", "utilization,", "expansion", "of", "health", "service", "and", "empowerment", "of", "women", "are", "needed.", "KEY", "WORDS:", "safe", "delivery,", "skilled", "attendants,", "and", "maternal", "health", "service", "utilization.", "INTRODUCTION", "Globally", "about", "585,000", "women", "die", "each", "year", "due", "to", "conditions", "related", "to", "pregnancy", "and", "child", "birth", "99%", "of", "which", "occur", "in", "developing", "countries", "(1).", "Over", "three", "quarter", "of", "maternal", "deaths", "are", "due", "to", "causes", "directly", "related", "to", "pregnancy", "and", "childbirth", "(2).", "The", "complications", "that", "cause", "the", "deaths", "and", "disabilities", "of", "mothers", "affect", "the", "unborn", "fetus.", "These", "deaths", "could", "be", "avoided", "if", "preventive", "measures", "were", "taken", "and", "adequate", "cares", "available", "particularly", "during", "pregnancy,", "childbirth", "and", "postpartum", "period", "through", "obstetric", "care", "services.", "More", "than", "60%", "of", "maternal", "deaths", "occur", "immediately", "following", "delivery,", "with", "more", "than", "half", "occurring", "within", "a", "day", "of", "delivery", "(3-4).", "--------------------------------------------------------", "1Department", "of", "Population", "&", "Family", "Health,", "College", "of", "Public", "Health", "and", "Medical", "Sciences,", "Jimma", "University" ]

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[ "Int.", "J.", "Mol.", "Sci.", "2012,", "13,", "9959-9970;", "doi:10.3390/ijms13089959", "OPEN", "ACCESS", "International", "Journal", "of", "Molecular", "Sciences", "ISSN", "1422-0067", "www.mdpi.com/journal/ijms", "Article", "Chick", "Chorioallantoic", "Membrane", "(CAM)", "Assay", "as", "an", "In", "Vivo", "Model", "to", "Study", "the", "Effect", "of", "Newly", "Identified", "Molecules", "on", "Ovarian", "Cancer", "Invasion", "and", "Metastasis", "Noor", "A.", "Lokman", "1,", "Alison", "S.", "F.", "Elder", "1,", "Carmela", "Ricciardelli", "1", "and", "Martin", "K.", "Oehler", "1,2,*", "1", "Research", "Centre", "for", "Reproductive", "Health,", "School", "of", "Paediatrics", "and", "Reproductive", "Health,", "Robinson", "Institute,", "University", "of", "Adelaide,", "Adelaide,", "South", "Australia", "5000,", "Australia;", "E-Mails:", "noor.lokman@adelaide.edu.au", "(N.A.L.);", "alison.elder@adelaide.edu.au", "(A.S.F.E.);", "carmela.ricciardelli@adelaide.edu.au", "(C.R.)", "2", "Department", "of", "Gynaecological", "Oncology,", "Royal", "Adelaide", "Hospital,", "Adelaide,", "South", "Australia", "5000,", "Australia", "*", "Author", "to", "whom", "correspondence", "should", "be", "addressed;", "E-Mail:", "martin.oehler@adelaide.edu.au;", "Tel.:", "+61-8-8222-4816;", "Fax:", "+61-8-8222-5952.", "Received:", "2", "July", "2012;", "in", "revised", "form:", "27", "July", "2012", "/", "Accepted:", "2", "August", "2012", "/", "Published:", "10", "August", "2012", "Abstract:", "The", "majority", "of", "ovarian", "cancer", "patients", "present", "with", "advanced", "disease", "and", "despite", "aggressive", "treatment,", "prognosis", "remains", "poor.", "Significant", "improvement", "in", "ovarian", "cancer", "survival", "will", "require", "the", "development", "of", "more", "effective", "molecularly", "targeted", "therapeutics.", "Commonly,", "mouse", "models", "are", "used", "for", "the", "in", "vivo", "assessment", "of", "potential", "new", "therapeutic", "targets", "in", "ovarian", "cancer.", "However,", "animal", "models", "are", "costly", "and", "time", "consuming.", "Other", "models,", "such", "as", "the", "chick", "embryo", "chorioallantoic", "membrane", "(CAM)", "assay,", "are", "therefore", "an", "attractive", "alternative.", "CAM", "assays", "have", "been", "widely", "used", "to", "study", "angiogenesis", "and", "tumor", "invasion", "of", "colorectal,", "prostate", "and", "brain", "cancers.", "However,", "there", "have", "been", "limited", "studies", "that", "have", "used", "CAM", "assays", "to", "assess", "ovarian", "cancer", "invasion", "and", "metastasis.", "We", "have", "therefore", "developed", "a", "CAM", "assay", "protocol", "to", "monitor", "the", "metastatic", "properties", "of", "ovarian", "cancer", "cells", "(OVCAR-3,", "SKOV-3", "and", "OV-90)", "and", "to", "study", "the", "effect", "of", "potential", "therapeutic", "molecules", "in", "vivo.", "The", "results", "from", "the", "CAM", "assay", "are", "consistent", "with", "cancer", "cell", "motility", "and", "invasion", "observed", "in", "in", "vitro", "assays.", "Our", "results", "demonstrate", "that", "the", "CAM", "assay", "is", "a", "robust", "and", "cost", "effective", "model", "to", "study", "ovarian", "cancer", "cell", "metastasis.", "It", "is", "therefore", "a", "very", "useful", "in", "vivo", "model", "for", "screening", "of", "potential", "novel", "therapeutics." ]

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[ "Hindawi", "Publishing", "Corporation", "Journal", "of", "Obesity", "Volume", "2012,", "Article", "ID", "735465,", "11", "pages", "doi:10.1155/2012/735465", "Research", "Article", "Unraveling", "the", "Relationship", "between", "Smoking", "and", "Weight:", "The", "Role", "of", "Sedentary", "Behavior", "Annette", "Kaufman,1", "Erik", "M.", "Augustson,2", "and", "Heather", "Patrick3", "1", "Cancer", "Prevention", "Fellowship", "Program,", "Office", "of", "the", "Associate", "Director,", "Behavioral", "Research", "Program,", "Division", "of", "Cancer", "Control", "and", "Population", "Sciences,", "National", "Cancer", "Institute,", "Bethesda,", "MD", "20852,", "USA", "2", "Tobacco", "Control", "Research", "Branch,", "Behavioral", "Research", "Program,", "Division", "of", "Cancer", "Control", "and", "Population", "Sciences,", "National", "Cancer", "Institute,", "Bethesda,", "MD", "20852,", "USA", "3", "Health", "Behaviors", "Research", "Branch,", "Behavioral", "Research", "Program,", 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"A", "number", "of", "physiological", "mechanisms", "have", "been", "hypothesized", "to", "explain", "this", "pattern,", "but", "few", "studies", "have", "explored", "the", "possible", "role", "of", "behavioral", "factors.", "Using", "data", "from", "the", "cross-sectional", "National", "Health", "and", "Nutrition", "Examination", "Survey", "1999–2006,", "this", "descriptive", "study", "explored", "the", "associations", "among", "smoking", "status,", "sedentary", "behavior,", "and", "two", "anthropometric", "measures", "(BMI", "and", "waist", "circumference", "(WC)).", "Sedentary", "behavior", "was", "significantly", "higher", "among", "current", "smokers", "compared", "to", "never", "and", "former", "smokers;", "former", "smokers", "had", "higher", "levels", "of", "sedentary", "behavior", "compared", "to", "never", "smokers.", "The", "association", "between", "smoking", "status", "and", "anthropometric", "outcomes", "was", "moderated", "by", "sedentary", "behavior,", "with", "current", "smokers", "evidencing", "higher", "BMI", "and", "WC", "at", "higher", "levels", "of", "sedentary", "behavior", "compared", "to", "lower", "levels", "of", "sedentary", "behavior.", "Results", "are", "discussed", "in", "terms", "of", "their", "implications", "for", "interventions,", "particularly", "with", "respect", "to", "postcessation", "weight", "gain.", "1.", "Background", "Obesity", "and", "tobacco", "use", "are", "the", "two", "leading", "causes", "of", "preventable", "death", "and", "disease", "in", "the", "United", "States", "[1].", "Despite", "declines", "in", "smoking", "prevalence", "from", "a", "peak", "in", "the", "1960s,", "tobacco", "use", "remains", "the", "leading", "cause", "of", "preventable", "death", "and", "disease", "in", "the", "USA", "[2].", "It", "is", "estimated", "that", "440,000", "Americans", "die", "prematurely", "each", "year", "as", "a", "result", "of", "tobacco", "use", "and", "exposure", "[3].", "Approximately", "20.6%", "of", "USA", "adults", "are", "current", "smokers,", "defined", "as", "smoking", "at", "least", "100", "cigarettes", "during", "their", "lifetime", "and", "every", "day", "or", "some", "days", "currently", "[4].", "As", "smoking", "rates", "have", "declined,", "obesity", "rates", "(having", "a", "body", "mass", "index", "(BMI)", "of", "30", "or", "higher)", "have", "doubled", "in", "the", "USA", "since", "1980", "with", "recent", "data", "indicating", "that", "more", "than", "33%", "of", "USA", "adults", "are", "obese", "[5].", "The", "rate", "of", "mortality", "due", "to", "overweight/obesity", "is", "estimated", "to", "account", "for", "approximately", "365,000", "deaths", "yearly", "[6].", "Research", "indicates", "that", "smoking", "and", "body", "weight", "are", "interrelated,", "but", "the", "relationship", "is", "complex", "and", "not", "well", "understood.", "In", "general,", "cigarette", "smoking", "has", "an", "inverse", "association", "with", "body", "weight", "or", "BMI", "[7–9],", "and", "smoking", "cessation", "has", "been", "linked", "to", "weight", "gain", "[8,", "10,", "11].", "Few", "studies", "have", "examined", "the", "relationship", "between", "smoking", "and", "body", "shape,", "specifically", "central", "adiposity.", "Some", "stud-", "ies", "suggest", "that", "smokers", "have", "greater", "abdominal", "obesity", "compared", "to", "nonsmokers", "[12–14].", "Independent", "of", "overall", "adiposity,", "having", "a", "larger", "waist", "circumference", "(WC),", "or", "android", "body", "shape,", "is", "associated", "with", "mortality", "in", "adults", "age", "50", "and", "older", "and", "metabolic", "disease", "risk", "[15–17].", "Body", "shape,", "rather", "than", "BMI,", "may", "better", "explain", "why", "smokers", "have", "a", "higher", "risk", "of", "metabolic", "syndrome,", "in", "particular", "type", "2", "diabetes", "[18].", "A", "number", "of", "biological", "mechanisms", "have", "been", "proposed", "to", "explain", "this", "relationship", 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[ "Bradley", "et", "al.", "Arthritis", "Research", "&", "Therapy", "2010,", "12:R141", "http://arthritis-research.com/content/12/4/R141", "R", "E", "S", "E", "A", "R", "C", "H", "A", "R", "T", "I", "C", "L", "E", "Open", "Access", "Effect", "of", "duloxetine", "in", "patients", "with", "fibromyalgia:", "tiredness", "subgroups", "Laurence", "A", "Bradley1,", "Robert", "Bennett2,", "Irwin", "J", "Russell3,", "Madelaine", "M", "Wohlreich4*,", "Amy", "S", "Chappell5,6,", "Fujun", "Wang7,", "Deborah", "N", "D’Souza8,", "Harvey", "Moldofsky9", "Abstract", "Introduction:", "This", "study", "tested", "the", "hypothesis", "that", "baseline", "ratings", "of", "fatigue/tiredness", "would", "be", "negatively", "associated", "with", "the", "efficacy", "of", "duloxetine", "on", "measures", "of", "pain", "and", "functional", "ability", "in", "patients", "with", "fibromyalgia.", "Methods:", "A", "post", "hoc", "analysis", "of", "pooled", "data", "from", "4", "double-blind,", "placebo-controlled", "studies", "of", "duloxetine", "in", "fibromyalgia", "was", "performed.", "The", "fibromyalgia", "impact", "questionnaire", "(FIQ)", "tiredness", "item", "score", "(0", "to", "10", "scale)", "was", "used", "to", "define", "tiredness", "subgroups.", "Patients", "were", "stratified", "into", "3", "subgroups:", "mild", "(0", "to", "3),", "moderate", "(4", "to", "6),", "and", "severe", "(7", "to", "10)", "tiredness.", "Analysis", "of", "covariance", "models", "and", "logistic", "regressions", "were", "used", "to", "test", "treatment-by-", "tiredness", "subgroup", "interactions.", "Results:", "Data", "from", "the", "first", "3", "months", "are", "included", "in", "this", "post", "hoc", "analysis", "(duloxetine", "N", "=", "797,", "placebo", "N", "=", "535).", "At", "baseline,", "the", "distribution", "of", "tiredness", "severity", "in", "the", "duloxetine", "and", "placebo", "groups", "respectively", "was", "3.64%", "and", "3.75%", "mild,", "16.71%", "and", "15.57%", "moderate,", "and", "79.65%", "and", "80.68%", "severe.", "Rates", "of", "clinically", "significant", "(≥30%", "and", "≥50%)", "improvement", "in", "brief", "pain", "inventory", "(BPI)", "average", "pain", "were", "similar", "across", "the", "tiredness", "subgroups.", "Tiredness", "severity", "at", "baseline", "was", "not", "negatively", "associated", "with", "the", "effects", "of", "duloxetine", "on", "patients’", "reports", "of", "functional", "ability", "using", "the", "FIQ", "total", "score,", "FIQ", "measures", "of", "physical", "impairment,", "interference", "with", "work,", "pain,", "stiffness,", "and", "depression", "and", "the", "medical", "outcomes", "study", "short", "form-36", "(SF-36).", "Conclusions:", "Studies", "of", "duloxetine", "in", "fibromyalgia", "have", "demonstrated", "clinically", "significant", "improvements", "in", "pain", "and", "functional", "ability", "(FIQ,", "SF-36).", "This", "post", "hoc", "analysis", "of", "data", "shows", "that", "the", "efficacy", "of", "duloxetine", "among", "patients", "with", "fibromyalgia", "does", "not", "vary", "as", "a", "function", "of", "baseline", "ratings", "of", "fatigue/tiredness.", "Introduction", "Fibromyalgia", "is", "a", "disorder", "that", "is", "found", "in", "approximately", "2%", "of", "the", "general", "population", "and", "is", "characterized", "by", "chronic", "widespread", "pain", "and", "tenderness", "[1].", "Additional", "symptoms", "that", "often", "accompany", "fibromyalgia", "are", "tired-", "ness", "or", "fatigue,", "depressed", "mood,", "sleep", "disturbance,", "and", "headache", "[2,3].", "We", "will", "use", "the", "term", "‘tiredness’", "through-", "out", "this", "report,", "due", "to", "our", "decision", "to", "use", "the", "fibro-", "myalgia", "impact", "questionnaire", "(FIQ)", "outcome", "measure,", "unless", "we", "refer", "specifically", "to", "studies", "that", "have", "used", "measures", "of", "‘fatigue’.", "Duloxetine,", "a", "potent", "reuptake", "inhibitor", "of", "serotonin", "and", "norepinephrine,", "was", "approved", "in", "the", "USA", "for", "the", "management", "of", "fibromyalgia", "in", "June", "2008.", "Preclinical", "*", "Correspondence:", "mwmd@lilly.com", "4Lilly", "Research", "Laboratories,", "Lilly", "Corporate", "Center,", "Indianapolis,", "IN", "46285,", "USA", "models", "of", "central", "sensitization", "suggest", "that", "duloxetine", "is", "efficacious", "in", "the", "treatment", "of", "patients", "with", "persistent/", "chronic", "pain.", "In", "rodents,", "duloxetine", "has", "demonstrated", "efficacy", "in", "the", "formalin", "and", "capsaicin", "models", "of", "persis-", "tent", "pain,", "as", "well", "as", "in", "the", "partial", "sciatic", "nerve", "ligation", "and", "L5/L6", "spinal", "nerve", "ligation", "models", "of", "neuropathic", "pain", "[4,5].", "Duloxetine", "is", "efficacious", "in", "the", "treatment", "of", "the", "painful", "physical", "symptoms", "associated", "with", "depres-", "sion", "and", "the", "pain", "associated", "with", "diabetic", "neuropathy", "in", "nondepressed", "patients", "[6,7].", "The", "results", "of", "four", "placebo-", "controlled", "clinical", "trials", "of", "duloxetine", "in", "the", "treatment", "of", "fibromyalgia", "have", "been", "previously", "reported", "[8-11].", "Patients", "with", "fibromyalgia", "frequently", "report", "moderate", "to", "severe", "fatigue", "and", "the", "prevalence", "of", "fatigue", "in", "patients", "with", "fibromyalgia", "(76%)", "is", "almost", "double", "that", "of", "patients", "with", "osteoarthritis", "or", "rheumatoid", "arthritis", "(41%)", "[12,13].", "An", "evidence-based", "review", "of", "the", "literature", "on", "chronic", "pain", "found", "a", "highly", "consistent", "association", "©", "2010", "Bradley", "et", "al.;", "licensee", "BioMed", "Central", "Ltd.", "This", "is", "an", "open", "access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "License", "(http://creativecommons.org/licenses/by/2.0),", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited." ]

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[ "Hindawi", "Publishing", "Corporation", "PPAR", "Research", "Volume", "2012,", "Article", "ID", "513865,", "12", "pages", "doi:10.1155/2012/513865", "Review", "Article", "The", "Case", "for", "the", "Use", "of", "PPARγ", "Agonists", "as", "an", "Adjunctive", "Therapy", "for", "Cerebral", "Malaria", "Lena", "Serghides", "Sandra", "A.", "Rotman", "Laboratories,", "McLaughlin-Rotman", "Centre", "for", "Global", "Health,", "Toronto", "General", "Hospital", "University", "Health", "Network,", "101", "College", "Street,", "Suite", "10-359,", "Toronto,", "ON,", "Canada", "M5G", "1L7", "Correspondence", "should", "be", "addressed", "to", "Lena", "Serghides,", "lena.serghides@utoronto.ca", "Received", "7", "January", "2011;", "Accepted", "28", "February", "2011", "Academic", "Editor:", "Marion", "M.", "Chan", "Copyright", "©", "2012", "Lena", "Serghides.", "This", "is", "an", "open", "access", "article", "distributed", "under", "the", "Creative", "Commons", "Attribution", "License,", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited.", "Cerebral", "malaria", "is", "a", "severe", "complication", "of", "Plasmodium", "falciparum", "infection", "associated", "with", "high", "mortality", "even", "when", "highly", "effective", "antiparasitic", "therapy", "is", "used.", "Adjunctive", "therapies", "that", "modify", "the", "pathophysiological", "processes", "caused", "by", "malaria", "are", "a", "possible", "way", "to", "improve", "outcome.", "This", "review", "focuses", "on", "the", "utility", "of", "PPARγ", "agonists", "as", "an", "adjunctive", "therapy", "for", "the", "treatment", "of", "cerebral", "malaria.", "The", "current", "knowledge", "of", "PPARγ", "agonist", "use", "in", "malaria", "is", "summarized.", "Findings", "from", "experimental", "CNS", "injury", "and", "disease", "models", "that", "demonstrate", "the", "potential", "for", "PPARγ", "agonists", "as", "an", "adjunctive", "therapy", "for", "cerebral", "malaria", "are", "also", "discussed.", "1.", "Introduction", "Few", "diseases", "have", "the", "global", "health", "and", "economic", "impact", "of", "malaria", "[1].", "In", "2009,", "an", "estimated", "225", "million", "people", "were", "infected", "with", "malaria", "and", "close", "to", "a", "million", "people", "succumbed", "to", "their", "infection", "[2].", "Malaria", "is", "caused", "by", "api-", "complexan", "parasites", "belonging", "to", "the", "genus", "Plasmodium.", "Five", "species", "infect", "humans,", "Plasmodium", "falciparum,", "P.", "vivax,", "P.", "ovale,", "P.", "malariae,", "and", "most", "recently,", "P.", "knowlesi", "[3].", "The", "majority", "of", "morbidity", "and", "mortality", "is", "caused", "by", "P.", "falciparum", "infection,", "with", "the", "highest", "burden", "born", "by", "children", "and", "pregnant", "women.", "In", "the", "absence", "of", "prompt", "and", "effective", "treatment,", "P.", "falciparum", "infection", "can", "progress", "quickly,", "rapidly", "becoming", "severe", "and", "fatal.", "The", "rise", "in", "drug-", "resistant", "parasites", "complicates", "the", "administration", "of", "effective", "treatment.", "Severe", "malaria", "has", "multiple", "manifestations", "that", "can", "occur", "singly", "or", "in", "combination.", "They", "include", "hyperpar-", "asitemia,", "high", "fever,", "haemoglobinuria,", "acute", "renal", "failure,", "acute", "pulmonary", "edema,", "metabolic", "acidosis", "and", "respiratory", "distress,", "hypoglycemia,", "anemia,", "and", "cerebral", "malaria,", "which", "is", "characterized", "by", "coma", "and", "convulsions.", "Cerebral", "malaria", "has", "the", "highest", "mortality", "rate", "of", "all", "the", "severe", "complications", "and", "is", "associated", "with", "long-term", "cognitive", "and", "neurological", "deficits", "in", "surviving", "children", "[4–6].", "Intravenous", "artesunate", "is", "now", "the", "standard", "of", "care", "for", "severe", "malaria", "in", "both", "adults", "and", "children", "following", "the", "landmark", "SEAQUAMAT", "and", "AQUAMAT", "trials", "that", "demonstrated", "the", "superiority", "of", "artesunate", "over", "quinine", "in", "adults", "and", "in", "children", "[7,", "8].", "However,", "even", "with", "the", "improved", "efficacy", "of", "artesunate,", "fatality", "rates", "remained", "high,", "15%", "in", "adults", "and", "10.9%", "in", "children.", "Adjunctive", "therapies,", "defined", "as", "therapies", "administered", "in", "combination", "with", "antiparasitic", "drugs", "that", "modify", "pathophysiological", "processes", "caused", "by", "malaria,", "have", "been", "pursued", "as", "a", "way", "to", "improve", "the", "outcome", "of", "severe", "malaria.", "Adjunctive", "therapies", "may", "also", "help", "extend", "the", "efficacy", "of", "antiparasitic", "drugs,", "an", "important", "consideration", "given", "the", "emergence", "of", "artemisinin", "resistance", "[9,", "10].", "Several", "adjunctive", "therapeutic", "strategies", "have", "been", "tested", "in", "P.", "falciparum", "cerebral", "and", "severe", "malaria", "so", "far,", "unfortunately", "with-out", "much", "success", "(see", "[11]", "for", "a", "recent", "review).", "A", "number", "of", "adjunctive", "therapies", "(includ-", "ing", "nitric", "oxide,", "arginine,", "erythropoietin,", "levamisole)", "have", "demonstrated", "encouraging", "results", "in", "experimental", "models", "of", "cerebral", "malaria", "or", "in", "clinical", "trials", "in", "uncomplicated", "malaria", "and", "are", "awaiting", "evaluation", "in", "severe", "malaria", "[11].", "This", "review", "will", "focus", "on", "the", "utility", "of", "PPARγ", "agonists", "as", "an", "adjunctive", "therapy", "for", "the", "treatment", "of", "cerebral", "malaria.", "The", "current", "knowledge", "of", "PPARγ", "agonist", "use", "in", "malaria", "will", "be", "summarized.", "We", "will", "also", "summarize", "data", "on", "additional" ]

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[ "Hindawi", "Publishing", "Corporation", "Sarcoma", "Volume", "2010,", "Article", "ID", "353679,", "3", "pages", "doi:10.1155/2010/353679", "Case", "Report", "Recurrent", "Endometrial", "Stromal", "Sarcoma:", "Treatment", "with", "a", "Progestin", "and", "Gonadotropin", "Releasing", "Hormone", "Agonist", "Nefertiti", "Chianti", "duPont", "and", "Philip", "John", "DiSaia", "Division", "of", "Gynecologic", "Oncology,", "Department", "of", "Obstetrics", "and", "Gynecology,", "University", "of", "California,", "Irvine", "College", "of", "Medicine,", "Orange,", "CA", "92868,", "USA", "Correspondence", "should", "be", "addressed", "to", "Nefertiti", "Chianti", "duPont,", "nefertiti.dupont@roswellpark.org", "Received", "2", "September", "2009;", "Revised", "24", "March", "2010;", "Accepted", "8", "April", "2010", "Academic", "Editor:", "Michael", "Leahy", "Copyright", "©", "2010", "N.", "C.", "duPont", "and", "P.", "J.", "DiSaia.", "This", "is", "an", "open", "access", "article", "distributed", "under", "the", "Creative", "Commons", "Attribution", "License,", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited.", "Endometrial", "stromal", "sarcoma", "(ESS)", "formerly", "classified", "as", "low-grade", "endometrial", "stromal", "sarcoma", "is", "a", "rare", "uterine", "malignancy", "with", "a", "good", "prognosis", "despite", "a", "tendency", "to", "recur.", "Primary", "surgical", "management", "for", "ESS", "includes", "total", "abdominal", "hysterectomy", "and", "bilateral", "salpingo-oophorectomy.", "Patients", "with", "ESS", "have", "long", "disease-free", "survival", "rates", "when", "treated", "with", "primary", "surgical", "therapy,", "but", "nearly", "fifty", "percent", "of", "these", "patients", "will", "recur.", "We", "present", "the", "case", "of", "a", "patient", "with", "recurrent", "ESS", "who", "had", "an", "excellent", "response", "to", "combined", "therapy", "with", "megestrol", "and", "leuprolide.", "1.", "Introduction", "First", "reported", "in", "1908,", "endometrial", "stromal", "sarcoma", "(ESS)", "is", "a", "rare", "uterine", "tumor", "known", "for", "its", "slow", "growth", "[1].", "Originally", "known", "as", "interstitial", "endometrioma,", "endolym-", "phatic", "stromal", "myosis,", "or", "low-grade", "endometrial", "stromal", "sarcoma", "ESS", "is", "recognized", "by", "its", "infiltrating", "margins", "and", "low", "mitotic", "activity", "[2–4].", "Endometrial", "stromal", "sarcomas", "represent", "0.2%", "of", "all", "genital", "tract", "malignancies", "and", "were", "previously", "subdivided", "into", "low-", "or", "high-grade", "categories", "based", "upon", "their", "mitotic", "index.", "High-grade", "endometrial", "stromal", "sarcomas", "are", "now", "termed", "poorly", "differentiated", "or", "undifferentiated", "uterine", "sarcomas", "due", "to", "its", "aggressive", "clinical", "course", "[5–10].", "Typically", "diagnosed", "postoperatively", "on", "hysterectomy", "specimens,", "ESS", "has", "an", "indolent", "course", "and", "recurrent", "disease", "can", "occur", "up", "to", "twenty", "years", "after", "diagnosis.", "Primary", "ESS", "is", "treated", "surgically", "with", "a", "total", "abdominal", "hysterectomy", "and", "bilateral", "salpingo-oophorectomy", "and", "routine", "lymphadenec-", "tomy", "has", "not", "been", "found", "to", "improve", "overall", "survival", "rates", "[1,", "3,", "7,", "8].", "Recurrent", "ESS", "is", "commonly", "treated", "with", "progestins", "like", "other", "endometrial", "cancers", "but", "there", "is", "no", "consensus", "regarding", "optimal", "management", "[5].", "ESS", "is", "hormonally", "responsive", "and", "contains", "estrogen", "and", "progesterone", "receptors", "[5,", "11–13].", "Patients", "with", "retained", "ovaries", "after", "a", "hysterec-", "tomy", "or", "those", "who", "receive", "estrogen", "hormone", "replacement", "have", "high", "recurrence", "rates;", "therefore,", "single", "agent", "estrogen", "replacement", "therapy", "is", "not", "recommended", "[5].", "Progestins", "however", "are", "commonly", "used", "in", "the", "adjuvant", "setting", "to", "treat", "ESS", "[5].", "The", "mechanism", "of", "action", "of", "progestins", "is", "to", "bind", "progesterone", "receptors", "and", "cause", "downregulation", "of", "gene", "transcription", "leading", "to", "decreased", "endometrial", "gland", "and", "stromal", "proliferation", "[11,", "14].", "Diminished", "endometrial", "gland", "and", "stromal", "proliferation", "make", "progestins", "beneficial", "for", "use", "in", "the", "adjuvant", "setting", "and", "at", "the", "time", "of", "disease", "recurrence.", "In", "addition,", "gonadotropin", "releasing", "hormone", "(GnRH)", "agonists", "downregulate", "GnRH", "receptors", "in", "the", "anterior", "pituitary", "leading", "to", "a", "hypoestrogenic", "state.", "Here,", "we", "present", "the", "long-term", "followup", "of", "a", "patient", "with", "recurrent", "endometrial", "stromal", "sarcoma", "treated", "with", "a", "progestin", "and", "GnRH", "agonist", "with", "excellent", "results.", "2.", "Case", "Report", "A", "41-year-old", "woman", "gravida", "2", "para", "1", "with", "a", "body", "mass", "index", "of", "25", "presented", "with", "menorrhagia,", "pelvic", "pain,", "and", "dysmenorrhea.", "Her", "past", "medical", "history", "was", "unremarkable.", "Her", "past", "surgical", "history", "was", "pertinent", "for", "a", "bilateral" ]

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[ "Huang", "et", "al.", "Journal", "of", "Cardiothoracic", "Surgery", "2010,", "5:88", "http://www.cardiothoracicsurgery.org/content/5/1/88", "R", "E", "S", "E", "A", "R", "C", "H", "A", "R", "T", "I", "C", "L", "E", "Open", "Access", "Lung", "abscess", "predicts", "the", "surgical", "outcome", "in", "patients", "with", "pleural", "empyema", "Hung-Che", "Huang1,", "Heng-Chung", "Chen1,", "Hsin-Yuan", "Fang2*,", "Yi-Chieh", "Lin1,", "Chin-Yen", "Wu1,", "Ching-Yuan", "Cheng1", "Abstract", "Objectives:", "Most", "cases", "of", "pleural", "empyema", "are", "caused", "by", "pulmonary", "infections,", "which", "are", "usually", "combined", "with", "pneumonia", "or", "lung", "abscess.", "The", "mortality", "of", "patients", "with", "pleural", "empyema", "remains", "high", "(up", "to", "20%).", "It", "also", "contributes", "to", "higher", "hospital", "costs", "and", "longer", "hospital", "stays.", "We", "studied", "pleural", "empyema", "with", "combined", "lung", "abscess", "to", "determine", "if", "abscess", "was", "associated", "with", "mortality.", "Methods:", "From", "January", "2004", "to", "December", "2006,", "we", "retrospectively", "reviewed", "259", "patients", "diagnosed", "with", "pleural", "empyema", "who", "received", "thoracscopic", "decortications", "of", "the", "pleura", "in", "a", "single", "medical", "center.", "We", "evaluated", "their", "clinical", "data", "and", "analyzed", "their", "chest", "computed", "tomography", "scans.", "Outcomes", "of", "pleural", "empyema", "were", "compared", "between", "groups", "with", "and", "without", "lung", "abscess.", "Results:", "Twenty-two", "pleural", "empyema", "patients", "had", "lung", "abscesses.", "Clinical", "data", "showed", "significantly", "higher", "incidences", "in", "the", "lung", "abscess", "group", "of", "pre-operative", "leukocytosis,", "need", "for", "an", "intensive", "care", "unit", "stay", "and", "mortality.", "Conclusion:", "Patients", "with", "pleural", "empyema", "and", "lung", "abscess", "have", "higher", "intensive", "care", "unit", "admission", "rate,", "higher", "mortality", "during", "30", "days", "and", "overall", "mortality", "than", "patients", "with", "pleural", "empyema.", "The", "odds", "ratio", "of", "lung", "abscess", "is", "4.685.", "Physician", "shall", "pay", "more", "attention", "on", "high", "risk", "patient", "of", "lung", "abscess", "for", "early", "detection", "and", "management.", "Background", "Pleural", "empyema", "is", "one", "of", "the", "serious", "complications", "of", "pneumonia,", "and", "increases", "the", "morbidity", "and", "mortality", "due", "to", "pneumonia", "[1-3].", "About", "5%", "of", "patients", "with", "pneumonia", "suffer", "from", "pleural", "empyema", "[4,5].", "About", "65,000", "patients", "in", "the", "United", "State", "and", "the", "United", "King-", "dom", "suffer", "annually", "from", "pleural", "empyema", "or", "a", "compli-", "cated", "parapneumonic", "effusion.", "The", "mortality", "of", "patients", "with", "pleural", "empyema", "is", "up", "to", "20%", "and", "contributes", "to", "higher", "hospital", "costs.", "Inflammatory", "mechanisms", "and", "alterations", "in", "the", "balance", "of", "pleural", "fibrinolysis", "have", "been", "implicated", "in", "the", "pathophysiology", "of", "infectious", "pleural", "effusion.", "Pleural", "empyema", "is", "associated", "with", "fibrin", "deposition", "over", "pleural", "surfaces", "due", "to", "inhibition", "of", "the", "fibrinolysis", "system", "[6,7].", "Parapneumonic", "effusions", "progress", "through", "exudative", "and", "fibrinopurulent", "stages", "and", "terminate", "in", "empyema", "in", "the", "organized", "stage.", "The", "*", "Correspondence:", "d93421104@ntu.edu.tw", "2Department", "of", "Surgery,", "China", "Medical", "University", "Hospital,", "China", "Medical", "University,", "2", "Yude", "Road,", "Taichung,", "404,", "Taiwan", "Full", "list", "of", "author", "information", "is", "available", "at", "the", "end", "of", "the", "article", "clinical", "courses", "of", "patients", "with", "parapneumonic", "effu-", "sions", "or", "pleural", "empyema", "are", "varied.", "Lung", "abscess", "is", "defined", "as", "a", "circumscribed", "collection", "of", "pus", "in", "the", "lung,", "which", "leads", "to", "formation", "of", "a", "cavity.", "It", "develops", "when", "a", "localized", "area", "of", "parenchymal", "infection", "becomes", "necro-", "tic", "and", "then", "cavitates.", "It", "most", "commonly", "occurs", "second-", "ary", "to", "aspiration", "in", "patients", "with", "poor", "dentition", "or", "as", "a", "complication", "of", "necrotizing", "pneumonia.", "Lung", "abscess", "has", "previously", "been", "thought", "to", "be", "a", "rare", "condition", "of", "empyema", "and", "parapneumonic", "effusions.", "About", "90%", "of", "patients", "with", "lung", "abscesses", "been", "cured", "by", "antibiotics", "therapies", "simply", "[8].", "Surgical", "resection", "of", "lung", "abscess", "is", "rare", "when", "medical", "treatments", "fail.", "Pleural", "empyema", "and", "lung", "abscess", "are", "both", "a", "part", "of", "low", "respiratory", "tract", "infection.", "According", "to", "the", "clinical", "observation,", "pleural", "empyema", "and", "lung", "abscesses", "may", "happen", "on", "the", "same", "patient.", "However,", "the", "strategies", "of", "these", "two", "diseases", "are", "so", "different.", "It", "is", "interesting", "whether", "the", "surgical", "results", "are", "the", "same", "of", "empyema", "patients", "with", "and", "without", "lung", "abscesses.", "We", "compared", "©", "2010", "Huang", "et", "al;", "licensee", "BioMed", "Central", "Ltd.", "This", "is", "an", "Open", "Access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "License", "(http://creativecommons.org/licenses/by/2.0),", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited." ]

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[ "Spreading", "Patterns", "of", "the", "Influenza", "A", "(H1N1)", "Pandemic", "Sergio", "de", "Picoli", "Junior1*,", "Jorge", "Juarez", "Vieira", "Teixeira2,", "Haroldo", "Valentin", "Ribeiro1,3,", "Luis", "Carlos", "Malacarne1,", "Ricardo", "Paupitz", "Barbosa", "dos", "Santos1,", "Renio", "dos", "Santos", "Mendes1,3", "1", "Departamento", "de", "F´ısica,", "Universidade", "Estadual", "de", "Maringa´,", "Maringa´,", "Parana´,", "Brazil,", "2", "Departamento", "de", "Ana´lises", "Cl´ınicas", "e", "Biomedicina,", "Universidade", "Estadual", "de", "Maringa´,", "Maringa´,", "Parana´,", "Brazil,", "3", "National", "Institute", "of", "Science", "and", "Technology", "for", "Complex", "Systems,", "Rio", "de", "Janeiro,", "Rio", "de", "Janeiro,", "Brazil", "Abstract", "We", "investigate", "the", "dynamics", "of", "the", "2009", "influenza", "A", "(H1N1/S-OIV)", "pandemic", "by", "analyzing", "data", "obtained", "from", "World", "Health", "Organization", "containing", "the", "total", "number", "of", "laboratory-confirmed", "cases", "of", "infections", "-", "by", "country", "-", "in", "a", "period", "of", "69", "days,", "from", "26", "April", "to", "3", "July,", "2009.", "Specifically,", "we", "find", "evidence", "of", "exponential", "growth", "in", "the", "total", "number", "of", "confirmed", "cases", "and", "linear", "growth", "in", "the", "number", "of", "countries", "with", "confirmed", "cases.", "We", "also", "find", "that,", "i)", "at", "early", "stages,", "the", "cumulative", "distribution", "of", "cases", "among", "countries", "exhibits", "linear", "behavior", "on", "log-log", "scale,", "being", "well", "approximated", "by", "a", "power", "law", "decay;", "ii)", "for", "larger", "times,", "the", "cumulative", "distribution", "presents", "a", "systematic", "curvature", "on", "log-log", "scale,", "indicating", "a", "gradual", "change", "to", "lognormal", "behavior.", "Finally,", "we", "compare", "these", "empirical", "findings", "with", "the", "predictions", "of", "a", "simple", "stochastic", "model.", "Our", "results", "could", "help", "to", "select", "more", "realistic", "models", "of", "the", "dynamics", "of", "influenza-type", "pandemics.", "Citation:", "Picoli", "Junior", "Sd,", "Teixeira", "JJV,", "Ribeiro", "HV,", "Malacarne", "LC,", "Santos", "RPBd,", "et", "al.", "(2011)", "Spreading", "Patterns", "of", "the", "Influenza", "A", "(H1N1)", "Pandemic.", "PLoS", "ONE", "6(3):", "e17823.", "doi:10.1371/journal.pone.0017823", "Editor:", "Paulo", "Ho,", "Instituto", "Butantan,", "Brazil", "Received", "November", "8,", "2010;", "Accepted", "February", "14,", "2011;", "Published", "March", "31,", "2011", "Copyright:", "2011", "Picoli", "Junior", "et", "al.", "This", "is", "an", "open-access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "License,", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "author", "and", "source", "are", "credited.", "Funding:", "This", "work", "was", "supported", "by", "CNPq", "(Conselho", "Nacional", "de", "Pesquisa)", "and", "CAPES", "(Coordenac¸a˜ode", "Aperfeic¸", "oamento", "de", "Pessoal", "de", "Nı´", "vel", "Superior)", "-", "Brazilian", "agencies.", "Competing", "Interests:", "The", "authors", "have", "declared", "that", "no", "competing", "interests", "exist.", "*", "E-mail:", "junior@dfi.uem.br", "Introduction", "The", "spread", "of", "infectious", "diseases", "is", "a", "threat", "to", "the", "world", "public", "health", "and", "a", "subject", "of", "great", "scientific", "interest.", "Influenza", "viruses,", "for", "example,", "circulate", "around", "the", "world", "every", "year", "and", "seasonal", "influenza", "is", "one", "of", "the", "most", "worrying", "respiratory", "infections", "of", "humans", "[1].", "From", "time", "to", "time", "new", "strains", "of", "influenza", "virus", "emerge", "and", "cause", "large-scale", "global", "pandemics", "–", "such", "as", "the", "2009", "influenza", "A", "(H1N1/S-OIV).", "The", "dynamics", "of", "influenza-type", "pandemics", "has", "been", "the", "focus", "of", "several", "scientific", "works", "which", "may", "provide", "necessary", "information", "to", "deal", "with", "future", "pandemic", "events", "[2–9].", "However,", "conventional", "modeling", "techniques", "are", "usually", "only", "able", "to", "provide", "a", "general", "idea", "of", "how", "a", "pandemic", "might", "evolve,", "since", "crucial", "information", "concerning", "model", "parameters", "is", "generally", "unavailable.", "Methods", "Here,", "we", "investigate", "the", "dynamics", "of", "influenza-type", "pandemics", "using", "techniques", "of", "statistical", "physics", "typically", "applied", "in", "the", "study", "of", "complex", "systems.", "We", "analyze", "a", "database", "-", "from", "World", "Health", "Organization", "-", "containing", "laboratory-confirmed", "cases", "of", "influenza", "A", "(H1N1/S-OIV)", "infections", "around", "the", "world", "[10].", "Specifically,", "we", "analyze", "the", "total", "number", "of", "laboratory-confirmed", "cases", "-", "by", "country", "-", "in", "a", "period", "of", "69", "days,", "from", "26", "April", "to", "3", "July,", "2009.", "We", "search", "for", "patterns", "of", "spread", "for", "the", "virus", "influenza", "A", "(H1N1/S-OIV).", "Basically,", "we", "investigate", "the", "growth", "in", "the", "total", "number", "of", "confirmed", "cases,", "the", "growth", "in", "the", "number", "of", "countries", "with", "confirmed", "cases", "and", "the", "cumulative", "distribution", "of", "cases", "among", "countries.", "We", "also", "propose", "a", "simple", "stochastic", "model", "which", "reproduces", "the", "main", "empirical", "findings", "obtained", "from", "the", "analysis", "of", "the", "database", "on", "the", "2009", "influenza", "A", "(H1N1/S-OIV)", "pandemic.", "Results", "First,", "we", "consider", "the", "time", "evolution", "of", "the", "global", "number", "of", "confirmed", "cases,", "Y(t).", "At", "a", "given", "time", "t,", "the", "total", "number", "of", "cases", "Y", "is", "given", "by", "the", "sum", "of", "y", "over", "all", "countries.", "In", "Fig.", "1A", "we", "show", "Y(t)", "in", "comparison", "with", "an", "exponential", "curve,", "given", "by", "the", "equation", "dY", "~lY", ",", "with", "l~0:05", "(compare", "with", "results", "reported", "in", "ref.", "dt", "[11]).", "This", "result", "suggests", "that", "the", "total", "number", "of", "confirmed", "cases", "exhibits", "an", "exponential", "growth.", "However,", "a", "systematic", "deviation", "of", "the", "exponential", "behavior", "can", "be", "observed", "for", "smaller", "times", "(t", ",", "20", "days).", "In", "addition,", "Fig.", "1B", "shows", "the", "time", "evolution", "of", "the", "total", "number", "of", "countries", "with", "confirmed", "cases,", "W(t).", "Observe", "that", "W(t)", "exhibits", "approximately", "a", "linear", "growth", "in", "all", "the", "period", "considered.", "Next,", "we", "investigate", "the", "distribution", "of", "confirmed", "cases", "among", "countries", "and", "its", "time", "evolution.", "In", "order", "to", "reduce", "statistical", "fluctuations,", "it", "is", "common", "to", "consider", "the", "cumulative", "distribution", "R(y)~", "Ð", "P(y’)dy’.", "Here,", "y", "is", "the", "number", "of", "confirmed", "cases", "in", "a", "given", "country", "and", "P(y)", "is", "the", "probability", "distribution", "function", "(PDF)", "of", "y.", "The", "empirical", "cumulative", "distribution", "R(y),", "for", "initial", "times,", "is", "shown", "in", "Fig.", "2A.", "In", "this", "range,", "R(y)", "presents", "linear", "behavior", "on", "log-log", "scale", "being", "well", "described", "by", "a", "power", "law", "decay,", "R(y)*y{a,", "1", "ð", "Þ", "where", "a", "is", "the", "power", "law", "exponent.", "The", "time", "evolution", "of", "the", "power", "law", "exponent", "a", "is", "shown", "in", "Fig.", "2B.", "Observe", "that", "a", "stays", "approximately", "constant,", "0.35,a,0.040,", "for", "21", "days.", "For", "larger", "times,", "R(y)", "gradually", "deviates", "from", "the", "power", "law", "behavior", "(Supplementary", "Figure).", "In", "this", "range,", "R(y)has", "a", "modest", "negative", "curvature", "everywhere", "(see", "Fig.", "3A)", "and", "is", "in", "good", "PLoS", "ONE", "|", "www.plosone.org", "1", "March", "2011", "|", "Volume", "6", "|", "Issue", "3", "|", "e17823" ]

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[ "Mechanisms", "of", "KGF", "Mediated", "Signaling", "in", "Pancreatic", "Duct", "Cell", "Proliferation", "and", "Differentiation", "Benjamin", "Uzan,", "Florence", "Figeac,", "Bernard", "Portha,", "Jamileh", "Movassat*", "Laboratory", "of", "Pathophysiology", "of", "Nutrition,", "Paris", "Diderot-", "Paris", "7", "University,", "Department", "of", "Life", "Science,", "CNRS/UMR", "7059,", "Paris,", "France", "Abstract", "Background:", "Keratinocyte", "growth", "factor", "(KGF;", "palifermin)", "is", "a", "growth", "factor", "with", "a", "high", "degree", "of", "specificity", "for", "epithelial", "cells.", "KGF", "is", "an", "important", "effector", "of", "epithelial", "growth", "and", "tissue", "homeostasis", "in", "various", "organs", "including", "the", "pancreas.", "Here", "we", "investigated", "the", "intracellular", "signaling", "pathways", "involved", "in", "the", "mediation", "of", "pancreatic", "ductal", "cell", "proliferation", "and", "differentiation", "induced", "by", "exogenous", "KGF", "during", "beta-cell", "regeneration", "in", "diabetic", "rat.", "Methodology", "and", "Results:", "In", "vitro", "and", "in", "vivo", "duct", "cell", "proliferation", "was", "measured", "by", "BrdU", "incorporation", "assay.", "The", "implication", "of", "MAPK-ERK1/2", "in", "the", "mediation", "of", "KGF-induced", "cell", "proliferation", "was", "determined", "by", "inactivation", "of", "this", "pathway,", "using", "the", "pharmacological", "inhibitor", "or", "antisense", "morpholino-oligonucleotides", "against", "MEK1.", "In", "vivo", "KGF-induced", "duct", "cell", "differentiation", "was", "assessed", "by", "the", "immunolocalization", "of", "PDX1", "and", "Glut2", "in", "ductal", "cells", "and", "the", "implication", "of", "PI3K/AKT", "in", "this", "process", "was", "investigated.", "We", "showed", "that", "KGF", "exerted", "a", "potent", "mitogenic", "effect", "on", "ductal", "cells.", "Both", "in", "vitro", "and", "in", "vivo,", "its", "effect", "on", "cell", "proliferation", "was", "mediated", "through", "the", "activation", "of", "ERK1/2", "as", "evidenced", "by", "the", "abolition", "of", "duct", "cell", "proliferation", "in", "the", "context", "of", "MEK/ERK", "inactivation.", "In", "vivo,", "KGF", "treatment", "triggered", "ductal", "cell", "differentiation", "as", "revealed", "by", "the", "expression", "of", "PDX1", "and", "Glut2", "in", "a", "subpopulation", "of", "ductal", "cells", "via", "a", "PI3K-dependent", "mechanism.", "Conclusion:", "Here", "we", "show", "that", "KGF", "promotes", "beta-cell", "regeneration", "by", "stimulating", "duct", "cell", "proliferation", "in", "vivo.", "Moreover,", "we", "demonstrated", "for", "the", "first", "time", "that", "KGF", "directly", "induces", "the", "expression", "of", "PDX1", "in", "some", "ductal", "cells", "thus", "inducing", "beta-cell", "neogenesis.", "We", "further", "explored", "the", "molecular", "mechanisms", "involved", "in", "these", "processes", "and", "showed", "that", "the", "effects", "of", "KGF", "on", "duct", "cell", "proliferation", "are", "mediated", "by", "the", "MEK-ERK1/2", "pathway,", "while", "the", "KGF-induced", "cell", "differentiation", "is", "mediated", "by", "the", "PI3K/AKT", "pathway.", "These", "findings", "might", "have", "important", "implications", "for", "the", "in", "vivo", "induction", "of", "duct-to-beta", "cell", "neogenesis", "in", "patients", "with", "beta-cell", "deficiency.", "Citation:", "Uzan", "B,", "Figeac", "F,", "Portha", "B,", "Movassat", "J", "(2009)", "Mechanisms", "of", "KGF", "Mediated", "Signaling", "in", "Pancreatic", "Duct", "Cell", "Proliferation", "and", "Differentiation.", "PLoS", "ONE", "4(3):", "e4734.", "doi:10.1371/journal.pone.0004734", "Editor:", "Kathrin", "Maedler,", "University", "of", "Bremen,", "Germany", "Received", "August", "7,", "2008;", "Accepted", "January", "13,", "2009;", "Published", "March", "6,", "2009", "Copyright:", "2009", "Uzan", "et", "al.", "This", "is", "an", "open-access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "License,", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "author", "and", "source", "are", "credited.", "Funding:", "The", "authors", "are", "supported", "by", "grants", "from", "the", "Centre", "National", "de", "la", "Recherche", "Scientifique/CNRS.", "Florence", "Figeac", "is", "a", "recipient", "of", "a", "fellowship", "from", "the", "Ministe`re", "de", "l’Enseignement", "Supe´rieur", "et", "de", "la", "Recherche.", "The", "funders", "had", "no", "role", "in", "study", "design,", "data", "collection", "and", "analysis,", "decision", "to", "publish,", "or", "preparation", "of", "the", "manuscript.", "Competing", "Interests:", "The", "authors", "have", "declared", "that", "no", "competing", "interests", "exist.", "*", "E-mail:", "movassat@paris7.jussieu.fr", "Introduction", "The", "shortage", "of", "islet", "for", "transplantation", "is", "a", "major", "obstacle", "for", "the", "wide", "application", "of", "beta", "cell", "replacement", "therapy", "in", "type", "1", "diabetic", "patients.", "To", "make", "such", "a", "therapy", "readily", "available,", "new", "sources", "of", "insulin-producing", "cells", "must", "be", "identified.", "Pancreatic", "duct", "cells", "represent", "such", "an", "alternative", "source", "for", "generation", "of", "new", "beta", "cells", "in", "vitro", "[1].", "Duct", "compartment", "has", "also", "implications", "in", "type", "2", "diabetes", "(T2D),", "since", "T2D", "is", "associated", "with", "beta", "cell", "loss,", "and", "the", "in", "situ", "induction", "of", "beta", "cell", "neogenesis", "from", "ductal", "progenitor", "cells", "may", "help", "to", "restore", "the", "beta", "cell", "mass", "in", "the", "pancreas", "of", "type", "2", "diabetic", "patients.", "Therefore,", "characterization", "of", "stimuli", "with", "potential", "to", "induce", "the", "expansion", "of", "duct", "cells", "and/or", "to", "drive", "their", "differentiation", "into", "beta", "cells", "is", "of", "great", "importance.", "A", "variety", "of", "growth", "factors", "have", "been", "described", "to", "induce", "growth", "and", "differentiation", "of", "ductal", "cells.", "Fibroblast", "growth", "factors", "(FGFs)", "comprise", "a", "growing", "group", "of", "structurally", "related", "polypeptide", "mitogens", "with", "more", "than", "20", "members,", "most", "of", "which", "stimulate", "proliferation", "of", "a", "variety", "of", "cell", "types", "[2,3].", "Keratinocyte", "growth", "factor,", "also", "called", "FGF7,", "is", "a", "member", "of", "the", "FGF", "family.", "KGF", "is", "a", "paracrine-acting", "mitogen", "produced", "by", "cells", "of", "mesenchymal", "origin.", "It", "acts", "exclusively", "through", "a", "subset", "of", "FGF", "receptor", "isoforms", "(FGFR2IIIb)", "expressed", "predominantly", "by", "epithelial", "cells", "and", "therefore", "is", "a", "specific", "mitogen", "for", "these", "cells", "[4].", "Preclinical", "data", "from", "several", "animal", "models", "have", "demonstrated", "that", "recombinant", "human", "KGF", "could", "enhance", "the", "regenerative", "capacity", "of", "epithelial", "tissues", "and", "protect", "them", "from", "a", "variety", "of", "toxic", "exposures", "[3].", "We", "and", "others", "have", "previously", "reported", "that", "KGF", "induces", "ductal", "cell", "proliferation", "in", "the", "pancreas", "[5–8]", "and", "promotes", "beta", "cell", "regeneration", "in", "neonatal", "streptozotocin", "diabetic", "rats", "[6].", "However", "the", "molecular", "mechanisms", "underlying", "the", "stimulation", "of", "beta", "cell", "regeneration", "through", "the", "induction", "of", "ductal", "cell", "proliferation", "and", "beta", "cell", "neogenesis", "by", "KGF", "are", "not", "known.", "The", "present", "study", "was", "undertaken", "to", "investigate", "the", "intracel-", "lular", "signaling", "pathways", "which", "mediate", "the", "growth", "promoting", "effects", "of", "KGF", "(palifermin)", "in", "pancreatic", "ducts", "and", "to", "dissect", "the", "key", "steps", "of", "duct-to-beta", "cell", "differentiation", "induced", "by", "KGF", "in", "a", "model", "of", "neonatal", "diabetes", "in", "rat.", "In", "our", "study,", "we", "have", "established", "that", "KGF", "acts", "on", "ductal", "cells", "by", "the", "the", "activation", "of", "distinct", "signaling", "pathways", "to", "promote", "beta", "PLoS", "ONE", "|", "www.plosone.org", "1", "March", "2009", "|", "Volume", "4", "|", "Issue", "3", "|", "e4734" ]

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[ "SOD3", "Reduces", "Inflammatory", "Cell", "Migration", "by", "Regulating", "Adhesion", "Molecule", "and", "Cytokine", "Expression", "Juha", "P.", "Laurila1,", "Lilja", "E.", "Laatikainen1,", "Maria", "D.", "Castellone2,", "Mikko", "O.", "Laukkanen1*", "1", "Medicity", "Research", "Laboratory,", "University", "of", "Turku,", "Turku,", "Finland,", "2", "Institute", "of", "Experimental", "Endocrinology", "and", "Oncology", "(CNR),", "Department", "of", "Biology", "and", "Cellular", "and", "Molecular", "Pathology,", "University", "of", "Naples", "Federico", "II,", "Naples,", "Italy", "Abstract", "Inflammatory", "cell", "migration", "characteristic", "of", "ischemic", "damages", "has", "a", "dual", "role", "providing", "the", "tissue", "with", "factors", "needed", "for", "tissue", "injury", "recovery", "simultaneously", "causing", "deleterious", "development", "depending", "on", "the", "quality", "and", "the", "quantity", "of", "infiltrated", "cells.", "Extracellular", "superoxide", "dismutase", "(SOD3)", "has", "been", "shown", "to", "have", "an", "anti-inflammatory", "role", "in", "ischemic", "injuries", "where", "it", "increases", "the", "recovery", "process", "by", "activating", "mitogen", "signal", "transduction", "and", "increasing", "cell", "proliferation.", "However,", "SOD3", "derived", "effects", "on", "inflammatory", "cytokine", "and", "adhesion", "molecule", "expression,", "which", "would", "explain", "reduced", "inflammation", "in", "vascular", "lesions,", "has", "not", "been", "properly", "characterized.", "In", "the", "present", "work", "the", "effect", "of", "SOD3", "on", "the", "inflammatory", "cell", "extravasation", "was", "studied", "in", "vivo", "in", "rat", "hind", "limb", "ischemia", "and", "mouse", "peritonitis", "models", "by", "identifying", "the", "migrated", "cells", "and", "analyzing", "SOD3-derived", "response", "on", "inflammatory", "cytokine", "and", "adhesion", "molecule", "expression.", "SOD3", "overexpression", "significantly", "reduced", "TNFa,", "IL1a,", "IL6,", "MIP2,", "and", "MCP-1", "cytokine", "and", "VCAM,", "ICAM,", "P-selectin,", "and", "E-", "selectin", "adhesion", "molecule", "expressions", "in", "injured", "tissues.", "Consequently", "the", "mononuclear", "cell,", "especially", "CD68+", "monocyte", "and", "CD3+", "T", "cell", "infiltration", "were", "significantly", "decreased", "whereas", "granulocyte", "migration", "was", "less", "affected.", "According", "to", "our", "data", "SOD3", "has", "a", "selective", "anti-inflammatory", "role", "in", "ischemic", "damages", "preventing", "the", "migration", "of", "reactive", "oxygen", "producing", "monocyte/macrophages,", "which", "in", "excessive", "amounts", "could", "potentially", "further", "intensify", "the", "tissue", "injuries", "therefore", "suggesting", "potential", "for", "SOD3", "in", "treatment", "of", "inflammatory", "disorders.", "Citation:", "Laurila", "JP,", "Laatikainen", "LE,", "Castellone", "MD,", "Laukkanen", "MO", "(2009)", "SOD3", "Reduces", "Inflammatory", "Cell", "Migration", "by", "Regulating", "Adhesion", "Molecule", "and", "Cytokine", "Expression.", "PLoS", "ONE", "4(6):", "e5786.", "doi:10.1371/journal.pone.0005786", "Editor:", "Eshel", "Ben-Jacob,", "Tel", "Aviv", "University,", "Israel", "Received", "April", "15,", "2009;", "Accepted", "May", "8,", "2009;", "Published", "June", "4,", "2009", "Copyright:", "2009", "Laurila", "et", "al.", "This", "is", "an", "open-access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "License,", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "author", "and", "source", "are", "credited.", "Funding:", "Academy", "of", "Finland,", "Sigrid", "Juselius", "Foundation,", "Paolo", "Foundation,", "TUBS", "graduation", "school.", "The", "funders", "had", "no", "role", "in", "study", "design,", "data", "collection", "and", "analysis,", "decision", "to", "publish,", "or", "preparation", "of", "the", "manuscript.", "Competing", "Interests:", "The", "authors", "have", "declared", "that", "no", "competing", "interests", "exist.", "*", "E-mail:", "Mikko.Laukkanen@utu.fi", "Introduction", "The", "inflammatory", "process", "is", "initiated", "by", "endothelial", "cell", "(EC)", "activation", "comprising", "upregulation", "of", "chemokines", "and", "cell", "adhesion", "molecules,", "leukocyte", "activation", "and", "transmigration,", "and", "secretion", "of", "proinflammatory", "factors", "by", "leukocytes", "[1].", "The", "inflammatory", "reaction", "is", "necessary", "for", "tissue", "recovery", "as", "it", "provides", "the", "correct", "cytokine", "signals", "and", "cell", "machinery", "to", "clear", "up", "the", "site", "for", "regeneration", "of", "the", "tissue", "[2].", "However,", "uncontrolled", "inflammation", "has", "unfavorable", "effects", "on", "the", "course", "of", "tissue", "healing", "since", "the", "inflammatory", "cells", "are", "also", "capable", "of", "inducing", "tissue", "damage", "[2]", "and", "therefore", "many", "conditions", "involving", "inflammation,", "e.g.", "autoimmune", "diseases", "and", "tissue", "transplantations,", "are", "treated", "with", "immunosuppressants", "to", "reduce", "harmful", "leukocyte", "infiltration.", "Among", "the", "most", "potent", "drugs", "are", "glucocorticoids", "that", "downregulate", "the", "expression", "of", "numerous", "inflammatory", "chemokines,", "cytokines", "and", "adhesion", "molecules", "[3–", "5],", "which,", "however,", "are", "not", "entirely", "without", "adverse", "effects", "such", "as", "delayed", "myocardial", "tissue", "healing,", "osteoporosis,", "and", "blood", "vessel", "calcification", "[6–9].", "The", "most", "prominent", "outcome", "in", "the", "initial", "phase", "of", "inflammation", "is", "the", "enhanced", "production", "of", "cytokines,", "such", "as", "TNF-a", "and", "IL-1,", "and", "chemokines,", "such", "as", "monocyte", "chemoat-", "tractant", "protein-1", "(MCP-1)", "[10,11],", "which", "further", "induce", "expression", "of", "a", "number", "of", "inflammatory", "cytokines", "[4].", "Many", "of", "the", "stimulus-specific", "pathways", "converge", "in", "the", "production", "of", "superoxide", "(O22)", "and", "hydrogen", "peroxide", "(H2O2)", "as", "signal", "mediators,", "which", "in", "turn", "result", "in", "e.g.", "NFkB", "activation", "responsible", "for", "numerous", "stress-related", "functions", "[12–14].", "Leukocytes", "are", "thus", "recruited", "by", "expression", "of", "various", "cell", "adhesion", "molecules,", "e.g.", "selectins,", "and", "intercellular", "and", "vascular", "cell", "adhesion", "molecules", "(ICAM-1", "and", "VCAM-1,", "respectively)", "[15,16].", "They", "promote", "rolling", "and", "firm", "adhesion", "of", "leukocytes", "to", "endothelial", "wall,", "the", "necessary", "interactions", "preceding", "transmigration", "[17].", "To", "aid", "leukocyte", "migration", "the", "vessel", "wall", "cells", "change", "their", "morphology", "by", "assuming", "cytoskeletal", "and", "cell-cell", "junction", "modifications", "in", "response", "to", "e.g.", "ligand", "binding", "to", "ICAM-1", "and", "VCAM-1", "[18–20],", "and", "when", "stimulated", "by", "O22", "or", "TNF-a", "[21,22].", "Previously,", "it", "has", "been", "shown", "that", "extracellular", "superoxide", "dismutase", "(SOD3)", "can", "attenuate", "tissue", "damage", "and", "inflammation", "but", "so", "far", "its", "mechanism", "of", "action", "has", "not", "been", "completely", "defined", "[23–27].", "Since", "excess", "inflammation", "prevents", "the", "tissue", "injury", "recovery", "we", "investigated", "in", "the", "present", "study", "the", "effect", "of", "SOD3", "overexpression", "on", "cell", "migration.", "We", "used", "two", "in", "vivo", "acute", "inflammation", "models", "to", "determine", "how", "SOD3", "affects", "leukocyte", "extravasation,", "and", "compared", "the", "results", "to", "efficacy", "of", "the", "glucocorticoid", "immunosuppressant", "dexamethasone.", "The", "mouse", "peritonitis", "and", "rat", "hind", "limb", "ischemia", "models", "have", "been", "characterized", "previously:", "they", "induce", "rapid", "infiltration", "of", "leuko-", "cytes", "to", "the", "peritoneal", "cavity", "and", "large", "femoral", "muscles,", "PLoS", "ONE", "|", "www.plosone.org", "1", "June", "2009", "|", "Volume", "4", "|", "Issue", "6", "|", "e5786" ]

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[ "Hindawi", "Publishing", "Corporation", "Dermatology", "Research", "and", "Practice", "Volume", "2010,", "Article", "ID", "365173,", "3", "pages", "doi:10.1155/2010/365173", "Case", "Report", "Angiosarcoma", "Mimicking", "Rhinophyma", "Maurizio", "Lo", "Presti,1", "Caterina", "Mazzella,1", "Ambra", "Monfrecola,1", "and", "Jessica", "Falleti2", "1", "Department", "of", "Pathology", "Systematics,", "Section", "of", "Dermatology,", "University", "Federico", "II", "of", "Naples,", "via", "S.", "Pansini", "5,", "80131", "Naples,", "Italy", "2", "Department", "of", "Biomorphological", "and", "Functional", "Science,", "Section", "of", "Pathology,", "University", "Federico", "II", "of", "Naples,", "80131", "Naples,", "Italy", "Correspondence", "should", "be", "addressed", "to", "Caterina", "Mazzella,", "caterinamazzella@libero.it", "Received", "1", "March", "2010;", "Accepted", "12", "April", "2010", "Academic", "Editor:", "Bruce", "Robert", "Smoller", "Copyright", "©", "2010", "Maurizio", "Lo", "Presti", "et", "al.", "This", "is", "an", "open", "access", "article", "distributed", "under", "the", "Creative", "Commons", "Attribution", "License,", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited.", "We", "report", "the", "case", "of", "a", "61-year-old", "man", "showing", "persistent", "erythematous", "macules,", "plaques,", "and", "partially", "confluent", "nodules", "with", "irregular", "borders,", "developed", "on", "his", "nose", "for", "one", "year.", "During", "that", "time", "the", "patient", "underwent", "several", "dermatological", "consultations,", "and", "all", "produced", "the", "same", "diagnosis:", "rhinophyma.", "So", "antibiotic", "and", "steroid", "treatment", "was", "carried", "out", "without", "any", "improvement", "while", "the", "lesions", "kept", "growing.", "When", "the", "patient", "came", "to", "our", "observation,", "physical", "examination", "revealed", "large,", "infiltrative,", "oedematous,", "erythematous", "plaques", "and", "rare", "nodules,", "with", "superficial", "telangiectatic", "vessels.", "Cervical", "lymphadenopathy", "was", "not", "detectable.", "Routine", "laboratory", "analysis", "was", "normal.", "Punch", "biopsy", "was", "performed,", "and", "histopathology", "and", "immunohistochemical", "studies", "were", "consistent", "with", "cutaneous", "angiosarcoma.", "This", "is", "the", "report", "of", "a", "face", "angiosarcoma", "with", "an", "unusual", "and", "very", "deceptive", "clinical", "presentation.", "1.", "Introduction", "Angiosarcoma", "(AS)", "is", "a", "rare", "malignant", "vascular", "tumour", "that", "arises", "in", "skin", "or", "superficial", "soft", "tissue", "in", "60%", "of", "cases", "[1].", "It", "mainly", "appears", "on", "the", "head", "and", "neck", "of", "elderly", "patients.", "Clinical", "manifestations", "of", "AS", "are", "characterized", "by", "erythematous", "plaques,", "macules,", "or", "nodules", "and", "sometimes", "by", "chronic", "edema", "of", "the", "face.", "Diagnosis", "may", "often", "be", "delayed", "by", "the", "variable", "presentation", "and", "the", "benign", "appearance", "of", "the", "lesion,", "therefore,", "histological", "features", "are", "fundamental", "for", "a", "correct", "diagnosis.", "The", "prognosis", "is", "poor", "because", "the", "tumour", "is", "aggressive", "with", "high", "local", "recurrence", "and", "early", "metastasis.", "2.", "Case", "Report", "A", "61-year-old", "man", "came", "to", "our", "department", "with", "erythema-", "tous", "macules,", "plaques", "and", "also", "rare", "nodules", "with", "irregular", "borders,", "localized", "on", "the", "nose,", "developed", "for", "about", "one", "year", "(Figure", "1).", "Before", "examination", "at", "our", "clinic,", "the", "patient", "was", "repeat-", "edly", "treated", "for", "rosacea/rhinophyma", "with", "oral", "tetracyclines,", "metronidazole,", "and", "steroids", "without", "significant", "improve-", "ment.", "He", "also", "suffered", "of", "hypertension,", "ischemic", "heart", "disease,", "and", "benign", "prostatic", "hyperplasia.", "Histopathologic", "examination", "of", "skin", "biopsy,", "taken", "from", "a", "nodule,", "showed", "vascular", "proliferation", "lined", "by", "atypical", "and", "plump", "endothelial", "cells", "in", "the", "dermis;", "immunohistochem-", "istry", "proved", "the", "positivity", "of", "neoplastic", "endothelial", "cells", "for", "CD31", "and", "CD34", "(Figures", "2(a),", "2(b)).", "Based", "on", "the", "clinical", "and", "histopathological", "findings,", "diagnosis", "of", "angiosarcoma", "of", "the", "nose", "was", "established.", "Total", "body", "CT,", "showing", "no", "significant", "findings,", "was", "performed,", "and", "then,", "according", "to", "consolidated", "cooperation,", "and", "also", "following", "his", "own", "desire,", "the", "patient", "has", "been", "put", "under", "oncologists", "care,", "undertaking", "Rx", "therapy", "(electron", "beam).", "3.", "Discussion", "Angiosarcoma", "(AS)", "is", "rare,", "amounting", "for", "less", "than", "2%", "of", "all", "sarcomas.", "Skin", "and", "superficial", "soft", "tissue", "are", "the", "most", "common", "locations", "(60%", "of", "cases)", "[2]", "with", "high", "rate", "of", "lymph", "node", "and", "systemic", "metastasis", "and", "reported", "5-year", "survival", "of", "10%", "to", "35%", "[3]." ]

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[ "Detection", "of", "Gene", "Expression", "in", "an", "Individual", "Cell", "Type", "within", "a", "Cell", "Mixture", "Using", "Microarray", "Analysis", "Penelope", "A.", "Bryant1,2,3,", "Gordon", "K.", "Smyth4,", "Roy", "Robins-Browne2,5,", "Nigel", "Curtis1,2,3*", "1", "Department", "of", "Paediatrics,", "The", "University", "of", "Melbourne,", "Royal", "Children’s", "Hospital", "Melbourne,", "Parkville,", "Victoria,", "Australia,", "2", "Microbiology", "&", "Infectious", "Diseases", "Research", "Group,", "Murdoch", "Children’s", "Research", "Institute,", "Royal", "Children’s", "Hospital", "Melbourne,", "Parkville,", "Victoria,", "Australia,", "3", "Infectious", "Diseases", "Unit,", "Department", "of", "General", "Medicine,", "Royal", "Children’s", "Hospital", "Melbourne,", "Parkville,", "Victoria,", "Australia,", "4", "Bioinformatics", "Division,", "Walter", "and", "Eliza", "Hall", "Institute", "of", "Medical", "Research,", "Parkville,", "Victoria,", "Australia,", "5", "Department", "of", "Microbiology", "&", "Immunology,", "University", "of", "Melbourne,", "Parkville,", "Victoria,", "Australia", "Abstract", "Background:", "A", "central", "issue", "in", "the", "design", "of", "microarray-based", "analysis", "of", "global", "gene", "expression", "is", "the", "choice", "between", "using", "cells", "of", "single", "type", "and", "a", "mixture", "of", "cells.", "This", "study", "quantified", "the", "proportion", "of", "lipopolysaccharide", "(LPS)", "induced", "differentially", "expressed", "monocyte", "genes", "that", "could", "be", "measured", "in", "peripheral", "blood", "mononuclear", "cells", "(PBMC),", "and", "determined", "the", "extent", "to", "which", "gene", "expression", "in", "the", "non-monocyte", "cell", "fraction", "diluted", "or", "obscured", "fold", "changes", "that", "could", "be", "detected", "in", "the", "cell", "mixture.", "Methodology/Principal", "Findings:", "Human", "PBMC", "were", "stimulated", "with", "LPS,", "and", "monocytes", "were", "then", "isolated", "by", "positive", "(Mono+)", "or", "negative", "(Mono2)", "selection.", "The", "non-monocyte", "cell", "fraction", "(MonoD)", "remaining", "after", "positive", "selection", "of", "monocytes", "was", "used", "to", "determine", "the", "effect", "of", "non-monocyte", "cells", "on", "overall", "expression.", "RNA", "from", "LPS-stimulated", "PBMC,", "Mono+,", "Mono2", "and", "MonoD", "samples", "was", "co-hybridised", "with", "unstimulated", "RNA", "for", "each", "cell", "type", "on", "oligonucleotide", "microarrays.", "There", "was", "a", "positive", "correlation", "in", "gene", "expression", "between", "PBMC", "and", "both", "Mono+", "(0.77)", "and", "Mono2", "(0.61–", "0.67)", "samples.", "Analysis", "of", "individual", "genes", "that", "were", "differentially", "expressed", "in", "Mono+", "and", "Mono2", "samples", "showed", "that", "the", "ability", "to", "detect", "expression", "of", "some", "genes", "was", "similar", "when", "analysing", "PBMC,", "but", "for", "others,", "differential", "expression", "was", "either", "not", "detected", "or", "changed", "in", "the", "opposite", "direction.", "As", "a", "result", "of", "the", "dilutional", "or", "obscuring", "effect", "of", "gene", "expression", "in", "non-monocyte", "cells,", "overall", "about", "half", "of", "the", "statistically", "significant", "LPS-induced", "changes", "in", "gene", "expression", "in", "monocytes", "were", "not", "detected", "in", "PBMC.", "However,", "97%", "of", "genes", "with", "a", "four", "fold", "or", "greater", "change", "in", "expression", "in", "monocytes", "after", "LPS", "stimulation,", "and", "almost", "all", "(96–100%)", "of", "the", "top", "100", "most", "differentially", "expressed", "monocyte", "genes", "were", "detected", "in", "PBMC.", "Conclusions/Significance:", "The", "effect", "of", "non-responding", "cells", "in", "a", "mixture", "dilutes", "or", "obscures", "the", "detection", "of", "subtle", "changes", "in", "gene", "expression", "in", "an", "individual", "cell", "type.", "However,", "for", "studies", "in", "which", "only", "the", "most", "highly", "differentially", "expressed", "genes", "are", "of", "interest,", "separating", "and", "analysing", "individual", "cell", "types", "may", "be", "unnecessary.", "Citation:", "Bryant", "PA,", "Smyth", "GK,", "Robins-Browne", "R,", "Curtis", "N", "(2009)", "Detection", "of", "Gene", "Expression", "in", "an", "Individual", "Cell", "Type", "within", "a", "Cell", "Mixture", "Using", "Microarray", "Analysis.", "PLoS", "ONE", "4(2):", "e4427.", "doi:10.1371/journal.pone.0004427", "Editor:", "Sui", "Huang,", "University", "of", "Calgary,", "Canada", "Received", "July", "17,", "2008;", "Accepted", "December", "12,", "2008;", "Published", "February", "12,", "2009", "Copyright:", "2009", "Bryant", "et", "al.", "This", "is", "an", "open-access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "License,", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "author", "and", "source", "are", "credited.", "Funding:", "This", "study", "was", "supported", "by", "a", "grant", "from", "the", "National", "Health", "and", "Medical", "Research", "Council", "and", "National", "Heart", "Foundation", "of", "Australia.", "Dr.", "Bryant", "was", "the", "recipient", "of", "a", "European", "Society", "of", "Paediatric", "Infectious", "Diseases", "Fellowship", "Award", "and", "a", "University", "of", "Melbourne", "Research", "Scholarship.", "The", "funders", "had", "no", "role", "in", "study", "design,", "data", "collection", "and", "analysis,", "decision", "to", "publish,", "or", "preparation", "of", "the", "manuscript.", "Competing", "Interests:", "The", "authors", "have", "declared", "that", "no", "competing", "interests", "exist.", "*", "E-mail:", "nigel.curtis@rch.org.au", "Introduction", "The", "choice", "between", "using", "cells", "of", "a", "single", "type", "and", "a", "mixture", "of", "cells", "in", "microarray-based", "analysis", "of", "global", "gene", "expression", "is", "difficult.", "Analysing", "cells", "of", "one", "type,", "such", "as", "monocytes[1,2,3],", "necessitates", "an", "isolation", "step", "that", "may", "be", "technically", "difficult[4]", "and", "which", "may", "induce", "non-specific", "changes", "in", "gene", "expression.", "Analysing", "a", "cell", "mixture,", "such", "as", "peripheral", "blood", "mononuclear", "cells", "(PBMC)[5,6,7],", "is", "simpler", "but", "gene", "expression", "changes", "in", "cells", "of", "a", "specific", "cell", "type,", "particularly", "if", "present", "in", "small", "numbers,", "may", "not", "be", "detected.", "Specifically,", "significant", "changes", "of", "gene", "expression", "in", "the", "cell", "type", "of", "interest", "may", "be", "undetectable", "as", "a", "result", "of", "the", "dilutional", "effect", "of", "a", "majority", "of", "non-responding", "cells", "or", "obscured", "by", "opposite", "responses", "in", "other", "cell", "types.", "In", "addition,", "it", "is", "impossible", "to", "attribute", "observed", "differential", "expression", "to", "individ-", "ual", "cell", "types.", "This", "study", "compared", "gene", "expression", "in", "PBMC", "with", "expression", "in", "monocytes", "alone", "after", "stimulation", "with", "lipopolysaccharide", "(LPS)", "as", "a", "paradigm", "for", "determining", "the", "extent", "to", "which", "changes", "in", "gene", "expression", "in", "a", "particular", "cell", "type", "can", "be", "detected", "in", "a", "cell", "mixture.", "A", "strategy", "was", "used", "that", "preserved", "the", "advantage", "of", "the", "cellular", "interactions", "of", "PBMC", "but", "which", "allowed", "detection", "of", "gene", "expression", "from", "an", "individual", "cell", "type", "by", "separating", "monocytes", "after", "stimulation", "of", "PBMC", "ex", "vivo.", "Analysis", "was", "undertaken", "in", 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[ "Percutaneous", "management", "of", "a", "saphenous", "vein", "graft", "perforation", "using", "a", "covered", "stent", "and", "final", "coil", "embolization", "technique", "Image", "Ben", "Glover,", "Paul", "Johnston,", "Mark", "Spence", "Royal", "Victoria", "Hospital,", "Belfast,", "Great", "Britain", "Submitted:", "23", "January", "2010", "Accepted:", "28", "January", "2010", "Arch", "Med", "Sci", "2010;", "6,", "6:", "991-992", "DOI:", "10.5114/aoms.2010.19317", "Copyright", "©", "2010", "Termedia", "&", "Banach", "A", "b", "s", "t", "r", "a", "c", "t", "Coronary", "artery", "perforation", "as", "a", "result", "of", "percutaneous", "coronary", "intervention", "is", "a", "rare", "complication", "which", "may", "result", "in", "cardiac", "tamponade,", "myocardial", "infarction", "and", "death.", "Perforation", "of", "a", "saphenous", "vein", "graft", "is", "unusual", "and", "generally", "requires", "surgical", "intervention.", "We", "describe", "a", "novel", "percutaneous", "approach", "that", "facilitated", "the", "successful", "management", "of", "a", "potentially", "catastrophic", "saphenous", "vein", "graft", "(SVG)", "perforation.", "Key", "words:", "vein", "graft", "perforation", "Coronary", "artery", "perforation", "as", "a", "result", "of", "percutaneous", "coronary", "intervention", "(PCI)", "is", "a", "rare", "complication", "(0.1%)", "[1]", "which", "may", "result", "in", "cardiac", "tamponade,", "myocardial", "infarction", "and", "death.", "The", "main", "predictors", "of", "coronary", "perforations", "are", "clinical", "(elderly,", "female", "gender),", "pharma-", "cological", "(use", "of", "glycoprotein", "IIb/IIIa", "inhibitors),", "angiographic", "(small", "tortuous", "and", "calcified", "vessels)", "and", "procedural", "(stiff", "hydrophilic", "wires,", "arte-", "ry", "to", "balloon", "ratio", "of", ">", "1.2-1.3,", "use", "of", "atherectomy", "device)", "[1,", "2].", "We", "describe", "a", "novel", "approach", "that", "facilitated", "the", "successful", "management", "of", "a", "po-", "tentially", "catastrophic", "saphenous", "vein", "graft", "(SVG)", "perforation.", "A", "68-year-old", "female", "treated", "with", "CABG", "5", "years", "previously", "was", "referred", "for", "PCI", "after", "angiography", "demonstrated", "a", "significant", "SVG", "to", "the", "first", "obtuse", "marginal", "(OM)", "lesion.", "At", "PCI", "(right", "transradial", "access,", "6", "Fr", "Left", "Coronary", "Bypass", "(LCB)", "guide", "catheter", "(Cordis", "Corporation,", "New", "Jersey,", "USA))", "the", "SVG", "was", "found", "to", "be", "occluded.", "A", "Pilot", "50", "wire", "(Abbott", "Laboratories,", "Illinois,", "USA)", "crossed", "the", "occlusion", "easily", "and", "the", "stenosis", "was", "pre-dilated", "with", "a", "2.0", "mm", "and", "a", "4.0", "mm", "balloon.", "Contrast", "injection", "via", "an", "Export", "catheter", "demonstrated", "intraluminal", "wire", "position", "and", "a", "good", "sized", "distal", "OM.", "A", "4.5", "×", "24", "Liberte", "stent", "(Boston", "Scientific,", "Natick,", "USA)", "was", "deployed", "at", "17", "atmospheres", "resulting", "in", "a", "class", "3", "perforation", "(Figure", "1A),", "tachycardia", "and", "hypotension", "[2].", "The", "stent", "balloon", "was", "immediately", "positioned", "within", "the", "stent", "and", "inflated", "to", "control", "the", "perforation.", "Intravenous", "protamine", "was", "administered", "and", "a", "transthoracic", "echocardiogram", "showed", "a", "posterior", "pericardial", "effusion", "with", "compression", "of", "the", "posterior", "left", "atrial", "wall", "in", "a", "position", "almost", "impossible", "to", "treat", "with", "percutaneous", "pericardiocentesis", "(Figure", "1B).", "With", "the", "inflated", "balloon", "controlling", "the", "perforation", "a", "second", "8", "French", "LCB", "guide", "catheter", "was", "introduced", "from", "the", "femoral", "artery", "and", "positioned", "at", "Corresponding", "author:", "Ben", "Glover,", "MD", "Royal", "Victoria", "Hospital", "Grosvenor", "Road,", "Belfast,", "BT12", "6BA", "Phone:", "+44", "028", "9024", "05", "03", "E-mail:", "ben.glover@hotmail.com" ]

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[ "Wang", "et", "al.", "BMC", "Immunology", "2011,", "12:21", "http://www.biomedcentral.com/1471-2172/12/21", "R", "E", "S", "E", "A", "R", "C", "H", "A", "R", "T", "I", "C", "L", "E", "Open", "Access", "CTLA4", "is", "expressed", "on", "mature", "dendritic", "cells", "derived", "from", "human", "monocytes", "and", "influences", "their", "maturation", "and", "antigen", "presentation", "Xiong", "B", "Wang1*†,", "Zhong", "Z", "Fan1†,", "Doina", "Anton3,", "Annika", "V", "Vollenhoven3,", "Zhen", "H", "Ni1,", "Xiao", "F", "Chen2,", "Ann", "K", "Lefvert3", "Abstract", "Background:", "Dendritic", "cells", "(DCs)", "initiate", "immune", "responses", "through", "their", "direct", "interaction", "with", "effector", "cells.", "However,", "the", "mechanism", "by", "which", "DC", "activity", "is", "regulated", "is", "not", "well", "defined.", "Previous", "studies", "have", "shown", "that", "CTLA4", "on", "T", "cells", "regulates", "DCs", "function", "by", "“cross-talk”.", "We", "investigated", "whether", "there", "is", "an", "intrinsic", "regulatory", "mechanism", "in", "DCs,", "with", "CTLA4", "as", "a", "candidate", "regulator.", "Results:", "We", "confirmed", "via", "RT-PCR", "and", "flow", "cytometry", "the", "natural", "expression", "of", "CTLA4", "on", "mature", "DCs", "derived", "from", "human", "monocytes.", "Approximately", "8%", "CD1a-positive", "cells", "express", "CTLA4", "both", "on", "surface", "and", "intracellular,", "whereas", "10%", "CD1a-negative", "cells", "express", "CTLA4", "intracellularly,", "but", "little", "expression", "was", "observed", "on", "the", "cell", "surface.", "The", "cross-linking", "of", "CTLA4", "inhibits", "DCs", "maturation", "and", "antigen", "presentation", "in", "vitro,", "but", "does", "not", "inhibit", "endocytosis.", "Conclusions:", "CTLA4", "is", "expressed", "by", "DCs", "and", "plays", "an", "inhibitory", "role.", "CTLA4-expressing", "DCs", "may", "represent", "a", "group", "of", "regulatory", "DCs.", "Because", "of", "its", "wide", "distribution", "on", "different", "cell", "types,", "CTLA4", "may", "play", "a", "general", "role", "in", "regulating", "immune", "responses.", "Background", "Dendritic", "cells", "(DCs)", "are", "sparsely", "distributed", "in", "tissues", "and", "the", "circulation,", "but", "they", "are", "nevertheless", "important.", "They", "function", "as", "professional", "antigen-presenting", "cells", "(APCs)", "in", "antigen", "capture,", "processing,", "and", "presentation", "to", "CD4+", "and", "CD8+", "T", "cells", "[1].", "DCs", "can", "be", "produced", "in", "vitro", "by", "a", "number", "of", "procedures,", "starting", "from", "CD34+", "hemopoietic", "progenitor", "cells", "(from", "peripheral", "blood", "or", "bone", "marrow)", "cultured", "with", "tumor", "necrosis", "factor", "a", "(TNFa)", "and", "granulocyte", "macrophage-colony-stimulating", "factor", "(GM-CSF),", "or", "from", "human", "blood", "monocytes", "cul-", "tured", "with", "GM-CSF,", "interleukin", "4", "(IL-4),", "or", "IL-13.", "Immature", "DCs", "(iDCs),", "which", "have", "a", "high", "capacity", "for", "antigen", "uptake", "and", "processing,", "but", "a", "low", "capacity", "to", "sti-", "mulate", "T-cell", "proliferation,", "can", "be", "further", "differentiated", "in", "vitro", "to", "mature", "DCs", "(mDCs),", "which", "have", "a", "high", "capa-", "city", "for", "antigen", "presentation,", "by", "treatment", "with", "TNFa,", "*", "Correspondence:", "xiongbiao6@yahoo.com", "†", "Contributed", "equally", "1Laboratory", "center,", "Putuo", "Hospital,", "Shanghai", "University", "of", "Traditional", "Chinese", "Medicine.", "200062,", "China", "Full", "list", "of", "author", "information", "is", "available", "at", "the", "end", "of", "the", "article", "lipopolysaccharide", "(LPS),", "IL-1,", "or", "CD40L.", "Many", "costi-", "mulatory", "factors", "are", "expressed", "by", "DCs", "and", "play", "impor-", "tant", "roles", "in", "the", "communication", "between", "DCs", "and", "immunocompetent", "cells", "[2,3].", "The", "functions", "of", "DCs", "are", "also", "regulated", "by", "the", "mutual", "cross-talk", "between", "costi-", "mulatory", "molecules", "[3].", "The", "additional", "expression", "of", "activating", "costimulatory", "molecules", "that", "favor", "the", "inter-", "action", "between", "DCs", "and", "T", "cells", "further", "enhances", "the", "ability", "of", "DCs", "to", "generate", "antitumor", "immune", "responses.", "Activating", "costimulatory", "molecules", "that", "have", "been", "upre-", "gulated", "on", "DCs", "by", "genetic", "engineering", "include", "the", "CD40", "ligand", "(CD40L)", "[4-6],", "CD70", "[7],", "4-1BBL", "[8],", "the", "OX40", "ligand", "(OX40L)", "[9],", "and", "the", "receptor", "activator", "of", "NF-", "B", "(RANK)/RANK", "ligand", "(RANKL)", "[10].", "CTLA4", "(CD152)", "is", "an", "inhibitory", "costimulatory", "mole-", "cule.", "The", "expression", "and", "function", "of", "CTLA4", "in", "T", "cells", "have", "been", "well", "studied", "and", "the", "effect", "of", "CTLA4", "on", "DCs", "has", "also", "been", "studied.", "CTLA4", "acts", "as", "a", "ligand", "to", "induce", "interferon", "g", "(IFNg)", "production", "by", "DCs", "and", "to", "prevent", "T-cell", "responses", "via", "a", "mechanism", "that", "involves", "trypto-", "phan", "catabolism", "[11].", "CTLA4-immunoglobulin", "(Ig)", "may", "inhibit", "DC", "function", "through", "the", "B7", "receptor", "on", "DCs,", "©", "2011", "Wang", "et", "al;", "licensee", "BioMed", "Central", "Ltd.", "This", "is", "an", "Open", "Access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "License", "(http://creativecommons.org/licenses/by/2.0),", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited." ]

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[ "BMC", "Neuroscience", "Research", "article", "Serotonin", "5-HT2A", "and", "5-HT6", "receptors", "in", "the", "prefrontal", "cortex", "of", "Alzheimer", "and", "normal", "aging", "patients", "Dietrich", "E", "Lorke1,2,", "Gang", "Lu2,3,", "Eric", "Cho2", "and", "David", "T", "Yew*2", "BioMed", "Central", "Open", "Access", "Address:", "1Department", "of", "Anatomy,", "Faculty", "of", "Medicine", "and", "Health", "Sciences,", "UAE", "University,", "Box", "17666,", "Al", "Ain,", "United", "Arab", "Emirates,", "2Department", "of", "Anatomy,", "Chinese", "University", "of", "Hong", "Kong,", "Shatin,", "N.T.,", "Hong", "Kong", "and", "3Kunming", "Medical", "College,", "Kunming,", "Yunnan,", "China", "Email:", "Dietrich", "E", "Lorke", "-", "lorke@uaeu.ac.ae;", "Gang", "Lu", "-", "lugang@surgery.cuhk.edu.hk;", "Eric", "Cho", "-", "eric-cho@ana.cuhk.edu.hk;", "David", "T", "Yew*", "-", "david-yew@cuhk.edu.hk", "*", "Corresponding", "author", "Published:", "27", "April", "2006", "BMC", "Neuroscience", "2006,", "7:36", "doi:10.1186/1471-2202-7-36", "This", "article", "is", "available", "from:", "http://www.biomedcentral.com/1471-2202/7/36", "Received:", "12", "December", "2005", "Accepted:", "27", "April", "2006", "©", "2006", "Lorke", "et", "al;", "licensee", "BioMed", "Central", "Ltd.", "This", "is", "an", "Open", "Access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "License", "(http://creativecommons.org/licenses/by/2.0),", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited.", "Abstract", "Background:", "It", "has", "been", "hypothesized", "that", "alterations", "of", "the", "serotonergic", "system", "contribute", "to", "neuropsychiatric", "symptoms", "in", "Alzheimer", "disease", "(AD).", "Cellular", "expressions", "of", "the", "two", "serotonergic", "receptors", "5-HT2A", "and", "5-HT6", "have", "therefore", "been", "determined", "by", "immunohistochemistry", "in", "the", "prefrontal", "cortex", "of", "patients", "with", "AD", "(n=6)", "and", "normal", "age-matched", "controls", "(n", "=", "7).", "Results:", "In", "normal", "aging", "patients,", "5-HT2A", "label", "was", "mainly", "observed", "in", "large", "pyramidal", "cells,", "but", "to", "a", "lesser", "extent", "also", "in", "small", "pyramidal", "cells", "and", "in", "stellate", "cells", "of", "cortical", "layers", "II-VI.", "In", "AD,", "a", "similar", "distribution", "was", "observed,", "but", "density", "of", "positive", "cells", "was", "significantly", "reduced", "by", "33%.", "In", "aging", "control", "patients,", "the", "5-HT6", "receptor", "was", "expressed", "by", "pyramidal", "cells", "and", "occasional", "stellate", "cells,", "not", "only", "of", "layers", "II-V,", "but", "also", "of", "layer", "I,", "where", "a", "distinct", "label", "was", "observed", "in", "neurons", "and", "surrounding", "fibers.", "5-HT6", "receptor", "expression", "in", "AD", "patients", "had", "the", "same", "pattern,", "but", "was", "significantly", "decreased", "by", "40%.", "Conclusion:", "Our", "results", "indicate", "that", "a", "decline", "in", "neurons", "expressing", "5-HT2A,", "but", "also", "5-HT6", "receptors", "may", "play", "a", "role", "in", "the", "etiopathology", "of", "neuropsychiatric", "symptoms", "in", "AD.", "Background", "Alzheimer", "disease", "(AD),", "the", "most", "common", "cause", "of", "dementia", "in", "the", "elderly,", "is", "clinically", "characterized", "by", "pro-", "gressive", "cognitive", "impairment", "associated", "with", "severe", "neu-", "ropsychiatric", "disturbances.", "These", "behavioral", "and", "psychological", "symptoms", "of", "dementia", "(BPSD)", "include", "hal-", "lucinations,", "delusions,", "aggressive", "behavior,", "overactivity,", "anxieties", "and", "affective", "disturbances", "[1,2].", "Whereas", "the", "decline", "in", "cognitive", "functions", "can", "be", "largely", "related", "to", "cholinergic", "dysfunction", "arising", "from", "disruption", "of", "basal", "forebrain", "cholinergic", "pathways", "(cholinergic", "hypothesis)", "[1,3,4],", "impaired", "balance", "between", "several", "neurotransmit-", "ters", "has", "been", "implicated", "in", "the", "pathogenesis", "of", "BPSP", "[2,5-", "7],", "with", "serotonin", "(5-HT)", "playing", "a", "pivotal", "role", "[2,8-10].", "The", "actions", "of", "5-HT", "are", "mediated", "through", "seven", "major", "receptors", "classes,", "5-HT1–7,", "comprising", "a", "total", "of", "14", "distinct", "mammalian", "5-HT", "receptor", "subtypes", "(for", "review,", "see", "[11]).", "The", "5-HT2A", "receptor", "has", "attracted", "most", "interest", "because", "of", "its", "possible", "participation", "in", "behavioral", "alterations", "in", "AD.", "5-HT2A", "is", "localized", "in", "the", "cortex", "and", "caudate", "and", "is", "involved", "in", "anxiety", "[10].", "5-HT2A", "receptors", "mediate", "the", "psychotomimetic", "effects", "of", "hallucinogens", "[11-13],", "and", "alterations", "in", "binding", "characteristics", "to", "this", "receptor", "have", "been", "observed", "in", "the", "prefrontal", "cortex", "of", "patients", "suffer-", "Page", "1", "of", "8", "(page", "number", "not", "for", "citation", "purposes)" ]

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[ "de", "Fine", "Olivarius", "et", "al.", "BMC", "Public", "Health", "2011,", "11:80", "http://www.biomedcentral.com/1471-2458/11/80", "R", "E", "S", "E", "A", "R", "C", "H", "A", "R", "T", "I", "C", "L", "E", "Open", "Access", "Prevalence", "and", "progression", "of", "visual", "impairment", "in", "patients", "newly", "diagnosed", "with", "clinical", "type", "2", "diabetes:", "a", "6-year", "follow", "up", "study", "Niels", "de", "Fine", "Olivarius1*,", "Volkert", "Siersma1,", "Gitte", "Juul", "Almind1,", "Niels", "Vesti", "Nielsen2", "Abstract", "Background:", "Many", "diabetic", "patients", "fear", "visual", "loss", "as", "the", "worst", "consequence", "of", "diabetes.", "In", "most", "studies", "the", "main", "eye", "pathology", "is", "assigned", "as", "the", "cause", "of", "visual", "impairment.", "This", "study", "analysed", "a", "broad", "range", "of", "possible", "ocular", "and", "non-ocular", "predictors", "of", "visual", "impairment", "prospectively", "in", "patients", "newly", "diagnosed", "with", "clinical", "type", "2", "diabetes.", "Methods:", "Data", "were", "from", "a", "population-based", "cohort", "of", "1,241", "persons", "newly", "diagnosed", "with", "clinical,", "often", "symptomatic", "type", "2", "diabetes", "aged", "≥", "40", "years.", "After", "6", "years,", "807", "patients", "were", "followed", "up.", "Standard", "eye", "examinations", "were", "done", "by", "practising", "ophthalmologists.", "Results:", "At", "diabetes", "diagnosis", "median", "age", "was", "65.5", "years.", "Over", "6", "years,", "the", "prevalence", "of", "blindness", "(visual", "acuity", "of", "best", "seeing", "eye", "≤", "0.1)", "rose", "from", "0.9%", "(11/1,241)", "to", "2.4%", "(19/807)", "and", "the", "prevalence", "of", "moderate", "visual", "impairment", "(>", "0.1;", "<", "0.5)", "rose", "from", "5.4%", "(67/1,241)", "to", "6.7%", "(54/807).", "The", "incidence", "(95%", "confidence", "interval)", "of", "blindness", "was", "40.2", "(25.3-63.8)", "per", "10,000", "patient-years.", "Baseline", "predictors", "of", "level", "of", "visual", "acuity", "(age,", "age-related", "macular", "degeneration", "(AMD),", "cataract,", "living", "alone,", "low", "self-rated", "health,", "and", "sedentary", "life-style)", "and", "speed", "of", "continued", "visual", "loss", "(age,", "AMD,", "diabetic", "retinopathy", "(DR),", "cataract,", "living", "alone,", "and", "high", "fasting", "triglycerides)", "were", "identified.", "Conclusions:", "In", "a", "comprehensive", "assessment", "of", "predictors", "of", "visual", "impairment,", "even", "in", "a", "health", "care", "system", "allowing", "self-referral", "to", "free", "eye", "examinations,", "treatable", "eye", "pathologies", "such", "as", "DR", "and", "cataract", "emerge", "together", "with", "age", "as", "the", "most", "notable", "predictors", "of", "continued", "visual", "loss", "after", "diabetes", "diagnosis.", "Our", "results", "underline", "the", "importance", "of", "eliminating", "barriers", "to", "efficient", "eye", "care", "by", "increasing", "patients’", "and", "primary", "care", "practitioners’", "awareness", "of", "the", "necessity", "of", "regular", "eye", "examinations", "and", "timely", "surgical", "treatment.", "Background", "In", "Europe", "and", "the", "United", "States", "severe", "visual", "impair-", "ment", "may", "be", "2-3", "times", "more", "common", "among", "people", "with", "diabetes", "than", "in", "the", "general", "population", "[1,2],", "but", "this", "difference", "decreases", "with", "age", "[2].", "Diabetic", "retinopa-", "thy", "(DR)", "is", "regarded", "as", "the", "cause", "of", "blindness", "in", "5-15%", "of", "the", "blind", "in", "the", "general", "population", "[3-5]", "and", "in", "30-50%", "of", "blind", "type", "2", "diabetic", "patients", "[6,7].", "There", "are,", "however,", "huge", "regional", "differences", "in", "presumed", "causes", "of", "blindness", "across", "the", "world", "[8].", "DR", "is", "considered", "the", "*", "Correspondence:", "olivarius@sund.ku.dk", "1The", "Research", "Unit", "for", "General", "Practice", "and", "Section", "of", "General", "Practice,", "Department", "of", "Public", "Health,", "University", "of", "Copenhagen,", "Copenhagen,", "Denmark", "Full", "list", "of", "author", "information", "is", "available", "at", "the", "end", "of", "the", "article", "leading", "cause", "of", "blindness", "among", "people", "of", "working", "age", "in", "many", "countries", "[3-5],", "while", "age-related", "macular", "degeneration", "(AMD)", "is", "considered", "the", "leading", "cause", "in", "people", "over", "65", "years", "[3-5,9].", "Diabetes", "with", "even", "mildly", "to", "moderately", "impaired", "sight", "has", "a", "negative", "impact", "on", "perceived", "quality", "of", "life", "and", "psychosocial", "functioning", "giving", "rise", "to", "feelings", "of", "vulnerability,", "worries", "about", "the", "future", "and", "loss", "of", "inde-", "pendence", "and", "mobility", "[10-12].", "A", "sizeable", "proportion", "of", "type", "2", "diabetic", "patients", "fear", "visual", "loss", "intensely", "[13]", "and", "consider", "loss", "of", "vision", "the", "worst", "complication", "of", "diabetes", "[10].", "For", "the", "health", "practitioner", "visual", "acuity", "is", "a", "ubiquitous", "and", "handy", "measure", "of", "visual", "function,", "but", "visual", "acuity", "is", "not", "a", "suitable", "measure", "of", "future", "visual", "loss", "as", "the", "sight-threatening", "eye", "pathologies", "often", "are", "©", "2011", "de", "Fine", "Olivarius", "et", "al;", "licensee", "BioMed", "Central", "Ltd.", "This", "is", "an", "Open", "Access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "License", "(http://creativecommons.org/licenses/by/2.0),", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited." ]

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[ "Hindawi", "Publishing", "Corporation", "Gastroenterology", "Research", "and", "Practice", "Volume", "2011,", "Article", "ID", "410971,", "6", "pages", "doi:10.1155/2011/410971", "Review", "Article", "Refeeding", "Syndrome:", "A", "Literature", "Review", "L.", "U.", "R.", "Khan,", "J.", "Ahmed,", "S.", "Khan,", "and", "J.", "MacFie", "The", "Combined", "Gastroenterology", "Research", "Unit,", "Scarborough", "Hospital,", "Woodland", "Drive,", "Scarborough", "YO12", "6QL,", "UK", "Correspondence", "should", "be", "addressed", "to", "J.", "Ahmed,", "drjag@hotmail.co.uk", "Received", "1", "June", "2010;", "Revised", "21", "July", "2010;", "Accepted", "3", "August", "2010", "Academic", "Editor:", "Re´my", "Meier", "Copyright", "©", "2011", "L.", "U.", "R.", "Khan", "et", "al.", "This", "is", "an", "open", "access", "article", "distributed", "under", "the", "Creative", "Commons", "Attribution", "License,", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited.", "Refeeding", "syndrome", "(RFS)", "describes", "the", "biochemical", "changes,", "clinical", "manifestations,", "and", "complications", "that", "can", "occur", "as", "a", "consequence", "of", "feeding", "a", "malnourished", "catabolic", "individual.", "RFS", "has", "been", "recognised", "in", "the", "literature", "for", "over", "fifty", "years", "and", "can", "result", "in", "serious", "harm", "and", "death.", "Crude", "estimates", "of", "incidence,", "morbidity,", "and", "mortality", "are", "available", "for", "specific", "populations.", "RFS", "can", "occur", "in", "any", "individual", "but", "more", "commonly", "occurs", "in", "at-risk", "populations.", "Increased", "awareness", "amongst", "healthcare", "professionals", "is", "likely", "to", "reduce", "morbidity", "and", "mortality.", "This", "review", "examines", "the", "physiology", "of", "RFS", "and", "describes", "the", "clinical", "manifestations.", "A", "management", "strategy", "is", "described.", "The", "importance", "of", "a", "multidisciplinary", "approach", "is", "emphasized.", "1.", "Introduction", "RFS", "is", "well", "recognised.", "It", "occurs", "after", "the", "reintroduction", "of", "feeding", "after", "a", "period", "of", "starvation", "or", "fasting", "[1].", "RFS", "describes", "a", "series", "of", "metabolic", "and", "biochemical", "changes", "that", "occur", "as", "a", "consequence", "of", "reintroduction", "of", "feeding", "after", "a", "period", "of", "starvation", "or", "fasting.", "This", "unfavorable", "metabolic", "response", "causes", "nonimmune-mediated", "harm", "to", "the", "body", "and", "can", "be", "mild,", "moderate,", "or", "severe.", "Although,", "the", "physiol-", "ogy", "and", "pathophysiology", "are", "well", "known,", "the", "circumstances", "under", "which", "RFS", "occurs,", "the", "clinical", "manifestations,", "and", "the", "management", "of", "these", "patients", "are", "less", "clear", "[2,", "3].", "1.1.", "Methods.", "A", "PubMed", "search", "for", "the", "terms", "“refeeding", "syndrome”", "AND", "“hypophosphataemia”", "generated", "two", "hun-", "dred", "and", "seven", "separate", "articles.", "There", "were", "no", "randomized", "controlled", "trials", "identified.", "1.2.", "Physiology.", "With", "food", "in", "abundance,", "carbohydrates", "provide", "for", "most", "of", "our", "energy", "requirements.", "Glucose,", "the", "principal", "product", "of", "carbohydrate", "digestion,", "is", "actively", "cotransported", "along", "with", "sodium", "at", "the", "intestinal", "brush", "border", "against", "a", "concentration", "gradient.", "Glucose", "enters", "the", "portal", "circulation", "by", "facilitated", "diffusion", "and", "blood", "sugar", "levels", "rise.", "This", "stimulates", "the", "release", "of", "the", "peptide", "hormone", "insulin", "from", "pancreatic", "islet", "cells.", "Insulin", "secretion", "has", "several", "effects.", "It", "promotes", "glucose", "uptake", "and", "storage", "(glycogenesis),", "inhibits", "the", "breakdown", "of", "fats", "(lipolysis),", "and", "increases", "cellular", "uptake", "of", "potassium.", "When", "glycogen", "stor-", "age", "capacity", "is", "exceeded,", "lipogenesis", "occurs", "with", "nonoxidised", "glucose", "being", "converted", "to", "fat", "and", "stored", "as", "triglycerides", "in", "adipose", "tissue.", "Together,", "the", "consequence", "is", "for", "blood", "glucose", "levels", "to", "fall", "with", "a", "concomitant", "reduction", "in", "insulin", "secretion", "[4].", "With", "starvation,", "levels", "of", "glucose", "begin", "to", "fall", "within", "24", "to", "72", "hours.", "This", "results", "in", "the", "release", "of", "the", "peptide", "hormone", "glucagon", "and", "a", "reduction", "in", "insulin", "secretion", "[10].", "Glucose", "levels", "are", "maintained", "by", "glycogenolysis", "but", "glycogen", "stores", "rarely", "last", "more", "than", "72", "hours", "[11].", "Glucose", "homeostasis", "is", "essential", "because", "certain", "tissues,", "such", "as", "brain,", "erythrocytes,", "and", "cells", "of", "the", "renal", "medulla", "are", "obligate", "glucose", "users", "[12].", "These", "demands", "for", "glucose", "are", "met", "by", "the", "process", "of", "gluconeogenesis", "by", "which", "noncarbohydrate", "sources", "are", "metabolized", "to", "glucose.", "The", "most", "important", "of", "these", "is", "the", "muscle", "protein", "alanine.", "In", "addition,", "fatty", "acid", "oxidation", "in", "liver", "hepatocytes", "generates", "ketone", "bodies.", "These", "are", "converted", "to", "acetyl-coenzyme-A", "generating", "energy", "via", "the", "Kreb’s", "cycle.", "Further", "energy", "production", "from", "lactate", "and", "pyruvate", "(the", "products", "of", "glycolysis)", "and", "amino", "acids", "occurs", "via", "the", "Cori", "cycle", "[4].", "In", "summary,", "metabolic", "adaptation", "occurs", "to", "ensure", "survival", "on", "fat", "fuel", "economy", "[13].", "There", "is", "a", "resultant", "loss", "of", "body", "fat", "and", "protein", "and", "an", "accompanying", "depletion", "of", "potassium,", "phosphate,", "and", "magnesium", "[14,", "15]." ]

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[ "Liet", "et", "al.", "BMC", "Pediatrics", "2011,", "11:92", "http://www.biomedcentral.com/1471-2431/11/92", "C", "A", "S", "E", "R", "E", "P", "O", "R", "T", "Open", "Access", "Respiratory", "support", "by", "neurally", "adjusted", "ventilatory", "assist", "(NAVA)", "in", "severe", "RSV-related", "bronchiolitis:", "a", "case", "series", "report", "Jean-Michel", "Liet1*,", "Jean-Marc", "Dejode1†,", "Nicolas", "Joram1†,", "Bénédicte", "Gaillard-Le", "Roux1†,", "Pierre", "Bétrémieux2†", "and", "Jean-Christophe", "Rozé1†", "Abstract", "Background:", "Neurally", "adjusted", "ventilatory", "assist", "(NAVA)", "is", "a", "new", "mode", "of", "mechanical", "ventilation", "controlled", "by", "diaphragmatic", "electrical", "signals.", "The", "electrical", "signals", "allow", "synchronization", "of", "ventilation", "to", "spontaneous", "breathing", "efforts", "of", "a", "child,", "as", "well", "as", "permitting", "pressure", "assistance", "proportional", "to", "the", "electrical", "signal.", "NAVA", "provides", "equally", "fine", "synchronization", "of", "respiratory", "support", "and", "pressure", "assistance", "varying", "with", "the", "needs", "of", "the", "child.", "NAVA", "has", "mainly", "been", "studied", "in", "children", "who", "underwent", "cardiac", "surgery", "during", "the", "period", "of", "weaning", "from", "a", "respirator.", "Case", "presentation:", "We", "report", "here", "a", "series", "of", "3", "children", "(1", "month,", "3", "years,", "and", "28", "days", "old)", "with", "severe", "respiratory", "distress", "due", "to", "RSV-related", "bronchiolitis", "requiring", "invasive", "mechanical", "ventilation", "with", "a", "high", "level", "of", "oxygen", "(FiO2", "≥50%)", "for", "whom", "NAVA", "facilitated", "respiratory", "support.", "One", "of", "these", "children", "had", "diagnosis", "criteria", "for", "acute", "lung", "injury,", "another", "for", "acute", "respiratory", "distress", "syndrome.", "Establishment", "of", "NAVA", "provided", "synchronization", "of", "mechanical", "ventilatory", "support", "with", "the", "breathing", "efforts", "of", "the", "children.", "Respiratory", "rate", "and", "inspiratory", "pressure", "became", "extremely", "variable,", "varying", "at", "each", "cycle,", "while", "children", "were", "breathing", "easily", "and", "smoothly.", "All", "three", "children", "demonstrated", "less", "oxygen", "requirements", "after", "introducing", "NAVA", "(57", "±", "6%", "to", "42", "±", "18%).", "This", "improvement", "was", "observed", "while", "peak", "airway", "pressure", "decreased", "(28", "±", "3", "to", "15", "±", "5", "cm", "H2O).", "In", "one", "child,", "NAVA", "facilitated", "the", "management", "of", "acute", "respiratory", "distress", "syndrome", "with", "extensive", "subcutaneous", "emphysema.", "Conclusions:", "Our", "findings", "highlight", "the", "feasibility", "and", "benefit", "of", "NAVA", "in", "children", "with", "severe", "RSV-related", "bronchiolitis.", "NAVA", "provides", "a", "less", "aggressive", "ventilation", "requiring", "lower", "inspiratory", "pressures", "with", "good", "results", "for", "oxygenation", "and", "more", "comfort", "for", "the", "children.", "Background", "Neurally", "adjusted", "ventilatory", "assist", "(NAVA)", "is", "a", "new", "method", "of", "assisted", "ventilation", "that", "can", "be", "used", "for", "chil-", "dren", "regardless", "of", "weight", "and", "age.", "This", "ventilation", "mode", "is", "controlled", "by", "diaphragmatic", "electrical", "signals", "through", "a", "gastric", "tube", "with", "specific", "electrodes", "on", "its", "surface.", "The", "collected", "electrical", "signals", "allow", "synchronization", "of", "venti-", "lation", "to", "spontaneous", "breathing", "efforts", "of", "a", "child,", "as", "well", "as", "providing", "pressure", "assistance", "proportional", "to", "the", "*", "Correspondence:", "jeanmichel.liet@chu-nantes.fr", "†", "Contributed", "equally", "1Unité", "de", "Réanimation", "Pédiatrique,", "Hôpital", "Mère-Enfant", "Faïencerie,", "CHU", "de", "Nantes,", "38", "Boulevard", "Jean-Monnet,", "44093", "Nantes,", "France", "Full", "list", "of", "author", "information", "is", "available", "at", "the", "end", "of", "the", "article", "electrical", "signal", "and", "thus", "to", "the", "output", "of", "the", "child’s", "respiratory", "centers.", "NAVA", "has", "mainly", "been", "studied", "in", "children", "who", "under-", "went", "cardiac", "surgery", "[1-3]", "during", "the", "period", "of", "weaning", "from", "a", "respirator.", "We", "report", "here", "a", "series", "of", "3", "children", "with", "severe", "respiratory", "distress", "due", "to", "respiratory", "syncy-", "tial", "virus", "(RSV)", "bronchiolitis", "for", "whom", "NAVA", "facilitated", "respiratory", "support.", "Case", "Presentation", "Our", "unit", "is", "a", "12-bed", "tertiary", "care", "university", "hospital", "pediatric", "intensive", "care", "unit.", "Recruitment", "is", "both", "medi-", "cal", "and", "surgical.", "NAVA", "has", "been", "used", "in", "our", "unit", "for", "weaning", "children", "from", "a", "respirator", "who", "were", "operated", "©", "2011", "Liet", "et", "al;", "licensee", "BioMed", "Central", "Ltd.", "This", "is", "an", "Open", "Access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "License", "(http://creativecommons.org/licenses/by/2.0),", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited." ]

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[ "Open", "Access", "Renkawitz", "et", "al.", "BMC", "Musculoskeletal", "Disorders", "2011,", "12:192", "http://www.biomedcentral.com/1471-2474/12/192", "S", "T", "U", "D", "Y", "P", "R", "O", "T", "O", "C", "O", "L", "Minimally", "invasive", "computer-navigated", "total", "hip", "arthroplasty,", "following", "the", "concept", "of", "femur", "first", "and", "combined", "anteversion:", "design", "of", "a", "blinded", "randomized", "controlled", "trial", "Tobias", "Renkawitz1*,", "Martin", "Haimerl2,", "Lars", "Dohmen2,", "Sabine", "Gneiting2,", "Melanie", "Wegner2,", "Nicole", "Ehret2,", "Claudia", "Buchele2,", "Mario", "Schubert2,", "Philipp", "Lechler1,", "Michael", "Woerner1,", "Ernst", "Sendtner1,", "Tibor", "Schuster3,", "Kurt", "Ulm3,", "Robert", "Springorum1", "and", "Joachim", "Grifka1", "Abstract", "Background:", "Impingement", "can", "be", "a", "serious", "complication", "after", "total", "hip", "arthroplasty", "(THA),", "and", "is", "one", "of", "the", "major", "causes", "of", "postoperative", "pain,", "dislocation,", "aseptic", "loosening,", "and", "implant", "breakage.", "Minimally", "invasive", "THA", "and", "computer-navigated", "surgery", "were", "introduced", "several", "years", "ago.", "We", "have", "developed", "a", "novel,", "computer-", "assisted", "operation", "method", "for", "THA", "following", "the", "concept", "of", "“femur", "first\"/\"combined", "anteversion”,", "which", "incorporates", "various", "aspects", "of", "performing", "a", "functional", "optimization", "of", "the", "cup", "position,", "and", "comprehensively", "addresses", "range", "of", "motion", "(ROM)", "as", "well", "as", "cup", "containment", "and", "alignment", "parameters.", "Hence,", "the", "purpose", "of", "this", "study", "is", "to", "assess", "whether", "the", "artificial", "joint’s", "ROM", "can", "be", "improved", "by", "this", "computer-assisted", "operation", "method.", "Second,", "the", "clinical", "and", "radiological", "outcome", "will", "be", "evaluated.", "Methods/Design:", "A", "registered", "patient-", "and", "observer-blinded", "randomized", "controlled", "trial", "will", "be", "conducted.", "Patients", "between", "the", "ages", "of", "50", "and", "75", "admitted", "for", "primary", "unilateral", "THA", "will", "be", "included.", "Patients", "will", "be", "randomly", "allocated", "to", "either", "receive", "minimally", "invasive", "computer-navigated", "“femur", "first”", "THA", "or", "the", "conventional", "minimally", "invasive", "THA", "procedure.", "Self-reported", "functional", "status", "and", "health-related", "quality", "of", "life", "(questionnaires)", "will", "be", "assessed", "both", "preoperatively", "and", "postoperatively.", "Perioperative", "complications", "will", "be", "registered.", "Radiographic", "evaluation", "will", "take", "place", "up", "to", "6", "weeks", "postoperatively", "with", "a", "computed", "tomography", "(CT)", "scan.", "Component", "position", "will", "be", "evaluated", "by", "an", "independent", "external", "institute", "on", "a", "3D", "reconstruction", "of", "the", "femur/", "pelvis", "using", "image-processing", "software.", "Postoperative", "ROM", "will", "be", "calculated", "by", "an", "algorithm", "which", "automatically", "determines", "bony", "and", "prosthetic", "impingements.", "Discussion:", "In", "the", "past,", "computer", "navigation", "has", "improved", "the", "accuracy", "of", "component", "positioning.", "So", "far,", "there", "are", "only", "few", "objective", "data", "quantifying", "the", "risks", "and", "benefits", "of", "computer", "navigated", "THA.", "Therefore,", "this", "study", "has", "been", "designed", "to", "compare", "minimally", "invasive", "computer-navigated", "“femur", "first”", "THA", "with", "a", "conventional", "technique", "for", "minimally", "invasive", "THA.", "The", "results", "of", "this", "trial", "will", "be", "presented", "as", "soon", "as", "they", "become", "available.", "Trial", "registration", "number:", "DRKS00000739", "*", "Correspondence:", "t.renkawitz@asklepios.com", "1Department", "of", "Orthopaedic", "Surgery,", "Regensburg", "University", "Medical", "Center,", "Germany", "Full", "list", "of", "author", "information", "is", "available", "at", "the", "end", "of", "the", "article", "©", "2011", "Renkawitz", "et", "al;", "licensee", "BioMed", "Central", "Ltd.", "This", "is", "an", "Open", "Access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "License", "(http://creativecommons.org/licenses/by/2.0),", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited." ]

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[ "SYSTEMS", "NEUROSCIENCE", "3D", "standard", "brain", "of", "the", "red", "flour", "beetle", "Tribolium", "castaneum:", "a", "tool", "to", "study", "metamorphic", "development", "and", "adult", "plasticity", "David", "Dreyer1,2,", "Holger", "Vitt1,", "Stefan", "Dippel", "1,3,", "Brigitte", "Goetz1,", "Basil", "el", "Jundi", "1,", "Martin", "Kollmann1,", "Wolf", "Huetteroth1,4", "and", "Joachim", "Schachtner", "1*", "1", "Department", "of", "Biology,", "Animal", "Physiology,", "Philipps-University", "Marburg,", "Marburg,", "Germany", "2", "Department", "of", "Biology,", "Animal", "Navigation,", "University", "of", "Oldenburg,", "Oldenburg,", "Germany", "3", "Department", "of", "Developmental", "Biology,", "Johann-Friedrich-Blumenbach-Institute", "for", "Zoology", "and", "Anthropol,", "Georg-August-University", "Göttingen,", "Göttingen,", "Germany", "4", "Department", "of", "Neurobiology,", "University", "of", "Massachusetts", "Medical", "School,", "Worcester,", "MA,", "USA", "ORIGINAL", "RESEARCH", "ARTICLE", "published:", "03", "March", "2010", "doi:", "10.3389/neuro.06.003.2010", "Edited", "by:", "Randolf", "Menzel,", "Freie", "Universität", "Berlin,", "Germany", "Reviewed", "by:", "Monika", "Stengl,", "Universität", "Kassel,", "Germany", "*Correspondence:", "Joachim", "Schachtner,", "Department", "of", "Biology,", "Animal", "Physiology,", "Philipps-", "University", "Marburg,", "Karl-von-Frisch-Str.", "8,", "D-35032", "Marburg,", "Germany.", "e-mail:", "schachtj@staff.uni-marburg.de", "The", "red", "flour", "beetleTribolium", "castaneum", "is", "emerging", "as", "a", "further", "standard", "insect", "model", "beside", "Drosophila.", "Its", "genome", "is", "fully", "sequenced", "and", "it", "is", "susceptible", "for", "genetic", "manipulations", "including", "RNA-interference.", "We", "use", "this", "beetle", "to", "study", "adult", "brain", "development", "and", "plasticity", "primarily", "with", "respect", "to", "the", "olfactory", "system.", "In", "the", "current", "study,", "we", "provide", "3D", "standard", "brain", "atlases", "of", "freshly", "eclosed", "adult", "female", "and", "male", "beetles", "(A0).The", "atlases", "include", "eight", "paired", "and", "three", "unpaired", "neuropils", "including", "antennal", "lobes", "(ALs),", "optic", "lobe", "neuropils,", "mushroom", "body", "calyces", "and", "pedunculi,", "and", "central", "complex.", "For", "each", "of", "the", "two", "standard", "brains,", "we", "averaged", "brain", "areas", "of", "20", "individual", "brains.", "Additionally,", "we", "characterized", "eight", "selected", "olfactory", "glomeruli", "from", "10", "A0", "female", "and", "male", "beetles", "respectively,", "which", "we", "could", "unequivocally", "recognize", "from", "individual", "to", "individual", "owing", "to", "their", "size", "and", "typical", "position", "in", "the", "ALs.", "In", "summary,", "comparison", "of", "the", "averaged", "neuropil", "volumes", "revealed", "no", "sexual", "dimorphism", "in", "any", "of", "the", "reconstructed", "neuropils", "in", "A0", "Tribolium", "brains.", "Both,", "the", "female", "and", "male", "3D", "standard", "brain", "are", "also", "used", "for", "interspecies", "comparisons,", "and,", "importantly,", "will", "serve", "as", "future", "volumetric", "references", "after", "genetical", "manipulation", "especially", "regarding", "metamorphic", "development", "and", "adult", "plasticity.", "Keywords:", "brain,", "olfactory", "system,", "antennal", "lobe,", "insect,", "neuropil,", "digital", "neuroanatomy,", "coleoptera", "INTRODUCTION", "The", "red", "flour", "beetle", "Tribolium", "castaneum", "Herbst,", "1797", "(Bonneton,", "2008),", "which", "is", "a", "major", "pest", "of", "stored", "grains,", "grain", "products,", "and", "other", "dried", "food,", "is", "emerging", "as", "a", "further", "standard", "insect", "model", "beside", "Drosophila.", "It’s", "powerful", "reverse", "genetics", "(systemic", "RNA-interference;", "Bucher", "et", "al.,", "2002;", "Tomoyasu", "and", "Denell,", "2004;", "Tomoyasu", "et", "al.,", "2008),", "the", "recently", "published", "full", "genomic", "sequence", "(Richards", "et", "al.,", "2008)", "and", "the", "established", "transgenesis", "systems", "(Berghammer", "et", "al.,", "1999)", "transform", "Tribolium", "into", "a", "primary", "model", "system.", "Since", "recently,", "an", "insertional", "mutagen-", "esis", "screen", "database", "provides", "mutants", "and", "enhancer", "trap", "lines", "for", "the", "growing", "Tribolium", "community", "(http://134.76.20.145/", "Default.aspx).", "Meanwhile,", "Tribolium", "has", "become", "one", "of", "the", "most", "important", "models", "in", "the", "field", "of", "evolution", "and", "development", "(“evo-devo”)", "because", "its", "development", "is", "more", "“insect", "typical”,", "compared", "to", "that", "of", "the", "classical", "system", "Drosophila", "(Klingler,", "2004).", "Currently,", "only", "little", "information", "on", "the", "brain", "or", "its", "embryonic", "and", "metamorphic", "development", "is", "available.", "With", "our", "pioneering", "study", "we", "provide", "for", "the", "first", "time", "anatomical", "descrip-", "tions", "for", "most", "of", "the", "brain", "areas", "of", "adult", "Tribolium", "including", "3D", "reconstructions", "and", "an", "average", "brain", "atlas", "for", "selected", "brain", "neuropils.", "With", "the", "latter,", "we", "present", "the", "first", "standardization", "of", "a", "coleopteran", "brain.", "Brains", "are", "typically", "organized", "in", "defined", "neuropils,", "which", "can", "usually", "be", "characterized", "by", "their", "spatial", "location,", "gross", "anatomy,", "and", "often", "by", "a", "certain", "function.", "For", "example,", "the", "olfactory", "bulbs", "of", "vertebrates", "and", "the", "antennal", "lobes", "(ALs)", "of", "insects", "have", "been", "attributed", "to", "be", "the", "first", "processing", "centers", "for", "olfactory", "informa-", "tion", "(for", "a", "review", "see", "Hildebrand", "and", "Shepherd,", "1997).", "Compared", "to", "most", "vertebrate", "brains,", "insect", "brains", "are", "miniature", "versions", "being", "typically", "comprised", "of", "a", "lower", "number", "of", "neurons", "and", "neuropils.", "Owing", "to", "the", "lower", "complexity", "and", "certain", "technical", "advantages,", "insects", "have", "been", "widely", "used", "as", "models", "to", "study", "principal", "mechanisms", "of", "information", "processing", "and", "integra-", "tion,", "in", "the", "context", "of", "defined", "sensory", "inputs", "but", "also", "complex", "behaviors", "including", "learning", "and", "memory", "formation", "(e.g.", "Menzel,", "2001;", "Heisenberg,", "2003).", "Brains", "of", "animals", "of", "the", "same", "or", "of", "evolutionary", "related", "species", "typically", "share", "the", "same", "principal", "organization.", "For", "example", "in", "neopteran", "insects,", "the", "central", "olfactory", "pathway", "seems", "to", "be", "well", "conserved", "(Strausfeld", "et", "al.,", "1998;", "Schachtner", "et", "al.,", "2005).", "However,", "even", "within", "the", "same", "species,", "no", "brain", "is", "identical", "with", "the", "next,", "differing", "in", "size", "and", "shape", "of", "certain", "brain", "neuropils.", "These", "indi-", "vidual", "differences", "can", "result", "from", "a", "variety", "of", "parameters", "which", "are", "influencing", "brain", "organization", "during", "development", "but", "also", "during", "adulthood.", "In", "insects,", "such", "factors", "include", "brood", "temperature,", "sex,", "age,", "and", "experience", "(Groh", "et", "al.,", "2004;", "Technau,", "2007;", "Molina", "and", "O’Donnell,", "2008).", "To", "study", "sexual", "brain", "dimorphism", "or", "the", "influence", "of", "defined", "parameters", "(ranging", "from", "single", "molecules", "to", "social", "experience)", "on", "brain", "development", "or", "adult", "plasticity,", "average", "or", "standardized", "brains", "or", "brain", "areas", "are", "needed", "to", "relate", "individual", "variations", "to", "Frontiers", "in", "Systems", "Neuroscience", "www.frontiersin.org", "March", "2010", "|", "Volume", "4", "|", "Article", "3", "|", "1" ]

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[ "e", "n", "i", "c", "i", "d", "e", "M", "l", "a", "t", "n", "e", "m", "i", "r", "e", "p", "x", "E", "f", "o", "l", "a", "n", "r", "u", "o", "J", "e", "h", "T", "CORRESPONDENCE", "Diane", "Mathis", "OR", "Christophe", "Benoist:", "cbdm@hms.harvard.edu", "The", "Rockefeller", "University", "Press", "$30.00", "J.", "Exp.", "Med.", "Vol.", "206", "No.", "6", "1245-1252", "www.jem.org/cgi/doi/10.1084/jem.20090300", "B", "R", "I", "E", "F", "D", "E", "F", "I", "N", "I", "T", "I", "V", "E", "R", "E", "P", "O", "RT", "Neonatal", "tolerance", "revisited:", "a", "per", "inatal", "window", "for", "Aire", "control", "of", "autoimmunity", "Mireia", "Guerau-de-Arellano,1,2", "Marianne", "Martinic,1,2", "Christophe", "Benoist,1,2", "and", "Diane", "Mathis1,2", "1Section", "on", "Immunology", "and", "Immunogenetics,", "Joslin", "Diabetes", "Center,", "and", "2Department", "of", "Medicine,", "Brigham", "and", "Women’s", "Hospital,", "Harvard", "Medical", "School,", "Boston,", "MA", "02215", "There", "has", "long", "been", "conceptual", "and", "experimental", "support", "for,", "but", "also", "challenges", "to,", "the", "notion", "that", "the", "initial", "period", "of", "the", "immune", "system’s", "development", "is", "particularly", "important", "for", "the", "establishment", "of", "tolerance", "to", "self.", "The", "display", "of", "self-antigens", "by", "thymic", "epithelial", "cells", "is", "key", "to", "inducing", "tolerance", "in", "the", "T", "lymphocyte", "compartment,", "a", "process", "enhanced", "by", "the", "Aire", "transcription", "factor.", "Using", "a", "doxycycline-regulated", "transgene", "to", "target", "Aire", "expression", "to", "the", "thymic", "epithelium,", "complementing", "the", "Aire", "knockout", "in", "a", "temporally", "controlled", "manner,", "we", "find", "that", "Aire", "is", "essential", "in", "the", "perinatal", "period", "to", "prevent", "the", "multiorgan", "autoimmunity", "that", "is", "typical", "of", "Aire", "deficiency.", "Surprisingly,", "Aire", "could", "be", "shut", "down", "soon", "thereafter", "and", "remain", "off", "for", "long", "periods,", "with", "few", "deleterious", "consequences.", "The", "lymphopenic", "state", "present", "in", "neonates", "was", "a", "factor", "in", "this", "dichotomy", "because", "inducing", "lymphopenia", "during", "Aire", "turnoff", "in", "adults", "recreated", "the", "disease,", "which,", "conversely,", "could", "be", "ameliorated", "by", "supplementing", "neonates", "with", "adult", "lymphocytes.", "In", "short,", "Aire", "expression", "during", "the", "perinatal", "period", "is", "both", "necessary", "and", "sufficient", "to", "induce", "long-lasting", "tolerance", "and", "avoid", "autoimmunity.", "Aire-controlled", "mechanisms", "of", "central", "tolerance", "are", "largely", "dispensable", "in", "the", "adult,", "as", "a", "previously", "tolerized", "T", "cell", "pool", "can", "buffer", "newly", "generated", "autoreactive", "T", "cells", "that", "might", "emerge.", "Adaptive", "immune", "systems", "face", "the", "challenge", "of", "discriminating", "between", "foreign", "antigens,", "against", "which", "a", "response", "may", "have", "to", "be", "mounted,", "and", "self-constituents,", "which", "should", "be", "ignored", "or", "tolerated.", "Although", "there", "are", "multiple", "theoret-", "ical", "solutions", "to", "the", "challenge", "of", "self/nonself", "discrimination,", "Burnet", "and", "Fenner", "(1)", "proposed", "as", "a", "corollary", "to", "the", "clonal", "selection", "theory", "that", "the", "problem", "can", "be", "solved", "on", "the", "basis", "of", "time", "considerations;", "any", "antigen", "to", "which", "the", "im-", "mune", "system", "is", "exposed", "in", "the", "fetal", "or", "early", "neonatal", "stages", "is", "flagged", "as", "self", "and", "induces", "long-", "term", "tolerance.", "Lederberg", "(2)", "extended", "this", "no-", "tion", "by", "postulating", "that", "immature", "lymphocytes", "have", "a", "heightened", "sensitivity", "to", "tolerance", "in-", "duction.", "This", "“newborn", "privilege”", "was", "tested", "by", "introducing", "foreign", "molecules", "as", "surrogates", "for", "self,", "and,", "indeed,", "it", "did", "prove", "possible", "to", "in-", "duce", "tolerance", "by", "administration", "of", "allogeneic", "cells,", "viruses,", "or", "proteins", "to", "neonates", "but", "not", "in", "adults", "(3–6).", "However,", "neonatal", "exposure", "was", "not", "always", "tolerogenic,", "and", "the", "outcome", "was", "clearly", "dose", "dependent", "(7,", "8).", "Although", "related", "obser-", "vations", "already", "existed", "in", "the", "literature,", "the", "strongest", "challenge", "to", "the", "notion", "of", "neonatal", "tolerance", "induction", "came", "from", "a", "trio", "of", "studies", "published", "in", "1996", "(9–11),", "which", "showed", "that", "neonatal", "lymphocytes", "could", "mount", "full", "im-", "mune", "responses", "under", "the", "appropriate", "conditions.", "Ridge", "et", "al.", "(9)", "pointed", "out", "that", "the", "differential", "effects", "of", "fetal", "versus", "adult", "exposure", "to", "alloge-", "neic", "cells", "highlighted", "by", "the", "Medawar", "group,", "long", "a", "linchpin", "of", "neonatal", "tolerance,", "may", "have", "been", "due", "simply", "to", "the", "large", "disparities", "in", "doses", "(relative", "to", "body", "size)", "administered", "at", "the", "two", "stages.", "As", "a", "result,", "the", "notion", "of", "neonatal", "toler-", "ance", "was", "questioned", "in", "the", "field,", "and", "more", "at-", "tention", "was", "given", "to", "the", "influence", "of", "concomitant", "triggering", "of", "the", "innate", "immune", "system", "by", "in-", "flammatory", "and", "microbial", "ligands.", "One", "issue", "with", "experimental", "testing", "of", "neo-", "natal", "tolerance", "induction", "has", "been", "that,", "going", "back", "to", "the", "1950s,", "investigations", "mainly", "relied", "on", "the", "administration", "of", "allogeneic", "or", "xenogeneic", "molecules", "in", "the", "tolerization", "and/or", "test", "steps", "but", "©", "2009", "Guerau-de-Arellano", "et", "al.", "This", "article", "is", "distributed", "under", "the", "terms", "of", "an", "Attribution–Noncommercial–Share", "Alike–No", "Mirror", "Sites", "license", "for", "the", "first", "six", "months", "after", "the", "publication", "date", "(see", "http://www.jem.org/misc/terms.shtml).", "After", "six", "months", "it", "is", "available", "under", "a", "Creative", "Commons", "License", "(Attribution–", "Noncommercial–Share", "Alike", "3.0", "Unported", "license,", "as", "described", "at", "http://creative-", "commons.org/licenses/by-nc-sa/3.0/).", "1245" ]

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[ "Veerkamp", "et", "al.", "BMC", "Proceedings", "2010,", "4(Suppl", "1):S9", "http://www.biomedcentral.com/1753-6561/4/S1/S9", "P", "R", "O", "C", "E", "E", "D", "I", "N", "G", "S", "Open", "Access", "Simultaneous", "QTL", "detection", "and", "genomic", "breeding", "value", "estimation", "using", "high", "density", "SNP", "chips", "Roel", "F", "Veerkamp1*,", "Klara", "L", "Verbyla1,2,", "Han", "A", "Mulder1,", "Mario", "P", "L", "Calus1", "From", "13th", "European", "workshop", "on", "QTL", "mapping", "and", "marker", "assisted", "selection", "Wageningen,", "The", "Netherlands.", "20-21", "April", "2009", "Abstract", "Background:", "The", "simulated", "dataset", "of", "the", "13th", "QTL-MAS", "workshop", "was", "analysed", "to", "i)", "detect", "QTL", "and", "ii)", "predict", "breeding", "values", "for", "animals", "without", "phenotypic", "information.", "Several", "parameterisations", "considering", "all", "SNP", "simultaneously", "were", "applied", "using", "Gibbs", "sampling.", "Results:", "Fourteen", "QTL", "were", "detected", "at", "the", "different", "time", "points.", "Correlations", "between", "estimated", "breeding", "values", "were", "high", "between", "models,", "except", "when", "the", "model", "was", "used", "that", "assumed", "that", "all", "SNP", "effects", "came", "from", "one", "distribution.", "The", "model", "that", "used", "the", "selected", "14", "SNP", "found", "associated", "with", "QTL,", "gave", "close", "to", "unity", "correlations", "with", "the", "full", "parameterisations.", "Conclusions:", "Nine", "out", "of", "18", "QTL", "were", "detected,", "however", "the", "six", "QTL", "for", "inflection", "point", "were", "missed.", "Models", "for", "genomic", "selection", "were", "indicated", "to", "be", "fairly", "robust,", "e.g.", "with", "respect", "to", "accuracy", "of", "estimated", "breeding", "values.", "Still,", "it", "is", "worthwhile", "to", "investigate", "the", "number", "QTL", "underlying", "the", "quantitative", "traits,", "before", "choosing", "the", "model", "used", "for", "genomic", "selection.", "Background", "High", "density", "SNP", "chips", "with", "~50,000", "SNPs", "have", "become", "available", "for", "most", "livestock", "species.", "Breeding", "value", "estimation", "using", "all", "these", "SNPs", "simultaneously", "is", "expected", "to", "yield", "the", "highest", "accuracy", "[1].", "Several", "para-", "meterisations", "of", "the", "SNP", "effects", "in", "the", "statistical", "model", "have", "been", "suggested", "[2-5].", "The", "objectives", "of", "this", "study", "were", "to", "accurately", "identify", "QTL", "and", "predict", "breeding", "values", "in", "the", "simulated", "data", "of", "the", "13th", "QTL-MAS", "workshop,", "using", "different", "parameterisations", "for", "the", "SNP", "effects.", "Methods", "The", "simulated", "data", "of", "the", "13th", "QTL-MAS", "workshop", "is", "described", "Coster", "et", "al.", "[6].", "Simulated", "data", "were", "analysed", "per", "time", "point,", "and", "for", "QTL", "detection,", "the", "change", "between", "traits", "at", "subsequent", "time", "points", "was", "also", "used.", "*", "Correspondence:", "Roel.Veerkamp@wur.nl", "1Animal", "Breeding", "and", "Genomics", "Centre,", "ASG", "Wageningen", "UR,", "PO", "Box", "65,", "8200", "AB", "Lelystad,", "The", "Netherlands", "A", "pedigree", "based", "model", "was", "fitted", "using", "ASREML", "[7].", "The", "Gibbs", "sampler", "described", "initially", "by", "Meuwissen", "and", "Goddard", "[1]", "and", "Calus", "et", "al.", "[4,5]", "was", "used", "for", "models", "including", "the", "SNP", "parameterisations.", "The", "general", "model", "used", "was:", "nloc", "2", "yi", "", "", "", "animali", "", "", "", "haplotypeijk", "", "ei", ",", "where", "yi", "is", "j1", "k1", "the", "phenotypic", "record", "of", "animal", "i,", "µ", "is", "the", "average", "phe-", "notypic", "performance,", "animali", "is", "the", "random", "polygenic", "effect", "for", "animal", "i,", "haplotypeijk", "is", "a", "random", "effect", "for", "a", "paternal", "(k", "=", "1)", "or", "maternal", "(k", "=", "2)", "haplotype", "at", "locus", "j", "(of", "nloc", "loci)", "of", "animal", "i,", "and", "ei", "is", "a", "random", "residual", "for", "animal", "i.", "The", "first", "parameterisation", "was", "a", "simple", "BLUP", "model", "with", "the", "additive", "relationship", "matrix", "between", "the", "animals", "only.", "Other", "parameterisations", "assumed", "the", "SNP", "effects", "came", "from", "one", "distribution", "(SNP1),", "i.e.", "BayesA,", "from", "two", "distributions", "(SNP2", "i.e.", "BayesC),", "or", "from", "three", "distributions", "allowing", "for", "small,", "medium", "and", "large", "SNP", "effects", "(SNP3).", "A", "further", "parameterisation", "assumed", "a", "©", "2010", "Veerkamp", "et", "al;", "licensee", "BioMed", "Central", "Ltd.", "This", "is", "an", "open", "access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "License", "(http://creativecommons.org/licenses/by/2.0),", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited." ]

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[ "Fluch", "et", "al.", "BMC", "Research", "Notes", "2011,", "4:401", "http://www.biomedcentral.com/1756-0500/4/401", "R", "E", "S", "E", "A", "R", "C", "H", "A", "R", "T", "I", "C", "L", "E", "Open", "Access", "Characterization", "of", "variable", "EST", "SSR", "markers", "for", "Norway", "spruce", "(Picea", "abies", "L.)", "Silvia", "Fluch1*,", "Agnes", "Burg1,", "Dieter", "Kopecky1,", "Andreas", "Homolka1,", "Nadine", "Spiess1", "and", "Giovanni", "G", "Vendramin2", "Abstract", "Background:", "Norway", "spruce", "is", "widely", "distributed", "across", "Europe", "and", "the", "predominant", "tree", "of", "the", "Alpine", "region.", "Fast", "growth", "and", "the", "fact", "that", "timber", "can", "be", "harvested", "cost-effectively", "in", "relatively", "young", "populations", "define", "its", "status", "as", "one", "of", "the", "economically", "most", "important", "tree", "species", "of", "Northern", "Europe.", "In", "this", "study,", "EST", "derived", "simple", "sequence", "repeat", "(SSR)", "markers", "were", "developed", "for", "the", "assessment", "of", "putative", "functional", "diversity", "in", "Austrian", "Norway", "spruce", "stands.", "Results:", "SSR", "sequences", "were", "identified", "by", "analyzing", "14,022", "publicly", "available", "EST", "sequences.", "Tri-nucleotide", "repeat", "motifs", "were", "most", "abundant", "in", "the", "data", "set", "followed", "by", "penta-", "and", "hexa-nucleotide", "repeats.", "Specific", "primer", "pairs", "were", "designed", "for", "sixty", "loci.", "Among", "these,", "27", "displayed", "polymorphism", "in", "a", "testing", "population", "of", "16", "P.", "abies", "individuals", "sampled", "across", "Austria", "and", "in", "an", "additional", "screening", "population", "of", "96", "P.", "abies", "individuals", "from", "two", "geographically", "distinct", "Austrian", "populations.", "Allele", "numbers", "per", "locus", "ranged", "from", "two", "to", "17", "with", "observed", "heterozygosity", "ranging", "from", "0.075", "to", "0.99.", "Conclusions:", "We", "have", "characterized", "variable", "EST", "SSR", "markers", "for", "Norway", "spruce", "detected", "in", "expressed", "genes.", "Due", "to", "their", "moderate", "to", "high", "degree", "of", "variability", "in", "the", "two", "tested", "screening", "populations,", "these", "newly", "developed", "SSR", "markers", "are", "well", "suited", "for", "the", "analysis", "of", "stress", "related", "functional", "variation", "present", "in", "Norway", "spruce", "populations.", "Background", "Natural", "populations", "of", "Picea", "abies", "L.", "(Norway", "spruce)", "are", "found", "from", "north-western", "Europe", "outside", "perma-", "frost", "areas", "down", "to", "northern", "Greece,", "westwards", "to", "the", "Massif", "Central", "(France)", "and", "east", "to", "the", "Ural", "Mountains.", "Picea", "abies", "is", "growing", "above", "400-500", "m", "and", "ascends", "close", "to", "2000", "m", "in", "the", "Alps.", "Studies", "on", "genetic", "variation", "based", "on", "allozymes", "have", "shown", "that", "Picea", "abies", "genetic", "differentiation", "among", "populations", "is", "rather", "low", "over", "its", "whole", "distribution", "range", "[1,2].", "Previous", "studies", "on", "the", "genetic", "structure", "of", "P.", "abies", "using", "organelle", "markers", "showed", "pronounced", "differentiation", "between", "north-east", "boreal", "origins", "and", "areas", "in", "the", "central", "European", "moun-", "tains", "[3,4],", "supporting", "the", "hypothesis", "of", "two", "distinct", "main", "glacial", "refugia", "as", "postulated", "from", "pollen", "data", "[5].", "Initial", "reports", "on", "the", "occurrence", "of", "SSRs", "in", "conifers", "such", "as", "Pinus", "radiata", "[6],", "Pinus", "sylvestris", "[7]", "or", "Picea", "*", "Correspondence:", "silvia.fluch@ait.ac.at", "1AIT", "Austrian", "Institute", "of", "Technology", "GmbH,", "Health", "&", "Environment", "Department,", "Bioresources,", "3430", "Tulln,", "Austria", "Full", "list", "of", "author", "information", "is", "available", "at", "the", "end", "of", "the", "article", "abies", "[8]", "have", "shown", "that", "marker", "development", "for", "such", "complex", "genomes", "is", "difficult.", "Frequently", "several", "DNA", "fragments", "in", "addition", "to", "the", "expected", "ones", "are", "amplified", "when", "using", "primers", "flanking", "putative", "SSR", "regions.", "This", "can", "be", "attributed", "to", "the", "very", "large", "size", "of", "the", "conifer", "genomes,", "with", "Norway", "spruce", "having", "39.140", "Mb", "in", "the", "diploid", "genome", "(2n", "=", "24)", "as", "well", "as", "the", "high", "proportion", "of", "repetitive", "DNA", "in", "the", "conifer", "genomes", "[9].", "These", "repetitive", "elements", "as", "well", "as", "pseudogenes", "frequently", "produce", "complex", "amplification", "products", "from", "multiple", "loci", "[10,11].", "To", "overcome", "this", "problem,", "Scotti", "et", "al.", "[12]", "showed", "that", "by", "isolating", "di-nucleotide", "SSRs", "from", "cDNA", "libraries", "of", "conifer", "species", "this", "problem", "can", "be", "over-", "come", "relying", "on", "the", "fact", "that", "expressed", "genes", "are", "less", "likely", "to", "be", "of", "repetitive", "nature", "in", "the", "genome.", "Following", "this", "line", "of", "exploiting", "the", "advantages", "of", "publicly", "available", "data", "on", "expressed", "sequences", "(ESTs)", "as", "source", "for", "marker", "development", "[13]", "as", "described", "also", "by", "Rungis", "et", "al.", "[14]", "for", "conifers,", "we", "used", "Norway", "spruce", "EST", "sequences", "from", "NCBI", "for", "in", "silico", "identification", "of", "SSR", "regions", "which", "could", "serve", "for", "marker", "development.", "©", "2011", "Fluch", "et", "al;", "licensee", "BioMed", "Central", "Ltd.", "This", "is", "an", "open", "access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "License", "(http://creativecommons.org/licenses/by/2.0),", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited." ]

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[ "J", "Neurol", "(2011)", "258:212–217", "DOI", "10.1007/s00415-010-5712-3", "O", "R", "I", "G", "I", "N", "A", "L", "C", "O", "M", "M", "U", "N", "I", "C", "A", "T", "I", "O", "N", "Cold", "paresis", "in", "multifocal", "motor", "neuropathy", "Dirk", "C.", "G.", "Straver", "•", "Jan-Thies", "H.", "van", "Asseldonk", "•", "Nicolette", "C.", "Notermans", "•", "John", "H.", "J.", "Wokke", "•", "Leonard", "H.", "van", "den", "Berg", "•", "Hessel", "Franssen", "Received:", "25", "May", "2010", "/", "Revised:", "9", "August", "2010", "/", "Accepted:", "11", "August", "2010", "/", "Published", "online:", "28", "August", "2010", "The", "Author(s)", "2010.", "This", "article", "is", "published", "with", "open", "access", "at", "Springerlink.com", "Abstract", "Increased", "weakness", "during", "cold", "(cold", "paresis)", "was", "reported", "in", "single", "cases", "of", "multifocal", "motor", "neuropa-", "thy", "(MMN).", "This", "was", "unexpected", "because", "demyelination", "is", "a", "feature", "of", "MMN", "and", "symptoms", "of", "demyelination", "improve,", "rather", "than", "worsen,", "in", "cold.", "It", "was", "hypothesized", "that", "cold", "paresis", "in", "MMN", "does", "not", "reflect", "demyelination", "only,", "but", "may", "indicate", "the", "existence", "of", "inflammatory", "nerve", "lesions", "with", "permanently", "depolarized", "axons", "that", "only", "just", "conduct", "at", "normal", "temperature,", "but", "fail", "at", "lower", "tempera-", "tures.", "We", "investigated", "symptoms", "of", "cold", "paresis", "in", "50", "MMN", "patients,", "48", "chronic", "inflammatory", "demyelinating", "polyneuropathy", "(CIDP)", "patients,", "35", "progressive", "spinal", "muscular", "atrophy", "(PSMA)", "patients,", "and", "25", "chronic", "idio-", "pathic", "axonal", "polyneuropathy", "patients.", "We", "also", "investi-", "gated", "symptoms", "of", "increased", "weakness", "during", "warmth", "(heat", "paresis).", "Cold", "paresis", "was", "reported", "more", "often", "than", "heat", "paresis.", "Cold", "paresis", "was", "most", "frequently", "reported", "in", "MMN.", "Multivariate", "analysis", "indicated", "that", "MMN", "patients", "had", "a", "4-", "to", "6-fold", "higher", "risk", "of", "reporting", "cold", "paresis", "than", "CIDP", "or", "PSMA", "patients.", "Because", "cold", "paresis", "is", "not", "consistent", "with", "demyelination,", "the", "lesions", "in", "MMN", "may", "involve", "other", "mechanisms", "than", "demyelination", "only.", "In", "conclusion,", "symptoms", "of", "cold", "paresis", "are", "common", "in", "D.", "C.", "G.", "Straver", "J.-T.", "H.", "van", "Asseldonk", "N.", "C.", "Notermans", "J.", "H.", "J.", "Wokke", "L.", "H.", "van", "den", "Berg", "H.", "Franssen", "Neuromuscular", "Disease", "Group,", "Department", "of", "Neurology,", "Rudolf", "Magnus", "Institute", "of", "Neuroscience,", "University", "Medical", "Center", "Utrecht,", "Heidelberglaan", "100,", "3584", "CX", "Utrecht,", "The", "Netherlands", "H.", "Franssen", "(&)", "Department", "of", "Neurology,", "F02.230,", "University", "Medical", "Center", "Utrecht,", "PO", "Box", "85500,", "3508", "GA", "Utrecht,", "The", "Netherlands", "e-mail:", "H.Franssen@umcutrecht.nl", "123", "peripheral", "nervous", "system", "disorders,", "particularly", "in", "MMN.", "This", "supports", "the", "above-described", "hypothesis.", "Keywords", "Multifocal", "motor", "neuropathy", "Chronic", "inflammatory", "demyelinating", "polyneuropathy", "Chronic", "idiopathic", "axonal", "polyneuropathy", "Progressive", "spinal", "muscular", "atrophy", "Cold", "paresis", "Abbreviations", "CB", "Conduction", "block", "CIAP", "Chronic", "idiopathic", "axonal", "polyneuropathy", "CIDP", "Chronic", "inflammatory", "demyelinating", "polyneuropathy", "MMN", "Multifocal", "motor", "neuropathy", "PSMA", "Progressive", "spinal", "muscular", "atrophy", "Introduction", "The", "effect", "of", "temperature", "on", "symptoms", "of", "neurological", "disorders", "is", "complicated", "and", "has", "not", "been", "fully", "explored,", "neither", "in", "patients,", "nor", "in", "physiological", "research.", "A", "well-", "known", "effect", "is", "the", "worsening", "of", "symptoms", "in", "multiple", "sclerosis", "after", "a", "hot", "bath", "[20,", "25].", "In", "peripheral", "neuropa-", "thies,", "similar", "effects", "were", "described.", "In", "a", "patient", "with", "chronic", "inflammatory", "demyelinating", "polyneuropathy", "(CIDP),", "symptoms", "considerably", "increased", "during", "fever", "and", "in", "seven", "patients", "with", "various", "demyelinating", "neuropathies,", "electrophysiological", "signs", "of", "conduction", "block", "increased", "after", "warming", "and", "decreased", "after", "cooling", "[4,", "8,", "20].", "This", "so-called", "heat", "paresis", "may", "occur", "in", "demyelinating", "disor-", "ders", "and", "is", "caused", "by", "an", "unfavorable", "combination", "of", "fac-", "tors", "that", "block", "saltatory", "conduction", "between", "an", "active", "node" ]

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[ "Cancer", "Cell", "International", "ICNATNERCNERATCIOELNLAL", "Primary", "research", "Lack", "of", "p53", "function", "promotes", "radiation-induced", "mitotic", "catastrophe", "in", "mouse", "embryonic", "fibroblast", "cells", "Fiorenza", "Ianzini*1,", "Alessandro", "Bertoldo2,", "Elizabeth", "A", "Kosmacek2,", "Stacia", "L", "Phillips1", "and", "Michael", "A", "Mackey3", "BioMed", "Central", "Open", "Access", "Address:", "1Departments", "of", "Pathology,", "Radiation", "Oncology,", "and", "Biomedical", "Engineering,", "University", "of", "Iowa,", "Iowa", "City,", "IA", "52242,", "USA,", "2Department", "of", "Biomedical", "Engineering,", "University", "of", "Iowa,", "Iowa", "City,", "IA", "52242,", "USA", "and", "3Departments", "of", "Biomedical", "Engineering", "and", "Pathology,", "University", "of", "Iowa,", "Iowa", "City,", "IA", "52242,", "USA", "Email:", "Fiorenza", "Ianzini*", "-", "fiorenza-ianzini@uiowa.edu;", "Alessandro", "Bertoldo", "-", "alessandro_bertoldo@yahoo.com;", "Elizabeth", "A", "Kosmacek", "-", "ekosmace@engineering.uiowa.edu;", "Stacia", "L", "Phillips", "-", "stacia-phillips@uiowa.edu;", "Michael", "A", "Mackey", "-", "michael-", "mackey@uiowa.edu", "*", "Corresponding", "author", "Published:", "26", "April", "2006", "Cancer", "Cell", "International", "2006,", "6:11", "doi:10.1186/1475-2867-6-11", "This", "article", "is", "available", "from:", "http://www.cancerci.com/content/6/1/11", "Received:", "21", "February", "2006", "Accepted:", "26", "April", "2006", "©", "2006", "Ianzini", "et", "al;", "licensee", "BioMed", "Central", "Ltd.", "This", "is", "an", "Open", "Access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "License", "(http://creativecommons.org/licenses/by/2.0),", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited.", "Abstract", "Background:", "We", "have", "demonstrated", "that", "in", "some", "human", "cancer", "cells", "both", "chronic", "mild", "heat", "and", "ionizing", "radiation", "exposures", "induce", "a", "transient", "block", "in", "S", "and", "G2", "phases", "of", "the", "cell", "cycle.", "During", "this", "delay,", "cyclin", "B1", "protein", "accumulates", "to", "supranormal", "levels,", "cyclin", "B1-dependent", "kinase", "is", "activated,", "and", "abrogation", "of", "the", "G2/M", "checkpoint", "control", "occurs", "resulting", "in", "mitotic", "catastrophe", "(MC).", "Results:", "Using", "syngenic", "mouse", "embryonic", "fibroblasts", "(MEF)", "with", "wild-type", "or", "mutant", "p53,", "we", "now", "show", "that,", "while", "both", "cell", "lines", "exhibit", "delays", "in", "S/G2", "phase", "post-irradiation,", "the", "mutant", "p53", "cells", "show", "elevated", "levels", "of", "cyclin", "B1", "followed", "by", "MC,", "while", "the", "wild-type", "p53", "cells", "present", "both", "a", "lower", "accumulation", "of", "cyclin", "B1", "and", "a", "lower", "frequency", "of", "MC.", "Conclusion:", "These", "results", "are", "in", "line", "with", "studies", "reporting", "the", "role", "of", "p53", "as", "a", "post-", "transcriptional", "regulator", "of", "cyclin", "B1", "protein", "and", "confirm", "that", "dysregulation", "of", "cyclin", "B1", "promote", "radiation-induced", "MC.", "These", "findings", "might", "be", "exploited", "to", "design", "strategies", "to", "augment", "the", "yield", "of", "MC", "in", "tumor", "cells", "that", "are", "resistant", "to", "radiation-induced", "apoptosis.", "Introduction", "Mitotic", "catastrophe", "(MC)", "has", "been", "observed", "following", "alterations", "in", "specific", "cellular", "proteins,", "or", "by", "treatment", "of", "cells", "with", "chemicals,", "heat,", "and/or", "ionizing", "radiation", "[1-", "13].", "MC", "is", "characterized", "by", "an", "aberrant", "nuclear", "morphol-", "ogy", "observed", "following", "premature", "entry", "into", "mitosis", "[10]", "and", "often", "results", "in", "the", "generation", "of", "aneuploid", "and", "poly-", "ploid", "cell", "progeny.", "The", "initiating", "event", "in", "this", "process", "involves", "the", "premature", "entry", "of", "cells", "into", "mitosis;", "cells", "undergo", "a", "spontaneous", "chromosome", "condensation", "that", "produces", "chromosome", "morphologies", "very", "similar", "to", "those", "observed", "when", "metaphase", "cells", "are", "fused", "with", "cells", "located", "late", "in", "the", "cell", "cycle", "[11].", "Thus", "we", "consider", "these", "abnormal", "mitotic", "figures", "as", "indicative", "of", "cells", "undergoing", "spontaneous", "premature", "chromosome", "condensation", "(SPCC).", "These", "cells", "entering", "into", "mitosis", "prematurely", "often", "either", "fail", "to", "achieve", "cytokinesis", "or", "divide", "and", "fuse", "shortly", "thereafter,", "and", "later", "exhibit", "the", "features", "of", "MC.", "These", "cells", "almost", "always", "die", "[9];", "however,", "some", "studies", "have", "suggested", "that", "a", "small", "fraction", "of", "cells", "might", "survive", "Page", "1", "of", "8", "(page", "number", "not", "for", "citation", "purposes)" ]

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[ "The", "Role", "of", "Actin", "Turnover", "in", "Retrograde", "Actin", "Network", "Flow", "in", "Neuronal", "Growth", "Cones", "David", "Van", "Goor,", "Callen", "Hyland,", "Andrew", "W.", "Schaefer,", "Paul", "Forscher*", "Department", "of", "Molecular,", "Cellular,", "and", "Developmental", "Biology,", "Yale", "University,", "New", "Haven,", "Connecticut,", "United", "States", "of", "America", "Abstract", "The", "balance", "of", "actin", "filament", "polymerization", "and", "depolymerization", "maintains", "a", "steady", "state", "network", "treadmill", "in", "neuronal", "growth", "cones", "essential", "for", "motility", "and", "guidance.", "Here", "we", "have", "investigated", "the", "connection", "between", "depolymerization", "and", "treadmilling", "dynamics.", "We", "show", "that", "polymerization-competent", "barbed", "ends", "are", "concentrated", "at", "the", "leading", "edge", "and", "depolymerization", "is", "distributed", "throughout", "the", "peripheral", "domain.", "We", "found", "a", "high-to-low", "G-actin", "gradient", "between", "peripheral", "and", "central", "domains.", "Inhibiting", "turnover", "with", "jasplakinolide", "collapsed", "this", "gradient", "and", "lowered", "leading", "edge", "barbed", "end", "density.", "Ultrastructural", "analysis", "showed", "dramatic", "reduction", "of", "leading", "edge", "actin", "filament", "density", "and", "filament", "accumulation", "in", "central", "regions.", "Live", "cell", "imaging", "revealed", "that", "the", "leading", "edge", "retracted", "even", "as", "retrograde", "actin", "flow", "rate", "decreased", "exponentially.", "Inhibition", "of", "myosin", "II", "activity", "before", "jasplakinolide", "treatment", "lowered", "baseline", "retrograde", "flow", "rates", "and", "prevented", "leading", "edge", "retraction.", "Myosin", "II", "activity", "preferentially", "affected", "filopodial", "bundle", "disassembly", "distinct", "from", "the", "global", "effects", "of", "jasplakinolide", "on", "network", "turnover.", "We", "propose", "that", "growth", "cone", "retraction", "following", "turnover", "inhibition", "resulted", "from", "the", "persistence", "of", "myosin", "II", "contractility", "even", "as", "leading", "edge", "assembly", "rates", "decreased.", "The", "buildup", "of", "actin", "filaments", "in", "central", "regions", "combined", "with", "monomer", "depletion", "and", "reduced", "polymerization", "from", "barbed", "ends", "suggests", "a", "mechanism", "for", "the", "observed", "exponential", "decay", "in", "actin", "retrograde", "flow.", "Our", "results", "show", "that", "growth", "cone", "motility", "is", "critically", "dependent", "on", "continuous", "disassembly", "of", "the", "peripheral", "actin", "network.", "Citation:", "Van", "Goor", "D,", "Hyland", "C,", "Schaefer", "AW,", "Forscher", "P", "(2012)", "The", "Role", "of", "Actin", "Turnover", "in", "Retrograde", "Actin", "Network", "Flow", "in", "Neuronal", "Growth", "Cones.", "PLoS", "ONE", "7(2):", "e30959.", "doi:10.1371/journal.pone.0030959", "Editor:", "Cara", "Gottardi,", "Northwestern", "University", "Feinberg", "School", "of", "Medicine,", "United", "States", "of", "America", "Received", "October", "7,", "2011;", "Accepted", "December", "28,", "2011;", "Published", "February", "16,", "2012", "Copyright:", "2012", "Van", "Goor", "et", "al.", "This", "is", "an", "open-access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "License,", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "author", "and", "source", "are", "credited.", "Funding:", "This", "work", "was", "supported", "by", "National", "Institutes", "of", "Health", "grants", "RO1-NS28695", "and", "RO1", "NS51786", "to", "P.F.", "and", "the", "Nikon", "Partners-in-Research", "Program.", "The", "funders", "had", "no", "role", "in", "study", "design,", "data", "collection", "and", "analysis,", "decision", "to", "publish,", "or", "preparation", "of", "the", "manuscript.", "Competing", "Interests:", "Paul", "Forscher", "was", "a", "‘‘Nikon", "Partner", "in", "Research’’", "during", "some", "of", "the", "period", "this", "research", "was", "conducted.", "This", "program", "gave", "his", "group", "access", "to", "loaned", "imaging", "equipment", "for", "the", "experiments.", "There", "was", "no", "personal", "compensation", "involved", "nor", "did", "the", "agreement", "in", "any", "way", "infringe", "on", "the", "freedom", "to", "share", "and", "publish", "the", "authors’", "scientific", "results.", "Moreover,", "this", "agreement", "does", "not", "alter", "the", "authors’", "adherence", "to", "all", "the", "PLoS", "ONE", "policies", "on", "sharing", "data", "and", "materials.", "*", "E-mail:", "paul.forscher@yale.edu", "Introduction", "Growth", "cone", "structure", "and", "motility", "emerge", "from", "the", "balance", "of", "actin", "filament", "polymerization,", "depolymerization,", "transport,", "and", "cross-linking", "into", "various", "network", "architectures.", "Motile", "actin", "structures", "continuously", "consume", "energy", "and", "cycle", "their", "compo-", "nents.", "As", "structure", "is", "continuously", "turned", "over,", "the", "system", "can", "respond", "rapidly", "to", "extracellular", "guidance", "cues;", "small", "changes", "affe-", "cting", "actin", "structure", "may", "lead", "to", "rapid", "changes", "in", "growth", "cone", "morphology", "and", "behavior.", "In", "the", "absence", "of", "changes", "in", "substrate", "or", "soluble", "guidance", "cues,", "actin", "filament", "polymerization,", "depoly-", "merization,", "and", "transport", "maintain", "a", "steady-state", "balance", "where", "there", "is", "little", "change", "in", "position", "and", "growth", "cone", "morphology", "despite", "continuous", "retrograde", "actin", "flux.", "In", "such", "a", "system,", "perturbations", "of", "a", "single", "process", "can", "reveal", "information", "on", "the", "interdependency", "of", "the", "other", "processes", "in", "maintaining", "the", "steady-", "state", "balance.", "Actin", "assembly", "at", "the", "leading", "edge", "produces", "filopodia", "and", "veil", "structures", "which", "are", "transported", "centripetally", "by", "a", "process", "called", "retrograde", "flow.", "Both", "leading", "edge", "polymerization", "and", "myosin", "II", "contractility", "contribute", "to", "retrograde", "actin", "movement.", "Addition", "of", "actin", "subunits", "between", "the", "polymerized", "actin", "array", "and", "the", "leading", "edge", "membrane", "pushes", "the", "entire", "network", "centripetally", "[1].", "According", "to", "the", "dynamic", "network", "contraction", "model", "[2],", "myosin", "II", "localized", "in", "the", "transition", "zone", "(Fig.", "1", "and", "Fig.", "S1D–F)", "generates", "contractile", "force,", "which", "propagates", "through", "the", "me-", "chanical", "continuum", "of", "the", "actin", "array", "and", "displaces", "the", "entire", "network.", "Retrograde", "flow", "rate", "is", "affected", "by", "myosin", "II", "activity.", "Flow", "rates", "decrease", "up", "to", "50%", "in", "growth", "cones", "exposed", "to", "the", "myosin", "II", "ATPase", "inhibitor", "blebbistatin", "and", "residual", "retrograde", "flow", "can", "largely", "be", "accounted", "for", "by", "the", "force", "of", "leading", "edge", "polymerization", "[3].", "Filopodia", "and", "veil", "actin", "are", "continuously", "assembled", "and", "tran-", "sported", "rearward", "by", "retrograde", "flow.", "The", "half-life", "of", "growth", "cone", "veil", "actin", "has", "been", "estimated", "to", "be", "1–3", "min", "whereas", "filopodial", "actin", "bundles", "are", "considerably", "more", "stable", "[4]", "and", "their", "recycling", "requires", "non-muscle", "myosin", "II", "[3].", "To", "maintain", "the", "growth", "cone", "periphery", "in", "a", "steady", "state", "both", "of", "these", "actin", "structures", "must", "be", "continuously", "recycled.", "Despite", "the", "potential", "mechanistic", "impor-", "tance", "of", "filament", "recycling", "in", "regulation", "of", "growth", "cone", "motility,", "very", "little", "is", "known", "about", "the", "kinetics", "or", "spatial", "characteristics", "of", "this", "processes.", "In", "the", "current", "study", "we", "use", "jasplakinolide,", "a", "cyclic", "depsipeptide", "from", "the", "marine", "sponge", "Jaspis", "johnstoni,", "to", "inhibit", "network", "turnover", "and", "investigate", "acute", "effects", "on", "actin", "filament", "structure", "and", "dynamic", "behavior.", "Jasplakinolide", "cooperatively", "binds", "and", "stabi-", "PLoS", "ONE", "|", "www.plosone.org", "1", "February", "2012", "|", "Volume", "7", "|", "Issue", "2", "|", "e30959" ]

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[ "Nakanishi-Minami", "et", "al.", "Diabetology", "&", "Metabolic", "Syndrome", "2012,", "4:6", "http://www.dmsjournal.com/content/4/1/6", "S", "H", "O", "R", "T", "R", "E", "P", "O", "R", "T", "DIABETOLOGY", "&", "METABOLIC", "SYNDROME", "Open", "Access", "Metabolic", "syndrome", "correlates", "intracoronary", "stenosis", "detected", "by", "multislice", "computed", "tomography", "in", "male", "subjects", "with", "sleep-", "disordered", "breathing", "Tomoko", "Nakanishi-Minami1,", "Ken", "Kishida1,2,6*,", "Yasuhiko", "Nakagawa1,", "Munetaka", "Nishio3,", "Chisa", "Nakagawa4,", "Yoshiharu", "Nishida3,", "Koji", "Yanagi3,", "Ryoko", "Yoshida5,", "Tohru", "Funahashi1,2", "and", "Iichiro", "Shimomura1", "Abstract", "Background:", "Sleep-disordered", "breathing", "(SDB),", "especially", "obstructive", "sleep", "apnea", "(OSA),", "has", "frequent", "complications", "include", "hypertension,", "dyslipidemia", "and", "insulin", "resistance", "based", "on", "abdominal", "obesity", "or", "excess", "visceral", "fat", "(called", "Syndrome", "Z).", "OSA", "is", "a", "potential", "risk", "factor", "for", "cardiovascular", "diseases.", "The", "clinical", "characteristics", "of", "Japanese", "OSA", "subjects", "with", "OSA", "remain", "unclear.", "The", "present", "study", "investigated", "prevalence", "and", "predictive", "factors", "of", "intracoronary", "stenosis", "detected", "by", "multislice", "computed", "tomography", "(MSCT)", "in", "Japanese", "male", "subjects", "with", "SDB/OSA.", "Findings:", "The", "study", "(O-VFStudy)", "subjects", "were", "39", "Japanese", "men", "with", "SDB/OSA", "who", "underwent", "all-night", "cardiorespiratory", "monitoring", "with", "fully", "attended", "polysomnography,", "and", "moreover", "both", "fat", "computed", "tomography", "(CT)", "scan", "and", "64-row", "MSCT", "coronary", "angiography.", "The", "prevalence", "of", "coronary", "stenosis", "in", "this", "selected", "population", "with", "SDB/OSA", "was", "15%.", "Logistic", "regression", "analysis", "showed", "a", "significant", "relationship", "between", "age-adjusted", "CAD", "and", "metabolic", "syndrome", "(p", "<", "0.05),", "but", "not", "serum", "adiponectin", "levels", "and", "nocturnal", "fall", "in", "adiponectin.", "Subjects", "with", "the", "metabolic", "syndrome", "had", "significantly", "higher", "prevalence", "of", "CAD", "(31.3", "versus", "4.3%,", "p", "=", "0.033),", "and", "lower", "levels", "of", "serum", "adiponectin", "(4.5", "±", "0.6", "versus", "6.4", "±", "0.6", "μg/mL,", "p", "=", "0.014),", "compared", "with", "groups", "without", "the", "metabolic", "syndrome.", "Conclusions:", "The", "present", "study", "describes", "that", "the", "prevalence", "of", "greater", "than", "50%", "intracoronary", "stenotic", "lesions", "detected", "by", "MSCT", "was", "15%", "and", "the", "metabolic", "syndrome", "was", "correlated", "with", "intracoronary", "stenosis", "detected", "by", "MSCT", "in", "Japanese", "SDB/OSA", "subjects.", "Trial", "Registration:", "UMIN", "000002997", "https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr.cgi?", "function=brows&action=brows&type=summary&recptno=R000003633&language=E.", "Keywords:", "Coronary", "Stenosis,", "Sleep", "apnea-hypopnea,", "Visceral", "fat,", "Adiponectin", "Background", "Sleep-disordered", "breathing", "(SDB),", "especially", "obstructive", "sleep", "apnea", "(OSA),", "is", "a", "potential", "risk", "factor", "for", "cardio-", "vascular", "diseases,", "including", "coronary", "artery", "disease", "(CAD)", "and", "stroke", "[1-3].", "OSA", "is", "common", "in", "middle-age", "men", "[4],", "and", "frequent", "complications", "include", "*", "Correspondence:", "kkishida@imed2.med.osaka-u.ac.jp", "1Department", "of", "Metabolic", "Medicine,", "Graduate", "School", "of", "Medicine,", "Osaka", "University,", "Suita,", "Osaka", "565-0871,", "Japan", "Full", "list", "of", "author", "information", "is", "available", "at", "the", "end", "of", "the", "article", "hypertension,", "dyslipidemia", "and", "insulin", "resistance", "based", "on", "abdominal", "obesity", "or", "excess", "visceral", "fat", "[5-8].", "Visc-", "eral", "fat", "is", "a", "huge", "endocrine", "organ", "producing", "a", "variety", "of", "bioactive", "substances,", "conceptualized", "as", "‘adipocytokines’", "[9].", "Our", "group", "discovered", "adiponectin", "as", "an", "adipocyto-", "kine", "in", "the", "human", "adipose", "cDNA", "library", "[10],", "which", "has", "anti-atherosclerotic", "property", "[11].", "We", "have", "recently", "demonstrated", "that,", "1)", "production", "of", "adiponectin", "is", "dys-", "regulated", "in", "intra-abdominal", "obese", "patients", "with", "severe", "OSA", "[12,13],", "and", "2)", "night-time", "onset", "of", "acute", "coronary", "©", "2012", "Nakanishi-Minami", "et", "al;", "licensee", "BioMed", "Central", "Ltd.", "This", "is", "an", "Open", "Access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "License", "(http://creativecommons.org/licenses/by/2.0),", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited." ]

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[ "Shi", "et", "al.", "Radiation", "Oncology", "2012,", "7:114", "http://www.ro-journal.com/content/7/1/114", "R", "E", "S", "E", "A", "R", "C", "H", "Open", "Access", "Computed", "tomography-guided", "permanent", "brachytherapy", "for", "locoregional", "recurrent", "gastric", "cancer", "Liangrong", "Shi1,", "Changping", "Wu1*,", "Jun", "Wu1,", "Wenjie", "Zhou1,", "Mei", "Ji1,", "Hongyu", "Zhang1,", "Jiemin", "Zhao1,", "Yuanquan", "Huang2,", "Honglei", "Pei3,", "Zhong", "Li4,", "Jingfang", "Ju5", "and", "Jingting", "Jiang1*", "Abstract", "Background:", "Locoregional", "recurrence", "is", "the", "typical", "pattern", "of", "recurrence", "in", "gastric", "cancer,", "and", "cannot", "be", "removed", "by", "surgery", "in", "most", "of", "the", "patients.", "We", "aimed", "to", "evaluate", "the", "feasibility", "and", "efficacy", "of", "computed", "tomography", "(CT)-guided", "brachytherapy", "for", "patients", "with", "locoregional", "recurrent", "gastric", "cancer.", "Materials", "and", "methods:", "We", "reviewed", "the", "case", "histories", "of", "28", "patients", "with", "locoregional", "recurrent", "gastric", "cancer", "that", "were", "selected", "for", "CT-", "guided", "brachytherapy", "by", "a", "multidisciplinary", "team.", "The", "clinical", "data", "of", "the", "patients", "including", "patient", "characteristics,", "treatment", "parameters,", "short-term", "effects,", "and", "survival", "data", "were", "collected", "and", "analyzed.", "Results:", "15-75", "125I", "seeds", "were", "implanted", "into", "each", "patient", "to", "produce", "a", "minimal", "peripheral", "dose", "(MPD)", "100-", "160", "Gy.", "Median", "day", "0", "dosimetry", "was", "significant", "for", "the", "following:", "V100", "(the", "volume", "treated", "with", "the", "prescription", "dose)", "95.8%", "(90.2-120.5%)", "and", "D90", "(prescription", "dose", "received", "by", "at", "least", "90%", "of", "the", "volume)", "105.2%", "(98.0-124.6%)", "of", "prescription", "dose.", "No", "serious", "complications", "occurred", "during", "the", "study.", "Two", "months", "after", "brachytherapy,", "complete", "response,", "partial", "response", "and", "progressive", "disease", "were", "observed", "in", "50.0%,", "28.6%", "and", "21.4%", "of", "patients,", "respectively.", "The", "median", "survival", "time", "was", "22.0", "±", "5.2", "months,", "and", "the", "1,", "2,and", "3-year", "survival", "rate", "was", "89", "±", "6%,", "52", "±", "10%", "and", "11", "±", "7%,", "respectively.", "A", "univariate", "analysis", "showed", "that", "the", "tumor", "size", "was", "a", "significant", "predictor", "of", "overall", "survival", "(P", "=", "0.034).", "Patients", "with", "tumors", "<3", "cm", "had", "relatively", "higher", "complete", "response", "rate", "(66.7%),", "compared", "to", "those", "with", "tumors", ">3", "cm", "(30.8%).", "The", "PTV", "(planning", "target", "volume)", "smaller", "than", "45", "cm3", "was", "significantly", "correlated", "with", "achieving", "complete", "tumor", "eradication", "in", "the", "treated", "region", "(P", "=", "0.020).", "Conclusions:", "For", "selected", "patients", "with", "limited", "locoregional", "recurrent", "gastric", "cancer,", "CT-guided", "brachytherapy", "using", "125I", "seeds", "implantation", "can", "provide", "a", "high", "local", "control", "rate,", "with", "minimal", "trauma.", "Keywords:", "Gastric", "cancer,", "Surgery,", "Locoregional", "recurrence,", "Brachytherapy,", "Iodine-125", "seed", "Introduction", "Despite", "a", "remarkable", "decline", "of", "the", "incidence", "during", "the", "second", "half", "of", "the", "20th", "century,", "gastric", "cancer", "still", "remains", "as", "the", "fourth", "most", "common", "cancer", "worldwide", "and", "the", "second", "most", "common", "cause", "of", "cancer-related", "death", "[1].", "Nearly", "two-thirds", "of", "gastric", "cancer", "cases", "occur", "in", "developing", "countries", "and", "42%", "in", "China", "alone", "[2].", "The", "prognosis", "of", "locally", "advanced", "gastric", "cancer", "remains", "*", "Correspondence:", "wcpjjt@163.com;", "jjtnew@163.com", "1Department", "of", "Oncology,", "The", "Third", "Affiliated", "Hospital,", "Soochow", "University,", "185", "Juqian", "Street,", "Changzhou", "213003,", "Jiangsu", "Province,", "China", "Full", "list", "of", "author", "information", "is", "available", "at", "the", "end", "of", "the", "article", "dismal", "even", "after", "potentially", "curative", "resection,", "adjuvant", "chemotherapy", "and", "radiotherapy", "[3].", "The", "5-year", "overall", "survival", "(OS)", "rates", "remain", "between", "30%", "to", "40%", "[3,4].", "Tumor", "recurrence", "is", "the", "main", "cause", "of", "the", "failure", "of", "treatment.", "Prospective", "studies", "have", "shown", "that", "the", "recurrence", "of", "gastric", "cancer", "was", "most", "commonly", "involved", "with", "locoregional", "recurrence,", "heamatogenous", "metastasis,", "and", "peritoneal", "lesions", "[5-7].", "Most", "of", "the", "patients", "with", "recurrent", "gastric", "cancer", "present", "advanced", "progression,", "such", "as", "multiple", "heamatogenous", "metastasis,", "extensive", "lymphatic.", "In", "such", "cases,", "systemic", "chemotherapy", "is", "the", "only", "potential", "treatment", "available", "to", "patients.", "However,", "for", "©", "2012", "Shi", "et", "al.;", "licensee", "BioMed", "Central", "Ltd.", "This", "is", "an", "Open", "Access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "License", "(http://creativecommons.org/licenses/by/2.0),", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited." ]

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[ "The", "Nitric", "Oxide", "Pathway", "Provides", "Innate", "Antiviral", "Protection", "in", "Conjunction", "with", "the", "Type", "I", "Interferon", "Pathway", "in", "Fibroblasts", "Devangi", "R.", "Mehta,", "Ali", "A.", "Ashkar,", "Karen", "L.", "Mossman*", "Department", "of", "Pathology", "and", "Molecular", "Medicine,", "McMaster", "Immunology", "Research", "Centre,", "Michael", "DeGroote", "Institute", "for", "Infectious", "Disease", "Research,", "McMaster", "University,", "Hamilton,", "Ontario,", "Canada", "Abstract", "The", "innate", "host", "response", "to", "virus", "infection", "is", "largely", "dominated", "by", "the", "production", "of", "type", "I", "interferon", "and", "interferon", "stimulated", "genes.", "In", "particular,", "fibroblasts", "respond", "robustly", "to", "viral", "infection", "and", "to", "recognition", "of", "viral", "signatures", "such", "as", "dsRNA", "with", "the", "rapid", "production", "of", "type", "I", "interferon;", "subsequently,", "fibroblasts", "are", "a", "key", "cell", "type", "in", "antiviral", "protection.", "We", "recently", "found,", "however,", "that", "primary", "fibroblasts", "deficient", "for", "the", "production", "of", "interferon,", "interferon", "stimulated", "genes,", "and", "other", "cytokines", "and", "chemokines", "mount", "a", "robust", "antiviral", "response", "against", "both", "DNA", "and", "RNA", "viruses", "following", "stimulation", "with", "dsRNA.", "Nitric", "oxide", "is", "a", "chemical", "compound", "with", "pleiotropic", "functions;", "its", "production", "by", "phagocytes", "in", "response", "to", "interferon-c", "is", "associated", "with", "antimicrobial", "activity.", "Here", "we", "show", "that", "in", "response", "to", "dsRNA,", "nitric", "oxide", "is", "rapidly", "produced", "in", "primary", "fibroblasts.", "In", "the", "presence", "of", "an", "intact", "interferon", "system,", "nitric", "oxide", "plays", "a", "minor", "but", "significant", "role", "in", "antiviral", "protection.", "However,", "in", "the", "absence", "of", "an", "interferon", "system,", "nitric", "oxide", "is", "critical", "for", "the", "protection", "against", "DNA", "viruses.", "In", "primary", "fibroblasts,", "NF-kB", "and", "interferon", "regulatory", "factor", "1", "participate", "in", "the", "induction", "of", "inducible", "nitric", "oxide", "synthase", "expression,", "which", "subsequently", "produces", "nitric", "oxide.", "As", "large", "DNA", "viruses", "encode", "multiple", "and", "diverse", "immune", "modulators", "to", "disable", "the", "interferon", "system,", "it", "appears", "that", "the", "nitric", "oxide", "pathway", "serves", "as", "a", "secondary", "strategy", "to", "protect", "the", "host", "against", "viral", "infection", "in", "key", "cell", "types,", "such", "as", "fibroblasts,", "that", "largely", "rely", "on", "the", "type", "I", "interferon", "system", "for", "antiviral", "protection.", "Citation:", "Mehta", "DR,", "Ashkar", "AA,", "Mossman", "KL", "(2012)", "The", "Nitric", "Oxide", "Pathway", "Provides", "Innate", "Antiviral", "Protection", "in", "Conjunction", "with", "the", "Type", "I", "Interferon", "Pathway", "in", "Fibroblasts.", "PLoS", "ONE", "7(2):", "e31688.", "doi:10.1371/journal.pone.0031688", "Editor:", "William", "P.", "Halford,", "Southern", "Illinois", "University", "School", "of", "Medicine,", "United", "States", "of", "America", "Received", "January", "4,", "2012;", "Accepted", "January", "11,", "2012;", "Published", "February", "21,", "2012", "Copyright:", "2012", "Mehta", "et", "al.", "This", "is", "an", "open-access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "License,", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "author", "and", "source", "are", "credited.", "Funding:", "This", "study", "was", "funded", "by", "a", "Canadian", "Institutes", "of", "Health", "Research", "operating", "grant", "(MOP", "57669)", "to", "KLM.", "The", "funder", "had", "no", "role", "in", "study", "design,", "data", "collection", "and", "analysis,", "decision", "to", "publish,", "or", "preparation", "of", "the", "manuscript.", "Competing", "Interests:", "The", "authors", "have", "declared", "that", "no", "competing", "interests", "exist.", "*", "E-mail:", "mossk@mcmaster.ca", "Introduction", "A", "central", "theme", "today", "in", "medical", "research", "is", "understanding", "the", "delicate", "balance", "of", "interactions", "between", "a", "pathogen", "and", "its", "host.", "These", "interactions", "dictate", "the", "pathological", "consequences", "of", "infections.", "It", "is", "well", "recognized", "that", "the", "innate", "immune", "response", "against", "pathogens", "focuses", "on", "detection", "of", "highly", "conserved", "pathogen-associated", "molecular", "patterns", "(PAMPs)", "that", "are", "distinct", "from", "the", "host.", "Host", "pathogen", "recognition", "receptors", "have", "evolved", "to", "recognize", "patterns", "such", "as", "nucleic", "acids", "from", "pathogens", "including", "bacteria", "and", "viruses", "[1].", "The", "first", "line", "of", "defence", "against", "invading", "pathogens", "is", "the", "rapid", "and", "robust", "production", "of", "type", "I", "interferon", "(IFN),", "a", "family", "of", "cytokines", "with", "potent", "immune", "stimulatory", "and", "pathogen-controlling", "properties.", "Fibroblasts", "are", "amongst", "the", "first", "cell", "types", "involved", "in", "the", "line", "of", "defence", "against", "numerous", "pathogens.", "Fibroblasts", "are", "widely", "distributed", "in", "organisms", "[2]", "and", "play", "an", "important", "role", "in", "the", "transition", "from", "innate", "to", "adaptive", "immunity", "[3,4].", "This", "role", "is", "largely", "a", "result", "of", "cytokine", "production", "[5],", "most", "notably", "IFNb,", "which", "was", "originally", "termed", "fibroblast", "IFN.", "As", "such,", "fibroblasts", "are", "important", "effectors", "of", "the", "early", "innate", "immune", "response.", "Indeed,", "in", "a", "recent", "study,", "non-hematopoietic", "cells,", "and", "fibroblasts", "in", "particular,", "were", "shown", "to", "mediate", "protection", "against", "an", "emerging", "viral", "infection", "through", "a", "type", "I", "IFN", "response", "[6].", "As", "all", "viruses", "are", "thought", "to", "make", "double-stranded", "RNA", "(dsRNA)", "as", "a", "by-product", "of", "their", "replication", "cycles,", "this", "molecule", "is", "a", "potent", "producer", "of", "type", "I", "IFN", "and", "as", "such,", "is", "commonly", "used", "to", "study", "innate", "immune", "responses", "to", "virus", "infection.", "DsRNA", "can", "be", "recognized", "by", "three", "different", "families", "of", "pathogen", "recognition", "receptors,", "the", "toll-like", "receptors", "(TLRs),", "the", "retinoic", "acid", "inducible", "gene", "I", "(RIG-I)-like", "receptors", "(RLRs)", "and", "the", "nucleotide", "oligomer-", "ization", "domain-like", "receptors", "(NLRs);", "these", "bind", "dsRNA", "and", "initiate", "cellular", "signaling", "pathways", "[7,8].", "The", "TLRs", "and", "RLRs", "elicit", "antiviral", "pathways", "involving", "type", "I", "and", "type", "III", "IFNs", "and", "cytokine", "production,", "whereas", "NLRs", "elicit", "caspase", "1", "activation", "for", "IL-1b", "maturation", "[7,8].", "In", "fibroblasts,", "IFN", "is", "typically", "made", "upon", "detection", "of", "viral", "dsRNA", "by", "TLR-3", "and", "the", "RLRs,", "RIG-I", "and", "melanoma", "differentiation-associated", "gene", "5", "(MDA5).", "These", "pathways", "converge", "on", "NF-kB", "and", "IFN", "regulatory", "factor", "3", "(IRF3),", "which,", "upon", "activation,", "are", "important", "for", "cytokine", "and", "IFNb", "production.", "Type", "I", "IFN,", "such", "as", "IFNb,", "signal", "through", "the", "JAK-STAT", "pathway,", "which", "includes", "IRF9", "as", "an", "essential", "component.", "This", "signaling", "leads", "to", "the", "induction", "of", "IRF7,", "which", "amplifies", "the", "cellular", "antiviral", "response", "through", "the", "generation", "of", "IFNa", "species", "and", "IFN", "stimulated", "genes", "(ISGs)", "[8].", "In", "the", "prototypic", "antiviral", "response,", "IRF3", "and", "early", "production", "of", "type", "I", "IFN", "and", "ISGs", "are", "arguably", "the", "most", "important", "events", "in", "combating", "infection.", "In", "humans,", "inborn", "errors", "that", "impair", "the", "PLoS", "ONE", "|", "www.plosone.org", "1", "February", "2012", "|", "Volume", "7", "|", "Issue", "2", "|", "e31688" ]

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[ "Phosphorylcholine", "Allows", "for", "Evasion", "of", "Bactericidal", "Antibody", "by", "Haemophilus", "influenzae", "Sarah", "E.", "Clark1,", "Julian", "Snow2,", "Jianjun", "Li3,", "Tracey", "A.", "Zola1,", "Jeffrey", "N.", "Weiser1*", "1", "Department", "of", "Microbiology,", "University", "of", "Pennsylvania,", "Philadelphia,", "Pennsylvania,", "United", "States", "of", "America,", "2", "Department", "of", "Chemistry", "and", "Biochemistry,", "University", "of", "the", "Sciences,", "Philadelphia,", "Pennsylvania,", "United", "States", "of", "America,", "3", "Institute", "for", "Biological", "Sciences,", "National", "Research", "Council", "Canada,", "Ottawa,", "Ontario,", "Canada", "Abstract", "The", "human", "pathogen", "Haemophilus", "influenzae", "has", "the", "ability", "to", "quickly", "adapt", "to", "different", "host", "environments", "through", "phase", "variation", "of", "multiple", "structures", "on", "its", "lipooligosaccharide", "(LPS),", "including", "phosphorylcholine", "(ChoP).", "During", "colonization", "with", "H.", "influenzae,", "there", "is", "a", "selection", "for", "ChoP+", "phase", "variants.", "In", "a", "murine", "model", "of", "nasopharyngeal", "colonization,", "this", "selection", "is", "lost", "in", "the", "absence", "of", "adaptive", "immunity.", "Based", "on", "previous", "data", "highlighting", "the", "importance", "of", "natural", "antibody", "in", "limiting", "H.", "influenzae", "colonization,", "the", "effect", "of", "ChoP", "expression", "on", "antibody", "binding", "and", "its", "bactericidal", "activity", "was", "investigated.", "Flow", "cytometric", "analysis", "revealed", "that", "ChoP+", "phase", "variants", "had", "decreased", "binding", "of", "antibody", "to", "LPS", "epitopes", "compared", "to", "ChoP2", "phase", "variants.", "This", "difference", "in", "antibody", "binding", "correlated", "with", "increased", "survival", "of", "ChoP+", "phase", "variants", "in", "the", "presence", "of", "antibody-dependent,", "complement-mediated", "killing.", "ChoP+", "phase", "variants", "were", "also", "more", "resistant", "to", "trypsin", "digestion,", "suggesting", "a", "general", "effect", "on", "the", "physical", "properties", "of", "the", "outer", "membrane.", "Moreover,", "ChoP-mediated", "protection", "against", "antibody", "binding", "correlated", "with", "increased", "resilience", "of", "outer", "membrane", "integrity.", "Collectively,", "these", "data", "suggest", "that", "ChoP", "expression", "provides", "a", "selective", "advantage", "during", "colonization", "through", "ChoP-mediated", "effects", "on", "the", "accessibility", "of", "bactericidal", "antibody", "to", "the", "cell", "surface.", "Citation:", "Clark", "SE,", "Snow", "J,", "Li", "J,", "Zola", "TA,", "Weiser", "JN", "(2012)", "Phosphorylcholine", "Allows", "for", "Evasion", "of", "Bactericidal", "Antibody", "by", "Haemophilus", "influenzae.", "PLoS", "Pathog", "8(3):", "e1002521.", "doi:10.1371/journal.ppat.1002521", "Editor:", "Nina", "Salama,", "Fred", "Hutchinson", "Cancer", "Research", "Center,", "United", "States", "of", "America", "Received", "September", "20,", "2011;", "Accepted", "December", "20,", "2011;", "Published", "March", "1,", "2012", "Copyright:", "2012", "Clark", "et", "al.", "This", "is", "an", "open-access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "License,", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "author", "and", "source", "are", "credited.", "Funding:", "This", "work", "was", "supported", "by", "the", "US", "Public", "Health", "Service", "(AI44231", "and", "AI38446)", "and", "by", "the", "University", "of", "Pennsylvania", "Cell", "and", "Molecular", "Biology", "Training", "Grant", "(T32", "GM", "7229-35).", "The", "funders", "had", "no", "role", "in", "study", "design,", "data", "collection", "and", "analysis,", "decision", "to", "publish,", "or", "preparation", "of", "the", "manuscript.", "Competing", "Interests:", "The", "authors", "have", "declared", "that", "no", "competing", "interests", "exist.", "*", "E-mail:", "weiser@mail.med.upenn.edu", "Introduction", "Haemophilus", "influenzae", "is", "an", "extracellular,", "gram-negative", "patho-", "gen", "that", "is", "a", "primary", "causative", "agent", "of", "otitis", "media", "in", "children", "and", "is", "also", "frequently", "isolated", "from", "adults", "with", "pneumonia", "and", "exacerbations", "of", "chronic", "obstructive", "pulmonary", "disease", "(COPD)", "[1–5].", "Colonization", "of", "the", "upper", "respiratory", "tract", "with", "H.", "influenzae", "is", "common", "and", "is", "the", "first", "step", "in", "disease", "development,", "as", "H.", "influenzae", "carriage", "is", "associated", "with", "recurrent", "otitis", "media", "episodes", "in", "children", "[6,7].", "While", "the", "Hib", "conjugate", "vaccine", "has", "greatly", "reduced", "the", "burden", "of", "disease", "caused", "by", "type", "b", "H.", "influenzae", "[8,9],", "non-typeable", "H.", "influenzae", "(NTHi)", "strains,", "which", "are", "unencapsu-", "lated,", "remain", "a", "common", "source", "of", "respiratory", "tract", "infections.", "Vaccine", "strategies", "targeting", "NTHi", "strains", "are", "complicated", "by", "the", "high", "variability", "of", "outer", "membrane", "antigens", "[10,11].", "One", "of", "the", "structurally", "diverse", "molecules", "on", "the", "surface", "of", "H.", "influenzae", "is", "the", "lipopolysaccharide", "(LPS).", "The", "LPS", "of", "H.", "influenzae", "is", "truncated", "compared", "to", "the", "LPS", "of", "other", "gram-negative", "bacteria.", "It", "contains", "no", "repetitive", "O", "antigen", "side", "chains", "and", "is", "also", "referred", "to", "as", "lipooligosaccharide", "(LOS)", "[12,13].", "H.", "influenzae", "LPS", "consists", "of", "lipid", "A", "attached", "to", "3-deoxy-", "D-manno-oct-2-ulosonic", "acid", "(KDO),", "with", "three", "conserved", "inner", "core", "heptoses", "to", "which", "various", "oligosaccharide", "extensions,", "and", "other", "non-carbohydrate", "molecules,", "can", "be", "attached", "[14].", "Mass", "spectrometry", "(MS)", "analysis", "of", "different", "H.", "influenzae", "isolates", "has", "revealed", "a", "significant", "level", "of", "diversity", "in", "LPS", "structures", "[15–21].", "For", "example,", "the", "length", "and", "composition", "of", "the", "hexose", "extensions", "from", "the", "inner", "core", "heptoses,", "as", "well", "as", "the", "attachment", "of", "molecules", "such", "as", "sialic", "acid", "and", "glycine,", "varies", "both", "between", "different", "strains", "and", "within", "glycoforms", "of", "the", "same", "isolate.", "A", "major", "source", "of", "LPS", "variability", "in", "H.", "influenzae", "is", "on-off", "switching,", "or", "phase", "variation,", "involving", "LPS", "biosynthesis", "genes", "[22,23].", "One", "of", "the", "phase", "variable", "molecules", "expressed", "on", "H.", "influenzae", "LPS", "is", "phosphorylcholine.", "Phosphorylcholine", "[(CH3)3N", "+", "CH2CH2PO42],", "or", "ChoP,", "is", "a", "small,", "zwitterionic", "molecule", "that", "is", "covalently", "attached", "to", "the", "LPS", "through", "its", "phosphate", "group.", "ChoP", "is", "a", "surface", "structure", "of", "a", "number", "of", "bacteria", "in", "addition", "to", "H.", "influenzae,", "particularly", "those", "found", "in", "the", "respiratory", "tract,", "including", "Streptococcus", "pneumoniae,", "Pseudomonas", "aeruginosa,", "and", "Neisseria", "species", "[24–26].", "ChoP", "is", "also", "a", "component", "of", "eukaryotic", "membrane", "lipids", "in", "the", "form", "of", "phosphatidylcholine.", "H.", "influenzae", "must", "acquire", "choline", "from", "the", "environment,", "and", "turnover", "of", "host", "lipids", "can", "be", "a", "major", "source", "of", "choline", "during", "colonization", "[27,28].", "Choline", "import,", "phosphor-", "ylation,", "and", "attachment", "to", "H.", "influenzae", "LPS", "is", "controlled", "by", "genes", "in", "the", "lic1", "locus.", "The", "choline", "kinase", "gene", "lic1A", "contains", "a", "tetranucleotide", "repeat", "that", "is", "responsible", "for", "ChoP", "phase", "variation.", "Slipped-strand", "mispairing", "within", "the", "repeat", "region", "of", "lic1A", "creates", "a", "translational", "on-off", "switch", "controlling", "ChoP", "expression", "[29].", "As", "a", "result,", "the", "control", "of", "ChoP", "attachment", "to", "the", "LPS", "is", "stochastic,", "and", "phase", "variation", "occurs", "at", "a", "high", "frequency", "[30].", "Phase", "variation", "of", "ChoP", "expression", "may", "provide", "a", "mechanism", "for", "Haemophilus", "to", "display", "a", "variety", "of", "phenotypes,", "allowing", "rapid", "PLoS", "Pathogens", "|", "www.plospathogens.org", "1", "March", "2012", "|", "Volume", "8", "|", "Issue", "3", "|", "e1002521" ]

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[ "Acta", "Crystallographica", "Section", "E", "Structure", "Reports", "Online", "ISSN", "1600-5368", "3,5-Dimethoxy-N,N-bis(2-pyridyl-", "methyl)aniline", "Hongjuan", "Li,*", "Xianping", "Dai", "and", "Jufeng", "Sun", "School", "of", "Pharmacy,", "Binzhou", "Medical", "College,", "Yantai", "264003,", "People’s", "Republic", "of", "China", "Correspondence", "e-mail:", "hjli80@163.com", "Received", "12", "November", "2009;", "accepted", "16", "November", "2009", "Key", "indicators:", "single-crystal", "X-ray", "study;", "T", "=", "113", "K;", "mean", "(C–C)", "=", "0.002", "A˚;", "R", "factor", "=", "0.041;", "wR", "factor", "=", "0.113;", "data-to-parameter", "ratio", "=", "18.0.", "In", "the", "title", "molecule,", "C20H21N3O2,", "the", "benzene", "ring", "forms", "dihedral", "angles", "of", "80.8", "(1)", "and", "83.5", "(1)", "with", "the", "two", "terminal", "pyridine", "rings.", "In", "the", "crystal", "structure,", "weak", "intermolecular", "C—H", "O", "hydrogen", "bonds", "link", "the", "molecules", "into", "chains", "propagating", "in", "[001].", "Related", "literature", "For", "general", "background", "to", "organic", "ligand-based", "crystal", "materials,", "see:", "Desiraju", "(2007);", "Moulton", "&", "Zaworotko", "(2001).", "For", "related", "structures,", "see:", "Frisch", "&", "Cahil", "(2008);", "Shattock", "et", "al.", "(2008);", "Shirman", "et", "al.", "(2008).", "Experimental", "Crystal", "data", "C20H21N3O2", "Mr", "=", "335.40", "Monoclinic,", "P21=c", "a", "=", "15.630", "(3)", "A˚", "b", "=", "5.9562", "(12)", "A˚", "c", "=", "20.088", "(4)", "A˚", "=", "111.55", "(3)", "V", "=", "1739.3", "(6)", "A˚", "3", "Z", "=", "4", "Data", "collection", "Rigaku", "Saturn", "CCD", "area-detector", "diffractometer", "Absorption", "correction:", "multi-scan", "(CrystalClear;", "Rigaku/MSC,", "2005)", "Tmin", "=", "0.978,", "Tmax", "=", "0.983", "Refinement", "R[F", "2", ">", "2", "(F", "2)]", "=", "0.041", "wR(F", "2)", "=", "0.113", "S", "=", "1.10", "4106", "reflections", "Table", "1", "Hydrogen-bond", "geometry", "(A˚", ",", ").", "organic", "compounds", "Mo", "K", "radiation", "=", "0.08", "mm", "1", "T", "=", "113", "K", "0.27", "0.25", "0.20", "mm", "14749", "measured", "reflections", "4106", "independent", "reflections", "3258", "reflections", "with", "I", ">", "2", "(I)", "Rint", "=", "0.038", "228", "parameters", "H-atom", "parameters", "constrained", "max", "=", "0.22", "e", "A˚", "3", "min", "=", "0.21", "e", "A˚", "3", "D—H", "A", "C14—H14", "O2i", "D—H", "0.95", "H", "2.49", "A", "D", "A", "3.3050", "(15)", "D—H", "A", "144", "Symmetry", "code:", "(i)", "x;", "y", "þ", "32;", "z", "12.", "Data", "collection:", "CrystalClear", "(Rigaku/MSC,", "2005);", "cell", "refinement:", "CrystalClear;", "data", "reduction:", "CrystalClear;", "program(s)", "used", "to", "solve", "structure:", "SHELXS97", "(Sheldrick,", "2008);", "program(s)", "used", "to", "refine", "structure:", "SHELXL97", "(Sheldrick,", "2008);", "molecular", "graphics:", "ORTEPIII", "(Burnett", "&", "Johnson,", "1996);", "software", "used", "to", "prepare", "material", "for", "publication:", "SHELXL97", "and", "PLATON", "(Spek,", "2009).", "The", "authors", "are", "grateful", "to", "the", "Binzhou", "Medical", "College", "for", "financial", "support", "(grant", "No.", "BY2007KJ13).", "Supplementary", "data", "and", "figures", "for", "this", "paper", "are", "available", "from", "the", "IUCr", "electronic", "archives", "(Reference:", "CV2657).", "References", "Burnett,", "M.", "N.", "&", "Johnson,", "C.", "K.", "(1996).", "ORTEPIII.", "Report", "ORNL-6895.", "Oak", "Ridge", "National", "Laboratory,", "Tennessee,", "USA.", "Desiraju,", "G.", "R.", "(2007).", "Angew.", "Chem.", "Int.", "Ed.", "45,", "8342–8356.", "Frisch,", "M.", "&", "Cahil,", "C.", "L.", "(2008).", "Cryst.", "Growth.", "Des.", "8,", "2921–2928.", "Moulton,", "B.", "&", "Zaworotko,", "M.", "J.", "(2001).", "Chem.", "Rev.", "101,", "1629–1658.", "Rigaku/MSC", "(2005).", "CrystalClear.", "Rigaku/MSC,", "The", "Woodlands,", "Texas,", "USA.", "Shattock,", "T.", "R.,", "Arora,", "K.", "K.,", "Vishweshwar,", "P.", "&", "Zaworotko,", "M.", "J.", "(2008).", "Cryst.", "Growth.", "Des.", "8,", "4533–4545.", "Sheldrick,", "G.", "M.", "(2008).", "Acta", "Cryst.", "A64,", "112–122.", "Shirman,", "T.,", "Lamere,", "J.-F.,", "Shimon,", "L.", "J.", "W.,", "Gupta,", "T.,", "Martin,", "J.", "M.", "L.", "&", "van", "der", "Boom,", "M.", "E.", "(2008).", "Cryst.", "Growth.", "Des.", "8,", "3066–3072.", "Spek,", "A.", "L.", "(2009).", "Acta", "Cryst.", "D65,", "148–155.", "Acta", "Cryst.", "(2009).", "E65,", "o3139", "doi:10.1107/S1600536809048685", "Li", "et", "al.", "o3139" ]

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[ "BMC", "Family", "Practice", "Research", "article", "The", "knowledge", "and", "expectations", "of", "parents", "about", "the", "role", "of", "antibiotic", "treatment", "in", "upper", "respiratory", "tract", "infection", "–", "a", "survey", "among", "parents", "attending", "the", "primary", "physician", "with", "their", "sick", "child", "Shlomo", "Vinker*,", "Adi", "Ron", "and", "Eliezer", "Kitai", "BioMed", "Central", "Open", "Access", "Address:", "Department", "of", "Family", "Medicine,", "Tel", "Aviv", "Sackler", "school", "of", "Medicine,", "Tel", "Aviv,", "Israel", "Email:", "Shlomo", "Vinker*", "-", "vinker01@inter.net.il;", "Adi", "Ron", "-", "yoninadi@netvision.net.il;", "Eliezer", "Kitai", "-", "drkitai@netvision.net.il", "*", "Corresponding", "author", "Published:", "30", "December", "2003", "BMC", "Family", "Practice", "2003,", "4:20", "This", "article", "is", "available", "from:", "http://www.biomedcentral.com/1471-2296/4/20", "Received:", "25", "June", "2003", "Accepted:", "30", "December", "2003", "©", "2003", "Shlomo", "et", "al;", "licensee", "BioMed", "Central", "Ltd.", "This", "is", "an", "Open", "Access", "article:", "verbatim", "copying", "and", "redistribution", "of", "this", "article", "are", "permitted", "in", "all", "media", "for", "any", "purpose,", "provided", "this", "notice", "is", "preserved", "along", "with", "the", "article's", "original", "URL.", "Upper", "respiratory", "tract", "infectionantibioticschildrenparentsknowledgeattitude", "Abstract", "Background:", "Upper", "respiratory", "tract", "infections", "(URTI)", "are", "common.", "The", "etiologic", "factor", "is", "usually", "viral,", "but", "many", "physicians", "prescribe", "antibiotics.", "We", "aimed", "to", "evaluate", "parents'", "expectations", "of", "and", "knowledge", "about", "the", "role", "of", "antibiotics", "in", "childhood", "URTI.", "Methods:", "The", "study", "was", "conducted", "in", "thirteen", "primary", "care", "pediatric", "clinics.", "Parents", "of", "children", "aged", "3", "months", "to", "6", "years", "who", "attended", "with", "URTI", "symptoms", "were", "included", "when", "it", "was", "the", "first", "attendance", "in", "the", "current", "illness.", "Questionnaire", "about", "the", "current", "illness,", "reasons", "for", "attending", "and", "expectations", "from", "the", "visit,", "knowledge", "about", "URTI", "was", "filled", "before", "the", "visit.", "Results:", "In", "122", "visits", "the", "average", "age", "was", "2.8", "±", "1.9", "years.", "The", "main", "reasons", "for", "the", "visit", "were", "to", "avoid", "complications", "(81%)", "and", "to", "be", "examined", "(78%).", "Expected", "treatment", "was:", "cough", "suppressants", "(64%),", "anti-congestants", "(57%),", "paracetamol", "(56%),", "natural", "remedies", "(53%)", "and", "antibiotics", "(25%).", "In", "28%", "the", "child", "had", "received", "antibiotics", "in", "past", "URTI.", "Only", "37%", "thought", "that", "antibiotics", "would", "not", "help", "in", "URTI", "and", "27%", "knew", "that", "URTI", "is", "a", "self-limited", "disease.", "61%", "knew", "that", "URTI", "is", "a", "viral", "disease.", "Younger", "parental", "age", "and", "higher", "education", "were", "associated", "with", "lower", "expectations", "to", "receive", "antibiotics", "(p", "=", "0.01,", "p", "<", "0.005", "respectively).", "While", "previous", "antibiotic", "treatment", "(p", "<", "0.001),", "past", "perceived", "complications", "(p", "=", "0.05)", "and", "the", "thought", "that", "antibiotics", "help", "in", "URTI", "(p", "<", "0.001)", "were", "associated", "with", "a", "greater", "expectation", "for", "antibiotics.", "Conclusions:", "A", "quarter", "of", "the", "parents", "attending", "the", "physician", "with", "URTI", "are", "expecting", "to", "get", "antibiotics.", "Predictors", "were", "lower", "education,", "older", "parental", "age,", "receiving", "antibiotics", "in", "the", "past", "and", "the", "belief", "that", "antibiotics", "help", "in", "URTI.", "Background", "Patients", "with", "Upper", "Respiratory", "Tract", "Infection", "(URTI)", "constitute", "a", "major", "part", "of", "the", "primary", "care", "physician's", "workload", "during", "the", "winter", "months", "[1].", "In", "most", "cases", "the", "etiologic", "factor", "is", "viral", "and", "there", "is", "no", "need", "for", "antibiotic", "treatment", "[2,3].", "Many", "physicians", "continue", "to", "prescribe", "antibiotic", "treatment", "for", "URTI,", "knowing", "that", "antibiotics", "do", "not", "help", "viral", "infection", "and", "despite", "the", "development", "of", "resistant", "bacterial", "strains.", "Page", "1", "of", "6", "(page", "number", "not", "for", "citation", "purposes)" ]

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[ "Galdeano", "et", "al.", "BMC", "Gastroenterology", "2011,", "11:64", "http://www.biomedcentral.com/1471-230X/11/64", "R", "E", "S", "E", "A", "R", "C", "H", "A", "R", "T", "I", "C", "L", "E", "Open", "Access", "Impact", "of", "a", "probiotic", "fermented", "milk", "in", "the", "gut", "ecosystem", "and", "in", "the", "systemic", "immunity", "using", "a", "non-severe", "protein-energy-malnutrition", "model", "in", "mice", "Carolina", "Maldonado", "Galdeano1,2,", "Ivanna", "Novotny", "Núñez1,", "Alejandra", "de", "Moreno", "de", "LeBlanc1,", "Esteban", "Carmuega3,", "Ricardo", "Weill4", "and", "Gabriela", "Perdigón1,2*", "Abstract", "Background:", "Malnutrition", "affects", "the", "immune", "response,", "causing", "a", "decrease", "of", "defence", "mechanisms", "and", "making", "the", "host", "more", "susceptible", "to", "infections.", "Probiotics", "can", "reconstitute", "the", "intestinal", "mucosa", "and", "stimulate", "local", "and", "systemic", "immunity.", "The", "aim", "of", "this", "work", "was", "evaluate", "the", "effects", "of", "a", "probiotic", "fermented", "milk", "as", "a", "complement", "of", "a", "re-nutrition", "diet,", "on", "the", "recovery", "of", "the", "intestinal", "barrier,", "and", "mucosal", "and", "systemic", "immune", "functions", "in", "a", "murine", "model", "of", "non-severe", "protein-energy-malnutrition.", "Its", "potential", "protection", "against", "Salmonella", "enterica", "serovar", "Typhimurium", "(S.", "Typhimurium)", "infection", "was", "also", "analyzed.", "Methods:", "Mice", "were", "undernourished", "and", "divided", "into", "3", "groups", "according", "to", "the", "dietary", "supplement", "received", "during", "re-nutrition", "(milk,", "probiotic", "fermented", "milk", "or", "its", "bacterial", "free", "supernatant)", "and", "compared", "to", "well-", "nourished", "and", "malnourished", "mice.", "They", "were", "sacrificed", "previous", "to", "the", "re-nutrition", "and", "5", "days", "post", "re-nutrition.", "The", "phagocytic", "activity", "of", "macrophages", "from", "spleen", "and", "peritoneum", "and", "the", "changes", "in", "the", "intestinal", "histology", "and", "microbiota", "were", "evaluated.", "Different", "immune", "cell", "populations", "and", "cytokine", "productions", "were", "analyzed", "in", "the", "small", "intestine", "tissues.", "The", "effect", "of", "the", "re-nutrition", "supplements", "on", "the", "systemic", "immunity", "using", "OVA", "antigen", "and", "against", "an", "infection", "with", "S.", "Typhimurium", "was", "also", "studied.", "Results:", "Probiotic", "fermented", "milk", "was", "the", "most", "effective", "re-nutrition", "diet", "that", "improved", "the", "intestinal", "microbiota.", "Its", "administration", "also", "increased", "the", "number", "of", "IgA+", "cells,", "macrophages", "and", "dendritic", "cells.", "The", "production", "of", "different", "cytokine", "(IFN-g,", "TNF-a,", "IL-12)", "by", "these", "cells", "and", "the", "phagocytic", "activity", "in", "peritoneum", "and", "spleen", "was", "also", "increased.", "This", "re-nutrition", "diet", "also", "stimulated", "the", "systemic", "immune", "response", "against", "OVA", "antigen", "which", "was", "diminished", "after", "the", "malnutrition", "period", "and", "also", "improved", "the", "host", "response", "against", "S.", "Typhimurium,", "decreasing", "the", "spread", "of", "pathogenic", "bacteria", "to", "the", "liver", "and", "the", "spleen.", "The", "importance", "of", "the", "metabolites", "released", "during", "milk", "fermentation", "was", "also", "demonstrated", "through", "the", "analysis", "of", "the", "bacterial", "free", "supernatant", "obtained", "from", "the", "probiotic", "fermented", "milk,", "but", "the", "whole", "product", "showed", "the", "best", "effects", "in", "the", "parameters", "evaluated", "in", "this", "study.", "Conclusions:", "The", "administration", "of", "probiotic", "fermented", "milk", "as", "a", "dietary", "supplement", "during", "the", "re-nutrition", "process", "in", "a", "murine", "immunodeficiency", "model", "by", "malnutrition", "could", "be", "a", "good", "adjuvant", "diet", "to", "improve", "the", "gut", "and", "systemic", "immune", "response", "for", "the", "protection", "against", "Salmonella", "infection.", "*", "Correspondence:", "perdigon@cerela.org.ar", "1Centro", "de", "Referencia", "para", "Lactobacilos", "(CERELA-CONICET).", "Chacabuco", "145,", "San", "Miguel", "de", "Tucumán", "(T4000ILC)", "Tucumán.", "Argentina", "Full", "list", "of", "author", "information", "is", "available", "at", "the", "end", "of", "the", "article", "©", "2011", "Galdeano", "et", "al;", "licensee", "BioMed", "Central", "Ltd.", "This", "is", "an", "Open", "Access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "License", "(http://creativecommons.org/licenses/by/2.0),", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited." ]

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[ "Fallani", "et", "al.", "Nonlinear", "Biomedical", "Physics", "2010,", "4(Suppl", "1):S8", "http://www.nonlinearbiomedphys.com/content/4/S1/S8", "P", "R", "O", "C", "E", "E", "D", "I", "N", "G", "S", "Open", "Access", "A", "graph-theoretical", "approach", "in", "brain", "functional", "networks.", "Possible", "implications", "in", "EEG", "studies", "Fabrizio", "De", "Vico", "Fallani1,2,", "Luciano", "da", "Fontoura", "Costa5,", "Francisco", "Aparecido", "Rodriguez5,", "Laura", "Astolfi1,3,", "Giovanni", "Vecchiato1,2,", "Jlenia", "Toppi1,3,", "Gianluca", "Borghini1,", "Febo", "Cincotti1,", "Donatella", "Mattia1,", "Serenella", "Salinari3,", "Roberto", "Isabella4,", "Fabio", "Babiloni1,2*", "From", "Consciousness", "and", "its", "Measures:", "Joint", "Workshop", "for", "COST", "Actions", "NeuroMath", "and", "Consciousness", "Limassol,", "Cyprus.", "29", "November", "–", "1", "December", "2009", "Abstract", "Background:", "Recently,", "it", "was", "realized", "that", "the", "functional", "connectivity", "networks", "estimated", "from", "actual", "brain-", "imaging", "technologies", "(MEG,", "fMRI", "and", "EEG)", "can", "be", "analyzed", "by", "means", "of", "the", "graph", "theory,", "that", "is", "a", "mathematical", "representation", "of", "a", "network,", "which", "is", "essentially", "reduced", "to", "nodes", "and", "connections", "between", "them.", "Methods:", "We", "used", "high-resolution", "EEG", "technology", "to", "enhance", "the", "poor", "spatial", "information", "of", "the", "EEG", "activity", "on", "the", "scalp", "and", "it", "gives", "a", "measure", "of", "the", "electrical", "activity", "on", "the", "cortical", "surface.", "Afterwards,", "we", "used", "the", "Directed", "Transfer", "Function", "(DTF)", "that", "is", "a", "multivariate", "spectral", "measure", "for", "the", "estimation", "of", "the", "directional", "influences", "between", "any", "given", "pair", "of", "channels", "in", "a", "multivariate", "dataset.", "Finally,", "a", "graph", "theoretical", "approach", "was", "used", "to", "model", "the", "brain", "networks", "as", "graphs.", "These", "methods", "were", "used", "to", "analyze", "the", "structure", "of", "cortical", "connectivity", "during", "the", "attempt", "to", "move", "a", "paralyzed", "limb", "in", "a", "group", "(N=5)", "of", "spinal", "cord", "injured", "patients", "and", "during", "the", "movement", "execution", "in", "a", "group", "(N=5)", "of", "healthy", "subjects.", "Results:", "Analysis", "performed", "on", "the", "cortical", "networks", "estimated", "from", "the", "group", "of", "normal", "and", "SCI", "patients", "revealed", "that", "both", "groups", "present", "few", "nodes", "with", "a", "high", "out-degree", "value", "(i.e.", "outgoing", "links).", "This", "property", "is", "valid", "in", "the", "networks", "estimated", "for", "all", "the", "frequency", "bands", "investigated.", "In", "particular,", "cingulate", "motor", "areas", "(CMAs)", "ROIs", "act", "as", "‘‘hubs’’", "for", "the", "outflow", "of", "information", "in", "both", "groups,", "SCI", "and", "healthy.", "Results", "also", "suggest", "that", "spinal", "cord", "injuries", "affect", "the", "functional", "architecture", "of", "the", "cortical", "network", "sub-serving", "the", "volition", "of", "motor", "acts", "mainly", "in", "its", "local", "feature", "property.", "In", "particular,", "a", "higher", "local", "efficiency", "El", "can", "be", "observed", "in", "the", "SCI", "patients", "for", "three", "frequency", "bands,", "theta", "(3-6", "Hz),", "alpha", "(7-12", "Hz)", "and", "beta", "(13-29", "Hz).", "By", "taking", "into", "account", "all", "the", "possible", "pathways", "between", "different", "ROI", "couples,", "we", "were", "able", "to", "separate", "clearly", "the", "network", "properties", "of", "the", "SCI", "group", "from", "the", "CTRL", "group.", "In", "particular,", "we", "report", "a", "sort", "of", "compensatory", "mechanism", "in", "the", "SCI", "patients", "for", "the", "Theta", "(3-6", "Hz)", "frequency", "band,", "indicating", "a", "higher", "level", "of", "“activation”", "Ω", "within", "the", "cortical", "network", "during", "the", "motor", "task.", "The", "activation", "index", "is", "directly", "related", "to", "diffusion,", "a", "type", "of", "dynamics", "that", "underlies", "several", "biological", "systems", "including", "possible", "spreading", "of", "neuronal", "activation", "across", "sev-", "eral", "cortical", "regions.", "Conclusions:", "The", "present", "study", "aims", "at", "demonstrating", "the", "possible", "applications", "of", "graph", "theoretical", "approaches", "in", "the", "analyses", "of", "brain", "functional", "connectivity", "from", "EEG", "signals.", "In", "particular,", "the", "methodological", "aspects", "of", "the", "i)", "cortical", "activity", "from", "scalp", "EEG", "signals,", "ii)", "functional", "connectivity", "estimations", "iii)", "graph", "theoretical", "indexes", "are", "emphasized", "in", "the", "present", "paper", "to", "show", "their", "impact", "in", "a", "real", "application.", "*", "Correspondence:", "fabio.babiloni@uniroma1.it", "1IRCCS", "“Fondazione", "Santa", "Lucia”,", "Rome,", "Italy", "©", "2010", "Babiloni", "et", "al;", "licensee", "BioMed", "Central", "Ltd.", "This", "is", "an", "open", "access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "License", "(http://creativecommons.org/licenses/by/2.0),", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited." ]

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[ "REVIEW", "ARTICLE", "published:", "09", "March", "2012", "doi:", "10.3389/fphar.2012.00035", "Regulation", "of", "aldo–keto", "reductases", "in", "human", "diseases", "Wei-Dong", "Chen", "and", "Yanqiao", "Zhang*", "Department", "of", "Integrative", "Medical", "Sciences,", "Northeast", "Ohio", "Medical", "University,", "Rootstown,", "OH,", "USA", "Edited", "by:", "Yi", "Jin,", "University", "of", "Pennsylvania,", "USA", "Reviewed", "by:", "Wen", "Xie,", "University", "of", "Pittsburgh,", "USA", "Kwang-Huei", "Lin,", "Chang-Gung", "University,", "Taiwan", "*Correspondence:", "Yanqiao", "Zhang,", "Department", "of", "Integrative", "Medical", "Sciences,", "Northeast", "Ohio", "Medical", "University,", "4209", "State", "Route", "44,", "Rootstown,", "OH", "44272,", "USA.", "e-mail:", "yzhang@neomed.edu", "The", "aldo–keto", "reductases", "(AKRs)", "are", "a", "superfamily", "of", "NAD(P)H-linked", "oxidoreductases,", "which", "reduce", "aldehydes", "and", "ketones", "to", "their", "respective", "primary", "and", "secondary", "alcohols.", "AKR", "enzymes", "are", "increasingly", "being", "recognized", "to", "play", "an", "important", "role", "in", "the", "transfor-", "mation", "and", "detoxification", "of", "aldehydes", "and", "ketones", "generated", "during", "drug", "detoxification", "and", "xenobiotic", "metabolism.", "Many", "transcription", "factors", "have", "been", "identified", "to", "regulate", "the", "expression", "of", "human", "AKR", "genes,", "which", "could", "have", "profound", "effects", "on", "the", "metabolism", "of", "endogenous", "mediators", "and", "detoxication", "of", "chemical", "carcinogens.", "This", "review", "summarizes", "the", "current", "knowledge", "on", "AKR", "regulation", "by", "transcription", "factors", "and", "other", "mediators", "in", "human", "diseases.", "Keywords:", "aldo–keto", "reductase,", "regulation,", "response", "element,", "transcription", "factor,", "human", "disease", "INTRODUCTION", "The", "aldo–keto", "reductases", "(AKRs)", "are", "a", "superfamily", "of", "NAD(P)H-", "linked", "oxidoreductases,", "which", "primarily", "catalyze", "the", "reduction", "of", "aldehydes", "and", "ketones", "to", "primary", "and", "secondary", "alcohols,", "respec-", "tively", "(Penning", "and", "Drury,", "2007).", "AKRs", "are", "generally", "soluble,", "cytosolic", "monomeric", "(37", "kDa)", "enzymes", "and", "are", "present", "in", "both", "prokaryotes", "and", "eukaryotes.", "These", "enzymes", "share", "a", "common", "pro-", "tein", "fold,", "a", "(β/α)8", "or", "a", "triosephosphate", "isomerase", "(TIM)-barrel,", "and", "have", "an", "active", "site", "in", "the", "C-terminal", "face", "(Jez", "et", "al.,", "1997a,b;", "Barski", "et", "al.,", "2008).", "Most", "AKRs", "use", "pyridine", "nucleotide", "as", "cofac-", "tors", "and", "catalyze", "simple", "oxidation–reduction", "reactions", "involved", "in", "the", "metabolism", "of", "sugar", "aldehydes,", "reactive", "lipid", "aldehydes,", "ketoprostaglandins,", "and", "ketosteroids.", "Aldo–keto", "reductases", "consist", "of", "15", "families", "which", "have", "more", "than", "100", "members", "(Barski", "et", "al.,", "2008).", "There", "are", "13", "human", "AKR", "proteins", "that", "fall", "into", "3", "families", "AKR1,", "AKR6,", "and", "AKR7", "(Table", "1).", "The", "detailed", "information", "is", "available", "at", "http://www.med.upenn.edu/akr,", "an", "AKR", "superfamily", "homepage,", "maintained", "by", "Dr.", "T.", "Penning", "at", "the", "University", "of", "Pennsylvania.", "The", "human", "AKR", "enzymes", "include", "AKR1A1", "(aldehyde", "reductase),", "AKR1B1", "and", "AKR1B10", "(aldose", "reductases),", "AKR1C1–C4", "(hydrox-", "ysteroid", "dehydrogenases),", "AKR1D1", "(steroid", "5β-reductase),", "the", "AKR6", "family", "(AKR6A3,", "A5,", "and", "A9;", "Kvβ", "proteins),", "and", "the", "AKR7", "family", "(AKR7A2", "and", "AKR7A3;", "aflatoxin", "aldehyde", "reduc-", "tases).", "These", "human", "AKR", "enzymes", "can", "catalyze", "many", "meta-", "bolic", "oxidation–reduction", "reactions", "of", "numerous", "endogenous", "and", "exogenous", "substrates,", "including", "glucose,", "steroids,", "carcino-", "gens,", "reactive", "aldehydes,", "and", "a", "variety", "of", "carbonyl-containing", "drugs.", "To", "date,", "the", "AKR", "enzymes", "have", "been", "implicated", "in", "a", "num-", "ber", "of", "human", "diseases.", "It", "is", "known", "that", "AKR1A1,", "AKR1B10,", "and", "AKR1C1–C3", "are", "involved", "in", "tobacco-induced", "carcinogen-", "esis", "(Hsu", "et", "al.,", "2001;", "Penning,", "2005;", "Jin", "and", "Penning,", "2007;", "Zhang", "et", "al.,", "2008;", "Liu", "et", "al.,", "2009a).", "Inhibition", "of", "AKR1B1", "is", "able", "to", "alleviate", "diabetic", "complications.", "Through", "mediating", "oxida-", "tive", "stress-induced", "inflammatory", "signals,", "AKR1B1", "plays", "a", "role", "in", "inflammation-related", "diseases", "such", "as", "sepsis", "and", "colon", "cancer", "(Ramana,", "2011).", "AKR1B1", "and", "AKR1B10", "regulate", "the", "develop-", "ment", "and", "progression", "of", "human", "liver,", "breast,", "and", "lung", "cancers", "through", "detoxifying", "reactive", "carbonyls,", "retinoic", "acid", "homeostatic", "regulation,", "and", "lipid", "metabolism", "(Liu", "et", "al.,", "2009a;", "Diez-Dacal", "et", "al.,", "2011).", "AKR1C1–C3", "enzymes", "are", "involved", "in", "prostate", "and", "breast", "carcinogenesis", "(Penning", "and", "Byrns,", "2009).", "Mutations", "in", "AKR1D1", "gene", "in", "patients", "lead", "to", "neonatal", "cholestasis,", "hepatitis,", "and", "liver", "failure", "(Lemonde", "et", "al.,", "2003;", "Barski", "et", "al.,", "2008).", "AKR7A", "proteins", "protect", "liver", "from", "acetaminophen-induced", "hepatotoxic-", "ity", "by", "enhancing", "hepatocellular", "antioxidant", "defense", "(Ahmed", "et", "al.,", "2011).", "Because", "AKR", "enzymes", "are", "increasingly", "being", "recognized", "to", "play", "a", "role", "in", "various", "diseases,", "understanding", "the", "regulation", "of", "human", "AKR", "genes", "may", "help", "us", "develop", "novel", "therapeutic", "approaches.", "In", "this", "review,", "we", "summarize", "the", "regulation", "of", "AKRs", "by", "transcription", "factors,", "mediators,", "and", "pathological", "conditions.", "THE", "REGULATION", "OF", "AKRs", "Many", "transcription", "factors", "have", "been", "identified", "to", "regulate", "the", "expression", "of", "human", "AKR", "genes,", "which", "could", "have", "profound", "effects", "on", "the", "metabolism", "of", "endogenous", "mediators", "and", "detox-", "ication", "of", "chemical", "carcinogens.", "Several", "classes", "of", "transcription", "enhancer", "elements", "have", "been", "identified", "in", "the", "upstream", "pro-", "moter", "region", "of", "AKR", "genes", "that", "include", "nuclear", "receptor", "response", "elements,", "AP-1", "binding", "sites,", "the", "xenobiotic", "response", "elements", "(XRE),", "osmotic", "response", "elements", "(ORE),", "estrogen", "response", "ele-", "ments", "(ERE),", "and", "antioxidant", "response", "elements", "(ARE;", "Ko", "et", "al.,", "1997;", "Burczynski", "et", "al.,", "1999;", "Lou", "et", "al.,", "2006;", "Penning", "and", "Drury,", "2007).", "AKR1A1", "AKR1A1,", "a", "ubiquitously", "expressed", "enzyme,", "is", "a", "well-known", "cytosolic,", "NADPH-dependent", "and", "monomeric", "oxidoreductase.", "AKR1A1", "participates", "in", "carbonyl", "reductions", "of", "chemotherapeutic", "drugs.", "Protein", "and", "mRNA", "levels", "of", "AKR1A1", "in", "irinotecan-resistant", "LoVo", "cells", "are", "higher", "than", "in", "human", "colon", "adenocarcinoma", "LoVo", "cells", "(Peng", "et", "al.,", "2010).", "Recent", "studies", "suggest", "that", "overexpression", "www.frontiersin.org", "March", "2012", "|", "Volume", "3", "|", "Article", "35", "|", "1" ]

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[ "Vascular", "Health", "and", "Risk", "Management", "Open", "Access", "Full", "Text", "Article", "Dovepress", "open", "access", "to", "scientific", "and", "medical", "research", "O", "R", "i", "g", "i", "N", "A", "L", "R", "E", "s", "E", "A", "R", "c", "H", "costs", "and", "outcomes", "of", "noncardioembolic", "ischemic", "stroke", "in", "a", "managed", "care", "population", "Nicole", "M", "Engel-Nitz1", "stephen", "D", "sander", "2", "carolyn", "Harley", "3", "gabriel", "gomez", "Rey", "1", "Hemal", "shah", "2", "1Health", "Economic", "and", "Outcomes", "Research,", "i3", "innovus,", "Eden", "Prairie,", "MN,", "UsA;", "2Health", "Economic", "and", "Outcomes", "Research,", "Boehringer", "ingelheim", "Pharmaceuticals,", "inc.,", "Ridgefield,", "cT,", "UsA;", "3Health", "Economic", "and", "Outcomes", "Research,", "i3", "innovus,", "Palo", "Alto,", "c", "A,", "UsA", "correspondence:", "Nicole", "M", "Engel-Nitz", "i3", "innovus,", "Health", "Economic", "and", "Outcomes", "Research,", "An", "ingenix", "company,", "12125", "Technology", "Drive,", "Eden", "Prairie,", "MN", "55344,", "UsA", "Tel", "+1", "952", "833", "8048", "Fax", "+1", "952", "833", "6045", "Email", "nicole.engel-nitz@i3innovus.com", "submit", "your", "manuscript", "|", "www.dovepress.com", "Dovepress", "DOI:", "10.2147/VHRM.S10851", "Purpose:", "To", "evaluate", "the", "clinical", "outcomes", "and", "incremental", "health", "care", "costs", "of", "ischemic", "stroke", "in", "a", "US", "managed", "care", "population.", "Patients", "and", "methods:", "A", "retrospective", "cohort", "analysis", "was", "done", "on", "patients", "(aged", "18+", "years)", "hospitalized", "with", "noncardioembolic", "ischemic", "stroke", "from", "January", "1,", "2002,", "through", "December", "31,", "2003,", "identified", "from", "commercial", "health", "plan", "administrative", "claims.", "New", "or", "recurrent", "stroke", "was", "based", "on", "history", "in", "the", "previous", "12", "months,", "with", "index", "date", "defined", "as", "first", "date", "ofindication", "of", "stroke.", "A", "control", "group", "without", "stroke", "or", "transient", "ischemic", "attack", "(TIA)", "was", "matched", "(1:3)", "on", "age,", "sex,", "and", "geographic", "region,", "with", "an", "index", "date", "defined", "as", "the", "first", "medical", "claim", "during", "the", "patient", "identification", "period.", "Patients", "with", "atrial", "fibrillation", "or", "mitral", "value", "abnormalities", "were", "excluded.", "Ischemic", "stroke", "and", "control", "cohorts", "were", "compared", "on", "4-year", "clinical", "outcomes", "and", "1-year", "costs.", "Results:", "Of", "2180", "ischemic", "stroke", "patients,", "1808", "(82.9%)", "had", "new", "stroke", "and", "372", "(17.1%)", "had", "a", "recurrent", "stroke.", "Stroke", "patients", "had", "higher", "unadjusted", "rates", "of", "additional", "stroke,", "TIA,", "and", "fatal", "outcomes", "compared", "with", "the", "6540", "matched", "controls.", "Recurrent", "stroke", "patients", "had", "higher", "rates", "of", "adverse", "clinical", "outcomes", "compared", "with", "new", "stroke", "patients;", "costs", "attributed", "to", "recurrent", "stroke", "were", "also", "higher.", "Stroke", "patients", "were", "2.4", "times", "more", "likely", "to", "be", "hospitalized", "in", "follow-up", "compared", "with", "controls", "(hazard", "ratio", "[HR]", "2.4,", "95%", "confidence", "interval", "[CI]:", "2.2,", "2.6).", "Occurrence", "of", "stroke", "following", "discharge", "was", "21", "times", "more", "likely", "among", "patients", "with", "index", "stroke", "compared", "with", "controls", "(HR", "21.0,", "95%", "CI:", "16.1,", "27.3).", "Stroke", "was", "also", "predictive", "of", "death", "(HR", "1.8,", "95%", "CI:", "1.3,", "2.5).", "Controlling", "for", "covariates,", "stroke", "patients", "had", "significantly", "higher", "costs", "compared", "with", "control", "patients", "in", "the", "year", "following", "the", "index", "event.", "Conclusion:", "Noncardioembolic", "ischemic", "stroke", "patients", "had", "significantly", "poorer", "outcomes", "and", "higher", "costs", "compared", "with", "controls.", "Recurrent", "stroke", "appears", "to", "contribute", "substantially", "to", "these", "higher", "rates", "of", "adverse", "outcomes", "and", "costs.", "Keywords:", "burden", "of", "illness,", "stroke/cerebrovascular", "accident,", "cardiovascular", "disease,", "claims", "analysis,", "costs", "of", "care,", "health", "care", "outcomes", "Background", "Stroke", "is", "a", "major", "cause", "of", "serious,", "long-term", "disability,", "mortality,", "and", "institutionalization,", "and", "it", "accounts", "for", "substantial", "use", "of", "health", "care", "resources.1–4", "When", "considered", "separately", "from", "other", "cardiovascular", "diseases,", "stroke", "ranks", "third", "among", "all", "causes", "of", "death,", "following", "diseases", "of", "the", "heart", "and", "cancer.5", "Among", "survivors,", 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[ "Aygören-Pürsün", "et", "al.", "Allergy,", "Asthma", "&", "Clinical", "Immunology", "2010,", "6:21", "http://www.aacijournal.com/content/6/1/21", "R", "E", "S", "E", "A", "R", "C", "H", "ALLERGY,", "ASTHMA", "&", "CLINICAL", "IMMUNOLOGY", "Open", "Access", "On", "demand", "treatment", "and", "home", "therapy", "of", "hereditary", "angioedema", "in", "Germany", "-", "the", "Frankfurt", "experience", "Emel", "Aygören-Pürsün*,", "Inmaculada", "Martinez-Saguer,", "Eva", "Rusicke,", "Thomas", "Klingebiel,", "Wolfhart", "Kreuz", "Abstract", "Background:", "Manifestation", "of", "acute", "edema", "in", "hereditary", "angioedema", "(HAE)", "is", "characterized", "by", "interindividual", "and", "intraindividual", "variability", "in", "symptom", "expression", "over", "time.", "Flexible", "therapy", "options", "are", "needed.", "Methods:", "We", "describe", "and", "report", "on", "the", "outcomes", "of", "the", "highly", "individualized", "approach", "to", "HAE", "therapy", "practiced", "at", "our", "HAE", "center", "in", "Frankfurt", "(Germany).", "Results:", "The", "HAE", "center", "at", "the", "Frankfurt", "University", "Hospital", "currently", "treats", "450", "adults", "with", "HAE", "or", "AAE", "and", "107", "pediatric", "HAE", "patients", "with", "highly", "individualized", "therapeutic", "approaches.", "73.9%", "of", "the", "adult", "patients", "treat", "HAE", "attacks", "by", "on-demand", "therapy", "with", "pasteurized", "pd", "C1-INH", "concentrate,", "9.8%", "use", "additional", "prophylaxis", "with", "attenuated", "androgens,", "1%", "of", "the", "total", "patient", "population", "in", "Frankfurt", "has", "been", "treated", "with", "Icatibant", "up", "to", "now.", "In", "addition", "adult", "and", "selected", "pediatric", "patients", "with", "a", "high", "frequency", "of", "severe", "attacks", "are", "instructed", "to", "apply", "individual", "replacement", "therapy", "(IRT)", "with", "pasteurized", "pd", "C1-INH", "concentrate.", "Improvement", "on", "Quality", "of", "Life", "items", "was", "shown", "for", "these", "patients", "compared", "to", "previous", "long-term", "danazol", "prophylaxis.", "Home", "treatment", "of", "HAE", "patients", "was", "developed", "in", "the", "Frankfurt", "HAE", "center", "in", "line", "with", "experiences", "in", "hemophilia", "therapy", "and", "has", "so", "far", "been", "implemented", "over", "a", "period", "of", "28", "years.", "At", "present", "248", "(55%)", "of", "the", "adult", "patients", "and", "26", "(24%)", "of", "the", "pediatric", "patients", "are", "practicing", "home", "treatment", "either", "as", "on", "demand", "or", "IRT", "treatment.", "Conclusions:", "In", "conclusion,", "the", "individualized", "home", "therapies", "provided", "by", "our", "HAE", "center,", "aim", "to", "limit", "the", "disruption", "to", "normal", "daily", "activities", "that", "occurs", "for", "many", "HAE", "patients.", "Furthermore,", "we", "seek", "to", "optimize", "the", "economic", "burden", "of", "the", "disease", "while", "offering", "a", "maximum", "quality", "of", "life", "to", "our", "patients.", "Introduction", "On", "demand", "treatment", "of", "acute", "angioedema", "in", "HAE", "type", "I", "and", "II", "Hereditary", "angioedema", "(HAE)", "is", "based", "on", "a", "hereditary,", "life-long", "deficiency", "of", "C1-esterase-inhibitor", "(C1-INH).", "Patients", "with", "HAE", "suffer", "from", "recurrent,", "localized,", "acute", "edema", "attacks", "that", "can", "affect", "any", "body", "location.", "Mainly", "affected", "are", "subcutaneous", "tissues", "or", "mucous", "membranes,", "the", "gastrointestinal", "tract,", "and", "the", "throat,", "the", "latter", "leading", "to", "potentially", "life-threatening", "laryngeal", "edema.", "Manifestation", "of", "acute", "edema", "in", "hereditary", "angioedema", "is", "characterized", "by", "interindividual", "and", "intraindividual", "variability", "in", "symptom", "expression", "over", "*", "Correspondence:", "eap@em.uni-frankfurt.de", "Centre", "of", "Pediatrics", "III,", "Department", "of", "Hematology,", "Oncology", "and", "Hemostasis,", "Comprehensive", "Care", "Centre", "for", "Thrombosis", "and", "Hemostasis,", "Johann", "Wolfgang", "Goethe", "University", "Hospital,", "Frankfurt", "am", "Main,", "Germany", "time.", "The", "onset", "of", "the", "next", "attack,", "its", "location", "and", "its", "severity", "are", "unpredictable.", "Treatment", "options", "adapted", "on", "the", "specific", "needs", "of", "the", "individual", "patient", "need", "to", "be", "implemented", "based", "on", "the", "type", "and", "frequency", "of", "HAE", "attacks", "and", "should", "be", "re-evaluated", "from", "time", "to", "time", "[1,2].", "Worldwide,", "five", "different", "therapy", "options", "for", "on", "demand", "therapy", "of", "acute", "attacks", "based", "on", "three", "distinct", "pathophysiological", "approaches", "are", "currently", "under", "clini-", "cal", "investigation", "or", "already", "approved", "in", "different", "coun-", "tries.", "For", "replacement", "of", "lacking", "or", "dysfunctional", "C1-INH,", "three", "different", "C1-INH", "concentrates", "-", "two", "plasma-derived", "(pd)", "and", "one", "expressed", "in", "transgenic", "rabbits", "-", "are", "available", "or", "under", "investigation.", "Antagon-", "ism", "of", "the", "bradykinin", "B2-receptor,", "which", "is", "supposed", "to", "largely", "convey", "the", "increase", "in", "vascular", "permeability", "lead-", "ing", "to", "acute", "angioedema", "in", "HAE,", "via", "the", "B2-receptor", "©", "2010", "Aygören-Pürsün", "et", "al;", "licensee", "BioMed", "Central", "Ltd.", "This", "is", "an", "Open", "Access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "License", "(http://creativecommons.org/licenses/by/2.0),", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited." ]

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[ "Borel", "et", "al.", "BMC", "Microbiology", "2010,", "10:201", "http://www.biomedcentral.com/1471-2180/10/201", "R", "E", "S", "E", "A", "R", "C", "H", "A", "R", "T", "I", "C", "L", "E", "Open", "Access", "Mixed", "infections", "with", "Chlamydia", "and", "porcine", "epidemic", "diarrhea", "virus", "-", "a", "new", "in", "vitro", "model", "of", "chlamydial", "persistence", "Nicole", "Borel1*,", "Claudia", "Dumrese2,", "Urs", "Ziegler2,", "Andrea", "Schifferli1,", "Carmen", "Kaiser1,", "Andreas", "Pospischil1", "Abstract", "Background:", "Chlamydiae", "induce", "persistent", "infections,", "which", "have", "been", "associated", "with", "a", "wide", "range", "of", "chronic", "diseases", "in", "humans", "and", "animals.", "Mixed", "infections", "with", "Chlamydia", "and", "porcine", "epidemic", "diarrhea", "virus", "(PEDV)", "may", "result", "in", "generation", "of", "persistent", "chlamydial", "infections.", "To", "test", "this", "hypothesis,", "an", "in", "vitro", "model", "of", "dual", "infection", "with", "cell", "culture-adapted", "PEDV", "and", "Chlamydia", "abortus", "or", "Chlamydia", "pecorum", "in", "Vero", "cells", "was", "established.", "Results:", "Infected", "cultures", "were", "investigated", "by", "immunofluorescence", "(IF),", "transmission", "electron", "microscopy", "(TEM)", "and", "re-infection", "experiments.", "By", "IF,", "Chlamydia-infected", "cells", "showed", "normal", "inclusions", "after", "39", "hpi.", "Dual", "infections", "with", "Chlamydia", "abortus", "revealed", "a", "heterogenous", "mix", "of", "inclusion", "types", "including", "small", "inclusions", "consisting", "of", "aberrant", "bodies", "(ABs),", "medium-sized", "inclusions", "consisting", "of", "ABs", "and", "reticulate", "bodies", "and", "normal", "inclusions.", "Only", "aberrant", "inclusions", "were", "observable", "in", "dual", "infection", "experiments", "with", "Chlamydia", "pecorum", "and", "PEDV.", "TEM", "examinations", "of", "mixed", "infections", "with", "Chlamydia", "abortus", "and", "Chlamydia", "pecorum", "revealed", "aberrant", "chlamydial", "inclusions", "containing", "reticulate-like,", "pleomorphic", "ABs,", "which", "were", "up", "to", "2", "μm", "in", "diameter.", "No", "re-differentiation", "into", "elementary", "bodies", "(EBs)", "was", "detected.", "In", "re-infection", "experiments,", "co-infected", "cells", "produced", "fewer", "EBs", "than", "monoinfected", "cells.", "Conclusions:", "In", "the", "present", "study", "we", "confirm", "that", "PEDV", "co-infection", "alters", "the", "developmental", "cycle", "of", "member", "species", "of", "the", "family", "Chlamydiaceae,", "in", "a", "similar", "manner", "to", "other", "well-described", "persistence", "induction", "methods.", "Interestingly,", "this", "effect", "appears", "to", "be", "partially", "species-specific", "as", "Chlamydia", "pecorum", "appears", "more", "sensitive", "to", "PEDV", "co-infection", "than", "Chlamydia", "abortus,", "as", "evidenced", "by", "TEM", "and", "IF", "observations", "of", "a", "homogenous", "population", "of", "aberrant", "inclusions", "in", "PEDV", "-", "Chlamydia", "pecorum", "co-infections.", "Background", "Chlamydiae", "are", "implicated", "in", "a", "wide", "variety", "of", "diseases", "in", "both", "animals", "and", "humans.", "Although", "acute", "infections", "in", "animal", "chlamydioses", "are", "the", "most", "commonly", "reported,", "chronic", "chlamydial", "infections", "are", "also", "asso-", "ciated", "with", "a", "variety", "of", "diseases", "in", "humans", "and", "animals.", "These", "latter", "infections", "are", "characterized", "by", "inflamma-", "tion", "and", "scarring", "resulting", "in", "significant", "damage", "of", "the", "host.", "A", "causative", "role", "in", "chronic", "diseases", "requires", "that", "chlamydiae", "persist", "within", "infected", "tissue", "for", "extended", "periods", "of", "time.", "Current", "theories,", "based", "primarily", "on", "in", "vitro", "data,", "suggest", "that", "chlamydial", "persistence,", "and", "the", "resulting", "chronic", "inflammation,", "is", "linked", "to", "*", "Correspondence:", "n.borel@access.uzh.ch", "1Institute", "of", "Veterinary", "Pathology,", "Vetsuisse", "Faculty,", "University", "of", "Zurich,", "Zurich,", "Switzerland", "morphological", "and", "metabolic", "conversion", "of", "the", "actively", "replicating", "and", "intracellular", "reticulate", "body", "(RB)", "into", "an", "alternative,", "non-replicative", "form", "known", "as", "an", "aberrant", "body", "(AB)", "[1].", "In", "vitro,", "alterations", "of", "the", "normal", "devel-", "opmental", "cycle", "of", "Chlamydia", "trachomatis", "and", "Chlamy-", "dia", "pneumoniae", "can", "be", "induced", "by", "Interferon-g", "(IFN-g),", "tumor", "necrosis", "factor-a", "(TNF-a)", "and", "penicillin", "G", "expo-", "sure", "as", "well", "as", "amino", "acid", "or", "iron", "deprivation", "and", "monocyte", "infection", "[2,3].", "To", "date,", "in", "vitro", "models", "for", "animal", "pathogens,", "Chlamydia", "abortus", "and", "Chlamydia", "pecorum", "have", "not", "been", "described", "although", "both", "organ-", "isms", "are", "associated", "with", "chronic", "disease", "in", "koalas", "and", "small", "ruminants", "[1].", "In", "pigs,", "several", "chlamydial", "species,", "including", "Chlamy-", "dia", "abortus,", "Chlamydia", "psittaci,", "Chlamydia", "pecorum", "and", "Chlamydia", "suis,", "have", "been", "implicated", "in", "a", "variety", "of", "©", "2010", "Borel", "et", "al;", "licensee", "BioMed", "Central", "Ltd.", "This", "is", "an", "Open", "Access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "License", "(http://creativecommons.org/licenses/by/2.0),", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited." ]

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[ "BMC", "Pregnancy", "and", "Childbirth", "2BC2M0a0Cs2Pe,rergneapncoyratnd", "Childbirth", "x", "Intrauterine", "pregnancy", "following", "low-dose", "gonadotropin", "ovulation", "induction", "and", "direct", "intraperitoneal", "insemination", "for", "severe", "cervical", "stenosis", "E", "Scott", "Sills*1,2", "and", "Gianpiero", "D", "Palermo3", "Address:", "1Georgia", "Reproductive", "Specialists", "LLC;", "Atlanta,", "Georgia", "USA,", "2Division", "of", "Reproductive", "Endocrinology", "and", "Infertility,", "Department", "of", "Obstetrics", "and", "Gynecology,", "Atlanta", "Medical", "Center;", "Atlanta,", "Georgia", "USA", "and", "3Cornell", "Institute", "for", "Reproductive", "Medicine,", "Weill", "Medical", "College", "of", "Cornell", "University;", "New", "York,", "New", "York", "USA", "E-mail:", "E", "Sills*", "-", "dr.sills@ivf.com;", "Gianpiero", "D", "Palermo", "-", "gdpalerm@med.cornell.edu", "*Corresponding", "author", "BioMed", "Central", "Open", "Access", "Published:", "26", "November", "2002", "BMC", "Pregnancy", "and", "Childbirth", "2002,", "2:9", "This", "article", "is", "available", "from:", "http://www.biomedcentral.com/1471-2393/2/9", "Received:", "25", "September", "2002", "Accepted:", "26", "November", "2002", "©", "2002", "Sills", "and", "Palermo;", "licensee", "BioMed", "Central", "Ltd.", "This", "is", "an", "Open", "Access", "article:", "verbatim", "copying", "and", "redistribution", "of", "this", "article", "are", "permitted", "in", "all", "media", "for", "any", "purpose,", "provided", "this", "notice", "is", "preserved", "along", "with", "the", "article's", "original", "URL.", "Keywords:", "cervical", "factor", "infertility,", "intraperitoneal", "insemination,", "ovulation", "induction", "Abstract", "Background:", "We", "present", "a", "case", "of", "primary", "infertility", "related", "to", "extreme", "cervical", "stenosis,", "a", "subset", "of", "cervical", "factor", "infertility", "which", "accounts", "for", "approximately", "5%", "of", "all", "clinical", "infertility", "referrals.", "Case", "presentation:", "A", "37", "year-old", "nulligravida", "was", "successfully", "treated", "with", "ovulation", "induction", "via", "recombinant", "follicle", "stimulating", "hormone", "(FSH)", "and", "direct", "intraperitoneal", "insemination", "(IPI).", "Anticipating", "controlled", "ovarian", "hyperstimulation", "with", "in", "vitro", "fertilization/embryo", "transfer", "(IVF),", "the", "patient", "underwent", "hysteroscopy", "and", "cervical", "recanalization,", "but", "safe", "intrauterine", "access", "was", "not", "possible", "due", "to", "severe", "proximal", "cervical", "stricture.", "Hysterosalpingogram", "established", "bilateral", "tubal", "patency", "and", "confirmed", "an", "irregular", "cervical", "contour.", "Since", "the", "cervical", "canal", "could", "not", "be", "traversed,", "neither", "standard", "intrauterine", "insemination", "nor", "transcervical", "embryo", "transfer", "could", "be", "offered.", "Prepared", "spermatozoa", "were", "therefore", "placed", "intraperitoneally", "at", "both", "tubal", "fimbria", "under", "real-time", "transvaginal", "sonographic", "guidance", "using", "a", "17", "gage", "single-lumen", "IVF", "needle.", "Supplementary", "progesterone", "was", "administered", "as", "200", "mg/d", "lozenge", "(troche)", "plus", "200", "mg/d", "rectal", "suppository,", "maintained", "from", "the", "day", "following", "IPI", "to", "the", "8th", "gestational", "week.", "A", "singleton", "intrauterine", "pregnancy", "was", "achieved", "after", "the", "second", "ovulation", "induction", "attempt.", "Conclusions:", "In", "this", "report,", "we", "outline", "the", "relevance", "of", "cervical", "factor", "infertility", "to", "reproductive", "medicine", "practice.", "Additionally,", "our", "andrology", "evaluation,", "ovulation", "induction", "approach,", "spermatozoa", "preparation,", "and", "insemination", "technique", "in", "such", "cases", "are", "described.", "Background", "Cervical", "factor", "infertility", "accounts", "for", "~5%", "of", "all", "clinical", "infertility", "referrals,", "and", "common", "treatments", "for", "cervical", "stenosis", "include", "gamete", "or", "zygote", "intrafallopian", "transfer,", "and", "corrective", "surgical", "procedures", "designed", "to", "lyse", "stric-", "tures", "responsible", "for", "stenosis.", "However,", "intrauterine", "in-", "semination", "(IUI)", "is", "usually", "suggested", "early", "as", "an", "appropriate", "therapeutic", "consideration", "when", "semen", "pa-", "rameters", "are", "normal", "and", "the", "suspicion", "for", "tubal", "pathology", "is", "low.", "However,", "should", "the", "cervical", "canal", "be", "tortuous", "or", "Page", "1", "of", "5", "(page", "number", "not", "for", "citation", "purposes)" ]

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[ "Heinrich", "et", "al.", "BMC", "Cancer", "2011,", "11:346", "http://www.biomedcentral.com/1471-2407/11/346", "S", "T", "U", "D", "Y", "P", "R", "O", "T", "O", "C", "O", "L", "Open", "Access", "Adjuvant", "gemcitabine", "versus", "NEOadjuvant", "gemcitabine/oxaliplatin", "plus", "adjuvant", "gemcitabine", "in", "resectable", "pancreatic", "cancer:", "a", "randomized", "multicenter", "phase", "III", "study", "(NEOPAC", "study)", "Stefan", "Heinrich1,", "Bernhard", "Pestalozzi2,", "Mickael", "Lesurtel3,", "Frederik", "Berrevoet4,", "Stéphanie", "Laurent5,", "Jean-Robert", "Delpero6,", "Jean-Luc", "Raoul7,", "Phillippe", "Bachellier8,", "Patrick", "Dufour9,", "Markus", "Moehler10,", "Achim", "Weber11,", "Hauke", "Lang1,", "Xavier", "Rogiers4", "and", "Pierre-Alain", "Clavien3*", "Abstract", "Background:", "Despite", "major", "improvements", "in", "the", "perioperative", "outcome", "of", "pancreas", "surgery,", "the", "prognosis", "of", "pancreatic", "cancer", "after", "curative", "resection", "remains", "poor.", "Adjuvant", "chemotherapy", "increases", "disease-free", "and", "overall", "survival,", "but", "this", "treatment", "cannot", "be", "offered", "to", "a", "significant", "proportion", "of", "patients", "due", "to", "the", "surgical", "morbidity.", "In", "contrast,", "almost", "all", "patients", "can", "receive", "(neo)adjuvant", "chemotherapy", "before", "surgery.", "This", "treatment", "is", "safe", "and", "effective,", "and", "has", "resulted", "in", "a", "median", "survival", "of", "26.5", "months", "in", "a", "recent", "phase", "II", "trial.", "Moreover,", "neoadjuvant", "chemotherapy", "improves", "the", "nutritional", "status", "of", "patients", "with", "pancreatic", "cancer.", "This", "multicenter", "phase", "III", "trial", "(NEOPAC)", "has", "been", "designed", "to", "explore", "the", "efficacy", "of", "neoadjuvant", "chemotherapy.", "Methods/Design:", "This", "is", "a", "prospective", "randomized", "phase", "III", "trial.", "Patients", "with", "resectable", "cytologically", "proven", "adenocarcinoma", "of", "the", "pancreatic", "head", "are", "eligible", "for", "this", "study.", "All", "patients", "must", "be", "at", "least", "18", "years", "old", "and", "must", "provide", "written", "informed", "consent.", "An", "infiltration", "of", "the", "superior", "mesenteric", "vein", ">", "180°", "or", "major", "visceral", "arteries", "are", "considered", "exclusion", "criteria.", "Eligible", "patients", "will", "be", "randomized", "to", "surgery", "followed", "by", "adjuvant", "gemcitabine", "(1000", "mg/m2)", "for", "6", "months", "or", "neoadjuvant", "chemotherapy", "(gemcitabine", "1000", "mg/m2,", "oxaliplatin", "100", "mg/m2)", "followed", "by", "surgery", "and", "the", "same", "adjuvant", "treatment.", "Neoadjuvant", "chemotherapy", "is", "given", "four", "times", "every", "two", "weeks.", "The", "staging", "as", "well", "as", "the", "restaging", "protocol", "after", "neoadjuvant", "chemotherapy", "include", "computed", "tomography", "of", "chest", "and", "abdomen", "and", "diagnostic", "laparoscopy.", "The", "primary", "study", "endpoint", "is", "progression-free", "survival.", "According", "to", "the", "sample", "size", "calculation,", "155", "patients", "need", "to", "be", "randomized", "to", "each", "treatment", "arm.", "Disease", "recurrence", "will", "be", "documented", "by", "scheduled", "computed", "tomography", "scans", "9,", "12,", "15,", "21", "and", "thereafter", "every", "6", "months", "until", "disease", "progression.", "For", "quality", "control,", "circumferential", "resection", "margins", "are", "marked", "intraoperatively,", "and", "representative", "histological", "sections", "will", "be", "centrally", "reviewed", "by", "a", "dedicated", "pathologist.", "Discussion:", "The", "NEOPAC", "study", "will", "determine", "the", "efficacy", "of", "neoadjuvant", "chemotherapy", "in", "pancreatic", "cancer", "for", "the", "first", "time", "and", "offers", "a", "unique", "potential", "for", "translational", "research.", "Furthermore,", "this", "trial", "will", "provide", "the", "unbiased", "overall", "survival", "of", "all", "patients", "undergoing", "surgery", "for", "resectable", "cancer", "of", "the", "pancreatic", "head.", "Trial", "registration:", "clinicalTrials.gov", "NCT01314027", "*", "Correspondence:", "clavien@access.uzh.ch", "3Visceral", "and", "Transplantation", "Surgery,", "University", "Hospital", "of", "Zurich,", "Raemistrasse", "100,", "8091", "Zuerich,", "Switzerland", "Full", "list", "of", "author", "information", "is", "available", "at", "the", "end", "of", "the", "article", "©", "2011", "Heinrich", "et", "al;", "licensee", "BioMed", "Central", "Ltd.", "This", "is", "an", "Open", "Access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "License", "(http://creativecommons.org/licenses/by/2.0),", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited." ]

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[ "Acta", "Crystallographica", "Section", "E", "Structure", "Reports", "Online", "ISSN", "1600-5368", "Methyl", "3-(4-bromophenyl)-2-(1H-indol-", "3-ylmethyl)-5-[1-(4-methoxyphenyl)-4-", "oxo-2-phenylazetidin-2-yl]-4-nitro-", "pyrrolidine-2-carboxylate", "S.", "Nirmala,a", "E.", "Theboral", "Sugi", "Kamala,a", "L.", "Sudha,b*", "N.", "Arumugamc", "and", "R.", "Raghunathanc", "aDepartment", "of", "Physics,", "Easwari", "Engineering", "College,", "Ramapuram,", "Chennai", "600", "089,", "India,", "bDepartment", "of", "Physics,", "SRM", "University,", "Ramapuram", "Campus,", "Chennai", "600", "089,", "India,", "and", "cDepartment", "of", "Organic", "Chemistry,", "University", "of", "Madras,", "Guindy", "Campus,", "Chennai", "600", "025,", "India", "Correspondence", "e-mail:", "sudharose18@gmail.com", "Received", "10", "April", "2008;", "accepted", "12", "May", "2008", "Key", "indicators:", "single-crystal", "X-ray", "study;", "T", "=", "293", "K;", "mean", "(C–C)", "=", "0.004", "A˚;", "R", "factor", "=", "0.040;", "wR", "factor", "=", "0.120;", "data-to-parameter", "ratio", "=", "19.7.", "In", "the", "title", "compound,", "C37H33BrN4O6,", "the", "pyrrolidine", "ring", "adopts", "an", "envelope", "conformation.", "The", "-lactam", "ring", "is", "planar", "and", "makes", "dihedral", "angles", "of", "70.16", "(13)", "and", "28.32", "(13)", "with", "the", "phenyl", "and", "4-methoxyphenyl", "rings,", "respectively.", "The", "molecular", "packing", "is", "stabilized", "by", "intramolecular", "C—H", "O", "interactions", "and", "the", "crystal", "packing", "is", "determined", "by", "inter-", "molecular", "N—H", "O", "hydrogen", "bonds,", "and", "C—H", "O", "and", "C—H", "interactions.", "Related", "literature", "For", "related", "literature,", "see:", "Kamala", "et", "al.", "(2008);", "Lukacs", "&", "Ohno", "(1990);", "Sundari", "Bhaskaran", "et", "al.", "(2006);", "Suzuki", "et", "al.", "(1994);", "Yang", "et", "al.", "(1987);", "Amal", "Raj", "et", "al.", "(2003);", "Cremer", "&", "Pople", "(1975);", "Nardelli", "(1995);", "U¨", "lku¨", "et", "al.", "(1997).", "Experimental", "Crystal", "data", "C37H33BrN4O6", "Mr", "=", "709.58", "Monoclinic,", "Cc", "a", "=", "11.3988", "(4)", "A˚", "organic", "compounds", "b", "=", "34.8587", "(13)", "A˚", "c", "=", "8.7039", "(3)", "A˚", "=", "100.982", "(2)", "V", "=", "3395.1", "(2)", "A˚", "3", "Z", "=", "4", "Data", "collection", "Bruker", "Kappa", "APEX2", "diffractometer", "Absorption", "correction:", "multi-scan", "(Blessing,", "1995)", "Tmin", "=", "0.703,", "Tmax", "=", "0.769", "Refinement", "R[F", "2", ">", "2", "(F", "2)]", "=", "0.040", "wR(F", "2)", "=", "0.120", "S", "=", "1.04", "8532", "reflections", "433", "parameters", "2", "restraints", "Table", "1", "Hydrogen-bond", "geometry", "(A˚", ",", ").", "D—H", "A", "C11—H11", "O4", "C4—H4", "O4i", "C31—H31", "O4ii", "N1—H1A", "O5iii", "C18—H18", "Cgiv", "D—H", "0.98", "0.93", "0.93", "0.86", "0.93", "Mo", "K", "radiation", "=", "1.26", "mm", "1", "T", "=", "293", "(2)", "K", "0.30", "0.22", "0.22", "mm", "37282", "measured", "reflections", "8532", "independent", "reflections", "6397", "reflections", "with", "I", ">", "2", "(I)", "Rint", "=", "0.028", "H-atom", "parameters", "constrained", "max", "=", "0.43", "e", "A˚", "3", "0.37", "e", "A˚", "3", "min", "=", "Absolute", "structure:", "Flack", "(1983),", "4142", "Friedel", "pairs", "Flack", "parameter:", "0.008", "(6)", "H", "2.27", "2.57", "2.55", "2.02", "2.80", "A", "D", "A", "2.717", "(3)", "3.186", "(3)", "3.399", "(3)", "2.820", "(3)", "3.641", "(4)", "D—H", "A", "107", "124", "152", "155", "151", "Symmetry", "codes:", "(i)", "x;", "y;", "z", "1;", "(ii)", "x;", "y", "þ", "2;", "z", "12;", "(iii)", "x", "þ", "12;", "y", "þ", "32;", "z", "12;", "(iv)", "x;", "y;", "z", "þ", "1.", "Cg", "is", "the", "centroid", "of", "the", "indole", "benzene", "ring.", "Data", "collection:", "APEX2", "(Bruker,", "2004);", "cell", "refinement:", "APEX2", "and", "SAINT", "(Bruker,", "2004);", "data", "reduction:", "SAINT", "and", "XPREP", "(Bruker,", "2004);", "program(s)", "used", "to", "solve", "structure:", "SHELXS97", "(Sheldrick,", "2008);", "program(s)", "used", "to", "refine", "structure:", "SHELXL97", "(Sheldrick,", "2008);", "molecular", "graphics:", "ORTEP-3", "(Farrugia,", "1997);", "software", "used", "to", "prepare", "material", "for", "publication:", "PLATON", "(Spek,", "2003).", "SN", "thanks", "Professor", "M.", "N.", "Ponnuswamy,", "Department", "of", "Crystallography", "and", "Biophysics,", "University", "of", "Madras,", "India,", "for", "his", "guidance", "and", "valuable", "suggestions.", "SN", "thanks", "SRM", "management,", "India,", "for", "their", "support.", "Supplementary", "data", "and", "figures", "for", "this", "paper", "are", "available", "from", "the", "IUCr", "electronic", "archives", "(Reference:", "RK2086).", "References", "Amal", "Raj,", "A.,", "Raghunathan,", "R.,", "Sridevi", "Kumari,", "M.", "R.", "&", "Raman,", "N.", "(2003).", "Bioorg.", "Med.", "Chem.", "11,", "407–409.", "Blessing,", "R.", "H.", "(1995).", "Acta", "Cryst.", "A51,", "33–38.", "Bruker", "(2004).", "APEX2,", "SAINT", "and", "XPREP.", "Bruker", "AXS", "Inc.,", "Madison,", "Wisconsin,", "USA.", "Cremer,", "D.", "&", "Pople,", "J.", "A.", "(1975).", "J.", "Am.", "Chem.", "Soc.", "97,", "1354–1358.", "Farrugia,", "L.", "J.", "(1997).", "J.", "Appl.", "Cryst.", "30,", "565.", "Flack,", "H.", "D.", "(1983).", "Acta", "Cryst.", "A39,", "876–881.", "Kamala,", "E.", "T.", "S.,", "Nirmala,", "S.,", "Sudha,", "L.,", "Arumugam,", "N.", "&", "Raghanathan,", "R.", "(2008).", "Acta", "Cryst.", "E64,", "o716–o717.", "Lukacs,", "G.", "&", "Ohno,", "M.", "(1990).", "Editors.", "Recent", "Progress", "in", "the", "Chemical", "Synthesis", "of", "Antibiotics.", "Berlin:", "Springer.", "Nardelli,", "M.", "(1995).", "J.", "Appl.", "Cryst.", "28,", "659.", "Sheldrick,", "G.", "M.", "(2008).", "Acta", "Cryst.", "A64,", "112–122.", "Spek,", "A.", "L.", "(2003).", "J.", "Appl.", "Cryst.", "36,", "7–13.", "Acta", "Cryst.", "(2008).", "E64,", "o1095–o1096", "doi:10.1107/S1600536808014190", "Nirmala", "et", "al.", "o1095" ]

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[ "Wang", "et", "al.", "Journal", "of", "Neuroinflammation", "2011,", "8:134", "http://www.jneuroinflammation.com/content/8/1/134", "R", "E", "V", "I", "E", "W", "Toll-like", "receptors", "in", "cerebral", "ischemic", "inflammatory", "injury", "Yan-Chun", "Wang1†,", "Sen", "Lin2†", "and", "Qing-Wu", "Yang1*", "JOURNAL", "OF", "NEUROINFLAMMATION", "Open", "Access", "Abstract", "Cerebral", "ischemia", "triggers", "acute", "inflammation,", "which", "has", "been", "associated", "with", "an", "increase", "in", "brain", "damage.", "The", "mechanisms", "that", "regulate", "the", "inflammatory", "response", "after", "cerebral", "ischemia", "are", "multifaceted.", "An", "important", "component", "of", "this", "response", "is", "the", "activation", "of", "the", "innate", "immune", "system.", "However,", "details", "of", "the", "role", "of", "the", "innate", "immune", "system", "within", "the", "complex", "array", "of", "mechanisms", "in", "cerebral", "ischemia", "remain", "unclear.", "There", "have", "been", "recent", "great", "strides", "in", "our", "understanding", "of", "the", "innate", "immune", "system,", "particularly", "in", "regard", "to", "the", "signaling", "mechanisms", "of", "Toll-like", "receptors", "(TLRs),", "whose", "primary", "role", "is", "the", "initial", "activation", "of", "immune", "cell", "responses.", "So", "far,", "few", "studies", "have", "examined", "the", "role", "of", "TLRs", "in", "cerebral", "ischemia.", "However,", "work", "with", "experimental", "models", "of", "ischemia", "suggests", "that", "TLRs", "are", "involved", "in", "the", "enhancement", "of", "cell", "damage", "following", "ischemia,", "and", "their", "absence", "is", "associated", "with", "lower", "infarct", "volumes.", "It", "may", "be", "possible", "that", "therapeutic", "targets", "could", "be", "designed", "to", "modulate", "activities", "of", "the", "innate", "immune", "system", "that", "would", "attenuate", "cerebral", "brain", "damage.", "Ischemic", "tolerance", "is", "a", "protective", "mechanism", "induced", "by", "a", "variety", "of", "preconditioning", "stimuli.", "Interpreting", "the", "molecular", "mechanism", "of", "ischemic", "tolerance", "will", "open", "investigative", "avenues", "into", "the", "treatment", "of", "cerebral", "ischemia.", "In", "this", "review,", "we", "discuss", "the", "critical", "role", "of", "TLRs", "in", "mediating", "cerebral", "ischemic", "injury.", "We", "also", "summarize", "evidence", "demonstrating", "that", "cerebral", "preconditioning", "downregulates", "pro-", "inflammatory", "TLR", "signaling,", "thus", "reducing", "the", "inflammation", "that", "exacerbates", "ischemic", "brain", "injury.", "Keywords:", "cerebral", "ischemia,", "Toll-like", "receptors", "(TLRs),", "inflammation,", "innate", "immunity", "Introduction", "Cerebral", "ischemia,", "the", "most", "common", "cerebrovascular", "disease,", "is", "one", "of", "the", "leading", "causes", "of", "morbidity", "and", "mortality", "around", "the", "world.", "However,", "many", "details", "of", "the", "pathogenesis", "of", "cerebral", "ischemia", "are", "not", "fully", "known.", "Cerebral", "ischemia", "is", "a", "condition", "of", "complex", "pathology", "that", "includes", "several", "inflammatory", "events,", "such", "as", "aggregation", "of", "inflammatory", "cells", "and", "upregula-", "tion", "of", "cytokines.", "Particularly,", "accumulating", "evidence", "suggests", "that", "Toll-like", "receptors", "(TLRs)", "are", "important", "mediators", "of", "cerebral", "ischemic", "injury.", "Therefore,", "under-", "standing", "TLRs", "and", "their", "relationship", "to", "cerebrovascular", "disease", "is", "becoming", "increasingly", "important", "to", "basic", "and", "clinical", "scientists.", "TLRs", "are", "key", "receptors", "in", "the", "mammalian", "innate", "immune", "response", "to", "infectious", "microorganisms,", "but", "are", "*", "Correspondence:", "yangqwmlys@hotmail.com", "†", "Contributed", "equally", "1Department", "of", "Neurology,", "Daping", "Hospital,", "Third", "Military", "Medical", "University,", "Changjiang", "Branch", "Road", "No.", "10,", "Yuzhong", "District,", "Chongqing", "400042,", "PR", "China", "Full", "list", "of", "author", "information", "is", "available", "at", "the", "end", "of", "the", "article", "also", "activated", "by", "host-derived", "molecules.", "The", "associa-", "tion", "between", "TLRs", "and", "the", "activation", "of", "a", "variety", "of", "downstream", "inflammatory", "cascades", "has", "been", "established", "in", "cerebral", "ischemia,", "as", "well", "as", "an", "involvement", "in", "inflammatory", "injury.", "Additionally,", "many", "diverse", "neuro-", "protective", "networks", "may", "redirect", "TLR", "signaling", "as", "one", "mechanism", "of", "endogenous", "protection.", "The", "purpose", "of", "this", "review", "is", "to", "(1)", "summarize", "cur-", "rent", "knowledge", "on", "TLR", "signaling;", "(2)", "examine", "the", "evi-", "dence", "implicating", "TLRs", "in", "cerebral", "ischemia", "injury,", "(3)", "outline", "known", "mechanisms", "of", "TLR-mediated", "neuronal", "damage,", "and", "(4)", "summarize", "the", "information", "on", "other", "molecules", "involved", "in", "TLR", "signaling.", "The", "latter", "may", "help", "identify", "potential", "clinical", "targets", "for", "preventing", "TLR-mediated", "cerebral", "ischemic", "injury.", "The", "innate", "immune", "response", "in", "the", "central", "nervous", "system", "(CNS)", "It", "was", "initially", "believed", "that", "innate", "immunity", "was", "an", "immunological", "program", "engaged", "by", "peripheral", "organs", "to", "maintain", "homeostasis", "after", "nonspecific", "stress", "and", "©", "2011", "Wang", "et", "al;", "licensee", "BioMed", "Central", "Ltd.", "This", "is", "an", "Open", "Access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "License", "(http://creativecommons.org/licenses/by/2.0),", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited." ]

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[ "Journal", "of", "Medical", "Case", "Reports", "Case", "report", "Bullet-induced", "synovitis", "as", "a", "cause", "of", "secondary", "osteoarthritis", "of", "the", "hip", "joint:", "A", "case", "report", "and", "review", "of", "literature", "Muhammad", "A", "Rehman1,", "Masood", "Umer2,", "Yasir", "J", "Sepah*3", "and", "Muhammad", "A", "Wajid2", "BioMed", "Central", "Open", "Access", "Address:", "1Resident", "Section", "of", "Orthopedics,", "Department", "of", "Surgery", "Aga", "Khan", "University", "Hospital,", "Karachi-74800,", "Pakistan,", "2Assistant", "Professor", "Section", "of", "Orthopedics,", "Department", "of", "Surgery", "Aga", "Khan", "University", "Hospital,", "Karachi-74800,", "Pakistan", "and", "3Department", "of", "Surgery", "(Orthopedics)", "Aga", "Khan", "University", "Medical", "College,", "Karachi-74800,", "Pakistan", "Email:", "Muhammad", "A", "Rehman", "-", "aamir.rehman@aku.edu;", "Masood", "Umer", "-", "masood.umer@aku.edu;", "Yasir", "J", "Sepah*", "-", "jamalyasir@gmail.com;", "Muhammad", "A", "Wajid", "-", "muhammad.wajid@aku.edu", "*", "Corresponding", "author", "Published:", "5", "December", "2007", "Journal", "of", "Medical", "Case", "Reports", "2007,", "1:171", "doi:10.1186/1752-1947-1-171", "Received:", "17", "May", "2007", "Accepted:", "5", "December", "2007", "This", "article", "is", "available", "from:", "http://www.jmedicalcasereports.com/content/1/1/171", "©", "2007", "Rehman", "et", "al;", "licensee", "BioMed", "Central", "Ltd.", "This", "is", "an", "Open", "Access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "License", "(http://creativecommons.org/licenses/by/2.0),", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited.", "Abstract", "Background:", "With", "increasing", "prevalence", "of", "gunshot", "injuries", "we", "are", "seeing", "more", "patients", "with", "retained", "bullet", "fragments", "lodged", "in", "their", "bodies.", "Embedded", "lead", "bullets", "are", "usually", "considered", "inert", "after", "their", "kinetic", "energy", "has", "dissipated", "hence", "these", "are", "not", "removed", "routinely.", "However,", "exposure", "of", "any", "foreign", "body", "to", "synovial", "fluid", "may", "lead", "to", "rapid", "degradation", "and", "hence", "result", "in", "systemic", "absorption,", "causing", "local", "and", "systemic", "symptoms.", "We", "present", "the", "case", "of", "a", "thirty", "year", "old", "man", "who", "came", "to", "our", "out", "patient", "department", "with", "a", "history", "of", "progressive,", "severe", "hip", "pain", "ten", "years", "after", "a", "gun", "shot", "injury", "to", "his", "right", "hip.", "Conclusion:", "The", "common", "belief", "that", "intraarticular", "bullets", "should", "not", "be", "removed", "has", "no", "benefit", "and", "may", "result", "in", "unwanted", "long", "term", "complications.", "Introduction", "With", "increasing", "prevalence", "of", "gunshot", "injuries", "we", "are", "see-", "ing", "more", "and", "more", "patients", "with", "retained", "bullet", "frag-", "ments", "lodged", "in", "their", "bodies", "[1].", "Embedded", "lead", "particles", "are", "usually", "considered", "inert", "after", "their", "kinetic", "energy", "has", "dissipated", "hence", "these", "are", "not", "removed", "routinely.", "Removal", "is", "indicated", "if", "they", "impinge", "on", "vital", "structures", "or", "are", "easily", "accessible", "during", "operation", "for", "other", "reasons", "[2-", "5].", "A", "review", "of", "literature", "shows", "that", "retained", "intra-articu-", "lar", "bullets", "have", "been", "associated", "with", "significant", "morbidity", "[6-9],", "joint", "degeneration", "and", "ultimately", "resulting", "in", "joint", "replacement.", "Intra-articular", "bullet", "fragments", "behave", "differently", "due", "to", "direct", "contact", "with", "synovial", "fluid.", "Lead", "being", "soluble", "in", "synovial", "fluid", "[3,10]", "can", "cause", "both", "local", "and", "systemic", "effects.", "Lead", "poisoning", "from", "retained", "intra", "articular", "bul-", "lets", "has", "been", "recognized", "in", "the", "literature", "since", "1867", "[3,11-", "13].", "Although", "in", "most", "of", "the", "cases", "the", "cause", "of", "arthropa-", "thy", "is", "not", "known", "but", "it's", "attributed", "mainly", "to", "mechanical", "forces", "along", "with", "local", "effects", "of", "lead", "poisoning", "[3,4,6,7,10,14].", "A", "retained", "bullet", "can", "not", "only", "produce", "foreign", "body", "reaction,", "mechanical", "articular", "cartilage", "dam-", "age", "and", "proliferative", "synovitis,", "leading", "to", "destructive", "arthritis", "but", "can", "also", "lead", "to", "systemic", "absorption", "of", "lead.", "However,", "there", "is", "considerable", "variation", "in", "extent", "of", "lead", "absorption,", "onset", "of", "time", "to", "symptoms,", "severity", "of", "symp-", "toms", "and", "toxicity", "[13].", "Symptoms", "of", "systemic", "lead", "poi-", "soning", "are", "usually", "vague;", "headache,", "nausea,", "fatigue", "and", "abdominal", "pain", "[15].", "Page", "1", "of", "4", "(page", "number", "not", "for", "citation", "purposes)" ]

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[ "Epidemiology", "1", "London", "School", "of", "Hygiene", "&", "Tropical", "Medicine,", "London,", "UK;", "2", "National", "Institute", "for", "Medical", "Research", "(NIMR),", "Mwanza,", "Tanzania;", "3", "African", "Medical", "and", "Research", "Foundation", "(AMREF),", "Mwanza,", "Tanzania;", "4", "St", "George’s", "Hospital,", "London,", "UK", "Correspondence", "to:", "Kathy", "Baisley,", "Department", "of", "Epidemiology", "&", "Population", "Health,", "Keppel", "Street,", "London,", "WC1E", "7HT,", "UK;", "kathy.baisley@", "lshtm.ac.uk", "Accepted", "15", "May", "2009", "Published", "Online", "First", "26", "May", "2009", "This", "paper", "is", "freely", "available", "online", "under", "the", "BMJ", "Journals", "unlocked", "scheme,", "see", "http://", "sti.bmj.com/info/unlocked.dtl", "370", "Bacterial", "vaginosis", "in", "female", "facility", "workers", "in", "north-western", "Tanzania:", "prevalence", "and", "risk", "factors", "K", "Baisley,1,2", "J", "Changalucha,2", "H", "A", "Weiss,1", "K", "Mugeye,3", "D", "Everett,1,2", "I", "Hambleton,1,2", "P", "Hay,4", "D", "Ross,1", "C", "Tanton,1,2", "T", "Chirwa,1,2", "R", "Hayes,1", "D", "Watson-Jones1,3", "ABSTRACT", "Objectives:", "To", "determine", "prevalence", "of,", "and", "risk", "factors", "for,", "bacterial", "vaginosis", "(BV)", "among", "herpes", "simplex", "virus", "(HSV)", "2", "seropositive", "Tanzanian", "women", "at", "enrolment", "into", "a", "randomised,", "placebo-controlled", "trial", "of", "HSV", "suppressive", "treatment.", "Methods:", "1305", "HSV-2", "seropositive", "women", "aged", "16–35", "years", "working", "in", "bars,", "guesthouses", "and", "similar", "facilities", "were", "interviewed,", "examined", "and", "tested", "for", "HIV,", "syphilis,", "Neisseria", "gonorrhoeae,", "Chlamydia", "trachomatis,", "BV,", "candidiasis", "and", "trichomoniasis.", "Factors", "associated", "with", "BV", "were", "analysed", "using", "logistic", "regression", "to", "estimate", "odds", "ratios", "and", "95%", "confidence", "intervals.", "Results:", "BV", "prevalence", "was", "62.9%;", "prevalence", "of", "Nugent", "score", "9–10", "was", "16.1%.", "Independent", "risk", "factors", "for", "BV", "were", "work", "facility", "type,", "fewer", "dependents,", "increasing", "alcohol", "consumption,", "sex", "in", "the", "last", "week", "(adjusted", "OR", "2.03;", "95%", "CI", "1.57", "to", "2.62),", "using", "cloths", "or", "cotton", "wool", "for", "menstrual", "hygiene,", "HIV", "(adjusted", "OR", "1.41;", "95%", "CI", "1.09", "to", "1.83)", "and", "Trichomonas", "vaginalis", "infection.", "There", "was", "no", "association", "between", "BV", "and", "the", "frequency", "or", "method", "of", "vaginal", "cleansing.", "However,", "BV", "was", "less", "prevalent", "among", "women", "who", "reported", "inserting", "sub-", "stances", "to", "dry", "the", "vagina", "for", "sex", "(adjusted", "OR", "0.44;", "95%", "CI", "0.25", "to", "0.75).", "Conclusion:", "BV", "was", "extremely", "prevalent", "among", "our", "study", "population", "of", "HSV-2", "positive", "female", "facility", "workers", "in", "North-western", "Tanzania.", "Although", "recent", "sex", "was", "associated", "with", "increased", "BV", "prevalence,", "vaginal", "drying", "was", "associated", "with", "lower", "BV", "prevalence.", "Further", "studies", "of", "the", "effects", "of", "specific", "practices", "on", "vaginal", "flora", "are", "warranted.", "Bacterial", "vaginosis", "(BV)", "is", "one", "of", "the", "most", "common", "vaginal", "infections", "worldwide.", "It", "is", "char-", "acterised", "by", "vaginal", "flora", "changes,", "including", "a", "decrease", "in", "lactobacilli,", "particularly", "those", "that", "produce", "hydrogen", "peroxide,", "and", "an", "increase", "in", "anaerobic", "and", "facultative", "anaerobic", "bacteria.", "BV", "has", "been", "associated", "with", "a", "variety", "of", "adverse", "health", "outcomes,", "including", "preterm", "delivery,1", "intrauterine", "infection,1", "pelvic", "inflammatory", "disease", "(PID)2", "and", "other", "gynaecological", "complications.3", "BV", "may", "also", "increase", "susceptibility", "to", "HIV", "and", "other", "sexually", "transmitted", "infections", "(STIs),4–6", "and", "in", "prospective", "studies", "BV", "has", "been", "associated", "with", "the", "acquisition", "of", "HIV", "and", "herpes", "simplex", "virus", "(HSV)", "type", "2.7–11", "BV", "may", "also", "facilitate", "HIV", "and", "HSV-2", "transmission", "by", "increasing", "the", "frequency", "of", "genital", "shedding", "of", "the", "virus.12", "The", "aetiology", "of", "BV", "remains", "poorly", "understood,", "although", "sexual", "activity", "and", "vaginal", "hygiene", "practices", "have", "been", "associated", "with", "BV.4", "13–16", "Reproductive", "hormones", "are", "also", "thought", "to", "play", "a", "role", "in", "the", "regulation", "of", "vaginal", "flora.17", "18", "In", "sub-", "Saharan", "Africa,", "the", "prevalence", "of", "BV", "is", "very", "high,", "ranging", "from", "30–51%", "in", "community", "based", "stu-", "dies.6", "10", "A", "high", "prevalence", "has", "also", "been", "reported", "among", "African–American", "women", "with", "estimates", "of", "up", "to", "50%", "in", "population-based", "surveys.19", "The", "reasons", "for", "this", "are", "unclear.", "Prevention", "of", "BV,", "and", "any", "impact", "that", "this", "might", "have", "on", "reducing", "the", "risk", "of", "HIV", "acquisition,", "will", "depend", "in", "part", "on", "identification", "of", "risk", "factors", "for", "BV", "that", "are", "susceptible", "to", "interventions.", "We", "report", "on", "the", "factors", "associated", "with", "BV", "prevalence", "at", "baseline", "in", "a", "cohort", "of", "women", "at", "high", "risk", "of", "STI", "working", "in", "bars,", "guesthouses", "and", "similar", "facilities", "in", "Tanzania.", "These", "women", "were", "enrolled", "into", "a", "trial", "of", "the", "effect", "of", "HSV-2", "suppressive", "treatment", "on", "HIV", "incidence,", "and", "on", "genital", "HIV", "and", "HSV-2", "viral", "shedding", "in", "women", "who", "are", "HIV", "positive.", "MATERIALS", "AND", "METHODS", "Study", "population", "A", "randomised,", "double-blind,", "placebo-controlled", "trial", "of", "acyclovir", "400", "mg", "twice", "daily", "suppressive", "treatment", "was", "conducted", "in", "women", "HSV-2", "seropositive", "in", "the", "Lake", "Victoria", "region", "of", "Tanzania.", "In", "total,", "1305", "women", "aged", "16–35", "years", "working", "in", "bars,", "guesthouses", "and", "similar", "facilities", "were", "enrolled", "in", "three", "phases", "from", "January", "2004", "to", "May", "2006.", "Trial", "procedures", "have", "been", "described", "previously.20", "Screening,", "enrolment", "and", "3-monthly", "follow-up", "visits", "were", "conducted", "at", "mobile", "clinics", "established", "in", "19", "communities", "in", "high", "HIV-", "transmission", "areas.", "Women", "were", "followed", "for", "12–", "30", "months", "depending", "on", "phase", "of", "enrolment.", "At", "screening,", "after", "informed", "consent,", "partici-", "pants", "were", "tested", "for", "antibodies", "to", "HSV-2", "and", "HIV,", "and", "interviewed", "about", "sociodemographic", "details,", "sexual", "behaviour", "and", "intravaginal", "practices", "(IVP).", "Eligible", "women", "were", "given", "an", "appointment", "to", "attend", "the", "mobile", "clinic", "8–12", "weeks", "later;", "women", "were", "asked", "to", "avoid", "vaginal", "cleansing", "before", "attending", "the", "visit.", "To", "be", "eligible,", "women", "had", "to", "be", "HSV-2", "seropositive,", "have", "no", "history", "of", "epilepsy,", "able", "to", "give", "informed", "consent,", "not", "planning", "to", "move", "out", "of", "the", "study", "site,", "not", "breastfeeding", "and", "not", "pregnant", "or", "planning", "preg-", "nancy", "during", "follow-up.", "At", "enrolment,", "participants", "were", "tested", "for", "pregnancy", "and", "were", "asked", "about", "recent", "sexual", "behaviour", "and", "IVP.", "Women", "were", "examined", "for", "symptoms", "of", "reproductive", "tract", "infections", "(RTI),", "and", "blood", "and", "genital", "samples", "were", "collected.", "Participants", "were", "offered", "syndromic", "management", "Sex", "Transm", "Infect", "2009;85:370–375.", "doi:10.1136/sti.2008.035543" ]

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[ "BMC", "Infectious", "Diseases", "Research", "article", "Geographic", "distribution", "and", "genetic", "diversity", "of", "the", "Ehrlichia", "sp.", "from", "Panola", "Mountain", "in", "Amblyomma", "americanum", "Amanda", "D", "Loftis*1,9,", "Tonya", "R", "Mixson1,", "Ellen", "Y", "Stromdahl2,", "Michael", "J", "Yabsley3,4,", "Laurel", "E", "Garrison5,", "Phillip", "C", "Williamson6,", "Robert", "R", "Fitak7,", "Paul", "A", "Fuerst7,", "Daryl", "J", "Kelly7", "and", "Keith", "W", "Blount8", "Address:", "1Centers", "for", "Disease", "Control", "and", "Prevention,", "Atlanta,", "GA", "30333,", "USA,", "2U.S.", "Army", "Center", "for", "Health", "Promotion", "and", "Preventive", "Medicine,", "Entomological", "Sciences", "Program,", "Aberdeen", "Proving", "Ground,", "MD", "21010-5403,", "USA,", "3Daniel", "B.", "Warnell", "School", "of", "Forestry", "and", "Natural", "Resources,", "University", "of", "Georgia,", "Athens,", "GA", "30602,", "USA,", "4Southeastern", "Cooperative", "Wildlife", "Disease", "Study,", "Department", "of", "Population", "Health,", "College", "of", "Veterinary", "Medicine,", "University", "of", "Georgia,", "Athens,", "GA", "30602,", "USA,", "5Georgia", "Division", "of", "Public", "Health,", "Atlanta,", "GA", "30303-3186,", "USA,", "6DNA/", "Identity", "Laboratory,", "Department", "of", "Pathology", "and", "Human", "Identification,", "University", "of", "North", "Texas", "Health", "Science", "Center,", "Ft.", "Worth,", "TX", "76107-", "2699,", "USA,", "7Department", "of", "Evolution,", "Ecology", "and", "Organismal", "Biology,", "The", "Ohio", "State", "University,", "Columbus,", "OH", "43210-1293,", "USA,", "8Air", "Force", "Research", "Laboratory,", "Brooks", "City-Base,", "TX", "78235,", "USA", "and", "9266", "N.", "Lincoln", "St.,", "Laramie,", "WY", "82070,", "USA", "Email:", "Amanda", "D", "Loftis*", "-", "adloftis@gmail.com;", "Tonya", "R", "Mixson", "-", "zdy0@cdc.gov;", "Ellen", "Y", "Stromdahl", "-", "ellen.stromdahl@us.army.mil;", "Michael", "J", "Yabsley", "-", "myabsley@vet.uga.edu;", "Laurel", "E", "Garrison", "-", "legarrison@dhr.state.ga.us;", "Phillip", "C", "Williamson", "-", "phwilliam@hsc.unt.edu;", "Robert", "R", "Fitak", "-", "fitak.2@osu.edu;", "Paul", "A", "Fuerst", "-", "fuerst.1@osu.edu;", "Daryl", "J", "Kelly", "-", "kelly.350@osu.edu;", "Keith", "W", "Blount", "-", "keith.blount@brooks.af.mil", "BioMed", "Central", "Open", "Access", "*", "Corresponding", "author", "Published:", "23", "April", "2008", "BMC", "Infectious", "Diseases", "2008,", "8:54", "doi:10.1186/1471-2334-8-54", "This", "article", "is", "available", "from:", "http://www.biomedcentral.com/1471-2334/8/54", "Received:", "9", "November", "2007", "Accepted:", "23", "April", "2008", "©", "2008", "Loftis", "et", "al;", "licensee", "BioMed", "Central", "Ltd.", "This", "is", "an", "Open", "Access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "License", "(http://creativecommons.org/licenses/by/2.0),", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited.", "Abstract", "Background:", "A", "novel", "Ehrlichia,", "closely", "related", "to", "Ehrlichia", "ruminantium,", "was", "recently", "discovered", "from", "Panola", "Mountain", "State", "Park,", "GA,", "USA.", "We", "conducted", "a", "study", "to", "determine", "if", "this", "agent", "was", "recently", "introduced", "into", "the", "United", "States.", "Methods:", "We", "developed", "a", "sensitive", "PCR", "assay", "based", "on", "the", "conserved", "gltA", "(citrate", "synthase)", "gene", "and", "tested", "DNA", "samples", "extracted", "from", "1964", "field-collected", "and", "1835", "human-biting", "Amblyomma", "americanum", "from", "23", "eastern", "states", "of", "the", "USA.", "Results:", "The", "novel", "agent", "was", "detected", "in", "36", "ticks", "collected", "from", "10", "states", "between", "1998", "and", "2006.", "Infected", "ticks", "were", "collected", "both", "from", "vegetation", "(n", "=", "14,", "0.7%)", "and", "from", "humans", "(n", "=", "22,", "1.2%).", "Fragments", "of", "the", "conserved", "gltA", "gene", "and", "the", "variable", "map1", "gene", "were", "sequenced", "from", "positive", "samples.", "Two", "distinct", "clades,", "with", "10.5%", "nucleic", "acid", "divergence", "over", "the", "730", "bp", "map1", "sequence,", "were", "identified.", "Conclusion:", "These", "data", "suggest", "that", "the", "Panola", "Mountain", "Ehrlichia", "was", "not", "recently", "introduced", "to", "the", "United", "States;", "this", "agent", "has", "an", "extensive", "distribution", "throughout", "the", "range", "of", "its", "tick", "vector,", "has", "been", "present", "in", "some", "locations", "for", "several", "years,", "and", "displays", "genetic", "variability.", "Furthermore,", "people", "in", "several", "states", "were", "exposed", "to", "this", "agent", "through", "the", "bite", "of", "infected", "ticks,", "underscoring", "the", "potential", "public", "health", "risk", "of", "this", "emerging", "ehrlichiosis.", "Page", "1", "of", "7", "(page", "number", "not", "for", "citation", "purposes)" ]

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[ "Erez", "et", "al.", "BMC", "Pregnancy", "and", "Childbirth", "2012,", "12:82", "http://www.biomedcentral.com/1471-2393/12/82", "R", "E", "S", "E", "A", "R", "C", "H", "A", "R", "T", "I", "C", "L", "E", "Open", "Access", "Early", "preterm", "delivery", "due", "to", "placenta", "previa", "is", "an", "independent", "risk", "factor", "for", "a", "subsequent", "spontaneous", "preterm", "birth", "Offer", "Erez1*,", "Lena", "Novack2,", "Vered", "Klaitman1,", "Idit", "Erez-Weiss3,", "Ruthy", "Beer-Weisel1,", "Doron", "Dukler1", "and", "Moshe", "Mazor1", "Abstract", "Background:", "To", "determine", "whether", "patients", "with", "placenta", "previa", "who", "delivered", "preterm", "have", "an", "increased", "risk", "for", "recurrent", "spontaneous", "preterm", "birth.", "Methods:", "This", "retrospective", "population", "based", "cohort", "study", "included", "patients", "who", "delivered", "after", "a", "primary", "cesarean", "section", "(n", "=", "9983).", "The", "rate", "of", "placenta", "previa,", "its", "recurrence,", "and", "the", "risk", "for", "recurrent", "preterm", "birth", "were", "determined.", "Results:", "Patients", "who", "had", "a", "placenta", "previa", "at", "the", "primary", "CS", "pregnancy", "had", "an", "increased", "risk", "for", "its", "recurrence", "[crude", "OR", "of", "2.65", "(95%", "CI", "1.3-5.5)].", "The", "rate", "of", "preterm", "birth", "in", "patients", "with", "placenta", "previa", "in", "the", "primary", "CS", "pregnancy", "was", "55.9%;", "and", "these", "patients", "had", "a", "higher", "rate", "of", "recurrent", "preterm", "delivery", "than", "the", "rest", "of", "the", "study", "population", "(p", "<", ".001).", "Among", "patients", "with", "placenta", "previa", "in", "the", "primary", "CS", "pregnancy,", "those", "who", "delivered", "preterm", "had", "a", "higher", "rate", "of", "recurrent", "spontaneous", "preterm", "birth", "regardless", "of", "the", "location", "of", "their", "placenta", "in", "the", "subsequent", "delivery", "[OR", "3.09", "(95%", "CI", "2.1-4.6)].", "In", "comparison", "to", "all", "patients", "with", "who", "had", "a", "primary", "cesarean", "section,", "patients", "who", "had", "placenta", "previa", "and", "delivered", "preterm", "had", "an", "independent", "increased", "risk", "for", "recurrent", "preterm", "birth", "[OR", "of", "3.6", "(95%", "CI", "1.5-8.5)].", "Conclusions:", "Women", "with", "placenta", "previa,", "who", "deliver", "preterm,", "especially", "before", "34", "weeks", "of", "gestation,", "are", "at", "increased", "risk", "for", "recurrent", "spontaneous", "preterm", "birth", "regardless", "to", "the", "site", "of", "placental", "implantation", "in", "the", "subsequent", "pregnancy.", "Thus,", "strict", "follow", "up", "by", "high", "risk", "pregnancies", "specialist", "is", "recommended.", "Keywords:", "Preterm", "birth,", "Placenta,", "Recurrent", "preterm", "delivery,", "Vaginal", "bleeding,", "Short", "cervix,", "Placenta", "previa", "Background", "Placenta", "previa", "is", "a", "risk", "factor", "for", "preterm", "birth,", "and", "contributes", "to", "about", "5%", "of", "all", "preterm", "deliveries.", "[1]", "The", "prevalence", "of", "placenta", "previa", "is", "0.3-0.5%", "of", "pregnancies", "[2-10],", "and", "the", "risk", "for", "this", "complication", "increases", "according", "to", "the", "number", "of", "prior", "cesarean", "deliveries", "[11-14].", "Placenta", "previa", "is", "associated", "with", "an", "increased", "maternal", "morbidity", "including", "the", "need", "for", "blood", "and", "blood", "products", "transfusion,", "urgent", "cesarean", "section,", "and", "cesarean", "hysterectomy.", "Moreover,", "a", "higher", "rate", "of", "peri-", "natal", "mortality", "and", "morbidity,", "especially", "respiratory", "*", "Correspondence:", "erezof@bgu.ac.il", "1Department", "of", "Obstetrics", "and", "Gynecology,", "Soroka", "University", "Medical", "Center,", "School", "of", "Medicine,", "Faculty", "of", "Health", "Sciences,", "Ben", "Gurion", "University", "of", "the", "Negev,", "P", "O", "Box", "151,", "Beer", "Sheva", "84101,", "Israel", "Full", "list", "of", "author", "information", "is", "available", "at", "the", "end", "of", "the", "article", "distress", "syndrome", "and", "anemia", "are", "associated", "with", "this", "abnormal", "placentation", "[15,16].", "Most", "of", "the", "patients", "with", "placenta", "previa", "are", "delivered", "preterm", "[4,17],", "and", "these", "deliveries", "are", "regarded", "as", "indi-", "cated", "preterm", "births", "due", "to", "excessive", "maternal", "hemorrhage.", "Nevertheless,", "recent", "evidence", "suggests", "that", "other", "mechanisms", "aside", "bleeding", "may", "lead", "to", "preterm", "birth", "in", "women", "with", "placenta", "previa", "[18,19].", "Patients", "with", "placenta", "previa", "who", "delivered", "preterm", "had", "a", "higher", "rate", "of", "intra-amniotic", "infection/inflammation", "than", "those", "who", "delivered", "at", "term", "[18],", "suggesting", "that", "similarly", "to", "spontaneous", "preterm", "birth,", "intra-amniotic", "infection", "or", "inflammation", "may", "contribute", "to", "the", "process", "of", "preterm", "parturition", "in", "patients", "with", "placenta", "previa.", "Moreover,", "women", "with", "this", "complication", "who", "had", "a", "short", "cervical", "length", "have", "an", "increased", "risk", "to", "deliver", "preterm", "[20-22].", "©", "2012", "Erez", "et", "al.;", "licensee", "BioMed", "Central", "Ltd.", "This", "is", "an", "Open", "Access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "License", "(http://creativecommons.org/licenses/by/2.0),", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited." ]

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[ "Hindawi", "Publishing", "Corporation", "Journal", "of", "Biomedicine", "and", "Biotechnology", "Volume", "2012,", "Article", "ID", "274150,", "8", "pages", "doi:10.1155/2012/274150", "Review", "Article", "Are", "Basophils", "Important", "Mediators", "for", "Helminth-Induced", "Th2", "Immune", "Responses?", "A", "Debate", "Sonia", "Leon-Cabrera", "and", "Ana", "Flisser", "Departamento", "de", "Microbiolog´ıa", "y", "Parasitolog´ıa,", "Facultad", "de", "Medicina,", "Universidad", "Nacional", "Auto´noma", "de", "M´exico,", "04510", "M´exico,", "DF,", "Mexico", "Correspondence", "should", "be", "addressed", "to", "Ana", "Flisser,", "flisser@unam.mx", "Received", "27", "May", "2011;", "Accepted", "8", "December", "2011", "Academic", "Editor:", "Abhay", "R.", "Satoskar", "Copyright", "©", "2012", "S.", "Leon-Cabrera", "and", "A.", "Flisser.", "This", "is", "an", "open", "access", "article", "distributed", "under", "the", "Creative", "Commons", "Attribution", "License,", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited.", "Helminth", "parasites", "induce", "Th2", "immune", "responses.", "Immunological", "mechanisms", "leading", "to", "Th2", "induction", "are", "mainly", "dependent", "on", "IL-4.", "However,", "early", "source", "of", "IL-4", "has", "not", "been", "precisely", "identified.", "Noticeably,", "basophils", "seem", "to", "be", "important", "mediators", "for", "inducing", "and", "maintaining", "the", "Th2", "response", "probably", "because", "they", "secrete", "IL-4", "and", "exert", "functions", "similar", "to", "APCs.", "Nevertheless,", "recent", "experimental", "evidence", "points", "that", "DCs", "could", "be", "also", "significant", "participants", "during", "this", "process.", "The", "involvement", "of", "basophils", "during", "memory", "responses", "is", "also", "discussed.", "1.", "Introduction", "Intestinal", "helminth", "infections", "still", "represent", "a", "public", "health", "problem", "in", "many", "developing", "tropical", "and", "subtropical", "coun-", "tries", "affecting", "the", "health", "of", "human", "beings", "and", "of", "livestock", "[1,", "2].", "CD4+", "T", "cells", "are", "the", "main", "cellular", "mediators", "in", "host", "helminth", "interactions.", "In", "response", "to", "different", "antigens,", "these", "cells", "differentiate", "in", "four", "types", "of", "T-helper", "cells", "Th1,", "Th2,", "Th17,", "and", "regulatory", "T", "cells.", "Helminths", "and", "their", "anti-", "gens", "induce", "Th2", "immune", "responses,", "and", "protection", "against", "these", "parasites", "seems", "to", "be", "dependent", "on", "this", "polarization.", "Th2-cells", "secrete", "type", "2", "cytokines", "such", "as", "interleukin-4", "(IL-4),", "IL-5,", "IL-9,", "IL-13,", "but", "non-T", "cells", "including", "basophils,", "mast", "cells,", "B", "cells,", "and", "eosinophils", "can", "also", "produce", "them.", "The", "initial", "priming", "for", "Th2", "differentiation", "is", "dependent", "on", "the", "IL-4", "receptor", "α", "chain", "(IL-4R)", "and", "transcription", "factors", "STAT6", "and", "GATA3,", "as", "well", "as", "processing", "and", "presenting", "anti-", "gens", "from", "antigen", "presenting", "cells", "(APCs)", "and", "upregulation", "of", "costimulatory", "molecules", "[3].", "A", "type", "2", "immune", "response", "is", "characterized", "by", "activation", "and", "expansion", "of", "CD4+", "Th2-", "cells,", "mucosal", "epithelial", "cells,", "eosinophils,", "basophils,", "produc-", "tion", "of", "immunoglobulin", "E", "(IgE)", "and", "mast", "cell,", "and", "goblet", "cell", "hyperplasia", "[4].", "Moreover,", "basophils", "and", "mast", "cells", "are", "activated", "by", "IgE-immune", "complexes", "through", "crosslinked-", "high-affinity", "Fc", "receptors", "(FcRs)", "for", "IgE", "located", "on", "the", "cell", "surface.", "Then,", "these", "cells", "are", "able", "to", "degranulate", "and", "release", "cytokines,", "chemokines,", "proteases,", "serotonin,", "histamine,", "and", "heparin,", "resulting", "in", "smooth", "muscle", "hypercontractibility,", "in-", "creased", "permeability,", "and", "inflammatory", "cell", "recruitment", "that,", "accompanied", "by", "mucus", "production,", "will", "facilitate", "clear-", "ance", "of", "parasites", "(Figure", "1).", "Basic", "aspects", "about", "activation", "of", "Th1-", "and", "Th17-type", "immune", "responses", "are", "well", "characterized.", "Nevertheless,", "the", "immunological", "mechanisms", "leading", "towards", "induction", "of", "Th2", "immune", "responses", "remain", "to", "be", "elucidated.", "Early", "production", "of", "IL-4", "is", "essential", "for", "Th2", "differentiation", "[3].", "Dendritic", "cells", "(DCs)", "are", "efficient", "APCs", "that", "express", "costim-", "ulatory", "molecules", "CD40", "and", "CD86", "and", "produce", "cytokines", "(IL-12,", "IL-13,", "and", "IL-6)", "necessary", "for", "the", "activation", "and", "differentiation", "of", "CD4+", "T", "cells", "during", "Th1", "or", "Th17", "responses", "[5].", "However,", "DCs", "are", "not", "able", "to", "produce", "IL-4.", "Recently,", "it", "has", "been", "documented", "that", "basophils", "are", "in-", "volved", "in", "development", "and", "amplification", "of", "type", "2", "immune", "responses", "during", "helminth", "infections,", "because", "they", "are", "capa-", "ble", "of", "producing", "and", "secreting", "IL-4", "in", "response", "to", "helminth", "antigens", "and", "by", "crosslinking", "of", "antigen-specific", "IgE", "complex-", "es.", "Furthermore,", "it", "has", "been", "suggested", "the", "possible", "role", "of", "basophils", "as", "APCs,", "since", "they", "constitutively", "express", "MHC-", "class-II,", "costimulatory", "molecules", "such", "as", "CD40,", "CD80,", "and", "CD86,", "and", "the", "lymph-node-homing", "receptor", "CD62L", "[6–8]." ]

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[ "JCB", "Report", "A", "novel", "Apaf-1–independent", "putative", "caspase-2", "activation", "complex", "Stuart", "H.", "Read,1", "Belinda", "C.", "Baliga,1", "Paul", "G.", "Ekert,2", "David", "L.", "Vaux,2", "and", "Sharad", "Kumar1,3", "1Hanson", "Institute,", "Frome", "Road,", "Adelaide,", "Australia", "5000", "2Walter", "and", "Eliza", "Hall", "Institute", "of", "Medical", "Research,", "Melbourne,", "Australia", "3050", "3Department", "of", "Medicine,", "Adelaide", "University,", "Adelaide,", "Australia", "5005", "C", "tion.", "In", "stress-induced", "apoptosis,", "the", "mitochondrial", "aspase", "activation", "is", "a", "key", "event", "in", "apoptosis", "execu-", "pathway", "of", "caspase", "activation", "is", "believed", "to", "be", "of", "central", "importance.", "In", "this", "pathway,", "cytochrome", "c", "released", "from", "mitochondria", "facilitates", "the", "formation", "of", "an", "Apaf-1", "apoptosome", "that", "recruits", "and", "activates", "caspase-9.", "Recent", "data", "indicate", "that", "in", "some", "cells", "caspase-9", "may", "not", "be", "the", "initiator", "caspase", "in", "stress-mediated", "apoptosis", "because", "caspase-2", "is", "required", "upstream", "of", "mitochondria", "for", "the", "release", "of", "cytochrome", "c", "and", "other", "apoptogenic", "factors.", "To", "determine", "how", "caspase-2", "is", "activated,", "we", "have", "studied", "the", "formation", "of", "a", "complex", "that", "mediates", "caspase-2", "activation.", "Using", "gel", "filtration", "analysis", "of", "cell", "lysates,", "we", "show", "that", "caspase-2", "is", "spontaneously", "recruited", "to", "a", "large", "protein", "complex", "independent", "of", "cytochrome", "c", "and", "Apaf-1", "and", "that", "recruitment", "of", "caspase-2", "to", "this", "complex", "is", "sufficient", "to", "mediate", "its", "activation.", "Using", "substrate-binding", "assays,", "we", "also", "provide", "the", "first", "evidence", "that", "caspase-2", "activation", "may", "occur", "without", "processing", "of", "the", "precursor", "molecule.", "Our", "data", "are", "consistent", "with", "a", "model", "where", "caspase-2", "activation", "occurs", "by", "oligomerization,", "independent", "of", "the", "Apaf-1", "apoptosome.", "Introduction", "The", "execution", "of", "apoptosis", "is", "performed", "by", "a", "family", "of", "cysteine", "proteases", "known", "as", "caspases", "(for", "review", "see", "Nicholson,", "1999).", "Caspases", "are", "present", "as", "zymogens", "in", "most", "animal", "cells", "and", "are", "activated", "in", "response", "to", "apoptotic", "signals.", "The", "apoptotic", "signals", "first", "lead", "to", "the", "activation", "of", "so", "called", "“initiator", "caspases,”", "such", "as", "caspase-8", "and", "caspase-9.", "These", "caspases", "contain", "specific", "protein–protein", "interaction", "domains", "in", "their", "NH2", "termini", "that", "allow", "them", "to", "be", "recruited", "to", "death-signaling", "complexes", "promoting", "their", "activation", "by", "an", "autocatalytic", "mechanism", "(for", "review", "see", "Kumar,", "1999).", "Once", "the", "initiator", "caspases", "are", "activated,", "they", "process", "and", "activate", "downstream", "effector", "caspases,", "such", "as", "caspase-3,", "-6", "and", "-7,", "which", "are", "responsible", "for", "the", "cleavage", "of", "several", "proteins", "in", "dying", "cells", "(Nicholson,", "1999).", "In", "mammals,", "there", "are", "two", "main", "caspase", "activation", "pathways:", "the", "death", "receptor", "pathway", "and", "the", "mitochondrial", "pathway", "(Kumar,", "1999;", "Nicholson,", "1999).", "In", "the", "first", "pathway,", "TNF", "Address", "correspondence", "to", "Sharad", "Kumar,", "Hanson", "Institute,", "P.O.", "Box", "14,", "Rundle", "Mall,", "Adelaide,", "Australia", "5000.", "Tel.:", "61-8-8222-3738.", "Fax:", "61-8-8222-3139.", "E-mail:", "sharad.kumar@imvs.sa.gov.au", "*Abbreviations", "used", "in", "this", "paper:", "CARD,", "caspase", "recruitment", "domain;", "DISC,", "death-inducing", "signaling", "complex;", "FADD,", "Fas-associated", "protein", "with", "death", "domain.", "Key", "words:", "apoptosis;", "caspase", "activation;", "apoptosome;", "caspase-9;", "initiator", "caspase", "", "The", "Rockefeller", "University", "Press,", "0021-9525/2002/12/739/7", "$5.00", "The", "Journal", "of", "Cell", "Biology,", "Volume", "159,", "Number", "5,", "December", "9,", "2002", "739–745", "http://www.jcb.org/cgi/doi/10.1083/jcb.200209004", "receptor", "family", "members", "recruit", "Fas-associated", "protein", "with", "death", "domain", "(FADD),*", "an", "adaptor", "molecule", "that", "in", "turn", "recruits", "caspase-8", "to", "the", "death-inducing", "signaling", "complex", "(DISC).", "Recruitment", "of", "caspase-8", "to", "DISC", "results", "in", "its", "activation.", "The", "mitochondrial", "pathway", "of", "caspase", "activation", "is", "regulated", "by", "the", "Bcl-2", "family", "of", "proteins", "and", "involves", "cyto-", "chrome", "c", "and", "Apaf-1–mediated", "activation", "of", "caspase-9.", "During", "stress", "signaling,", "cytochrome", "c", "released", "from", "mito-", "chondria", "binds", "Apaf-1,", "resulting", "in", "a", "conformational", "change", "that", "facilitates", "oligomerization", "of", "Apaf-1", "into", "an", "apoptosome", "and", "subsequent", "caspase", "recruitment", "domain", "(CARD)–mediated", "recruitment", "and", "activation", "of", "caspase-9", "(Acehan", "et", "al.,", "2002).", "Interestingly,", "initiator", "caspase", "DRONC", "activation", "in", "Drosophila", "cells", "does", "not", "seem", "to", "require", "release", "of", "cytochrome", "c", "from", "mitochondria", "(Dorstyn", "et", "al.,", "2002).", "Although", "caspase-9", "is", "generally", "believed", "to", "be", "the", "initiator", "caspase", "in", "stress-induced", "apoptosis,", "recent", "studies", "suggest", "that", "caspase-2", "can", "act", "upstream", "of", "mitochondria", "(Lassus", "et", "al.,", "2002;", "Robertson", "et", "al.,", "2002).", "The", "new", "findings", "indicate", "that", "caspase-2", "is", "the", "initiator", "caspase", "in", "stress-induced", "apoptosis,", "whereas", "apoptosome", "mediated", "caspase-9,", "and", "subsequently", "caspase-3,", "activation", "may", "mainly", "serve", "as", "an", "amplification", "loop", "(Kumar", "and", "Vaux,", "2002).", "Caspase-2,", "the", "first", "discovered", "apoptotic", "mammalian", "caspase,", "has", "been", "implicated", "in", "a", "variety", "of", "cell", "death", "pathways,", "and", "consistent", "with", "an", "initiator", "role", "it", "is", "activated", "rapidly", "in", "response", "to", "diverse", "death", "stimuli", "(Kumar", "et", "739" ]

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[ "Iranian", "J", "Publ", "Health,", "Vol.", "40,", "No.4,", "2011,", "pp.89-98", "Original", "Article", "Physical", "Activity,", "Nutrition,", "and", "Dyslipidemia", "in", "Middle-Aged", "Women", "MA", "Delavar", "1,", "*MS", "Lye", "2,", "STBS", "Hassan", "2,", "GL", "Khor", "3,", "P", "Hanachi4", "1Fatemezahra", "Infertility", "and", "Reproductive", "Health", "Research", "Center,", "Department", "of", "Midwifery,", "Babol", "University", "of", "Medical", "Sciences,", "Babol,", "Iran", "2Dept.", "of", "Community", "Health,", "Faculty", "of", "Medicine", "and", "Health", "Sciences,", "Universiti", "Putra", "Malaysia", "3School", "of", "Pharmacy", "and", "Health", "Sciences,", "International", "Medical", "University,", "Malaysia", "4Dept.", "of", "Women", "Research,", "Alzahra", "University,", "Tehran,", "Iran", "(Received", "28", "Mar", "2011;", "accepted", "12", "Oct", "2011)", "Abstract", "Background:", "Cardiovascular", "disease", "is", "a", "major", "cause", "of", "death", "throughout", "the", "world.", "The", "aim", "of", "this", "study", "was", "to", "as-", "sess", "the", "prevalence", "of", "overweight/obesity,", "central", "obesity,", "hypertension", "and", "dyslipidemia,", "as", "well", "as", "dietary", "factors", "contributing", "to", "the", "development", "of", "dyslipidemia", "among", "middle-aged", "women.", "Methods:", "The", "research", "design", "of", "the", "present", "study", "was", "a", "population-based", "cross-sectional", "study;", "anthropometric", "meas-", "ures", "and", "blood", "chemistry", "were", "obtained.", "Physical", "activity", "was", "measured", "using", "the", "original", "International", "Physical", "Activity", "Questionnaires", "Long", "Form", "while", "food", "frequency", "questionnaire", "(FFQ)", "was", "used", "in", "assessing", "individual’s", "habit-", "ual", "intake.", "Overall,", "809", "women,", "30-50", "years", "of", "age", "from", "fourteen", "active", "urban", "Primary", "Healthcare", "Centers", "(PHC)", "in", "Babol", "City,", "northern", "Iran,", "were", "obtained", "from", "1,905", "households", "across", "operational", "areas", "of", "14", "PHC", "using", "systematic", "random", "sampling", "method.", "Results:", "The", "prevalence", "rates", "of", "women", "classified", "as", "overweight/obese,", "with", "central", "obesity,", "hypertension", "and", "dyslip-", "idemia", "were", "82.8%,", "75.5%,", "14.6%", "and", "63.4%,", "respectively.", "Total", "physical", "activity", "did", "not", "correlate", "with", "cholesterol", "ratio.", "Soybean", "protein", "was", "inversely", "associated", "with", "cholesterol", "ratio", "(rho=-0.18,", "P≤", "0.001).", "The", "adjusted", "OR", "for", "dyslipidemia", "in", "women", "with", "moderate", "protein", "intake", "was", "significantly", "higher", "than", "in", "women", "with", "high", "and", "low", "intake", "(OR=2.31;", "95%", "CI=", "1.61,", "3.30).", "No", "significant", "associations", "were", "found", "between", "dyslipidemia", "and", "carbohydrate,", "fat", "intake", "or", "physical", "activity.", "Conclusion:", "This", "study", "showed", "very", "high", "prevalence", "of", "cardiovascular", "disease", "risk", "factors", "among", "Iranian", "middle-aged", "women.", "A", "more", "detailed", "study", "is", "suggested", "to", "develop", "definitively", "recommendations", "for", "the", "primary", "and", "secondary", "prevention", "of", "cardiovascular", "disease", "for", "the", "Iranian", "population.", "Keywords:", "Nutrition,", "Physical", "activity,", "Dyslipidemia,", "Women's", "health", "Introduction", "Cardiovascular", "disease", "is", "recognized", "as", "the", "most", "common", "cause", "of", "death", "worldwide", "(1).", "Over-", "weight/obesity,", "hypertension,", "dyslipidemia,", "and", "other", "manifestations", "are", "major", "risk", "factors", "(2).", "Improved", "long-term", "outcomes", "have", "been", "at-", "tained", "as", "a", "result", "of", "physicians'", "recommendations", "for", "dietary", "practices", "and", "physical", "activity", "that", "lead", "to", "several", "favorable", "parameters", "such", "as", "a", "healthier", "waist", "circumference", "and", "improved", "body", "mass", "index,", "lower", "blood", "pressure,", "improved", "HDL-", "cholesterol,", "and", "triglyceride", "levels", "(3).", "HDL-", "cholesterol", "is", "protective", "against", "cardiovascular", "disease", "and", "decreases", "cardiovascular", "morbidity", "and", "mortality", "(4).", "A", "meta-analysis", "has", "shown", "*Corresponding", "Author:", "Tel:", "+60", "3", "89472410,", "Fax:", "+60", "3", "8945", "0151,", "E-mail", "address:lyems9@yahoo.com", "Published", "by", "Tehran", "University", "of", "Medical", "Sciences", "(www.tums.ac.ir)" ]

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"euploidies", "and", "tumor", "formation.", "We", "found", "that", "chromo-", "some", "misalignment", "and", "lagging", "are", "the", "primary", "mitotic", "errors", "responsible", "for", "the", "observed", "aneuploidization.", "High", "Bub1", "levels", "resulted", "in", "aberrant", "Bub1", "kinase", "activity", "and", "hyperactivation", "of", "Aurora", "B", "kinase.", "When", "Aurora", "B", "activity", "is", "suppressed,", "pharmacologically", "or", "via", "BubR1", "overexpression,", "chromosome", "segregation", "errors", "caused", "by", "Bub1", "overexpression", "are", "largely", "corrected.", "Impor-", "tantly,", "Bub1", "transgenic", "mice", "overexpressing", "Bub1", "devel-", "oped", "various", "kinds", "of", "spontaneous", "tumors", "and", "showed", "accelerated", "Myc-induced", "lymphomagenesis.", "Our", "results", "establish", "that", "Bub1", "has", "oncogenic", "properties", "and", "suggest", "that", "Aurora", "B", "is", "a", "critical", "target", "through", "which", "over-", "expressed", "Bub1", "drives", "aneuploidization", "and", "tumorigenesis.", "Introduction", "During", "M", "phase,", "replicated", "chromosomes", "are", "evenly", "distributed", "into", "daughter", "cells.", "Inaccurate", "chromosome", "segregation", "can", "re-", "sult", "in", "the", "loss", "or", "gain", "of", "whole", "chromosomes,", "a", "status", "referred", "to", "as", "aneuploidy", "(Ricke", "et", "al.,", "2008).", "Aneuploidy", "is", "observed", "in", "80–90%", "of", "human", "cancers", "and", "associated", "with", "poor", "clinical", "outcome,", "but", "its", "role", "in", "malignant", "cell", "transformation", "remains", "ambiguous", "(Holland", "and", "Cleveland,", "2009;", "Schvartzman", "et", "al.,", "2010).", "To", "ensure", "faithful", "chromosome", "segregation,", "eukaryotic", "cells", "have", "developed", "a", "surveillance", "system,", "the", "mitotic", "checkpoint,", "which", "delays", "anaphase", "onset", "until", "all", "kinetochores", "are", "properly", "attached", "to", "microtubules", "emanating", "from", "opposite", "spindle", "poles", "(Nezi", "and", "Musacchio,", "2009).", "One", "of", "the", "core", "components", "of", "this", "checkpoint", "is", "Bub1", "(Roberts", "et", "al.,", "1994;", "Taylor", "and", "McKeon,", "1997).", "In", "prophase,", "this", "serine/threonine", "protein", "kinase", "accumulates", "at", "unattached", "kinetochores", "where", "it", "mediates", "the", "recruitment", "of", "Mad1–Mad2", "dimers", "(Sharp-Baker", "and", "Chen,", "2001;", "Meraldi", "and", "Sorger,", "2005;", "Jeganathan", "et", "al.,", "2007).", "These", "Mad1–Mad2", "dimers", "produce", "a", "diffusible", "anaphase", "wait", "signal", "consisting", "of", "protein", "complexes", "of", "Bub3,", "BubR1,", "and", "Mad2", "(Sudakin", "et", "al.,", "2001;", "Luo", "et", "al.,", "2002;", "Sironi", "et", "al.,", "2002;", "Kulukian", "et", "al.,", "2009).", "These", "complexes", "bind", "to", "and", "inhibit", "Cdc20,", "the", "activating", "subunit", "of", "the", "anaphase-promoting", "complex/cyclosome", "(APC/C),", "an", "E3", "ubiquitin", "ligase", "that", "regulates", "orderly", "separation", "of", "chromosomes", "by", "targeting", "various", "cell", "cycle", "regulators", "for", "degradation", "by", "the", "26S", "proteasome", "at", "specific", "mitotic", "stages", "(Peters,", "2006).", "Bub1", "not", "only", "regulates", "APC/C", "activity", "via", "kinetochore", "recruitment", "of", "Mad1–Mad2,", "but", "has", "also", "been", "pro-", "posed", "to", "inhibit", "APC/C", "activity", "directly", "through", "phosphorylation", "of", "Cdc20", "(Chung", "and", "Chen,", "2003;", "Tang", "et", "al.,", "2004a).", "In", "addition", "to", "the", "Mad", "proteins,", "several", "other", "mitotic", "pro-", "teins", "are", "dependent", "on", "Bub1", "for", "efficient", "recruitment", "to", "un-", "attached", "kinetochores,", "including", "BubR1,", "Cenp-E,", "and", "Sgo1", "(Sharp-Baker", "and", "Chen,", "2001;", "Tang", "et", "al.,", "2004b;", "Morrow", "et", "al.,", "2005;", "Jeganathan", "et", "al.,", "2007;", "Perera", "et", "al.,", "2007).", "BubR1", "and", "Cenp-E", "both", "function", "in", "microtubule–kinetochore", "attachment", "and", "failure", "to", "recruit", "these", "proteins", "at", "unattached", "kinetochores", "is", "known", "to", "cause", "chromosome", "missegregation", "(Wood", "et", "al.,", "1997;", "Yao", "et", "al.,", "2000;", "Lampson", "and", "Kapoor,", "2005;", "Malureanu", "et", "al.,", "2009).", "Sgo1,", "on", "the", "other", "hand,", "acts", "to", "maintain", "centro-", "meric", "cohesion", "of", "duplicated", "chromosomes", "until", "bi-orientation", "has", "been", "accomplished", "(Tang", "et", "al.,", "2004b;", "Boyarchuk", "et", "al.,", "2007;", "Kawashima", "et", "al.,", "2010).", "The", "current", "model", "is", "that", "Bub1", "Correspondence", "to", "Jan", "van", "Deursen:", "vandeursen.jan@mayo.edu", "Abbreviations", "used", "in", "this", "paper:", "CAGGS,", "CMV", "early", "enhancer/chicken", "-actin;", "CPC,", "chromosome", "passenger", "complex;", "HA,", "hemagglutinin;", "MEF,", "mouse", "embryonic", "fibroblast;", "PMSCS,", "premature", "sister", "chromatid", "separation.", "©", "2011", "Ricke", "et", "al.", "This", "article", "is", "distributed", "under", "the", "terms", "of", "an", "Attribution–", "Noncommercial–Share", "Alike–No", "Mirror", "Sites", "license", "for", "the", "first", "six", "months", "after", "the", "pub-", "lication", "date", "(see", "http://www.rupress.org/terms).", "After", "six", "months", "it", "is", "available", "under", "a", "Creative", "Commons", "License", "(Attribution–Noncommercial–Share", "Alike", "3.0", "Unported", "license,", "as", "described", "at", "http://creativecommons.org/licenses/by-nc-sa/3.0/).", "The", "Rockefeller", "University", "Press", "$30.00", "J.", "Cell", "Biol.", "Vol.", "193", "No.", "6", "1049–1064", "www.jcb.org/cgi/doi/10.1083/jcb.201012035", "JCB", "1049" ]

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[ "Ishida", "et", "al.", "Annals", "of", "Clinical", "Microbiology", "and", "Antimicrobials", "2011,", "10:3", "http://www.ann-clinmicrob.com/content/10/1/3", "R", "E", "S", "E", "A", "R", "C", "H", "Open", "Access", "Synthetic", "arylquinuclidine", "derivatives", "exhibit", "antifungal", "activity", "against", "Candida", "albicans,", "Candida", "tropicalis", "and", "Candida", "parapsilopsis", "Kelly", "Ishida1,", "Juliany", "Cola", "Fernandes", "Rodrigues2,", "Simon", "Cammerer3,", "Julio", "A", "Urbina4,", "Ian", "Gilbert3,", "Wanderley", "de", "Souza2,5,", "Sonia", "Rozental1*", "Abstract", "Background:", "Sterol", "biosynthesis", "is", "an", "essential", "pathway", "for", "fungal", "survival,", "and", "is", "the", "biochemical", "target", "of", "many", "antifungal", "agents.", "The", "antifungal", "drugs", "most", "widely", "used", "to", "treated", "fungal", "infections", "are", "compounds", "that", "inhibit", "cytochrome", "P450-dependent", "C14a-demethylase", "(CYP51),", "but", "other", "enzymes", "of", "this", "pathway,", "such", "as", "squalene", "synthase", "(SQS)", "which", "catalyses", "the", "first", "committed", "step", "in", "sterol", "biosynthesis,", "could", "be", "viable", "targets.", "The", "aim", "of", "this", "study", "was", "to", "evaluate", "the", "antifungal", "activity", "of", "SQS", "inhibitors", "on", "Candida", "albicans,", "Candida", "tropicalis", "and", "Candida", "parapsilopsis", "strains.", "Methods:", "Ten", "arylquinuclidines", "that", "act", "as", "SQS", "inhibitors", "were", "tested", "as", "antiproliferative", "agents", "against", "three", "ATCC", "strains", "and", "54", "clinical", "isolates", "of", "Candida", "albicans,", "Candida", "tropicalis", "and", "Candida", "parapsilopsis.", "Also,", "the", "morphological", "alterations", "induced", "in", "the", "yeasts", "by", "the", "experimental", "compounds", "were", "evaluated", "by", "fluorescence", "and", "transmission", "electron", "microscopy.", "Results:", "The", "most", "potent", "arylquinuclidine", "derivative", "(3-[1’-{4’-(benzyloxy)-phenyl}]-quinuclidine-2-ene)", "(WSP1267)", "had", "a", "MIC50", "of", "2", "μg/ml", "for", "all", "species", "tested", "and", "MIC90", "varying", "from", "4", "μg/ml", "to", "8", "μg/ml.", "Ultrathin", "sections", "of", "C.", "albicans", "treated", "with", "1", "μg/ml", "of", "WSP1267", "showed", "several", "ultrastructural", "alterations,", "including", "(a)", "loss", "of", "cell", "wall", "integrity,", "(b)", "detachment", "of", "the", "plasma", "membrane", "from", "the", "fungal", "cell", "wall,", "(c)", "accumulation", "of", "small", "vesicles", "in", "the", "periplasmic", "region,", "(d)", "presence", "of", "large", "electron-dense", "vacuoles", "and", "(e)", "significantly", "increased", "cell", "size", "and", "cell", "wall", "thickness.", "In", "addition,", "fluorescence", "microscopy", "of", "cells", "labelled", "with", "Nile", "Red", "showed", "an", "accumulation", "of", "lipid", "droplets", "in", "the", "cytoplasm", "of", "treated", "yeasts.", "Nuclear", "staining", "with", "DAPI", "revealed", "the", "appearance", "of", "uncommon", "yeast", "buds", "without", "a", "nucleus", "or", "with", "two", "nuclei.", "Conclusion:", "Taken", "together,", "our", "data", "demonstrate", "that", "arylquinuclidine", "derivatives", "could", "be", "useful", "as", "lead", "compounds", "for", "the", "rational", "synthesis", "of", "new", "antifungal", "drugs.", "Background", "Candidiasis", "is", "the", "most", "common", "fungal", "infection;", "it", "is", "found", "all", "over", "the", "world.", "Candida", "spp.", "isolates", "are", "the", "fourth", "most", "common", "microorganisms", "found", "in", "blood-", "stream", "infections", "and", "are", "particularly", "prevalent", "among", "patients", "hospitalised", "for", "long", "periods", "who", "have", "been", "exposed", "to", "antibiotics,", "immunosuppressive", "therapy,", "*", "Correspondence:", "rozental@biof.ufrj.br", "1Laboratório", "de", "Biologia", "Celular", "de", "Fungos,", "Instituto", "de", "Biofísica", "Carlos", "Chagas", "Filho,", "Universidade", "Federal", "do", "Rio", "de", "Janeiro,", "Avenida", "Carlos", "Chagas", "Filho", "373,", "Bloco", "C,", "Sala", "C0-026,", "Cidade", "Universitária,", "21.941-902,", "Rio", "de", "Janeiro/RJ,", "Brazil", "Full", "list", "of", "author", "information", "is", "available", "at", "the", "end", "of", "the", "article", "parenteral", "nutrition,", "and", "multiple", "invasive", "medical", "pro-", "cedures", "[1].", "Systemic", "fungal", "infections", "are", "generally", "dif-", "ficult", "to", "diagnose", "and", "hard", "to", "treat,", "having", "an", "attributable", "mortality", "rate", "of", "near", "40%", "[1].", "Although", "Candida", "albicans", "is", "the", "species", "most", "frequently", "isolated", "from", "those", "patients,", "being", "responsible", "for", "more", "than", "half", "of", "candidiasis", "cases,", "the", "incidence", "of", "other", "species,", "such", "as", "Candida", "parapsilopsis", "and", "Candida", "tropicalis,", "is", "increasing", "[2].", "Most", "current", "therapies", "to", "treat", "fungal", "infections", "are", "based", "on", "disrupting", "fungal", "membrane", "homeostasis.", "The", "most", "commonly", "used", "groups", "of", "antifungal", "agents", "are", "©", "2011", "Ishida", "et", "al;", "licensee", "BioMed", "Central", "Ltd.", "This", "is", "an", "Open", "Access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "License", "(http://creativecommons.org/licenses/by/2.0),", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited." ]

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[ "JCB", "Article", "Activation", "of", "ErbB2", "receptor", "tyrosine", "kinase", "supports", "invasion", "of", "endothelial", "cells", "by", "Neisseria", "meningitidis", "Isabelle", "Hoffmann,1", "Emmanuel", "Eugène,2", "Xavier", "Nassif,2", "Pierre-Olivier", "Couraud,1", "and", "Sandrine", "Bourdoulous1", "1Laboratoire", "d’Immuno-Pharmacologie", "Moléculaire,", "Centre", "National", "de", "la", "Recherche", "Scientifique,", "Institut", "Cochin", "de", "Génétique", "Moléculaire,", "75014", "Paris,", "France", "2Laboratoire", "de", "Microbiologie,", "Institut", "National", "de", "la", "Santé", "et", "de", "la", "Recherche", "Médicale,", "Faculté", "de", "Médecine", "Necker-Enfants", "Malades,", "75015", "Paris,", "France", "Efamily", "of", "epidermal", "growth", "factor", "(EGF)", "receptors", "rbB2", "is", "a", "receptor", "tyrosine", "kinase", "belonging", "to", "the", "which", "is", "generally", "involved", "in", "cell", "differentiation,", "proliferation,", "and", "tumor", "growth,", "and", "activated", "by", "het-", "erodimerization", "with", "the", "other", "members", "of", "the", "family.", "We", "show", "here", "that", "type", "IV", "pilus–mediated", "adhesion", "of", "Neisseria", "meningitidis", "onto", "endothelial", "cells", "induces", "tyrosyl", "phos-", "phorylation", "and", "massive", "recruitment", "of", "ErbB2", "underneath", "the", "bacterial", "colonies.", "However,", "neither", "the", "phosphorylation", "status", "nor", "the", "cellular", "localization", "of", "the", "EGF", "receptors,", "ErbB3", "or", "ErbB4,", "were", "affected", "in", "infected", "cells.", "ErbB2", "phosphorylation", "induced", "by", "N.", "meningitidis", "provides", "docking", "sites", "for", "the", "kinase", "src", "and", "leads", "to", "its", "subsequent", "activation.", "Specific", "inhibition", "of", "either", "ErbB2", "and/or", "src", "activity", "reduces", "bacterial", "internalization", "into", "endothelial", "cells", "without", "affecting", "bacteria-induced", "actin", "cytoskeleton", "reorganization", "or", "ErbB2", "recruitment.", "Moreover,", "inhibition", "of", "both", "actin", "polymerization", "and", "the", "ErbB2/src", "pathway", "totally", "prevents", "bacterial", "entry.", "Altogether,", "our", "results", "pro-", "vide", "new", "insight", "into", "ErbB2", "function", "by", "bringing", "evidence", "of", "a", "bacteria-induced", "ErbB2", "clustering", "leading", "to", "src", "kinase", "phosphorylation", "and", "activation.", "This", "pathway,", "in", "cooperation", "with", "the", "bacteria-induced", "reorganization", "of", "the", "actin", "cytoskeleton,", "is", "required", "for", "the", "efficient", "internalization", "of", "N.", "meningitidis", "into", "endothelial", "cells,", "an", "essential", "process", "enabling", "this", "pathogen", "to", "cross", "host", "cell", "barriers.", "Introduction", "The", "ErbB", "family", "of", "receptor", "tyrosine", "kinases", "(RTKs)*", "com-", "prises", "four", "closely", "related", "members:", "EGF", "receptor", "(EGFR;", "also", "termed", "ErbB1),", "ErbB2/Neu,", "ErbB3,", "and", "ErbB4.", "These", "receptors", "are", "activated", "by", "numerous", "ErbB-specific", "ligands,", "each", "containing", "an", "EGF-like", "domain", "which", "confers", "binding", "specificity", "(for", "review", "see", "Olayioye", "et", "al.,", "2000).", "These", "ligands,", "which", "are", "produced", "as", "transmembrane", "precursors", "and", "are", "processed", "and", "released", "by", "proteolysis,", "bind", "the", "extra-", "cellular", "domain", "of", "ErbB", "receptors", "and", "lead", "to", "the", "formation", "of", "both", "homo-", "and", "heterodimers.", "No", "soluble", "ligand", "for", "ErbB2", "has", "yet", "been", "discovered.", "However,", "increasing", "evi-", "dence", "suggests", "that", "the", "primary", "function", "of", "ErbB2", "is", "as", "a", "Address", "correspondence", "to", "Sandrine", "Bourdoulous,", "Laboratoire", "d’Im-", "muno-Pharmacologie", "Moléculaire,", "Centre", "National", "de", "la", "Recherche", "Sci-", "entifique", "UPR", "415,", "Institut", "Cochin", "de", "Génétique", "Moléculaire,", "22", "rue", "Méchain,", "75014", "Paris,", "France.", "Tel.:", "(33)", "1-40-51-64-34.", "Fax:", "(33)", "1-40-", "51-64-30.", "E-mail:", "bourdoulous@cochin.inserm.fr", "*Abbreviations", "used", "in", "this", "paper:", "EGFR,", "EGF", "receptor;", "GST,", "glu-", "tathione", "S-transferase;", "HBMEC,", "human", "bone", "marrow", "endothelial", "cell;", "MAPK,", "mitogen-activated", "protein", "kinase;", "RTK,", "receptor", "tyrosine", "kinase;", "SH2,", "src", "homology", "2.", "Key", "words:", "ErbB2;", "homodimerization;", "src;", "Neisseria", "meningitidis;", "invasion", "", "The", "Rockefeller", "University", "Press,", "0021-9525/2001/10/133/11", "$5.00", "The", "Journal", "of", "Cell", "Biology,", "Volume", "155,", "Number", "1,", "October", "1,", "2001", "133–143", "http://www.jcb.org/cgi/doi/10.1083/jcb.200106148", "coreceptor,", "since", "ErbB2", "is", "the", "preferred", "heterodimerization", "partner", "for", "all", "other", "ErbB", "family", "members", "(Tzahar", "et", "al.,", "1996;", "Graus-Porta", "et", "al.,", "1997)", "and", "plays", "a", "role", "in", "the", "po-", "tentiation", "of", "ErbB", "receptor", "signaling", "(Beerli", "et", "al.,", "1995;", "Graus-Porta", "et", "al.,", "1995).", "Dimerization", "stimulates", "the", "in-", "trinsic", "tyrosine", "kinase", "activity", "of", "the", "receptors", "and", "triggers", "autophosphorylation", "of", "specific", "tyrosine", "residues", "within", "the", "cytoplasmic", "domains.", "These", "phosphorylated", "residues", "pro-", "vide", "docking", "sites", "for", "proteins", "which", "contain", "src", "homology", "2", "(SH2)", "or", "phosphotyrosine", "binding", "domains", "and", "which", "are", "involved", "in", "the", "regulation", "of", "intracellular", "signaling", "cascades.", "All", "ErbB", "family", "members", "couple", "via", "the", "adaptors", "Shc", "and/or", 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[ "Available", "online", "http://arthritis-research.com/content/11/3/R66", "Research", "article", "Vol11No3", "Identification", "of", "novel", "genetic", "susceptibility", "loci", "for", "Behçet's", "disease", "using", "a", "genome-wide", "association", "study", "Open", "Access", "Yiping", "Fei1,2,", "Ryan", "Webb2,3,", "Beth", "L", "Cobb2,4,", "Haner", "Direskeneli5,", "Güher", "Saruhan-Direskeneli6", "and", "Amr", "H", "Sawalha1,2,7", "1Department", "of", "Medicine,", "University", "of", "Oklahoma", "Health", "Sciences", "Center,", "825", "NE", "13th", "Street,", "Oklahoma", "City,", "OK", "73104,", "USA", "2Arthritis", "&", "Immunology", "Program,", "Oklahoma", "Medical", "Research", "Foundation,", "825", "NE", "13th", "Street,", "Oklahoma", "City,", "OK", "73104,", "USA", "3College", "of", "Public", "Health,", "University", "of", "Oklahoma", "Health", "Sciences", "Center,", "825", "NE", "13th", "Street,", "Oklahoma", "City,", "OK", "73104,", "USA", "4JK", "Autoimmunity", "Inc.,", "755", "Research", "Parkway,", "Oklahoma", "City,", "OK", "73104,", "USA", "5Division", "of", "Rheumatology,", "Department", "of", "Internal", "Medicine,", "Marmara", "University", "Medical", "School,", "Tophanelioglu", "Cad.", "13/15,", "34662,", "Uskudar,", "Istanbul,", "Turkey", "6Department", "of", "Physiology,", "Istanbul", "Faculty", "of", "Medicine,", "Istanbul", "University,", "Capa", "34093,", "Istanbul,", "Turkey", "7US", "Department", "of", "Veterans", "Affairs", "Medical", "Center,", "921", "NE", "13th", "Street,", "Oklahoma", "City,", "OK", "73104,", "USA", "Corresponding", "author:", "Amr", "H", "Sawalha,", "amr-sawalha@ouhsc.edu", "Received:", "31", "Mar", "2009", "Revisions", "requested:", "28", "Apr", "2009", "Revisions", "received:", "3", "May", "2009", "Accepted:", "14", "May", "2009", "Published:", "14", "May", "2009", "Arthritis", "Research", "&", "Therapy", "2009,", "11:R66", "(doi:10.1186/ar2695)", "This", "article", "is", "online", "at:", "http://arthritis-research.com/content/11/3/R66", "©", "2009", "Fei", "et", "al.;", "licensee", "BioMed", "Central", "Ltd.", "This", "is", "an", "open", "access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "License", "(http://creativecommons.org/licenses/by/2.0),", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "work", "is", "properly", "cited.", "Abstract", "Introduction", "Behçet's", "disease", "is", "a", "chronic", "systemic", "inflammatory", "disease", "that", "remains", "incompletely", "understood.", "Herein,", "we", "perform", "the", "first", "genome-wide", "association", "study", "in", "Behçet's", "disease.", "Methods", "Using", "DNA", "pooling", "technology", "and", "the", "Affymetrix", "500K", "arrays,", "we", "identified", "possible", "candidate", "gene", "associations", "with", "Behçet's", "disease", "in", "a", "cohort", "of", "152", "Behçet's", "disease", "patients", "and", "172", "healthy", "ethnically", "matched", "controls.", "Genetic", "loci", "that", "were", "identified", "in", "the", "pooling", "study", "were", "genotyped", "in", "patients", "and", "controls", "using", "TaqMan", "genotyping", "technology.", "Results", "We", "identified", "genetic", "associations", "between", "Behçet's", "disease", "and", "single-nucleotide", "polymorphisms", "(SNPs)", "in", "KIAA1529,", "CPVL,", "LOC100129342,", "UBASH3B,", "and", "UBAC2", "(odds", "ratio", "=", "2.04,", "2.26,", "1.84,", "1.71,", "and", "1.61,", "respectively;", "P", "value", "=", "4.2", "×", "10-5,", "1.0", "×", "10-4,", "3.0", "×", "10-4,", "1.5", "×", "10-3,", "and", "5.8", "×", "10-3,", "respectively).", "Among", "the", "associated", "SNPs,", "the", "Behçet's", "disease-risk", "allele", "in", "rs2061634", "leads", "to", "substitution", "of", "serine", "to", "cysteine", "at", "amino", "acid", "position", "995", "(S995C)", "in", "the", "KIAA1529", "protein.", "Conclusions", "Using", "an", "unbiased", "whole-genome", "genetic", "association", "approach,", "we", "identified", "novel", "candidate", "genetic", "loci", "that", "are", "associated", "with", "increased", "susceptibility", "for", "Behçet's", "disease.", "These", "findings", "will", "help", "to", "better", "understand", "the", "pathogenesis", "of", "Behçet's", "disease", "and", "identify", "novel", "targets", "for", "therapeutic", "intervention.", "Introduction", "Behçet's", "disease", "is", "a", "chronic", "relapsing", "systemic", "inflammatory", "disease", "characterized", "by", "the", "presence", "of", "oro-genital", "ulcers,", "cutaneous", "manifestations,", "and", "uveitis.", "The", "disease", "can", "also", "lead", "to", "vascular", "complications", "such", "as", "arterial", "and", "venous", "thrombosis,", "central", "nervous", "system", "vasculitis,", "arthritis,", "and", "gastrointestinal", "involvement", "[1].", "The", "etiology", "of", "Behçet's", "dis-", "ease", "is", "not", "fully", "understood.", "Therefore,", "treatment", "remains", "insufficient", "and", "relies", "on", "non-specific", "immunosuppressive", "medications,", "with", "significant", "side", "effects.", "Evidence", "for", "a", "genetic", "contribution", "to", "the", "pathogenesis", "of", "the", "disease", "comes", "from", "strong", "familial", "aggregation,", "the", "strong", "predominance", "in", "patients", "with", "Mediterranean", "or", "Asian", "ancestry,", "and", "the", "con-", "firmed", "association", "with", "HLA-B51", "in", "several", "ethnic", "groups", "[2-", "4].", "It", "is", "estimated", "that", "the", "association", "with", "HLA-B51", "in", "Behçet's", "disease", "accounts", "for", "only", "~20%", "of", "the", "relative", "risk", "in", "siblings", "CI:", "confidence", "interval;", "CPVL:", "carboxypeptidase,", "vitellogenic-like;", "HWE:", "Hardy-Weinberg", "equilibrium;", "OR:", "odds", "ratio;", "SD:", "standard", "deviation;", "SNP:", "single-nucleotide", "polymorphism;", "UBA:", "ubiquitin-associated", "domain;", "UBAC2:", "ubiquitin-associated", "domain", "containing", "2;", "UBASH3A:", "ubiquitin", "asso-", "ciated", "and", "SH3", "domain", "containing,", "A;", "UBASH3B:", "ubiquitin", "associated", "and", "SH3", "domain", "containing,", "B.", "Page", "1", "of", "7", "(page", "number", "not", "for", "citation", "purposes)" ]

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[ "organic", "compounds", "Acta", "Crystallographica", "Section", "E", "Structure", "Reports", "Online", "ISSN", "1600-5368", "2-(o-Tolyloxy)pyrimidine", "Nasir", "Shah", "Bakhtiar,", "Zanariah", "Abdullah", "and", "Seik", "Weng", "Ng*", "Department", "of", "Chemistry,", "University", "of", "Malaya,", "50603", "Kuala", "Lumpur,", "Malaysia", "Correspondence", "e-mail:", "seikweng@um.edu.my", "Received", "7", "July", "2009;", "accepted", "8", "July", "2009", "Key", "indicators:", "single-crystal", "X-ray", "study;", "T", "=", "153", "K;", "mean", "(C–C)", "=", "0.003", "A˚;", "R", "factor", "=", "0.033;", "wR", "factor", "=", "0.088;", "data-to-parameter", "ratio", "=", "9.1.", "The", "title", "compound,", "C11H10N2O,", "crystallizes", "with", "two", "mol-", "ecules", "in", "the", "asymmetric", "unit.", "The", "angle", "at", "the", "ether", "O", "atom", "is", "widened", "to", "118.13", "(15)", "[117.89", "(16)", "for", "the", "second", "molecule", "in", "the", "asymmetric", "unit];", "the", "six-membered", "rings", "subtend", "a", "dihedral", "angle", "of", "84.3", "(1)", "[87.4", "(1)", "in", "the", "second", "molecule].", "Related", "literature", "For", "2-phenoxypyrimidine,", "see:", "Shah", "Bakhtiar", "et", "al.", "(2009).", "Experimental", "Crystal", "data", "C11H10N2O", "Mr", "=", "186.21", "Orthorhombic,", "Pca21", "a", "=", "7.5197", "(2)", "A˚", "b", "=", "12.7997", "(3)", "A˚", "c", "=", "20.3238", "(4)", "A˚", "Data", "collection", "Bruker", "SMART", "APEX", "diffractometer", "Absorption", "correction:", "none", "12792", "measured", "reflections", "Refinement", "R[F", "2", ">", "2", "(F", "2)]", "=", "0.033", "wR(F", "2)", "=", "0.088", "S", "=", "1.02", "2317", "reflections", "255", "parameters", "V", "=", "1956.16", "(8)", "A˚", "3", "Z", "=", "8", "Mo", "K", "radiation", "=", "0.08", "mm", "1", "T", "=", "153", "K", "0.35", "0.25", "0.15", "mm", "2317", "independent", "reflections", "2030", "reflections", "with", "I", ">", "2", "(I)", "Rint", "=", "0.028", "1", "restraint", "H-atom", "parameters", "constrained", "max", "=", "0.16", "e", "A˚", "3", "min", "=", "0.19", "e", "A˚", "3", "Data", "collection:", "APEX2", "(Bruker,", "2008);", "cell", "refinement:", "SAINT", "(Bruker,", "2008);", "data", "reduction:", "SAINT;", "program(s)", "used", "to", "solve", "structure:", "SHELXS97", "(Sheldrick,", "2008);", "program(s)", "used", "to", "refine", "structure:", "SHELXL97", "(Sheldrick,", "2008);", "molecular", "graphics:", "X-", "SEED", "(Barbour,", "2001);", "software", "used", "to", "prepare", "material", "for", "publication:", "publCIF", "(Westrip,", "2009).", "We", "thank", "the", "University", "of", "Malaya", "(FP047/2008", "C,", "RG027/", "09AFR)", "for", "supporting", "this", "study.", "Supplementary", "data", "and", "figures", "for", "this", "paper", "are", "available", "from", "the", "IUCr", "electronic", "archives", "(Reference:", "BT2995).", "References", "Barbour,", "L.", "J.", "(2001).", "J.", "Supramol.", "Chem.", "1,", "189–191.", "Bruker", "(2008).", "APEX2", "and", "SAINT.", "Bruker", "AXS", "Inc.,", "Madison,", "Wisconsin,", "USA.", "Shah", "Bakhtiar,", "N.,", "Abdullah,", "Z.", "&", "Ng,", "S.", "W.", "(2009).", "Acta", "Cryst.", "E65,", "o114.", "Sheldrick,", "G.", "M.", "(2008).", "Acta", "Cryst.", "A64,", "112–122.", "Westrip,", "S.", "P.", "(2009).", "publCIF.", "In", "preparation.", "o1880", "Shah", "Bakhtiar", "et", "al.", "doi:10.1107/S1600536809026609", "Acta", "Cryst.", "(2009).", "E65,", "o1880" ]

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[ "www.impactjournals.com/oncotarget/", "Oncotarget,", "March,", "Vol.2,", "No", "3", "Personalizing", "Therapy", "with", "Targeted", "Agents", "in", "Non-Small", "Cell", "Lung", "Cancer", "Rodrigo", "Dienstmann1,", "Pablo", "Martinez2,", "Enriqueta", "Felip2", "1", "Molecular", "Therapeutic", "Research", "Unit,", "Medical", "Oncology", "Service,", "Vall", "d’Hebron", "University", "Hospital", "and", "Vall", "d’Hebron", "Institute", "of", "Oncology,", "Barcelona", "2", "Thoracic", "Neoplasms", "Unit,", "Medical", "Oncology", "Service,", "Vall", "d’Hebron", "University", "Hospital", "and", "Vall", "d’Hebron", "Institute", "of", "Oncology,", "Barcelona,", "Spain", "Correspondence", "to:", "Enriqueta", "Felip,", "email:", "efelip@vhebron.net", "Keywords:", "ALK,", "EGFR,", "KRAS,", "lung", "cancer,", "targeted", "therapy", "Received:", "March", "12,", "2011,", "Accepted:", "March", "23,", "2011,", "Published:", "March", "23,", "2011", "Copyright:", "©", "Dienstmann", "et", "al.", "This", "is", "an", "open-access", "article", "distributed", "under", "the", "terms", "of", "the", "Creative", "Commons", "Attribution", "License,", "which", "permits", "unrestricted", "use,", "distribution,", "and", "reproduction", "in", "any", "medium,", "provided", "the", "original", "author", "and", "source", "are", "credited.", "AbstrAct:", "In", "the", "last", "6", "years,", "since", "the", "first", "reports", "of", "an", "association", "between", "somatic", "mutations", "in", "epidermal", "growth", "factor", "receptor", "(EGFR)", "exons", "19", "and", "21", "and", "response", "to", "EGFR", "tyrosine", "kinase", "inhibitors", "(TKIs),", "treatment", "of", "non-small", "cell", "lung", "cancer", "(NSCLC)", "has", "changed", "dramatically.", "Based", "on", "laboratory", "and", "clinical", "observations,", "investigators", "have", "anticipated", "that", "these", "mutations", "could", "be", "predictive", "of", "response", "to", "EGFR", "TKIs", "and", "numerous", "studies", "have", "confirmed", "that", "the", "presence", "of", "mutation", "was", "associated", "with", "longer", "survival", "in", "patients", "receiving", "targeted", "therapy.", "Prospective", "trials", "comparing", "standard", "platinum-based", "chemotherapy", "with", "EGFR", "TKIs", "in", "patients", "with", "and", "without", "activating", "EGFR", "mutations", "validated", "the", "predictive", "value", "of", "molecular", "selection", "of", "patients", "for", "first-line", "treatment", "of", "advanced", "NSCLC.", "Recently,", "preclinical", "and", "first-", "in-human", "studies", "have", "demonstrated", "impressive", "activity", "of", "ALK", "TKI", "in", "tumors", "harboring", "ALK", "rearrangement.", "In", "this", "article,", "we", "review", "current", "data", "on", "molecular", "biology", "of", "lung", "cancer", "and", "evidence-based", "patient", "selection", "for", "targeted", "therapy.", "IntroductIon", "Lung", "cancer", "is", "the", "most", "frequent", "cause", "of", "cancer-", "related", "death", "worldwide.", "Non-small", "cell", "lung", "cancer", "(NSCLC)", "accounts", "for", "85%", "of", "all", "lung", "cancers", "[1].", "Only", "a", "minority", "of", "NSCLC", "patients", "is", "suitable", "for", "radical", "treatment", "as", "curative", "care.", "Most", "patients", "have", "advanced", "disease", "at", "diagnosis", "and", "palliative", "therapy", "is", "the", "mainstay", "of", "management.", "Conventional", "chemotherapy", "of", "NSCLC", "has", "apparently", "reached", "a", "plateau", "of", "effectiveness", "in", "improving", "survival", "of", "lung", "cancer", "patients,", "and", "treatment", "outcomes", "must", "still", "be", "considered", "disappointing", "[2].", "Based", "on", "a", "better", "understanding", "of", "the", "biology", "of", "lung", "cancer,", "targeted", "therapies", "are", "also", "available", "to", "treat", "patients", "with", "NSCLC.", "Predictive", "markers", "of", "response", "to", "these", "agents", "are", "undergoing", "prospective", "validation", "and", "promising", "results", "have", "been", "reported.", "The", "epidermal", "growth", "factor", "receptor", "(EGFR)", "signaling", "pathway", "is", "importantly", "implicated", "in", "tumor", "cell", "growth,", "local", "invasion,", "angiogenesis,", "metastasis,", "protein", "translation", "and", "cell", "metabolism.", "It", "activates", "two", "major", "pathways", "in", "solid", "tumors,", "RAS/RAF/MAPK/ERK", "and", "PI3K/AKT/mTOR,", "as", "seen", "in", "Figure", "1", "[3].", "Molecular", "aberrations", "on", "the", "EGFR", "pathway", "are", "the", "most", "commonly", "studied", "predictive", "biomarkers", "of", "response/", "resistance", "to", "targeted", "agents", "in", "lung", "cancer.", "This", "review", "delineates", "the", "current", "role", "of", "EGFR", "inhibitors", "in", "the", "treatment", "of", "advanced", "NSCLC", "according", "to", "EGFR", "and", "KRAS", "status", "of", "the", "tumor,", "strategies", "to", "overcome", "resistance", "to", "agents", "targeting", "EGFR", "and", "also", "discusses", "other", "recently", "discovered", "molecular", "aberration", "in", "lung", "cancer,", "ALK", "rearrangement,", "which", "is", "being", "efficiently", "targeted", "with", "ALK", "inhibitors.", "EGFr", "p", "Athw", "Ay:", "molEculAr", "AbErrA", "tIons,", "AntI-EGFr", "thErApy", "And", "prEdIctIvE", "mArkErs", "oF", "rEsponsE", "NSCLC", "is", "associated", "with", "EGFR", "overexpression", "in", "up", "to", "80%", "of", "the", "patients", "and", "a", "high", "EGFR", "gene", "copy", "number", "is", "found", "in", "nearly", "60%", "of", "the", "cases", "[4-6].", "Mutation", "of", "the", "EGFR", "proto-oncogene", "is", "found", "in", "10%", "to", "20%", "of", "www.impactjournals.com/oncotarget", "165", "Oncotarget", "2011;", "2:", "165", "-", "177" ]

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