Search results for "Immune system"

showing 10 items of 2885 documents

2020

Tumor-necrosis-factor-alpha-induced protein 3 (TNFAIP3), or A20, is a ubiquitin-modifying protein and negative regulator of canonical nuclear factor κB (NF-κB) signaling. Several single-nucleotide polymorphisms in TNFAIP3 are associated with autoimmune diseases, suggesting a role in tissue inflammation. While the role of A20 in peripheral immune cells has been well investigated, less is known about its role in the central nervous system (CNS). Here, we show that microglial A20 is crucial for maintaining brain homeostasis. Without microglial A20, CD8+ T cells spontaneously infiltrate the CNS and acquire a viral response signature. The combination of infiltrating CD8+ T cells and activated A2…

MicrogliaCentral nervous systemNF-κBBiologyGeneral Biochemistry Genetics and Molecular BiologyCell biologychemistry.chemical_compoundmedicine.anatomical_structureImmune systemchemistryDownregulation and upregulationimmune system diseaseshemic and lymphatic diseasesmedicineCytotoxic T cellNeuroinflammationCD8Cell Reports
researchProduct

The inorganic polymer, polyphosphate, blocks binding of SARS-CoV-2 spike protein to ACE2 receptor at physiological concentrations

2020

Graphical abstract The inorganic physiological polymer, polyphosphate, blocks binding of SARS-CoV-2 spike protein to ACE2 receptor at physiological concentrations. This discovery proposes polyphosphate as a new member of the host's antiviral innate immune defense.

Models Molecular0301 basic medicineAntiviral AgentsBiochemistryArticle03 medical and health scienceschemistry.chemical_compound0302 clinical medicinePolyphosphatesPolyphosphateHuman Umbilical Vein Endothelial Cellsotorhinolaryngologic diseasesHumansPlateletReceptorneoplasmsPharmacologychemistry.chemical_classificationBinding assayInnate immune systemSARS-CoV-2 spike S-proteinLigand binding assayPolyphosphateCOVID-19pathological conditions signs and symptomsdigestive system diseasesCOVID-19 Drug TreatmentAmino acidsurgical procedures operative030104 developmental biologyEnzymechemistryBiochemistry030220 oncology & carcinogenesisSpike Glycoprotein CoronavirusNanoparticlesAlkaline phosphataseAngiotensin-Converting Enzyme 2Protein BindingReceptors CoronavirusBiochemical Pharmacology
researchProduct

Role of HLA-B α-3 domain amino acid position 194 in HIV disease progression

2013

HLA class I molecules play a role in the regulation of innate immune response. Therefore, the interaction of HLA class I molecules with different activating and inhibitory receptors leads to balancing the immune response. Among the different family of receptors, NK receptors KIR3DL1/S1 and LIR1, play a major role. Aim of this study was to evaluate the role of amino acid polymorphic positions of HLA class I molecules interacting with NK receptors in HIV progression. In order to minimize the influence of viral variability, a cohort of children with a nosocomial monophyletic HIV-1 infection from the Benghazi Children Hospital has been evaluated. To assess the role of single amino acid position…

Models MolecularGene ExpressionKIR3DS1HIV InfectionsPeptide bindingLeukocyte Immunoglobulin-like Receptor B1ModelsImmunologicReceptorsInnateReceptors ImmunologicChildReceptorGeneticschemistry.chemical_classificationCross Infectioneducation.field_of_studyReceptors KIR3DL1Polymorphism Genetic; Models Molecular; Humans; Disease Progression; Gene Expression; HLA-B Antigens; Immunity Innate; Child; Receptors KIR3DL1; Protein Binding; HIV-1; Binding Sites; Receptors KIR3DS1; Receptors Immunologic; HIV Infections; Antigens CD; Protein Structure Tertiary; Signal Transduction; Amino Acid Substitution; Cross InfectionHLA-BCDAmino acidDisease ProgressionKIR3DL1Protein BindingSignal TransductionReceptors KIR3DS1Protein StructureImmunologyPopulationHuman leukocyte antigenBiologyGeneticKIR3DL1Antigens CDHumansPolymorphismAntigenseducationMolecular BiologySettore MED/04 - Patologia GeneralePolymorphism GeneticBinding SitesInnate immune systemImmunityMolecularImmunity InnateProtein Structure TertiaryAmino Acid SubstitutionchemistryHLA-B AntigensImmunologyHIV-1TertiaryMolecular Immunology
researchProduct

Identification of a novel activating mutation (Y842C) within the activation loop of FLT3 in patients with acute myeloid leukemia (AML).

2004

Fms-like tyrosine kinase 3 (FLT3) receptor mutations as internal tandem duplication (ITD) or within the kinase domain are detected in up to 35% of patients with acute myeloid leukemia (AML). N-benzoyl staurosporine (PKC412), a highly effective inhibitor of mutated FLT3 receptors, has significant antileukemic efficacy in patients with FLT3-mutated AML. Mutation screening of FLT3 exon 20 in AML patients (n = 110) revealed 2 patients with a novel mutation (Y842C) within the highly conserved activation loop of FLT3. FLT3-Y842C-transfected 32D cells showed constitutive FLT3 tyrosine phosphorylation and interleukin 3 (IL-3)-independent growth. Treatment with PKC412 led to inhibition of proliferat…

Models MolecularImmunologyBiologymedicine.disease_causeBiochemistryCell Linechemistry.chemical_compoundMicefluids and secretionshemic and lymphatic diseasesProto-Oncogene ProteinsmedicineSTAT5 Transcription FactorAnimalsHumansTyrosinePhosphotyrosineMutationCell CycleMyeloid leukemiaReceptor Protein-Tyrosine Kinaseshemic and immune systemsTyrosine phosphorylationCell BiologyHematologymedicine.diseaseMilk ProteinsProtein Structure TertiaryDNA-Binding ProteinsEnzyme ActivationLeukemiaLeukemia Myeloid AcutechemistryGene Expression Regulationfms-Like Tyrosine Kinase 3embryonic structuresFms-Like Tyrosine Kinase 3MutationCancer researchTrans-ActivatorsTyrosineSignal transductionTyrosine kinaseSignal TransductionBlood
researchProduct

Recent findings on phenoloxidase activity and antimicrobial activity of hemocyanins

2003

Models MolecularInnate immune systemMonophenol MonooxygenaseTyrosinasemedicine.medical_treatmentImmunologyAntimicrobial peptidesHemocyaninBiologyAntimicrobialMicrobiologyAnti-Infective AgentsBiochemistryHemocyaninsMetalloproteinsmedicineAnimalsArthropodsDevelopmental BiologyDevelopmental & Comparative Immunology
researchProduct

Gain-of-function mutations in IFIH1 cause a spectrum of human disease phenotypes associated with upregulated type I interferon signaling.

2014

The type I interferon system is integral to human antiviral immunity. However, inappropriate stimulation or defective negative regulation of this system can lead to inflammatory disease. We sought to determine the molecular basis of genetically uncharacterized cases of the type I interferonopathy Aicardi-Goutières syndrome, and of other patients with undefined neurological and immunological phenotypes also demonstrating an upregulated type I interferon response. We found that heterozygous mutations in the cytosolic double-stranded RNA receptor gene IFIH1 (MDA5) cause a spectrum of neuro-immunological features consistently associated with an enhanced interferon state. Cellular and biochemica…

Models MolecularInterferon-Induced Helicase IFIH1Molecular Sequence DataHDE NEU PEDElectrophoretic Mobility Shift AssayBiologymedicine.disease_causeNervous System MalformationsReal-Time Polymerase Chain ReactionArticleDEAD-box RNA HelicasesImmune systemAutoimmune Diseases of the Nervous SystemDownregulation and upregulationAnalysis of Variance; Autoimmune Diseases of the Nervous System; Base Sequence; DEAD-box RNA Helicases; Electrophoretic Mobility Shift Assay; Exome; HEK293 Cells; Humans; Interferon Type I; Microsatellite Repeats; Molecular Sequence Data; Mutation; Nervous System Malformations; Real-Time Polymerase Chain Reaction; Sequence Analysis DNA; Signal Transduction; Spectrum Analysis; Models Molecular; Phenotype; GeneticsModelsInterferonGeneticsmedicineHumansExomeMutationAnalysis of VarianceBase SequenceSpectrum AnalysisMolecularRNAMDA5DNASequence Analysis DNAMolecular biology3. Good healthInterferon Tipo IHEK293 CellsPhenotypeInterferon Type IMutationCancer researchSignal transductionSequence AnalysisInterferon type Imedicine.drugMicrosatellite RepeatsSignal TransductionNature genetics
researchProduct

Heterogeneity at the HLA-DRB1 locus and risk for multiple sclerosis.

2006

Variation in major histocompatibility complex genes on chromosome 6p21.3, specifically the human leukocyte antigen HLA-DR2 or DRB1*1501-DQB1*0602 extended haplotype, confers risk for multiple sclerosis (MS). Previous studies of DRB1 variation and both MS susceptibility and phenotypic expression have lacked statistical power to detect modest genotypic influences, and have demonstrated conflicting results. Results derived from analyses of 1339 MS families indicate DRB1 variation influences MS susceptibility in a complex manner. DRB1*15 was strongly associated in families (P=7.8x10(-31)), and a dominant DRB1*15 dose effect was confirmed (OR=7.5, 95% CI=4.4-13.0, P<0.0001). A modest dose effect…

Models MolecularMaleSequence Homologyimmune system diseasesModelsRisk FactorsDatabases GeneticAdult Alleles Amino Acid Sequence Databases; Genetic Female Genetic Variation Genotype HLA-DR Antigens; chemistry/genetics HLA-DRB1 Chains Humans Male Middle Aged Models; Molecular Molecular Sequence Data Multiple Sclerosis; Chronic Progressive; genetics/immunology Multiple Sclerosis; genetics/immunology Phenotype Risk Factors Sequence Homology; Amino Acidskin and connective tissue diseasesHLA-DRB1Genetics (clinical)GeneticsGeneral MedicineMultiple Sclerosis Chronic ProgressiveMiddle AgedAmino AcidChronic ProgressivePhenotypeFemalemusculoskeletal diseasesAdultMultiple SclerosisGenotypeMolecular Sequence DataLocus (genetics)Human leukocyte antigenBiologyDatabases. Alleles phenotype heterogeneity human leukocyte antigens age of onset chromosomes genes genotype haplotypesmultiple sclerosis relapsing-remitting genetics disability primary progressive multiple sclerosis hla-drb1 gene illness length severity of illnessGeneticGenetic variationGeneticsmedicineHumansAmino Acid SequenceAlleleMolecular BiologyAllelesSequence Homology Amino AcidMultiple sclerosisHaplotypeGenetic VariationMolecularHLA-DR Antigensmedicine.diseasegenetics/immunologychemistry/geneticsImmunologyAge of onsetHLA-DRB1 Chains
researchProduct

A modified dinucleotide motif specifies tRNA recognition by TLR7

2014

RNA can function as a pathogen-associated molecular pattern (PAMP) whose recognition by the innate immune system alerts the body to an impending microbial infection. The recognition of tRNA as either self or nonself RNA by TLR7 depends on its modification patterns. In particular, it is known that the presence of a ribose methylated guanosine at position 18, which is overrepresented in self-RNA, antagonizes an immune response. Here, we report that recognition extends to the next downstream nucleotide and the effectively recognized molecular detail is actually a methylated dinucleotide. The most efficient nucleobases combination of this motif includes two purines, while pyrimidines diminish t…

Models MolecularMolecular Sequence DataGuanosineBiologySubstrate Specificitychemistry.chemical_compoundRNA TransferRiboseHumansNucleotideBinding siteLetter to the EditorMolecular BiologyCells Culturedchemistry.chemical_classificationGeneticsBinding SitesInnate immune systemBase Sequencevirus diseasesRNAMethylationToll-Like Receptor 7chemistryTransfer RNANucleic Acid ConformationProtein BindingRNA
researchProduct

The Molecular Anatomy of Human Hsp60 and its Similarity with that of Bacterial Orthologs and Acetylcholine Receptor Reveal a Potential Pathogenetic R…

2012

Heat-shock protein 60 (Hsp60) is ubiquitous and highly conserved being present in eukaryotes and prokaryotes, including pathogens. This chaperonin, although typically a mitochondrial protein, can also be found in other intracellular sites, extracellularly, and in circulation. Thus, it can signal the immune system and participate in the development of inflammation and immune reactions. Both phenomena can be elicited by human and foreign Hsp60 (e.g., bacterial GroEL), when released into the blood by infectious agents. Consequently, all these Hsp60 proteins become part of a complex autoimmune response characterized by multiple cross reactions because of their structural similarities. In this s…

Models MolecularMolecular Sequence Datachemical and pharmacologic phenomenaAnti-Chaperonin ImmunityBiologymedicine.disease_causecomplex mixturesEpitopeProtein Structure SecondaryHsp60; Myasthenia Gravis; Anti-Chaperonin Immunity; Chlamydia trachomatis; Chlamydia pneumoniae; AChRα1MicrobiologyChaperoninCellular and Molecular NeuroscienceImmune systemChlamydia trachomatiBacterial ProteinsChlamydia pneumoniaeMyasthenia GravisAChRα1medicineHumansReceptors CholinergicAmino Acid SequenceAcetylcholine receptorSequence Homology Amino AcidfungiImmunityCell BiologyGeneral MedicineChaperonin 60Hsp60GroELMyasthenia GraviMolecular mimicryImmunologyHSP60Chlamydia trachomatis
researchProduct

Complete subunit sequences, structure and evolution of the 6 x 6-mer hemocyanin from the common house centipede, Scutigera coleoptrata.

2003

Hemocyanins are large oligomeric copper-containing proteins that serve for the transport of oxygen in many arthropod species. While studied in detail in the Chelicerata and Crustacea, hemocyanins had long been considered unnecessary in the Myriapoda. Here we report the complete molecular structure of the hemocyanin from the common house centipede Scutigera coleoptrata (Myriapoda: Chilopoda), as deduced from 2D-gel electrophoresis, MALDI-TOF mass spectrometry, protein and cDNA sequencing, and homology modeling. This is the first myriapod hemocyanin to be fully sequenced, and allows the investigation of hemocyanin structure-function relationship and evolution. S. coleoptrata hemocyanin is a 6…

Models MolecularProtein Conformationmedicine.medical_treatmentMolecular Sequence DataMyriapodachemical and pharmacologic phenomenaBiochemistryEvolution MolecularMonophylymedicineAnimalsAmino Acid SequenceCloning MolecularArthropodsPhylogenybiologyMandibulatahemic and immune systemsHemocyaninAnatomybiology.organism_classificationProtein SubunitsEvolutionary biologyHemocyaninsChelicerataArthropodCentipedeSequence AlignmentScutigera coleoptrataEuropean journal of biochemistry
researchProduct