Search results for "Proteins"

showing 10 items of 10069 documents

MTOR inhibitor-based combination therapies for pancreatic cancer

2018

Background: Although the mechanistic target of rapamycin (MTOR) kinase, included in the mTORC1 and mTORC2 signalling hubs, has been demonstrated to be active in a significant fraction of patients with pancreatic ductal adenocarcinoma (PDAC), the value of the kinase as a therapeutic target needs further clarification. Methods: We used Mtor floxed mice to analyse the function of the kinase in context of the pancreas at the genetic level. Using a dual-recombinase system, which is based on the flippase-FRT (Flp-FRT) and Cre-loxP recombination technologies, we generated a novel cellular model, allowing the genetic analysis of MTOR functions in tumour maintenance. Cross-species validation and pha…

therapeutic resistance0301 basic medicineCancer ResearchCell SurvivalMAP Kinase Signaling Systempancreatic cancerAntineoplastic AgentsContext (language use)Mechanistic Target of Rapamycin Complex 2mTORC1Mechanistic Target of Rapamycin Complex 1BiologymTORC2BortezomibMice03 medical and health sciencesCell Line TumorPancreatic cancermedicineAnimalsHumansExtracellular Signal-Regulated MAP KinasesMechanistic target of rapamycinPI3K/AKT/mTOR pathwayBenzoxazolesKinaseMTORTOR Serine-Threonine Kinasesmedicine.diseaseddc:3. Good healthPancreatic NeoplasmsPyrimidines030104 developmental biologyOncologybiology.proteinCancer researchCamptothecinTOR Serine-Threonine KinasesPhosphatidylinositol 3-KinaseTranslational TherapeuticsProto-Oncogene Proteins c-aktBiologieCarcinoma Pancreatic Ductal
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Heat Shock Protein 60 in Hepatocellular Carcinoma: Insights and Perspectives

2020

Heat shock protein 60 (HSP60) is a mitochondrial chaperone that is implicated in physiological and pathological processes. For instance, it contributes to protein folding and stability, translocation of mitochondrial proteins, and apoptosis. Variations in the expression levels of HSP60 have been correlated to various diseases and cancers, including hepatocellular carcinoma (HCC). Unlike other HSPs which clearly increase in some cancers, data about HSP60 levels in HCC are controversial and difficult to interpret. In the current review, we summarize and simplify the current knowledge about the role of HSP60 in HCC. In addition, we highlight the possibility of its targeting, using chemical com…

therapeutic resistancechaperoninanimal structureslcsh:Biology (General)fungiheat shock proteinscancer therapychaperoneschemical and pharmacologic phenomenahepatocellular carcinomacomplex mixtureslcsh:QH301-705.5digestive system diseasesFrontiers in Molecular Biosciences
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Response to the Letter to the editor regarding “Targeting NUPR1 with the small compound ZZW-115 is an efficient strategy to treat hepatocellular carc…

2021

therapyCancer ResearchCarcinoma HepatocellularLetter to the editorbusiness.industryLiver Neoplasmshepatocellular carcinomamedicine.diseaseNeoplasm ProteinsGene Expression Regulation NeoplasticOncologyHepatocellular carcinomaCancer researchHumansMedicineStress ProteinsbusinessCancer Letters
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EFFECTS OF THYROID HORMONES ON TWO PUTATIVE RNA-BINDING PROTEINS EXPRESSED IN DEVELOPING RAT BRAIN.

2005

thyroid hormones rat brain RNA-binding proteins
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Single-cell analysis of population context advances RNAi screening at multiple levels

2012

Isogenic cells in culture show strong variability, which arises from dynamic adaptations to the microenvironment of individual cells. Here we study the influence of the cell population context, which determines a single cell's microenvironment, in image‐based RNAi screens. We developed a comprehensive computational approach that employs Bayesian and multivariate methods at the single‐cell level. We applied these methods to 45 RNA interference screens of various sizes, including 7 druggable genome and 2 genome‐wide screens, analysing 17 different mammalian virus infections and four related cell physiological processes. Analysing cell‐based screens at this depth reveals widespread RNAi‐induce…

toImage ProcessingDruggabilityGenomeImage analysis0302 clinical medicineComputer-AssistedSX00 SystemsX.ch2604 Applied MathematicsSingle-cell analysisRNA interferenceModels2400 General Immunology and MicrobiologyImage Processing Computer-AssistedViralRNA Small Interfering0303 health scienceseducation.field_of_studyApplied MathematicsSystems BiologyGenomics10124 Institute of Molecular Life SciencesCell biologycell variabilityComputational Theory and MathematicsCellular MicroenvironmentVirus DiseasesVirusesRNA ViralRNA InterferenceSingle-Cell AnalysisGeneral Agricultural and Biological SciencesInformation SystemsSystems biologyVirus infectionPopulationContext (language use)Genomics1100 General Agricultural and Biological SciencesBiologySmall InterferingModels BiologicalGeneral Biochemistry Genetics and Molecular BiologySX08 LipidX03 medical and health sciencesViral ProteinsCell-to-cell variability; Image analysis; Population context; RNAi; Virus infection1300 General Biochemistry Genetics and Molecular BiologyHumansComputer Simulationeducation030304 developmental biologyGeneral Immunology and MicrobiologyCell-to-cell variabilityReproducibility of ResultsBayes TheoremcellBiologicalPopulation contextRNAi570 Life sciences; biologyRNA030217 neurology & neurosurgeryHeLa CellsMolecular Systems Biology
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Double copies of blaKPC-3::Tn4401a on an IncX3 plasmid in Klebsiella pneumoniae successful clone ST512 from Italy

2015

ABSTRACT A carbapenem-resistant sequence type 512 (ST512) Klebsiella pneumoniae carbapenemase 3 (KPC-3)-producing K. pneumoniae strain showing a novel variant plasmid content was isolated in Palermo, Italy, in 2014. ST512 is a worldwide successful clone associated with the spread of bla KPC genes located on the IncFIIk pKpQIL plasmid. In our ST512 strain, the bla KPC-3 gene was unusually located on an IncX3 plasmid, whose complete sequence was determined. Two copies of bla KPC-3 ::Tn 4401a caused by intramolecular transposition events were detected in the plasmid.

transposonsequence analysispolymerase chain reactionDrug ResistanceGene DosageSettore MED/42 - Igiene Generale E Applicatabacterial proteinbeta-Lactamaseopen reading framecarbapenemasePlasmidminocyclineplasmid DNAmeropenemPharmacology (medical)geneticscolistincefpodoximeceftazidime610 Medicine & healthCarbapenemBacterialpolymyxin Btimentingene expression regulationbacteriumKlebsiella pneumoniae carbapenemase 3 producing Klebsiella pneumoniae3. Good healthantiinfective agentmicrobial sensitivity testKlebsiella pneumoniaeItalypriority journaltigecyclineMultipleclone (Java method)cefotaxime030106 microbiologyKlebsiella pneumoniae carbapenemase 3tobramycinMicrobial Sensitivity Testsgentamicinpiperacillin plus tazobactamchemistryGene dosageArticleMicrobiology03 medical and health sciencesComplete sequenceClone CellOpen Reading FramesertapenemBacterial Proteinsmultidrug resistanceextensively drug resistant bacteriumAnti-Bacterial AgentcefepimePharmacologylevofloxacinmicrobiologycefoxitinbiochemical phenomena metabolism and nutritionbacterial infections and mycosesVirologyAnti-Bacterial Agents; Bacterial Proteins; Carbapenems; Clone Cells; Drug Resistance Multiple Bacterial; Gene Dosage; Italy; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests; Open Reading Frames; Plasmids; beta-Lactamases; DNA Transposable Elements; Gene Expression Regulation Bacterial; Pharmacology (medical); Pharmacology; Infectious Diseasesantibiotic sensitivityClone CellsKlebsiella InfectionsceftriaxoneCarbapenemsbacterial genetics0301 basic medicinemolecular cloningSettore MED/07 - Microbiologia E Microbiologia ClinicaKlebsiella pneumoniaeTransposition (music)Drug Resistance Multiple Bacterialpolycyclic compoundsgenetic screeningcell clonecarbapenem derivativeKlebsiella infectionunclassified drugAnti-Bacterial AgentsInfectious Diseasesbacterial genePlasmidsenzymologydoripenemBiologyminimum inhibitory concentrationbeta-Lactamasesbeta lactamaseMechanisms of ResistanceciprofloxacinAmikacin; aztreonam; carbapenemase; cefepime; cefotaxime; cefoxitin; cefpodoxime; ceftazidime; ceftriaxone; ciprofloxacin; colistin; cotrimoxazole; doripenem; doxycycline; ertapenem; gentamicin; imipenem; Klebsiella pneumoniae carbapenemase 3; levofloxacin; meropenem; minocycline; piperacillin plus tazobactam; plasmid DNA; polymyxin B; tigecycline; timentin; tobramycin; unclassified drug; antiinfective agent; bacterial protein; beta lactamase; carbapenem derivative; transposon antibiotic sensitivity; Article; bacterial gene; bacterial genetics; bacterial strain; bacterium; bacterium detection; bacterium isolation; Escherichia coli; extensively drug resistant bacterium; gene dosage; genetic screening; Italy; Klebsiella pneumoniae; Klebsiella pneumoniae carbapenemase 3 producing Klebsiella pneumoniae; minimum inhibitory concentration; molecular cloning; nonhuman; polymerase chain reaction; priority journal; sequence analysis; cell clone; chemistry; drug effects; enzymology; gene expression regulation; genetics; isolation and purification; Klebsiella infection; Klebsiella pneumoniae; metabolism; microbial sensitivity test; microbiology; multidrug resistance; open reading frame; plasmid; transposon Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Carbapenems; Clone Cells; DNA Transposable Elements; Drug Resistance Multiple Bacterial; Gene Dosage; Gene Expression Regulation Bacterial; Italy; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests; Open Reading Frames; Plasmidsplasmidbacterium isolationEscherichia coliGeneAmikacinbacterium detectionnonhumandoxycyclineisolation and purificationGene Expression Regulation Bacterialbiology.organism_classificationbacterial straincotrimoxazoleOpen reading frameDNA Transposable Elementdrug effectsDNA Transposable Elementsmetabolismaztreonamimipenem
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The prolyl-isomerase PIN1 is essential for nuclear Lamin-B structure and function and protects heterochromatin under mechanical stress.

2021

Summary: Chromatin organization plays a crucial role in tissue homeostasis. Heterochromatin relaxation and consequent unscheduled mobilization of transposable elements (TEs) are emerging as key contributors of aging and aging-related pathologies, including Alzheimer’s disease (AD) and cancer. However, the mechanisms governing heterochromatin maintenance or its relaxation in pathological conditions remain poorly understood. Here we show that PIN1, the only phosphorylation-specific cis/trans prolyl isomerase, whose loss is associated with premature aging and AD, is essential to preserve heterochromatin. We demonstrate that this PIN1 function is conserved from Drosophila to humans and prevents…

transposonsNeocortexMiceHeterochromatinProlyl isomeraseDrosophila ProteinsBiology (General)PhosphorylationRNA Small InterferingTissue homeostasisCells CulturedSettore ING-INF/05 - Sistemi Di Elaborazione Delle InformazioniNeuronsLamin Type BChemistryHP1phosphorylationneurodegenerationnuclear envelopePeptidylprolyl IsomeraseCell biologyDrosophila heterochromatin HP1 Lamin mechanical stress neurodegeneration nuclear envelope phosphorylation PIN1 transposonsNuclear laminaDrosophilaRNA InterferencePremature agingQH301-705.5HeterochromatinNuclear EnvelopeDrosophila; heterochromatin; HP1; Lamin; mechanical stress; neurodegeneration; nuclear envelope; phosphorylation; PIN1; transposonsSettore BIO/11 - Biologia MolecolareSettore MED/08 - Anatomia PatologicaGeneral Biochemistry Genetics and Molecular BiologyPIN1Alzheimer DiseaseSettore MED/05 - Patologia ClinicaAnimalsHumansHeterochromatin maintenancemechanical stressheterochromatinmechanical streMice Inbred C57BLNIMA-Interacting Peptidylprolyl IsomeraseChromobox Protein Homolog 5DNA Transposable ElementsHeterochromatin protein 1Stress MechanicalLaminLaminCell reports
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Hydrogen isotopes (δ2H) of polyunsaturated fatty acids track bioconversion by zooplankton

2022

1. Organisms at the base of aquatic food webs synthesize essential nutrients, such as omega-3 polyunsaturated fatty acids (n-3 PUFA), which are transferred to consumers at higher trophic levels. Many consumers, requiring n-3 long-chain (LC) PUFA, such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), have limited ability to biosynthesize them from the essential dietary precursor α-linolenic acid (ALA) and thus rely on dietary provision of LC-PUFA. 2. We investigated LC-PUFA metabolism in freshwater zooplankton using stable hydrogen isotopes (δ2H) of fatty acids as tracers. We conducted feeding experiments with the freshwater keystone grazer Daphnia to quantify changes in the δ2…

trophic ecologyzooplanktonbioconversionecophysiologyrehevöityminenfungiDaphnia magnaplanktoncompound-specific stable isotopesrasvahapotvesiekosysteemitessential fatty acidsGC-IRMStrophic upgradingekofysiologiaeutrophicationisotooppianalyysivesikirputlipids (amino acids peptides and proteins)ravintoaineetdeuteriumravintoverkot
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Experimental Evolution Reveals a Genetic Basis for Membrane-Associated Virus Release

2021

Many animal viruses replicate and are released from cells in close association to membranes. However, whether this is a passive process or is controlled by the virus remains poorly understood. Importantly, the genetic basis and evolvability of membrane-associated viral shedding have not been investigated. To address this, we performed a directed evolution experiment using coxsackievirus B3, a model enterovirus, in which we repeatedly selected the free-virion or the fast-sedimenting membrane-associated viral subpopulations. The virus responded to this selection regime by reproducibly fixing a series of mutations that altered the extent of membrane-associated viral shedding, as revealed by fu…

ultra-deep sequencingUltra-deep sequencingvirusesMutagenesis (molecular biology technique)Viral transmissionBiologyAcademicSubjects/SCI01180Virus03 medical and health sciencesGeneticsViral sheddingdirected evolutionMolecular BiologyEcology Evolution Behavior and SystematicsDiscoveriesEnterovirus030304 developmental biology0303 health sciencesExperimental evolution030306 microbiologyenterovirusviral transmissionAcademicSubjects/SCI01130Directed evolutionVirologyvirus–membrane interactionsBiological EvolutionVirus ReleaseVirus–membrane interactions3. Good healthEnterovirus B HumanVirus SheddingEvolvabilityCapsidAmino Acid SubstitutionDirected evolutionCapsid ProteinsGenetic FitnessMolecular Biology and Evolution
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Regulation of type 1 fimbriae synthesis and biofilm formation by the transcriptional regulator LrhA of Escherichia coli

2005

Type 1 fimbriae ofEscherichia colifacilitate attachment to the host mucosa and promote biofilm formation on abiotic surfaces. The transcriptional regulator LrhA, which is known as a repressor of flagellar, motility and chemotaxis genes, regulates biofilm formation and expression of type 1 fimbriae. Whole-genome expression profiling revealed that inactivation oflrhAresults in an increased expression of structural components of type 1 fimbriae.In vitro, LrhA bound to the promoter regions of the twofimrecombinases (FimB and FimE) that catalyse the inversion of thefimApromoter, and to the invertible element itself. TranslationallacZfusions with these genes and quantification offimEtranscript le…

urinary-tractphase variationFimbrialac operonRepressorsuicide vectorBiologyFlagellummedicine.disease_causeMicrobiologyBacterial AdhesionMicrobiologylysr homologMiceglobal regulatorh-nsEscherichia colimedicineAnimalsHumansgenetic-analysisPromoter Regions GeneticEscherichia coliEscherichia coli InfectionsOligonucleotide Array Sequence AnalysisPhase variationRegulation of gene expressionfim switchEscherichia coli ProteinsGene Expression ProfilingBiofilmGene Expression Regulation Bacterialbiochemical phenomena metabolism and nutritionintegration host factorBiofilmsFimbriae BacterialMutationUrinary Tract Infectionsvirulence determinantsTranscription Factors
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