2025
Immune inhibitory receptor agonist therapeutics
Lovewell R, Langermann S, Flies D. Immune inhibitory receptor agonist therapeutics. Frontiers In Immunology 2025, 16: 1566869. PMID: 40207220, DOI: 10.3389/fimmu.2025.1566869.Peer-Reviewed Original ResearchConceptsAgonist suppressionSurface of immune cellsCheckpoint inhibitorsStimulatory cellsStimulatory receptorsSuppressive cellsDysregulated inflammationImmune cellsPre-clinicalTreat diseasesDisease settingsAgonistsImmune systemImmune pathwaysClinical therapeuticsTherapeutic interventionsDiseaseReceptorsCellular levelTherapeuticsCellsPathwayInduced signalsAutoimmunityInflammation
2024
Zika virus exists in enterocytes and enteroendocrine cells of the Aedes aegypti midgut
Chen T, Raduwan H, Marín-López A, Cui Y, Fikrig E. Zika virus exists in enterocytes and enteroendocrine cells of the Aedes aegypti midgut. IScience 2024, 27: 110353. PMID: 39055935, PMCID: PMC11269924, DOI: 10.1016/j.isci.2024.110353.Peer-Reviewed Original ResearchAedes aegypti midgutEnteroendocrine cellsSingle-cell RNA sequencingIntestinal stem cellsVirus infectionPathogen interactionsExpressed genesRNA sequencingCopy numberTranscriptomic changesFunctional studiesInfected cellsZika virus infectionEnteroendocrineBlood digestionRNA copy numberCellular levelCell processesGenesMidgutPotential targetCell clustersCellsEnterocytesViral infection
2023
Brain developmental and cortical connectivity changes in transgenic monkeys carrying the human-specific duplicated gene SRGAP2C
Meng X, Lin Q, Zeng X, Jiang J, Li M, Luo X, Chen K, Wu H, Hu Y, Liu C, Su B. Brain developmental and cortical connectivity changes in transgenic monkeys carrying the human-specific duplicated gene SRGAP2C. National Science Review 2023, 10: nwad281. PMID: 38090550, PMCID: PMC10712708, DOI: 10.1093/nsr/nwad281.Peer-Reviewed Original ResearchTransgenic monkeysDeep layer neuronsFetal neurogenesisMyelination levelsSynaptic maturationLongitudinal MRITransgenic miceSynaptic connectionsBrain developmentConnectivity changesBrain connectivityOccipital regionMolecular pathwaysBrainMotor planningMonkeysEnergy metabolismHuman brainCellular levelEnlarged brainExtracellular matrixPrior studiesHumansNeurogenesisGenesAcetate controls endothelial-to-mesenchymal transition
Zhu X, Wang Y, Soaita I, Lee H, Bae H, Boutagy N, Bostwick A, Zhang R, Bowman C, Xu Y, Trefely S, Chen Y, Qin L, Sessa W, Tellides G, Jang C, Snyder N, Yu L, Arany Z, Simons M. Acetate controls endothelial-to-mesenchymal transition. Cell Metabolism 2023, 35: 1163-1178.e10. PMID: 37327791, PMCID: PMC10529701, DOI: 10.1016/j.cmet.2023.05.010.Peer-Reviewed Original ResearchConceptsTGF-β signalingChronic vascular diseaseTGF-β receptor ALK5Mesenchymal transitionInduction of EndMTVascular diseaseMolecular basisPositive feedback loopReceptor ALK5Cellular levelSMADs 2Novel targetEndMT inductionMetabolic modulationMetabolic basisFibrotic stateSignalingPotential treatmentEndMTTGFDiseaseActivationInductionACSS2PDK4Three-dimensional imaging of vascular development in the mouse epididymis.
Damon-Soubeyrand C, Bongiovanni A, Chorfa A, Goubely C, Pirot N, Pardanaud L, Piboin-Fragner L, Vachias C, Bravard S, Guiton R, Thomas J, Saez F, Kocer A, Tardivel M, Drevet J, Henry-Berger J. Three-dimensional imaging of vascular development in the mouse epididymis. ELife 2023, 12 PMID: 37310207, PMCID: PMC10264076, DOI: 10.7554/elife.82748.Peer-Reviewed Original ResearchConceptsProtection of spermatozoaComplex immune functionsAccessory tubulesVascular developmentMouse epididymisCellular levelSecretory roleImportant playersMale fertilityMale reproductive systemOrgan clearingMature adult miceReproductive systemTransgenic mouse modelFunctional maturationPeripheral toleranceBlood markersImmune responseLymphatic networkImmune functionKey determinantMouse modelSurvival of spermatozoaAdult miceImmune systemRottlerin-Liposome Inhibits the Endocytosis of Feline Coronavirus Infection
Choi J, Jung S, Choi I, Kang Y, Lee D, Lee S, Park S, Song C, Choi I, Lee J, Oh C. Rottlerin-Liposome Inhibits the Endocytosis of Feline Coronavirus Infection. Veterinary Sciences 2023, 10: 380. PMID: 37368766, PMCID: PMC10302841, DOI: 10.3390/vetsci10060380.Peer-Reviewed Original ResearchFeline infectious peritonitisFeline coronavirus infectionSystemic granulomatous inflammationDose-dependent mannerFCoV replicationGranulomatous inflammationAntiviral effectInfectious peritonitisPotential treatmentFatal diseaseHigh mortalityCoronavirus infectionFeline coronavirusAntiviral propertiesWorth further investigationFurther investigationCellular levelFCoV.Inhibition efficacyPeritonitisInflammationRottlerinLater stagesHigh-throughput combined voltage-clamp/current-clamp analysis of freshly isolated neurons
Ghovanloo M, Tyagi S, Zhao P, Kiziltug E, Estacion M, Dib-Hajj S, Waxman S. High-throughput combined voltage-clamp/current-clamp analysis of freshly isolated neurons. Cell Reports Methods 2023, 3: 100385. PMID: 36814833, PMCID: PMC9939380, DOI: 10.1016/j.crmeth.2022.100385.Peer-Reviewed Original ResearchConceptsDorsal root ganglion neuronsCurrent-clamp recordingsCurrent-clamp analysisVoltage-gated sodium channelsPatch-clamp techniqueExcitable cellsGanglion neuronsElectrophysiological recordingsNeuronal cellsNeuronsGold standard methodologySodium channelsCellular levelRobotic instrumentsCellsDrug screeningSame cellsIntact tissueRecordings
2022
Cellular Heterogeneity and Molecular Reprogramming of the Host Response during Influenza Acute Lung Injury
Guo K, Yombo D, Schmit T, Wang Z, Navaeiseddighi Z, Sathish V, Mathur R, Wu M, De Kumar B, Hur J, Khan N. Cellular Heterogeneity and Molecular Reprogramming of the Host Response during Influenza Acute Lung Injury. Journal Of Virology 2022, 96: e01246-22. PMID: 36286482, PMCID: PMC9645213, DOI: 10.1128/jvi.01246-22.Peer-Reviewed Original ResearchConceptsAcute lung injuryLung injuryIAV infectionHost responseDysregulated host responseExuberant host responseOutcome of interferonTotal immune cellsMonocyte-derived macrophagesSingle-cell RNA sequencing analysisChemokine responsesAcute injuryCellular levelImmune cellsNonimmune cellsBarrier integrityMyeloid cellsTherapeutic interventionsCellular heterogeneityInjuryChemokine signalingNonhematopoietic cellsInfectionRNA sequencing analysisMechanistic associationDeciphering Spatial Protein–Protein Interactions in Brain Using Proximity Labeling
Mathew B, Bathla S, Williams KR, Nairn AC. Deciphering Spatial Protein–Protein Interactions in Brain Using Proximity Labeling. Molecular & Cellular Proteomics 2022, 21: 100422. PMID: 36198386, PMCID: PMC9650050, DOI: 10.1016/j.mcpro.2022.100422.Peer-Reviewed Original ResearchConceptsProtein-protein interactionsProximity labelingBiological functionsComplex protein-protein interactionsProximity labeling methodProtein-DNA interactionsCell-cell communicationMost biological functionsDistinct cell typesProtein-RNANerve cell functionCell typesBiomolecular complexesCellular levelPhysical interactionProteomeCell functionSpecific subsetProteinSynaptic plasticityComplete catalogLabeling methodRecent advancesPowerful toolAxonal projectionsSpatial profiling of chromatin accessibility in mouse and human tissues
Deng Y, Bartosovic M, Ma S, Zhang D, Kukanja P, Xiao Y, Su G, Liu Y, Qin X, Rosoklija GB, Dwork AJ, Mann JJ, Xu ML, Halene S, Craft JE, Leong KW, Boldrini M, Castelo-Branco G, Fan R. Spatial profiling of chromatin accessibility in mouse and human tissues. Nature 2022, 609: 375-383. PMID: 35978191, PMCID: PMC9452302, DOI: 10.1038/s41586-022-05094-1.Peer-Reviewed Original ResearchConceptsChromatin accessibilityATAC-seqSpecific epigenetic landscapesChromatin accessibility profilingCell fate decisionsEpigenetic informationEpigenetic landscapeGenome scaleFate decisionsAccessible genomeCell identityEpigenetic underpinningsNext-generation sequencingGene regulatorsCell statesMouse embryosSpatial biologySpatial transcriptomicsCell typesCellular levelImmune cell typesDistinct organizationHuman tissuesProfilingSpatial profilingCross-platform analysis reveals cellular and molecular landscape of glioblastoma invasion
Chen AT, Xiao Y, Tang X, Baqri M, Gao X, Reschke M, Sheu WC, Long G, Zhou Y, Deng G, Zhang S, Deng Y, Bai Z, Kim D, Huttner A, Kunes R, Günel M, Moliterno J, Saltzman WM, Fan R, Zhou J. Cross-platform analysis reveals cellular and molecular landscape of glioblastoma invasion. Neuro-Oncology 2022, 25: 482-494. PMID: 35901838, PMCID: PMC10013636, DOI: 10.1093/neuonc/noac186.Peer-Reviewed Original ResearchConceptsCrystallin alpha BTumor invasionGBM invasionHistology samplesMolecular landscapeTreatment of glioblastomaPostoperative recurrenceGBM patientsInvasive glioblastomaResection modelGlioblastomaNon-invasive counterpartsGBM samplesGlioblastoma invasionCD44PatientsInvasionAlpha BCellular levelTranscriptomic featuresRNA sequencing dataRecurrenceHistology stainsLevelsDisease
2021
Computational insights into the membrane fusion mechanism of SARS-CoV-2 at the cellular level
Wang J, Maschietto F, Guberman-Pfeffer MJ, Reiss K, Allen B, Xiong Y, Lolis E, Batista VS. Computational insights into the membrane fusion mechanism of SARS-CoV-2 at the cellular level. Computational And Structural Biotechnology Journal 2021, 19: 5019-5028. PMID: 34540146, PMCID: PMC8442599, DOI: 10.1016/j.csbj.2021.08.053.Peer-Reviewed Original ResearchMembrane fusion mechanismMembrane fusionSpike trimerNeutral amino acid transporterHost cellular membranesAmino acid transportersCentral stalkCentral poreHost membraneFusion mechanismCellular membranesAcid transportersMolecular levelViral membraneCellular levelEnzymatic activityChoreographic eventFusion peptideAntiviral inhibitorsDrug designAttractive targetInitial bindingMembraneConformational constraintsSpike glycoprotein
2018
Layer-specific reduced neuronal density in the orbitofrontal cortex of older adults with obsessive–compulsive disorder
de Oliveira K, Grinberg L, Hoexter M, Brentani H, Suemoto C, Nery F, Lima L, Alho A, Farfel J, Ferretti-Rebustini R, Leite R, Moretto A, da Silva A, Lafer B, Miguel E, Nitrini R, Jacob-Filho W, Heinsen H, Pasqualucci C. Layer-specific reduced neuronal density in the orbitofrontal cortex of older adults with obsessive–compulsive disorder. Brain Structure And Function 2018, 224: 191-203. PMID: 30298291, DOI: 10.1007/s00429-018-1752-8.Peer-Reviewed Original ResearchConceptsObsessive-compulsive disorderMedial orbitofrontalOrbitofrontal cortexNeuronal densityOCD casesLower neuron densityCortical-subcortical circuitryOFC abnormalitiesEfferent targetsNeuron densityClinical evaluationAnterolateral areaControl groupCognitive impairmentAutopsy serviceOrbitofrontal regionsAnteromedialOlder adultsControl casesOFC areasCortexConsistent evidenceDisordersCellular levelTotalRole of phosphate sensing in bone and mineral metabolism
Chande S, Bergwitz C. Role of phosphate sensing in bone and mineral metabolism. Nature Reviews Endocrinology 2018, 14: 637-655. PMID: 30218014, PMCID: PMC8607960, DOI: 10.1038/s41574-018-0076-3.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsPi transportersSignal transductionPi homeostasisCellular phosphate homeostasisPhosphate homeostasisExpression of Pi transportersPi-sensing mechanismEssential structural componentIntracellular signal transductionPi transportMulticellular organismsInositol pyrophosphatesIntracellular Pi levelsDomain proteinsRegulation of FGF23 expressionPlasma membranePhosphate sensingDisorders of phosphate homeostasisCell metabolismExtracellular matrixCellular levelHomeostasisTransductionGenetic disordersOrganisms
2017
Adding dimension to cellular mechanotransduction: Advances in biomedical engineering of multiaxial cell-stretch systems and their application to cardiovascular biomechanics and mechano-signaling
Friedrich O, Schneidereit D, Nikolaev Y, Nikolova-Krstevski V, Schürmann S, Wirth-Hücking A, Merten A, Fatkin D, Martinac B. Adding dimension to cellular mechanotransduction: Advances in biomedical engineering of multiaxial cell-stretch systems and their application to cardiovascular biomechanics and mechano-signaling. Progress In Biophysics And Molecular Biology 2017, 130: 170-191. PMID: 28647645, DOI: 10.1016/j.pbiomolbio.2017.06.011.Peer-Reviewed Original ResearchConceptsFocal adhesion complexesCell-substrate junctionLive-cell imagingMechanosensitive ion channelsDirect mechanistic studiesAdhesion complexesCellular mechanotransductionMembrane junctionsIntracellular signalingMechanotransduction researchCellular stretchCellular modelIon channelsCellular levelCell membraneMechanotransductionIndividual cardiomyocytesBiomedical engineeringMechanical wall stressMembraneMechanistic studiesCellsStretch deviceCardiomyocytesElastomeric membraneDomain-Targeted Metabolomics Delineates the Heterocycle Assembly Steps of Colibactin Biosynthesis
Trautman EP, Healy AR, Shine EE, Herzon SB, Crawford JM. Domain-Targeted Metabolomics Delineates the Heterocycle Assembly Steps of Colibactin Biosynthesis. Journal Of The American Chemical Society 2017, 139: 4195-4201. PMID: 28240912, PMCID: PMC5831107, DOI: 10.1021/jacs.7b00659.Peer-Reviewed Original ResearchConceptsNonribosomal peptide synthetasesPolyketide synthasesModular polyketide synthasesSite-directed mutagenesisCombination of genesCellular metabolic levelsColibactin biosynthesisMultidomain proteinsProtein domainsPeptide synthetasesCatalytic domainControl pathwaysProtein biochemicalPathway analysisCertain Escherichia coliComplete deletionHybrid pathwayEscherichia coliFunctional readoutBiosynthesisCatalytic mechanismCellular levelMetabolic levelPathwayGenesBlockade of Rho-associated protein kinase (ROCK) inhibits the contractility and invasion potential of cancer stem like cells
Srinivasan S, Ashok V, Mohanty S, Das A, Das S, Kumar S, Sen S, Purwar R. Blockade of Rho-associated protein kinase (ROCK) inhibits the contractility and invasion potential of cancer stem like cells. Oncotarget 2017, 5: 21418-21428. PMID: 28199964, PMCID: PMC5400594, DOI: 10.18632/oncotarget.15248.Peer-Reviewed Original ResearchConceptsCancer stem like cellsRho-Associated Protein KinaseProtein kinaseInvasive potentialCancer metastasisCell invasive potentialBreast cancer cell linesCancer cell linesTreatment of cancer metastasisNon-CSCsCollagen degradation assayPrevention of cancer metastasisCell contractilityRegulating invasionCell invasionMolecular mechanismsDe-adhesionDegradation assayCell linesROCK pathwayCellular levelKinaseCellsPharmacological targetsDegradation capacityCellular levels of Grb2 and cytoskeleton stability are correlated in a neurodegenerative scenario
Majumder P, Roy K, Singh BK, Jana NR, Mukhopadhyay D. Cellular levels of Grb2 and cytoskeleton stability are correlated in a neurodegenerative scenario. Disease Models & Mechanisms 2017, 10: 655-669. PMID: 28360125, PMCID: PMC5451165, DOI: 10.1242/dmm.027748.Peer-Reviewed Original ResearchConceptsAD-like conditionsDisease manifestCytoskeletal architecturePak1 proteinCytoskeleton stabilityAD mouse brainCytoskeletal proteinsGrb2 overexpressionGrb2Β-amyloid oligomersPotential new strategyCellular levelNeuronal lossAD patientsPreventive roleCytoskeletonProteinMouse brainBrain tissueExtracellular accumulationPotent inducerMolecular featuresUnique roleDomain levelCytoskeletal
2016
Glutamate Counteracts Dopamine/PKA Signaling via Dephosphorylation of DARPP-32 Ser-97 and Alteration of Its Cytonuclear Distribution
Nishi A, Matamales M, Musante V, Valjent E, Kuroiwa M, Kitahara Y, Rebholz H, Greengard P, Girault JA, Nairn AC. Glutamate Counteracts Dopamine/PKA Signaling via Dephosphorylation of DARPP-32 Ser-97 and Alteration of Its Cytonuclear Distribution. Journal Of Biological Chemistry 2016, 292: 1462-1476. PMID: 27998980, PMCID: PMC5270488, DOI: 10.1074/jbc.m116.752402.Peer-Reviewed Original ResearchConceptsProtein phosphatase 1Ser-97PKA signalingDARPP-32Thr-34Activation of PP2A.Multiple cellular levelsProtein DARPP-32Phosphatase 1Heterotrimer complexPKA actionPhosphorylation stateNuclear localizationThr-75Phosphatase assaysDephosphorylationDARPP-32 phosphorylationCultured striatal neuronsSer-130Cellular levelSignalingPhosphorylationMajor siteStriatal neuronsGlutamateKidney Tubular Ablation of Ocrl/Inpp5b Phenocopies Lowe Syndrome Tubulopathy
Inoue K, Balkin DM, Liu L, Nandez R, Wu Y, Tian X, Wang T, Nussbaum R, De Camilli P, Ishibe S. Kidney Tubular Ablation of Ocrl/Inpp5b Phenocopies Lowe Syndrome Tubulopathy. Journal Of The American Society Of Nephrology 2016, 28: 1399-1407. PMID: 27895154, PMCID: PMC5407733, DOI: 10.1681/asn.2016080913.Peer-Reviewed Original ResearchConceptsEarly embryonic lethalityTransporter 5Dent's diseaseIndependent endocytosisEmbryonic lethalityRedundant functionsType 2 inositolHuman phenotypesProximal tubule endocytosisOculocerebrorenal syndromeGenetic ablationCellular levelGermline knockoutLowe syndromeEndocytosisMouse backgroundMice resultsMutationsInositolLow molecular weight proteinuriaINPP5BParalogsProximal tubule functionDramatic effectOCRL
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