2023
Dysregulation of alternative splicing in spinocerebellar ataxia type 1
Olmos V, Thompson E, Gogia N, Luttik K, Veeranki V, Ni L, Sim S, Chen K, Krause D, Lim J. Dysregulation of alternative splicing in spinocerebellar ataxia type 1. Human Molecular Genetics 2023, 33: 138-149. PMID: 37802886, PMCID: PMC10979408, DOI: 10.1093/hmg/ddad170.Peer-Reviewed Original ResearchConceptsAlternative splicing eventsSpinocerebellar ataxia type 1Splicing eventsAtaxin-1Ataxia type 1Mutant ataxin-1Alternative splicingGene expressionMisregulated alternative splicingCell-autonomous mannerDifferential gene expressionNew biological pathwaysMolecular mechanistic insightsDrosophila modelGenetic manipulationBulk RNABiological pathwaysPolyglutamine tractNeurodegenerative phenotypeAutonomous mannerMechanistic insightsSplicingPotential therapeutic strategyMouse cerebellumExpressionModeling HIV-1 nuclear entry with nucleoporin-gated DNA-origami channels
Shen Q, Feng Q, Wu C, Xiong Q, Tian T, Yuan S, Shi J, Bedwell G, Yang R, Aiken C, Engelman A, Lusk C, Lin C, Xiong Y. Modeling HIV-1 nuclear entry with nucleoporin-gated DNA-origami channels. Nature Structural & Molecular Biology 2023, 30: 425-435. PMID: 36807645, PMCID: PMC10121901, DOI: 10.1038/s41594-023-00925-9.Peer-Reviewed Original ResearchConceptsNuclear pore complexHIV-1 nuclear entryNuclear entryNuclear importNPC central channelPore complexHost nucleusCapsid dockingVirus genomeAffinity gradientNup153Central channelMechanistic insightsMolecular interactionsCapsidNucleoporinsNup358Nup62GenomeNucleusVirusDockingVirus-1 infectionImportComplexesCXCL8/CXCR2 signaling mediates bone marrow fibrosis and is a therapeutic target in myelofibrosis
Dunbar A, Kim D, Lu M, Farina M, Bowman R, Yang J, Park Y, Karzai A, Xiao W, Zaroogian Z, O’Connor K, Mowla S, Gobbo F, Verachi P, Martelli F, Sarli G, Xia L, Elmansy N, Kleppe M, Chen Z, Xiao Y, McGovern E, Snyder J, Krishnan A, Hill C, Cordner K, Zouak A, Salama M, Yohai J, Tucker E, Chen J, Zhou J, McConnell T, Migliaccio A, Koche R, Rampal R, Fan R, Levine R, Hoffman R. CXCL8/CXCR2 signaling mediates bone marrow fibrosis and is a therapeutic target in myelofibrosis. Blood 2023, 141: 2508-2519. PMID: 36800567, PMCID: PMC10273167, DOI: 10.1182/blood.2022015418.Peer-Reviewed Original ResearchConceptsConstitutive JAK/STATHematopoietic stem/progenitor cellsJAK/STATBone marrow fibrosisStem/progenitor cellsMPN cellsMarrow fibrosisHuman cancersMyeloproliferative neoplasmsPrimary cellsProgenitor cellsMechanistic insightsPharmacologic inhibitionGenetic deletionSignaling contributesGene signatureJAK inhibitor therapyTherapeutic targetingEnhanced proliferationCritical roleTherapeutic targetCXCL8/MF developmentMF pathogenesisInhibitor therapy
2022
Is it the time to integrate novel sequencing technologies into clinical practice?
VanOudenhove J, Halene S, Mendez L. Is it the time to integrate novel sequencing technologies into clinical practice? Current Opinion In Hematology 2022, 30: 70-77. PMID: 36602939, DOI: 10.1097/moh.0000000000000754.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsNovel sequencing technologiesSequencing technologiesUnprecedented biological insightsNext-generation sequencing techniquesDNA sequencing technologiesHigh-throughput NGSRare cell populationsBiological insightsMultiomics approachSequencing techniquesGenotype-phenotype correlationClonal diversityCellular resolutionMechanistic insightsCell populationsPhenotype correlationMyeloid diseasesClonesClonal hierarchyClonal haematopoiesisResidual clonesInsightsSeqDiversityImproved captureElements of the ERAD ubiquitin ligase Doa10 regulating sequential poly-ubiquitylation of its targets
Mehrtash A, Hochstrasser M. Elements of the ERAD ubiquitin ligase Doa10 regulating sequential poly-ubiquitylation of its targets. IScience 2022, 25: 105351. PMID: 36325070, PMCID: PMC9619350, DOI: 10.1016/j.isci.2022.105351.Peer-Reviewed Original ResearchC-terminal elementsUbiquitin ligase Doa10RING-CH domainDoa10 substratesSubstrate ubiquitylationRetrotranslocation channelSingle ubiquitinIntragenic suppressionCofactor-binding regionPolyubiquitin chainsDoa10E3 ubiquitinER proteinsTruncation analysisStructural predictionsStructure predictionUBC6Ubc7UbiquitylationDirect roleMechanistic insightsE2 bindsUbiquitinBindsERADNeighboring mutation‐mediated enhancement of dengue virus infectivity and spread
Chen L, Zhang X, Guo X, Peng W, Zhu Y, Wang Z, Yu X, Shi H, Li Y, Zhang L, Wang L, Wang P, Cheng G. Neighboring mutation‐mediated enhancement of dengue virus infectivity and spread. EMBO Reports 2022, 23: embr202255671. PMID: 36197120, PMCID: PMC9638853, DOI: 10.15252/embr.202255671.Peer-Reviewed Original ResearchIsoform-specific inhibition of FGFR signaling achieved by a de-novo-designed mini-protein
Park JS, Choi J, Cao L, Mohanty J, Suzuki Y, Park A, Baker D, Schlessinger J, Lee S. Isoform-specific inhibition of FGFR signaling achieved by a de-novo-designed mini-protein. Cell Reports 2022, 41: 111545. PMID: 36288716, PMCID: PMC9636537, DOI: 10.1016/j.celrep.2022.111545.Peer-Reviewed Original ResearchConceptsFibroblast growth factor receptorC isoformsFibroblast growth factor ligandsLigand-binding regionSilico design strategyIsoform-specific inhibitionGrowth factor ligandsAlternative splicingCellular signalingRegulated processGrowth factor receptorDevelopment of therapeuticsFGFR isoformsFactor ligandCellular analysisFactor receptorMechanistic insightsKlotho proteinSpecific interactionsMB7Distinct subsetsHigh affinitySplicingSignalingFGFTick tock, tick tock: Mouse culture and tissue aging captured by an epigenetic clock
Minteer C, Morselli M, Meer M, Cao J, Higgins‐Chen A, Lang SM, Pellegrini M, Yan Q, Levine ME. Tick tock, tick tock: Mouse culture and tissue aging captured by an epigenetic clock. Aging Cell 2022, 21: e13553. PMID: 35104377, PMCID: PMC8844113, DOI: 10.1111/acel.13553.Peer-Reviewed Original ResearchConceptsMouse embryonic fibroblastsDNA methylationEpigenetic agingImportant chromatin regulatorsPolycomb group (PcG) factorsAnti-aging interventionsChromatin regulatorsEmbryonic fibroblastsCellular senescenceTissue agingCellular agingEpigenetic clocksMultiple tissuesMouse tissuesCaloric restrictionMechanistic insightsAging changesKidney fibroblastsReduced representationTime pointsPhysiological agingMouse culturesSuch alterationsTick-TockTissueA bidirectional competitive interaction between circHomer1 and Homer1b within the orbitofrontal cortex regulates reversal learning
Hafez A, Zimmerman A, Papageorgiou G, Chandrasekaran J, Amoah S, Lin R, Lozano E, Pierotti C, Dell'Orco M, Hartley B, Alural B, Lalonde J, Esposito J, Berretta S, Squassina A, Chillotti C, Voloudakis G, Shao Z, Fullard J, Brennand K, Turecki G, Roussos P, Perlis R, Haggarty S, Perrone-Bizzozero N, Brigman J, Mellios N. A bidirectional competitive interaction between circHomer1 and Homer1b within the orbitofrontal cortex regulates reversal learning. Cell Reports 2022, 38: 110282. PMID: 35045295, PMCID: PMC8809079, DOI: 10.1016/j.celrep.2021.110282.Peer-Reviewed Original ResearchConceptsImportance of circRNAsRNA-binding proteinSynaptic gene expressionCircular RNAsGene expressionOrbitofrontal cortexCompetitive interactionsComplete rescuePsychiatric disordersKnockdownSynaptic expressionMechanistic insightsBrain functionMRNAHomer1bBehavioral flexibilityNeuronal culturesExpressionBiogenesisCircRNAsRNAProteinRegulatesReversal learningDisorders
2021
YAP1 nuclear efflux and transcriptional reprograming follow membrane diminution upon VSV-G-induced cell fusion
Feliciano D, Ott CM, Espinosa-Medina I, Weigel AV, Benedetti L, Milano KM, Tang Z, Lee T, Kliman HJ, Guller SM, Lippincott-Schwartz J. YAP1 nuclear efflux and transcriptional reprograming follow membrane diminution upon VSV-G-induced cell fusion. Nature Communications 2021, 12: 4502. PMID: 34301937, PMCID: PMC8302681, DOI: 10.1038/s41467-021-24708-2.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingAMP-Activated Protein KinasesAnimalsBiological TransportCell FusionCell LineCell Line, TumorCell MembraneCell NucleusCells, CulturedGiant CellsHEK293 CellsHumansMembrane GlycoproteinsMiceRNA-SeqSignal TransductionTranscription FactorsTranscription, GeneticViral Envelope ProteinsYAP-Signaling ProteinsConceptsCell cycle arrestCell fusionNew cellular statesPlasma membrane surface areaRNA-seq analysisCell fusion systemTranscriptional programsNutrient stressCellular statesTranscriptional changesNuclear effluxCytoplasmic glucoseExtrinsic cuesUndifferentiated cellsGlucose transporterFused cellsMechanistic insightsMembrane surface areaNew functionsEndocytosisYAP1 inhibitionEnergetic stateSyncytiaCellsVSVSmart-RRBS for single-cell methylome and transcriptome analysis
Gu H, Raman AT, Wang X, Gaiti F, Chaligne R, Mohammad AW, Arczewska A, Smith ZD, Landau DA, Aryee MJ, Meissner A, Gnirke A. Smart-RRBS for single-cell methylome and transcriptome analysis. Nature Protocols 2021, 16: 4004-4030. PMID: 34244697, PMCID: PMC8672372, DOI: 10.1038/s41596-021-00571-9.Peer-Reviewed Original ResearchConceptsSingle cellsProtein-coding genesSingle-cell methylomesSame single cellMulti-omics approachRare cell populationsSmart-seq2Transcriptional statesDNA methylomeTranscriptome analysisImportant mechanistic insightsEpigenetic modificationsDNA methylationDissected tissue samplesGenomic DNAHundreds of cellsCellular heterogeneityFlow sortingRegulatory consequencesMethylomeEpigenetic promoterMechanistic insightsCell populationsCellsTypical single cellMethylation of dual-specificity phosphatase 4 controls cell differentiation
Su H, Jiang M, Senevirathne C, Aluri S, Zhang T, Guo H, Xavier-Ferrucio J, Jin S, Tran NT, Liu SM, Sun CW, Zhu Y, Zhao Q, Chen Y, Cable L, Shen Y, Liu J, Qu CK, Han X, Klug CA, Bhatia R, Chen Y, Nimer SD, Zheng YG, Iancu-Rubin C, Jin J, Deng H, Krause DS, Xiang J, Verma A, Luo M, Zhao X. Methylation of dual-specificity phosphatase 4 controls cell differentiation. Cell Reports 2021, 36: 109421. PMID: 34320342, PMCID: PMC9110119, DOI: 10.1016/j.celrep.2021.109421.Peer-Reviewed Original ResearchMeSH KeywordsAdultAnimalsArginineCell DifferentiationCell LineChildDual-Specificity PhosphatasesEnzyme StabilityFemaleHEK293 CellsHumansMaleMAP Kinase Signaling SystemMegakaryocytesMethylationMice, Inbred C57BLMiddle AgedMitogen-Activated Protein Kinase PhosphatasesMyelodysplastic Syndromesp38 Mitogen-Activated Protein KinasesPolyubiquitinProtein-Arginine N-MethyltransferasesProteolysisRepressor ProteinsUbiquitinationYoung AdultConceptsDual-specificity phosphataseCell differentiationSingle-cell transcriptional analysisP38 MAPKControls cell differentiationE3 ligase HUWE1Knockdown screeningMK differentiationTranscriptional analysisMegakaryocyte differentiationProtein kinaseP38 axisP38 activationPRMT1Transcriptional signatureContext of thrombocytopeniaMK cellsMechanistic insightsPharmacological inhibitionDifferentiationMethylationMAPKPhosphataseUbiquitinylationActivationIntegration of evidence across human and model organism studies: A meeting report
Palmer RHC, Johnson EC, Won H, Polimanti R, Kapoor M, Chitre A, Bogue MA, Benca‐Bachman C, Parker CC, Verma A, Reynolds T, Ernst J, Bray M, Bin Kwon S, Lai D, Quach BC, Gaddis NC, Saba L, Chen H, Hawrylycz M, Zhang S, Zhou Y, Mahaffey S, Fischer C, Sanchez‐Roige S, Bandrowski A, Lu Q, Shen L, Philip V, Gelernter J, Bierut LJ, Hancock DB, Edenberg HJ, Johnson EO, Nestler EJ, Barr PB, Prins P, Smith DJ, Akbarian S, Thorgeirsson T, Walton D, Baker E, Jacobson D, Palmer AA, Miles M, Chesler EJ, Emerson J, Agrawal A, Martone M, Williams RW. Integration of evidence across human and model organism studies: A meeting report. Genes Brain & Behavior 2021, 20: e12738. PMID: 33893716, PMCID: PMC8365690, DOI: 10.1111/gbb.12738.Peer-Reviewed Original ResearchModel organism studiesModel organismsOrganism studiesDeeper mechanistic insightsPhenotypic dataGenomic researchOmics dataHuman geneticsMechanistic insightsEpigeneticsComputational biologyDiverse groupGeneticsBiological sciencesOrganismsBiologySpeciesHumansFair Data SharingData integrationCurrent toolsNew opportunitiesFundamental gapGrappling with the tick microbiome
Narasimhan S, Swei A, Abouneameh S, Pal U, Pedra JHF, Fikrig E. Grappling with the tick microbiome. Trends In Parasitology 2021, 37: 722-733. PMID: 33962878, PMCID: PMC8282638, DOI: 10.1016/j.pt.2021.04.004.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsTick microbiomeRelated tick speciesMultiple human pathogensHost preferenceSequencing technologiesTick biologyHuman pathogensMicrobiomeMechanistic insightsTick speciesLife cycleIxodes pacificusIxodes scapularisIxodid ticksCausative agentNorth AmericaBorrelia burgdorferiPredominant vectorBiological variablesHabitatsPacificusBiologySpeciesPathogensLoss of Ftsj1 perturbs codon-specific translation efficiency in the brain and is associated with X-linked intellectual disability
Nagayoshi Y, Chujo T, Hirata S, Nakatsuka H, Chen C, Takakura M, Miyauchi K, Ikeuchi Y, Carlyle B, Kitchen R, Suzuki T, Katsuoka F, Yamamoto M, Goto Y, Tanaka M, Natsume K, Nairn A, Suzuki T, Tomizawa K, Wei F. Loss of Ftsj1 perturbs codon-specific translation efficiency in the brain and is associated with X-linked intellectual disability. Science Advances 2021, 7: eabf3072. PMID: 33771871, PMCID: PMC7997516, DOI: 10.1126/sciadv.abf3072.Peer-Reviewed Original ResearchTransfer RNAsTranslation efficiencyAberrant synaptic plasticityIntellectual disabilitySubset of genesPatient-derived cellsRibosome profilingKO miceSynaptic organizationSteady-state levelsKnockout miceMolecular pathogenesisSynaptic plasticityMemory deficitsSynaptic morphologyAnticodon regionPhe codonsBrainSlow decodingMechanistic insightsMiceFTSJ1GenesMethylationDisability(E)-N-(2-(3, 5-Dimethoxystyryl) phenyl) furan-2-carboxamide (BK3C231) induces cytoprotection in CCD18-Co human colon fibroblast cells through Nrf2/ARE pathway activation
Tan H, Thomas N, Inayat-Hussain S, Chan K. (E)-N-(2-(3, 5-Dimethoxystyryl) phenyl) furan-2-carboxamide (BK3C231) induces cytoprotection in CCD18-Co human colon fibroblast cells through Nrf2/ARE pathway activation. Scientific Reports 2021, 11: 4773. PMID: 33637843, PMCID: PMC7910600, DOI: 10.1038/s41598-021-83163-7.Peer-Reviewed Original ResearchConceptsGlutamate-cysteine ligase catalytic subunitGlutathione S-transferaseNrf2/ARE pathway activationDissociation of Nrf2New mechanistic insightsCatalytic subunitNrf2/ARE pathwayN-furanPromoter activityMolecular mechanismsResponse elementCytoprotective proteinsInhibitory proteinS-transferaseQuinone oxidoreductase 1Mitochondrial damageCytoprotective enzymesMechanistic insightsARE pathwayProtein expressionFactor 2Pathway activationNuclear factorNormal cellsFibroblast cellsCooperative function of synaptophysin and synapsin in the generation of synaptic vesicle-like clusters in non-neuronal cells
Park D, Wu Y, Lee SE, Kim G, Jeong S, Milovanovic D, De Camilli P, Chang S. Cooperative function of synaptophysin and synapsin in the generation of synaptic vesicle-like clusters in non-neuronal cells. Nature Communications 2021, 12: 263. PMID: 33431828, PMCID: PMC7801664, DOI: 10.1038/s41467-020-20462-z.Peer-Reviewed Original ResearchConceptsNon-neuronal cellsSV clustersSynaptic vesiclesSmall synaptic-like microvesiclesSV membrane proteinsSynaptic-like microvesiclesSV proteinsDiffuse cytosolic distributionMembrane proteinsReconstitution systemCytosolic distributionCooperative functionSuch vesiclesMechanistic insightsLiquid-like propertiesPowerful modelPhysiological formationProteinSynapsinVesiclesCellsSynaptic transmissionAssembly of structuresDefining featureLiquid condensate
2020
The mosquito taste system and disease control
Baik LS, Carlson JR. The mosquito taste system and disease control. Proceedings Of The National Academy Of Sciences Of The United States Of America 2020, 117: 32848-32856. PMID: 33372129, PMCID: PMC7776869, DOI: 10.1073/pnas.2013076117.Peer-Reviewed Original ResearchConceptsVectors of diseaseNew mechanistic insightsMosquito olfactionGeographical rangeVector speciesMechanistic insightsSpeciesMosquito controlAfflict hundredsDiverse groupCurrent knowledgeWealth of opportunitiesMosquitoesClimate changeTaste systemInsectsEnormous rangeHabitatsUnderstanding of tasteOrganismsEggsNew strategyOlfactionTechnological advancesUnderstandingControl of Murine Primordial Follicle Growth Activation by IκB/NFκB Signaling
Wright CJ, Cari EL, Sandoval J, Bales E, Sam PK, Zarate MA, Polotsky AJ, Kallen AN, Johnson J. Control of Murine Primordial Follicle Growth Activation by IκB/NFκB Signaling. Reproductive Sciences 2020, 27: 2063-2074. PMID: 32542534, PMCID: PMC7529825, DOI: 10.1007/s43032-020-00225-3.Peer-Reviewed Original ResearchConceptsPrimordial follicle growth activationLargest human genome-wide association studyGrowth activationHuman genome-wide association studiesGenome-wide association studiesLigand/receptor interactionsTranscription factor NFκBInhibitory protein IκBαAssociation studiesIκB proteinsWild-type controlsInhibitory proteinProtein IκBαPrimordial stageNFκB signalingMechanistic insightsReceptor interactionProteinMurine ovariesNFκB pathwayKey membersNFκBSubunit p65NFκB activationIκBβNonuniform growth and surface friction determine bacterial biofilm morphology on soft substrates
Fei C, Mao S, Yan J, Alert R, Stone H, Bassler B, Wingreen N, Košmrlj A. Nonuniform growth and surface friction determine bacterial biofilm morphology on soft substrates. Proceedings Of The National Academy Of Sciences Of The United States Of America 2020, 117: 7622-7632. PMID: 32193350, PMCID: PMC7148565, DOI: 10.1073/pnas.1919607117.Peer-Reviewed Original ResearchConceptsBiofilm matrix productionBiofilm morphologyBacterial biofilmsAvailability of nutrientsDistinct spatiotemporal patternsImportant physiological consequencesAgar substrateMatrix productionMechanistic insightsPhysiological consequencesBiofilmsSoft substratesSimilar morphologyDiffusion of nutrientsPattern formation processNutrientsBasic mechanismsAgar concentrationEukaryotesMorphological patternsMorphogenesisFundamental determinantsOrganismsGrowthVibrio
This site is protected by hCaptcha and its Privacy Policy and Terms of Service apply