2025
Modulation of the thiol redox proteome by sugarcane ash-derived silica nanoparticles: insights into chronic kidney disease of unknown etiology
Stem A, Michel C, Harris P, Rogers K, Gibb M, Roncal-Jimenez C, Reisdorph R, Johnson R, Roede J, Fritz K, Brown J. Modulation of the thiol redox proteome by sugarcane ash-derived silica nanoparticles: insights into chronic kidney disease of unknown etiology. Particle And Fibre Toxicology 2025, 22: 3. PMID: 39910563, PMCID: PMC11800628, DOI: 10.1186/s12989-025-00619-8.Peer-Reviewed Original ResearchMeSH KeywordsBasic Helix-Loop-Helix Transcription FactorsCell LineChronic Kidney Diseases of Uncertain EtiologyHumansKidney Tubules, ProximalNanoparticlesOccupational ExposureOxidation-ReductionOxidative StressProteomeProteomicsReactive Oxygen SpeciesReceptors, Aryl HydrocarbonRenal Insufficiency, ChronicSaccharumSilicon DioxideSulfhydryl CompoundsConceptsProximal convoluted tubulesActivation of aryl hydrocarbon receptorExposure to silica nanoparticlesDisease of unknown etiologyReactive oxygen speciesKidney proximal convoluted tubuleIncreased reactive oxygen species generationChronic kidney diseaseSignaling pathwayIntroductionChronic kidney diseaseHK-2 cellsReactive oxygen species generationProfile in vitroPotential mechanisms of toxicityMembrane hyperpolarizationCKD progressionUnknown etiologyGeneration of reactive oxygen speciesMitochondrial membrane hyperpolarizationOxygen species generationAryl hydrocarbon receptorEnergy metabolismKidney diseaseConvoluted tubulesMechanisms of toxicity
2024
A role for the kinetochore protein, NUF2, in ribosome biogenesis.
Brown T, Pichurin J, Parrado C, Kabeche L, Baserga S. A role for the kinetochore protein, NUF2, in ribosome biogenesis. Molecular Biology Of The Cell 2024, 36: ar16. PMID: 39705402, PMCID: PMC11809303, DOI: 10.1091/mbc.e24-08-0337.Peer-Reviewed Original ResearchConceptsPre-rRNA transcriptionNucleolar stress pathwayRibosome biogenesisPre-rRNASiRNA depletionSubunit of RNA polymerase IGenome-wide siRNA screenMCF10A human breast epithelial cellsRNA polymerase IHuman breast epithelial cellsBreast epithelial cellsKinetochore proteinsMitotic kinetochoresEukaryotic cellsPolymerase ISiRNA screenProtein partnersNUF2Sub-complexCell-based assaysProtein componentsRibosomeStress pathwaysTranscriptionProteinAn integrative TAD catalog in lymphoblastoid cell lines discloses the functional impact of deletions and insertions in human genomes.
Li C, Bonder M, Syed S, Jensen M, Gerstein M, Zody M, Chaisson M, Talkowski M, Marschall T, Korbel J, Eichler E, Lee C, Shi X. An integrative TAD catalog in lymphoblastoid cell lines discloses the functional impact of deletions and insertions in human genomes. Genome Research 2024, 34: 2304-2318. PMID: 39638559, PMCID: PMC11694747, DOI: 10.1101/gr.279419.124.Peer-Reviewed Original ResearchMeSH KeywordsCell LineChromatinGene Expression RegulationGenome, HumanHumansMutagenesis, InsertionalConceptsTopologically associating domainsTopologically associating domains boundariesImpact of structural variantsLymphoblastoid cell linesStructural variantsHuman genomeGene regulationAdjacent TADsHuman lymphoblastoid cell linesCell linesSub-TADGenomic structureInsulate genesChromatin architectureImpact of deletionChromatin structureGenomeAberrant regulationAnalysis pipelineMammalian speciesGenesCCREsFunctional impactChromatinRegulationExpression of Random Sequences and de novo Evolved Genes From the Mouse in Human Cells Reveals Functional Diversity and Specificity
Aldrovandi S, Castro J, Ullrich K, Karger A, Luria V, Tautz D. Expression of Random Sequences and de novo Evolved Genes From the Mouse in Human Cells Reveals Functional Diversity and Specificity. Genome Biology And Evolution 2024, 16: evae175. PMID: 39663928, PMCID: PMC11635099, DOI: 10.1093/gbe/evae175.Peer-Reviewed Original ResearchConceptsOpen reading frameGene open reading frameCellular regulatory pathwaysNoncoding DNAReading frameHuman cell linesHuman genomeAlpha-helicesGrowth experimentsCellular physiologyFunctional diversityPositive selectionBeta-sheetTranscriptomic responseRegulatory pathwaysAdaptive advantageHuman cellsGenesCell clonesCell linesSequenceClonesRandom sequencePathwayCellsMaresin-1 Ameliorates Sepsis-Induced Microglial Activation Through Modulation of the P38 MAPK Pathway
Dai M, Sun S, Dai Y, Dou X, Yang J, Chen X, Yang D, Lin Y. Maresin-1 Ameliorates Sepsis-Induced Microglial Activation Through Modulation of the P38 MAPK Pathway. Neurochemical Research 2024, 50: 26. PMID: 39565476, DOI: 10.1007/s11064-024-04280-z.Peer-Reviewed Original ResearchConceptsSepsis-induced neuroinflammationM1-type microgliaPro-inflammatory markersPhosphorylation of p38 MAPKP38 MAPK pathwayP38 MAPKDysregulated immune response to infectionMouse cecum ligationImmune response to infectionExpression of pro-inflammatory markersInhibited phosphorylation of p38 MAPKInduce neuronal degenerationMAPK pathwayPuncture (CLP)-induced sepsis modelPotential therapeutic roleP38 MAPK inhibitor SB203580Combination of SB203580Response to infectionMicroglial cell markersLife-threatening diseaseMAPK inhibitor SB203580Co-administrationCell markersCLP modelCecum ligationMachine-guided design of cell-type-targeting cis-regulatory elements
Gosai S, Castro R, Fuentes N, Butts J, Mouri K, Alasoadura M, Kales S, Nguyen T, Noche R, Rao A, Joy M, Sabeti P, Reilly S, Tewhey R. Machine-guided design of cell-type-targeting cis-regulatory elements. Nature 2024, 634: 1211-1220. PMID: 39443793, PMCID: PMC11525185, DOI: 10.1038/s41586-024-08070-z.Peer-Reviewed Original ResearchConceptsCis-regulatory elementsCell typesActivation of off-target cellsGene expressionCell type-specific expressionSynthetic cis-regulatory elementsCell-type specificityHuman genomeUnique cell typeTissue identityBiotechnological applicationsTissue specificityIn vitro validationCell linesCre activitySequenceGenesNatural sequenceDevelopmental timeExpressionCellsGenomeTested in vivoMotifOff-target cellsThe West Nile virus genome harbors essential riboregulatory elements with conserved and host-specific functional roles
Huston N, Tsao L, Brackney D, Pyle A. The West Nile virus genome harbors essential riboregulatory elements with conserved and host-specific functional roles. Proceedings Of The National Academy Of Sciences Of The United States Of America 2024, 121: e2312080121. PMID: 38985757, PMCID: PMC11260092, DOI: 10.1073/pnas.2312080121.Peer-Reviewed Original ResearchConceptsWest Nile virus genomeWest Nile virusPositive-sense RNA virusesFunctional roleArthropod cell linesRiboregulatory elementsGenome foldingFlaviviral genomeRNA genomeIncreasing global threatVirus genomeGenomeRNA virusesStructural homologyHost-dependentSecondary structureLack of effective therapeuticsFunctional validationLocked nucleic acidStructural insightsRNA drugsCell linesArthropod-borneNucleic acidsAntisense locked nucleic acidPreventing MMP23-mediated cleavage of podocyte RARRES1: a novel strategy to halt chronic kidney disease progression?
Medina Rangel P, Ishibe S. Preventing MMP23-mediated cleavage of podocyte RARRES1: a novel strategy to halt chronic kidney disease progression? Kidney International 2024, 106: 16-18. PMID: 38906649, DOI: 10.1016/j.kint.2024.05.004.Peer-Reviewed Original ResearchStrand-resolved mutagenicity of DNA damage and repair
Anderson C, Talmane L, Luft J, Connelly J, Nicholson M, Verburg J, Pich O, Campbell S, Giaisi M, Wei P, Sundaram V, Connor F, Ginno P, Sasaki T, Gilbert D, López-Bigas N, Semple C, Odom D, Aitken S, Taylor M. Strand-resolved mutagenicity of DNA damage and repair. Nature 2024, 630: 744-751. PMID: 38867042, PMCID: PMC11186772, DOI: 10.1038/s41586-024-07490-1.Peer-Reviewed Original ResearchConceptsDNA damageDNA damage-induced mutationsSingle-base resolutionCancer genome evolutionDamage-induced mutationsRepair of DNA damageNucleotide excision repairGenome evolutionMultiple distinct mutationsDNA accessibilityGenomic conditionsReplicative strandProcess genomesDNA base damageTranslesion polymerasesExcision repairDNAMutation patternsMutationsBase damageRepair efficiencyStrandsAlkyl adductsReplicationIdentity fidelityIn silico model development and optimization of in vitro lung cell population growth
Mostofinejad A, Romero D, Brinson D, Marin-Araujo A, Bazylak A, Waddell T, Haykal S, Karoubi G, Amon C. In silico model development and optimization of in vitro lung cell population growth. PLOS ONE 2024, 19: e0300902. PMID: 38748626, PMCID: PMC11095723, DOI: 10.1371/journal.pone.0300902.Peer-Reviewed Original ResearchVascular mimicry as a facilitator of melanoma brain metastasis
Provance O, Oria V, Tran T, Caulfield J, Zito C, Aguirre-Ducler A, Schalper K, Kluger H, Jilaveanu L. Vascular mimicry as a facilitator of melanoma brain metastasis. Cellular And Molecular Life Sciences 2024, 81: 188. PMID: 38635031, PMCID: PMC11026261, DOI: 10.1007/s00018-024-05217-z.Peer-Reviewed Original ResearchConceptsVascular mimicryBrain metastasesMouse model of metastatic melanomaIncreased risk of metastasisAssociated with tumor volumeMelanoma brain metastasesRisk of metastasisSurvival of miceFuture treatment regimensCell line modelsTumor suppressor pathwayMetastatic melanomaTumor volumeSolid tumorsTreatment regimensTumor typesPoor prognosisHippo tumor suppressor pathwayIncreased riskMouse modelDownstream targets YAPMelanomaMetastasisSuppressor pathwayTumorUBR5 promotes antiviral immunity by disengaging the transcriptional brake on RIG-I like receptors
Yang D, Geng T, Harrison A, Cahoon J, Xing J, Jiao B, Wang M, Cheng C, Hill R, Wang H, Vella A, Cheng G, Wang Y, Wang P. UBR5 promotes antiviral immunity by disengaging the transcriptional brake on RIG-I like receptors. Nature Communications 2024, 15: 780. PMID: 38278841, PMCID: PMC10817939, DOI: 10.1038/s41467-024-45141-1.Peer-Reviewed Original ResearchConceptsUbiquitin protein ligase E3 component N-recognin 5RIG-IImmune response to RNA virusesResponse to RNA virusesRetinoic acid-inducible gene ILysine 63-linked ubiquitinationAntiviral immune responseRNA virus infectionViral RNA sensorsKnockout cell linesInitiation of antiviral immune responsesBoost antiviral immune responseImmune responsePosttranslational regulationTranscriptional brakeGene IEpigenetic repressorsRNA virusesDe-SUMOylationRNA sensorsUbiquitinWild type littermatesIncreased viral replicationTRIM28Transcription[Methods to Increase the Efficiency of Knock-in of a Construct Encoding the HIV-1 Fusion Inhibitor, MT-C34 Peptide, into the CXCR4 Locus in the CEM/R5 T Cell Line].
Golubev D, Komkov D, Shepelev M, Mazurov D, Kruglova N. [Methods to Increase the Efficiency of Knock-in of a Construct Encoding the HIV-1 Fusion Inhibitor, MT-C34 Peptide, into the CXCR4 Locus in the CEM/R5 T Cell Line]. Молекулярная Биология 2024, 58: 575-589. PMID: 39709562, DOI: 10.31857/s0026898424040044, edn: incwav.Peer-Reviewed Original ResearchConceptsNuclear localization signalNonhomologous end joiningDNA nuclear targeting sequencesKnock-inDNA repairNonhomologous end-joining pathwayNuclear targeting sequenceCXCR4 locusDNA-dependent protein kinase inhibitorBlock DNA repairKnock-in efficiencyEffective gene therapy approachGenome editing technologyTranscription factor NF-kBLocalization signalTreat HIV infectionGene therapy approachesTarget sequenceDonor plasmidCas9 nucleaseCas9 proteinEnd joiningDNA modificationsPrimary human cellsProtein kinase inhibitors[Donor DNA Modification with Cas9 Targeting Sites Improves the Efficiency of MTC34 Knock-in into the CXCR4 Locus].
Shepelev M, Komkov D, Golubev D, Borovikova S, Mazurov D, Kruglova N. [Donor DNA Modification with Cas9 Targeting Sites Improves the Efficiency of MTC34 Knock-in into the CXCR4 Locus]. Молекулярная Биология 2024, 58: 590-600. PMID: 39709563, DOI: 10.31857/s0026898424040058, edn: incoyt.Peer-Reviewed Original ResearchConceptsCas9 target sitesDouble-strand breaksCell genomeGenetic constructsDonor DNAKnock-inDonor plasmid DNAKnock-in efficiencyGenome editing technologyInduce double-strand breaksProximal nucleotidesPAM sitesDonor plasmidDonor sequenceDNA modificationsGenomeIn vitroInduced cleavageCRISPR/Cas9 systemCas9Editing technologyDNAPlasmid DNAT cell linesTarget cell genome
2023
Fiber alignment in 3D collagen networks as a biophysical marker for cell contractility
Böhringer D, Bauer A, Moravec I, Bischof L, Kah D, Mark C, Grundy T, Görlach E, O'Neill G, Budday S, Strissel P, Strick R, Malandrino A, Gerum R, Mak M, Rausch M, Fabry B. Fiber alignment in 3D collagen networks as a biophysical marker for cell contractility. Matrix Biology 2023, 124: 39-48. PMID: 37967726, PMCID: PMC10872942, DOI: 10.1016/j.matbio.2023.11.004.Peer-Reviewed Original ResearchConceptsCellular traction forcesTraction forceHepatic stellate cellsMatrix remodelingGlioblastoma cell linesFiber orientationCell contractilityDrug screening assaysLocal fiber orientationCell forcesRho-kinaseFiber alignmentStellate cellsCell linesScreening assayFiber networkCellsPython packageMechanical propertiesForce reconstructionBiopolymer matrixRemodelingInduced deformationQualitative proxyCollagen networkExploiting a rodent cell block for intrinsic resistance to HIV-1 gene expression in human T cells
Behrens R, Rajashekar J, Bruce J, Evans E, Hansen A, Salazar-Quiroz N, Simons L, Ahlquist P, Hultquist J, Kumar P, Sherer N. Exploiting a rodent cell block for intrinsic resistance to HIV-1 gene expression in human T cells. MBio 2023, 14: e00420-23. PMID: 37676006, PMCID: PMC10653828, DOI: 10.1128/mbio.00420-23.Peer-Reviewed Original ResearchConceptsCyclin T1Species-specific differencesViral gene expressionGene expressionHost proteinsIntron-containing viral RNAsBroad-spectrum resistanceHost cell biologyCRISPR/Cas9 geneLatency reversal agentsIsogenic cell linesHuman T cellsEfficient HIV-1 transcriptionHIV-1 gene expressionCell linesViral RNA transcriptionT cellsSpecies-specific regionsCell-intrinsic defectHIV-1 virion productionHousekeeping proteinsNuclear exportRNA transcriptionCell biologyCas9 geneSugarcane ash and sugarcane ash-derived silica nanoparticles alter cellular metabolism in human proximal tubular kidney cells
Stem A, Rogers K, Roede J, Roncal-Jimenez C, Johnson R, Brown J. Sugarcane ash and sugarcane ash-derived silica nanoparticles alter cellular metabolism in human proximal tubular kidney cells. Environmental Pollution 2023, 332: 121951. PMID: 37301454, PMCID: PMC10321436, DOI: 10.1016/j.envpol.2023.121951.Peer-Reviewed Original ResearchConceptsSugarcane ashPre-harvest burningHarvesting of sugarcaneDisrupt metabolic activitiesProximal convoluted tubulesProximal tubular kidney cellsAsh exposureExposure levelsSugarcane cuttingEstimated exposure levelsOxygen consumption rateConsumption rateCKDuSugarcaneAshAgricultural communitiesChronic kidney diseaseCellular energetic pathwaysEpidemic of chronic kidney diseaseEnergetic pathwaysBurnCellular metabolismSugarcane stalksExposureHeat stressMultifocal heterotopic ossification in a man with germline variants of LIM Mineralization Protein‐1 (LMP‐1)
Sangadala S, Shore E, Xu M, Bergwitz C, Lozano‐Calderon S, Lin A, Boden S, Kaplan F. Multifocal heterotopic ossification in a man with germline variants of LIM Mineralization Protein‐1 (LMP‐1). American Journal Of Medical Genetics Part A 2023, 191: 2164-2174. PMID: 37218523, DOI: 10.1002/ajmg.a.63304.Peer-Reviewed Original ResearchConceptsLIM mineralization protein-1Bone morphogenetic protein (BMP) pathwayGermline variantsBone morphogenetic proteinRecombinant BMP-2LMP-1Gene-disease relationshipsC2C12 cellsGenetic analysisIntracellular proteinsWT proteinHeterotopic ossificationProtein pathwayOsteoblast markersWT cellsBMP-2Protein 1Coding variantsGene-diseaseProtein levelsControl cellsPathogenic variantsLMP-1 variantsCo-transfectionMC3T3 cellsCell-free fetal DNA impairs trophoblast migration in a TLR9-dependent manner and can be reversed by hydroxychloroquine
León-Martínez D, Lynn T, Abrahams V. Cell-free fetal DNA impairs trophoblast migration in a TLR9-dependent manner and can be reversed by hydroxychloroquine. Journal Of Reproductive Immunology 2023, 157: 103945. PMID: 37062109, DOI: 10.1016/j.jri.2023.103945.Peer-Reviewed Original ResearchConceptsToll-like receptor 9Aspirin-triggered lipoxinsODN 2216Pathogenesis of preeclampsiaTLR9-dependent mannerNovel therapeutic approachesTrophoblast cell modelReceptor 9CpG oligodeoxynucleotideTLR9 inhibitorPlacental functionTherapeutic approachesCell-free fetal DNACpG motifsTherapeutic agentsHCQPreeclampsiaHydroxychloroquineFetal DNACell viabilityCffDNAMolecular underpinningsCell modelInhibitionASAModeling 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 infectionImportComplexes
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