2025
Decoding human brain evolution: Insights from genomics
Liu Y, Li M, Segal A, Zhang M, Sestan N. Decoding human brain evolution: Insights from genomics. Current Opinion In Neurobiology 2025, 92: 103033. PMID: 40334295, DOI: 10.1016/j.conb.2025.103033.Peer-Reviewed Original ResearchConceptsHuman brain evolutionNonhuman primatesBrain evolutionHigh-throughput functional screeningSingle-cell resolutionAdvanced cognitive abilitiesGenetic basisCognitive abilitiesFunctional screeningGenetic changesGenetic underpinningsBrain featuresLiving relativesHuman-specific featuresComprehensive atlasGenomic profilingHuman brainFunctional specializationMolecular levelA genetically informed brain atlas for enhancing brain imaging genomics
Bao J, Wen J, Chang C, Mu S, Chen J, Shivakumar M, Cui Y, Erus G, Yang Z, Yang S, Wen Z, Zhao Y, Kim D, Duong-Tran D, Saykin A, Zhao B, Davatzikos C, Long Q, Shen L. A genetically informed brain atlas for enhancing brain imaging genomics. Nature Communications 2025, 16: 3524. PMID: 40229250, PMCID: PMC11997130, DOI: 10.1038/s41467-025-57636-6.Peer-Reviewed Original ResearchConceptsBrain imaging genomicsImaging genomicsComplex traits/diseasesSNP heritabilityFunctional annotationGenetic architecturePolygenic risk scoresGenomic investigationsGenetic ancestryDiscovery powerBrain atlasesHuman brain structureGenetic determinantsNeuroanatomical heterogeneityGenomeNeuroanatomical variationImaging endophenotypesBrain structuresMolecular levelBrain voxelsHeritabilityPhenotypic correlationsGiant regionGeneticsBrain conditions
2024
Proteolethargy is a pathogenic mechanism in chronic disease
Dall'Agnese A, Zheng M, Moreno S, Platt J, Hoang A, Kannan D, Dall'Agnese G, Overholt K, Sagi I, Hannett N, Erb H, Corradin O, Chakraborty A, Lee T, Young R. Proteolethargy is a pathogenic mechanism in chronic disease. Cell 2024, 188: 207-221.e30. PMID: 39610243, PMCID: PMC11724756, DOI: 10.1016/j.cell.2024.10.051.Peer-Reviewed Original ResearchPathogenic signalsExcessive reactive oxygen speciesMobility phenotypeCellular functionsAffected proteinsPathogenic mechanismsReactive oxygen speciesCysteine residuesSpectra of proteinsProtein mobilityPathogenic stimuliPathogenic featuresOxygen speciesMolecular levelCellular mechanismsDiverse chronic diseasesProteinChronic diseasesLysosomal TMEM106B interacts with galactosylceramidase to regulate myelin lipid metabolism
Takahashi H, Perez-Canamas A, Lee C, Ye H, Han X, Strittmatter S. Lysosomal TMEM106B interacts with galactosylceramidase to regulate myelin lipid metabolism. Communications Biology 2024, 7: 1088. PMID: 39237682, PMCID: PMC11377756, DOI: 10.1038/s42003-024-06810-5.Peer-Reviewed Original ResearchConceptsMyelin lipid metabolismCo-immunoprecipitation assaysSulfated derivative sulfatideLipid metabolismAssociated with multiple neurological disordersCo-ImmunoprecipitationTMEM106BTransmembrane proteinsAmyloid fibrilsTMEM106B deficiencyHypomyelinating leukodystrophyAlzheimer's diseasePhysiological functionsFrontotemporal dementiaMolecular levelNeurodegenerative brainGalactosylceramidaseLipidomic analysisMultiple neurological disordersMetabolismMyelin lipidsDecreased levelsEndolysosomesAmyloidGalactosylceramidase activityPolyMatch: Novel Libraries, Algorithms, and Visualizations for Discovering Polymers and Chemical Series
Koelmel J, Stelben P, Oranzi N, Kummer M, Godri D, Qi J, Rennie E, Lin E, Weil D, Pollitt K. PolyMatch: Novel Libraries, Algorithms, and Visualizations for Discovering Polymers and Chemical Series. Journal Of The American Society For Mass Spectrometry 2024, 35: 413-420. PMID: 38301121, DOI: 10.1021/jasms.3c00313.Peer-Reviewed Original ResearchAccurate mass matchingChemical moietiesQ-TOF instrumentMS/MS libraryPolymer databaseSeries polymersEsterified speciesLC-HRMS/MSHomologous seriesMass matchingFunctional groupsRepeat unitsAdvancement of materials sciencePolyethylene glycolContaining fragmentsMaterials scienceMoietyDegree of unsaturationPolymerPhysicochemical propertiesChemical speciesFragment coverageHTML linksIterative exclusionMolecular level
2023
Chemical labeling and proteomics for characterization of unannotated small and alternative open reading frame-encoded polypeptides
Chen Y, Cao X, Loh K, Slavoff S. Chemical labeling and proteomics for characterization of unannotated small and alternative open reading frame-encoded polypeptides. Biochemical Society Transactions 2023, 51: 1071-1082. PMID: 37171061, PMCID: PMC10317152, DOI: 10.1042/bst20221074.Peer-Reviewed Original ResearchConceptsChemical labelingAlternative open reading framesOpen reading frameLimited sequence homologyMammalian genomesGene classesProtein domainsQuantitative proteomicsReading frameSequence homologyBiological roleProteomic discoveryMolecular levelSmORFsCell proliferationProteomicsInteractomeGenomeSpecific propertiesExperimental techniquesLabelingHomologyPolypeptideProteinFunctionalization
2022
Restricting α-synuclein transport into mitochondria by inhibition of α-synuclein–VDAC complexation as a potential therapeutic target for Parkinson’s disease treatment
Rajendran M, Queralt-Martín M, Gurnev P, Rosencrans W, Rovini A, Jacobs D, Abrantes K, Hoogerheide D, Bezrukov S, Rostovtseva T. Restricting α-synuclein transport into mitochondria by inhibition of α-synuclein–VDAC complexation as a potential therapeutic target for Parkinson’s disease treatment. Cellular And Molecular Life Sciences 2022, 79: 368. PMID: 35718804, PMCID: PMC11072225, DOI: 10.1007/s00018-022-04389-w.Peer-Reviewed Original ResearchConceptsVoltage-dependent anion channelVDAC poreProtein-membrane bindingRegulating mitochondrial functionProximity ligation assayInvolvement of alpha-synucleinMembrane bindingMitochondrial respirationMitochondrial functionHeLa cellsLigation assayLipid membranesHexokinase 2MitochondriaTranslocation processComplex inhibitionAnion channelFluorescence correlation spectroscopyAlpha-synucleinMolecular levelMitochondrial toxicityASynTranslocationPeptide therapeuticsTherapeutic targetAn actionable annotation scoring framework for gas chromatography-high-resolution mass spectrometry
Koelmel J, Xie H, Price E, Lin E, Manz K, Stelben P, Paige M, Papazian S, Okeme J, Jones D, Barupal D, Bowden J, Rostkowski P, Pennell K, Nikiforov V, Wang T, Hu X, Lai Y, Miller G, Walker D, Martin J, Pollitt K. An actionable annotation scoring framework for gas chromatography-high-resolution mass spectrometry. Exposome 2022, 2: osac007. PMID: 36483216, PMCID: PMC9719826, DOI: 10.1093/exposome/osac007.Peer-Reviewed Original ResearchGas chromatography-high resolution mass spectrometryMass spectrometryHigh-resolution mass spectrometryPositive chemical ionizationResolution mass spectrometryChemical ionizationChemical dataElectron ionizationGC-HRMSMolecular ionsAccurate massNegative ionizationExposomics studiesChemical identificationCompound annotationChemical annotationRetention indicesIsotopic patternsSpectrometryIonizationRetention timeMolecular levelConfident annotationComprehensive characterizationCorresponding biological responsesPersonalized medicine and disorders of consciousness
Fins J. Personalized medicine and disorders of consciousness. 2022, 131-140. DOI: 10.1093/oso/9780198863465.003.0010.Peer-Reviewed Original ResearchPersonalized medicineNext-generation personalized medicineDisorders of consciousnessDevelopment of therapeuticsDomain of personalized medicineAccurate diagnostic classificationPathological phenotypesUnique biologyTherapeutic responseMolecular levelIndividual diseasesGuiding treatmentCare of patientsPersonalized therapySide effectsTherapeutic effectMinimally conscious stateBiological characteristicsMolecular biomarkersBiologyDiseaseCharacterize diseaseNeural circuitryPatientsDiagnostic classificationAssessing the External Exposome Using Wearable Passive Samplers and High-Resolution Mass Spectrometry among South African Children Participating in the VHEMBE Study
Koelmel JP, Lin EZ, DeLay K, Williams AJ, Zhou Y, Bornman R, Obida M, Chevrier J, Pollitt K. Assessing the External Exposome Using Wearable Passive Samplers and High-Resolution Mass Spectrometry among South African Children Participating in the VHEMBE Study. Environmental Science And Technology 2022, 56: 2191-2203. PMID: 35089017, DOI: 10.1021/acs.est.1c06481.Peer-Reviewed Original ResearchConceptsHigh-resolution mass spectrometryMass spectrometryAirborne chemical exposuresPassive samplersVenda Health ExaminationChemical exposureChildren's personal exposureSpectrometryPersonal exposureChemicalsMolecular levelSouth African childrenMiddle-income countriesHealth examinationExternal exposomeCombustion productsAfrican childrenAirborne chemicalsHealth effectsEnvironmental exposuresDyeAssessment periodPlasticizerExposureDichlorodiphenyldichloroethane
2021
Enhanced specificity mutations perturb allosteric signaling in CRISPR-Cas9
Nierzwicki L, East K, Morzan U, Arantes P, Batista V, Lisi G, Palermo G. Enhanced specificity mutations perturb allosteric signaling in CRISPR-Cas9. ELife 2021, 10: e73601. PMID: 34908530, PMCID: PMC8741213, DOI: 10.7554/elife.73601.Peer-Reviewed Original ResearchConceptsHNH domainAllosteric communicationCatalytic HNH domainDNA recognition regionSpecificity-enhancing mutationsGenome editing capabilitiesAllosteric signalingAllosteric signalMutations perturbAllosteric hotspotsSpecificity enhancementCas9 endonucleaseMutational studiesDNA recognitionAllosteric connectivityAllosteric roleMolecular toolsAllosteric structureRecognition regionMolecular levelBiochemical studiesDNA cleavageSolution NMRMutationsCatalytic siteComputational 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 glycoproteinEvaluation of high salinity tolerance in Pongamia pinnata (L.) Pierre by a systematic analysis of hormone‐metabolic network
Marriboina S, Sharma K, Sengupta D, Yadavalli AD, Sharma RP, Attipalli R. Evaluation of high salinity tolerance in Pongamia pinnata (L.) Pierre by a systematic analysis of hormone‐metabolic network. Physiologia Plantarum 2021, 173: 1514-1534. PMID: 34165187, DOI: 10.1111/ppl.13486.Peer-Reviewed Original ResearchConceptsSalt-treated plantsCarbon exchange rateSalt stressSalinity toleranceJasmonic acid levelsSalt stress conditionsRelative water contentHigh salinity toleranceExpression of genesGene expression analysisPongamia pinnata (L.) PierreBiofuel treeSalinity stressPlant productivitySodium sequestrationExpression analysisZeatin contentProton exchangersDismutase geneStress conditionsMolecular levelSaline environmentsMetabolic adaptationLeavesGenes
2020
Vitamin B12 and folic acid alleviate symptoms of nutritional deficiency by antagonizing aryl hydrocarbon receptor
Kim DJ, Venkataraman A, Jain PC, Wiesler EP, DeBlasio M, Klein J, Tu SS, Lee S, Medzhitov R, Iwasaki A. Vitamin B12 and folic acid alleviate symptoms of nutritional deficiency by antagonizing aryl hydrocarbon receptor. Proceedings Of The National Academy Of Sciences Of The United States Of America 2020, 117: 15837-15845. PMID: 32571957, PMCID: PMC7355044, DOI: 10.1073/pnas.2006949117.Peer-Reviewed Original ResearchConceptsAryl hydrocarbon receptorMethylation of DNAHuman cancer samplesHydrocarbon receptorAhR transcriptional activityAhR target genesFA deficiencyOne-carbon cycleAhR agonistsFolic acid functionAhR nuclear localizationLower transcriptionNuclear localizationTarget genesGene inductionHigher transcriptionTranscriptional activityXRE bindingDe novo generationCycle proteinsBirth defectsErythroid progenitorsFas functionMolecular levelFA uptakeDifferences in self-association between kindlin-2 and kindlin-3 are associated with differential integrin binding
Kadry YA, Maisuria EM, Huet-Calderwood C, Calderwood DA. Differences in self-association between kindlin-2 and kindlin-3 are associated with differential integrin binding. Journal Of Biological Chemistry 2020, 295: 11161-11173. PMID: 32546480, PMCID: PMC7415974, DOI: 10.1074/jbc.ra120.013618.Peer-Reviewed Original ResearchConceptsKindlin-3Kindlin-2Focal adhesionsIntegrin cytoplasmic domainTransmembrane adhesion receptorsComparative sequence analysisLive-cell imagingAbility of cellsCytoplasmic domainF3 subdomainsMammalian cellsCytoplasmic componentsExtracellular environmentAdhesion receptorsKindlinSequence analysisIntegrin familySelf-associationIntegrin bindingPhysiological importanceMolecular levelPoint mutationsProteinCellsAdhesionEnvironmental lipidomics: understanding the response of organisms and ecosystems to a changing world
Koelmel JP, Napolitano MP, Ulmer CZ, Vasiliou V, Garrett TJ, Yost RA, Prasad MNV, Godri Pollitt KJ, Bowden JA. Environmental lipidomics: understanding the response of organisms and ecosystems to a changing world. Metabolomics 2020, 16: 56. PMID: 32307636, DOI: 10.1007/s11306-020-01665-3.Peer-Reviewed Original ResearchConceptsNutrient cyclesEnvironmental stressorsDiverse biological rolesEnvironmental changesResponse of organismsEssential biological functionsHistorical environmental changesAnthropogenic induced changesClass of moleculesMillions of yearsLipidomics applicationsClimate changeBiological functionsMechanisms of toxicityBiological roleEcosystem responsesChemical environmentDirect targetPersistent compoundsCertain lipidsMolecular levelOrganismsGlobal climate changeMembrane fluidityMost toxinsDesigning for a green chemistry future
Zimmerman JB, Anastas PT, Erythropel HC, Leitner W. Designing for a green chemistry future. Science 2020, 367: 397-400. PMID: 31974246, DOI: 10.1126/science.aay3060.Peer-Reviewed Original Research
2019
Making Engineered 3D DNA Crystals Robust
Li Z, Liu L, Zheng M, Zhao J, Seeman N, Mao C. Making Engineered 3D DNA Crystals Robust. Journal Of The American Chemical Society 2019, 141: 15850-15855. PMID: 31553173, DOI: 10.1021/jacs.9b06613.Peer-Reviewed Original ResearchConceptsDNA crystalsDNA nanotechnologyMacroscopic devicesCovalent bondsProtein entrapmentSticky endsCrystal stabilityCrystal shellsCrystal contactsNew opportunitiesComplex architectureCrystalsMolecular levelNanotechnologyFabricationBiocatalysisApplicationsKey obstacleBondsDevicesScaffoldsShellArchitectureMatryoshka dollsStabilityBiocatalytic Reversal of Advanced Glycation End Product Modification
Kim NY, Goddard TN, Sohn S, Spiegel DA, Crawford J. Biocatalytic Reversal of Advanced Glycation End Product Modification. ChemBioChem 2019, 20: 2402-2410. PMID: 31013547, PMCID: PMC6768434, DOI: 10.1002/cbic.201900158.Peer-Reviewed Original ResearchConceptsImproved catalytic propertiesCondensation of sugarsLysine structureStructural homology analysisCatalytic propertiesSite-directed mutagenesisLead catalystFree amino acid formAcid formEnzyme variantsMaillard reactionHomology analysisCausal agentAuthentic ligandMolecular levelAdvanced glycation end product modificationAmino acid formMnmCLack of toolsAdvanced glycation end productsCatalystPeptidomimeticsLigandsVariantsMoleculesThe mucin-selective protease StcE enables molecular and functional analysis of human cancer-associated mucins
Malaker SA, Pedram K, Ferracane MJ, Bensing BA, Krishnan V, Pett C, Yu J, Woods EC, Kramer JR, Westerlind U, Dorigo O, Bertozzi CR. The mucin-selective protease StcE enables molecular and functional analysis of human cancer-associated mucins. Proceedings Of The National Academy Of Sciences Of The United States Of America 2019, 116: 7278-7287. PMID: 30910957, PMCID: PMC6462054, DOI: 10.1073/pnas.1813020116.Peer-Reviewed Original ResearchConceptsModular protein domainsProtein domainsSecreted proteinsMucin domainFunctional analysisHuman diseasesMucin biologyGlycosylation patternsCultured cellsMolecular levelCell surfaceSequence coverageKey playersBacterial proteasesCancer-associated mucinsDiscrete peptidesBiological ligandsProteaseHuman mucinsGlycoform analysisStcESiglec-9Domain structureMass spectrometryDomain
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