2025
γ-secretase facilitates retromer-mediated retrograde transport
Takeo Y, Crite M, Mehmood K, DiMaio D. γ-secretase facilitates retromer-mediated retrograde transport. Journal Of Cell Science 2025, 138: jcs263538. PMID: 39865938, PMCID: PMC11883284, DOI: 10.1242/jcs.263538.Peer-Reviewed Original ResearchConceptsTrans-Golgi networkTransport of protein cargoRetrograde protein traffickingCation-independent mannose-6-phosphate receptorCellular transmembrane proteinsMannose-6-phosphate receptorAssociation with cargoHuman epithelial cellsBinds retromerRetromer subunitsRetromer cargoRab7-GTPShiga toxinRetrograde transportCultured human epithelial cellsProtein traffickingRetromerCatalytic subunitTransmembrane domainTransmembrane proteinsProtein cargoCellular cargoTarget proteinsFunctional consequencesCholera toxin
2024
Bending stiffness of Toxoplasma gondii actin filaments
Cao W, Sladewski T, Heaslip A, De La Cruz E. Bending stiffness of Toxoplasma gondii actin filaments. Journal Of Biological Chemistry 2024, 301: 108101. PMID: 39706262, PMCID: PMC11786770, DOI: 10.1016/j.jbc.2024.108101.Peer-Reviewed Original ResearchConceptsActin filamentsD-loopMechanical properties of actin filamentsFilament subunitsSkeletal muscle actin filamentsProperties of actin filamentsSkeletal muscle actinMuscle actin filamentsFilament length distributionApicomplexan parasite Toxoplasma gondiiIntersubunit salt bridgesOrganelle inheritancePointed-endSubunit interactionsNeighboring subunitUnique assembly propertiesSalt bridgesSubunitFunctional consequencesSubunit dissociationVisible densityActinSubunit incorporationParasite Toxoplasma gondiiFilamentsCYP2C gene polymorphisms in North African populations
Messaoudi M, Pakstis A, Boussetta S, Ben Ammar Elgaaied A, Kidd K, Cherni L. CYP2C gene polymorphisms in North African populations. Molecular Biology Reports 2024, 51: 1145. PMID: 39532754, DOI: 10.1007/s11033-024-10093-8.Peer-Reviewed Original ResearchConceptsNorth African populationsCYP2C genesHuman CYP2C genesSuperfamily of genesAfrican populationsRegulatory regionsIntronic SNPGenetic variationHaplotype frequenciesChromosome 10Pharmacogenetic markersFunctional consequencesGenesResponse to medical treatmentSNPsTunisian populationCYP2C9Drug metabolismForeign chemicalsCYP2C19North AfricansBackgroundCytochrome P450Clinically useful drugsGene polymorphismsPrincipal component analysisPrioritizing disease-related rare variants by integrating gene expression data
Guo H, Urban A, Wong H. Prioritizing disease-related rare variants by integrating gene expression data. PLOS Genetics 2024, 20: e1011412. PMID: 39348415, PMCID: PMC11466430, DOI: 10.1371/journal.pgen.1011412.Peer-Reviewed Original ResearchConceptsGene expression dataRare variantsExpression dataRare variant association methodsExcess of rare variantsImpact of rare variantsContext of human diseaseHuman genetic variationGenetic variationGene expressionComplex diseasesHuman diseasesGenesMolecular mechanismsFunctional consequencesRare variant typesAlzheimer's diseaseVariant typeVariantsAssociation methodStatistical frameworkSimulation studySample sizeOmicsAlzheimerClinical features and multiomics profiles indicate coagulation and platelet dysfunction in COVID-19 viral sepsis
Xiao Z, Lin M, Song N, Wu X, Hou J, Wang L, Tian X, An C, Dela Cruz C, Sharma L, Chang D. Clinical features and multiomics profiles indicate coagulation and platelet dysfunction in COVID-19 viral sepsis. IScience 2024, 27: 110110. PMID: 38974472, PMCID: PMC11225851, DOI: 10.1016/j.isci.2024.110110.Peer-Reviewed Original ResearchViral sepsisCausative agent of sepsisAgent of sepsisCases of sepsisSusceptibility to secondary bacterial infectionsNon-sepsis patientsSecondary bacterial infectionPlatelet activation pathwaysMetabolomic characteristicsPlatelet dysfunctionSepsis phenotypesClinical featuresSystemic disease phenotypeSepsis patientsSepsisCOVID-19 pathologyBacterial infectionsProteomic signatureDisease phenotypeComplement proteinsBacterial pathogensProteomic dataActivation pathwayFunctional consequencesPathway proteinsTTN truncation variants produce sarcomere-integrating proteins of uncertain functional significance
Hinson J, Campbell S. TTN truncation variants produce sarcomere-integrating proteins of uncertain functional significance. Journal Of Clinical Investigation 2024, 134: e175206. PMID: 38226618, PMCID: PMC10786689, DOI: 10.1172/jci175206.Peer-Reviewed Original ResearchConceptsTruncating variantsSubcellular localizationTitin truncating variantsComplex proteinsSarcomere integrityGenetic lesionsTitin proteinDilated CardiomyopathyFunctional consequencesProteinVariable penetranceSarcomeric dysfunctionImpaired cardiac contractilityTitinSarcomeric structural integrityAlternative therapeutic approachCardiac contractilityVariantsPotential mechanismsTherapeutic approachesHaploinsufficiencyDCM samples
2023
Structural basis for activation of CB1 by an endocannabinoid analog
Krishna Kumar K, Robertson M, Thadhani E, Wang H, Suomivuori C, Powers A, Ji L, Nikas S, Dror R, Inoue A, Makriyannis A, Skiniotis G, Kobilka B. Structural basis for activation of CB1 by an endocannabinoid analog. Nature Communications 2023, 14: 2672. PMID: 37160876, PMCID: PMC10169858, DOI: 10.1038/s41467-023-37864-4.Peer-Reviewed Original ResearchConceptsCannabinoid receptor 1Activation of cannabinoid receptor 1Molecular dynamics simulationsLigand-binding pocketDesigning effective drugsECB anandamideDynamics simulationsBinding pocketAllosteric modulatorsLigand interactionsEndocannabinoidFunctional consequencesLigandEndogenous ligandActivate G proteinsECBG protein-coupled receptorsSignaling ComplexMolecular detailsStructural basisAnandamideCannabinoidSignaling assaysG-proteinReceptor 1
2022
Whole exome sequencing in dense families suggests genetic pleiotropy amongst Mendelian and complex neuropsychiatric syndromes
Ganesh S, Vemula A, Bhattacharjee S, Mathew K, Ithal D, Navin K, Nadella R, Viswanath B, Sullivan P, Jain S, Purushottam M. Whole exome sequencing in dense families suggests genetic pleiotropy amongst Mendelian and complex neuropsychiatric syndromes. Scientific Reports 2022, 12: 21128. PMID: 36476812, PMCID: PMC9729597, DOI: 10.1038/s41598-022-25664-7.Peer-Reviewed Original ResearchConceptsSequence kernel association testKernel association testWhole-exome sequencing studiesExome sequencing studiesUnique genesGenetic architectureCase-control association analysisDeleterious variantsSequencing studiesWhole-exome sequencingMendelian syndromesAssociation analysisCriteria of rarityPleiotropic influenceGenesWES studyFunctional consequencesSignificant overrepresentationGenetic pleiotropyExome sequencingAffected individualsFamilyImportant insightsUnrelated controlsAssociation TestGlucocorticoids mediate transcriptome‐wide alternative polyadenylation: Potential mechanistic and clinical implications
Nguyen T, Liu D, Gao H, Ye Z, Lee J, Wei L, Yu J, Zhang L, Wang L, Ordog T, Weinshilboum R. Glucocorticoids mediate transcriptome‐wide alternative polyadenylation: Potential mechanistic and clinical implications. Clinical And Translational Science 2022, 15: 2758-2771. PMID: 36128656, PMCID: PMC9652440, DOI: 10.1111/cts.13402.Peer-Reviewed Original ResearchConceptsAlternative polyadenylationTranscriptome-wide alternative polyadenylationAssociated with multiple biological processesRegulating alternative polyadenylationGenetic regulatory mechanismsRNA-binding proteinsTranslation-related pathwaysGlucocorticoid-mediated expressionInvestigated transcriptome-wideMultiple biological processesCell type-specificHuman B lymphoblastoid cell lineTranscriptome-widePotential functional mechanismsRNA transcriptsGenetic variantsB-lymphoblastoid cell linesGene expressionRegulatory mechanismsBiological processesAntiviral inhibitorsImpact of glucocorticoidsDisease phenotypeGenesFunctional consequencesBRCA2 BRC missense variants disrupt RAD51-dependent DNA repair
Jimenez-Sainz J, Mathew J, Moore G, Lahiri S, Garbarino J, Eder JP, Rothenberg E, Jensen RB. BRCA2 BRC missense variants disrupt RAD51-dependent DNA repair. ELife 2022, 11: e79183. PMID: 36098506, PMCID: PMC9545528, DOI: 10.7554/elife.79183.Peer-Reviewed Original ResearchConceptsHomology-directed repairDNA double-strand breaksFork protectionReplication fork protectionRad51 nucleoprotein filamentsMissense mutationsSingle amino acid substitutionRad51-ssDNA complexesDouble-strand breaksUnknown functional consequencesBRCA2 VUSAmino acid substitutionsGenome stabilityNucleoprotein filamentDNA repairRepeat regionSpacer regionBRCA2 proteinBenign allelesCellular responsesAcid substitutionsFunctional consequencesFrameshift mutationGene predisposeBRC2Mating-driven variability in olfactory local interneuron wiring
Chou YH, Yang CJ, Huang HW, Liou NF, Panganiban MR, Luginbuhl D, Yin Y, Taisz I, Liang L, Jefferis GSXE, Luo L. Mating-driven variability in olfactory local interneuron wiring. Science Advances 2022, 8: eabm7723. PMID: 35179957, PMCID: PMC8856614, DOI: 10.1126/sciadv.abm7723.Peer-Reviewed Original Research
2021
Mutations of the histone linker H1–4 in neurodevelopmental disorders and functional characterization of neurons expressing C-terminus frameshift mutant H1.4
Tremblay MW, Green MV, Goldstein BM, Aldridge AI, Rosenfeld JA, Streff H, Tan WD, Craigen W, Bekheirnia N, Al Tala S, West AE, Jiang YH. Mutations of the histone linker H1–4 in neurodevelopmental disorders and functional characterization of neurons expressing C-terminus frameshift mutant H1.4. Human Molecular Genetics 2021, 31: 1430-1442. PMID: 34788807, PMCID: PMC9271223, DOI: 10.1093/hmg/ddab321.Peer-Reviewed Original ResearchConceptsC-terminusGenome-wide transcriptome analysisRahman syndromeUnderstanding of mutationsHistone H1.4Neuronal genesTranscriptome analysisAbnormal C-terminusFunctional categoriesFunctional characterizationN-terminusNeuropeptide signalingDe novo heterozygous mutationsSupport of pathogenicitySmall insertionsFunctional consequencesNovo heterozygous mutationRat hippocampal neuronsFrameshift mutationMutationsH1.4Rare genetic disorderSevere intellectual disabilityGenesClinical featuresThe genetic structure of the Turkish population reveals high levels of variation and admixture
Kars ME, Başak AN, Onat OE, Bilguvar K, Choi J, Itan Y, Çağlar C, Palvadeau R, Casanova JL, Cooper DN, Stenson PD, Yavuz A, Buluş H, Günel M, Friedman JM, Özçelik T. The genetic structure of the Turkish population reveals high levels of variation and admixture. Proceedings Of The National Academy Of Sciences Of The United States Of America 2021, 118: e2026076118. PMID: 34426522, PMCID: PMC8433500, DOI: 10.1073/pnas.2026076118.Peer-Reviewed Original ResearchConceptsGenetic structureTR populationGenome-wide association studiesRuns of homozygosityGenomes Project populationsHigh inbreeding coefficientsDisease gene discoveryHigh-quality haplotypesPotential medical relevanceGene discoveryExtensive admixturePhenotypic consequencesWhole genomeGenetic basisInbreeding coefficientSpecific genesRare rangeGenome variantsAssociation studiesGenetic relationshipsFunctional consequencesWhole exomeSpecific phenotypesGenotype imputationMedical relevancePhase separation in immune signalling
Xiao Q, McAtee CK, Su X. Phase separation in immune signalling. Nature Reviews Immunology 2021, 22: 188-199. PMID: 34230650, PMCID: PMC9674404, DOI: 10.1038/s41577-021-00572-5.Peer-Reviewed Original ResearchConceptsGene I proteinImmune signaling pathwaysCyclic GMP-AMP synthaseSubstantial conformational changesNew biophysical principleGMP-AMP synthaseCell receptorB cell receptorCytosolic eventsSignal transductionImmune signalingSignaling pathwaysI proteinConformational changesLigand engagementDownstream adaptorsInterferon genesImmune receptorsBiophysical principlesLiquid-liquid phase separationFunctional consequencesT cell receptorPathogenic stimuliSpatial reorganizationOutstanding questionsNon-Genetic Diversity in Chemosensing and Chemotactic Behavior
Moore JP, Kamino K, Emonet T. Non-Genetic Diversity in Chemosensing and Chemotactic Behavior. International Journal Of Molecular Sciences 2021, 22: 6960. PMID: 34203411, PMCID: PMC8268644, DOI: 10.3390/ijms22136960.Peer-Reviewed Original ResearchThe NIH Somatic Cell Genome Editing program
Saha K, Sontheimer EJ, Brooks PJ, Dwinell MR, Gersbach CA, Liu DR, Murray SA, Tsai SQ, Wilson RC, Anderson DG, Asokan A, Banfield JF, Bankiewicz KS, Bao G, Bulte JWM, Bursac N, Campbell JM, Carlson DF, Chaikof EL, Chen ZY, Cheng RH, Clark KJ, Curiel DT, Dahlman JE, Deverman BE, Dickinson ME, Doudna JA, Ekker SC, Emborg ME, Feng G, Freedman BS, Gamm DM, Gao G, Ghiran IC, Glazer PM, Gong S, Heaney JD, Hennebold JD, Hinson JT, Khvorova A, Kiani S, Lagor WR, Lam KS, Leong KW, Levine JE, Lewis JA, Lutz CM, Ly DH, Maragh S, McCray PB, McDevitt TC, Mirochnitchenko O, Morizane R, Murthy N, Prather RS, Ronald JA, Roy S, Roy S, Sabbisetti V, Saltzman WM, Santangelo PJ, Segal DJ, Shimoyama M, Skala MC, Tarantal AF, Tilton JC, Truskey GA, Vandsburger M, Watts JK, Wells KD, Wolfe SA, Xu Q, Xue W, Yi G, Zhou J. The NIH Somatic Cell Genome Editing program. Nature 2021, 592: 195-204. PMID: 33828315, PMCID: PMC8026397, DOI: 10.1038/s41586-021-03191-1.Peer-Reviewed Original ResearchConceptsDownstream functional consequencesGenome modificationHuman genomeGenome editingGenome editorsSomatic cellsHuman cellsFunctional consequencesBiomedical research communityGenomeLarge animalsBiological systemsCellsHuman healthHuman biological systemsEditingVivoAnimal modelsNew therapiesNew opportunitiesWide rangeConsortium
2020
Complex mosaic structural variations in human fetal brains
Sekar S, Tomasini L, Proukakis C, Bae T, Manlove L, Jang Y, Scuderi S, Zhou B, Kalyva M, Amiri A, Mariani J, Sedlazeck F, Urban AE, Vaccarino F, Abyzov A. Complex mosaic structural variations in human fetal brains. Genome Research 2020, 30: gr.262667.120. PMID: 33122304, PMCID: PMC7706730, DOI: 10.1101/gr.262667.120.Peer-Reviewed Original ResearchConceptsSingle nucleotide variantsCopy number variantsStructural variantsMegabase-scale copy number variantsHuman fetal brainFunctional consequencesMobile element insertionsSimilar functional consequencesFetal brainMosaic single-nucleotide variantsAdult brain neuronsStructural variationsPotential functional consequencesKilobase scaleDNA eventsGenomic fragmentDifferent chromosomesElement insertionsClonal approachHuman brain cellsFetal human brainNucleotide variantsReplication errorsHuman brainNumber variantsSurfing on Membrane Waves: Microvilli, Curved Membranes, and Immune Signaling
Orbach R, Su X. Surfing on Membrane Waves: Microvilli, Curved Membranes, and Immune Signaling. Frontiers In Immunology 2020, 11: 2187. PMID: 33013920, PMCID: PMC7516127, DOI: 10.3389/fimmu.2020.02187.Peer-Reviewed Original ResearchMeSH KeywordsActin CytoskeletonAnimalsCarrier ProteinsCell LineCell MembraneCell ShapeCyclodextrinsCytokinesGlycocalyxHumansLymphocyte ActivationMembrane LipidsMembrane ProteinsMiceMicrofilament ProteinsMicroscopy, Electron, ScanningMicrovilliReceptors, Antigen, T-CellSignal TransductionStress, MechanicalSurface PropertiesSynaptosomesT-LymphocytesConceptsFunctional consequencesFinger-like membrane protrusionsT cell signalingSuper-resolution microscopyLocal membrane curvatureActin cytoskeletonMembrane protrusionsSignal transductionCell signalingMembrane curvatureCurved membranesImmune signalingBiochemical activityUnique compartmentLymphocyte microvilliMicrovillus formationCell typesLocal membraneCytoskeletonSignalingMicrovilliMembraneBody of evidenceMembrane wavesImportant roleRNA-binding proteins in neurological development and disease
Prashad S, Gopal PP. RNA-binding proteins in neurological development and disease. RNA Biology 2020, 18: 972-987. PMID: 32865115, PMCID: PMC8216196, DOI: 10.1080/15476286.2020.1809186.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsRNA-binding proteinGene expressionDisease-linked RNA-binding proteinsHigh-throughput transcriptomic analysisRNA processing stepsAberrant RNA metabolismAberrant RNA processingRecent exciting studiesRNA processingRNA metabolismMRNA traffickingAlternative splicingMultifunctional proteinTranscriptomic analysisSplicing misregulationMRNA stabilityMolecular mechanismsProtein resultsNeuronal homeostasisNeurodevelopmental defectsNeuronal proteinsFunctional consequencesPleiotropic effectsSpatiotemporal controlProteinThe role of somatic mosaicism in brain disease
Jourdon A, Fasching L, Scuderi S, Abyzov A, Vaccarino FM. The role of somatic mosaicism in brain disease. Current Opinion In Genetics & Development 2020, 65: 84-90. PMID: 32622340, PMCID: PMC7749073, DOI: 10.1016/j.gde.2020.05.002.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus Statements
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