2025
Orchestrating Neural Development Through mRNA Translation Regulation
Rodrigue B, Sajish M, Salmaso N, Aguilar‐Valles A. Orchestrating Neural Development Through mRNA Translation Regulation. Journal Of Neurochemistry 2025, 169: e70128. PMID: 40509688, PMCID: PMC12163303, DOI: 10.1111/jnc.70128.Peer-Reviewed Original ResearchConceptsMRNA translation regulationRegulation of mRNA translationMammalian/mechanistic target of rapamycin complex 1MRNA translationTranslational regulationFragile X Messenger Ribonucleoprotein 1Neural developmentGene expressionRegulation of gene expressionCell fate decisionsControlling gene expressionControl of brain developmentTarget of rapamycin complex 1Integrated stress responseNeuronal growth conesDysregulation of mRNA translationRapamycin complex 1Fate decisionsSubcellular compartmentsTranscriptional controlSignaling cascadesFragile X syndromeAxon guidanceMammalian/mechanistic targetStem cell proliferationMapping pesticide-induced metabolic alterations in human gut bacteria
Chen L, Yan H, Di S, Guo C, Zhang H, Zhang S, Gold A, Wang Y, Hu M, Wu D, Johnson C, Wang X, Zhu J. Mapping pesticide-induced metabolic alterations in human gut bacteria. Nature Communications 2025, 16: 4355. PMID: 40348778, PMCID: PMC12065874, DOI: 10.1038/s41467-025-59747-6.Peer-Reviewed Original ResearchConceptsModulating gut microbiota compositionGut bacteria speciesGut microbial speciesHuman gut bacteriaGut microbiota compositionGut bacterial metabolismPesticide exposureHost healthGut bacteriaMicrobiota compositionMicrobial speciesBacterial metabolismBacteria speciesMolecular mechanismsComprehensive atlasLipid metabolismGutIn vivo mouse modelPesticidesHostMetabolismSpeciesInteractive atlasMouse modelMetabolic changesPredicting adenine base editing efficiencies in different cellular contexts by deep learning
Kissling L, Mollaysa A, Janjuha S, Mathis N, Marquart K, Weber Y, Moon W, Lin P, Fan S, Muramatsu H, Vadovics M, Allam A, Pardi N, Tam Y, Krauthammer M, Schwank G. Predicting adenine base editing efficiencies in different cellular contexts by deep learning. Genome Biology 2025, 26: 115. PMID: 40340964, PMCID: PMC12060317, DOI: 10.1186/s13059-025-03586-7.Peer-Reviewed Original ResearchConceptsBase editing efficiencyEditing efficiencyCell linesPathogenic mutationsBase editingPrimary cells in vivoBase editing screensBase editing outcomesCells in vivoHEK293T cellsAdenine base editingIn vivo settingTarget lociT cellsLipid nanoparticlesCellular contextTarget sequenceMRNA deliveryBase pairsOn-target editingBystander effectEditing outcomesBase editorsIn vitro datasetsMurine liverLiver lipid droplet cholesterol content is a key determinant of metabolic dysfunction–associated steatohepatitis
Sakuma I, Gaspar R, Nasiri A, Dufour S, Kahn M, Zheng J, LaMoia T, Guerra M, Taki Y, Kawashima Y, Yimlamai D, Perelis M, Vatner D, Petersen K, Huttasch M, Knebel B, Kahl S, Roden M, Samuel V, Tanaka T, Shulman G. Liver lipid droplet cholesterol content is a key determinant of metabolic dysfunction–associated steatohepatitis. Proceedings Of The National Academy Of Sciences Of The United States Of America 2025, 122: e2502978122. PMID: 40310463, DOI: 10.1073/pnas.2502978122.Peer-Reviewed Original ResearchConceptsCholine-deficient l-amino acid-defined high-fat dietBempedoic acidLiver fibrosisLiver diseaseL-amino acid-defined high-fat dietAdvanced liver diseaseCholesterol contentHSD17B13 variantsHigh-fat dietTotal liver cholesterol contentTreated miceActivate signaling pathwaysVariant rs738409Liver cholesterol contentLiver lipidsFibrotic responsePromote inflammationTherapeutic approachesSteatotic liver diseaseDietary cholesterol supplementationFibrosisHuman liver samplesI148MAntisense oligonucleotidesProgressive formPreclinical Activity of Datopotamab Deruxtecan, an Antibody-Drug Conjugate Targeting Trophoblast Cell-Surface Antigen 2, in Uterine Serous Carcinoma.
Greenman M, Demirkiran C, Bellone S, Hartwich T, McNamara B, Ettorre V, Santin N, Sethi N, Yang-Hartwich Y, Papatla K, Ratner E, Santin A. Preclinical Activity of Datopotamab Deruxtecan, an Antibody-Drug Conjugate Targeting Trophoblast Cell-Surface Antigen 2, in Uterine Serous Carcinoma. Cancer Research Communications 2025, 5: 774-782. PMID: 40299780, PMCID: PMC12062949, DOI: 10.1158/2767-9764.crc-25-0057.Peer-Reviewed Original ResearchConceptsTrophoblast cell surface antigen 2Uterine serous carcinomaAntibody-dependent cell-mediated cytotoxicityAntibody-drug conjugatesCell-mediated cytotoxicitySerous carcinomaPreclinical activityCell linesTargets trophoblast cell-surface antigen-2Presence of peripheral blood lymphocytesTreatment of uterine serous carcinomaInduce antibody-dependent cell-mediated cytotoxicityPrimary USC cell linesRecurrent uterine serous carcinomaUSC xenograftsUterine serous carcinoma cell linesAntigen 2In vivoPrimary tumor cell linesTROP2 overexpressionBiomarker-targeted therapiesControl ADCChromium release assayHigher recurrence rateTumor growth suppressionNatural killer cells’ functional impairment drives the immune escape of pre-malignant clones in early-stage myelodysplastic syndromes
Rodriguez-Sevilla J, Ganan-Gomez I, Kumar B, Thongon N, Ma F, Chien K, Kim Y, Yang H, Loghavi S, Tan R, Adema V, Li Z, Tanaka T, Uryu H, Kanagal-Shamanna R, Al-Atrash G, Bejar R, Banerjee P, Lynn Cha S, Montalban-Bravo G, Dougherty M, Fernandez Laurita M, Wheeler N, Jia B, Papapetrou E, Izzo F, Dueñas D, McAllen S, Gu Y, Todisco G, Ficara F, Della Porta M, Jain A, Takahashi K, Clise-Dwyer K, Halene S, Bertilaccio M, Garcia-Manero G, Daher M, Colla S. Natural killer cells’ functional impairment drives the immune escape of pre-malignant clones in early-stage myelodysplastic syndromes. Nature Communications 2025, 16: 3450. PMID: 40216768, DOI: 10.1038/s41467-025-58662-0.Peer-Reviewed Original ResearchConceptsHematopoietic stem cellsMyelodysplastic syndromeImmune escapeMyelodysplastic syndrome hematopoietic stem cellsNatural killer (NK) cellsAberrant hematopoietic stem cellsEarly-stage myelodysplastic syndromeDevelopment of myelodysplastic syndromeStage of myelodysplastic syndromeAdoptive cell therapyFunctional in vitro studiesNatural killer cellsTime of diagnosisPreclinical in vivo studiesPre-malignant clonesDisease-related comorbiditiesPre-malignant stageSlow down disease progressionRegenerate hematopoiesisClonal cytopeniaNK cellsImmune surveillanceKiller cellsHealthy donorsPharmacological therapyThe bridge-like lipid transport protein VPS13C/PARK23 mediates ER–lysosome contacts following lysosome damage
Wang X, Xu P, Bentley-DeSousa A, Hancock-Cerutti W, Cai S, Johnson B, Tonelli F, Shao L, Talaia G, Alessi D, Ferguson S, De Camilli P. The bridge-like lipid transport protein VPS13C/PARK23 mediates ER–lysosome contacts following lysosome damage. Nature Cell Biology 2025, 27: 776-789. PMID: 40211074, PMCID: PMC12081312, DOI: 10.1038/s41556-025-01653-6.Peer-Reviewed Original ResearchConceptsDisease genesResponse to lysosomal damageSurface of lysosomesER–lysosome contactsParkinson's disease genesDelivery to lysosomesLipid transport proteinsLysosomal damageVPS13 proteinsLysosomal surfaceDisease proteinsGenetic studiesDamaged lysosomesVPS13CLysosomal stressLipid transportLysosomesInhibited stateMembrane perturbationRab7Lysosomal dysfunctionProteinVps13LipidGenesPreclinical and clinical sex differences in the effects of alcohol on measures of brain dopamine: a systematic review
Barrios N, Riordan W, Garcia-Rivas V, Peltier M, Roberts W, Verplaetse T, Kohler R, Zhou H, Banini B, McKee S, Cosgrove K, Zakiniaeiz Y. Preclinical and clinical sex differences in the effects of alcohol on measures of brain dopamine: a systematic review. Biology Of Sex Differences 2025, 16: 24. PMID: 40200334, DOI: 10.1186/s13293-025-00706-7.Peer-Reviewed Original ResearchConceptsAlcohol use disorderAlcohol-induced dopamine releaseEffects of alcoholSex differencesAlcohol exposureDopamine measurementsMu-opioid receptorsDopamine releaseEffects of sexProgression of alcohol use disorderDopamine D1 receptor availabilityAlcohol use disorder developmentEffects of prenatal alcohol exposureD1 receptor availabilityStriatal dopamine concentrationsAir-exposed controlsAlcohol-exposed animalsMu-opioid receptor activationPrenatal alcohol exposureDuration of alcohol exposureVentral striatumBrain dopamineReward processingNeurobiological mechanismsReceptor availabilityMIF as an oncogenic driver of low‐heterogeneity melanomas
Tran T, Sánchez‐Zuno G, Kulkarni R, Kluger H, Bucala R. MIF as an oncogenic driver of low‐heterogeneity melanomas. Molecular Oncology 2025, 19: 1295-1298. PMID: 40131169, PMCID: PMC12077282, DOI: 10.1002/1878-0261.70031.Peer-Reviewed Original ResearchConceptsMacrophage migration inhibitory factorImproving therapeutic outcomesMigration inhibitory factorPotential therapeutic utilityImmune landscapeMelanoma clonesImmune escapeT cellsImmunoregulatory cytokinesTumor heterogeneityTumor progressionOncogenic driversPathway inhibitorTherapeutic outcomesTumor evolutionInhibitory factorCell proliferationMelanomaTumorCellsAntagonistCytokinesTiming Matters: Lessons From Perinatal Neurogenesis in the Olfactory Bulb
Liberia T, Han K, Spence N, Meller S, Martin‐Lopez E, Greer C. Timing Matters: Lessons From Perinatal Neurogenesis in the Olfactory Bulb. The Journal Of Comparative Neurology 2025, 533: e70045. PMID: 40128105, DOI: 10.1002/cne.70045.Peer-Reviewed Original ResearchConceptsOlfactory bulbGranule cellsTiming of neurogenesisProjection neuronsCoding of odor informationSynaptic circuitsInhibitory granule cellsDendrites of projection neuronsLocal synaptic circuitsMitral cellsOdor processingSynaptic integrationPlexiform layerOdor informationAnatomical configurationLaminar distributionEmbryogenesis to adulthoodNeurogenesisSecondary dendritesMaturation patternGlomeruliNeuronsDevelopmental continuumCellsBulbUric Acid Stroke Cerebroprotection Transcended Sex, Age, and Comorbidities in a Multicenter Preclinical Trial
Patel R, Kumskova M, Kodali H, Budnik I, Kuznetsov V, Jain A, Jha A, Thedens D, Dhanesha N, Sutariya B, Nagarkatti K, Lamb J, Kamat P, Shi Y, Avery B, Imai T, Jin X, Chauhan A, Boisserand L, Khan M, Dhandapani K, Sanganahalli B, Sansing L, Hess D, Koehler R, McCullough L, Aronowski J, Ayata C, Diniz M, Lyden P, Planas A, Chamorro A, Chauhan A, Leira E, Investigators O. Uric Acid Stroke Cerebroprotection Transcended Sex, Age, and Comorbidities in a Multicenter Preclinical Trial. Stroke 2025, 56: 965-973. PMID: 40091742, PMCID: PMC11932773, DOI: 10.1161/strokeaha.124.048748.Peer-Reviewed Original ResearchConceptsUA-treated animalsPrimary functional outcomeFunctional outcomesMiddle cerebral artery filament occlusionModified intention-to-treat populationIntention-to-treat populationUric acidHuman clinical trialsImprove functional outcomesStudy drugIntravenous salineEffects of UARelevant to patientsClinical trialsPrimary outcomeSaline controlsSecondary outcomesPreclinical trialsDay 2Survival rateDay 7Filament occlusionGroups of animalsComorbiditiesDiverse comorbiditiesWild Florida mottled ducks demonstrate strong heterogeneity in their humoral innate immune response.
Ayala A, Cheng M, Hellinger T, McBride K, Webb J, Fanning A, Snyder P, Ferragamo M, Garcia S, Sterner N, Bischoff K, Almagro-Moreno S, Ogbunugafor C. Wild Florida mottled ducks demonstrate strong heterogeneity in their humoral innate immune response. PLOS ONE 2025, 20: e0312653. PMID: 40096078, PMCID: PMC11913296, DOI: 10.1371/journal.pone.0312653.Peer-Reviewed Original ResearchConceptsFlorida mottled ducksAmerican Type Culture CollectionMottled ducksHumoral innate immune responseType Culture CollectionInnate immune responseVibrio sppEndemic subspeciesHabitat conversionInnate immune systemEco-immunologyCulture CollectionE. coliAnas platyrhynchosSubspeciesPeninsular FloridaConservation needsEffects of climate changeEcological covariatesHumoral innate immune systemBactericidal assayDucksResponse to agingWaterborne pathogensPathogensAdding insult to injury: the spectrum of tubulointerstitial responses in acute kidney injury
Baker M, Cantley L. Adding insult to injury: the spectrum of tubulointerstitial responses in acute kidney injury. Journal Of Clinical Investigation 2025, 135: e188358. PMID: 40091836, PMCID: PMC11910233, DOI: 10.1172/jci188358.Peer-Reviewed Original ResearchConceptsAcute kidney injuryTubular epithelial cellsKidney injuryTubular cellsCases of acute kidney injuryImmune-mediated processPersistence of inflammationBiphasic immune responseChronic kidney diseaseCell deathTubular cell injuryLymphocyte subsetsTubular repairCell cycle arrestOutflow obstructionTEC differentiationPreclinical findingsLymphocytic infiltrationProinflammatory macrophagesKidney diseaseModulate inflammationImmune responseActivated macrophagesMetabolic reprogrammingTubular castsTranscriptomic Alterations Induced by Tetrahydrocannabinol in SIV/HIV Infection: A Systematic Review
Valizadeh A, Veenhuis R, Bradley B, Xu K. Transcriptomic Alterations Induced by Tetrahydrocannabinol in SIV/HIV Infection: A Systematic Review. International Journal Of Molecular Sciences 2025, 26: 2598. PMID: 40141240, PMCID: PMC11942185, DOI: 10.3390/ijms26062598.Peer-Reviewed Original ResearchConceptsSimian immunodeficiency virus (SIV)-infected macaquesPrevalence of cannabis useSIV-infected macaquesChronic immune activationHIV-infected human cellsEpithelial cell proliferationModulate immune responsesSystematic reviewSIV/HIV infectionHIV infectionPreclinical evidencePathways related to inflammationImmune activationCannabis useMicro-RNA expressionImmunomodulatory roleImmunomodulatory effectsReduce inflammationImmune responseTetrahydrocannabinolComprehensive searchCell proliferationTranscriptomic alterationsMethodological qualityPWHNotch1 Signalling Is Downregulated by Aerobic Exercise, Leading to Improvement of Hepatic Metabolism in Obese Mice
Gaspar R, Macêdo A, Nakandakari S, Muñoz V, Abud G, Vieira R, de Sousa Neto I, Pavan I, da Silva L, Simabuco F, da Silva A, Salgado W, Marchini J, Nonino C, Cintra D, Ropelle E, Pajvani U, de Freitas E, Pauli J. Notch1 Signalling Is Downregulated by Aerobic Exercise, Leading to Improvement of Hepatic Metabolism in Obese Mice. Liver International 2025, 45: e70068. PMID: 40078075, DOI: 10.1111/liv.70068.Peer-Reviewed Original ResearchConceptsNotch1 signalingAerobic exerciseRegulation of hepatic glucoseObese miceImpact of aerobic exerciseEffects of Notch1 signalingAerobic exercise trainingMTORC1 pathway activationNotch1 pathwayObese individualsTissue of obese miceCross-sectional studyNotch1 mRNA levelsMitochondrial respirationExercise trainingLivers of obese individualsTreadmill runningGluconeogenic enzymesHepG2 cell lineLipid accumulationTraining groupHepatic glucoseHepatic metabolismNotch1 proteinPathway activationMAP Kinase Phosphatase-5 Deficiency Improves Endurance Exercise Capacity
Perales J, Lawan A, Bajpeyi S, Han S, Bennett A, Min K. MAP Kinase Phosphatase-5 Deficiency Improves Endurance Exercise Capacity. Cells 2025, 14: 410. PMID: 40136658, PMCID: PMC11941502, DOI: 10.3390/cells14060410.Peer-Reviewed Original ResearchConceptsResponse to aerobic exerciseEndurance exercise capacityAerobic exerciseExercise capacityProgressive exercise stress testExercise training programEnhance endurance performanceCardiac adaptationPhysiological cardiac adaptationExercise stress testExercise habituationEndurance performanceRunning distanceCardiovascular healthTreadmill exerciseTraining programExerciseImproving cardiovascular functionSedentary miceTreadmillCardiac muscleEnduranceMitogen-activated protein kinaseMuscleStress testDepletion of Fkbp5 Protects Against the Rapid Decline in Ovarian Reserve Induced by Prenatal Stress in Female Offspring of Wild-Type Mice
Moore M, Cetinkaya-Un B, Sarkar P, Kayisli U, Semerci-Gunay N, Teng M, Lockwood C, Guzeloglu-Kayisli O. Depletion of Fkbp5 Protects Against the Rapid Decline in Ovarian Reserve Induced by Prenatal Stress in Female Offspring of Wild-Type Mice. International Journal Of Molecular Sciences 2025, 26: 2471. PMID: 40141115, PMCID: PMC11942629, DOI: 10.3390/ijms26062471.Peer-Reviewed Original ResearchConceptsOvarian reservePrenatal stressFKBP51 levelsPostnatal ovarian functionReduced ovarian reserveOvarian steroid synthesisWild-type miceMaternal restraint stressPrenatal stress groupPrenatally stressed offspringExpression of FKBP51Inhibit glucocorticoidProgesterone receptorTertiary folliclesEmbryonic day 8Granulosa cellsOvarian functionRestraint stressSteroidogenic enzymesMiddle-aged groupOvarian expressionFollicle atresiaPrenatal stress effectsDay 8Steroid synthesisSubcellular proteomics and iPSC modeling uncover reversible mechanisms of axonal pathology in Alzheimer’s disease
Cai Y, Kanyo J, Wilson R, Bathla S, Cardozo P, Tong L, Qin S, Fuentes L, Pinheiro-de-Sousa I, Huynh T, Sun L, Mansuri M, Tian Z, Gan H, Braker A, Trinh H, Huttner A, Lam T, Petsalaki E, Brennand K, Nairn A, Grutzendler J. Subcellular proteomics and iPSC modeling uncover reversible mechanisms of axonal pathology in Alzheimer’s disease. Nature Aging 2025, 5: 504-527. PMID: 40065072, PMCID: PMC11922768, DOI: 10.1038/s43587-025-00823-3.Peer-Reviewed Original ResearchConceptsAlzheimer's diseaseProximity labeling approachIPSC-derived neuronsSubcellular proteomicsCytoskeleton dynamicsPhosphorylated mTOR levelsDystrophic neuritesLipid transportBiological processesProtein turnoverAD modelHuman induced pluripotent stem cellsAmyloid depositsIPSC modelsProteomicsInduced pluripotent stem cellsPluripotent stem cellsMTOR inhibitionTherapeutic targetAxonal pathologyLabeling approachMTOR levelsMouse brainSpheroid formationAlzheimerMulticilia dynamically transduce Sonic Hedgehog signaling to regulate choroid plexus functions
Mao S, Song R, Jin S, Pang S, Jovanovic A, Zimmerman A, Li P, Wu X, Wendland M, Lin K, Chen W, Choksi S, Chen G, Holtzman M, Reiter J, Wan Y, Xuan Z, Xiang Y, Xu C, Upadhyayula S, Hess H, He L. Multicilia dynamically transduce Sonic Hedgehog signaling to regulate choroid plexus functions. Cell Reports 2025, 44: 115383. PMID: 40057957, DOI: 10.1016/j.celrep.2025.115383.Peer-Reviewed Original ResearchConceptsCSF productionChoroid plexusCerebrospinal fluidSonic hedgehog signalingWater channel AQP1Increased CSF productionHedgehog signalingChoroid plexus functionMotile ciliaMulticiliaSensory ciliaShh signalingNeonatal hydrocephalusSonic hedgehogCiliary lengthRegulate CSF productionSignal intensityCiliary ultrastructureChoroidEpithelial monolayersAQP1Developmental dynamicsCiliaATP1A2PlexusAn atypical atherogenic chemokine that promotes advanced atherosclerosis and hepatic lipogenesis
El Bounkari O, Zan C, Yang B, Ebert S, Wagner J, Bugar E, Kramer N, Bourilhon P, Kontos C, Zarwel M, Sinitski D, Milic J, Jansen Y, Kempf W, Sachs N, Maegdefessel L, Ji H, Gokce O, Riols F, Haid M, Gerra S, Hoffmann A, Brandhofer M, Avdic M, Bucala R, Megens R, Willemsen N, Messerer D, Schulz C, Bartelt A, Harm T, Rath D, Döring Y, Gawaz M, Weber C, Kapurniotu A, Bernhagen J. An atypical atherogenic chemokine that promotes advanced atherosclerosis and hepatic lipogenesis. Nature Communications 2025, 16: 2297. PMID: 40055309, DOI: 10.1038/s41467-025-57540-z.Peer-Reviewed Original ResearchConceptsApoE-/- miceHyperlipidemic apoE-/- miceCoronary artery diseaseDecreased plasma lipid levelsPlasma lipid levelsHepatic lipid accumulationAtherogenic chemokinesFoam-cell formationFLIM-FRET microscopyArtery diseasePlasma concentrationsVascular inflammationInflammatory conditionsMetabolic dysfunctionAtherosclerotic patientsLipid accumulationAdvanced atherosclerosisMyocardial infarctionLipid levelsSuppressed hepatic lipid accumulationAdvanced atherogenesisCarotid plaquesDisease severityIschemic strokeChemokines
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