2025
Amino acid patterns predict white matter integrity measures in the brain in patients across the Alzheimer’s disease continuum
Goharmanesh F, Masmoie M, Nasiri H, Sadat-Madani S, Namin S, Damizadeh M, Shakeri S, Sodeifian F, Rajabpour-Sanati A, Bahrainian B, Mohammadi Y, Shushtari A, Mayeli M. Amino acid patterns predict white matter integrity measures in the brain in patients across the Alzheimer’s disease continuum. Metabolic Brain Disease 2025, 40: 227. PMID: 40531346, DOI: 10.1007/s11011-025-01647-1.Peer-Reviewed Original ResearchConceptsWhite matter integrityMean diffusivityDiffusion tensor imagingFractional anisotropyAlzheimer's Disease Neuroimaging InitiativeAxial diffusivityAA metabolic pathwaysReduced white matter integrityDisease continuumDTI-derived metricsWhite matter integrity measuresWhite matter microstructural integrityAD patientsCross-sectional studyUltra-high performance liquid chromatographyPotential therapeutic targetRadial diffusivityDecreased FAIncreased MDStudy groupEarly diagnosisProgression markersAlzheimer's disease continuumAmino acidsMild cognitive impairmentElevation of hepatic de novo lipogenesis in mice with overnutrition is dependent on multiple substrates
Strober J, Siebel S, Murray S, Rodríguez M, Rodriguez-Navas Gonzalez C, Vatner D. Elevation of hepatic de novo lipogenesis in mice with overnutrition is dependent on multiple substrates. Journal Of Lipid Research 2025, 66: 100838. PMID: 40499904, DOI: 10.1016/j.jlr.2025.100838.Peer-Reviewed Original ResearchCarbon entryAntisense oligonucleotidesIncreased hepatic TG contentGlutamic-pyruvic transaminase 2Amino acidsChronic overnutritionDevelopment of novel therapiesDecreased hepatic triglyceride contentTCA cycle metabolitesInsulin-resistant subjectsIncreased de novo lipogenesisMultiple amino acidsAntisense oligonucleotide treatmentPrevention of dyslipidemiaHepatic triglyceride contentOverfed miceTG contentHepatic de novo lipogenesisHepatic TG contentC57BL6/J miceLactate dehydrogenase ANovel therapiesMultiple substratesMetabolic syndromeCarbon sourceSeparation of telomere protection from length regulation by two different point mutations at amino acid 492 of RTEL1
Smoom R, May C, Lichtental D, Bar-Ness K, Rangel R, Khoury J, Nachmani D, Avrahami D, Ahangari F, Skordalakes E, Kaminski N, Kaestner K, Tzfati Y. Separation of telomere protection from length regulation by two different point mutations at amino acid 492 of RTEL1. Nucleic Acids Research 2025, 53: gkaf507. PMID: 40530700, PMCID: PMC12203905, DOI: 10.1093/nar/gkaf507.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SubstitutionAnimalsDisease Models, AnimalDNA DamageDNA HelicasesDyskeratosis CongenitaFetal Growth RetardationGrowth DisordersHematopoiesisHumansIntellectual DisabilityLimb Deformities, CongenitalLungMiceMicrocephalyPoint MutationTelomereTelomere HomeostasisX-Linked Intellectual DisabilityConceptsHoyeraal-Hreidarsson syndromeTelomere protectionLength regulationTelomere length regulationTelomere-related diseasesTelomere biology disordersDNA helicaseMouse genomeGenome stabilityMouse modelMouse telomeresAberrant hematopoiesisGenomic instabilityPoint mutationsHouse miceTelomeric DNA damageAnaphase bridgesRTEL1Amino acidsTelomereMechanistic rolesDNA damageMutationsIsoleucine mutationGenomeCysteine depletion triggers adipose tissue thermogenesis and weight loss
Lee A, Orliaguet L, Youm Y, Maeda R, Dlugos T, Lei Y, Coman D, Shchukina I, Andhey P, Smith S, Ravussin E, Stadler K, Chen B, Artyomov M, Hyder F, Horvath T, Schneeberger M, Sugiura Y, Dixit V. Cysteine depletion triggers adipose tissue thermogenesis and weight loss. Nature Metabolism 2025, 7: 1204-1222. PMID: 40461845, PMCID: PMC12198010, DOI: 10.1038/s42255-025-01297-8.Peer-Reviewed Original ResearchConceptsWeight lossWhite adipose tissueAdipose browningCaloric restrictionAdipose tissueDietary amino acidsCysteine depletionSulphur amino acids cysteineIncreased energy expenditureAdipose tissue thermogenesisIncreased fat utilizationMetabolic inflammationNoradrenaline signalingOrganismal metabolismAdipose thermogenesisObese miceBrowning of adipocytesIncreased heat productionBrownRemoval of cysteineCore body temperatureAmino acidsEnergy expenditureAmino acid cysteineFat utilizationIntegration of metabolite and transcriptome profiles of cultivated and wild rice to unveil gene regulatory networks and key genes determining rice source and sink strength
Singh A, Mathan J, Dwivedi A, Rani R, Ranjan A. Integration of metabolite and transcriptome profiles of cultivated and wild rice to unveil gene regulatory networks and key genes determining rice source and sink strength. Functional & Integrative Genomics 2025, 25: 97. PMID: 40310586, DOI: 10.1007/s10142-025-01606-0.Peer-Reviewed Original ResearchConceptsWild rice accessionsWild riceCultivated varietiesSink strengthRice accessionsHub genesGene co-expression modulesPathways related to photosynthesisGene co-expression networksGene regulatory networksAmino acidsZinc finger proteinCo-expression modulesHigher photosynthesis rateCrop yield increasesCo-expression networkFatty acid metabolismFinger proteinRegulatory networksTranscriptional regulationTranscriptome comparisonFlag leavesPhotosynthesis ratePhotosynthetic leavesRice varietiesEukaryotic Microproteins
Jaunbocus N, Ebenki V, Su H, Slavoff S. Eukaryotic Microproteins. Annual Review Of Biochemistry 2025, 94: 1-28. PMID: 40245354, PMCID: PMC12207985, DOI: 10.1146/annurev-biochem-080124-012840.Peer-Reviewed Original ResearchRelationship between Immunogenicity and Protein Structure at Amino Acid Substitution Sites of Blood Group Antigens
Howe J, Stack G. Relationship between Immunogenicity and Protein Structure at Amino Acid Substitution Sites of Blood Group Antigens. Blood 2025 PMID: 40163810, DOI: 10.1182/blood.2024025071.Peer-Reviewed Original ResearchProtein structureAa substitutionsBlood group antigensThree-dimensional protein structuresAmino acid substitution sitesAmino acidsGroup antigensSurface-accessible loopsInvestigating protein structureStructure predictionProtein regionsB strandsTertiary structureFlexible regionsInformatics analysisAlphaFold2ProteinAminoImmunogenic antigensSitesDeterminants of immunogenicitySubstitutionPolypeptideConfidence scoresDisordered coilsHepatic PKA Mediates Liver and Pancreatic α-Cell Cross Talk
Bao K, Berger J, Na E, Su Q, Halasz G, Sleeman M, Okamoto H. Hepatic PKA Mediates Liver and Pancreatic α-Cell Cross Talk. Diabetes 2025, 74: 885-897. PMID: 40095004, PMCID: PMC12097458, DOI: 10.2337/db24-0958.Peer-Reviewed Original ResearchConceptsAmino acid catabolismGlucagon receptorControlling amino acid metabolismDownstream effectorsGlucagon receptor blockadeA cellsElevated plasma amino acidsAmino acidsAlpha cell massPlasma amino acidsCatabolism of amino acidsPKA knockdownAmino acid metabolismGlucagon-stimulated hepatic glucose productionCatabolic genesGcgr signalingPancreatic A cellsEPAC2 knockdownGNASHyperplasiaHepatic glucose productionDownstream factorsAcid metabolismCell massEpac2LILRB3 genetic variation is associated with kidney transplant failure in African American recipients
Sun Z, Yi Z, Wei C, Wang W, Ren T, Cravedi P, Tedla F, Ward S, Azeloglu E, Schrider D, Li Y, Khan A, Zanoni F, Fu J, Ali S, Liu S, Liang D, Liu T, Li H, Xi C, Vy T, Mosoyan G, Sun Q, Kumar A, Zhang Z, Farouk S, Campell K, Ochando J, Lee K, Coca S, Xiang J, Connolly P, Gallon L, O’Connell P, Colvin R, Menon M, Nadkarni G, He J, Kraft M, Jiang X, Zhang X, Kiryluk K, Cherukuri A, Lakkis F, Zhang W, Chen S, Heeger P, Zhang W. LILRB3 genetic variation is associated with kidney transplant failure in African American recipients. Nature Medicine 2025, 31: 1677-1687. PMID: 40065170, DOI: 10.1038/s41591-025-03568-z.Peer-Reviewed Original ResearchSingle-nucelotide polymorphismsAssociated with death-censored graft lossDeath-censored graft lossGenetic variationGraft lossImmunoreceptor tyrosine-based inhibitory motifTyrosine-based inhibitory motifAA individualsApolipoprotein L1Rate of graft lossEnd-stage renal diseaseMissense mutationsInhibitory motifRNA sequencingKidney transplant outcomesKidney transplant failureMultiomics analysisImmune-related diseasesAmino acidsAfrican American recipientsTransplant cohortTransplant failureTransplant outcomesAnalysis of bloodProspective studyAutosomal dominant SLURP1 variants cause palmoplantar keratoderma and progressive symmetric erythrokeratoderma
Jiang X, Mortlock R, Lomakin I, Zhou J, Hu R, Cossio M, Bunick C, Choate K. Autosomal dominant SLURP1 variants cause palmoplantar keratoderma and progressive symmetric erythrokeratoderma. British Journal Of Dermatology 2025, 192: 896-906. PMID: 39913669, PMCID: PMC12036768, DOI: 10.1093/bjd/ljaf049.Peer-Reviewed Original ResearchProgressive symmetric erythrokeratodermaAmino acidsGenetic variantsPathogenic variantsNF-kB signalingPalmoplantar keratodermaSpatial transcriptomicsPatient keratinocytesWhole-exome sequencingSLURP1 expressionIn silico predictionVariant consequencesSignal peptideMal de MeledaExome sequencingSecreted proteinsHealthy control cellsInnate immune activationIn silico modelsPhenotypic spectrumControl cellsConfirmed with mass spectrometryAminoAutosomal dominant transmissionTranscriptomeEngineering a genomically recoded organism with one stop codon
Grome M, Nguyen M, Moonan D, Mohler K, Gurara K, Wang S, Hemez C, Stenton B, Cao Y, Radford F, Kornaj M, Patel J, Prome M, Rogulina S, Sozanski D, Tordoff J, Rinehart J, Isaacs F. Engineering a genomically recoded organism with one stop codon. Nature 2025, 639: 512-521. PMID: 39910296, PMCID: PMC11903333, DOI: 10.1038/s41586-024-08501-x.Peer-Reviewed Original Research
2024
Bioinformatics analysis of myelin-microbe interactions suggests multiple types of molecular mimicry in the pathogenesis of multiple sclerosis
Bigdeli A, Ghaderi-Zefrehei M, Lesch B, Behmanesh M, Arab S. Bioinformatics analysis of myelin-microbe interactions suggests multiple types of molecular mimicry in the pathogenesis of multiple sclerosis. PLOS ONE 2024, 19: e0308817. PMID: 39775333, PMCID: PMC11684644, DOI: 10.1371/journal.pone.0308817.Peer-Reviewed Original ResearchConceptsBile salt hydrolaseMyelin oligodendrocyte glycoproteinBioinformatics approachProtein structureMyelin basic proteinIn silico bioinformatics approachesAmino acidsIdentical amino acidsAmino acid sequenceCapsid protein structureCentral nervous systemAspergillus speciesAcid sequenceBacterial proteinsMultiple sclerosisMyelin sheath componentsBiological insightsGut flora metabolitesBioinformatics analysisMOG proteinPathogenesis of multiple sclerosisCNS diseaseWzyBacteriaProteinHuman HDAC6 senses valine abundancy to regulate DNA damage
Jin J, Meng T, Yu Y, Wu S, Jiao C, Song S, Li Y, Zhang Y, Zhao Y, Li X, Wang Z, Liu Y, Huang R, Qin J, Chen Y, Cao H, Tan X, Ge X, Jiang C, Xue J, Yuan J, Wu D, Wu W, Jiang C, Wang P. Human HDAC6 senses valine abundancy to regulate DNA damage. Nature 2024, 637: 215-223. PMID: 39567688, DOI: 10.1038/s41586-024-08248-5.Peer-Reviewed Original ResearchConceptsHuman histone deacetylase 6Active DNA demethylationDNA demethylationValine deprivationDNA damageTen-eleven translocationRegulating DNA damageHistone deacetylase 6Repeat domainTherapeutic efficacy of PARP inhibitorsBind valineEfficacy of PARP inhibitorsCellular functionsPatient-derived xenograft modelsCytoplasmic shuttlingInduce DNA damageBranched amino acidsProtein synthesisAmino acidsIntracellular levelsPARP inhibitorsDNALevels of valineTumor growthTherapeutic efficacyIdentifying the minimal sets of distance restraints for FRET‐assisted protein structural modeling
Liu Z, Grigas A, Sumner J, Knab E, Davis C, O'Hern C. Identifying the minimal sets of distance restraints for FRET‐assisted protein structural modeling. Protein Science 2024, 33: e5219. PMID: 39548730, PMCID: PMC11568256, DOI: 10.1002/pro.5219.Peer-Reviewed Original ResearchConceptsForster resonance energy transferProtein structure determination techniquesCellular environmentProtein structure modelingAmino acid pairsConformational changesProteins in vivoForster resonance energy transfer studiesCrowded cellular environmentStructure determination techniquesDynamics in vivoStructures in vivoInduce conformational changesProtein structureResonance energy transferRoot-mean-square deviationAcid pairsInter-residue restraintsStructural ensemblesAmino acidsNon-physiological environmentsProteinDistance restraintsNucleic acidsAminoNo evidence that mutations in SARS-CoV-2 variants of concern derive from homologous fragments in gut microbiota
Parry R, Lytras S, Petrone M, Wille M, Crits-Christoph A, Gifford R, Saito A, Smura T, Peacock T. No evidence that mutations in SARS-CoV-2 variants of concern derive from homologous fragments in gut microbiota. Journal Of Virology 2024, 98: e01468-24. PMID: 39494907, PMCID: PMC11650967, DOI: 10.1128/jvi.01468-24.Peer-Reviewed Original ResearchBacterial sequencesViral RNA-dependent RNA polymeraseRNA-dependent RNA polymeraseSARS-CoV-2 variantsBacterial protein sequencesSARS-CoV-2 proteinsEvolution of mutationsRNA polymeraseIntrahost diversityProtein sequencesHomologous fragmentsNucleotide sequenceProtein databaseTemplate-switchingGut microbiotaSARS-CoV-2 VOCsViral genomeSARS-CoV-2Mutated fragmentsAmino acidsRdRpMutationsSequenceViral replicationProteinSalp14 epitope-based mRNA vaccination induces early recognition of a tick bite
Cui Y, Cibichakravarthy B, Tang X, Alameh M, Dwivedi G, Weissman D, Fikrig E. Salp14 epitope-based mRNA vaccination induces early recognition of a tick bite. Vaccine 2024, 42: 126304. PMID: 39236403, PMCID: PMC11416896, DOI: 10.1016/j.vaccine.2024.126304.Peer-Reviewed Original ResearchTick bite siteGuinea pigsMRNA-LNPMRNA vaccinesBite siteImmunized guinea pigsTiters of IgGIxodes scapularis ticksDevelopment of erythemaLipid nanoparticlesSkin of guinea pigsI. scapularisTicksErythemaHistamine activityPigsTick bitesCarboxyl terminusRepeated exposureExposure of animalsAmino acidsSalivary proteinsVaccineMRNAGuineaIdentifying the minimal sets of distance restraints for FRET‐assisted protein structural modeling
Liu Z, Grigas A, Sumner J, Knab E, Davis C, O'Hern C. Identifying the minimal sets of distance restraints for FRET‐assisted protein structural modeling. Protein Science 2024, 33 PMID: 38800659, PMCID: PMC11118665, DOI: 10.1002/pro.5219.Peer-Reviewed Original ResearchForster resonance energy transferProtein structure determination techniquesCellular environmentProtein structure modelingAmino acid pairsConformational changesForster resonance energy transfer studiesCrowded cellular environmentStructure determination techniquesInduce conformational changesProtein structureResonance energy transferRoot-mean-square deviationAcid pairsInter-residue restraintsStructural ensemblesAmino acidsNon-physiological environmentsProteinDistance restraintsNucleic acidsAminoMD simulationsFRET pairsOrganellesZearalenone-induced hepatointestinal toxicity in laying hens: unveiling the role of gut microbiota and fecal metabolites
Wang L, Deng Z, Huang J, Li T, Jiang J, Wang W, Sun Y, Deng Y. Zearalenone-induced hepatointestinal toxicity in laying hens: unveiling the role of gut microbiota and fecal metabolites. Poultry Science 2024, 103: 104221. PMID: 39241615, PMCID: PMC11406091, DOI: 10.1016/j.psj.2024.104221.Peer-Reviewed Original ResearchGut microbiotaGut microbial community compositionGut microbial diversityLaying hensMicrobial community compositionMetabolism of amino acidsNonribosomal peptidesCommunity compositionRRNA sequencingExacerbated liver damageFusarium speciesMicrobial diversityFirmicutes/Bacteroidetes ratioNucleic acid degradationInflammatory cell infiltrationABC transportersAspartate aminotransferaseEstrogenic disordersLactobacillus abundanceDecreased villus heightHigher abundanceMicrobiotaIntestinal oxidative stressZearalenone groupsAmino acidsLysosomal TBK1 responds to amino acid availability to relieve Rab7-dependent mTORC1 inhibition
Talaia G, Bentley-DeSousa A, Ferguson S. Lysosomal TBK1 responds to amino acid availability to relieve Rab7-dependent mTORC1 inhibition. The EMBO Journal 2024, 43: 3948-3967. PMID: 39103493, PMCID: PMC11405869, DOI: 10.1038/s44318-024-00180-8.Peer-Reviewed Original ResearchTANK-binding kinase 1MTORC1 activityAmino acid-dependent mTORC1 activationOrganelle quality controlRegulate cell growthElevated amino acid levelsAmino acid levelsAssociated with amyotrophic lateral sclerosisIncreased mTORC1 activityCellular demandSerine 72Amino acid availabilityLysosomal homeostasisSignaling proteinsMacromolecule degradationSites of amino acidsCell growthLysosomal poolMTORC1 inhibitionKinase 1Lysosomal functionAmino acidsInnate immunityLysosomesAmyotrophic lateral sclerosisVitamin B5 metabolism is essential for vacuolar and mitochondrial functions and drug detoxification in fungi
Choi J, Gihaz S, Munshi M, Singh P, Vydyam P, Hamel P, Adams E, Sun X, Khalimonchuk O, Fuller K, Ben Mamoun C. Vitamin B5 metabolism is essential for vacuolar and mitochondrial functions and drug detoxification in fungi. Communications Biology 2024, 7: 894. PMID: 39043829, PMCID: PMC11266677, DOI: 10.1038/s42003-024-06595-7.Peer-Reviewed Original ResearchConceptsSusceptibility of fungiRegulation of genesMetabolism of fatty acidsVacuolar morphologySaccharomyces cerevisiaeAcetyl-CoAEukaryotic pathogensGenetic evidenceGenetic regulationCellular processesAntifungal drugsCo-enzyme ADrug detoxificationAntifungal therapyDrug-resistant strainsFungal infectionsMitochondrial functionFungiAmino acidsAR-12Vitamin B5Synthase activityPathwayExcellent targetGlobal health threat
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