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Lipocalin 2 stimulates bone fibroblast growth factor 23 production in chronic kidney disease

Bone Research 2021年第3期9卷 385-395页

作者： Guillaume Courbon Connor Francis Claire Gerber Samantha Neuburg Xueyan Wang emily lynch Tamara Isakova Jodie LBabitt Myles Wolf Aline Martin Valentin David Division of Nephrology and Hypertension Department of Medicineand Center for Translational Metabolism and HealthInstitute for Public Health and MedicineNorthwestern University Feinberg School of MedicineChicagoILUSA Nephrology Division Program in Membrane BiologyMassachusetts General HospitalHarvard Medical SchoolBostonMAUSA Division of Nephrology Department of Medicineand Duke Clinical Research InstituteDuke University School of MedicineDurhamNCUSA

Bone-produced fibroblast growth factor 23(FGF23)increases in response to inflammation and iron deficiency and contributes to cardiovascular mortality in chronic kidney disease(CKD).Neutrophil gelatinase-associated lipocalin(NGAL or lipocalin 2;LCN2 the murine homolog)is a pro-inflammatory and iron-shuttling molecule that is secreted in response to kidney injury and may promote CKD *** investigated bone FGF23 regulation by circulating *** 23 weeks,Col4a3KO mice showed impaired kidney function,increased levels of kidney and serum LCN2,increased bone and serum FGF23,anemia,and left ventricular hypertrophy(LVH).Deletion of Lcn2 in CKD mice did not improve kidney function or anemia but prevented the development of LVH and improved survival in association with marked reductions in serum ***2 deletion specifically prevented FGF23 elevations in response to inflammation,but not iron deficiency or phosphate,and administration of LCN2 increased serum FGF23 in healthy and CKD mice by stimulating Fgf23 transcription via activation of cAMP-mediated signaling in bone *** results show that kidney-produced LCN2 is an important mediator of increased FGF23 production by bone in response to inflammation and in ***2 inhibition might represent a potential therapeutic approach to lower FGF23 and improve outcomes in CKD.

关键词： FGF23 kidney inflammation

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The insect-killing bacterium Photorhabdus luminescens has the lowest mutation rate among bacteria

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Marine Life Science & Technology 2021年第1期3卷 20-27页

作者： Jiao Pan emily Williams Way Sung Michael lynch Hongan Long Institute of Evolution and Marine Biodiversity KLMMEOcean University of ChinaQingdao 266003China Center for Mechanisms of Evolution The Biodesign InstituteArizona State UniversityTempeAZ 85281USA Department of Bioinformatics and Genomics University of North CarolinaCharlotteNC 28223USA

Mutation is a primary source of genetic variation that is used to power *** studies,however,have shown that most mutations are deleterious and,as a result,extremely low mutation rates might be benefcial for *** a mutation accumulation experiment,an unbiased method for mutation study,we found an extremely low base-substitution mutation rate of 5.94×10^(-11) per nucleotide site per cell division(95%Poisson confdence intervals:4.65×10^(-11),7.48×10^(-11))and indel mutation rate of 8.25×10^(-12) per site per cell division(95%confdence intervals:3.96×10^(-12),1.52×10^(-11))in the bacterium Photorhabdus luminescens *** mutations are strongly A/T-biased with a mutation bias of 10.28 in the A/T *** has been hypothesized that the ability for selection to lower mutation rates is inversely proportional to the efective population size(drift-barrier hypothesis)and we found that the efective population size of this bacterium is signifcantly greater than most other *** fnding further decreases the lower-bounds of bacterial mutation rates and provides evidence that extreme levels of replication fdelity can evolve within organisms that maintain large efective population sizes.

关键词： Neutral evolution Mutation accumulation Mutation spectrum Drift-barrier hypothesis Lower-limit of mutation rate

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