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In vivo mouse models to study bile acid synthesis and signaling

国际肝胆胰疾病杂志:英文版 2023年第5期22卷 466-473页

作者： Anisha Bhattacharya rulaiha e taylor Grace L Guo Department of Pharmacology and Toxicology Ernest Mario School of PharmacyRutgersThe State University of New JerseyPiscatawayNew JerseyUSA Rutgers Center for Lipid Research RutgersThe State University of New JerseyNew BrunswickNew JerseyUSA environmental and Occupational Health Sciences Institute RutgersThe State University of New JerseyPiscatawayNew JerseyUSA VA New Jersey Health Care System Veterans Administration Medical CenterEast OrangeNew JerseyUSA

The synthesis of bile acids(BAs)is carried out by complex pathways characterized by sequential chemical reactions in the liver through various cytochromes P450(CYP)and other enzymes.Maintaining the integrity of these pathways is crucial for normal physiological function in mammals,encompassing hepatic and neurological processes.Studying on the deficiencies in BA synthesis genes offers valuable insights into the significance of BAs in modulating farnesoid X receptor(FXR)signaling and metabolic homeostasis.By creating mouse knockout(KO)models,researchers can manipulate deficiencies in genes involved in BA synthesis,which can be used to study human diseases with BA dysregulation.These KO mouse models allow for a more profound understanding of the functions and regulations of genes responsible for BA synthesis.Furthermore,KO mouse models shed light on the distinct characteristics of individual BA and their roles in nuclear receptor signaling.Notably,alterations of BA synthesis genes in mouse models have distinct differences when compared to human diseases caused by the same BA synthesis gene deficiencies.This review summarizes several mouse KO models used to study BA synthesis and related human diseases,including mice deficient in Cyp7a1,Cyp27a1,Cyp7a1/Cyp27a1,Cyp8b1,Cyp7b1,Cyp2c70,Cyp2a12,and Cyp2c70/Cyp2a12,as well as germ-free mice.

关键词： Bile acid Species difference Farnesoid X receptor Liver diseases

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effects of intestine-specific deletion of fibroblast growth factor 15 on alcoholic liver disease development in mice

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Liver Research 2022年第2期6卷 84-92页

作者： Bo Kong Mingxing Huang rulaiha e.taylor Daniel Rizzolo Katherine D.Otersen Grace L.Guo Department of Pharmacology and Toxicology Ernest Mario School of PharmacyRutgersThe State University of New JerseyPiscatawayNJUSA Department of Infectious Diseases The Fifth Affiliated Hospital of Sun Yat-sen UniversityZhuhaiGuangdongChina environmental and Occupational Health Sciences Institute RutgersThe State University of New JerseyPiscatawayNJUSA Rutgers Center for Lipid Research RutgersThe State University of New JerseyPiscatawayNJUSA VA New Jersey Health Care System Veterans Administration Medical CenterEast OrangeNJUSA

Background and aims:Alcoholic liver disease(ALD)is an important and growing cause for the development of chronic liver diseases in the world.Bile acid(BA)levels are increased in patients with ALD anddysregulation of BA homeostasis worsens ALD.BA synthesis is critically regulated by fibroblast growthfactor(FGF)15 in mice and FGF19 in humans.FGF15/19 are mainly produced in the ileum and their mainfunction is to suppress BA synthesis in the liver through the activation of fibroblast growth factor receptor 4(FGFR4)on hepatocytes.The effects of intestine-specific Fgf15 deficiency on the development ofALD were determined in the current study.Methods:enterocyte-specific Fgf15 knockout mice(Fgf15intint^(-/-))and the established mouse model bychronic and binge ethanol feeding(NIAAA model)were adapted in this study.Results:The Fgf15intint^(-/-)mice had increased BA pool size,consistent with negative effects of FGF15-FGFR4signaling on BA synthesis.There were not obviously physical and hepatic histological abnormalitiespresented in Fgf15intint^(-/-)mice compared to wild-type mice.Following alcohol treatment,the Fgf15intint^(-/-)mice exhibited a higher degree of liver injury,increased hepatic expression of Cd14,a receptor forlipopolysaccharide expressed in the liver,and increased hepatic lipid levels.We did not observe alterations in the levels of fibrosis in the liver or expression of genes involved in hepatic fibrosis,regardless ofgenotypes or following the alcohol treatment.Conclusions:FGF15 may prevent hepatic steatosis in the development of ALD in mice,and maintainingFGF19/FGFR4 signaling may be critical in the prevention and/or treatment of ALD in humans in thefuture.

关键词： Fibroblast growth factor 15(FGF15) Farnesoid X receptor(FXR) Bile acid(BA) Alcoholic fatty liver disease Alcoholic steatohepatitis

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Attenuated retinoic acid signaling is among the early responses in mouse uterus approaching embryo attachment

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生殖与发育医学(英文) 2024年第1期08卷 61-65页

作者： Diao Honglu Xiao Shuo Zhou Tong Martin taylor e. Watford Wendy T. Ye Xiaoqin Department of Infectious Diseases Department of Physiology and Pharmacology College of Veterinary Medicine 3. University of Georgia 4. Athens 5. GA 30602 6. USA Department of Physiology and Cell Biology University of Nevada 9. Reno School of Medicine 10. Reno 11. NV 89557

The uterus is transiently receptive for embryo implantation. It remains to be understood why the uterus does not reject a semi-allogeneic embryo (to the biological mother) or an allogeneic embryo (to a surrogate) for implantation. To gain insights, we examined uterine early response genes approaching embryo attachment on day 3 post coitum (D3) at 22 hours when blue dye reaction, an indication of embryo attachment, had not manifested in mice. C57BL/6 pseudo-pregnant (control) and pregnant mouse uteri were collected on D3 at 22 hours for microarray analysis. The self-assembling-manifold (SAM) algorithm identified 21,858 unique probesets. Principal component analysis indicated a clear separation between the pseudo-pregnant and pregnant groups. There were 106 upregulated and five downregulated protein-coding genes in the pregnant uterus with fold change (fc) >1.5 andq value ene ontology (GO) analysis of the 106 upregulated genes revealed 38 significant GO biological process (GOBP) terms (P em were associated with immune responses, with a dominant natural killer (NK) cell activation signature. Among the top eight upregulated protein-coding genes,Cyp26a1 inactivates retinoic acid (RA) whileLrat promotes vitamin A storage, both of which are expected to attenuate RA bioavailability;Atp6v0d2 andGjb2 play roles in ion transport and transmembrane transport;Gzmb,Gzmc, andIl2rb are involved in immune responses; andTdo2 is important for kynurenine pathway. Most of these genes or their related pathways have functions in immune regulations. RA signaling has been implicated in immune tolerance and immune homeostasis, and uterine NK cells have been implicated in immunotolerance at the maternal-fetal interface in the placenta. The mechanisms of immune responses approaching embryo attachment remain to be elucidated. The coordinated effects of the early response genes may hold the keys to the question of why the uterus does not reject an implanting embryo.

关键词： embryo attachment Pseudo-pregnant uterus Pregnant uterus Natural killer cell activation signature Retinoic acid bioavailability Transmembrane transport and ion transport

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Ground-based and additional science support for SMILe

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earth and Planetary Physics 2024年第1期8卷 275-298页

作者： J.A.Carter M.Dunlop C.Forsyth K.Oksavik e.Donovon A.Kavanagh S.e.Milan T.Sergienko R.C.Fear D.G.Sibeck M.Connors T.Yeoman X.Tan M.G.G.T.taylor K.McWilliams J.Gjerloev R.Barnes D.D.Billet G.Chisham A.Dimmock M.P.Freeman D.-S.Han M.D.Hartinger S.-Y.W.Hsieh Z.-J.Hu M.K.James L.Juusola K.Kauristie e.A.Kronberg M.Lester J.Manuel J.Matzka I.McCrea Y.Miyoshi J.Rae L.Ren F.Sigernes e.Spanswick K.Sterne A.Steuwer T.Sun M.-T.Walach B.Walsh C.Wang J.Weygand J.Wild J.Yan J.Zhang Q.-H.Zhang Planetary Sciences Group School of Physics and AstronomyUniversity of LeicesterUniversity RoadLeicesterLE17RHUK Rutherford Appleton Laboratory Space Science Technology Facilities CouncilOxfordshireUK School of Space and environment Beihang UniversityBeijing 100191China Key Laboratory of Space environment Monitoring and Information Processing Ministry of Industry and Information TechnologyBeijing 100017China Department of Space and Climate Physics UCLMullard Space Science LaboratoryHolmbury St.MaryDorkingSurreyRH56NTUK Birkeland Centre for Space Science Department of Physics and Technology.University of BergenBergenNorway Department of Physics and Astronomy University of Calgary2500 University DriveCalgaryAlbertaCanada T2N 1N4 British Antarctic Survey CambridgeUK Swedish Institute of Space Physics KirunaSweden West Highfield Campus University of SouthamptonUniversity RoadSO171BJUK Goddard Space Flight Center NASAGreenbeltMarylandUSA Athabasca University AthabascaCanada eSTeC European Space AgencyNetherlands University of Saskatchewan SaskatoonCanada The Johns Hopkins University Applied Physics Laboratory LaurelMarylandUSA Swedish Institude of Space Physics UppsalaSE 75121Sweden Tongji University Shanghai 200092China Center for Space Plasma Physics Space Science Institute4765 Walnut Street Suite BBoulderColorado80301USA Polar Research Institute of China Shanghai 200136China Finnish Meteorological Institute(FMI) Finland Department of earth and environmental Sciences(Geophysics) Ludwig Maximilian University of Munich(LMU)MunichTheresienstr.41MunichD-80333Germany Canadian Space Agency MontrealCanada GFZ German Research Centre for Geosciences PotsdamGermany Nagoya University Institute for Space Earth Environment ResearchCenter for Integrated Data ScienceNagoyaAichiJP 464-8601 Northumbria University Newcastle upon TyneTyne and WearUK NE18ST National Space Science Center Chinese Academy SciencesBeijing 100190China Arctic Geophysics University Centre in Svalbard

The joint european Space Agency and Chinese Academy of Sciences Solar wind Magnetosphere Ionosphere Link explorer(SMILe)mission will explore global dynamics of the magnetosphere under varying solar wind and interplanetary magnetic field conditions,and simultaneously monitor the auroral response of the Northern Hemisphere ionosphere.Combining these large-scale responses with medium and fine-scale measurements at a variety of cadences by additional ground-based and space-based instruments will enable a much greater scientific impact beyond the original goals of the SMILe mission.Here,we describe current community efforts to prepare for SMILe,and the benefits and context various experiments that have explicitly expressed support for SMILe can offer.A dedicated group of international scientists representing many different experiment types and geographical locations,the Ground-based and Additional Science Working Group,is facilitating these efforts.Preparations include constructing an online SMILe Data Fusion Facility,the discussion of particular or special modes for experiments such as coherent and incoherent scatter radar,and the consideration of particular observing strategies and spacecraft conjunctions.We anticipate growing interest and community engagement with the SMILe mission,and we welcome novel ideas and insights from the solar-terrestrial community.

关键词： magnetosphere ionosphere magnetosphere-ionosphere coupling ground-based experimentation SMILe conjunctions missions

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Bile acid homeostasis in female mice deficient in Cyp7a1 and Cyp27a1

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Acta Pharmaceutica Sinica B 2021年第12期11卷 3847-3856页

作者： Daniel Rizzolo Bo Kong rulaiha e.taylora Anita Brinker Michael Goedken Brian Buckley Grace L.Guo Department of Pharmacology and Toxicology School of PharmacyRutgers UniversityPiscatawayNJ 08854USA environmental and Occupational Health Institute Rutgers UniversityPiscatawayNJ 08854USA Office of Research and economic Development Research Pathology ServicesRutgers UniversityPiscatawayNJ 08854USA Rutgers Center of Lipid Research Rutgers UniversityNew BrunswickNJ 08901USA Department of Veterans Affairs New Jersey Health Care System East OrangeNJ 07018USA

Bile acids(BAs) are amphipathic molecules important for metabolism of cholesterol,absorption of lipids and lipid soluble vitamins,bile flow,and regulation of gut microbiome.There are over 30 different BA species known to exist in humans and mice,which are endogenous modulators of at least 6 different membrane or nuclear receptors.This diversity of ligands and receptors play important roles in health and disease;however,the full functions of each individual BA in vivo remain unclear.We generated a mouse model lacking the initiating enzymes,CYP7 A1 and CYP27 A1,in the two main pathways of BA synthesis.Because females are more susceptible to BA related diseases,such as intrahepatic cholestasis of pregnancy,we expanded this model into female mice.The null mice of Cyp7 a1 and Cyp27 a1 were crossbred to create double knockout(DKO) mice.BA concentrations in female DKO mice had reductions in serum(63%),liver(83%),gallbladder(94%),and small intestine(85%),as compared to WT mice.Despite low BA levels,DKO mice had a similar expression pattern to that of WT mice for genes involved in BA regulation,synthesis,conjugation,and transport.Additionally,through treatment with a synthetic FXR agonist,GW4064,female DKO mice responded to FXR activation similarly to WT mice.

关键词： Bile acids Farnesoid X receptor Female Fibroblast growth factor 15 CYP7A1 CYP27A1

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Genome and clonal hematopoiesis stability contrasts with immune,cfDNA,mitochondrial,and telomere length changes during short duration spaceflight

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Precision Clinical Medicine 2024年第1期7卷 1-13页

作者： J.Sebastian Garcia-Medina Karolina Sienkiewicz S.Anand Narayanan eliah G.Overbey Kirill Grigorev Krista A.Ryon Marissa Burke Jacqueline Proszynski Braden Tierney Caleb M.Schmidt Nuria Mencia-Trinchant Remi Klotz Veronica Ortiz Jonathan Foox Christopher Chin Deena Najjar Irina Matei Irenaeus Chan Carlos Cruchaga Ashley Kleinman JangKeun Kim Alexander Lucaci Conor Loy Omary Mzava Iwijn De Vlaminck Anvita Singaraju Lynn e.taylor Julian C.Schmidt Michael A.Schmidt Kelly Blease Juan Moreno Andrew Boddicker Junhua Zhao Bryan Lajoie Andrew Altomare Semyon Kruglyak Shawn Levy Min Yu Duane C.Hassane Susan M.Bailey Kelly Bolton Jaime Mateus Christopher e.Mason Department of Physiology and Biophysics Weill Cornell MedicineCornell UniversityNew YorkNY 10021USA The HRH Prince Alwaleed Bin Talal Bin Abdulaziz Alsaud Institute for Computational Biomedicine Weill Cornell MedicineNew YorkNY 10021USA Department of Immunology Weill Cornell MedicineCornell UniversityNew YorkNY 10021USA Department of Stem Cell Biology and Regenerative Medicine Keck School of MedicineUniversity of Southern CaliforniaLos AngelesCA 90033USA Space exploration Technologies Corporation HawthomeCA 90250USA Sovaris Aerospace BoulderCO 80302USA Advanced Pattern Analysis&Human Performance Group BoulderCO 80302USA Children's Cancer and Blood Foundation Laboratories Departments of Pediatrics and Cell and Developmental BiologyDrukier Institute for Children's HealthMeyer Cancer CenterWeill Cornell MedicineNew YorkNY 10021USA Meyer Cancer Center Weill Cornell MedicineNew YorkNY 10065USA Department of Nutrition and Integrative Physiology Florida State UniversityTallahasseeFL 32306USA Department of Systems engineering Colorado State UniversityFort CollinsCO 80523USA element Biosciences San DiegoCA 10055USA Department of environmental and Radiological Health Sciences Colorado State UniversityFort CollinsCO 80523USA Cell and Molecular Biology Program Colorado State UniversityFort CollinsCO 80523USA BioAstra Inc New YorkNYUSA Washington University St Louis Oncology Division St.LouisMO 63100USA Meinig School of Biomedical engineering Cornell UniversityIthacaNY 14853USA The Feil Family Brain and Mind Research Institute Weill Cornell MedicineNY 10021USA WorldQuant Initiative for Quantitative Prediction Weill Cornell MedicineNew YorkNY 10021USA

Background The Inspiration4(I4)mission,the first all-civilian orbital flight mission,investigated the physiological effects of short-duration spaceflight through a multi-omic approach.Despite advances,there remains much to learn about human adaptation to spaceflight's unique challenges,including microgravity,immune system perturbations,and radiation exposure.Methods To provide a detailed genetics analysis of the mission,we collected dried blood spots pre-,during,and post-flight for DNA extraction.Telomere length was measured by quantitative PCR,while whole genome and cfDNA sequencing provided insight into genomic stability and immune adaptations.A robust bioinformatic pipeline was used for data analysis,including variant calling to assess mutational burden.Result Telomere elongation occurred during spaceflight and shortened after return to earth.Cell-free DNA analysis revealed increased immune cell signatures post-flight.No significant clonal hematopoiesis of indeterminate potential(CHIP)or whole-genome instability was observed.The long-term gene expression changes across immune cells suggested cellular adaptations to the space environment persisting months post-flight.Conclusion Our findings provide valuable insights into the physiological consequences of short-duration spaceflight,with telomere dynamics and immune cell gene expression adapting to spaceflight and persisting after return to earth.CHIP sequencing data will serve as a reference point for studying the early development of CHIP in astronauts,an understudied phenomenon as previous studies have focused on career astronauts.This study will serve as a reference point for future commercial and non-commercial spaceflight,low earth orbit(LeO)missions,and deep-space exploration.

关键词： genomes clonal hematopoiesis stability immune mitochondria ribosomes spaceflight

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Species diversity in restoration plantings: Important factors for increasing the diversity of threatened tree species in the restoration of the Araucaria forest ecosystem

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Plant Diversity 2019年第2期41卷 84-93页

作者： taylor e.Shaw School of Biological Sciences University of East Anglia Norwich Research Park

The Araucaria forest ecosystem in southern Brazil is highly threatened: less than one percent of the original forest remains, and what is left is a fragmented agro-mosaic of mostly early-to-late secondary forest patches among high-yield agriculture and timber monocultures. Forest restoration initiatives in this region aim to restore degraded areas, however the limited number of species used in restoration projects represents a missed opportunity for species-rich plantings. High diversity plantings represent a larger number of functional groups and provide a targeted conservation strategy for the high number of threatened species within this ecosystem. This study interviewed nurseries(Ns) and restoration practitioners(RPs) in Parana and Santa Catarina states to identify what species are being cultivated and planted, and what factors are driving the species selection process. An average of 20 species were reportedly used in restoration plantings, most of which are common, widespread species. Baseline data confirms that Ns and RPs have disproportionately low occurrences of threatened species in their inventories and plantings, supporting findings from previous research. Questionnaire responses reveal that opportunities for seed acquisition are an extremely important factor in order for nurseries to increase their diversity of cultivated species. Results also suggest that facilitating speciesrich plantings for restoration practitioners would only be feasible if it did not increase the time required to complete planting projects, as it would minimize their ability to keep costs low. This study proposes solutions for increasing the number of species used in restoration practicedsuch as developing a comprehensive species list, fostering knowledge-sharing between actors, creating seed sharing programs, and increasing coordination of planting projects. Long-term strategies involve complimenting traditional ex situ approaches with emerging inter-situ and quasi in situ conservation strategies which simultaneously provide lo

关键词： Restoration Araucaria forest Threatened species Nurseries Restoration practitioners Decision-making

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Bidirectional relationships of physical activity and gross motor skills before and after summer break:Application of a cross-lagged panel model

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Journal of Sport and Health Science 2022年第2期11卷 244-251页

作者： Ryan D.Burns Yang Bai Wonwoo Byun taylor e.Colotti Christopher D.Pfledderer Sunku Kwon Timothy A.Brusseau Department of Health Kinesiologyand RecreationUniversity of UtahSalt Lake CityUT 84112USA

Background:Gross motor skills are postulated to have a bidirectional relationship with physical activity(PA);however,no study has tested this relationship before and after a summer break.The purpose of this study was to examine the bidirectional relationships between school PA and gross motor skills in children before and after a summer break.Methods:Participants were a sample of 440 children recruited from 3 low-income schools(age=8.9±1.2 years,mean±SD).PA was assessed as average school-day step counts using Yamax DigiWalker pedometers(Yamasa Tokei Keiki,Tokyo,Japan)worn for 5 consecutive school days.Gross motor skills were assessed using the Test for Gross Motor Development,3 rd edition.Data were collected at 2 timepoints:at the end of spring semester(T1)and at the beginning of the subsequent fall semester(T2).An age-and body mass index-adjusted cross-lagged model was employed to relate T1 school step counts with T2 gross motor skills and T1 gross motor skills with T2 school step counts.Results:T1 gross motor skills significantly predicted T2 school step counts(β=0.24,95%confidence interval(95%CI):0.08-0.40,p=0.003);however,Tl school step counts did not predict T2 gross motor skills(β=0.04,95%CI:-0.06 to 0.14,p=0.445).The model explained 35.4%and 15.9%of the variances of T2 gross motor skills and T2 school step counts,respectively.Additional analyses indicated that these relationships were driven primarily by ball skills.Conclusion:The relationship between gross motor skills and school PA was not bidirectional;however,higher gross motor skills,specifically ball skills,predicted higher school PA after a 3-month summer break.

关键词： Children Motor competence Physical activity Schools

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Keeping an ear out:size relationship of the tympanic bullae and pinnae in bandicoots and bilbies(Marsupialia:Peramelemorphia)

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Current Zoology 2022年第3期68卷 251-264页

作者： Melissa C.taylor Kenny J.TRAVOUILLON Margaret e.ANDReW Patricia A.FLeMING Natalie M.WARBURTON Terrestrial ecosystem Science and Sustainability Harry Butler InstituteMurdoch University90 South StMurdochWA 6150Australia Collections and Research Western Australian MuseumWelshpoolWA 6106Australia

Bandicoots and bilbies(Order Peramelemorphia)occupy a broad range of habitats across Australia and New Guinea,from open,arid deserts to dense forests.This once diverse group has been particularly vulnerable to habitat loss and introduced eutherian predators,and numerous species extinctions and range retractions have occurred.Understanding reasons for this loss requires greater understanding of their biology.Morphology of the pinnae and tympanic bullae varies markedly among species.As hearing is important for both predator avoidance and prey location,the variability in ear morphology could reflect specialization and adaptation to specific environments,and therefore be of conservation relevance.We measured 798 museum specimens representing 29 species of Peramelemorphia.Controlling for phylogenetic relatedness and head length,pinna surface area was weakly negatively correlated with average precipitation(rainfall being our surrogate measure of vegetation productivity/complexity),and there were no environmental correlates with effective diameter(pinna width).Controlling for phylogenetic relatedness and skull length,tympanic bulla volume was negatively correlated with precipitation.Species that inhabited drier habitats,which would be open and allow sound to carry further with less obstruction,had relatively larger pinnae and tympanic bullae.In contrast,species from higher rainfall habitats,where sounds would be attenuated and diffused by dense vegetation,had the smallest pinnae and bullae,suggesting that low-frequency hearing is not as important in these habitats.Associations with temperature did not reach statistical significance.These findings highlight linkages between hearing traits and habitat that can inform conservation and management strategies for threatened species.

关键词： external ear hearing ecology marsupial middle ear sound perception

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Kinetics of hydrogen peroxide quenching following UV/H_(2)O_(2)advanced oxidation by thiosulfate,bisulfite,and chlorine in drinking water treatment

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Frontiers of environmental Science & engineering 2023年第12期17卷 59-69页

作者： Tianyi Chen Lizbeth taylor-edmonds Susan Andrews Ron Hofmann Department of Civil and Mineral engineering University of TorontoTorontoOntario M5S 1A4Canada

Residual H_(2)O_(2)from UV/H_(2)O_(2)treatment can be quenched by thiosulfate,bisulfite,and chlorine,but the kinetics of these reactions have not been reported under the full range of practical conditions.In this study,the rates of H_(2)O_(2)quenching by these compounds were compared in different water matrices,temperatures,pH,and when using different forms of bisulfite and chlorine.In general,it was confirmed that thiosulfate would be too slow to serve as a quenching agent in most practical scenarios.At pH 7-8.5,chlorine tends to quench H_(2)O_(2)more than 20 times faster than bisulfite in the various conditions tested.An important observation was that in lightly-buffered water(e.g.,alkalinity of 20 mg/L as CaCO_(3)),the form of chlorine can have a large impact on quenching rate,with gaseous chlorine slowing the reaction due to its lowering of the pH,and hypochlorite having the opposite effect.These impacts will become less significant when water buffer capacity(i.e.,alkalinity)increases(e.g.,to 80 mg/L as CaCO_(3)).In addition,water temperature should be considered as the time required to quench H_(2)O_(2)by chlorine at 4℃is up to 3 times longer than at 20℃.

关键词： UV/H_(2)O_(2) H_(2)O_(2) quenching Chlorine type Water alkalinity Temperature

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