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In vivo mouse models to study bile acid synthesis and signaling

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Hepatobiliary & Pancreatic Diseases International 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 *** the integrity of these pathways is crucial for normal physiological function in mammals,encompassing hepatic and neurological *** on the deficiencies in BA synthesis genes offers valuable insights into the significance of BAs in modulating farnesoid X receptor(FXr)signaling and metabolic *** 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 *** KO mouse models allow for a more profound understanding of the functions and regulations of genes responsible for BA ***,KO mouse models shed light on the distinct characteristics of individual BA and their roles in nuclear receptor ***,alterations of BA synthesis genes in mouse models have distinct differences when compared to human diseases caused by the same BA synthesis gene *** 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

early calcium dysregulation in Alzheimer's disease:setting the stage for synaptic dysfunction

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Science China(Life Sciences) 2011年第8期54卷 752-762页

作者： Shreaya CHAKrOBOrTY grace e.STUTZMANN Department of Neuroscience Rosalind Franklin University/the Chicago Medical School

Alzheimer's disease(AD) is an irreversible and progressive neurodegenerative disorder with no known cure or clear understanding of the mechanisms involved in the disease *** plaques,neurofibrillary tangles and neuronal loss,though characteristic of AD,are late stage markers whose impact on the most devastating aspect of AD,namely memory loss and cognitive deficits,are still *** studies demonstrate that structural and functional breakdown of synapses may be the underlying factor in AD-linked cognitive *** common element that presents with several features of AD is disrupted neuronal calcium *** intracellular calcium levels are functionally linked to presenilin mutations,Apoe4 expression,amyloid plaques,tau tangles and synaptic *** this review,we discuss the role of AD-linked calcium signaling alterations in neurons and how this may be linked to synaptic dysfunctions at both early and late stages of the disease.

关键词： calcium Alzheimer's neuron synaptic dysfunction plasticity er ryanodine CICr

Antiplasmodial and analgesic activities of Clausena anisata

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Asian Pacific Journal of Tropical Medicine 2012年第3期5卷 214-219页

作者： Jude e Okokon ette O etebong John A Udobang grace e essien Department of Pharmacology and Toxicology Faculty of PharmacyUniversity of UyoUyoNigeria

Objective:Antiplasmodial and analgesic activities of the leaf extract and fractions of Clausena anisata(***) were evaluated for antimalarial and analgesic ***:The crude leaf extract(39-117mg/kg) and fractions(chloroform and acqeous;78mg/kg) of C. anisata were investigated for antiplasmodial activity against chloroquine-sensitive Plasmodium berghei(***) infections in mice using suppressive,prophylactic and curative models and analgesic activity against acetic acid,formalin and heat-induced ***,5 mg/kg and pyrimethamine,1.2mg/kg were used as positive *** films made from tail blood of each mouse were used to assess the level of parasitaemia of the ***:The extract and its fractions dose-dependently reduced parasitaemia induced by chloroquine-sensitive *** in prophylactic,suppressive and curative models in *** reductions were statistically significant(Pey also improved the mean survival time(MST) from 17 to 21 days relative to control(Pemically and thermally-induced pains,the extract inhibited acetic acid and formalin-induced inflammation as well as hot plate-induced pain in *** inhibitions were statistically significant(Pe-dependent fashion. Conclusions:The antiplasmodial and analgesic effects of this plant may in part be mediated through its chemical constituents and it can be concluded that the *** possess significant antimalarial and analgesic properties.

关键词： Clausena anisata antiplasmodial antimalarial analgesic

Tribo-charging of binary mixtures composed of coarse and fine particles in gas-solid pipe flow

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Particuology 2019年第2期17卷 101-109页

作者： Haifeng Wang Farzam Fotovat Xiaotao T. Bi John r. grace Department of Chemical engineering China University of Mining and Technology. Xuzliou 221166 China Department of Chemical and Petroleum engineering Sharif University of Technology Azadi Avenue P.O. Box 11365-9465 Tehran Iran Fluidization research Centre Department of Chemical and Biological Engineering University of British Columbia. Vancouver V6T 1Z3 Canada

experiments were conducted to investigate the effect of adding fines on the tribo-charging of coarse glass beads. Four types of fines, i.e., copper, stainless steel, uncoated and silver-coated fine glass beads, mixed w让h 240-830 μm glass beads were conveyed by air through a stainless-steel spiral pipe acting as a tribo-charger. regardless of the type or electrical conductivity of the fine particles tested, adding small amounts of fines (up to 10wt%) to coarse glass beads resulted in a sharp increase in the mass and surface charge densities of the particles. In gen eral, the profiles of the mass and surface charge den sides of the fine-coarse particle mixtures as a function of the mixture composition were determined by the relative magnitude of contact potential differences and the total surface areas of all the comp on ents. The domi nant particle tri bo-electrification mecha nism switched from coarse particle-wall con tacts to fine particle-wall contacts when the fines weight percentage in the mixture exceeded 10%. A model was developed to predict the mass charge density of bi nary mixtures as a function of the mixture composition.

关键词： Tribo-charging electrostatics Fine particles Binary mixture Gas-solid flow

Propagation of TDP-43 proteinopathy in neurodegenerative disorders

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Neural regeneration research 2022年第7期17卷 1498-1500页

作者： rachel Keszycki Pouya Jamshidi Allegra Kawles grace Minogue Margaret e.Flanagan Colleen r.Zaccard M-Marsel Mesulam Tamar Gefen Changiz Geula Mesulam Center for Cognitive Neurology and Alzheimer’s Disease Feinberg School of MedicineNorthwestern UniversityChicagoILUSA Department of Psychiatry and Behavioral Sciences Feinberg School of MedicineNorthwestern UniversityChicagoILUSA Department of Pathology Feinberg School of MedicineNorthwestern UniversityChicagoILUSA Department of Physiology Feinberg School of MedicineNorthwestern UniversityChicagoILUSA Department of Cell and Developmental Biology Feinberg School of MedicineNorthwestern UniversityChicagoILUSA

Neurodegenerative disorders are characterized by disruptions to neuronal function and circuitry,leading to a variety of clinical syndromes depending on the affected neuroanatomic regions(Geula,1998).Many proteinopathies implicated in neurodegenerative diseases are characterized by the pathologic accumulation of proteins into inclusions that are initially deposited in specific areas of the brain and spread widely with disease progression.

关键词： degenerative disorders clinical

The IBI1 receptor ofβ-Aminobutyric Acid Interacts with VOZ Transcription Factors to regulate Abscisic Acid Signaling and Callose-Associated Defense

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Molecular Plant 2020年第10期13卷 1455-1469页

作者： roland e.Schwarzenbacher grace Wardell Joost Stassen emily Guest Peijun Zhang estrella Luna Jurriaan Ton P3 Institute for Plant and Soil Biology Department of Animal and Plant SciencesThe University of SheffieldSheffield S102TNUK School of Biosciences University of BirminghamBirmingham B152TTUK

extemal and internal signals can prime the plant immune system for a faster and/or stronger response to pathogen attack.β-aminobutyric acid(BABA)is an endogenous stress metabolite that induces broad-spectrum disease resistance in *** perception in Arabidopsis is mediated by the aspartyl trNA synthetase IBI1,which activates priming of multiple immune responses,including callose-associated cell wall defenses that are under control by abscisic acid(ABA).However,the immediate signaling components after BABA perception by IBI1,as well as the regulatory role of ABA therein,remain ***,we have studied the early signaling events controlling IBI1-dependent BABA-induced resistance(BABAIr),using untargeted transcriptome and protein interaction *** analysis revealed that IBI1-dependent expression of BABA-Ir against the biotrophic oomycete Hyaloperonospora arabidopsidis is associated with suppression of ABA-inducible abiotic stress *** interaction studies identified the VOZ1 and VOZ2 transcription factors(TFs)as IBI1-interacting partners,which are transcrip-tionally induced by ABA but suppress pathogen-induced expression of ABA-dependent ***,we show that VOZ TFs require nuclear localization for their contribution to BABA-Ir by mediating augmented expression of callose-associated ***,our study indicates that the IBI1-VOZ signaling module channels pathogen-induced ABA signaling toward cell wall defense while simultaneously suppressing abiotic stress-responsive genes.

关键词： IBI1 priming abscisic acid β-aminobutyric acid callose e-MTAB-8720

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 *** 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 *** diversity of ligands and receptors play important roles in health and disease;however,the full functions of each individual BA in vivo remain *** generated a mouse model lacking the initiating enzymes,CYP7 A1 and CYP27 A1,in the two main pathways of BA *** females are more susceptible to BA related diseases,such as intrahepatic cholestasis of pregnancy,we expanded this model into female *** null mice of Cyp7 a1 and Cyp27 a1 were crossbred to create double knockout(DKO) *** concentrations in female DKO mice had reductions in serum(63%),liver(83%),gallbladder(94%),and small intestine(85%),as compared to WT *** low BA levels,DKO mice had a similar expression pattern to that of WT mice for genes involved in BA regulation,synthesis,conjugation,and ***,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

Fluid-rock interaction experiments with andesite at 100℃ for potential carbon storage in geothermal reservoirs

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Deep Underground Science and engineering 2024年第3期3卷 369-382页

作者： grace e.Belshaw elisabeth Steer Yukun Ji Herwin Azis Benyamin Sapiie Bagus Muljadi Veerle Vandeginste School of Chemistry University of NottinghamNottinghamUK Geoenergy research Centre University of NottinghamNottinghamUK British Geological Survey KeyworthUK State Key Laboratory of Intelligent Construction and Healthy Operation and Maintenance of Deep Underground engineering China University of Mining and TechnologyXuzhouChina PT Supreme energy JakartaIndonesia Faculty of earth Sciences and Technology Institut Teknologi BandungBandungIndonesia Faculty of engineering University of NottinghamNottinghamUK Department of Materials engineering KU LeuvenCampus BrugesBrugesBelgium

Geothermal energy extraction often results in the release of naturally occurring carbon dioxide(CO_(2))as a *** on carbon storage using volcanic rock types other than basalt under both acidic and elevated temperature conditions has been limited so *** study uses batch reactor experiments at 100℃ to investigate the dissolution of andesite rock samples obtained from an active geothermal reservoir in Sumatra(Indonesia).The samples are subjected to reactions with neutral-pH fluids and acidic fluids,mimicking the geochemical responses upon reinjection of geothermal fluids,either without or with dissolved acidic gases,*** elemental analysis reveals the release of Ca^(2+)ions into the fluids through the dissolution of *** overall dissolution rate of the rock samples is 2.4×10^(–11)to 4.2×10^(–11)mol/(m^(2)·s),based on the Si release during the initial 7 h of the *** dissolution rates are about two orders of magnitude lower than those reported for basaltic rocks under similar reaction *** study offers valuable insights into the potential utilization of andesite reservoirs for effective CO_(2) storage via mineralization.

关键词： andesite carbon sequestration geothermal reservoirs plagioclase dissolution

Morpho-anatomical characterization of rhododendron subsessile rendle,an endangered species of the Cordillera Central range,Philippines

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Journal of Forestry research 2021年第1期32卷 241-247页

作者： Mabel grace V.Bitayan Starleene S.Cervantes Jones T.Napaldet College of Teacher education Benguet State UniversityLa TrinidadBenguetPhilippines Biology Department College of Arts and SciencesBenguet State UniversityLa TrinidadBenguetPhilippines

Conservation of endangered plant species requires a prerequisite basic knowledge of their taxonomy and *** in the Cordillera Central range,several species have not been studied,even though this area harbors a unique type of vegetation not found in other parts of the *** study documents the morpho-anatomical characteristics of rhododendron subsessile rendle,one of the unique and endangered fl ora in the *** species exhibits a morphology typical of plants in high elevations,being a hardy shrub with small tough leaves,and showy pink fl owers that rival those of commercial rhododendron *** fi ndings on the species morphology include a variable number of corolla lobes,stamens and a description of its fruits and *** anatomical features of the species are reported here for the fi rst *** plant exhibits a typical dicot anatomy with dorsiventral leaves,woody stem and root system with the usual arrangement of periderm followed by secondary phloem,vascular cambium,secondary xylem with vessel elements and pith(in the case of the stem).A unique characteristic was identifi ed as the biseriate upper epidermis of the *** themorphological and anatomical features of the species should prove valuable as input baseline information in formulating measures for its conservation.

关键词： Taxonomy Biodiversity conservation Biseriate epidermis Variable stamens