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Molecular regulation of calcium-sensing receptor(CaSR)-mediated signaling

Chronic Diseases and Translational Medicine 2024年第3期10卷 167-194页

作者： Li Tian Corey Andrews Qiuyun Yan jenny j.yang Department of Chemistry Center for Diagnostics and TherapeuticsAdvanced Translational Imaging FacilityGeorgia State UniversityAtlantaGeorgiaUSA

Calcium-sensing receptor(CaSR),a family C G-protein-coupled receptor,plays a crucial role in regulating calcium homeostasis by sensing small concentration changes of extracellular Ca^(2+),Mg^(2+),amino acids(e.g.,L-Trp and L-Phe),small peptides,anions(e.g.,HCO_(3)^(-)and PO_(4)^(3-)),and ***-mediated intracellular Ca^(2+)signaling regulates a diverse set of cellular processes including gene transcription,cell proliferation,differentiation,apoptosis,muscle contraction,and neuronal *** of CaSR with mutations results in diseases such as autosomal dominant hypocalcemia,familial hypocalciuric hypercalcemia,and neonatal severe *** also influences calciotropic disorders,such as osteoporosis,and noncalciotropic disorders,such as cancer,Alzheimer's disease,and pulmonary arterial *** study first reviews recent advances in biochemical and structural determination of the framework of CaSR and its interaction sites with natural ligands,as well as exogenous positive allosteric modulators and negative allosteric *** establishment of the first CaSR protein-protein interactome network revealed 94 novel players involved in protein processing in endoplasmic reticulum,trafficking,cell surface expression,endocytosis,degradation,and signaling *** roles of these proteins in Ca^(2+)-dependent cellular physiological processes and in CaSR-dependent cellular signaling provide new insights into the molecular basis of diseases caused by CaSR mutations and dysregulated CaSR activity caused by its protein interactors and facilitate the design of therapeutic agents that target CaSR and other family C G-protein-coupled receptors.

关键词： calcium signaling calcium-sensing receptor G-protein-coupled receptors structure trafficking

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The hills and valleys of calcium signaling

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Science China(Life Sciences) 2016年第8期59卷 743-748页

作者： Michael X.Zhu Biguang Tuo jenny j.yang Department of Integrative Biology and Pharmacology Mc Govern Medical School The University of Texas Health Science Center at Houston Department of Gastroenterology Affiliated Hospital Zunyi Medical College and Digestive Disease Institute of Guizhou Province Department of Chemistry Center for Diagnostics and Therapeutics Georgia State University

Calcium is important for *** over the last several decades have gradually revealed the critical involvement of calcium,especially its ionic form(Ca^(2+)),in every aspect of life forms on *** them,a great deal of work has been done to illustrate how Ca2+levels are regulated in the cytoplasm and how many of the cytosolic enzymes and sig-

关键词： Ca The hills and valleys of calcium signaling

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Role of lysosomal trafficking regulator in autophagic lysosome reformation in neurons:a disease perspective

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Neural Regeneration Research 2024年第5期19卷 957-958页

作者： Prashant Sharma jenny Serra-Vinardell Wendy j.Introne May Christine V.Malicdan NIH Undiagnosed Diseases Program Common FundOffice of the DirectorNational Institutes of HealthBethesdaMDUSA Human Biochemical Genetics Section Medical Genetics BranchNational Human Genome Research InstituteNational Institutes of HealthBethesdaMDUSA(Serra-Vinardell JIntrone)

Lysosomes are discrete organelles that act as recycling centers for extracellular and intracellular materials,playing a pivotal role in maintaining cellular *** acidic environment,maintained by numerous hydrolytic enzymes,facilitates substrate *** in lysosomal processes can lead to abnormal substrate degradation,significantly impacting cellular *** energy-demanding cells,such as post-mitotic neurons,are especially vulnerable to these changes,often resulting in neurological ***,a conserved catabolic process,requires extensive lysosomal *** plays a key role in removing unnecessary intracellular components,ensuring cellular homeostasis,and promoting cell survival during stress conditions such as starvation,infection,or cellular damage.

关键词： homeostasis lysosomal removing

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Design and Application of a Novel Class of Sensors to Monitor Ca2+ Fast Dynamics

Design and Application of a Novel Class of Sensors to Monito...

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第九届全国钙信号和细胞功能研讨会

作者： Florence Reddish Hing-Cheung Wong Irene Weber Giovanni Gadda Osvaldo Delbono Kyril Solntsev jenny j.yang Department of Chemistry Center for Diagnostics and TherapeuticsGeorgia State UniversityAtlantaGA 30303 Department of Chemistry Center for Diagnostics and TherapeuticsGeorgia State UniversityAtlantaGA 30303 Department of Internal Medicine Section on Gerontology and Geriatric Medicine.Wake Forest University School of MedicineWinston-SalemNC 27157 Shcool of Chemistry and Biochemistry Georgia Institute of TechnologyAtlantaGA 30332

A maior barrier to understanding specific spatio-temporal patterns of intracellular Ca signaling is the lack of targetable sensors with desire kinetic,metal selectivity, and optical properties to measure Ca dynamics at specific cellular environments such as ER/SR for fast Ca transients including EC coupling and neuron *** lab has created a novel class of genetically encoded Ca indicators using enhanced green fluorescent protein(EGFP)and the red fluorescent protein mCherry aided by several of our developed computational *** of them,CatchER(Calcium

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Impact of inorganic and organic pollutants from a Belgian wastewater treatment plant on adjacent surface and groundwaters

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Frontiers of Environmental Science & Engineering 2024年第4期18卷 75-90页

作者： Mingyue Luo Yiqi Su Delphine jenny Vandeputte Yuwei jia Guanlei Li Willy Baeyens Marijke Huysmans Marc Elskens Yue Gao Analytical Environmental and Geo-Chemistry Department(AMGC)Vrije Universiteit Brussel(VUB)Pleinlaan 21050 BrusselsBelgium Hydrology and Hydraulic Engineering(HYDR) Vrije Universiteit Brussel(VUB)Pleinlaan 21050 BrusselsBelgium

Under the pressure of global droughts and water shortage,it is essential to evolve toward a sustainable and robust water *** possible avenue is the maximum reuse of treated wastewater,but the quality of which determines its ***,inorganic(Cd,Pb,Cr,Ni,Cu,and As)and organic(xenoestrogens and polycyclic aromatic contaminants,PACs)contaminants were monthly monitored in an effluent of the wastewater treatment plant(WWTP),the surrounding surface waters and the local groundwater in *** and particulate concentrations of inorganic contaminants in these water bodies were *** addition,Diffusive Gradients in Thin-films(DGT)was used in situ to obtain bioavailable metal *** the WWTP effluent and surface waters,only Ni exceeds the Annual Average-Environmental Quality Standard(AA-EQS),while in the groundwater,dissolved As was the predominant ***,in the surface and effluent waters the highest lability degrees were observed for Cd and *** concentrations of these metal species in the effluent water were lower than in the other water ***-organic pollutants,xenoestrogens and PACs were analyzed by dual Estrogen and Aryl hydrocarbon Receptor-Chemical Activated LUciferase gene eXpression(ER&AhR-CALUX)*** the annual averaged(AA)bioequivalent concentration of E2(0.18 ng/L)is below the AA-EQS standard(0.4 ng/L),and the bioequivalent concentration of benzo[a]pyrene never exceeded the maximum admissible concentration(MAC),the reclamation and reuse of treated wastewater for groundwater replenishment and agricultural irrigation should pose no environmental problems,at least in a short-term.

关键词： Metal contaminants DGT Labile metal fractions ERE/AhR-CALUX BEQ Xenoestrogens and polycyclic aromatic contaminants

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A functional tacrolimus-releasing nerve wrap for enhancing nerve regeneration following surgical nerve repair

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Neural Regeneration Research 2025年第1期20卷 291-304页

作者： Simeon C.Daeschler Katelyn j.W.So Konstantin Feinberg Marina Manoraj jenny Cheung jennifer Zhang Kaveh Mirmoeini jPaul Santerre Tessa Gordon Gregory HBorschel SickKids Research Institute Neuroscience and Mental Health ProgramTorontoONCanada Institute of Biomaterials and Biomedical Engineering University of TorontoTorontoONCanada Indiana University School of Medicine IndianapolisINUSA Division of Plastic and Reconstructive Surgery the Hospital for Sick ChildrenTorontoONCanada Translational Biology and Engineering Program Ted Rogers Centre for Heart ResearchInstitute of Biomedical EngineeringFaculty of DentistryUniversity of TorontoTorontoONCanada

Axonal regeneration following surgical nerve repair is slow and often incomplete,resulting in poor functional recovery which sometimes contributes to lifelong ***,there are no FDA-approved therapies available to promote nerve *** accelerates axonal regeneration,but systemic side effects presently outweigh its potential benefits for peripheral nerve *** authors describe herein a biodegradable polyurethane-based drug delivery system for the sustained local release of tacrolimus at the nerve repair site,with suitable properties for scalable production and clinical application,aiming to promote nerve regeneration and functional recovery with minimal systemic drug *** is encapsulated into co-axially electrospun polycarbonate-urethane nanofibers to generate an implantable nerve wrap that releases therapeutic doses of bioactive tacrolimus over 31 *** and drug loading are adjustable for applications in small and large caliber nerves,and the wrap degrades within 120 days into biocompatible *** released from the nerve wrap promotes axon elongation in vitro and accelerates nerve regeneration and functional recovery in preclinical nerve repair models while off-target systemic drug exposure is reduced by 80%compared with systemic *** its surgical suitability and preclinical efficacy and safety,this system may provide a readily translatable approach to support axonal regeneration and recovery in patients undergoing nerve surgery.

关键词： biodegradable local drug delivery nerve injury nerve regeneration nerve wrap tacrolimus

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Iodoacetic acid exposure alters the transcriptome in mouse ovarian antral follicles

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journal of Environmental Sciences 2022年第7期34卷 46-57页

作者： Andressa Gonsioroski Mary Laws Vasiliki E.Mourikes Alison Neff jenny Drnevich Michael j.Plewa jodi A.Flaws Department of Comparative Biosciences University of Illinois Urbana-ChampaignUrbanaIllinois 61801USA Roy j.Carver Biotechnology Center University of Illinois Urbana-ChampaignUrbanaIllinois 61801USA Department of Crop Sciences and the Safe Global Water Institute University of Illinois Urbana-ChampaignUrbanaIllinois 61801USA

Iodoacetic acid(IAA) is an unregulated water disinfection byproduct that is an ovarian toxicant. However, the mechanisms of action underlying IAA toxicity in ovarian follicles remain unclear. Thus, we determined whether IAA alters gene expression in ovarian follicles in mice. Adult female mice were dosed with water or IAA(10 or 500 mg/L) in the water for 35-40 days. Antral follicles were collected for RNA-sequencing analysis and sera were collected to measure estradiol. RNA-sequencing analysis identified 1063 differentially expressed genes(DEGs) in the 10 and 500 mg/L IAA groups(false discovery rate FDR < 0.1), respectively, compared to controls. Gene Ontology Enrichment analysis showed that DEGs were involved with RNA processing and regulation of angiogenesis(10 mg/L) and the cell cycle and cell division(500 mg/L). Pathway Enrichment analysis showed that DEGs were involved in the phosphatidylinositol 3-kinase and protein kinase B(PI3K-Akt), gonadotropin-releasing hormone(Gn RH), estrogen, and insulin signaling pathways(10 mg/L). Pathway Enrichment analysis showed that DEGs were involved in the oocyte meiosis, Gn RH, and oxytocin signaling pathways(500 mg/L). RNA-sequencing analysis identified 809 DEGs when comparing the 500 and 10 mg/L IAA groups(FDR < 0.1). DEGs were related to ribosome, translation, m RNA processing, oxidative phosphorylation, chromosome, cell cycle, cell division, protein folding, and the oxytocin signaling pathway. Moreover, IAA exposure significantly decreased estradiol levels(500 mg/L) compared to control. This study identified key candidate genes and pathways involved in IAA toxicity and can help to further understand the molecular mechanisms of IAA toxicity in ovarian follicles.

关键词： Disinfection byproducts Iodoacetic acid Ovary Ovarian follicles Steroidogenesis Endocrine disruptors

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The calcium sensing receptor: from calcium sensing to signaling

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Science China(Life Sciences) 2015年第1期58卷 14-27页

作者： ZHANG Chen MILLER Cassandra Lynn BROWN Edward M yang jenny j. Department of Chemistry Georgia State University Center for Diagnostics and Therapeutics Georgia State University Division of Endocrinology Diabetes and HypertensionDepartment of MedicineBrigham and Women's Hospital

The Ca2+-sensing receptor(the Ca SR),a G-protein-coupled receptor,regulates Ca2+ homeostasis in the body by monitoring extracellular levels of Ca2+([Ca2+]o) and responding to a diverse array of *** in the Ca2+-sensing receptor result in hypercalcemic or hypocalcemic disorders,such as familial hypocalciuric hypercalcemia,neonatal severe primary hyperparathyroidism,and autosomal dominant hypocalcemic *** evidence suggests that the Ca SR plays multiple roles extending well beyond not only regulating the level of extracellular Ca2+ in the human body,but also controlling a diverse range of biological *** this review,we focus on the structural biology of the Ca SR,the ligand interaction sites as well as their relevance to the disease associated *** systematic summary will provide a comprehensive exploration of how the Ca SR integrates extracellular Ca2+ into intracellular Ca2+ signaling.

关键词： G蛋白偶联受体低血钙症敏感信令高钙血症结构生物学甲状旁腺常染色体

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Multi-Institutional US Experience of the Occlutech AFR Device in Congenital and Acquired Heart Disease

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Congenital Heart Disease 2022年第1期17卷 107-116页

作者： Barry O’Callaghan jenny Zablah joseph Vettukattil Daniel Levi Morris Salem Allison Cabalka jason Anderson Makram Ebeid Ryan Alexy Gareth j.Morgan The Heart Institute Children’s Hospital ColoradoAuroraUSA Pediatric Cardiology Helen DeVos Children’s HospitalGrand RapidsUSA Pediatric Cardiology UCLA HealthMattel Children’s HospitalLos AngelesUSA Pediatric Cardiology UCLA Medical CentreLos AngelesUSA Pediatric Cardiology Mayo ClinicRochesterUSA Pediatric Cardiology University of Mississippi Medical CenterJacksonUSA Pediatric Cardiology Riley Hospital for Children at Indiana University HealthIndianapolisUSA

Objectives:To detail the US multi-institutional experience with the Occlutech©(Occlutech International AB,Helsingborg,Sweden)atrial flow regulator(AFR)in children and adults with acquired or congenital heart ***:The creation of a long-term atrial communication is desirable in several cardiovascular disease phenotypes,most notably pulmonary arterial hypertension,disorders of increased left ventricular filling and increased cavopulmonary pressures in patients with a Fontan type ***:Patients were identified for inclusion from the AFR device manufacturer *** was collected using a RedCap database following IRB approval.8 weeks of follow up data was sought for each patient based on available *** was analyzed and summarized using ***:We report the experience of 6 US centers in the implantation of AFR devices in 15 patients,across a wide age range,with different disease phenotypes and a variety of *** was technically successful in all patients and improvement was noted in both clinical and hemodynamic *** were no immediate or intermediate term complications reported.3 patients died remote from *** deaths were not felt to be related to the AFR device or related procedural ***:Compassionate use of the AFR device in children and adults with congenital&acquired heart disease is technically feasible and produces beneficial short term hemodynamic and symptomatic *** uptake of this technique and treatment at specialist centers has the potential to provide significant benefits to a variety of complex patients with currently limited treatment options and indeterminate prognosis.

关键词： Congenital heart disease pulmonary hypertension left atrial hypertension single ventricle palliation diastolic heart failure

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Impact of extended-infusion piperacillin-tazobactam in a Canadian community hospital

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Infectious Medicine 2023年第1期2卷 31-35页

作者： April j.Chan Gerald Lebovic Michael Wan Yan Chen Elizabeth Leung Bradley j.Langford jenny Seah Linda R.Taggart Mark Downing Department of Pharmacy Unity Health TorontoTorontoOntarioCanada University of Toronto TorontoOntarioCanada Division of Infectious Diseases Unity Health TorontoTorontoOntarioCanada Public Health Ontario TorontoOntarioCanada Hotel Dieu Shaver Health and Rehabilitation Centre St.CatharinesOntarioCanada

Background:Studies have demonstrated improved clinical outcomes with extended infusion(EI)piperacillin/tazobactam(TZP)compared to standard infusion(SI).However,there is less evidence on its benefits in noncritically-ill ***-wide EI TZP was implemented at our site on February 21,*** objectives were to compare clinical,safety and economic outcomes between EI and SI ***:A retrospective cohort study of all adult patients who received EI TZP(3.375 g IV q8h infused over 4 hours and SI TZP for≥48 hours during 3 years pre-and postimplementation was *** primary study outcome was 14-day mortality while secondary outcomes included length of hospital stay(LOS),nursing plus pharmacy cost,occurrence of Clostridioides difficile infection,readmission within 30 days and change in Pseudomonas aeruginosa minimum inhibitory concentration(MIC)distribution for *** primary outcome and binary secondary outcomes were analyzed using a logistic regression *** was examined using time to event *** was examined using linear regression ***:Overall,2034 patients received EI TZP and 1364 patients received SI *** TZP was associated with lower odds of mortality(OR 0.76,95%CI 0.63-0.91),lower odds of *** infection(OR 0.59,95%CI 0.41-0.84)and 8%lower cost(estimate 0.92,95%CI 0.87-0.98)compared to SI ***:Hospital-wide implementation of EI TZP was associated with lower odds of 14-day mortality and incidence of *** infection with cost savings at our institution.

关键词： Antimicrobial stewardship Piperacillin/tazobactam Extended-infusion

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