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

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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

Pathological links between stroke and cardiac arrest

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Chinese Neurosurgical Journal 2017年第1期3卷 40-43页

作者： Shaila Ghanekar Sydney corey Trenton Lippert Cesar V.Borlongan Center of Excellence for Aging and Brain Repair Department of Neurosurgery and Brain Repair University of South Florida Morsani College of Medicine 12901 Bruce B.Downs Blvd Tampa 33612 FL USA

There may be a pathological connection between cardiac failure and ischemic *** this article we describe pertinent research that demonstrates subsequent death of cardiac and neural myocytes in the post ischemic stroke *** stroke therapy overlooks the connection between cardiac and cerebrovascular events and fails to address the shared risk *** pre-clinical stroke investigations have provided evidence that suggests the presence of an indirect cell death pathway in which toxic molecules emanate from the stroke brain and trigger cardiac cell *** the other hand,other studies highlight the presence of a reverse cell death cascade in which toxic molecules from the heart,following cardiac arrest,travel to the brain and induce ischemic cell *** examination of these putative cell death pathways between ischemic stroke and cardiac arrest will prompt the advancement of innovative treatments specifically targeting both diseases,leading to ameliorated clinical results of patients diagnosed with heart failure and ischemic stroke.

关键词： Cerebral ischemia Heart disease Stem cells

Characterization of a novel mouse model with genetic deletion of CD177

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Protein & Cell 2015年第2期6卷 117-126页

作者： Qing Xie Julia Klesney-Tait Kathy Keck corey Parlet Nicholas Borcherding Ryan Kolb Wei Li Lorraine Tygrett Thomas Waldschmidt Alicia Olivier Songhai Chen Guang-Hui Liu Guang-Hui Liu Xiangrui Li Weizhou Zhang College of Veterinary Medicine Nanjing Agricultural University Nanjing 210095 China Department of Pathology Holden Comprehensive Cancer Center Carver College of Medicine/University of Iowa Iowa IA 52242 USA Department of Internal Medicine Carver College of Medicine/University of Iowa Iowa IA 52242 USA Department of Pharmacology Carver College of Medicine/University of Iowa Iowa IA 52242 USA National Laboratory of Biomacromolecules Institute of Biophysics Chinese Academy of Sciences Beijing 100101 China Beijing Institute for Brain Disorders Beijing 100069 China

Neutrophils play an essential role in the innate immune response to infection. Neutrophils migrate from the vasculature into the tissue in response to infection. Recently, a neutrophil cell surface receptor, CD177, was shown to help mediate neutrophil migration across the endothelium through interactions with PECAMI. We examined a publicly available gene array dataset of CD177 expression from human neutrophils following pulmonary endotoxin instillation. Among all 22,214 genes examined, CD177 mRNA was the most upregu- lated following endotoxin exposure. The high level of CD177 expression is also maintained in airspace neu- trophils, suggesting a potential involvement of CD177 in neutrophil infiltration under infectious diseases. To determine the role of CD177 in neutrophils in vivo, we constructed a CD177-genetic knockout mouse model. The mice with homozygous deletion of CD177 have no discernible phenotype and no significant change in immune cells, other than decreased neutrophil counts in peripheral blood. We examined the role of CD177 in neutrophil accumulation using a skin infection model with Staphylococcus aureus. CD177 deletion reducedneutrophil counts in inflammatory skin caused by S. aureus. Mechanistically we found that CD177 deletion in mouse neutrophils has no significant impact in CXCLI/ KC- or fMLP-induced migration, but led to significant cell death. Herein we established a novel genetic mouse model to study the role of CD177 and found that CD177 plays an important role in neutrophils.

关键词： CD177 neutrophil mouse model geneticdeletion

Translational lab-to-clinic hurdles in stem cell therapy

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Chinese Neurosurgical Journal 2016年第4期2卷 229-232页

作者： Sydney corey Trenton Lippert Cesar V.Borlongan Center of Excellence for Aging and Brain Repair Department of Neurosurgery and Brain Repair University of South Florida Morsani College of Medicine 12901 Bruce B.Downs Blvd Tampa FL 33612 USA

Several experimental therapeutics have been demonstrated to be safe and effective in animal models of neurological disorders,but have failed when they reached the *** factors that affected the poor clinical outcomes include the lack of proper treatment controls and clinically relevant animal *** failure of lab-to-clinic translation has plagued many neuroprotective drugs for *** this in mind,the stem cell therapy field has cautiously approached translating stem cell products for clinical application,in that a negative clinical trial may hinder the entire regenerative medicine ***,we discuss the many translational challenges associated with stem cell therapy in the setting of stroke.

关键词： Physical therapy Cerebral ischemia Neurogenesis Cell transplantation

Role of arthropod communities in bioenergy crop litter decomposition

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Insect Science 2013年第5期20卷 671-678页

作者： Arthur R. Zangerl Saber Miresmailli Paul Nabity Allen Lawrance Alan Yanahan corey A. Mitchell Kristina J. Anderson-Teixeira Mark B. David May R. Berenbaum Evan H. DeLucia Department of Entomology Energy Bioscience Institute Department of Plant Biology Institute of Genomic Biology Department of Natural Resources and Environmental Sciences University of Illinois Urbana IL 61801 USA

The extensive land use conversion expected to occur to meet demands for bioenergy feedstock production will likely have widespread impacts on agroecosystem biodiversity and ecosystem services, including carbon sequestration. Although arthropod detritivores are known to contribute to litter decomposition and thus energy flow and nutrient cycling in many plant communities, their importance in bioenergy feedstock communities has not yet been assessed. We undertook an experimental study quantifying rates of litter mass loss and nutrient cycling in the presence and absence of these organisms in three bioenergy feedstock crops—miscanthus （Miscanthus x giganteus）, switchgrass （Panicum virgatum）, and a planted prairie community. Overall arthropod abundance and litter decomposition rates were similar in all three communities. Despite effective reduction of arthropods in experimental plots via insecticide application, litter decomposition rates, inorganic nitrogen leaching, and carbon–nitrogen ratios did not differ significantly between control （with arthropods） and treatment （without arthropods） plots in any of the three community types. Our findings suggest that changes in arthropod faunal composition associated with widespread adoption of bioenergy feedstock crops may not be associated with profoundly altered arthropod-mediated litter decomposition and nutrient release.

关键词： biodiversity bioenergy decomposition detritivore land use change prairie

Distributed Sensor Logging: As Easy as a Mesh of Yoyos

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International Journal of Communications, Network and System Sciences 2013年第6期6卷 309-315页

作者： corey Wallis Alison Hutton Steve Brown Romana Challans Paul Gardner-Stephen School of Computer Science Engineering and Mathematics Flinders University Adelaide Australia

The Mass Gathering Data Acquisition and Analysis (MaGDAA) project involved the development of hardware and software solutions to facilitate the rapid and effective collection of autonomous and survey based data during mass gathering events. The aim of the project was the development and trial of a purpose-built Open Hardware based environment monitoring sensor prototypes using IOIO (pronounced “yoyo”) boards. Data from these sensors, and other devices, was collected using Open Source software running on Android powered mobile phones, tablets and other open hardware based platforms. Data was shared using a Wi-Fi mesh network based on an Open Source project called The Serval Project. Additional data in the form of survey based questionnaires were collected using ODK Collect, one of the applications in the Open Data Kit suite. The MaGDAA project demonstrated that it is possible for researchers (through the use of Open Source software and Open Hardware) to own, visualise, and share data without the difficulties of setting up and maintaining servers. MaGDAA proved to be an effective infrastructure independent sensor logging network that enables a broad range of data collection (demographic, predispositions, motivations, psychosocial and environmental influencers and modifiers of audience behaviour, cultural value) in the field of mass gathering research.

关键词： Sensor Logging Open Source Software Open Source Hardware Automated Data Acquisition Surveying

DMP1 prevents osteocyte alterations,FGF23 elevation and left ventricular hypertrophy in mice with chronic kidney disease

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Bone Research 2019年第2期7卷 171-182页

作者： corey Dussold Claire Gerber Samantha White Xueyan Wang Lixin Qi Connor Francis Maralee Capella Guillaume Courbon Jingya Wang Chaoyuan Li Jian Q. Feng Tamara Isakova Myles Wolf Valentin David Aline Martin Division of Nephrology and Hypertension Center for Translational Metabolism and HealthFeinberg School of MedicineNorthwestern UniversityChicagoIL 60611USA Department of Biomedical Sciences Texas A&M College of DentistryDallasTX 75246USA Division of Nephrology Department of Medicineand Duke Clinical Research InstituteDuke University School of MedicineDurhamNC 27708USA

During chronic kidney disease (CKD),alterations in bone and mineral metabolism include increased production of the hormone fibroblast growth factor 23 (FGF23) that may contribute to cardiovascular *** osteocyte protein dentin matrix protein 1 (DMP1) reduces FGF23 and enhances bone mineralization,but its effects in CKD are *** tested the hypothesis that DMP1 supplementation in CKD would improve bone health,prevent FGF23 elevations and minimize consequent adverse cardiovascular *** investigated DMP1 regulation and effects in wild-type (WT) mice and the Col4a3^-/- mouse model of ***4a3^-/- mice demonstrated impaired kidney function,reduced bone DMP1 expression,reduced bone mass,altered osteocyte morphology and connectivity,increased osteocyte apoptosis,increased serum FGF23,hyperphosphatemia,left ventricular hypertrophy (LVH),and reduced *** or pharmacological supplementation of DMP1 in Col4a3^-/- mice prevented osteocyte apoptosis,preserved osteocyte networks,corrected bone mass,partially lowered FGF23 levels by attenuating NFAT-induced FGF23 transcription,and further increased serum *** impaired kidney function and worsened hyperphosphatemia,DMP1 prevented development of LVH and improved Col4a3^-/- *** data suggest that CKD reduces DMP1 expression,whereas its restoration represents a potential therapeutic approach to lower FGF23 and improve bone and cardiac health in CKD.

关键词： alterations ventricular hypertrophy chronic kidney disease

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Routine abortion training matters for obstetrics and gynecology residents

作者： (美)Lisa Krissoff Boehm (美)Steven H. corey

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Open Journal of Obstetrics and Gynecology 2013年第10期3卷 727-731页

作者： Sahnah Lim corey Westover Rini B. Ratan Maryam Guiahi Department of Obstetrics and Gynecology Columbia University New York USA Department of Obstetrics and Gynecology University of Colorado Anshutz Aurora USA John Hopkins School of Public Health Baltimore USA

Background: We set out to compare resident perspective regarding self-rated ability to perform abortion procedures, abortion attitudes and satisfaction with training at programs with routine and optional abortion training. Methods: We distributed surveys and conducted 1-h focus groups for 62 residents at six New York City OB/GYN programs;three offer routine abortion training. We compared resident survey responses at programs with routine versus optional training regarding self-rated ability to perform abortion procedures, abortion attitudes and satisfaction with training. We reviewed focus group transcripts to understand differences related to satisfaction with abortion training. Results: Residents at routine programs reported higher proportions of self-rated ability to perform abortion procedures (all surveyed procedures p ≤ 0.05) and were more likely to fully participate in abortion services than residents at optional programs (42/45 vs. 12/17, p = 0.03). Residents at routine programs were more likely to be “very satisfied” with training (44/45 vs. 12/17, p < 0.001) based on three aspects of training: patient care management, self-rated ability to perform abortion procedures and rotation characteristics. Conclusion: Residents who received routine abortion training have higher rates of self-reported procedural competency and are more likely to be satisfied with training than residents who were offered optional training.

关键词： Family Planning Abortion Training Obstetrics and Gynecology