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Characterization of a novel murine Sost ERT2 Cre model targeting osteocytes

bone Research 2019年第1期7卷 41-53页

作者： Delphine b.Maurel Tsutomu Matsumoto Julian A.Vallejo mark L.Johnson Sarah L.Dallas Yukiko Kitase Marco brotto Michael J.Wacker Marie A.Harris Stephen E.Harris Lynda F.bonewald Department of Oral and Craniofacial Sciences University of Missouri-Kansas City School of DentistryKansas CityMOUSA Department of Anatomy and Cell biology Indiana University School of MedicineIndianapolisINUSA bone.Muscle Collaborative Sciences College of Nursing and Health InnovationUniversity of Texas at ArlingtonArlingtonUSA Department of biomedical Sciences University of Missouri-Kansas City School of MedicineKansas CityMOUSA University of Texas Health Science Center San AntonioTXUSA Department of Orthopaedic Surgery Indiana University School of MedicineIndianapolisINUSA Pharmaceutical Sciences Department Universite de BordeauxBio-TisINSERM Unité1026 BioTis146 Rue Léo Saignat33076 BordeauxFrance

Transgenic mice are widely used to delete or overexpress genes in a cell specific manner to advance knowledge of bone biology,function and *** numerous Cre models exist to target gene recombination in osteoblasts and osteoclasts,few target osteocytes specifically,particularly mature *** goal was to create a spatial and temporal conditional Cre model using tamoxifen to induce Cre activity in mature osteocytes using a bac construct containing the 5’and 3’regions of the Sost gene(Sost ERT2 Cre).Four founder lines were crossed with the Ai9 Cre reporter *** founder line showed high and specific activity in mature *** and organs were imaged and fluorescent signal *** no activity was observed in 2 day old pups,by 2 months of age some osteocytes were positive as osteocyte Cre activity became spontaneous or‘leaky’with *** percentage of positive osteocytes increased following tamoxifen injection,especially in males,with 43%to 95%positive cells compared to 19%to 32%in *** signal was observed in any bone surface cell,bone marrow,nor in muscle with or without tamoxifen *** spontaneous signal was observed in any other ***,with tamoxifen injection,a few positive cells were observed in kidney,eye,lung,heart and *** other organs,28 in total,were negative with tamoxifen ***,with age,a muscle phenotype was apparent in the Sost-ERT2 Cre ***,although this mouse model may be useful for targeting gene deletion or expression to mature osteocytes,the muscle phenotype may restrict the use of this model to specific applications and should be considered when interpreting data.

关键词： cell knowledge model

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Cost Analysis of Surgical Approaches Performed by Residents for bladder Outlet Obstruction: Laser versus Loop

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Open Journal of Urology 2012年第2期2卷 33-37页

作者： Samuel H. Eaton Courtney K. Rowe mark b. DelPapa Lori b. Lerner Harvard Longwood Program Boston USA Northwestern University Chicago USA VA boston Healthcare System Boston USA

Purpose: Few studies have analyzed cost differences between holmium laser enucleation of the prostate (HoLEP) and transurethral resection of the prostate (TURP), and none as regards resident training. We compared these costs at a teaching institution with residents from two boston programs. Methods: We reviewed all patients who underwent TURP (January 2007-August 2010) or HoLEP (April 2008-August 2010) with residents, excluding those with prostate cancer, simultaneous procedures at the same time, or prior urethral procedures. Operative approach was determined following consultation between the senior resident and the attending surgeon. Operative, postoperative, and urologic follow-up costs were captured and analyzed from day of surgery to 6 months post-operatively. Costs were calculated by the Department of Decision Support Services. Results: 38 HoLEP and 23 TURP patients met inclusion criteria. The two groups were comparable with the exception of higher ASA score and anticoagulation use in the HoLEP group. Despite a decreased hospital stay (0.42 vs. 1.25 days), total costs for HoLEP were higher than TURP ($8380.00 vs. $5861.78 p be weighed against HoLEP benefits, which include less morbidity, shorter hospital stays and faster recovery times.

关键词： Holmium Laser benign Prostatic Hyperplasia Cost Resident

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卡城名蛙 4

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丛书名： black Cat有声名著阶梯阅读

2004年

作者：（美）mark Twain （美）Gina D. b. Clemen改写

《black Cat有声名著阶梯阅读》精选世界经典作品,也包括富于创意的现代作品,既有脍炙人口的小说、戏剧,又有非小说类的文化知识读物,本书为其中的一册。

ISBN: (纸本)7561735839

关键词：中篇小说英语近代美国

来源：畅想之星图书光盘版（南... 评论

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Arylamine N-acetyltransferase 2 genotype-dependent N-acetylation of isoniazid in cryopreserved human hepatocytes

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Acta Pharmaceutica Sinica b 2017年第4期7卷 517-522页

作者： mark A.Doll Raúl A.Salazar-González Srineil bodduluri David W.Hein Department of Pharmacology and Toxicology and James Graham brown Cancer Center University of LouisvilleLouisvilleKY 40202USA

Cryopreserved human hepatocytes were used to investigate the role of arylamine N-acetyltransferase 2 (NAT2; EC 2.***.1.5) polymorphism on the N-acetylation of isoniazid (INH). NAT2 genotype was determined by Taqman allelic discrimination assay and INH N-acetylation was measured by high performance liquid chromatography. INH N-acetylation rates in vitro exhibited a robust and highly significant (Pbolism. N-acetylation rates in situ were INH concentration- and time-dependent. Following incubation for 24 h with 12.5 or 100 µmol/L INH, acetyl-INH concentrations varied significantly (P = 0.0023 and P = 0.0002) across cryopreserved human hepatocytes samples from rapid, intermediate, and slow acetylators, respectively. The clear association between NAT2 genotype and phenotype supports use of NAT2 genotype to guide INH dosing strategies in the treatment and prevention of tuberculosis.

关键词： Isoniazid N-Acetyltransferase 2 Acetylation polymorphism Human hepatocytes Genotype Phenotype

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Supplying the trip to antibody production-nutrients,signaling,and the programming of cellular metabolism in the mature b lineage

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Cellular & Molecular Immunology 2022年第3期19卷 352-369页

作者： mark R.boothby Shawna K.brookens Ariel L.Raybuck Sung Hoon Cho Department of Pathology Microbiology&ImmunologyMolecular Pathogenesis DivisionVanderbilt University Medical CenterNashvilleTN37232USA Department of Medicine Rheumatology&Immunology DivisionVanderbilt University Medical CenterNashvilleTN37232USA Cancer biology Program Vanderbilt UniversityNashvilleTN37232USA Vanderbilt Institute of Infection Inflammationand ImmunologyNashvilleTN37232USA

The COVID pandemic has refreshed and expanded recognition of the vital role that sustained antibody(Ab)secretion plays in our immune defenses against microbes and of the importance of vaccines that elicit Ab protection against *** this backdrop,it is especially timely to review aspects of the molecular programming that govern how the cells that secrete Abs arise,persist,and meet the challenge of secreting vast amounts of these *** plasmablasts and plasma cells(PCs)are the primary sources of secreted Abs,the process leading to the existence of these cell types starts with naive b lymphocytes that proliferate and differentiate toward several potential *** each step,cells reside in specific microenvironments in which they not only receive signals from cytokines and other cell surface receptors but also draw on the interstitium for *** in turn influence flux through intermediary metabolism and sensor enzymes that regulate gene transcription,translation,and *** review will focus on nutrient supply and how sensor mechanisms influence distinct cellular stages that lead to PCs and their adaptations as factories dedicated to Ab *** findings of this group and others,sometimes exhibiting differences,will be summarized with regard to the journey to a distinctive metabolic program in PCs.

关键词： b lymphocyte Plasma cell Intermediary metabolism Glucose Glutamine Fatty acid Signal transduction

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Compatibility of beauveria bassiana with Neoseiulus barkeri for Control of Frankliniella occidentalis

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Journal of Integrative Agriculture 2015年第1期14卷 98-105页

作者： WU Sheng-yong GAO Yu-lin XU Xue-nong mark S Goettel LEI Zhong-ren State Key Laboratory for biology of Plant Diseases and Insect Pests I nstitute of Plant ProtectionChinese Academy of Agricultural Sciences Lethbridge Research Centre Agriculture and Agri-Food Canada

The entomopathogenic fungus beauveria bassiana （balsamo） Vuillemin and predatory mite Neoseiulus barked Hughes are effective biological control agents of Frankliniella occidentalis Pergande （Thysanoptera： Thripidae）, one of the most important pests of ornamentals and vegetables world-wide. Combined application of both may enhance control efficiency. The functional response for N. barked on the first instar larvae of western flower thrips which were infected by b. bassiana for 12 and 24 h in the laboratory （（25＋1）℃, （70＋5）% RH, L：D=16 h：8 h） was determined. The virulence of b. bassiana against the second instar and pupae of the thrips attacked by N. barked were also tested. The results showed that N. barked exhibited a Holling type II functional response on treated thrips. After having been treated with the fungus for 12 h and then offered to the predator, thrips were more vulnerable to be killed by N. barked. The second instar larvae and pupae of the thrips which had been attacked by predatory mites were markedly more susceptible to b. bassiana infection than normal thrips; the cumulative corrected mortality of b. bassiana of the second instar and pupae which were attacked by N. barked were 57 and 94%, respectively, compared to 35 and 80% in controls on the day 8. These findings highlight the potential use of b. bassiana in combination with N. barkeri to control F. occidentalis.

关键词： beauveria bassiana Neoseiulus barkeri Frankfiniella occidentalis functional response virulence

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A comparing study of defect generation in IN738LC superalloy fabricated by laser powder bed fusion:Continuous-wave mode versus pulsed-wave mode

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Journal of Materials Science & Technology 2021年第31期90卷 45-57页

作者： Chuan Guo Yang Zhou Xinggang Li Xiaogang Hu Zhen Xu Enjie Dong Qiang Zhu R.mark Ward Department of Mechanical and Energy Engineering Southern University of Science and TechnologyShenzhen 518055China Shenzhen Key Laboratory for Additive Manufacturing of High-performance materials Shenzhen 518055China School of Metallurgy and Materials University of BirminghamEdgbastonBirmingham B152TTUnited Kingdom Academy for Advanced Interdisciplinary Studies Southern University of Science and TechnologyShenzhen 518055China

Inconel 738 LC samples were fabricated using laser powder bed fusion under continuous-wave and pulsed-wave ***,surface quality and mechanical properties were compared to evaluate the printing quality between these 2 laser beam *** results show that the application of pulsed wave could effectively eliminate cracking in the as-fabricated sample,despite 0.046%porosity *** microstructure analysis revealed that the refinement of grains by the pulsed-wave laser beam was the main contributor in eliminating the *** this refinement was ascribed to the higher cooling rate under the discontinuous radiation of laser beam proofed by the numerical *** the pore formation was related to Rayleigh instability and residual bubbles in the sample under the pulsed-wave mode,while pores were less detrimental to the mechanical properties than ***,the part under the pulsed-wave mode exhibited superior mechanical performance compared to that under the continuous-wave mode.

关键词： Laser powder bed fusion Continuous-wave mode Pulsed-wave mode Nickel-based superalloy Defect generation

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Pnpt1 mediates NLRP3 inflammasome activation by MAVS and metabolic reprogramming in macrophages

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Cellular & Molecular Immunology 2023年第2期20卷 131-142页

作者： Chia George Hsu Wenjia Li mark Sowden Camila Lage Chávez bradford C.berk Department of Medicine Aab Cardiovascular Research InstituteUniversity of RochesterRochesterNYUSA Department of Cardiovascular Medicine Ruijin HospitalShanghai Jiao Tong University School of Medicine200025ShanghaiChina

Polyribonucleotide nucleotidyltransferase 1(Pnpt1)plays critical roles in mitochondrial homeostasis by controlling mitochondrial RNA(mt-RNA)processing,trafficking and ***1 deficiency results in mitochondrial dysfunction that triggers a type I interferon response,suggesting a role in ***,the role of Pnpt1 in inflammasome activation remains largely *** this study,we generated myeloid-specific Pnpt1-knockout mice and demonstrated that Pnpt1 depletion enhanced interleukin-1 beta(IL-1β)and interleukin-18(IL-18)secretion in a mouse sepsis *** cultured peritoneal and bone marrow-derived macrophages,we demonstrated that Pnpt1 regulated NLRP3 inflammasome-dependent IL-1βrelease in response to lipopolysaccharide(LPS),followed by nigericin,ATP or poly(I:C)***1 deficiency in macrophages increased glycolysis after LPS administration and mt-reactive oxygen species(mt-ROS)after NLRP3 inflammasome ***1 activation of the inflammasome was dependent on increased glycolysis and the expression of mitochondrial antiviral-signaling protein(MAVS)but not NF-κb ***,these data suggest that Pnpt1 is an important mediator of inflammation,as shown by activation of the NLRP3 inflammasome in murine sepsis and cultured macrophages.

关键词： Pnpt1 Inflammasome Mitochondria Macrophage

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Cardiac adverse events of immune checkpoint inhibitors in oncology patients:A systematic review and meta-analysis

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World Journal of Cardiology 2020年第11期12卷 584-598页

作者： Nso Nso Daniel Antwi-Amoabeng bryce D beutler mark b Ulanja Jasmine Ghuman Ahmed Hanfy Joyce Nimo-boampong Sirri Atanga Rajkumar Doshi Sostanie Enoru Nageshwara Gullapalli Department of Medicine Icahn School of Medicine at Mount SinaiQueensNY 10029United States Department of Internal Medicine University of NevadaReno School of MedicineRenoNV 89502United States Department of Radiology University of Southern CaliforniaKeck School of MedicineLos AngelesCA 90033United States Department of Internal Medicine Warren Alpert Medical School of Brown UniversityProvidenceRI 02903United States Department of Medicine United Health Services Wilson Medical CenterJohnson CityNY 13790United States Department of Cardiovascular Disease SUNY Downstate Health Science UniversityBrooklynNY 11203United States

bACKGROUND Immune checkpoint inhibitors(ICIs)are novel therapeutic agents used for various types of *** have revolutionized cancer treatment and improved clinical outcomes among cancer ***,immune-related adverse effects of ICI therapy are *** immune-related adverse events(irAEs)are rare but potentially life-threatening *** To estimate the incidence of cardiovascular irAEs among patients undergoing ICI therapy for various *** We conducted this systematic review and meta-analysis by searching PubMed,Cochrane CENTRAL,Web of Science,and SCOPUS databases for relevant interventional trials reporting cardiovascular *** performed a single-arm meta-analysis using OpenMeta[Analyst]software of the following outcomes:Myocarditis,pericardial effusion,heart failure,cardiomyopathy,atrial fibrillation,myocardial infarction,and cardiac *** assessed the heterogeneity using the I2 test and managed to solve it with Cochrane’s leave-one-out *** risk of bias was performed with the Cochrane’s risk of bias *** A total of 26 studies were *** incidence of irAEs follows:Myocarditis:0.5%[95%confidence interval(CI):0.1%-0.9%];Pericardial effusion:0.5%(95%CI:0.1%-1.0%);Heart failure:0.3%(95%CI:0.0%-0.5%);Cardiomyopathy:0.3%(95%CI:-0.1%-0.6%);atrial fibrillation:4.6%(95%CI:1.0%-14.1%);Myocardial infarction:0.4%(95%CI:0.0%-0.7%);and Cardiac arrest:0.4%(95%CI:0.1%-0.8%).CONCLUSION The most common cardiovascular irAEs were atrial fibrillation,myocarditis,and pericardial *** rare,data from post market surveillance will provide estimates of the long-term prevalence and prognosis in patients with ICIassociated cardiovascular complications.

关键词： Atrial fibrillation Cancer Immune checkpoint inhibitors Immunotherapy Cardiovascular adverse events Pericardial effusion

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Simultaneous screening and classification of diabetic retinopathy and age-related macular degeneration based on fundus photos——a prospective analysis of the RetCAD system

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International Journal of Ophthalmology(English edition) 2022年第12期15卷 1985-1993页

作者： Christos Skevas Hanah Weindler Max Levering Jonne Engelberts mark van Grinsven Toam Katz University Clinic Eppendorf Hamburg Hamburg 20246Germany Thirona b.V. Toernooiveld 3006525 ECNijmegenThe Netherlands

AIM:To assess the accuracy of an artificial intelligence(AI)based software(Ret CAD,Thirona,The Netherlands)to identify and grade age-related macular degeneration(AMD)and diabetic retinopathy(DR)simultaneously based on fundus ***:This prospective study included 1245 eyes of 630 patients attending an ophthalmology day-care *** photos were acquired and parallel graded by the Ret CAD AI software and by an expert reference examiner for image quality,and staging of AMD and *** was provided by a second expert examiner in case of disagreement between the AI software and the reference *** analysis was performed on eye-level and on patient-level,by summarizing the individual image level-gradings into and eye-level or patient-level score,*** performance of the Ret CAD system was measured using receiver operating characteristics(ROC)analysis and sensitivity and specificity for both AMD and DR were ***:The Ret CAD achieved an area under the ROC(Az)of 0.926 with a sensitivity of 84.6%at a specificity of 84.0%for image *** image level,the Ret CAD software achieved Az values of 0.964 and 0.961 with sensitivity/specificity pairs of 98.2%/79.1%and 83.9%/93.3%for AMD and DR,*** patient level,the Ret CAD software achieved Az values of 0.960 and 0.948 with sensitivity/specificity pairs of 97.3%/73.3%and 80.0%/90.1%for AMD and DR,*** adjudication by the second expert examiner sensitivity/specificity increases on patient-level to 98.6%/78.3%and 100.0%/92.3%for AMD and DR,***:The Ret CAD offers very good sensitivity and specificity compared to manual grading by experts and is in line with that obtained by similar automated grading *** Ret CAD AI software enables simultaneous grading of both AMD and DR based on the same fundus *** sensitivity may be adjusted according to the desired acceptable sensitivity and *** simplicity cloud base i

关键词： RetCAD age-related macular degeneration diabetic retinopathy

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