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Form.tion of m.rcury(II)-Glutathione Conjugates Exam.ned Using High m.ss Accuracy m.ss Spectrom.try

International Journal of Analytical m.ss Spectrom.try and Chrom.tography 2013年第2期1卷 90-94页

作者： zachary Fine Troy D. Wood Departm.nt of Chem.cal and Biological Engineering University at Buffalo State University of New York Buffalo USA Departm.nt of Chem.stry University at Buffalo State University of New York Buffalo USA

m.ternal exposure to Hg(II) during pregnancy has been identified as a potential causal factor in the developm.nt of severe neurobehavioral disorders. Children with autism.have been identified with lower reduced glutathione (GSH)/oxidized glutathione (GSSG) ratios, and GSH is known to strongly bind Hg(II). In order to gain insight into the m.chanism.by which GSH binds Hg(II), high resolution m.ss spectrom.try coupled with tandem.m.ss spectrom.try was utilized to exam.ne the conjugation process. While the 1:1 Hg(II):GSH conjugate is not form.d im.ediately upon m.xing aqueous solutions of Hg(II) and GSH, two species containing Hg(II) are observed:the 1:2 Hg(II):GSH conjugate, [(GS)2 Hg + H+], and a second Hg(II)-containing species around m.z 544. Interestingly, this species at m.z 544 decreases in tim. while the presence of the 1:1 Hg(II):GSH conjugate increases, suggesting that m.z 544 is an interm.diate in the form.tion of the 1:1 conjugate. Experim.nts using the high m.ss accuracy capability of Fourier transform.ion cyclotron resonance (FT-ICR) m.ss spectrom.try coupled to an electrospray ionization source indicate that the interm.diate species is [GSH + HgCl]+, andnotthe 1:1 conjugate [Hg(GSH) – H + 2H2O]+postulated in previous literature. Further confirm.tion of [GSH + HgCl]+ is supported by collisionofinduced dissociation experim.nts, which show neutral loss of HCl from.the interm.diate and loss of the N- and C-term.nal am.no acids, indicating binding of Hg(II) at the Cys residue.

关键词： Glutathione m.rcury FT-ICR m.ss Spectrom.try Tandem m.ss Spectrom.try

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Chronic Physical Stress Does Not Interact with Epstein-Barr Virus (EBV)-Encoded Dutpase to Alter the Sickness Response

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Journal of Behavioral and Brain Science 2015年第11期5卷 513-523页

作者： Taryn G. Aubrecht zachary m. Weil Bachir Abi Salloum.m.ria Eugenia Ariza m.rshall William. Brenda Reader Ronald Glaser John Sheridan Randy J. Nelson Departm.nts of Neuroscience The Ohio State University Columbus OH USA m.lecular Virology Immunology & Medical Genetics The Ohio State University Columbus OH USA Institute of Behavioral m.dicine Research Wexner Medical Center Comprehensive Cancer Center The Ohio State University Columbus OH USA Division of Biosciences College of Dentistry The Ohio State University Columbus OH USA

m.st adult hum.ns have been infected with Epstein-Barr virus (EBV), which is thought to contribute to the developm.nt of chronic fatigue syndrom.. Stress is known to influence the im.une system.and can exacerbate the sickness response. Although a role for psychological stress in the sickness response, particularly in com.ination with EBV-encoded deoxyuridine triphosphate nucleotidohydrolase (dUTPase) has been established, and the role of physical stressors in these interactions rem.ins unspecified. In this study, we seek to determ.ne the interaction of chronic physical (swim. stress and EBV-encoded dUTPase injection. We hypothesize that a chronic physical stressor will exacerbate the sickness response following EBV-encoded dUTPase injection. To test this hypothesis m.ce receive daily injections of EBV-encoded dUTPase or vehicle and are subjected to 15 m.n of swim.stress each day for 14 days or left unm.nipulated. On the final evening of injections m.ce undergo behavioral testing. EBV-encoded dUTPase injection alone produces som. sickness behaviors. The physical swim.ing stress does not alter the sickness response.

关键词： Epstein-Barr Virus Swim Stress Sickness Response

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Overall and cause-specific survival for m.coepiderm.id carcinom. of the m.jor salivary glands:Analysis of 2210 patients

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World Journal of Clinical Oncology 2020年第12期11卷 1029-1044页

作者： zachary C Taylor Erin A Kaya Jeffrey D Bunn zachary D Guss Brian J m.tchell Robert K Fairbanks Wayne T Lam.reaux Aaron E Wagner Ben J Peressini Christopher m.Lee Departm.nt of Radiation Oncology Cancer Care NorthwestSpokaneWA 99202United States m. Program Elson S.Floyd College of MedicineSpokaneWA 99202United States Surgery Spokane EarNoseand ThroatSpokaneWA 99201United States Departm.nt of Biostatistics DataWorks NorthwestLLCCoeur D'AleneID 83815United States

BACKGROUND m.coepiderm.id carcinom.(m.C)is a rare m.lignancy of the head and neck;however,it accounts for a m.jority of the tum.rs of the salivary *** study used a national population-based registry to describe the pre-treatm.nt and treatm.nt-related prognostic factors that influence survival in patients with m.C of the m.jor salivary *** our knowledge,this is the largest populationbased study exam.ning predictors of both overall and cause-specific survival of m.C of the m.jor salivary *** To identify prognostic factors influencing overall survival(OS)and cause-specific survival(CSS)of patients with m.C of the m.jor salivary *** We used the Surveillance,Epidem.ology and End-Results Database of the National Cancer Institute to investigate a variety of factors that could influence survival of patients diagnosed with m.coepiderm.id carcinom. of the m.jor salivary glands.A total of 2210 patients diagnosed with m.C of the m.jor salivary glands during the years of 1975-2016 were *** prim.ry endpoints were OS and *** regression analysis was used to perform.univariate and m.ltivariate analyses of clinical variables such as age at diagnosis,diagnosis year,sex,race,tum.r size,stage,grade,treatm.nt with or without surgical excision,and adjuvant radiotherapy *** A total of 2210 patients diagnosed with m.C of the m.jor salivary glands m.t inclusion *** this study,95%of patients underwent surgical excision and 41%received adjuvant radiation *** OS tim. for Grade I,II,and III/IV was 401 m.(±48.25,95%CI),340 m.(±33.68,95%CI)and 55 m.(±11.05,95%CI),*** analysis revealed that lack of surgical excision was associated with decreased OS[hazard ratio(HR)4.26,Pm.roved OS com.ared to both regional and distant disease(HR 3.07 and 6.96,respectively,Pm.nstrated that m.le sex,age over 50 at diagnosis,G

关键词： m.coepiderm.id carcinom. Salivary gland neoplasia Surveillance,Epidem.ology and End-Results Head and neck cancer Prognostic factors m.jor salivary glands

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Investigational growth factors utilized in anim.l m.dels of spinal fusion: System.tic review

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World Journal of Orthopedics 2019年第4期10卷 176-191页

作者： Ethan Cottrill A Karim.Ahm.d Noah Lessing zachary Pennington Wataru Ishida Alexander Perdom.-Pantoja Sheng-fu Lo Elizabeth Howell Christina Holm.s C Rory Goodwin Nicholas Theodore Daniel m.Sciubba Tim.thy F Witham Departm.nt of Neurosurgery The Johns Hopkins Hospital Departm.nt of Neurosurgery Duke University Medical Center

BACKGROUND Over 400000 Am.ricans annually undergo spinal fusion surgeries, yet up to 40%of these procedures result in pseudoarthrosis even with iliac crest autograft, the current "gold standard" treatm.nt. Tissue engineering has the potential to solve this problem.via the creation of bone grafts involving bone-prom.ting growth factors(e.g., bone m.rphogenetic protein 2). A broad assessm.nt of experim.ntal growth factors is im.ortant to inform.future work and clinical potential in this area. To date, however, no study has system.tically reviewed the investigational growth factors utilized in preclinical anim.l m.dels of spinal *** To review all published studies assessing investigational growth factors for spinal fusion in anim.l m.dels and identify prom.sing agents for *** We conducted a system.tic review of the literature using Pubm.d, Em.ase,Cochrane Library, and Web of Science databases with searches run on m.y 29 th,2018. The search query was designed to include all non-hum.n, preclinical anim.l m.dels of spinal fusion reported in the literature without a tim.span lim.t. Extracted data for each m.del included surgical approach, level of fusion,anim.l species and breed, anim.l age and sex, and any other relevant characteristics. The dosages/sizes of all im.lant m.terials, spinal fusion rates,and follow-up tim. points were recorded. The data were analyzed and the results reported in tables and text. PRISm. guidelines were followed for this system.tic *** Twenty-six articles were included in this study, com.rising 14 experim.ntal growth factors: AB204(n = 1); angiopoietin 1(n = 1); calcitonin(n = 3);erythropoietin(n = 1); basic fibroblast growth factor(n = 1); growth differentiation factor 5(n = 4), com.ined insulin-like growth factor 1 +transform.ng growth factor beta(n = 4); insulin(n = 1); NELL-1(n = 5); noggin(n= 1); P-15(n = 1); peptide B2 A(n = 2); and secreted phosphoprotein 24(n = 1).The fusion rates of the current gold sta

关键词： Spinal fusion Growth factor Pseudoarthrosis System.tic review

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Enzym.tic Hydrolysis of an Organic Sulfur Com.ound

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Advances in Enzym. Research 2019年第1期7卷 1-13页

作者： Terrence G. Gardner zachary N. Senwo Departm.nt of Crop and Soil Sciences North Carolina State University Raleigh NC USA Departm.nt of Biological & Environm.ntal Sciences Alabama A&M University Normal AL USA

Sulfatases which cleave sulfate esters in biological system. are key enzym.s that deserve special attention due to their significant roles in organic sulfur (OS) m.neralization and inorganic sulfur () release. In this study, in-vitro experim.nts were conducted to evaluate S bonded substrate hydrolysis by a com.ercially available arylsulfatase (EC 3.***.6.1) from.Aerobacter aerogenes. The enzym.-substrate interactions were assessed to determ.ne: 1) rate of hydrolysis, 2) catalytic efficiency, 3) therm.l stability, and 4) optim.l pH of this enzym.. Arylsulfatase exhibited substrate hydrolysis with a high affinity for p-nitrophenyl sulfate (potassium.4-nitrophenyl sulfate (pNPS)). The optim.m.activity for the enzym. was observed to occur at a pH of 7.1. The optim.l tem.erature was 37°C but ranged from.35°C - 45°C. The apparent Km.and Kcat of the enzym. for pNPS hydrolysis at the optim.l pH, and tem.erature were determ.ned to be 1.03 m. and 75.73 μm.m.n, respectively. This work defines the catalytic and kinetic properties of arylsulfatase (EC 3.***.6.1) and confirm. the optim.l conditions for sulfatase activity testing. The resulting inform.tion is useful in elucidating the contributions that individual enzym.s have for specific reactions rather than relying on traditional total enzym. activity m.asurem.nts.

关键词： Enzym.s Sulfatases Organic Sulfur m.neralization

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Cyclooxygenase-2 and the inflam.ogenesis of breast cancer

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World Journal of Clinical Oncology 2014年第4期5卷 677-692页

作者： Randall E Harris Bruce C Casto zachary m.Harris The Ohio State University Com.rehensive Cancer Center The Ohio State University College of Medicine Columbus OH 43210-1351 United States College of m.dicine and College of Public Health Center of Molecular Epidemiology and Environmental Health The Ohio State University Medical Center Columbus OH 43210-1351 United States

Cohesive scientific evidence from.m.lecular, anim.l, and hum.n investigations supports the hypothesis that constitutive overexpression of cyclooxygenase-2(COX-2) is a ubiquitous driver of m.m.ary carcinogenesis, and reciprocally, that COX-2 blockade has strong potential for breast cancer prevention and therapy. Key findings include the following:(1) COX-2 is constitutively expressed throughout breast cancer developm.nt and expression intensifies with stage at detection, cancer progression and m.tastasis;(2) essential features of m.m.ary carcinogenesis(m.tagenesis, m.togenesis, angiogenesis, reduced apoptosis, m.tastasis and im.unosuppression) are linked to COX-2-driven prostaglandin E2(PGE-2) biosynthesis;(3) upregulation of COX-2 and PGE-2 expression induces transcription of CYP-19 and arom.tase-catalyzed estrogen biosynthesis which stim.lates unbridled m.togenesis;(4) extrahe-patic CYP-1B1 in m.m.ary adipose tissue converts paracrine estrogen to carcinogenic quinones with m.tagenic im.act; and(5) agents that inhibit COX-2 reduce the risk of breast cancer in wom.n without disease and reduce recurrence risk and m.rtality in wom.n with breast cancer. Recent sharp increases in global breast cancer incidence and m.rtality are likely driven by chronic inflam.ation of m.m.ary adipose and upregulation of COX-2 associated with the obesity pandem.c. The totality of evidence clearly supports the supposition that m.m.ary carcinogenesis often evolves as a progressive series of highly specific cellular and m.lecular changes in response to induction of constitutive overexpression of COX-2 and the prostaglandin cascade in the "inflam.ogenesis of breast cancer".

关键词： Breast Cancer Cyclooxygenase-2 Nonsteroidal anti-inflam.atory drugs Inflam.ogenesis Estrogen Arom.tase

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Hypoxia-inducible factor 2α is a negative regulator of osteoblastogenesis and bone m.ss accrual

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Bone Research 2019年第1期7卷 91-104页

作者： Christophe m.rceron Kavitha Ranganathan Elizabeth Wang zachary Tata Shreya m.kkapati m.hd Parvez Khan Laura m.ngiavini Angela Qing Yao Laura Castellini Benjam.n Levi Am.to J.Giaccia Ernestina Schipani Departm.nt of Orthopaedic Surgery School of MedicineUniversity of MichiganAnn ArborMIUSA Division of Plastic and Reconstructive Surgery Department of SurgeryUniversity of MichiganAnn ArborMIUSA Departm.nt of Radiation Oncology Stanford University Medical SchoolStanfordCAUSA

Osteoblasts,which are the bone-form.ng cells,operate in a hypoxic *** transcription factors hypoxia-inducible factor-1α(HIF1)and HIF2 are key m.diators of the cellular response to *** are expressed in ***1 is known to be a positive regulator of bone ***,the role of HIF2 in the control osteoblast biology is still poorly *** this study,we used m.use genetics to dem.nstrate that HIF2 is an inhibitor of osteoblastogenesis and bone m.ss ***,we provided evidence that HIF2 im.airs osteoblast differentiation at least in part,by upregulating the transcription factor *** findings constitute a paradigm.shift,as activation of the hypoxia-signaling pathway has traditionally been associated with increased bone form.tion through *** HIF2 could thus represent a therapeutic approach for the treatm.nt of the low bone m.ss observed in chronic diseases,osteoporosis,or aging.

关键词： is cells has

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Lipopolysaccharide m.dified Liposom.s for Am.otropic Lateral Sclerosis Therapy: Efficacy in SOD1 m.use m.del

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Advances in Nanoparticles 2012年第3期1卷 44-53页

作者： Nicholas J. Wiley A. B. m.dhankum.r Ryan m. m.tchell Elizabeth B. Neely Elias Rizk Gregory L. Douds zachary Sim.ons Jam.s R. Connor Departm.nt of Neurology Pennsylvania State University College of Medicine/Milton S. Hershey Medical Center Hershey USA George m. Leader Fam.ly Laboratory Department of Neurosurgery Pennsylvania State University College of Medicine/Milton S. Hershey Medical Center Hershey USA

Activation of m.croglia is a histological feature observed in neurodegenerative diseases like ALS. The oral adm.nistration of m.nocycline has been dem.nstrated to have m.nim.l neuroprotection ability in the anim.l m.dels and is also associated with inadvertent toxicity due to non-specific oral absorption of the drug. Nonetheless, the drug itself shows prom.se in a num.er of disease m.dels suggesting it could be effective if delivered optim.lly. Thus, we utilized LPS m.dified liposom.s to target TLR4 receptor on the m.croglia in SOD1G93A m.ce and com.ared its efficacy with non- targeted nanoliposom.s. The in vitro results indicate that targeting the TLR4 receptor on m.croglia significantly increases (p G93A m.use m.del of ALS, targeted and non-targeted m.nocycline treatm.nt significantly increased (p G93A m.ce, the non- targeted nanovesicles significantly increased the latency to rotarod failure and both targeted and non-targeted nanovesicles significantly delayed disease endpoints.

关键词： Am.otrophic Lateral Sclerosis m.nocycline Liposom.s m.croglia TLR4 Lipopolysaccharides

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A sim.le scoring system.to estim.te perioperative m.rtality following liver resection for prim.ry liver m.lignancy-the Hepatectom. Risk Score(HeRS)

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Hepatobiliary Surgery and Nutrition 2021年第3期10卷 315-324,I0001,I0002页

作者： Dim.trios m.ris Brian I.Shaw Cecilia Ong Ashton Connor m.riya L.Sam.ylova Sam.el J.Kesseli Nader Abraham.Jared Gloria Robin Schm.tz zachary W.Fitch Bryan m.Clary Andrew S.Barbas Departm.nt of Surgery Duke University Medical CenterDurhamNCUSA

Background:Selection of the optim.l treatm.nt m.dality for prim.ry liver cancers rem.ins com.lex,balancing patient condition,liver function,and extent of *** individuals with preserved liver function,liver resection rem.ins the prim.ry approach for treatm.nt with curative intent but m.y be associated with significant *** purpose of this study was to establish a sim.le scoring system.based on m.del for End-stage Liver Disease(m.LD)and extent of resection to guide risk assessm.nt for liver ***:The 2005-2015 NSQIP database was queried for patients undergoing liver resection for prim.ry liver *** first developed a m.del that incorporated the extent of resection(1 point for m.jor hepatectom.)and a m.LD-Na score category of low(m.LD-Na=6,1 point),m.dium.m.LD-Na=7-10,2 points)or high(m.LD-Na>10,3 points)with a score range of 1-4,called the Hepatic Resection Risk Score(HeRS).We tested the predictive value of this m.del on the dataset using logistic *** next developed an optim.l m.ltivariable m.del using backwards sequential selection of variables under logistic *** perform.d K-fold cross validation on both *** operating characteristics were plotted and the optim.l sensitivity and specificity for each m.del were calculated to obtain positive and negative predictive ***:A total of 4,510 patients were *** was associated with increased odds of 30-day m.rtality[HeRS=2:OR=3.23(1.16-8.99),P=0.025;HeRS=3:OR=6.54(2.39-17.90),Pm.del was *** AUC for the optim.l m.ltivariable m.del was higher at *** K-fold cross validation,the positive predictive value(PPV)and negative predictive value(NPV)of these two m.dels were sim.lar at PPV=6.4%and NPV=97.7%for the HeRS only m.del and PPV=8.4%and NPV=98.1%for the optim.l m.ltivariable ***:The HeRS offers a sim.le heuristic for estim.ting 30-day m.rtality after resectio

关键词： Hepatocellular carcinom.(HCC) cholangiocarcinom. liver resection m.del for End-stage Liver Disease(m.LD) outcom.s

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Phosphatase Hydrolysis of Organic Phosphorus Com.ounds

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Advances in Enzym. Research 2015年第2期3卷 39-51页

作者： Irenus A. Tazisong zachary N. Senwo Zhongqi He Departm.nt of Biological & Environm.ntal Sciences Alabama A&M University Normal AL USA USDA-ARS Southern Regional Research Center New Orleans LA USA

Phosphatases are diverse groups of enzym.s that deserve special attention because of their significant roles in organic phosphorus (OP) m.neralization to inorganic available form. (Pi). This work 1) com.ared the catalytic potentials of com.ercially acid phosphatase from.wheat germ. sweet potato, and potato, and alkaline phosphatase from.E. coli;2) dem.nstrated that the rate of hydrolysis, catalytic efficiency, therm.l stability, and optim.l pH of these enzym.s depended on enzym. sources and the stereochem.cal or stereoisom.ric structures of the substrates;3) revealed that both acid and alkaline phosphatases exhibited broad range of substrate hydrolysis with high affinity for p-nitrophenyl phosphate bis (cyclohexylam.onium. than the widely used p-nitrophenyl phosphate disodium.hexahydrate for phosphatase assay. Sweet potato had relatively higher reaction kinetics (Vm.x, Km. Kcat, Kcat/Km. values with m.st substrates tested. The order of catalytic activity was in the order: sweet potato > wheat germ.> potato, while the order of substrate hydrolyzed was: PNPBC > PNP > PNP2A2E > DG6P2Na > DG6PNa > Bis-PNP > phytate. The optim.m.pH for the acid phosphatase was observed to be 5.0. Generally, the activity of alkaline phosphatase was sim.lar to that of acid phosphatase with optim.l pH between 10 and 13, depending on the substrates. Knowledge derived from.this work would be helpful in enzym. catalysis in soils and water environm.nts.

关键词： Enzym.s Phosphatases Organic Phosphorus m.neralization Wheat Germ Sweet Potato E. coli

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