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Tyrosine metabolic enzymes from insects and mammals：A comparative perspective

Insect Science 2014年第1期21卷 13-19页

作者： christopher john vavricka Qian Han Prajwalini Mehere Haizhen Ding Bruce M. Christensen and Jianyong Li Research Network of Immunity and Health (RNIH) Beijing Institutes of Life Science Chinese Academy of Sciences BeUing China Department of Biochemistry Virginia Polytechnic and State University Blacksburg VA 24061 USA Department of Tuberculosis The Foundation for Medical Research Mumbai India and Department of Pathobiology University of Wisconsin-Madison Madison Wl 53706 USA

Differences in the metabolism of tyrosine between insects and mammals present an interesting example of molecular evolution. Both insects and mammals possess finetuned systems of enzymes to meet their specific demands for tyrosine metabolites; however, more homologous enzymes involved in tyrosine metabolism have emerged in many insect species. Without knowledge of modem genomics, one might suppose that mammals, which are generally more complex than insects and require tyrosine as a precur sor for important catecholamine neurotransmitters and for melanin, should possess more enzymes to control tyrosine metabolism. Therefore, the question of why insects actually possess more tyrosine metabolic enzymes is quite interesting. It has long been known that insects rely heavily on tyrosine metabolism for cuticle hardening and for innate immune responses, and these evolutionary constraints are likely the key answers to this question. In terms of melanogenesis, mammals also possess a high level of regulation; yet mam malian systems possess more mechanisms for detoxification whereas insects accelerate pathways like melanogenesis and therefore must bear increased oxidative pressure. Our research group has had the opportunity to characterize the structure and function of many key proteins involved in tyrosine metabolism from both insects and mammals. In this mini review we will give a brief overview of our research on tyrosine metabolic enzymes in the scope of an evolutionary perspective of mammals in comparison to insects.

关键词： arylalkylamine N-acetyltransferase (aaNAT) Enzymology L-DOPAdecarboxylase (DDC) melanogenesis tyrosine metabolism

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Adventures and lessons of an American biochemist in China

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Protein & Cell 2011年第8期2卷 601-603页

作者： christopher J.vavricka CAS Key Laboratory of Pathogenic Microbiology and Immunology Institute of MicrobiologyChinese Academy of SciencesBeijing 100101China

It’s very interesting how events often lead up to each other seemingly by chance,but appear almost perfectly planned out when looking *** the past two years,I have worked as an International Young Scientist Research Fellow at the Institute of Microbiology,Chinese Academy of Sciences in Beijing,*** people ask me,especially Chinese graduate students,why an American would choose to come to China as a postdoctoral researcher.

关键词： looking doctor perfectly

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In silico characterization of the functional and structural modules of the hemagglutinin protein from the swine-origin influenza virus A (H1N1)-2009

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Science China(Life Sciences) 2010年第6期53卷 633-642页

作者： christopher vavricka GAO George F CAS Key Laboratory of Pathogenic Microbiology and Immunology Institute of MicrobiologyChinese Academy of Sciences Graduate University of Chinese Academy of Sciences China-Japan Joint Laboratory of Molecular Immunology and Molecular Microbiology Institute of MicrobiologyChinese Academy of Sciences Beijing Institutes of Life Science Chinese Academy of Sciences

The 2009 swine-origin influenza virus (S-OIV,H1N1 subtype) has developed into a new pandemic influenza as announced by the World Health *** order to uncover clues about the determinants for virulence and pathogenicity of the virus,we characterized the functional modules of the surface glycoprotein hemagglutinin (HA),the most important protein in molecular epidemiology and pathogenesis of influenza *** analyzed receptor binding sites,basic patch,neutralization antibody epitopes and T cell epitopes in the HA protein of the current S-OIV according to the corresponding functional and structural modules previously characterized in other H1 HA molecules or HA molecules of other *** compared their differences and similarities *** on the amino acids defined as the functional and structural modules,the HA protein of 2009 S-OIV should specifically bind to the human 2,*** D225G/E mutation in HA,which is found in some isolates,may confer dual binding specificity to the 2,3and 2,6-receptor based on previously reported *** HA variant contains two basic patches,one of which results in increased basicity,suggesting enhanced membrane fusion *** 2009 S-OIV HA also has an extra glycosylation site at position *** of the five antibody neutralization epitopes identified in A/RP/8/34(H1N1) were exposed,but the other was hidden by a glycosylation *** previously identified cytotoxic T cell epitopes in various HA molecules were summarized and their corresponding sequences in 2009 S-OIV HA were *** results are critical for understanding the pathogenicity of the virus and host immune response against the virus.

关键词： 2009 S-OIV hemagglutinin in silico structural and functional modules

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Melanization in living organisms: a perspective of species evolution

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Protein & Cell 2010年第9期1卷 830-841页

作者： christopher J vavricka Bruce M.Christensen Jianyong Li CAS Key Laboratory of Pathogenic Microbiology and Immunology Institute of MicrobiologyChinese Academy of Sciences(CASPMI)Beijing 100101China Department of Pathobiology University of Wisconsin-MadisonMadisonWI 53706USA Department of Biochemistry Virginia TechBlacksburgVA 24061USA

Eumelanin is a heteropolymer that is generally composed of hydroxylated indole residues and plays diverse protective functions in various *** is derived from the amino acid tyrosine and production of melanin is a highly complex oxidative process with a number of steps that can either proceed enzymatically or *** melanin plays important protective roles in many species,during melanization,particularly in steps that can proceed non-enzymatically,many toxic intermediates are produced,including semiquinones,dopaquinone,indole-quinones and moreover,the production of many reactive oxygen *** mitigate the production of reactive species,a number of proteins that regulate the biochemical process of melanization have evolved in various living species,which is closely related to adaptation and physiological *** this communication,we discuss differences between non-enzymatic and enzymatic processes of melanization and the enzymatic regulation of melanization in difference species with an emphasis on differences between mammals and *** between melanization and insect sclerotization is also emphasized which raises some interesting questions about the current models of these pathways.

关键词： melanization melanogenesis sclerotization tanning dopa tyrosinase dopachrome tautomerase

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What job can a bug give?A controversy over the arsenic-guzzling bacterium cultured by NASA

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Protein & Cell 2011年第4期2卷 261-263页

作者： Mingwei Sun christopher J.vavricka Baoli Zhu CAS Key Laboratory of Pathogenic Microbiology and Immunology Institute of MicrobiologyChinese Academy of Sciences(CASPMI)Beijing 100101China College of Life Sciences University of Science and Technology of ChinaHefei 230027China

The mysteries of life’s evolution on our planet drive us to explore the limits of *** forms on Earth as we know are composed of six essential elements:carbon,hydrogen,oxygen,nitrogen,sulfur and ***,a recently published research work funded by the National Aeronautics and Space Administration(NASA),USA,has almost shaken the fundamental knowledge about what is life made of on *** research team led by NASA astrobiologist Felisa Wolfe-Simon described a microbe isolated from California’s Mono Lake that could sustain its growth by using toxic chemical arsenic(As)instead of phosphorus(P).This surprising discovery was published online by Science Express on December 2 last year(Wolfe-Simon et al.,2010,online).If the authors of the paper were right,we would have to expand our definition of life on this *** arsenic-bug they grew was dubbed GFAJ-1,which interestingly stands for“Give Felisa A Job.”

关键词： bug planet Express

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Deterministic epidemic models overestimate the basic reproduction number of observed outbreaks

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Infectious Disease Modelling 2024年第3期9卷 680-688页

作者： Wajid Ali christopher E.Overton Robert R.Wilkinson Kieran J.Sharkey Department of Mathematical Sciences University of LiverpoolPeach StreetLiverpoolL697ZXEnglandUnited Kingdom Department of Applied Mathematics Liverpool John Moores UniversityByrom StreetLiverpoolL35UXEnglandUnited Kingdom

The basic reproduction number,R_(0),is a well-known quantifier of epidemic ***,a class of existing methods for estimating R_(0)from incidence data early in the epidemic can lead to an over-estimation of this *** particular,when fitting deterministic models to estimate the rate of spread,we do not account for the stochastic nature of epidemics and that,given the same system,some outbreaks may lead to epidemics and some may ***,an observed epidemic that we wish to control is a major *** amounts to implicit selection for major outbreaks which leads to the over-estimation *** formally characterised the split between major and minor outbreaks by using Otsu's method which provides us with a working *** show that by conditioning a‘deterministic’model on major outbreaks,we can more reliably estimate the basic reproduction number from an observed epidemic trajectory.

关键词： Estimating R_(0) Simple birth-death process Major outbreak Conditioned epidemic Stochastic fade-out

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Special features of the 2009 pandemic swine-origin influenza AH1N1 hemagglutinin and neuraminidase

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Chinese Science Bulletin 2011年第17期56卷 1747-1752页

作者： vavricka christopher john LIU Yue LI Qing SHI Yi WU Yan SUN YePing QI JianXun GAO George Fu CAS Key Laboratory of Pathogenic Microbiology and Immunology Institute of Microbiology Chinese Academy of Sciences Beijing 100101 China School of Life Sciences University of Science and Technology of China Hefei 230027 China Graduate University of Chinese Academy of Sciences Beijing 100049 China 4 Beijing Institutes of Life Sciences Chinese Academy of Sciences Belting 100101 China

Since the 2009 pandemic H1N1 swine-origin influenza A virus (09 S-OIV) has reminded the world about the global threat of the ever changing influenza virus,many questions regarding the detailed re-assortment of influenza viruses yet remain *** A virus is the causative agent of the pandemic flu and contains 2 major antigenic glycoproteins on its surface:(i) hemagglutinin (HA);and (ii) neuraminidase (NA).The structures of the 09 S-OIV HA and NA proteins (09H1 and 09N1) have recently been resolved in our laboratory and provide some clues as to why the 09 S-OIV re-assortment virus is highly infectious with severe consequences in *** example,the 09H1 is highly similar to the HA of the 1918 influenza A pandemic virus in overall structure and especially in regards to its 5 defined antibody binding *** 09N1,its most distinctive feature is the lack of a 150-loop active site cavity,which was previously predicted to be present in all N1 NAs,and we hypothesize that the 150-loop may play a important role in the substrate specificity (α2,3 or α2,6 linked sialic acid receptors) and enzymatic mechanism of influenza *** of the HA and NA with special characteristics for the 09 S-OIV might contribute to its high increased transmissibility in humans.

关键词： A型流感病毒神经氨酸酶血凝素猪抗原表位底物特异性 NAS 活性部位

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Prehospital transdermal glyceryl trinitrate for ultra- acute ischaemic stroke: data from the RIGHT- 2 randomised sham- controlled ambulance trial

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Stroke & Vascular Neurology 2024年第1期9卷 38-49,I0035-I0046页

作者： Jason Philip Appleton Lisa J Woodhouse Craig S Anderson Sandeep Ankolekar Lesley Cala Mark Dixon Timothy J England Kailash Krishnan Grant Mair Keith W Muir john Potter christopher I Price Marc Randall Thompson G Robinson Christine Roffe Else C Sandset Jeffrey L Saver Angela Shone Aloysius Niroshan Siriwardena Joanna M Wardlaw Nikola Sprigg Philip M Bath Stroke University Hospitals Birmingham NHS Foundation TrustBirminghamUK Institute of Applied HealthResearch University of Birmingham College of Medical and Dental SciencesBirminghamUK Stroke Trials Unit Mental Health and Clinical NeurosciencesUniversity of NottinghamNottinghamUK Faculty of Medicine The George Institute for Global HealthSydneyNew South WalesAustralia The George Institute China at Peking University Health Science Center BeijingChina Neurology Royal Prince Alfred HospitalSydney Health PartnersSydneyNew South WalesAustralia Department of Neurology King's College Hospital NHS Foundation TrustLondonUK Faculty of Health and Medical Sciences University of Western AustraliaCrawleyWestern AustraliaAustralia East Midlands Ambulance Service NHS Trust NottinghamUK Stroke Queen's Medical CentreNottingham University Hospitals NHS TrustNottinghamUK Centre for Clinical Brain Sciences Dementia Research InstituteUniveristy of EdinburghEdinburghUK Institute of Neurology and Psychology University of GlasgowGlasgowUK Bob Champion Research and Education Building University of East AngliaNorwichUK Institute of Neuroscience Newcastle UniversityNewcastle upon TyneUK Department of Neurology Leeds Teaching Hospitals NHS TrustLeedsUK Department of Cardiovascular Sciences and NIHR Leicester Biomedical Research Centre University of LeicesterLeicesterUK Stroke Research in Stoke Institute for Science and Technology in MedicineKeele UniversityStoke-on TrentUK Department of Neurology Oslo University HospitalOsloNorway Research and Development Norwegian Air Ambulance FoundationOsloNorway Department of Neurology and Comprehensive Stroke Center David Geffen School of MedicineUCLALos AngelesCaliforniaUSA Research and Graduate Services University of NottinghamNottinghamUK Community and Health Research Unit University of LincolnLincolnUK

Background The effect of transdermal glyceryl trinitrate(GTN,a nitrovasodilator)on clinical outcome when administered before hospital admission in suspected stroke patients is ***,we assess the safety and efficacy of GTN in the prespecified subgroup of patients who had an ischaemic stroke within the Rapid Intervention with Glyceryl trinitrate in Hypertensive stroke Trial-2(RIGHT-2).Methods RIGHT-2 was an ambulance-based multicentre sham-controlled blinded-endpoint study with patients randomised within 4hours of *** primary outcome was a shift in scores on the modified Rankin scale(mRS)at day *** outcomes included death;a global analysis(Wei-Lachin test)containing Barthel Index,EuroQol-5D,mRS,telephone interview for cognitive status-modified and Zung depression scale;and neuroimaging-determined‘brain frailty’*** were reported as n(%),mean(SD),median[IQR],adjusted common OR(acOR),mean difference or Mann-Whitney difference(MWD)with 95%*** 597 of 1149(52%)patients had a final diagnosis of ischaemic stroke;age 75(12)years,premorbid mRS>2107(18%),Glasgow Coma Scale 14(2)and time from onset to randomisation 67[45,108]***‘brain frailty’was common:median score 2[2,3](range 0–3).At day 90,GTN did not influence the primary outcome(acOR for increased disability 1.15,95%CI 0.85 to 1.54),death or global analysis(MWD 0.00,95%CI-0.10 to 0.09).In subgroup analyses,there were non-significant interactions suggesting GTN may be associated with more death and dependency in participants randomised within 1hour of symptom onset and in those with more severe *** In patients who had an ischaemic stroke,ultra-acute administration of transdermal GTN in the ambulance did not improve clinical outcomes in a population with more clinical and radiological frailty than seen in previous in-hospital *** IS ALREADY KNOWN ON THIS TOPIC⇒Transdermal glyceryl trinitrate(GTN)was associat-ed with less death and dependency in those w

关键词： Glasgow nitrate random

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Tyrosine aminotransferase: biochemical and structural properties and molecular dynamics simulations

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Protein & Cell 2010年第11期1卷 1023-1032页

作者： Prajwalini Mehere Qian Han Justin A.Lemkul christopher J.vavricka Howard Robinson David R.Bevan Jianyong Li Department of Biochemistry Virginia TechBlacksburgVA 24061USA CAS Key Laboratory of Pathogenic Microbiology and Immunology Institute of MicrobiologyChinese Academy of SciencesBeijing 100101China Biology Department Brookhaven National LaboratoryUptonNY 11973USA

Tyrosine aminotransferase(TAT)catalyzes the transamination of tyrosine and other aromatic amino *** enzyme is thought to play a role in tyrosinemia type II,hepatitis and hepatic carcinoma *** objective of this study is to investigate its biochemical and structural characteristics and substrate specificity in order to provide insight regarding its involvement in these *** TAT(mTAT)was cloned from a mouse cDNA library,and its recombinant protein was produced using Escherichia coli cells and purified using various chromatographic *** recombinant mTAT is able to catalyze the transamination of tyrosine usingα-ketoglutaric acid as an amino group acceptor at neutral *** enzyme also can use glutamate and phenylalanine as amino group donors and p-hydroxyphenylpyruvate,phenylpyruvate and alpha-ketocaproic acid as amino group *** macromolecular crystallography we have determined the mTAT crystal structure at 2.9Å*** crystal structure revealed the interaction between the pyridoxal-5′-phosphate cofactor and the enzyme,as well as the formation of a disulphide *** detection of disulphide bond provides some rational explanation regarding previously observed TAT inactivation under oxidative conditions and reactivation of the inactive TAT in the presence of a reducing *** dynamics simulations using the crystal structures of Trypanosoma cruzi TAT and human TAT provided further insight regarding the substrate-enzyme interactions and substrate *** biochemical and structural properties of TAT and the binding of its cofactor and the substrate may help in elucidation of the mechanism of TAT inhibition and activation.

关键词： tyrosine aminotransferase crystal structure substrate specificity tyrosine tyrosinemia

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Crystal structure of the swine-origin A (H1N1)- 2009 influenza A virus hemagglutinin (HA) reveals similar antigenicity to that of the 1918 pandemic virus

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Protein & Cell 2010年第5期1卷 459-467页

作者： Wei Zhang Jianxun Qi Yi Shi Qing Li Feng Gao Yeping Sun Xishan Lu Qiong Lu christopher J.vavricka Di Liu Jinghua Yan George F.Gao CAS Key Laboratory of Pathogenic Microbiology and Immunology Institute of MicrobiologyChinese Academy of SciencesBeijing 100101China Graduate University Chinese Academy of SciencesBeijing 100049China College of Life Science University of Science and Technology of ChinaHefei 230027China Institute of Biophysics Chinese Academy of SciencesBeijing 100101China College of Veterinary Medicine China Agricultural UniversityBeijing 100094China Network Information Center Institute of MicrobiologyChinese Academy of SciencesBeijing 100101China Beijing Institutes of Life Science Chinese Academy of SciencesBeijing 100101China

Influenza virus is the causative agent of the seasonal and occasional pandemic *** current H1N1 influenza pandemic,announced by the WHO in June 2009,is highly contagious and responsible for global economic losses and *** the H1N1 gene segments have three origins in terms of host species,the virus has been named swine-origin influenza virus(S-OIV)due to a predominant swine origin.2009 S-OIV has been shown to highly resemble the 1918 pandemic virus in many *** is responsible for the host range and receptor binding of the virus and is therefore a primary indicator for the potential of *** sequence analysis of the 2009 S-OIV hemagglutinin(HA)reveals its closest relationship to that of the 1918 pandemic influenza virus,however,analysis at the structural level is necessary to critically assess the functional *** this report,we report the crystal structure of soluble hemagglutinin H1(09H1)at 2.9Å,illustrating that the 09H1 is very similar to the 1918 pandemic HA(18H1)in overall structure and the structural modules,including the five defined antiboby(Ab)-binding *** results provide an explanation as to why sera from the survivors of the 1918 pandemics can neutralize the 2009 S-OIV,and people born around the 1918 are resistant to the current pandemic,yet younger generations are more susceptible to the 2009 pandemic.

关键词： Influenza virus pandemic 2009 1918 S-OIV hemagglutinin(HA) structure

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