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  • 1
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    Incorporation of a non-human glycan mediates human susceptibility to a bacterial toxin (2008)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2008-10-31
    Description: AB(5) toxins comprise an A subunit that corrupts essential eukaryotic cell functions, and pentameric B subunits that direct target-cell uptake after binding surface glycans. Subtilase cytotoxin (SubAB) is an AB(5) toxin secreted by Shiga toxigenic Escherichia coli (STEC), which causes serious gastrointestinal disease in humans. SubAB causes haemolytic uraemic syndrome-like pathology in mice through SubA-mediated cleavage of BiP/GRP78, an essential endoplasmic reticulum chaperone. Here we show that SubB has a strong preference for glycans terminating in the sialic acid N-glycolylneuraminic acid (Neu5Gc), a monosaccharide not synthesized in humans. Structures of SubB-Neu5Gc complexes revealed the basis for this specificity, and mutagenesis of key SubB residues abrogated in vitro glycan recognition, cell binding and cytotoxicity. SubAB specificity for Neu5Gc was confirmed using mouse tissues with a human-like deficiency of Neu5Gc and human cell lines fed with Neu5Gc. Despite lack of Neu5Gc biosynthesis in humans, assimilation of dietary Neu5Gc creates high-affinity receptors on human gut epithelia and kidney vasculature. This, and the lack of Neu5Gc-containing body fluid competitors in humans, confers susceptibility to the gastrointestinal and systemic toxicities of SubAB. Ironically, foods rich in Neu5Gc are the most common source of STEC contamination. Thus a bacterial toxin's receptor is generated by metabolic incorporation of an exogenous factor derived from food.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2723748/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2723748/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Byres, Emma -- Paton, Adrienne W -- Paton, James C -- Lofling, Jonas C -- Smith, David F -- Wilce, Matthew C J -- Talbot, Ursula M -- Chong, Damien C -- Yu, Hai -- Huang, Shengshu -- Chen, Xi -- Varki, Nissi M -- Varki, Ajit -- Rossjohn, Jamie -- Beddoe, Travis -- R01 AI068715-01A1/AI/NIAID NIH HHS/ -- R01 AI068715-02/AI/NIAID NIH HHS/ -- England -- Nature. 2008 Dec 4;456(7222):648-52. doi: 10.1038/nature07428. Epub 2008 Oct 29.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Protein Crystallography Unit and ARC Centre of Excellence for Structural and Functional Microbial Genomics, Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria 3800, Australia.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18971931" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Bacterial Toxins/chemistry/genetics/*metabolism/*toxicity ; Cell Death/drug effects ; Cell Line ; Crystallography, X-Ray ; Escherichia coli Proteins/*chemistry/genetics/metabolism/*toxicity ; Humans ; Mice ; Microscopy, Fluorescence ; Models, Molecular ; Neuraminic Acids/administration & dosage/*metabolism/pharmacology ; Polysaccharides/*chemistry/*metabolism ; Protein Binding ; Protein Subunits ; Shiga-Toxigenic Escherichia coli/chemistry/pathogenicity ; Sialic Acids/chemistry/metabolism ; Species Specificity ; Substrate Specificity ; Subtilisins/*chemistry/genetics/metabolism/*toxicity ; Survival Analysis
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
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  • 2
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    The genome of the kinetoplastid parasite, Leishmania major (2005)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2005-07-16
    Description: Leishmania species cause a spectrum of human diseases in tropical and subtropical regions of the world. We have sequenced the 36 chromosomes of the 32.8-megabase haploid genome of Leishmania major (Friedlin strain) and predict 911 RNA genes, 39 pseudogenes, and 8272 protein-coding genes, of which 36% can be ascribed a putative function. These include genes involved in host-pathogen interactions, such as proteolytic enzymes, and extensive machinery for synthesis of complex surface glycoconjugates. The organization of protein-coding genes into long, strand-specific, polycistronic clusters and lack of general transcription factors in the L. major, Trypanosoma brucei, and Trypanosoma cruzi (Tritryp) genomes suggest that the mechanisms regulating RNA polymerase II-directed transcription are distinct from those operating in other eukaryotes, although the trypanosomatids appear capable of chromatin remodeling. Abundant RNA-binding proteins are encoded in the Tritryp genomes, consistent with active posttranscriptional regulation of gene expression.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1470643/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1470643/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ivens, Alasdair C -- Peacock, Christopher S -- Worthey, Elizabeth A -- Murphy, Lee -- Aggarwal, Gautam -- Berriman, Matthew -- Sisk, Ellen -- Rajandream, Marie-Adele -- Adlem, Ellen -- Aert, Rita -- Anupama, Atashi -- Apostolou, Zina -- Attipoe, Philip -- Bason, Nathalie -- Bauser, Christopher -- Beck, Alfred -- Beverley, Stephen M -- Bianchettin, Gabriella -- Borzym, Katja -- Bothe, Gordana -- Bruschi, Carlo V -- Collins, Matt -- Cadag, Eithon -- Ciarloni, Laura -- Clayton, Christine -- Coulson, Richard M R -- Cronin, Ann -- Cruz, Angela K -- Davies, Robert M -- De Gaudenzi, Javier -- Dobson, Deborah E -- Duesterhoeft, Andreas -- Fazelina, Gholam -- Fosker, Nigel -- Frasch, Alberto Carlos -- Fraser, Audrey -- Fuchs, Monika -- Gabel, Claudia -- Goble, Arlette -- Goffeau, Andre -- Harris, David -- Hertz-Fowler, Christiane -- Hilbert, Helmut -- Horn, David -- Huang, Yiting -- Klages, Sven -- Knights, Andrew -- Kube, Michael -- Larke, Natasha -- Litvin, Lyudmila -- Lord, Angela -- Louie, Tin -- Marra, Marco -- Masuy, David -- Matthews, Keith -- Michaeli, Shulamit -- Mottram, Jeremy C -- Muller-Auer, Silke -- Munden, Heather -- Nelson, Siri -- Norbertczak, Halina -- Oliver, Karen -- O'neil, Susan -- Pentony, Martin -- Pohl, Thomas M -- Price, Claire -- Purnelle, Benedicte -- Quail, Michael A -- Rabbinowitsch, Ester -- Reinhardt, Richard -- Rieger, Michael -- Rinta, Joel -- Robben, Johan -- Robertson, Laura -- Ruiz, Jeronimo C -- Rutter, Simon -- Saunders, David -- Schafer, Melanie -- Schein, Jacquie -- Schwartz, David C -- Seeger, Kathy -- Seyler, Amber -- Sharp, Sarah -- Shin, Heesun -- Sivam, Dhileep -- Squares, Rob -- Squares, Steve -- Tosato, Valentina -- Vogt, Christy -- Volckaert, Guido -- Wambutt, Rolf -- Warren, Tim -- Wedler, Holger -- Woodward, John -- Zhou, Shiguo -- Zimmermann, Wolfgang -- Smith, Deborah F -- Blackwell, Jenefer M -- Stuart, Kenneth D -- Barrell, Bart -- Myler, Peter J -- R01 AI040599/AI/NIAID NIH HHS/ -- R01 AI053667/AI/NIAID NIH HHS/ -- U01 AI040599/AI/NIAID NIH HHS/ -- Wellcome Trust/United Kingdom -- New York, N.Y. -- Science. 2005 Jul 15;309(5733):436-42.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire CB10 1SA, UK. alicat@sanger.ac.uk〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/16020728" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Chromatin/genetics/metabolism ; Gene Expression Regulation ; Genes, Protozoan ; Genes, rRNA ; *Genome, Protozoan ; Glycoconjugates/biosynthesis/metabolism ; Leishmania major/chemistry/*genetics/metabolism ; Leishmaniasis, Cutaneous/parasitology ; Lipid Metabolism ; Membrane Proteins/biosynthesis/chemistry/genetics/metabolism ; Molecular Sequence Data ; Multigene Family ; Protein Biosynthesis ; Protein Processing, Post-Translational ; Protozoan Proteins/biosynthesis/chemistry/genetics/metabolism ; RNA Processing, Post-Transcriptional ; RNA Splicing ; RNA, Protozoan/genetics/metabolism ; *Sequence Analysis, DNA ; Transcription, Genetic
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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  • 3
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    Immunization by avian H5 influenza hemagglutinin mutants with altered receptor binding specificity (2007)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2007-08-11
    Description: Influenza virus entry is mediated by the receptor binding domain (RBD) of its spike, the hemagglutinin (HA). Adaptation of avian viruses to humans is associated with HA specificity for alpha2,6- rather than alpha2,3-linked sialic acid (SA) receptors. Here, we define mutations in influenza A subtype H5N1 (avian) HA that alter its specificity for SA either by decreasing alpha2,3- or increasing alpha2,6-SA recognition. RBD mutants were used to develop vaccines and monoclonal antibodies that neutralized new variants. Structure-based modification of HA specificity can guide the development of preemptive vaccines and therapeutic monoclonal antibodies that can be evaluated before the emergence of human-adapted H5N1 strains.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2367145/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2367145/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Yang, Zhi-Yong -- Wei, Chih-Jen -- Kong, Wing-Pui -- Wu, Lan -- Xu, Ling -- Smith, David F -- Nabel, Gary J -- Z99 AI999999/Intramural NIH HHS/ -- New York, N.Y. -- Science. 2007 Aug 10;317(5839):825-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Vaccine Research Center, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health, Building 40, Room 4502, Mailstop Code MSC-3005, 40 Convent Drive, Bethesda, MD 20892, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17690300" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antibodies, Monoclonal/immunology ; Antibodies, Viral/immunology ; Carbohydrate Conformation ; Cell Line ; Female ; Genes, Viral ; Hemagglutination Inhibition Tests ; Hemagglutinin Glycoproteins, Influenza Virus/*genetics/*immunology/metabolism ; Humans ; Influenza A Virus, H5N1 Subtype/*genetics/*immunology/metabolism ; Influenza Vaccines/immunology ; Mice ; Mice, Inbred BALB C ; Molecular Sequence Data ; *Mutation ; Neutralization Tests ; Receptors, Virus/*metabolism ; Sialic Acids/*metabolism ; Vaccination
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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  • 4
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    From The Cover: Cochaperone immunophilin FKBP52 is critical to uterine receptivity for embryo implantation (2005)
    National Academy of Sciences
    Details
    Publication Date: 2005-09-21
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
    Published by National Academy of Sciences
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  • 5
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    Identification of mRNA splicing factors as the endothelial receptor for carbohydrate-dependent lung colonization of cancer cells (2009)
    National Academy of Sciences
    Details
    Publication Date: 2009-02-13
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
    Published by National Academy of Sciences
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  • 6
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    Antibodies against Man 1,2-Man 1,2-Man oligosaccharide structures recognize envelope glycoproteins from HIV-1 and SIV strains (2009)
    Oxford University Press
    Details
    Publication Date: 2009-11-17
    Print ISSN: 0959-6658
    Electronic ISSN: 1460-2423
    Topics: Biology , Medicine
    Published by Oxford University Press
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  • 7
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    The T1-T2 study: evolution of aerosol properties downwind of Mexico City (2007)
    Copernicus
    Details
    Publication Date: 2007-03-23
    Description: As part of a major atmospheric chemistry and aerosol field program carried out in March 2006, a study was conducted in the area to the north and northeast of Mexico City to investigate the evolution of aerosols and their associated optical properties in the first few hours after their emission. The focus of the T1-T2 aerosol study was to investigate changes in the specific absorption αABS (absorption per unit mass, with unit of m2 g−1) of black carbon as it aged and became coated with compounds such as sulfate and organic carbon, evolving from an external to an internal mixture. Such evolution has been reported in previous studies. The T1 site was located just to the north of the Mexico City metropolitan area; the T2 site was situated approximately 35 km farther to the northeast. Nephelometers, particle soot absorption photometers, photoacoustic absorption spectrometers, and organic and elemental carbon analyzers were used to measure the optical properties of the aerosols and the carbon concentrations at each of the sites. Radar wind profilers and radiosonde systems helped to characterize the meteorology and to identify periods when transport from Mexico City over T1 and T2 occurred. Organic and elemental carbon concentrations at T1 showed diurnal cycles reflecting the nocturnal and early morning buildup from nearby sources, while concentrations at T2 appeared to be more affected by transport from Mexico City. Specific absorption during transport periods was lower than during other times, consistent with the likelihood of fresher emissions being found when the winds blew from Mexico City over T1 and T2. The specific absorption at T2 was larger than at T1, which is also consistent with the expectation of more aged particles with encapsulated black carbon being found at the more distant location. In situ measurements of single scattering albedo with an aircraft and a ground station showed general agreement with column-averaged values derived from rotating shadowband radiometer data, although some differences were found that may be related to boundary-layer evolution.
    Print ISSN: 1680-7316
    Electronic ISSN: 1680-7324
    Topics: Geosciences
    Published by Copernicus on behalf of European Geosciences Union.
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  • 8
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    The T1-T2 study: evolution of aerosol properties downwind of Mexico City (2006)
    Copernicus
    Details
    Publication Date: 2006-12-12
    Description: As part of a major atmospheric chemistry and aerosol field program carried out in March of 2006, a study was conducted in the area to the north and northeast of Mexico City to investigate the evolution of aerosols and their associated optical properties in the first few hours after their emission. The focus of the T1-T2 aerosol study was to investigate changes in the specific absorption αABS (absorption per unit mass, with unit of m2 g−1) of black carbon as it aged and became coated with compounds such as sulfate and organic carbon, evolving from an external to an internal mixture. Such evolution has been reported in previous studies. The T1 site was located just to the north of the Mexico City metropolitan area; the T2 site was situated approximately 35 km farther to the northeast. Nephelometers, particle soot absorption photometers, photoacoustic absorption photometers, and organic and elemental carbon analyzers were used to measure the optical properties of the aerosols and the carbon concentrations at each of the sites. Radar wind profilers and radiosonde systems helped to characterize the meteorology and to identify periods when transport from Mexico City over T1 and T2 occurred. Organic and elemental carbon concentrations at T1 showed diurnal cycles reflecting the nocturnal and early morning buildup from nearby sources, while concentrations at T2 appeared to be more affected by transport from Mexico City. Specific absorption during transport periods was lower than during other times, consistent with the likelihood of fresher emissions being found when the winds blew from Mexico City over T1 and T2. The specific absorption at T2 was larger than at T1, which is also consistent with the expectation of more aged particles with encapsulated black carbon being found at the more distant location. In situ measurements of single scattering albedo with an aircraft and a ground station showed general agreement with column-averaged values derived from rotating shadowband radiometer data, although some differences were found that may be related to boundary-layer evolution.
    Electronic ISSN: 1680-7375
    Topics: Geosciences
    Published by Copernicus on behalf of European Geosciences Union.
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