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  • Animals  (7)
  • Life and Medical Sciences
  • Geophysics
  • Nature Publishing Group (NPG)  (7)
  • 1
    Publication Date: 2008-01-04
    Description: Mammalian homologues of Drosophila melanogaster transient receptor potential (TRP) are a large family of multimeric cation channels that act, or putatively act, as sensors of one or more chemical factor. Major research objectives are the identification of endogenous activators and the determination of cellular and tissue functions of these channels. Here we show the activation of TRPC5 (canonical TRP 5) homomultimeric and TRPC5-TRPC1 heteromultimeric channels by extracellular reduced thioredoxin, which acts by breaking a disulphide bridge in the predicted extracellular loop adjacent to the ion-selectivity filter of TRPC5. Thioredoxin is an endogenous redox protein with established intracellular functions, but it is also secreted and its extracellular targets are largely unknown. Particularly high extracellular concentrations of thioredoxin are apparent in rheumatoid arthritis, an inflammatory joint disease that disables millions of people worldwide. We show that TRPC5 and TRPC1 are expressed in secretory fibroblast-like synoviocytes from patients with rheumatoid arthritis, that endogenous TRPC5-TRPC1 channels of the cells are activated by reduced thioredoxin, and that blockade of the channels enhances secretory activity and prevents the suppression of secretion by thioredoxin. The data indicate the presence of a previously unrecognized ion-channel activation mechanism that couples extracellular thioredoxin to cell function.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2645077/" 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/PMC2645077/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Xu, Shang-Zhong -- Sukumar, Piruthivi -- Zeng, Fanning -- Li, Jing -- Jairaman, Amit -- English, Anne -- Naylor, Jacqueline -- Ciurtin, Coziana -- Majeed, Yasser -- Milligan, Carol J -- Bahnasi, Yahya M -- Al-Shawaf, Eman -- Porter, Karen E -- Jiang, Lin-Hua -- Emery, Paul -- Sivaprasadarao, Asipu -- Beech, David J -- 077424/Wellcome Trust/United Kingdom -- 083857/Wellcome Trust/United Kingdom -- 18475/Arthritis Research UK/United Kingdom -- BB/D524875/1/Biotechnology and Biological Sciences Research Council/United Kingdom -- Wellcome Trust/United Kingdom -- England -- Nature. 2008 Jan 3;451(7174):69-72. doi: 10.1038/nature06414.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute of Membrane and Systems Biology, Garstang Building, Faculty of Biological Sciences, University of Leeds, Leeds LS2 9JT, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18172497" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Arthritis, Rheumatoid/metabolism/pathology ; Cell Line ; Disulfides/chemistry/metabolism ; Electric Conductivity ; Humans ; Oxidation-Reduction/drug effects ; Patch-Clamp Techniques ; Rabbits ; TRPC Cation Channels/*agonists/chemistry/*metabolism ; Thioredoxins/chemistry/*pharmacology
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  • 2
    Publication Date: 2014-12-18
    Description: Interventions that delay ageing mobilize mechanisms that protect and repair cellular components, but it is unknown how these interventions might slow the functional decline of extracellular matrices, which are also damaged during ageing. Reduced insulin/IGF-1 signalling (rIIS) extends lifespan across the evolutionary spectrum, and in juvenile Caenorhabditis elegans also allows the transcription factor DAF-16/FOXO to induce development into dauer, a diapause that withstands harsh conditions. It has been suggested that rIIS delays C. elegans ageing through activation of dauer-related processes during adulthood, but some rIIS conditions confer robust lifespan extension unaccompanied by any dauer-like traits. Here we show that rIIS can promote C. elegans longevity through a program that is genetically distinct from the dauer pathway, and requires the Nrf (NF-E2-related factor) orthologue SKN-1 acting in parallel to DAF-16. SKN-1 is inhibited by IIS and has been broadly implicated in longevity, but is rendered dispensable for rIIS lifespan extension by even mild activity of dauer-related processes. When IIS is decreased under conditions that do not induce dauer traits, SKN-1 most prominently increases expression of collagens and other extracellular matrix genes. Diverse genetic, nutritional, and pharmacological pro-longevity interventions delay an age-related decline in collagen expression. These collagens mediate adulthood extracellular matrix remodelling, and are needed for ageing to be delayed by interventions that do not involve dauer traits. By genetically delineating a dauer-independent rIIS ageing pathway, our results show that IIS controls a broad set of protective mechanisms during C. elegans adulthood, and may facilitate elucidation of processes of general importance for longevity. The importance of collagen production in diverse anti-ageing interventions implies that extracellular matrix remodelling is a generally essential signature of longevity assurance, and that agents promoting extracellular matrix youthfulness may have systemic benefit.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4352135/" 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/PMC4352135/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ewald, Collin Y -- Landis, Jess N -- Porter Abate, Jess -- Murphy, Coleen T -- Blackwell, T Keith -- 5T32DK007260/DK/NIDDK NIH HHS/ -- GM062891/GM/NIGMS NIH HHS/ -- P30 DK036836/DK/NIDDK NIH HHS/ -- P30DK036836/DK/NIDDK NIH HHS/ -- R01 GM062891/GM/NIGMS NIH HHS/ -- England -- Nature. 2015 Mar 5;519(7541):97-101. doi: 10.1038/nature14021. Epub 2014 Dec 15.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Joslin Diabetes Center, One Joslin Place, Boston, Massachusetts 02215, USA [2] Harvard Stem Cell Institute, 7 Divinity Avenue, Cambridge, Massachusetts 02138, USA [3] Department of Genetics, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, Massachusetts 02215, USA. ; Department of Molecular Biology, Lewis-Sigler Institute for Integrative Genomics, Princeton University, 148 Carl Icahn Laboratory, Washington Road, Princeton, New Jersey 08544, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25517099" target="_blank"〉PubMed〈/a〉
    Keywords: Aging/physiology ; Animals ; Caenorhabditis elegans/growth & development/*metabolism ; Caenorhabditis elegans Proteins/*metabolism ; Collagen/biosynthesis/genetics/*metabolism ; DNA-Binding Proteins/*metabolism ; Extracellular Matrix/metabolism ; Forkhead Transcription Factors ; Insulin/*metabolism ; Insulin-Like Growth Factor I/*metabolism ; Larva/growth & development ; Longevity/*physiology ; *Signal Transduction ; Transcription Factors/*metabolism
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  • 3
    Publication Date: 2012-10-13
    Description: The US National Institute of Neurological Disorders and Stroke convened major stakeholders in June 2012 to discuss how to improve the methodological reporting of animal studies in grant applications and publications. The main workshop recommendation is that at a minimum studies should report on sample-size estimation, whether and how animals were randomized, whether investigators were blind to the treatment, and the handling of data. We recognize that achieving a meaningful improvement in the quality of reporting will require a concerted effort by investigators, reviewers, funding agencies and journal editors. Requiring better reporting of animal studies will raise awareness of the importance of rigorous study design to accelerate scientific progress.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3511845/" 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/PMC3511845/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Landis, Story C -- Amara, Susan G -- Asadullah, Khusru -- Austin, Chris P -- Blumenstein, Robi -- Bradley, Eileen W -- Crystal, Ronald G -- Darnell, Robert B -- Ferrante, Robert J -- Fillit, Howard -- Finkelstein, Robert -- Fisher, Marc -- Gendelman, Howard E -- Golub, Robert M -- Goudreau, John L -- Gross, Robert A -- Gubitz, Amelie K -- Hesterlee, Sharon E -- Howells, David W -- Huguenard, John -- Kelner, Katrina -- Koroshetz, Walter -- Krainc, Dimitri -- Lazic, Stanley E -- Levine, Michael S -- Macleod, Malcolm R -- McCall, John M -- Moxley, Richard T 3rd -- Narasimhan, Kalyani -- Noble, Linda J -- Perrin, Steve -- Porter, John D -- Steward, Oswald -- Unger, Ellis -- Utz, Ursula -- Silberberg, Shai D -- P01 NS012151/NS/NINDS NIH HHS/ -- P30 MH062261/MH/NIMH NIH HHS/ -- R01 NS006477/NS/NINDS NIH HHS/ -- R01 NS034774/NS/NINDS NIH HHS/ -- R01 NS041574/NS/NINDS NIH HHS/ -- T32 MH020016/MH/NIMH NIH HHS/ -- T32 NS007280/NS/NINDS NIH HHS/ -- UL1 RR024160/RR/NCRR NIH HHS/ -- Z99 NS999999/Intramural NIH HHS/ -- England -- Nature. 2012 Oct 11;490(7419):187-91. doi: 10.1038/nature11556.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉National Institute of Neurological Disorders and Stroke, NIH, Bethesda, Maryland 20892, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23060188" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Publishing/*standards/trends ; Random Allocation ; Research Design/*standards ; Sample Size ; Statistics as Topic
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  • 4
    Publication Date: 2012-01-24
    Description: Hypertension affects one billion people and is a principal reversible risk factor for cardiovascular disease. Pseudohypoaldosteronism type II (PHAII), a rare Mendelian syndrome featuring hypertension, hyperkalaemia and metabolic acidosis, has revealed previously unrecognized physiology orchestrating the balance between renal salt reabsorption and K(+) and H(+) excretion. Here we used exome sequencing to identify mutations in kelch-like 3 (KLHL3) or cullin 3 (CUL3) in PHAII patients from 41 unrelated families. KLHL3 mutations are either recessive or dominant, whereas CUL3 mutations are dominant and predominantly de novo. CUL3 and BTB-domain-containing kelch proteins such as KLHL3 are components of cullin-RING E3 ligase complexes that ubiquitinate substrates bound to kelch propeller domains. Dominant KLHL3 mutations are clustered in short segments within the kelch propeller and BTB domains implicated in substrate and cullin binding, respectively. Diverse CUL3 mutations all result in skipping of exon 9, producing an in-frame deletion. Because dominant KLHL3 and CUL3 mutations both phenocopy recessive loss-of-function KLHL3 mutations, they may abrogate ubiquitination of KLHL3 substrates. Disease features are reversed by thiazide diuretics, which inhibit the Na-Cl cotransporter in the distal nephron of the kidney; KLHL3 and CUL3 are expressed in this location, suggesting a mechanistic link between KLHL3 and CUL3 mutations, increased Na-Cl reabsorption, and disease pathogenesis. These findings demonstrate the utility of exome sequencing in disease gene identification despite the combined complexities of locus heterogeneity, mixed models of transmission and frequent de novo mutation, and establish a fundamental role for KLHL3 and CUL3 in blood pressure, K(+) and pH homeostasis.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3278668/" 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/PMC3278668/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Boyden, Lynn M -- Choi, Murim -- Choate, Keith A -- Nelson-Williams, Carol J -- Farhi, Anita -- Toka, Hakan R -- Tikhonova, Irina R -- Bjornson, Robert -- Mane, Shrikant M -- Colussi, Giacomo -- Lebel, Marcel -- Gordon, Richard D -- Semmekrot, Ben A -- Poujol, Alain -- Valimaki, Matti J -- De Ferrari, Maria E -- Sanjad, Sami A -- Gutkin, Michael -- Karet, Fiona E -- Tucci, Joseph R -- Stockigt, Jim R -- Keppler-Noreuil, Kim M -- Porter, Craig C -- Anand, Sudhir K -- Whiteford, Margo L -- Davis, Ira D -- Dewar, Stephanie B -- Bettinelli, Alberto -- Fadrowski, Jeffrey J -- Belsha, Craig W -- Hunley, Tracy E -- Nelson, Raoul D -- Trachtman, Howard -- Cole, Trevor R P -- Pinsk, Maury -- Bockenhauer, Detlef -- Shenoy, Mohan -- Vaidyanathan, Priya -- Foreman, John W -- Rasoulpour, Majid -- Thameem, Farook -- Al-Shahrouri, Hania Z -- Radhakrishnan, Jai -- Gharavi, Ali G -- Goilav, Beatrice -- Lifton, Richard P -- KL2 RR024138/RR/NCRR NIH HHS/ -- KL2 RR024138-07/RR/NCRR NIH HHS/ -- P30 DK079310/DK/NIDDK NIH HHS/ -- P30 DK079310-04S1/DK/NIDDK NIH HHS/ -- P30-DK079310/DK/NIDDK NIH HHS/ -- UL1-RR024139/RR/NCRR NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2012 Jan 22;482(7383):98-102. doi: 10.1038/nature10814.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Genetics and Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, Connecticut 06510, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22266938" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Base Sequence ; Blood Pressure/genetics ; Carrier Proteins/chemistry/*genetics ; Cohort Studies ; Cullin Proteins/chemistry/*genetics ; Electrolytes ; Exons/genetics ; Female ; Gene Expression Profiling ; Genes, Dominant/genetics ; Genes, Recessive/genetics ; Genotype ; Homeostasis/genetics ; Humans ; Hydrogen-Ion Concentration ; Hypertension/complications/*genetics/physiopathology ; Male ; Mice ; Models, Molecular ; Molecular Sequence Data ; Mutation/*genetics ; Phenotype ; Potassium/metabolism ; Pseudohypoaldosteronism/complications/*genetics/physiopathology ; Sodium Chloride/metabolism ; Water-Electrolyte Imbalance/complications/*genetics/physiopathology
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  • 5
    Publication Date: 2015-03-25
    Description: No large group of recently extinct placental mammals remains as evolutionarily cryptic as the approximately 280 genera grouped as 'South American native ungulates'. To Charles Darwin, who first collected their remains, they included perhaps the 'strangest animal[s] ever discovered'. Today, much like 180 years ago, it is no clearer whether they had one origin or several, arose before or after the Cretaceous/Palaeogene transition 66.2 million years ago, or are more likely to belong with the elephants and sirenians of superorder Afrotheria than with the euungulates (cattle, horses, and allies) of superorder Laurasiatheria. Morphology-based analyses have proved unconvincing because convergences are pervasive among unrelated ungulate-like placentals. Approaches using ancient DNA have also been unsuccessful, probably because of rapid DNA degradation in semitropical and temperate deposits. Here we apply proteomic analysis to screen bone samples of the Late Quaternary South American native ungulate taxa Toxodon (Notoungulata) and Macrauchenia (Litopterna) for phylogenetically informative protein sequences. For each ungulate, we obtain approximately 90% direct sequence coverage of type I collagen alpha1- and alpha2-chains, representing approximately 900 of 1,140 amino-acid residues for each subunit. A phylogeny is estimated from an alignment of these fossil sequences with collagen (I) gene transcripts from available mammalian genomes or mass spectrometrically derived sequence data obtained for this study. The resulting consensus tree agrees well with recent higher-level mammalian phylogenies. Toxodon and Macrauchenia form a monophyletic group whose sister taxon is not Afrotheria or any of its constituent clades as recently claimed, but instead crown Perissodactyla (horses, tapirs, and rhinoceroses). These results are consistent with the origin of at least some South American native ungulates from 'condylarths', a paraphyletic assembly of archaic placentals. With ongoing improvements in instrumentation and analytical procedures, proteomics may produce a revolution in systematics such as that achieved by genomics, but with the possibility of reaching much further back in time.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Welker, Frido -- Collins, Matthew J -- Thomas, Jessica A -- Wadsley, Marc -- Brace, Selina -- Cappellini, Enrico -- Turvey, Samuel T -- Reguero, Marcelo -- Gelfo, Javier N -- Kramarz, Alejandro -- Burger, Joachim -- Thomas-Oates, Jane -- Ashford, David A -- Ashton, Peter D -- Rowsell, Keri -- Porter, Duncan M -- Kessler, Benedikt -- Fischer, Roman -- Baessmann, Carsten -- Kaspar, Stephanie -- Olsen, Jesper V -- Kiley, Patrick -- Elliott, James A -- Kelstrup, Christian D -- Mullin, Victoria -- Hofreiter, Michael -- Willerslev, Eske -- Hublin, Jean-Jacques -- Orlando, Ludovic -- Barnes, Ian -- MacPhee, Ross D E -- England -- Nature. 2015 Jun 4;522(7554):81-4. doi: 10.1038/nature14249. Epub 2015 Mar 18.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] BioArCh, University of York, York YO10 5DD, UK [2] Department of Human Evolution, Max Planck Institute for Evolutionary Anthropology, 04103 Leipzig, Germany. ; BioArCh, University of York, York YO10 5DD, UK. ; Department of Earth Sciences, Natural History Museum, London SW7 5BD, UK. ; Centre for GeoGenetics, Natural History Museum of Denmark, University of Copenhagen, Oster Voldgade 5-7, 1350 Copenhagen K, Denmark. ; Institute of Zoology, Zoological Society of London, London NW1 4RY, UK. ; CONICET- Division Paleontologia de Vertebrados, Museo de La Plata. Facultad de Ciencias Naturales y Museo de La Plata, Universidad Nacional de La Plata. Paseo del Bosque s/n, B1900FWA, La Plata, Argentina. ; Seccion Paleontologia de Vertebrados. Museo Argentino de Ciencias Naturales "Bernardino Rivadavia", 470 Angel Gallardo Av., C1405DJR, Buenos Aires, Argentina. ; Institute of Anthropology, Johannes Gutenberg-University, Anselm-Franz-von-Bentzel-Weg 7, D-55128 Mainz, Germany. ; Department of Chemistry, University of York, York YO10 5DD, UK. ; Bioscience Technology Facility, Department of Biology, University of York, York YO10 5DD, UK. ; Department of Biological Sciences, Virginia Polytechnic Institute and State University, Blacksburg, Virginia 24061, USA. ; Target Discovery Institute, Nuffield Department of Medicine, University of Oxford, Roosevelt Drive, Oxford OX3 7FZ, UK. ; Applications Development, Bruker Daltonik GmbH, 28359 Bremen, Germany. ; Novo Nordisk Foundation Center for Protein Research, Faculty of Health Sciences, University of Copenhagen, Blegdamsvej 3b, 2200 Copenhagen, Denmark. ; Department of Materials Science and Metallurgy, University of Cambridge, Cambridge CB3 0FS, UK. ; Smurfit Institute of Genetics, Trinity College Dublin, Dublin 2, Ireland. ; 1] BioArCh, University of York, York YO10 5DD, UK [2] Institute for Biochemistry and Biology, Karl-Liebknecht-Strasse 24-25, 14476 Potsdam OT Golm, Germany. ; Department of Human Evolution, Max Planck Institute for Evolutionary Anthropology, 04103 Leipzig, Germany. ; Department of Mammalogy, American Museum of Natural History, New York, New York 10024, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25799987" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Bone and Bones/chemistry ; Cattle ; Collagen Type I/*chemistry/genetics ; Female ; *Fossils ; Mammals/*classification ; Perissodactyla/classification ; *Phylogeny ; Placenta ; Pregnancy ; Proteomics ; South America
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  • 6
    Publication Date: 2012-05-12
    Description: R-spondin proteins strongly potentiate Wnt signalling and function as stem-cell growth factors. Despite the biological and therapeutic significance, the molecular mechanism of R-spondin action remains unclear. Here we show that the cell-surface transmembrane E3 ubiquitin ligase zinc and ring finger 3 (ZNRF3) and its homologue ring finger 43 (RNF43) are negative feedback regulators of Wnt signalling. ZNRF3 is associated with the Wnt receptor complex, and inhibits Wnt signalling by promoting the turnover of frizzled and LRP6. Inhibition of ZNRF3 enhances Wnt/beta-catenin signalling and disrupts Wnt/planar cell polarity signalling in vivo. Notably, R-spondin mimics ZNRF3 inhibition by increasing the membrane level of Wnt receptors. Mechanistically, R-spondin interacts with the extracellular domain of ZNRF3 and induces the association between ZNRF3 and LGR4, which results in membrane clearance of ZNRF3. These data suggest that R-spondin enhances Wnt signalling by inhibiting ZNRF3. Our study provides new mechanistic insights into the regulation of Wnt receptor turnover, and reveals ZNRF3 as a tractable target for therapeutic exploration.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hao, Huai-Xiang -- Xie, Yang -- Zhang, Yue -- Charlat, Olga -- Oster, Emma -- Avello, Monika -- Lei, Hong -- Mickanin, Craig -- Liu, Dong -- Ruffner, Heinz -- Mao, Xiaohong -- Ma, Qicheng -- Zamponi, Raffaella -- Bouwmeester, Tewis -- Finan, Peter M -- Kirschner, Marc W -- Porter, Jeffery A -- Serluca, Fabrizio C -- Cong, Feng -- England -- Nature. 2012 Apr 29;485(7397):195-200. doi: 10.1038/nature11019.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Novartis Institutes for Biomedical Research, 250 Massachusetts Avenue, Cambridge, Massachusetts 02139, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22575959" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Polarity/physiology ; Colorectal Neoplasms/genetics ; DNA-Binding Proteins/deficiency/genetics/metabolism ; Feedback, Physiological ; Female ; Frizzled Receptors/metabolism ; HEK293 Cells ; Humans ; Low Density Lipoprotein Receptor-Related Protein-6/metabolism ; Male ; Mice ; Mice, Knockout ; Oncogene Proteins/deficiency/genetics/metabolism ; Protein Stability ; Protein Structure, Tertiary ; Receptors, G-Protein-Coupled/deficiency/genetics/metabolism ; Receptors, Wnt/*metabolism ; Thrombospondins/*metabolism ; Ubiquitin-Protein Ligases/chemistry/*deficiency/genetics/*metabolism ; Ubiquitination ; Wnt Signaling Pathway ; Xenopus ; Zebrafish ; beta Catenin/metabolism
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  • 7
    Publication Date: 2015-01-09
    Description: Yeasts, which have been a component of the human diet for at least 7,000 years, possess an elaborate cell wall alpha-mannan. The influence of yeast mannan on the ecology of the human microbiota is unknown. Here we show that yeast alpha-mannan is a viable food source for the Gram-negative bacterium Bacteroides thetaiotaomicron, a dominant member of the microbiota. Detailed biochemical analysis and targeted gene disruption studies support a model whereby limited cleavage of alpha-mannan on the surface generates large oligosaccharides that are subsequently depolymerized to mannose by the action of periplasmic enzymes. Co-culturing studies showed that metabolism of yeast mannan by B. thetaiotaomicron presents a 'selfish' model for the catabolism of this difficult to breakdown polysaccharide. Genomic comparison with B. thetaiotaomicron in conjunction with cell culture studies show that a cohort of highly successful members of the microbiota has evolved to consume sterically-restricted yeast glycans, an adaptation that may reflect the incorporation of eukaryotic microorganisms into the human diet.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cuskin, Fiona -- Lowe, Elisabeth C -- Temple, Max J -- Zhu, Yanping -- Cameron, Elizabeth A -- Pudlo, Nicholas A -- Porter, Nathan T -- Urs, Karthik -- Thompson, Andrew J -- Cartmell, Alan -- Rogowski, Artur -- Hamilton, Brian S -- Chen, Rui -- Tolbert, Thomas J -- Piens, Kathleen -- Bracke, Debby -- Vervecken, Wouter -- Hakki, Zalihe -- Speciale, Gaetano -- Munoz-Munoz, Jose L -- Day, Andrew -- Pena, Maria J -- McLean, Richard -- Suits, Michael D -- Boraston, Alisdair B -- Atherly, Todd -- Ziemer, Cherie J -- Williams, Spencer J -- Davies, Gideon J -- Abbott, D Wade -- Martens, Eric C -- Gilbert, Harry J -- 097907/Wellcome Trust/United Kingdom -- BB/G016127/1/Biotechnology and Biological Sciences Research Council/United Kingdom -- GM090080/GM/NIGMS NIH HHS/ -- MOP-68913/Canadian Institutes of Health Research/Canada -- WT097907AIA/Wellcome Trust/United Kingdom -- England -- Nature. 2015 Jan 8;517(7533):165-9. doi: 10.1038/nature13995.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Institute for Cell and Molecular Biosciences, Newcastle University, Newcastle-upon-Tyne NE2 4HH, UK [2] Complex Carbohydrate Research Center, The University of Georgia, 315 Riverbend Road, Athens, Georgia 30602, USA. ; Institute for Cell and Molecular Biosciences, Newcastle University, Newcastle-upon-Tyne NE2 4HH, UK. ; Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, Michigan 48109 USA. ; Department of Chemistry, University of York, York YO10 5DD, UK. ; School of Chemistry and Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Parkville, Victoria 3010, Australia. ; Interdisciplinary Biochemistry Graduate Program, Indiana University, 800 E. Kirkwood Avenue, Bloomington, Indiana 47405, USA. ; Department of Chemistry, Indiana University, 800 E. Kirkwood Avenue, Bloomington, Indiana 47405, USA. ; Department of Pharmaceutical Chemistry, University of Kansas School of Pharmacy, 2095 Constant Avenue, Lawrence, Kansas 66047, USA. ; Oxyrane, 9052 Ghent, Belgium. ; Complex Carbohydrate Research Center, The University of Georgia, 315 Riverbend Road, Athens, Georgia 30602, USA. ; Agriculture and Agri-Food Canada, Lethbridge Research Centre, Lethbridge, Alberta T1J 4B1, Canada. ; Biochemistry and Microbiology, University of Victoria, Victoria, British Columbia V8P 5C2, Canada. ; USDA, Agricultural Research Service, National Laboratory for Agriculture and the Environment, Ames, Iowa 50011, USA. ; 1] Complex Carbohydrate Research Center, The University of Georgia, 315 Riverbend Road, Athens, Georgia 30602, USA [2] Agriculture and Agri-Food Canada, Lethbridge Research Centre, Lethbridge, Alberta T1J 4B1, Canada.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25567280" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Bacteroidetes/cytology/enzymology/genetics/*metabolism ; Biological Evolution ; Carbohydrate Conformation ; Diet ; Enzymes/genetics/metabolism ; Female ; Gastrointestinal Tract/*microbiology ; Genetic Loci/genetics ; Germ-Free Life ; Glycoproteins/chemistry/metabolism ; Humans ; Male ; Mannans/chemistry/*metabolism ; Mannose/metabolism ; Mice ; *Models, Biological ; Models, Molecular ; Oligosaccharides/chemistry/metabolism ; Periplasm/enzymology ; Yeasts/*chemistry
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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