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  1. Article ; Online: Awareness of Racial and Ethnic Bias and Potential Solutions to Address Bias With Use of Health Care Algorithms.

    Jain, Anjali / Brooks, Jasmin R / Alford, Cleothia C / Chang, Christine S / Mueller, Nora M / Umscheid, Craig A / Bierman, Arlene S

    JAMA health forum

    2023  Volume 4, Issue 6, Page(s) e231197

    Abstract: Importance: Algorithms are commonly incorporated into health care decision tools used by health systems and payers and thus affect quality of care, access, and health outcomes. Some algorithms include a patient's race or ethnicity among their inputs and ...

    Abstract Importance: Algorithms are commonly incorporated into health care decision tools used by health systems and payers and thus affect quality of care, access, and health outcomes. Some algorithms include a patient's race or ethnicity among their inputs and can lead clinicians and decision-makers to make choices that vary by race and potentially affect inequities.
    Objective: To inform an evidence review on the use of race- and ethnicity-based algorithms in health care by gathering public and stakeholder perspectives about the repercussions of and efforts to address algorithm-related bias.
    Design, setting, and participants: Qualitative methods were used to analyze responses. Responses were initially open coded and then consolidated to create a codebook, with themes and subthemes identified and finalized by consensus. This qualitative study was conducted from May 4, 2021, through December 7, 2022. Forty-two organization representatives (eg, clinical professional societies, universities, government agencies, payers, and health technology organizations) and individuals responded to the request for information.
    Main outcomes and measures: Identification of algorithms with the potential for race- and ethnicity-based biases and qualitative themes.
    Results: Forty-two respondents identified 18 algorithms currently in use with the potential for bias, including, for example, the Simple Calculated Osteoporosis Risk Estimation risk prediction tool and the risk calculator for vaginal birth after cesarean section. The 7 qualitative themes, with 31 subthemes, included the following: (1) algorithms are in widespread use and have significant repercussions, (2) bias can result from algorithms whether or not they explicitly include race, (3) clinicians and patients are often unaware of the use of algorithms and potential for bias, (4) race is a social construct used as a proxy for clinical variables, (5) there is a lack of standardization in how race and social determinants of health are collected and defined, (6) bias can be introduced at all stages of algorithm development, and (7) algorithms should be discussed as part of shared decision-making between the patient and clinician.
    Conclusions and relevance: This qualitative study found that participants perceived widespread and increasing use of algorithms in health care and lack of oversight, potentially exacerbating racial and ethnic inequities. Increasing awareness for clinicians and patients and standardized, transparent approaches for algorithm development and implementation may be needed to address racial and ethnic biases related to algorithms.
    MeSH term(s) Pregnancy ; Humans ; Female ; Cesarean Section ; Delivery of Health Care ; Ethnicity ; Health Facilities ; Bias
    Language English
    Publishing date 2023-06-02
    Publishing country United States
    Document type Journal Article
    ISSN 2689-0186
    ISSN (online) 2689-0186
    DOI 10.1001/jamahealthforum.2023.1197
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Development of a Protease Biosensor Based on a Dimerization-Dependent Red Fluorescent Protein.

    Mitchell, Aaron C / Alford, Spencer C / Hunter, Sean A / Kannan, Deepti / Parra Sperberg, R Andres / Chang, Cheryl H / Cochran, Jennifer R

    ACS chemical biology

    2017  Volume 13, Issue 1, Page(s) 66–72

    Abstract: Dysregulated activity of the protease matriptase is a key contributor to aggressive tumor growth, cancer metastasis, and osteoarthritis. Methods for the detection and quantification of matriptase activity and inhibition would be useful tools. To address ... ...

    Abstract Dysregulated activity of the protease matriptase is a key contributor to aggressive tumor growth, cancer metastasis, and osteoarthritis. Methods for the detection and quantification of matriptase activity and inhibition would be useful tools. To address this need, we developed a matriptase-sensitive protein biosensor based on a dimerization-dependent red fluorescent protein (ddRFP) reporter system. In this platform, two adjoining protein domains, connected by a protease-labile linker, produce fluorescence when assembled and are nonfluorescent when the linker is cleaved by matriptase. A panel of ddRFP-based matriptase biosensor designs was created that contained different linker lengths between the protein domains. These constructs were characterized for linker-specific cleavage, matriptase activity, and matriptase selectivity; a biosensor containing a RSKLRVGGH linker (termed B4) was expressed at high yields and displayed both high catalytic efficiency and matriptase specificity. This biosensor detects matriptase inhibition by soluble and yeast cell surface expressed inhibitor domains with up to a 5-fold dynamic range and also detects matriptase activity expressed by human cancer cell lines. In addition to matriptase, we highlight a strategy that can be used to create effective biosensors for quantifying activity and inhibition of other proteases of interest.
    MeSH term(s) Biosensing Techniques/methods ; Blotting, Western ; Cell Line, Tumor ; Drug Evaluation, Preclinical/instrumentation ; Drug Evaluation, Preclinical/methods ; Escherichia coli/genetics ; Humans ; Luminescent Proteins/chemistry ; Luminescent Proteins/genetics ; Luminescent Proteins/metabolism ; Peptide Hydrolases/analysis ; Peptide Hydrolases/metabolism ; Protein Multimerization ; Serine Endopeptidases/analysis ; Serine Endopeptidases/metabolism ; Serine Proteinase Inhibitors/pharmacology ; Structure-Activity Relationship ; Red Fluorescent Protein
    Chemical Substances Luminescent Proteins ; Serine Proteinase Inhibitors ; Peptide Hydrolases (EC 3.4.-) ; Serine Endopeptidases (EC 3.4.21.-) ; matriptase (EC 3.4.21.-)
    Language English
    Publishing date 2017-12-12
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
    ISSN 1554-8937
    ISSN (online) 1554-8937
    DOI 10.1021/acschembio.7b00715
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Coastal inundation regime moderates the short-term effects of sediment and soil additions on seawater oxygen and greenhouse gas dynamics

    Peter Regier / Nicholas D. Ward / Alex Izquierdo / Andrew H. Baldwin / Donnie Day / Julia McElhinny / Kaizad Patel / Rodrigo Vargas / Jianqiu Zheng / Exchange Consortium / Allison Myers-Pigg / Silver Alford / Michael P. Back / Vanessa Bailey / Jade Bolinger / Madison Bowe / Maxim I. Boyanov / Jacob A. Cianci-Gaskill / Nathan A. Conroy /
    Matthew J. Cooper / Alex Demeo / Kyle Derby / Derek Detweiler / Suzanne Devres-Zimmerman / Erin Eberhard / Keryn Gedan / LeeAnn Haaf / Khadijah K. Homolka / Erin Johnson / Kenneth M. Kemner / Aliya Khan / Matthew Kirwan / Payton Kittaka / Erika Koontz / Adam Langley / Riley Leff / Scott Lerberg / Allison M. Lewis / Sairah Malkin / Amy M. Marcarelli / Steven E. McMurray / Tyler Messerschmidt / Taylor C. Michael / Holly A. Michael / Elizabeth C. Minor / Brian Moye / Thomas J. Mozdzer / Allison N. Myers-Pigg / Neubauer Scott / Cooper G. Norris / Edward J. O'Loughlin / Opal Otenburg / Andrea Pain / Kaizad F. Patel / Stephanie C. Pennington / Michael Philben / Evan Phillips / Dannielle Pratt / J. Alan Roebuck Jr. / Lauren Sage / Daniel Sandborn / Stacy Smith / Alex Smith / Samina Soin-Voshell / Bongkeun Song / Amanda Sprague-Getsy / Kari St Laurent / Lorie Staver / Alice Stearns / Lucie Stetten / Rebecca Swerida / Ethan J. Theuerkauf / Katherine Tully / Elizabeth Watson / Coreen Weilminster

    Frontiers in Marine Science, Vol

    a microcosm experiment

    2023  Volume 10

    Abstract: The frequency and persistence of tidal inundation varies along the coastal terrestrial-aquatic interface, from frequently inundated wetlands to rarely inundated upland forests. This inundation gradient controls soil and sediment biogeochemistry and ... ...

    Abstract The frequency and persistence of tidal inundation varies along the coastal terrestrial-aquatic interface, from frequently inundated wetlands to rarely inundated upland forests. This inundation gradient controls soil and sediment biogeochemistry and influence the exchange of soils and sediments from terrestrial to aquatic domains. Although a rich literature exist on studies of the influence of tidal waters on the biogeochemistry of coastal ecosystem soils, few studies have experimentally addressed the reverse question: How do soils (or sediments) from different coastal ecosystems influence the biogeochemistry of the tidal waters that inundate them? To better understand initial responses of coastal waters that flood coastal wetlands and uplands, we conducted short-term laboratory experiments where seawater was amended with sediments and soils collected across regional gradients of inundation exposure (i.e., frequently to rarely inundated) for 14 sites across the Mid-Atlantic, USA. Measured changes in dissolved oxygen and greenhouse gas concentrations were used to calculate gas consumption or production rates occurring during seawater exposure to terrestrial materials. We also measured soil and water physical and chemical properties to explore potential drivers. We observed higher oxygen consumption rates for seawater incubated with soils/sediments from frequently inundated locations and higher carbon dioxide production for seawater incubated with soils from rarely inundated transect locations. Incubations with soil from rarely inundated sites produced the highest global warming potential, primarily driven by carbon dioxide and secondarily by nitrous oxide. We also found environmental drivers of gas rates varied notably between transect locations. Our findings indicate that seawater responses to soil and sediment inputs across coastal terrestrial-aquatic interfaces exhibit some consistent patterns and high intra- and inter-site variability, suggesting potential biogeochemical feedback loops as inundation regimes ...
    Keywords greenhouse gases ; dissolved oxygen ; aquatic carbon cycle ; terrestrial-aquatic interface ; coastal inundation ; Science ; Q ; General. Including nature conservation ; geographical distribution ; QH1-199.5
    Subject code 550
    Language English
    Publishing date 2023-12-01T00:00:00Z
    Publisher Frontiers Media S.A.
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article ; Online: The International Atomic Energy Agency International Doubly Labelled Water Database: Aims, Scope and Procedures.

    Speakman, John R / Pontzer, Herman / Rood, Jennifer / Sagayama, Hiroyuki / Schoeller, Dale A / Westerterp, Klaas R / Wong, William W / Yamada, Yosuke / Loechl, Cornelia / Murphy-Alford, Alexia J

    Annals of nutrition & metabolism

    2019  Volume 75, Issue 2, Page(s) 114–118

    Abstract: Background: The doubly labelled water (DLW) method is an isotope-based technique that quantifies total energy expenditure (TEE) over periods of 1-3 weeks from the differential elimination of stable isotopes of oxygen and hydrogen. The method was ... ...

    Abstract Background: The doubly labelled water (DLW) method is an isotope-based technique that quantifies total energy expenditure (TEE) over periods of 1-3 weeks from the differential elimination of stable isotopes of oxygen and hydrogen. The method was invented in the 1950s, but limited ability to measure low isotope enrichments combined with the high cost of isotopes meant it only became feasible to use in humans in the 1980s. It is still relatively expensive to use, and alone small samples are unable to tackle some of the important questions surrounding energy balance such as how have expenditures changed over time and how do expenditures differ with age, between sexes and in different environments?
    Summary: By combining information across studies, answers to such questions may be possible. The International Atomic Energy Agency (IAEA) DLW database was established to pool DLW data across multiple studies. It was initiated by the main labs currently using the method and is hosted by the IAEA. At present, the database contains 6,621 measures of TEE by DLW from individuals in 23 countries, along with various additional data on the study participants. Key Messages: The IAEA DLW database is a key resource enabling future studies of energy demands.
    MeSH term(s) Adult ; Body Weight ; Breast Feeding ; Databases, Factual ; Deuterium/administration & dosage ; Deuterium/analysis ; Energy Intake ; Energy Metabolism ; Female ; Humans ; Infant ; International Agencies ; Male ; Malnutrition/epidemiology ; Overnutrition/epidemiology ; Oxygen Isotopes/administration & dosage ; Oxygen Isotopes/analysis ; Pregnancy ; Water Supply
    Chemical Substances Oxygen Isotopes ; Oxygen-18 ; Deuterium (AR09D82C7G)
    Language English
    Publishing date 2019-11-19
    Publishing country Switzerland
    Document type Congress ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 392341-1
    ISSN 1421-9697 ; 0250-6807 ; 1018-9688
    ISSN (online) 1421-9697
    ISSN 0250-6807 ; 1018-9688
    DOI 10.1159/000503668
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Modified Sialic Acids on Mucus and Erythrocytes Inhibit Influenza A Virus Hemagglutinin and Neuraminidase Functions.

    Barnard, Karen N / Alford-Lawrence, Brynn K / Buchholz, David W / Wasik, Brian R / LaClair, Justin R / Yu, Hai / Honce, Rebekah / Ruhl, Stefan / Pajic, Petar / Daugherity, Erin K / Chen, Xi / Schultz-Cherry, Stacey L / Aguilar, Hector C / Varki, Ajit / Parrish, Colin R

    Journal of virology

    2020  Volume 94, Issue 9

    Abstract: Sialic acids (Sia) are the primary receptors for influenza viruses and are widely displayed on cell surfaces and in secreted mucus. Sia may be present in variant forms that ... ...

    Abstract Sialic acids (Sia) are the primary receptors for influenza viruses and are widely displayed on cell surfaces and in secreted mucus. Sia may be present in variant forms that include
    MeSH term(s) A549 Cells ; Animals ; Dogs ; Erythrocytes/metabolism ; Female ; Hemagglutinin Glycoproteins, Influenza Virus/metabolism ; Hemagglutinins/metabolism ; Humans ; Influenza A virus/metabolism ; Influenza A virus/physiology ; Influenza, Human/metabolism ; Madin Darby Canine Kidney Cells ; Male ; Mice ; Mixed Function Oxygenases/metabolism ; Mucus/metabolism ; N-Acetylneuraminic Acid/metabolism ; Neuraminidase/metabolism ; Orthomyxoviridae/metabolism ; Receptors, Virus/metabolism ; Saliva/chemistry
    Chemical Substances Hemagglutinin Glycoproteins, Influenza Virus ; Hemagglutinins ; O-acetyl sialic acid ; Receptors, Virus ; Mixed Function Oxygenases (EC 1.-) ; CMPacetylneuraminate monooxygenase (EC 1.14.18.2) ; Neuraminidase (EC 3.2.1.18) ; N-Acetylneuraminic Acid (GZP2782OP0)
    Keywords covid19
    Language English
    Publishing date 2020-04-16
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 80174-4
    ISSN 1098-5514 ; 0022-538X
    ISSN (online) 1098-5514
    ISSN 0022-538X
    DOI 10.1128/JVI.01567-19
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: High-throughput analysis and protein engineering using microcapillary arrays.

    Chen, Bob / Lim, Sungwon / Kannan, Arvind / Alford, Spencer C / Sunden, Fanny / Herschlag, Daniel / Dimov, Ivan K / Baer, Thomas M / Cochran, Jennifer R

    Nature chemical biology

    2015  Volume 12, Issue 2, Page(s) 76–81

    Abstract: We describe a multipurpose technology platform, termed μSCALE (microcapillary single-cell analysis and laser extraction), that enables massively parallel, quantitative biochemical and biophysical measurements on millions of protein variants expressed ... ...

    Abstract We describe a multipurpose technology platform, termed μSCALE (microcapillary single-cell analysis and laser extraction), that enables massively parallel, quantitative biochemical and biophysical measurements on millions of protein variants expressed from yeast or bacteria. μSCALE spatially segregates single cells within a microcapillary array, enabling repeated imaging, cell growth and protein expression. We performed high-throughput analysis of cells and their protein products using a range of fluorescent assays, including binding-affinity measurements and dynamic enzymatic assays. A precise laser-based extraction method allows rapid recovery of live clones and their genetic material from microcapillaries for further study. With μSCALE, we discovered a new antibody against a clinical cancer target, evolved a fluorescent protein biosensor and engineered an enzyme to reduce its sensitivity to its inhibitor. These protein analysis and engineering applications each have unique assay requirements and different host organisms, highlighting the flexibility and technical capabilities of the μSCALE platform.
    MeSH term(s) Bacterial Proteins/analysis ; Biosensing Techniques/instrumentation ; Chemistry Techniques, Analytical/instrumentation ; Flow Cytometry ; Fluorescent Dyes/chemistry ; Fungal Proteins/analysis ; Gene Library ; Protein Array Analysis/instrumentation ; Protein Binding ; Protein Engineering/instrumentation ; Single-Cell Analysis/instrumentation
    Chemical Substances Bacterial Proteins ; Fluorescent Dyes ; Fungal Proteins
    Language English
    Publishing date 2015-12-07
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 2202962-X
    ISSN 1552-4469 ; 1552-4450
    ISSN (online) 1552-4469
    ISSN 1552-4450
    DOI 10.1038/nchembio.1978
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article: The International Atomic Energy Agency International Doubly Labelled Water Database: Aims, Scope and Procedures

    Speakman, John R. / Pontzer, Herman / Rood, Jennifer / Sagayama, Hiroyuki / Schoeller, Dale A. / Westerterp, Klaas R. / Wong, William W. / Yamada, Yosuke / Loechl, Cornelia / Murphy-Alford, Alexia J.

    Annals of Nutrition and Metabolism

    2019  Volume 75, Issue 2, Page(s) 114–118

    Abstract: Background: The doubly labelled water (DLW) method is an isotope-based technique that quantifies total energy expenditure (TEE) over periods of 1–3 weeks from the differential elimination of stable isotopes of oxygen and hydrogen. The method was invented ...

    Institution Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, China
    Institute of Biological and Environmental Sciences, University of Aberdeen, Aberdeen, United Kingdom
    Evolutionary Anthropology, Duke University, Durham, North Carolina, USA
    Duke Global Health Institute, Duke University, Durham, North Carolina, USA
    Pennington Biomedical Research Center, Baton Rouge, Louisiana, USA
    Faculty of Health and Sports Sciences, University of Tsukuba, Tsukuba, Japan
    Biotechnology Center and Nutritional Sciences, University of Wisconsin, Madison, Wisconsin, USA
    Nutrition and Translational Research in Metabolism, University of Maastricht, Maastricht, The Netherlands
    USDA/ARS Children’s Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, Texas, USA
    National Institute of Health and Nutrition, National Institutes of Biomedical Innovation, Health and Nutrition, Tokyo, Japan
    Division of Human Health, Department of Nuclear Sciences and Applications, International Atomic Energy Agency, Vienna, Austria
    Abstract Background: The doubly labelled water (DLW) method is an isotope-based technique that quantifies total energy expenditure (TEE) over periods of 1–3 weeks from the differential elimination of stable isotopes of oxygen and hydrogen. The method was invented in the 1950s, but limited ability to measure low isotope enrichments combined with the high cost of isotopes meant it only became feasible to use in humans in the 1980s. It is still relatively expensive to use, and alone small samples are unable to tackle some of the important questions surrounding energy balance such as how have expenditures changed over time and how do expenditures differ with age, between sexes and in different environments? Summary: By combining information across studies, answers to such questions may be possible. The International Atomic Energy Agency (IAEA) DLW database was established to pool DLW data across multiple studies. It was initiated by the main labs currently using the method and is hosted by the IAEA. At present, the database contains 6,621 measures of TEE by DLW from individuals in 23 countries, along with various additional data on the study participants. Key Messages: The IAEA DLW database is a key resource enabling future studies of energy demands.
    Keywords Energy expenditure ; Doubly labelled water ; Nutrition ; Obesity ; Food requirements
    Language English
    Publishing date 2019-11-19
    Publisher S. Karger AG
    Publishing place Basel, Switzerland
    Document type Article
    Note Meeting Report
    ZDB-ID 392341-1
    ISSN 1421-9697 ; 0250-6807 ; 1018-9688
    ISSN (online) 1421-9697
    ISSN 0250-6807 ; 1018-9688
    DOI 10.1159/000503668
    Database Karger publisher's database

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  8. Article ; Online: Human total, basal and activity energy expenditures are independent of ambient environmental temperature.

    Zhang, Xueying / Yamada, Yosuke / Sagayama, Hiroyuki / Ainslie, Philip N / Blaak, Ellen E / Buchowski, Maciej S / Close, Graeme L / Cooper, Jamie A / Das, Sai Krupa / Dugas, Lara R / Gurven, Michael / El Hamdouchi, Asmaa / Hu, Sumei / Joonas, Noorjehan / Katzmarzyk, Peter / Kraus, William E / Kushner, Robert F / Leonard, William R / Martin, Corby K /
    Meijer, Erwin P / Neuhouser, Marian L / Ojiambo, Robert M / Pitsiladis, Yannis P / Plasqui, Guy / Prentice, Ross L / Racette, Susan B / Ravussin, Eric / Redman, Leanne M / Reynolds, Rebecca M / Roberts, Susan B / Sardinha, Luis B / Silva, Analiza M / Stice, Eric / Urlacher, Samuel S / Van Mil, Edgar A / Wood, Brian M / Murphy-Alford, Alexia J / Loechl, Cornelia / Luke, Amy H / Rood, Jennifer / Schoeller, Dale A / Westerterp, Klaas R / Wong, William W / Pontzer, Herman / Speakman, John R

    iScience

    2022  Volume 25, Issue 8, Page(s) 104682

    Abstract: Lower ambient temperature ( ... ...

    Abstract Lower ambient temperature (T
    Language English
    Publishing date 2022-06-28
    Publishing country United States
    Document type Journal Article
    ISSN 2589-0042
    ISSN (online) 2589-0042
    DOI 10.1016/j.isci.2022.104682
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: Effect of benzyl alcohol on recombinant human interleukin-1 receptor antagonist structure and hydrogen-deuterium exchange.

    Alford, John R / Fowler, Andrew C / Wuttke, Deborah S / Kerwin, Bruce A / Latypov, Ramil F / Carpenter, John F / Randolph, Theodore W

    Journal of pharmaceutical sciences

    2011  Volume 100, Issue 10, Page(s) 4215–4224

    Abstract: Benzyl alcohol, a preservative commonly added to multidose therapeutic protein formulations, can accelerate aggregation of recombinant human interleukin-1 receptor antagonist (rhIL-1ra). To investigate the interactions between benzyl alcohol and rhIL-1ra, ...

    Abstract Benzyl alcohol, a preservative commonly added to multidose therapeutic protein formulations, can accelerate aggregation of recombinant human interleukin-1 receptor antagonist (rhIL-1ra). To investigate the interactions between benzyl alcohol and rhIL-1ra, we used nuclear magnetic resonance to observe the effect of benzyl alcohol on the chemical shifts of amide resonances of rhIL-1ra and to measure hydrogen-deuterium exchange rates of individual rhIL-1ra residues. Addition of 0.9% benzyl alcohol caused significant chemical shifts of amide resonances for residues 90-97, suggesting that these solvent-exposed residues participate in the binding of benzyl alcohol. In contrast, little perturbation of exchange rates was observed in the presence of either sucrose or benzyl alcohol.
    MeSH term(s) Benzyl Alcohol/chemistry ; Benzyl Alcohol/metabolism ; Binding Sites ; Chemistry, Pharmaceutical ; Deuterium Exchange Measurement ; Humans ; Interleukin 1 Receptor Antagonist Protein/chemistry ; Interleukin 1 Receptor Antagonist Protein/metabolism ; Magnetic Resonance Spectroscopy ; Models, Molecular ; Preservatives, Pharmaceutical/chemistry ; Preservatives, Pharmaceutical/metabolism ; Protein Aggregates ; Protein Binding ; Protein Conformation ; Recombinant Proteins/chemistry ; Structure-Activity Relationship ; Technology, Pharmaceutical/methods ; Temperature
    Chemical Substances IL1RN protein, human ; Interleukin 1 Receptor Antagonist Protein ; Preservatives, Pharmaceutical ; Protein Aggregates ; Recombinant Proteins ; Benzyl Alcohol (LKG8494WBH)
    Language English
    Publishing date 2011-05-05
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 3151-3
    ISSN 1520-6017 ; 0022-3549
    ISSN (online) 1520-6017
    ISSN 0022-3549
    DOI 10.1002/jps.22601
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: The effects of modified sialic acids on mucus and erythrocytes on influenza A virus HA and NA functions

    Barnard, Karen N. / Alford-Lawrence, Brynn K. / Buchholz, David W. / Wasik, Brian R. / LaClair, Justin R. / Yu, Hai / Honce, Rebekah / Ruhl, Stefan / Pajic, Petar / Daugherity, Erin K. / Chen, Xi / Schultz-Cherry, Stacey L. / Aguilar, Hector C. / Varki, Ajit / Parrish, Colin R.

    bioRxiv

    Abstract: Sialic acids (Sia) are the primary receptors for influenza viruses, and are widely displayed on cell surfaces and in secreted mucus. Sia may be present in variant forms that include O-acetyl modifications at C4, C7, C8, and C9 positions, and N-acetyl or ... ...

    Abstract Sialic acids (Sia) are the primary receptors for influenza viruses, and are widely displayed on cell surfaces and in secreted mucus. Sia may be present in variant forms that include O-acetyl modifications at C4, C7, C8, and C9 positions, and N-acetyl or N-glycolyl at C5. They can also vary in their linkages, including α2-3 or α2-6-linkages. Here, we analyzed the distribution of modified Sia in cells and tissues of wild-type mice, or in mice lacking cytidine 5’-monophosphate-N-acetylneuraminic acid hydroxylase (CMAH) enzyme that synthesizes N-glycolyl modifications (Neu5Gc). We also examined the variation of Sia forms on erythrocytes and saliva from different animals. To determine the effect of Sia modifications on influenza A virus (IAV) infection, we tested for effects on hemagglutinin (HA) binding and neuraminidase (NA) cleavage. We confirmed that 9-O-acetyl, 7,9-O-acetyl, 4-O-acetyl, and Neu5Gc modifications are widely but variably expressed in mouse tissues, with the highest levels detected in the respiratory and gastrointestinal tracts. Secreted mucins in saliva and surface proteins of erythrocytes showed a great degree of variability in display of modified Sia between different species. IAV HA from different virus strains showed consistently reduced binding to both Neu5Gc and O-acetyl modified Sia; however, while IAV NA were inhibited by Neu5Gc and O-acetyl modifications, there was significant variability between NA types. The modifications of Sia in mucus may therefore have potent effects on the functions of IAV, and may affect both pathogens and the normal flora of different mucosal sites. Sialic acids (Sia) are involved in many different cellular functions and are receptors for many pathogens. Sia come in many chemically modified forms but we lack a clear understanding of how they alter the interactions with microbes. Here we examine the expression of modified Sia in mouse tissues, on secreted mucus in saliva, and on erythrocytes, including those from IAV host species and animals used in IAV research. These Sia forms varied considerably between different animals, and their inhibitory effects on IAV NA and HA activities and on bacterial sialidases (neuraminidases) suggest a host-variable protective role in secreted mucus.
    Keywords covid19
    Publisher BioRxiv; MedRxiv
    Document type Article ; Online
    DOI 10.1101/800300
    Database COVID19

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