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  1. Article: Immunogenetic Association Underlying Severe COVID-19.

    McCoy, Kendall / Peterson, Autumn / Tian, Yun / Sang, Yongming

    Vaccines

    2020  Volume 8, Issue 4

    Abstract: SARS-CoV2 has caused the current pandemic of new coronavirus disease 2019 (COVID-19) worldwide. Clinical outcomes of COVID-19 illness range broadly from asymptotic and mild to a life-threatening situation. This casts uncertainties for defining host ... ...

    Abstract SARS-CoV2 has caused the current pandemic of new coronavirus disease 2019 (COVID-19) worldwide. Clinical outcomes of COVID-19 illness range broadly from asymptotic and mild to a life-threatening situation. This casts uncertainties for defining host determinants underlying the disease severity. Recent genetic analyses based on extensive clinical sample cohorts using genome-wide association studies (GWAS) and high throughput sequencing curation revealed genetic errors and gene loci associated with about 20% of life-threatening COVID-19 cases. Significantly, most of these critical genetic loci are enriched in two immune signaling pathways, i.e., interferon-mediated antiviral signaling and chemokine-mediated/inflammatory signaling. In line with these genetic profiling studies, the broad spectrum of COVID-19 illness could be explained by immuno-pathological regulation of these critical immunogenetic pathways through various epigenetic mechanisms, which further interconnect to other vital components such as those in the renin-angiotensin-aldosterone system (RAAS) because of its direct interaction with the virus causing COVID-19. Together, key genes unraveled by genetic profiling may provide targets for precisely early risk diagnosis and prophylactic design to relieve severe COVID-19. The confounding epigenetic mechanisms may be key to understanding the clinical broadness of COVID-19 illness.
    Language English
    Publishing date 2020-11-20
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2703319-3
    ISSN 2076-393X
    ISSN 2076-393X
    DOI 10.3390/vaccines8040700
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Immunogenetic Association Underlying Severe COVID-19

    Kendall McCoy / Autumn Peterson / Yun Tian / Yongming Sang

    Vaccines, Vol 8, Iss 700, p

    2020  Volume 700

    Abstract: SARS-CoV2 has caused the current pandemic of new coronavirus disease 2019 (COVID-19) worldwide. Clinical outcomes of COVID-19 illness range broadly from asymptotic and mild to a life-threatening situation. This casts uncertainties for defining host ... ...

    Abstract SARS-CoV2 has caused the current pandemic of new coronavirus disease 2019 (COVID-19) worldwide. Clinical outcomes of COVID-19 illness range broadly from asymptotic and mild to a life-threatening situation. This casts uncertainties for defining host determinants underlying the disease severity. Recent genetic analyses based on extensive clinical sample cohorts using genome-wide association studies (GWAS) and high throughput sequencing curation revealed genetic errors and gene loci associated with about 20% of life-threatening COVID-19 cases. Significantly, most of these critical genetic loci are enriched in two immune signaling pathways, i.e., interferon-mediated antiviral signaling and chemokine-mediated/inflammatory signaling. In line with these genetic profiling studies, the broad spectrum of COVID-19 illness could be explained by immuno-pathological regulation of these critical immunogenetic pathways through various epigenetic mechanisms, which further interconnect to other vital components such as those in the renin–angiotensin–aldosterone system (RAAS) because of its direct interaction with the virus causing COVID-19. Together, key genes unraveled by genetic profiling may provide targets for precisely early risk diagnosis and prophylactic design to relieve severe COVID-19. The confounding epigenetic mechanisms may be key to understanding the clinical broadness of COVID-19 illness.
    Keywords COVID-19 ; interferon signaling ; chemokine signaling ; genome-wide association ; epigenetic regulation ; Medicine ; R
    Subject code 610
    Language English
    Publishing date 2020-11-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: Structure and evolution of ENTH and VHS/ENTH-like domains in tepsin.

    Archuleta, Tara L / Frazier, Meredith N / Monken, Anderson E / Kendall, Amy K / Harp, Joel / McCoy, Airlie J / Creanza, Nicole / Jackson, Lauren P

    Traffic (Copenhagen, Denmark)

    2017  Volume 18, Issue 9, Page(s) 590–603

    Abstract: Tepsin is currently the only accessory trafficking protein identified in adaptor-related protein 4 (AP4)-coated vesicles originating at the trans-Golgi network (TGN). The molecular basis for interactions between AP4 subunits and motifs in the tepsin C- ... ...

    Abstract Tepsin is currently the only accessory trafficking protein identified in adaptor-related protein 4 (AP4)-coated vesicles originating at the trans-Golgi network (TGN). The molecular basis for interactions between AP4 subunits and motifs in the tepsin C-terminus have been characterized, but the biological role of tepsin remains unknown. We determined X-ray crystal structures of the tepsin epsin N-terminal homology (ENTH) and VHS/ENTH-like domains. Our data reveal unexpected structural features that suggest key functional differences between these and similar domains in other trafficking proteins. The tepsin ENTH domain lacks helix0, helix8 and a lipid binding pocket found in epsin1/2/3. These results explain why tepsin requires AP4 for its membrane recruitment and further suggest ENTH domains cannot be defined solely as lipid binding modules. The VHS domain lacks helix8 and thus contains fewer helices than other VHS domains. Structural data explain biochemical and biophysical evidence that tepsin VHS does not mediate known VHS functions, including recognition of dileucine-based cargo motifs or ubiquitin. Structural comparisons indicate the domains are very similar to each other, and phylogenetic analysis reveals their evolutionary pattern within the domain superfamily. Phylogenetics and comparative genomics further show tepsin within a monophyletic clade that diverged away from epsins early in evolutionary history (~1500 million years ago). Together, these data provide the first detailed molecular view of tepsin and suggest tepsin structure and function diverged away from other epsins. More broadly, these data highlight the challenges inherent in classifying and understanding protein function based only on sequence and structure.
    MeSH term(s) Adaptor Proteins, Vesicular Transport/chemistry ; Adaptor Proteins, Vesicular Transport/metabolism ; Binding Sites ; Clathrin/metabolism ; Humans ; Protein Structure, Secondary/physiology ; Ubiquitin/metabolism ; trans-Golgi Network/chemistry ; trans-Golgi Network/metabolism
    Chemical Substances Adaptor Proteins, Vesicular Transport ; CLINT1 protein, human ; Clathrin ; Ubiquitin ; tepsin protein, human
    Language English
    Publishing date 2017-07-10
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 1483852-7
    ISSN 1600-0854 ; 1398-9219
    ISSN (online) 1600-0854
    ISSN 1398-9219
    DOI 10.1111/tra.12499
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  4. Article ; Online: Extracellular circular RNA profiles in plasma and urine of healthy, male college athletes

    Elizabeth Hutchins / Rebecca Reiman / Joseph Winarta / Taylor Beecroft / Ryan Richholt / Matt De Both / Khalouk Shahbander / Elizabeth Carlson / Alex Janss / Ashley Siniard / Chris Balak / Ryan Bruhns / Timothy G. Whitsett / Roger McCoy / Matthew Anastasi / April Allen / Brian Churas / Matthew Huentelman / Kendall Van Keuren-Jensen

    Scientific Data, Vol 8, Iss 1, Pp 1-

    2021  Volume 12

    Abstract: Measurement(s) transcriptome • RNA(circular) Technology Type(s) RNA sequencing Factor Type(s) biofluid Sample Characteristic - Organism Homo sapiens Machine-accessible metadata file describing the reported data: https://doi.org/10.6084/m9.figshare ... ...

    Abstract Measurement(s) transcriptome • RNA(circular) Technology Type(s) RNA sequencing Factor Type(s) biofluid Sample Characteristic - Organism Homo sapiens Machine-accessible metadata file describing the reported data: https://doi.org/10.6084/m9.figshare.14991822
    Keywords Science ; Q
    Language English
    Publishing date 2021-10-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  5. Article ; Online: Extracellular circular RNA profiles in plasma and urine of healthy, male college athletes.

    Hutchins, Elizabeth / Reiman, Rebecca / Winarta, Joseph / Beecroft, Taylor / Richholt, Ryan / De Both, Matt / Shahbander, Khalouk / Carlson, Elizabeth / Janss, Alex / Siniard, Ashley / Balak, Chris / Bruhns, Ryan / Whitsett, Timothy G / McCoy, Roger / Anastasi, Matthew / Allen, April / Churas, Brian / Huentelman, Matthew / Van Keuren-Jensen, Kendall

    Scientific data

    2021  Volume 8, Issue 1, Page(s) 276

    Abstract: Circular RNA (circRNA) are a recently discovered class of RNA characterized by a covalently-bonded back-splice junction. As circRNAs are inherently more stable than other RNA species, they may be detected extracellularly in peripheral biofluids and ... ...

    Abstract Circular RNA (circRNA) are a recently discovered class of RNA characterized by a covalently-bonded back-splice junction. As circRNAs are inherently more stable than other RNA species, they may be detected extracellularly in peripheral biofluids and provide novel biomarkers. While circRNA have been identified previously in peripheral biofluids, there are few datasets for circRNA junctions from healthy controls. We collected 134 plasma and 114 urine samples from 54 healthy, male college athlete volunteers, and used RNASeq to determine circRNA content. The intersection of six bioinformatic tools identified 965 high-confidence, characteristic circRNA junctions in plasma and 72 in urine. Highly-expressed circRNA junctions were validated by qRT-PCR. Longitudinal samples were collected from a subset, demonstrating circRNA expression was stable over time. Lastly, the ratio of circular to linear transcripts was higher in plasma than urine. This study provides a valuable resource for characterization of circRNA in plasma and urine from healthy volunteers, one that can be developed and reassessed as researchers probe the circRNA contents of biofluids across physiological changes and disease states.
    MeSH term(s) Adolescent ; Athletes ; Healthy Volunteers ; Humans ; Male ; RNA, Circular/blood ; RNA, Circular/urine ; RNA-Seq ; Young Adult
    Chemical Substances RNA, Circular
    Language English
    Publishing date 2021-10-28
    Publishing country England
    Document type Dataset ; Journal Article
    ZDB-ID 2775191-0
    ISSN 2052-4463 ; 2052-4463
    ISSN (online) 2052-4463
    ISSN 2052-4463
    DOI 10.1038/s41597-021-01056-w
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Total Extracellular Small RNA Profiles from Plasma, Saliva, and Urine of Healthy Subjects.

    Yeri, Ashish / Courtright, Amanda / Reiman, Rebecca / Carlson, Elizabeth / Beecroft, Taylor / Janss, Alex / Siniard, Ashley / Richholt, Ryan / Balak, Chris / Rozowsky, Joel / Kitchen, Robert / Hutchins, Elizabeth / Winarta, Joseph / McCoy, Roger / Anastasi, Matthew / Kim, Seungchan / Huentelman, Matthew / Van Keuren-Jensen, Kendall

    Scientific reports

    2017  Volume 7, Page(s) 44061

    Abstract: Interest in circulating RNAs for monitoring and diagnosing human health has grown significantly. There are few datasets describing baseline expression levels for total cell-free circulating RNA from healthy control subjects. In this study, total ... ...

    Abstract Interest in circulating RNAs for monitoring and diagnosing human health has grown significantly. There are few datasets describing baseline expression levels for total cell-free circulating RNA from healthy control subjects. In this study, total extracellular RNA (exRNA) was isolated and sequenced from 183 plasma samples, 204 urine samples and 46 saliva samples from 55 male college athletes ages 18-25 years. Many participants provided more than one sample, allowing us to investigate variability in an individual's exRNA expression levels over time. Here we provide a systematic analysis of small exRNAs present in each biofluid, as well as an analysis of exogenous RNAs. The small RNA profile of each biofluid is distinct. We find that a large number of RNA fragments in plasma (63%) and urine (54%) have sequences that are assigned to YRNA and tRNA fragments respectively. Surprisingly, while many miRNAs can be detected, there are few miRNAs that are consistently detected in all samples from a single biofluid, and profiles of miRNA are different for each biofluid. Not unexpectedly, saliva samples have high levels of exogenous sequence that can be traced to bacteria. These data significantly contribute to the current number of sequenced exRNA samples from normal healthy individuals.
    MeSH term(s) Adolescent ; Adult ; Cell-Free Nucleic Acids/analysis ; Cell-Free Nucleic Acids/isolation & purification ; Humans ; Male ; RNA/analysis ; RNA/blood ; RNA/isolation & purification ; RNA/urine ; Saliva/chemistry ; Young Adult
    Chemical Substances Cell-Free Nucleic Acids ; RNA (63231-63-0)
    Language English
    Publishing date 2017-03-17
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2615211-3
    ISSN 2045-2322 ; 2045-2322
    ISSN (online) 2045-2322
    ISSN 2045-2322
    DOI 10.1038/srep44061
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Act now against new NHS competition regulations: an open letter to the BMA and the Academy of Medical Royal Colleges calls on them to make a joint public statement of opposition to the amended section 75 regulations.

    Davis, Jacky / Banks, Ian / Wrigley, David / Peedell, Clive / Pollock, Alyson / McPherson, Klim / McKee, Martin / Irving, William L / Crome, Peter / Greenhalgh, Trisha / Holland, Walter / Evans, David / Maryon-Davis, Alan / Smyth, Alan / Fleming, Peter / Coleman, Michel / Sharp, Deborah J / Whincup, Peter / Logan, Stuart /
    Cook, Derek / Moore, Robert / Rawaf, Salman / McEewen, J / West, Robert / Yudkin, John S / Clarke, Aileen / Finer, Nick / Domizio, Paola / Bambra, Clare / Jones, Anna / Feder, Gene / Scott-Samuel, Alex / Irvine, Louise / Sharma, Ajay / Fitchett, Mike / Boomla, Kambiz / Folb, Jonathan / Paul, Ashish / McCoy, David / Tallis, Ray / Burgess-Allen, Jilla / Edwards, Mark / Tomlinson, Jonathon / Colvin, Deborah / Gore, Jonathan / Brown, Kirsten / Mitchel, Sarah / Lau, Alice / Sayer, Mel / Clark, Leon / Silverman, Ruth / Marmot, Saul / Rainbow, Daniel / Carter, Lucy / Mann, Nick / Fielding, Richard / Logan, Jane / Tebboth, Louise / Arnold, Natasha / Stobbart, Kate / Cabot, Kate / Finer, Sarah / Edwards, Martin / Davies, David / Buttivant, Helen / Kraemer, Sebastian / Newell, Jo / Griffiths, Alun / Fitzgerald, Richard / Macgibbon, Robert / Lee, Alan / Macklon, A F / Hobson, Esther / Jenner, David / Jacobson, Bobbie / Timmis, Alison / Salim, Asad / Evans-Jones, John / Caan, Woody / Awsare, Ninaad / Pride, Neil / Suckling, Ruth / Bratty, Catherine / Rossiter, Brian / Hawkins, David / Currie, Jonny / Camilleri-Ferrante, Corinne / Fluxman, Jonathan / Bhatti, Osman / Anson, James / Etherington, Robert / Lawrence, David / Fell, Henry / Clarke, Edward / Ormerod, Julian / Ormerod, Oliver / Ireland, Maggie / Duncan, John A T / Chandy, Rajiv / Mindell, Jennifer / Mullen, Paul / Bennett-Richards, Phillip / Hirst, Julie / Murphy, E / Martin, P / Lowes, Simon / Grunewald, Richard / Reeve, Joanne / Schweiger, Martin / Coates, Jonathan / Farrelly, George / Chamberlain, M A / Lewis, Geoffrey / Young, Jane / Scott, Brian / Gibbs, John / Landers, Aileen / Deveson, Pete / Ingrams, Grant / Leigh, Martha / Gawler, Jeff / Ford, Amy / Nixon, Jonathan / McCartney, Margaret / Bareford, David / Singh, Surinder / Lockwood, Kate / Cripwell, Michael / Ehrhardt, Peter / Bell, David / Wortley, Pam / Tomlinson, Laurie / Hotchkiss, Julie / Ford, Steven / Turner, Gill / Reissman, Gerard / Lewis, David / Johnstone, Chris / Tomson, Mike / Torabi, Payam / Tomson, D / Tulloch, Alex / Johnston, Sally / Dickinson, Jane / McElderry, Elisabeth / Ross, Wendy / Holt, Kim / Logan, Mary / Klonin, Hilary / Danby, Jude / Goodger, V / Puntis, John / Dickson, Harriet / Gould, Derek A / Livingstone, Anna / Lefevre, Dianne / Kendall, Bryony / Singh, G / Hall, Peter / Darling, Jonathan / Hamlyn, Adrian N / Patel, Anita / Erskine, Jonathan / Fisher, Brian / Hughes, Richard / Highton, Clare / Venning, Helen / Singer, Ron / Brearey, Steve / Sikorski, Jim / Paintin, David / Feehally, John / Savage, Wendy / Freud, Kathy McAdam / Holt, Victoria J / Gill, Alison / Waterston, Tony / Souza, Richard de / Hopkinson, Nicholas / Beadsworth, Mike / Franks, Andrea / Daley, Helen / Cullinan, Paul / Basarab, Adriana / Gurling, Hugh / Zinkin, Pam / Kirwin, Simon / Buhrs, Ernst / Brown, Raymond / West, Andrew / Marlowe, Gary / Fellows, Griffith / Main, John / Applebee, Jackie / Koperski, M / Jones, Phil / Macfarlane, Alison / Beer, Naomi / Mason, Rebecca / Eisner, Maggie / Smailes, Alison / Timms, Philip / Knight, David / Jones, Coral / Wesby, Barbara / Lyttelton, Laura / Morrison, Richard / Bossano, David / Walker, Jonathan / Davies, Gerry / Godfrey, Peter / Wolfe, Ingrid / Nsutebu, Emmanuel / Stevenson, Nicola / Cheeroth, Sheila / Miller, Jo / Johnson, Guy / Noor, R / Hall, Alyson / Bostock, David / Michael, Benedict / Sharvill, John / Macpherson, Jamie / Ma, Richard / Middleton, John / Jeffreys, Anne / Cole, Jim / Boswell, John P / Bury, Bob / Mitchison, Sally / Kinmonth, Ann-Louise / Young, Gail / Maclennan, Iain / Munday, Pat

    BMJ (Clinical research ed.)

    2013  Volume 346, Page(s) f1819

    MeSH term(s) Academies and Institutes ; Dissent and Disputes/legislation & jurisprudence ; Health Care Reform/legislation & jurisprudence ; Health Care Reform/organization & administration ; Humans ; Insurance, Health ; Managed Competition/legislation & jurisprudence ; Managed Competition/organization & administration ; Politics ; Privatization ; Societies, Medical ; State Medicine/legislation & jurisprudence ; State Medicine/organization & administration ; United Kingdom
    Language English
    Publishing date 2013-03-20
    Publishing country England
    Document type Journal Article
    ZDB-ID 1362901-3
    ISSN 1756-1833 ; 0959-8154 ; 0959-8146 ; 0959-8138 ; 0959-535X ; 1759-2151
    ISSN (online) 1756-1833
    ISSN 0959-8154 ; 0959-8146 ; 0959-8138 ; 0959-535X ; 1759-2151
    DOI 10.1136/bmj.f1819
    Database MEDical Literature Analysis and Retrieval System OnLINE

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