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  1. Article ; Online: Implications of Endogenous Retroelements in the Etiopathogenesis of Systemic Lupus Erythematosus

    Kennedy C. Ukadike / Tomas Mustelin

    Journal of Clinical Medicine, Vol 10, Iss 4, p

    2021  Volume 856

    Abstract: Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disease. While its etiology remains elusive, current understanding suggests a multifactorial process with contributions by genetic, immunologic, hormonal, and environmental factors. A ... ...

    Abstract Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disease. While its etiology remains elusive, current understanding suggests a multifactorial process with contributions by genetic, immunologic, hormonal, and environmental factors. A hypothesis that combines several of these factors proposes that genomic elements, the L1 retrotransposons, are instrumental in SLE pathogenesis. L1 retroelements are transcriptionally activated in SLE and produce two proteins, ORF1p and ORF2p, which are immunogenic and can drive type I interferon (IFN) production by producing DNA species that activate cytosolic DNA sensors. In addition, these two proteins reside in RNA-rich macromolecular assemblies that also contain well-known SLE autoantigens like Ro60. We surmise that cells expressing L1 will exhibit all the hallmarks of cells infected by a virus, resulting in a cellular and humoral immune response similar to those in chronic viral infections. However, unlike exogenous viruses, L1 retroelements cannot be eliminated from the host genome. Hence, dysregulated L1 will cause a chronic, but perhaps episodic, challenge for the immune system. The clinical and immunological features of SLE can be at least partly explained by this model. Here we review the support for, and the gaps in, this hypothesis of SLE and its potential for new diagnostic, prognostic, and therapeutic options in SLE.
    Keywords systemic lupus erythematosus ; retroelements ; L1 ; LINE-1 ; reverse transcriptase ; type I interferons ; Medicine ; R
    Subject code 610
    Language English
    Publishing date 2021-02-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: Six new species and one new subspecies of noctuid moths from western United States of America and Mexico (Lepidoptera, Noctuidae)

    Lars G. Crabo / Paul C. Hammond / Tomas Mustelin / David L. Wikle

    ZooKeys, Vol 788, Iss , Pp 201-

    2018  Volume 239

    Abstract: Six new species and one new subspecies of Noctuidae are described from western United States of America and Baja California, Mexico: Dolocucullia poolei Crabo & Hammond, sp. n. (Cuculliinae), Plagiomimicus yakama Crabo & Wikle, sp. n., Plagiomimicus ... ...

    Abstract Six new species and one new subspecies of Noctuidae are described from western United States of America and Baja California, Mexico: Dolocucullia poolei Crabo & Hammond, sp. n. (Cuculliinae), Plagiomimicus yakama Crabo & Wikle, sp. n., Plagiomimicus yakama mojave Wikle & Crabo, ssp. n., Plagiomimicus incomitatus Mustelin, sp. n. (Amphipyrinae), Sympistis ferrirena Crabo, sp. n. (Oncocnemidinae), Aseptis harpi Crabo & Mustelin, sp. n., and Hypotrix lactomellis Wikle & Crabo, sp. n. (Noctuinae). The adults and genitalia of these species are described, illustrated, and compared to similar related moths. The larvae of the Plagiomimicus tepperi species group, unknown previously, are reported to feed on several species of Brickellia Ell. (Asteraceae). The early stages of Plagiomimicus yakama mojave are described and late instars are illustrated.
    Keywords Zoology ; QL1-991
    Subject code 590
    Language English
    Publishing date 2018-10-01T00:00:00Z
    Publisher Pensoft Publishers
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article: Five new species and three new subspecies of Erebidae and Noctuidae (Insecta, Lepidoptera) from Northwestern North America, with notes on Chytolita Grote (Erebidae) and Hydraecia Guenée (Noctuidae).

    Crabo, Lars G / Davis, Melanie / Hammond, Paul / Tomas Mustelin / Jon Shepard

    ZooKeys

    2013  , Issue 264, Page(s) 85–123

    Abstract: Several taxonomic issues in the moth families Erebidae and Noctuidae are addressed for Northwestern North America. Drasteria parallelaCrabo & Mustelin andCycnia oregonensis tristisCrabo in the Erebidae and Eudryas brevipennis bonneville Shepard & Crabo, ... ...

    Abstract Several taxonomic issues in the moth families Erebidae and Noctuidae are addressed for Northwestern North America. Drasteria parallelaCrabo & Mustelin andCycnia oregonensis tristisCrabo in the Erebidae and Eudryas brevipennis bonneville Shepard & Crabo, Resapamea diluvius Crabo, Resapamea angelika Crabo, Resapamea mammuthus Crabo, Fishia nigrescens Hammond & Crabo, and Xestia perquiritata orcaCrabo & Hammond in the Noctuidae are described as new. The following new synonyms are proposed: Chytolita petrealis Grote with Herminea morbidalis Guenée; Gortyna columbia Barnes & Benjamin and Gortyna ximena Barnes & Benjamin with Gortyna obliqua Harvey; and Hydroecia pallescens Smith with Hydroecia medialis Smith. The type locality of Gortyna intermedia Barnes & Benjamin is restricted to Lundbreck, Municipality of Crowsnest Pass, Alberta, Canada.
    Language English
    Publishing date 2013-02-06
    Publishing country Bulgaria
    Document type Journal Article
    ZDB-ID 2445640-8
    ISSN 1313-2970 ; 1313-2989
    ISSN (online) 1313-2970
    ISSN 1313-2989
    DOI 10.3897/zookeys.264.4304
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Distal lung epithelial progenitor cell function declines with age

    Julie K. Watson / Philip Sanders / Rebecca Dunmore / Guglielmo Rosignoli / Yvon Julé / Emma L. Rawlins / Tomas Mustelin / Richard May / Deborah Clarke / Donna K. Finch

    Scientific Reports, Vol 10, Iss 1, Pp 1-

    2020  Volume 12

    Abstract: Abstract Tissue stem cell exhaustion is a key hallmark of aging, and in this study, we characterised its manifestation in the distal lung. We compared the lungs of 3- and 22-month old mice. We examined the gross morphological changes in these lungs, the ... ...

    Abstract Abstract Tissue stem cell exhaustion is a key hallmark of aging, and in this study, we characterised its manifestation in the distal lung. We compared the lungs of 3- and 22-month old mice. We examined the gross morphological changes in these lungs, the density and function of epithelial progenitor populations and the epithelial gene expression profile. Bronchioles became smaller in their cross-sectional area and diameter. Using long-term EdU incorporation analysis and immunohistochemistry, we found that bronchiolar cell density remained stable with aging, but inferred rates of bronchiolar club progenitor cell self-renewal and differentiation were reduced, indicative of an overall slowdown in cellular turnover. Alveolar Type II progenitor cell density and self-renewal were maintained per unit tissue area with aging, but rates of inferred differentiation into Type I cells, and indeed overall density of Type I cells was reduced. Microarray analysis revealed age-related changes in multiple genes, including some with roles in proliferation and differentiation, and in IGF and TGFβ signalling pathways. By characterising how lung stem cell dynamics change with aging, this study will elucidate how they contribute to age-related loss of pulmonary function, and pathogenesis of common age-related pulmonary diseases.
    Keywords Medicine ; R ; Science ; Q
    Subject code 610
    Language English
    Publishing date 2020-06-01T00:00:00Z
    Publisher Nature Publishing Group
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  5. Article ; Online: Five new species and three new subspecies of Erebidae and Noctuidae (Insecta, Lepidoptera) from Northwestern North America, with notes on Chytolita Grote (Erebidae) and Hydraecia Guenée (Noctuidae)

    Lars Crabo / Melanie Davis / Paul Hammond / Tomas Mustelin / Jon Shepard

    ZooKeys, Vol 264, Iss 0, Pp 85-

    2013  Volume 123

    Abstract: Several taxonomic issues in the moth families Erebidae and Noctuidae are addressed for Northwestern North America. Drasteria parallela Crabo & Mustelin and Cycnia oregonensis tristis Crabo in the Erebidae and Eudryas brevipennis bonneville Shepard & ... ...

    Abstract Several taxonomic issues in the moth families Erebidae and Noctuidae are addressed for Northwestern North America. Drasteria parallela Crabo & Mustelin and Cycnia oregonensis tristis Crabo in the Erebidae and Eudryas brevipennis bonneville Shepard & Crabo, Resapamea diluvius Crabo, Resapamea angelika Crabo, Resapamea mammuthus Crabo, Fishia nigrescens Hammond & Crabo, and Xestia perquiritata orca Crabo & Hammond in the Noctuidae are described as new. The following new synonyms are proposed: Chytolita petrealis Grote with Herminea morbidalis Guenée; Gortyna columbia Barnes & Benjamin and Gortyna ximena Barnes & Benjamin with Gortyna obliqua Harvey; and Hydroecia pallescens Smith with Hydroecia medialis Smith. The type locality of Gortyna intermedia Barnes & Benjamin is restricted to Lundbreck, Municipality of Crowsnest Pass, Alberta, Canada.
    Keywords Zoology ; QL1-991
    Language English
    Publishing date 2013-02-01T00:00:00Z
    Publisher Pensoft Publishers
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  6. Article ; Online: Characterization of the Hypercitrullination Reaction in Human Neutrophils and Other Leukocytes

    Yebin Zhou / Tiziana Di Pucchio / Gary P. Sims / Nanette Mittereder / Tomas Mustelin

    Mediators of Inflammation, Vol

    2015  Volume 2015

    Keywords Pathology ; RB1-214 ; Medicine ; R
    Language English
    Publishing date 2015-01-01T00:00:00Z
    Publisher Hindawi Publishing Corporation
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  7. Article ; Online: Evidence for a direct link between PAD4-mediated citrullination and the oxidative burst in human neutrophils

    Yebin Zhou / Ling-Ling An / Raghothama Chaerkady / Nanette Mittereder / Lori Clarke / Taylor S. Cohen / Bo Chen / Sonja Hess / Gary P. Sims / Tomas Mustelin

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

    2018  Volume 13

    Abstract: Abstract Neutrophils are critical for the defense against pathogens, in part through the extrusion of extracellular DNA traps, phagocytosis, and the production of reactive oxygen species. Neutrophils may also play an important role in the pathogenesis of ...

    Abstract Abstract Neutrophils are critical for the defense against pathogens, in part through the extrusion of extracellular DNA traps, phagocytosis, and the production of reactive oxygen species. Neutrophils may also play an important role in the pathogenesis of rheumatoid arthritis (RA) through the activation of protein arginine deiminases (PADs) that citrullinate proteins that subsequently act as autoantigens. We report that PAD4 is physically associated with the cytosolic subunits of the oxidative burst machinery, p47phox (also known as neutrophil cytosol factor 1, NCF1) and p67phox (NCF2). Activation of PAD4 by membranolytic insults that result in high levels of intracellular calcium (higher than physiological neutrophil activation) leads to rapid citrullination of p47phox/NCF1 and p67phox/NCF2, as well as their dissociation from PAD4. This dissociation prevents the assembly of an active NADPH oxidase complex and an oxidative burst in neutrophils stimulated by phorbol-ester or immune complexes. In further support of a substrate-to-inactive enzyme interaction, small-molecule PAD inhibitors also disrupt the PAD4-NCF complex and reduce oxidase activation and phagocytic killing of Staphylococcus aureus. This novel role of PAD4 in the regulation of neutrophil physiology suggests that targeting PAD4 with active site inhibitors for the treatment of RA may have a broader impact on neutrophil biology than just inhibition of citrullination.
    Keywords Medicine ; R ; Science ; Q
    Language English
    Publishing date 2018-10-01T00:00:00Z
    Publisher Nature Publishing Group
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  8. Article ; Online: Novel Vectors for Co-Expression of Two Proteins in E. coli

    Natalya Kholod / Tomas Mustelin

    BioTechniques, Vol 31, Iss 2, Pp 322-

    2001  Volume 328

    Abstract: Two new vectors, pAC28 and pEGST, for the co-expression of recombinant genes in E. coli were developed. This two-plasmid system allows for an efficient expression and purification of large amounts of protein-protein complexes formed in bacterial cells. ... ...

    Abstract Two new vectors, pAC28 and pEGST, for the co-expression of recombinant genes in E. coli were developed. This two-plasmid system allows for an efficient expression and purification of large amounts of protein-protein complexes formed in bacterial cells. We have utilized this new system to express and isolate a stable complex of two human proteins, hematopoietic cell tyrosine phosphatase (HePTP) and mitogen-activated proteins kinase Erk2. This approach is useful for biochemical and structural studies of protein-protein interactions.
    Keywords Biology (General) ; QH301-705.5
    Language English
    Publishing date 2001-08-01T00:00:00Z
    Publisher Future Science Ltd
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  9. Article: Five new species and three new subspecies of Erebidae and Noctuidae (Insecta, Lepidoptera) from Northwestern North America, with notes on Chytolita Grote (Erebidae) and Hydraecia Guenée (Noctuidae)

    Crabo, Lars G / Davis, Melanie / Hammond, Paul / Tomas Mustelin / Jon Shepard

    ZooKeys. 2013 Feb. 6, v. 264

    2013  

    Abstract: Several taxonomic issues in the moth families Erebidae and Noctuidae are addressed for Northwestern North America. Drasteria parallelaCrabo & Mustelin andCycnia oregonensis tristisCrabo in the Erebidae and Eudryas brevipennis bonneville Shepard & Crabo, ... ...

    Abstract Several taxonomic issues in the moth families Erebidae and Noctuidae are addressed for Northwestern North America. Drasteria parallelaCrabo & Mustelin andCycnia oregonensis tristisCrabo in the Erebidae and Eudryas brevipennis bonneville Shepard & Crabo, Resapamea diluvius Crabo, Resapamea angelika Crabo, Resapamea mammuthus Crabo, Fishia nigrescens Hammond & Crabo, and Xestia perquiritata orcaCrabo & Hammond in the Noctuidae are described as new. The following new synonyms are proposed: Chytolita petrealis Grote with Herminea morbidalis Guenée; Gortyna columbia Barnes & Benjamin and Gortyna ximena Barnes & Benjamin with Gortyna obliqua Harvey; and Hydroecia pallescens Smith with Hydroecia medialis Smith. The type locality of Gortyna intermedia Barnes & Benjamin is restricted to Lundbreck, Municipality of Crowsnest Pass, Alberta, Canada.
    Keywords Erebidae ; Gortyna ; Hydraecia ; Xestia ; moths ; new species ; new subspecies ; Alberta
    Language English
    Dates of publication 2013-0206
    Size p. 85-123.
    Publishing place Pensoft Publishers
    Document type Article
    Note NAL-light
    ZDB-ID 2445640-8
    ISSN 1313-2970 ; 1313-2989
    ISSN (online) 1313-2970
    ISSN 1313-2989
    DOI 10.3897/zookeys.264.4304
    Database NAL-Catalogue (AGRICOLA)

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  10. Article ; Online: Characterization of new substrates targeted by Yersinia tyrosine phosphatase YopH.

    María Luisa de la Puerta / Antonio G Trinidad / María del Carmen Rodríguez / Jori Bogetz / Mariano Sánchez Crespo / Tomas Mustelin / Andrés Alonso / Yolanda Bayón

    PLoS ONE, Vol 4, Iss 2, p e

    2009  Volume 4431

    Abstract: YopH is an exceptionally active tyrosine phosphatase that is essential for virulence of Yersinia pestis, the bacterium causing plague. YopH breaks down signal transduction mechanisms in immune cells and inhibits the immune response. Only a few substrates ...

    Abstract YopH is an exceptionally active tyrosine phosphatase that is essential for virulence of Yersinia pestis, the bacterium causing plague. YopH breaks down signal transduction mechanisms in immune cells and inhibits the immune response. Only a few substrates for YopH have been characterized so far, for instance p130Cas and Fyb, but in view of YopH potency and the great number of proteins involved in signalling pathways it is quite likely that more proteins are substrates of this phosphatase. In this respect, we show here YopH interaction with several proteins not shown before, such as Gab1, Gab2, p85, and Vav and analyse the domains of YopH involved in these interactions. Furthermore, we show that Gab1, Gab2 and Vav are not dephosphorylated by YopH, in contrast to Fyb, Lck, or p85, which are readily dephosphorylated by the phosphatase. These data suggests that YopH might exert its actions by interacting with adaptors involved in signal transduction pathways, what allows the phosphatase to reach and dephosphorylate its susbstrates.
    Keywords Medicine ; R ; Science ; Q
    Language English
    Publishing date 2009-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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