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  1. Article ; Online: Context-specific regulation of surface and soluble IL7R expression by an autoimmune risk allele

    Hussein Al-Mossawi / Nicole Yager / Chelsea A. Taylor / Evelyn Lau / Sara Danielli / Jelle de Wit / James Gilchrist / Isar Nassiri / Elise A. Mahe / Wanseon Lee / Laila Rizvi / Seiko Makino / Jane Cheeseman / Matt Neville / Julian C. Knight / Paul Bowness / Benjamin P. Fairfax

    Nature Communications, Vol 10, Iss 1, Pp 1-

    2019  Volume 11

    Abstract: Interleukin-7 (IL-7) is a central cytokine in T cell homeostasis. Here the authors show that allelic variation at rs6897932, an autoimmune GWAS risk allele at IL7R, regulates surface and soluble IL-7R in stimulated monocytes, indicating a function of ... ...

    Abstract Interleukin-7 (IL-7) is a central cytokine in T cell homeostasis. Here the authors show that allelic variation at rs6897932, an autoimmune GWAS risk allele at IL7R, regulates surface and soluble IL-7R in stimulated monocytes, indicating a function of monocytes in IL-7-related autoimmunity.
    Keywords Science ; Q
    Language English
    Publishing date 2019-10-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: Context-specific regulation of surface and soluble IL7R expression by an autoimmune risk allele

    Hussein Al-Mossawi / Nicole Yager / Chelsea A. Taylor / Evelyn Lau / Sara Danielli / Jelle de Wit / James Gilchrist / Isar Nassiri / Elise A. Mahe / Wanseon Lee / Laila Rizvi / Seiko Makino / Jane Cheeseman / Matt Neville / Julian C. Knight / Paul Bowness / Benjamin P. Fairfax

    Nature Communications, Vol 10, Iss 1, Pp 1-

    2019  Volume 11

    Abstract: Interleukin-7 (IL-7) is a central cytokine in T cell homeostasis. Here the authors show that allelic variation at rs6897932, an autoimmune GWAS risk allele at IL7R, regulates surface and soluble IL-7R in stimulated monocytes, indicating a function of ... ...

    Abstract Interleukin-7 (IL-7) is a central cytokine in T cell homeostasis. Here the authors show that allelic variation at rs6897932, an autoimmune GWAS risk allele at IL7R, regulates surface and soluble IL-7R in stimulated monocytes, indicating a function of monocytes in IL-7-related autoimmunity.
    Keywords Science ; Q
    Language English
    Publishing date 2019-10-01T00:00:00Z
    Publisher Nature Publishing Group
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article: Genomic mapping of the MHC transactivator CIITA using an integrated ChIP-seq and genetical genomics approach

    Wong, Daniel / Benjamin P Fairfax / Evelyn Lau / Julian C Knight / Katharine Plant / Kenneth Chan / Peter Humburg / Seiko Makino / Vivek Naranbhai / Wanseon Lee

    Genome biology. 2014 Oct., v. 15, no. 10

    2014  

    Abstract: BACKGROUND: The master transactivator CIITA is essential to the regulation of Major Histocompatibility Complex (MHC) class II genes and an effective immune response. CIITA is known to modulate a small number of non-MHC genes involved in antigen ... ...

    Abstract BACKGROUND: The master transactivator CIITA is essential to the regulation of Major Histocompatibility Complex (MHC) class II genes and an effective immune response. CIITA is known to modulate a small number of non-MHC genes involved in antigen presentation such as CD74 and B2M but its broader genome-wide function and relationship with underlying genetic diversity has not been resolved. RESULTS: We report the first genome-wide ChIP-seq map for CIITA and complement this by mapping inter-individual variation in CIITA expression as a quantitative trait. We analyse CIITA recruitment for pathophysiologically relevant primary human B cells and monocytes, resting and treated with interferon-gamma, in the context of the epigenomic regulatory landscape and DNA-binding proteins associated with the CIITA enhanceosome including RFX, CREB1/ATF1 and NFY. We confirm recruitment to proximal promoter sequences in MHC class II genes and more distally involving the canonical CIITA enhanceosome. Overall, we map 843 CIITA binding intervals involving 442 genes and find 95% of intervals are located outside the MHC and 60% not associated with RFX5 binding. Binding intervals are enriched for genes involved in immune function and infectious disease with novel loci including major histone gene clusters. We resolve differentially expressed genes associated in trans with a CIITA intronic sequence variant, integrate with CIITA recruitment and show how this is mediated by allele-specific recruitment of NF-kB. CONCLUSIONS: Our results indicate a broader role for CIITA beyond the MHC involving immune-related genes. We provide new insights into allele-specific regulation of CIITA informative for understanding gene function and disease.
    Keywords antigen presentation ; gene expression ; gene expression regulation ; genetic variation ; genomics ; histones ; humans ; immune response ; infectious diseases ; interferon-gamma ; loci ; major histocompatibility complex ; monocytes ; multigene family ; promoter regions ; quantitative traits ; transactivators ; transcription factor NF-kappa B
    Language English
    Dates of publication 2014-10
    Size p. 494.
    Publishing place Springer-Verlag
    Document type Article
    ZDB-ID 2040529-7
    ISSN 1474-760X ; 1465-6914 ; 1465-6906
    ISSN (online) 1474-760X ; 1465-6914
    ISSN 1465-6906
    DOI 10.1186/s13059-014-0494-z
    Database NAL-Catalogue (AGRICOLA)

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  4. Article: Innate Immune Activity Conditions the Effect of Regulatory Variants upon Monocyte Gene Expression

    Fairfax, Benjamin P / Chris McGee / Daniel Wong / Evelyn Lau / Julian C. Knight / Katharine Plant / Luke Jostins / Peter Humburg / Robert Andrews / Seiko Makino / Vivek Naranbhai

    Science. 2014 Mar. 7, v. 343, no. 6175

    2014  

    Abstract: Immune Variation It is difficult to determine the mechanistic consequences of context-dependent genetic variants, some of which may be related to disease (see the Perspective by Gregersen). Two studies now report on the effects of stimulating ... ...

    Abstract Immune Variation It is difficult to determine the mechanistic consequences of context-dependent genetic variants, some of which may be related to disease (see the Perspective by Gregersen). Two studies now report on the effects of stimulating immunological monocytes and dendritic cells with proteins that can elicit a response to bacterial or viral infection and assess the functional links between genetic variants and profiles of gene expression. M. N. Lee et al. (10.1126/science.1246980) analyzed the expression of more than 400 genes, in dendritic cells from 30 healthy subjects, which revealed how expression quantitative trait loci (eQTLs) affect gene expression within the interferon-β and the Toll-like receptor 3 and 4 pathways. Fairfax et al. (10.1126/science.1246949) performed a genome-wide analysis to show that many eQTLs affected monocyte gene expression in a stimulus- or time-specific manner.
    Keywords bacterial infections ; dendritic cells ; gene expression ; genes ; genetic variation ; genomics ; health status ; immune response ; innate immunity ; interferon-beta ; monocytes ; quantitative trait loci ; Toll-like receptor 3 ; viral diseases of animals and humans
    Language English
    Dates of publication 2014-0307
    Size p. 1246949.
    Publishing place American Association for the Advancement of Science
    Document type Article
    ZDB-ID 128410-1
    ISSN 1095-9203 ; 0036-8075
    ISSN (online) 1095-9203
    ISSN 0036-8075
    DOI 10.1126/science.1246949
    Database NAL-Catalogue (AGRICOLA)

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  5. Article ; Online: Alexithymia is associated with greater risk of chronic pain and negative affect and with lower life satisfaction in a general population

    Mao Shibata / Toshiharu Ninomiya / Mark P Jensen / Kozo Anno / Koji Yonemoto / Seiko Makino / Rie Iwaki / Koji Yamashiro / Toshiyuki Yoshida / Yuko Imada / Chiharu Kubo / Yutaka Kiyohara / Nobuyuki Sudo / Masako Hosoi

    PLoS ONE, Vol 9, Iss 3, p e

    the Hisayama Study.

    2014  Volume 90984

    Abstract: INTRODUCTION: Chronic pain is a significant health problem worldwide, with a prevalence in the general population of approximately 40%. Alexithymia -- the personality trait of having difficulties with emotional awareness and self-regulation -- has been ... ...

    Abstract INTRODUCTION: Chronic pain is a significant health problem worldwide, with a prevalence in the general population of approximately 40%. Alexithymia -- the personality trait of having difficulties with emotional awareness and self-regulation -- has been reported to contribute to an increased risk of several chronic diseases and health conditions, and limited research indicates a potential role for alexithymia in the development and maintenance of chronic pain. However, no study has yet examined the associations between alexithymia and chronic pain in the general population. METHODS: We administered measures assessing alexithymia, pain, disability, anxiety, depression, and life satisfaction to 927 adults in Hisayama, Japan. We classified the participants into four groups (low-normal alexithymia, middle-normal alexithymia, high-normal alexithymia, and alexithymic) based on their responses to the alexithymia measure. We calculated the risk estimates for the criterion measures by a logistic regression analysis. RESULTS: Controlling for demographic variables, the odds ratio (OR) for having chronic pain was significantly higher in the high-normal (OR: 1.49, 95% CI: 1.07-2.09) and alexithymic groups (OR: 2.56, 95% CI: 1.47-4.45) compared to the low-normal group. Approximately 40% of the participants belonged to these two high-risk groups. In the subanalyses of the 439 participants with chronic pain, the levels of pain intensity, disability, depression, and anxiety were significantly increased and the degree of life satisfaction was decreased with elevating alexithymia categories. CONCLUSIONS: The findings demonstrate that, in the general population, higher levels of alexithymia are associated with a higher risk of having chronic pain. The early identification and treatment of alexithymia and negative affect may be beneficial in preventing chronic pain and reducing the clinical and economic burdens of chronic pain. Further research is needed to determine if this association is due to a causal effect of alexithymia on the ...
    Keywords Medicine ; R ; Science ; Q
    Subject code 150
    Language English
    Publishing date 2014-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  6. Article ; Online: Differential clonal evolution in oesophageal cancers in response to neo-adjuvant chemotherapy

    John M. Findlay / Francesc Castro-Giner / Seiko Makino / Emily Rayner / Christiana Kartsonaki / William Cross / Michal Kovac / Danny Ulahannan / Claire Palles / Richard S. Gillies / Thomas P. MacGregor / David Church / Nicholas D. Maynard / Francesca Buffa / Jean-Baptiste Cazier / Trevor A. Graham / Lai-Mun Wang / Ricky A. Sharma / Mark Middleton /
    Ian Tomlinson

    Nature Communications, Vol 7, Iss 1, Pp 1-

    2016  Volume 13

    Abstract: Oesophageal adenocarcinoma is often treated with chemotherapy before surgery. Here, the authors sequence cancer samples before and after chemotherapy and examine how the genome changes, focusing on changes in driver gene mutations and differential clonal ...

    Abstract Oesophageal adenocarcinoma is often treated with chemotherapy before surgery. Here, the authors sequence cancer samples before and after chemotherapy and examine how the genome changes, focusing on changes in driver gene mutations and differential clonal evolution between good and poor responders.
    Keywords Science ; Q
    Language English
    Publishing date 2016-04-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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