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  • 1
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publikationsdatum: 2018-11-30
    Schlagwort(e): Immunology
    Print ISSN: 0036-8075
    Digitale ISSN: 1095-9203
    Thema: Biologie , Chemie und Pharmazie , Geologie und Paläontologie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
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  • 2
    Publikationsdatum: 2018-11-30
    Beschreibung: Limited proteolysis of gasdermin D (GSDMD) generates an N-terminal pore-forming fragment that controls pyroptosis in macrophages. GSDMD is processed via inflammasome-activated caspase-1 or -11. It is currently unknown whether macrophage GSDMD can be processed by other mechanisms. Here, we describe an additional pathway controlling GSDMD processing. The inhibition of TAK1 or IB kinase (IKK) by the Yersinia effector protein YopJ elicits RIPK1- and caspase-8–dependent cleavage of GSDMD, which subsequently results in cell death. GSDMD processing also contributes to the NLRP3 inflammasome–dependent release of interleukin-1β (IL-1β). Thus, caspase-8 acts as a regulator of GSDMD-driven cell death. Furthermore, this study establishes the importance of TAK1 and IKK activity in the control of GSDMD cleavage and cytotoxicity.
    Schlagwort(e): Immunology
    Print ISSN: 0036-8075
    Digitale ISSN: 1095-9203
    Thema: Biologie , Chemie und Pharmazie , Geologie und Paläontologie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
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  • 3
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publikationsdatum: 2018-12-14
    Schlagwort(e): Immunology
    Print ISSN: 0036-8075
    Digitale ISSN: 1095-9203
    Thema: Biologie , Chemie und Pharmazie , Geologie und Paläontologie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
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  • 4
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publikationsdatum: 2018-12-14
    Beschreibung: Immunoglobulin E (IgE) antibodies protect against helminth infections but can also cause life-threatening allergic reactions. Despite their role in human health, the cells that produce these antibodies are rarely observed and remain enigmatic. We isolated single IgE B cells from individuals with food allergies and used single-cell RNA sequencing to elucidate the gene expression and splicing patterns unique to these cells. We identified a surprising example of convergent evolution in which IgE antibodies underwent identical gene rearrangements in unrelated individuals. Through the acquisition of variable region mutations, these IgE antibodies gained high affinity and unexpected cross-reactivity to the clinically important peanut allergens Ara h 2 and Ara h 3. These findings provide insight into IgE B cell transcriptomics and enable biochemical dissection of this antibody class.
    Schlagwort(e): Immunology
    Print ISSN: 0036-8075
    Digitale ISSN: 1095-9203
    Thema: Biologie , Chemie und Pharmazie , Geologie und Paläontologie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
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  • 5
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publikationsdatum: 2018-08-17
    Beschreibung: The binding of DNA to cyclic GMP–AMP synthase (cGAS) leads to the production of the secondary messenger cyclic GMP–AMP (cGAMP), which activates innate immune responses. We have shown that DNA binding to cGAS robustly induced the formation of liquidlike droplets in which cGAS was activated. The disordered and positively charged cGAS N terminus enhanced cGAS-DNA phase separation by increasing the valencies of DNA binding. Long DNA was more efficient in promoting cGAS liquid phase separation and cGAS enzyme activity than short DNA. Moreover, free zinc ions enhanced cGAS enzyme activity both in vitro and in cells by promoting cGAS-DNA phase separation. These results demonstrated that the DNA-induced phase transition of cGAS promotes cGAMP production and innate immune signaling.
    Schlagwort(e): Immunology
    Print ISSN: 0036-8075
    Digitale ISSN: 1095-9203
    Thema: Biologie , Chemie und Pharmazie , Geologie und Paläontologie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
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  • 6
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publikationsdatum: 2018-08-17
    Schlagwort(e): Immunology
    Print ISSN: 0036-8075
    Digitale ISSN: 1095-9203
    Thema: Biologie , Chemie und Pharmazie , Geologie und Paläontologie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
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  • 7
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publikationsdatum: 2018-08-17
    Schlagwort(e): Immunology
    Print ISSN: 0036-8075
    Digitale ISSN: 1095-9203
    Thema: Biologie , Chemie und Pharmazie , Geologie und Paläontologie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
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  • 8
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publikationsdatum: 2018-08-24
    Schlagwort(e): Immunology
    Print ISSN: 0036-8075
    Digitale ISSN: 1095-9203
    Thema: Biologie , Chemie und Pharmazie , Geologie und Paläontologie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
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  • 9
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publikationsdatum: 2018-10-19
    Schlagwort(e): Immunology
    Print ISSN: 0036-8075
    Digitale ISSN: 1095-9203
    Thema: Biologie , Chemie und Pharmazie , Geologie und Paläontologie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
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  • 10
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publikationsdatum: 2018-11-16
    Schlagwort(e): Immunology
    Print ISSN: 0036-8075
    Digitale ISSN: 1095-9203
    Thema: Biologie , Chemie und Pharmazie , Geologie und Paläontologie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
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  • 11
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publikationsdatum: 2018-04-27
    Schlagwort(e): Immunology
    Print ISSN: 0036-8075
    Digitale ISSN: 1095-9203
    Thema: Biologie , Chemie und Pharmazie , Geologie und Paläontologie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
    Standort Signatur Erwartet Verfügbarkeit
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  • 12
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publikationsdatum: 2018-10-19
    Schlagwort(e): Immunology
    Print ISSN: 0036-8075
    Digitale ISSN: 1095-9203
    Thema: Biologie , Chemie und Pharmazie , Geologie und Paläontologie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
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  • 13
    Publikationsdatum: 2018-10-19
    Beschreibung: Host injury triggers feedback mechanisms that limit tissue damage. Conventional type 1 dendritic cells (cDC1s) express dendritic cell natural killer lectin group receptor-1 (DNGR-1), encoded by the gene Clec9a , which senses tissue damage and favors cross-presentation of dead-cell material to CD8 + T cells. Here we find that DNGR-1 additionally reduces host-damaging inflammatory responses induced by sterile and infectious tissue injury in mice. DNGR-1 deficiency leads to exacerbated caerulein-induced necrotizing pancreatitis and increased pathology during systemic Candida albicans infection without affecting fungal burden. This effect is B and T cell–independent and attributable to increased neutrophilia in DNGR-1–deficient settings. Mechanistically, DNGR-1 engagement activates SHP-1 and inhibits MIP-2 (encoded by Cxcl2 ) production by cDC1s during Candida infection. This consequently restrains neutrophil recruitment and promotes disease tolerance. Thus, DNGR-1–mediated sensing of injury by cDC1s serves as a rheostat for the control of tissue damage, innate immunity, and immunopathology.
    Schlagwort(e): Immunology
    Print ISSN: 0036-8075
    Digitale ISSN: 1095-9203
    Thema: Biologie , Chemie und Pharmazie , Geologie und Paläontologie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
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  • 14
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publikationsdatum: 2018-11-09
    Schlagwort(e): Immunology
    Print ISSN: 0036-8075
    Digitale ISSN: 1095-9203
    Thema: Biologie , Chemie und Pharmazie , Geologie und Paläontologie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
    Standort Signatur Erwartet Verfügbarkeit
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  • 15
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publikationsdatum: 2018-11-09
    Schlagwort(e): Immunology
    Print ISSN: 0036-8075
    Digitale ISSN: 1095-9203
    Thema: Biologie , Chemie und Pharmazie , Geologie und Paläontologie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
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  • 16
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publikationsdatum: 2018-11-09
    Schlagwort(e): Immunology
    Print ISSN: 0036-8075
    Digitale ISSN: 1095-9203
    Thema: Biologie , Chemie und Pharmazie , Geologie und Paläontologie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
    Standort Signatur Erwartet Verfügbarkeit
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  • 17
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publikationsdatum: 2018-03-30
    Schlagwort(e): Immunology
    Print ISSN: 0036-8075
    Digitale ISSN: 1095-9203
    Thema: Biologie , Chemie und Pharmazie , Geologie und Paläontologie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
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  • 18
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publikationsdatum: 2018-04-13
    Schlagwort(e): Immunology
    Print ISSN: 0036-8075
    Digitale ISSN: 1095-9203
    Thema: Biologie , Chemie und Pharmazie , Geologie und Paläontologie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
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  • 19
    Publikationsdatum: 2018-05-04
    Beschreibung: Deficiency of C1q, the initiator of the complement classical pathway, is associated with the development of systemic lupus erythematosus (SLE). Explaining this association in terms of abnormalities in the classical pathway alone remains problematic because C3 deficiency does not predispose to SLE. Here, using a mouse model of SLE, we demonstrate that C1q, but not C3, restrains the response to self-antigens by modulating the mitochondrial metabolism of CD8 + T cells, which can themselves propagate autoimmunity. C1q deficiency also triggers an exuberant effector CD8 + T cell response to chronic viral infection leading to lethal immunopathology. These data establish a link between C1q and CD8 + T cell metabolism and may explain how C1q protects against lupus, with implications for the role of viral infections in the perpetuation of autoimmunity.
    Schlagwort(e): Immunology
    Print ISSN: 0036-8075
    Digitale ISSN: 1095-9203
    Thema: Biologie , Chemie und Pharmazie , Geologie und Paläontologie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
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  • 20
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publikationsdatum: 2018-05-25
    Schlagwort(e): Immunology
    Print ISSN: 0036-8075
    Digitale ISSN: 1095-9203
    Thema: Biologie , Chemie und Pharmazie , Geologie und Paläontologie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
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  • 21
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publikationsdatum: 2018-05-04
    Schlagwort(e): Immunology
    Print ISSN: 0036-8075
    Digitale ISSN: 1095-9203
    Thema: Biologie , Chemie und Pharmazie , Geologie und Paläontologie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
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  • 22
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publikationsdatum: 2018-03-23
    Beschreibung: The fine line between human health and disease can be driven by the interplay between host and microbial factors. This "metagenome" regulates cancer initiation, progression, and response to therapies. Besides the capacity of distinct microbial species to modulate the pharmacodynamics of chemotherapeutic drugs, symbiosis between epithelial barriers and their microbial ecosystems has a major impact on the local and distant immune system, markedly influencing clinical outcome in cancer patients. Efficacy of cancer immunotherapy with immune checkpoint antibodies can be diminished with administration of antibiotics, and superior efficacy is observed with the presence of specific gut microbes. Future strategies of precision medicine will likely rely on novel diagnostic and therapeutic tools with which to identify and correct defects in the microbiome that compromise therapeutic efficacy.
    Schlagwort(e): Immunology
    Print ISSN: 0036-8075
    Digitale ISSN: 1095-9203
    Thema: Biologie , Chemie und Pharmazie , Geologie und Paläontologie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
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  • 23
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publikationsdatum: 2018-03-30
    Schlagwort(e): Immunology
    Print ISSN: 0036-8075
    Digitale ISSN: 1095-9203
    Thema: Biologie , Chemie und Pharmazie , Geologie und Paläontologie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
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  • 24
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publikationsdatum: 2018-06-15
    Schlagwort(e): Immunology
    Print ISSN: 0036-8075
    Digitale ISSN: 1095-9203
    Thema: Biologie , Chemie und Pharmazie , Geologie und Paläontologie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
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  • 25
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publikationsdatum: 2018-02-16
    Schlagwort(e): Immunology
    Print ISSN: 0036-8075
    Digitale ISSN: 1095-9203
    Thema: Biologie , Chemie und Pharmazie , Geologie und Paläontologie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
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  • 26
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publikationsdatum: 2018-02-23
    Schlagwort(e): Immunology
    Print ISSN: 0036-8075
    Digitale ISSN: 1095-9203
    Thema: Biologie , Chemie und Pharmazie , Geologie und Paläontologie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
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  • 27
    Publikationsdatum: 2018-01-12
    Beschreibung: After priming, naïve CD8 + T lymphocytes establish specific heritable transcription programs that define progression to long-lasting memory cells or to short-lived effector cells. Although lineage specification is critical for protection, it remains unclear how chromatin dynamics contributes to the control of gene expression programs. We explored the role of gene silencing by the histone methyltransferase Suv39h1. In murine CD8 + T cells activated after Listeria monocytogenes infection, Suv39h1-dependent trimethylation of histone H3 lysine 9 controls the expression of a set of stem cell–related memory genes. Single-cell RNA sequencing revealed a defect in silencing of stem/memory genes selectively in Suv39h1 -defective T cell effectors. As a result, Suv39h1 -defective CD8 + T cells show sustained survival and increased long-term memory reprogramming capacity. Thus, Suv39h1 plays a critical role in marking chromatin to silence stem/memory genes during CD8 + T effector terminal differentiation.
    Schlagwort(e): Immunology
    Print ISSN: 0036-8075
    Digitale ISSN: 1095-9203
    Thema: Biologie , Chemie und Pharmazie , Geologie und Paläontologie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
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  • 28
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publikationsdatum: 2018-02-03
    Schlagwort(e): Immunology
    Print ISSN: 0036-8075
    Digitale ISSN: 1095-9203
    Thema: Biologie , Chemie und Pharmazie , Geologie und Paläontologie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
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  • 29
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publikationsdatum: 2018-03-06
    Schlagwort(e): Immunology
    Print ISSN: 0036-8075
    Digitale ISSN: 1095-9203
    Thema: Biologie , Chemie und Pharmazie , Geologie und Paläontologie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
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  • 30
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publikationsdatum: 2018-03-06
    Schlagwort(e): Immunology
    Print ISSN: 0036-8075
    Digitale ISSN: 1095-9203
    Thema: Biologie , Chemie und Pharmazie , Geologie und Paläontologie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
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  • 31
    Publikationsdatum: 2018-03-06
    Beschreibung: Interleukin-2 (IL-2) is a cytokine required for effector T cell expansion, survival, and function, especially for engineered T cells in adoptive cell immunotherapy, but its pleiotropy leads to simultaneous stimulation and suppression of immune responses as well as systemic toxicity, limiting its therapeutic use. We engineered IL-2 cytokine-receptor orthogonal ( ortho ) pairs that interact with one another, transmitting native IL-2 signals, but do not interact with their natural cytokine and receptor counterparts. Introduction of ortho IL-2Rβ into T cells enabled the selective cellular targeting of ortho IL-2 to engineered CD4 + and CD8 + T cells in vitro and in vivo, with limited off-target effects and negligible toxicity. Ortho IL-2 pairs were efficacious in a preclinical mouse cancer model of adoptive cell therapy and may therefore represent a synthetic approach to achieving selective potentiation of engineered cells.
    Schlagwort(e): Immunology
    Print ISSN: 0036-8075
    Digitale ISSN: 1095-9203
    Thema: Biologie , Chemie und Pharmazie , Geologie und Paläontologie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
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  • 32
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publikationsdatum: 2018-01-12
    Schlagwort(e): Immunology
    Print ISSN: 0036-8075
    Digitale ISSN: 1095-9203
    Thema: Biologie , Chemie und Pharmazie , Geologie und Paläontologie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
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  • 33
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publikationsdatum: 2018-01-12
    Schlagwort(e): Immunology
    Print ISSN: 0036-8075
    Digitale ISSN: 1095-9203
    Thema: Biologie , Chemie und Pharmazie , Geologie und Paläontologie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
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  • 34
    Publikationsdatum: 2017-08-25
    Beschreibung: The small intestine contains CD4 + CD8αα + double-positive intraepithelial lymphocytes (DP IELs), which originate from intestinal CD4 + T cells through down-regulation of the transcription factor Thpok and have regulatory functions. DP IELs are absent in germ-free mice, which suggests that their differentiation depends on microbial factors. We found that DP IEL numbers in mice varied in different vivaria, correlating with the presence of Lactobacillus reuteri . This species induced DP IELs in germ-free mice and conventionally-raised mice lacking these cells. L. reuteri did not shape the DP-IEL-TCR (TCR, T cell receptor) repertoire but generated indole derivatives of tryptophan that activated the aryl-hydrocarbon receptor in CD4 + T cells, allowing Thpok down-regulation and differentiation into DP IELs. Thus, L. reuteri , together with a tryptophan-rich diet, can reprogram intraepithelial CD4 + T cells into immunoregulatory T cells.
    Schlagwort(e): Immunology
    Print ISSN: 0036-8075
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    Thema: Biologie , Chemie und Pharmazie , Geologie und Paläontologie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
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  • 35
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publikationsdatum: 2017-09-08
    Schlagwort(e): Immunology
    Print ISSN: 0036-8075
    Digitale ISSN: 1095-9203
    Thema: Biologie , Chemie und Pharmazie , Geologie und Paläontologie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
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  • 36
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publikationsdatum: 2017-08-25
    Schlagwort(e): Immunology
    Print ISSN: 0036-8075
    Digitale ISSN: 1095-9203
    Thema: Biologie , Chemie und Pharmazie , Geologie und Paläontologie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
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  • 37
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publikationsdatum: 2017-09-08
    Schlagwort(e): Immunology
    Print ISSN: 0036-8075
    Digitale ISSN: 1095-9203
    Thema: Biologie , Chemie und Pharmazie , Geologie und Paläontologie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
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  • 38
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publikationsdatum: 2017-09-08
    Schlagwort(e): Immunology
    Print ISSN: 0036-8075
    Digitale ISSN: 1095-9203
    Thema: Biologie , Chemie und Pharmazie , Geologie und Paläontologie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
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  • 39
    Publikationsdatum: 2017-09-08
    Beschreibung: Humans inhale mold conidia daily and typically experience lifelong asymptomatic clearance. Conidial germination into tissue-invasive hyphae can occur in individuals with defects in myeloid function, although the mechanism of myeloid cell–mediated immune surveillance remains unclear. By monitoring fungal physiology in vivo, we demonstrate that lung neutrophils trigger programmed cell death with apoptosis-like features in Aspergillus fumigatus conidia, the most prevalent human mold pathogen. An antiapoptotic protein, AfBIR1, opposes this process by inhibiting fungal caspase activation and DNA fragmentation in the murine lung. Genetic and pharmacologic studies indicate that AfBIR1 expression and activity underlie conidial susceptibility to NADPH (reduced form of nicotinamide adenine dinucleotide phosphate) oxidase-dependent killing and, in turn, host susceptibility to invasive aspergillosis. Immune surveillance exploits a fungal apoptosis-like programmed cell death pathway to maintain sterilizing immunity in the lung.
    Schlagwort(e): Immunology
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    Thema: Biologie , Chemie und Pharmazie , Geologie und Paläontologie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
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  • 40
    Publikationsdatum: 2017-09-08
    Beschreibung: Antigen-presenting cells (APCs) occupy diverse anatomical tissues, but their tissue-restricted homeostasis remains poorly understood. Here, working with mouse models of inflammation, we found that mechanistic target of rapamycin (mTOR)–dependent metabolic adaptation was required at discrete locations. mTOR was dispensable for dendritic cell (DC) homeostasis in secondary lymphoid tissues but necessary to regulate cellular metabolism and accumulation of CD103 + DCs and alveolar macrophages in lung. Moreover, while numbers of mTOR-deficient lung CD11b + DCs were not changed, they were metabolically reprogrammed to skew allergic inflammation from eosinophilic T helper cell 2 (T H 2) to neutrophilic T H 17 polarity. The mechanism for this change was independent of translational control but dependent on inflammatory DCs, which produced interleukin-23 and increased fatty acid oxidation. mTOR therefore mediates metabolic adaptation of APCs in distinct tissues, influencing the immunological character of allergic inflammation.
    Schlagwort(e): Immunology
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    Thema: Biologie , Chemie und Pharmazie , Geologie und Paläontologie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
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  • 41
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publikationsdatum: 2017-07-14
    Schlagwort(e): Immunology
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    Thema: Biologie , Chemie und Pharmazie , Geologie und Paläontologie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
    Standort Signatur Erwartet Verfügbarkeit
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  • 42
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publikationsdatum: 2017-08-04
    Schlagwort(e): Immunology
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    Thema: Biologie , Chemie und Pharmazie , Geologie und Paläontologie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
    Standort Signatur Erwartet Verfügbarkeit
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  • 43
    Publikationsdatum: 2017-08-04
    Beschreibung: The microbiota is known to modulate the host response to influenza infection through as-yet-unclear mechanisms. We hypothesized that components of the microbiota exert effects through type I interferon (IFN), a hypothesis supported by analysis of influenza in a gain-of-function genetic mouse model. Here we show that a microbially associated metabolite, desaminotyrosine (DAT), protects from influenza through augmentation of type I IFN signaling and diminution of lung immunopathology. A specific human-associated gut microbe, Clostridium orbiscindens, produced DAT and rescued antibiotic-treated influenza-infected mice. DAT protected the host by priming the amplification loop of type I IFN signaling. These findings show that specific components of the enteric microbiota have distal effects on responses to lethal infections through modulation of type I IFN.
    Schlagwort(e): Immunology
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    Thema: Biologie , Chemie und Pharmazie , Geologie und Paläontologie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
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  • 44
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publikationsdatum: 2017-10-06
    Schlagwort(e): Immunology
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    Thema: Biologie , Chemie und Pharmazie , Geologie und Paläontologie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
    Standort Signatur Erwartet Verfügbarkeit
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  • 45
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publikationsdatum: 2017-10-06
    Beschreibung: Neutrophils have been implicated as harmful cells in a variety of inappropriate inflammatory conditions where they injure the host, leading to the death of the neutrophils and their subsequent phagocytosis by monocytes and macrophages. Here we show that in a fully repairing sterile thermal hepatic injury, neutrophils also penetrate the injury site and perform the critical tasks of dismantling injured vessels and creating channels for new vascular regrowth. Upon completion of these tasks, they neither die at the injury site nor are phagocytosed. Instead, many of these neutrophils reenter the vasculature and have a preprogrammed journey that entails a sojourn in the lungs to up-regulate CXCR4 (C-X-C motif chemokine receptor 4) before entering the bone marrow, where they undergo apoptosis.
    Schlagwort(e): Immunology
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    Thema: Biologie , Chemie und Pharmazie , Geologie und Paläontologie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
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  • 46
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publikationsdatum: 2017-10-13
    Schlagwort(e): Immunology
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    Thema: Biologie , Chemie und Pharmazie , Geologie und Paläontologie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
    Standort Signatur Erwartet Verfügbarkeit
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  • 47
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publikationsdatum: 2017-10-13
    Schlagwort(e): Immunology
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    Thema: Biologie , Chemie und Pharmazie , Geologie und Paläontologie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
    Standort Signatur Erwartet Verfügbarkeit
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  • 48
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publikationsdatum: 2017-12-01
    Schlagwort(e): Immunology
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    Thema: Biologie , Chemie und Pharmazie , Geologie und Paläontologie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
    Standort Signatur Erwartet Verfügbarkeit
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  • 49
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publikationsdatum: 2017-12-01
    Schlagwort(e): Immunology
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    Thema: Biologie , Chemie und Pharmazie , Geologie und Paläontologie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
    Standort Signatur Erwartet Verfügbarkeit
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  • 50
    Publikationsdatum: 2017-12-01
    Beschreibung: Platelet and fibrin clots occlude blood vessels in hemostasis and thrombosis. Here we report a noncanonical mechanism for vascular occlusion based on neutrophil extracellular traps (NETs), DNA fibers released by neutrophils during inflammation. We investigated which host factors control NETs in vivo and found that two deoxyribonucleases (DNases), DNase1 and DNase1-like 3, degraded NETs in circulation during sterile neutrophilia and septicemia. In the absence of both DNases, intravascular NETs formed clots that obstructed blood vessels and caused organ damage. Vascular occlusions in patients with severe bacterial infections were associated with a defect to degrade NETs ex vivo and the formation of intravascular NET clots. DNase1 and DNase1-like 3 are independently expressed and thus provide dual host protection against deleterious effects of intravascular NETs.
    Schlagwort(e): Immunology
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    Thema: Biologie , Chemie und Pharmazie , Geologie und Paläontologie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
    Standort Signatur Erwartet Verfügbarkeit
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  • 51
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publikationsdatum: 2017-11-24
    Schlagwort(e): Immunology
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    Thema: Biologie , Chemie und Pharmazie , Geologie und Paläontologie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
    Standort Signatur Erwartet Verfügbarkeit
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  • 52
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publikationsdatum: 2017-05-19
    Schlagwort(e): Immunology
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    Thema: Biologie , Chemie und Pharmazie , Geologie und Paläontologie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
    Standort Signatur Erwartet Verfügbarkeit
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  • 53
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publikationsdatum: 2017-03-10
    Beschreibung: Author: John F. Foley
    Schlagwort(e): Immunology
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    Thema: Biologie , Chemie und Pharmazie , Geologie und Paläontologie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
    Standort Signatur Erwartet Verfügbarkeit
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  • 54
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publikationsdatum: 2017-04-21
    Schlagwort(e): Immunology
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    Thema: Biologie , Chemie und Pharmazie , Geologie und Paläontologie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
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  • 55
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publikationsdatum: 2017-05-05
    Schlagwort(e): Immunology
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    Thema: Biologie , Chemie und Pharmazie , Geologie und Paläontologie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
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  • 56
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publikationsdatum: 2017-05-05
    Schlagwort(e): Immunology
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    Thema: Biologie , Chemie und Pharmazie , Geologie und Paläontologie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
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  • 57
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publikationsdatum: 2017-05-05
    Beschreibung: Interleukin 10 (IL-10) is an anti-inflammatory cytokine that plays a critical role in the control of immune responses. However, its mechanisms of action remain poorly understood. Here, we show that IL-10 opposes the switch to the metabolic program induced by inflammatory stimuli in macrophages. Specifically, we show that IL-10 inhibits lipopolysaccharide-induced glucose uptake and glycolysis and promotes oxidative phosphorylation. Furthermore, IL-10 suppresses mammalian target of rapamycin (mTOR) activity through the induction of an mTOR inhibitor, DDIT4. Consequently, IL-10 promotes mitophagy that eliminates dysfunctional mitochondria characterized by low membrane potential and a high level of reactive oxygen species. In the absence of IL-10 signaling, macrophages accumulate damaged mitochondria in a mouse model of colitis and inflammatory bowel disease patients, and this results in dysregulated activation of the NLRP3 inflammasome and production of IL-1β.
    Schlagwort(e): Immunology
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    Thema: Biologie , Chemie und Pharmazie , Geologie und Paläontologie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
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  • 58
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publikationsdatum: 2017-04-15
    Schlagwort(e): Immunology
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    Thema: Biologie , Chemie und Pharmazie , Geologie und Paläontologie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
    Standort Signatur Erwartet Verfügbarkeit
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  • 59
    Publikationsdatum: 2017-04-15
    Beschreibung: Immunotherapy has clinical activity in certain virally associated cancers. However, the tumor antigens targeted in successful treatments remain poorly defined. We used a personalized immunogenomic approach to elucidate the global landscape of antitumor T cell responses in complete regression of human papillomavirus–associated metastatic cervical cancer after tumor-infiltrating adoptive T cell therapy. Remarkably, immunodominant T cell reactivities were directed against mutated neoantigens or a cancer germline antigen, rather than canonical viral antigens. T cells targeting viral tumor antigens did not display preferential in vivo expansion. Both viral and nonviral tumor antigen–specific T cells resided predominantly in the programmed cell death 1 (PD-1)–expressing T cell compartment, which suggests that PD-1 blockade may unleash diverse antitumor T cell reactivities. These findings suggest a new paradigm of targeting nonviral antigens in immunotherapy of virally associated cancers.
    Schlagwort(e): Immunology
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    Thema: Biologie , Chemie und Pharmazie , Geologie und Paläontologie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
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  • 60
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publikationsdatum: 2017-01-06
    Beschreibung: Author: Priscilla Kelly
    Schlagwort(e): Immunology
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    Thema: Biologie , Chemie und Pharmazie , Geologie und Paläontologie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
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  • 61
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publikationsdatum: 2017-01-27
    Beschreibung: Author: Caroline Ash
    Schlagwort(e): Immunology
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    Thema: Biologie , Chemie und Pharmazie , Geologie und Paläontologie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
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  • 62
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publikationsdatum: 2016-06-24
    Beschreibung: Author: John F. Foley
    Schlagwort(e): Immunology
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    Thema: Biologie , Chemie und Pharmazie , Geologie und Paläontologie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
    Standort Signatur Erwartet Verfügbarkeit
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  • 63
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publikationsdatum: 2016-07-22
    Beschreibung: Author: John F. Foley
    Schlagwort(e): Immunology
    Print ISSN: 0036-8075
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    Thema: Biologie , Chemie und Pharmazie , Geologie und Paläontologie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
    Standort Signatur Erwartet Verfügbarkeit
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  • 64
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publikationsdatum: 2016-07-01
    Beschreibung: Autoimmune diseases share a grim similarity with cancer: People's own cells become their enemies. But a study published online in Science reveals a happier parallel, suggesting that a therapy designed to harness the immune system to attack cancer cells may also cull the turncoat immune cells behind certain autoimmune diseases. The approach relies on chimeric antigen receptor T cells, or CAR T cells: immune cells genetically modified to home in on a desired target on cancer cells or—in this case—on rogue B cells, another immune cell type. The new study only gauged the CAR T cells' capabilities in the lab dish and in mouse models of pemphigus vulgaris, an autoimmune condition in which B cells secrete antibodies that attack a protein in skin and mucous membrane. But some scientists are already calling the approach, which specifically targets the errant B cells, a breakthrough. Author: Mitch Leslie
    Schlagwort(e): Immunology
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    Thema: Biologie , Chemie und Pharmazie , Geologie und Paläontologie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
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  • 65
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publikationsdatum: 2016-06-24
    Beschreibung: Effective immune responses rely on balancing lymphocyte stability and plasticity. Lymphocytes have regulatory circuits that control phenotypic and functional identity. Stable circuits maintain homeostasis and prevent autoimmunity. But plasticity is needed to integrate new environmental inputs and generate immune responses that subdue the eliciting agent without damaging tissue. Regulatory T cells (Tregs) are a subset of CD4+ T cells that control effector T cell responses and prevent excessive inflammation and autoimmunity (1, 2). On page 1581 in this issue, Sujino et al. (3) report that intestinal Tregs convert into CD4+ intraepithelial T cells (CD4IELs) to adapt to the local intestinal environment, thus identifying the intestinal epithelium as a compartment that enforces lymphocyte plasticity. Authors: Marco Colonna, Luisa Cervantes-Barragan
    Schlagwort(e): Immunology
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    Thema: Biologie , Chemie und Pharmazie , Geologie und Paläontologie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
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  • 66
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publikationsdatum: 2016-06-03
    Beschreibung: Innate immune cells act as a surveillance system, detecting and responding to pathogens and endogenous danger signals. The complex patterns of signals they receive are detected by a variety of pattern recognition receptors (PRRs). On page 1232 of this issue, Zanoni et al. (1) find that innate immune responses to microbial products do not occur in a vacuum; rather, there is a complex array of danger signals in surrounding damaged tissue that can determine an immune cell type–specific response to pathogens. They describe a host-derived lipid that binds to a PRR to induce a hyperactive innate immune response that enhances long-lived protective immunity against invading microbes. Authors: Brooke A. Napier, Denise M. Monack
    Schlagwort(e): Immunology
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    Thema: Biologie , Chemie und Pharmazie , Geologie und Paläontologie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
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  • 67
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publikationsdatum: 2016-06-03
    Beschreibung: Author: John F. Foley
    Schlagwort(e): Immunology
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    Thema: Biologie , Chemie und Pharmazie , Geologie und Paläontologie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
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  • 68
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publikationsdatum: 2016-06-10
    Beschreibung: Author: Kristen L. Mueller
    Schlagwort(e): Immunology
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    Thema: Biologie , Chemie und Pharmazie , Geologie und Paläontologie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
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  • 69
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publikationsdatum: 2016-04-22
    Beschreibung: Author: Kristen L. Mueller
    Schlagwort(e): Immunology
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    Thema: Biologie , Chemie und Pharmazie , Geologie und Paläontologie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
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  • 70
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publikationsdatum: 2016-03-18
    Beschreibung: Helminth and protozoan parasites are the most common infectious agents of humans living in developing countries and represent an important disease burden, particularly through their ability to cause physical and intellectual growth retardation in young children (1, 2). Type 2 immune responses promote efficient expulsion of intestinal parasites such as helminths by driving a “weep and sweep” response that involves mucous production, fluid secretion, and increased intestinal motility. These same responses in susceptible individuals cause the symptoms of allergy after exposure to pollens and certain food antigens. The generation of type 2 immunity in response to helminth parasites requires the secretion of cytokines by intestinal epithelial cells, but the source and induction of cytokine secretion have been unclear. Three studies (3–5), including a report by Howitt et al. (5) on page 1329 of this issue, reveal a key role for a rare intestinal cell—the tuft or brush cell—in driving type 2 immunity. Author: Nicola Harris
    Schlagwort(e): Immunology
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  • 71
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publikationsdatum: 2016-03-18
    Beschreibung: Author: L. Bryan Ray
    Schlagwort(e): Immunology
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    Thema: Biologie , Chemie und Pharmazie , Geologie und Paläontologie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
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  • 72
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publikationsdatum: 2016-03-04
    Beschreibung: T helper lymphocytes play essential roles in the adaptive immune system. They come in distinct types defined by unique transcriptional programs that control their development and functions. Among these, T helper 17 (TH17) cells are important in protecting mucosal surfaces against fungal and bacterial infections. In addition, TH17 cells contribute to the pathogenesis of multiple autoimmune diseases (1). A recent study (2) adds yet another layer of complexity to the biology of these complex cells—an RNA helicase and a long noncoding RNA (lncRNA) that act together to control their effector functions. Authors: Maninjay K. Atianand, Katherine A. Fitzgerald
    Schlagwort(e): Immunology
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  • 73
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publikationsdatum: 2016-03-04
    Beschreibung: Author: Kristen L. Mueller
    Schlagwort(e): Immunology
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    Thema: Biologie , Chemie und Pharmazie , Geologie und Paläontologie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
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  • 74
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publikationsdatum: 2016-03-11
    Beschreibung: Author: John F. Foley
    Schlagwort(e): Immunology
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    Thema: Biologie , Chemie und Pharmazie , Geologie und Paläontologie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
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  • 75
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publikationsdatum: 2016-05-06
    Beschreibung: Author: John F. Foley
    Schlagwort(e): Immunology
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    Thema: Biologie , Chemie und Pharmazie , Geologie und Paläontologie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
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  • 76
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publikationsdatum: 2016-04-01
    Beschreibung: Author: Kristen L. Mueller
    Schlagwort(e): Immunology
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    Thema: Biologie , Chemie und Pharmazie , Geologie und Paläontologie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
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  • 77
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    American Association for the Advancement of Science (AAAS)
    Publikationsdatum: 2016-01-20
    Beschreibung: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Underwood, Emily -- New York, N.Y. -- Science. 2015 Dec 4;350(6265):1188-90. doi: 10.1126/science.350.6265.1188.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26785475" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Aging/blood/genetics/*physiology ; Animals ; Biological Clocks/genetics/*physiology ; Biomarkers/blood/metabolism ; DNA/genetics ; DNA Methylation ; Epigenesis, Genetic ; Humans ; Mice ; Rats ; Telomere Homeostasis
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    Thema: Biologie , Chemie und Pharmazie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
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  • 78
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    Unbekannt
    American Association for the Advancement of Science (AAAS)
    Publikationsdatum: 2016-01-20
    Beschreibung: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Scheid, Johannes F -- New York, N.Y. -- Science. 2015 Dec 4;350(6265):1175. doi: 10.1126/science.aad7133.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Massachusetts General Hospital, Boston, MA 02114, USA. The Rockefeller University, New York, NY 10021, USA. fscheid@partners.org.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26785466" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Animals ; Antibodies, Monoclonal/genetics/immunology/isolation & purification ; Antibodies, Neutralizing/genetics/*immunology/isolation & purification ; B-Lymphocytes/*immunology ; Cell Separation/methods ; HIV Antibodies/genetics/*immunology/isolation & purification ; HIV Infections/*blood ; Humans ; Immunologic Memory ; Mice ; env Gene Products, Human Immunodeficiency Virus/*immunology
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    Thema: Biologie , Chemie und Pharmazie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
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  • 79
    Publikationsdatum: 2016-01-20
    Beschreibung: Mitochondrial morphology is shaped by fusion and division of their membranes. Here, we found that adult myocardial function depends on balanced mitochondrial fusion and fission, maintained by processing of the dynamin-like guanosine triphosphatase OPA1 by the mitochondrial peptidases YME1L and OMA1. Cardiac-specific ablation of Yme1l in mice activated OMA1 and accelerated OPA1 proteolysis, which triggered mitochondrial fragmentation and altered cardiac metabolism. This caused dilated cardiomyopathy and heart failure. Cardiac function and mitochondrial morphology were rescued by Oma1 deletion, which prevented OPA1 cleavage. Feeding mice a high-fat diet or ablating Yme1l in skeletal muscle restored cardiac metabolism and preserved heart function without suppressing mitochondrial fragmentation. Thus, unprocessed OPA1 is sufficient to maintain heart function, OMA1 is a critical regulator of cardiomyocyte survival, and mitochondrial morphology and cardiac metabolism are intimately linked.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wai, Timothy -- Garcia-Prieto, Jaime -- Baker, Michael J -- Merkwirth, Carsten -- Benit, Paule -- Rustin, Pierre -- Ruperez, Francisco Javier -- Barbas, Coral -- Ibanez, Borja -- Langer, Thomas -- New York, N.Y. -- Science. 2015 Dec 4;350(6265):aad0116. doi: 10.1126/science.aad0116.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute for Genetics, University of Cologne, 50674 Cologne, Germany. Max-Planck-Institute for Biology of Aging, Cologne, Germany. ; Myocardial Pathophysiology Area, Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain. ; Institute for Genetics, University of Cologne, 50674 Cologne, Germany. ; INSERM UMR 1141, Hopital Robert Debre, Paris, France. Universite Paris 7, Faculte de Medecine Denis Diderot, Paris, France. ; Centre for Metabolomics and Bioanalysis (CEMBIO), Faculty of Pharmacy, Universidad San Pablo CEU, Campus Monteprincipe, Boadilla del Monte, 28668 Madrid, Spain. ; Myocardial Pathophysiology Area, Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain. Department of Cardiology, Instituto de Investigacion Sanitaria (IIS), Fundacion Jimenez Diaz Hospital, Madrid, Spain. thomas.langer@uni-koeln.de bibanez@cnic.es. ; Institute for Genetics, University of Cologne, 50674 Cologne, Germany. Max-Planck-Institute for Biology of Aging, Cologne, Germany. Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany. Center for Molecular Medicine (CMMC), University of Cologne, Cologne, Germany. thomas.langer@uni-koeln.de bibanez@cnic.es.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26785494" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Animals ; Cardiomyopathy, Dilated/genetics/metabolism/pathology ; Diet, High-Fat ; Embryonic Development ; Female ; GTP Phosphohydrolases ; Gene Deletion ; Heart/embryology ; Heart Failure/genetics/*metabolism/pathology ; Male ; Metalloendopeptidases/genetics ; Metalloproteases/genetics/metabolism ; Mice ; Mice, Knockout ; Mitochondria, Heart/*metabolism/ultrastructure ; *Mitochondrial Degradation ; *Mitochondrial Dynamics ; Mitochondrial Proteins/genetics/metabolism ; Muscle, Skeletal/enzymology ; Myocardium/*metabolism/pathology ; Myocytes, Cardiac/enzymology/pathology ; Proteolysis
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    Thema: Biologie , Chemie und Pharmazie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
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  • 80
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    American Association for the Advancement of Science (AAAS)
    Publikationsdatum: 2016-01-20
    Beschreibung: Mitochondria generate adenosine 5'-triphosphate (ATP) and are a source of potentially toxic reactive oxygen species (ROS). It has been suggested that the gradual mitochondrial dysfunction that is observed to accompany aging could in fact be causal to the aging process. Here we review findings that suggest that age-dependent mitochondrial dysfunction is not sufficient to limit life span. Furthermore, mitochondrial ROS are not always deleterious and can even stimulate pro-longevity pathways. Thus, mitochondrial dysfunction plays a complex role in regulating longevity.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wang, Ying -- Hekimi, Siegfried -- MOP-114891/Canadian Institutes of Health Research/Canada -- MOP-123295/Canadian Institutes of Health Research/Canada -- MOP-97869/Canadian Institutes of Health Research/Canada -- New York, N.Y. -- Science. 2015 Dec 4;350(6265):1204-7. doi: 10.1126/science.aac4357.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biology, McGill University, Montreal, Quebec H3A 1B1, Canada. ; Department of Biology, McGill University, Montreal, Quebec H3A 1B1, Canada. siegfried.hekimi@mcgill.ca.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26785479" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Adenosine Triphosphate/*metabolism ; Animals ; Caenorhabditis elegans Proteins/genetics ; Electron Transport/genetics ; Electron Transport Complex III/genetics ; Longevity/genetics/*physiology ; Mice ; Mice, Knockout ; Mitochondria/genetics/*metabolism ; Point Mutation ; Reactive Oxygen Species/*metabolism
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    Thema: Biologie , Chemie und Pharmazie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
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  • 81
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    American Association for the Advancement of Science (AAAS)
    Publikationsdatum: 2016-01-20
    Beschreibung: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cleary, Allison S -- New York, N.Y. -- Science. 2015 Dec 4;350(6265):1174-5. doi: 10.1126/science.aad7103.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Pennsylvania State University College of Medicine, Hershey PA 17078, USA. acleary@hmc.psu.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26785463" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Animals ; Breast Neoplasms/genetics/metabolism/*pathology ; Clone Cells/metabolism/pathology ; Female ; Mammary Neoplasms, Experimental/genetics/metabolism/*pathology ; Mice ; Neoplasms, Basal Cell/genetics/metabolism/pathology ; Wnt1 Protein/genetics/*metabolism ; ras Proteins/genetics/metabolism
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    Thema: Biologie , Chemie und Pharmazie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
    Standort Signatur Erwartet Verfügbarkeit
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  • 82
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    American Association for the Advancement of Science (AAAS)
    Publikationsdatum: 2016-01-20
    Beschreibung: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cohen, Jon -- New York, N.Y. -- Science. 2015 Dec 4;350(6265):1186-7. doi: 10.1126/science.350.6265.1186.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26785474" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Animals ; Caenorhabditis elegans/genetics/physiology ; Caenorhabditis elegans Proteins/genetics/physiology ; Caloric Restriction ; Death ; Humans ; Hydra/genetics/physiology ; Longevity/genetics/*physiology ; Mice ; Mutation ; Phosphatidylinositol 3-Kinases/genetics/physiology
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    Thema: Biologie , Chemie und Pharmazie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
    Standort Signatur Erwartet Verfügbarkeit
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  • 83
    Publikationsdatum: 2016-01-20
    Beschreibung: In developing hearts, changes in the cardiac metabolic milieu during the perinatal period redirect mitochondrial substrate preference from carbohydrates to fatty acids. Mechanisms responsible for this mitochondrial plasticity are unknown. Here, we found that PINK1-Mfn2-Parkin-mediated mitophagy directs this metabolic transformation in mouse hearts. A mitofusin (Mfn) 2 mutant lacking PINK1 phosphorylation sites necessary for Parkin binding (Mfn2 AA) inhibited mitochondrial Parkin translocation, suppressing mitophagy without impairing mitochondrial fusion. Cardiac Parkin deletion or expression of Mfn2 AA from birth, but not after weaning, prevented postnatal mitochondrial maturation essential to survival. Five-week-old Mfn2 AA hearts retained a fetal mitochondrial transcriptional signature without normal increases in fatty acid metabolism and mitochondrial biogenesis genes. Myocardial fatty acylcarnitine levels and cardiomyocyte respiration induced by palmitoylcarnitine were concordantly depressed. Thus, instead of transcriptional reprogramming, fetal cardiomyocyte mitochondria undergo perinatal Parkin-mediated mitophagy and replacement by mature adult mitochondria. Mitophagic mitochondrial removal underlies developmental cardiomyocyte mitochondrial plasticity and metabolic transitioning of perinatal hearts.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4747105/" 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/PMC4747105/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gong, Guohua -- Song, Moshi -- Csordas, Gyorgy -- Kelly, Daniel P -- Matkovich, Scot J -- Dorn, Gerald W 2nd -- HL058493/HL/NHLBI NIH HHS/ -- HL108943/HL/NHLBI NIH HHS/ -- HL122124/HL/NHLBI NIH HHS/ -- HL128071/HL/NHLBI NIH HHS/ -- HL59888/HL/NHLBI NIH HHS/ -- R01 HL058493/HL/NHLBI NIH HHS/ -- R01 HL059888/HL/NHLBI NIH HHS/ -- R01 HL108943/HL/NHLBI NIH HHS/ -- R01 HL128071/HL/NHLBI NIH HHS/ -- New York, N.Y. -- Science. 2015 Dec 4;350(6265):aad2459. doi: 10.1126/science.aad2459. Epub 2015 Dec 3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for Pharmacogenomics, Department of Internal Medicine, Washington University School of Medicine, St. Louis, MO, USA. ; Department of Pathology, Anatomy, and Cell Biology, Thomas Jefferson University, Philadelphia, PA, USA. ; Center for Metabolic Origins of Disease, Cardiovascular Metabolism Program, Sanford Burnham Prebys Medical Discovery Institute, Orlando, FL, USA. ; Center for Pharmacogenomics, Department of Internal Medicine, Washington University School of Medicine, St. Louis, MO, USA. gdorn@dom.wustl.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26785495" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Animals ; Cellular Reprogramming ; GTP Phosphohydrolases/genetics/metabolism ; Heart/*embryology ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Mitochondria, Heart/metabolism/*physiology/ultrastructure ; Mitochondrial Degradation/genetics/*physiology ; Mitochondrial Dynamics ; Myocardium/*metabolism/ultrastructure ; Myocytes, Cardiac/metabolism/ultrastructure ; Protein Kinases/metabolism ; Ubiquitin-Protein Ligases/genetics/*metabolism
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    Thema: Biologie , Chemie und Pharmazie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
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  • 84
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    American Association for the Advancement of Science (AAAS)
    Publikationsdatum: 2016-01-20
    Beschreibung: Research into stem cells and aging aims to understand how stem cells maintain tissue health, what mechanisms ultimately lead to decline in stem cell function with age, and how the regenerative capacity of somatic stem cells can be enhanced to promote healthy aging. Here, we explore the effects of aging on stem cells in different tissues. Recent research has focused on the ways that genetic mutations, epigenetic changes, and the extrinsic environmental milieu influence stem cell functionality over time. We describe each of these three factors, the ways in which they interact, and how these interactions decrease stem cell health over time. We are optimistic that a better understanding of these changes will uncover potential strategies to enhance stem cell function and increase tissue resiliency into old age.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Goodell, Margaret A -- Rando, Thomas A -- P01 AG036695/AG/NIA NIH HHS/ -- R01 AG047820/AG/NIA NIH HHS/ -- R01 AR062185/AR/NIAMS NIH HHS/ -- R37 AG023806/AG/NIA NIH HHS/ -- New York, N.Y. -- Science. 2015 Dec 4;350(6265):1199-204. doi: 10.1126/science.aab3388.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Stem Cells and Regenerative Medicine Center, Center for Cell and Gene Therapy, and Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA. goodell@bcm.edu rando@stanford.edu. ; Glenn Center for the Biology of Aging and Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA 94305, USA, and Center for Regenerative Rehabilitation, Veterans Administration Palo Alto Health Care System, Palo Alto, CA 94304, USA. goodell@bcm.edu rando@stanford.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26785478" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Adult Stem Cells/*physiology ; Aging/*physiology ; Animals ; Cell Aging ; Epigenesis, Genetic ; Genetic Drift ; *Health ; Humans ; Mice ; Mutation ; Organ Specificity ; Selection, Genetic
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  • 85
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    American Association for the Advancement of Science (AAAS)
    Publikationsdatum: 2016-03-12
    Beschreibung: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kupferschmidt, Kai -- New York, N.Y. -- Science. 2016 Mar 11;351(6278):1143. doi: 10.1126/science.351.6278.1143.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26965608" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Acinetobacter/*growth & development ; Animals ; *Death ; Humans ; Mice ; Moraxellaceae/*growth & development ; Rhizobiaceae/*growth & development ; Time Factors
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    Thema: Biologie , Chemie und Pharmazie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
    Standort Signatur Erwartet Verfügbarkeit
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  • 86
    Publikationsdatum: 2016-02-26
    Beschreibung: In most animal species, juvenile growth is marked by an exponential gain in body weight and size. Here we show that the microbiota of infant mice sustains both weight gain and longitudinal growth when mice are fed a standard laboratory mouse diet or a nutritionally depleted diet. We found that the intestinal microbiota interacts with the somatotropic hormone axis to drive systemic growth. Using monocolonized mouse models, we showed that selected lactobacilli promoted juvenile growth in a strain-dependent manner that recapitulated the microbiota's effect on growth and the somatotropic axis. These findings show that the host's microbiota supports juvenile growth. Moreover, we discovered that lactobacilli strains buffered the adverse effects of chronic undernutrition on the postnatal growth of germ-free mice.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Schwarzer, Martin -- Makki, Kassem -- Storelli, Gilles -- Machuca-Gayet, Irma -- Srutkova, Dagmar -- Hermanova, Petra -- Martino, Maria Elena -- Balmand, Severine -- Hudcovic, Tomas -- Heddi, Abdelaziz -- Rieusset, Jennifer -- Kozakova, Hana -- Vidal, Hubert -- Leulier, Francois -- New York, N.Y. -- Science. 2016 Feb 19;351(6275):854-7. doi: 10.1126/science.aad8588.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institut de Genomique Fonctionnelle de Lyon, Universite de Lyon, Ecole Normale Superieure de Lyon, Centre National de la Recherche Scientifique, Universite Claude Bernard Lyon 1, Unite Mixte de Recherche 5242, 46 Allee d'Italie, 69364 Lyon Cedex 07, France. Laboratory of Gnotobiology, Institute of Microbiology of the Czech Academy of Sciences, v. v. i., Novy Hradek, Czech Republic. ; Institut de Genomique Fonctionnelle de Lyon, Universite de Lyon, Ecole Normale Superieure de Lyon, Centre National de la Recherche Scientifique, Universite Claude Bernard Lyon 1, Unite Mixte de Recherche 5242, 46 Allee d'Italie, 69364 Lyon Cedex 07, France. Laboratoire CarMeN, Universite Lyon 1, Unite Mixte de Recherche INSERM U-1060 et INRA U-1397, Faculte de Medecine Lyon-Sud, Chemin du Grand Revoyet, 69600 Oullins, France. ; Institut de Genomique Fonctionnelle de Lyon, Universite de Lyon, Ecole Normale Superieure de Lyon, Centre National de la Recherche Scientifique, Universite Claude Bernard Lyon 1, Unite Mixte de Recherche 5242, 46 Allee d'Italie, 69364 Lyon Cedex 07, France. ; Laboratory of Gnotobiology, Institute of Microbiology of the Czech Academy of Sciences, v. v. i., Novy Hradek, Czech Republic. ; UMR203 BF2I, Biologie Fonctionnelle Insectes et Interactions, Universite de Lyon, INRA, INSA-Lyon, F-69621 Villeurbanne, France. ; Laboratoire CarMeN, Universite Lyon 1, Unite Mixte de Recherche INSERM U-1060 et INRA U-1397, Faculte de Medecine Lyon-Sud, Chemin du Grand Revoyet, 69600 Oullins, France.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26912894" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Animals ; Body Weight/*physiology ; Diet ; Femur/growth & development ; Gastrointestinal Microbiome/*physiology ; Lactobacillus plantarum/*physiology ; Malnutrition/*microbiology/*physiopathology ; Mice ; Mice, Inbred BALB C ; Weight Gain/*physiology
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    Thema: Biologie , Chemie und Pharmazie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
    Standort Signatur Erwartet Verfügbarkeit
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  • 87
    Publikationsdatum: 2016-01-23
    Beschreibung: Mono-ubiquitination of Fancd2 is essential for repairing DNA interstrand cross-links (ICLs), but the underlying mechanisms are unclear. The Fan1 nuclease, also required for ICL repair, is recruited to ICLs by ubiquitinated (Ub) Fancd2. This could in principle explain how Ub-Fancd2 promotes ICL repair, but we show that recruitment of Fan1 by Ub-Fancd2 is dispensable for ICL repair. Instead, Fan1 recruitment--and activity--restrains DNA replication fork progression and prevents chromosome abnormalities from occurring when DNA replication forks stall, even in the absence of ICLs. Accordingly, Fan1 nuclease-defective knockin mice are cancer-prone. Moreover, we show that a Fan1 variant in high-risk pancreatic cancers abolishes recruitment by Ub-Fancd2 and causes genetic instability without affecting ICL repair. Therefore, Fan1 recruitment enables processing of stalled forks that is essential for genome stability and health.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4770513/" 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/PMC4770513/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lachaud, Christophe -- Moreno, Alberto -- Marchesi, Francesco -- Toth, Rachel -- Blow, J Julian -- Rouse, John -- WT096598MA/Wellcome Trust/United Kingdom -- Medical Research Council/United Kingdom -- New York, N.Y. -- Science. 2016 Feb 19;351(6275):846-9. doi: 10.1126/science.aad5634. Epub 2016 Jan 21.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Medical Research Council Protein Phosphorylation and Ubiquitylation Unit, College of Life Sciences, Sir James Black Centre, University of Dundee, Dundee DD1 5EH, Scotland, UK. ; Centre for Gene Regulation and Expression, College of Life Sciences, Sir James Black Centre, University of Dundee, Dundee DD1 5EH, Scotland, UK. ; School of Veterinary Medicine, College of Medical, Veterinary and Life Sciences, University of Glasgow, Bearsden Road, Glasgow G61 1QH, UK. ; Medical Research Council Protein Phosphorylation and Ubiquitylation Unit, College of Life Sciences, Sir James Black Centre, University of Dundee, Dundee DD1 5EH, Scotland, UK. j.rouse@dundee.ac.uk.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26797144" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Amino Acid Sequence ; Animals ; *Chromosome Aberrations ; DNA Repair ; *DNA Replication ; Endodeoxyribonucleases/genetics/*metabolism ; Fanconi Anemia Complementation Group D2 Protein/genetics/*metabolism ; Female ; Gene Knock-In Techniques ; Genetic Predisposition to Disease ; Genomic Instability/*genetics ; Liver Neoplasms/genetics/pathology ; Lung Neoplasms/genetics/pathology ; Lymphoma/genetics/pathology ; Male ; Mice ; Mice, Inbred C57BL ; Molecular Sequence Data ; Pancreatic Neoplasms/*genetics ; *Ubiquitination
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    Thema: Biologie , Chemie und Pharmazie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
    Standort Signatur Erwartet Verfügbarkeit
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  • 88
    Publikationsdatum: 2016-03-19
    Beschreibung: Maintaining energy homeostasis is crucial for the survival and health of organisms. The brain regulates feeding by responding to dietary factors and metabolic signals from peripheral organs. It is unclear how the brain interprets these signals. O-GlcNAc transferase (OGT) catalyzes the posttranslational modification of proteins by O-GlcNAc and is regulated by nutrient access. Here, we show that acute deletion of OGT from alphaCaMKII-positive neurons in adult mice caused obesity from overeating. The hyperphagia derived from the paraventricular nucleus (PVN) of the hypothalamus, where loss of OGT was associated with impaired satiety. These results identify O-GlcNAcylation in alphaCaMKII neurons of the PVN as an important molecular mechanism that regulates feeding behavior.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4817221/" 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/PMC4817221/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lagerlof, Olof -- Slocomb, Julia E -- Hong, Ingie -- Aponte, Yeka -- Blackshaw, Seth -- Hart, Gerald W -- Huganir, Richard L -- N01-HV-00240/HV/NHLBI NIH HHS/ -- P01 HL107153/HL/NHLBI NIH HHS/ -- P01HL107153/HL/NHLBI NIH HHS/ -- R01 DK061671/DK/NIDDK NIH HHS/ -- R01 NS036715/NS/NINDS NIH HHS/ -- R01DK6167/DK/NIDDK NIH HHS/ -- R01NS036715/NS/NINDS NIH HHS/ -- Intramural NIH HHS/ -- New York, N.Y. -- Science. 2016 Mar 18;351(6279):1293-6. doi: 10.1126/science.aad5494.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Solomon H. Snyder Department of Neuroscience, Kavli Neuroscience Discovery Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. Department of Biological Chemistry, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. ; National Institute on Drug Abuse + National Institutes of Health/Johns Hopkins University Graduate Partnership Program, Baltimore, MD 21224, USA. ; Solomon H. Snyder Department of Neuroscience, Kavli Neuroscience Discovery Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. ; Solomon H. Snyder Department of Neuroscience, Kavli Neuroscience Discovery Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. Intramural Research Program, Neuronal Circuits and Behavior Unit, National Institute on Drug Abuse, Baltimore, MD 21224, USA. ; Department of Biological Chemistry, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. ; Solomon H. Snyder Department of Neuroscience, Kavli Neuroscience Discovery Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. rhuganir@jhmi.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26989246" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Acetylglucosamine/metabolism ; Animals ; Calcium-Calmodulin-Dependent Protein Kinase Type 2/metabolism ; Energy Metabolism/genetics/*physiology ; Feeding Behavior/*physiology ; Gene Deletion ; Homeostasis/genetics ; Hyperphagia/*genetics ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; N-Acetylglucosaminyltransferases/genetics/*physiology ; Neurons/enzymology ; Obesity/genetics ; Paraventricular Hypothalamic Nucleus/cytology/enzymology/*physiology ; Protein Processing, Post-Translational ; Satiety Response/physiology
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    Thema: Biologie , Chemie und Pharmazie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
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  • 89
    facet.materialart.
    Unbekannt
    American Association for the Advancement of Science (AAAS)
    Publikationsdatum: 2016-02-27
    Beschreibung: Oocytes differentiate in diverse species by receiving organelles and cytoplasm from sister germ cells while joined in germline cysts or syncytia. Mouse primordial germ cells form germline cysts, but the role of cysts in oogenesis is unknown. We find that mouse germ cells receive organelles from neighboring cyst cells and build a Balbiani body to become oocytes, whereas nurselike germ cells die. Organelle movement, Balbiani body formation, and oocyte fate determination are selectively blocked by low levels of microtubule-dependent transport inhibitors. Membrane breakdown within the cyst and an apoptosis-like process are associated with organelle transfer into the oocyte, events reminiscent of nurse cell dumping in Drosophila We propose that cytoplasmic and organelle transport plays an evolutionarily conserved and functionally important role in mammalian oocyte differentiation.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lei, Lei -- Spradling, Allan C -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2016 Apr 1;352(6281):95-9. doi: 10.1126/science.aad2156. Epub 2016 Feb 25.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute Research Laboratories, Department of Embryology, Carnegie Institution for Science, 3520 San Martin Drive, Baltimore, MD 21218, USA. spradling@ciwemb.edu leile@med.umich.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26917595" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Animals ; Apoptosis ; Biological Evolution ; Cytoplasm/physiology/ultrastructure ; Female ; Giant Cells/*cytology ; Mice ; Microtubules/drug effects/physiology ; Oocytes/*cytology ; *Oogenesis ; Organelles/*physiology
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    Thema: Biologie , Chemie und Pharmazie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
    Standort Signatur Erwartet Verfügbarkeit
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  • 90
    Publikationsdatum: 2016-01-30
    Beschreibung: Cystic fibrosis (CF) is caused by mutations in the gene that encodes the cystic fibrosis transmembrane conductance regulator (CFTR) anion channel. In humans and pigs, the loss of CFTR impairs respiratory host defenses, causing airway infection. But CF mice are spared. We found that in all three species, CFTR secreted bicarbonate into airway surface liquid. In humans and pigs lacking CFTR, unchecked H(+) secretion by the nongastric H(+)/K(+) adenosine triphosphatase (ATP12A) acidified airway surface liquid, which impaired airway host defenses. In contrast, mouse airways expressed little ATP12A and secreted minimal H(+); consequently, airway surface liquid in CF and non-CF mice had similar pH. Inhibiting ATP12A reversed host defense abnormalities in human and pig airways. Conversely, expressing ATP12A in CF mouse airways acidified airway surface liquid, impaired defenses, and increased airway bacteria. These findings help explain why CF mice are protected from infection and nominate ATP12A as a potential therapeutic target for CF.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Shah, Viral S -- Meyerholz, David K -- Tang, Xiao Xiao -- Reznikov, Leah -- Abou Alaiwa, Mahmoud -- Ernst, Sarah E -- Karp, Philip H -- Wohlford-Lenane, Christine L -- Heilmann, Kristopher P -- Leidinger, Mariah R -- Allen, Patrick D -- Zabner, Joseph -- McCray, Paul B Jr -- Ostedgaard, Lynda S -- Stoltz, David A -- Randak, Christoph O -- Welsh, Michael J -- 5T32GM007337/GM/NIGMS NIH HHS/ -- DK054759/DK/NIDDK NIH HHS/ -- F30 HL123239/HL/NHLBI NIH HHS/ -- F30HL123239/HL/NHLBI NIH HHS/ -- HL091842/HL/NHLBI NIH HHS/ -- HL117744/HL/NHLBI NIH HHS/ -- HL51670/HL/NHLBI NIH HHS/ -- K08HL097071/HL/NHLBI NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2016 Jan 29;351(6272):503-7. doi: 10.1126/science.aad5589.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Medicine, University of Iowa, Iowa City, IA 52242, USA. Department of Molecular Physiology and Biophysics, Pappajohn Biomedical Institute, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA. ; Department of Pathology, University of Iowa, Iowa City, IA 52242, USA. ; Department of Medicine, University of Iowa, Iowa City, IA 52242, USA. Howard Hughes Medical Institute, University of Iowa, Iowa City, IA 52242, USA. ; Department of Medicine, University of Iowa, Iowa City, IA 52242, USA. ; Department of Pediatrics University of Iowa, Iowa City, IA 52242, USA. ; Department of Microbiology, University of Iowa, Iowa City, IA 52242, USA. ; Department of Pediatrics University of Iowa, Iowa City, IA 52242, USA. Department of Microbiology, University of Iowa, Iowa City, IA 52242, USA. ; Department of Medicine, University of Iowa, Iowa City, IA 52242, USA. Department of Molecular Physiology and Biophysics, Pappajohn Biomedical Institute, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA. Department of Biomedical Engineering, College of Engineering, University of Iowa, Iowa City, IA 52242, USA. ; Department of Medicine, University of Iowa, Iowa City, IA 52242, USA. Department of Molecular Physiology and Biophysics, Pappajohn Biomedical Institute, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA. Howard Hughes Medical Institute, University of Iowa, Iowa City, IA 52242, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26823428" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Acids/metabolism ; Animals ; Bicarbonates/metabolism ; Cystic Fibrosis/*metabolism/*microbiology ; H(+)-K(+)-Exchanging ATPase/genetics/*metabolism ; Humans ; Hydrogen-Ion Concentration ; Lung/*metabolism/*microbiology ; Mice ; Mice, Inbred CFTR/genetics/metabolism ; Mice, Transgenic ; Swine
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    Thema: Biologie , Chemie und Pharmazie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
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  • 91
    Publikationsdatum: 2016-01-02
    Beschreibung: Several recent studies link parental environments to phenotypes in subsequent generations. In this work, we investigate the mechanism by which paternal diet affects offspring metabolism. Protein restriction in mice affects small RNA (sRNA) levels in mature sperm, with decreased let-7 levels and increased amounts of 5' fragments of glycine transfer RNAs (tRNAs). In testicular sperm, tRNA fragments are scarce but increase in abundance as sperm mature in the epididymis. Epididymosomes (vesicles that fuse with sperm during epididymal transit) carry RNA payloads matching those of mature sperm and can deliver RNAs to immature sperm in vitro. Functionally, tRNA-glycine-GCC fragments repress genes associated with the endogenous retroelement MERVL, in both embryonic stem cells and embryos. Our results shed light on sRNA biogenesis and its dietary regulation during posttesticular sperm maturation, and they also link tRNA fragments to regulation of endogenous retroelements active in the preimplantation embryo.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sharma, Upasna -- Conine, Colin C -- Shea, Jeremy M -- Boskovic, Ana -- Derr, Alan G -- Bing, Xin Y -- Belleannee, Clemence -- Kucukural, Alper -- Serra, Ryan W -- Sun, Fengyun -- Song, Lina -- Carone, Benjamin R -- Ricci, Emiliano P -- Li, Xin Z -- Fauquier, Lucas -- Moore, Melissa J -- Sullivan, Robert -- Mello, Craig C -- Garber, Manuel -- Rando, Oliver J -- DP1ES025458/DP/NCCDPHP CDC HHS/ -- R01HD080224/HD/NICHD NIH HHS/ -- UL1 TR000161/TR/NCATS NIH HHS/ -- UL1 TR001453/TR/NCATS NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2016 Jan 22;351(6271):391-6. doi: 10.1126/science.aad6780. Epub 2015 Dec 31.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA 01605, USA. ; Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA. Program in Bioinformatics and Integrative Biology, University of Massachusetts Medical School, Worcester, MA 01605, USA. ; Department of Obstetrics, Gynecology and Reproduction, Universite Laval, Centre Hospitalier Universitaire de Quebec Research Center, Quebec City, Quebec G1V 4G2, Canada. ; RNAi Therapeutics Institute, University of Massachusetts Medical School, Worcester, MA 01605, USA. ; Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA 01605, USA. RNAi Therapeutics Institute, University of Massachusetts Medical School, Worcester, MA 01605, USA. ; Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA 01605, USA. RNAi Therapeutics Institute, University of Massachusetts Medical School, Worcester, MA 01605, USA. Howard Hughes Medical Institute, University of Massachusetts Medical School, Worcester, MA 01605, USA. ; Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA. RNAi Therapeutics Institute, University of Massachusetts Medical School, Worcester, MA 01605, USA. Howard Hughes Medical Institute, University of Massachusetts Medical School, Worcester, MA 01605, USA. ; Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA 01605, USA. oliver.rando@umassmed.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26721685" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Animals ; Blastocyst/metabolism ; Diet, Protein-Restricted ; Epididymis/metabolism ; *Fertilization ; *Gene Expression Regulation ; Male ; Mice ; MicroRNAs/metabolism ; RNA, Transfer, Gly/*metabolism/*physiology ; Retroelements/genetics ; *Sperm Maturation ; Spermatozoa/*metabolism ; Testis/metabolism
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    Thema: Biologie , Chemie und Pharmazie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
    Standort Signatur Erwartet Verfügbarkeit
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  • 92
    facet.materialart.
    Unbekannt
    American Association for the Advancement of Science (AAAS)
    Publikationsdatum: 2016-01-02
    Beschreibung: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Leslie, Mitch -- New York, N.Y. -- Science. 2016 Jan 1;351(6268):13. doi: 10.1126/science.351.6268.13.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26721982" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Animals ; DNA/chemistry/genetics/metabolism ; *Epigenesis, Genetic ; Male ; Metabolism/*genetics ; Mice ; RNA, Transfer/genetics/*metabolism ; *Spermatozoa
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    Thema: Biologie , Chemie und Pharmazie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
    Standort Signatur Erwartet Verfügbarkeit
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  • 93
    facet.materialart.
    Unbekannt
    American Association for the Advancement of Science (AAAS)
    Publikationsdatum: 2016-04-02
    Beschreibung: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Leslie, Mitch -- New York, N.Y. -- Science. 2016 Apr 1;352(6281):21-3. doi: 10.1126/science.352.6281.21.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27034353" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Animals ; B-Lymphocytes/*immunology ; Diabetes Mellitus, Type 1/immunology ; Infection/*immunology ; Inflammation/*immunology ; Lymph Nodes/cytology/*immunology ; Mice ; Pancreas/immunology ; T-Lymphocytes/*immunology
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    Thema: Biologie , Chemie und Pharmazie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
    Standort Signatur Erwartet Verfügbarkeit
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  • 94
    Publikationsdatum: 2016-01-02
    Beschreibung: CRISPR/Cas9-mediated genome editing holds clinical potential for treating genetic diseases, such as Duchenne muscular dystrophy (DMD), which is caused by mutations in the dystrophin gene. To correct DMD by skipping mutant dystrophin exons in postnatal muscle tissue in vivo, we used adeno-associated virus-9 (AAV9) to deliver gene-editing components to postnatal mdx mice, a model of DMD. Different modes of AAV9 delivery were systematically tested, including intraperitoneal at postnatal day 1 (P1), intramuscular at P12, and retro-orbital at P18. Each of these methods restored dystrophin protein expression in cardiac and skeletal muscle to varying degrees, and expression increased from 3 to 12 weeks after injection. Postnatal gene editing also enhanced skeletal muscle function, as measured by grip strength tests 4 weeks after injection. This method provides a potential means of correcting mutations responsible for DMD and other monogenic disorders after birth.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4760628/" 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/PMC4760628/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Long, Chengzu -- Amoasii, Leonela -- Mireault, Alex A -- McAnally, John R -- Li, Hui -- Sanchez-Ortiz, Efrain -- Bhattacharyya, Samadrita -- Shelton, John M -- Bassel-Duby, Rhonda -- Olson, Eric N -- DK-099653/DK/NIDDK NIH HHS/ -- HL-077439/HL/NHLBI NIH HHS/ -- HL-093039/HL/NHLBI NIH HHS/ -- HL-111665/HL/NHLBI NIH HHS/ -- R01 DK099653/DK/NIDDK NIH HHS/ -- R01 HL077439/HL/NHLBI NIH HHS/ -- R01 HL093039/HL/NHLBI NIH HHS/ -- R01 HL111665/HL/NHLBI NIH HHS/ -- U01 HL100401/HL/NHLBI NIH HHS/ -- U01-HL-100401/HL/NHLBI NIH HHS/ -- U54 HD 087351/HD/NICHD NIH HHS/ -- New York, N.Y. -- Science. 2016 Jan 22;351(6271):400-3. doi: 10.1126/science.aad5725. Epub 2015 Dec 31.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA. Hamon Center for Regenerative Science and Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA. Sen. Paul D. Wellstone Muscular Dystrophy Cooperative Research Center, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA. ; Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA. ; Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA. Hamon Center for Regenerative Science and Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA. Sen. Paul D. Wellstone Muscular Dystrophy Cooperative Research Center, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA. eric.olson@utsouthwestern.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26721683" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Animals ; *CRISPR-Cas Systems ; Dependovirus ; Disease Models, Animal ; Dystrophin/*genetics ; Exons/genetics ; Female ; Forelimb/physiopathology ; Genetic Therapy/*methods ; Genome/genetics ; Hand Strength ; Male ; Mice ; Mice, Inbred mdx ; Muscle, Skeletal/metabolism ; Muscular Dystrophy, Duchenne/genetics/*therapy ; Myocardium/metabolism
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  • 95
    Publikationsdatum: 2016-01-23
    Beschreibung: Differentiated macrophages can self-renew in tissues and expand long term in culture, but the gene regulatory mechanisms that accomplish self-renewal in the differentiated state have remained unknown. Here we show that in mice, the transcription factors MafB and c-Maf repress a macrophage-specific enhancer repertoire associated with a gene network that controls self-renewal. Single-cell analysis revealed that, in vivo, proliferating resident macrophages can access this network by transient down-regulation of Maf transcription factors. The network also controls embryonic stem cell self-renewal but is associated with distinct embryonic stem cell-specific enhancers. This indicates that distinct lineage-specific enhancer platforms regulate a shared network of genes that control self-renewal potential in both stem and mature cells.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Soucie, Erinn L -- Weng, Ziming -- Geirsdottir, Laufey -- Molawi, Kaaweh -- Maurizio, Julien -- Fenouil, Romain -- Mossadegh-Keller, Noushine -- Gimenez, Gregory -- VanHille, Laurent -- Beniazza, Meryam -- Favret, Jeremy -- Berruyer, Carole -- Perrin, Pierre -- Hacohen, Nir -- Andrau, J-C -- Ferrier, Pierre -- Dubreuil, Patrice -- Sidow, Arend -- Sieweke, Michael H -- P01AG036695/AG/NIA NIH HHS/ -- New York, N.Y. -- Science. 2016 Feb 12;351(6274):aad5510. doi: 10.1126/science.aad5510. Epub 2016 Jan 21.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Centre d'Immunologie de Marseille-Luminy, Universite Aix-Marseille, UM2, Campus de Luminy, Case 906, 13288 Marseille Cedex 09, France. INSERM, U1104, Marseille, France. CNRS, UMR 7280, Marseille, France. Centre de Recherche en Cancerologie de Marseille, INSERM (U1068), CNRS (U7258), Universite Aix-Marseille (UM105), Marseille, France. sieweke@ciml.univ-mrs.fr erinn.soucie@inserm.fr arend@stanford.edu. ; Department of Pathology, Stanford University, Stanford, CA 94305-5324, USA. ; Centre d'Immunologie de Marseille-Luminy, Universite Aix-Marseille, UM2, Campus de Luminy, Case 906, 13288 Marseille Cedex 09, France. INSERM, U1104, Marseille, France. CNRS, UMR 7280, Marseille, France. ; Centre d'Immunologie de Marseille-Luminy, Universite Aix-Marseille, UM2, Campus de Luminy, Case 906, 13288 Marseille Cedex 09, France. INSERM, U1104, Marseille, France. CNRS, UMR 7280, Marseille, France. Max-Delbruck-Centrum fur Molekulare Medizin in der Helmholtz-Gemeinschaft, 10 Robert-Rossle-Strasse, 13125 Berlin, Germany. ; Broad Institute of Harvard University and MIT, Cambridge, MA 02142, USA. ; Centre d'Immunologie de Marseille-Luminy, Universite Aix-Marseille, UM2, Campus de Luminy, Case 906, 13288 Marseille Cedex 09, France. INSERM, U1104, Marseille, France. CNRS, UMR 7280, Marseille, France. Institut de Genetique Moleculaire de Montpellier, CNRS UMR 5535, 1919 Route de Mende, 34293 Montpellier, France. ; Centre de Recherche en Cancerologie de Marseille, INSERM (U1068), CNRS (U7258), Universite Aix-Marseille (UM105), Marseille, France. ; Department of Pathology, Stanford University, Stanford, CA 94305-5324, USA. Department of Genetics, Stanford University, Stanford, CA 94305, USA. sieweke@ciml.univ-mrs.fr erinn.soucie@inserm.fr arend@stanford.edu. ; Centre d'Immunologie de Marseille-Luminy, Universite Aix-Marseille, UM2, Campus de Luminy, Case 906, 13288 Marseille Cedex 09, France. INSERM, U1104, Marseille, France. CNRS, UMR 7280, Marseille, France. Max-Delbruck-Centrum fur Molekulare Medizin in der Helmholtz-Gemeinschaft, 10 Robert-Rossle-Strasse, 13125 Berlin, Germany. sieweke@ciml.univ-mrs.fr erinn.soucie@inserm.fr arend@stanford.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26797145" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Animals ; Cell Differentiation/*genetics ; Cell Lineage/*genetics ; Cell Proliferation ; Cells, Cultured ; Down-Regulation ; Embryonic Stem Cells/*cytology ; Enhancer Elements, Genetic/*physiology ; *Gene Expression Regulation ; Gene Regulatory Networks ; Macrophages/*cytology ; MafB Transcription Factor/metabolism ; Mice ; Proto-Oncogene Proteins c-maf/metabolism ; Single-Cell Analysis ; Transcriptional Activation
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    Thema: Biologie , Chemie und Pharmazie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
    Standort Signatur Erwartet Verfügbarkeit
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  • 96
    Publikationsdatum: 2016-04-23
    Beschreibung: Tissue-resident memory T (Trm) cells permanently localize to portals of pathogen entry, where they provide immediate protection against reinfection. To enforce tissue retention, Trm cells up-regulate CD69 and down-regulate molecules associated with tissue egress; however, a Trm-specific transcriptional regulator has not been identified. Here, we show that the transcription factor Hobit is specifically up-regulated in Trm cells and, together with related Blimp1, mediates the development of Trm cells in skin, gut, liver, and kidney in mice. The Hobit-Blimp1 transcriptional module is also required for other populations of tissue-resident lymphocytes, including natural killer T (NKT) cells and liver-resident NK cells, all of which share a common transcriptional program. Our results identify Hobit and Blimp1 as central regulators of this universal program that instructs tissue retention in diverse tissue-resident lymphocyte populations.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Mackay, Laura K -- Minnich, Martina -- Kragten, Natasja A M -- Liao, Yang -- Nota, Benjamin -- Seillet, Cyril -- Zaid, Ali -- Man, Kevin -- Preston, Simon -- Freestone, David -- Braun, Asolina -- Wynne-Jones, Erica -- Behr, Felix M -- Stark, Regina -- Pellicci, Daniel G -- Godfrey, Dale I -- Belz, Gabrielle T -- Pellegrini, Marc -- Gebhardt, Thomas -- Busslinger, Meinrad -- Shi, Wei -- Carbone, Francis R -- van Lier, Rene A W -- Kallies, Axel -- van Gisbergen, Klaas P J M -- New York, N.Y. -- Science. 2016 Apr 22;352(6284):459-63. doi: 10.1126/science.aad2035.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Microbiology and Immunology, The University of Melbourne, The Peter Doherty Institute for Infection and Immunity, Melbourne, Australia. Australian Research Council (ARC) Centre of Excellence in Advanced Molecular Imaging, University of Melbourne, Melbourne, Australia. lkmackay@unimelb.edu.au kallies@wehi.edu.au k.vangisbergen@sanquin.nl. ; Research Institute of Molecular Pathology (IMP), Vienna Biocenter (VBC), Vienna, Austria. ; Department of Hematopoiesis, Sanquin Research and Landsteiner Laboratory, Academic Medical Center (AMC), University of Amsterdam, Amsterdam, Netherlands. ; The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia. Department of Medical Biology, The University of Melbourne, Melbourne, Australia. ; Department of Blood Cell Research, Sanquin Research and Landsteiner Laboratory, AMC, University of Amsterdam, Amsterdam, Netherlands. ; Department of Microbiology and Immunology, The University of Melbourne, The Peter Doherty Institute for Infection and Immunity, Melbourne, Australia. ; Department of Hematopoiesis, Sanquin Research and Landsteiner Laboratory, Academic Medical Center (AMC), University of Amsterdam, Amsterdam, Netherlands. The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia. Department of Medical Biology, The University of Melbourne, Melbourne, Australia. Department of Experimental Immunology, AMC, Amsterdam, Netherlands. ; Department of Microbiology and Immunology, The University of Melbourne, The Peter Doherty Institute for Infection and Immunity, Melbourne, Australia. Australian Research Council (ARC) Centre of Excellence in Advanced Molecular Imaging, University of Melbourne, Melbourne, Australia. ; The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia. Department of Computing and Information Systems, The University of Melbourne, Melbourne, Australia. ; The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia. Department of Medical Biology, The University of Melbourne, Melbourne, Australia. lkmackay@unimelb.edu.au kallies@wehi.edu.au k.vangisbergen@sanquin.nl. ; Department of Hematopoiesis, Sanquin Research and Landsteiner Laboratory, Academic Medical Center (AMC), University of Amsterdam, Amsterdam, Netherlands. The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia. Department of Medical Biology, The University of Melbourne, Melbourne, Australia. Department of Experimental Immunology, AMC, Amsterdam, Netherlands. lkmackay@unimelb.edu.au kallies@wehi.edu.au k.vangisbergen@sanquin.nl.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27102484" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Animals ; Gastrointestinal Tract/immunology ; *Gene Expression Regulation ; Genes, Regulator/genetics/*physiology ; Immunologic Memory/*genetics ; Kidney/immunology ; Killer Cells, Natural/*immunology ; Liver/immunology ; Lymphocyte Activation ; Mice ; Mice, Knockout ; Natural Killer T-Cells/*immunology ; Skin/immunology ; Transcription Factors/genetics/*physiology ; Transcription, Genetic ; Up-Regulation
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    Digitale ISSN: 1095-9203
    Thema: Biologie , Chemie und Pharmazie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
    Standort Signatur Erwartet Verfügbarkeit
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  • 97
    Publikationsdatum: 2016-02-26
    Beschreibung: T cell-mediated destruction of insulin-producing beta cells in the pancreas causes type 1 diabetes (T1D). CD4 T cell responses play a central role in beta cell destruction, but the identity of the epitopes recognized by pathogenic CD4 T cells remains unknown. We found that diabetes-inducing CD4 T cell clones isolated from nonobese diabetic mice recognize epitopes formed by covalent cross-linking of proinsulin peptides to other peptides present in beta cell secretory granules. These hybrid insulin peptides (HIPs) are antigenic for CD4 T cells and can be detected by mass spectrometry in beta cells. CD4 T cells from the residual pancreatic islets of two organ donors who had T1D also recognize HIPs. Autoreactive T cells targeting hybrid peptides may explain how immune tolerance is broken in T1D.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Delong, Thomas -- Wiles, Timothy A -- Baker, Rocky L -- Bradley, Brenda -- Barbour, Gene -- Reisdorph, Richard -- Armstrong, Michael -- Powell, Roger L -- Reisdorph, Nichole -- Kumar, Nitesh -- Elso, Colleen M -- DeNicola, Megan -- Bottino, Rita -- Powers, Alvin C -- Harlan, David M -- Kent, Sally C -- Mannering, Stuart I -- Haskins, Kathryn -- 1K01DK094941/DK/NIDDK NIH HHS/ -- 1R01DK081166/DK/NIDDK NIH HHS/ -- 5U01DK89572/DK/NIDDK NIH HHS/ -- DK104211/DK/NIDDK NIH HHS/ -- New York, N.Y. -- Science. 2016 Feb 12;351(6274):711-4. doi: 10.1126/science.aad2791.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Immunology and Microbiology, University of Colorado School of Medicine, Denver, Anschutz Medical Campus, Aurora, CO 80045, USA. thomas.delong@ucdenver.edu katie.haskins@ucdenver.edu. ; Department of Immunology and Microbiology, University of Colorado School of Medicine, Denver, Anschutz Medical Campus, Aurora, CO 80045, USA. ; Pharmaceutical Sciences, University of Colorado School of Medicine, Aurora, CO 80045, USA. ; Immunology and Diabetes Unit, St. Vincent's Institute of Medical Research, 9 Princes Street, Fitzroy, Victoria 3065, Australia. ; Department of Medicine, Diabetes Division, Diabetes Center of Excellence, University of Massachusetts Medical School, Worcester, MA, USA. ; Institute of Cellular Therapeutics, Allegheny-Singer Research Institute, Allegheny Health Network, Pittsburgh, PA, USA. ; Division of Diabetes, Endocrinology, and Metabolism, Department of Medicine, and Department of Molecular Physiology and Biophysics, Vanderbilt University Medical Center, Nashville, TN, USA. VA Tennessee Valley Healthcare System, Nashville, TN, USA. ; Immunology and Diabetes Unit, St. Vincent's Institute of Medical Research, 9 Princes Street, Fitzroy, Victoria 3065, Australia. University of Melbourne, Department of Medicine, St. Vincent's Hospital, Fitzroy, Victoria 3065, Australia.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26912858" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Amino Acid Sequence ; Animals ; C-Peptide/chemistry/*immunology ; CD4-Positive T-Lymphocytes/*immunology ; Clone Cells ; Diabetes Mellitus, Experimental/*immunology/pathology ; Diabetes Mellitus, Type 1/*immunology/pathology ; Epitopes/*immunology ; Immune Tolerance ; Insulin-Secreting Cells/*immunology/pathology ; Mice ; Mice, Inbred NOD ; Molecular Sequence Data ; Peptides/chemistry/immunology
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    Thema: Biologie , Chemie und Pharmazie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
    Standort Signatur Erwartet Verfügbarkeit
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  • 98
    Publikationsdatum: 2016-01-02
    Beschreibung: Frame-disrupting mutations in the DMD gene, encoding dystrophin, compromise myofiber integrity and drive muscle deterioration in Duchenne muscular dystrophy (DMD). Removing one or more exons from the mutated transcript can produce an in-frame mRNA and a truncated, but still functional, protein. In this study, we developed and tested a direct gene-editing approach to induce exon deletion and recover dystrophin expression in the mdx mouse model of DMD. Delivery by adeno-associated virus (AAV) of clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 endonucleases coupled with paired guide RNAs flanking the mutated Dmd exon23 resulted in excision of intervening DNA and restored the Dmd reading frame in myofibers, cardiomyocytes, and muscle stem cells after local or systemic delivery. AAV-Dmd CRISPR treatment partially recovered muscle functional deficiencies and generated a pool of endogenously corrected myogenic precursors in mdx mouse muscle.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Tabebordbar, Mohammadsharif -- Zhu, Kexian -- Cheng, Jason K W -- Chew, Wei Leong -- Widrick, Jeffrey J -- Yan, Winston X -- Maesner, Claire -- Wu, Elizabeth Y -- Xiao, Ru -- Ran, F Ann -- Cong, Le -- Zhang, Feng -- Vandenberghe, Luk H -- Church, George M -- Wagers, Amy J -- 1DP2OD004345/OD/NIH HHS/ -- 5DP1-MH100706/DP/NCCDPHP CDC HHS/ -- 5PN2EY018244/EY/NEI NIH HHS/ -- 5R01DK097768-03/DK/NIDDK NIH HHS/ -- 5U01HL100402/HL/NHLBI NIH HHS/ -- P50 HG005550/HG/NHGRI NIH HHS/ -- T2GM007753/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2016 Jan 22;351(6271):407-11. doi: 10.1126/science.aad5177. Epub 2015 Dec 31.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Stem Cell and Regenerative Biology, Harvard University, and Harvard Stem Cell Institute, Cambridge, MA 02138, USA. Biological and Biomedical Sciences Program, Harvard Medical School, Boston, MA 02115, USA. ; Department of Stem Cell and Regenerative Biology, Harvard University, and Harvard Stem Cell Institute, Cambridge, MA 02138, USA. Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA. ; Department of Stem Cell and Regenerative Biology, Harvard University, and Harvard Stem Cell Institute, Cambridge, MA 02138, USA. ; Biological and Biomedical Sciences Program, Harvard Medical School, Boston, MA 02115, USA. Department of Genetics, Harvard Medical School, Boston, MA 02115, USA. ; Division of Genetics and Program in Genomics, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA. ; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA. McGovern Institute for Brain Research, Department of Brain and Cognitive Science, and Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. ; Grousbeck Gene Therapy Center, Schepens Eye Research Institute, and Massachusetts Eye and Ear Infirmary, 20 Staniford Street, Boston, MA 02114, USA. ; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA. ; Department of Stem Cell and Regenerative Biology, Harvard University, and Harvard Stem Cell Institute, Cambridge, MA 02138, USA. amy_wagers@harvard.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26721686" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Animals ; CRISPR-Cas Systems ; Clustered Regularly Interspaced Short Palindromic Repeats ; Dependovirus ; Disease Models, Animal ; Exons ; Frameshift Mutation ; Genetic Therapy/*methods ; Mice ; Mice, Inbred mdx ; Muscle, Skeletal/metabolism ; Muscular Dystrophy, Duchenne/genetics/*therapy ; Myocardium/metabolism ; RNA, Messenger/genetics ; Satellite Cells, Skeletal Muscle/*metabolism ; Sequence Deletion ; Transduction, Genetic/*methods
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    Thema: Biologie , Chemie und Pharmazie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
    Standort Signatur Erwartet Verfügbarkeit
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  • 99
    Publikationsdatum: 2016-01-28
    Beschreibung: Genes encoding human beta-type globin undergo a developmental switch from embryonic to fetal to adult-type expression. Mutations in the adult form cause inherited hemoglobinopathies or globin disorders, including sickle cell disease and thalassemia. Some experimental results have suggested that these diseases could be treated by induction of fetal-type hemoglobin (HbF). However, the mechanisms that repress HbF in adults remain unclear. We found that the LRF/ZBTB7A transcription factor occupies fetal gamma-globin genes and maintains the nucleosome density necessary for gamma-globin gene silencing in adults, and that LRF confers its repressive activity through a NuRD repressor complex independent of the fetal globin repressor BCL11A. Our study may provide additional opportunities for therapeutic targeting in the treatment of hemoglobinopathies.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4778394/" 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/PMC4778394/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Masuda, Takeshi -- Wang, Xin -- Maeda, Manami -- Canver, Matthew C -- Sher, Falak -- Funnell, Alister P W -- Fisher, Chris -- Suciu, Maria -- Martyn, Gabriella E -- Norton, Laura J -- Zhu, Catherine -- Kurita, Ryo -- Nakamura, Yukio -- Xu, Jian -- Higgs, Douglas R -- Crossley, Merlin -- Bauer, Daniel E -- Orkin, Stuart H -- Kharchenko, Peter V -- Maeda, Takahiro -- R01 AI084905/AI/NIAID NIH HHS/ -- R01 HL032259/HL/NHLBI NIH HHS/ -- R56 DK105001/DK/NIDDK NIH HHS/ -- New York, N.Y. -- Science. 2016 Jan 15;351(6270):285-9. doi: 10.1126/science.aad3312.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Hematology, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA. ; Department of Biomedical Informatics, Harvard Medical School, Boston, MA 02115, USA. ; Division of Hematology/Oncology, Boston Children's Hospital, Department of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Stem Cell Institute, Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA. ; School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, NSW 2052, Australia. ; Medical Research Council, Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, Oxford University, Oxford, UK. ; Cell Engineering Division, RIKEN BioResource Center, Tsukuba, Ibaraki, Japan. ; Cell Engineering Division, RIKEN BioResource Center, Tsukuba, Ibaraki, Japan. Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Ibaraki, Japan. ; Division of Hematology/Oncology, Boston Children's Hospital, Department of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Stem Cell Institute, Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA. Children's Research Institute, Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA. ; Division of Hematology/Oncology, Boston Children's Hospital, Department of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Stem Cell Institute, Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA. Howard Hughes Medical Institute, Boston, MA 02115, USA. ; Department of Biomedical Informatics, Harvard Medical School, Boston, MA 02115, USA. peter.kharchenko@post.harvard.edu tmaeda@partners.org. ; Division of Hematology, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA. peter.kharchenko@post.harvard.edu tmaeda@partners.org.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26816381" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Anemia, Sickle Cell/genetics ; Animals ; Carrier Proteins/genetics/*metabolism ; Cell Line ; Chromatin/metabolism ; DNA-Binding Proteins/genetics/*metabolism ; Erythroblasts/cytology ; Erythropoiesis/genetics ; Fetal Hemoglobin/*genetics ; *Gene Silencing ; Humans ; Mice ; Mice, Knockout ; Nuclear Proteins/genetics/*metabolism ; Repressor Proteins/genetics/*metabolism ; Sequence Deletion ; Thalassemia/genetics ; Transcription Factors/genetics/*metabolism ; gamma-Globins/*genetics
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    Thema: Biologie , Chemie und Pharmazie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
    Standort Signatur Erwartet Verfügbarkeit
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  • 100
    Publikationsdatum: 2016-04-30
    Beschreibung: Wakefulness is driven by the widespread release of neuromodulators by the ascending arousal system. Yet, it is unclear how these substances orchestrate state-dependent, global changes in neuronal activity. Here, we show that neuromodulators induce increases in the extracellular K(+) concentration ([K(+)]e) in cortical slices electrically silenced by tetrodotoxin. In vivo, arousal was linked to AMPA receptor-independent elevations of [K(+)]e concomitant with decreases in [Ca(2+)]e, [Mg(2+)]e, [H(+)]e, and the extracellular volume. Opposite, natural sleep and anesthesia reduced [K(+)]e while increasing [Ca(2+)]e, [Mg(2+)]e, and [H(+)]e as well as the extracellular volume. Local cortical activity of sleeping mice could be readily converted to the stereotypical electroencephalography pattern of wakefulness by simply imposing a change in the extracellular ion composition. Thus, extracellular ions control the state-dependent patterns of neural activity.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ding, Fengfei -- O'Donnell, John -- Xu, Qiwu -- Kang, Ning -- Goldman, Nanna -- Nedergaard, Maiken -- NS078167/NS/NINDS NIH HHS/ -- NS078304/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 2016 Apr 29;352(6285):550-5. doi: 10.1126/science.aad4821.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for Translational Neuromedicine, University of Rochester Medical Center, Rochester, NY 14642, USA. Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. ; Center for Translational Neuromedicine, University of Rochester Medical Center, Rochester, NY 14642, USA. ; Center for Translational Neuromedicine, University of Rochester Medical Center, Rochester, NY 14642, USA. Center for Basic and Translational Neuroscience, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen 2200, Denmark. nedergaard@urmc.rochester.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27126038" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Animals ; Calcium/analysis/metabolism ; Cations/analysis/*metabolism ; Cerebral Cortex/chemistry/drug effects/*physiology ; Electroencephalography ; Magnesium/analysis/metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Neurons/drug effects/metabolism/physiology ; Neurotransmitter Agents/metabolism/pharmacology ; Potassium/*metabolism ; Receptors, AMPA/metabolism ; Sleep/drug effects/*physiology ; Sodium Channel Blockers/pharmacology ; Tetrodotoxin/pharmacology ; Wakefulness/drug effects/*physiology
    Print ISSN: 0036-8075
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    Thema: Biologie , Chemie und Pharmazie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
    Standort Signatur Erwartet Verfügbarkeit
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