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  • 1
    Online-Ressource
    Online-Ressource
    American Association for the Advancement of Science (AAAS) ; 2016
    In:  Science Vol. 351, No. 6268 ( 2016-01), p. 48-52
    In: Science, American Association for the Advancement of Science (AAAS), Vol. 351, No. 6268 ( 2016-01), p. 48-52
    Kurzfassung: Target of rapamycin (TOR), a conserved protein kinase and central controller of cell growth, functions in two structurally and functionally distinct complexes: TORC1 and TORC2. Dysregulation of mammalian TOR (mTOR) signaling is implicated in pathologies that include diabetes, cancer, and neurodegeneration. We resolved the architecture of human mTORC1 (mTOR with subunits Raptor and mLST8) bound to FK506 binding protein (FKBP)–rapamycin, by combining cryo–electron microscopy at 5.9 angstrom resolution with crystallographic studies of Chaetomium thermophilum Raptor at 4.3 angstrom resolution. The structure explains how FKBP-rapamycin and architectural elements of mTORC1 limit access to the recessed active site. Consistent with a role in substrate recognition and delivery, the conserved amino-terminal domain of Raptor is juxtaposed to the kinase active site.
    Materialart: Online-Ressource
    ISSN: 0036-8075 , 1095-9203
    RVK:
    RVK:
    Sprache: Englisch
    Verlag: American Association for the Advancement of Science (AAAS)
    Publikationsdatum: 2016
    ZDB Id: 128410-1
    ZDB Id: 2066996-3
    ZDB Id: 2060783-0
    SSG: 11
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 2
    Online-Ressource
    Online-Ressource
    JSTOR ; 2000
    In:  The German Quarterly Vol. 73, No. 2 ( 2000-21), p. 229-
    In: The German Quarterly, JSTOR, Vol. 73, No. 2 ( 2000-21), p. 229-
    Materialart: Online-Ressource
    ISSN: 0016-8831
    RVK:
    Sprache: Unbekannt
    Verlag: JSTOR
    Publikationsdatum: 2000
    ZDB Id: 2066373-0
    ZDB Id: 207506-4
    SSG: 7,20
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 3
    Online-Ressource
    Online-Ressource
    Oxford University Press (OUP) ; 2021
    In:  Brain Vol. 144, No. 6 ( 2021-07-28), p. 1764-1773
    In: Brain, Oxford University Press (OUP), Vol. 144, No. 6 ( 2021-07-28), p. 1764-1773
    Kurzfassung: Functional recovery after stroke is dose-dependent on the amount of rehabilitative training. However, rehabilitative training is subject to motivational hurdles. Decision neuroscience formalizes drivers and dampers of behaviour and provides strategies for tipping motivational trade-offs and behaviour change. Here, we used one such strategy, upfront voluntary choice restriction (‘precommitment’), and tested if it can increase the amount of self-directed rehabilitative training in severely impaired stroke patients. In this randomized controlled study, stroke patients with working memory deficits (n = 83) were prescribed daily self-directed gamified cognitive training as an add-on to standard therapy during post-acute inpatient neurorehabilitation. Patients allocated to the precommitment intervention could choose to restrict competing options to self-directed training, specifically the possibility to meet visitors. This upfront choice restriction was opted for by all patients in the intervention group and highly effective. Patients in the precommitment group performed the prescribed self-directed gamified cognitive training twice as often as control group patients who were not offered precommitment [on 50% versus 21% of days, Pcorr = 0.004, d = 0.87, 95% confidence interval (CI95%) = 0.31 to 1.42], and, as a consequence, reached a 3-fold higher total training dose (90.21 versus 33.60 min, Pcorr = 0.004, d = 0.83, CI95% = 0.27 to 1.38). Moreover, add-on self-directed cognitive training was associated with stronger improvements in visuospatial and verbal working memory performance (Pcorr = 0.002, d = 0.72 and Pcorr = 0.036, d = 0.62). Our neuroscientific decision add-on intervention strongly increased the amount of effective cognitive training performed by severely impaired stroke patients. These results warrant a full clinical trial to link decision-based neuroscientific interventions directly with clinical outcome.
    Materialart: Online-Ressource
    ISSN: 0006-8950 , 1460-2156
    RVK:
    Sprache: Englisch
    Verlag: Oxford University Press (OUP)
    Publikationsdatum: 2021
    ZDB Id: 1474117-9
    SSG: 12
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 4
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 118, No. 17 ( 2021-04-27)
    Kurzfassung: G protein–coupled receptor 182 (GPR182) has been shown to be expressed in endothelial cells; however, its ligand and physiological role has remained elusive. We found GPR182 to be expressed in microvascular and lymphatic endothelial cells of most organs and to bind with nanomolar affinity the chemokines CXCL10, CXCL12, and CXCL13. In contrast to conventional chemokine receptors, binding of chemokines to GPR182 did not induce typical downstream signaling processes, including G q - and G i -mediated signaling or β-arrestin recruitment. GPR182 showed relatively high constitutive activity in regard to β-arrestin recruitment and rapidly internalized in a ligand-independent manner. In constitutive GPR182-deficient mice, as well as after induced endothelium-specific loss of GPR182, we found significant increases in the plasma levels of CXCL10, CXCL12, and CXCL13. Global and induced endothelium-specific GPR182-deficient mice showed a significant decrease in hematopoietic stem cells in the bone marrow as well as increased colony-forming units of hematopoietic progenitors in the blood and the spleen. Our data show that GPR182 is a new atypical chemokine receptor for CXCL10, CXCL12, and CXCL13, which is involved in the regulation of hematopoietic stem cell homeostasis.
    Materialart: Online-Ressource
    ISSN: 0027-8424 , 1091-6490
    RVK:
    RVK:
    Sprache: Englisch
    Verlag: Proceedings of the National Academy of Sciences
    Publikationsdatum: 2021
    ZDB Id: 209104-5
    ZDB Id: 1461794-8
    SSG: 11
    SSG: 12
    Standort Signatur Einschränkungen Verfügbarkeit
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