TY  - JOUR
A1  - Jost, Priska
A1  - Klein, Franziska
A1  - Brand, Benjamin
A1  - Wahl, Vanessa
A1  - Wyatt, Amanda
A1  - Yildiz, Daniela
A1  - Boehm, Ulrich
A1  - Niemeyer, Barbara A.
A1  - Vaeth, Martin
A1  - Alansary, Dalia
T1  - Acute downregulation but not genetic ablation of murine MCU impairs suppressive capacity of regulatory CD4 T cells
JF  - International Journal of Molecular Sciences
N2  - By virtue of mitochondrial control of energy production, reactive oxygen species (ROS) generation, and maintenance of Ca\(^{2+}\) homeostasis, mitochondria play an essential role in modulating T cell function. The mitochondrial Ca\(^{2+}\) uniporter (MCU) is the pore-forming unit in the main protein complex mediating mitochondrial Ca\(^{2+}\) uptake. Recently, MCU has been shown to modulate Ca\(^{2+}\) signals at subcellular organellar interfaces, thus fine-tuning NFAT translocation and T cell activation. The mechanisms underlying this modulation and whether MCU has additional T cell subpopulation-specific effects remain elusive. However, mice with germline or tissue-specific ablation of Mcu did not show impaired T cell responses in vitro or in vivo, indicating that ‘chronic’ loss of MCU can be functionally compensated in lymphocytes. The current work aimed to specifically investigate whether and how MCU influences the suppressive potential of regulatory CD4 T cells (Treg). We show that, in contrast to genetic ablation, acute siRNA-mediated downregulation of Mcu in murine Tregs results in a significant reduction both in mitochondrial Ca\(^{2+}\) uptake and in the suppressive capacity of Tregs, while the ratios of Treg subpopulations and the expression of hallmark transcription factors were not affected. These findings suggest that permanent genetic inactivation of MCU may result in compensatory adaptive mechanisms, masking the effects on the suppressive capacity of Tregs.
KW  - mitochondrial calcium uniporter
KW  - regulatory T cells
KW  - suppressive capacity
Y1  - 2023
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-313621
SN  - 1422-0067
VL  - 24
IS  - 9
ER  - 
TY  - CHAP
A1  - Klein, Martin
ED  - Hochschild, Joshua P.
ED  - Nevitt, Turner C.
ED  - Wood, Adam
ED  - Borbély, Gábor
T1  - Metaphors, Dead and Alive
T2  - Metaphysics Through Semantics: The Philosophical Recovery of the Medieval Mind
N2  - This paper examins how the medieval distinction between proper and improper signification can give a plausible explanation of both metaphorical use and the usual transformations a language can undergo. I will show how Thomas Aquinas distinguishes between ordinary ambiguous terms and metaphors, whereas William of Ockham and Walter Burley do not leave room for this distinction. I will argue that Ockham’s conception of transfer of sense through subsequent institution of words is best thought of as an explanation of how ordinary usage can contain ambiguities, whereas Burley’s conception of transfer of sense without new imposition is more plausible when it comes to explaining metaphors. If metaphorical use is lumped together with equivocation, the account of how they work cannot do full justice to either, an insight that we already find in Peter Abelard, if not in Boethius.
KW  - Aquinas
KW  - Ockham
KW  - Burley
KW  - metaphor
KW  - equivocation
KW  - signification
KW  - imposition
KW  - transference
Y1  - 2023
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-359678
UR  - https://link.springer.com/chapter/10.1007/978-3-031-15026-5_8
N1  - Subject to Springer Nature’s AM terms of use (https://www.springernature.com/gp/open-research/policies/accepted-manuscript-terms).
PB  - Springer
ER  -