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  - JOUR
A1  - Gámez-Virués, Sagrario
A1  - Perović, David J.
A1  - Gossner, Martin M.
A1  - Börschig, Carmen
A1  - Blüthgen, Nico
A1  - de Jong, Heike
A1  - Simons, Nadja K.
A1  - Klein, Alexandra-Maria
A1  - Krauss, Jochen
A1  - Maier, Gwen
A1  - Scherber, Christoph
A1  - Steckel, Juliane
A1  - Rothenwöhrer, Christoph
A1  - Steffan-Dewenter, Ingolf
A1  - Weiner, Christiane N.
A1  - Weisser, Wolfgang
A1  - Werner, Michael
A1  - Tscharntke, Teja
A1  - Westphal, Catrin
T1  - Landscape simplification filters species traits and drives biotic homogenization
JF  - Nature Communications
N2  - Biodiversity loss can affect the viability of ecosystems by decreasing the ability of communities to respond to environmental change and disturbances. Agricultural intensification is a major driver of biodiversity loss and has multiple components operating at different spatial scales: from in-field management intensity to landscape-scale simplification. Here we show that landscape-level effects dominate functional community composition and can even buffer the effects of in-field management intensification on functional homogenization, and that animal communities in real-world managed landscapes show a unified response (across orders and guilds) to both landscape-scale simplification and in-field intensification. Adults and larvae with specialized feeding habits, species with shorter activity periods and relatively small body sizes are selected against in simplified landscapes with intense in-field management. Our results demonstrate that the diversity of land cover types at the landscape scale is critical for maintaining communities, which are functionally diverse, even in landscapes where in-field management intensity is high.
KW  - land-use intensity
KW  - community functional-responses
KW  - body-size
KW  - agricultural intensification
KW  - sustainable intensification
KW  - managed grasslands
KW  - biodiversity
KW  - diversity
KW  - heterogenity
KW  - butterflies
Y1  - 2015
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-141925
VL  - 6
IS  - 8568
ER  - 
TY  - JOUR
A1  - Dech, Stefan
A1  - Holzwarth, Stefanie
A1  - Asam, Sarah
A1  - Andresen, Thorsten
A1  - Bachmann, Martin
A1  - Boettcher, Martin
A1  - Dietz, Andreas
A1  - Eisfelder, Christina
A1  - Frey, Corinne
A1  - Gesell, Gerhard
A1  - Gessner, Ursula
A1  - Hirner, Andreas
A1  - Hofmann, Matthias
A1  - Kirches, Grit
A1  - Klein, Doris
A1  - Klein, Igor
A1  - Kraus, Tanja
A1  - Krause, Detmar
A1  - Plank, Simon
A1  - Popp, Thomas
A1  - Reinermann, Sophie
A1  - Reiners, Philipp
A1  - Roessler, Sebastian
A1  - Ruppert, Thomas
A1  - Scherbachenko, Alexander
A1  - Vignesh, Ranjitha
A1  - Wolfmueller, Meinhard
A1  - Zwenzner, Hendrik
A1  - Kuenzer, Claudia
T1  - Potential and challenges of harmonizing 40 years of AVHRR data: the TIMELINE experience
JF  - Remote Sensing
N2  - Earth Observation satellite data allows for the monitoring of the surface of our planet at predefined intervals covering large areas. However, there is only one medium resolution sensor family in orbit that enables an observation time span of 40 and more years at a daily repeat interval. This is the AVHRR sensor family. If we want to investigate the long-term impacts of climate change on our environment, we can only do so based on data that remains available for several decades. If we then want to investigate processes with respect to climate change, we need very high temporal resolution enabling the generation of long-term time series and the derivation of related statistical parameters such as mean, variability, anomalies, and trends. The challenges to generating a well calibrated and harmonized 40-year-long time series based on AVHRR sensor data flown on 14 different platforms are enormous. However, only extremely thorough pre-processing and harmonization ensures that trends found in the data are real trends and not sensor-related (or other) artefacts. The generation of European-wide time series as a basis for the derivation of a multitude of parameters is therefore an extremely challenging task, the details of which are presented in this paper.
KW  - AVHRR
KW  - Earth Observation
KW  - harmonization
KW  - time series analysis
KW  - climate related trends
KW  - automatic processing
KW  - Europe
KW  - TIMELINE
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-246134
SN  - 2072-4292
VL  - 13
IS  - 18
ER  - 
TY  - JOUR
A1  - Dammert, Marcel A.
A1  - Brägelmann, Johannes
A1  - Olsen, Rachelle R.
A1  - Böhm, Stefanie
A1  - Monhasery, Niloufar
A1  - Whitney, Christopher P.
A1  - Chalishazar, Milind D.
A1  - Tumbrink, Hannah L.
A1  - Guthrie, Matthew R.
A1  - Klein, Sebastian
A1  - Ireland, Abbie S.
A1  - Ryan, Jeremy
A1  - Schmitt, Anna
A1  - Marx, Annika
A1  - Ozretić, Luka
A1  - Castiglione, Roberta
A1  - Lorenz, Carina
A1  - Jachimowicz, Ron D.
A1  - Wolf, Elmar
A1  - Thomas, Roman K.
A1  - Poirier, John T.
A1  - Büttner, Reinhard
A1  - Sen, Triparna
A1  - Byers, Lauren A.
A1  - Reinhardt, H. Christian
A1  - Letai, Anthony
A1  - Oliver, Trudy G.
A1  - Sos, Martin L.
T1  - MYC paralog-dependent apoptotic priming orchestrates a spectrum of vulnerabilities in small cell lung cancer
JF  - Nature Communications
N2  - MYC paralogs are frequently activated in small cell lung cancer (SCLC) but represent poor drug targets. Thus, a detailed mapping of MYC-paralog-specific vulnerabilities may help to develop effective therapies for SCLC patients. Using a unique cellular CRISPR activation model, we uncover that, in contrast to MYCN and MYCL, MYC represses BCL2 transcription via interaction with MIZ1 and DNMT3a. The resulting lack of BCL2 expression promotes sensitivity to cell cycle control inhibition and dependency on MCL1. Furthermore, MYC activation leads to heightened apoptotic priming, intrinsic genotoxic stress and susceptibility to DNA damage checkpoint inhibitors. Finally, combined AURK and CHK1 inhibition substantially prolongs the survival of mice bearing MYC-driven SCLC beyond that of combination chemotherapy. These analyses uncover MYC-paralog-specific regulation of the apoptotic machinery with implications for genotype-based selection of targeted therapeutics in SCLC patients.
KW  - genetic engineering
KW  - oncogenes
KW  - small-cell lung cancer
KW  - targeted therapies
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-223569
VL  - 10
ER  -