TY - GEN A1 - Iwert, C. A1 - Stein, J. A1 - Appelt, C. A1 - Vogt, K. A1 - Rainer, R. J. A1 - Tummler, K. A1 - Mühle, K. A1 - Stanko, K. A1 - Schumann, J. A1 - Uebe, D. A1 - Jürchott, K. A1 - Lisec, Jan A1 - Janek, K. A1 - Gille, C. A1 - Textoris-Taube, K. A1 - Sai, S. A1 - Petersen, A. A1 - Kühl, A. A. A1 - Klipp, E. A1 - Meisel, C. A1 - Sawitzki, B. T1 - TCAIM controls effector T cell generation by preventing Mitochondria-Endoplasmic Reticulum Contact Site-initiated Cholesterol Biosynthesis N2 - T cells need to adapt their cellular metabolism for effector cell differentiation. This relies on alterations in mitochondrial physiology. Which signals and molecules regulate those alterations remains unclear. We recently reported, that the mitochondrial protein TCAIM inhibits activation-induced changes in mitochondrial morphology and function and thus, CD effector T cell formation. Using conditional TCAIM knock-in (KI) and knockout (KO) mice, w now show that it also applies to CD8+ T cells and more importantly, delineate the molecular processes in mitochondria by which TCAIM controls effector cell differentiation. TCAIM KI resulted in reduced activation-induced HIF1α protein expression. Metabolomics and transcriptional data in combination with mathematical flux modeling revealed an impaired induction of anabolic pathways, especially of the mevalonate pathway and cholesterol biosynthesis in TCAIM KI CD8+ T cells. Addition of cholesterol completely rescued HIF1α protein expression, activation and proliferation of TCAIM KI CD8+ T cells. At the molecular level, TCAIM delayed activation-induced mitochondria-ER contact (MERC) formation by binding to MERC promoting proteins such as RMD3 and VDAC2. In summary, we demonstrate that TCAIM suppresses effector cell differentiation by inhibiting MERC formation, which induce HIF1α-mediated increase in cellular metabolism and cholesterol biosynthesis. KW - Mass Spectroscopy KW - Metabolomics KW - Cancer PY - 2021 UR - https://nbn-resolving.org/urn:nbn:de:kobv:b43-533543 UR - https://www.biorxiv.org/content/10.1101/2021.04.20.440500v1 DO - https://doi.org/10.1101/2021.04.20.440500 VL - April SP - 1 EP - 45 PB - Cold Spring Harbor Laboratory AN - OPUS4-53354 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - JOUR A1 - Schaepe, Kaija A1 - R. Bhandari, D. A1 - Werner, J. A1 - Henss, A. A1 - Pirkl, A. A1 - Kleine-Boymann, M. A1 - Rohnke, M. A1 - Wenisch, S. A1 - Neumann, E. A1 - Janek, J. A1 - Spengler, B. T1 - Imaging of lipids in native human bone sections using TOF-secondary ion mass spectrometry, atmospheric pressure scanning microprobe matrix-assisted laser desorption/ionization orbitrap mass spectrometry, and orbitrap-secondary ion mass spectrometry N2 - A method is described for high-resolution label-free molecular imaging of human bone tissue. To preserve the lipid content and the heterogeneous structure of osseous tissue, 4 μm thick human bone sections were prepared via cryoembedding and tape-assisted cryosectioning, circumventing the application of organic solvents and a decalcification step. A protocol for comparative mass spectrometry imaging (MSI) on the same section was established for initial analysis with time-of-flight secondary ion mass spectrometry (TOF-SIMS) at a lateral resolution of 10 μm to <500 nm, followed by atmospheric pressure scanning microprobe matrix-assisted laser desorption/ionization (AP-SMALDI) Orbitrap MSI at a lateral resolution of 10 μm. This procedure ultimately enabled MSI of lipids, providing the lateral localization of major lipid classes such as glycero-, glycerophospho-, and sphingolipids. Additionally, the applicability of the recently emerged Orbitrap-TOF-SIMS hybrid system was exemplarily examined and compared to the before-mentioned MSI methods. KW - ToF-SIMS KW - MALDI KW - Mass spectrometry imaging KW - Lipids KW - Osteoporosis KW - Bone KW - Surface analysis PY - 2018 UR - https://pubs.acs.org/doi/10.1021/acs.analchem.8b00892 DO - https://doi.org/10.1021/acs.analchem.8b00892 SN - 0003-2700 SN - 1520-6882 VL - 90 IS - 15 SP - 8856 EP - 8864 PB - ACS Publ. CY - Washington, DC AN - OPUS4-45730 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - JOUR A1 - Kienle, L. A1 - Duppel, V. A1 - Mogwitz, B. A1 - Janek, J. A1 - Kreutzbruck, Marc A1 - Leineweber, A. A1 - Simon, A. T1 - Synthesis - real structure - property: the showcase of silver-rich Ag2Se N2 - The structures and properties of silver selenide samples strongly depend on the method of preparation. Thin films prepared by pulsed laser deposition (PLD) contain lamellae of two low-temperature modifications of Ag2Se whose structures were analyzed in detail by electron microscopy techniques. Besides the stable and known Naumannite-type phase (LT1), a metastable phase was observed (LT2), and the phase transformation was examined in situ. Via cooling and annealing, LT2 becomes dominant in thin films, thus enabling solving the structure of LT2 by electron diffraction. These experiments and HRTEM point to an Acanthite-type (stable low-temperature modification of Ag2S) structure of LT2. Rapid-quenching procedures were applied for the first synthesis of LT2 as bulk sample. Depending on the conditions of melt spinning experiments, well-defined products were formed. In one series, we found a separation of LT1 and LT2 into distinct morphologies, i.e. microspheres and dendrites, respectively. The results on the magnetoresistance of the rapidly quenched materials support previous work. PY - 2011 DO - https://doi.org/10.1021/cg200167j SN - 1528-7483 VL - 11 IS - 6 SP - 2412 EP - 2421 PB - American Chemical Society CY - Washington, DC, USA AN - OPUS4-25388 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - JOUR A1 - Kienle, L. A1 - Duppel, V. A1 - Mogwitz, B. A1 - Korte, C. A1 - Kreutzbruck, Marc A1 - Janek, J. T1 - Real structures and structural modifications of Ag2+xSe thin films KW - Ag clusters KW - MR KW - LT PY - 2007 DO - https://doi.org/10.1017/S1431927607082013 SN - 1431-9276 SN - 1435-8115 VL - 13 IS - Suppl 3 SP - 402 EP - 403 PB - Cambridge University Press CY - New York, NY AN - OPUS4-19242 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - JOUR A1 - Kienle, L. A1 - Duppel, V. A1 - Lembke, G. A1 - Mogwitz, B. A1 - Janek, J. A1 - Kreutzbruck, Marc A1 - Simon, A. T1 - Microstructure and magnetoresistance of heterogeneous gold-rich Ag3Au1.1Te2 N2 - Dispersions of very small non-magnetic metal particles or inclusions in a non-magnetic semiconductor matrix are well known to produce unusually large and linear magnetoresistance effects. So far these materials were limited to the binary silver-rich chalcogenides Ag2Se and Ag2Te. In this contribution Ag3AuTe2 was selected as a first candidate for a ternary matrix material, thus offering enhanced capabilities for the generation of heterogeneous microstructure and spatially varying composition on the nanoscale. In gold-rich Ag3Au1.1Te2 two kinds of inhomogeneities are present, namely Au deposits with a size on the micron scale and an inhomogeneous distribution of Au and Ag within the matrix. The matrix consists of micron-sized grains with the structure type of Ag3AuTe2 as studied by electron microscopy. Like the binary silver chalcogenide phases, the material also shows a large and linear magnetoresistance effect. The transversal magnetoresistance effect was measured between 20 K and 270 K in magnetic fields up to B = 5 T. The results are discussed on the basis of existing models for a large and linear positive MR effect. KW - Petzite KW - Magnetosensor KW - Electron microscopy KW - Nonstoichiometry KW - Magnetoresistance PY - 2010 DO - https://doi.org/10.1016/j.solidstatesciences.2010.07.029 SN - 1293-2558 SN - 1873-3085 VL - 12 IS - 10 SP - 1770 EP - 1778 PB - Elsevier CY - Amsterdam AN - OPUS4-22281 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - JOUR A1 - Kreutzbruck, Marc A1 - Lembke, G. A1 - Mogwitz, B. A1 - Korte, C. A1 - Janek, J. T1 - Linear magnetoresistance in Ag2+deltaSe thin films N2 - In the nonstoichiometric low-temperature phase of silver selenide a very small silver excess within the semiconducting silver selenide matrix in the order of 0.01% is sufficient to generate a linear magnetoresistance (LMR) of more than 300% at 5 T, which does not saturate at fields up to 60 T. Different theoretical models have been proposed to explain this unusual magnetoresistance (MR) behavior, among them a random resistor network consisting of four-terminal resistor units. According to this model the LMR and the crossover field from linear to quadratic behavior are primarily controlled by both the spatial distribution of the charge-carrier mobility and its average value, being essentially functions of the local and average compositions. Here we report measurements on silver-rich thin AgxSe films with a thickness between 20 nm and 2 µm, which show an increasing average mobility in conjunction with an enhanced MR for increasing film thickness. We found a linear scaling between the size of the transverse LMR and the crossover field, as predicted by the theory. For films thinner than about 100 nm the MR with field directed in the sample plane shows a breakdown of the LMR, revealing the physical length scale of the inhomegeneities in thin AgxSe devices. KW - Carrier mobility KW - Magnetoresistance KW - Semiconductor materials KW - Semiconductor thin films KW - Silver vompounds KW - Stoichiometry PY - 2009 DO - https://doi.org/10.1103/PhysRevB.79.035204 SN - 1098-0121 SN - 0163-1829 SN - 0556-2805 SN - 1095-3795 SN - 1550-235X VL - 79 IS - 3 SP - 035204-1 - 035204-5 PB - American Institute of Physics CY - Melville, NY AN - OPUS4-18930 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER -