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Institute
- Theodor-Boveri-Institut für Biowissenschaften (66)
- Institut für Anorganische Chemie (52)
- Klinik und Poliklinik für Nuklearmedizin (44)
- Institut für Psychologie (43)
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Schriftenreihe
Sonstige beteiligte Institutionen
- Johns Hopkins School of Medicine (18)
- Johns Hopkins University School of Medicine (5)
- Johns Hopkins School of Medicine, Baltimore, MD, U.S. (4)
- Department of Biomedical Imaging, National Cerebral and Cardiovascular Research Center, Suita, Japan (2)
- Division of Medical Technology and Science, Department of Medical Physics and Engineering, Course of Health Science, Osaka University Graduate School of Medicine, Suita Japan (2)
- Institut for Molecular Biology and CMBI, Department of Genomics, Stem Cell Biology and Regenerative Medicine, Leopold-Franzens-University Innsbruck, Innsbruck, Austria (2)
- Institut für Optik und Atomare Physik, Technische Universität Berlin, 10623 Berlin, Germany (2)
- International Max Planck Research School Molecular Biology, University of Göttingen, Germany (2)
- Johns Hopkins School of Medicine, The Russell H Morgan Department of Radiology and Radiological Science, Baltimore, MD, USA (2)
- Laboratory for Chemistry and Life Science, Institute of Innovative Research, Tokyo Institute of Technology, Yokohama 226-8503, Japan (2)
Wagner, N. ; Crippa, L. ; Amaricci, A. ; Hansmann, P. ; Klett, M. ; König, E. J. ; Schäfer, T. ; Di Sante, D. ; Cano, J. ; Millis, A. J. ; Georges, A. ; Sangiovanni, G.
The topological classification of electronic band structures is based on symmetry properties of Bloch eigenstates of single-particle Hamiltonians. In parallel, topological field theory has opened the doors to the formulation and characterization of non-trivial phases of matter driven by strong electron-electron interaction. Even though important examples of topological Mott insulators have been constructed, the relevance of the underlying non-interacting band topology to the physics of the Mott phase has remained unexplored. Here, we show that the momentum structure of the Green’s function zeros defining the “Luttinger surface" provides a topological characterization of the Mott phase related, in the simplest description, to the one of the single-particle electronic dispersion. Considerations on the zeros lead to the prediction of new phenomena: a topological Mott insulator with an inverted gap for the bulk zeros must possess gapless zeros at the boundary, which behave as a form of “topological antimatter” annihilating conventional edge states. Placing band and Mott topological insulators in contact produces distinctive observable signatures at the interface, revealing the otherwise spectroscopically elusive Green’s function zeros.
Djakovic, Lara ; Hennig, Thomas ; Reinisch, Katharina ; Milić, Andrea ; Whisnant, Adam W. ; Wolf, Katharina ; Weiß, Elena ; Haas, Tobias ; Grothey, Arnhild ; Jürges, Christopher S. ; Kluge, Michael ; Wolf, Elmar ; Erhard, Florian ; Friedel, Caroline C. ; Dölken, Lars
Herpes simplex virus 1 (HSV-1) infection and stress responses disrupt transcription termination by RNA Polymerase II (Pol II). In HSV-1 infection, but not upon salt or heat stress, this is accompanied by a dramatic increase in chromatin accessibility downstream of genes. Here, we show that the HSV-1 immediate-early protein ICP22 is both necessary and sufficient to induce downstream open chromatin regions (dOCRs) when transcription termination is disrupted by the viral ICP27 protein. This is accompanied by a marked ICP22-dependent loss of histones downstream of affected genes consistent with impaired histone repositioning in the wake of Pol II. Efficient knock-down of the ICP22-interacting histone chaperone FACT is not sufficient to induce dOCRs in ΔICP22 infection but increases dOCR induction in wild-type HSV-1 infection. Interestingly, this is accompanied by a marked increase in chromatin accessibility within gene bodies. We propose a model in which allosteric changes in Pol II composition downstream of genes and ICP22-mediated interference with FACT activity explain the differential impairment of histone repositioning downstream of genes in the wake of Pol II in HSV-1 infection.
Haake, Markus ; Haack, Beatrice ; Schäfer, Tina ; Harter, Patrick N. ; Mattavelli, Greta ; Eiring, Patrick ; Vashist, Neha ; Wedekink, Florian ; Genssler, Sabrina ; Fischer, Birgitt ; Dahlhoff, Julia ; Mokhtari, Fatemeh ; Kuzkina, Anastasia ; Welters, Marij J. P. ; Benz, Tamara M. ; Sorger, Lena ; Thiemann, Vincent ; Almanzar, Giovanni ; Selle, Martina ; Thein, Klara ; Späth, Jacob ; Gonzalez, Maria Cecilia ; Reitinger, Carmen ; Ipsen-Escobedo, Andrea ; Wistuba-Hamprecht, Kilian ; Eichler, Kristin ; Filipski, Katharina ; Zeiner, Pia S. ; Beschorner, Rudi ; Goedemans, Renske ; Gogolla, Falk Hagen ; Hackl, Hubert ; Rooswinkel, Rogier W. ; Thiem, Alexander ; Romer Roche, Paula ; Joshi, Hemant ; Pühringer, Dirk ; Wöckel, Achim ; Diessner, Joachim E. ; Rüdiger, Manfred ; Leo, Eugen ; Cheng, Phil F. ; Levesque, Mitchell P. ; Goebeler, Matthias ; Sauer, Markus ; Nimmerjahn, Falk ; Schuberth-Wagner, Christine ; Felten, Stefanie von ; Mittelbronn, Michel ; Mehling, Matthias ; Beilhack, Andreas ; van der Burg, Sjoerd H. ; Riedel, Angela ; Weide, Benjamin ; Dummer, Reinhard ; Wischhusen, Jörg
Immune checkpoint blockade therapy is beneficial and even curative for some cancer patients. However, the majority don’t respond to immune therapy. Across different tumor types, pre-existing T cell infiltrates predict response to checkpoint-based immunotherapy. Based on in vitro pharmacological studies, mouse models and analyses of human melanoma patients, we show that the cytokine GDF-15 impairs LFA-1/β2-integrin-mediated adhesion of T cells to activated endothelial cells, which is a pre-requisite of T cell extravasation. In melanoma patients, GDF-15 serum levels strongly correlate with failure of PD-1-based immune checkpoint blockade therapy. Neutralization of GDF-15 improves both T cell trafficking and therapy efficiency in murine tumor models. Thus GDF-15, beside its known role in cancer-related anorexia and cachexia, emerges as a regulator of T cell extravasation into the tumor microenvironment, which provides an even stronger rationale for therapeutic anti-GDF-15 antibody development.
Frank, Erik T. ; Kesner, Lucie ; Liberti, Joanito ; Helleu, Quentin ; LeBoeuf, Adria C. ; Dascalu, Andrei ; Sponsler, Douglas B. ; Azuma, Fumika ; Economo, Evan P. ; Waridel, Patrice ; Engel, Philipp ; Schmitt, Thomas ; Keller, Laurent
Infected wounds pose a major mortality risk in animals. Injuries are common in the ant Megaponera analis, which raids pugnacious prey. Here we show that M. analis can determine when wounds are infected and treat them accordingly. By applying a variety of antimicrobial compounds and proteins secreted from the metapleural gland to infected wounds, workers reduce the mortality of infected individuals by 90%. Chemical analyses showed that wound infection is associated with specific changes in the cuticular hydrocarbon profile, thereby likely allowing nestmates to diagnose the infection state of injured individuals and apply the appropriate antimicrobial treatment. This study demonstrates that M. analis ant societies use antimicrobial compounds produced in the metapleural glands to treat infected wounds and reduce nestmate mortality.
McFleder, Rhonda L. ; Makhotkina, Anastasiia ; Groh, Janos ; Keber, Ursula ; Imdahl, Fabian ; Peña Mosca, Josefina ; Peteranderl, Alina ; Wu, Jingjing ; Tabuchi, Sawako ; Hoffmann, Jan ; Karl, Ann-Kathrin ; Pagenstecher, Axel ; Vogel, Jörg ; Beilhack, Andreas ; Koprich, James B. ; Brotchie, Jonathan M. ; Saliba, Antoine-Emmanuel ; Volkmann, Jens ; Ip, Chi Wang
Inflammation in the brain and gut is a critical component of several neurological diseases, such as Parkinson’s disease (PD). One trigger of the immune system in PD is aggregation of the pre-synaptic protein, α-synuclein (αSyn). Understanding the mechanism of propagation of αSyn aggregates is essential to developing disease-modifying therapeutics. Using a brain-first mouse model of PD, we demonstrate αSyn trafficking from the brain to the ileum of male mice. Immunohistochemistry revealed that the ileal αSyn aggregations are contained within CD11c+ cells. Using single-cell RNA sequencing, we demonstrate that ileal CD11c\(^+\) cells are microglia-like and the same subtype of cells is activated in the brain and ileum of PD mice. Moreover, by utilizing mice expressing the photo-convertible protein, Dendra2, we show that CD11c\(^+\) cells traffic from the brain to the ileum. Together these data provide a mechanism of αSyn trafficking between the brain and gut.
Pathogen-specific innate immune response patterns are distinctly affected by genetic diversity
(2023)
Häder, Antje ; Schäuble, Sascha ; Gehlen, Jan ; Thielemann, Nadja ; Buerfent, Benedikt C. ; Schüller, Vitalia ; Hess, Timo ; Wolf, Thomas ; Schröder, Julia ; Weber, Michael ; Hünniger, Kerstin ; Löffler, Jürgen ; Vylkova, Slavena ; Panagiotou, Gianni ; Schumacher, Johannes ; Kurzai, Oliver
Innate immune responses vary by pathogen and host genetics. We analyze quantitative trait loci (eQTLs) and transcriptomes of monocytes from 215 individuals stimulated by fungal, Gram-negative or Gram-positive bacterial pathogens. We identify conserved monocyte responses to bacterial pathogens and a distinct antifungal response. These include 745 response eQTLs (reQTLs) and corresponding genes with pathogen-specific effects, which we find first in samples of male donors and subsequently confirm for selected reQTLs in females. reQTLs affect predominantly upregulated genes that regulate immune response via e.g., NOD-like, C-type lectin, Toll-like and complement receptor-signaling pathways. Hence, reQTLs provide a functional explanation for individual differences in innate response patterns. Our identified reQTLs are also associated with cancer, autoimmunity, inflammatory and infectious diseases as shown by external genome-wide association studies. Thus, reQTLs help to explain interindividual variation in immune response to infection and provide candidate genes for variants associated with a range of diseases.
Natural DNA storage allows cellular differentiation, evolution, the growth of our children and controls all our ecosystems. Here, we discuss the fundamental aspects of DNA storage and recent advances in this field, with special emphasis on natural processes and solutions that can be exploited. We point out new ways of efficient DNA and nucleotide storage that are inspired by nature. Within a few years DNA-based information storage may become an attractive and natural complementation to current electronic data storage systems. We discuss rapid and directed access (e.g. DNA elements such as promotors, enhancers), regulatory signals and modulation (e.g. lncRNA) as well as integrated high-density storage and processing modules (e.g. chromosomal territories). There is pragmatic DNA storage for use in biotechnology and human genetics. We examine DNA storage as an approach for synthetic biology (e.g. light-controlled nucleotide processing enzymes). The natural polymers of DNA and RNA offer much for direct storage operations (read-in, read-out, access control). The inbuilt parallelism (many molecules at many places working at the same time) is important for fast processing of information. Using biology concepts from chromosomal storage, nucleic acid processing as well as polymer material sciences such as electronical effects in enzymes, graphene, nanocellulose up to DNA macramé , DNA wires and DNA-based aptamer field effect transistors will open up new applications gradually replacing classical information storage methods in ever more areas over time (decades).
The work proposes possible designs of active regions for a mode-locked interband cascade laser emitting in the mid infrared. For that purpose we investigated the electronic structure properties of respectively modified GaSb-based type II W-shaped quantum wells, including the effect of external bias in order to simultaneously fulfil the requirements for both the absorber as well as the gain sections of a device. The results show that introducing multiple InAs layers in type II InAs/GaInSb quantum wells or introducing a tensely-strained GaAsSb layer into “W-shaped” type II QWs offers significant difference in optical transitions’ oscillator strengths (characteristic lifetimes) of the two oppositely polarized parts of such a laser, being promising for utilization in mode-locked devices.
Healthy functioning of the female reproductive tract (FRT) depends on balanced and dynamic regulation by hormones during the menstrual cycle, pregnancy and childbirth. The mucosal epithelial lining of different regions of the FRT—ovaries, fallopian tubes, uterus, cervix and vagina—facilitates the selective transport of gametes and successful transfer of the zygote to the uterus where it implants and pregnancy takes place. It also prevents pathogen entry. Recent developments in three-dimensional (3D) organoid systems from the FRT now provide crucial experimental models that recapitulate the cellular heterogeneity and physiological, anatomical and functional properties of the organ in vitro. In this review, we summarise the state of the art on organoids generated from different regions of the FRT. We discuss the potential applications of these powerful in vitro models to study normal physiology, fertility, infections, diseases, drug discovery and personalised medicine.