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Year of publication
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- Conference Proceeding (1)
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Has Fulltext
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Keywords
- Hadron-Hadron Scattering (2)
- Jets and Jet Substructure (2)
- Quark-Gluon Plasma (2)
- Alleles (1)
- Amino acid analysis (1)
- BPTF (1)
- Bipolar disorder (1)
- Boosted Jets (1)
- COVID-19 (1)
- Collective Flow (1)
Institute
Zhang, Rong ; Gehlen, Jan ; Kawalia, Amit ; Melissari, Maria-Theodora ; Dakal, Tikam Chand ; Menon, Athira M. ; Höfele, Julia ; Riedhammer, Korbinian ; Waffenschmidt, Lea ; Fabian, Julia ; Breuer, Katinka ; Kalanithy, Jeshurun ; Hilger, Alina Christine ; Sharma, Amit ; Hölscher, Alice ; Boemers, Thomas M. ; Pauly, Markus ; Leutner, Andreas ; Fuchs, Jörg ; Seitz, Guido ; Ludwikowski, Barbara ; Gomez, Barbara ; Hubertus, Jochen ; Heydweiller, Andreas ; Kurz, Ralf ; Leonhardt, Johannes ; Kosch, Ferdinand ; Holland-Cunz, Stefan ; Münsterer, Oliver ; Ure, Beno ; Schmiedeke, Eberhard ; Neser, Jörg ; Degenhardt, Petra ; Märzheuser, Stefanie ; Kleine, Katharina ; Schäfer, Mattias ; Spychalski, Nicole ; Deffaa, Oliver J. ; Gosemann, Jan-Hendrik ; Lacher, Martin ; Heilmann-Heimbach, Stefanie ; Zwink, Nadine ; Jenetzky, Ekkehart ; Ludwig, Michael ; Grote, Phillip ; Schumacher, Johannes ; Thiele, Holger ; Reutter, Heiko
Introduction: Esophageal atresia with or without tracheoesophageal fistula (EA/TEF) occurs approximately 1 in 3.500 live births representing the most common malformation of the upper digestive tract. Only half a century ago, EA/TEF was fatal among affected newborns suggesting that the steady birth prevalence might in parts be due to mutational de novo events in genes involved in foregut development.
Methods: To identify mutational de novo events in EA/TEF patients, we surveyed the exome of 30 case-parent trios. Identified and confirmed de novo variants were prioritized using in silico prediction tools. To investigate the embryonic role of genes harboring prioritized de novo variants we performed targeted analysis of mouse transcriptome data of esophageal tissue obtained at the embryonic day (E) E8.5, E12.5, and postnatal.
Results: In total we prioritized 14 novel de novo variants in 14 different genes (APOL2, EEF1D, CHD7, FANCB, GGT6, KIAA0556, NFX1, NPR2, PIGC, SLC5A2, TANC2, TRPS1, UBA3, and ZFHX3) and eight rare de novo variants in eight additional genes (CELSR1, CLP1, GPR133, HPS3, MTA3, PLEC, STAB1, and PPIP5K2). Through personal communication during the project, we identified an additional EA/TEF case-parent trio with a rare de novo variant in ZFHX3. In silico prediction analysis of the identified variants and comparative analysis of mouse transcriptome data of esophageal tissue obtained at E8.5, E12.5, and postnatal prioritized CHD7, TRPS1, and ZFHX3 as EA/TEF candidate genes. Re-sequencing of ZFHX3 in additional 192 EA/TEF patients did not identify further putative EA/TEF-associated variants.
Conclusion: Our study suggests that rare mutational de novo events in genes involved in foregut development contribute to the development of EA/TEF.
Bass, Steffen A. ; Belkacem, Mohamed ; Bleicher, Marcus ; Brandstetter, Mathias ; Bravina, Larissa ; Ernst, Christoph ; Gerland, Lars ; Hofmann, Max ; Hofmann, Sigurd ; Konopka, Jens ; Mao, Guangjun ; Neise, Ludwig ; Soff, Sven ; Spieles, Christian ; Weber, Henning ; Winckelmann, Luke Andreas ; Stöcker, Horst ; Greiner, Walter ; Hartnack, Christoph ; Aichelin, Jörg ; Amelin, Nikolai
In this paper, the concepts of microscopic transport theory are introduced and the features and shortcomings of the most commonly used ansatzes are discussed. In particular, the Ultrarelativistic Quantum Molecular Dynamics (UrQMD) transport model is described in great detail. Based on the same principles as QMD and RQMD, it incorporates a vastly extended collision term with full baryon-antibaryon symmetry, 55 baryon and 32 meson species. Isospin is explicitly treated for all hadrons. The range of applicability stretches from E lab < 100$ MeV/nucleon up to E lab> 200$ GeV/nucleon, allowing for a consistent calculation of excitation functions from the intermediate energy domain up to ultrarelativistic energies. The main physics topics under discussion are stopping, particle production and collective flow.
Junghans, Arnd Rudolf ; Beyer, Roland ; Claußner, Jürgen ; Kögler, Toni ; Urlaß, Sebastian ; Bemmerer, Daniel ; Ferrari, Anna ; Schwengner, Ronald ; Wagner, Andreas ; Dietz, Mirco ; Frotscher, Axel ; Grieger, Marcel ; Hensel, Thomas ; Koppitz, Martina ; Ludwig, Felix ; Turkat, Steffen ; Nolte, Ralf ; Pirovano, Elisa ; Kopecky, Stefan ; Nyman, Markus ; Plompen, Arjan J. M. ; Schillebeeckx, Peter ; Borris, Erik ; Reifarth, René ; Veltum, Daniel ; Weigand, Mario ; Glorius, Jan ; Görres, Joachim ; Oberlack, Uwe ; Wenz, Daniel
Neutron total cross sections are an important source of experimental data in the evaluation of neutron-induced cross sections. The sum of all neutron-induced reaction cross sections can be determined with a precision of a few per cent in a relative measurement. The neutron spectrum of the photoneutron source nELBE extends in the fast region from about 100 keV to 10 MeV and has favourable conditions for transmission measurements due to the low instantaneous flux of neutrons and low gamma-flash background. Several materials of interest (in part included in the CIELO evaluation or on the HPRL of OECD/NEA) have been investigated: 197Au [1, 2], natFe [2], natW [2], 238U, natPt, 4He, natO, natNe, natXe. For gaseous targets high pressure gas cells with flat end-caps have been built that hold up to 200 bar pressure. The experimental setup will be presented including results from several transmission experiments and the data analysis leading to the total cross sections will be discussed.
Vorobjev, Gleb ; Andre, Christiane ; Barth, Winfried ; Berdermann, Elèni ; Clemente, Gianluigi ; Ciobanu, Mircea Iuliu ; Dahl, Ludwig ; Forck, Peter ; Gerhard, Peter ; Haseitl, Rainer ; Herfurth, Frank ; Kaiser, Michael ; Kaufmann, Wolfgang ; Kester, Oliver ; Kluge, Heinz Jürgen ; Kotovski, Nikita ; Kozhuharov, Christophor ; Maier, Michael ; Quint, Wolfgang ; Reiter, Andreas ; Sokolov, Alexey ; Stöhlker, Thomas ; Pfister, Jochen ; Ratzinger, Ulrich ; Schempp, Alwin
The HITRAP linear decelerator currently being set up at GSI will provide slow, few keV/u highly charged ions for atomic physics experiments. The expected beam intensity is up to 105 ions per shot. To optimize phase and amplitude of the RF systems intensity, bunch length and kinetic energy of the particles need to be monitored. The bunch length that we need to fit is about 2 ns, which is typically measured by capacitive pickups. However, they do not work for the low beam intensities that we face. We investigated the bunch length with a fast CVD diamond detector working in single particle counting mode. Averaging over 8 shots yields a clear, regular picture of the bunched beam. Energy measurements by capacitive pickups are limited by the presence of intense primary and partially decelerated beam and hence make tuning of the IH-structure impossible. The energy of the decelerated fraction of the beam behind the first deceleration cavity was determined to about 10 % accuracy with a permanent dipole magnet combined with a MCP. Better detector calibration should help reaching the required 1%. Design of the detectors as well as the results of the measurements will be presented.
Gutwein, Paul ; Schramme, Anja ; Abdel-Bakky, Mohamed Sadek ; Doberstein, Kai ; Hauser, Ingeborg A. ; Ludwig, Andreas ; Altevogt, Peter ; Gauer, Stefan ; Hillmann, Anja ; Weide, Thomas ; Jespersen, Christine ; Eberhardt, Wolfgang ; Pfeilschifter, Josef
Background: The importance of the Notch signaling in the development of glomerular diseases has been recently described. Therefore we analyzed in podocytes the expression and activity of ADAM10, one important component of the Notch signaling complex. Methods: By Western blot, immunofluorescence and immunohistochemistry analysis we characterized the expression of ADAM10 in human podocytes, human urine and human renal tissue. Results: We present evidence, that differentiated human podocytes possessed increased amounts of mature ADAM10 and released elevated levels of L1 adhesion molecule, one well known substrate of ADAM10. By using specific siRNA and metalloproteinase inhibitors we demonstrate that ADAM10 is involved in the cleavage of L1 in human podocytes. Injury of podocytes enhanced the ADAM10 mediated cleavage of L1. In addition, we detected ADAM10 in urinary podocytes from patients with kidney diseases and in tissue sections of normal human kidney. Finally, we found elevated levels of ADAM10 in urinary vesicles of patients with glomerular kidney diseases. Conclusions: The activity of ADAM10 in human podocytes may play an important role in the development of glomerular kidney diseases.
Frank, Pinar ; Siebenhofer, Bernhard ; Hanzer, Theresa ; Geiss, Andreas F. ; Schadauer, Florian ; Reiner-Rozman, Ciril ; Durham, Bill ; Loew, Leslie M. ; Ludwig, Bernd ; Richter, Oliver-Matthias H. ; Nowak, Christoph ; Naumann, Renate L. C.
As a surrogate of live cells, proteo-lipobeads are presented, encapsulating functional membrane proteins in a strict orientation into a lipid bilayer. Assays can be performed just as on live cells, for example using fluorescence measurements. As a proof of concept, we have demonstrated proton transport through cytochrome c oxidase.
Huettmann, Carolina ; Stelljes, Matthias ; Sivalingam, Sugirthan ; Fobker, Manfred ; Vrachimis, Alexis ; Exler, Anne ; Wenning, Christian Ernst Johannes ; Wempe, Carola ; Penke, Matthias ; Buness, Andreas ; Ludwig, Kerstin ; Muckenthaler, Martina ; Steinbicker, Andrea U.
The adult human body contains about 4 g of iron. About 1–2 mg of iron is absorbed every day, and in healthy individuals, the same amount is excreted. We describe a patient who presents with severe iron deficiency anemia with hemoglobin levels below 6 g/dL and ferritin levels below 30 ng/mL. Although red blood cell concentrates and intravenous iron have been substituted every month for years, body iron stores remain depleted. Diagnostics have included several esophago-gastro-duodenoscopies, colonoscopies, MRI of the liver, repetitive bone marrow biopsies, psychological analysis, application of radioactive iron to determine intact erythropoiesis, and measurement of iron excretion in urine and feces. Typically, gastrointestinal bleeding is a major cause of iron loss. Surprisingly, intestinal iron excretion in stool in the patient was repetitively increased, without gastrointestinal bleeding. Furthermore, whole exome sequencing was performed in the patient and additional family members to identify potential causative genetic variants that may cause intestinal iron loss. Under different inheritance models, several rare mutations were identified, two of which (in CISD1 and KRI1) are likely to be functionally relevant. Intestinal iron loss in the current form has not yet been described and is, with high probability, the cause of the severe iron deficiency anemia in this patient.
Maaser, Anna ; Forstner, Andreas Josef ; Strohmaier, Jana ; Hecker, Julian ; Ludwig, Kerstin ; Sivalingam, Sugirthan ; Streit, Fabian ; Degenhardt, Franziska ; Witt, Stephanie ; Reinbold, Céline S. ; Koller, Anna C. ; Raff, Ruth ; Heilmann-Heimbach, Stefanie ; Fischer, Sascha B. ; Herms, Stefan ; Hoffmann, Per ; Thiele, Holger ; Nürnberg, Peter ; Fier, Heide ; Orozco-Díaz, Guillermo ; Carmenate-Naranjo, Deinys ; Proenza-Barzaga, Niurka ; Auburger, Georg ; Andlauer, Till ; Cichon, Sven ; Marcheco-Teruel, Beatriz ; Mors, Ole ; Rietschel, Marcella ; Nöthen, Markus Maria
Bipolar disorder (BD) is a major psychiatric illness affecting around 1% of the global population. BD is characterized by recurrent manic and depressive episodes, and has an estimated heritability of around 70%. Research has identified the first BD susceptibility genes. However, the underlying pathways and regulatory networks remain largely unknown. Research suggests that the cumulative impact of common alleles with small effects explains only around 25–38% of the phenotypic variance for BD. A plausible hypothesis therefore is that rare, high penetrance variants may contribute to BD risk. The present study investigated the role of rare, nonsynonymous, and potentially functional variants via whole exome sequencing in 15 BD cases from two large, multiply affected families from Cuba. The high prevalence of BD in these pedigrees renders them promising in terms of the identification of genetic risk variants with large effect sizes. In addition, SNP array data were used to calculate polygenic risk scores for affected and unaffected family members. After correction for multiple testing, no significant increase in polygenic risk scores for common, BD-associated genetic variants was found in BD cases compared to healthy relatives. Exome sequencing identified a total of 17 rare and potentially damaging variants in 17 genes. The identified variants were shared by all investigated BD cases in the respective pedigree. The most promising variant was located in the gene SERPING1 (p.L349F), which has been reported previously as a genome-wide significant risk gene for schizophrenia. The present data suggest novel candidate genes for BD susceptibility, and may facilitate the discovery of disease-relevant pathways and regulatory networks.
Clemen, Christoph Stephan ; Marko, Marija ; Strucksberg, Karl-Heinz ; Behrens, Juliane ; Wittig, Ilka ; Gärtner, Linda ; Winter, Lilli ; Chevessier, Frederic ; Matthias, Jan ; Türk, Matthias ; Tangavelou, Karthikeyan ; Schütz, Johanna ; Arhzaouy, Khalid ; Klopffleisch, Karsten ; Hanisch, Franz-Georg ; Rottbauer, Wolfgang ; Blümcke, Ingmar ; Just, Steffen ; Eichinger, Ludwig ; Hofmann, Andreas ; Schröder, Rolf
Protein turnover and quality control by the proteasome is of paramount importance for cell homeostasis. Dysfunction of the proteasome is associated with aging processes and human diseases such as neurodegeneration, cardiomyopathy, and cancer. The regulation, i.e. activation and inhibition of this fundamentally important protein degradation system, is still widely unexplored. We demonstrate here that the evolutionarily highly conserved type II triple-A ATPase VCP and the proteasome inhibitor PSMF1/PI31 interact directly, and antagonistically regulate proteasomal activity. Our data provide novel insights into the regulation of proteasomal activity.