28 Works

Supplementary mass spectonomy data to analyse generation of spliced mutant Kras/RAC2 epitopes

Gerald Willimsky
In vitro proteasome processing of neo-splicetopes does not predict their presentation in vivo Proteasome catalyzed peptide splicing (PCPS) of cancer-driving antigens could generate attractive neoepitopes to be targeted by TCR-based adoptive T cell therapy. Based on a spliced peptide prediction algorithm TCRs were generated against putative KRASG12V and RAC2P29L derived neo-splicetopes with high HLA-A*02:01 binding affinity. TCRs generated in mice with a diverse human TCR repertoire specifically recognized the respective target peptides with high efficacy....

Data from: A large fraction of HLA class I ligands are proteasome-generated spliced peptides

Juliane Liepe, Fabio Marino, John Sidney, Anita Jeko, Daniel E. Bunting, Alessandro Sette, Peter M. Kloetzel, Michael P. H. Stumpf, Albert J. R. Heck & Michele Mishto
The proteasome generates the epitopes presented on human leukocyte antigen (HLA) class I molecules that elicit CD8+ T cell responses. Reports of proteasome-generated spliced epitopes exist, but they have been regarded as rare events. Here, however, we show that the proteasome-generated spliced peptide pool accounts for one-third of the entire HLA class I immunopeptidome in terms of diversity and one-fourth in terms of abundance. This pool also represents a unique set of antigens, possessing particular...

Minor neuropsychological deficits in patients with subjective cognitive decline

Steffen Wolfsgruber, Luca Kleineidam, Jannis Guski, Alexandra Polcher, Ingo Frommann, Sandra Roeske, Eike Jakob Spruth, Christina Franke, Josef Priller, Ingo Kilimann, Stefan Teipel, Katharina Buerger, Daniel Janowitz, Christoph Laske, Martina Buchmann, Oliver Peters, Felix Menne, Manuel Fuentes Casan, Jens Wiltfang, Claudia Bartels, Emrah Düzel, Coraline Metzger, Wenzel Glanz, Manuela Thelen, Annika Spottke … & Michael Wagner
Objective: To determine the nature and extent of minor neuropsychological deficits in patients with subjective cognitive decline (SCD) and their association with cerebrospinal fluid (CSF) biomarkers of Alzheimer’s disease (AD). Method: We analyzed data from n=449 cognitively normal participants (n=209 healthy controls, n=240 SCD patients) from an interim data release of the German Center for Neurodegenerative Diseases Longitudinal Cognitive Impairment and Dementia Study (DELCODE). An extensive neuropsychological test battery was applied at baseline for which...

Data from: Quantitative time-resolved analysis reveals intricate, differential regulation of standard- and immuno-proteasomes

Juliane Liepe, Hermann-Georg Holzhütter, Elena Bellavista, Peter M. Kloetzel, Michael P. H. Stumpf & Michele Mishto
Proteasomal protein degradation is a key determinant of protein half-life and hence of cellular processes ranging from basic metabolism to a host of immunological processes. Despite its importance the mechanisms regulating proteasome activity are only incompletely understood. Here we use an iterative and tightly integrated experimental and modelling approach to develop, explore and validate mechanistic models of proteasomal peptide-hydrolysis dynamics. The 20S proteasome is a dynamic enzyme and its activity varies over time because of...

Sepsis geht alle an!

Rainer Petzina, Herwig Gerlach, Manuela Forster, Christiane Hartog & Matthias Gründling

Sepsis geht alle an! Handlungsempfehlung für Ärztinnen und Ärzte, Pflegekräfte und Angehörige anderer Gesundheitsberufe

, Rainer Petzina, Antje Erler, Ruth Hecker, Manuela Forster, Christiane Hartog, Frank Köhler, Hervig Gerlach, Delia Strunz, Susanne Eberl, Heinrich Geiss, Matthias Gründling, Iris Juditzki, Andreas Podbielski & Arbe Trumann
1. Auflage, Juni 2020

Data from: Investigating the zoonotic origin of the West African Ebola epidemic

Almudena Marí Saéz, Sabrina Weiss, Kathrin Nowak, Vincent Lapeyre, Fee Zimmermann, Ariane Düx, Hjalmar S. Kühl, Moussa Kaba, Sébastien Regnaut, Kevin Merkel, Andreas Sachse, Ursula Thiesen, Lili Villányi, Christophe Boesch, Piotr W. Dabrowski, Aleksandar Radonic, Andreas Nitsche, Siv Aina J. Leendertz, Stefan Petterson, Stephan Becker, Verena Krähling, Emmanuel Couacy-Hymann, Chantal Akoua-Koffi, Natalie Weber, Lars Schaade … & Fabian H. Leendertz
The severe Ebola virus disease epidemic occurring in West Africa stems from a single zoonotic transmission event to a 2-year-old boy in Meliandou, Guinea. We investigated the zoonotic origins of the epidemic using wildlife surveys, interviews, and molecular analyses of bat and environmental samples. We found no evidence for a concurrent outbreak in larger wildlife. Exposure to fruit bats is common in the region, but the index case may have been infected by playing in...

Data from: Re-assessing the diversity of negative strand RNA viruses in insects

Simon Käfer, Sofia Paraskevopoulou, Florian Zirkel, Nicolas Wieseke, Alexander Donath, Malte Petersen, Terry C. Jones, Shanlin Liu, Xin Zhou, Martin Middendorf, Sandra Junglen, Bernhard Misof & Christian Drosten
The spectrum of viruses in insects is important for subjects as diverse as public health, veterinary medicine, food production, and biodiversity conservation. The traditional interest in vector-borne diseases of humans and livestock has drawn the attention of virus studies to hematophagous insect species. However, these represent only a tiny fraction of the broad diversity of Hexapoda, the most speciose group of animals. Here, we systematically probed the diversity of negative strand RNA viruses in the...

Data from: Patellar tendon stiffness is not reduced during pregnancy

Marie Elena Bey, Robert Marzilger, Larry Hinkson, Adamantios Arampatzis & Kirsten Legerlotz
It is believed that hormonal changes during pregnancy lead to an increased compliance in ligaments and tendons, increasing the risk to suffer from connective tissue injuries particularly during exercise. While the laxity of the pelvic ligaments may increase to facilitate childbirth, to our knowledge no study has ever investigated the mechanical properties of human tendons in different stages of pregnancy. Thus, the purpose of our longitudinal study was to investigate the mechanical properties of the...

Data for: Effect of using a cognitive aid on content and feasibility of debriefings of simulated emergencies

Julia Freytag, Fabian Stroben, Wolf Hautz, Dorothea Penders & Juliane Kämmer
Background Adverse events in patient care are often caused by failures in teamwork. Simulation training and its debriefing can contribute to improving teamwork and thus patient care. When conducting debriefings, there are several design factors that can potentially influence learning outcomes. This study examines the use of a cognitive aid to help structure the content of debriefings and compares it with debriefings that are merely roughly structured. In addition, the feasibility of the debriefing, the...

Data from: Predictors of new remote cerebral microbleeds after intravenous thrombolysis for ischemic stroke

Tim Bastian Braemswig, Kersten Villringer, Guillaume Turc, Hebun Erdur, Jochen B. Fiebach, Heinrich J. Audebert, Matthias Endres, Christian H. Nolte & Jan F. Scheitz
Objective: To assess the frequency, associated factors, and underlying vasculopathy of new remote cerebral microbleeds (CMB), as well as the risk of concomitant hemorrhagic complications related to new CMBs, after intravenous thrombolysis (IVT) in acute stroke patients. Methods: We conducted an observational study using data from our local thrombolysis registry. We included consecutive stroke patients with MRI (3-Tesla)-based IVT and a follow-up MRI the next day between 2008–2017 (n=396). Only CMBs located outside of the...

Data from: Hodge decomposition of wall shear stress vector fields characterizing biological flows

Faniry H. Razafindrazaka, Pavel Yevtushenko, Konstantin Poelke, Konrad Polthier & Leonid Goubergrits
A discrete boundary-sensitive Hodge decomposition is proposed as a central tool for the analysis of wall shear stress (WSS) vector fields in aortic blood flows. The method is based on novel results for the smooth and discrete Hodge-Morrey-Friedrichs decomposition on manifolds with boundary and subdivides the WSS vector field into five components: gradient (curl-free), co-gradient (divergence-free), and three harmonic fields induced from the boundary, which are called the center, Neumann and Dirichlet fields. First, an...

Hygiene in der Arztpraxis - Infektionsprävention in der ambulanten Versorgung

Tobias Kramer, Andreas Suck, Hedwig François-Kettner, Petra Gastmeier, Bernd Gruber, Katja Heinze, Elena Kortemeyer, Moritz Liewer, Pamela Reißner, Katharina Rubin, Cornelia Schmitz, Anke Westerberg, Cornelia Winten & Conny Wiebe-Franzen
Die Handlungsempfehlung wendet sich an Sie als Ärzte, Betreiber und Medizinische Fachangestellte (MFA) in ambulanten Praxen und Medizinischen Versorgungszentren (MVZ) sowie an zugehörige Ausbildungsbereiche. Durch ausgewählte praxisnahe Beispiele gibt Ihnen die Handlungsempfehlung die Möglichkeit, Infektionsrisiken im täglichen Umgang mit ihren Patienten zu identifizieren. Die Empfehlungen beleuchten eine Auswahl relevanter Aspekte zur Sicherung ihrer Patienten und Mitarbeitenden. Sie bilden den Stand des aktuellen Wissens ab und stellen in ihrer Umsetzung eine Mindestanforderung dar. Daher fokussiert die...

Data from: Clinical presentation and management of SMART syndrome

Sebastian F. Winter, Joshua P. Klein, Eugene J. Vaios, Philipp Karschnia, Eudocia Q. Lee, Helen A. Shih, Franziska Loebel & Jorg Dietrich
Stroke-like migraine attacks after radiation therapy (SMART) syndrome represents a rare but serious condition manifesting years after cranial radiation therapy (RT). Characterized by migraine-type headaches, stroke-like deficits and/or seizures and MR imaging abnormalities, including cortical gyriform enhancement in irradiated brain regions, SMART remains diagnostically and therapeutically challenging. Distinction from tumor progression is difficult and treatment options are limited. Although frequently reversible, SMART episodes can recur and effectuate persistent neurologic and/or imaging sequelae.

Current Advances, Challenges, and Opportunities in Stroke Research, Management, and Care

Julius Emmrich, Samuel Knauss & Matthias Endres
Stroke is the second leading cause of death (after heart disease) and a major cause of disability worldwide. Also called a brain attack, typical symptoms of stroke include sudden one-sided weakness and numbness in the face and arm as well as altered speech. Most strokes are ischaemic strokes where arterial blood flow to the brain is interrupted by an embolism or thrombosis. Strokes are less frequently caused by haemorrhage. Non-contrast cranial computed tomography (CT) imaging,...

A comprehensive survey among statistical members of medical ethics committees in Germany on their personal impression of completeness and correctness of biostatistical aspects of submitted study protocols

Geraldine Rauch
Original data of a comprehensive survey among statistical members of medical ethics committees in Germany on their personal impression of completeness and correctness of biostatistical aspects of submitted study protocols. To enable reproduction of the results presented in the corresponding paper, the final dataset is freely available here, without any information on the medical ethics committee’s federal state to avoid any risk of potential re-identification.

Intravital quantification reveals dynamic calcium concentration changes across B cell differentiation stages

Carolin Ulbricht, Ruth Leben, Asylkhan Rakhymzhan, Frank Kirchhoff, Lars Nitschke, Helena Radbruch, Raluca Niesner & Anja Hauser
Calcium is a universal second messenger present in all eukaryotic cells. The mobilization and storage of Ca2+ ions drives a number of signaling-related processes, stress-responses or metabolic changes, all of which are relevant for the development of immune cells and their adaption to pathogens. Here, we introduce the FRET-reporter mouse YellowCaB expressing the genetically encoded calcium indicator TN-XXL in B lymphocytes. Calcium-induced conformation change of TN-XXL results in FRET-donor quenching measurable by two-photon fluorescence lifetime...

Prospective Quantification of CSF Biomarkers in Antibody-Mediated Encephalitis

Gregory Day, Melanie L. Yarbrough, Peter Körtvelyessy, Harald Prüss, Robert C. Bucelli, Marvin J. Fritzler, Warren Mason, David F. Tang-Wai, Claude Steriade, Julien Hébert, Rachel L. Henson, Elizabeth M. Herries, Jack H. Ladenson, A. Sebastian Lopez-Chiriboga, Neill R. Graff-Radford, John C. Morris & Anne Fagan
Objective: To determine whether neuronal and neuroaxonal injury, neuroinflammation, and synaptic dysfunction associate with clinical course and outcomes in antibody-mediated encephalitis (AME), we measured biomarkers of these processes in CSF from patients presenting with AME and cognitively normal individuals. Methods: Biomarkers of neuronal (total tau, VILIP-1) and neuroaxonal damage (neurofilament light chain [NfL]), inflammation (YKL-40), and synaptic function (neurogranin, SNAP-25) were measured in CSF obtained from 45 patients at the time of diagnosis of NMDA...

Der Kinder-und Jugendgesundheitsdienst

Peter Tinnemann & Ute Teichert

Sepsis geht alle an! Was Sie darüber wissen sollten

Rainer Petzina, , Antje Erler, Ruth Hecker, Christiane Hartog, Frank Köhler, Manuela Forster, Herwig Gerlach, Delia Strunz, Susanne Ebert, Eike Eymers, Jutta F. Maywald Kessel & Arne Tumann
1. Auflage, Juni 2020

Data from: Presynaptic GABAB receptors functionally uncouple somatostatin interneurons from the active hippocampal network

Sam A. Booker, Harumi Harada, Claudio Elguate, Julia Bank, Bartos Marlene, Akos Kulik & Imre Vida
Information processing in cortical neuronal networks relies on properly balanced excitatory and inhibitory neurotransmission. A ubiquitous motif for maintaining this balance is the somatostatin interneuron (SOM-IN) feedback microcircuit. Here, we investigate the modulation of this microcircuit by presynaptic GABAB receptors (GABABRs) in the rat hippocampus. Whole-cell recordings from SOM-INs reveal that both excitatory and inhibitory synaptic inputs are strongly inhibited by GABABRs, while optogenetic activation of the interneurons shows that their inhibitory output is also...

Unvalidated R source code

Geraldine Rauch
Univalidated R source code implmenting a performance comparison of adaptive sample size recalculation rules including in particular the new performance score by Herrmann et al. (2019)

Appendix: Association between hemostatic profile and migraine: a Mendelian randomization analysis

Yanjun Guo, Pamela Rist, Maria Sabater-Lleal, Paul De Vries, Nicholas Smith, Paul Ridker, Tobias Kurth & Daniel Chasman
Objective: To assess support for a causal relationship between hemostatic measures and migraine susceptibility using genetic instrumental analysis. Methods: Two-sample Mendelian randomization (MR) instrumental leveraging available genome-wide association study (GWAS) summary statistics was applied to hemostatic measures as potential causal for migraine and its subtypes, migraine with aura (MA) and migraine without aura (MO). Twelve blood-based measures of hemostasis were examined, including plasma level or activity of eight hemostatic factors and two fibrinopeptides together with...

Data from: 7 Tesla MRI of the ex vivo human brain at 100 micron resolution

Brian L. Edlow, Azma Mareyam, Andreas Horn, Jonathan R. Polimeni, Thomas Witzel, M. Dylan Tisdall, Jean Augustinack, Jason P. Stockmann, Bram R. Diamond, Allison Stevens, Lee S. Tirrell, Rebecca D. Folkerth, Lawrence L. Wald, Bruce Fischl & Andre Van Der Kouwe
We present an ultra-high resolution MRI dataset of an ex vivo human brain specimen. The brain specimen was donated by a 58-year-old woman who had no history of neurological disease and died of non-neurological causes. After fixation in 10% formalin, the specimen was imaged on a 7 Tesla MRI scanner at 100 µm isotropic resolution using a custom-built 31-channel receive array coil. Single-echo multi-flip Fast Low-Angle SHot (FLASH) data were acquired over 100 hours of...

Data from: Reliability of single-use PEEP-valves attached to self-inflating bags during manual ventilation of neonates – an in vitro study

Julia Christine Hartung, Silke Wilitzki, Marta Thio-Lluch, Arjan B. Te Pas, Gerd Schmalisch & Charles Christoph Roehr
Introduction International resuscitation guidelines suggest to use positive end-expiratory pressure (PEEP) during manual ventilation of neonates. Aim of our study was to test the reliability of self-inflating bags (SIB) with single-use PEEP valves regarding PEEP delivery and the effect of different peak inflation pressures (PIP) and ventilation rates (VR) on the delivered PEEP. Methods Ten new single-use PEEP valves from 5 manufacturers were tested by ventilating an intubated 1kg neonatal manikin containing a lung model...

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  • Charité
  • Charité - University Medicine Berlin
  • University Hospital Schleswig-Holstein
  • Vivantes Klinikum
  • Becton Dickinson (Germany)
  • Massachusetts General Hospital
  • Sana Klinikum
  • Humboldt University of Berlin
  • Johnson & Johnson (Germany)
  • Klinik Bavaria