New paper out: Dataset: A therapeutic non-self-reactive SARS-CoV-2 antibody protects from lung pathology in a COVID-19 hamster model. Kreye et al, v1: Kreye, Jakob; Reincke, Momsen; Kornau, Hans-Christian; et al.
  http://dlvr.it/TSZhj0 | Please share #dzne #papers
Dataset: A therapeutic non-self-reactive SARS-CoV-2 antibody protects from lung pathology in a COVID-19 hamster model. Kreye et al, v1 - DZNEPUB

The emergence of SARS-CoV-2 led to pandemic spread of coronavirus disease 2019 (COVID-19), manifesting with respiratory symptoms and multi-organ dysfunction. Detailed characterization of virus-neutralizing antibodies and target epitopes is needed to understand COVID-19 pathophysiology and guide immunization strategies. Among 598 human monoclonal antibodies (mAbs) from ten COVID-19 patients, we identified 40 strongly neutralizing mAbs. The most potent mAb CV07-209 neutralized authentic SARS-CoV-2 with IC50 of 3.1 ng/ml. Crystal structures of two mAbs in complex with the SARS-CoV-2 receptor-binding domain at 2.55 and 2.70 Å revealed a direct block of ACE2 attachment. Interestingly, some of the near-germline SARS-CoV-2 neutralizing mAbs reacted with mammalian self-antigens. Prophylactic and therapeutic application of CV07-209 protected hamsters from SARS-CoV-2 infection, weight loss and lung pathology. Our results show that non-self-reactive virus-neutralizing mAbs elicited during SARS-CoV-2 infection are a promising therapeutic strategy. Kreye, Jakob; Reincke, Momsen; Kornau, Hans-Christian; Sanchez Sendin, Elisa; Dietert, Kristina; Wilson, Ian A.; Prüß, Harald

New paper out: Dataset: PNN unit analysis, v1: Dityatev, Alexander; Dityatev, Alexander
  http://dlvr.it/TSZMhD | Please share #dzne #papers
Dataset: PNN unit analysis, v1 - DZNEPUB

- APNU 1.1 and 2.0 Fiji scripts and Licences - pdf files with a EJN paper to be cited using APNU 1.1 and a Cells paper to be cited using APNU 2.0 - Two raw images of PNNs in control and ketamine-treated rats (any can be selected after running the Fiji script, zoomed, and used for selection of PNN units) - Traced PNN units in control and ketamine-treated rats (can be opened in Fiji) - Exel file with all measured PNN units (group 1 is control, group 2 is Ketamine), all cells, all animals, all analyses Dityatev, Alexander; Dityatev, Alexander

New paper out: Dataset: Early IFN-a signatures and persistent dysfunction are distinguishing features of NK cells in severe COVID-19, v2: Kraemer, Benjamin; Schultze, Joachim L.; Krämer, Benjamin; et al.
  http://dlvr.it/TSZDMX | Please share #dzne #papers
Dataset: Early IFN-a signatures and persistent dysfunction are distinguishing features of NK cells in severe COVID-19, v2 - DZNEPUB

Supplemental tables of the publication 'Early IFN-a signatures and persistent dysfunction are distinguishing features of NK cells in severe COVID-19' Benjamin Krämer et al., 2021. Sup. Table S1: Cohort details [related to all Figures] Sup. Table S2: marker for NK selection and NK subtype marker gene list from the scRNA-seq analyses cohort 1 [related to Figure 2A+D+C and S2A] Sup. Table S3: Module marker gene list and function analysis from the scRNA-seq analyses cohort 1 [related to Figure 2B] Sup. Table S4: Module marker gene list, function analysis, TF and ligand prediction from the scRNA-seq analyses cohort 1 [related to Figure 3C] Sup. Table S5: List of antibodies used for multi-color flow cytometry [related to Figures 1, S1, 2, S2, 3, S3, S4 S6, 7, S7] Sup. Table S6: Number of donors, samples and cells by experiment [related to all figures] Sup. Table S7: Oligo-Primer sequences [related to STAR methods] Benjamin Krämer, Rainer Knoll, Lorenzo Bonaguro, Michael ToVinh, Jan Raabe, Rosario Astaburuaga-García, Jonas Schulte-Schrepping, Kim Melanie Kaiser, Gereon J. Rieke, Jenny Bischoff, Malte B. Monin, Christoph Hoffmeister, Stefan Schlabe, Elena De Domenico, Nico Reusch, Kristian Händler, Gary Reynolds, Nils Blüthgen, Gudrun Hack, Claudia Finnemann, Hans D. Nischalke, Christian P. Strassburg, Emily Stephenson, Yapeng Su, Louis Gardner, Dan Yuan, Daniel Chen, Jason Goldman, Philipp Rosenstiel, Susanne V. Schmidt, Eicke Latz, Kevin Hrusovsky, Andrew J. Ball, Joe M. Johnson, Paul-Albert Koenig, Florian I. Schmidt, Muzlifah Haniffa, James R. Heath, Beate M. Kümmerer, Verena Keitel, Björn Jensen, Paula Stubbemann, Florian Kurth, Leif E. Sander, Birgit Sawitzki, Deutsche COVID-19 OMICS Initiative (DeCOI), Anna C. Aschenbrenner, Joachim L. Schultze, Jacob Nattermann Summary Longitudinal analyses of the innate immune system including earliest time points are essential to understand the immunopathogenesis and clinical course of COVID-19. Here, we performed a detailed characterization of natural killer cells in 205 patients (403 samples, day 2-41 after symptom onset) from four independent cohorts using single-cell transcriptomics and proteomics together with functional studies. We found elevated IFN-α plasma levels in early severe COVD-19 alongside increased NK cell expression of ISGs and genes involved in IFN-α signaling, while upregulation of TNF-induced genes was observed in moderate disease. NK cells exert anti-SARS-CoV-2 activity but are functionally impaired in severe COVID-19. Further, NK cell dysfunction may be relevant for development of fibrotic lung disease in severe COVID-19, as NK cells exhibited impaired anti-fibrotic activity. Our study indicates preferential IFN-α and TNF responses in severe and moderate COVID-19, respectively, and associates prolonged IFN-α-induced NK cell response with poorer disease outcome. Kraemer, Benjamin; Schultze, Joachim L.; Krämer, Benjamin; Bonaguro, Lorenzo; Nattermann, Jacob; Knoll, Rainer; ToVinh, Michael; Raabe, Jan; Aschenbrenner, Anna C.

New paper out: Dataset: Data and statistical analysis for research article on Deficiency in MT5-MMP Supports Branching of Human iPSCs-Derived Neurons and Reduces Expression of GLAST/S100 in iPSCs-Derived Astrocytes published in Cells by Arnst et al. (2021), v1: Dityatev, Alexander
  http://dlvr.it/TSZ4R2 | Please share #dzne #papers
Dataset: Data and statistical analysis for research article on Deficiency in MT5-MMP Supports Branching of Human iPSCs-Derived Neurons and Reduces Expression of GLAST/S100 in iPSCs-Derived Astrocytes published in Cells by Arnst et al. (2021), v1 - DZNEPUB

The data set includes original gel corresponding to Figure 1B and all measurements and statistical analyses used for other figures in the aforementioned article by Nikita Arnst, Pedro Belio-Maira, Laura García-González, Laurie Arnaud, Louise Greetham, Emmanuel Nivet, Santiago Rivera and Alexander Dityatev. We found that MT5-MMP-deficient neurons exhibited an increased number of primary and secondary neurites, as compared to isogenic hiPSC-derived neurons. Moreover, MT5-MMP-deficient astrocytes displayed higher surface area and volume compared to control astrocytes. The MT5-MMP-deficient astrocytes also exhibited decreased GLAST and S100β expression. These findings provide novel insights into the physiological role of MT5-MMP in human neurons and astrocytes, suggesting that therapeutic strategies targeting MT5-MMP should be controlled for potential side effects on astrocytic physiology and neuronal morphology. GraphPad Prism version 9.0 for Windows (GraphPad Software, San Diego, CA, USA) is necessary to read the data for figures 3, 5 ,6. Dityatev, Alexander

Yes - Hold On drum cover

YouTube
New paper out: Dataset: Chimeric autoantibody receptor T cells deplete NMDA receptor-specific B cells. Reincke et al, v1: Reincke, Momsen; Von Wardenburg, Niels; Homeyer, Marie; et al.
  http://dlvr.it/TSYfWd | Please share #dzne #papers
Dataset: Chimeric autoantibody receptor T cells deplete NMDA receptor-specific B cells. Reincke et al, v1 - DZNEPUB

Here we provide raw data and graphpad prism analysis on the animal studies, western blot, histology and ELISpot published in 'Chimeric autoantibody receptor T cells deplete NMDA receptor-specific B cells.' Reincke et al Reincke, Momsen; Von Wardenburg, Niels; Homeyer, Marie; Neurologie, Charite Universitatsmedizin Berlin Klinik fur Neurologie mit Experimenteller; Erkrankungen, Deutsches Zentrum fur Neurodegenerative

New paper out: Dataset: Validity and value of metabolic connectivity in mouse models of β-amyloid and tauopathy, v2: Ruch, Francois; Ruch, Francois
  http://dlvr.it/TSYR55 | Please share #dzne #papers
Dataset: Validity and value of metabolic connectivity in mouse models of β-amyloid and tauopathy, v2 - DZNEPUB

The goal of the current work was to analyze and validate metabolic regional network alterations in three different AD mouse models (β-amyloid and tau) by use of 2-deoxy-2-[18F]fluoro-d-glucose positron emission tomography (FDG-PET) imaging. We compared the results of FDG-µPET MC with conventional VOI-based analysis and behavioral assessment in the Morris water maze (MWM). MC proved to be an accurate and robust indicator of functional connectivity loss in AD mouse models when sample sizes ≥12 are considered. MC loss was observed throughout all brain regions in tauopathy mice, whereas β-amyloid indicated MC loss mainly in spatial learning areas and subcortical networks. This study established a methodological basis for the utilization of MC in different mouse models of AD. MC has the potential to serve as a read-out of pathological changes within neuronal networks in AD models. Ruch, Francois; Ruch, Francois

New paper out: Dataset: Discovering unifying disease recovery dynamics in COVID-19. Frishberg et al., v1: Frishberg, Amit; Shen-Orr, Shai; Frishberg, Amit; et al.
  http://dlvr.it/TSYCGp | Please share #dzne #papers
Dataset: Discovering unifying disease recovery dynamics in COVID-19. Frishberg et al., v1 - DZNEPUB

Supplementary tables for Frishberg et al. 2022 (Cell Reports Medicine).. Frishberg, Amit; Shen-Orr, Shai; Frishberg, Amit; Schultze, Joachim; Kox, Matthijs; Theis, Fabian

New paper out: Data from: Microglial motility is modulated by neuronal activity and correlates with dendritic spine plasticity in the hippocampus of awake mice: Nebeling, Felix; Fuhrmann, Martin; Diseases, German Center for Neurodegenerative
  http://dlvr.it/TSXkYX | Please share #dzne #papers
Data from: Microglial motility is modulated by neuronal activity and correlates with dendritic spine plasticity in the hippocampus of awake mice - DZNEPUB

Microglia, the resident immune cells of the brain, play a complex role in health and disease. They actively survey the brain parenchyma by physically interacting with other cells and structurally shaping the brain. Yet the mechanisms underlying microglial motility and significance for synapse stability, especially in the hippocampus during adulthood, remain widely unresolved. Here we investigated the effect of neuronal activity on microglial motility and the implications for the formation and survival of dendritic spines on hippocampal CA1 neurons in vivo. We used repetitive two-photon in vivo imaging in the hippocampus of awake and anesthetized mice to simultaneously study the motility of microglia and their interaction with dendritic spines. We found that CA3 to CA1 input is sufficient to modulate microglial process motility. Simultaneously, more dendritic spines emerged in mice after awake compared to anesthetized imaging. Interestingly, the rate of microglial contacts with individual dendritic spines and dendrites was associated with the stability, removal, and emergence of dendritic spines. These results suggest that microglia might sense neuronal activity via neurotransmitter release and actively participate in synaptic rewiring of the hippocampal neural network during adulthood. Further, this study has profound relevance for hippocampal learning and memory processes. Nebeling, Felix; Fuhrmann, Martin; Diseases, German Center for Neurodegenerative

New paper out: Dataset: Data from: A human iPSC model of tauopathies engineered for 4R tau isoform expression endogenously develops late-stage neuronal tau pathology: Dannert, Angelika; Schulz, Nathalie; Klimmt, Julien; et al.
  http://dlvr.it/TSXVgR | Please share #dzne #papers
Dataset: Data from: A human iPSC model of tauopathies engineered for 4R tau isoform expression endogenously develops late-stage neuronal tau pathology - DZNEPUB

Tauopathies, such as Alzheimer’s disease and Frontotemporal Dementia, are common neurodegenerative diseases characterized by misfolding, hyperphosphorylation, and aggregation of Tau. Molecular mechanisms underlying Tauopathies are still poorly understood, in part due to a lack of human models endogenously developing major disease hallmarks. Adult Tau isoform expression contributes to Tau pathogenesis but is challenging to replicate in human stem-cell-derived systems, which impedes the formation of late-stage disease phenotypes and, hence, the research on underlying mechanisms and drug development. Here, we show that induction of adult human brain-like 4R Tau isoform expression enables endogenous formation of late-stage Tauopathy hallmarks in iPSC-derived neurons engineered to contain synergistic Tau mutations. Neurons accumulated seeding-competent, hyper-phosphorylated, fibrillar Tau in tangle-like structures. Furthermore, exclusive expression of mutant 4R in the absence of the 3R Tau isoform disproportionately intensified pathology, resulting in highly abundant Tau misfolding and aggregation. Finally, we provide proof-of-principle that our model can be translationally applied both to test chemical disease modulators and evaluate a human Tau PET tracer. Collectively, our model enables novel investigations on endogenous mechanisms of human Tauopathy formation, suggesting a central role of 4R Tau isoform expression for pathogenesis in human neurons. Moreover, it may also serve as a platform supporting urgently needed development of disease-modifying drugs. Dannert, Angelika; Schulz, Nathalie; Klimmt, Julien; Knez, Lea; Groschup, Bernhard; Gonçalves, Carolina; Carraro, Caterina; Schifferer, Martina; Brendel, Matthias; Paquet, Dominik