TY  - JOUR
A1  - Straub, Tobias
A1  - Freudenberg, Marina A.
A1  - Schleicher, Ulrike
A1  - Bogdan, Christian
A1  - Gasteiger, Georg
A1  - Pircher, Hanspeter
T1  - Bacterial coinfection restrains antiviral CD8 T-cell response via LPS-induced inhibitory NK cells
JF  - Nature Communications
N2  - Infection of specific pathogen-free mice with lymphocytic choriomeningitis virus (LCMV) is a widely used model to study antiviral T-cell immunity. Infections in the real world, however, are often accompanied by coinfections with unrelated pathogens. Here we show that in mice, systemic coinfection with E. coli suppresses the LCMV-specific cytotoxic T-lymphocyte (CTL) response and virus elimination in a NK cell- and TLR2/4-dependent manner. Soluble TLR4 ligand LPS also induces NK cell-mediated negative CTL regulation during LCMV infection. NK cells in LPS-treated mice suppress clonal expansion of LCMV-specific CTLs by a NKG2D- or NCR1-independent but perforin-dependent mechanism. These results suggest a TLR4-mediated immunoregulatory role of NK cells during viral-bacterial coinfections.
KW  - Bacterial infection
KW  - infection
KW  - lymphocyte activation
KW  - viral infection
Y1  - 2018
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-240075
VL  - 9
ER  - 
TY  - JOUR
A1  - Vujanić, Gordan M.
A1  - Gessler, Manfred
A1  - Ooms, Ariadne H. A. G.
A1  - Collini, Paola
A1  - Coulomb-l'Hermine, Aurore
A1  - D'Hooghe, Ellen
A1  - de Krijger, Ronald R.
A1  - Perotti, Daniela
A1  - Pritchard-Jones, Kathy
A1  - Vokuhl, Christian
A1  - van den Heuvel-Eibrink, Marry M.
A1  - Graf, Norbert
T1  - The UMBRELLA SIOP–RTSG 2016 Wilms tumour pathology and molecular biology protocol
JF  - Nature Reviews Urology
N2  - On the basis of the results of previous national and international trials and studies, the Renal Tumour Study Group of the International Society of Paediatric Oncology (SIOP–RTSG) has developed a new study protocol for paediatric renal tumours: the UMBRELLA SIOP–RTSG 2016 protocol (the UMBRELLA protocol). Currently, the overall outcomes of patients with Wilms tumour are excellent, but subgroups with poor prognosis and increased relapse rates still exist. The identification of these subgroups is of utmost importance to improve treatment stratification, which might lead to reduction of the direct and late effects of chemotherapy. The UMBRELLA protocol aims to validate new prognostic factors, such as blastemal tumour volume and molecular markers, to further improve outcome. To achieve this aim, large, international, high-quality databases are needed, which dictate optimization and international harmonization of specimen handling and comprehensive sampling of biological material, refine definitions and improve logistics for expert review. To promote broad implementation of the UMBRELLA protocol, the updated SIOP–RTSG pathology and molecular biology protocol for Wilms tumours has been outlined, which is a consensus from the SIOP–RTSG pathology panel.
KW  - molecular biology
KW  - paediatric cancer
KW  - pathology
KW  - renal cancer
Y1  - 2018
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-233265
VL  - 15
ER  - 
TY  - JOUR
A1  - Tan, Z. B.
A1  - Elo, T.
A1  - Puska, A.
A1  - Sarkar, J.
A1  - Lähteenmäki, P.
A1  - Duerr, F.
A1  - Gould, C.
A1  - Molenkamp, L. W.
A1  - Nagaev, K. E.
A1  - Hakonen, P. J.
T1  - Hanbury-Brown and Twiss exchange and non-equilibrium-induced correlations in disordered, four-terminal graphene-ribbon conductor
JF  - Scientific Reports
N2  - We have investigated current-current correlations in a cross-shaped conductor made of graphene. The mean free path of charge carriers is on the order of the ribbon width which leads to a hybrid conductor where there is diffusive transport in the device arms while the central connection region displays near ballistic transport. Our data on auto and cross correlations deviate from the predictions of Landauer-Büttiker theory, and agreement can be obtained only by taking into account contributions from non-thermal electron distributions at the inlets to the semiballistic center, in which the partition noise becomes strongly modified. The experimental results display distinct Hanbury – Brown and Twiss (HBT) exchange correlations, the strength of which is boosted by the non-equilibrium occupation-number fluctuations internal to this hybrid conductor. Our work demonstrates that variation in electron coherence along atomically-thin, two-dimensional conductors has significant implications on their noise and cross correlation properties.
KW  - conductive hybrid
KW  - partition noise
KW  - occupation number fluctuations
KW  - current-current correlation
KW  - device arm
Y1  - 2018
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-240348
VL  - 8
ER  - 
TY  - JOUR
A1  - Woodcock, B. A.
A1  - Garratt, M. P. D.
A1  - Powney, G. D.
A1  - Shaw, R. F.
A1  - Osborne, J. L.
A1  - Soroka, J.
A1  - Lindström, S. A. M.
A1  - Stanley, D.
A1  - Ouvrard, P.
A1  - Edwards, M. E.
A1  - Jauker, F.
A1  - McCracken, M. E.
A1  - Zou, Y.
A1  - Potts, S. G.
A1  - Rundlöf, M.
A1  - Noriega, J. A.
A1  - Greenop, A.
A1  - Smith, H. G.
A1  - Bommarco, R.
A1  - van der Werf, W.
A1  - Stout, J. C.
A1  - Steffan-Dewenter, I.
A1  - Morandin, L.
A1  - Bullock, J. M.
A1  - Pywell, R. F.
T1  - Meta-analysis reveals that pollinator functional diversity and abundance enhance crop pollination and yield
JF  - Nature Communications
N2  - How insects promote crop pollination remains poorly understood in terms of the contribution of functional trait differences between species. We used meta-analyses to test for correlations between community abundance, species richness and functional trait metrics with oilseed rape yield, a globally important crop. While overall abundance is consistently important in predicting yield, functional divergence between species traits also showed a positive correlation. This result supports the complementarity hypothesis that pollination function is maintained by non-overlapping trait distributions. In artificially constructed communities (mesocosms), species richness is positively correlated with yield, although this effect is not seen under field conditions. As traits of the dominant species do not predict yield above that attributed to the effect of abundance alone, we find no evidence in support of the mass ratio hypothesis. Management practices increasing not just pollinator abundance, but also functional divergence, could benefit oilseed rape agriculture.
KW  - agroecology
KW  - agriculture
KW  - ecosystem services
KW  - environmental sciences
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-233787
VL  - 10
ER  - 
TY  - JOUR
A1  - Went, Molly
A1  - Sud, Amit
A1  - Speedy, Helen
A1  - Sunter, Nicola J.
A1  - Försti, Asta
A1  - Law, Philip J.
A1  - Johnson, David C.
A1  - Mirabella, Fabio
A1  - Holroyd, Amy
A1  - Li, Ni
A1  - Orlando, Giulia
A1  - Weinhold, Niels
A1  - van Duin, Mark
A1  - Chen, Bowang
A1  - Mitchell, Jonathan S.
A1  - Mansouri, Larry
A1  - Juliusson, Gunnar
A1  - Smedby, Karin E
A1  - Jayne, Sandrine
A1  - Majid, Aneela
A1  - Dearden, Claire
A1  - Allsup, David J.
A1  - Bailey, James R.
A1  - Pratt, Guy
A1  - Pepper, Chris
A1  - Fegan, Chris
A1  - Rosenquist, Richard
A1  - Kuiper, Rowan
A1  - Stephens, Owen W.
A1  - Bertsch, Uta
A1  - Broderick, Peter
A1  - Einsele, Hermann
A1  - Gregory, Walter M.
A1  - Hillengass, Jens
A1  - Hoffmann, Per
A1  - Jackson, Graham H.
A1  - Jöckel, Karl-Heinz
A1  - Nickel, Jolanta
A1  - Nöthen, Markus M.
A1  - da Silva Filho, Miguel Inacio
A1  - Thomsen, Hauke
A1  - Walker, Brian A.
A1  - Broyl, Annemiek
A1  - Davies, Faith E.
A1  - Hansson, Markus
A1  - Goldschmidt, Hartmut
A1  - Dyer, Martin J. S.
A1  - Kaiser, Martin
A1  - Sonneveld, Pieter
A1  - Morgan, Gareth J.
A1  - Hemminki, Kari
A1  - Nilsson, Björn
A1  - Catovsky, Daniel
A1  - Allan, James M.
A1  - Houlston, Richard S.
T1  - Genetic correlation between multiple myeloma and chronic lymphocytic leukaemia provides evidence for shared aetiology
JF  - Blood Cancer Journal
N2  - The clustering of different types of B-cell malignancies in families raises the possibility of shared aetiology. To examine this, we performed cross-trait linkage disequilibrium (LD)-score regression of multiple myeloma (MM) and chronic lymphocytic leukaemia (CLL) genome-wide association study (GWAS) data sets, totalling 11,734 cases and 29,468 controls. A significant genetic correlation between these two B-cell malignancies was shown (Rg = 0.4, P = 0.0046). Furthermore, four of the 45 known CLL risk loci were shown to associate with MM risk and five of the 23 known MM risk loci associate with CLL risk. By integrating eQTL, Hi-C and ChIP-seq data, we show that these pleiotropic risk loci are enriched for B-cell regulatory elements and implicate B-cell developmental genes. These data identify shared biological pathways influencing the development of CLL and, MM and further our understanding of the aetiological basis of these B-cell malignancies.
KW  - cancer genetics
KW  - myeloma
Y1  - 2018
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-233627
VL  - 9
ER  - 
TY  - JOUR
A1  - Wen, Lai
A1  - Feil, Susanne
A1  - Wolters, Markus
A1  - Thunemann, Martin
A1  - Regler, Frank
A1  - Schmidt, Kjestine
A1  - Friebe, Andreas
A1  - Olbrich, Marcus
A1  - Langer, Harald
A1  - Gawaz, Meinrad
A1  - de Wit, Cor
A1  - Feil, Robert
T1  - A shear-dependent NO-cGMP-cGKI cascade in platelets acts as an auto-regulatory brake of thrombosis
JF  - Nature Communications
N2  - Mechanisms that limit thrombosis are poorly defined. One of the few known endogenous platelet inhibitors is nitric oxide (NO). NO activates NO sensitive guanylyl cyclase (NO-GC) in platelets, resulting in an increase of cyclic guanosine monophosphate (cGMP). Here we show, using cGMP sensor mice to study spatiotemporal dynamics of platelet cGMP, that NO-induced cGMP production in pre-activated platelets is strongly shear-dependent. We delineate a new mode of platelet-inhibitory mechanotransduction via shear-activated NO-GC followed by cGMP synthesis, activation of cGMP-dependent protein kinase I (cGKI), and suppression of Ca2+ signaling. Correlative profiling of cGMP dynamics and thrombus formation in vivo indicates that high cGMP concentrations in shear-exposed platelets at the thrombus periphery limit thrombosis, primarily through facilitation of thrombus dissolution. We propose that an increase in shear stress during thrombus growth activates the NO-cGMP-cGKI pathway, which acts as an auto-regulatory brake to prevent vessel occlusion, while preserving wound closure under low shear.
KW  - calcium signalling
KW  - fluorescence imaging
KW  - platelets
KW  - thrombosis
Y1  - 2018
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-233616
VL  - 9
ER  - 
TY  - JOUR
A1  - Welz, M.
A1  - Eickhoff, S.
A1  - Abdullah, Z.
A1  - Trebicka, J.
A1  - Gartlan, K. H.
A1  - Spicer, J. A.
A1  - Demetris, A. J.
A1  - Akhlaghi, H.
A1  - Anton, M.
A1  - Manske, K.
A1  - Zehn, D.
A1  - Nieswandt, B.
A1  - Kurts, C.
A1  - Trapani, J. A.
A1  - Knolle, P.
A1  - Wohlleber, D.
A1  - Kastenmüller, W.
T1  - Perforin inhibition protects from lethal endothelial damage during fulminant viral hepatitis
JF  - Nature Communications
N2  - CD8 T cells protect the liver against viral infection, but can also cause severe liver damage that may even lead to organ failure. Given the lack of mechanistic insights and specific treatment options in patients with acute fulminant hepatitis, we develop a mouse model reflecting a severe acute virus-induced CD8 T cell-mediated hepatitis. Here we show that antigen-specific CD8 T cells induce liver damage in a perforin-dependent manner, yet liver failure is not caused by effector responses targeting virus-infected hepatocytes alone. Additionally, CD8 T cell mediated elimination of cross-presenting liver sinusoidal endothelial cells causes endothelial damage that leads to a dramatically impaired sinusoidal perfusion and indirectly to hepatocyte death. With the identification of perforin-mediated killing as a critical pathophysiologic mechanism of liver failure and the protective function of a new class of perforin inhibitor, our study opens new potential therapeutic angles for fulminant viral hepatitis.
KW  - cytotoxic T cells
KW  - hepatology
KW  - imaging the immune system
KW  - viral infection
Y1  - 2018
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-233593
VL  - 9
ER  - 
TY  - JOUR
A1  - Walker, Brian A.
A1  - Mavrommatis, Konstantinos
A1  - Wardell, Christopher P.
A1  - Ashby, T. Cody
A1  - Bauer, Michael
A1  - Davies, Faith
A1  - Rosenthal, Adam
A1  - Wang, Hongwei
A1  - Qu, Pingping
A1  - Hoering, Antje
A1  - Samur, Mehmet
A1  - Towfic, Fadi
A1  - Ortiz, Maria
A1  - Flynt, Erin
A1  - Yu, Zhinuan
A1  - Yang, Zhihong
A1  - Rozelle, Dan
A1  - Obenauer, John
A1  - Trotter, Matthew
A1  - Auclair, Daniel
A1  - Keats, Jonathan
A1  - Bolli, Niccolo
A1  - Fulciniti, Mariateresa
A1  - Szalat, Raphael
A1  - Moreau, Phillipe
A1  - Durie, Brian
A1  - Stewart, A. Keith
A1  - Goldschmidt, Hartmut
A1  - Raab, Marc S.
A1  - Einsele, Hermann
A1  - Sonneveld, Pieter
A1  - San Miguel, Jesus
A1  - Lonial, Sagar
A1  - Jackson, Graham H.
A1  - Anderson, Kenneth C.
A1  - Avet-Loiseau, Herve
A1  - Munshi, Nikhil
A1  - Thakurta, Anjan
A1  - Morgan, Gareth
T1  - A high-risk, Double-Hit, group of newly diagnosed myeloma identified by genomic analysis
JF  - Leukemia
N2  - Patients with newly diagnosed multiple myeloma (NDMM) with high-risk disease are in need of new treatment strategies to improve the outcomes. Multiple clinical, cytogenetic, or gene expression features have been used to identify high-risk patients, each of which has significant weaknesses. Inclusion of molecular features into risk stratification could resolve the current challenges. In a genome-wide analysis of the largest set of molecular and clinical data established to date from NDMM, as part of the Myeloma Genome Project, we have defined DNA drivers of aggressive clinical behavior. Whole-genome and exome data from 1273 NDMM patients identified genetic factors that contribute significantly to progression free survival (PFS) and overall survival (OS) (cumulative R2 = 18.4% and 25.2%, respectively). Integrating DNA drivers and clinical data into a Cox model using 784 patients with ISS, age, PFS, OS, and genomic data, the model has a cumlative R2 of 34.3% for PFS and 46.5% for OS. A high-risk subgroup was defined by recursive partitioning using either a) bi-allelic TP53 inactivation or b) amplification (≥4 copies) of CKS1B (1q21) on the background of International Staging System III, comprising 6.1% of the population (median PFS = 15.4 months; OS = 20.7 months) that was validated in an independent dataset. Double-Hit patients have a dire prognosis despite modern therapies and should be considered for novel therapeutic approaches.
KW  - cancer genomics
KW  - risk factors
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-233299
VL  - 33
ER  - 
TY  - JOUR
A1  - Wegert, Jenny
A1  - Vokuhl, Christian
A1  - Collord, Grace
A1  - Del Castillo Velasco-Herrera, Martin
A1  - Farndon, Sarah J.
A1  - Guzzo, Charlotte
A1  - Jorgensen, Mette
A1  - Anderson, John
A1  - Slater, Olga
A1  - Duncan, Catriona
A1  - Bausenwein, Sabrina
A1  - Streitenberger, Heike
A1  - Ziegler, Barbara
A1  - Furtwängler, Rhoikos
A1  - Graf, Norbert
A1  - Stratton, Michael R.
A1  - Campbell, Peter J.
A1  - Jones, David TW
A1  - Koelsche, Christian
A1  - Pfister, Stefan M.
A1  - Mifsud, William
A1  - Sebire, Neil
A1  - Sparber-Sauer, Monika
A1  - Koscielniak, Ewa
A1  - Rosenwald, Andreas
A1  - Gessler, Manfred
A1  - Behjati, Sam
T1  - Recurrent intragenic rearrangements of EGFR and BRAF in soft tissue tumors of infants
JF  - Nature Communications
N2  - Soft tissue tumors of infancy encompass an overlapping spectrum of diseases that pose unique diagnostic and clinical challenges. We studied genomes and transcriptomes of cryptogenic congenital mesoblastic nephroma (CMN), and extended our findings to five anatomically or histologically related soft tissue tumors: infantile fibrosarcoma (IFS), nephroblastomatosis, Wilms tumor, malignant rhabdoid tumor, and clear cell sarcoma of the kidney. A key finding is recurrent mutation of EGFR in CMN by internal tandem duplication of the kinase domain, thus delineating CMN from other childhood renal tumors. Furthermore, we identify BRAF intragenic rearrangements in CMN and IFS. Collectively these findings reveal novel diagnostic markers and therapeutic strategies and highlight a prominent role of isolated intragenic rearrangements as drivers of infant tumors.
KW  - cancer
KW  - genetics
Y1  - 2018
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-233446
VL  - 9
ER  - 
TY  - JOUR
A1  - Waldherr, Max
A1  - Lundt, Nils
A1  - Klaas, Martin
A1  - Betzold, Simon
A1  - Wurdack, Matthias
A1  - Baumann, Vasilij
A1  - Estrecho, Eliezer
A1  - Nalitov, Anton
A1  - Cherotchenko, Evgenia
A1  - Cai, Hui
A1  - Ostrovskaya, Elena A.
A1  - Kavokin, Alexey V.
A1  - Tongay, Sefaattin
A1  - Klembt, Sebastian
A1  - Höfling, Sven
A1  - Schneider, Christian
T1  - Observation of bosonic condensation in a hybrid monolayer MoSe2-GaAs microcavity
JF  - Nature Communications
N2  - Bosonic condensation belongs to the most intriguing phenomena in physics, and was mostly reserved for experiments with ultra-cold quantum gases. More recently, it became accessible in exciton-based solid-state systems at elevated temperatures. Here, we demonstrate bosonic condensation driven by excitons hosted in an atomically thin layer of MoSe2, strongly coupled to light in a solid-state resonator. The structure is operated in the regime of collective strong coupling between a Tamm-plasmon resonance, GaAs quantum well excitons, and two-dimensional excitons confined in the monolayer crystal. Polariton condensation in a monolayer crystal manifests by a superlinear increase of emission intensity from the hybrid polariton mode, its density-dependent blueshift, and a dramatic collapse of the emission linewidth, a hallmark of temporal coherence. Importantly, we observe a significant spin-polarization in the injected polariton condensate, a fingerprint for spin-valley locking in monolayer excitons. Our results pave the way towards highly nonlinear, coherent valleytronic devices and light sources.
KW  - polaritons
KW  - two-dimensional materials
Y1  - 2018
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-233280
VL  - 9
ER  -