Abstract:
:Ductal occlusion has been postulated to precipitate focal pancreatic inflammation, while the nature of the primary occluding agents has remained elusive. Neutrophils make use of histone citrullination by peptidyl arginine deiminase-4 (PADI4) in contact to particulate agents to extrude decondensed chromatin as neutrophil extracellular traps (NETs). In high cellular density, NETs form macroscopically visible aggregates. Here we show that such aggregates form inside pancreatic ducts in humans and mice occluding pancreatic ducts and thereby driving pancreatic inflammation. Experimental models indicate that PADI4 is critical for intraductal aggregate formation and that PADI4-deficiency abrogates disease progression. Mechanistically, we identify the pancreatic juice as a strong instigator of neutrophil chromatin extrusion. Characteristic single components of pancreatic juice, such as bicarbonate ions and calcium carbonate crystals, induce aggregated NET formation. Ductal occlusion by aggregated NETs emerges as a pathomechanism with relevance in a plethora of inflammatory conditions involving secretory ducts.
journal_name
Nat Communjournal_title
Nature communicationsauthors
Leppkes M,Maueröder C,Hirth S,Nowecki S,Günther C,Billmeier U,Paulus S,Biermann M,Munoz LE,Hoffmann M,Wildner D,Croxford AL,Waisman A,Mowen K,Jenne DE,Krenn V,Mayerle J,Lerch MM,Schett G,Wirtz S,Neurath MF,Herrmdoi
10.1038/ncomms10973subject
Has Abstractpub_date
2016-03-11 00:00:00pages
10973issn
2041-1723pii
ncomms10973journal_volume
7pub_type
杂志文章abstract::The original version of this Article contained errors in Figures 1 and 3. In Fig. 1b, the label 'IP-PBP3' above the second of the three blots incorrectly read 'IP-PBP1B'. In Fig. 3b, the label 'PBP1B' under the first bar of each chart incorrectly read 'PBP1A'. These errors have been corrected in both the PDF and HTML ...
journal_title:Nature communications
pub_type: 杂志文章,已发布勘误
doi:10.1038/s41467-019-08410-y
更新日期:2019-01-30 00:00:00
abstract::Schizophrenia and bipolar disorder are major psychiatric disorders with high heritability and overlapping genetic variance. Here we perform a genome-wide association study in an ethnically homogeneous cohort of 904 schizophrenia cases and 1,640 controls drawn from the Ashkenazi Jewish population. We identify a novel g...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/ncomms3739
更新日期:2013-01-01 00:00:00
abstract::AML1-ETO (AE) is a fusion transcription factor, generated by the t(8;21) translocation, that functions as a leukemia promoting oncogene. Here, we demonstrate that TATA-Box Binding Protein Associated Factor 1 (TAF1) associates with K43 acetylated AE and this association plays a pivotal role in the proliferation of AE-e...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-019-12735-z
更新日期:2019-10-29 00:00:00
abstract::Prediction of Indian summer monsoon rainfall (ISMR) is at the heart of tropical climate prediction. Despite enormous progress having been made in predicting ISMR since 1886, the operational forecasts during recent decades (1989-2012) have little skill. Here we show, with both dynamical and physical-empirical models, t...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/ncomms8154
更新日期:2015-05-18 00:00:00
abstract::Human Ebp1 is a member of the proliferation-associated 2G4 (PA2G4) family and plays an important role in cancer regulation. Ebp1 shares the methionine aminopeptidase (MetAP) fold and binds to mature 80S ribosomes for translational control. Here, we present a cryo-EM single particle analysis reconstruction of Ebp1 boun...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-020-14603-7
更新日期:2020-02-07 00:00:00
abstract::Intercellular signaling is indispensable for single cells to form complex biological structures, such as biofilms, tissues and organs. The genetic tools available for engineering intercellular signaling, however, are quite limited. Here we exploit the chemical diversity of biological small molecules to de novo design ...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-020-17993-w
更新日期:2020-08-24 00:00:00
abstract::Interfacial reactions between electrode and electrolyte are critical, either beneficial or detrimental, for the performance of rechargeable batteries. The general approaches of controlling interfacial reactions are either applying a coating layer on cathode or modifying the electrolyte chemistry. Here we demonstrate a...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-019-11299-2
更新日期:2019-08-01 00:00:00
abstract::Toll-like receptor 7 (TLR7) senses microbial-derived RNA but can also potentially respond to self-derived RNA. To prevent autoimmune responses, TLR7 is thought to localize in endolysosomes. Contrary to this view, we show here that TLR7 is present on the cell surface of immune cells and that TLR7 responses can be inhib...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/ncomms7119
更新日期:2015-02-04 00:00:00
abstract::A universally accepted explanation for why liquids sometimes vitrify rather than crystallize remains hotly pursued, despite the ubiquity of glass in our everyday lives, the utilization of the glass transition in innumerable modern technologies, and nearly a century of theoretical and experimental investigation. Among ...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-018-07977-2
更新日期:2019-01-08 00:00:00
abstract::An amendment to this paper has been published and can be accessed via a link at the top of the paper. ...
journal_title:Nature communications
pub_type: 已发布勘误
doi:10.1038/s41467-020-14820-0
更新日期:2020-02-21 00:00:00
abstract::A metal-organic hybrid perovskite (CH3NH3PbI3) with three-dimensional framework of metal-halide octahedra has been reported as a low-cost, solution-processable absorber for a thin-film solar cell with a power-conversion efficiency over 20%. Low-dimensional layered perovskites with metal halide slabs separated by the i...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-017-00261-9
更新日期:2017-08-01 00:00:00
abstract::Quasicrystals, materials with aperiodic long-range order, have been found in intermetallics, soft materials such as colloids and supermolecules, and also in two-dimensional monolayer films. Here we present the first example of three-dimensional growth of a single-element quasicrystalline film. Using a hitherto unexplo...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/ncomms3715
更新日期:2013-01-01 00:00:00
abstract::Bioluminescent organisms are likely to have an evolutionary drive towards high radiance. As such, bio-optimized materials derived from them hold great promise for photonic applications. Here, we show that biologically produced fluorescent proteins retain their high brightness even at the maximum density in solid state...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/ncomms6722
更新日期:2014-12-08 00:00:00
abstract::The widespread use of fuel cells is currently limited by the lack of efficient and cost-effective catalysts for the oxygen reduction reaction. Iron-based non-precious metal catalysts exhibit promising activity and stability, as an alternative to state-of-the-art platinum catalysts. However, the identity of the active ...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/ncomms12582
更新日期:2016-08-19 00:00:00
abstract::Seismic tomography provides unique constraints on the morphology, the deformation, and (indirectly) the rheology of subducting slabs. We use teleseismic double-difference P-wave tomography to image with unprecedented clarity the structural complexity of the Izu-Bonin slab. We resolve a tear in the slab in the mantle t...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-019-09279-7
更新日期:2019-03-21 00:00:00
abstract::There are concerns that pneumococcal conjugate vaccines (PCVs) in sub-Saharan Africa sub-optimally interrupt Streptococcus pneumoniae vaccine-serotype (VT) carriage and transmission. Here we assess PCV carriage using rolling, prospective nasopharyngeal carriage surveys between 2015 and 2018, 3.6-7.1 years after Malawi...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-020-15786-9
更新日期:2020-05-06 00:00:00
abstract::Disordered mechanical systems, when strongly deformed, have complex configuration spaces with multiple stable states and pathways connecting them. The topology of such pathways determines which states are smoothly accessible from any part of configuration space. Controlling this topology would allow us to limit access...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-018-06720-1
更新日期:2018-10-16 00:00:00
abstract::Phonons are the main source of relaxation in molecular nanomagnets, and different mechanisms have been proposed in order to explain the wealth of experimental findings. However, very limited experimental investigations on phonons in these systems have been performed so far, yielding no information about their dispersi...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-020-15475-7
更新日期:2020-04-09 00:00:00
abstract::Secondary multidrug transporters use ion concentration gradients to energize the removal from cells of various antibiotics. The Escherichia coli multidrug transporter MdfA exchanges a single proton with a single monovalent cationic drug molecule. This stoichiometry renders the efflux of divalent cationic drugs energet...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/ncomms5615
更新日期:2014-08-08 00:00:00
abstract::In weakly spin-orbit coupled materials, the spin-selective nature of recombination can give rise to large magnetic-field effects, e.g. on the electro-luminescence of molecular semiconductors. Although silicon has weak spin-orbit coupling, observing spin-dependent recombination through magneto-electroluminescence is ch...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-017-02804-6
更新日期:2018-01-26 00:00:00
abstract::Amazon forests have experienced frequent and severe droughts in the past two decades. However, little is known about the large-scale legacy of droughts on carbon stocks and dynamics of forests. Using systematic sampling of forest structure measured by LiDAR waveforms from 2003 to 2008, here we show a significant loss ...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-018-05668-6
更新日期:2018-08-09 00:00:00
abstract::Quantum fluctuations give rise to van der Waals and Casimir forces that dominate the interaction between electrically neutral objects at sub-micron separations. Under the trend of miniaturization, such quantum electrodynamical effects are expected to play an important role in micro- and nano-mechanical devices. Nevert...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/ncomms2842
更新日期:2013-01-01 00:00:00
abstract::Mitochondrial Ca(2+) uptake through the recently discovered Mitochondrial Calcium Uniporter (MCU) is controlled by its gatekeeper Mitochondrial Calcium Uptake 1 (MICU1). However, the physiological and pathological role of MICU1 remains unclear. Here we show that MICU1 is vital for adaptation to postnatal life and for ...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/ncomms10955
更新日期:2016-03-09 00:00:00
abstract::The need for active and stable oxidation catalysts is driven by the demands in production of valuable chemicals, remediation of hydrocarbon pollutants and energy sustainability. Traditional approaches focus on oxygen-activating oxides as support which provides the oxygen activation at the catalyst-support peripheral i...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-020-18017-3
更新日期:2020-08-21 00:00:00
abstract::In the human hematopoietic system, rare self-renewing multipotent long-term hematopoietic stem cells (LT-HSCs) are responsible for the lifelong production of mature blood cells and are the rational target for clinical regenerative therapies. However, the heterogeneity in the hematopoietic stem cell compartment and var...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-019-12726-0
更新日期:2019-10-18 00:00:00
abstract::The original version of this Article contained errors in Fig. 3. In panel a, bars from a chart depicting the percentage of antibody-positive individuals in non-infectious and infectious groups were inadvertently included in place of bars depicting the percentage of infectious individuals, as described in the Article a...
journal_title:Nature communications
pub_type: 杂志文章,已发布勘误
doi:10.1038/s41467-018-03769-w
更新日期:2018-04-11 00:00:00
abstract::Transcription initiation involves the coordinated activities of large multimeric complexes, but little is known about their biogenesis. Here we report several principles underlying the assembly and topological organization of the highly conserved SAGA and NuA4 co-activator complexes, which share the Tra1 subunit. We s...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-019-13243-w
更新日期:2019-11-20 00:00:00
abstract::Chloride intracellular channel 4 (CLIC4) is a mammalian homologue of EXC-4 whose mutation is associated with cystic excretory canals in nematodes. Here we show that CLIC4-null mouse embryos exhibit impaired renal tubulogenesis. In both developing and developed kidneys, CLIC4 is specifically enriched in the proximal tu...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/ncomms10412
更新日期:2016-01-20 00:00:00
abstract::Understanding the response of granular matter to intrusion of solid objects is key to modelling many aspects of behaviour of granular matter, including plastic flow. Here we report a general model for such a quasistatic process. Using a range of experiments, we first show that the relation between the penetration dept...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-018-03344-3
更新日期:2018-03-16 00:00:00
abstract::Angiogenesis is essential for tissue development, wound healing and tissue perfusion, with its dysregulation linked to tumorigenesis, rheumatoid arthritis and heart disease. Here we show that pro-angiogenic stimuli couple to NADPH oxidase-dependent generation of oxidants that catalyse an activating intermolecular-disu...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/ncomms8920
更新日期:2015-08-10 00:00:00