Search results for "Triggering"
showing 10 items of 25 documents
Interleukin-22 and interleukin-22-producing NKp44+ natural killer cells in subclinical gut inflammation in ankylosing spondylitis
2012
Objective The intestinal inflammation observed in patients with ankylosing spondylitis (AS) is characterized by an overexpression of interleukin-23 (IL-23). IL-23 is known to regulate IL-22 production through lamina propria NKp44+ natural killer (NK) cells, which are thought to be involved in protective mucosal mechanisms. This study was undertaken to evaluate the frequency of NKp44+ NK cells and the expression of IL-22 in the ileum of AS patients. Methods Tissue NKp44+ NK cells, NKp46+ NK cells, and IL-22–producing cells were analyzed by flow cytometry. Quantitative gene expression analysis of IL-22, IL-23, IL-17, STAT-3, and mucin 1 (MUC-1) was performed by reverse transcriptase–polymeras…
Inhibition of the NKp30 activating receptor by pp65 of human cytomegalovirus.
2005
Human cytomegalovirus, a chief pathogen in immunocompromised people, can persist in a healthy immunocompetent host throughout life without being eliminated by the immune system. Here we show that pp65, the main tegument protein of human cytomegalovirus, inhibited natural killer cell cytotoxicity by an interaction with the activating receptor NKp30. This interaction was direct and specific, leading to dissociation of the linked CD3zeta from NKp30 and, consequently, to reduced killing. Thus, pp65 is a ligand for the NKp30 receptor and demonstrates a unique mechanism by which an intracellular viral protein causes general suppression of natural killer cell cytotoxicity by specific interaction w…
Distinct Signaling Cascades of TREM-1, TLR and NLR in Neutrophils and Monocytic Cells
2013
Triggering receptor expressed on myeloid cells 1 (TREM-1) is an important mediator of innate inflammatory responses in microbial infections and sepsis. TREM-1 ligation on neutrophils (PMN) or monocytes results in the production of proinflammatory cytokines. Engagement of TREM-1 induces the activation of MAP kinases as well as rapid Ca<sup>2+</sup> mobilization. However, a detailed understanding of TREM-1 signaling pathways is currently lacking. We evaluated the TREM-1 signaling hierarchy in monocytic cells and found that the acute myeloid leukemia cell line MUTZ-3 expresses TREM-1 in a natural and functional manner. We compared essential signaling molecules of the TREM-1, TLR an…
Deep-seated gravitational slope deformations in western Sicily: Controlling factors, triggering mechanisms, and morphoevolutionary models
2014
Abstract A study of deep-seated gravitational slope deformation (DSGSD) phenomena affecting areas of various geological and geomorphological settings in western Sicily is described. Western Sicily is underlain by a thin-skinned imbricate wedge of Meso–Cenozoic carbonate and siliciclastic rocks that formed by the stacking of several thrust nappes over the Iblean foreland. Locally, the original thrust sheets are folded and cut by high-angle faults. Large areas of western Sicily now display high relief energy due to Plio-Pleistocene block-faulting and uplifting, and the Quaternary morphogenetic phases are characterised by incision, thereby triggering widespread DSGSDs. To identify controlling …
Using synchrotrons and XFELs for time-resolved X-ray crystallography and solution scattering experiments on biomolecules
2015
International audience; Time-resolved structural information is key to understand the mechanism of biological processes, such as catalysis and signalling. Recent developments in X-ray sources as well as data collection and analysis methods are making routine time-resolved X-ray crystallography and solution scattering experiments a real possibility for structural biologists. Here we review the information that can be obtained from these techniques and discuss the considerations that must be taken into account when designing a time-resolved experiment.
Dynamic Triggering of Mud Volcano Eruptions During the 2016–2017 Central Italy Seismic Sequence
2017
©2017. American Geophysical Union. All Rights Reserved. On 24 August 2016 a seismic event (Mw6.0) was the first of the long Central Italy sequence (ongoing at the end of 2017) of medium-to-high magnitude earthquakes, with nine Mw≥5 up to October 2017, and with about 74.000 seismic events registered after 1 year. The largest was the Mw6.5 30 October 2016 event near Norcia. After the major seismic events, 17 mud volcanoes erupted around Monteleone di Fermo village (Marche region). Mud volcano eruptions generally occurred a few hours to a few days after the main earthquakes, suggesting a seismic triggering. We analyzed the peak ground velocities and dynamic stresses during the three largest ea…
A multidisciplinary approach to the evaluation of the mechanism that triggered the Cerda landslide (Sicily, Italy).
2005
Abstract The present paper describes a multidisciplinary approach to the evaluation of a seismically triggered landslide that occurred in the Cerda area (Italy) on September 6, 2002, about 1 h after an earthquake took place in the south Tyrrhenian Sea. The study was focused on an analysis of the role of the seismic input in triggering the landslide, in view of the evidence that no other mass movement was recorded in the adjacent areas despite geological and geomorphological spatial homogeneity. The studied area is located on a slope of the western flank of the Fiume Imera Settentrionale (Northern Sicily), which is made up of clayey–arenitic rocks. The slope inclines gently but is not unifor…
Deployment of the ATLAS High-Level Trigger
2006
The ATLAS combined test beam in the second half of 2004 saw the first deployment of the ATLAS High-Level Trigger (HLT). The next steps are deployment on the pre-series farms in the experimental area during 2005, commissioning and cosmics tests with the full detector in 2006 and collisions in 2007. This paper reviews the experience gained in the test beam, describes the current status and discusses the further enhancements to be made. We address issues related to the dataflow, integration of selection algorithms, testing, software distribution, installation and improvements.
The Stalk Domain of NKp30 Contributes to Ligand Binding and Signaling of a Preassembled NKp30-CD3ζ Complex
2016
The natural cytotoxicity receptor (NCR) NKp30 (CD337) is a key player for NK cell immunosurveillance of infections and cancer. The molecular details of ligand recognition and its connection to CD3ζ signaling remain unsolved. Here, we show that the stalk domain (129KEHPQLGAGTVLLLR143) of NKp30 is very sensitive to sequence alterations, as mutations lead to impaired ligand binding and/or signaling capacity. Surprisingly, the stalk domains of NKp30 and NKp46, another NCR employing CD3ζ for signaling, were not exchangeable without drastic deficiencies in folding, plasma membrane targeting, and/or ligand-induced receptor signaling. Further mutational studies, N-glycosylation mapping, and plasma …
Mechanisms of NK Cell Activation and Clinical Activity of the Therapeutic SLAMF7 Antibody, Elotuzumab in Multiple Myeloma
2018
Multiple myeloma (MM) is a bone marrow plasma cell neoplasm and is the second most-common hematologic malignancy. Despite advances in therapy, MM remains largely incurable. Elotuzumab is a humanized IgG1 monoclonal antibody targeting SLAMF7, which is highly expressed on myeloma cells, and the antibody is approved for the treatment of relapsed and/or refractory (RR) MM in combination with lenalidomide and dexamethasone. Elotuzumab can stimulate robust antibody-dependent cellular cytotoxicity (ADCC) through engaging with FcγRIIIA (CD16) on NK cells and antibody-dependent cellular phagocytosis (ADCP) by macrophages. Interestingly, SLAMF7 is also expressed on cytolytic NK cells, which also expr…