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https://www.readbyqxmd.com/read/29212904/dendritic-cell-ripk1-maintains-immune-homeostasis-by-preventing-inflammation-and-autoimmunity
#1
Joanne A O'Donnell, Jesse Lehman, Justine E Roderick, Dalia Martinez-Marin, Matija Zelic, Ciara Doran, Nicole Hermance, Stephen Lyle, Manolis Pasparakis, Katherine A Fitzgerald, Ann Marshak-Rothstein, Michelle A Kelliher
Necroptosis is a form of cell death associated with inflammation; however, the biological consequences of chronic necroptosis are unknown. Necroptosis is mediated by RIPK1, RIPK3, and MLKL kinases but in hematopoietic cells RIPK1 has anti-inflammatory roles and functions to prevent necroptosis. Here we interrogate the consequences of chronic necroptosis on immune homeostasis by deleting Ripk1 in mouse dendritic cells. We demonstrate that deregulated necroptosis results in systemic inflammation, tissue fibrosis, and autoimmunity...
December 6, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29211760/the-serine-protease-homolog-spheroide-is-involved-in-sensing-of-pathogenic-gram-positive-bacteria
#2
Jelena Patrnogic, Vincent Leclerc
In Drosophila, recognition of pathogens such as Gram-positive bacteria and fungi triggers the activation of proteolytic cascades and the subsequent activation of the Toll pathway. This response can be achieved by either detection of pathogen associated molecular patterns or by sensing microbial proteolytic activities ("danger signals"). Previous data suggested that certain serine protease homologs (serine protease folds that lack an active catalytic triad) could be involved in the pathway. We generated a null mutant of the serine protease homolog spheroide (sphe)...
2017: PloS One
https://www.readbyqxmd.com/read/29208712/crystal-structure-of-human-irak1
#3
Li Wang, Qi Qiao, Ryan Ferrao, Chen Shen, John M Hatcher, Sara J Buhrlage, Nathanael S Gray, Hao Wu
Interleukin 1 (IL-1) receptor-associated kinases (IRAKs) are serine/threonine kinases that play critical roles in initiating innate immune responses against foreign pathogens and other types of dangers through their role in Toll-like receptor (TLR) and interleukin 1 receptor (IL-1R) mediated signaling pathways. Upon ligand binding, TLRs and IL-1Rs recruit adaptor proteins, such as myeloid differentiation primary response gene 88 (MyD88), to the membrane, which in turn recruit IRAKs via the death domains in these proteins to form the Myddosome complex, leading to IRAK kinase activation...
December 5, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29208681/hemitam-a-single-tyrosine-motif-that-packs-a-punch
#4
REVIEW
Björn Bauer, Alexander Steinle
Innate immune cells sense danger through a plethora of germline-encoded receptors that recognize pathogen-associated molecular patterns (PAMPs) or cellular molecules that are exposed only by stressed, infected, malignant, or dead cells. Many of these danger-sensing receptors belong to the C-type lectin-like superfamily (CLSF) and therefore are called C-type lectin-like receptors (CTLRs). Certain activating CTLRs, namely, CLEC-2, Dectin-1, DNGR-1, NKp80, and NKp65, which are encoded by genes that are clustered together in a subregion of the mammalian natural killer gene complex (NKC), use a single copy tyrosine signaling module termed the hemi-immunoreceptor tyrosine-based activation motif (hemITAM)...
December 5, 2017: Science Signaling
https://www.readbyqxmd.com/read/29204376/mobile-cardiac-health-care-monitoring-and-notification-with-real-time-tachycardia-and-bradycardia-arrhythmia-detection
#5
Mina Golzar, Faranak Fotouhi-Ghazvini, Hossein Rabbani, Fahimeh Sadat Zakeri
Background: The increasing trend of heart disease has turned the attention of researchers toward the use of portable connected technologies. The necessity of continuous special care for cardiovascular patients is an inevitable fact. Methods: In this research, a new wireless electrocardiographic (ECG) signal-monitoring system based on smartphone is presented. This system has two main sections. The first section consists of a sensor which receives ECG signals via an amplifier, then filters and digitizes the signal, and prepares it to be transmitted...
October 2017: Journal of Medical Signals and Sensors
https://www.readbyqxmd.com/read/29203707/extracellular-cell-stress-heat-shock-proteins-immune-responses-and-disease-an-overview
#6
REVIEW
A Graham Pockley, Brian Henderson
Extracellular cell stress proteins are highly conserved phylogenetically and have been shown to act as powerful signalling agonists and receptors for selected ligands in several different settings. They also act as immunostimulatory 'danger signals' for the innate and adaptive immune systems. Other studies have shown that cell stress proteins and the induction of immune reactivity to self-cell stress proteins can attenuate disease processes. Some proteins (e.g. Hsp60, Hsp70, gp96) exhibit both inflammatory and anti-inflammatory properties, depending on the context in which they encounter responding immune cells...
January 19, 2018: Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
https://www.readbyqxmd.com/read/29203017/driver-behavior-analysis-for-right-turn-drivers-at-signalized-intersections-using-shrp-2-naturalistic-driving-study-data
#7
Jianqing Wu, Hao Xu
INTRODUCTION: Understanding driver behavior is important for traffic safety and operation, especially at intersections where different traffic movements conflict. While most driver-behavior studies are based on simulation, this paper documents the analysis of driver-behavior at signalized intersections with the SHRP 2 Naturalistic Driving Study (NDS) data. This study analyzes the different influencing factors on the operation (speed control) and observation of right-turn drivers. METHOD: A total of 300 NDS trips at six signalized intersections were used, including the NDS time-series sensor data, the forward videos and driver face videos...
December 2017: Journal of Safety Research
https://www.readbyqxmd.com/read/29202211/acute-haemarthrosis-in-the-haemophilia-a-rat-generates-a-local-and-systemic-proinflammatory-response
#8
Karin M Lövgren, Kristine R Christensen, Wiktor Majewski, Olga Østrup, Søren Skov, Bo Wiinberg
Background Replacement therapy with coagulation factor VIII (FVIII) concurrent with bleeds (on-demand) in haemophilia A (HA) patients has been hypothesized to increase the risk for antidrug antibodies (inhibitors). A danger signal environment, characterized by tissue damage and inflammation at the site of a bleed, is thought to contribute to the anti-FVIII response. The nature of this inflammatory reaction is, however, not fully known, and new insights will be valuable for both managing inhibitors and understanding arthropathy development...
November 2017: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/29192209/mineral-particles-stimulate-innate-immunity-through-neutrophil-extracellular-traps-containing-hmgb1
#9
Hsin-Hsin Peng, Yu-Ju Liu, David M Ojcius, Chiou-Mei Lee, Ren-Hao Chen, Pei-Rong Huang, Jan Martel, John D Young
Calcium phosphate-based mineralo-organic particles form spontaneously in the body and may represent precursors of ectopic calcification. We have shown earlier that these particles induce activation of caspase-1 and secretion of IL-1β by macrophages. However, whether the particles may produce other effects on immune cells is unclear. Here, we show that these particles induce the release of neutrophil extracellular traps (NETs) in a size-dependent manner by human neutrophils. Intracellular production of reactive oxygen species is required for particle-induced NET release by neutrophils...
November 30, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29190116/alarmins-in-frozen-shoulder-a-molecular-association-between-inflammation-and-pain
#10
Jonathon Z B Cher, Moeed Akbar, Susan Kitson, Lindsay A N Crowe, Emma Garcia-Melchor, Stephen C Hannah, Michael McLean, Umberto G Fazzi, Shauna C Kerr, George A C Murrell, Neal L Millar
BACKGROUND: The pathophysiological mechanisms behind proliferation of fibroblasts and deposition of dense collagen matrix in idiopathic frozen shoulder remain unclear. Alarmins (also known as danger signals) are endogenous molecules that are released into the extracellular milieu after infection or tissue injury and that signal cell and tissue damage. PURPOSE: To investigate whether the presence of alarmins is higher in patients with idiopathic frozen shoulder than in control subjects...
November 1, 2017: American Journal of Sports Medicine
https://www.readbyqxmd.com/read/29189388/cd11c-targeted-delivery-of-dna-to-dendritic-cells-leads-to-cgas-and-sting-dependent-maturation
#11
Marlene F Laursen, Esben Christensen, Laura L T Degn, Kasper Jønsson, Martin R Jakobsen, Ralf Agger, Emil Kofod-Olsen
Immunotherapeutic activation of tumor-specific T cells has proven to be an interesting approach in anticancer treatment. Particularly, anti-CTLA-4 and anti-PD-1/PD-L1 treatment looks promising, and conceivably, even better clinical results might be obtained if such treatment could be combined with boosting the existing tumor-specific T-cell response. One way to achieve this could be by increasing the level of maturation of dendritic cells locally and in the draining lymph nodes. When exposed to cancer cells, dendritic cells may spontaneously mature because of danger-associated molecular patterns derived from the tumor cells...
November 17, 2017: Journal of Immunotherapy
https://www.readbyqxmd.com/read/29186971/reactive-oxygen-species-and-oncoprotein-signaling-a-dangerous-liaison
#12
Stephen Jun Fei Chong, Jolin Xiao Hui Lai, Jie Qing Eu, Gregory Bellot, Shazib Pervaiz
SIGNIFICANCE: There is evidence to implicate reactive oxygen species (ROS) in tumorigenesis and its progression. This has been associated with the interplay between ROS and oncoproteins, resulting in enhanced cellular proliferation and survival. Recent Advances: To date, studies have investigated specific contributions of the crosstalk between ROS and signaling networks in cancer initiation and progression. These investigations have challenged the established dogma of ROS as agents of cell death by demonstrating a secondary function that fuels cell proliferation and survival...
November 30, 2017: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/29177863/methods-to-study-cell-swelling-induced-inflammasome-activation
#13
Vincent Compan, Pablo Pelegrín
Cells present ancestral conserved mechanisms to maintain their volume in response to alterations in environmental osmolarity. Changes in environmental osmolarities are therefore conserved as primitive stress signals. Innate immune cells, such as macrophages, express receptors to respond and shape immune response to stress, damage, or infection. The NLRP3 inflammasome is a multiprotein complex expressed in macrophages that senses pathogen- and danger-associated signals. The basic mechanisms of cell swelling and regulatory volume decrease are sensed by the NLRP3 inflammasome...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29175512/altering-d1-receptor-activity-in-the-basolateral-amygdala-impairs-fear-suppression-during-a-safety-cue
#14
Ka H Ng, Michael W Pollock, Phillip J Urbanczyk, Susan Sangha
Accurate discrimination among cues signifying reward, danger or safety initiates the proper emotional response in order to guide behavior. Appropriate conditioned inhibition of fear in the presence of a safety cue would allow an organism to engage in reward seeking behaviors. There is currently little known about the mechanisms of reward, fear and safety cue discrimination and how a safety cue can inhibit fear and release reward seeking from inhibition. Here we assess reward, fear and safety cue learning together using a behavioral paradigm that has identified neurons that discriminate among these cues in the basolateral amygdala (BLA) (Sangha, Chadick, & Janak, 2013)...
November 22, 2017: Neurobiology of Learning and Memory
https://www.readbyqxmd.com/read/29175308/differential-use-of-danger-and-safety-signals-in-an-animal-model-of-anxiety-vulnerability-the-behavioral-economics-of-avoidance
#15
Kevin M Spiegler, Ashley M Fortress, Kevin C H Pang
Differential processing of danger and safety signals may underlie symptoms of anxiety disorders and posttraumatic stress disorder. One symptom common to these disorders is pathological avoidance. The present study examined whether danger and safety signals influence avoidance differently in anxiety-vulnerable Wistar-Kyoto (WKY) rats and Sprague Dawley (SD) rats. SD and WKY rats were tested in a novel progressive ratio avoidance task with and without danger or safety signals. Two components of reinforcement, hedonic value and motivation, were determined by fitting an exponentiated demand equation to the data...
November 22, 2017: Progress in Neuro-psychopharmacology & Biological Psychiatry
https://www.readbyqxmd.com/read/29173725/hyaluronan-and-hyaluronan-fragments
#16
Mary K Cowman
The glycosaminoglycan hyaluronan (HA) is a key component of the microenvironment surrounding cells. In healthy tissues, HA molecules have extremely high molecular mass and consequently large hydrodynamic volumes. Tethered to the cell surface by clustered receptor proteins, HA molecules crowd each other, as well as other macromolecular species. This leads to severe nonideality in physical properties of the biomatrix, because steric exclusion leads to an increase in effective concentration of the macromolecules...
2017: Advances in Carbohydrate Chemistry and Biochemistry
https://www.readbyqxmd.com/read/29169644/liquid-chromatography-coupled-to-tandem-mass-spectrometry-for-detecting-ten-allergens-in-complex-and-incurred-foodstuffs
#17
M Planque, T Arnould, M Dieu, P Delahaut, P Renard, N Gillard
Food allergy is a considerable heath problem, as undesirable contaminations by allergens during food production are still widespread and may be dangerous for human health. To protect the population, laboratories need to develop reliable analytical methods in order to detect allergens in various food products. Currently, a large majority of allergen-related food recalls concern bakery products. It is therefore essential to detect allergens in unprocessed and processed foodstuffs. In this study, we developed a method for detecting ten allergens in complex (chocolate, ice cream) and processed (cookie, sauce) foodstuffs, based on ultra-high performance liquid chromatography coupled to tandem mass spectrometry (UHPLC-MS/MS)...
November 20, 2017: Journal of Chromatography. A
https://www.readbyqxmd.com/read/29169102/a-novel-framework-to-evaluate-pedestrian-safety-at-non-signalized-locations
#18
Ting Fu, Luis Miranda-Moreno, Nicolas Saunier
This paper proposes a new framework to evaluate pedestrian safety at non-signalized crosswalk locations. In the proposed framework, the yielding maneuver of a driver in response to a pedestrian is split into the reaction and braking time. Hence, the relationship of the distance required for a yielding maneuver and the approaching vehicle speed depends on the reaction time of the driver and deceleration rate that the vehicle can achieve. The proposed framework is represented in the distance-velocity (DV) diagram and referred as the DV model...
November 20, 2017: Accident; Analysis and Prevention
https://www.readbyqxmd.com/read/29167375/loss-of-apobec1-rna-editing-function-in-microglia-exacerbates-age-related-cns-pathophysiology
#19
Daniel C Cole, Youngcheul Chung, Khatuna Gagnidze, Kaitlyn H Hajdarovic, Violeta Rayon-Estrada, Dewi Harjanto, Benedetta Bigio, Judit Gal-Toth, Teresa A Milner, Bruce S McEwen, F Nina Papavasiliou, Karen Bulloch
Microglia (MG), a heterogeneous population of phagocytic cells, play important roles in central nervous system (CNS) homeostasis and neural plasticity. Under steady-state conditions, MG maintain homeostasis by producing antiinflammatory cytokines and neurotrophic factors, support myelin production, and remove synapses and cellular debris, as well as participating in "cross-correction," a process that supplies neurons with key factors for executing autophagy-lysosomal function. As sentinels for the immune system, MG also detect "danger" signals (pathogenic or traumatic insult), become activated, produce proinflammatory cytokines, and recruit monocytes and dendritic cells to the site of damage through a breached blood-brain barrier or via brain lymphatics...
November 22, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29162744/atp-promotes-the-fast-migration-of-dendritic-cells-through-the-activity-of-pannexin-1-channels-and-p2x7-receptors
#20
Pablo J Sáez, Pablo Vargas, Kenji F Shoji, Paloma A Harcha, Ana-María Lennon-Duménil, Juan C Sáez
Upon its release from injured cells, such as infected, transformed, inflamed, or necrotic cells, extracellular adenosine-5'-triphosphate (ATP) acts as a danger signal that recruits phagocytes, such as neutrophils, macrophages, and dendritic cells (DCs), to the site of injury. The sensing of extracellular ATP occurs through purinergic (P2) receptors. We investigated the cellular mechanisms linking purinergic signaling to DC motility. We found that ATP stimulated fast DC motility through an autocrine signaling loop, which was initiated by the activation of P2X7 receptors and further amplified by pannexin 1 (Panx1) channels...
November 21, 2017: Science Signaling
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