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Danger signal

Johannes Laengle, Judith Stift, Agnes Bilecz, Brigitte Wolf, Andrea Beer, Balazs Hegedus, Stefan Stremitzer, Patrick Starlinger, Dietmar Tamandl, Dietmar Pils, Michael Bergmann
Preclinical models indicate that DNA damage induces type I interferon (IFN), which is crucial for the induction of an anti-tumor immune response. In human cancers, however, the association between DNA damage and an immunogenic cell death (ICD), including the release and sensing of danger signals, the subsequent ER stress response and a functional IFN system, is less clear. Methods: Neoadjuvant-treated colorectal liver metastases (CLM) patients, undergoing liver resection in with a curative intent, were retrospectively enrolled in this study (n=33)...
2018: Theranostics
Rafał Stryjek, Berenika Mioduszewska, Ewelina Spaltabaka-Gędek, Grzegorz R Juszczak
The ability to avoid predators is crucial to wild prey animals' survival. Potential danger is signalled, among others, by the presence of predator scents. These odors are used in research both to trigger and to study fear reactions in laboratory animals; they are also employed as repellents against pest rodent species. In our study, we assessed nine predator-derived odors for their effectiveness in eliciting avoidance responses in a free-living colony of Norway rats (Rattus norvegicus). The rats were studied in a field setting...
June 21, 2018: Scientific Reports
Anliang Huang, Jinhu Ma, Liyan Huang, Fan Yang, Ping Cheng
Tumor associated antigen (TAA) induces both humoral immunity and cellular immunity. The T cell-mediated immune response has an important role in the immune response induced by TAA. The hepatitis B virus X protein (HBx) sequence is mapped with Custer of differentiation (CD)8+ T cell (CTL) epitopes, while a large number of studies have indicated that HBx may enhance the autophagy. In our previous study, a novel hepatocellular carcinoma vaccine was designed that was an irradiated HBx modified hepatocellular carcinoma cell vaccine in autophagic form, which significantly induced antitumor immune responses in vivo ...
June 2018: Oncology Letters
Dániel Törőcsik, Dóra Kovács, Szilárd Póliska, Zita Szentkereszty-Kovács, Marianna Lovászi, Katalin Hegyi, Andrea Szegedi, Christos C Zouboulis, Mona Ståhle
Toll-like receptors (TLR) 2 and 4 are active in sebaceous glands and play a central role in the development of acne. Still, there is only limited knowledge on their effect on sebocytes. In this work we performed global gene expression profile analysis with functional clustering of the differentially regulated genes of TLR1/2 (PAM3CSK4)- and TLR4 (lipopolysaccharide [LPS])-activated SZ95 sebocytes. Both TLR1/2- and 4-activation promoted inflammation in a similar manner already at an early time-point (6 hours), regulating genes involved in inflammation, wound healing and chemotaxis reflecting a more complex cytokine and chemokine regulation than previously known...
2018: PloS One
Kun Wang, Shuman Wen, Lianghua He, Ang Li, Yan Li, Haiqing Dong, Wei Li, Tianbin Ren, Donglu Shi, Yongyong Li
One of the major challenges in vaccine design has been the over dependence on incorporation of abundant adjuvants, that in fact is in violation of the 'minimalist' principle. In the present study, a compact nanovaccine derived from a near whole antigen (up to 97 wt%) was developed. The nanovaccine structure was stabilized by free cysteines within each antigen (ovalbumin, OVA) which were tempo-spatially exposed and heat-driven to form extensive intermolecular disulfide network. This process enables the engineering of a nanovaccine upon integration of the danger signal (CpG-SH) into the network during the synthetic process...
June 21, 2018: ACS Nano
Sylvie Breton, Dennis Brown
BACKGROUND: Serious and often fatal acute kidney injury (AKI) is frequently seen after major surgery, local and remote organ damage, and sepsis. It is associated with uncontrolled inflammation, and is usually diagnosed only after the kidneys have gone through significant and often irreversible damage. SUMMARY: During our work involving another type of kidney disease that leads to acid-base disorders of the blood, we unexpectedly found high levels of a protein called the P2Y14 "purinergic" receptor, in specialized kidney epithelial cells called intercalated cells (ICs)...
2018: Annals of Nutrition & Metabolism
Kim Maree O'Sullivan, Sharon Lee Ford, Anthony Longano, A Richard Kitching, Stephen R Holdsworth
In anti-neutrophil cytoplasmic antibody associated vasculitis (AAV), toll like receptors (TLRs) may be engaged by infection associated patterns and by endogenous danger signals, linking infection and innate inflammation with this autoimmune disease. This study examined intrarenal TLR2, TLR4 and TLR9 expression and renal injury in AAV, testing the hypothesis that increased TLR expression correlates with renal injury. Patients with AAV exhibited both glomerular and tubulointerstitial expression of TLR2, TLR4 and TLR9, with TLR4 being the most prominent in both compartments...
June 20, 2018: American Journal of Physiology. Renal Physiology
Mariusz Z Ratajczak, Mateusz Adamiak, Magda Kucia, William Tse, Janina Ratajczak, Wieslaw Wiktor-Jedrzejczak
Innate immunity plays an important role in orchestrating the immune response, and the complement cascade (ComC) is a major component of this ancient defense system, which is activated by the classical-, alternative-, or mannan-binding lectin (MBL) pathways. However, the MBL-dependent ComC-activation pathway has been somewhat underappreciated for many years; recent evidence indicates that it plays a crucial role in regulating the trafficking of hematopoietic stem/progenitor cells (HSPCs) by promoting their egress from bone marrow (BM) into peripheral blood (PB)...
2018: Frontiers in Immunology
Catherine E Vrentas, Robert G Schaut, Paola M Boggiatto, Steven C Olsen, Fayyaz S Sutterwala, Mahtab Moayeri
The inflammasome serves as a mechanism by which the body senses damage or danger. These multiprotein complexes form in the cytosol of myeloid, epithelial and potentially other cell types to drive caspase-1 cleavage and the secretion of the pro-inflammatory cytokines IL-1β and IL-18. Different types of inflammasomes, centered on (and named after) their cytosolic NLRs, respond to signals from bacteria, fungi, and viruses, as well as "sterile inflammatory" triggers. Despite the large body of research accumulated on rodent and human inflammasomes over the past 15 years, only recently have studies expanded to consider the role of inflammasomes in veterinary and wildlife species...
July 2018: Veterinary Immunology and Immunopathology
Benjamin Banai, Lasse Laustsen, Irena Pavela Banai, Kosta Bovan
Previous studies have shown that voters rely on sexually dimorphic traits that signal masculinity and dominance when they choose political leaders. For example, voters exert strong preferences for candidates with lower pitched voices because these candidates are perceived as stronger and more competent. Moreover, experimental studies demonstrate that conservative voters, more than liberals, prefer political candidates with traits that signal dominance, probably because conservatives are more likely to perceive the world as a threatening place and to be more attentive to dangerous and threatening contexts...
April 2018: Evolutionary Psychology: An International Journal of Evolutionary Approaches to Psychology and Behavior
Rabah M Al Abdi, Ahmad E Alhitary, Enas W Abdul Hay, Areen K Al-Bashir
The aim of this study was to design a system to diagnose chronic stress, based on blunted reactivity of the autonomic nervous system (ANS) to cognitive load (CL). The system concurrently measures CL-induced variations in pupil diameter (PD), heart rate (HR), pulse wave amplitude (PWA), galvanic skin response (GSR), and breathing rate (BR). Measurements were recorded from 58 volunteers whose stress level was identified using the State-Trait Anxiety Inventory. Number-multiplication questions were used as CLs...
June 18, 2018: Medical & Biological Engineering & Computing
Marina Babic, Chiara Romagnani
Current medicine and medical science puts great effort into elucidating the basis of chronicity and finding appropriate treatments for inflammatory diseases; however, the mechanisms driving aberrant immune responses are mostly unknown and deserve further study. Of particular interest is the identification of checkpoints that regulate the function and differentiation of pro-inflammatory cells during pathogenesis, along with means of their modulation for therapeutic purposes. Natural killer group 2, member D (NKG2D) is a potent activator of the immune system, known as a sensor for "induced-self" ligands, i...
2018: Frontiers in Immunology
Karam Kim, Hye Jeong Kim, Bert Binas, Jin Hyun Kang, Il Yup Chung
Danger-associated molecular patterns (DAMPs) play a proinflammatory role in the pathogenesis of airway obstructive diseases such as severe asthma and chronic obstructive pulmonary disease. The NLRP3 inflammasome is a cytosolic multiprotein platform that activates the caspase-1 pathway in response to inflammatory stimuli such as DAMPs. ATP and S100 proteins are newly identified DAMPs that accumulate in inflamed airways. We previously demonstrated that S100A8, S100A9, and S100A12 induce production and secretion of MUC5AC, a major mucin in the conducting airway mucosa...
June 12, 2018: Biochemical and Biophysical Research Communications
Georgina Flórez-Grau, Irati Zubizarreta, Raquel Cabezón, Pablo Villoslada, Daniel Benitez-Ribas
The identification of activated T-lymphocytes restricted to myelin-derived immunogenic peptides in multiple sclerosis (MS) and aquaporin-4 water channel in neuromyelitis optica (NMO) in the blood of patients opened the possibility for developing highly selective and disease-specific therapeutic approaches. Antigen presenting cells and in particular dendritic cells (DCs) represent a strategy to inhibit pro-inflammatory T helper cells. DCs are located in peripheral and lymphoid tissues and are essential for homeostasis of T cell-dependent immune responses...
2018: Frontiers in Immunology
Wenzhe Yu, Mengru Tao, Yueliang Zhao, Xiaoqian Hu, Mingfu Wang
Advanced glycation end products (AGEs) could interact with the receptor for AGE (RAGE) as a sterile danger signal to induce inflammation. 4′-methoxyresveratrol (4′MR), a polyphenol derived from Dipterocarpaceae, has not been studied for its anti-inflammation effects. In the present study, we sought to explore the protective role of 4′MR in AGEs-induced inflammatory model using RAW264.7 macrophages. 4′MR significantly inhibited gene expression of pro-inflammatory cytokines and chemokines, such as interleukin 1β (IL-1β), interleukin 6 (IL-6), tumor necrosis factor-alpha (TNF-α) and monocyte chemoattractant protein-1 (MCP-1), as well as two typical pro-inflammatory enzymes, inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX2)...
June 14, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
S Mallory Burns, Christopher W Cunningham, Susan L Mercer
Fentanyl rose to prominence as an alternative analgesic to morphine nearly 50 years ago; today, fentanyl has re-emerged as a dangerous recreational substance. The increased potency and analgesic effect of fentanyl are advantageous in the treatment of pain but are also responsible for the rise in unintentional opioid overdose deaths. In response to this crisis, fentanyl, its analogues, and even precursors are under heightened regulatory scrutiny. Despite this controversial history, derivatization of fentanyl has resulted in numerous synthetic analogues that provide valuable insights into opioid receptor binding and signaling events...
June 12, 2018: ACS Chemical Neuroscience
Danica E Goggin, Parwinder Kaur, Mechelle J Owen, Stephen B Powles
Background and Aims: Resistance to synthetic auxin herbicides such as 2,4-dichlorophenoxyacetic acid (2,4-D) is increasing in weed populations worldwide, which is of concern given the recent introduction of synthetic auxin-resistant transgenic crops. Due to the complex mode of action of the auxinic herbicides, the mechanisms of evolved resistance remain largely uncharacterized. The aims of this study were to assess the level of diversity in resistance mechanisms in 11 populations of the problem weed Raphanus raphanistrum, and to use a high-throughput, whole-genome transcriptomic analysis on one resistant and one susceptible population to identify important changes in gene expression in response to 2,4-D...
June 11, 2018: Annals of Botany
Eun-Young Lee, Sunghoon Kim, Myung Hee Kim
Despite remarkable advances in medical science, infection-associated diseases remain among the leading causes of death worldwide. There is a great deal of interest and concern at the rate at which new pathogens are emerging and causing significant human health problems. Expanding our understanding of how cells regulate signaling networks to defend against invaders and retain cell homeostasis will reveal promising strategies against infection. It has taken scientists decades to appreciate that eukaryotic aminoacyl-tRNA synthetases (ARSs) play a role as global cell signaling mediators to regulate cell homeostasis, beyond their intrinsic function as protein synthesis enzymes...
June 8, 2018: Biochemical Pharmacology
Kelly Bruno, Sarah A Woller, Yury I Miller, Tony L Yaksh, Mark Wallace, Graham Beaton, Krishnan Chakravarthy
Toll-like receptors (TLRs) are a family of pattern-recognition receptors that initiate signaling in innate and adaptive immune pathways. The highly conserved family of transmembrane proteins are comprised of an extracellular domain that recognizes exogenous and endogenous danger molecules and an ectodomain that activates downstream pathways in response. Recent studies suggest that continuous activation or dysregulation of TLR signaling may contribute to chronic disease states. The receptor is located not only on inflammatory cells (meningeal and peripheral macrophages) but on neuraxial glia (microglia and astrocytes), schwann cells, fibroblasts, dorsal root ganglia and dorsal horn neurons...
June 7, 2018: Pain
Yun-Fen Hung, Chiung-Ya Chen, Wan-Chen Li, Ting-Fang Wang, Yi-Ping Hsueh
The neuronal innate immune system recognizes endogenous danger signals and regulates neuronal development and function. Toll-like receptor 7 (TLR7), one of the TLRs that trigger innate immune responses in neurons, controls neuronal morphology. To further assess the function of TLR7 in the brain, we applied next generation sequencing to investigate the effect of Tlr7 deletion on gene expression in hippocampal and cortical mixed cultures and on mouse behaviors. Since previous in vivo study suggested that TLR7 is more critical for neuronal morphology at earlier developmental stages, we analyzed two time-points (4 and 18 DIV) to represent young and mature neurons, respectively...
June 7, 2018: Brain, Behavior, and Immunity
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