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https://www.readbyqxmd.com/read/28231510/lipopolyplex-potentiates-anti-tumor-immunity-of-mrna-based-vaccination
#1
Stefano Persano, Maria L Guevara, Zhaoqi Li, Junhua Mai, Mauro Ferrari, Pier Paolo Pompa, Haifa Shen
mRNA-based vaccines have the benefit of triggering robust anti-cancer immunity without the potential danger of genome integration from DNA vaccines or the limitation of antigen selection from peptide vaccines. Yet, a conventional mRNA vaccine comprising of condensed mRNA molecules in a positively charged protein core structure is not effectively internalized by the antigen-presenting cells. It cannot offer sufficient protection for mRNA molecules from degradation by plasma and tissue enzymes either. Here, we have developed a lipopolyplex mRNA vaccine that consists of a poly-(β-amino ester) polymer mRNA core encapsulated into a 1,2-dioleoyl-sn-glycero-3-ethylphosphocholine/1,2-dioleoyl-sn-glycero-3-phosphatidyl-ethanolamine/1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[amino(polyethylene glycol)-2000 (EDOPC/DOPE/DSPE-PEG) lipid shell...
February 20, 2017: Biomaterials
https://www.readbyqxmd.com/read/28227270/deep-learning-framework-for-detection-of-hypoglycemic-episodes-in-children-with-type-1-diabetes
#2
Phyo Phyo San, Sai Ho Ling, Hung T Nguyen, Phyo Phyo San, Sai Ho Ling, Hung T Nguyen, Sai Ho Ling, Hung T Nguyen, Phyo Phyo San
Most Type 1 diabetes mellitus (T1DM) patients have hypoglycemia problem. Low blood glucose, also known as hypoglycemia, can be a dangerous and can result in unconsciousness, seizures and even death. In recent studies, heart rate (HR) and correct QT interval (QTc) of the electrocardiogram (ECG) signal are found as the most common physiological parameters to be effected from hypoglycemic reaction. In this paper, a state-of-the-art intelligent technology namely deep belief network (DBN) is developed as an intelligent diagnostics system to recognize the onset of hypoglycemia...
August 2016: Conference Proceedings: Annual International Conference of the IEEE Engineering in Medicine and Biology Society
https://www.readbyqxmd.com/read/28226552/patient-specific-detection-of-ventricular-tachycardia-in-remote-continuous-health-devices
#3
Amit Juneja, Michael Marefat, Amit Juneja, Michael Marefat, Amit Juneja, Michael Marefat
Ventricular Tachycardia (VT) is a dangerous arrhythmic event which can lead to sudden cardiac death if not detected and taken care of in time. This work uses non-linear features derived from Recurrence Quantification Analysis (RQA) along with Kolmogorov complexity, by analyzing the ECG signals, to train a classifier which can predict VT prior to their onset in remote continuous health devices. Compressed ECG signal along with amplitude ranges extracted from the ECG signal are used as features to strengthen the classifier...
August 2016: Conference Proceedings: Annual International Conference of the IEEE Engineering in Medicine and Biology Society
https://www.readbyqxmd.com/read/28219022/rationale-for-stimulator-of-interferon-genes-targeted-cancer-immunotherapy
#4
REVIEW
Thaiz Rivera Vargas, Isis Benoit-Lizon, Lionel Apetoh
The efficacy of checkpoint inhibitor therapy illustrates that cancer immunotherapy, which aims to foster the host immune response against cancer to achieve durable anticancer responses, can be successfully implemented in a routine clinical practice. However, a substantial proportion of patients does not benefit from this treatment, underscoring the need to identify alternative strategies to defeat cancer. Despite the demonstration in the 1990's that the detection of danger signals, including the nucleic acids DNA and RNA, by dendritic cells (DCs) in a cancer setting is essential for eliciting host defence, the molecular sensors responsible for recognising these danger signals and eliciting anticancer immune responses remain incompletely characterised, possibly explaining the disappointing results obtained so far upon the clinical implementation of DC-based cancer vaccines...
February 17, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28210842/uric-acid-as-a-novel-biomarker-for-bone-marrow-function-and-incipient-hematopoietic-reconstitution-after-aplasia-in-patients-with-hematologic-malignancies
#5
Sebastian P Haen, Vicky Eyb, Nora Mirza, Aline Naumann, Andreas Peter, Markus W Löffler, Christoph Faul, Wichard Vogel, Wolfgang A Bethge, Hans-Georg Rammensee, Lothar Kanz, Martin Heni
PURPOSE: Prolonged aplasia and graft failure (GF) represent life-threatening complications after hematopoietic cell transplantation (HCT) requiring suitable biomarkers for early detection and differentiation between GF and poor graft function (PGF). Uric acid (UA) is a strong immunological danger signal. METHODS: Laboratory results were analyzed from patients undergoing either allogeneic or autologous HCT or induction chemotherapy for acute leukemia (n = 50 per group, n = 150 total)...
February 16, 2017: Journal of Cancer Research and Clinical Oncology
https://www.readbyqxmd.com/read/28193238/transient-ikk2-activation-in-astrocytes-initiates-selective-non-cell-autonomous-neurodegeneration
#6
Michael Lattke, Stephanie N Reichel, Alexander Magnutzki, Alireza Abaei, Volker Rasche, Paul Walther, Dinis P Calado, Boris Ferger, Thomas Wirth, Bernd Baumann
BACKGROUND: Neuroinflammation is associated with a wide range of neurodegenerative disorders, however the specific contribution to individual disease pathogenesis and selective neuronal cell death is not well understood. Inflammatory cerebellar ataxias are neurodegenerative diseases occurring in various autoimmune/inflammatory conditions, e.g. paraneoplastic syndromes. However, how inflammatory insults can cause selective cerebellar neurodegeneration in the context of these diseases remains open, and appropriate animal models are lacking...
February 13, 2017: Molecular Neurodegeneration
https://www.readbyqxmd.com/read/28191008/the-nlrp3-and-pyrin-inflammasomes-implications-in-the-pathophysiology-of-autoinflammatory-diseases
#7
REVIEW
Carlos de Torre-Minguela, Pablo Mesa Del Castillo, Pablo Pelegrín
Inflammasomes are multiprotein complexes that critically control different aspects of innate and adaptive immunity. Among them we could highlight the release of pro-inflammatory cytokines that induce and maintain the inflammatory response. Usually, inflammasomes result from oligomerization of a nucleotide-binding domain-like receptor (NLR) after sensing different pathogenic or endogenous sterile dangerous signals; however, other proteins such as absent in melanoma 2, retinoic acid-inducible gene I, or pyrin could also form inflammasome platforms...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28185389/palmitic-acid-stimulates-interleukin-8-via-the-tlr4-nf-%C3%AE%C2%BAb-ros-pathway-and-induces-mitochondrial-dysfunction-in-bovine-oviduct-epithelial-cells
#8
Ayaka Ohtsu, Hazuki Tanaka, Kotomi Seno, Hisataka Iwata, Takehito Kuwayama, Koumei Shirasuna
PROBLEM: We investigated the effect of palmitic acid (PA), a major saturated fatty acid in NEFA, on bovine oviduct epithelial cells (OECs) during in vitro cell culture. METHOD OF STUDY: Bovine oviductal tissues ipsilateral to the corpus luteum were collected 1-3 days after ovulation; the OECs were isolated and cultured. RESULTS: PA increased lipid accumulation and activated caspase-3 in OECs, resulting in decreased cell proliferation. PA also stimulated the secretion of inflammatory cytokine interleukin (IL)-8 depending on TLR4, NF-κB activation, and reactive oxygen species (ROS) production...
February 10, 2017: American Journal of Reproductive Immunology: AJRI
https://www.readbyqxmd.com/read/28182526/hippocampal-processing-of-ambiguity-enhances-fear-memory
#9
Ugwechi Amadi, Seh Hong Lim, Elizabeth Liu, Michael V Baratta, Ki A Goosens
Despite the ubiquitous use of Pavlovian fear conditioning as a model for fear learning, the highly predictable conditions used in the laboratory do not resemble real-world conditions, in which dangerous situations can lead to unpleasant outcomes in unpredictable ways. In the current experiments, we varied the timing of aversive events after predictive cues in rodents and discovered that temporal ambiguity of aversive events greatly enhances fear. During fear conditioning with unpredictably timed aversive events, pharmacological inactivation of the dorsal hippocampus or optogenetic silencing of cornu ammonis 1 cells during aversive negative prediction errors prevented this enhancement of fear without affecting fear learning for predictable events...
February 2017: Psychological Science
https://www.readbyqxmd.com/read/28179110/oxidized-and-original-article-degraded-mitochondrial-polynucleotides-demps-especially-rna-are-potent-immunogenic-regulators-in-primary-mouse-macrophages
#10
Abhinav R Saxena, Linda Y Gao, Shachi Srivatsa, Elizabeth Z Bobersky, Sivakumar Periasamy, Danielle T Hunt, Kyle E Altman, Dana R Crawford
Certain mitochondrial components can act as damage-associated molecular patterns (DAMPs) or danger signals, triggering a proinflammatory response in target (usually immune) cells. We previously reported the selective degradation of mitochondrial DNA and RNA in response to cellular oxidative stress, and the immunogenic effect of this DNA in primary mouse astrocytes. Here, we extend these studies to assess the immunogenic role of both mitochondrial DNA and RNA isolated from hydrogen peroxide (HP) treated HA1 cells (designated "DeMPs" for degraded mitochondrial polynucleotides) using mouse bone marrow derived macrophages (BMDMs), a conventional immune cell type...
February 4, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28178282/trypanosoma-cruzi-high-mobility-group-b-tchmgb-can-act-as-an-inflammatory-mediator-on-mammalian-cells
#11
Pamela Cribb, Virginia Perdomo, Victoria L Alonso, Romina Manarin, Jorge Barrios-Payán, Brenda Marquina-Castillo, Luis Tavernelli, Rogelio Hernández-Pando
BACKGROUND: High Mobility Group B (HMGB) proteins are nuclear architectural factors involved in chromatin remodeling and important nuclear events. HMGBs also play key roles outside the cell acting as alarmins or Damage-associated Molecular Patterns (DAMPs). In response to a danger signal these proteins act as immune mediators in the extracellular milieu. Moreover, these molecules play a central role in the pathogenesis of many autoimmune and both infectious and sterile inflammatory chronic diseases...
February 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28167651/contact-collaboration-and-conflict-signal-integration-of-syk-coupled-c-type-lectin-receptors
#12
REVIEW
Jenny Ostrop, Roland Lang
Several spleen tyrosine kinase-coupled C-type lectin receptors (CLRs) have emerged as important pattern recognition receptors for infectious danger. Because encounter with microbial pathogens leads to the simultaneous ligation of several CLRs and TLRs, the signals emanating from different pattern recognition receptors have to be integrated to achieve appropriate biological responses. In this review, we briefly summarize current knowledge about ligand recognition and core signaling by Syk-coupled CLRs. We then address mechanisms of synergistic and antagonistic crosstalk between different CLRs and with TLRs...
February 15, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28167650/alarmins-feel-the-stress
#13
REVIEW
Peleg Rider, Elena Voronov, Charles A Dinarello, Ron N Apte, Idan Cohen
Over the last decade, danger-associated molecular pattern molecules, or alarmins, have been recognized as signaling mediators of sterile inflammatory responses after trauma and injury. In contrast with the accepted passive release models suggested by the "danger hypothesis," it was recently shown that alarmins can also directly sense and report damage by signaling to the environment when released from live cells undergoing physiological stress, even without loss of subcellular compartmentalization. In this article, we review the involvement of alarmins such as IL-1α, IL-33, IL-16, and high-mobility group box 1 in cellular and physiological stress, and suggest a novel activity of these molecules as central initiators of sterile inflammation in response to nonlethal stress, a function we denote "stressorins...
February 15, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28166870/causes-consequences-and-countermeasures-to-driver-fatigue-in-the-rail-industry-the-train-driver-perspective
#14
A J Filtness, A Naweed
Fatigue is an important workplace risk management issue. Within the rail industry, the passing of a stop signal (signal passed at danger; SPAD) is considered to be one of the most major safety breaches which can occur. Train drivers are very aware of the negative consequences associated with a SPAD. Therefore, SPADs provide a practical and applied safety relevant context within which to structure a discussion on fatigue. Focus groups discussing contributing factors to SPADs were undertaken at eight passenger rail organisations across Australia and New Zealand (n = 28 drivers)...
April 2017: Applied Ergonomics
https://www.readbyqxmd.com/read/28163301/homeostasis-altering-molecular-processes-as-mechanisms-of-inflammasome-activation
#15
REVIEW
Adrian Liston, Seth L Masters
The innate immune system uses a distinct set of germline-encoded pattern recognition receptors (PRRs) to initiate downstream inflammatory cascades. This recognition system is in stark contrast to the adaptive immune system, which relies on highly variable, randomly generated antigen receptors. A key limitation of the innate immune system's reliance on fixed PRRs is its inflexibility in responding to rapidly evolving pathogens. Recent advances in our understanding of inflammasome activation suggest that the innate immune system also has sophisticated mechanisms for responding to pathogens for which there is no fixed PRR...
February 6, 2017: Nature Reviews. Immunology
https://www.readbyqxmd.com/read/28155242/sensory-neuron-regulation-of-gastrointestinal-inflammation-and-bacterial-host-defence
#16
N Y Lai, K Mills, I M Chiu
Sensory neurons in the gastrointestinal tract have multifaceted roles in maintaining homeostasis, detecting danger and initiating protective responses. The gastrointestinal tract is innervated by three types of sensory neurons: dorsal root ganglia, nodose/jugular ganglia and intrinsic primary afferent neurons. Here, we examine how these distinct sensory neurons and their signal transducers participate in regulating gastrointestinal inflammation and host defence. Sensory neurons are equipped with molecular sensors that enable neuronal detection of diverse environmental signals including thermal and mechanical stimuli, inflammatory mediators and tissue damage...
February 2, 2017: Journal of Internal Medicine
https://www.readbyqxmd.com/read/28154552/chemokines-associated-with-pathologic-responses-to-orthopedic-implant-debris
#17
REVIEW
Nadim J Hallab, Joshua J Jacobs
Despite the success in returning people to health saving mobility and high quality of life, the over 1 million total joint replacements implanted in the US each year are expected to eventually fail after approximately 15-25 years of use, due to slow progressive subtle inflammation to implant debris compromising the bone implant interface. This local inflammatory pseudo disease state is primarily caused by implant debris interaction with innate immune cells, i.e., macrophages. This implant debris can also activate an adaptive immune reaction giving rise to the concept of implant-related metal sensitivity...
2017: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/28149007/calcium-a-cell-cycle-commander-drives-colon-cancer-cell-diffpoptosis
#18
REVIEW
Ahmed A Abd-Rabou
The story of the cell commonder, calcium, reaches into all corners of the cell and controls cell proliferation, differentiation, function, and even death. The calcium-driven eukaryotic revolution is one of the great turning points in the life history, happened about two billion years later when it was converted from a dangerous killer that had to be kept out of cell into the cell master which drives the cell. This review article will take the readers to a tour of tissues chosen to best show the calcium's many faces (proliferator, differentiator, and killer)...
March 2017: Indian Journal of Clinical Biochemistry: IJCB
https://www.readbyqxmd.com/read/28147281/the-atypical-ubiquitin-e2-conjugase-ube2l3-is-an-indirect-caspase-1-target-and-controls-il-1%C3%AE-secretion-by-inflammasomes
#19
Matthew J G Eldridge, Julia Sanchez-Garrido, Gil Ferreira Hoben, Philippa J Goddard, Avinash R Shenoy
Caspase-1 activation by inflammasome signaling scaffolds initiates inflammation and antimicrobial responses. Caspase-1 proteolytically converts newly induced pro-interleukin 1 beta (IL-1β) into its mature form and directs its secretion, triggering pyroptosis and release of non-substrate alarmins such as interleukin 1 alpha (IL-1α) and HMGB1. While some caspase-1 substrates involved in these events are known, the identities and roles of non-proteolytic targets remain unknown. Here, we use unbiased proteomics to show that the UBE2L3 ubiquitin conjugase is an indirect target of caspase-1...
January 31, 2017: Cell Reports
https://www.readbyqxmd.com/read/28144998/p2y12-receptors-in-primary-microglia-activate-nuclear-factor-of-activated-t-cell-signaling-to-induce-c-c-chemokine-3-expression
#20
Hidetoshi Tozaki-Saitoh, Hiroyuki Miyata, Tomohiro Yamashita, Katsuyuki Matsushita, Makoto Tsuda, Kazuhide Inoue
Microglia are widely accepted as surveillants in the central nervous system that are continually searching the local environment for signs of injury. Following an inflammatory situation, microglia alter their morphology, extend ramified processes, and undergo cell body hypertrophy. Extracellular nucleotides are recognized as a danger signal by microglia. ADP acting on P2Y12 receptors induce process extension of microglia thereby attracting microglia to the site of adenosine tri-phosphate/ADP leaking or release...
January 31, 2017: Journal of Neurochemistry
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