Search results for: Neutron Activation Analysis

Authors: Jianli Dong, Fangling Xu, Gengming Huang

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Human endogenous retroviral elements (HERVs) comprise approximately 8% of the human genome. They are thought to be germline-integrated genetic remnants of retroviral infections. Although HERV sequences are highly defective, some, especially the K type (HERV-K), have been shown to be expressed and may have biological activities in the pathogenesis of cancer, chronic inflammation and autoimmune diseases. We found that HERV-K GAG and ENV proteins were strongly expressed in pleomorphic melanoma cells. We also detected a critical role of HERV-K ENV in mediating intercellular fusion and colony formation of melanoma cells. Interestingly, we found that levels of HERV-K GAG and ENV expression correlated with the activation of ERK and loss of p16INK4A in melanoma cells, and inhibition of MEK or CDK4, especially in combination, reduced HERV-K expression in melanoma cells. We also performed a reverse transcription-polymerase chain reaction (RT-PCR) assay using DNase I digestion to remove “contaminating” HERV-K genomic DNA and examined HERV-K RNA expression in plasma samples from HIV-1 infected individuals. We found a covariation between HERV-K RNA expression and CD4 cell counts in HIV-1 positive samples. Although a causal link between HERV-K activation and melanoma development, and between HERV-K activation, HIV-1 infection and CD4 cell count have yet to be determined, existing data support the further research efforts in HERV-K.

Keywords: CD4 cell, HERV-K, HIV-1, melanoma

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Authors: Dong-Gyu Leem, Ji-Sun Shin, Sang Yoon Choi, Kyung-Tae Lee

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In this study, we focused on the anti-proliferative effects of panaxydol, a C17 polyacetylenic compound derived from Panax ginseng roots, against various human cancer cells. We treated with panaxydol to various cancer cells and panaxydol treatment was found to significantly inhibit the proliferation of human lung cancer cells (A549) and human pancreatic cancer cells (AsPC-1 and MIA PaCa-2), of which AsPC-1 cells were most sensitive to its treatment. DNA flow cytometric analysis indicated that panaxydol blocked cell cycle progression at the G1 phase in A549 cells, which accompanied by a parallel reduction of protein expression of cyclin-dependent kinase (CDK) 2, CDK4, CDK6, cyclin D1 and cyclin E. CDK inhibitors (CDKIs), such as p21CIP1/WAF1 and p27KIP1, were gradually upregulated after panaxydol treatment at the protein levels. Furthermore, panaxydol induced the activation of p53 in A549 cells. In addition, panaxydol also induced apoptosis of AsPC-1 and MIA PaCa-2 cells, as shown by accumulation of subG1 and apoptotic cell populations. Panaxydol triggered the activation of caspase-3, -8, -9 and the cleavage of poly (ADP-ribose) polymerase (PARP). Reduction of mitochondrial transmembrane potential by panaxydol was determined by staining with dihexyloxacarbocyanine iodide. Furthermore, panaxydol suppressed the levels of anti-apoptotic proteins, XIAP and Bcl-2, and increased the levels of proapoptotic proteins, Bax and Bad. In addition, panaxydol inhibited the activation of Akt and extracellular signal-regulated kinase (ERK) and activated the p38 mitogen-activated protein kinase kinase (MAPK). Our results suggest that panaxydol is an anti-tumor compound that causes p53-mediated cell cycle arrest and apoptosis via mitochondrial apoptotic pathway in various cancer cells.

Keywords: apoptosis, cancer, G1 arrest, panaxydol

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Authors: Virgil Miranda, Gissele Mosqueda, Pablo Delgado, Yimesker Yihun

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Muscular fatigue affects the muscle activation that is needed for producing the desired clinical outcome. Integrating optimal muscle relaxation periods into a variety of health care rehabilitation protocols is important to maximize the efficiency of the therapy. In this study, four muscle relaxation periods (30, 60, 90, and 120 seconds) and their effectiveness in producing consistent muscle activation of the muscle biceps brachii between sets of elbow flexion and extension task was investigated among a sample of 10 subjects with no disabilities. The same resting periods were then utilized in a controlled exoskeleton-based exercise for a sample size of 5 subjects and have shown similar results. On average, the muscle activity of the biceps brachii decreased by 0.3% when rested for 30 seconds, and it increased by 1.25%, 0.76%, and 0.82% when using muscle relaxation periods of 60, 90, and 120 seconds, respectively. The preliminary results suggest that a muscle relaxation period of about 60 seconds is needed for optimal continuous muscle activation within rehabilitation regimens. Robot-based rehabilitation is good to produce repetitive tasks with the right intensity, and knowing the optimal resting period will make the automation more effective.

Keywords: rest intervals, muscle biceps brachii, robot rehabilitation, muscle fatigue

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Authors: Miroslava Hujová, Patricia Rabello Monich, Jozef Kraxner, Dusan Galusek, Enrico Bernardo

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Inorganic waste upcycling offers a solution how to avoid landfilling and how to save raw materials at the same time. However, its practical implementations in Slovakia and elsewhere in Europe, are rather limited despite the potential smaller countries like Slovakia have their advantage in closely-knitted inorganic materials industry. One part of discussion should include an overview of wastes that can be possibly used for upcycling, i.e. fly ashes, red mud, glass cullets, vitrified bottom ashes etc. These wastes can be processed by a variety of strategies, the one of our choice, alkali activation, opens the possibility for the formation of novel materials at almost negligible energetic expense. In the research, these materials are characterized by comprehensive means (X-Ray Fluorescece, Diffraction methods, Thermal Analysis, Scanning Electron Microscopy, Mechanical tests and Chemical stability), which time and time again demonstrate their competitive properties against traditional materials available at the market. It is just a question for discussion why these materials do not receive more significant attention from industry and there is pressing interest for the solution of standing situation.

Keywords: upcycling, inorganic wastes, glass ceramics, alkali-activation

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Authors: Apoorva Vinod, Archana Mathur, Snehanshu Saha

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Though there exists a plethora of Activation Functions (AFs) used in single and multiple hidden layer Neural Networks (NN), their behavior always raised curiosity, whether used in combination or singly. The popular AFs –Sigmoid, ReLU, and Tanh–have performed prominently well for shallow and deep architectures. Most of the time, AFs are used singly in multi-layered NN, and, to the best of our knowledge, their performance is never studied and analyzed deeply when used in combination. In this manuscript, we experiment with multi-layered NN architecture (both on shallow and deep architectures; Convolutional NN and VGG16) and investigate how well the network responds to using two different AFs (Sigmoid-Tanh, Tanh-ReLU, ReLU-Sigmoid) used alternately against a traditional, single (Sigmoid-Sigmoid, Tanh-Tanh, ReLUReLU) combination. Our results show that using two different AFs, the network achieves better accuracy, substantially lower loss, and faster convergence on 4 computer vision (CV) and 15 Non-CV (NCV) datasets. When using different AFs, not only was the accuracy greater by 6-7%, but we also accomplished convergence twice as fast. We present a case study to investigate the probability of networks suffering vanishing and exploding gradients when using two different AFs. Additionally, we theoretically showed that a composition of two or more AFs satisfies Universal Approximation Theorem (UAT).

Keywords: activation function, universal approximation function, neural networks, convergence

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Authors: Yu-Chen Hu

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Gene editing by CRISPR and gene regulation by microRNA or CRISPR activation have dramatically changed the way to manipulate cellular gene expression and cell fate. In recent years, various gene editing and gene manipulation technologies have been applied to control stem cell differentiation to enhance tissue regeneration. This research will focus on how to develop CRISPR, CRISPR activation (CRISPRa), CRISPR inhibition (CRISPRi), as well as bi-directional CRISPR-AI gene regulation technologies to control cell differentiation and bone regeneration. Moreover, in this study, CRISPR/Cas13d-mediated RNA editng for miRNA editing and bone regeneration will be discussed.

Keywords: gene therapy, bone regeneration, stem cell, CRISPR, gene regulation

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Authors: Onuchukwu Chika Christian, Chukwude Augustine Ejike

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We carried out a statistical analyse of microglitches events on a sample of radio pulsars. The distribution of microglitch events in frequency (ν) and first frequency derivatives ν˙ indicates that the size of a microglitch and sign combinations of events in ν and ν˙ are purely randomized. Assuming that the probability of a given size of a microglitch event occurring scales inversely as the absolute size of the event in both ν and ν˙, we constructed a cumulative distribution function (CDF) for the absolute sizes of microglitches. In most of the pulsars, the theoretical CDF matched the observed values. This is an indication that microglitches in pulsar may be interpreted as an avalanche process in which angular momentum is transferred erratically from the flywheel-like superfliud interior to the slowly decelerating solid crust. Analysis of the waiting time indicates that it is purely Poisson distributed with mean microglitch rate <γ> ∼ 0.98year^−1 for all the pulsars in our sample and <γ> / <∆T> ∼ 1. Correlation analysis, showed that the relative absolute size of microglitch event strongly with the rotation period of the pulsar with correlation coefficient r ∼ 0.7 and r ∼ 0.5 respectively for events in ν and ν˙. The mean glitch rate and number of microglitches (Ng) showed some dependence on spin down rate (r ∼ −0.6) and the characteristic age of the pulsar (τ) with (r ∼ −0.4/− 0.5).

Keywords: method-data analysis, star, neutron-pulsar, general

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Authors: E. A. Krasikov

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As the service life of an operating nuclear power plant (NPP) increases, the potential misunderstanding of the degradation of aging components must receive more attention. Integrity assurance analysis contributes to the effective maintenance of adequate plant safety margins. In essence, the reactor pressure vessel (RPV) is the key structural component determining the NPP lifetime. Environmentally induced cracking in the stainless steel corrosion-preventing cladding of RPV’s has been recognized to be one of the technical problems in the maintenance and development of light-water reactors. Extensive cracking leading to failure of the cladding was found after 13000 net hours of operation in JPDR (Japan Power Demonstration Reactor). Some of the cracks have reached the base metal and further penetrated into the RPV in the form of localized corrosion. Failures of reactor internal components in both boiling water reactors and pressurized water reactors have increased after the accumulation of relatively high neutron fluences (5´1020 cm–2, E>0,5MeV). Therefore, in the case of cladding failure, the problem arises of hydrogen (as a corrosion product) embrittlement of irradiated RPV steel because of exposure to the coolant. At present when notable progress in plasma physics has been obtained practical energy utilization from fusion reactors (FR) is determined by the state of material science problems. The last includes not only the routine problems of nuclear engineering but also a number of entirely new problems connected with extreme conditions of materials operation – irradiation environment, hydrogenation, thermocycling, etc. Limiting data suggest that the combined effect of these factors is more severe than any one of them alone. To clarify the possible influence of the in-service synergistic phenomena on the FR structural materials properties we have studied hydrogen-irradiated steel interaction including alternating hydrogenation and heat treatment (annealing). Available information indicates that the life of the first wall could be expanded by means of periodic in-place annealing. The effects of neutron fluence and irradiation temperature on steel/hydrogen interactions (adsorption, desorption, diffusion, mechanical properties at different loading velocities, post-irradiation annealing) were studied. Experiments clearly reveal that the higher the neutron fluence and the lower the irradiation temperature, the more hydrogen-radiation defects occur, with corresponding effects on the steel mechanical properties. Hydrogen accumulation analyses and thermal desorption investigations were performed to prove the evidence of hydrogen trapping at irradiation defects. Extremely high susceptibility to hydrogen embrittlement was observed with specimens which had been irradiated at relatively low temperature. However, the susceptibility decreases with increasing irradiation temperature. To evaluate methods for the RPV’s residual lifetime evaluation and prediction, more work should be done on the irradiated metal–hydrogen interaction in order to monitor more reliably the status of irradiated materials.

Keywords: hydrogen, radiation, stability, structural steel

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Authors: Ludmila A. Gavriliuc, Jerry McLarty, Heather E. Kleiner, J. Michael Mathis

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Abstract -- Background: The citrus coumarine Auraptene (Aur) is an effective chemopreventive agent, as manifested in many models of diseases and cancer. Nuclear factor erythroid 2-related factor (Nrf2) is an important regulator of genes induced by oxidative stress, such as glutathione S-transferases, heme oxygenase-1, and peroxiredoxin 1, by activating the antioxidant response element (ARE). Genetic and biochemical evidence has demonstrated that glutathione (GSH) and glutathione-dependent enzymes, glutathione reductase (GR), glutathione peroxidases (GPs), glutathione S-transferases (GSTs) are responsible for the control of intracellular reduction-oxidation status and participate in cellular adaptation to oxidative stress. The effect of Aur on the activity of GR, GPs (Se-GP and Se-iGP), and content of GSH in the liver, kidney, and spleen is insufficiently explored. Aim: Our goal was the examination of the Aur influence on the redox-system of GSH in Nrf2 wild type and Nrf2 knockout mice via activation of Nrf2 and ARE. Methods: Twenty female mice, 10 Nrf2 wild-type (WT) and 10 Nrf2 (-/-) knockout (KO), were bred and genotyped for our study. The activity of GR, Se-GP, Se-iGP, GST, G6PD, CytP450 reductase, catalase (Cat), and content of GSH were analyzed in the liver, kidney, and spleen using Spectrophotometry methods. The results of the specific activity of enzymes and the amount of GSH were analyzed with ANOVA and Spearman statistical methods. Results: Aur (200 mg/kg) treatment induced hepatic GST, GR, Se-GP activity and inhibited their activity in the spleen of mice, most likely via activation of the ARE through Nrf2. Activation in kidney Se-GP and G6PD by Aur is also controlled, apparently through Nrf2. Results of the non-parametric Spearman correlation analysis indicated the strong positive correlation between GR and G6PD only in the liver in WT control mice (r=+0.972; p < 0.005) and in the kidney KO control mice (r=+0.958; p < 0.005). The observed low content of GSH in the liver of KO mice indicated an increase in its participation in the neutralization of toxic substances with the absence of induction of GSH-dependent enzymes, such as GST, GR, Se-GP, and Se-iGP. Activation of CytP450 in kidney and spleen and Cat in the liver in KO mice probably revealed another regulatory mechanism for these enzymes. Conclusion: Thereby, obtained results testify that Aur can modulate the activity of genes and antioxidant enzymatic redox-system of GSH, responsible for the control of intracellular reduction-oxidation status.

Keywords: auraptene, glutathione, GST, Nrf2

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Authors: Michael K. Adu, Boniface K. Alese, Olumide S. Ogunnusi

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This paper brings to fore the inherent advantages in application of mobile agents to procure software products rather than downloading software content on the Internet. It proposes a system whereby the products come on compact disk with mobile agent as deliverable. The client/user purchases a software product, but must connect to the remote server of the software developer before installation. The user provides an activation code that activates mobile agent which is part of the software product on compact disk. The validity of the activation code is checked on connection at the developer’s end to ascertain authenticity and prevent piracy. The system is implemented by downloading two different software products as compare with installing same products on compact disk with mobile agent’s application. Downloading software contents from developer’s database as in the traditional method requires a continuously open connection between the client and the developer’s end, a fixed network is not economically or technically feasible. Mobile agent after being dispatched into the network becomes independent of the creating process and can operate asynchronously and autonomously. It can reconnect later after completing its task and return for result delivery. Response Time and Network Load are very minimal with application of Mobile agent.

Keywords: software products, software developer, internet, activation code, mobile agent

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Authors: A. P. Srivastava, D. Srivastava, D. J. Browne

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Relaxation dynamics of Zr44Cu40Al8Ag8 bulk metallic glass (BMG) has been probed using dynamic mechanical analyzer. The BMG sample was casted in the form of a plate of dimension 55 mm x 40 mm x 3 mm using tilt casting technique. X-ray diffraction and transmission electron microscope have been used for the microstructural characterization of as-cast BMG. For the mechanical spectroscopy study, samples in the form of a bar of size 55 mm X 2 mm X 3 mm were machined from the BMG plate. The mechanical spectroscopy was performed on dynamic mechanical analyzer (DMA) by 50 mm 3-point bending method in a nitrogen atmosphere. It was observed that two glass transition process were competing in supercooled liquid region around temperature 390°C and 430°C. The supercooled liquid state was completely characterized using DMA and differential scanning calorimeter (DSC). In addition to the main α-relaxation process, presence of β relaxation process around temperature 360°C; below the glass transition temperature was also observed. The β relaxation process could be described by Arrhenius law with the activation energy of 160 kJ/mole. The volume of the flow unit associated with this relaxation process has been estimated. The results from DMA study has been used to characterize the shear transformation zone in terms of activation volume and size. High fragility parameter value of 34 and higher activation volume indicates that this alloy could show good plasticity in supercooled liquid region. The possible mechanism for the relaxation processes has been discussed.

Keywords: DMA, glass transition, metallic glass, thermoplastic forming

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Authors: Beth Taylor, Kojima Mituaki, Atsushi Senda, Koji Morishita, Yasuhiro Otomo

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Intestinal ischaemia-reperfusion injury drives systemic inflammation and organ failure following trauma/haemorrhagic shock (T/HS), through the release of pro-inflammatory mediators into the mesenteric lymph (ML). However, changes in the biological function of ML are not fully understood, and therefore, a specific model of intestinal ischaemia-reperfusion injury is required to obtain ML for the study of its biological function upon inflammatory cells. ML obtained from a model of intestinal ischaemia-reperfusion injury was used to assess biological function upon inflammatory cells and investigate changes in the biological function of individual ML components. An additional model was used to determine the effect of vagal nerve stimulation (VNS) upon biological function. Rat ML was obtained by mesenteric lymphatic duct cannulation before and after occlusion of the superior mesenteric artery (SMAO). ML was incubated with human polymorphonuclear neutrophils (PMNs), monocytes and lymphocytes, and the biological function of these cells was assessed. ML was then separated into supernatant, exosome and micro-vesicle components, and biological activity was compared in monocytes. A model with an additional VNS phase was developed, in which the right cervical vagal nerve was exposed and stimulated, and ML collected for comparison of biological function with the conventional model. The biological function of ML was altered by intestinal ischaemia-reperfusion injury, increasing PMN activation, monocyte activation, and lymphocyte apoptosis. Increased monocyte activation was only induced by the exosome component of ML, with no significant changes induced by the supernatant or micro-vesicle components. VNS partially attenuated monocyte activation, but no attenuation of PMN activation was observed. Intestinal ischaemia-reperfusion injury induces changes in the biological function of ML upon both innate and adaptive inflammatory cells, supporting the role of intestinal ischaemia-reperfusion injury in driving systemic inflammation following T/HS. The exosome component of ML appears to be critical to the transport of pro-inflammatory mediators in ML. VNS partially attenuates changes in innate inflammatory cell biological activity observed, presenting possibilities for future novel treatment development in multiple organ failure patients.

Keywords: exosomes, inflammation, intestinal ischaemia, mesenteric lymph, vagal stimulation

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Authors: Strahinja Kovačević, Jelena Vladić, Senka Vidović, Zoran Zeković, Lidija Jevrić, Sanja Podunavac Kuzmanović

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Supercritical extracts of highly valuated medicinal plant Satureja montana were prepared by application of supercritical carbon dioxide extraction in the carbon dioxide pressure range from 125 to 350 bar and temperature range from 40 to 60°C. Using GC/MS method of analysis chemical profiles (aromatic constituents) of S. montana extracts were obtained. Self-training artificial neural networks were applied to predict the retention time of the analyzed terpenes in GC/MS system. The best ANN model obtained was multilayer perceptron (MLP 11-11-1). Hidden activation was tanh and output activation was identity with Broyden–Fletcher–Goldfarb–Shanno training algorithm. Correlation measures of the obtained network were the following: R(training) = 0.9975, R(test) = 0.9971 and R(validation) = 0.9999. The comparison of the experimental and predicted retention times of the analyzed compounds showed very high correlation (R = 0.9913) and significant predictive power of the established neural network.

Keywords: ANN regression, GC/MS, Satureja montana, terpenes

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Authors: Lídia E. O. Cruz, Adriano P. C. Calvo, Renato J. Soares, Regiane A. Carvalho

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Individuals with non-specific chronic low back pain may present altered movement patterns during functional activities. However, muscle behavior before and after performing a functional task with different load conditions is not yet fully understood. The aim of this study is to analyze lumbar muscle activity before and after performing the functional task of picking up and placing an object on the ground (with and without load) in individuals with nonspecific chronic low back pain. 20 subjects with nonspecific chronic low back pain and 20 healthy subjects participated in this study. A surface electromyography was performed in the ilio-costal, longissimus and multifidus muscles to evaluate lumbar muscle activity before and after performing the functional task of picking up and placing an object on the ground, with and without load. The symptomatic participants had greater lumbar muscle activation compared to the asymptomatic group, more evident in performing the task without load, with statistically significant difference (p = 0,033) between groups for the right multifidus muscle. This study showed that individuals with nonspecific chronic low back pain have higher muscle activation before and after performing a functional task compared to healthy participants.

Keywords: chronic low back pain, functional task, lumbar muscles, muscle activity

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Authors: Markus Bredel, Sindhu Nair, Hoa Q. Trummell, Rajani Rajbhandari, Christopher D. Willey, Lewis Z. Shi, Zhuo Zhang, William J. Placzek, James A. Bonner

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Purpose: EGFR-targeted monoclonal antibodies (mAbs) provide clinical benefit in some patients with H&N squamous cell carcinoma (HNSCC), but others progress with minimal response. Missense mutations in the EGFR ectodomain (ECD) can be acquired under mAb therapy by mimicking the effect of large deletions on receptor untethering and activation. Little is known about the contribution of EGFR ECD mutations to EGFR activation and anti-EGFR response in HNSCC. Methods: We selected patient-derived HNSCC cells (UM-SCC-1) for resistance to mAb Cetuximab (CTX) by repeated, stepwise exposure to mimic what may occur clinically and identified two concurrent EGFR ECD mutations (UM-SCC-1R). We examined the competence of the mutants to bind EGF ligand or CTX. We assessed the potential impact of the mutations through visual analysis of space-filling models of the native sidechains in the original structures vs. their respective side-chain mutations. We performed CRISPR in combination with site-directed mutagenesis to test for the effect of the mutants on ligand-independent EGFR activation and sorting. We determined the effects on receptor internalization, endocytosis, downstream signaling, and radiation sensitivity. Results: UM-SCC-1R cells carried two non-synonymous missense mutations (G33S and N56K) mapping to domain I in or near the EGF binding pocket of the EGFR ECD. Structural modeling predicted that these mutants restrict the adoption of a tethered, inactive EGFR conformation while not permitting association of EGFR with the EGF ligand or CTX. Binding studies confirmed that the mutant, untethered receptor displayed a reduced affinity for both EGF and CTX but demonstrated sustained activation and presence at the cell surface with diminished internalization and sorting for endosomal degradation. Single and double-mutant models demonstrated that the G33S mutant is dominant over the N56K mutant in its effect on EGFR activation and EGF binding. CTX-resistant UM-SCC-1R cells demonstrated cross-resistance to mAb Panitumuab but, paradoxically, remained sensitive to the reversible receptor tyrosine kinase inhibitor Erlotinib. Conclusions: HNSCC cells can select for EGFR ECD mutations under EGFR mAb exposure that converge to trap the receptor in an open, constitutively activated state. These mutants impede the receptor’s competence to bind mAbs and EGF ligand and alter its endosomal trafficking, possibly explaining certain cases of clinical mAb and radiation resistance.

Keywords: head and neck cancer, EGFR mutation, resistance, cetuximab

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Authors: Hannele Laaksonen, Seija Nyqvist, Kari Nurmes

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Objectives: In the year 2011 the City of Vaasa started to develop know-how in the technology and the introduction of services for aging people in cooperation with the Polytechnic Novia University of Applied Sciences and VAMK, University of Applied Sciences. The project´s targets included: to help elderly people to maintain their ability to function, to provide them social and physical activities, to prevent their social exclusion, to decrease their feelings of loneliness and insecurity and to develop their technical know-how. Methods: The project was built based on open source code, tailor-made service system and user interface for the elderly living at home and their families, based on the users´ expectations and experiences of services. Activation-TV®-project vas carried out 1.4.2011-31.3.2014. A pilot group of eight elderly persons, who were living at home, were selected to the project. All necessary technical means as well as guidance and teaching equipment were provided to the pilot group. The students of University of Applied Sciences (VAMK, Novia) and employees of Center of Ageing were made all programs to the Activation-TV®. The project group were interviewed after and before intervention. The data were evaluated both qualitatively and quantitatively. Results: The built service includes a video library, a group room for interactive programs and a personal room for bilateral meetings and direct shipment. The program is bilingual and produced in both national languages. The Activation TV® reduced elderly peoples´ (n=8) feelings of emptiness, added mental well-being and quality of life with social contacts. Relatives felt, that they were able to get in to older peoples´ everyday life with Activation TV®. Discussion: The built application was tailored to the model that has not been developed elsewhere in Finland. This model can be copied from one server to another and thus transferred to other municipalities but the program requires its own personnel system management and maintenance as well as program production cooperation between the different actors. This service can be used for the elderly who are living at home without dementia.

Keywords: mental well-being, quality of life, elderly people, Finland

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Authors: Nafisa Komilova, Plamena Angelova, Andrey Abramov, Ulugbek Mirkhodjaev

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Parkinson’s disease (PD) is a progressive neurodegenerative disorder which is induced by the loss of dopaminergic neurons in the midbrain. The mechanism of neurodegeneration is associated with the aggregation of misfolded proteins, oxidative stress, and mitochondrial disfunction. Considering this, the process of removal of unwanted organelles or proteins by autophagy is vitally important in neurons, and activation of these processes could be protective in PD. Short-time acidification of cytosol can activate mitophagy and autophagy, and here we used sodium pyruvate and sodium lactate in human fibroblasts with PD mutations (Pink1, Pink1/Park2, α-syn triplication, A53T) to induce changes in intracellular pH. We have found that both lactate and pyruvate in millimolar concentrations can induce short-time acidification of cytosol in these cells. It induced activation of mitophagy and autophagy in control and PD fibroblasts and protected against cell death. Importantly, the application of lactate to acute brain slices of control and Pink1 knockout mice also induced a reduction of pH in neurons and astrocytes that increase the level of mitophagy. Thus, acidification of cytosol by compounds which play important role in cell metabolism also can activate mitophagy and autophagy and protect cells in the familial form of PD.

Keywords: Parkinson's disease, mutations, mitophagy, autophagy

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Authors: Eduardo Kanagushiku Pereira, Frank Gregory Cavalcante da Silva, Barbara Soares Gonçalves, Ana Lúcia Bergamasco Galastri, Ronei Luciano Mamoni

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The inflammatory response initiates after the recognition of pathogens by receptors expressed by innate immune cells. Among these receptors, the NLRP3 was associated with the recognition of pathogenic fungi in experimental models. NLRP3 operates forming a multiproteic complex called inflammasome, which actives caspase-1, responsible for the production of the inflammatory cytokines IL-1beta and IL-18. In this study, we aimed to investigate the involvement of NLRP3 in the inflammatory response elicited in macrophages against Paracoccidioides brasiliensis (Pb), the etiologic agent of PCM. Macrophages were differentiated from THP-1 cells by treatment with phorbol-myristate-acetate. Following differentiation, macrophages were stimulated by Pb yeast cells for 24 hours, after previous treatment with specific NLRP3 (3,4-methylenedioxy-beta-nitrostyrene) and/or caspase-1 (VX-765) inhibitors, or specific inhibitors of pathways involved in NLRP3 activation such as: Reactive Oxigen Species (ROS) production (N-Acetyl-L-cysteine), K+ efflux (Glibenclamide) or phagossome acidification (Bafilomycin). Quantification of IL-1beta and IL-18 in supernatants was performed by ELISA. Our results showed that the production of IL-1beta and IL-18 by THP-1-derived-macrophages stimulated with Pb yeast cells was dependent on NLRP3 and caspase-1 activation, once the presence of their specific inhibitors diminished the production of these cytokines. Furthermore, we found that the major pathways involved in NLRP3 activation, after Pb recognition, were dependent on ROS production and K+ efflux. In conclusion, our results showed that NLRP3 participates in the recognition of Pb yeast cells by macrophages, leading to the activation of the NLRP3-inflammasome and production of IL-1beta and IL-18. Together, these cytokines can induce an inflammatory response against P. brasiliensis, essential for the establishment of the initial inflammatory response and for the development of the subsequent acquired immune response.

Keywords: inflammation, IL-1beta, IL-18, NLRP3, Paracoccidioidomycosis

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Authors: Gina Leisching, Ray-Dean Pietersen, Carel Van Heerden, Paul Van Helden, Ian Wiid, Bienyameen Baker

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The distinguishing factors that characterize the host response to infection with virulent Mycobacterium tuberculosis (M.tb) are largely confounding. We present an infection study with two genetically closely related M.tb strains that have vastly different pathogenic characteristics. The early host response to infection with these detergent-free cultured strains was analyzed through RNAseq in an attempt to provide information on the subtleties which may ultimately contribute to the virulent phenotype. Murine bone marrow-derived macrophages (BMDMs) were infected with either a hyper- (R5527) or hypovirulent (R1507) Beijing M. tuberculosis clinical isolate. RNAseq revealed 69 differentially expressed host genes in BMDMs during comparison of these two transcriptomes. Pathway analysis revealed activation of the stress-induced and growth inhibitory Gadd45 signaling pathway in hypervirulent infected BMDMs. Upstream regulators of interferon activation such as and IRF3 and IRF7 were predicted to be upregulated in hypovirulent-infected BMDMs. Additional analysis of the host immune response through ELISA and qPCR included the use of human THP-1 macrophages where a robust proinflammatory response was observed after infection with the hypervirulent strain. RNAseq revealed two early-response genes (IER3 and SAA3) and two host-defence genes (OASL1 and SLPI) that were significantly upregulated by the hypervirulent strain. The role of these genes under M.tb infection conditions are largely unknown but here we provide validation of their presence with use of qPCR and Western blot. Further analysis into their biological role under infection with virulent M.tb is required.

Keywords: host-response, Mycobacterium tuberculosis, RNAseq, virulence

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Authors: Mohammadjavad Yaghoubi, Arul Arulrajah, Mahdi M. Disfani, Suksun Horpibulsuk, Myint W. Bo, Stephen P. Darmawan

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This paper investigates the changes in the strength development of a high water content soft soil stabilised with alkaline activation of fly ash (FA) to use in deep soil mixing (DSM) technology. The content of FA was 20% by dry mass of soil, and the alkaline activator was sodium silicate (Na2SiO3). Samples were cured for 3, 7, 14, 28 and 56 days to evaluate the effect of curing time on strength development. To study the effect of adding slag (S) to the mixture on the strength development, 5% S was replaced with FA. In addition, the effect of the initial unit weight of samples on strength development was studied by preparing specimens with two different static compaction stresses. This was to replicate the field conditions where during implementing the DSM technique, the pressure on the soil while being mixed, increases with depth. Unconfined compression strength (UCS), scanning electron microscopy (SEM) and energy-dispersive X-ray spectroscopy (EDS) tests were conducted on the specimens. The results show that adding S to the FA based geopolymer activated by Na2SiO3 decreases the strength. Furthermore, samples prepared at a higher unit weight demonstrate greater strengths. Moreover, samples prepared at lower unit weight reached their final strength at about 14 days of curing, whereas the strength development continues to 56 days for specimens prepared at a higher unit weight.

Keywords: alkaline activation, curing time, fly ash, geopolymer, slag

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Authors: Parichehr Sharifi, Konrad Reschke, Hans-Liudger Dienel

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Psychological intervention generally targets changes in attitudes and behavior. Working with DUIs is part of traffic psychologists’ work. The primary goal of this field is to reduce the probability of re-conspicuous of the delinquent driver. One of these measurements in Germany is IFT courses for DUI s. The IFT course was designed by the Institute for Therapy Research. Participants are drivers who have fallen several times or once with a blood alcohol concentration of 1.6 per mill and who have completed a medical-psychological assessment (MPU) with the result of the course recommendation. The course covers four sessions of 3.5 hours each (1 hour / 60 m) and in a period of 3 to 4 weeks in the group discussion. This work analyzes interventions for the rehabilitation of DUI (Drunk Drivers offenders) offenders in groups under the aspect of activating psychological resources. From the aspect of sustainability, they should also have long-term consequences for the maintenance of unproblematic driving behavior in terms of the activation of resources. It is also addressing a selected consistency-theory-based intervention effect, activating psychological resources. So far, this has only been considered in the psychotherapeutic field but never in the field of traffic psychology. The methodology of this survey is one qualitative and three quantitative. In four sub-studies, it will be examined which measurements can determine the resources and how traffic psychological interventions can strengthen resources. The results of the studies have the following implications for traffic psychology research and practice: (1) In the field of traffic psychology intervention for the restoration of driving fitness, it can be stated that aspects of resource activation in this work have been investigated for the first time by qualitative and quantitative methods. (2) The resource activation could be confirmed based on the determined results as an effective factor of traffic psychological intervention. (3) Two sub-studies show a range of resources and resource activation options that must be given greater emphasis in traffic psychology interventions: - Social resource activation - improvement of the life skills of participants - Reactivation of existing social support options - Re-experiencing self-esteem, self-assurance, and acceptance of traffic-related behaviors. (4) In revising the IFT-§70 course, as well as other courses on recreating aptitude for DUI, new traffic-specific resource-enabling interventions against alcohol abuse should be developed to further enhance the courses through motivational, cognitive, and behavioral effects of resource activation, Resource-activating interventions can not only be integrated into behavioral group interventions but can also be applied in psychodynamic, psychodynamic (individual psychological) and other contexts of individual traffic psychology. The results are indicative but clearly show that personal resources can be strengthened through traffic psychology interventions. In the research, practice, training, and further education of traffic psychology, the aspect of primary resource activation (Grawe, 1999), therefore, always deserves the greatest attention for the rehabilitation of DUIs and Traffic safety.

Keywords: traffic safety, psychological resources, activating of resources, intervention programs for alcohol offenders, empowerment

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Authors: Elif Unveren, Ozlem Bozkurt

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Emotion processing happens when someone has a negative, stressful experience and gets over it in time, and it is a different experience for every person. As to look into emotion processing can be categorised by intensity, awareness, coordination, speed, accuracy and response. It may vary depending on people’s age, sex and conditions. Each emotion processing shows different activation patterns in different brain regions. Activation is significantly higher in the right frontal areas. The highest activation happens in extended frontotemporal areas during the processing of happiness, sadness and disgust. Those emotions also show widely disturbed differences and get produced earlier than anger and fear. For different occasions, listed variables may have less or more importance. A borderline personality disorder is a condition that creates an unstable personality, sudden mood swings and unpredictability of actions. According to a study that was made with healthy people and people who had BPD, there were significant differences in some categories of emotion processing, such as intensity, awareness and accuracy. According to another study that was made to show the emotional processing differences between puberty and was made for only females who were between the ages of 11 and 17, it was perceived that for different ages and hormone levels, different parts of the brain are used to understand the given task. Also, in the different study that was made for kids that were between the age of 4 and 15, it was observed that the older kids were processing emotion more intensely and expressing it to a greater extent. There was a significant increase in fear and disgust in those matters. To sum up, we can say that the activity of undertaking negative experiences is a unique thing for everybody for many different reasons.

Keywords: age, sex, conditions, brain regions, emotion processing

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Authors: Ji Hye Im, Nguyen T. T. Phuong, Keon Wook Kang

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Estrogens are important for the development and growth of estrogen receptor (ER)-positive breast cancer, for which anti-estrogen therapy is one of the most effective treatments. However, its efficacy can be limited by either de novo or acquired resistance. Aromatase is a key enzyme for the biosynthesis of estrogens, and inhibition of this enzyme leads to profound hypoestrogenism. Here, we found that the basal expression and activity of aromatase were significantly increased in tamoxifen (TAM)-resistant human breast cancer (TAMR-MCF-7) cells compared to control MCF-7 cells. We further revealed that aromatase immunoreactivity in tumor tissues was increased in recurrence group after TAM therapy compared to non-recurrence group after TAM therapy. Phosphorylation of Akt, extracellular signal-regulated kinase (ERK), and p38 kinase were all increased in TAMR-MCF-7 cells. Inhibition of phosphoinositide 3-kinase (PI3K) suppressed the transactivation of the aromatase gene and its enzyme activity. Furthermore, we have also shown that PI3K/Akt-dependent cAMP-response element binding protein (CREB) activation was required for the enhanced expression of aromatase in TAMR-MCF-7 cells. Our findings suggest that aromatase expression is up-regulated in TAM-resistant breast cancer via PI3K/Akt-dependent CREB activation.

Keywords: TAMR-MCF-7, CREB, estrogen receptor, aromatase

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Authors: Shweta Jha, Digambar Darekar, Krishna Kadam

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Major Depressive Disorder (MDD) is one of the most common of psychiatric disorders. It has a wide range of symptoms, aetiologies and risk factors, and these reasons make MDD affect not only the primary patient, but also their family, caregivers and associates; by negatively impacting their self dignity, economic condition and self-confidence. Thus, it is important to help individuals suffering from MDD learn adaptive mechanism and deal effectively with their environment, with that aim this study focused on a comparative therapeutic intervention using Behaviour Activation (BA), Rational Emotive Behaviour Therapy (REBT) and Waiting list control (WLC) for management of MDD. This study apart from enhancing personal skills will also help us understand which therapeutic method would be more beneficial in treating and prolonging relapse in patients with MDD in Indian population. Fifteen individuals following application of inclusion and exclusion criteria were selected as study samples. They were randomly assigned to three treatment groups. Ten sessions of therapy, forty-five minutes each according to the proposed sessions plan were conducted for each group. The individuals selected as samples were re–assessed after 2 months and 6 months post intervention. The overall result showed that individuals treated with BA and REBT showed more improvement in comparison to those in WLC.

Keywords: behaviour activation, major depressive disorder, rational emotive behaviour therapy, therapeutic intervention

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Authors: Gheorghe Ionita, Sebastian Brad, Ioan Stefanescu

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In any fusion device, tritium plays a key role both as a fuel component and, due to its radioactivity and easy incorporation, as tritiated water (HTO). As for the ITER project, to reduce the constant potential of tritium emission, there will be implemented a Water Detritiation System (WDS) and an Isotopic Separation System (ISS). In the same time, during operation of fission CANDU reactors, the tritium content increases in the heavy water used as moderator and cooling agent (due to neutron activation) and it has to be reduced, too. In Romania, at the National Institute for Cryogenics and Isotopic Technologies (ICIT Rm-Valcea), there is an Experimental Pilot Plant for Tritium Removal (Exp. TRF), with the aim of providing technical data on the design and operation of an industrial plant for heavy water depreciation of CANDU reactors from Cernavoda NPP. The selected technology is based on the catalyzed isotopic exchange process between deuterium and liquid water (LPCE) combined with the cryogenic distillation process (CD). This paper presents an updated review of activities in the field carried out in Romania after the year 2000 and in particular those related to the development and operation of Tritium Removal Experimental Pilot Plant. It is also presented a comparison between the experimental pilot plant and industrial plant to be implemented at Cernavoda NPP. The similarities between the experimental pilot plant from ICIT Rm-Valcea and water depreciation and isotopic separation systems from ITER are also presented and discussed. Many aspects or 'opened issues' relating to WDS and ISS could be checked and clarified by a special research program, developed within ExpTRF. By these achievements and results, ICIT Rm - Valcea has proved its expertise and capability concerning tritium management therefore its competence may be used within ITER project.

Keywords: ITER project, heavy water detritiation, tritium removal, isotopic exchange

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Authors: Olumayede Emmanuel Gbenga, Adeniyi Azeez Adebayo

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Carbonyls are the first-generation products from tropospheric degradation reactions of volatile organic compounds (VOCs). This computational study examined the mechanism of removal of carbonyls from the atmosphere via hydroxyl radical. The kinetics of the reactions were computed from the activation energy (using enthalpy (ΔH**) and Gibbs free energy (ΔG**). The minimum energy path (MEP) analysis reveals that in all the molecules, the products have more stable energy than the reactants, which implies that the forward reaction is more thermodynamically favorable. The hydrogen abstraction of the aromatic aldehyde, especially without methyl substituents, is more kinetically favorable compared with the other aldehydes in the order of aromatic (without methyl or meta methyl) > alkene (short chain) > diene > long-chain aldehydes. The activation energy is much lower for the forward reaction than the backward, indicating that the forward reactions are more kinetically stable than their backward reaction. In terms of thermodynamic stability, the aromatic compounds are found to be less favorable in comparison to the aliphatic. The study concludes that the chemistry of the carbonyl bond of the aldehyde changed significantly from the reactants to the products.

Keywords: atmospheric carbonyls, oxidation, mechanism, kinetic, thermodynamic

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Authors: Francesca La Rosa , Marina Saresella, Mario Clerici, Michael Heneka

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Neuroinflammation plays a key role in the modulation of the pathogenesis of neurodegenerative disorder such as Alzheimer's Disease (AD). Microglia, the main immune effector of the brain, are able to migrate to sites of Amyloid-beta (Aβ) deposition to eliminate Aβ phagocytosis upon activation by multiple receptors: Toll like receptors and scavenger receptors. The issue of whether microglia are able to eliminate pathological lesions such as neurofibrillary tangles or senile plaques from AD brain still remains the matter of controversy. Recent data suggest that the Nod Like Receptor 3 (NLRP3), multiprotein inflammasome complexes, plays a role in AD, as its activation in the microglia by Aβ triggers. IL-1β is produced as a biologically inactive pro-form and requires caspase-1 for activation and secretion. Caspase-1 activity is controlled by inflammasomes. We investigate about the importance of inflammasomes complex in the Aβ phagocytosis and its degradation. The preliminary results of phagocytosis assay and immunofluorescent experiment on primary Microglia cells to lipopolysaccharide (LPS) an Aβ exposure show that a previous treatment with LPS reduce Aβ phagocytosis. Different results were obtained in Primary Microglia wild type, NLRP3 and ASC Knockout suggesting a real inflammasomes involvement in Alzheimer's pathology. Inflammasomes inactivation reduces the production of inflammatory cytokines prolonging the protective activity of microglia and Aβ clearance, featuring a typical microglia phenotype of the early stage of AD disease.

Keywords: Alzheimer disease, innate immunity, neuroinflammation, NLRP3

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Authors: Jonathan Andres Pullas Navarrete, Ernesto Hale de la Torre Chauvin

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In this work, the antibacterial effect of activated carbon fibers (ACF) impregnated with ionic silver particles was studied. ACF were prepared from samples of cotton woven wastes (cotton based fabrics 5x10 cm) by applying a chemical activation procedure with H3PO4. This treatment was performed using several H3PO4: Cotton based fabrics weight ratios (1:2–2:1), temperatures (600–900 ºC) and activation times (0.5–2 h). The ACF obtained under the best activation conditions showed BET surface area of 1103 m2/g; this result along with iodine index demonstrated the microporous nature of the fibers herein obtained. Then, the obtained fibers were impregnated with ionic silver particles by immersion in 0.1 and 0.5 M AgNO3 solutions followed by drying and thermal decomposition in order to fix the silver particles in the structure of ACF. It was determined that the presence of Ag ions lowered the BET surface area of the ACF in approximately 17 % due to the obstruction of the porosities along the carbonized structure. Finally, the antibacterial effect of the ACF impregnated with silver was studied through direct counting method for coliforms. The antibacterial activity of the impregnated fibers was demonstrated, and it was attributed to the strongly inhibition of bacteria growth because of chemical properties of the particles of silver inside the ACF. This behavior was demonstrated at concentrations of silver as low as 0.035 % w/w.

Keywords: activated carbon, adsorption, antibacterial activity, coliforms, surface area

Procedia PDF Downloads 282

Authors: Eun Young Choi, So Hui Choe, Jin Yi Hyeon, Ji Young Jin, Bo Ram Keum, Jong Min Lim, Hyung Rae Cho, Kwang Keun Cho, In Soon Choi

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This research analyzed the effect of β-glucan that is expected to alleviate the production of inflammatory mediator in macrophagocyte, which was processed by the lipopolysaccharide (LPS) of Escherichia, a pathogen related to allergy. The incubated layer was used for nitric oxide (NO) analysis. The DNA-binding activation of the small unit of NF-κB was measured using ELISA-based kit. In RAW264.7 cells that were vitalized by E.coli LPS, β-glucan inhibited both the combatant and rendering phases of inducible NO synthase (iNOS)-derived NO. β-glucan increased the expression of heme oxygenase-1 (HO-1) in the cell that was stimulated by E.coli LPS, and HO-1 activation was inhibited by SnPP. This shows that NO production induced by LPS is related to the inhibition effect of β-glucan. The phosphorylation of JNK and p38 induced by LPS were not influenced by β-glucan, and IκB-α decomposition was not influenced either. Instead, β-glucan remarkably inhibited the phosphorylation of STAT1 that was induced by E.coli LPS. Overall, β-glucan inhibited the production of NO in macrophagocyte that was vitalized by E.coli LPS through HO-1 induction and STAT1 pathways inhibition in this research. As the host inflammation reaction control by β-glucan weakens the progress of allergy, β-glucan can be used as an effective treatment method.

Keywords: β-glucan, lipopolysaccharide (LPS), nitric oxide (NO), RAW264.7 cells, STAT1

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Authors: Jihoon Yang, Jeong II Choi

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Mincle is expressed in macrophages and is members of immunoreceptors induced after exposure to various stimuli and stresses. Mincle receptor activation promotes the production of these substances by increasing the transcription of inflammatory cytokines and chemokines. Cytokines, which play an important role in the initiation and maintenance of such inflammatory pain diseases, have a significant effect on sensory neurons in addition to their enhancement and inhibitory effects on immune and inflammatory cells as mediators of cell interaction. Glial cells in the central nervous system play a critical role in development and maintenance of chronic pain states. Microglia are tissue-resident macrophages in the central nervous system, and belong to a group of mononuclear phagocytes. In the central nervous system, mincle receptor is present in neurons and glial cells of the brain.This study was performed to identify the Mincle receptor in the spinal cord and to investigate the effect of Mincle receptor activation on nociception and the changes of microglia. Materials and Methods: C-type lectins(Mincle) was identified in spinal cord of Male Sprague–Dawley rats. Then, mincle receptor ligand (TDB), via an intrathecal catheter. Mechanical allodynia was measured using von Frey test to evaluate the effect of intrathecal injection of TDB. Result: The present investigation shows that the intrathecal administration of TDB in the rat produces a reliable and quantifiable mechanical hyperalgesia. In addition, The mechanical hyperalgesia after TDB injection gradually developed over time and remained until 10 days. Mincle receptor is identified in the spinal cord, mainly expressed in neuronal cells, but not in microglia or astrocyte. These results suggest that activation of mincle receptor pathway in neurons plays an important role in inducing activation of microglia and inducing mechanical allodynia.

Keywords: mincle, spinal cord, pain, microglia

Procedia PDF Downloads 159