Search results for: microglia activation

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: Yu-Wen Cheng, Jau-Der Ho, Liang-Huan Wu, Fan-Li Lin, Li-Huei Chen, Hung-Ming Chang, Yueh-Hsiung Kuo, George Hsiao

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Retina glial activation and neuroinflammation have been confirmed to cause devastating responses in retinodegenerative diseases. The expression and activation of matrix metalloproteinase (MMP)-9 and inducible nitric oxide synthase (iNOS) could be exerted as the crucial pathological factors in glaucoma- and blue light-induced retinal injuries. The present study aimed to investigate the retinoprotective effects and mechanisms of fungal ingredient 3,4-dihydroxybenzalacetone (DBL) isolated from Phellinus linteus in the retinal glial activation and retinodegenerative animal models. According to the cellular studies, DBL significantly and concentration-dependently abrogated MMP-9 activation and expression in TNFα-stimulated retinal Müller (rMC-1) cells. We found the inhibitory activities of DBL were strongly through the STAT- and ERK-dependent pathways. Furthermore, DBL dramatically attenuated MMP-9 activation in the stimulated Müller cells exposed to conditioned media from LPS-stimulated microglia BV-2 cells. On the other hand, DBL strongly suppressed LPS-induced production of NO and ROS and expression of iNOS in microglia BV-2 cells. Consistently, the phosphorylation of STAT was substantially blocked by DBL in LPS-stimulated microglia BV-2 cells. In the evaluation of retinoprotective functions, the high IOP-induced scotopic electroretinographic (ERG) deficit and blue light-induced abnormal pupillary light response (PLR) were assessed. The deficit scotopic ERG responses markedly recovered by DBL in a rat model of glaucoma-like ischemia/reperfusion (I/R)-injury. DBL also reduced the aqueous gelatinolytic activity and retinal MMP-9 expression in high IOP-injured conditions. Additionally, DBL could restore the abnormal PLR and reduce retinal MMP-9 activation. In summary, DBL could ameliorate retinal neuroinflammation and MMP-9 activation by predominantly inhibiting STAT3 activation in the retinal Müller cells and microglia, which exhibits therapeutic potential for glaucoma and other retinal degenerative diseases.

Keywords: glaucoma, blue light, DBL, retinal Müller cell, MMP-9, STAT, Microglia, iNOS, ERG, PLR

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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

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Authors: Esshili Awatef, Manitz Marie-Pierre, Eßlinger Manuela, Gerhardt Alexandra, Plümper Jennifer, Wachholz Simone, Friebe Astrid, Juckel Georg

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Maternal immune activation (MIA) resulting from maternal viral infection during pregnancy is a known risk factor for schizophrenia. The neural mechanisms by which maternal infections increase the risk for schizophrenia remain unknown, although the prevailing hypothesis argues that an activation of the maternal immune system induces changes in the maternal-fetal environment that might interact with fetal brain development. It may lead to an activation of fetal microglia inducing long-lasting functional changes of these cells. Based on post-mortem analysis showing an increased number of activated microglial cells in patients with schizophrenia, it can be hypothesized that these cells contribute to disease pathogenesis and may actively be involved in gray matter loss observed in such patients. In the present study, we hypothesize that prenatal treatment with the inflammatory agent Poly(I:C) during embryogenesis at contributes to microglial activation in the offspring, which may, therefore, represent a contributing factor to the pathogenesis of schizophrenia and underlines the need for new pharmacological treatment options. Pregnant rats were treated with intraperitoneal injections a single dose of Poly(I:C) or saline on gestation day 17. Brains of control and Poly(I:C) offspring, were removed and into 20-μm-thick coronal sections were cut by using a Cryostat. Brain slices were fixed and immunostained with ba1 antibody. Subsequently, Iba1-immunoreactivity was detected using a secondary antibody, goat anti-rabbit. The sections were viewed and photographed under microscope. The immunohistochemical analysis revealed increases in microglia cell number in the prefrontal cortex, in offspring of poly(I:C) treated-rats as compared to the controls injected with NaCl. However, no significant differences were observed in microglia activation in the cerebellum among the groups. Prenatal immune challenge with Poly(I:C) was able to induce long-lasting changes in the offspring brains. This lead to a higher activation of microglia cells in the prefrontal cortex, a brain region critical for many higher brain functions, including working memory and cognitive flexibility. which might be implicated in possible changes in cortical neuropil architecture in schizophrenia. Further studies will be needed to clarify the association between microglial cells activation and schizophrenia-related behavioral alterations.

Keywords: Microglia, neuroinflammation, PolyI:C, schizophrenia

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Authors: Laura Bellassen, Idit Shachar

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Multiple sclerosis (MS) is a chronic neurological disorder characterized by demyelination of the central nervous system (CNS), leading to a wide range of physical and cognitive impairments. Myeloid cells in the CNS, such microglia and border associated macrophage cells, participate in the neuroinflammation in MS. Activation of those cells in MS contributes to the inflammatory response in the CNS and recruitment of immune cells in the this compartment. SLAMF5 is a cell surface receptor that functions as a homophilic adhesion molecule, whose signaling can activate or inhibit leukocyte function. In the current study we followed the expression and function of SLAMF5 in myeloid cells in the CNS and in the periphery in the murine model for MS, the experimental autoimmune encephalomyelitis model (EAE). Our results show that SLAMF5 deficiency or blocking decreases the expression of activation molecules and costimulatory molecules such as MHCII and CD80, resulting in delayed onset and reduced progression of the disease. Moreover, blocking SLAMF5 in peripheral monocytes derived from MS patients and iPSC-derived microglia cells, controls the expression of HLA-DR and CD80. Thus, SLAMF5 is a regulator of myeloid cells function and can serve as a therapeutic target in autoimmune disorders as Multiple Sclerosis.

Keywords: multiple sclerosis, EAE model, myeloid cells, new antibody, neuroimmunology

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Authors: Amelia J. McFarland, Andrew K. Davey, Shailendra Anoopkumar-Dukie

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Microglia are the resident macrophage population of the central nervous system (CNS), contributing to both innate and adaptive immune response, and brain homeostasis. Activation of microglia occurs in response to a multitude of pathogenic stimuli in their microenvironment; this induces morphological and functional changes, resulting in a state of acute neuroinflammation which facilitates injury resolution. Adequate microglial function is essential for the health of the neuroparenchyma, with microglial dysfunction implicated in numerous CNS pathologies. Given the critical role that these macrophage-derived cells play in CNS homeostasis, there is a high demand for microglial models suitable for use in neuroscience research. The isolation of primary human microglia, however, is both difficult and costly, with microglial activation an unwanted but inevitable result of the extraction process. Consequently, there is a need for the development of alternative experimental models which exhibit morphological, biochemical and functional characteristics of human microglia without the difficulties associated with primary cell lines. In this study, our aim was to evaluate whether THP-1 human peripheral blood monocytes would display microglial-like qualities following an induced differentiation, and, therefore, be suitable for use as surrogate microglia. To achieve this aim, THP-1 human peripheral blood monocytes from acute monocytic leukaemia were differentiated with a range of phorbol 12-myristate 13-acetate (PMA) concentrations (50-200 nM) using two different protocols: a 5-day continuous PMA exposure or a 3-day continuous PMA exposure followed by a 5-day rest in normal media. In each protocol and at each PMA concentration, microglial-like cell morphology was assessed through crystal violet staining and the presence of CD-14 microglial / macrophage cell surface marker. Lipopolysaccharide (LPS) from Escherichia coli (055: B5) was then added at a range of concentrations from 0-10 mcg/mL to activate the PMA-differentiated THP-1 cells. Functional microglial-like behavior was evaluated by quantifying the release of prostaglandin (PG)-E2 and pro-inflammatory cytokines interleukin (IL)-1β and tumour necrosis factor (TNF)-α using mediator-specific ELISAs. Furthermore, production of global reactive oxygen species (ROS) and nitric oxide (NO) were determined fluorometrically using dichlorodihydrofluorescein diacetate (DCFH-DA) and diaminofluorescein diacetate (DAF-2-DA) respectively. Following PMA-treatment, it was observed both differentiation protocols resulted in cells displaying distinct microglial morphology from 10 nM PMA. Activation of differentiated cells using LPS significantly augmented IL-1β, TNF-α and PGE2 release at all LPS concentrations under both differentiation protocols. Similarly, a significant increase in DCFH-DA and DAF-2-DA fluorescence was observed, indicative of increases in ROS and NO production. For all endpoints, the 5-day continuous PMA treatment protocol yielded significantly higher mediator levels than the 3-day treatment and 5-day rest protocol. Our data, therefore, suggests that the differentiation of THP-1 human monocyte cells with PMA yields a homogenous microglial-like population which, following stimulation with LPS, undergo activation to release a range of pro-inflammatory mediators associated with microglial activation. Thus, the use of PMA-differentiated THP-1 cells represents a suitable microglial model for in vitro research.

Keywords: differentiation, lipopolysaccharide, microglia, monocyte, neuroscience, THP-1

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Authors: Fatemeh Keshavarz

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Background: Schizophrenia is a disease of the nervous system, and immune system disorders can affect its pathogenesis. Activation of microglia, proinflammatory cytokines, disruption of the blood-brain barrier (BBB) due to inflammation, activation of autoreactive B cells, and consequently the production of autoantibodies against system antigens are among the immune processes involved in neurological diseases. interleukin 32 (IL-32) a proinflammatory cytokine that important player in the activation of the innate and adaptive immune responses. This study aimed to measure the serum level of IL-32 as well as the frequency of autoantibody positivity against several nervous system antigens in patients with schizophrenia. Material and Methods: This study was conducted on 40 patients with schizophrenia and 40 healthy individuals in the control group. Serum IL-32 levels were measured by ELISA. The frequency of autoantibodies against Hu, Ri, Yo, Tr, CV2, Amphiphysin, SOX1, Zic4, ITPR1, CARP, GAD, Recoverin, Titin, and Ganglioside antigens were measured by indirect immunofluorescence method. Results: Serum IL-32 levels in patients with schizophrenia were significantly higher compared to the control group. Autoantibodies were positive in 8 patients for GAD antigen and 5 patients for Ri antigen, which showed a significant relationship compared to the control group. Autoantibodies were also positive in 2 patients for CV2, in 1 patient for Hu, and in 1 patient for CARP. Negative results were reported for other antigens. Conclusion: Our findings suggest that elevated the serum IL-32 level and autoantibody positivity against several nervous system antigens may be involved in the pathogenesis of schizophrenia.

Keywords: schizophrenia, microglia, autoantibodies, IL-32

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Authors: Yi-Feng Kao, Huey-Jine Chai, Chin-I Chang, Yi-Chen Chen, June-Ru Chen

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Microglia is a macrophage that resides in brain, and overactive microglia may result in brain neuron damage or inflammation. In this study, the phospholipids was extracted from squid skin and manufactured into a liposome (SQ liposome) to mimic apoptotic body. We then evaluated anti-inflammatory effects of SQ liposome on mouse microglial cell line (BV-2) by lipopolysaccharide (LPS) induction. First, the major phospholipid constituents in the squid skin extract were including 46.2% of phosphatidylcholine, 18.4% of phosphatidylethanolamine, 7.7% of phosphatidylserine, 3.5% of phosphatidylinositol, 4.9% of Lysophosphatidylcholine and 19.3% of other phospholipids by HPLC-UV analysis. The contents of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in the squid skin extract were 11.8 and 28.7%, respectively. The microscopic images showed that microglia cells can engulf apoptotic cells or SQ-liposome. In cell based studies, there was no cytotoxicity to BV-2 as the concentration of SQ-liposome was less than 2.5 mg/mL. The LPS induced pro-inflammatory cytokines, including tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6), were significant suppressed (P < 0.05) by pretreated 0.03~2.5mg/ml SQ liposome. Oppositely, the anti-inflammatory cytokines transforming growth factor-beta (TGF-β) and interleukin-10 (IL-10) secretion were enhanced (P < 0.05). The results suggested that SQ-liposome possess anti-inflammatory properties on BV-2 and may be a good strategy for against neuro-inflammatory disease.

Keywords: apoptotic mimicry, neuroinflammation, microglia, squid processing by-products

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Authors: Alvin Han, Reema Shafi, Alishba Afaq, Jennifer Gommerman, Valeria Ramaglia, Shannon E. Dunn

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Adolescents engaged in contact-sports can suffer from recurrent brain concussions with no loss of consciousness and no need for hospitalization, yet they face the possibility of long-term neurocognitive problems. Recent studies suggest that head concussive injuries during adolescence can also predispose individuals to multiple sclerosis (MS). The underlying mechanisms of how brain concussions predispose to MS is not understood. Here, we hypothesize that: (1) recurrent brain concussions prime microglial cells, the tissue resident myeloid cells of the brain, setting them up for exacerbated responses when exposed to additional challenges later in life; and (2) brain concussions lead to the sensitization of myelin-specific T cells in the peripheral lymphoid organs. Towards addressing these hypotheses, we implemented a mouse model of closed head injury that uses a weight-drop device. First, we calibrated the model in male 12 week-old mice and established that a weight drop from a 3 cm height induced mild neurological symptoms (mean neurological score of 1.6+0.4 at 1 hour post-injury) from which the mice fully recovered by 72 hours post-trauma. Then, we performed immunohistochemistry on the brain of concussed mice at 72 hours post-trauma. Despite mice having recovered from all neurological symptoms, immunostaining for leukocytes (CD45) and IBA-1 revealed no peripheral immune infiltration, but an increase in the intensity of IBA1+ staining compared to uninjured controls, suggesting that resident microglia had acquired a more active phenotype. This microglia activation was most apparent in the white matter tracts in the brain and in the olfactory bulb. Immunostaining for the microglia-specific homeostatic marker TMEM119, showed a reduction in TMEM119+ area in the brain of concussed mice compared to uninjured controls, confirming a loss of this homeostatic signal by microglia after injury. Future studies will test whether single or repetitive concussive injury can worsen or accelerate autoimmunity in male and female mice. Understanding these mechanisms will guide the development of timed and targeted therapies to prevent MS from getting started in people at risk.

Keywords: concussion, microglia, microglial priming, multiple sclerosis

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Authors: Lourdes De Fátima Ibañez Valdés, Humberto Foyaca Sibat

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Background: Cysticercosis (Ct) is a preventable and eradicable zoonotic parasitic disease secondary to an infection caused by the larva form of pig tapeworm Taenia solium (Ts), which is mainly seen in people living in developing countries. However, the number of carriers in developed countries increases gradually due to globalization and uncontrolled migration. In this study, we look for the role played by autoimmune innate microglia (Mg) in the pathogenesis of intraparenchymal/subarachnoid neurocysticercosis. (I-SNCC)/ischemic -reperfusion injury (IRI). After reviewing this issue, we formulate some hypotheses regarding to the role of Mg in this process and deliver some novel therapeutic approaches for I- SNCC/IRI. Method: We searched the medical literature comprehensively, looking for published medical subject heading (MeSH) terms like "neurocysticercosis"; "pathogenesis of neurocysticercosis"; "comorbidity in NCC"; OR "I-SNCC"; OR "IRI;" OR "NCC/IS;" OR "Treatment of I-SNCC/IRI;" OR “MPC;” OR “ischemic stroke” OR “subarachnoid neurocysticercosis” OR “racemose neurocysticercosis” Results: All selected manuscripts were peer-reviewed, and we did not find publications related to Mga/I-SNCC/IRI. Comments and concluding remarks: We hypothesized the role played by Mg on the pathogenesis of I-SNCC the role of Mg during the colloid/nodular stage of INCC and racemose NCC and an associated ischemic stroke based on the well-known benefits of Mg polarization.

Keywords: Cysticercosis, neurocysticercosis, microglia activation, apoptosis, pyroptosis, necroptosis, PANoptosis, PANoptosome, infectious vasculitis, ischemic stroke, vascular dementia, racemose neurocysticercosis, subarachnoid neurocysticercosis, extra parenchymal neurocysticercosis

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Authors: Nidhi Chadha, A. K. Tiwari, Marilyn D. Milton, Anil K. Mishra

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Translocator protein (18 kDa) TSPO is highly expressed during microglia activation in neuroinflammation. Although a number of PET ligands have been developed for the visualization of activated microglia, one of the advantageous approaches is to develop potential optical imaging (OI) probe. Our study involves computational screening, synthesis and evaluation of TSPO ligand through various imaging modalities namely PET/SPECT/Optical. The initial computational screening involves pharmacophore modeling from the library designing having oxo-benzooxazol-3-yl-N-phenyl-acetamide groups and synthesis for visualization of efficacy of these compounds as multimodal imaging probes. Structure modeling of monomer, Ala147Thr mutated, parallel and anti-parallel TSPO dimers was performed and docking analysis was performed for distinct binding sites. Computational analysis showed pattern of variable binding profile of known diagnostic ligands and NBMP via interactions with conserved residues along with TSPO’s natural polymorphism of Ala147→Thr, which showed alteration in the binding affinity due to considerable changes in tertiary structure. Preliminary in vitro binding studies shows binding affinity in the range of 1-5 nm and selectivity was also certified by blocking studies. In summary, this skeleton was found to be potential probe for TSPO imaging due to ease in synthesis, appropriate lipophilicity and reach to specific region of brain.

Keywords: TSPO, molecular modeling, imaging, docking

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Authors: Lalita Subedi, Jae Kyoung Chae, Yong Un Park, Cho Kyo Hee, Lee Jae Hyuk, Kang Min Cheol, Sun Yeou Kim

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Neuroinflammation may mediate the relationship between low levels of estrogens and neurodegenerative disease. Estrogens are neuroprotective and anti-inflammatory in neurodegenerative disease models. Due to the long term side effects of estrogens, researches have been focused on finding an effective phytoestrogens for biological activities. Daidzein present in soybeans and its active metabolite equol (7-hydroxy-3-(4'-hydroxyphenyl)-chroman) bears strong antioxidant and anticancer showed more potent anti-inflammatory and neuroprotective role in neuroinflammatory model confirmed its in vitro activity with molecular mechanism through NF-κB pathway. Three major CNS cells Microglia (BV-2), Astrocyte (C6), Neuron (N2a) were used to find the effect of equol in inducible nitric oxide synthase (iNOS), cyclooxygenase (COX-2), MAPKs signaling proteins, apoptosis related proteins by western blot analysis. Nitric oxide (NO) and prostaglandin E2 (PGE2) was measured by the Gries method and ELISA, respectively. Cytokines like tumor necrosis factor-α (TNF-α) and IL-6 were also measured in the conditioned medium of LPS activated cells with or without equol. Equol inhibited the NO production, PGE-2 production and expression of COX-2 and iNOS in LPS-stimulated microglial cells at a dose dependent without any cellular toxicity. At the same time Equol also showed promising effect in modulation of MAPK’s and nuclear factor kappa B (NF-κB) expression with significant inhibition of the production of proinflammatory cytokine like interleukin -6 (IL-6), and tumor necrosis factor -α (TNF-α). Additionally, it inhibited the LPS activated microglia-induced neuronal cell death by downregulating the apoptotic phenomenon in neuronal cells. Furthermore, equol increases the production of neurotrophins like NGF and increase the neurite outgrowth as well. In conclusion the natural daidzein metabolite equol are more active than daidzein, which showed a promising effectiveness as an anti-neuroinflammatory and neuroprotective agent via downregulating the LPS stimulated microglial activation and neuronal apoptosis. This work was supported by Brain Korea 21 Plus project and High Value-added Food Technology Development Program 114006-4, Ministry of Agriculture, Food and Rural Affairs.

Keywords: apoptosis, equol, neuroinflammation, phytoestrogen

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Authors: Jiazhen Zhou, Youcai Zhao

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Waste tea is commonly generated in certain areas of China and its utilization has drawn a lot of concern nowadays. In this paper, highly microporous and mesoporous activated carbons were produced from waste tea by physical activation in the presence of water vapor in a tubular furnace. The effect of activation temperature on yield and pore properties of produced activated carbon are studied. The yield decreased with the increase of activation temperature. According to the Nitrogen adsorption isotherms, the micropore and mesopore are both developed in the activated carbon. The specific surface area and the mesopore volume fractions of the activated carbon increased with the raise of activation temperature. The maximum specific surface area attained 756 m²/g produced at activation temperature 900°C. The results showed that the activation temperature had a significant effect on the micro and mesopore volumes as well as the specific surface area.

Keywords: activated carbon, nitrogen adsorption isotherm, physical activation, waste tea

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Authors: Ilkham Gafurovich Atabaev, Khimmatali Nomozovich Juraev

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The activation energy of conductivity in p-i-n SiC structures fabricated by doping with Aluminum using the new low-temperature diffusion method is investigated. In this method, diffusion is stimulated by the flux of carbon and silicon vacancies created by surface oxidation. The activation energy of conductivity in the p - layer is 0.25 eV and it is close to the ionization energy of Aluminum in 4H-SiC from 0.21 to 0.27 eV for the hexagonal and cubic positions of aluminum in the silicon sublattice for weakly doped crystals. The conductivity of the i-layer (measured in the reverse biased diode) shows 2 activation energies: 0.02 eV and 0.62 eV. Apparently, the 0.62 eV level is a deep trap level and it is a complex of Aluminum with a vacancy. According to the published data, an analogous level system (with activation energies of 0.05, 0.07, 0.09 and 0.67 eV) was observed in the ion Aluminum doped 4H-SiC samples.

Keywords: activation energy, aluminum, low temperature diffusion, SiC

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Authors: Jade Edey, Andrew Bennett, Gareth Hathway

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Nuclear receptor-related 1 protein (also known as Nurr1 or NR4A2) is an orphan nuclear receptor which plays a vital role in the development, survival and maintenance of dopaminergic (DA) neurons particularly in the substantia nigra (SN). Increasing research has investigated Nurr1’s additional role within microglia and astrocytes where it has been suggested to act as a negative regulator of inflammation; potentially offering neuroprotection. Considering both DA neurodegeneration and neuroinflammation are commonly accepted constituents of Parkinson’s Disease (PD), understanding the mechanisms by which Nurr1 regulates inflammatory processes could provide an attractive therapeutic target. Nurr1 regulates inflammation via a transrepressive mechanism possibly dependent upon SUMOylation. In addition, Nurr1 can transactivate numerous genes involved in DA synthesis, such as Tyrosine Hydroxylase (TH). A C-terminal splice variant of Nurr1, Nurr-1a, has been reported in both neuronal and glial cells. However, research into its transcriptional activity is minimal. We employed in vitro methods such as SUMO-Pulldown experiments alongside Luciferase reporter assays to investigate the SUMOylation status and transactivation capabilities of Nurr1 and Nurr-1a respectively. The SUMO-Pulldown assay demonstrated Nurr-1a undergoes significantly more SUMO modification than its full-length variant. Consequently, despite having less transcriptional activation than Nurr1, Nurr1a may play a more prominent role in repression of microglial inflammation. Contrary to published literature we also identified that SUMOylation enhances transcriptional activation by Nurr1 and Nurr1a. SUMOylation-dependent increases in Nurr1 and Nurr1a transcriptional activation were only evident in neuronal SHSY5Y cells but not in HEK293 cells. This research provides novel insight into the regulation of Nurr-1a and indicates differential effects of SUMOylation dependent regulation in neuronal and inflammatory cells.

Keywords: nuclear receptors, Parkinson’s disease, inflammation, transcriptional regulation

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Authors: Zhihong Luo, Guangbin Zhu, Lulu Guo, Zhujun Lyu, Kun Luo

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Cycling life has become the threshold for the prospective application of Li-O₂ batteries, and the protection of Li anode has recently regarded as the key factor to the performance. Herein, a simple low rate pre-activation (20 cycles at 0.5 Ag⁻¹ and a capacity of 200 mAh g⁻¹) was employed to effectively improve the performance and cyclability of Li-O₂ batteries. The charge/discharge cycles at 1 A g⁻¹ with a capacity of 1000 mAh g⁻¹ were maintained for up to 290 times versus 55 times for the cell without pre-activation. The ultimate battery capacity and high rate discharge property were also largely enhanced. Morphology, XRD and XPS analyses reveal that the performance improvement is in close association with the formation of the smooth and compact surface layer formed on the Li anode after low rate pre-activation, which apparently alleviated the corrosion of Li anode and the passivation of cathode during battery cycling, and the corresponding mechanism was also discussed.

Keywords: lithium oxygen battery, pre-activation, cyclability, capacity

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Authors: Hangil Park, Hwayeon Song, Jingyung Sim

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In this study, a business ecosystem of a domestic space industry is comprehensively analyzed to derive the influence factors. The priority level of each element as well as the disparity between the ideal and reality are investigated through a literature review and an expert survey. The three major influence factors determined are: (a) investment scale and approach, (b) propulsion system, and (c) industrialization with overseas expansion. Related issues based on the current status are evaluated, followed by a proposed activation strategy. This research's findings offer a direction for R&D budget allocation and law system maintenance for the activation of the domestic space industry.

Keywords: space industry, activation, strategy, business ecosystem

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Authors: P. B. Sob, A. A. Alugongo, T. B. Tengen

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The activation volume of 6082T6 aluminum is investigated at different temperatures on grain size variants. The deformation activation volume was computed on the basis of the relationship between the Boltzmann’s constant k, the testing temperatures, the material strain rate sensitivity and the material yield stress of grain size variants. The material strain rate sensitivity is computed as a function of yield stress and strain rate of grain size variants. The effect of the material strain rate sensitivity and the deformation activation volume of 6082T6 aluminum at different temperatures of 3-D grain are discussed. It is shown that the strain rate sensitivities and activation volume are negative for the grain size variants during the deformation of nanostructured materials. It is also observed that the activation volume vary in different ways with the equivalent radius, semi minor axis radius, semi major axis radius and major axis radius. From the obtained results it is shown that the variation of activation volume increased and decreased with the testing temperature. It was revealed that, increased in strain rate sensitivity led to decrease in activation volume whereas increased in activation volume led to decrease in strain rate sensitivity.

Keywords: nanostructured materials, grain size variants, temperature, yield stress, strain rate sensitivity, activation volume

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Authors: Nootchanat Mairuae, Walaiporn Tongjaroenbuangam, Chalisa Louicharoen Cheepsunthorn, Poonlarp Cheepsunthorn

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The aim of this study was to investigate the anti-oxidative effect, the anti-inflammatory effects, and the molecular mechanisms of okra (Abelmoschus esculentus Linn.) on lipopolysaccharide (LPS)-stimulated BV2 microglial cells. The BV2 cells were treated with LPS in the presence or absence of okra. Reactive oxygen species (ROS) and nitric oxide (NO) production were measured using the ROS detection reagent DCF-DA and the Griess reaction, respectively. The phosphorylation levels of nuclear factor-kappa B (NF-kB) p65 was detected by Western blot assay. Treatment of BV2 microglia cells with okra was found to significantly suppress the LPS-induced inflammatory mediator NO as well as ROS compared to untreated cells. The levels of LPS-induced NF-kB p65 phosphorylation were significantly decreased following okra treatment too. These results show that okra exerts anti-oxidative and anti-inflammatory effects in LPS-stimulated BV2 microglial cells by suppressing the NF-κB pathway. This suggests okra might be a valuable agent for treatment of anti-neuroinflammatory diseases mediated by microglial cells.

Keywords: Abelmoschus esculentus Linn, microglia, neuroinflammation, reactive oxygen spicy

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Authors: L. Giraudet, O. Simonetti, G. de Tournadre, N. Dumelié, B. Clarenc, F. Reisdorffer

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In this paper we intend to give a comprehensive view of the saturation misbehavior of thin film transistors (TFTs) based on disordered semiconductors, such as most organic TFTs, and its link to the field activation of the mobility. Experimental evidence of the field activation of the mobility is given for disordered semiconductor based TFTs, when reducing the gate length. Saturation misbehavior is observed simultaneously. Advanced transport models have been implemented in a quasi-2D numerical TFT simulation software. From the numerical simulations it is clearly established that field activation of the mobility alone cannot explain the saturation misbehavior. Evidence is given that high longitudinal field gradient at the drain end of the channel is responsible for an excess charge accumulation, preventing saturation. The two combined effects allow reproducing the experimental output characteristics of short channel TFTs, with S-shaped characteristics and saturation failure.

Keywords: mobility field activation, numerical simulation, OTFT, saturation failure

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Authors: A. Azizi, M. Toubane, L. Chetibi

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Differential scanning calorimetry (DSC) is a widely used technique for the study of phase transformations, particularly in the study of precipitation. The kinetic of the precipitation and dissolution is always related to the concept of activation energy Ea. The determination of the activation energy gives important information about the kinetic of the precipitation reaction. In this work, we were interested in the study of the isothermal and non-isothermal treatments on the decomposition of the supersaturated solid solution in the alloy AZ91 (Mg-9 Al-Zn 1-0.2 Mn. mass fraction %), using Differential Calorimetric method. Through this method, the samples were heat treated up to 425° C, using different rates. To calculate the apparent activation energies associated with the formation of precipitated phases, we used different isoconversional methods. This study was supported by other analysis: X-ray diffraction and microhardness measurements.

Keywords: calorimetric, activation energy, AZ91 alloys, microstructural evolution

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Authors: Ravid Inbar

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CaMKII (calcium-calmodulin dependent protein kinase II) makes up 2% of the protein in our brain and has a critical role in memory formation and long-term potentiation of neurons. Despite this, research has yet to uncover the role of one of the domains on the activation of this kinase. The following proposes to express the protein without the hub domain in E. coli, leaving only the kinase and regulatory segment of the protein. Next, a series of kinase assays will be conducted to elucidate the role the hub domain plays on CaMKII sensitivity to calcium/calmodulin activation. The hub domain may be important for activation; however, it may also be a variety of domains working together to influence protein activation and not the hub alone. Characterization of a protein is critical to the future understanding of the protein's function, as well as for producing pharmacological targets in cases of patients with diseases.

Keywords: CaMKII, hub domain, kinase assays, kinase + reg seg

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Authors: M. Münch, R. Brandt

Abstract:

Martensitic steels with an ultimate tensile strength beyond 2000 MPa are applied in the powertrain of vehicles due to their excellent fatigue strength and high creep resistance. However, the creep controlling mechanism in martensitic steels at ambient temperatures up to 423 K is not evident. The purpose of this study is to review the low temperature creep (LTC) behavior of martensitic steels at temperatures from 363 K to 523 K. Thus, the validity of a logarithmic creep law is reviewed and the stress and temperature dependence of the creep parameters α and β are revealed. Furthermore, creep tests are carried out, which include stepped changes in temperature or stress, respectively. On one hand, the change of the creep rate due to a temperature step provides information on the magnitude of the activation energy of the LTC controlling mechanism and on the other hand, the stress step approach provides information on the magnitude of the activation volume. The magnitude, the temperature dependency, and the stress dependency of both material specific activation parameters may deliver a significant contribution to the disclosure of the nature of the LTC rate controlling mechanism.

Keywords: activation parameters, creep mechanisms, high strength steels, low temperature creep

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Authors: Su Bin Wang, Jin Hee Ahn, Tong-Shin Chang

Abstract:

The peroxisome proliferator-activated receptors (PPARs) are member of nuclear receptor superfamily that act as a ligand-activated transcription factors. Although platelets lack a nucleus, previous studies have shown that PPARγ agonists, rosiglitazone, inhibited platelet activation induced by collagen. In this study, we investigated the inhibitory effects of KR-62980, a newly synthesized PPARγ agonist, on collagen receptor-stimulated platelet activation. The specific tyrosine phosphorylations of key components (Syk, Vav1, Btk and PLCγ2) for collagen receptor signaling pathways were suppressed by KR-62980. KR-62980 also attenuated downstream responses including cytosolic calcium elevation, P-selectin surface exposure, and integrin αIIbβ3 activation. PPARγ was found to associate with multiple proteins within the LAT signaling complex in collagen-stimulated platelets. This association was prevented by KR-62980, indicating a potential mechanism for PPARγ function in collagen-stimulated platelet activation. Furthermore, KR-62980 inhibited platelet aggregation and adhesion in response to collagen in vitro and prolonged in vivo thrombotic response in carotid arteries of mice. Collectively, these data suggest that KR-62980 inhibits collagen-stimulated platelet activation and thrombus formation through modulating the collagen receptor signaling pathways.

Keywords: KR-62980, PPARγ, antiplatelet, thrombosis

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Authors: Rhoda Afriyie Mensah, Lin Jiang, Solomon Asante-Okyere, Xu Qiang, Cong Jin

Abstract:

Flammability analysis of extruded polystyrene (XPS) has become crucial due to its utilization as insulation material for energy efficient buildings. Using the Kissinger-Akahira-Sunose and Flynn-Wall-Ozawa methods, the degradation kinetics of two pure XPS from the local market, red and grey ones, were obtained from the results of thermogravity analysis (TG) and microscale combustion calorimetry (MCC) experiments performed under the same heating rates. From the experiments, it was discovered that red XPS released more heat than grey XPS and both materials showed two mass loss stages. Consequently, the kinetic parameters for red XPS were higher than grey XPS. A comparative evaluation of activation energies from MCC and TG showed an insignificant degree of deviation signifying an equivalent apparent activation energy from both methods. However, different activation energy profiles as a result of the different chemical pathways were presented when the dependencies of the activation energies on extent of conversion for TG and MCC were compared.

Keywords: flammability, microscale combustion calorimetry, thermogravity analysis, thermal degradation, kinetic analysis

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Authors: Karen E. Supan

Abstract:

Thermal degradation kinetics of switchgrass (Panicum virgatum) from the field, as well as in a pellet form, are presented. Thermogravimetric analysis tests were performed at heating rates of 10-40 K min⁻¹ in an inert atmosphere. The activation energy and the pre-exponential factor were calculated using the Ozawa/Flynn/Wall method as suggested by the ASTM Standard Test Method for Decomposition Kinetics by Thermogravimetry. Four stages were seen in the degradation: dehydration, active pyrolysis of hemicellulose, active pyrolysis of cellulose, and passive pyrolysis. The derivative mass loss peak for active pyrolysis of cellulose in the field-dried sample was much higher than the pelletized. The range of activation energy in the 0.15 – 0.70 conversion interval was 191 – 242 kJ mol⁻¹ for the field-dried and 130-192 kJ mol⁻¹ for the pellets. The highest activation energies were achieved at 0.50 conversion and were 242 kJ mol⁻¹ and 192 kJ mol⁻¹ for the field-dried and pellets, respectively. The thermal degradation and activation energies were comparable to switchgrass and other biomass reported in the literature.

Keywords: biomass, switchgrass, thermal degradation, thermogravimetric analysis

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Authors: Geeta Kumari, Prabu Vairakannu

Abstract:

Underground coal gasification (UCG) technology is an efficient and an economic in-situ clean coal technology, which converts unmineable coals into calorific valuable gases. This technology avoids ash disposal, coal mining, and storage problems. CO₂ gas can be a potential gasifying medium for UCG. CO₂ is a greenhouse gas and, the liberation of this gas to the atmosphere from thermal power plant industries leads to global warming. Hence, the capture and reutilization of CO₂ gas are crucial for clean energy production. However, the reactivity of high ash Indian coals with CO₂ needs to be assessed. In the present study, two varieties of Indian coals (low ash and high ash) are used for thermogravimetric analyses (TGA). Two low ash north east Indian coals (LAC) and a typical high ash Indian coal (HAC) are procured from the coal mines of India. Low ash coal with 9% ash (LAC-1) and 4% ash (LAC-2) and high ash coal (HAC) with 42% ash are used for the study. TGA studies are carried out to evaluate the activation energy for pyrolysis and gasification of coal under N₂ and CO₂ atmosphere. Coats and Redfern method is used to estimate the activation energy of coal under different temperature regimes. Volumetric model is assumed for the estimation of the activation energy. The activation energy estimated under different temperature range. The inherent properties of coals play a major role in their reactivity. The results show that the activation energy decreases with the decrease in the inherent percentage of coal ash due to the ash layer hindrance. A reverse trend was observed with volatile matter. High volatile matter of coal leads to the estimation of low activation energy. It was observed that the activation energy under CO₂ atmosphere at 400-600°C is less as compared to N₂ inert atmosphere. At this temperature range, it is estimated that 15-23% reduction in the activation energy under CO₂ atmosphere. This shows the reactivity of CO₂ gas with higher hydrocarbons of the coal volatile matters. The reactivity of CO₂ with the volatile matter of coal might occur through dry reforming reaction in which CO₂ reacts with higher hydrocarbon, aromatics of the tar content. The observed trend of Ea in the temperature range of 150-200˚C and 400-600˚C is HAC > LAC-1 >LAC-2 in both N₂ and CO₂ atmosphere. At the temperature range of 850-1000˚C, higher activation energy is estimated when compared to those values in the temperature range of 400-600°C. Above 800°C, char gasification through Boudouard reaction progressed under CO₂ atmosphere. It was observed that 8-20 kJ/mol of activation energy is increased during char gasification above 800°C compared to volatile matter pyrolysis between the temperature ranges of 400-600°C. The overall activation energy of the coals in the temperature range of 30-1000˚C is higher in N₂ atmosphere than CO₂ atmosphere. It can be concluded that higher hydrocarbons such as tar effectively undergoes cracking and reforming reactions in presence of CO₂. Thus, CO₂ gas is beneficial for the production of high calorific value syngas using high ash Indian coals.

Keywords: clean coal technology, CO₂ gasification, activation energy, underground coal gasification

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Authors: Jamshaid Ul Rahman, Faiza Makhdoom, Dianchen Lu

Abstract:

Activation functions play a decisive role in determining the capacity of Deep Neural Networks (DNNs) as they enable neural networks to capture inherent nonlinearities present in data fed to them. The prior research on activation functions primarily focused on the utility of monotonic or non-oscillatory functions, until Growing Cosine Unit (GCU) broke the taboo for a number of applications. In this paper, a Convolutional Neural Network (CNN) model named as ASU-CNN is proposed which utilizes recently designed activation function ASU across its layers. The effect of this non-monotonic and oscillatory function is inspected through feature map visualizations from different convolutional layers. The optimization of proposed network is offered by Adam with a fine-tuned adjustment of learning rate. The network achieved promising results on both training and testing data for the classification of CIFAR-10. The experimental results affirm the computational feasibility and efficacy of the proposed model for performing tasks related to the field of computer vision.

Keywords: amplifying sine unit, activation function, convolutional neural networks, oscillatory activation, image classification, CIFAR-10

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Authors: Getenet Aseged Zeleke

Abstract:

The aim of this project was to study the synthesis of activated carbon from low-cost animal beef and the characterization of the product obtained. The bone was carbonized in an inert atmosphere at three different temperatures (500°C, 700oC and 900°C) in an electric furnace, followed by activation with hydrochloric acid. The activated animal bone charcoals obtained were characterized by using scanning electron microscopy (SEM)to observe the effect of activation compared to the unactivated bone charcoal. The following parameters were also determined: ash content, moisture content, volatile content, fixed carbon, pH, pore volume and bulk (apparent) density. The characterization result showed that the activated bone charcoal has good properties and is compared favorably with other reference activated carbons.

Keywords: bones, carbonization, activation, characterization, activated carbon

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Authors: Yi-Hui Lai, Chih-Hsiang Yang, Li-Chung Hsu

Abstract:

The inflammasome is a protein complex that modulates caspase-1 activity, resulting in proteolytic cleavage of proinflammatory cytokines such as IL-1β and IL-18, into their bioactive forms. It has been shown that the inflammasomes play a crucial role in the clearance of pathogenic infection and tissue repair. However, dysregulated inflammasome activation contributes to a wide range of human diseases such as cancers and auto-inflammatory diseases. Yet, regulation of NLRP3 inflammasome activation remains largely unknown. We discovered a novel DEAD box protein, whose biological function has not been reported, not only negatively regulates NLRP3 inflammasome activation by interfering NLRP3 inflammasome assembly and cellular localization but also mitigate pyroptosis upon pathogen evasion. The DEAD-box protein is the first DEAD-box protein gets involved in modulation of the inflammasome activation. In our study, we found that caspase-1 activation and mature IL-1β production were largely enhanced upon LPS challenge in the DEAD box-containing protein- deleted THP-1 macrophages and bone marrow-derived macrophages (BMDMs). In addition, this DEAD box-containing protein migrates from the nucleus to the cytoplasm upon LPS stimulation, which is required for its inhibitory role in NLRP3 inflammasome activation. The DEAD box-containing protein specifically interacted with the LRR motif of NLRP3 via its DEAD domain. Furthermore, due to the crucial role of the NLRP3 LRR domain in the recruitment of NLRP3 to mitochondria and binding to its adaptor ASC, we found that the interaction of NLRP3 and ASC was downregulated in the presence of the DEAD box-containing protein. In addition to the mechanical study, we also found that this DEAD box protein protects host cells from inflammasome-triggered cell death in response to broad-ranging pathogens such as Candida albicans, Streptococcus pneumoniae, etc., involved in nosocomial infections and severe fever shock. Collectively, our results suggest that this novel DEAD box molecule might be a key therapeutic strategy for various infectious diseases.

Keywords: inflammasome, inflammation, innate immunity, pyroptosis

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