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https://www.readbyqxmd.com/read/28318221/crystal-structure-of-a-homogeneous-igg-fc-glycoform-with-the-n-glycan-designed-to-maximize-the-antibody-dependent-cellular-cytotoxicity
#1
Chia-Lin Chen, Jen-Chi Hsu, Chin-Wei Lin, Chia-Hung Wang, Ming-Hung Tsai, Chung-Yi Wu, Chi-Huey Wong, Che Ma
N-glycosylation on IgG modulates Fc conformation and effector functions. An IgG-Fc contains a human sialo-complex type (hSCT) glycan of biantennary structure with two α2,6-sialylations and without core-fucosylation is an optimized glycoform developed to enhance the antibody dependent cellular cytotoxicity (ADCC). hSCT modification not only enhances the binding affinity to Fc receptors in the presence of antigen, but also in some cases provides gain-of-function effector activity. We used enzymatic glyco-engineering to prepare an IgG-Fc with homogeneous hSCT attached to each CH2 domain, and solved its crystal structure...
March 20, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/28315344/further-analysis-of-the-inhibition-by-agmatine-on-the-cardiac-sympathetic-outflow-role-of-the-%C3%AE-2-adrenoceptor-subtypes
#2
Luis Cobos-Puc, Hilda Aguayo-Morales, Janeth Ventura-Sobrevilla, Diana Luque-Contreras, Miguel Chin-Chan
This study has investigated the role of the α2-adrenoceptor subtypes involved in the inhibition of the cardiac sympathetic outflow induced by intravenous (i.v) infusions of agmatine. Therefore, we analysed the effect of an i.v. bolus injections of the selective antagonists BRL 44408 (300μg/kg; α2A), imiloxan (3000μg/kg; α2B), and JP-1302 (300μg/kg; α2C) given separately, and their combinations: BRL 44408 plus Imiloxan, JP 1302 plus imiloxan, BRL 44408 plus JP-1302, BRL 44408 plus imiloxan plus JP-1302 on the cardiac sympatho-inhibition of agmatine...
March 14, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28302567/alpha2-adrenoceptor-agonists-trigger-prolactin-signaling-in-breast-cancer-cells
#3
Lilian Fedra Castillo, Ezequiel M Rivero, Vincent Goffin, Isabel Alicia Lüthy
Breast cancer is the most frequent malignancy among women worldwide. We have described the expression of α2-adrenoceptors in breast cancer cell lines, associated with increased cell proliferation and tumor growth. A mitogenic autocrine/paracrine loop of prolactin (Prl) has been described in breast cancer cells. We hypothesized that the α2-adrenergic enhancement of proliferation could be mediated, at least in part, by this Prl loop. In both T47D and MCF-7 cell lines, the incubation with the α2-adrenergic agonist dexmedetomidine significantly increased Prl release into the culture medium (measured by the Nb2 bioassay), this effect being reversed by the α2-adrenergic antagonist rauwolscine...
March 14, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28302458/the-effects-of-dexmedetomidine-pretreatment-on-the-pro-and-anti-inflammation-systems-after-spinal-cord-injury-in-rats
#4
Hui Rong, Zhibin Zhao, Jiying Feng, Yishan Lei, Hao Wu, Rao Sun, Zuoxia Zhang, Bailing Hou, Wei Zhang, YuE Sun, Xiaoping Gu, Zhengliang Ma, Yue Liu
Excessive inflammatory responses play important roles in the aggravation of secondary damage to an injured spinal cord. Dexmedetomidine (DEX), a selective α2-adrenoceptor agonist, has recently been implied to be neuroprotective in clinical anesthesia, but the underlying mechanism is elusive. As signaling through Toll-like receptor 4 (TLR4) and nicotinic receptors (nAChRs, notably α7nAChR) play important roles in the pro- and anti-inflammation systems in the central nervous system, respectively, this study investigated whether and how they were modulated by DEX pretreatment in a rat model of spinal cord compression...
March 14, 2017: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/28300552/monoaminergic-modulation-of-gabaergic-transmission-onto-cerebellar-globular-cells
#5
Moritoshi Hirono, Soichi Nagao, Yuchio Yanagawa, Shiro Konishi
Cerebellar Purkinje cells (PCs) project their axon collaterals to underneath of the PC layer and make GABAergic synaptic contacts with globular cells, a subgroup of Lugaro cells. GABAergic transmission derived from the PC axon collaterals is so powerful that it could inhibit globular cells and regulate their firing patterns. However, the physiological properties and implications of the GABAergic synapses on globular cells remain unknown. Using whole-cell patch-clamp recordings from globular cells in the mouse cerebellum, we examined the monoaminergic modulation of GABAergic inputs to these cells...
March 11, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28295363/angiotensin-ii-activates-cav-1-2-ca-2-channels-through-%C3%AE-arrestin2-and-casein-kinase-2-in-mouse-immature-cardiomyocytes
#6
Toshihide Kashihara, Tsutomu Nakada, Katsuhiko Kojima, Toshikazu Takeshita, Mitsuhiko Yamada
Angiotensin II (AngII), the main effector peptide of the renin-angiotensin system, plays important roles in cardiovascular regulation in the perinatal period. Despite the well-known stimulatory effect of AngII on vascular contraction, little is known about regulation of contraction of the immature heart by AngII. Here we found that AngII significantly increased the peak amplitude of twitch Ca(2+) transients by robustly activating L-type CaV 1.2 Ca(2+) (CaV 1.2) channels in mouse immature but not mature cardiomyocytes...
March 15, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28293239/major-histocompatibility-complex-class-i-chain-related-a-mica-molecules-relevance-in-solid-organ-transplantation
#7
REVIEW
Ajay Kumar Baranwal, Narinder K Mehra
An ever growing number of reports on graft rejection and/or failure even with good HLA matches have highlighted an important role of non-HLA antigens in influencing allograft immunity. The list of non-HLA antigens that have been implicated in graft rejection in different types of organ transplantation has already grown long. Of these, the Major Histocompatibility Complex class I chain-related molecule A (MICA) is one of the most polymorphic and extensively studied non-HLA antigenic targets especially in the kidney transplantation...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28289219/modulating-igg-effector-function-by-fc-glycan-engineering
#8
Tiezheng Li, David J DiLillo, Stylianos Bournazos, John P Giddens, Jeffrey V Ravetch, Lai-Xi Wang
IgG antibodies contain a conserved N-glycosylation site on the Fc domain to which a complex, biantennary glycan is attached. The fine structures of this glycan modulate antibody effector functions by affecting the binding affinity of the Fc to diverse Fc receptor family members. For example, core fucosylation significantly decreases antibody-dependent cellular cytotoxicity (ADCC), whereas terminal α2,6-sialylation plays a critical role in the anti-inflammatory activity of human i.v. immunoglobulin therapy...
March 13, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28287848/immunomodulating-and-immunoresistance-properties-of-cancer-initiating-cells-implications-for-the-clinical-success-of-immunotherapy
#9
Cristina Maccalli, Giorgio Parmiani, Soldano Ferrone
Cancer-initiating cells (CICs) represent a relatively rare subpopulation of cells endowed with self-renewal, stemness properties, tumorigenicity in immunodeficient mice, and resistance to standard therapies as well as to immunotherapy. Here, we review the biological and immunological characteristics of CICs with special focus on the immunomodulating mechanisms they utilize to escape from immunosurveillance. The recently developed immunotherapeutic strategies have yielded remarkable clinical results in many types of tumors, indicating that indeed a patient's immune system can mount an immune response, which is effective in controlling tumor growth...
March 13, 2017: Immunological Investigations
https://www.readbyqxmd.com/read/28286770/dexmedetomidine-attenuates-lipopolysaccharide-induced-mcp-1-expression-in-primary-astrocyte
#10
Huan Liu, Jacques R J Davis, Zhi-Lin Wu, Amro Faez Abdelgawad
Background. Neuroinflammation which presents as a possible mechanism of delirium is associated with MCP-1, an important proinflammatory factor which is expressed on astrocytes. It is known that dexmedetomidine (DEX) possesses potent anti-inflammatory properties. This study aimed to investigate the potential effects of DEX on the production of MCP-1 in lipopolysaccharide-stimulated astrocytes. Materials and Methods. Astrocytes were treated with LPS (10 ng/ml, 50 ng/ml, 100 ng/ml, and 1000 ng/ml), DEX (500 ng/mL), LPS (100 ng/ml), and DEX (10, 100, and 500 ng/mL) for a duration of three hours; expression levels of MCP-1 were measured by real-time PCR...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28284612/pathogenicity-and-transmission-of-triple-reassortant-h3n2-swine-influenza-a-viruses-is-attenuated-following-turkey-embryo-propagation
#11
Shobana Raghunath, Raghavendra Sumanth Pudupakam, Jagadeeswaran Deventhiran, Rahul Tevatia, Tanya Leroith
Genetic lineages of swine influenza A viruses (SIVs) have recently been established in Turkeys in the United States. To identify molecular determinants that are involved in virulence and transmission of SIVs to Turkeys, we sequentially passaged two triple reassortant H3N2 SIV isolates from Minnesota in ten day old specific-pathogen free (SPF) Turkey embryos and tested them in seven-day old Turkey poults. We found that SIV replication in Turkey embryos led to minimal mutations in and around the receptor binding and antigenic sites of the HA molecule, while other gene segments were unchanged...
March 2017: Veterinary Microbiology
https://www.readbyqxmd.com/read/28282577/therapeutic-efficacy-of-a-co-blockade-of-il-13-and-il-25-on-airway-inflammation-and-remodeling-in-a-mouse-model-of-asthma
#12
Fang-Qi Zhang, Xin-Peng Han, Fang Zhang, Xuan Ma, Dong Xiang, Xue-Min Yang, Hai-Feng Ou-Yang, Zhikui Li
Repeated airway inflammation and unremitting remodeling provoke irreversible pulmonary dysfunction and resistance to current drugs in patients with chronic bronchial asthma. Interleukin (IL)-13 and IL-25 play an important role in airway inflammation and remodeling in asthma. We aimed to investigate whether co-inhibiting IL-13 and IL-25 can effectively down-regulate allergen-induced airway inflammation and remodeling in mice. Mice with asthma induced by chronic exposure to ovalbumin (OVA) were given soluble IL-13 receptor α2 (sIL-13R) or soluble IL-25 receptor (sIL-25R) protein alone and in combination to neutralize the bioactivity of IL-13 and IL-25, and relevant airway inflammation and remodeling experiments were performed...
March 7, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28267561/pharmacological-and-antihyperalgesic-properties-of-the-novel-%C3%AE-2-3-preferring-gabaa-receptor-ligand-mp-iii-024
#13
Bradford D Fischer, Raymond J Schlitt, Bryan Z Hamade, Sabah Rehman, Margot Ernst, Michael M Poe, Guanguan Li, Revathi Kodali, Leggy A Arnold, James M Cook
γ-Aminobutyric acid type A (GABAA) receptors are located in spinal nociceptive circuits where they modulate the transmission of pain sensory signals from the periphery to higher centers. Benzodiazepine-type drugs bind GABAA, receptors containing α1, α2, α3, and α5 subunits (α1GABAA, α2GABAA, α3GABAA, and α5GABAA receptors, respectively) through which they inhibit the transmission of these signals. However, the role of these different GABAA receptor subtypes in the antihyperalgisic properties of benzodiazepine-type drugs has not been characterized fully and is limited by currently available compounds...
March 3, 2017: Brain Research Bulletin
https://www.readbyqxmd.com/read/28251651/effect-of-the-%C3%AE-2-receptor-agonists-medetomidine-detomidine-xylazine-and-romifidine-on-the-ketamine-metabolism-in-equines-assessed-with-enantioselective-capillary-electrophoresis
#14
Friederike A Sandbaumhüter, Regula Theurillat, Regula Bettschart-Wolfensberger, Wolfgang Thormann
The combination of ketamine and an α2 -receptor agonist is often used in veterinary medicine. Four different α2 -receptor agonists, medetomidine, detomidine, xylazine and romifidine, which differ in their chemical structure and thus in selectivity for the α2 -receptor and in the sedative and analgesic potency, are typically employed during surgery of equines. Recovery following anesthesia with ketamine and an α2 -receptor agonist is dependent on the α2 -receptor agonist. This prompted us to investigate i) the inhibition characteristics for the N-demethylation of ketamine to norketamine and ii) the formation of the ketamine metabolites norketamine, 6-hydroxynorketamine (6HNK) and 5,6-dehydronorketamine (DHNK) in presence of the four α2 -receptor agonists and equine liver microsomes...
March 2, 2017: Electrophoresis
https://www.readbyqxmd.com/read/28250278/glucosamine-suppresses-osteoclast-differentiation-through-the-modulation-of-glycosylation-including-o-glcnacylation
#15
Tomoharu Takeuchi, Aya Sugimoto, Nao Imazato, Mayumi Tamura, Sachie Nakatani, Kenji Kobata, Yoichiro Arata
Osteoclasts represent the only bone resorbing cells in an organism. In this study, we investigated the effect of glucosamine (GlcN), a nutrient used to prevent joint pain and bone loss, on the osteoclastogenesis of murine macrophage-like RAW264 cells. GlcN supplementation suppressed the upregulation of osteoclast-specific genes (tartrate-resistant acid phosphatase (TRAP), cathepsin K, matrix metallopeptidase 9, and nuclear factor of activated T cell c1 (NFATc1)), receptor activator of nuclear factor-κB ligand (RANKL)-dependent upregulation of TRAP enzyme activity, and the formation of TRAP-positive multinuclear cells more effectively than N-acetylglucosamine (GlcNAc), which we have previously shown to inhibit osteoclast differentiation...
2017: Biological & Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/28249817/the-direct-actions-of-cannabidiol-and-2-arachidonoyl-glycerol-at-gabaa-receptors
#16
T Bakas, P S van Nieuwenhuijzen, S O Devenish, I S McGregor, J C Arnold, M Chebib
Cannabidiol (CBD) is a major non-intoxicating component of cannabis and possesses anti-epileptic, anxiolytic and anti-hyperalgesic properties. The mechanism of action of CBD in producing such effects remains unclear. Despite evidence that some endogenous and synthetic cannabinoids interact with GABAA receptors, no-one has yet investigated the effects of CBD. Here we used two-electrode voltage clamp electrophysiology to compare the actions of CBD with those of the major central endocannabinoid, 2-arachidonoyl glycerol (2-AG) on human recombinant GABAA receptors (synaptic α1-6βγ2 and extrasynaptic α4β2δ) expressed on Xenopus oocytes...
February 27, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28240721/cucurbitacin-iia-exerts-antidepressant-like-effects-on-mice-exposed-to-chronic-unpredictable-mild-stress
#17
Shi-Meng Zhou, Shao-Yu Guan, Le Yang, Liu-Kun Yang, Lu Wang, Hui-Fang Nie, Xiang Li, Ming-Gao Zhao, Qi Yang, Hong Wu
Cucurbitacin IIa (CuIIa) is the major active component of the Helmseya amabilis root and is known to have antiviral and anti-inflammatory effects. In this study, we examined the antidepressant-like effects of CuIIa in a mouse model of chronic unpredictable mild stress (CUMS) and investigated the possible underlying mechanisms. To evaluate the antidepressant-like effects of CuIIa on depression-like behaviors, mice were subjected to the open-field test, the elevated plus-maze test, the forced-swimming test, and the tail-suspension test...
February 24, 2017: Neuroreport
https://www.readbyqxmd.com/read/28239660/%C3%AE-2-adrenergic-blockade-rescues-hypoglossal-motor-defense-against-obstructive-sleep-apnea
#18
Gang Song, Chi-Sang Poon
Decreased noradrenergic excitation of hypoglossal motoneurons during sleep causing hypotonia of pharyngeal dilator muscles is a major contributor to the pathogenesis of obstructive sleep apnea (OSA), a widespread disease for which treatment options are limited. Previous OSA drug candidates targeting various excitatory/inhibitory receptors on hypoglossal motoneurons have proved unviable in reactivating these neurons, particularly during rapid-eye-movement (REM) sleep. To identify a viable drug target, we show that the repurposed α2-adrenergic antagonist yohimbine potently reversed the depressant effect of REM sleep on baseline hypoglossal motoneuron activity (a first-line motor defense against OSA) in rats...
February 23, 2017: JCI Insight
https://www.readbyqxmd.com/read/28237805/noradrenergic-regulation-of-plasticity-marker-expression-in-the-adult-rodent-piriform-cortex
#19
Krishna C Vadodaria, Sudhirkumar U Yanpallewar, Mayur Vadhvani, Devyani Toshniwal, L Cameron Liles, Karen S Rommelfanger, David Weinshenker, Vidita A Vaidya
The adult rodent piriform cortex has been reported to harbor immature neurons that express markers associated with neurodevelopment and plasticity, namely polysialylated neural cell adhesion molecule (PSA-NCAM) and doublecortin (DCX). We characterized the expression of PSA-NCAM and DCX across the rostrocaudal axis of the rat piriform cortex and observed higher numbers of PSA-NCAM and DCX positive cells in the posterior subdivision. As observed in the rat piriform cortex, Nestin-GFP reporter mice also revealed a similar gradient of GFP-positive cells with an increasing rostro-caudal gradient of expression...
February 23, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28235547/intermittent-hypercapnic-hypoxia-effects-on-the-nicotinic-acetylcholine-receptors-in-the-developing-piglet-hippocampus-and-brainstem
#20
Arunnjah Vivekanandarajah, Atqiya Aishah, Karen A Waters, Rita Machaalani
This study investigated the effects of acute (1 day) vs repeated (4 days) exposure to intermittent hypercapnic hypoxia (IHH) on the immunohistochemical expression of α2, α3, α5, α7, α9 and β2 nicotinic acetylcholine receptor (nAChR) subunits in the developing piglet hippocampus and brainstem medulla, and how prior nicotine exposure alters the response to acute IHH. Five piglet groups included: 1day IHH (1D IHH, n=9), 4days IHH (4D IHH, n=8), controls exposed only to air cycles for 1day (1D Air, n=6) or 4days (4D Air, n=5), and pre-exposed to nicotine for 13days prior to 1day IHH (Nic+1D IHH, n=7)...
February 22, 2017: Neurotoxicology
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