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https://www.readbyqxmd.com/read/29165651/functional-conservation-of-the-ama1-host-cell-invasion-ligand-between-p-falciparum-and-p-vivax-a-novel-platform-to-accelerate-vaccine-and-drug-development
#1
Damien R Drew, Paul R Sanders, Gretchen Weiss, Paul R Gilson, Brendan S Crabb, James G Beeson
P. vivax and P. falciparum malaria species have diverged significantly in receptor-ligand interactions and host-cell invasion. One protein common to both is the merozoite invasion ligand AMA1. While the general structure of AMA1 is similar between species, their sequences are divergent. Surprisingly, it was possible to genetically replace PfAMA1 with PvAMA1 in P. falciparum parasites. PvAMA1 could complement PfAMA1 function and supported efficient invasion of erythrocytes by P. falciparum. Genetically-modified P...
November 20, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/29164431/response-of-the-gabaergic-system-to-axotomy-of-the-rat-facial-nerve
#2
Reika Kikuchi, Makoto Hamanoue, Maasa Koshimoto, Shinichi Kohsaka, Kazuyuki Nakajima
The responses of inhibitory neurons/synapses to motoneuron injury in the cranial nervous system remain to be elucidated. In this study, we analyzed GABAA receptor (GABAAR) and GABAergic neurons at the protein level in the transected rat facial nucleus. Immunoblotting revealed that the GABAARα1 protein levels in the axotomized facial nucleus decreased significantly 5-14 days post-insult, and these levels remained low for 5 weeks. Immunohistochemical analysis indicated that the GABAARα1-expressing cells were motoneurons...
November 21, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/29163789/prostaglandin-e2-and-pd-1-mediated-inhibition-of-antitumor-ctl-responses-in-the-human-tumor-microenvironment
#3
Jie Miao, Xu Lu, Yuefeng Hu, Chunmei Piao, Xuan Wu, Xuesong Liu, Caiting Huang, Yue Wang, Dan Li, Jingwei Liu
Accumulating evidence indicates that inflammation plays a critical role in cancer development; however, mechanisms of immunosuppression hinder productive anti-tumor immunity to limit immunopathology. Tumor-specific cytotoxic T lymphocyte (CTL) dysfunction or exhaustion by upregulating inhibitory receptors such as programmed cell death 1 (PD-1) in tumor-bearing hosts is one such mechanism. Identification and blockade of the pathways that induce CTL dysfunction has been shown to partially restore CTL function in tumor-bearing hosts...
October 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/29163518/mixed-signals-co-stimulation-in-invariant-natural-killer-t-cell-mediated-cancer-immunotherapy
#4
REVIEW
Susannah C Shissler, Michael S Lee, Tonya J Webb
Invariant natural killer T (iNKT) cells are an integral component of the immune system and play an important role in antitumor immunity. Upon activation, iNKT cells can directly kill malignant cells as well as rapidly produce cytokines that stimulate other immune cells, making them a front line defense against tumorigenesis. Unfortunately, iNKT cell number and activity are reduced in multiple cancer types. This anergy is often associated with upregulation of co-inhibitory markers such as programmed death-1...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29163509/downregulated-il-21-response-and-t-follicular-helper-cell-exhaustion-correlate-with-compromised-cd8-t-cell-immunity-during-chronic-toxoplasmosis
#5
Magali M Moretto, SuJin Hwang, Imtiaz A Khan
CD8 T cells are important for maintaining the chronicity of Toxoplasma gondii infection. In a T. gondii encephalitis susceptible model, we recently demonstrated that CD4 T cells play an essential helper role in the maintenance of the effector response and CD8 T cell dysfunctionality was linked to CD4 T cell exhaustion. However, CD4 T cells are constituted of different subsets with various functions and the population(s) providing help to the CD8 T cells has not yet been determined. In the present study, T follicular helper cells (Tfh), which are known to be essential for B cell maturation and are one of the main sources of IL-21, were significantly increased during chronic toxoplasmosis...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29163499/fc%C3%AE%C2%B5ri-%C3%AE-chain-negatively-modulates-dectin-1-responses-in-dendritic-cells
#6
Yi-Gen Pan, Yen-Ling Yu, Chi-Chien Lin, Lewis L Lanier, Ching-Liang Chu
The inhibitory effect of immunoreceptor tyrosine-based activation motif (ITAM)-containing adapters DAP12 and FcεRI γ-chain (FcRγ) has been found in many immune functions. Herein, we have further explored the role of these adapters in C-type lectin receptors response. We identified that FcRγ, but not DAP12, could negatively regulate the Dectin-1 responses in dendritic cells (DCs). Loss of FcRγ or both DAP12 and FcRγ enhanced the maturation and cytokine production in DCs upon Dectin-1 activation compared to normal cells, whereas DCs lacking only DAP12 showed little changes...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29163487/baicalin-inhibits-nod-like-receptor-family-pyrin-containing-domain-3-inflammasome-activation-in-murine-macrophages-by-augmenting-protein-kinase-a-signaling
#7
Chen-Guang Li, Liang Yan, Feng-Yi Mai, Zi-Jian Shi, Li-Hui Xu, Yan-Yun Jing, Qing-Bing Zha, Dong-Yun Ouyang, Xian-Hui He
The flavonoid baicalin has been reported to possess potent anti-inflammatory activities by suppressing inflammatory signaling pathways. However, whether baicalin can suppress the activation of NOD-like receptor (NLR) family, pyrin containing domain 3 (NLRP3) inflammasome in macrophages is largely unknown. Here, we showed that baicalin treatment dose-dependently inhibited adenosine triphosphate (ATP) or nigericin-induced NLRP3 inflammasome activation, as revealed by the decreased release of mature interleukin (IL)-1β, active caspase-1p10, and high-mobility group box-1 protein from lipopolysaccharide (LPS)-primed bone marrow-derived macrophages...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29163357/a-journey-through-the-gonadotropin-inhibitory-hormone-system-of-fish
#8
REVIEW
José A Muñoz-Cueto, José A Paullada-Salmerón, María Aliaga-Guerrero, Mairi E Cowan, Ishwar S Parhar, Takayoshi Ubuka
Gonadotropin-inhibitory hormone (GnIH) is a hypothalamic neuropeptide that belongs to the RFamide peptide family and was first identified in the quail brain. From the discovery of avian GnIH, orthologous GnIH peptides have been reported in a variety of vertebrates, including mammals, amphibians, teleosts and agnathans, but also in protochordates. It has been clearly established that GnIH suppresses reproduction in avian and mammalian species through its inhibitory actions on brain GnRH and pituitary gonadotropins...
2017: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/29163062/difference-in-perseverative-errors-during-a-visual-attention-task-with-auditory-distractors-in-alpha-9-nicotinic-receptor-subunit-wild-type-and-knock-out-mice
#9
Pascal Jorratt, Paul H Delano, Carolina Delgado, Alexies Dagnino-Subiabre, Gonzalo Terreros
The auditory efferent system is a neural network that originates in the auditory cortex and projects to the cochlear receptor through olivocochlear (OC) neurons. Medial OC neurons make cholinergic synapses with outer hair cells (OHCs) through nicotinic receptors constituted by α9 and α10 subunits. One of the physiological functions of the α9 nicotinic receptor subunit (α9-nAChR) is the suppression of auditory distractors during selective attention to visual stimuli. In a recent study we demonstrated that the behavioral performance of alpha-9 nicotinic receptor knock-out (KO) mice is altered during selective attention to visual stimuli with auditory distractors since they made less correct responses and more omissions than wild type (WT) mice...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/29163043/combination-therapy-in-fragile-x-syndrome-possibilities-and-pitfalls-illustrated-by-targeting-the-mglur5-and-gaba-pathway-simultaneously
#10
Shimriet Zeidler, Helen de Boer, Renate K Hukema, Rob Willemsen
Fragile X syndrome (FXS) is the most common monogenetic cause of intellectual disability and autism. The disorder is characterized by altered synaptic plasticity in the brain. Synaptic plasticity is tightly regulated by a complex balance of different synaptic pathways. In FXS, various synaptic pathways are disrupted, including the excitatory metabotropic glutamate receptor 5 (mGluR5) and the inhibitory γ-aminobutyric acid (GABA) pathways. Targeting each of these pathways individually, has demonstrated beneficial effects in animal models, but not in patients with FXS...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/29162865/gaba-a-receptor-coupling-junction-and-pore-gabrb3-mutations-are-linked-to-early-onset-epileptic-encephalopathy
#11
Ciria C Hernandez, Yujia Zhang, Ningning Hu, Dingding Shen, Wangzhen Shen, Xiaoyan Liu, Weijing Kong, Yuwu Jiang, Robert L Macdonald
GABAA receptors are brain inhibitory chloride ion channels. Here we show functional analyses and structural simulations for three de novo missense mutations in the GABAA receptor β3 subunit gene (GABRB3) identified in patients with early-onset epileptic encephalopathy (EOEE) and profound developmental delay. We sought to obtain insights into the molecular mechanisms that might link defects in GABAA receptor biophysics and biogenesis to patients with EOEE. The mutant residues are part of conserved structural domains such as the Cys-loop (L170R) and M2-M3 loop (A305V) that form the GABA binding/channel gating coupling junction and the channel pore (T288N), which are functionally coupled during receptor activation...
November 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29162646/nkg2d-dependent-anti-tumor-effects-of-chemotherapy-and-radiotherapy-against-glioblastoma
#12
Tobias Weiss, Hannah Schneider, Manuela Silginer, Alexander Steinle, Martin N Pruschy, Bojan Polic, Michael Weller, Patrick Roth
PURPOSE: NKG2D is a potent activating immune cell receptor and glioma cells express the cognate ligands (NKG2DL). These ligands are inducible by cellular stress and temozolomide (TMZ) or irradiation (IR), the standard treatment of glioblastoma, could affect their expression. However, a role of NKG2DL for the efficacy of TMZ and IR has never been addressed. EXPERIMENTAL DESIGN: We assessed the effect of TMZ and IR on NKG2DL in vitro and in vivo in a variety of murine and human glioblastoma models including glioma-initiating cells and a cohort of paired glioblastoma samples from patients before and after therapy...
November 21, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29162115/opportunities-for-topical-antimicrobial-therapy-permeation-of-canine-skin-by-fusidic-acid
#13
Sian-Marie Frosini, Ross Bond, Anette Loeffler, Jo Larner
BACKGROUND: Staphylococcal infection of the canine epidermis and hair follicle is amongst the commonest reasons for antimicrobial prescribing in small animal veterinary practice. Topical therapy with fusidic acid (FA) is an attractive alternative to systemic therapy based on low minimum inhibitory concentrations (MICs, commonly <0.03 mg/l) documented in canine pathogenic staphylococci, including strains of MRSA and MRSP (methicillin-resistant Staphylococcus aureus and S. pseudintermedius)...
November 21, 2017: BMC Veterinary Research
https://www.readbyqxmd.com/read/29162108/reduced-suppressive-effect-of-%C3%AE-2-adrenoceptor-agonist-on-fibrocyte-function-in-severe-asthma
#14
Chun-Yu Lo, Charalambos Michaeloudes, Pankaj K Bhavsar, Chien-Da Huang, Po-Jui Chang, Chun-Hua Wang, Han-Pin Kuo, Kian Fan Chung
BACKGROUND: Patients with severe asthma have increased airway remodelling and elevated numbers of circulating fibrocytes with enhanced myofibroblastic differentiation capacity, despite being treated with high doses of corticosteroids, and long acting β2-adrenergic receptor (AR) agonists (LABAs). We determined the effect of β2-AR agonists, alone or in combination with corticosteroids, on fibrocyte function. METHODS: Non-adherent non-T cells from peripheral blood mononuclear cells isolated from healthy subjects and patients with non-severe or severe asthma were treated with the β2-AR agonist, salmeterol, in the presence or absence of the corticosteroid dexamethasone...
November 21, 2017: Respiratory Research
https://www.readbyqxmd.com/read/29161398/role-of-gabaa-receptor-subtypes-in-the-behavioural-effects-of-intravenous-general-anaesthetics
#15
C J Weir, S J Mitchell, J J Lambert
Since the introduction of general anaesthetics into clinical practice, researchers have been mystified as to how these chemically disparate drugs act to produce their dramatic effects on central nervous system function and behaviour. Scientific advances, particularly during the last 25 years, have now begun to reveal the molecular mechanisms underpinning their behavioural effects. For certain i.v. general anaesthetics, such as etomidate and propofol, a persuasive case can now be made that the GABAA receptor, a major inhibitory receptor in the mammalian central nervous system, is an important target...
December 1, 2017: British Journal of Anaesthesia
https://www.readbyqxmd.com/read/29161354/p140cap-regulates-gabaergic-synaptogenesis-and-development-of-hippocampal-inhibitory-circuits
#16
Isabella Russo, Daniela Gavello, Elisabetta Menna, David Vandael, Carola Veglia, Noemi Morello, Irene Corradini, Elisa Focchi, Annalisa Alfieri, Costanza Angelini, Federico Tommaso Bianchi, Alessandro Morellato, Andrea Marcantoni, Marco Sassoè-Pognetto, Matteo Maria Ottaviani, Latefa Yekhlef, Maurizio Giustetto, Stefano Taverna, Valentina Carabelli, Michela Matteoli, Emilio Carbone, Emilia Turco, Paola Defilippi
The neuronal scaffold protein p140Cap was investigated during hippocampal network formation. p140Cap is present in presynaptic GABAergic terminals and its genetic depletion results in a marked alteration of inhibitory synaptic activity. p140Cap-/- cultured neurons display higher frequency of miniature inhibitory postsynaptic currents (mIPSCs) with no changes of their mean amplitude. Consistent with a potential presynaptic alteration of basal GABA release, p140Cap-/- neurons exhibit a larger synaptic vesicle readily releasable pool, without any variation of single GABAA receptor unitary currents and number of postsynaptic channels...
November 17, 2017: Cerebral Cortex
https://www.readbyqxmd.com/read/29161035/synthesis-of-photoswitchable-%C3%AE-9-tetrahydrocannabinol-derivatives-enables-optical-control-of-cannabinoid-receptor-1-signaling
#17
Matthias Westphal, Michael Andreas Schafroth, Roman Sarott, Michael Imhof, Christian Bold, Philipp Leippe, Amey Dhopeshwarkar, Jessica Grandner, Vsevolod Katritch, Ken Mackie, Dirk Trauner, Erick M Carreira, James Allen Frank
The cannabinoid receptor 1 (CB1) is an inhibitory G protein-coupled receptor abundantly expressed in the central nerv-ous system. It has rich pharmacology and largely accounts for the recreational use of cannabis. We describe efficient asymmetric syntheses of four photoswitchable Δ(9)-tetrahydrocannabinol derivatives (azo-THCs) from a central building block 3-Br-THC. Using electrophysiology and a FRET-based cAMP assay, two compounds are identified as potent CB1 agonists that change their effect upon illumination...
November 21, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/29160911/simultaneous-use-of-erythropoietin-and-lfm-a13-as-a-new-therapeutic-approach-for-colorectal-cancer
#18
Anna Tankiewicz-Kwedlo, Justyna Magdalena Hermanowicz, Tomasz Domaniewski, Krystyna Pawlak, Małgorzata Rusak, Anna Pryczynicz, Arkadiusz Surazynski, Tomasz Kaminski, Adam Kazberuk, Dariusz Pawlak
BACKGROUND AND PURPOSE: Bruton's tyrosine kinase (BTK) is a non-receptor tyrosine kinase involved in the activation of signaling pathways responsible for cell maturation and viability. BTK has previously been reported to be overexpressed in colon cancers. This kind of cancer is often accompanied by anemia, which is treated with an erythropoietin supplement. The goal of the present study was to assess the effects of combination therapy with erythropoietin beta (Epo) and LFM-A13 (BTK inhibitor) on colon cancer in in vitro and in vivo models...
November 21, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/29160850/analgesic-mechanisms-of-antidepressants-for-neuropathic-pain
#19
REVIEW
Hideaki Obata
Tricyclic antidepressants and serotonin noradrenaline reuptake inhibitors are used to treat chronic pain, such as neuropathic pain. Why antidepressants are effective for treatment of neuropathic pain and the precise mechanisms underlying their effects, however, remain unclear. The inhibitory effects of these antidepressants for neuropathic pain manifest more quickly than their antidepressive effects, suggesting different modes of action. Recent studies of animal models of neuropathic pain revealed that noradrenaline is extremely important for the inhibition of neuropathic pain...
November 21, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29159783/in-vitro-study-of-the-effects-of-denosumab-on-giant-cell-tumor-of-bone-comparison-with-zoledronic-acid
#20
Isao Shibuya, Masamichi Takami, Arei Miyamoto, Akiko Karakawa, Akira Dezawa, Shigeru Nakamura, Ryutaro Kamijo
Giant cell tumor of bone (GCTB) is a locally aggressive primary bone tumor that contains numerous osteoclasts formed from marrow-derived precursors through receptor activator of nuclear factor κ-B ligand (RANKL), an osteoclast differentiation factor expressed in neoplastic cells of GCTB. Denosumab, a fully human monoclonal antibody targeting RANKL, has recently been used for the treatment of GCTB, and superior treatment effects have been reported. The aim of this work was to elucidate the mechanism of action of denosumab, and the differences between denosumab and zoledronic acid at the level of GCTB cells...
November 20, 2017: Pathology Oncology Research: POR
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