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https://www.readbyqxmd.com/read/28340354/mechanism-of-substrate-translocation-in-an-alternating-access-transporter
#1
Naomi R Latorraca, Nathan M Fastman, A J Venkatakrishnan, Wolf B Frommer, Ron O Dror, Liang Feng
Transporters shuttle molecules across cell membranes by alternating among distinct conformational states. Fundamental questions remain about how transporters transition between states and how such structural rearrangements regulate substrate translocation. Here, we capture the translocation process by crystallography and unguided molecular dynamics simulations, providing an atomic-level description of alternating access transport. Simulations of a SWEET-family transporter initiated from an outward-open, glucose-bound structure reported here spontaneously adopt occluded and inward-open conformations...
March 23, 2017: Cell
https://www.readbyqxmd.com/read/28340336/a-dna-based-t-cell-receptor-reveals-a-role-for-receptor-clustering-in-ligand-discrimination
#2
Marcus J Taylor, Kabir Husain, Zev J Gartner, Satyajit Mayor, Ronald D Vale
A T cell mounts an immune response by measuring the binding strength of its T cell receptor (TCR) for peptide-loaded MHCs (pMHC) on an antigen-presenting cell. How T cells convert the lifetime of the extracellular TCR-pMHC interaction into an intracellular signal remains unknown. Here, we developed a synthetic signaling system in which the extracellular domains of the TCR and pMHC were replaced with short hybridizing strands of DNA. Remarkably, T cells can discriminate between DNA ligands differing by a single base pair...
March 23, 2017: Cell
https://www.readbyqxmd.com/read/28339776/effect-of-acute-millimeter-wave-exposure-on-dopamine-metabolism-of-ngf-treated-pc12-cells
#3
Alexis J Haas, Yann Le Page, Maxim Zhadobov, Ronan Sauleau, Yves Le Dréan, Christian Saligaut
Several forthcoming wireless telecommunication systems will use electromagnetic frequencies at millimeter waves (MMWs), and technologies developed around the 60-GHz band will soon know a widespread distribution. Free nerve endings within the skin have been suggested to be the targets of MMW therapy which has been used in the former Soviet Union. So far, no studies have assessed the impact of MMW exposure on neuronal metabolism. Here, we investigated the effects of a 24-h MMW exposure at 60.4 GHz, with an incident power density (IPD) of 5 mW/cm², on the dopaminergic turnover of NGF-treated PC12 cells...
February 24, 2017: Journal of Radiation Research
https://www.readbyqxmd.com/read/28338973/inflammation-autoimmunity-and-hypertension-the-essential-role-of-tissue-transglutaminase
#4
Chen Liu, Rodney E Kellems, Yang Xia
Inflammatory cytokines cause hypertension when introduced into animals. Additional evidence indicates that cytokines induce the production of autoantibodies that activate the AT1 angiotensin receptor (AT1R). Extensive evidence shows that these autoantibodies, termed AT1-AA, contribute to hypertension. We review here recent studies showing that cytokine-induced hypertension and AT1-AA production require the ubiquitous enzyme, tissue transglutaminase (TG2). We consider 3 mechanisms by which TG2 may contribute to hypertension...
March 13, 2017: American Journal of Hypertension
https://www.readbyqxmd.com/read/28338646/type-iv-secretion-and-signal-transduction-of-helicobacter-pylori-caga-through-interactions-with-host-cell-receptors
#5
REVIEW
Steffen Backert, Nicole Tegtmeyer
Helicobacter pylori is a highly successful human bacterium, which is exceptionally equipped to persistently inhabit the human stomach. Colonization by this pathogen is associated with gastric disorders ranging from chronic gastritis and peptic ulcers to cancer. Highly virulent H. pylori strains express the well-established adhesins BabA/B, SabA, AlpA/B, OipA, and HopQ, and a type IV secretion system (T4SS) encoded by the cag pathogenicity island (PAI). The adhesins ascertain intimate bacterial contact to gastric epithelial cells, while the T4SS represents an extracellular pilus-like structure for the translocation of the effector protein CagA...
March 24, 2017: Toxins
https://www.readbyqxmd.com/read/28338417/a-3d-tissue-printing-approach-for-validation-of-diffusion-tensor-imaging-in-skeletal-muscle
#6
David B Berry, Shangting You, John Warner, Lawrence R Frank, Shaochen Chen, Samuel R Ward
The ability to noninvasively assess skeletal muscle microstructure, which predicts function and disease, would be of significant clinical value. One method that holds this promise is diffusion tensor magnetic resonance imaging (DT-MRI), which is sensitive to the microscopic diffusion of water within tissues and has become ubiquitous in neuroimaging as a way of assessing neuronal structure and damage. However, its application to the assessment of changes in muscle microstructure associated with injury, pathology, or age remains poorly defined, because it is difficult to precisely control muscle microstructural features in vivo...
March 24, 2017: Tissue Engineering. Part A
https://www.readbyqxmd.com/read/28338196/study-on-the-proliferation-of-human-gastric-cancer-cell-ags-by-activation-of-egfr-in-h2o2
#7
Q Wang, W Shen, G-Q Tao, J Sun, L-P Shi
OBJECTIVE: This study is to investigate the effect of low concentration hydrogen peroxide (H2O2) on the proliferation of gastric cancer AGS cell line in vitro and the mechanism. MATERIALS AND METHODS: AGS cells were treated with different low concentrations of H2O2 (1, 0.1, 0.01, and 0.001 μm) for 48 hours. The effect of H2O2 concentration gradient on the activity of AGS cell activities was detected by methyl thiazolyl tetrazolium (MTT) method. The expression of the epidermal growth factor receptor (EGFR) and its downstream signaling pathway extracellular signal-regulated kinase (ERK) protein in H2O2 was detected by Western blot method; moreover, the effect of H2O2 on intracellular reactive oxygen species (ROS) in AGS cells was observed under the fluorescence microscope and quantitative analysis by flow cytometry...
March 2017: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/28337643/recombinant-heat-shock-protein-27-hsp27-hspb1-protects-against-cadmium-induced-oxidative-stress-and-toxicity-in-human-cervical-cancer-cells
#8
Daiana G Alvarez-Olmedo, Veronica S Biaggio, Geremy A Koumbadinga, Nidia N Gómez, Chunhua Shi, Daniel R Ciocca, Zarah Batulan, Mariel A Fanelli, Edward R O'Brien
Cadmium (Cd) is a carcinogen with several well-described toxicological effects in humans, but its molecular mechanisms are still not fully understood. Overexpression of heat shock protein 27 (HSP27/HSPB1)-a multifunctional protein chaperone-has been shown to protect cells from oxidative damage and apoptosis triggered by Cd exposure. The aims of this work were to investigate the potential use of extracellular recombinant HSP27 to prevent/counteract Cd-induced cellular toxicity and to evaluate if peroxynitrite was involved in the development of Cd-induced toxicity...
March 24, 2017: Cell Stress & Chaperones
https://www.readbyqxmd.com/read/28337264/ip3r-and-ryr-calcium-channels-are-involved-in-neonatal-rat-cardiac-myocyte-hypertrophy-induced-by-tumor-necrosis-factor-%C3%AE
#9
Gui-Jun Wang, Lian-Yi Guo, Hong-Xin Wang, Yu-Sheng Yao
To investigate which calcium channels are involved in cardiac myocyte hypertrophy induced by TNF-α, cultured cardiomyocytes were treated with 100 μg/L TNF-α. In addition, three different calcium channel blockers (2-APB, ryanodine and nifedipine) were used, and the effects of each calcium channel blocker on cardiac hypertrophy induced by TNF-α were carefully observed. Measurements included cytosolic calcium transients ([Ca(2+)]i), the level of intracellular calcium in individual cells, cell protein content, cell protein synthesis and cell volume...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28337244/rat-liver-enzyme-release-depends-on-blood-flow-bearing-physical-forces-acting-in-endothelium-glycocalyx-rather-than-on-liver-damage
#10
Julieta A Díaz-Juárez, Rolando Hernández-Muñoz
We have found selective elevation of serum enzyme activities in rats subjected to partial hepatectomy (PH), apparently controlled by hemodynamic flow-bearing physical forces. Here, we assess the involvement of stretch-sensitive calcium channels and calcium mobilization in isolated livers, after chemical modifications of the endothelial glycocalyx and changing perfusion directionality. Inhibiting in vivo protein synthesis, we found that liver enzyme release is influenced by de novo synthesis of endothelial glycocalyx components, and released enzymes are confined into a liver "pool...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/28336823/-regulatory-mechanism-of-calcium-metabolism
#11
Keiichi Ozono
It is often difficult for terrestrial animals to take enough calcium. To maintain serum or extracellular calcium levels is very important for muscle and nerve function. Two major regulators to increase the serum calcium levels are parathyroid hormone(PTH)and vitamin D. PTH binds to the G protein coupling receptor, PTH1R, and increases intracellular cAMP levels. Impirement in the PTH signalling causes many diseases such as pseudohypoparathyroidism and acrodysostosis with hormone resistance. Vitamin D is activated to 1,25-dihydroxyvitamin D[1,25(OH)2D]by two steps of hydroxylation which occurs in the Liver and Kidney...
2017: Clinical Calcium
https://www.readbyqxmd.com/read/28336525/extracellular-tdp-43-aggregates-target-mapk-mak-mrk-overlapping-kinase-mok-and-trigger-caspase-3-il-18-signaling-in-microglia
#12
María M Leal-Lasarte, Jaime M Franco, Adahir Labrador-Garrido, David Pozo, Cintia Roodveldt
Dysregulated microglial responses are central in neurodegenerative proteinopathies, including amyotrophic lateral sclerosis (ALS) and frontotemporal lobar disease (FTLD). Pathologic TDP-43, which is typically found in intracellular inclusions, is a misfolding protein with emerging roles in ALS and FTLD. Recently, TDP-43 species have been found in extracellular fluids of patients; however, the overall implications of TDP-43-mediated signaling linked to neuroinflammation are poorly understood. Our work-the first, to our knowledge, to focus on innate immunity responses to TDP-43 aggregates-shows that such species are internalized by microglia and cause abnormal mobilization of endogenous TDP-43...
March 23, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28336490/novel-therapeutic-interventions-for-pseudoachondroplasia
#13
Karen L Posey, Jacqueline T Hecht
Pseudoachondroplasia (PSACH), a severe short-limbed dwarfing condition, is associated with life-long joint pain and early onset osteoarthritis. PSACH is caused by mutations in cartilage oligomeric matrix protein (COMP), a pentameric matricellular protein expressed primarily in cartilage and other musculoskeletal tissues. Mutations in COMP diminish calcium binding and as a result perturb protein folding and export to the extracellular matrix. Mutant COMP is retained in the endoplasmic reticulum (ER) of growth plate chondrocytes resulting in massive intracellular COMP retention...
March 21, 2017: Bone
https://www.readbyqxmd.com/read/28335738/genome-wide-expression-profiling-establishes-novel-modulatory-roles-of-vitamin-c-in-thp-1-human-monocytic-cell-line
#14
Sakshi Dhingra Batra, Malobi Nandi, Kriti Sikri, Jaya Sivaswami Tyagi
BACKGROUND: Vitamin C (vit C) is an essential dietary nutrient, which is a potent antioxidant, a free radical scavenger and functions as a cofactor in many enzymatic reactions. Vit C is also considered to enhance the immune effector function of macrophages, which are regarded to be the first line of defence in response to any pathogen. The THP-1 cell line is widely used for studying macrophage functions and for analyzing host cell-pathogen interactions. RESULTS: We performed a genome-wide temporal gene expression and functional enrichment analysis of THP-1 cells treated with 100 μM of vit C, a physiologically relevant concentration of the vitamin...
March 23, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28335600/redox-potential-sensitive-n-acetyl-cysteine-prodrug-nanoparticles-inhibit-the-activation-of-microglia-and-improve-neuronal-survival
#15
Eleni Markoutsa, Peisheng Xu
One hallmark of neuroinflammation is the activation of microglia, which triggers the production and release of reactive oxygen species (ROS), nitrate, nitrite, and cytokines. N-acetyl cysteine (NAC) is a free radical scavenger that is involved in the intracellular and extracellular detoxification of ROS in the brain. However, the clinical application of NAC is limited by its low bioavailability and short half-life. Herein, NAC was conjugated to a polymer through disulfide bond to form a NAC-prodrug nanoparticle (NAC-NP)...
March 23, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28334940/aav9-delivered-bispecific-nanobody-attenuates-amyloid-burden-in-the-gelsolin-amyloidosis-mouse-model
#16
Adriaan Verhelle, Nisha Nair, Inge Everaert, Wouter Van Overbeke, Lynn Supply, Olivier Zwaenepoel, Cindy Peleman, Jo Van Dorpe, Tony Lahoutte, Nick Devoogdt, Wim Derave, Marinee K Chuah, Thierry Vanden Driessche, Jan Gettemans
Gelsolin amyloidosis is a dominantly inherited, incurable type of amyloidosis. A single point mutation in the gelsolin gene (G654A is most common) results in the loss of a Ca2+  binding site in the second gelsolin domain. Consequently, this domain partly unfolds and exposes an otherwise buried furin cleavage site at the surface. During secretion of mutant plasma gelsolin consecutive cleavage by furin and MT1-MMP results in the production of 8 and 5 kDa amyloidogenic peptides. Nanobodies that are able to (partly) inhibit furin or MT1-MMP proteolysis have previously been reported...
February 21, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28334866/c9orf72-and-rab7l1-regulate-vesicle-trafficking-in-amyotrophic-lateral-sclerosis-and-frontotemporal-dementia
#17
Yoshitsugu Aoki, Raquel Manzano, Yi Lee, Ruxandra Dafinca, Misako Aoki, Andrew G L Douglas, Miguel A Varela, Chaitra Sathyaprakash, Jakub Scaber, Paola Barbagallo, Pieter Vader, Imre Mäger, Kariem Ezzat, Martin R Turner, Naoki Ito, Samanta Gasco, Norihiko Ohbayashi, Samir El Andaloussi, Shin'ichi Takeda, Mitsunori Fukuda, Kevin Talbot, Matthew J A Wood
A non-coding hexanucleotide repeat expansion in intron 1 of the C9orf72 gene is the most common cause of amyotrophic lateral sclerosis and frontotemporal dementia (C9ALS/FTD), however, the precise molecular mechanism by which the C9orf72 hexanucleotide repeat expansion directs C9ALS/FTD pathogenesis remains unclear. Here, we report a novel disease mechanism arising due to the interaction of C9ORF72 with the RAB7L1 GTPase to regulate vesicle trafficking. Endogenous interaction between C9ORF72 and RAB7L1 was confirmed in human SH-SY5Y neuroblastoma cells...
February 23, 2017: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/28333382/regulation-and-function-of-extracellular-nicotinamide-phosphoribosyltransferase-visfatin
#18
Federico Carbone, Luca Liberale, Aldo Bonaventura, Alessandra Vecchiè, Matteo Casula, Michele Cea, Fiammetta Monacelli, Irene Caffa, Santina Bruzzone, Fabrizio Montecucco, Alessio Nencioni
Nicotinamide phosphoribosyltransferase (NAMPT) is an adipokine-enzyme, which was described as to play bioactivities both in the intracellular and in the extracellular environment. However, while the functions of intracellular NAMPT (iNAMPT) are well known, much less is known on extracellular NAMPT (eNAMPT), also called visfatin or pre-B cell colony-enhancing factor. iNAMPT catalyzes the rate-limiting step in the NAD+ biosynthesis pathway from nicotinamide. Its inhibition severely reduces intracellular NAD+ levels, achieving anti-inflammatory and anti-cancer effects...
March 16, 2017: Comprehensive Physiology
https://www.readbyqxmd.com/read/28333308/fluconazole-treatment-enhances-extracellular-release-of-red-pigments-in-the-fungus-monascus-purpureus
#19
Sunil H Koli, Rahul K Suryawanshi, Chandrashekar D Patil, Satish V Patil
Traditional methods for the production of food grade pigments from fungus Monascus spp. are mostly relying on submerged fermentation. However, cell bound nature and intracellular accumulation of pigments in Monascus spp is the major hurdle in pigment production by submerged fermentation. The present study focused on the investigation of the effect of the antifungal agent, fluconazole on red pigment production from Monascus purpureus (NMCC-PF01). At the optimized concentration of fluconazole (30 μg/ml), pigment production was found to be enhanced by 88% after 96 h and it remained constant even after further incubation up to 168 h...
March 15, 2017: FEMS Microbiology Letters
https://www.readbyqxmd.com/read/28333195/genome-wide-genetic-analyses-highlight-mitogen-activated-protein-kinase-mapk-signaling-in-the-pathogenesis-of-endometriosis
#20
Outi Uimari, Nilufer Rahmioglu, Dale R Nyholt, Katy Vincent, Stacey A Missmer, Christian Becker, Andrew P Morris, Grant W Montgomery, Krina T Zondervan
STUDY QUESTION: Do genome-wide association study (GWAS) data for endometriosis provide insight into novel biological pathways associated with its pathogenesis? SUMMARY ANSWER: GWAS analysis uncovered multiple pathways that are statistically enriched for genetic association signals, analysis of Stage A disease highlighted a novel variant in MAP3K4, while top pathways significantly associated with all endometriosis and Stage A disease included several mitogen-activated protein kinase (MAPK)-related pathways...
February 9, 2017: Human Reproduction
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