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https://www.readbyqxmd.com/read/29779223/gene-editing-vectors-for-studying-nicotinic-acetylcholine-receptors-in-cholinergic-transmission
#1
Can Peng, Yijin Yan, Veronica J Kim, Staci E Engle, Jennifer N Berry, J Michael McIntosh, Rachael L Neve, Ryan M Drenan
Nicotinic acetylcholine receptors (nAChRs), prototype members of the cys-loop ligand gated ion channel family, are key mediators of cholinergic transmission in the central nervous system. Despite their importance, technical gaps exist in our ability to dissect the function of individual subunits in the brain. To overcome these barriers, we designed CRISPR/Cas9 small guide RNA sequences (sgRNAs) for production of loss-of-function alleles in mouse nAChR genes. These sgRNAs were validated in vitro via deep sequencing...
May 19, 2018: European Journal of Neuroscience
https://www.readbyqxmd.com/read/29779049/biochemical-and-functional-interplay-between-ion-channels-and-the-components-of-the-dystrophin-associated-glycoprotein-complex
#2
REVIEW
Margarita Leyva-Leyva, Alejandro Sandoval, Ricardo Felix, Ricardo González-Ramírez
Dystrophin is a cytoskeleton-linked membrane protein that binds to a larger multiprotein assembly called the dystrophin-associated glycoprotein complex (DGC). The deficiency of dystrophin or the components of the DGC results in the loss of connection between the cytoskeleton and the extracellular matrix with significant pathophysiological implications in skeletal and cardiac muscle as well as in the nervous system. Although the DGC plays an important role in maintaining membrane stability, it can also be considered as a versatile and flexible molecular complex that contribute to the cellular organization and dynamics of a variety of proteins at specific locations in the plasma membrane...
May 19, 2018: Journal of Membrane Biology
https://www.readbyqxmd.com/read/29779042/combining-theoretical-and-experimental-data-to-decipher-cftr-3d-structures-and-functions
#3
Brice Hoffmann, Ahmad Elbahnsi, Pierre Lehn, Jean-Luc Décout, Fabio Pietrucci, Jean-Paul Mornon, Isabelle Callebaut
Cryo-electron microscopy (cryo-EM) has recently provided invaluable experimental data about the full-length cystic fibrosis transmembrane conductance regulator (CFTR) 3D structure. However, this experimental information deals with inactive states of the channel, either in an apo, quiescent conformation, in which nucleotide-binding domains (NBDs) are widely separated or in an ATP-bound, yet closed conformation. Here, we show that 3D structure models of the open and closed forms of the channel, now further supported by metadynamics simulations and by comparison with the cryo-EM data, could be used to gain some insights into critical features of the conformational transition toward active CFTR forms...
May 19, 2018: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/29778900/hereditary-sensory-neuropathy-type-1-associated-deoxysphingolipids-cause-neurotoxicity-acute-calcium-handling-abnormalities-and-mitochondrial-dysfunction-in-vitro
#4
Emma R Wilson, Umaiyal Kugathasan, Andrey Y Abramov, Alex J Clark, David L H Bennett, Mary M Reilly, Linda Greensmith, Bernadett Kalmar
Hereditary sensory neuropathy type 1 (HSN-1) is a peripheral neuropathy most frequently caused by mutations in the SPTLC1 or SPTLC2 genes, which code for two subunits of the enzyme serine palmitoyltransferase (SPT). SPT catalyzes the first step of de novo sphingolipid synthesis. Mutations in SPT result in a change in enzyme substrate specificity, which causes the production of atypical deoxysphinganine and deoxymethylsphinganine, rather than the normal enzyme product, sphinganine. Levels of these abnormal compounds are elevated in blood of HSN-1 patients and this is thought to cause the peripheral motor and sensory nerve damage that is characteristic of the disease, by a largely unresolved mechanism...
May 17, 2018: Neurobiology of Disease
https://www.readbyqxmd.com/read/29778846/efficacy-and-tolerability-of-treatment-with-lacosamide-postmarketing-experience-from-the-middle-east-region
#5
Maher Arabi, Taoufik Alsaadi, Wassim Nasreddine, Jasem Al-Hashel, Maya Dirani, Ahmad Beydoun
PURPOSE: Lacosamide (LCM) was recently introduced in the Middle East. The aim of this study was to evaluate the safety, tolerability, and efficacy of LCM in patients with focal onset seizures and determine if our results are comparable with those derived from Western countries. METHODS: This is a retrospective analysis from two medical centers on consecutive patients diagnosed as having focal onset seizures and treated with add-on LCM. The primary efficacy variables were the 50% responder and seizure-free rates, and the secondary outcome variables included the percentages of patients who achieved seizure remission during the last 6-month follow-up period and the percentages of discontinuation due to lack of efficacy or tolerability...
May 17, 2018: Epilepsy & Behavior: E&B
https://www.readbyqxmd.com/read/29778743/separation-of-chloroform-from-a-dilute-solution-using-a-cyclic-peptide-nanotube-a-molecular-dynamics-study
#6
Xin Zhao, Jian Fen Fan, Xia Lan Si, Ling Ling Zhang, Meng Nan Qu
This work firstly explored the potential application of a cyclic peptide nanotube (CPNT) in the separation of chloroform from a dilute solution. Four hydrophobic CPNTs of 8 × (WL)4,5 and 8 × (AL)4,5 all exhibit excellent adsorption characteristics to chloroform. The CPNT diameter, side chain structures and the concentration of chloroform in a solution all affect the adsorption characteristics of chloroform. CHCl3 molecules are overwhelmingly adsorbed on the surfaces of these CPNTs as a cluster, and sporadically reside inside the channels, consistent with the chloroform's potentials of mean force (PMFs) inside and outside the channels...
May 10, 2018: Journal of Molecular Graphics & Modelling
https://www.readbyqxmd.com/read/29778719/effect-of-heptanol-and-ethanol-on-excitation-wave-propagation-in-a-neonatal-rat-ventricular-myocyte-monolayer
#7
A D Podgurskaya, V A Tsvelaya, S R Frolova, I Y Kalita, N N Kudryashova, K I Agladze
In this work, the action of heptanol and ethanol was investigated in a two-dimensional (2D) model of cardiac tissue: the neonatal rat ventricular myocyte monolayer. Heptanol is known in electrophysiology as a gap junction uncoupler but may also inhibit voltage-gated ionic channels. Ethanol is often associated with the occurrence of arrhythmias. These substances influence sodium, calcium, and potassium channels, but the complete mechanism of action of heptanol and ethanol remains unknown. The optical mapping method was used to measure conduction velocities (CVs) in concentrations of 0...
May 17, 2018: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/29778700/paediatric-cystolitholapaxy-through-the-mitrofanoff-monti-channel
#8
J S Thomas, N Smeulders, F Yankovic, S Undre, I Mushtaq, P-J López, P Cuckow
INTRODUCTION: Bladder calculi are a known complication of bladder augmentation. Open cystolithotomy remains the preferred option for treating large or multiple stones. Increasingly, however, minimal access techniques have been used. Reports of Mitrofanoff cystolitholapaxy are rare and have been limited to adults. This study presented a two centre series of children treated by cystolitholapaxy via the Mitrofanoff/Monti channel. MATERIALS AND METHODS: With institutional approval the current study retrospectively reviewed and identified 14 patients, on a prospective database, who underwent Mitrofanoff cystolitholapaxy to treat bladder calculi at two independent institutions in the UK and Chile between 2004 and 2016...
April 4, 2018: Journal of Pediatric Urology
https://www.readbyqxmd.com/read/29778689/network-analysis-of-a-proposed-exit-pathway-for-protons-to-the-p-side-of-cytochrome-c-oxidase
#9
Xiuhong Cai, Kamran Haider, Jianxun Lu, Slaven Radic, Chang Yun Son, Qiang Cui, M R Gunner
Cytochrome c Oxidase (CcO) reduces O2 , the terminal electron acceptor, to water in the aerobic respiration electron transport chain. The energy released by O2 reductions is stored by removing eight protons from the high pH, N-side, of the membrane with four used for chemistry in the active site and four pumped to the low pH, P-side. The proton transfers must occur along controllable proton pathways that prevent energy dissipating movement towards the N-side. The CcO N-side has well established D- and K-channels to deliver protons to the protein interior...
May 17, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29778594/differetial-toxin-profiles-of-ciguatoxins-in-marine-organisms-chemistry-fate-and-global-distribution
#10
REVIEW
Lucía Soliño, Pedro Reis Costa
Ciguatoxins (CTXs) are fish metabolism products and a result of biotransformation of precursor gambiertoxins produced, in the first instance, by benthic dinoflagellates Gambierdiscus and Fukuyoa. Ciguatoxins are potent neurotoxins that selectively open voltage gated sodium channels in excitable cells causing the human food poisoning known as Ciguatera (CFP). Endemic from tropical areas in central Pacific and West Indian Ocean, and the Caribbean Sea, CTX may affects up to 500,000 people annually due to fish consumption...
May 17, 2018: Toxicon: Official Journal of the International Society on Toxinology
https://www.readbyqxmd.com/read/29778509/longitudinal-observations-using-simultaneous-fmri-multiple-channel-electrophysiology-recording-and-chemical-microiontophoresis-in-the-rat-brain
#11
Saul Jaime, Jose E Cavazos, Yihong Yang, Hanbing Lu
BACKGROUND: fMRI blood oxygenation level-dependent (BOLD) signal has been widely used as a surrogate for neural activity. However, interpreting differences in BOLD fMRI based on underlying neuronal activity remains a challenge. Concurrent rsMRI data collection and electrophysiological recording in combination with microiontophoretically injected modulatory chemicals allows for improved understanding of the relationship between resting state BOLD and neuronal activity. NEW METHODS: Simultaneous fMRI, multi-channel intracortical electrophysiology and focal pharmacological manipulation data to be acquired longitudinally in rats for up to 2 months...
May 17, 2018: Journal of Neuroscience Methods
https://www.readbyqxmd.com/read/29778449/mechanisms-underlying-the-relaxation-by-a484954-a-eukaryotic-elongation-factor-2-kinase-inhibitor-in-rat-isolated-mesenteric-artery
#12
Tomoko Kodama, Muneyoshi Okada, Hideyuki Yamawaki
Eukaryotic elongation factor 2 kinase (eEF2K) is a calmodulin-related protein kinase which regulates protein translation. A484954 is an inhibitor of eEF2K. In the present study, we investigated the acute effects of A484954 on contractility of isolated blood vessels. Isometric contraction of rat isolated aorta and main branch of superior mesenteric artery (MA) was measured. Expression of an inward rectifier K+ (Kir ) channel subtype mRNA and protein was examined. A484954 caused relaxation in endothelium-intact [E (+)] and -denuded [E (-)] aorta or MA precontracted with noradrenaline (NA)...
May 2, 2018: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/29778431/microbiologic-assessment-of-flexible-gastrointestinal-endoscope-reprocessing-using-a-pump-assisted-sampling-technique-an-investigation-involving-all-endoscopy-units-in-tianjin-china
#13
Xue-Yue Ji, Pei-Yong Ning, Wei Zhang, Dong-Jing Yang, He Liu, Jun Liu, Jia Song, Chun-Nan Fei
BACKGROUND: Microbiologic surveillance of flexible gastrointestinal endoscopes is recommended in several guidelines as the primary means of identifying reprocessing failures. This study aimed to evaluate the contamination level and prevalence of bacteria of post-reprocessing endoscopes and to access whether using a pump-assisted sampling method (PASM) improves the sensitivity of culture. METHODS: All 59 endoscopy units in Tianjin, China, were investigated. The PASM and the conventional flushing sampling method (CFSM) were used to compare the results of the microbial culture...
May 16, 2018: American Journal of Infection Control
https://www.readbyqxmd.com/read/29777761/functional-organization-of-postsynaptic-glutamate-receptors
#14
REVIEW
Nicky Scheefhals, Harold D MacGillavry
Glutamate receptors are the most abundant excitatory neurotransmitter receptors in the brain, responsible for mediating the vast majority of excitatory transmission in neuronal networks. The AMPA- and NMDA-type ionotropic glutamate receptors (iGluRs) are ligand-gated ion channels that mediate the fast synaptic responses, while metabotropic glutamate receptors (mGluRs) are coupled to downstream signaling cascades that act on much slower timescales. These functionally distinct receptor sub-types are co-expressed at individual synapses, allowing for the precise temporal modulation of postsynaptic excitability and plasticity...
May 16, 2018: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/29777701/ropivacaine-inhibits-the-migration-of-esophageal-cancer-cells-via-sodium-channel-independent-but-prenylation-dependent-inhibition-of-rac1-jnk-paxillin-fak
#15
Yaqin Zhang, Xiaohong Peng, Qinghong Zheng
The direct anti-proliferative and pro-apoptotic effects of local anesthetics have been well documented in various cancers. However, whether local anesthetics affect cancer metastasis and their underlying molecular mechanisms are not well understood. In this work, we show that ropivacaine at the clinically relevant concentration significantly inhibits esophageal cancer cell migration. Interestingly, ropivacaine at the same concentration does not display inhibitory effects on esophageal cancer cell growth and survival...
May 16, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29777700/transient-receptor-potential-ankyrin-1-channels-are-involved-in-spontaneous-peptide-hormone-release-from-astrocytes
#16
Mai Takizawa, Kazuki Harada, Kazuaki Nakamura, Takashi Tsuboi
Astrocytes, a large population of glial cells, detect neurotransmitters and respond by increasing intracellular Ca2+ concentration ([Ca2+ ]i ) and releasing chemical molecules called gliotransmitters. Recently discovered Ca2+ influx through transient receptor potential ankyrin 1 (TRPA1) channels is reported to cause spontaneous [Ca2+ ]i increase in astrocytes. While several physiological functions of TRPA1-mediated spontaneous Ca2+ signal have been revealed, relation with gliotransmitter release, especially peptide hormone exocytosis is largely unknown...
May 16, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29777691/improving-electrical-properties-of-ipsc-cardiomyocytes-by-enhancing-cx43-expression
#17
Valentin Sottas, Carl-Mattheis Wahl, Mihnea C Trache, Michael Bartolf-Kopp, Sidney Cambridge, Markus Hecker, Nina D Ullrich
The therapeutic potential of induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) is limited by immature functional features including low impulse propagation and reduced cell excitability. Key players regulating electrical activity are voltage-gated Na+ channels (Nav 1.5) and gap junctions built from connexin-43 (Cx43). Here we tested the hypothesis that enhanced Cx43 expression increases intercellular coupling and influences excitability by modulating Nav 1.5. Using transgenic approaches, Cx43 and Nav 1...
May 16, 2018: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/29777637/thymol-inhibits-oral-squamous-cell-carcinoma-growth-via-mitochondria-mediated-apoptosis
#18
Jorge J De La Chapa, Prajjal Kanti Singha, Debbie R Lee, Cara B Gonzales
BACKGROUND: Thymol is a Transient Receptor Potential Ankyrin Subtype 1 channel, (TRPA1) agonist found in thyme and oregano. Thymol has antioxidant, anti-inflammatory, and antimicrobial properties; thus thymol is added to many commercially available products including Listerine mouthwash. Thymol is also cytotoxic to HL-60 (acute promyelotic leukemia) cells in vitro. Therefore, we evaluated the effects of thymol against oral squamous cell carcinoma (OSCC) and its anticancer mechanism-of-action...
May 19, 2018: Journal of Oral Pathology & Medicine
https://www.readbyqxmd.com/read/29777594/il-3-producing-basophils-are-required-to-exacerbate-airway-hyper-responsiveness-in-a-murine-inflammatory-model
#19
Rachel Rignault-Bricard, François Machavoine, Salah Mecheri, Olivier Hermine, Elke Schneider, Michel Dy, Maria Leite-de-Moraes
BACKGROUND: Basophils are commonly associated with allergic responses because of their ability to produce large amounts of pro-Th2 cytokines and histamine. However, the mechanisms through which bone marrow-resident basophils (BMRB) become fully competent cytokine and histamine producers in response to IgE crosslinking are poorly understood. Here, we sought to determine the role of IL-3 in promoting pro-Th2 basophils. METHODS: BMRB and basophils exposed to IL-3 in vitro and in vivo were evaluated for their production of Th2 cytokines and histamine in response to FcεRI crosslinking on both protein and gene expression levels...
May 19, 2018: Allergy
https://www.readbyqxmd.com/read/29777515/bottom-up-attention-capture-with-distractor-and-target-singletons-defined-in-the-same-color-dimension-is-not-a-matter-of-feature-uncertainty
#20
Hanna Weichselbaum, Ulrich Ansorge
In visual search, attention capture by an irrelevant color-singleton distractor in another feature dimension than the target is dependent on whether or not the distractor changes its feature: Capture is present if the irrelevant color distractor can take on different features across trials, but absent if the distractor takes on only one feature throughout all trials. This influence could be due to down-weighting of the entire color map. Here we tested whether a similar effect could also be brought about by down-weighting of specific color channels within the same maps...
May 18, 2018: Attention, Perception & Psychophysics
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