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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/29777761/functional-organization-of-postsynaptic-glutamate-receptors
#3
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/29777196/single-measurement-detection-of-individual-cell-ionic-oscillations-using-an-n-type-semiconductor-electrolyte-interface
#4
Mariusz Pietruszka, Monika Olszewska, Lukasz Machura, Edward Rówiński
Pollen tubes are used as models in studies on the type of tip-growth in plants. They are an example of polarised and rapid growth because pollen tubes are able to quickly invade the flower pistil in order to accomplish fertilisation. How different ionic fluxes are perceived, processed or generated in the pollen tube is still not satisfactorily understood. In order to measure the H+ , K+ , Ca2+ and Cl- fluxes of a single pollen tube, we developed an Electrical Lab on a Photovoltaic-Chip (ELoPvC) on which the evolving cell was immersed in an electrolyte of a germination medium...
May 18, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29777120/softness-induced-enhancement-in-net-throughput-of-non-linear-bio-fluids-in-nanofluidic-channel-under-edl-phenomenon
#5
Harshad Sanjay Gaikwad, Pranab Kumar Mondal, Somchai Wongwises
In this article, we describe the electro-hydrodynamics of non-Newtonian fluid in narrow fluidic channel with solvent permeable and ion-penetrable polyelectrolyte layer (PEL) grafted on channel surface with an interaction of non-overlapping electric double layer (EDL) phenomenon. In this analysis, we integrate power-law model in the momentum equation for describing the non-Newtonian rheology. The complex interplay between the non-Newtonian rheology and interfacial electrochemistry in presence of PEL on the walls leads to non-intuitive variations in the underlying flow dynamics in the channels...
May 18, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29776603/regulation-of-g-protein-%C3%AE-%C3%AE-signaling
#6
Kanishka Senarath, Dinesh Kankanamge, Saroopa Samaradivakara, Kasun Ratnayake, Mithila Tennakoon, Ajith Karunarathne
Heterotrimeric guanine nucleotide-binding proteins (G proteins) deliver external signals to the cell interior, upon activation by the external signal stimulated G protein-coupled receptors (GPCRs).While the activated GPCRs control several pathways independently, activated G proteins control the vast majority of cellular and physiological functions, ranging from vision to cardiovascular homeostasis. Activated GPCRs dissociate GαGDPβγ heterotrimer into GαGTP and free Gβγ. Earlier, GαGTP was recognized as the primary signal transducer of the pathway and Gβγ as a passive signaling modality that facilitates the activity of Gα...
2018: International Review of Cell and Molecular Biology
https://www.readbyqxmd.com/read/29775742/ryanodine-receptor-ca-2-release-channel-post-translational-modification-central-player-in-cardiac-and-skeletal-muscle-disease
#7
Amanda Denniss, Angela F Dulhunty, Nicole A Beard
Calcium release from internal stores is a quintessential event in excitation-contraction coupling in cardiac and skeletal muscle. The ryanodine receptor Ca2+ release channel is embedded in the internal sarcoplasmic reticulum Ca2+ store, which releases Ca2+ into the cytoplasm, enabling contraction. Ryanodine receptors form the hub of a macromolecular complex extending from the extracellular space to the sarcoplasmic reticulum lumen. Ryanodine receptor activity is influenced by the integrated effects of associated co-proteins, ions, and post-translational phosphor and redox modifications...
May 15, 2018: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/29773471/increased-spontaneous-firing-rates-in-auditory-midbrain-following-noise-exposure-are-specifically-abolished-by-a-kv3-channel-modulator
#8
Lucy A Anderson, Lara L Hesse, Nadia Pilati, Warren M H Bakay, Giuseppe Alvaro, Charles H Large, David McAlpine, Roland Schaette, Jennifer F Linden
Noise exposure has been shown to produce long-lasting increases in spontaneous activity in central auditory structures in animal models, and similar pathologies are thought to contribute to clinical phenomena such as hyperacusis or tinnitus in humans. Here we demonstrate that multi-unit spontaneous neuronal activity in the inferior colliculus (IC) of mice is significantly elevated four weeks following noise exposure at recording sites with frequency tuning within or near the noise exposure band, and this selective central auditory pathology can be normalised through administration of a novel compound that modulates activity of Kv3 voltage-gated ion channels...
April 30, 2018: Hearing Research
https://www.readbyqxmd.com/read/29772901/the-catch-22-of-predicting-herg-blockade-using-publicly-accessible-bioactivity-data
#9
Vishal Babu Siramshetty, Qiaofeng Chen, Prashanth Devarakonda, Robert Preissner
Drug-induced inhibition of the human Ether-à-go-go-Related Gene (hERG) encoded potassium ion (K+) channels can lead to fatal cardiotoxicity. Several marketed drugs and promising drug candidates were recalled due to this concern. Diverse modeling methods ranging from molecular similarity assessment to quantitative structure activity relationship analysis employing machine learning techniques have been applied to datasets of varying size and composition (number of blockers and non-blockers). In this study, we highlight the challenges involved in development of a robust classifier for predicting the hERG endpoint using bioactivity data extracted from the public domain...
May 17, 2018: Journal of Chemical Information and Modeling
https://www.readbyqxmd.com/read/29772843/the-role-of-trp-channels-in-the-metastatic-cascade
#10
REVIEW
Benedikt Fels, Etmar Bulk, Zoltán Pethő, Albrecht Schwab
A dysregulated cellular Ca2+ homeostasis is involved in multiple pathologies including cancer. Changes in Ca2+ signaling caused by altered fluxes through ion channels and transporters (the transportome) are involved in all steps of the metastatic cascade. Cancer cells thereby "re-program" and "misuse" the cellular transportome to regulate proliferation, apoptosis, metabolism, growth factor signaling, migration and invasion. Cancer cells use their transportome to cope with diverse environmental challenges during the metastatic cascade, like hypoxic, acidic and mechanical cues...
May 17, 2018: Pharmaceuticals
https://www.readbyqxmd.com/read/29772236/identification-and-characterization-of-circular-rnas-in-rapid-atrial-pacing-dog-atrial-tissue
#11
Wenfeng Shangguan, Xue Liang, Wen Shi, Tong Liu, Manman Wang, Guangping Li
Circular RNAs (circRNAs) have emerged as novel molecules of interest in gene regulation as other noncoding RNAs, and participating in the process of many diseases. However, the expression and functions of circRNAs in Rapid atrial pacing (RAP) dog atrial tissue still unknown. 12 canines were randomly assigned to control and pacing group. RAP at 500 beats per minute was maintained 14 days in the pacing group. The expression characterization of circRNAs were revealed by high-throughput sequencing. We totally predicted 15,990 circRNAs in dog atrial tissues...
May 14, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29771936/assigning-crystallographic-electron-densities-with-free-energy-calculations-the-case-of-the-fluoride-channel-fluc
#12
Igor Ariz-Extreme, Jochen S Hub
Approximately 90% of the structures in the Protein Data Bank (PDB) were obtained by X-ray crystallography or electron microscopy. Whereas the overall quality of structure is considered high, thanks to a wide range of tools for structure validation, uncertainties may arise from density maps of small molecules, such as organic ligands, ions or water, which are non-covalently bound to the biomolecules. Even with some experience and chemical intuition, the assignment of such disconnected electron densities is often far from obvious...
2018: PloS One
https://www.readbyqxmd.com/read/29771311/pathobiology-of-cardiac-dyssynchrony-and-resynchronization-therapy
#13
Uyên Châu Nguyên, Nienke J Verzaal, Frans A van Nieuwenhoven, Kevin Vernooy, Frits W Prinzen
Synchronous ventricular electrical activation is a prerequisite for adequate left ventricular (LV) systolic function. Conduction abnormalities such as left bundle branch block, and ventricular pacing lead to a dyssynchronous electrical activation sequence, which may have deleterious consequences. The present review attempts to connect the various processes involved in the development of 'dyssynchronopathy', and its correction by cardiac resynchronization therapy (CRT). Abnormal electrical impulse conduction leads to abnormal contraction, characterized by regional differences in timing as well as shortening patterns and amount of external work performed...
May 15, 2018: Europace: European Pacing, Arrhythmias, and Cardiac Electrophysiology
https://www.readbyqxmd.com/read/29771119/engineering-hollow-carbon-architecture-for-high-performance-k-ion-battery-anode
#14
De-Shan Bin, Xi-Jie Lin, Yong-Gang Sun, Yan-Song Xu, Ke Zhang, An-Min Cao, Lijun Wan
K-ion batteries (KIBs) are now drawing increasing research interest as an inexpensive alternative to Li-ion batteries (LIBs). However, due to the large size of K+, stable electrode materials capable of sustaining the repeated K+ in-tercalation/deintercalation cycles are extremely deficient especially if a satisfactory reversible capacity is expected. Herein, we demonstrated that the structural engineering of carbon into a hollow interconnected architecture, a shape similar to the neuron-cell network, promised high conceptual and technological potential for a high-performance KIBs anode...
May 17, 2018: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/29770866/meucin-49-a-multifunctional-scorpion-venom-peptide-with-bactericidal-synergy-with-neurotoxins
#15
Bin Gao, Julie Dalziel, Simone Tanzi, Shunyi Zhu
Besides key roles in prey capture and predator defense, scorpion venom also functions as internal immune agents protecting the venom gland from infection and external immune agents cleaning saprophytic microbes from their own body surfaces. However, antimicrobials (typically antimicrobial peptides, AMPs) in the venom often exist in low abundance that might exclude their immune role alone, leaving an open question with regard to their in vivo biological function. Here, we report the bactericidal activity of seven peptides isolated from the scorpion Mesobuthus eupeus venom, including one classical α-helical AMP and five ion channel-targeted neurotoxins...
May 16, 2018: Amino Acids
https://www.readbyqxmd.com/read/29769723/structure-of-a-volume-regulated-anion-channel-of-the-lrrc8-family
#16
Dawid Deneka, Marta Sawicka, Andy K M Lam, Cristina Paulino, Raimund Dutzler
Volume-regulated anion channels are activated in response to hypotonic stress. These channels are composed of closely related paralogues of the leucine-rich repeat-containing protein 8 (LRRC8) family that co-assemble to form hexameric complexes. Here, using cryo-electron microscopy and X-ray crystallography, we determine the structure of a homomeric channel of the obligatory subunit LRRC8A. This protein conducts ions and has properties in common with endogenous heteromeric channels. Its modular structure consists of a transmembrane pore domain followed by a cytoplasmic leucine-rich repeat domain...
May 16, 2018: Nature
https://www.readbyqxmd.com/read/29768467/alpha-7-nicotinic-receptors-attenuate-neurite-development-through-calcium-activation-of-calpain-at-the-growth-cone
#17
Justin R King, Nadine Kabbani
The α7 nicotinic acetylcholine receptor (nAChR) is a ligand-gated ion channel that plays an important role in cellular calcium signaling contributing to synaptic development and plasticity, and is a key drug target for the treatment of neurodegenerative conditions such as Alzheimer's disease. Here we show that α7 nAChR mediated calcium signals in differentiating PC12 cells activate the proteolytic enzyme calpain leading to spectrin breakdown, microtubule retraction, and attenuation in neurite growth. Imaging in growth cones confirms that α7 activation decreases EB3 comet motility in a calcium dependent manner as demonstrated by the ability of α7 nAChR, ryanodine, or IP3 receptor antagonists to block the effect of α7 nAChR on growth...
2018: PloS One
https://www.readbyqxmd.com/read/29768258/multiple-actions-of-rotenone-an-inhibitor-of-mitochondrial-respiratory-chain-on-ionic-currents-and-miniature-end-plate-potential-in-mouse-hippocampal-mhippoe-14-neurons
#18
Chin-Wei Huang, Kao-Min Lin, Te-Yu Hung, Yao-Chung Chuang, Sheng-Nan Wu
BACKGROUND/AIMS: Rotenone (Rot) is known to suppress the activity of complex I in the mitochondrial chain reaction; however, whether this compound has effects on ion currents in neurons remains largely unexplored. METHODS: With the aid of patch-clamp technology and simulation modeling, the effects of Rot on membrane ion currents present in mHippoE-14 cells were investigated. RESULTS: Addition of Rot produced an inhibitory action on the peak amplitude of INa with an IC50 value of 39...
May 11, 2018: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29768250/metabolic-regulation-of-synaptic-activity
#19
Sergei V Fedorovich, Tatyana V Waseem
Brain tissue is bioenergetically expensive. In humans, it composes approximately 2% of body weight and accounts for approximately 20% of calorie consumption. The brain consumes energy mostly for ion and neurotransmitter transport, a process that occurs primarily in synapses. Therefore, synapses are expensive for any living creature who has brain. In many brain diseases, synapses are damaged earlier than neurons start dying. Synapses may be considered as vulnerable sites on a neuron. Ischemic stroke, an acute disturbance of blood flow in the brain, is an example of a metabolic disease that affects synapses...
May 16, 2018: Reviews in the Neurosciences
https://www.readbyqxmd.com/read/29768036/greater-reductions-in-fat-preferences-in-calhm1-than-cd36-knockout-mice
#20
Anthony Sclafani, Karen Ackroff
Several studies indicate an important role of gustation in intake and preference for dietary fat. The present study compared fat preference deficits produced by deletion of CD36, a putative fatty acid taste receptor, and CALHM1, an ion channel responsible for release of the ATP neurotransmitter used by taste cells. Naïve CD36 knockout (KO) mice displayed reduced preferences for soybean oil emulsions (Intralipid) at low concentrations (0.1-1%) compared to wildtype (WT) mice in 24 h/day two-bottle tests. CALHM1 KO mice displayed even greater Intralipid preference deficits compared to WT and CD36 KO mice...
May 16, 2018: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
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