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https://www.readbyqxmd.com/read/29349559/a-mutant-hcn4-channel-in-a-family-with-bradycardia-left-bundle-branch-block-and-left-ventricular-noncompaction
#1
Ryosuke Yokoyama, Koshi Kinoshita, Yukiko Hata, Masayoshi Abe, Kenta Matsuoka, Keiichi Hirono, Masanobu Kano, Makoto Nakazawa, Fukiko Ichida, Naoki Nishida, Toshihide Tabata
We found that a female infant presenting with left bundle branch block and left ventricular noncompaction carries uninvestigated gene mutations HCN4(G811E), SCN5A(L1988R), DMD(S2384Y), and EMD(R203H). Here, we explored the possible pathogenicity of HCN4(G811E), which results in a G811E substitution in hyperpolarization-activated cyclic nucleotide-gated channel 4, the main subunit of the cardiac pacemaker channel. Voltage-clamp measurements in a heterologous expression system of HEK293T cells showed that HCN4(G811E) slightly reduced whole-cell HCN4 channel conductance, whereas it did not affect the gating kinetics, unitary conductance, or cAMP-dependent modulation of voltage-dependence...
January 18, 2018: Heart and Vessels
https://www.readbyqxmd.com/read/29347715/cusps-enable-line-attractors-for-neural-computation
#2
Zhuocheng Xiao, Jiwei Zhang, Andrew T Sornborger, Louis Tao
Line attractors in neuronal networks have been suggested to be the basis of many brain functions, such as working memory, oculomotor control, head movement, locomotion, and sensory processing. In this paper, we make the connection between line attractors and pulse gating in feed-forward neuronal networks. In this context, because of their neutral stability along a one-dimensional manifold, line attractors are associated with a time-translational invariance that allows graded information to be propagated from one neuronal population to the next...
November 2017: Physical Review. E
https://www.readbyqxmd.com/read/29345931/umbrella-sampling-and-x-ray-crystallographic-analysis-unveil-an-arg-asp-gate-facilitating-inhibitor-binding-inside-phosphopantetheine-adenylyltransferase-allosteric-cleft
#3
Abhisek Mondal, Rakesh Chatterjee, Saumen Datta
Phosphopantetheine adenylyltransferase (PPAT) is a rate limiting enzyme essential for biosynthesis of coenzyme A (CoA) which in turn is responsible to regulate the secretion of exotoxins via type III secretion system in Pseudomonas aeruginosa, causing severe health concerns ranging from nosocomial infections to respiratory failure. Acetyl Coenzyme A (AcCoA) is a newly reported inhibitor of PPAT, believed to regulate the cellular levels of CoA and thereby the pathogenesis. Very little is known so far regarding the mechanistic details of AcCoA binding inside PPAT binding cleft...
January 18, 2018: Journal of Physical Chemistry. B
https://www.readbyqxmd.com/read/29344776/dawning-of-a-new-era-in-trp-channel-structural-biology-by-cryo-electron-microscopy
#4
REVIEW
M Gregor Madej, Christine M Ziegler
Cryo-electron microscopy (cryo-EM) permits the determination of atomic protein structures by averaging large numbers of individual projection images recorded at cryogenic temperatures-a method termed single-particle analysis. The cryo-preservation traps proteins within a thin glass-like ice layer, making literally a freeze image of proteins in solution. Projections of randomly adopted orientations are merged to reconstruct a 3D density map. While atomic resolution for highly symmetric viruses was achieved already in 2009, the development of new sensitive and fast electron detectors has enabled cryo-EM for smaller and asymmetrical proteins including fragile membrane proteins...
January 17, 2018: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/29344669/clc-2-is-a-positive-modulator-of-oligodendrocyte-precursor-cell-differentiation-and-myelination
#5
Xiaolin Hou, Rui Zhang, Junyan Wang, Yunhong Li, Fan Li, Yan Zhang, Xiaomin Zheng, Ying Shen, Yin Wang, Liang Zhou
Oligodendrocytes (OLs) are myelin-forming cells that are present within the central nervous system. Impaired oligodendrocyte precursor cell (OPC) differentiation into mature OLs is a major cause of demyelination diseases. Therefore, identifying the underlying molecular mechanisms of OPC differentiation is crucial to understand the processes of myelination and demyelination. It has been acknowledged that various extrinsic and intrinsic factors are involved in the control of OPC differentiation; however, the function of ion channels, particularly the voltage‑gated chloride channel (CLC), in OPC differentiation and myelination are not fully understood...
January 17, 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29344121/a-five-gene-based-risk-score-with-high-prognostic-value-in-colorectal-cancer
#6
Yida Pan, Hongyang Zhang, Mingming Zhang, Jie Zhu, Jianghong Yu, Bangting Wang, Jigang Qiu, Jun Zhang
Colorectal cancer (CRC) is one of the most frequently occurring malignancies worldwide. The outcomes of patients with similar clinical symptoms or at similar pathological stages remain unpredictable. This inherent clinical diversity is most likely due to the genetic heterogeneity. The present study aimed to create a predicting tool to evaluate patient survival based on genetic profile. Firstly, three Gene Expression Omnibus (GEO) datasets (GSE9348, GSE44076 and GSE44861) were utilized to identify and validate differentially expressed genes (DEGs) in CRC...
December 2017: Oncology Letters
https://www.readbyqxmd.com/read/29343744/improved-linearity-with-polarization-coulomb-field-scattering-in-algan-gan-heterostructure-field-effect-transistors
#7
Peng Cui, Yuanjie Lv, Huan Liu, Aijie Cheng, Chen Fu, Zhaojun Lin
The single-tone power of the AlGaN/GaN heterostructure field-effect transistors (HFETs) with different gate widths was measured. A distinct improvement in device linearity was observed in the sample with a larger gate width. The analysis of the variation of the parasitic source access resistance showed that, as the gate bias is increased, the polarization Coulomb field scattering can offset the increased polar optical phonon scattering and improve the device linearity. This approach is shown to be effective in improving the device linearity of AlGaN/GaN HFETs...
January 17, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29342238/rhythmic-spontaneous-activity-mediates-the-age-related-decline-in-somatosensory-function
#8
Rachel K Spooner, Alex I Wiesman, Amy L Proskovec, Elizabeth Heinrichs-Graham, Tony W Wilson
Sensory gating is a neurophysiological process whereby the response to a second stimulus in a pair of identical stimuli is attenuated, and it is thought to reflect the capacity of the CNS to preserve neural resources for behaviorally relevant stimuli. Such gating is observed across multiple sensory modalities and is modulated by age, but the mechanisms involved are not understood. In this study, we examined somatosensory gating in 68 healthy adults using magnetoencephalography (MEG) and advanced oscillatory and time-domain analysis methods...
January 12, 2018: Cerebral Cortex
https://www.readbyqxmd.com/read/29338621/assessing-the-acute-effects-of-cdp-choline-on-sensory-gating-in-schizophrenia-a-pilot-study
#9
Robert Aidelbaum, Alain Labelle, Ashley Baddeley, Verner Knott
Deficient sensory gating (SG) in schizophrenia is associated with functional outcome and offers a therapeutic target as it is linked to the altered function/expression of the α7 nicotinic acetylcholine receptors (nAChRs). This study analyzed the effects of citicoline (CDP-choline), a supplement with α7 nAChRs agonist properties, on SG in a sample of schizophrenia (SZ) patients. Using a randomized, placebo-controlled, double-blind design the dose-dependent (500 mg, 1000 mg, 2000 mg) and baseline-dependent (deficient versus normal suppressors) effects of CDP-choline on SG were examined using the P50 event-related potential (ERP) index of SG...
January 1, 2018: Journal of Psychopharmacology
https://www.readbyqxmd.com/read/29338006/a-model-for-cooperative-gating-of-l-type-ca2-channels-and-its-effects-on-cardiac-alternans-dynamics
#10
Daisuke Sato, Rose E Dixon, Luis F Santana, Manuel F Navedo
In ventricular myocytes, membrane depolarization during the action potential (AP) causes synchronous activation of multiple L-type CaV1.2 channels (LTCCs), which trigger the release of calcium (Ca2+) from the sarcoplasmic reticulum (SR). This results in an increase in intracellular Ca2+ (Cai) that initiates contraction. During pulsus alternans, cardiac contraction is unstable, going from weak to strong in successive beats despite a constant heart rate. These cardiac alternans can be caused by the instability of membrane potential (Vm) due to steep AP duration (APD) restitution (Vm-driven alternans), instability of Cai cycling (Ca2+-driven alternans), or both, and may be modulated by functional coupling between clustered CaV1...
January 16, 2018: PLoS Computational Biology
https://www.readbyqxmd.com/read/29337221/venom-characterization-of-the-amazonian-scorpion-tityus-metuendus
#11
C V F Batista, J G Martins, R Restano-Cassulini, F I V Coronas, F Z Zamudio, R Procópio, L D Possani
The soluble venom from the scorpion Tityus metuendus was characterized by various methods. In vivo experiments with mice showed that it is lethal. Extended electrophysiological recordings using seven sub-types of human voltage gated sodium channels (hNav1.1 to 1.7) showed that it contains both α- and β-scorpion toxin types. Fingerprint analysis by mass spectrometry identified over 200 distinct molecular mass components. At least 60 sub-fractions were recovered from HPLC separation. Five purified peptides were sequenced by Edman degradation, and their complete primary structures were determined...
January 11, 2018: Toxicon: Official Journal of the International Society on Toxinology
https://www.readbyqxmd.com/read/29337047/imaging-flow-cytometry-a-method-for-examining-dynamic-native-foxo1-localization-in-human-lymphocytes
#12
Molly K Hritzo, Jean-Paul Courneya, Amit Golding
While flow cytometry can reliably assess surface and intracellular marker expression within small cell populations, it does not provide any information on protein localization. Several key transcription factors (TF) downstream of lymphocyte surface receptors are regulated by nuclear versus cytoplasmic localization, and one such TF is Forkhead box O1 (FOXO1). FOXO1 integrates antigen-binding, co-receptor activation and metabolic signals in lymphocytes, leading to proliferation and differentiation. Importantly, the nuclear or cytoplasmic localization of FOXO1 is key for gene expression leading to different lymphocyte phenotypes...
January 11, 2018: Journal of Immunological Methods
https://www.readbyqxmd.com/read/29335357/nonlinear-relationship-between-spike-dependent-calcium-influx-and-trpc-channel-activation-enables-robust-persistent-spiking-in-neurons-of-the-anterior-cingulate-cortex
#13
Stéphanie Ratté, Sergei Karnup, Steven A Prescott
Persistent spiking - the continuation of spiking after a stimulus ends - is thought to support working memory. Muscarinic receptor activation enables persistent spiking among synaptically isolated pyramidal neurons in anterior cingulate cortex (ACC) but a detailed characterization of that spiking is lacking and the underlying mechanisms remain unclear. Here we show that the rate of persistent spiking in ACC neurons is insensitive to the intensity and number of triggers but can be modulated by injected current, and that persistent spiking can resume after several seconds of hyperpolarization-imposed quiescence...
January 15, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29335280/mapping-protein-interactions-of-sodium-channel-nav1-7-using-epitope-tagged-gene-targeted-mice
#14
Alexandros H Kanellopoulos, Jennifer Koenig, Honglei Huang, Martina Pyrski, Queensta Millet, Stéphane Lolignier, Toru Morohashi, Samuel J Gossage, Maude Jay, John E Linley, Georgios Baskozos, Benedikt M Kessler, James J Cox, Annette C Dolphin, Frank Zufall, John N Wood, Jing Zhao
The voltage-gated sodium channel NaV1.7 plays a critical role in pain pathways. We generated an epitope-tagged NaV1.7 mouse that showed normal pain behaviours to identify channel-interacting proteins. Analysis of NaV1.7 complexes affinity-purified under native conditions by mass spectrometry revealed 267 proteins associated with Nav1.7 in vivo The sodium channel β3 (Scn3b), rather than the β1 subunit, complexes with Nav1.7, and we demonstrate an interaction between collapsing-response mediator protein (Crmp2) and Nav1...
January 15, 2018: EMBO Journal
https://www.readbyqxmd.com/read/29334982/genome-wide-identification-characterization-and-classification-of-ionotropic-glutamate-receptor-genes-iglurs-in-the-malaria-vector-anopheles-sinensis-diptera-culicidae
#15
Ting-Ting Wang, Feng-Ling Si, Zheng-Bo He, Bin Chen
BACKGROUND: Ionotropic glutamate receptors (iGluRs) are conserved ligand-gated ion channel receptors, and ionotropic receptors (IRs) were revealed as a new family of iGluRs. Their subdivision was unsettled, and their characteristics are little known. Anopheles sinensis is a major malaria vector in eastern Asia, and its genome was recently well sequenced and annotated. METHODS: We identified iGluR genes in the An. sinensis genome, analyzed their characteristics including gene structure, genome distribution, domains and specific sites by bioinformatic methods, and deduced phylogenetic relationships of all iGluRs in An...
January 15, 2018: Parasites & Vectors
https://www.readbyqxmd.com/read/29330604/driving-forces-of-translocation-through-bacterial-translocon-secyeg
#16
Denis G Knyazev, Roland Kuttner, Mirjam Zimmermann, Ekaterina Sobakinskaya, Peter Pohl
This review focusses on the energetics of protein translocation via the Sec translocation machinery. First we complement structural data about SecYEG's conformational rearrangements by insight obtained from functional assays. These include measurements of SecYEG permeability that allow assessment of channel gating by ligand binding and membrane voltage. Second we will discuss the power stroke and Brownian ratcheting models of substrate translocation and the role that the two models assign to the putative driving forces: (i) ATP (SecA) and GTP (ribosome) hydrolysis, (ii) interaction with accessory proteins, (iii) membrane partitioning and folding, (iv) proton motive force (PMF), and (v) entropic contributions...
January 12, 2018: Journal of Membrane Biology
https://www.readbyqxmd.com/read/29329711/colorimetric-logic-gate-for-alkaline-phosphatase-based-on-copper-ii-based-metal-organic-frameworks-with-peroxidase-like-activity
#17
Caihong Wang, Jie Gao, Yili Cao, Hongliang Tan
Nanozymes have been extensively exploited in the construction of colorimetric sensors in the past decade. However, as lack of specific recognition element, these sensors are mostly limited in the detection of hydrogen peroxide and its related agents. In this work, a colorimetric assay for the detection of alkaline phosphatase (ALP) activity was developed by employing copper (II)-based metal-organic frameworks (Cu-MOFs) as peroxidase mimic and pyrophosphate (PPi) as recognition element. Benefiting from its intrinsic porosity, Cu-MOFs built from one-step self-assembly showed a superior catalytic activity over horseradish peroxidase...
April 3, 2018: Analytica Chimica Acta
https://www.readbyqxmd.com/read/29329398/lenup-learning-nucleosome-positioning-from-dna-sequences-with-improved-convolutional-neural-networks
#18
Juhua Zhang, Wenbo Peng, Lei Wang
Motivation: Nucleosome positioning plays significant roles in proper genome packing and its accessibility to execute transcription regulation. Despite a multitude of nucleosome positioning resources available on line including experimental datasets of genome-wide nucleosome occupancy profiles and computational tools to the analysis on these data, the complex language of eukaryotic Nucleosome positioning remains incompletely understood. Results: Here, we address this challenge using an approach based on a state-of-the-art machine learning method...
January 10, 2018: Bioinformatics
https://www.readbyqxmd.com/read/29326172/diversity-and-connectivity-of-layer-5-somatostatin-expressing-interneurons-in-the-mouse-barrel-cortex
#19
Nigro Maximiliano José, Yoshiko Hashikawa, Bernardo Rudy
Inhibitory interneurons represent 10-15% of the neurons in the somatosensory cortex, and their activity powerfully shapes sensory processing. Three major groups of GABAergic interneurons have been defined according to developmental, molecular, morphological, electrophysiological, and synaptic features. Dendritic-targeting somatostatin-expressing interneurons (SST-INs) have been shown to display diverse morphological, electrophysiological and molecular properties and activity patterns in vivo. However, the correlation between these properties and SST-IN subtype is unclear...
January 11, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29324848/platelet-rich-plasma-to-treat-experimentally-induced-skin-wounds-in-animals-a-systematic-review-and-meta-analysis
#20
Adolfo Maria Tambella, Anna Rita Attili, Gilles Dupré, Andrea Cantalamessa, Stefano Martin, Vincenzo Cuteri, Sabrina Marcazzan, Massimo Del Fabbro
The objective of the study was to review current literature to determine whether the topical application of platelet-rich plasma (PRP) promotes healing in experimentally-induced full-thickness skin wounds in animals. The hypothesis was that the adjunct of PRP has a positive effect on wound healing. An electronic search was carried out on the following databases: Web of Science, Cochrane Library, PubMed, Research Gate, Cochrane Wounds Group, Veterinary Information Network. No publication date nor language restrictions were applied...
2018: PloS One
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