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https://www.readbyqxmd.com/read/28087700/two-small-molecules-restore-stability-to-a-sub-population-of-the-cystic-fibrosis-transmembrane-conductance-regulator-with-the-predominant-disease-causing-mutation
#1
Xin Meng, Yiting Wang, Xiaomeng Wang, Joe A Wrennall, Tracy L Rimington, Hongyu Li, Zhiwei Cai, Robert C Ford, David N Sheppard
Cystic fibrosis (CF) is caused by mutations that disrupt the plasma membrane expression, stability, and function of the cystic fibrosis transmembrane conductance regulator (CFTR) Cl- channel. Two small molecules, the CFTR corrector lumacaftor and the potentiator ivacaftor, are now used clinically to treat CF, although some studies suggest that they have counteracting effects on CFTR stability. Here, we investigated the impact of these compounds on the instability of F508del-CFTR, the most common CF mutation...
January 13, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28087430/ryanodine-receptor-1-polymorphism-is-not-associated-with-aneurysmal-subarachnoid-hemorrhage-or-its-clinical-sequelae
#2
Philipp Hendrix, Paul M Foreman, Mark R Harrigan, Winfield S Fisher, Nilesh A Vyas, Robert H Lipsky, Minkuan Lin, Beverly C Walters, R Shane Tubbs, Mohammadali M Shoja, Jean-Francois Pittet, Mali Mathru, Christoph J Griessenauer
OBJECTIVE: The pathophysiological mechanisms underlying cerebral vasospasm following aneurysmal subarachnoid hemorrhage (aSAH) remain poorly understand. Ryanodine receptors (RYR) are intracellular calcium channels involved in the regulation of vascular smooth muscle cells and cerebrovascular tone and diameter. Previous work reported an association between a RYR polymorphism and cerebral vasospasm. Here, we sought to assess the impact of that RYR polymorphism on aSAH and its clinical sequelae...
January 10, 2017: World Neurosurgery
https://www.readbyqxmd.com/read/28087313/an-m2-v27a-channel-blocker-demonstrates-potent-in-vitro-and-in-vivo-antiviral-activities-against-amantadine-sensitive-and-resistant-influenza-a-viruses
#3
Yanmei Hu, Rami Musharrafieh, Chunlong Ma, Jiantao Zhang, Donald F Smee, William F DeGrado, Jun Wang
Adamantanes such as amantadine (1) and rimantadine (2) are FDA-approved anti-influenza drugs that act by inhibiting the wild-type M2 proton channel from influenza A viruses, thereby inhibiting the uncoating of the virus. Although adamantanes have been successfully used for more than four decades, their efficacy was curtailed by emerging drug resistance. Among the limited number of M2 mutants that confer amantadine resistance, the M2-V27A mutant was found to be the predominant mutant under drug selection pressure, thereby representing a high profile antiviral drug target...
January 10, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28087079/the-stim-orai-coupling-interface-and-gating-of-the-orai1-channel
#4
REVIEW
Yandong Zhou, Xiangyu Cai, Robert M Nwokonko, Natalia A Loktionova, Youjun Wang, Donald L Gill
In virtually all cells, store-operated Ca(2+) entry signals are vital in controlling a spectrum of functions. The signals are mediated by STIM proteins in the ER and Orai channels in the PM which undergo a dynamic coupling process within discrete ER-PM junctional regions. This coupling is initiated by depletion of ER stored Ca(2+) triggering STIM proteins to undergo an intricate activation process. Thereafter, STIM proteins become trapped in the ER-PM junctions where they tether and gate PM Orai Ca(2+) channels...
January 8, 2017: Cell Calcium
https://www.readbyqxmd.com/read/28081108/integrated-all-optical-mimo-demultiplexer-for-mode-and-wavelength-division-multiplexed-transmission
#5
Daniele Melati, Andrea Alippi, Andrea Annoni, Nicola Peserico, Andrea Melloni
A photonic integrated circuit performing simultaneous mode and wavelength demultiplexing for few-mode-fiber transmission is demonstrated for the first time. The circuit is realized on an InP-based technological platform; it can handle up to eight mode- and wavelength-division-multiplexed (MDM/WDM) channels and allows all-optical multiple-input-multiple-output processing to unscramble mode mixing generated by fiber propagation. A single arrayed waveguide grating is used to demultiplex the WDM channels carried by all the propagating modes, optimizing circuit complexity, chip area, and operational stability...
January 15, 2017: Optics Letters
https://www.readbyqxmd.com/read/28078716/incorporating-food-web-dynamics-into-ecological-restoration-a-modeling-approach-for-river-ecosystems
#6
J Ryan Bellmore, Joseph R Benjamin, Michael Newsom, Jennifer A Bountry, Daniel Dombroski
Restoration is frequently aimed at the recovery of target species, but also influences the larger food web in which these species participate. Effects of restoration on this broader network of organisms can influence target species both directly and indirectly via changes in energy flow through food webs. To help incorporate these complexities into river restoration planning we constructed a model that links river food web dynamics to in-stream physical habitat and riparian vegetation conditions. We present an application of the model to the Methow River, Washington (USA), a location of on-going restoration aimed at recovering salmon...
January 12, 2017: Ecological Applications: a Publication of the Ecological Society of America
https://www.readbyqxmd.com/read/28077872/structural-basis-for-nutrient-acquisition-by-dominant-members-of-the-human-gut-microbiota
#7
Amy J Glenwright, Karunakar R Pothula, Satya P Bhamidimarri, Dror S Chorev, Arnaud Baslé, Susan J Firbank, Hongjun Zheng, Carol V Robinson, Mathias Winterhalter, Ulrich Kleinekathöfer, David N Bolam, Bert van den Berg
The human large intestine is populated by a high density of microorganisms, collectively termed the colonic microbiota, which has an important role in human health and nutrition. The survival of microbiota members from the dominant Gram-negative phylum Bacteroidetes depends on their ability to degrade dietary glycans that cannot be metabolized by the host. The genes encoding proteins involved in the degradation of specific glycans are organized into co-regulated polysaccharide utilization loci, with the archetypal locus sus (for starch utilisation system) encoding seven proteins, SusA-SusG...
January 11, 2017: Nature
https://www.readbyqxmd.com/read/28077727/asymmetries-of-dark-and-bright-negative-afterimages-are-paralleled-by-subcortical-on-and-off-post-stimulus-responses
#8
Hui Li, Xu Liu, Xiaohong Li, Yiliang Lu, Lothar Spillmann, Ian M Andolina, Wei Wang
: Humans are more sensitive to luminance decrements than increments, as evidenced by lower thresholds and shorter latencies for dark stimuli. This asymmetry is consistent with results of neurophysiological recordings in dorsal lateral-geniculate nucleus (dLGN) and primary visual cortex (V1) of cat and monkey. Specifically, V1 population responses demonstrate that darks elicit higher levels of activation than brights, and the latency of OFF responses in dLGN and V1 is shorter than that of ON responses...
January 11, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28076819/full-spectral-multiplexing-of-bioluminescence-resonance-energy-transfer-in-three-trpv-channels
#9
Hermanus Johannes Ruigrok, Guillaume Shahid, Bertrand Goudeau, Florence Poulletier de Gannes, Emmanuelle Poque-Haro, Annabelle Hurtier, Isabelle Lagroye, Pierre Vacher, Stéphane Arbault, Neso Sojic, Bernard Veyret, Yann Percherancier
Multiplexed bioluminescence resonance energy transfer (BRET) assays were developed to monitor the activation of several functional transient receptor potential (TRP) channels in live cells and in real time. We probed both TRPV1 intramolecular rearrangements and its interaction with Calmodulin (CaM) under activation by chemical agonists and temperature. Our BRET study also confirmed that: (1) capsaicin and heat promoted distinct transitions, independently coupled to channel gating, and that (2) TRPV1 and Ca(2+)-bound CaM but not Ca(2+)-free CaM were preassociated in resting live cells, while capsaicin activation induced both the formation of more TRPV1/CaM complexes and conformational changes...
January 10, 2017: Biophysical Journal
https://www.readbyqxmd.com/read/28076814/gsmtx4-mechanism-of-inhibiting-mechanosensitive-ion-channels
#10
Radhakrishnan Gnanasambandam, Chiranjib Ghatak, Anthony Yasmann, Kazuhisa Nishizawa, Frederick Sachs, Alexey S Ladokhin, Sergei I Sukharev, Thomas M Suchyna
GsMTx4 is a spider venom peptide that inhibits cationic mechanosensitive channels (MSCs). It has six lysine residues that have been proposed to affect membrane binding. We synthesized six analogs with single lysine-to-glutamate substitutions and tested them against Piezo1 channels in outside-out patches and independently measured lipid binding. Four analogs had ∼20% lower efficacy than the wild-type (WT) peptide. The equilibrium constants calculated from the rates of inhibition and washout did not correlate with the changes in inhibition...
January 10, 2017: Biophysical Journal
https://www.readbyqxmd.com/read/28076813/signatures-of-mechanosensitive-gating
#11
REVIEW
Richard G Morris
The question of how mechanically gated membrane channels open and close is notoriously difficult to address, especially if the protein structure is not available. This perspective highlights the relevance of micropipette-aspirated single-particle tracking-used to obtain a channel's diffusion coefficient, D, as a function of applied membrane tension, σ-as an indirect assay for determining functional behavior in mechanosensitive channels. While ensuring that the protein remains integral to the membrane, such methods can be used to identify not only the gating mechanism of a protein, but also associated physical moduli, such as torsional and dilational rigidity, which correspond to the protein's effective shape change...
January 10, 2017: Biophysical Journal
https://www.readbyqxmd.com/read/28076368/functional-laterality-of-task-evoked-activation-in-sensorimotor-cortex-of-preterm-infants-an-optimized-3-t-fmri-study-employing-a-customized-neonatal-head-coil
#12
Lukas Scheef, Jurek A Nordmeyer-Massner, Adam Pr Smith-Collins, Nicole Müller, Gaby Stegmann-Woessner, Jacob Jankowski, Jürgen Gieseke, Mark Born, Hermann Seitz, Peter Bartmann, Hans H Schild, Klaas P Pruessmann, Axel Heep, Henning Boecker
BACKGROUND: Functional magnetic resonance imaging (fMRI) in neonates has been introduced as a non-invasive method for studying sensorimotor processing in the developing brain. However, previous neonatal studies have delivered conflicting results regarding localization, lateralization, and directionality of blood oxygenation level dependent (BOLD) responses in sensorimotor cortex (SMC). Amongst the confounding factors in interpreting neonatal fMRI studies include the use of standard adult MR-coils providing insufficient signal to noise, and liberal statistical thresholds, compromising clinical interpretation at the single subject level...
2017: PloS One
https://www.readbyqxmd.com/read/28075597/a-class-of-electron-transporting-vinylogous-tetrathiafulvalenes-constructed-by-the-dimerization-of-core-expanded-naphthalenediimides
#13
Yunbin Hu, Zhongli Wang, Xu Zhang, Xiaodi Yang, Congwu Ge, Lina Fu, Xike Gao
The combination of the (1,3-dithiol-2-ylidene)malononitrile (DTYM) and/or (1,3-dithiol-2-ylidene)acetonitrile (DTYA) moieties with naphthalenediimide (NDI) core affords two singly linked NDI-based dimers, (DTYM-NDI-DTYA)2 (D1) and (NDI-DTYA)2 (D2), which both contain a dicyano-substituted vinylogous tetrathiafulvalene (TTF) unit. The synthesis, thermal/optical/electrochemical properties of D1 and D2, and their primary applications in n-channel organic thin film transistors are studied. The results demonstrate that these NDI-fused vinylogous TTFs are excellent electron acceptors, and their further applications are promising...
January 11, 2017: Organic Letters
https://www.readbyqxmd.com/read/28075010/stimulatory-actions-of-a-novel-thiourea-derivative-on-large-conductance-calcium-activated-potassium-channels
#14
Sheng-Nan Wu, Jyh-Haur Chern, Santai Shen, Hwei-Hisen Chen, Ying-Ting Hsu, Chih-Chin Lee, Ming-Huan Chan, Ming-Chi Lai, Feng-Shiun Shie
AIM: In this study, we examine whether an anti-inflammatory thiourea derivative, compound #326, actions on ion channels. METHODS: The effects of compound #326 on Ca(2+) -activated K(+) channels were evaluated by patch-clamp recordings obtained in cell-attached, inside-out or whole-cell configuration. RESULTS: In pituitary GH3 cells, compound #326 increased the amplitude of Ca(2+) -activated K(+) currents (IK(Ca) ) with an EC50 value of 11...
January 11, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28072912/temperature-mapping-in-hydrogel-matrices-using-unmodified-digital-camera
#15
Ghinwa H Darwish, Hassan H Fakih, Pierre Karam
We report a simple, generally applicable and noninvasive fluorescent method for mapping thermal fluctuations in hydrogel matrices using an unmodified commercially available digital single-lens reflex camera (DSLR). The nanothermometer is based on the complexation of short conjugated polyelectrolytes, poly-(phenylene ethynylene) carboxylate, with an amphiphilic polymer, polyvinylpyrrolidone, which is in turn trapped within the porous network of a gel matrix. Changes in the temperature lead to a fluorescent ratiometric response with a maximum relative sensitivity of 2...
January 10, 2017: Journal of Physical Chemistry. B
https://www.readbyqxmd.com/read/28072537/a-qm-mm-study-of-substituent-and-solvent-effects-on-the-excited-state-dynamics-of-the-photoactive-yellow-protein-chromophore
#16
Francisco Fernández García-Prieto, Aurora Muñoz-Losa, Ignacio Fdez Galván, M Luz Sánchez, Manuel Ángel Aguilar, M Elena Martín
Substituent and solvent effects on the excited state dynamics of the Photoactive Yellow Protein chromophore are studied using the average solvent electrostatic potential from molecular dynamics (ASEP/MD) method. Four molecular models were considered: the ester and thioester derivatives of the p-coumaric acid anion and their methyla ted derivatives. We found that the solvent produces dramatic modifications on the free energy profile of the S1 state: 1) Two twisted structures that are minima in gas phase could not be located in aqueous solution...
January 10, 2017: Journal of Chemical Theory and Computation
https://www.readbyqxmd.com/read/28072516/cobalt-based-single-ion-magnets-on-an-apatite-lattice-toward-patterned-arrays-for-magnetic-memories
#17
Pavel E Kazin, Mikhail A Zykin, Walter Schnelle, Yan V Zubavichus, Konstantin A Babeshkin, Victor A Tafeenko, Claudia Felser, Martin Jansen
Single-ion magnets (SIMs) that can maintain magnetization direction on an individual transition metal atom represent the smallest atomic-scale units for future magnetic data storage devices and molecular electronics. Here we present a robust extended inorganic solid hosting efficient SIM centers, as an alternative to molecular SIM crystals. We show that unique dioxocobaltate(II) ions, confined in the channels of strontium hydroxyapatite, exhibit classical SIM features with a large energy barrier for magnetization reversal (Ueff) of 51-59 cm(-1)...
January 10, 2017: Inorganic Chemistry
https://www.readbyqxmd.com/read/28070995/haplotype-of-platelet-receptor-p2ry12-gene-is-associated-with-residual-clopidogrel-on-treatment-platelet-reactivity
#18
Xiao-Yan Nie, Jun-Lei Li, Yong Zhang, Yang Xu, Xue-Li Yang, Yu Fu, Guang-Kai Liang, Yun Lu, Jian Liu, Lu-Wen Shi
OBJECTIVE: To investigate a possible association between common variations of the P2RY12 and the residual clopidogrel on-treatment platelet reactivity after adjusting for the influence of CYP2C19 tested by thromboelastography (TEG). METHODS: One hundred and eighty patients with acute coronary syndrome (ACS) treated with clopidogrel and aspirin were included and platelet function was assessed by TEG. Five selected P2RY12 single nucleotide polymorphisms (SNPs; rs6798347, rs6787801, rs6801273, rs6785930, and rs2046934), which cover the common variations in the P2RY12 gene and its regulatory regions, and three CYP2C19 SNPs ((*)2,(*)3,(*)17) were genotyped and possible haplotypes were analyzed...
2017: Journal of Zhejiang University. Science. B
https://www.readbyqxmd.com/read/28069412/influence-of-glutamic-acid-residues-and-ph-on-the-properties-of-transmembrane-helices
#19
Venkatesan Rajagopalan, Denise V Greathouse, Roger E Koeppe
Negatively charged side chains are important for the function of particular ion channels and certain other membrane proteins. To investigate the influence of single glutamic acid side chains on helices that span lipid-bilayer membranes, we have employed GWALP23 (acetyl-GGALW(5)LALALALALALALW(19)LAGA-amide) as a favorable host peptide framework. We substituted individual Leu residues with Glu residues (L12E or L14E or L16E) and incorporated specific (2)H-labeled alanine residues within the core helical region or near the ends of the sequence...
January 6, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28069061/association-between-physical-activity-and-sleep-disordered-breathing-in-male-japanese-workers-a-cross-sectional-study
#20
Hiroaki Itoh, Kazuhito Yokoyama, Takehisa Matsukawa, Fumihiko Kitamura
BACKGROUND: Whether physical activity reduces the risk of sleep-disordered breathing (SDB) for non-obese people remains unclear. The present cross-sectional study examined the association between physical activity and SDB among non-obese male Japanese workers. METHODS: All 200 workers in a company in Tokyo, Japan, who drove a motor vehicle as part of their job, were invited to be screened for SDB to prevent traffic accidents. Of these, 195 agreed to participate in this study...
January 9, 2017: BMC Research Notes
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