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https://www.readbyqxmd.com/read/29351458/differences-in-l-type-calcium-channel-activity-partially-underlie-the-regional-dichotomy-in-pumping-behavior-by-murine-peripheral-and-visceral-lymphatic-vessels
#1
Scott D Zawieja, Jorge A Castorena-Gonzalez, Joshua Scallan, Michael J Davis
We identified a regional dichotomy in murine lymphatic contractile function with regard to vessel location within either the periphery or visceral cavity. All vessels isolated from peripheral regions; cervical, popliteal, inguinal, axillary, and inter-nodal inguinal axillary (Ing-Ax) developed robust contractions with maximal ejection fractions (EFs) of 50-80% in our ex vivo isobaric myograph experiments. Conversely, vessels isolated from the visceral cavity (mesenteric, TD, and iliac) demonstrated maximal EFs below 15%...
January 5, 2018: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/29351457/important-role-of-endothelium-dependent-hyperpolarization-in-pulmonary-microcirculation-in-male-mice-implications-for-hypoxia-induced-pulmonary-hypertension
#2
Shuhei Tanaka, Takashi Shiroto, Shigeo Godo, Hiroki Saito, Yosuke Ikumi, Akiyo Ito, Shoko Kajitani, Saori Sato, Hiroaki Shimokawa
Endothelium-dependent hyperpolarization (EDH) plays important roles in systemic circulation, whereas its role in pulmonary circulation remains largely unknown. Furthermore, the underlying mechanisms of pulmonary hypertension (PH) also remain to be elucidated. We thus aimed to elucidate the role of EDH in pulmonary circulation in general and in PH in particular. In isolated perfused lung using male wild-type mice, endothelium-dependent relaxations to bradykinin (BK) were significantly reduced in the presence of Nω-nitro-L-arginine (L-NNA) by ~50% as compared with those in the presence of indomethacin, and the combination of apamin plus charybdotoxin abolished the residual relaxations, showing the comparable contributions of nitric oxide (NO) and EDH in pulmonary microcirculation under physiological conditions...
January 5, 2018: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/29351439/role-of-reactive-oxygen-species-and-sulfide-quinone-oxoreductase-in-hydrogen-sulfide-induced-contraction-of-rat-pulmonary-arteries
#3
Jesus Prieto-Lloret, Vladimir A Snetkov, Yasin Shaifta, Inmaculada Docio, Michelle J Connolly, Charles E Mackay, Greg A Knock, Jeremy Pt Ward, Philip I Aaronson
Application of H2S ('sulfide') elicits a complex contraction in rat pulmonary arteries (PA) comprising a small transient contraction (phase 1; Ph1) followed by relaxation and then a second, larger, and more sustained contraction (phase 2; Ph2). We investigated the mechanisms causing this response using isometric myography in rat second order PA, with Na2S as a sulfide donor. Both phases of contraction to 1000μM Na2S were attenuated by the pan-PKC inhibitor Gö6983 (3μM) and by 50μM ryanodine; the Ca2+ channel blocker nifedipine (1μM) was without effect...
December 28, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/29351282/a-four-component-model-of-the-action-potential-in-mouse-detrusor-smooth-muscle-cell
#4
Mithun Padmakumar, Keith L Brain, John S Young, Rohit Manchanda
BACKGROUND AND HYPOTHESIS: Detrusor smooth muscle cells (DSMCs) of the urinary bladder are electrically connected to one another via gap junctions and form a three dimensional syncytium. DSMCs exhibit spontaneous electrical activity, including passive depolarizations and action potentials. The shapes of spontaneous action potentials (sAPs) observed from a single DSM cell can vary widely. The biophysical origins of this variability, and the precise components which contribute to the complex shapes observed are not known...
2018: PloS One
https://www.readbyqxmd.com/read/29350528/proton-and-carbon-13-dynamic-nuclear-polarization-of-methylated-%C3%AE-cyclodextrins
#5
Filippo Caracciolo, Alessandra Lucini Paioni, Lucio Melone, Marta Filibian, Pietro Carretta
1 H and 13 C dynamic nuclear polarization has been studied in 13 C-enriched β - cyclodextrins doped with TEMPO free radical. 1 H and 13 C polarizations raised above 7.5 % and 7 % , respectively, and for both nuclear species the transfer of polarization from the electron spins appears to be consistent with a thermal mixing scenario for a concentration of 9 13 C nuclei per molecule. When the concentration is increased to 21 13 C nuclei per molecule a decrease in the spin-lattice relaxation and polarization build up rates is observed...
January 19, 2018: Journal of Physical Chemistry. B
https://www.readbyqxmd.com/read/29349559/a-mutant-hcn4-channel-in-a-family-with-bradycardia-left-bundle-branch-block-and-left-ventricular-noncompaction
#6
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/29346329/anti-phytopathogenic-and-cytotoxic-activities-of-crude-extracts-and-secondary-metabolites-of-marine-derived-fungi
#7
Dong-Lin Zhao, Dan Wang, Xue-Ying Tian, Fei Cao, Yi-Qiang Li, Cheng-Sheng Zhang
Thirty-one isolates belonging to eight genera in seven orders were identified from 141 strains that were isolated from several marine plants. Alternaria sp. and Fusarium sp. were found to be the predominant fungi. Evaluation of the anti-phytopathogenic bacterial and fungal activities, as well as the cytotoxicity of these 31 extracts, revealed that most of them displayed different levels of bioactivities. Due to their interesting bioactivities, two fungal strains-Fusarium equiseti (P18) and Alternaria sp. (P8)-were selected for chemical investigation and compounds 1-4 were obtained...
January 18, 2018: Marine Drugs
https://www.readbyqxmd.com/read/29345050/metabolic-alterations-in-a-rat-model-of-hepatic-ischemia-reperfusion-injury-in-vivo-hyperpolarized-13-c-mrs-and-metabolic-imaging
#8
Chung-Man Moon, Sang-Soo Shin, Nam-Yeol Lim, Seul-Kee Kim, Yang-Joon Kang, Hyoung-Ook Kim, Seung-Jin Lee, Byung-Hyun Beak, Gwang-Woo Jeong
BACKGROUND & AIMS: Despite a number of studies addressing the pathophysiology of hepatic IRI, a gold standard test for early diagnosis and evaluation of IRI remains elusive. This study investigated the metabolic alterations in a rat model of hepatic IRI using the in vivo hyperpolarized ¹³C MRS and metabolic imaging. METHODS: Hyperpolarized 13 C MRS with IVIM-DWI were performed on the liver of seven sham-operated control rats, and seven rats before and after hepatic IRI...
January 18, 2018: Liver International: Official Journal of the International Association for the Study of the Liver
https://www.readbyqxmd.com/read/29342276/a-predictive-quantitative-model-of-spiking-activity-and-stimulus-secretion-coupling-in-oxytocin-neurons
#9
Jorge Maícas-Royo, Gareth Leng, Duncan J MacGregor
Oxytocin neurons of the rat hypothalamus project to the posterior pituitary where they secrete their products into the bloodstream. The pattern and quantity of that release depends on the afferent inputs to the neurons, on their intrinsic membrane properties, and on non-linear interactions between spiking activity and exocytosis: a given number of spikes will trigger more secretion when they arrive close together. Here we present a quantitative computational model of oxytocin neurons that can replicate the results of a wide variety of published experiments...
January 12, 2018: Endocrinology
https://www.readbyqxmd.com/read/29339292/selective-hcn1-block-as-a-strategy-to-control-oxaliplatin-induced-neuropathy
#10
F Resta, L Micheli, A Laurino, V Spinelli, T Mello, L Sartiani, L Di Cesare Mannelli, E Cerbai, C Ghelardini, M N Romanelli, G Mannaioni, A Masi
Chemotherapy-Induced Peripheral Neuropathy (CIPN) is the most frequent adverse effect of pharmacological cancer treatments. The occurrence of neuropathy prevents the administration of fully-effective drug regimen, affects negatively the quality of life of patients, and may lead to therapy discontinuation. CIPN is currently treated with anticonvulsants, antidepressants, opioids and non-opioid analgesics, all of which are flawed by insufficient anti-hyperalgesic efficacy or addictive potential. Understandably, developing new drugs targeting CIPN-specific pathogenic mechanisms would dramatically improve efficacy and tolerability of anti-neuropathic therapies...
January 12, 2018: Neuropharmacology
https://www.readbyqxmd.com/read/29339138/hyperglycaemia-disrupts-conducted-vasodilation-in-the-resistance-vasculature-of-db-db-mice
#11
Hamish A L Lemmey, Xi Ye, Hong Ding, Chris R Triggle, Christopher J Garland, Kim A Dora
Vascular dysfunction in small resistance arteries is observed during chronic elevations in blood glucose. Hyperglycaemia-associated effects on endothelium-dependent vasodilation have been well characterized, but effects on conducted vasodilation in the resistance vasculature are not known. Small mesenteric arteries were isolated from healthy and diabetic db/db mice, which were used as a model of chronic hyperglycaemia. Endothelium-dependent vasodilation via the Gq/11-coupled proteinase activated receptor 2 (PAR2) was stimulated with the selective agonist SLIGRL...
January 12, 2018: Vascular Pharmacology
https://www.readbyqxmd.com/read/29336150/chemical-exchange-saturation-transfer-in-chemical-reactions-a-mechanistic-tool-for-nmr-detection-and-characterization-of-transient-intermediates
#12
N Lokesh, Andreas Seegerer, Johnny Hioe, Ruth M Gschwind
The low sensitivity of NMR and transient key intermediates below detection limit are the central problems studying reaction mechanisms by NMR. Sensitivity can be enhanced by hyperpolarization techniques such as dynamic nuclear polarization or the incorporation/interaction of special hyperpolarized molecules. However, all of these techniques require special equipment, are restricted to selective reactions or undesirably influence the reaction pathways. Here, we apply the Chemical Exchange Saturation Transfer (CEST) technique for the first time to NMR detect and characterize previously unobserved transient reaction intermediates in organocatalysis...
January 16, 2018: Journal of the American Chemical Society
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/29331741/extracellular-acidification-induces-ros-and-mptp-mediated-death-in-hek293-cells
#14
José Teixeira, Farhan Basit, Herman G Swarts, Marleen Forkink, Paulo J Oliveira, Peter H G M Willems, Werner J H Koopman
The extracellular pH (pHe) is a key determinant of the cellular (micro)environment and needs to be maintained within strict boundaries to allow normal cell function. Here we used HEK293 cells to study the effects of pHe acidification (24h), induced by mitochondrial inhibitors (rotenone, antimycin A) and/or extracellular HCl addition. Lowering pHe from 7.2 to 5.8 reduced cell viability by 70% and was paralleled by a decrease in cytosolic pH (pHc), hyperpolarization of the mitochondrial membrane potential (Δψ), increased levels of hydroethidine-oxidizing ROS and stimulation of protein carbonylation...
December 30, 2017: Redox Biology
https://www.readbyqxmd.com/read/29330867/preferential-cholinergic-excitation-of-corticopontine-neurons
#15
Arielle L Baker, Ryan J O'Toole, Allan T Gulledge
Pyramidal neurons in layer 5 of the neocortex comprise two broad classes of projection neurons: corticofugal neurons, including corticopontine (CPn) neurons, and intratelencephalic neurons, including commissural/callosal (COM) neurons. These non-overlapping neuron subpopulations represent discrete cortical output channels contributing to perception, decision making, and behaviour. CPn and COM neurons have distinct morphological and physiological characteristics, and divergent responses to modulatory transmitters such as serotonin and acetylcholine (ACh)...
January 12, 2018: Journal of Physiology
https://www.readbyqxmd.com/read/29330287/targeted-akt-inhibition-in-prostate-cancer-cells-and-spheroids-reduces-aerobic-glycolysis-and-generation-of-hyperpolarized-1-13c-lactate
#16
Sui Seng Tee, Izabela Suster, Steven Truong, Sangmoo Jeong, Roozbeh Eskandari, Valentina Di Gialleonardo, Julio A Alvarez, Hannah N Aldeborgh, Kayvan Keshari
The PI3K/AKT/mTOR (PAM) signaling pathway is frequently mutated in prostate cancer. Specific AKT inhibitors are now in advanced clinical trials and this study investigates the effect of MK2206, a non-ATP competitive inhibitor, on the cellular metabolism in the context of prostate cancer. A significant reduction in cell motility and aerobic glycolysis was observed in prostate cancer cells with treatment. These changes were not accompanied by a reduction in the ratio of high-energy phosphates or a change in total protein levels of enzymes (e...
January 12, 2018: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/29327374/dynamic-coronary-mr-angiography-in-a-pig-model-with-hyperpolarized-water
#17
Kasper Wigh Lipsø, Esben Søvsø Szocska Hansen, Rasmus Stilling Tougaard, Christoffer Laustsen, Jan Henrik Ardenkjaer-Larsen
PURPOSE: To investigate dynamic coronary MR angiography using hyperpolarized water as a positive contrast agent. Hyperpolarization can increase the signal by several orders of magnitude, and has recently been translated to human cardiac application. The aim was to achieve large 1 H signal enhancement to allow high-resolution imaging of the coronary arteries. METHODS: Protons in D2 O were hyperpolarized by dissolution dynamic nuclear polarization. A total of 18 mL of hyperpolarized water was injected into the coronary arteries of healthy pigs (N = 9; 3 injections in 3 animals)...
January 12, 2018: Magnetic Resonance in Medicine: Official Journal of the Society of Magnetic Resonance in Medicine
https://www.readbyqxmd.com/read/29327340/shank3-deficient-thalamocortical-neurons-show-hcn-channelopathy-and-alterations-in-intrinsic-electrical-properties
#18
Mengye Zhu, VinayKumar Idikuda, Jianbing Wang, Fusheng Wei, Virang Kumar, Nikhil Shah, Christopher B Waite, Qinglian Liu, Lei Zhou
Shank3 is a scaffolding protein that is highly enriched in excitatory synapses. Mutations in Shank3 gene have been linked to neuropsychiatric disorders especially the Autism Spectrum Disorders (ASD). Shank3 deficiency is known to cause impairments in synaptic transmission, but its effects on basic neuronal electrical properties that are more localized to the soma and proximal dendrites remain unclear. Here we confirmed that in heterologous expression systems two different Shank3 isoforms, Shank3A and Shank3C, significant increase the surface expression of the hyperpolarization-activated, cyclic-nucleotide-gated (HCN) channel...
January 12, 2018: Journal of Physiology
https://www.readbyqxmd.com/read/29326984/using-parahydrogen-to-hyperpolarize-amines-amides-carboxylic-acids-alcohols-phosphates-and-carbonates
#19
Wissam Iali, Peter J Rayner, Simon B Duckett
Hyperpolarization turns weak nuclear magnetic resonance (NMR) and magnetic resonance imaging (MRI) responses into strong signals, so normally impractical measurements are possible. We use parahydrogen to rapidly hyperpolarize appropriate 1H, 13C, 15N, and 31P responses of analytes (such as NH3) and important amines (such as phenylethylamine), amides (such as acetamide, urea, and methacrylamide), alcohols spanning methanol through octanol and glucose, the sodium salts of carboxylic acids (such as acetic acid and pyruvic acid), sodium phosphate, disodium adenosine 5'-triphosphate, and sodium hydrogen carbonate...
January 2018: Science Advances
https://www.readbyqxmd.com/read/29326302/role-of-clc-k-and-barttin-in-low-potassium-induced-sodium-chloride-cotransporter-activation-and-hypertension-in-mouse-kidney
#20
Naohiro Nomura, Wakana Shoda, Yuanlong Wang, Shintaro Mandai, Taisuke Furusho, Daiei Takahashi, Moko Zeniya, Eisei Sohara, Tatemitsu Rai, Shinichi Uchida
The sodium-chloride cotransporter (NCC) has been identified as a key molecule regulating potassium balance. The mechanisms of NCC regulation during low extracellular potassium concentrations have been studied in vitro. These studies have shown that hyperpolarization increased chloride efflux, leading to the activation of chloride-sensitive WNK kinases and their downstream molecules, including STE20/SPS1-related proline/alanine-rich kinase (SPAK) and NCC. However, this mechanism was not studied in vivo Previously, we developed the barttin hypomorphic mouse ( Bsndneo/neo mice), expressing very low levels of barttin and ClC-K channels, because barttin is an essential ß-subunit of ClC-K...
January 11, 2018: Bioscience Reports
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