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https://www.readbyqxmd.com/read/28646735/hyperpolarized-helium-3-magnetic-resonance-lung-imaging-of-non-sedated-infants-and-young-children-a-proof-of-concept-study
#1
Talissa A Altes, Craig H Meyer, Jaime F Mata, Deborah K Froh, Alix Paget-Brown, W Gerald Teague, Sean B Fain, Eduard E de Lange, Kai Ruppert, Martyn C Botfield, Mac A Johnson, John P Mugler
PURPOSE: To develop and evaluate a protocol for hyperpolarized helium-3 (HHe) ventilation magnetic resonance imaging (MRI) of the lungs of non-sedated infants and children. MATERIALS AND METHODS: HHe ventilation MRI was performed on seven children ≤4years old. Contiguous 2D-spiral helium-3 images were acquired sequentially with a scan time of ≤0.2s/slice. RESULTS: Motion-artifact-free, high signal-to-noise ratio (SNR) images of lung ventilation were obtained...
May 10, 2017: Clinical Imaging
https://www.readbyqxmd.com/read/28645621/two-delta-opioid-receptor-subtypes-are-functional-in-single-ventral-tegmental-area-neurons-and-can-interact-with-the-mu-opioid-receptor
#2
Elyssa B Margolis, Wakako Fujita, Lakshmi A Devi, Howard L Fields
The mu and delta opioid receptors (MOR and DOR) are highly homologous members of the opioid family of GPCRs. There is evidence that MOR and DOR interact, however the extent to which these interactions occur in vivo and affect synaptic function is unknown. There are two stable DOR subtypes: DPDPE sensitive (DOR1) and deltorphin II sensitive (DOR2); both are blocked by DOR selective antagonists. Robust motivational effects are produced by local actions of both MOR and DOR ligands in the ventral tegmental area (VTA)...
June 20, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28645458/pulmonary-3-he-magnetic-resonance-imaging-biomarkers-of-regional-airspace-enlargement-in-alpha-1-antitrypsin-deficiency
#3
Eric Lessard, Heather M Young, Anurag Bhalla, Damien Pike, Khadija Sheikh, David G McCormack, Alexei Ouriadov, Grace Parraga
RATIONALE AND OBJECTIVES: Thoracic x-ray computed tomography (CT) and hyperpolarized (3)He magnetic resonance imaging (MRI) provide quantitative measurements of airspace enlargement in patients with emphysema. For patients with panlobular emphysema due to alpha-1 antitrypsin deficiency (AATD), sensitive biomarkers of disease progression and response to therapy have been difficult to develop and exploit, especially those biomarkers that correlate with outcomes like quality of life. Here, our objective was to generate and compare CT and diffusion-weighted inhaled-gas MRI measurements of emphysema including apparent diffusion coefficient (ADC) and MRI-derived mean linear intercept (Lm) in patients with AATD, chronic obstructive pulmonary disease (COPD) ex-smokers, and elderly never-smokers...
June 20, 2017: Academic Radiology
https://www.readbyqxmd.com/read/28644918/heterogeneous-microtesla-sabre-enhancement-of-15n-nmr-signals
#4
Kirill V Kovtunov, Larisa M Kovtunova, Max E Gemeinhardt, Andrey V Bukhtiyarov, Jonathan Gesiorski, Valerii I Bukhtiyarov, Eduard Y Chekmenev, Igor V Koptyug, Boyd Goodson
The hyperpolarization of heteronuclei via Signal Amplification by Reversible Exchange (SABRE) was investigated under conditions of heterogeneous catalysis and microtesla magnetic fields. Immobilization of [IrCl(COD)(IMes)], [IMes = 1,3-bis(2,4,6-trimethylphenyl), imidazole-2-ylidene; COD = cyclooctadiene] catalyst onto silica particles modified with NH2(CH2)3- linkers engenders an effective heterogeneous SABRE (HET-SABRE) catalyst that was used to demonstrate ~102-fold enhancement of 15N NMR signals in pyridine at 9...
June 23, 2017: Angewandte Chemie
https://www.readbyqxmd.com/read/28644868/electrophysiological-alterations-in-a-murine-model-of-chronic-coxsackievirus-b3-myocarditis
#5
Sven Kaese, Robert Larbig, Matthias Rohrbeck, Gerrit Frommeyer, Dirk Dechering, Jan Olligs, Sabine Schönhofer-Merl, Rainer Wessely, Karin Klingel, Guiscard Seebohm, Lars Eckardt
INTRODUCTION: Coxsackievirus B3 (CVB3) is known to induce acute and chronic myocarditis. Most infections are clinically unapparent but some patients suffer from ventricular arrhythmias (VA) and sudden cardiac death (SCD). Studies showed that acute CVB3 infection may cause impaired function of cardiac ion channels, creating a proarrhythmic substrate. However, it is unknown whether low level CVB3+ expression in myocytes may cause altered cardiac electrophysiology leading to VA. METHODS: Cellular electrophysiology was used to analyze cellular action potentials (APs) and occurrence of afterdepolarizations from isolated cardiomyocytes of wildtype (WT) and transgenic CVB3ΔVP0 (CVB3+) mice...
2017: PloS One
https://www.readbyqxmd.com/read/28643773/a-cdc42-rhoa-regulatory-circuit-downstream-of-glycoprotein-ib-guides-transendothelial-platelet-biogenesis
#6
Sebastian Dütting, Frederique Gaits-Iacovoni, David Stegner, Michael Popp, Adrien Antkowiak, Judith M M van Eeuwijk, Paquita Nurden, Simon Stritt, Tobias Heib, Katja Aurbach, Oguzhan Angay, Deya Cherpokova, Niels Heinz, Ayesha A Baig, Maximilian G Gorelashvili, Frank Gerner, Katrin G Heinze, Jerry Ware, Georg Krohne, Zaverio M Ruggeri, Alan T Nurden, Harald Schulze, Ute Modlich, Irina Pleines, Cord Brakebusch, Bernhard Nieswandt
Blood platelets are produced by large bone marrow (BM) precursor cells, megakaryocytes (MKs), which extend cytoplasmic protrusions (proplatelets) into BM sinusoids. The molecular cues that control MK polarization towards sinusoids and limit transendothelial crossing to proplatelets remain unknown. Here, we show that the small GTPases Cdc42 and RhoA act as a regulatory circuit downstream of the MK-specific mechanoreceptor GPIb to coordinate polarized transendothelial platelet biogenesis. Functional deficiency of either GPIb or Cdc42 impairs transendothelial proplatelet formation...
June 15, 2017: Nature Communications
https://www.readbyqxmd.com/read/28638923/-reconstitution-of-large-conductance-calcium-activated-potassium-channels-into-artificial-planar-lipid-bilayers
#7
Jun Cheng, Xiao-Rong Zeng, Xiao-Qiu Tan, Peng-Yun Li, Jing Wen, Liang Mao, Yan Yang
This study was aimed to establish a method to create a stable planar lipid bilayer membranes (PLBMs), in which large conductance calcium-activated potassium channels (BKCa) were reconstituted. Using spreading method, PLBMs were prepared by decane lipid fluid consisting of N2-weathered mixture of phosphatidylcholine and cholesterol at 3:1 ratio. After successful incorporation of BKCa channel into PLBMs, single channel characteristics of BKCa were studied by patch clamp method. The results showed that i) the single channel conductance of BKCa was (206...
June 25, 2017: Sheng Li Xue Bao: [Acta Physiologica Sinica]
https://www.readbyqxmd.com/read/28637508/hyperpolarized-13-c-urea-myocardial-first-pass-perfusion-imaging-using-velocity-selective-excitation
#8
Maximilian Fuetterer, Julia Busch, Sophie M Peereboom, Constantin von Deuster, Lukas Wissmann, Miriam Lipiski, Thea Fleischmann, Nikola Cesarovic, Christian T Stoeck, Sebastian Kozerke
BACKGROUND: A velocity-selective binomial excitation scheme for myocardial first-pass perfusion measurements with hyperpolarized (13)C substrates, which preserves bolus magnetization inside the blood pool, is presented. The proposed method is evaluated against gadolinium-enhanced (1)H measurements in-vivo. METHODS: The proposed excitation with an echo-planar imaging readout was implemented on a clinical CMR system. Dynamic myocardial stress perfusion images were acquired in six healthy pigs after bolus injection of hyperpolarized (13)C urea with the velocity-selective vs...
June 21, 2017: Journal of Cardiovascular Magnetic Resonance
https://www.readbyqxmd.com/read/28630930/real-time-quantitative-analysis-of-metabolic-flux-in-live-cells-using-a-hyperpolarized-micromagnetic-resonance-spectrometer
#9
Sangmoo Jeong, Roozbeh Eskandari, Sun Mi Park, Julio Alvarez, Sui Seng Tee, Ralph Weissleder, Michael G Kharas, Hakho Lee, Kayvan R Keshari
Metabolic reprogramming is widely considered a hallmark of cancer, and understanding metabolic dynamics described by the conversion rates or "fluxes" of metabolites can shed light onto biological processes of tumorigenesis and response to therapy. For real-time analysis of metabolic flux in intact cells or organisms, magnetic resonance (MR) spectroscopy and imaging methods have been developed in conjunction with hyperpolarization of nuclear spins. These approaches enable noninvasive monitoring of tumor progression and treatment efficacy and are being tested in multiple clinical trials...
June 2017: Science Advances
https://www.readbyqxmd.com/read/28627764/illustration-of-a-simple-route-to-generate-strong-carbon-13-nmr-signals-that-are-detectable-for-several-minutes
#10
Simon Duckett, Soumya Roy, Philip Norcott, Peter J Rayner, Gary Gr Green
Nuclear Magnetic Resonance (NMR) and Magnetic Resonance Imaging (MRI) suffer from low sensitivity and limited nuclear spin memory lifetimes. While hyperpolarization techniques increase sensitivity there is also a desire to increase relaxation times to expand the range of applications addressable by these methods. Here we demonstrate a route to create hyperpolarized magnetization in ¹³C nuclear spin pairs that last much longer than normal lifetimes by storage in a singlet state. By combining molecular design and low-field storage with para-hydrogen derived hyperpolarization we achieve more than three-orders of signal amplification relative to equilibrium Zeeman polarization and an order of magnitude extension in state lifetime...
June 19, 2017: Chemistry: a European Journal
https://www.readbyqxmd.com/read/28626074/a-type-potassium-channels-contribute-to-prorenin-increase-of-firing-activity-in-hypothalamic-vasopressin-neurosecretory-neurons
#11
Soledad Pitra, Javier E Stern
Recent studies support an important contribution of prorenin (PR) and its receptor (PRR) to the regulation of hypothalamic sympathetic and neurosecretory outflows to the cardiovascular system, including systemic release of vasopressin (VP), both under physiological and cardiovascular disease conditions. Still, the identification of precise cellular mechanisms and neuronal/molecular targets remain unknown. We recently showed that PRR is expressed in VP neurons, and that their activation increases neuronal activity...
June 16, 2017: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/28624646/instantaneous-voltage-as-an-alternative-to-power-and-phase-based-interpretation-of-oscillatory-brain-activity
#12
Gerwin Schalk, Joshua Marple, Robert T Knight, William G Coon
For decades, oscillatory brain activity has been characterized primarily by measurements of power and phase. While many studies have linked those measurements to cortical excitability, their relationship to each other and to the physiological underpinnings of excitability is unclear. The recently proposed Function-through-Biased-Oscillations (FBO) hypothesis Schalk, addressed these issues by suggesting that the voltage potential at the cortical surface directly reflects the excitability of cortical populations, that this voltage is rhythmically driven away from a low resting potential (associated with depolarized cortical populations) towards positivity (associated with hyperpolarized cortical populations)...
June 14, 2017: NeuroImage
https://www.readbyqxmd.com/read/28623618/endothelin-1-decreases-excitability-of-the-dorsal-root-ganglion-neurons-via-etb-receptor
#13
Nandkishor K Mule, Jitendra N Singh, Kunal U Shah, Anil Gulati, Shyam S Sharma
Endothelin-1 (ET-1) has been demonstrated to be a pro-nociceptive as well as an anti-nociceptive agent. However, underlying molecular mechanisms for these pain modulatory actions remain unclear. In the present study, we evaluated the ability of ET-1 to alter the nociceptor excitability using a patch clamp technique in acutely dissociated rat dorsal root ganglion (DRG) neurons. ET-1 produced an increase in threshold current to evoke an action potential (I threshold) and hyperpolarization of resting membrane potential (RMP) indicating decreased excitability of DRG neurons...
June 16, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28623610/a-singular-role-of-ik1-promoting-the-development-of-cardiac-automaticity-during-cardiomyocyte-differentiation-by-ik1-induced-activation-of-pacemaker-current
#14
Yu Sun, Valeriy Timofeyev, Adrienne Dennis, Emre Bektik, Xiaoping Wan, Kenneth R Laurita, Isabelle Deschênes, Ronald A Li, Ji-Dong Fu
The inward rectifier potassium current (IK1) is generally thought to suppress cardiac automaticity by hyperpolarizing membrane potential (MP). We recently observed that IK1 could promote the spontaneously-firing automaticity induced by upregulation of pacemaker funny current (If) in adult ventricular cardiomyocytes (CMs). However, the intriguing ability of IK1 to activate If and thereby promote automaticity has not been explored. In this study, we combined mathematical and experimental assays and found that only IK1 and If, at a proper-ratio of densities, were sufficient to generate rhythmic MP-oscillations even in unexcitable cells (i...
June 16, 2017: Stem Cell Reviews
https://www.readbyqxmd.com/read/28621464/differences-in-excitability-properties-between-mg-ta-and-apb-motor-axons
#15
Cliff S Klein, Chen Ning Zhao, Hui Liu, Ping Zhou
INTRODUCTION: Excitability properties of motor nerves to different muscles are different, but the explanation is uncertain. We characterized motor axon excitability properties to the medial gastrocnemius (MG) in 27 adults, and made comparisons with the peroneal nerve to the tibialis anterior (TA) and median nerve to the abductor pollicis brevis (APB) in 10 subjects. METHODS: Recordings of multiple excitability properties were made using threshold tracking, stimulating the nerves at the wrist or knee...
June 16, 2017: Muscle & Nerve
https://www.readbyqxmd.com/read/28620066/mitochondrial-complex-iv-subunit-4-isoform-2-is-essential-for-acute-pulmonary-oxygen-sensing
#16
Natascha Sommer, Maik Huttemann, Oleg Pak, Susan Scheibe, Fenja Knöpp, Christopher Sinkler, Monika Malczyk, Mareike Gierhardt, Azadeh Esfandiary, Simone Kraut, Felix T Jonas, Christine Veith, Siddhesh Aras, Akylbek Sydykov, Nasim Alebrahimdehkordi, Klaudia Giehl, Matthias Hecker, Ralf P Brandes, Werner Seeger, Friedrich Grimminger, Hossein A Ghofrani, Ralph T Schermuly, Lawrence I Grossman, Norbert Weissmann
Rationale: Acute pulmonary oxygen sensing is essential to avoid life-threatening hypoxemia via hypoxic pulmonary vasoconstriction (HPV) which matches perfusion to ventilation. Hypoxia-induced mitochondrial superoxide release has been suggested as critical step in the signaling pathway underlying HPV. However, the identity of the primary oxygen sensor and mechanism of superoxide release in acute hypoxia, as well as its relevance for chronic pulmonary oxygen sensing remains unresolved. Objective: To investigate the role of the pulmonary specific isoform 2 of subunit 4 of mitochondrial complex IV (Cox4i2) and the subsequent mediators superoxide and hydrogen peroxide for pulmonary oxygen sensing and signaling...
June 15, 2017: Circulation Research
https://www.readbyqxmd.com/read/28614802/mitochondrial-dysregulation-and-glycolytic-insufficiency-functionally-impair-cd8-t-cells-infiltrating-human-renal-cell-carcinoma
#17
Peter J Siska, Kathryn E Beckermann, Frank M Mason, Gabriela Andrejeva, Allison R Greenplate, Adam B Sendor, Yun-Chen J Chiang, Armando L Corona, Lelisa F Gemta, Benjamin G Vincent, Richard C Wang, Bumki Kim, Jiyong Hong, Chiu-Lan Chen, Timothy N Bullock, Jonathan M Irish, W Kimryn Rathmell, Jeffrey C Rathmell
Cancer cells can inhibit effector T cells (Teff) through both immunomodulatory receptors and the impact of cancer metabolism on the tumor microenvironment. Indeed, Teff require high rates of glucose metabolism, and consumption of essential nutrients or generation of waste products by tumor cells may impede essential T cell metabolic pathways. Clear cell renal cell carcinoma (ccRCC) is characterized by loss of the tumor suppressor von Hippel-Lindau (VHL) and altered cancer cell metabolism. Here, we assessed how ccRCC influences the metabolism and activation of primary patient ccRCC tumor infiltrating lymphocytes (TIL)...
June 15, 2017: JCI Insight
https://www.readbyqxmd.com/read/28613875/modeling-of-polarization-transfer-kinetics-in-protein-hydration-using-hyperpolarized-water
#18
Jihyun Kim, Mengxiao Liu, Christian Hilty
Water-protein interactions play a central role in protein structure, dynamics, and function. These interactions, traditionally, have been studied using nuclear magnetic resonance (NMR) by measuring chemical exchange and nuclear Overhauser effect (NOE). Polarization transferred from hyperpolarized water can result in substantial transient signal enhancements of protein resonances due to these processes. Here, we use dissolution dynamic nuclear polarization and flow-NMR for measuring the pH dependence of transferred signals to the protein trypsin...
June 14, 2017: Journal of Physical Chemistry. B
https://www.readbyqxmd.com/read/28613412/myoendothelial-coupling-through-cx40-contributes-to-edh-induced-vasodilation-in-murine-renal-arteries-evidence-from-experiments-and-modelling
#19
Jens Christian Brasen, Cor de Wit, Charlotte Mehlin Sorensen
Regulation of renal vascular resistance plays a major role in controlling arterial blood pressure. The endothelium participates in this regulation as endothelial derived hyperpolarization plays a significant role in smaller renal arteries and arterioles but the exact mechanisms are still unknown AIM: to investigate the role of vascular gap junctions and potassium channels in the renal endothelial derived hyperpolarization. METHODS: in interlobar arteries from wild-type and connexin40 knock-out mice we assessed the role of calcium activated small (SK) and intermediate (IK) conductance potassium channels...
June 14, 2017: Acta Physiologica
https://www.readbyqxmd.com/read/28613276/genetic-loci-associated-with-heart-rate-variability-and-their-effects-on-cardiac-disease-risk
#20
Ilja M Nolte, M Loretto Munoz, Vinicius Tragante, Azmeraw T Amare, Rick Jansen, Ahmad Vaez, Benedikt von der Heyde, Christy L Avery, Joshua C Bis, Bram Dierckx, Jenny van Dongen, Stephanie M Gogarten, Philippe Goyette, Jussi Hernesniemi, Ville Huikari, Shih-Jen Hwang, Deepali Jaju, Kathleen F Kerr, Alexander Kluttig, Bouwe P Krijthe, Jitender Kumar, Sander W van der Laan, Leo-Pekka Lyytikäinen, Adam X Maihofer, Arpi Minassian, Peter J van der Most, Martina Müller-Nurasyid, Michel Nivard, Erika Salvi, James D Stewart, Julian F Thayer, Niek Verweij, Andrew Wong, Delilah Zabaneh, Mohammad H Zafarmand, Abdel Abdellaoui, Sulayma Albarwani, Christine Albert, Alvaro Alonso, Foram Ashar, Juha Auvinen, Tomas Axelsson, Dewleen G Baker, Paul I W de Bakker, Matteo Barcella, Riad Bayoumi, Rob J Bieringa, Dorret Boomsma, Gabrielle Boucher, Annie R Britton, Ingrid Christophersen, Andrea Dietrich, George B Ehret, Patrick T Ellinor, Markku Eskola, Janine F Felix, John S Floras, Oscar H Franco, Peter Friberg, Maaike G J Gademan, Mark A Geyer, Vilmantas Giedraitis, Catharina A Hartman, Daiane Hemerich, Albert Hofman, Jouke-Jan Hottenga, Heikki Huikuri, Nina Hutri-Kähönen, Xavier Jouven, Juhani Junttila, Markus Juonala, Antti M Kiviniemi, Jan A Kors, Meena Kumari, Tatiana Kuznetsova, Cathy C Laurie, Joop D Lefrandt, Yong Li, Yun Li, Duanping Liao, Marian C Limacher, Henry J Lin, Cecilia M Lindgren, Steven A Lubitz, Anubha Mahajan, Barbara McKnight, Henriette Meyer Zu Schwabedissen, Yuri Milaneschi, Nina Mononen, Andrew P Morris, Mike A Nalls, Gerjan Navis, Melanie Neijts, Kjell Nikus, Kari E North, Daniel T O'Connor, Johan Ormel, Siegfried Perz, Annette Peters, Bruce M Psaty, Olli T Raitakari, Victoria B Risbrough, Moritz F Sinner, David Siscovick, Johannes H Smit, Nicholas L Smith, Elsayed Z Soliman, Nona Sotoodehnia, Jan A Staessen, Phyllis K Stein, Adrienne M Stilp, Katarzyna Stolarz-Skrzypek, Konstantin Strauch, Johan Sundström, Cees A Swenne, Ann-Christine Syvänen, Jean-Claude Tardif, Kent D Taylor, Alexander Teumer, Timothy A Thornton, Lesley E Tinker, André G Uitterlinden, Jessica van Setten, Andreas Voss, Melanie Waldenberger, Kirk C Wilhelmsen, Gonneke Willemsen, Quenna Wong, Zhu-Ming Zhang, Alan B Zonderman, Daniele Cusi, Michele K Evans, Halina K Greiser, Pim van der Harst, Mohammad Hassan, Erik Ingelsson, Marjo-Riitta Järvelin, Stefan Kääb, Mika Kähönen, Mika Kivimaki, Charles Kooperberg, Diana Kuh, Terho Lehtimäki, Lars Lind, Caroline M Nievergelt, Chris J O'Donnell, Albertine J Oldehinkel, Brenda Penninx, Alexander P Reiner, Harriëtte Riese, Arie M van Roon, John D Rioux, Jerome I Rotter, Tamar Sofer, Bruno H Stricker, Henning Tiemeier, Tanja G M Vrijkotte, Folkert W Asselbergs, Bianca J J M Brundel, Susan R Heckbert, Eric A Whitsel, Marcel den Hoed, Harold Snieder, Eco J C de Geus
Reduced cardiac vagal control reflected in low heart rate variability (HRV) is associated with greater risks for cardiac morbidity and mortality. In two-stage meta-analyses of genome-wide association studies for three HRV traits in up to 53,174 individuals of European ancestry, we detect 17 genome-wide significant SNPs in eight loci. HRV SNPs tag non-synonymous SNPs (in NDUFA11 and KIAA1755), expression quantitative trait loci (eQTLs) (influencing GNG11, RGS6 and NEO1), or are located in genes preferentially expressed in the sinoatrial node (GNG11, RGS6 and HCN4)...
June 14, 2017: Nature Communications
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