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Samuel A Neymotin, Benjamin A Suter, Salvador Dura-Bernal, Gordon M G Shepherd, Michele Migliore, William W Lytton
Corticospinal neurons (SPI), thick-tufted pyramidal neurons in motor cortex layer 5B that project caudally via the medullary pyramids, display distinct class-specific electrophysiological properties in vitro: strong sag with hyperpolarization, lack of adaptation, and a nearly linear frequency-current (FI) relationship. We used our electrophysiological data to produce a pair of large archives of SPI neuron computer models in two model classes: 1. Detailed models with full reconstruction; 2. Simplified models with 6 compartments...
October 19, 2016: Journal of Neurophysiology
Mª Del Mar Blanquer-Rosselló, Reyniel Hernández-López, Pilar Roca, Jordi Oliver, Adamo Valle
BACKGROUND: The polyphenol resveratrol (RSV) is found in the skin of red grapes and has been reported to exhibit anticancer properties. The antitumor effects of RSV in the gastrointestinal tract have gained considerable interest due to the high exposure of this tissue to this dietary compound. One of the hallmarks of cancer cells is their particular metabolism mainly relying on glycolysis for ATP production rather than mitochondrial oxidative phosphorylation. Although RSV has been described to act as a calorie-restriction mimetic, modulating energy metabolism in normal tissues, little efforts have been done to study the effects of this polyphenol in the metabolism of cancer cells...
October 17, 2016: Biochimica et Biophysica Acta
Le Zhang, Alex Burant, Andrew McCallister, Victor Zhao, Karl M Koshlap, Simone Degan, Michael Antonacci, Rosa Tamara Branca
PURPOSE: To investigate the temperature dependence of the resonance frequency of lipid-dissolved xenon (LDX) and to assess the accuracy of LDX-based MR thermometry. METHODS: The chemical shift temperature dependence of water protons, methylene protons, and LDX was measured from samples containing tissues with varying fat contents using a high-resolution NMR spectrometer. LDX results were then used to acquire relative and absolute temperature maps in vivo and the results were compared with PRF-based MR thermometry...
October 19, 2016: Magnetic Resonance in Medicine: Official Journal of the Society of Magnetic Resonance in Medicine
Gargi Mahapatra, Ashwathy Varughese, Qinqin Ji, Icksoo Lee, Jenney Liu, Asmita Vaishnav, Christopher Sinkler, Alexandr A Kapralov, Carlos T Moraes, Thomas H Sanderson, Timothy L Stemmler, Lawrence I Grossman, Valerian E Kagan, Joseph S Brunzelle, Arthur R Salomon, Brian F P Edwards, Maik Hüttemann
Mammalian cytochrome c (Cytc) plays a key role in cellular life and death decisions, functioning as an electron carrier in the electron transport chain (ETC) and as a trigger of apoptosis when released from the mitochondria. However, its regulation is not well understood. We show that the major fraction of Cytc isolated from kidneys is phosphorylated on Thr28, leading to a partial inhibition of respiration in the reaction with cytochrome c oxidase. To further study the effect of Cytc phosphorylation in vitro, we generated Thr28Glu phosphomimetic Cytc, revealing superior behavior regarding protein stability and its ability to degrade reactive oxygen species compared to wild-type unphosphorylated Cytc...
October 7, 2016: Journal of Biological Chemistry
Yoshiaki Suzuki, Susumu Ohya, Hisao Yamamura, Wayne R Giles, Yuji Imaizumi
Large-conductance Ca(2+)-activated K(+) (BK) channels play essential roles in both excitable and non-excitable cells. For example, in chondrocytes, agonist-induced Ca(2+) release from intracellular store activates BK channels, and this hyperpolarizes these cells, augments Ca(2+) entry, and forms a positive feed-back mechanism for Ca(2+) signaling and stimulation-secretion coupling. In the present study, functional roles of a newly identified splice variant in the BK channel α subunit (BKαΔe2) were examined in a human chondrocyte cell line, OUMS-27, and in a HEK293 expression system...
October 7, 2016: Journal of Biological Chemistry
Cory M Smith, Terry J Housh, Nathaniel D M Jenkins, Ethan C Hill, Kristen C Cochrane, Amelia A Miramonti, Richard J Schmidt, Glen O Johnson
The purposes of the present study were to apply a unique method for the identification of the time course of changes in neuromuscular responses and to infer the motor unit activation strategies used to maintain force during a fatiguing, intermittent isometric workbout. Eleven men performed 50, 6 s intermittent isometric muscle actions of the leg extensors, each separated by 2 s of rest at 60% maximal voluntary isometric contraction (MVIC). Electromyographic (EMG) and mechanomyographic (MMG) amplitude (root mean square; RMS) and frequency (mean power frequency; MPF) were obtained from the vastus lateralis (VL) every 5 of the 50 repetitions and normalized as a percent of the initial repetition...
October 18, 2016: Physiological Measurement
Andrey N Pravdivtsev, Alexey S Kiryutin, Alexandra V Yurkovskaya, Hans-Martin Vieth, Konstantin L Ivanov
We propose a robust and highly efficient NMR technique to create singlet spin order from longitudinal spin magnetization in coupled spin-½ pairs and to perform backward conversion (singlet order)→magnetization. In this method we exploit adiabatic ramping of an RF-field in order to drive transitions between the singlet state and the T± triplet states of a spin pair under study. We demonstrate that the method works perfectly for both strongly and weakly coupled spin pairs, providing a conversion efficiency between the singlet spin order and magnetization, which is equal to the theoretical maximum...
October 6, 2016: Journal of Magnetic Resonance
Chloé Najac, Sabrina M Ronen
Metabolic reprogramming is an important hallmark of cancer. Alterations in many metabolic pathways support the requirement for cellular building blocks that are essential for cancer cell proliferation. This metabolic reprogramming can be imaged using magnetic resonance spectroscopy (MRS). H MRS can inform on alterations in the steady-state levels of cellular metabolites, but the emergence of hyperpolarized C MRS has now also enabled imaging of metabolic fluxes in real-time, providing a new method for tumor detection and monitoring of therapeutic response...
October 2016: Topics in Magnetic Resonance Imaging: TMRI
Keisuke Kaneko, Yuko Koyanagi, Yoshiyuki Oi, Masayuki Kobayashi
Propofol is a major intravenous anesthetic that facilitates GABAA receptor-mediated inhibitory synaptic currents and modulates Ih, K(+), and voltage-gated Na(+) currents. This propofol-induced modulation of ionic currents changes intrinsic membrane properties and repetitive spike firing in cortical pyramidal neurons. However, it has been unknown whether propofol modulates these electrophysiological properties in GABAergic neurons, which express these ion channels at different levels. This study examined whether pyramidal and GABAergic neuronal properties are differentially modulated by propofol in the rat insular cortical slice preparation...
October 13, 2016: Neuroscience
Wei Sun, Fei Yang, Yan Wang, Han Fu, Yan Yang, Chun-Li Li, Xiao-Liang Wang, Qing Lin, Jun Chen
Under physiological state, small- and medium-sized dorsal root ganglia (DRG) neurons are believed to mediate nociceptive behavioral responses to painful stimuli. However, recently it has been found that a number of large-sized neurons are also involved in nociceptive transmission under neuropathic conditions. Nonetheless, the underlying mechanisms that large-sized DRG neurons mediate nociception are poorly understood. In the present study, the role of large-sized neurons in bee venom (BV)-induced mechanical allodynia and the underlying mechanisms were investigated...
October 12, 2016: Neuropharmacology
Marivi Nabong Moen, Roar Fjær, El Hassan Hamdani, Jon K Laerdahl, Robin Johansen Menchini, Magnus Dehli Vigeland, Ying Sheng, Dag Erik Undlien, Bjørnar Hassel, Mustafa A Salih, Heba Y El Khashab, Kaja Kristine Selmer, Farrukh Abbas Chaudhry
Progressive myoclonus epilepsy is a heterogeneous group of disorders characterized by myoclonic and tonic-clonic seizures, ataxia and cognitive decline. We here present two affected brothers. At 9 months of age the elder brother developed ataxia and myoclonic jerks. In his second year he lost the ability to walk and talk, and he developed drug-resistant progressive myoclonus epilepsy. The cerebrospinal fluid level of glutamate was decreased while glutamine was increased. His younger brother manifested similar symptoms from 6 months of age...
October 14, 2016: Brain: a Journal of Neurology
Travis C Salzillo, Jingzhe Hu, Linda Nguyen, Nicholas Whiting, Jaehyuk Lee, Joseph Weygand, Prasanta Dutta, Shivanand Pudakalakatti, Niki Zacharias Millward, Seth T Gammon, Frederick F Lang, Amy B Heimberger, Pratip K Bhattacharya
This article reviews existing and emerging techniques of interrogating metabolism in brain cancer from well-established proton magnetic resonance spectroscopy to the promising hyperpolarized metabolic imaging and chemical exchange saturation transfer and emerging techniques of imaging inflammation. Some of these techniques are at an early stage of development and clinical trials are in progress in patients to establish the clinical efficacy. It is likely that in vivo metabolomics and metabolic imaging is the next frontier in brain cancer diagnosis and assessing therapeutic efficacy; with the combined knowledge of genomics and proteomics a complete understanding of tumorigenesis in brain might be achieved...
November 2016: Magnetic Resonance Imaging Clinics of North America
Jeremy W Gordon, Eugene Milshteyn, Irene Marco-Rius, Michael Ohliger, Daniel B Vigneron, Peder E Z Larson
PURPOSE: The purpose of this work was to explore the impact of slice profile effects on apparent diffusion coefficient (ADC) mapping of hyperpolarized (HP) substrates. METHODS: Slice profile effects were simulated using a Gaussian radiofrequency (RF) pulse with a variety of flip angle schedules and b-value ordering schemes. A long T1 water phantom was used to validate the simulation results, and ADC mapping of HP [(13) C,(15) N2 ]urea was performed on the murine liver to assess these effects in vivo...
October 13, 2016: Magnetic Resonance in Medicine: Official Journal of the Society of Magnetic Resonance in Medicine
Hooman Hamedani, Stephen Kadlecek, Yi Xin, Sarmad Siddiqui, Heather Gatens, Joseph Naji, Masaru Ishii, Maurizio Cereda, Milton Rossman, Rahim Rizi
PURPOSE: To present a method for simultaneous acquisition of alveolar oxygen tension (PA O2 ), specific ventilation (SV), and apparent diffusion coefficient (ADC) of hyperpolarized (HP) gas in the human lung, allowing reinterpretation of the PA O2 and SV maps to produce a map of oxygen uptake (R). METHOD: An imaging scheme was designed with a series of identical normoxic HP gas wash-in breaths to measure ADC, SV, PA O2 , and R in less than 2 min. Signal dynamics were fit to an iterative recursive model that regionally solved for these parameters...
October 13, 2016: Magnetic Resonance in Medicine: Official Journal of the Society of Magnetic Resonance in Medicine
Andrew M Wright, Agustin Zapata, Michael H Baumann, Joshua S Elmore, Alexander F Hoffman, Carl R Lupica
Clinical descriptions of cocaine addiction include compulsive drug seeking and maladaptive decision-making despite substantial aversive consequences. Research suggests that this may result from altered orbitofrontal cortex (OFC) function and its participation in outcome-based behavior. Clinical and animal studies also implicate serotonin in the regulation of OFC function in addiction and other neuropsychiatric disorders. Here we test the hypothesis that exposure to cocaine, through self-administration (CSA) or yoked-administration (CYA), alters the regulation of OFC function by 5-HT...
October 12, 2016: Cerebral Cortex
Mei Wang, Youyang Hu, Yifei Fan, Yan Guo, Fanglin Chen, Shuo Chen, Qinglin Li, Zhiwu Chen
BACKGROUND/AIM: H2S is a novel vasoactivator. To verify the hypothesis that H2S may act as an endothelium-derived hyperpolarizing factor (EDHF) in the rat cerebrovasculature, the role of H2S in endothelium-derived relaxing factor (EDRF)-mediated responses was investigated. METHODS: Cystathionine-γ-lyase (CSE) was knocked down with an siRNA technique. Artery diameter, hyperpolarization and Ca2+-activated K+ (KCa) current were measured. RESULTS: CSE knockdown was indicated by a decrease in protein and mRNA expression in the rat middle cerebral artery (MCA) and cerebral basilar artery (CBA)...
October 13, 2016: Journal of Vascular Research
Tahreema N Matin, Najib Rahman, Annabel H Nickol, Mitchell Chen, Xiaojun Xu, Neil J Stewart, Tom Doel, Vicente Grau, James M Wild, Fergus V Gleeson
Purpose To compare lobar ventilation and apparent diffusion coefficient (ADC) values obtained with hyperpolarized xenon 129 ((129)Xe) magnetic resonance (MR) imaging to quantitative computed tomography (CT) metrics on a lobar basis and pulmonary function test (PFT) results on a whole-lung basis in patients with chronic obstructive pulmonary disease (COPD). Materials and Methods The study was approved by the National Research Ethics Service Committee; written informed consent was obtained from all patients. Twenty-two patients with COPD (Global Initiative for Chronic Obstructive Lung Disease stage II-IV) underwent hyperpolarized (129)Xe MR imaging at 1...
October 12, 2016: Radiology
Khadija Sheikh, Fumin Guo, Dante P I Capaldi, Alexei Ouriadov, Rachel L Eddy, Sarah Svenningsen, Grace Parraga
PURPOSE: To develop and assess ultrashort echo-time (UTE) magnetic resonance imaging (MRI) biomarkers of lung function in asthma patients. MATERIALS AND METHODS: Thirty participants including 13 healthy volunteers and 17 asthmatics provided written informed consent to UTE and pulmonary function tests in addition to hyperpolarized-noble-gas 3T MRI and computed tomography (CT) for asthmatics only. The difference in MRI signal-intensity (SI) across four lung volumes (full-expiration, functional-residual-capacity [FRC], FRC+1L, and full-inspiration) was determined on a voxel-by-voxel basis to generate dynamic proton-density (DPD) maps...
October 12, 2016: Journal of Magnetic Resonance Imaging: JMRI
Julliane Vasconcelos Joviano-Santos, Artur Santos-Miranda, Humberto Cavalcante Joca, Jader Santos Cruz, Anderson José Ferreira
Angiotensin (Ang)-(1-7) has been proved to have cardio-protective effects. However, the effects of this peptide on in vivo cardiac arrhythmias and details regarding its mechanisms of action are still undetermined. The aim of this study was to investigate the protective effects of Ang-(1-7) against cardiac arrhythmias, its in vivo effects and cellular mechanisms of action. In vivo electrocardiography analysis upon inducement of arrhythmias using a combination of halothane and epinephrine were performed. To analyze the effects of Ang-(1-7) on cells, freshly ventricular cardiomyocytes were isolated...
October 12, 2016: Experimental Physiology
Tien-Sheng Tseng, Shih-Han Wang, Ting-Wei Chang, Hung-Mu Wei, Yu-June Wang, Keng-Chang Tsai, You-Di Liao, Chinpan Chen
The emergence of antibiotic-resistant microbial strains has become a public health issue and there is an urgent need to develop new anti-infective molecules. Although natural antimicrobial peptides (AMPs) can exert bactericidal activities, they have not shown clinical efficacy. The limitations of native peptides may be overcome with rational design and synthesis. Here, we provide evidence that the bactericidal activity of a synthetic peptide, GW-Q6, against Pseudomonas aeruginosa is mediated through outer membrane protein OprI...
2016: PloS One
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