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Tomohiro Yamazaki, Sylvie Souquere, Takeshi Chujo, Simon Kobelke, Yee Seng Chong, Archa H Fox, Charles S Bond, Shinichi Nakagawa, Gerard Pierron, Tetsuro Hirose
A class of long noncoding RNAs (lncRNAs) has architectural functions in nuclear body construction; however, specific RNA domains dictating their architectural functions remain uninvestigated. Here, we identified the domains of the architectural NEAT1 lncRNA that construct paraspeckles. Systematic deletion of NEAT1 portions using CRISPR/Cas9 in haploid cells revealed modular domains of NEAT1 important for RNA stability, isoform switching, and paraspeckle assembly. The middle domain, containing functionally redundant subdomains, was responsible for paraspeckle assembly...
June 21, 2018: Molecular Cell
Adrian Mirolo, Guillaume Viart, Eric Durand, Arnaud Savouré, Bénédicte Godin, Nathanaël Auquier, Olivier Raitière, Hélène Eltchaninoff, Frédéric Anselme
BACKGROUND: One of the most frequent complications of TAVI is the occurrence of atrioventricular (AV) conduction disorders secondary to AV node or His bundle injury leading to permanent pacemaker implantation (PPI). The objective was to quantify the rate of ventricular pacing (VP), according to post-TAVI indication for PPI, using recorded pacemaker memory. METHODS: From October 2009 to January 2017' all patients who had PPI following TAVI performed at Rouen University Hospital were included...
June 21, 2018: Pacing and Clinical Electrophysiology: PACE
Andrea Scholz, John Bothmer, Maurits Kok, Kornelia Hoschen, Stephen Daniels
BACKGROUND: Cebranopadol is a potent, first-in-class analgesic with a novel mechanistic approach combining nociceptin/orphanin FQ peptide (NOP) and opioid peptide receptor agonism. OBJECTIVE: We aim to evaluate, for the first time, the analgesic efficacy, safety, and tolerability of cebranopadol in patients suffering from moderate to severe acute pain following bunionectomy. STUDY DESIGN: We conducted a phase IIa, randomized, multi-center, double-blind, double-dummy, placebo- and active-controlled, parallel group clinical trial...
May 2018: Pain Physician
Klaus Schiene, Wolfgang Schröder, Klaus Linz, Stefanie Frosch, Thomas M Tzschentke, Ulla Jansen, Thomas Christoph
Cebranopadol is a novel, first-in-class analgesic with agonist activity at the nociceptin/orphanin FQ opioid peptide (NOP) receptor as well as the classical opioid peptide receptors. This study investigated the anti-hypersensitive effect of cebranopadol in a rat model of arthritic pain. Selective antagonists were used to probe the involvement of the NOP receptor and the µ-opioid peptide (MOP) receptors. Experimental mono-arthritis was induced by intra-articular injection of complete Freund's adjuvant into the left hind knee joint...
May 9, 2018: European Journal of Pharmacology
Diwakar Vyas, Aklilu W Alemu, Sean M McGinn, Stephane M Duval, Maik Kindermann, Karen A Beauchemin
The study objective was to evaluate the combined effects of supplementing monensin (MON) and the methane (CH4) inhibitor 3-nitrooxypropanol (NOP) on enteric CH4 emissions, growth rate and feed conversion efficiency of backgrounding and finishing beef cattle. Two hundred and forty crossbred steers were used in a 238-d feeding study and fed a backgrounding diet for the first 105-d (backgrounding phase), transition diets for 28 d, followed by a finishing diet for 105-d (finishing phase). Treatments were: 1) Control (no additive); 2) MON (monensin supplemented at 33 mg/kg DM; 3) NOP (3-nitrooxypropanol supplemented at 200 mg/kg DM for backgrounding or 125 mg/kg DM for finishing phase); 4) MONOP (33 mg/kg DM MON supplemented with either 200 mg/kg DM or 125 mg/kg DM NOP)...
May 5, 2018: Journal of Animal Science
Jung-Hye Choi, Sang-Heon Lee, Hae-Rim Kim, Kyung-Ann Lee
Ankylosing spondylitis (AS) is a chronic, progressive, and inflammatory disorder and causes chronic back pain. It is not unusual for patients with AS to have symptoms similar to neuropathic pain. We aimed to investigate the neuropathic pain (NeP) component in patients with AS using the painDETECT questionnaire (PD-Q) and to assess the relation between NeP and the disease characteristics of AS. A single-center prospective study was performed, including 105 patients. Patients with AS completed three questionnaires: PD-Q, Beck Depression Inventory (BDI), and Euro Quality of Life (EQ-5D) questionnaires...
April 30, 2018: Clinical Rheumatology
D Matthew Walentiny, Jason M Wiebelhaus, Patrick M Beardsley
BACKGROUND: Nociceptin/orphanin FQ (NOP) receptor ligands have shown efficacy as putative analgesics and can modulate the abuse-related effects of opioids, suggesting therapeutic applications. The discriminative stimulus effects of a drug are related to their subjective effects, a predictor of abuse potential. To determine whether activation of NOP receptors could alter the subjective effects of an abused opioid analgesic, a novel oxycodone discrimination was established in mice, characterized with positive and negative controls, and its expression evaluated with a NOP receptor agonist...
June 1, 2018: Drug and Alcohol Dependence
Luis Fernando García, Carmen Viera, Stano Pekár
Predators are traditionally classified as generalists and specialists based on the presence of adaptations that increase efficiency of prey capture and consumption and selection of particular prey types. Nevertheless, empirical evidence comparing foraging efficiency between generalist and specialist carnivores is scarce. We compared the prey-capture and feeding efficiency in a generalist and a specialist (araneophagous) spider predator. By using two related species, the generalist Harpactea rubicunda (Dysderidae) and the specialist Nops cf...
April 2, 2018: Die Naturwissenschaften
Clarisse Grèze, Bruno Pereira, Yves Boirie, Laurent Guy, Cyril Garrouste, Anne-Élisabeth Heng
Post-kidney transplantation outcomes in obese patients remain uncertain. The aim of this study is to compare patient and graft survival and post-transplant complications in obese patients and non-obese patients. We performed a retrospective analysis of a sample of 245kidney transplantations performed between 2008 and 2014 in Clermont-Ferrand. Obese patients and non-obese patients have been compared. Then we compared obese patients who have lost at least 5% of their weight (OPP) with obese patients who did not lose weight (OPS), and non-obese patients who have lost at least 5% of their weight (NOPP) with non-obese patients who did not lose weight (NOPS)...
March 27, 2018: Néphrologie & Thérapeutique
Paul P G Gauthier, Mark O Battle, Kevin L Griffin, Michael L Bender
A fundamental challenge in plant physiology is independently determining the rates of gross O2 production by photosynthesis and O2 consumption by respiration, photorespiration, and other processes. Previous studies on isolated chloroplasts or leaves have separately constrained net and gross O2 production (NOP and GOP, respectively) by labeling ambient O2 with 18 O while leaf water was unlabeled. Here, we describe a method to accurately measure GOP and NOP of whole detached leaves in a cuvette as a routine gas-exchange measurement...
May 2018: Plant Physiology
Akihiko Ozawa, Gloria Brunori, Andrea Cippitelli, Nicholas Toll, Jennifer Schoch, Brigitte L Kieffer, Lawrence Toll
BACKGROUND AND PURPOSE: The nociceptin/orphanin FQ opioid peptide (NOP) receptor system plays a significant role in the regulation of pain. This system functions differently in the spinal cord and brain. The mechanism by which the NOP receptor agonists regulate pain transmission in these regions is not clearly understood. Here, we investigate the peripheral and spinal NOP receptor distribution and antinociceptive effects of intrathecal nociceptin/orphanin FQ (N/OFQ) in chronic neuropathic pain...
March 26, 2018: British Journal of Pharmacology
M A Sohn, A Agha, P Steiner, A Hochrein, M Komm, R Ruppert, P Ritschl, F Aigner, I Iesalnieks
PURPOSE: Damage control strategy (DCS) is a two-staged procedure for the treatment of perforated diverticular disease complicated by generalized peritonitis. The aim of this retrospective multicenter cohort study was to evaluate the prognostic impact of an ongoing peritonitis at the time of second surgery. METHODS: Consecutive patients who underwent DCS for perforated diverticular disease of the sigmoid colon with generalized peritonitis at four surgical centers were included...
March 13, 2018: International Journal of Colorectal Disease
Kris Rutten, Wolfgang Schröder, Thomas Christoph, Thomas Koch, Thomas M Tzschentke
Agonists selectively acting at NOP, MOP, DOP and KOP receptors as well as mixed opioid receptor agonists are known to exert anti-hypersensitive efficacy in the rat spinal nerve ligation (SNL) model of neuropathic pain. To investigate the relative contribution of individual opioid receptor activation to the overall efficacy of mixed opioid receptor agonists, selective doses of respective opioid receptor antagonists have to be employed. In order to identify such selective antagonist doses, doses of the selective NOP, MOP, DOP and KOP receptor agonists Ro65-6570, morphine, SNC-80 and U50488H, that produced maximum efficacy without apparent side effects, were challenged by each of the receptor antagonists J-113397 (NOP receptor), naloxone (MOP receptor), naltrindole (DOP receptor) and nor-binaltorphimine (KOP receptor)...
May 15, 2018: European Journal of Pharmacology
Ryo Nishikawa, Kenji Yoshida, Yasuhiko Ebina, Mayumi Omoteda, Daisuke Miyawaki, Takeaki Ishihara, Yasuo Ejima, Hiroaki Akasaka, Hitoaki Satoh, Katsusuke Kyotani, Satoru Takahashi, Ryohei Sasaki
This study aimed to compare dosimetric parameters between non-optimized and optimized treatment planning (NOP and OP, respectively) of magnetic resonance imaging (MRI) -based intracavitary (IC) image-guided adaptive brachytherapy (IGABT) using the central shielding (CS) technique for cervical cancer. Fifty-three patients treated with external beam radiotherapy using CS and MRI-based IGABT with the IC approach alone were evaluated. The total high-risk clinical target volume (HR-CTV) D90 was aimed at >70 Gy equivalent dose in 2 Gy fractions (EQD2)...
March 6, 2018: Journal of Radiation Research
Dalibor Milić, Markus Dick, Daniel Mulnaes, Christopher Pfleger, Anna Kinnen, Holger Gohlke, Georg Groth
Synthetic peptides derived from ethylene-insensitive protein 2 (EIN2), a central regulator of ethylene signalling, were recently shown to delay fruit ripening by interrupting protein-protein interactions in the ethylene signalling pathway. Here, we show that the inhibitory peptide NOP-1 binds to the GAF domain of ETR1 - the prototype of the plant ethylene receptor family. Site-directed mutagenesis and computational studies reveal the peptide interaction site and a plausible molecular mechanism for the ripening inhibition...
March 1, 2018: Scientific Reports
Michael Camilleri
This is an editorial summarizing recent new developments in visceral analgesics. This promising field is important as a new approach to address abdominal pain with peripheral visceral analgesics is considered a key approach to addressing the current opioid crisis. Some of the novel compounds address peripheral pain mechanisms through modulation of opioid receptors through biased ligands, nociceptin/orphanin FQ opioid peptide (NOP) receptor or dual action on NOP and μ-opioid receptor, buprenorphine and morphiceptin analogs...
February 22, 2018: American Journal of Physiology. Gastrointestinal and Liver Physiology
Juan José López-Gómez, Beatriz Torres-Torres, Emilia Gómez-Hoyos, Nieves Fernández-Buey, Ana Ortolá-Buigues, Ángeles Castro-Lozano, Juan F Arenillas-Lara, Daniel A De Luis-Román
OBJECTIVE: The aim of this study were to understand the influence of a multidisciplinary care protocol in amyotrophic lateral sclerosis (ALS) on the change in the delay of remission to the nutrition specialist and the initial nutritional status. METHODS: A cohort study was performed in 43 patients with ALS who were referred to the Nutrition Unit between April 2015 and April 2017. Anthropometric parameters and diagnostic times were collected, and the nutritional status was studied through subjective global assessment (SGA)...
April 2018: Nutrition
Anat Galor, Leslie Small, William Feuer, Roy C Levitt, Konstantinos D Sarantopoulos, Gil Yosipovitch
Purpose: To evaluate associations between sensations of ocular itch and dry eye (DE) symptoms, including ocular pain, and DE signs. Methods: A cross-sectional study of 324 patients seen in the Miami Veterans Affairs eye clinic was performed. The evaluation consisted of questionnaires regarding ocular itch, DE symptoms, descriptors of neuropathic-like ocular pain (NOP), and evoked pain sensitivity testing on the forehead and forearm, followed by a comprehensive ocular surface examination including corneal mechanical sensitivity testing...
August 2017: Transactions of the American Ophthalmological Society
Laura Micheli, Elena Lucarini, Francesca Corti, Roberto Ciccocioppo, Girolamo Calò, Anna Rizzi, Carla Ghelardini, Lorenzo Di Cesare Mannelli
The development of tolerance to the antinociceptive effect is a main problem associated with the repeated administration of opioids. The progressively higher doses required to relieve pain reduce safety and exacerbate the side effects of classical opioid receptor agonists like morphine. Nociceptin/orphanin FQ (N/OFQ) and its NOP receptor constitute the fourth endogenous opioid system that is involved in the control of broad spectrum of biological functions, including pain transmission. Aim of this work was to evaluate the relevance of the N/OFQ-NOP system in morphine antinociceptive action and in the development of morphine tolerance in the rat...
March 15, 2018: European Journal of Pharmacology
Jae Joon Yoon, Ji A Song, Sue Youn Park, Jeong Il Choi
Background: Chronic pain reportedly exerts complex effects on immune function. Natural killer (NK) cells are lymphocytes that play a critical role in cellular and innate immunity. This study examined changes in the subset populations and cytotoxic activity of peripheral blood NK cells in patients with chronic pain. Methods: Thirty patients with chronic moderate-to-severe pain (group P) and age-matched pain-free subjects (group NoP) were enrolled. Peripheral whole blood was analyzed for the percentage and expression of NK cell surface markers (CD56 and CD16) by flow cytometry...
January 2018: Korean Journal of Pain
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