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https://www.readbyqxmd.com/read/28871958/control-of-ampa-receptor-activity-by-the-extracellular-loops-of-auxiliary-proteins
#1
Irene Riva, Clarissa Eibl, Rudolf Volkmer, Anna L Carbone, Andrew Jr Plested
At synapses throughout the mammalian brain, AMPA receptors form complexes with auxiliary proteins, including TARPs. However, how TARPs modulate AMPA receptor gating remains poorly understood. We built structural models of TARP-AMPA receptor complexes for TARPs γ2 and γ8, combining recent structural studies and de novo structure predictions. These models, combined with peptide binding assays, provide evidence for multiple interactions between GluA2 and variable extracellular loops of TARPs. Substitutions and deletions of these loops had surprisingly rich effects on the kinetics of glutamate-activated currents, without any effect on assembly...
August 30, 2017: ELife
https://www.readbyqxmd.com/read/28854690/performance-of-the-multitarget-mikrogen-chlamydia-trachomatis-igg-elisa-in-the-prediction-of-tubal-factor-infertility-tfi-in-subfertile-women-comparison-with-the-medac-momp-igg-elisa-plus
#2
Eleanne F van Ess, Sander Ouburg, Joke Spaargaren, Jolande A Land, Servaas A Morré
There is a need for more accurate Chlamydia trachomatis (CT) IgG antibody tests for tubal factor infertility (TFI) diagnostics. We evaluated the predictive value for TFI of Medac ELISA plus (MOMP) and multitarget Mikrogen ELISA (MOMP-CPAF-TARP). Based on Medac ELISA plus results, 183 subfertile women underwent either hysterosalpingography or laparoscopy to diagnose TFI. TFI was defined as extensive adhesions and/or distal occlusion of at least one tube. Women not fulfilling the definition of TFI served as controls...
September 29, 2017: Pathogens and Disease
https://www.readbyqxmd.com/read/28825787/structural-determinants-of-the-%C3%AE-8-tarp-dependent-ampa-receptor-antagonist
#3
Matthew R Lee, Kevin M Gardinier, Douglas L Gernert, Douglas A Schober, Rebecca A Wright, He Wang, Yuewei Qian, Jeffrey M Witkin, Eric S Nisenbaum, Akihiko S Kato
The forebrain specific AMPA receptor antagonist, LY3130481/CERC-611, which selectively antagonizes the AMPA receptors associated with TARP γ-8, an auxiliary subunit enriched in the forebrain, has potent antiepileptic activities without motor side effects. We designated the compounds with such activities as γ-8 TARP dependent AMPA receptor antagonists (γ-8 TDAAs). In this work, we further investigated the mechanisms of action using a radio-labeled γ-8 TDAA and ternary structural modeling with mutational validations to characterize the LY3130481 binding to γ-8...
August 21, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28814579/hepatosplenic-schistosomiasis-playing-hide-and-seek-with-an-elusive-parasite
#4
Martin Baekby, Henning Glerup, Katrine Stribolt, Britta Tarp
A 27-year-old man of Eritrean origin presented with persistent left-sided abdominal pain. Initial investigation showed signs of liver fibrosis, portal hypertension and splenomegaly. A diagnosis of hepatosplenic schistosomiasis was suspected on grounds of elevated total IgE, grey area antischistosomiasis antibodies and the high endemic status of his native country. However, repeated microscopy of faecal and urine samples, as well as rectal biopsies, failed to demonstrate schistosomal eggs. Finally, the diagnosis of hepatosplenic schistosomiasis was established through demonstration of a Schistosoma mansoni egg in a liver biopsy taken in an attempt to clarify the cause of the above findings...
August 16, 2017: BMJ Case Reports
https://www.readbyqxmd.com/read/28772007/the-impact-of-comorbidities-on-tumor-necrosis-factor-inhibitor-therapy-in-psoriatic-arthritis-a-population-based-cohort-study
#5
Christine Ballegaard, Pil Højgaard, Lene Dreyer, René Cordtz, Tanja Schjødt Jørgensen, Marie Skougaard, Simon Tarp, Lars Erik Kristensen
OBJECTIVE: The objective of this population-based cohort study was to investigate the impact of comorbidities on disease activity, treatment response and persistence with the first-tried tumor necrosis factor inhibitor (TNFi) in patients with psoriatic arthritis (PsA). METHODS: Data on patient characteristics, disease activity and treatment response and persistence was obtained from the DANBIO registry. Information on comorbidities according to the Charlson Comorbidity Index (CCI) was obtained through linkage with the Danish National Patient Register...
August 3, 2017: Arthritis Care & Research
https://www.readbyqxmd.com/read/28768197/dual-effects-of-tarp-%C3%AE-2-on-glutamate-efficacy-can-account-for-ampa-receptor-autoinactivation
#6
Ian D Coombs, David M MacLean, Vasanthi Jayaraman, Mark Farrant, Stuart G Cull-Candy
Fast excitatory transmission in the CNS is mediated mainly by AMPA-type glutamate receptors (AMPARs) associated with transmembrane AMPAR regulatory proteins (TARPs). At the high glutamate concentrations typically seen during synaptic transmission, TARPs slow receptor desensitization and enhance mean channel conductance. However, their influence on channels gated by low glutamate concentrations, as encountered during delayed transmitter clearance or synaptic spillover, is poorly understood. We report here that TARP γ-2 reduces the ability of low glutamate concentrations to cause AMPAR desensitization and enhances channel gating at low glutamate occupancy...
August 1, 2017: Cell Reports
https://www.readbyqxmd.com/read/28757050/electroencephalographic-cognitive-and-neurochemical-effects-of-ly3130481-cerc-611-a-selective-antagonist-of-tarp-%C3%AE-8-associated-ampa-receptors
#7
Jeffrey M Witkin, Jennifer Li, Gary Gilmour, Stephen N Mitchell, Guy Carter, Scott D Gleason, Wesley F Seidel, Brian J Eastwood, Andrew McCarthy, Warren J Porter, Jon Reel, Kevin M Gardinier, Akihiko S Kato, Keith A Wafford
6-[(1S)-1-[1-[5-(2-hydroxyethoxy)-2-pyridyl]pyrazol-3-yl]ethyl]-3H-1,3-benzothiazol-2-one (LY3130481 or CERC-611) is a selective antagonist of AMPA receptors containing transmembrane AMPA receptor regulatory protein (TARP) γ-8. This molecule has been characterized as a potent and efficacious anticonvulsant in an array of acute and chronic epilepsy models in rodents. The present set of experiments was designed to assess the effects of LY3130481 on the electroencephelogram (EEG), cognitive function, and neurochemical outflow...
July 27, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28749592/porphyrin-antennas-on-carbon-nanodots-excited-state-energy-and-electron-transduction
#8
Maurizio Prato, Francesca Arcudi, Volker Strauss, Luka Dordevic, Alejandro Cadranel, Dirk Guldi
We report the synthesis and electron donor-acceptor features of a novel nano-hybrid, in which the light harvesting and electron donating properties of a meso-tetraarylporphyrin (TArP) are combined with the electron accepting features of Nitrogen-Doped Carbon Nanodots (NCNDs). In particular, in a ultrafast process (> 1012 s-1), visible light excitation transforms the strongly quenched porphyrin singlet excited states into 225 ps lived charge separated states. On the other hand, ultraviolet light excitation triggers a non-resolvable transduction of singlet excited state energy from the NCNDs to the porphyrins, followed by the same charge separation observed upon visible light excitation...
July 27, 2017: Angewandte Chemie
https://www.readbyqxmd.com/read/28609687/off-tarp-emissions-distribution-and-efficacy-of-carbonated-fumigants-in-a-low-permeability-film-tarped-field
#9
Ruijun Qin, Suduan Gao, John E Thomas, Dong Wang, Bradley D Hanson
Carbonated fumigants have been shown to distribute quickly and uniformly in sandy soils and improve pest control efficacy for annual crops. Low permeability films, such as VaporSafe® (TIF), could further improve fumigant dispersion by effectively retaining the fumigant in soil; however, there is a concern that the TIF can lead to higher off-tarp edge emissions. An orchard field trial was conducted to determine the off-tarp emissions, distribution, efficacy, and fate of carbonated Telone® C35 [63.4% 1,3-dichloropropene (1,3-D), 34...
June 10, 2017: Science of the Total Environment
https://www.readbyqxmd.com/read/28586478/autoregulation-of-rbm10-and-cross-regulation-of-rbm10-rbm5-via-alternative-splicing-coupled-nonsense-mediated-decay
#10
Yue Sun, Yufang Bao, Wenjian Han, Fan Song, Xianfeng Shen, Jiawei Zhao, Ji Zuo, David Saffen, Wei Chen, Zefeng Wang, Xintian You, Yongbo Wang
Mutations in the spliceosomal RNA binding protein RBM10 cause TARP syndrome and are frequently observed in lung adenocarcinoma (LUAD). We have previously shown that RBM10 enhances exon skipping of its target genes, including its paralog RBM5. Here, we report that RBM10 negatively regulates its own mRNA and protein expression and that of RBM5 by promoting alternative splicing-coupled nonsense-mediated mRNA decay (AS-NMD). Through computational analysis and experimental validation, we identified RBM10-promoted skipping of exon 6 or 12 in RBM10 and exon 6 or 16 in RBM5 as the underlying AS-NMD events...
August 21, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28577551/clinical-diagnostic-exome-evaluation-for-an-infant-with-a-lethal-disorder-genetic-diagnosis-of-tarp-syndrome-and-expansion-of-the-phenotype-in-a-patient-with-a-newly-reported-rbm10-alteration
#11
Zöe Powis, Alexa Hart, Sara Cherny, Igor Petrik, Erika Palmaer, Sha Tang, Carolyn Jones
BACKGROUND: Diagnostic Exome Sequencing (DES) has been shown to be an effective tool for diagnosis individuals with suspected genetic conditions. CASE PRESENTATION: We report a male infant born with multiple anomalies including bilateral dysplastic kidneys, cleft palate, bilateral talipes, and bilateral absence of thumbs and first toes. Prenatal testing including chromosome analysis and microarray did not identify a cause for the multiple congenital anomalies. Postnatal diagnostic exome studies (DES) were utilized to find a molecular diagnosis for the patient...
June 2, 2017: BMC Medical Genetics
https://www.readbyqxmd.com/read/28559374/tarp-%C3%AE-2-is-required-for-inflammation-associated-ampa-receptor-plasticity-within-lamina-ii-of-the-spinal-cord-dorsal-horn
#12
Steve J Sullivan, Mark Farrant, Stuart G Cull-Candy
In the brain, transmembrane AMPAR regulatory proteins (TARPs) critically influence the distribution, gating, and pharmacology of AMPARs, but the contribution of these auxiliary subunits to AMPAR-mediated signaling in the spinal cord remains unclear. We found that the Type I TARP γ-2 (stargazin) is present in lamina II of the superficial dorsal horn, an area involved in nociception. Consistent with the notion that γ-2 is associated with surface AMPARs, CNQX, a partial agonist at AMPARs associated with Type I TARPs, evoked whole-cell currents in lamina II neurons, but such currents were severely attenuated in γ-2-lacking stargazer (stg/stg) mice...
June 21, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28553192/patient-satisfaction-with-videoconferencing-based-treatment-for-alcohol-use-disorders
#13
Kristine Tarp, Anna Mejldal, Anette S Nielsen
OBJECTIVES: The objectives of this study are (1) to compare the satisfaction between patients who have received treatment as usual face-to-face (TAU group) and patients who have received optional videoconferencing-based treatment for alcohol use disorders (TAU+I group); and (2) to elaborate on the TAU+I group's satisfaction with the treatment in general and the technical equipment. METHODS: The design consisted of mixed methods: a survey and a qualitative study...
June 2017: Addictive Disorders & Their Treatment
https://www.readbyqxmd.com/read/28511288/a-tele-health-follow-up-strategy-for-tight-control-of-disease-activity-in-rheumatoid-arthritis-results-of-the-non-inferiority-randomised-controlled-trail-the-tera-study
#14
Annette Thurah, Kristian Stengaard-Pedersen, Mette Axelsen, Ulrich Fredberg, Liv M V Schougaard, Niels H I Hjollund, Mogens Pfeiffer-Jensen, Trine B Laurberg, Ulrik Tarp, Kirsten Lomborg, Thomas Maribo
OBJECTIVE: To test the effect of patient-reported outcome (PRO) based tele-health follow-up for tight control of disease activity in patients with rheumatoid arthritis (RA), and the differences between tele-health follow-up performed by rheumatologists or rheumatology nurses. METHODS: A total of 294 patients were randomized (1:1:1) to either PRO-based tele-health follow-up carried out by a nurse (PRO-TN) or a rheumatologist (PRO-TR), or conventional out-patient follow-up by physicians...
May 16, 2017: Arthritis Care & Research
https://www.readbyqxmd.com/read/28490437/high-throughput-crispri-phenotyping-identifies-new-essential-genes-in-streptococcus-pneumoniae
#15
Xue Liu, Clement Gallay, Morten Kjos, Arnau Domenech, Jelle Slager, Sebastiaan P van Kessel, Kèvin Knoops, Robin A Sorg, Jing-Ren Zhang, Jan-Willem Veening
Genome-wide screens have discovered a large set of essential genes in the opportunistic human pathogen Streptococcus pneumoniae However, the functions of many essential genes are still unknown, hampering vaccine development and drug discovery. Based on results from transposon sequencing (Tn-seq), we refined the list of essential genes in S. pneumoniae serotype 2 strain D39. Next, we created a knockdown library targeting 348 potentially essential genes by CRISPR interference (CRISPRi) and show a growth phenotype for 254 of them (73%)...
May 10, 2017: Molecular Systems Biology
https://www.readbyqxmd.com/read/28487284/implementation-of-a-timed-electronic-assessment-driven-potassium-replacement-protocol
#16
Christopher Zielenski, Adam Crabtree, Tien Le, Alyse Marlatt, Dana Ng, Alan Tran
PURPOSE: The adherence to and effectiveness and safety of a timed, electronic, assessment-driven potassium-replacement protocol (TARP) were compared with an electronic nurse-driven replacement protocol (NRP) are reported. METHODS: A retrospective observational study was conducted in a community hospital evaluating protocol adherence, effectiveness, and safety for 2 potassium-replacement protocols. All adults on medical units with an order for potassium replacement per protocol during the 3-month trial periods were reviewed...
May 9, 2017: American Journal of Health-system Pharmacy: AJHP
https://www.readbyqxmd.com/read/28460289/effect-of-environmental-conditions-on-the-permeability-of-low-density-polyethylene-film-and-totally-impermeable-film-to-methyl-isothiocyanate-fumigant
#17
REVIEW
Wensheng Fang, Aocheng Cao, Dongdong Yan, Dawei Han, Jun Li, Xiaoman Liu, Yuan Li, Chanbin Ouyang, Qiuxia Wang
Fumigant methyl isothiocyanate (MITC) is a very promising alternative to methyl bromide, providing effective control of soil borne disease. However, there is a significant volatilization of MITC following fumigation because of its high application rates and high vapor pressure. Covering the soil surface with plastic tarps is a common approach used for restricting fumigant emissions to the atmosphere. To minimize atmospheric emissions of MITC by tarping, we determined the effect of temperature, humidity, and fumigant mixtures on the permeability to MITC of low density polyethylene film (LDPE) and totally impermeable film (TIF), using static sealed chambers...
December 1, 2017: Science of the Total Environment
https://www.readbyqxmd.com/read/28449386/influence-of-a-2-to-6-year-physical-education-intervention-on-scholastic-performance-the-champs-study-dk
#18
Anna Bugge, Sören Möller, Jakob Tarp, Charles H Hillman, Rodrigo Antunes Lima, Anne Kaer Gejl, Heidi Klakk, Niels Wedderkopp
The aim of this study was to investigate the influence of a school-based intervention with a tripling of physical education (PE) lessons from two (90 minutes) to six lessons per week (270 minutes) on scholastic performance. This study is part of the CHAMPS study-DK, a quasi-experimental study that began in 2008. The intervention group consisted of six schools, and the control group consisted of four matched schools (mean age at baseline=8.4 years, kindergarten class fourth grade). Academic performance was extracted from the national test system from 2010 to 2014 (Math and Danish were measured at third and sixth, and second, fourth and sixth grades, respectively)...
April 27, 2017: Scandinavian Journal of Medicine & Science in Sports
https://www.readbyqxmd.com/read/28429142/national-clinical-guidelines-for-non-surgical-treatment-of-patients-with-recent-onset-low-back-pain-or-lumbar-radiculopathy
#19
REVIEW
Mette Jensen Stochkendahl, Per Kjaer, Jan Hartvigsen, Alice Kongsted, Jens Aaboe, Margrethe Andersen, Mikkel Ø Andersen, Gilles Fournier, Betina Højgaard, Martin Bach Jensen, Lone Donbæk Jensen, Ture Karbo, Lilli Kirkeskov, Martin Melbye, Lone Morsel-Carlsen, Jan Nordsteen, Thorvaldur Skuli Palsson, Zoreh Rasti, Peter Frost Silbye, Morten Zebitz Steiness, Simon Tarp, Morten Vaagholt
PURPOSE: To summarise recommendations about 20 non-surgical interventions for recent onset (<12 weeks) non-specific low back pain (LBP) and lumbar radiculopathy (LR) based on two guidelines from the Danish Health Authority. METHODS: Two multidisciplinary working groups formulated recommendations based on the GRADE approach. RESULTS: Sixteen recommendations were based on evidence, and four on consensus. Management of LBP and LR should include information about prognosis, warning signs, and advise to remain active...
April 20, 2017: European Spine Journal
https://www.readbyqxmd.com/read/28358902/screening-for-ampa-receptor-auxiliary-subunit-specific-modulators
#20
Caleigh M Azumaya, Emily L Days, Paige N Vinson, Shaun Stauffer, Gary Sulikowski, C David Weaver, Terunaga Nakagawa
AMPA receptors (AMPAR) are ligand gated ion channels critical for synaptic transmission and plasticity. Their dysfunction is implicated in a variety of psychiatric and neurological diseases ranging from major depressive disorder to amyotrophic lateral sclerosis. Attempting to potentiate or depress AMPAR activity is an inherently difficult balancing act between effective treatments and debilitating side effects. A newly explored strategy to target subsets of AMPARs in the central nervous system is to identify compounds that affect specific AMPAR-auxiliary subunit complexes...
2017: PloS One
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