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https://www.readbyqxmd.com/read/29792594/an-nmdar-positive-and-negative-allosteric-modulator-series-share-a-binding-site-and-are-interconverted-by-methyl-groups
#1
Riley Perszyk, Brooke M Katzman, Hirofumi Kusumoto, Steven A Kell, Matthew P Epplin, Yesim A Tahirovic, Rhonda L Moore, David Menaldino, Pieter Burger, Dennis C Liotta, Stephen F Traynelis
N-methyl-d-aspartate receptors (NMDARs) are an important receptor in the brain and have been implicated in multiple neurological disorders. Many non-selective NMDAR-targeting drugs are poorly tolerated, leading to efforts to target NMDAR subtypes to improve the therapeutic index. We describe here a series of negative allosteric NMDAR modulators with submaximal inhibition at saturating concentrations. Modest changes to the chemical structure interconvert negative and positive modulation. All modulators share the ability to enhance agonist potency and are use-dependent, requiring the binding of both agonists before modulators act with high potency...
May 24, 2018: ELife
https://www.readbyqxmd.com/read/29791476/identifying-county-characteristics-associated-with-resident-well-being-a-population-based-study
#2
Brita Roy, Carley Riley, Jeph Herrin, Erica S Spatz, Anita Arora, Kenneth P Kell, John Welsh, Elizabeth Y Rula, Harlan M Krumholz
BACKGROUND: Well-being is a positively-framed, holistic assessment of health and quality of life that is associated with longevity and better health outcomes. We aimed to identify county attributes that are independently associated with a comprehensive, multi-dimensional assessment of individual well-being. METHODS: We performed a cross-sectional study examining associations between 77 pre-specified county attributes and a multi-dimensional assessment of individual US residents' well-being, captured by the Gallup-Sharecare Well-Being Index...
2018: PloS One
https://www.readbyqxmd.com/read/29777676/cognitive-effects-of-rhythmic-auditory-stimulation-in-parkinson-s-disease-a-p300-study
#3
Juan Lei, Nadine Conradi, Cornelius Abel, Stefan Frisch, Alla Brodski-Guerniero, Marcel Hildner, Christian A Kell, Jochen Kaiser, Maren Schmidt-Kassow
Rhythmic auditory stimulation (RAS) may compensate dysfunctions of the basal ganglia (BG), involved with intrinsic evaluation of temporal intervals and action initiation or continuation. In the cognitive domain, RAS containing periodically presented tones facilitates young healthy participants' attention allocation to anticipated time points, indicated by better performance and larger P300 amplitudes to periodic compared to random stimuli. Additionally, active auditory-motor synchronization (AMS) leads to a more precise temporal encoding of stimuli via embodied timing encoding than stimulus presentation adapted to the participants' actual movements...
May 16, 2018: Brain Research
https://www.readbyqxmd.com/read/29775456/maternal-obesogenic-diet-induces-endometrial-hyperplasia-an-early-hallmark-of-endometrial-cancer-in-a-diethylstilbestrol-mouse-model
#4
Theresa O Owuor, Michaela Reid, Lauren Reschke, Ian Hagemann, Suellen Greco, Zeel Modi, Kelle H Moley
Thirty-eight percent of US adult women are obese, meaning that more children are now born of overweight and obese mothers, leading to an increase in predisposition to several adult onset diseases. To explore this phenomenon, we developed a maternal obesity animal model by feeding mice a diet composed of high fat/ high sugar (HF/HS) and assessed both maternal diet and offspring diet on the development of endometrial cancer (ECa). We show that maternal diet by itself did not lead to ECa initiation in wildtype offspring of the C57Bl/6J mouse strain...
2018: PloS One
https://www.readbyqxmd.com/read/29750129/engineering-the-missing-link-in-biosynthetic-menthol-production-bacterial-isopulegone-isomerase
#5
Andrew Currin, Mark S Dunstan, Linus O Johannissen, Katherine A Hollywood, Maria Vinaixa, Adrian J Jervis, Neil Swainston, Nicholas J W Rattray, John M Gardiner, Douglas B Kell, Eriko Takano, Helen S Toogood, Nigel S Scrutton
The realization of a synthetic biology approach to microbial (1 R ,2 S ,5 R )-( - )-menthol ( 1 ) production relies on the identification of a gene encoding an isopulegone isomerase (IPGI), the only enzyme in the Mentha piperita biosynthetic pathway as yet unidentified. We demonstrate that Δ5-3-ketosteroid isomerase (KSI) from Pseudomonas putida can act as an IPGI, producing ( R )-(+)-pulegone (( R )- 2 ) from (+)- cis -isopulegone ( 3 ). Using a robotics-driven semirational design strategy, we identified a key KSI variant encoding four active site mutations, which confer a 4...
March 2, 2018: ACS Catalysis
https://www.readbyqxmd.com/read/29737927/in-office-endoscopic-laryngeal-laser-procedures-a-patient-safety-initiative
#6
Jennifer Anderson, Yael Bensoussan, Richard Townsley, Erika Kell
Objective To review complications of in-office endoscopic laryngeal laser procedures after implementation of standardized safety protocol. Methods A retrospective review was conducted of the first 2 years of in-office laser procedures at St Michaels Hospital after the introduction of a standardized safety protocol. The protocol included patient screening, procedure checklist with standardized reporting of processes, medications, and complications. Primary outcomes measured were complication rates of in-office laryngeal laser procedures...
May 1, 2018: Otolaryngology—Head and Neck Surgery
https://www.readbyqxmd.com/read/29734940/correction-to-dialectical-behaviour-therapy-for-treating-adults-and-adolescents-with-emotional-and-behavioural-dysregulation-study-protocol-of-a-coordinated-implementation-in-a-publicly-funded-health-service
#7
Daniel Flynn, Mary Kells, Mary Joyce, Catalina Suarez, Conall Gillespie
Upon publication of the original article (1) it was highlighted by the authors that there was just one error in the manuscript in the 'Sample size' subsection of the Methods/Design.
May 7, 2018: BMC Psychiatry
https://www.readbyqxmd.com/read/29721535/erratum-for-the-research-article-dynamic-conservation-for-migratory-species-by-m-reynolds-b-l-sullivan-e-hallstein-s-matsumoto-s-kelling-m-merrifield-d-fink-a-johnston-w-m-hochachka-n-e-bruns-m-e-reiter-s-veloz-c-hickey-n-elliot-l-martin-j-w-fitzpatrick-p-spraycar
#8
https://www.readbyqxmd.com/read/29707216/cutting-edges-and-weaving-threads-in-the-gene-editing-%C3%B0-evolution-reconciling-scientific-progress-with-legal-ethical-and-social-concerns
#9
Ana Nordberg, Timo Minssen, Sune Holm, Maja Horst, Kell Mortensen, Birger Lindberg Møller
Gene-editing technology, such as CRISPR/Cas9, holds great promise for the advancement of science and many useful applications technology. This foundational technology enables modification of the genetic structure of any living organisms with unprecedented precision. Yet, in order to enhance its potential for societal benefit, it is necessary to adapt rules and produce adequate regulations. This requires an interdisciplinary effort in legal thinking. Any legislative initiative needs to consider both the benefits and the problematic aspects of gene editing, from a broader societal and value-based perspective...
May 2018: Journal of Law and the Biosciences
https://www.readbyqxmd.com/read/29700043/enhancement-of-red-blood-cell-transfusion-compatibility-using-crispr-mediated-erythroblast-gene-editing
#10
Joseph Hawksworth, Timothy J Satchwell, Marjolein Meinders, Deborah E Daniels, Fiona Regan, Nicole M Thornton, Marieangela C Wilson, Johannes Gg Dobbe, Geert J Streekstra, Kongtana Trakarnsanga, Kate J Heesom, David J Anstee, Jan Frayne, Ashley M Toye
Regular blood transfusion is the cornerstone of care for patients with red blood cell (RBC) disorders such as thalassaemia or sickle-cell disease. With repeated transfusion, alloimmunisation often occurs due to incompatibility at the level of minor blood group antigens. We use CRISPR-mediated genome editing of an immortalised human erythroblast cell line (BEL-A) to generate multiple enucleation competent cell lines deficient in individual blood groups. Edits are combined to generate a single cell line deficient in multiple antigens responsible for the most common transfusion incompatibilities: ABO (Bombay phenotype), Rh (Rhnull ), Kell ( K 0 ), Duffy (Duffynull ), GPB (S- s- U- )...
April 26, 2018: EMBO Molecular Medicine
https://www.readbyqxmd.com/read/29698446/effects-of-noxious-stimuli-on-the-electroencephalogram-of-anaesthetised-chickens-gallus-gallus-domesticus
#11
Amanda E McIlhone, Ngaio J Beausoleil, Nikki J Kells, David J Mellor, Craig B Johnson
The reliable assessment and management of avian pain is important in the context of animal welfare. Overtly expressed signs of pain vary substantially between and within species, strains and individuals, limiting the use of behaviour in pain studies. Similarly, physiological indices of pain can also vary and may be confounded by influence from non-painful stimuli. In mammals, changes in the frequency spectrum of the electroencephalogram (EEG) recorded under light anaesthesia (the minimal anaesthesia model; MAM) have been shown to reliably indicate cerebral responses to noxious stimuli in a range of species...
2018: PloS One
https://www.readbyqxmd.com/read/29696237/the-interval-walking-in-colorectal-cancer-i-walk-crc-study-design-methods-and-recruitment-results-of-a-randomized-controlled-feasibility-trial
#12
Anna Banck-Petersen, Cecilie K Olsen, Sissal S Djurhuus, Anita Herrstedt, Sarah Thorsen-Streit, Mathias Ried-Larsen, Kell Østerlind, Jens Osterkamp, Peter-Martin Krarup, Kirsten Vistisen, Camilla S Mosgaard, Bente K Pedersen, Pernille Højman, Jesper F Christensen
Background: Low physical activity level is associated with poor prognosis in patients with colorectal cancer (CRC). To increase physical activity, technology-based platforms are emerging and provide intriguing opportunities to prescribe and monitor active lifestyle interventions. The "Interval Walking in Colorectal Cancer"(I-WALK-CRC) study explores the feasibility and efficacy a home-based interval-walking intervention delivered by a smart-phone application in order to improve cardio-metabolic health profile among CRC survivors...
March 2018: Contemporary Clinical Trials Communications
https://www.readbyqxmd.com/read/29681533/a-task-optimized-neural-network-replicates-human-auditory-behavior-predicts-brain-responses-and-reveals-a-cortical-processing-hierarchy
#13
Alexander J E Kell, Daniel L K Yamins, Erica N Shook, Sam V Norman-Haignere, Josh H McDermott
A core goal of auditory neuroscience is to build quantitative models that predict cortical responses to natural sounds. Reasoning that a complete model of auditory cortex must solve ecologically relevant tasks, we optimized hierarchical neural networks for speech and music recognition. The best-performing network contained separate music and speech pathways following early shared processing, potentially replicating human cortical organization. The network performed both tasks as well as humans and exhibited human-like errors despite not being optimized to do so, suggesting common constraints on network and human performance...
April 17, 2018: Neuron
https://www.readbyqxmd.com/read/29677541/tert-butyl-4-1-phenyl-1h-pyrazol-4-yl-methyl-piperazine-1-carboxylate-lqfm104-new-piperazine-derivative-with-antianxiety-and-antidepressant-like-effects-putative-role-of-serotonergic-system
#14
Dayane Moreira da Silva, Germán Sanz, Boniek Gontijo Vaz, Flávio Silva de Carvalho, Luciano Morais Lião, Danillo Ramos de Oliveira, Lorrane Kelle da Silva Moreira, Carina Sofia Cardoso, Adriane Ferreira de Brito, Daiany Priscilla Bueno da Silva, Fabio Fagundes da Rocha, Ianca Gontijo Cavalcante Santana, Pablinny Moreira Galdino, Elson Alves Costa, Ricardo Menegatti
The piperazine derivatives correspond to an extensive chemical class of compounds with numerous neuropharmacological activities, including antidepressant (e.g., nefazodone, trazodone) and anxiolytic (e.g., buspirone) properties. Therefore, aiming to identify a new antidepressant and antianxiety lead-compound, our group designed, synthesized, and investigated the effects of a new piperazine compound, namely, LQFM104, on the behavior of mice. Male albino Swiss mice were treated with LQFM104 prior to predictive behavioral tests as open field (OFT), elevated plus maze (EPM), forced swimming (FST), and tail suspension tests (TST)...
April 17, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29675950/risk-factors-for-red-blood-cell-alloimmunization-in-the-recipient-epidemiology-and-donor-evaluation-study-reds-iii-database
#15
Matthew S Karafin, Matt Westlake, Ronald G Hauser, Christopher A Tormey, Philip J Norris, Nareg H Roubinian, Yanyun Wu, Darrell J Triulzi, Steve Kleinman, Jeanne E Hendrickson
Despite the significance of red blood cell (RBC) alloimmunization, the lack of standardized registries in the US has prevented the completion of large studies. Data from 3·5 years of the Recipient Epidemiology and Donor Evaluation Study-III (REDS-III) recipient database, containing information from 12 hospitals, were studied. A RBC alloantibody responder had an antibody identified at any point during the study, and a non-responder had a negative antibody screen at least 15 days post-RBC transfusion. Demographics, blood type, ICD9/10 codes, and other potential correlates were evaluated...
April 19, 2018: British Journal of Haematology
https://www.readbyqxmd.com/read/29658114/proton-pump-inhibitor-use-and-cancer-mortality
#16
Siri A Tvingsholm, Christian Dehlendorff, Kell Østerlind, Søren Friis, Marja Jäättelä
Proton pump inhibitors (PPIs) are commonly used as a supplement to cancer therapy. Yet, their effect on cancer mortality is largely unknown. Using data from Danish nationwide registries and Cox models regressing of both propensity scores and drug use, we estimated hazard ratios (HRs) with 95% confidence intervals (CIs) for cancer-specific and noncancer death among PPI users (≥2 prescriptions within six months after diagnosis; n = 36,066) compared with nonusers (<2 prescriptions, n = 311,853) or users of histamine H2 -receptor antagonists (H2 RA; n = 5,152)...
April 15, 2018: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/29652631/-this-is-not-a-drill-activation-of-a-student-led-influenza-vaccination-point-of-distribution
#17
Lavonne M Adams, Sharon Canclini, Kelle Tillman
OBJECTIVE: To describe activation of a Point of Distribution (POD) in response to an influenza outbreak, highlighting the use of a student-led model. PARTICIPANTS: Faculty, staff, and students of X College of Nursing and Health Sciences, X University, as well as those located in its primary building. METHODS: In response to an August 2017 influenza outbreak, a vaccination clinic was conducted for a target population through POD activation...
April 13, 2018: Journal of American College Health: J of ACH
https://www.readbyqxmd.com/read/29643504/genome-evolution-across-1-011-saccharomyces-cerevisiae-isolates
#18
Jackson Peter, Matteo De Chiara, Anne Friedrich, Jia-Xing Yue, David Pflieger, Anders Bergström, Anastasie Sigwalt, Benjamin Barre, Kelle Freel, Agnès Llored, Corinne Cruaud, Karine Labadie, Jean-Marc Aury, Benjamin Istace, Kevin Lebrigand, Pascal Barbry, Stefan Engelen, Arnaud Lemainque, Patrick Wincker, Gianni Liti, Joseph Schacherer
Large-scale population genomic surveys are essential to explore the phenotypic diversity of natural populations. Here we report the whole-genome sequencing and phenotyping of 1,011 Saccharomyces cerevisiae isolates, which together provide an accurate evolutionary picture of the genomic variants that shape the species-wide phenotypic landscape of this yeast. Genomic analyses support a single 'out-of-China' origin for this species, followed by several independent domestication events. Although domesticated isolates exhibit high variation in ploidy, aneuploidy and genome content, genome evolution in wild isolates is mainly driven by the accumulation of single nucleotide polymorphisms...
April 11, 2018: Nature
https://www.readbyqxmd.com/read/29618664/macrophage-microrna-150-promotes-pathological-angiogenesis-as-seen-in-age-related-macular-degeneration
#19
Jonathan B Lin, Harsh V Moolani, Abdoulaye Sene, Rohini Sidhu, Pamela Kell, Joseph B Lin, Zhenyu Dong, Norimitsu Ban, Daniel S Ory, Rajendra S Apte
Macrophage aging is pathogenic in diseases of the elderly, including age-related macular degeneration (AMD), a leading cause of blindness in older adults. However, the role of microRNAs, which modulate immune processes, in regulating macrophage dysfunction and thereby promoting age-associated diseases is underexplored. Here, we report that microRNA-150 (miR-150) coordinates transcriptomic changes in aged murine macrophages, especially those associated with aberrant lipid trafficking and metabolism in AMD pathogenesis...
April 5, 2018: JCI Insight
https://www.readbyqxmd.com/read/29606020/hepatitis-b-reactivation-in-the-treatment-of-non-hodgkin-lymphoma
#20
Matthew Kelling, Lubomir Sokol, Samir Dalia
Chronic active hepatitis B infection (HBV) has been implicated in lymphomagenesis of non-Hodgkin lymphoma (NHL). Treatment of cancer including NHL with chemotherapy or immunotherapy can lead to HBV reactivation in previously infected patients. Serological testing of HBV prior to initiation of this therapy is recommended by several national and international medical agencies and expert panels. Patients with positive hepatitis B surface antigen (HBsAg) and anti-hepatitis B core antibody (anti-HBc ab) need to start antiviral therapy with entecavir or tenofovir prior to initiation of chemotherapy or immunotherapy and continue this treatment for 6 to 12 months after completion of cancer therapy to avoid late HBV reactivation...
January 2018: Cancer Control: Journal of the Moffitt Cancer Center
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