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David Sinclair

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https://www.readbyqxmd.com/read/27918560/genome-wide-chemical-mapping-of-o-glcnacylated-proteins-in-drosophila-melanogaster
#1
Ta-Wei Liu, Mike Myschyshyn, Donald A Sinclair, Samy Cecioni, Kevin Beja, Barry M Honda, Ryan D Morin, David J Vocadlo
N-Acetylglucosamine β-O-linked to nucleocytoplasmic proteins (O-GlcNAc) is implicated in the regulation of gene expression in organisms, from humans to Drosophila melanogaster. Within Drosophila, O-GlcNAc transferase (OGT) is one of the Polycomb group proteins (PcGs) that act through Polycomb group response elements (PREs) to silence homeotic (HOX) and other PcG target genes. Using Drosophila, we identify new O-GlcNAcylated PcG proteins and develop an antibody-free metabolic feeding approach to chemoselectively map genomic loci enriched in O-GlcNAc using next-generation sequencing...
December 5, 2016: Nature Chemical Biology
https://www.readbyqxmd.com/read/27911441/sirt1-protects-the-heart-from-er-stress-induced-cell-death-through-eif2%C3%AE-deacetylation
#2
Alexandre Prola, Julie Pires Da Silva, Arnaud Guilbert, Lola Lecru, Jérôme Piquereau, Maxance Ribeiro, Philippe Mateo, Mélanie Gressette, Dominique Fortin, Céline Boursier, Cindy Gallerne, Anaïs Caillard, Jane-Lise Samuel, Hélène François, David A Sinclair, Pierre Eid, Renée Ventura-Clapier, Anne Garnier, Christophe Lemaire
Over the past decade, endoplasmic reticulum (ER) stress has emerged as an important mechanism involved in the pathogenesis of cardiovascular diseases including heart failure. Cardiac therapy based on ER stress modulation is viewed as a promising avenue toward effective therapies for the diseased heart. Here, we tested whether sirtuin-1 (SIRT1), a NAD(+)-dependent deacetylase, participates in modulating ER stress response in the heart. Using cardiomyocytes and adult-inducible SIRT1 knockout mice, we demonstrate that SIRT1 inhibition or deficiency increases ER stress-induced cardiac injury, whereas activation of SIRT1 by the SIRT1-activating compound STAC-3 is protective...
December 2, 2016: Cell Death and Differentiation
https://www.readbyqxmd.com/read/27899157/disorders-of-sex-development-insights-from-targeted-gene-sequencing-of-a-large-international-patient-cohort
#3
Stefanie Eggers, Simon Sadedin, Jocelyn A van den Bergen, Gorjana Robevska, Thomas Ohnesorg, Jacqueline Hewitt, Luke Lambeth, Aurore Bouty, Ingrid M Knarston, Tiong Yang Tan, Fergus Cameron, George Werther, John Hutson, Michele O'Connell, Sonia R Grover, Yves Heloury, Margaret Zacharin, Philip Bergman, Chris Kimber, Justin Brown, Nathalie Webb, Matthew F Hunter, Shubha Srinivasan, Angela Titmuss, Charles F Verge, David Mowat, Grahame Smith, Janine Smith, Lisa Ewans, Carolyn Shalhoub, Patricia Crock, Chris Cowell, Gary M Leong, Makato Ono, Antony R Lafferty, Tony Huynh, Uma Visser, Catherine S Choong, Fiona McKenzie, Nicholas Pachter, Elizabeth M Thompson, Jennifer Couper, Anne Baxendale, Jozef Gecz, Benjamin J Wheeler, Craig Jefferies, Karen MacKenzie, Paul Hofman, Philippa Carter, Richard I King, Csilla Krausz, Conny M A van Ravenswaaij-Arts, Leendert Looijenga, Sten Drop, Stefan Riedl, Martine Cools, Angelika Dawson, Achmad Zulfa Juniarto, Vaman Khadilkar, Anuradha Khadilkar, Vijayalakshmi Bhatia, Vũ Chí Dũng, Irum Atta, Jamal Raza, Nguyen Thi Diem Chi, Tran Kiem Hao, Vincent Harley, Peter Koopman, Garry Warne, Sultana Faradz, Alicia Oshlack, Katie L Ayers, Andrew H Sinclair
BACKGROUND: Disorders of sex development (DSD) are congenital conditions in which chromosomal, gonadal, or phenotypic sex is atypical. Clinical management of DSD is often difficult and currently only 13% of patients receive an accurate clinical genetic diagnosis. To address this we have developed a massively parallel sequencing targeted DSD gene panel which allows us to sequence all 64 known diagnostic DSD genes and candidate genes simultaneously. RESULTS: We analyzed DNA from the largest reported international cohort of patients with DSD (278 patients with 46,XY DSD and 48 with 46,XX DSD)...
November 29, 2016: Genome Biology
https://www.readbyqxmd.com/read/27869525/oxidative-priority-meal-frequency-and-the-energy-economy-of-food-and-activity-implications-for-longevity-obesity-and-cardiometabolic-disease
#4
Raymond J Cronise, David A Sinclair, Andrew A Bremer
In most modern societies, the relationship that many individuals have with food has fundamentally changed from previous generations. People have shifted away from viewing food as primarily sustenance, and rather now seek out foods based on pure palatability or specific nutrition. However, it is far from clear what optimal nutrition is for the general population or specific individuals. We previously described the Food Triangle as a way to organize food based on an increasing energy density paradigm, and now expand on this model to predict the impact of oxidative priority and both nutrient and fiber density in relation to caloric load...
November 21, 2016: Metabolic Syndrome and related Disorders
https://www.readbyqxmd.com/read/27859665/attentional-biases-in-patients-with-alcohol-dependence-influence-of-coexisting-psychopathology
#5
Julia M A Sinclair, Matthew Garner, Sonja C Pasche, Thomas B Wood, David S Baldwin
OBJECTIVE: The effects of coexisting psychopathology on disorder-specific attentional biases in patients with alcohol dependence are uncertain. We undertook a cross-sectional study assessing attentional biases to alcohol-, depression-, and anxiety- related stimuli using the visual probe task in patients with alcohol dependence, attending a community alcohol service. METHODS: Using the visual probe task, we presented disorder-specific words (relating to alcohol, anxiety, and depression) for 500 ms and measured reaction times...
November 2016: Human Psychopharmacology
https://www.readbyqxmd.com/read/27836286/acylcarnitine-profiles-reflect-metabolic-vulnerability-for-necrotizing-enterocolitis-in-newborns-born-premature
#6
Karl G Sylvester, Zachary J Kastenberg, R Larry Moss, Gregory M Enns, Tina M Cowan, Gary M Shaw, David K Stevenson, Tiffany J Sinclair, Curt Scharfe, Kelli K Ryckman, Laura L Jelliffe-Pawlowski
OBJECTIVE: To evaluate the association between newborn acylcarnitine profiles and the subsequent development of necrotizing enterocolitis (NEC) with the use of routinely collected newborn screening data in infants born preterm. STUDY DESIGN: A retrospective cohort study was conducted with the use of discharge records for infants born preterm admitted to neonatal intensive care units in California from 2005 to 2009 who had linked state newborn screening results. A model-development cohort of 94 110 preterm births from 2005 to 2008 was used to develop a risk-stratification model that was then applied to a validation cohort of 22 992 births from 2009...
November 8, 2016: Journal of Pediatrics
https://www.readbyqxmd.com/read/27834380/hierarchical-zwitterionic-modification-of-a-sers-substrate-enables-real-time-drug-monitoring-in-blood-plasma
#7
Fang Sun, Hsiang-Chieh Hung, Andrew Sinclair, Peng Zhang, Tao Bai, Daniel David Galvan, Priyesh Jain, Bowen Li, Shaoyi Jiang, Qiuming Yu
Surface-enhanced Raman spectroscopy (SERS) is an ultrasensitive analytical technique with molecular specificity, making it an ideal candidate for therapeutic drug monitoring (TDM). However, in critical diagnostic media including blood, nonspecific protein adsorption coupled with weak surface affinities and small Raman activities of many analytes hinder the TDM application of SERS. Here we report a hierarchical surface modification strategy, first by coating a gold surface with a self-assembled monolayer (SAM) designed to attract or probe for analytes and then by grafting a non-fouling zwitterionic polymer brush layer to effectively repel protein fouling...
November 11, 2016: Nature Communications
https://www.readbyqxmd.com/read/27824221/school-based-interventions-for-preventing-hiv-sexually-transmitted-infections-and-pregnancy-in-adolescents
#8
REVIEW
Amanda J Mason-Jones, David Sinclair, Catherine Mathews, Ashraf Kagee, Alex Hillman, Carl Lombard
BACKGROUND: School-based sexual and reproductive health programmes are widely accepted as an approach to reducing high-risk sexual behaviour among adolescents. Many studies and systematic reviews have concentrated on measuring effects on knowledge or self-reported behaviour rather than biological outcomes, such as pregnancy or prevalence of sexually transmitted infections (STIs). OBJECTIVES: To evaluate the effects of school-based sexual and reproductive health programmes on sexually transmitted infections (such as HIV, herpes simplex virus, and syphilis), and pregnancy among adolescents...
November 8, 2016: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/27770718/a-framework-for-combining-a-motion-atlas-with-non-motion-information-to-learn-clinically-useful-biomarkers-application-to-cardiac-resynchronisation-therapy-response-prediction
#9
Devis Peressutti, Matthew Sinclair, Wenjia Bai, Thomas Jackson, Jacobus Ruijsink, David Nordsletten, Liya Asner, Myrianthi Hadjicharalambous, Christopher A Rinaldi, Daniel Rueckert, Andrew P King
We present a framework for combining a cardiac motion atlas with non-motion data. The atlas represents cardiac cycle motion across a number of subjects in a common space based on rich motion descriptors capturing 3D displacement, velocity, strain and strain rate. The non-motion data are derived from a variety of sources such as imaging, electrocardiogram (ECG) and clinical reports. Once in the atlas space, we apply a novel supervised learning approach based on random projections and ensemble learning to learn the relationship between the atlas data and some desired clinical output...
October 11, 2016: Medical Image Analysis
https://www.readbyqxmd.com/read/27732836/nad-replenishment-improves-lifespan-and-healthspan-in-ataxia-telangiectasia-models-via-mitophagy-and-dna-repair
#10
Evandro Fei Fang, Henok Kassahun, Deborah L Croteau, Morten Scheibye-Knudsen, Krisztina Marosi, Huiming Lu, Raghavendra A Shamanna, Sumana Kalyanasundaram, Ravi Chand Bollineni, Mark A Wilson, Wendy B Iser, Bradley N Wollman, Marya Morevati, Jun Li, Jesse S Kerr, Qiping Lu, Tyler B Waltz, Jane Tian, David A Sinclair, Mark P Mattson, Hilde Nilsen, Vilhelm A Bohr
Ataxia telangiectasia (A-T) is a rare autosomal recessive disease characterized by progressive neurodegeneration and cerebellar ataxia. A-T is causally linked to defects in ATM, a master regulator of the response to and repair of DNA double-strand breaks. The molecular basis of cerebellar atrophy and neurodegeneration in A-T patients is unclear. Here we report and examine the significance of increased PARylation, low NAD(+), and mitochondrial dysfunction in ATM-deficient neurons, mice, and worms. Treatments that replenish intracellular NAD(+) reduce the severity of A-T neuropathology, normalize neuromuscular function, delay memory loss, and extend lifespan in both animal models...
October 11, 2016: Cell Metabolism
https://www.readbyqxmd.com/read/27681670/nutrient-sensing-signal-transduction-and-immune-responses
#11
Jessica Walls, Linda Sinclair, David Finlay
Most cells in the body have a constant supply of nutrients, which are required to sustain cellular metabolism and functions. In contrast, cells of the immune system can encounter conditions with a limited nutrient supply during the course of an immune response. Cells of the immune system frequently operate in complex nutrient restricted microenvironments such as tumour or inflammatory sites. The concentrations of key nutrients such as glucose and certain amino acids, can be low at these sites, and this can have an impact upon immune cell function...
September 24, 2016: Seminars in Immunology
https://www.readbyqxmd.com/read/27667778/can-we-predict-ectotherm-responses-to-climate-change-using-thermal-performance-curves-and-body-temperatures
#12
Brent J Sinclair, Katie E Marshall, Mary A Sewell, Danielle L Levesque, Christopher S Willett, Stine Slotsbo, Yunwei Dong, Christopher D G Harley, David J Marshall, Brian S Helmuth, Raymond B Huey
Thermal performance curves (TPCs), which quantify how an ectotherm's body temperature (Tb ) affects its performance or fitness, are often used in an attempt to predict organismal responses to climate change. Here, we examine the key - but often biologically unreasonable - assumptions underlying this approach; for example, that physiology and thermal regimes are invariant over ontogeny, space and time, and also that TPCs are independent of previously experienced Tb. We show how a critical consideration of these assumptions can lead to biologically useful hypotheses and experimental designs...
November 2016: Ecology Letters
https://www.readbyqxmd.com/read/27647053/community-wide-interventions-to-prevent-skin-cancer-two-community-guide-systematic-reviews
#13
REVIEW
Paramjit K Sandhu, Randy Elder, Mona Patel, Mona Saraiya, Dawn M Holman, Frank Perna, Robert A Smith, David Buller, Craig Sinclair, Anthony Reeder, Jennifer Makin, Bronwen McNoe, Karen Glanz
CONTEXT: Skin cancer is a preventable and commonly diagnosed cancer in the U.S. Excessive ultraviolet radiation exposure is a known cause of skin cancer. This article presents updated results of two types of interventions evaluated in a previously published Community Guide systematic review: multicomponent community-wide interventions and mass media interventions when used alone. EVIDENCE ACQUISITION: Studies assessing multicomponent community-wide and mass media interventions to prevent skin cancer by reducing ultraviolet radiation exposure were evaluated using Community Guide systematic review methods...
October 2016: American Journal of Preventive Medicine
https://www.readbyqxmd.com/read/27630125/epigenetic-reprogramming-sensitizes-cml-stem-cells-to-combined-ezh2-and-tyrosine-kinase-inhibition
#14
Mary T Scott, Koorosh Korfi, Peter Saffrey, Lisa E M Hopcroft, Ross Kinstrie, Francesca Pellicano, Carla Guenther, Paolo Gallipoli, Michelle Cruz, Karen Dunn, Heather G Jorgensen, Jennifer E Cassels, Ashley Hamilton, Andrew Crossan, Amy Sinclair, Tessa L Holyoake, David Vetrie
: A major obstacle to curing chronic myeloid leukemia (CML) is residual disease maintained by tyrosine kinase inhibitor (TKI)-persistent leukemic stem cells (LSC). These are BCR-ABL1 kinase independent, refractory to apoptosis, and serve as a reservoir to drive relapse or TKI resistance. We demonstrate that Polycomb Repressive Complex 2 is misregulated in chronic phase CML LSCs. This is associated with extensive reprogramming of H3K27me3 targets in LSCs, thus sensitizing them to apoptosis upon treatment with an EZH2-specific inhibitor (EZH2i)...
September 14, 2016: Cancer Discovery
https://www.readbyqxmd.com/read/27625062/influenza-vaccination-for-healthcare-workers-in-the-uk-appraisal-of-systematic-reviews-and-policy-options
#15
Merav Kliner, Alex Keenan, David Sinclair, Sam Ghebrehewet, Paul Garner
BACKGROUND: The UK Department of Health recommends annual influenza vaccination for healthcare workers, but uptake remains low. For staff, there is uncertainty about the rationale for vaccination and evidence underpinning the recommendation. OBJECTIVES: To clarify the rationale, and evidence base, for influenza vaccination of healthcare workers from the occupational health, employer and patient safety perspectives. DESIGN: Systematic appraisal of published systematic reviews...
September 13, 2016: BMJ Open
https://www.readbyqxmd.com/read/27594836/head-to-head-comparison-of-short-term-treatment-with-the-nad-precursor-nicotinamide-mononucleotide-nmn-and-6-weeks-of-exercise-in-obese-female-mice
#16
Golam M Uddin, Neil A Youngson, David A Sinclair, Margaret J Morris
Obesity is well known to be a major cause of several chronic metabolic diseases, which can be partially counteracted by exercise. This is due, in part, to an upregulation of mitochondrial activity through increased nicotinamide adenine dinucleotide (NAD(+)). Recent studies have shown that NAD(+) levels can be increased by using the NAD(+) precursor, nicotinamide mononucleotide (NMN) leading to the suggestion that NMN could be a useful intervention in diet related metabolic disorders. In this study we compared the metabolic, and especially mitochondrial-associated, effects of exercise and NMN in ameliorating the consequences of high-fat diet (HFD) induced obesity in mice...
2016: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/27581336/ibis-an-or-ready-open-source-platform-for-image-guided-neurosurgery
#17
Simon Drouin, Anna Kochanowska, Marta Kersten-Oertel, Ian J Gerard, Rina Zelmann, Dante De Nigris, Silvain Bériault, Tal Arbel, Denis Sirhan, Abbas F Sadikot, Jeffery A Hall, David S Sinclair, Kevin Petrecca, Rolando F DelMaestro, D Louis Collins
PURPOSE: Navigation systems commonly used in neurosurgery suffer from two main drawbacks: (1) their accuracy degrades over the course of the operation and (2) they require the surgeon to mentally map images from the monitor to the patient. In this paper, we introduce the Intraoperative Brain Imaging System (IBIS), an open-source image-guided neurosurgery research platform that implements a novel workflow where navigation accuracy is improved using tracked intraoperative ultrasound (iUS) and the visualization of navigation information is facilitated through the use of augmented reality (AR)...
August 31, 2016: International Journal of Computer Assisted Radiology and Surgery
https://www.readbyqxmd.com/read/27572110/impact-of-abnormal-cerebrovascular-reactivity-on-bold-fmri-a-preliminary-investigation-of-moyamoya-disease
#18
Erin L Mazerolle, Yuhan Ma, David Sinclair, G Bruce Pike
Blood oxygen level-dependent (BOLD) functional magnetic resonance imaging (fMRI) studies of patients with cerebrovascular disease have largely ignored the confounds associated with abnormal cerebral blood flow, vascular reactivity and neurovascular coupling. We studied BOLD fMRI activation and cerebrovascular reactivity in moyamoya disease. To characterize the impact of remote vascular demands on BOLD fMRI measurements, we varied the vascular territories engaged by manipulating the experimental task performed by the participants...
August 30, 2016: Clinical Physiology and Functional Imaging
https://www.readbyqxmd.com/read/27568560/jnk-phosphorylates-sirt6-to-stimulate-dna-double-strand-break-repair-in-response-to-oxidative-stress-by-recruiting-parp1-to-dna-breaks
#19
Michael Van Meter, Matthew Simon, Gregory Tombline, Alfred May, Timothy D Morello, Basil P Hubbard, Katie Bredbenner, Rosa Park, David A Sinclair, Vilhelm A Bohr, Vera Gorbunova, Andrei Seluanov
The accumulation of damage caused by oxidative stress has been linked to aging and to the etiology of numerous age-related diseases. The longevity gene, sirtuin 6 (SIRT6), promotes genome stability by facilitating DNA repair, especially under oxidative stress conditions. Here we uncover the mechanism by which SIRT6 is activated by oxidative stress to promote DNA double-strand break (DSB) repair. We show that the stress-activated protein kinase, c-Jun N-terminal kinase (JNK), phosphorylates SIRT6 on serine 10 in response to oxidative stress...
September 6, 2016: Cell Reports
https://www.readbyqxmd.com/read/27565625/representativeness-of-the-participants-in-the-smoking-cessation-in-pregnancy-incentives-trial-cpit-a-cross-sectional-study
#20
Barnabas Bessing, Linda Bauld, Lesley Sinclair, Daniel F Mackay, William Spence, David M Tappin
BACKGROUND: The limited representativeness of trial samples may restrict external validity. The aim of this study was to ascertain the representativeness of the population enrolled in the Cessation in Pregnancy Incentives Trial (CPIT), a therapeutic exploratory study to examine the effectiveness of financial incentives for smoking cessation during pregnancy. METHODS: CPIT participants (n = 492) were compared with all self-reported smokers at maternity booking who did not participate in the trial (n = 1982)...
2016: Trials
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