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David Sinclair

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
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
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
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
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
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
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
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
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
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
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
Michael S Bonkowski, David A Sinclair
The sirtuins (SIRT1-7) are a family of nicotinamide adenine dinucleotide (NAD(+))-dependent deacylases with remarkable abilities to prevent diseases and even reverse aspects of ageing. Mice engineered to express additional copies of SIRT1 or SIRT6, or treated with sirtuin-activating compounds (STACs) such as resveratrol and SRT2104 or with NAD(+) precursors, have improved organ function, physical endurance, disease resistance and longevity. Trials in non-human primates and in humans have indicated that STACs may be safe and effective in treating inflammatory and metabolic disorders, among others...
August 24, 2016: Nature Reviews. Molecular Cell Biology
Jeff Aston, Chi Huynh, Anthony Sinclair, Keith Wilson, David Terry
INTRODUCTION: Children on long term medication may be under the care of more than one medical team including the patients GP. Children on chronic medication should be supported and their medications reviewed, especially in cases of polypharmacy. Medicines Use Reviews (MURs) were introduced into the pharmacy contract in 2005. The service was designed for community pharmacists to review patients on long term medication. The service specified that MURs were done on patients who can give consent and cannot be conducted with a parent or carer...
September 2016: Archives of Disease in Childhood
David Terry, Konstantinos Petridis, Matt Aiello, Anthony Sinclair, Chi Huynh, Louis Mazard, Hirminder Ubhi, Alex Terry, Elizabeth Hughes
AIM: There have been concerns about maintaining appropriate clinical staff levels in Emergency Departments in England.1 The aim of this study was to determine if Emergency Department attendees aged from 0-16 years could be managed by community pharmacists or hospital independent prescriber pharmacists with or without further advanced clinical practice training. METHOD: A prospective, 48 site, cross-sectional, observational study of patients attending Emergency Departments (ED) in England, UK was conducted...
September 2016: Archives of Disease in Childhood
Derek McKay, David Armstrong, Daniel Sadowski, Nicola Jones, Wallace MacNaughton, Paul Sinclair
No abstract text is available yet for this article.
2016: Canadian Journal of Gastroenterology & Hepatology
Hosam Al-Jehani, Kevin Petrecca, Phillipe Martel, David Sinclair, Denis Sirhan
BACKGROUND: Decompressive hemicraniectomy (DhC) is a life-saving surgical procedure being increasingly employed for malignant middle cerebral artery strokes. We examined the incidence of hemorrhagic transformation following DhC. METHODS: We retrospectively reviewed the charts and radiological images of patients who underwent DhC for malignant middle cerebral artery strokes. We classified the hemorrhagic events and assessed the short-term 30-day outcome associated with these events...
September 2016: Journal of Stroke and Cerebrovascular Diseases: the Official Journal of National Stroke Association
James F Markworth, Gunveen Kaur, Eliza G Miller, Amy E Larsen, Andrew J Sinclair, Krishna Rao Maddipati, David Cameron-Smith
In contrast to the well-characterized effects of specialized proresolving lipid mediators (SPMs) derived from eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), little is known about the metabolic fate of the intermediary long-chain (LC) n-3 polyunsaturated fatty acid (PUFA) docosapentaenoic acid (DPA). In this double blind crossover study, shifts in circulating levels of n-3 and n-6 PUFA-derived bioactive lipid mediators were quantified by an unbiased liquid chromatography-tandem mass spectrometry lipidomic approach...
July 26, 2016: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Lin Xiao, David Ohayon, Ian A McKenzie, Alexander Sinclair-Wilson, Jordan L Wright, Alexander D Fudge, Ben Emery, Huiliang Li, William D Richardson
We identified mRNA encoding the ecto-enzyme Enpp6 as a marker of newly forming oligodendrocytes, and used Enpp6 in situ hybridization to track oligodendrocyte differentiation in adult mice as they learned a motor skill (running on a wheel with unevenly spaced rungs). Within just 2.5 h of exposure to the complex wheel, production of Enpp6-expressing immature oligodendrocytes was accelerated in subcortical white matter; within 4 h, it was accelerated in motor cortex. Conditional deletion of myelin regulatory factor (Myrf) in oligodendrocyte precursors blocked formation of new Enpp6(+) oligodendrocytes and impaired learning within the same ∼2-3 h time frame...
September 2016: Nature Neuroscience
Keneisha Sinclair-McBride, David A Cole
A sample of 353 community adolescents (grades 9 to 12, 57.6 % female) participated in a 2-wave longitudinal study of eating behaviors (overeating, loss of control eating [LOC], and binge eating) and depression. The study addresses 4 hypotheses. (1) The prospective relations between eating behaviors and depressive symptoms will be reciprocal, with each predicting the other over time. (2) These relations will be stronger for girls than for boys. (3) These relations will be stronger for adolescents with high (not low) body mass index (BMI)...
July 11, 2016: Journal of Abnormal Child Psychology
Bruce Mitchell, Paul Verrills, David Vivian, Neels DuToit, Adele Barnard, Chantelle Sinclair
OBJECTIVE: Relative to the number of patients suffering chronic lumbar and cervical pain, fewer patients suffer persistent thoracic pain. Consequently there is less literature, with smaller sample sizes, reporting treatment of this cohort. Here, we assess peripheral nerve field stimulation (PNfS) as a potential treatment for chronic thoracic pain. MATERIALS AND METHODS: This study included 20 consecutive chronic thoracic pain sufferers that responded successfully to PNfS trial...
July 4, 2016: Neuromodulation: Journal of the International Neuromodulation Society
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