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And Lover Disease

Frederico Gerlinger-Romero, Alex B Addinsall, Richard M Lovering, Victoria C Foletta, Chris van der Poel, Paul A Della-Gatta, Aaron P Russell
Assessment of skeletal muscle contractile function is an important measurement for both clinical and research purposes. Numerous conditions can negatively affect skeletal muscle. This can result in a loss of muscle mass (atrophy) and/or loss of muscle quality (reduced force per unit of muscle mass), both of which are prevalent in chronic disease, muscle-specific disease, immobilization, and aging (sarcopenia). Skeletal muscle function in animals can be evaluated by a range of different tests. All tests have limitations related to the physiological testing environment, and the selection of a specific test often depends on the nature of the experiments...
January 17, 2019: Journal of Visualized Experiments: JoVE
Nirmal Vadgama, Douglas Lamont, John Hardy, Jamal Nasir, Ruth C Lovering
Stroke is a common disorder with significant morbidity and mortality, and complex aetiology involving both environmental and genetic risk factors. Although some of the major risk factors for stoke, such as smoking and hypertension, are well-documented, the underlying genetic and detailed molecular mechanisms remain elusive. Exploring the relevant biochemical pathways may contribute to the clinical diagnosis of stroke and shed light on its aetiology. A comparative proteomic analysis of blood serum of a pair of monozygotic (MZ) twins discordant for ischaemic stroke (IS) was performed using a label-free quantitative proteomics approach...
January 29, 2019: Molecular and Cellular Biochemistry
Toshio Tanaka, Atsuhiko Iuchi, Hiroshi Harada, Shoji Hashimoto
Wine, a widely consumed beverage, comprises several biophenols that promote health. Flavonoids, majorly present in red wine, have been shown to have antioxidant, anti-inflammatory, anticancer, and immunomodulatory activities. Regular consumption of red wine (100 mL/day) is estimated to provide an average of 88 mg of flavonoids, whereas recent epidemiological studies indicate that wine is one of the major sources of flavonoid intake amongst wine lovers in European countries (providing an average intake of 291⁻374 mg/day of flavonoids)...
January 15, 2019: Diseases (Basel)
V Michailowsky, H Li, B Mittra, S R Iyer, D A G Mazála, M Corrotte, Y Wang, E R Chin, R M Lovering, N W Andrews
BACKGROUND: Niemann-Pick disease type A (NPDA), a disease caused by mutations in acid sphingomyelinase (ASM), involves severe neurodegeneration and early death. Intracellular lipid accumulation and plasma membrane alterations are implicated in the pathology. ASM is also linked to the mechanism of plasma membrane repair, so we investigated the impact of ASM deficiency in skeletal muscle, a tissue that undergoes frequent cycles of injury and repair in vivo. METHODS: Utilizing the NPDA/B mouse model ASM-/- and wild type (WT) littermates, we performed excitation-contraction coupling/Ca2+ mobilization and sarcolemma injury/repair assays with isolated flexor digitorum brevis fibers, proteomic analyses with quadriceps femoris, flexor digitorum brevis, and tibialis posterior muscle and in vivo tests of the contractile force (maximal isometric torque) of the quadriceps femoris muscle before and after eccentric contraction-induced muscle injury...
January 5, 2019: Skeletal Muscle
Nora Franceschini, Claudia Giambartolomei, Paul S de Vries, Chris Finan, Joshua C Bis, Rachael P Huntley, Ruth C Lovering, Salman M Tajuddin, Thomas W Winkler, Misa Graff, Maryam Kavousi, Caroline Dale, Albert V Smith, Edith Hofer, Elisabeth M van Leeuwen, Ilja M Nolte, Lingyi Lu, Markus Scholz, Muralidharan Sargurupremraj, Niina Pitkänen, Oscar Franzén, Peter K Joshi, Raymond Noordam, Riccardo E Marioni, Shih-Jen Hwang, Solomon K Musani, Ulf Schminke, Walter Palmas, Aaron Isaacs, Adolfo Correa, Alan B Zonderman, Albert Hofman, Alexander Teumer, Amanda J Cox, André G Uitterlinden, Andrew Wong, Andries J Smit, Anne B Newman, Annie Britton, Arno Ruusalepp, Bengt Sennblad, Bo Hedblad, Bogdan Pasaniuc, Brenda W Penninx, Carl D Langefeld, Christina L Wassel, Christophe Tzourio, Cristiano Fava, Damiano Baldassarre, Daniel H O'Leary, Daniel Teupser, Diana Kuh, Elena Tremoli, Elmo Mannarino, Enzo Grossi, Eric Boerwinkle, Eric E Schadt, Erik Ingelsson, Fabrizio Veglia, Fernando Rivadeneira, Frank Beutner, Ganesh Chauhan, Gerardo Heiss, Harold Snieder, Harry Campbell, Henry Völzke, Hugh S Markus, Ian J Deary, J Wouter Jukema, Jacqueline de Graaf, Jacqueline Price, Janne Pott, Jemma C Hopewell, Jingjing Liang, Joachim Thiery, Jorgen Engmann, Karl Gertow, Kenneth Rice, Kent D Taylor, Klodian Dhana, Lambertus A L M Kiemeney, Lars Lind, Laura M Raffield, Lenore J Launer, Lesca M Holdt, Marcus Dörr, Martin Dichgans, Matthew Traylor, Matthias Sitzer, Meena Kumari, Mika Kivimaki, Mike A Nalls, Olle Melander, Olli Raitakari, Oscar H Franco, Oscar L Rueda-Ochoa, Panos Roussos, Peter H Whincup, Philippe Amouyel, Philippe Giral, Pramod Anugu, Quenna Wong, Rainer Malik, Rainer Rauramaa, Ralph Burkhardt, Rebecca Hardy, Reinhold Schmidt, Renée de Mutsert, Richard W Morris, Rona J Strawbridge, S Goya Wannamethee, Sara Hägg, Sonia Shah, Stela McLachlan, Stella Trompet, Sudha Seshadri, Sudhir Kurl, Susan R Heckbert, Susan Ring, Tamara B Harris, Terho Lehtimäki, Tessel E Galesloot, Tina Shah, Ulf de Faire, Vincent Plagnol, Wayne D Rosamond, Wendy Post, Xiaofeng Zhu, Xiaoling Zhang, Xiuqing Guo, Yasaman Saba, Abbas Dehghan, Adrie Seldenrijk, Alanna C Morrison, Anders Hamsten, Bruce M Psaty, Cornelia M van Duijn, Deborah A Lawlor, Dennis O Mook-Kanamori, Donald W Bowden, Helena Schmidt, James F Wilson, James G Wilson, Jerome I Rotter, Joanna M Wardlaw, John Deanfield, Julian Halcox, Leo-Pekka Lyytikäinen, Markus Loeffler, Michele K Evans, Stéphanie Debette, Steve E Humphries, Uwe Völker, Vilmundur Gudnason, Aroon D Hingorani, Johan L M Björkegren, Juan P Casas, Christopher J O'Donnell
Carotid artery intima media thickness (cIMT) and carotid plaque are measures of subclinical atherosclerosis associated with ischemic stroke and coronary heart disease (CHD). Here, we undertake meta-analyses of genome-wide association studies (GWAS) in 71,128 individuals for cIMT, and 48,434 individuals for carotid plaque traits. We identify eight novel susceptibility loci for cIMT, one independent association at the previously-identified PINX1 locus, and one novel locus for carotid plaque. Colocalization analysis with nearby vascular expression quantitative loci (cis-eQTLs) derived from arterial wall and metabolic tissues obtained from patients with CHD identifies candidate genes at two potentially additional loci, ADAMTS9 and LOXL4...
December 3, 2018: Nature Communications
Barbara Kramarz, Paola Roncaglia, Birgit H M Meldal, Rachael P Huntley, Maria J Martin, Sandra Orchard, Helen Parkinson, David Brough, Rina Bandopadhyay, Nigel M Hooper, Ruth C Lovering
The analysis and interpretation of high-throughput datasets relies on access to high-quality bioinformatics resources, as well as processing pipelines and analysis tools. Gene Ontology (GO, is a major resource for gene enrichment analysis. The aim of this project, funded by the Alzheimer's Research United Kingdom (ARUK) foundation and led by the University College London (UCL) biocuration team, was to enhance the GO resource by developing new neurological GO terms, and use GO terms to annotate gene products associated with dementia...
November 29, 2018: Genes
Sebastian Köhler, Leigh Carmody, Nicole Vasilevsky, Julius O B Jacobsen, Daniel Danis, Jean-Philippe Gourdine, Michael Gargano, Nomi L Harris, Nicolas Matentzoglu, Julie A McMurry, David Osumi-Sutherland, Valentina Cipriani, James P Balhoff, Tom Conlin, Hannah Blau, Gareth Baynam, Richard Palmer, Dylan Gratian, Hugh Dawkins, Michael Segal, Anna C Jansen, Ahmed Muaz, Willie H Chang, Jenna Bergerson, Stanley J F Laulederkind, Zafer Yüksel, Sergi Beltran, Alexandra F Freeman, Panagiotis I Sergouniotis, Daniel Durkin, Andrea L Storm, Marc Hanauer, Michael Brudno, Susan M Bello, Murat Sincan, Kayli Rageth, Matthew T Wheeler, Renske Oegema, Halima Lourghi, Maria G Della Rocca, Rachel Thompson, Francisco Castellanos, James Priest, Charlotte Cunningham-Rundles, Ayushi Hegde, Ruth C Lovering, Catherine Hajek, Annie Olry, Luigi Notarangelo, Morgan Similuk, Xingmin A Zhang, David Gómez-Andrés, Hanns Lochmüller, Hélène Dollfus, Sergio Rosenzweig, Shruti Marwaha, Ana Rath, Kathleen Sullivan, Cynthia Smith, Joshua D Milner, Dorothée Leroux, Cornelius F Boerkoel, Amy Klion, Melody C Carter, Tudor Groza, Damian Smedley, Melissa A Haendel, Chris Mungall, Peter N Robinson
The Human Phenotype Ontology (HPO)-a standardized vocabulary of phenotypic abnormalities associated with 7000+ diseases-is used by thousands of researchers, clinicians, informaticians and electronic health record systems around the world. Its detailed descriptions of clinical abnormalities and computable disease definitions have made HPO the de facto standard for deep phenotyping in the field of rare disease. The HPO's interoperability with other ontologies has enabled it to be used to improve diagnostic accuracy by incorporating model organism data...
November 22, 2018: Nucleic Acids Research
Tilahun Nigatu Haregu, Frederick M Wekesah, Shukri F Mohamed, Martin K Mutua, Gershim Asiki, Catherine Kyobutungi
BACKGROUND: Non-communicable diseases and unintentional injuries are emerging public health problems in sub-Saharan Africa. These threats have multiple risk factors with complex interactions. Though some studies have explored the magnitude and distribution of those risk factors in many populations in Kenya, an exploration of segmentation of population at a national level by risk profile, which is crucial for a differentiated approach, is currently lacking. The aim of this study was to examine patterns of non-communicable disease and injury risk through the identification of clusters and investigation of correlates of those clusters among Kenyan adult population...
November 7, 2018: BMC Public Health
Steven H Abman, Andrew T Lovering, Bradley A Maron
No abstract text is available yet for this article.
July 18, 2018: American Journal of Respiratory and Critical Care Medicine
Raffaele Ferrari, Demis A Kia, James E Tomkins, John Hardy, Nicholas W Wood, Ruth C Lovering, Patrick A Lewis, Claudia Manzoni
BACKGROUND: Genome wide association studies (GWAS) have helped identify large numbers of genetic loci that significantly associate with increased risk of developing diseases. However, translating genetic knowledge into understanding of the molecular mechanisms underpinning disease (i.e. disease-specific impacted biological processes) has to date proved to be a major challenge. This is primarily due to difficulties in confidently defining candidate genes at GWAS-risk loci. The goal of this study was to better characterize candidate genes within GWAS loci using a protein interactome based approach and with Parkinson's disease (PD) data as a test case...
June 13, 2018: BMC Genomics
Rachael P Huntley, Barbara Kramarz, Tony Sawford, Zara Umrao, Anastasia Kalea, Vanessa Acquaah, Maria J Martin, Manuel Mayr, Ruth C Lovering
MicroRNA regulation of key biological and developmental pathways is a rapidly expanding area of research, accompanied by vast amounts of experimental data. This data, however, is not widely available in bioinformatic resources, making it difficult for researchers to find and analyze microRNA-related experimental data and define further research projects. We are addressing this problem by providing two new bioinformatics data sets that contain experimentally verified functional information for mammalian microRNAs involved in cardiovascular-relevant, and other, processes...
August 2018: RNA
Andrew A Lover, Emily Dantzer, Bouasy Hongvanthong, Keobouphaphone Chindavongsa, Susie Welty, Tania Reza, Nimol Khim, Didier Menard, Adam Bennett
BACKGROUND: Lao People Democratic Republic (PDR; Laos), a landlocked country in Southeast Asia, has made important progress in reducing malaria morbidity and mortality in the past 5-6 years, and the northern provinces have very low reported incidence. To support national progress towards elimination, it is critical to verify and understand these changes in disease burden. METHODS: A two-stage cluster cross-sectional survey was conducted in four districts within four northern provinces (Khua, Phongsaly Province; Paktha, Bokeo Province; Nambak, Luang Prabang, and Muang Et, Huaphanh Province)...
June 1, 2018: Malaria Journal
Adam J Chicco, Catherine H Le, Erich Gnaiger, Hans C Dreyer, Jonathan B Muyskens, Angelo D'Alessandro, Travis Nemkov, Austin D Hocker, Jessica E Prenni, Lisa M Wolfe, Nathan M Sindt, Andrew T Lovering, Andrew W Subudhi, Robert C Roach
Metabolic responses to hypoxia play important roles in cell survival strategies and disease pathogenesis in humans. However, the homeostatic adjustments that balance changes in energy supply and demand to maintain organismal function under chronic low oxygen conditions remain incompletely understood, making it difficult to distinguish adaptive from maladaptive responses in hypoxia-related pathologies. We integrated metabolomic and proteomic profiling with mitochondrial respirometry and blood gas analyses to comprehensively define the physiological responses of skeletal muscle energy metabolism to 16 days of high-altitude hypoxia (5260 m) in healthy volunteers from the AltitudeOmics project...
May 4, 2018: Journal of Biological Chemistry
Paul Denny, Marc Feuermann, David P Hill, Ruth C Lovering, Helene Plun-Favreau, Paola Roncaglia
Autophagy is a fundamental cellular process that is well conserved among eukaryotes. It is one of the strategies that cells use to catabolize substances in a controlled way. Autophagy is used for recycling cellular components, responding to cellular stresses and ridding cells of foreign material. Perturbations in autophagy have been implicated in a number of pathological conditions such as neurodegeneration, cardiac disease and cancer. The growing knowledge about autophagic mechanisms needs to be collected in a computable and shareable format to allow its use in data representation and interpretation...
2018: Autophagy
Ruth C Lovering, Paola Roncaglia, Douglas G Howe, Stanley J F Laulederkind, Varsha K Khodiyar, Tanya Z Berardini, Susan Tweedie, Rebecca E Foulger, David Osumi-Sutherland, Nancy H Campbell, Rachael P Huntley, Philippa J Talmud, Judith A Blake, Ross Breckenridge, Paul R Riley, Pier D Lambiase, Perry M Elliott, Lucie Clapp, Andrew Tinker, David P Hill
BACKGROUND: A systems biology approach to cardiac physiology requires a comprehensive representation of how coordinated processes operate in the heart, as well as the ability to interpret relevant transcriptomic and proteomic experiments. The Gene Ontology (GO) Consortium provides structured, controlled vocabularies of biological terms that can be used to summarize and analyze functional knowledge for gene products. METHODS AND RESULTS: In this study, we created a computational resource to facilitate genetic studies of cardiac physiology by integrating literature curation with attention to an improved and expanded ontological representation of heart processes in the Gene Ontology...
February 2018: Circulation. Genomic and Precision Medicine
Frank Lovering, Paul Morgan, Christophe Allais, Ann Aulabaugh, Joanne Brodfuehrer, Jeanne Chang, Jotham Coe, WeiDong Ding, Heather Dowty, Margaret Fleming, Richard Frisbie, Julia Guzova, David Hepworth, Jayasankar Jasti, Steve Kortum, Ravi Kurumbail, Shashi Mohan, Nikolaos Papaioannou, Joseph W Strohbach, Fabien Vincent, Katherine Lee, Christoph W Zapf
Many diseases are believed to be driven by pathological levels of reactive oxygen species (ROS) and oxidative stress has long been recognized as a driver for inflammatory disorders. Apoptosis signal-regulating kinase 1 (ASK1) has been reported to be activated by intracellular ROS and its inhibition leads to a down regulation of p38-and JNK-dependent signaling. Consequently, ASK1 inhibitors may have the potential to treat clinically important inflammatory pathologies including renal, pulmonary and liver diseases...
February 10, 2018: European Journal of Medicinal Chemistry
Joseph W Duke, Igor M Gladstone, A William Sheel, Andrew T Lovering
What is the central question of this study? Adult survivors of preterm birth without (PRE) and with bronchopulmonary dysplasia (BPD) have airflow obstruction at rest and significant mechanical ventilatory constraints during exercise compared with those born at full term (CON). Do PRE/BPD have smaller airways, indexed via the dysanapsis ratio, than CON? What is the main finding and its importance? The dysanapsis ratio was significantly smaller in BPD and PRE compared with CON, with BPD having the smallest dysanapsis ratio...
February 1, 2018: Experimental Physiology
Aleksandra I Czerw, Urszula Religioni, Andrzej Deptała, Adam Fronczak
Introduction: Prostate cancer is the second most common type of carcinoma in men. The rate of prostate cancer has increased approximately fivefold lover the last 30 years. The purpose of the study was to evaluate coping strategies, pain management, illness acceptance, and adjustment to cancer in patients diagnosed with prostate carcinoma and the effect of socioeconomic variables on the above-mentioned issues. Material and methods: The study included 228 patients diagnosed with prostate cancer...
October 2017: Archives of Medical Science: AMS
Mohammad M Sultan, Rajiah Aldrin Denny, Ray Unwalla, Frank Lovering, Vijay S Pande
Bruton tyrosine kinase (BTK) is a key enzyme in B-cell development whose improper regulation causes severe immunodeficiency diseases. Design of selective BTK therapeutics would benefit from improved, in-silico structural modeling of the kinase's solution ensemble. However, this remains challenging due to the immense computational cost of sampling events on biological timescales. In this work, we combine multi-millisecond molecular dynamics (MD) simulations with Markov state models (MSMs) to report on the thermodynamics, kinetics, and accessible states of BTK's kinase domain...
November 15, 2017: Scientific Reports
Stephen J P Pratt, Shama R Iyer, Sameer B Shah, Richard M Lovering
Duchenne muscular dystrophy (DMD), caused by the absence of the protein dystrophin, is characterized as a neuromuscular disease in which muscle weakness, increased susceptibility to muscle injury, and inadequate repair appear to underlie the pathology. Considerable attention has been dedicated to studying muscle fiber damage, but there is little information to determine if damage from contraction-induced injury also occurs at or near the nerve terminal axon. Interestingly, both human patients and the mouse model for DMD (the mdx mouse) present fragmented neuromuscular junction (NMJ) morphology...
2018: Methods in Molecular Biology
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