Read by QxMD icon Read


Sandra Donkervoort, Sophelia H S Chan, Leslie H Hayes, Nathaniel Bradley, David Nguyen, Meganne E Leach, Payam Mohassel, Ying Hu, Mathula Thangarajh, Diana Bharucha-Goebel, Amanda Kan, Ronnie S L Ho, Christine A Reyes, Jessica Nance, Steven A Moore, A Reghan Foley, Carsten G Bönnemann
Mutations in ACTA1 cause a group of myopathies with expanding clinical and histopathological heterogeneity. We describe three patients with severe ACTA1-related myopathy who have muscle fiber cytoplasmic bodies but no classic nemaline rods. Patient 1 is a five-year-old boy who presented at birth with severe weakness and respiratory failure, requiring mechanical ventilation. Whole exome sequencing identified a heterozygous c.282C>A (p.Asn94Lys) ACTA1 mutation. Patients 2 and 3 were twin boys with hypotonia, severe weakness, and respiratory insufficiency at birth requiring mechanical ventilation...
March 2, 2017: Neuromuscular Disorders: NMD
Nanna Witting, Ulla Werlauff, Morten Duno, John Vissing
OBJECTIVE: Congenital myopathy as a nosologic entity has long been recognized, but knowledge of overall and subtype prevalence and phenotype-genotype relationship is scarce, especially in the adult population. METHODS: A national cohort of 107 patients ≥5 years diagnosed with congenital myopathy were prospectively assessed clinically, histologically, and genetically. RESULTS: Twenty-five patients were excluded because of atypical features or alternative etiologies...
April 2017: Neurology. Genetics
Satoko Miyatake, Satomi Mitsuhashi, Yukiko K Hayashi, Enkhsaikhan Purevjav, Atsuko Nishikawa, Eriko Koshimizu, Mikiya Suzuki, Kana Yatabe, Yuzo Tanaka, Katsuhisa Ogata, Satoshi Kuru, Masaaki Shiina, Yoshinori Tsurusaki, Mitsuko Nakashima, Takeshi Mizuguchi, Noriko Miyake, Hirotomo Saitsu, Kazuhiro Ogata, Mitsuru Kawai, Jeffrey Towbin, Ikuya Nonaka, Ichizo Nishino, Naomichi Matsumoto
Nemaline myopathy (NM) is a common form of congenital nondystrophic skeletal muscle disease characterized by muscular weakness of proximal dominance, hypotonia, and respiratory insufficiency but typically not cardiac dysfunction. Wide variation in severity has been reported. Intranuclear rod myopathy is a subtype of NM in which rod-like bodies are seen in the nucleus, and it often manifests as a severe phenotype. Although ten mutant genes are currently known to be associated with NM, only ACTA1 is associated with intranuclear rod myopathy...
January 5, 2017: American Journal of Human Genetics
Arne O Melleby, Mari E Strand, Andreas Romaine, Kate M Herum, Biljana Skrbic, Christen P Dahl, Ivar Sjaastad, Arnt E Fiane, Jorge Filmus, Geir Christensen, Ida G Lunde
Pressure overload is a frequent cause of heart failure. Heart failure affects millions of patients worldwide and is a major cause of morbidity and mortality. Cell surface proteoglycans are emerging as molecular players in cardiac remodeling, and increased knowledge about their regulation and function is needed for improved understanding of cardiac pathogenesis. Here we investigated glypicans (GPC1-6), a family of evolutionary conserved heparan sulfate proteoglycans anchored to the extracellular leaflet of the cell membrane, in experimental and clinical heart failure, and explored the function of glypican-6 in cardiac cells in vitro...
2016: PloS One
Li Ou, Michael J Przybilla, Chester B Whitley
Mucopolysaccharidosis type I (MPS I) is due to deficiency of α-l-iduronidase (IDUA) and subsequent storage of undegraded glycosaminoglycans (GAG). The severe form of the disease, known as Hurler syndrome, is characterized by mental retardation and neurodegeneration of unknown etiology. To identify potential biomarkers and unveil the neuropathology mechanism of MPS I disease, two-dimensional polyacrylamide gel electrophoresis (PAGE) and nanoliquid chromatography-tandem mass spectrometry (nanoLC-MS/MS) were applied to compare proteome profiling of brains from MPS I and control mice (5-month old)...
January 2017: Molecular Genetics and Metabolism
Kevin J Ashton, Melissa E Reichelt, S Jamal Mustafa, Bunyen Teng, Catherine Ledent, Lea M D Delbridge, Polly A Hofmann, R Ray Morrison, John P Headrick
Influences of adenosine 2A receptor (A2AR) activity on the cardiac transcriptome and genesis of endotoxemic myocarditis are unclear. We applied transcriptomic profiling (39 K Affymetrix arrays) to identify A2AR-sensitive molecules, revealed by receptor knockout (KO), in healthy and endotoxemic hearts. Baseline cardiac function was unaltered and only 37 A2AR-sensitive genes modified by A2AR KO (≥1.2-fold change, <5 % FDR); the five most induced are Mtr, Ppbp, Chac1, Ctsk and Cnpy2 and the five most repressed are Hp, Yipf4, Acta1, Cidec and Map3k2...
March 2017: Purinergic Signalling
Rudolf A Kley, Montse Olivé, Rolf Schröder
PURPOSE OF REVIEW: Myofibrillar myopathies (MFMs) are hereditary muscle disorders characterized by distinct histopathological features. This review provides an overview of recent research with respect to new disease genes, clinical phenotypes, insights into pathomechanisms and therapeutic strategies. RECENT FINDINGS: Beyond the known disease genes DES, FLNC, MYOT, CRYAB, ZASP, BAG3, FHL1 and TTN, mutations in PLEC, ACTA1, HSPB8 and DNAJB6 have also been associated with a MFM phenotype...
October 2016: Current Opinion in Neurology
Liu Yang, Ping Yu, Xiang Chen, Tao Cai
Nemaline myopathy (NM) constitutes a spectrum of primary skeletal muscle disorders, the diagnosis of which is based on muscle weakness and the visualization of nemaline bodies in muscle biopsies. Mutations in several NM causal genes have been attributed to the majority of NM cases, particularly mutations in nebulin and skeletal muscle α‑actin 1 (ACTA1), which are responsible for ~70% of cases; therefore, a genetic diagnostic strategy using targeted gene sequencing may potentially improve the diagnosis of suspected NM...
August 2016: Molecular Medicine Reports
S C Shin, E R Chung
We conducted DD-RT-PCR analysis to identify differentially expressed genes between high and low marbling score groups with extremely different IMF content of the longissimus lumborum muscles in Hanwoo. We detected 137 DEGs between two marbling score groups. Of these DEGs, 41 DEGs were highly expressed in the high marbling score group, whereas 96 DEGs showed a higher expression in the low marbling score group. Among them, we selected eight DEGs exhibiting the greatest differential expression levels between two marbling score groups...
November 2016: Meat Science
Yang Yang, Yiqiao Xing, Chaoqun Liang, Liya Hu, Fei Xu, Qi Mei
The present study aimed to identify biomarkers for peroxidasin (Pxdn) mutation-induced eye disorders and study the underlying mechanisms involved in this process. The microarray dataset GSE49704 was used, which encompasses 4 mouse samples from embryos with Pxdn mutation and 4 samples from normal tissues. After data preprocessing, the differentially expressed genes (DEGs) between Pxdn mutation and normal tissues were identified using the t-test in the limma package, followed by functional enrichment analysis...
June 2016: International Journal of Molecular Medicine
Chun Chan, Jun Fan, Andrew E Messer, Steve B Marston, Hiroyuki Iwamoto, Julien Ochala
In humans, more than 200 missense mutations have been identified in the ACTA1 gene. The exact molecular mechanisms by which, these particular mutations become toxic and lead to muscle weakness and myopathies remain obscure. To address this, here, we performed a molecular dynamics simulation, and we used a broad range of biophysical assays to determine how the lethal and myopathy-related H40Y amino acid substitution in actin affects the structure, stability, and function of this protein. Interestingly, our results showed that H40Y severely disrupts the DNase I-binding-loop structure and actin filaments...
August 2016: Biochimica et Biophysica Acta
Daniela Piga, Francesca Magri, Dario Ronchi, Stefania Corti, Denise Cassandrini, Eugenio Mercuri, Giorgio Tasca, Enrico Bertini, Fabiana Fattori, Antonio Toscano, Sonia Messina, Isabella Moroni, Marina Mora, Maurizio Moggio, Irene Colombo, Teresa Giugliano, Marika Pane, Chiara Fiorillo, Adele D'Amico, Claudio Bruno, Vincenzo Nigro, Nereo Bresolin, Giacomo Pietro Comi
Nemaline myopathy represents a group of clinically and genetically heterogeneous neuromuscular disorders. Different clinical-genetic entities have been characterized in the last few years, with implications for diagnostics and genetic counseling. Fifty percent of nemaline myopathy forms are due to NEB mutations, but genetic analysis of this large and complex gene by Sanger sequencing is time consuming and expensive. We selected 10 Italian patients with clinical and biopsy features suggestive for nemaline myopathy and negative for ACTA1, TPM2 and TPM3 mutations...
July 2016: Journal of Molecular Neuroscience: MN
Jennifer Tinklenberg, Hui Meng, Lin Yang, Fujun Liu, Raymond G Hoffmann, Mahua Dasgupta, Kenneth P Allen, Alan H Beggs, Edna C Hardeman, R Scott Pearsall, Robert H Fitts, Michael W Lawlor
Nemaline myopathies (NMs) are a group of congenital muscle diseases caused by mutations in at least 10 genes and associated with a range of clinical symptoms. NM is defined on muscle biopsy by the presence of cytoplasmic rod-like structures (nemaline rods) composed of cytoskeletal material. Myofiber smallness is also found in many cases of NM and may represent a cause of weakness that can be counteracted by treatment. We have used i.p. injection of activin type IIB receptor (ActRIIB)-mFc (an inhibitor of myostatin signaling) to promote hypertrophy and increase strength in our prior murine work; we therefore tested whether ActRIIB-mFc could improve weakness in NM mice through myofiber hypertrophy...
June 2016: American Journal of Pathology
Josine M de Winter, Barbara Joureau, Eun-Jeong Lee, Balázs Kiss, Michaela Yuen, Vandana A Gupta, Christopher T Pappas, Carol C Gregorio, Ger J M Stienen, Simon Edvardson, Carina Wallgren-Pettersson, Vilma-Lotta Lehtokari, Katarina Pelin, Edoardo Malfatti, Norma B Romero, Baziel G van Engelen, Nicol C Voermans, Sandra Donkervoort, C G Bönnemann, Nigel F Clarke, Alan H Beggs, Henk Granzier, Coen A C Ottenheijm
OBJECTIVE: Thin filament myopathies are among the most common nondystrophic congenital muscular disorders, and are caused by mutations in genes encoding proteins that are associated with the skeletal muscle thin filament. Mechanisms underlying muscle weakness are poorly understood, but might involve the length of the thin filament, an important determinant of force generation. METHODS: We investigated the sarcomere length-dependence of force, a functional assay that provides insights into the contractile strength of muscle fibers as well as the length of the thin filaments, in muscle fibers from 51 patients with thin filament myopathy caused by mutations in NEB, ACTA1, TPM2, TPM3, TNNT1, KBTBD13, KLHL40, and KLHL41...
June 2016: Annals of Neurology
G C Venturini, N B Stafuzza, D F Cardoso, F Baldi, M C Ledur, J O Peixoto, L El Faro, D P Munari
No abstract text is available yet for this article.
May 2016: Poultry Science
Tim Peters, Steffie Hermans-Beijnsberger, Abdelaziz Beqqali, Nicole Bitsch, Shinichi Nakagawa, Kannanganattu V Prasanth, Leon J de Windt, Ralph J van Oort, Stephane Heymans, Blanche Schroen
BACKGROUND: Long non-coding RNAs (lncRNAs) are a class of RNA molecules with diverse regulatory functions during embryonic development, normal life, and disease in higher organisms. However, research on the role of lncRNAs in cardiovascular diseases and in particular heart failure is still in its infancy. The exceptionally well conserved nuclear lncRNA Metastasis associated in lung adenocarcinoma transcript 1 (Malat-1) is a regulator of mRNA splicing and highly expressed in the heart...
2016: PloS One
Johan Lindqvist, Yotam Levy, Alisha Pati-Alam, Edna C Hardeman, Paul Gregorevic, Julien Ochala
OBJECTIVE: Nemaline myopathy, one of the most common congenital myopathies is associated with mutations in various genes including ACTA1. This disease is also characterised by various forms/degrees of muscle weakness with most cases being severe and resulting in death in infancy. Recent findings have provided valuable insight into the underlying pathophysiological mechanisms. Mutations in ACTA1 directly disrupt binding interactions between actin and myosin, and consequently the intrinsic force-generating capacity of muscle fibres...
February 17, 2016: Annals of Neurology
Justus Stenzig, Marc N Hirt, Alexandra Löser, Lena M Bartholdt, Jan-Tobias Hensel, Tessa R Werner, Mona Riemenschneider, Daniela Indenbirken, Thomas Guenther, Christian Müller, Norbert Hübner, Monika Stoll, Thomas Eschenhagen
DNA methylation affects transcriptional regulation and constitutes a drug target in cancer biology. In cardiac hypertrophy, DNA methylation may control the fetal gene program. We therefore investigated DNA methylation signatures and their dynamics in an in vitro model of cardiac hypertrophy based on engineered heart tissue (EHT). We exposed EHTs from neonatal rat cardiomyocytes to a 12-fold increased afterload (AE) or to phenylephrine (PE 20 µM) and compared DNA methylation signatures to control EHT by pull-down assay and DNA methylation microarray...
January 2016: Basic Research in Cardiology
J H Chen, R Yang, Y P Wang, W Zhang
OBJECTIVE: The purpose of this study was to screen key genes related to mechanisms and consequences of obstructive sleep apnea (OSA)-induced perturbations in visceral fat tissue depots. MATERIALS AND METHODS: Microarray data of GSE38792, comprising 10 visceral fat samples from OSA patients and 8 visceral fat samples from control subjects, was obtained from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were identified in visceral fat samples from OSA patients compared with controls using Bioconductor package limma...
November 2015: European Review for Medical and Pharmacological Sciences
Prasanna Vidyasekar, Pavithra Shyamsunder, Sanjeeb Kumar Sahoo, Rama Shanker Verma
3D cultures of stem cells can preserve differentiation potential or increase the efficiency of methods that induce differentiation. Mouse bone marrow-derived stromal cells (BMSCs) were cultured in 3D as scaffold-free spheroids or "mesoid bodies" (MBs) and as aggregates on poly(lactic) acid microspheres (MB/MS). 3D cultures demonstrated viable cells, interaction on multiple planes, altered cell morphology, and the formation of structures similar to epithelial cell bridges. Cell proliferation was limited in suspension cultures of MB and MB/MS; however, cells regained proliferative capacity when transferred to flat substrates of tissue culture plates (TCPs)...
February 2016: In Vitro Cellular & Developmental Biology. Animal
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"