196 results match your criteria hinge phenotype

Prevalence and characteristics of mitral valve prolapse in military young adults in Taiwan of the CHIEF Heart Study.

Sci Rep 2021 Feb 1;11(1):2719. Epub 2021 Feb 1.

Division of Cardiology, Department of Internal Medicine, Tri-Service General Hospital and National Defense Medical Center, Taipei, Taiwan.

The prevalence of mitral valve prolapse (MVP) among middle- and older-aged individuals is estimated to be 2-4% in Western countries. However, few studies have been conducted among Asian individuals and young adults. This study included a sample of 2442 consecutive military adults aged 18-39 years in Hualien, Taiwan. Read More

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February 2021

Anastral Spindle 3/Rotatin Stabilizes Sol narae and Promotes Cell Survival in .

Mol Cells 2021 Jan;44(1):13-25

Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 34141, Korea.

Apoptosis and compensatory proliferation, two intertwined cellular processes essential for both development and adult homeostasis, are often initiated by the mis-regulation of centrosomal proteins, damaged DNA, and defects in mitosis. Fly Anastral spindle 3 (Ana3) is a member of the pericentriolar matrix proteins and known as a key component of centriolar cohesion and basal body formation. We report here that is a suppressor of lethality induced by the overexpression of Sol narae (Sona), a metalloprotease in a disintegrin and metalloprotease with thrombospondin motif (ADAMTS) family. Read More

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January 2021

Biochemical and functional characterization of the SMC holocomplex from .

Microbiology (Reading) 2021 02;167(2)

Department of Molecular Nutrition, CSIR - Central Food Technological Research Institute (CFTRI), Mysore, Karnataka 570020, India.

Multi-subunit SMC complexes are required to perform essential functions, such as chromosome compaction, segregation and DNA repair, from bacteria to humans. Prokaryotic SMC proteins form complexes with two non-SMC subunits, ScpA and ScpB, to condense the chromosome. The mutants of both and genes in have been shown to display characteristic phenotypes such as growth defects and increased frequency of anucleate cells. Read More

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February 2021

Deciphering the Role of Filamin B Calponin-Homology Domain in Causing the Larsen Syndrome, Boomerang Dysplasia, and Atelosteogenesis Type I Spectrum Disorders via a Computational Approach.

Molecules 2020 Nov 26;25(23). Epub 2020 Nov 26.

Department of Biomedical Sciences, College of Health and Sciences, Qatar University, QU Health, Doha 2713, Qatar.

Filamins (FLN) are a family of actin-binding proteins involved in regulating the cytoskeleton and signaling phenomenon by developing a network with F-actin and FLN-binding partners. The FLN family comprises three conserved isoforms in mammals: FLNA, FLNB, and FLNC. FLNB is a multidomain monomer protein with domains containing an actin-binding N-terminal domain (ABD 1-242), encompassing two calponin-homology domains (assigned CH1 and CH2). Read More

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November 2020

Myeloma-Modified Adipocytes Exhibit Metabolic Dysfunction and a Senescence-Associated Secretory Phenotype.

Cancer Res 2021 02 20;81(3):634-647. Epub 2020 Nov 20.

Maine Medical Center Research Institute, Scarborough, Maine.

Bone marrow adipocytes (BMAd) have recently been implicated in accelerating bone metastatic cancers, such as acute myelogenous leukemia and breast cancer. Importantly, bone marrow adipose tissue (BMAT) expands with aging and obesity, two key risk factors in multiple myeloma disease prevalence, suggesting that BMAds may influence and be influenced by myeloma cells in the marrow. Here, we provide evidence that reciprocal interactions and cross-regulation of myeloma cells and BMAds play a role in multiple myeloma pathogenesis and treatment response. Read More

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February 2021

Geometry influences inflammatory host cell response and remodeling in tissue-engineered heart valves in-vivo.

Sci Rep 2020 11 16;10(1):19882. Epub 2020 Nov 16.

Institute for Regenerative Medicine (IREM), University of Zurich, Wagistrasse 12, 8952, Schlieren, Switzerland.

Regenerative tissue-engineered matrix-based heart valves (TEM-based TEHVs) may become an alternative to currently-used bioprostheses for transcatheter valve replacement. We recently identified TEM-based TEHVs-geometry as one key-factor guiding their remodeling towards successful long-term performance or failure. While our first-generation TEHVs, with a simple, non-physiological valve-geometry, failed over time due to leaflet-wall fusion phenomena, our second-generation TEHVs, with a computational modeling-inspired design, showed native-like remodeling resulting in long-term performance. Read More

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November 2020

Allosteric Priming of E. coli CheY by the Flagellar Motor Protein FliM.

Biophys J 2020 09 15;119(6):1108-1122. Epub 2020 Aug 15.

Computational Cell and Molecular Biology, the Francis Crick Institute, London, United Kingdom; Molecular Biology Consortium, Lawrence Berkeley National Laboratory, Berkeley, California. Electronic address:

Phosphorylation of Escherichia coli CheY protein transduces chemoreceptor stimulation to a highly cooperative flagellar motor response. CheY binds to the N-terminal peptide of the FliM motor protein (FliM). Constitutively active D13K-Y106W CheY has been an important tool for motor physiology. Read More

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September 2020

A Novel Siglec-4 Derived Spacer Improves the Functionality of CAR T Cells Against Membrane-Proximal Epitopes.

Front Immunol 2020 7;11:1704. Epub 2020 Aug 7.

R&D Reagents, Miltenyi Biotec B.V. & Co. KG, Bergisch Gladbach, Germany.

A domain that is often neglected in the assessment of chimeric antigen receptor (CAR) functionality is the extracellular spacer module. However, several studies have elucidated that membrane proximal epitopes are best targeted through CARs comprising long spacers, while short spacer CARs exhibit highest activity on distal epitopes. This finding can be explained by the requirement to have an optimal distance between the effector T cell and target cell. Read More

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The Art and Science of Selecting a CD123-Specific Chimeric Antigen Receptor for Clinical Testing.

Mol Ther Methods Clin Dev 2020 Sep 30;18:571-581. Epub 2020 Jun 30.

Department of Bone Marrow Transplant and Cellular Therapy, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.

Chimeric antigen receptor (CAR) T cells targeting CD123, an acute myeloid leukemia (AML) antigen, hold the promise of improving outcomes for patients with refractory/recurrent disease. We generated five lentiviral vectors encoding CD20, which may serve as a target for CAR T cell depletion, and 2 or 3 generation CD123-CARs since the benefit of two costimulatory domains is model dependent. Four CARs were based on the CD123-specific single-chain variable fragment (scFv) 26292 (292) and one CAR on the CD123-specific scFv 26716 (716), respectively. Read More

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September 2020

, First Identified in in 1910, Is Encoded by the Arylalkalamine N-Acetyltransferase (AANAT1) Gene.

G3 (Bethesda) 2020 09 2;10(9):3387-3398. Epub 2020 Sep 2.

Department of Biology, Duke University, Durham, NC 27708

The pigmentation mutation is a commonly used recombination marker characterized by a darkly pigmented region at the wing hinge. Identified in 1910 by Thomas Hunt Morgan, was characterized by Sturtevant as the most "workable" mutant in the rightmost region of the second chromosome and eventually localized to 2-107.0 and 60C1-2. Read More

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September 2020

Consequences of epigenetic derepression in facioscapulohumeral muscular dystrophy.

Clin Genet 2020 06 4;97(6):799-814. Epub 2020 Mar 4.

Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands.

Facioscapulohumeral muscular dystrophy (FSHD), a common hereditary myopathy, is caused either by the contraction of the D4Z4 macrosatellite repeat at the distal end of chromosome 4q to a size of 1 to 10 repeat units (FSHD1) or by mutations in D4Z4 chromatin modifiers such as Structural Maintenance of Chromosomes Hinge Domain Containing 1 (FSHD2). These two genotypes share a phenotype characterized by progressive and often asymmetric muscle weakening and atrophy, and common epigenetic alterations of the D4Z4 repeat. All together, these epigenetic changes converge the two genetic forms into one disease and explain the derepression of the DUX4 gene, which is otherwise kept epigenetically silent in skeletal muscle. Read More

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is required for axial elongation and segmentation in vertebrate embryos.

Biol Open 2020 02 11;9(2). Epub 2020 Feb 11.

Cancer Research UK Developmental Genetics Laboratory, CRUK London Research Institute

During vertebrate embryonic development, the formation of axial structures is driven by a population of stem-like cells that reside in a region of the tailbud called the chordoneural hinge (CNH). We have compared the mouse CNH transcriptome with those of surrounding tissues and shown that the CNH and tailbud mesoderm are transcriptionally similar, and distinct from the presomitic mesoderm. Amongst CNH-enriched genes are several that are required for axial elongation, including , , and , and androgen/oestrogen receptor nuclear signalling components such as We show that the pattern and duration of tailbud expression is conserved in mouse, zebrafish and chicken embryos, and that is required for axial elongation and somitogenesis in zebrafish embryos. Read More

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February 2020

Safety and feasibility of anti-CD19 CAR T cells with fully human binding domains in patients with B-cell lymphoma.

Nat Med 2020 02 20;26(2):270-280. Epub 2020 Jan 20.

Experimental Transplantation and Immunotherapy Branch, Center for Cancer Research, National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, MD, USA.

Anti-CD19 chimeric antigen receptor (CAR)-expressing T cells are an effective treatment for B-cell lymphoma, but often cause neurologic toxicity. We treated 20 patients with B-cell lymphoma on a phase I, first-in-human clinical trial of T cells expressing the new anti-CD19 CAR Hu19-CD828Z (NCT02659943). The primary objective was to assess safety and feasibility of Hu19-CD828Z T-cell therapy. Read More

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February 2020

A Novel G385E Variant in the Cold Region of the T3-Binding Domain of Thyroid Hormone Receptor Beta Gene and Investigations to Assess Its Clinical Significance.

Eur Thyroid J 2019 Dec 30;8(6):293-297. Epub 2019 Oct 30.

Department of Medicine, University of Chicago, Chicago, Illinois, USA.

Background: Resistance to thyroid hormone beta (RTHβ) is characterized by elevated thyroid hormone and unsuppressed thyroid-stimulating hormone (TSH), caused by thyroid hormone receptor beta gene () defects. Most mutations producing RTHβ phenotype are located in CG-rich regions of , encoding the T3-binding and hinge domains of the receptor. However, a region encompassing codons 384-425 is virtually devoid of RTHβ-causing mutations, termed "cold region. Read More

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December 2019

Exploring the role of elongation Factor-Like 1 (EFL1) in Shwachman-Diamond syndrome through molecular dynamics.

J Biomol Struct Dyn 2020 Oct 20;38(17):5219-5229. Epub 2019 Dec 20.

Consiglio Nazionale Delle Ricerche, Istituto di Cristallografia, Bari, Italy.

Shwachman-Diamond Syndrome (SDS) is an autosomal recessive disorder whose patients present mutations in two ribosome assembly proteins, the Shwachman-Bodian-Diamond Syndrome protein (SBDS) and the Elongation Factor-Like 1 (EFL1). Due to the lack of knowledge of the molecular mechanisms responsible for SDS pathogenesis, current therapy is nonspecific and focuses only at alleviating the symptoms. Building on the recent observation that EFL1 single-point mutations clinically manifest as SDS-like phenotype, we carried out comparative Molecular Dynamics (MD) simulations on three mutants, T127A, M882K and R1095Q and wild type EFL1. Read More

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October 2020

Analysis of CAR-Mediated Tonic Signaling.

Methods Mol Biol 2020 ;2086:223-236

Department of Hematology and Oncology, Hospital Clinic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.

CARs are synthetic receptors designed to drive antigen-specific activation upon binding of the scFv to its cognate antigen. However, CARs can also elicit different levels of ligand-independent constitutive signaling, also known as tonic signaling. Chronic T cell activation is observed in certain combinations of scFv, hinge, and costimulatory domains and may be increased due to high levels of CAR expression. Read More

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December 2020

GRP94 promotes brain metastasis by engaging pro-survival autophagy.

Neuro Oncol 2020 05;22(5):652-664

Biological Clues of the Invasive and Metastatic Phenotype Group, Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain.

Background: GRP94 is a glucose-regulated protein critical for survival in endoplasmic reticulum stress. Expression of GRP94 is associated with cellular transformation and increased tumorigenicity in breast cancer. Specifically, overexpression of GRP94 predicts brain metastasis (BM) in breast carcinoma patients with either triple negative or ErbB2 positive tumors. Read More

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The variability of SMCHD1 gene in FSHD patients: evidence of new mutations.

Hum Mol Genet 2019 12;28(23):3912-3920

Department of Biomedicine and Prevention, Tor Vergata University, Rome, 00133, Italy.

In this study, we investigated the sequence of (Structural Maintenance of Chromosomes flexible Hinge Domain containing 1) SMCHD1 gene in a cohort of clinically defined FSHD (facioscapulohumeral muscular dystrophy) patients in order to assess the distribution of SMCHD1 variants, considering the D4Z4 fragment size in terms of repeated units (RUs; short fragment: 1-7 RU, borderline: 8-10RU and normal fragment: >11RU). The analysis of SMCHD1 revealed the presence of 82 variants scattered throughout the introns, exons and 3'untranslated region (3'UTR) of the gene. Among them, 64 were classified as benign polymorphisms and 6 as VUS (variants of uncertain significance). Read More

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December 2019

SERPING1 mutation update: Mutation spectrum and C1 Inhibitor phenotypes.

Hum Mutat 2020 01 22;41(1):38-57. Epub 2019 Oct 22.

Centre de Référence des Angioedèmes (CREAK), Filière MaRIH, CHU Grenoble, Grenoble, France.

C1 inhibitor (C1Inh) deficiency is responsible for hereditary angioedema (C1-INH-HAE) and caused by variants of the SERPING1/C1INH/C1NH gene. C1Inh is the major control of kallikrein-kinin system. C1Inh deficiency leads to its uncontrolled activation, with subsequent generation of the vasoactive peptide bradykinin. Read More

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January 2020

The postembryonic transformation of the shell in emydine box turtles.

Evol Dev 2019 11 23;21(6):297-310. Epub 2019 Aug 23.

Department of Ecology, Evolution, and Organismal Biology, Iowa State University, Ames, Iowa, USA.

A key trend in the 210-million-year-old history of modern turtles was the evolution of shell kinesis, that is, shell movement during neck and limb retraction. Kinesis is hypothesized to enhance predator defense in small terrestrial and semiaquatic turtles and has evolved multiple times since the early Cretaceous. This complex phenotype is nonfunctional and far from fully differentiated following embryogenesis. Read More

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November 2019

SMCHD1 mutation spectrum for facioscapulohumeral muscular dystrophy type 2 (FSHD2) and Bosma arhinia microphthalmia syndrome (BAMS) reveals disease-specific localisation of variants in the ATPase domain.

J Med Genet 2019 10 26;56(10):693-700. Epub 2019 Jun 26.

Human Genetics, Leids Universitair Medisch Centrum, Leiden, The Netherlands.

Background: Variants in the Structural Maintenance of Chromosomes flexible Hinge Domain-containing protein 1 () can cause facioscapulohumeral muscular dystrophy type 2 (FSHD2) and the unrelated Bosma arhinia microphthalmia syndrome (BAMS). In FSHD2, pathogenic variants are found anywhere in SMCHD1 while in BAMS, pathogenic variants are restricted to the extended ATPase domain. Irrespective of the phenotypic outcome, both FSHD2-associated and BAMS-associated variants result in quantifiable local DNA hypomethylation. Read More

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October 2019

Calcification and extracellular matrix dysregulation in human postmortem and surgical aortic valves.

Heart 2019 11 5;105(21):1616-1621. Epub 2019 Jun 5.

Molecular Cardiovascular Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.

Objectives: Calcific aortic valve disease (CAVD) is a progressive disease ranging from aortic valve (AoV) sclerosis to AoV stenosis (AS), characterised by severe calcification with impaired leaflet function. Due to the lack of early symptoms, the pathological progression towards valve dysfunction is poorly understood. The early patterns of AoV calcification and altered extracellular matrix (ECM) organisation were analysed in individuals postmortem without clinical AS compared with clinical AS. Read More

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November 2019

Drug susceptibility and replication capacity of a rare HIV-1 subtype C protease hinge region variant.

Antivir Ther 2019 ;24(5):333-342

Protein Structure-Function Research Unit, School of Molecular and Cell Biology, University of Witwatersrand, Johannesburg, South Africa.

Background: Protease inhibitors form the main component of second-line antiretroviral treatment in South Africa. Despite their efficacy, mutations arising within the HIV-1 gag and protease coding regions contribute to the development of resistance against this class of drug. In this paper we investigate a South African HIV-1 subtype C Gag-protease that contains a hinge region mutation and insertion (N37T↑V). Read More

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Isolation of Fission Yeast Condensin Temperature-Sensitive Mutants with Single Amino Acid Substitutions Targeted to Hinge Domain.

G3 (Bethesda) 2019 05 7;9(5):1777-1783. Epub 2019 May 7.

G0 Cell Unit, Okinawa Institute of Science and Technology Graduate University, Onna-son, Okinawa 904-0495, Japan

Essential genes cannot be deleted from the genome; therefore, temperature-sensitive (ts) mutants and cold-sensitive (cs) mutants are very useful to discover functions of essential genes in model organisms such as and To isolate ts/cs mutants for essential genes of interest, error-prone mutagenesis (or random mutagenesis) coupled with selection has been widely used. However, this method often introduces multiple silent mutations, in addition to the mutation responsible for ts/cs, with the result that one cannot discern which mutation is responsible for the ts/cs phenotype. In addition, the location of the responsible mutation introduced is random, whereas it is preferable to isolate ts/cs mutants with single amino acid substitutions, located in a targeted motif or domain of the protein of interest. Read More

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Untargeted Metabolomics Differentiates l-Carnitine Treated Septic Shock 1-Year Survivors and Nonsurvivors.

J Proteome Res 2019 05 1;18(5):2004-2011. Epub 2019 Apr 1.

Emergency Medicine , University of Mississippi Medical Center , Jackson , Mississippi 39216 , United States.

l-Carnitine is a candidate therapeutic for the treatment of septic shock, a condition that carries a ≥40% mortality. Responsiveness to l-carnitine may hinge on unique metabolic profiles that are not evident from the clinical phenotype. To define these profiles, we performed an untargeted metabolomic analysis of serum from 21 male sepsis patients enrolled in a placebo-controlled l-carnitine clinical trial. Read More

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Antigenic "Hot- Spots" on the TSH Receptor Hinge Region.

Front Endocrinol (Lausanne) 2018 7;9:765. Epub 2019 Jan 7.

Thyroid Research Unit, Department of Medicine, James J. Peters VA Medical Center, Icahn School of Medicine at Mount Sinai, New York, NY, United States.

The TSH receptor (TSHR) hinge region was previously considered an inert scaffold connecting the leucine-rich ectodomain to the transmembrane region of the receptor. However, mutation studies have established the hinge region to be an extended hormone-binding site in addition to containing a region which is cleaved thus dividing the receptor into (A) and β (B) subunits. Furthermore, we have shown that monoclonal antibodies directed to the cleaved part of the hinge region (often termed "neutral" antibodies) can induce thyroid cell apoptosis in the absence of cyclic AMP signaling. Read More

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January 2019

A tyrosine kinase-activating variant Asn666Ser in PDGFRB causes a progeria-like condition in the severe end of Penttinen syndrome.

Eur J Hum Genet 2019 04 20;27(4):574-581. Epub 2018 Dec 20.

Department of Medical Genetics, Haukeland University Hospital, 5021, Bergen, Norway.

Missense variants located to the "molecular brake" in the tyrosine kinase hinge region of platelet-derived growth factor receptor-β, encoded by PFGFRB, can cause Penttinen-type (Val665Ala) and Penttinen-like (Asn666His) premature ageing syndromes, as well as infantile myofibromatosis (Asn666Lys and Pro660Thr). We have found the same de novo PDGFRB c.1997A>G p. Read More

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Genetics of anophthalmia and microphthalmia. Part 2: Syndromes associated with anophthalmia-microphthalmia.

Anne Slavotinek

Hum Genet 2019 Sep 30;138(8-9):831-846. Epub 2018 Oct 30.

Division of Genetics, Department of Pediatrics, University of California, San Francisco Room RH384C, 1550 4th St, San Francisco, CA, 94143-2711, USA.

As new genes for A/M are identified in the genomic era, the number of syndromes associated with A/M has greatly expanded. In this review, we provide a brief synopsis of the clinical presentation and molecular genetic etiology of previously characterized pathways involved in A/M, including the Sex-determining region Y-box 2 (SOX2), Orthodenticle Homeobox 2 (OTX2) and Paired box protein-6 (PAX6) genes, and the Stimulated by retinoic acid gene 6 homolog (STRA6), Aldehyde Dehydrogenase 1 Family Member A3 (ALDH1A3), and RA Receptor Beta (RARβ) genes that are involved in retinoic acid synthesis. Less common genetic causes of A/M, including genes involved in BMP signaling [Bone Morphogenetic Protein 4 (BMP4), Bone Morphogenetic Protein 7 (BMP7) and SPARC-related modular calcium-binding protein 1 (SMOC1)], genes involved in the mitochondrial respiratory chain complex [Holocytochrome c-type synthase (HCCS), Cytochrome C Oxidase Subunit 7B (COX7B), and NADH:Ubiquinone Oxidoreductase subunit B11 (NDUFB11)], the BCL-6 corepressor gene (BCOR), Yes-Associated Protein 1 (YAP1) and Transcription Factor AP-2 Alpha (TFAP2α), are more briefly discussed. Read More

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September 2019

Different clinicopathological features between Japanese siblings with facioscapulohumeral muscular dystrophy 2 with a novel nonsense SMCHD1 mutation (Arg552).

J Clin Neurosci 2018 Dec 13;58:215-217. Epub 2018 Oct 13.

Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan. Electronic address:

Facioscapulohumeral muscular dystrophy (FSHD) 2 is caused by a combination of heterozygous structural maintenance of chromosomes flexible hinge domain containing 1 (SMCHD1) mutation plus DNA hypomethylation on D4Z4. Here we report two Japanese FSHD2 siblings (brother and sister) with a new SMCHD1 nonsense mutation (a heterogeneous c. 1654C > T substitution, leading to a stop codon Arg552). Read More

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December 2018

Delayed trait development and the convergent evolution of shell kinesis in turtles.

Proc Biol Sci 2018 10 3;285(1888). Epub 2018 Oct 3.

Department of Ecology, Evolution, and Organismal Biology, Iowa State University, 2200 Osborn Drive, 251 Bessey Hall, Ames, IA, USA.

Understanding developmental processes is foundational to clarifying the mechanisms by which convergent evolution occurs. Here, we show how a key convergently evolving trait is slowly 'acquired' in growing turtles. Many functionally relevant traits emerge late in turtle ontogeny, owing to design constraints imposed by the shell. Read More

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October 2018