The double homeodomain protein DUX4c is associated with regenerating muscle fibers and RNA-binding proteins.

Background: We have previously demonstrated that double homeobox 4 centromeric (DUX4C) encoded for a functional DUX4c protein upregulated in dystrophic skeletal muscles. Based on gain- and loss-of-function studies we have proposed DUX4c involvement in muscle regeneration. Here, we provide further evidence for such a role in skeletal muscles from patients affected with facioscapulohumeral muscular dystrophy (FSHD).

Molecular and cellular biology of PCSK9: impact on glucose homeostasis.

Proprotein convertase substilisin/kexin 9 (PCSK9) inhibitors (PCSK9i) revolutionised the lipid-lowering therapy. However, a risk of type 2 diabetes mellitus (T2DM) is evoked under PCSK9i therapy. In this review, we summarise the current knowledge on the link of PCSK9 with T2DM.

Induction of a local muscular dystrophy using electroporation in vivo: an easy tool for screening therapeutics.

Intramuscular injection and electroporation of naked plasmid DNA (IMEP) has emerged as a potential alternative to viral vector injection for transgene expression into skeletal muscles. In this study, IMEP was used to express the DUX4 gene into mouse tibialis anterior muscle. DUX4 is normally expressed in germ cells and early embryo, and silenced in adult muscle cells where its pathological reactivation leads to Facioscapulohumeral muscular dystrophy.

Severe acute respiratory syndrome coronavirus 2: virus mutations in specific European populations.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is being intensively studied, particularly its evolution, in the increasingly available sequences between countries/continents with classical phylogenetic tree representation. More recently, certain protein mutations have been correlated with specific functional impacts. Our clinical data from patients suggest that clinical symptoms differ between European countries.

Olfactory and gustatory dysfunctions as a clinical presentation of mild-to-moderate forms of the coronavirus disease (COVID-19): a multicenter European study.

Objective: To investigate the occurrence of olfactory and gustatory dysfunctions in patients with laboratory-confirmed COVID-19 infection.

Methods: Patients with laboratory-confirmed COVID-19 infection were recruited from 12 European hospitals. The following epidemiological and clinical outcomes have been studied: age, sex, ethnicity, comorbidities, and general and otolaryngological symptoms.

Overexpression of the double homeodomain protein DUX4c interferes with myofibrillogenesis and induces clustering of myonuclei.

Background: Facioscapulohumeral muscular dystrophy (FSHD) is associated with DNA hypomethylation at the 4q35 D4Z4 repeat array. Both the causal gene DUX4 and its homolog DUX4c are induced. DUX4c is immunodetected in every myonucleus of proliferative cells, while DUX4 is present in only 1/1000 of myonuclei where it initiates a gene deregulation cascade.

Antisense Oligonucleotides Used to Target the DUX4 mRNA as Therapeutic Approaches in FaciosScapuloHumeral Muscular Dystrophy (FSHD).

FacioScapuloHumeral muscular Dystrophy (FSHD) is one of the most prevalent hereditary myopathies and is generally characterized by progressive muscle atrophy affecting the face, scapular fixators; upper arms and distal lower legs. The FSHD locus maps to a macrosatellite D4Z4 repeat array on chromosome 4q35. Each D4Z4 unit contains a gene; the most distal of which is flanked by a polyadenylation site on FSHD-permissive alleles, which allows for production of stable mRNAs.

Dux4 controls migration of mesenchymal stem cells through the Cxcr4-Sdf1 axis.

We performed transcriptome profiling of human immortalized myoblasts (MB) transiently expressing double homeobox transcription factor 4 (DUX4) and double homeobox transcription factor 4 centromeric (DUX4c) and identified 114 and 70 genes differentially expressed in DUX4- and DUX4c-transfected myoblasts, respectively. A significant number of differentially expressed genes were involved in inflammation, cellular migration and chemotaxis suggesting a role for DUX4 and DUX4c in these processes. DUX4 but not DUX4c overexpression resulted in upregulation of the CXCR4 (C-X-C motif Receptor 4) and CXCL12 (C-X-C motif ligand 12 also known as SDF1) expression in human immortalized myoblasts.

Homologous Transcription Factors DUX4 and DUX4c Associate with Cytoplasmic Proteins during Muscle Differentiation.

Hundreds of double homeobox (DUX) genes map within 3.3-kb repeated elements dispersed in the human genome and encode DNA-binding proteins. Among these, we identified DUX4, a potent transcription factor that causes facioscapulohumeral muscular dystrophy (FSHD).

The Role of D4Z4-Encoded Proteins in the Osteogenic Differentiation of Mesenchymal Stromal Cells Isolated from Bone Marrow.

Facioscapulohumeral muscular dystrophy (FSHD) is associated with an activation of the double homeobox 4 (DUX4) gene, which we previously identified within the D4Z4 repeated elements in the 4q35 subtelomeric region. The pathological DUX4 mRNA is derived from the most distal D4Z4 unit and extends unexpectedly within the flanking pLAM region, which provides an intron and polyadenylation signal. The conditions that are required to develop FSHD are a permissive allele providing the polyadenylation signal and hypomethylation of the D4Z4 repeat array compared with the healthy muscle.

FSHD myotubes with different phenotypes exhibit distinct proteomes.

Facioscapulohumeral muscular dystrophy (FSHD) is a progressive muscle disorder linked to a contraction of the D4Z4 repeat array in the 4q35 subtelomeric region. This deletion induces epigenetic modifications that affect the expression of several genes located in the vicinity. In each D4Z4 element, we identified the double homeobox 4 (DUX4) gene.

DUX4 expression in FSHD muscle cells: how could such a rare protein cause a myopathy?

Facioscapulohumeral muscular dystrophy (FSHD) is one of the most frequent hereditary muscle disorders. It is linked to contractions of the D4Z4 repeat array in 4q35. We have characterized the double homeobox 4 (DUX4) gene in D4Z4 and its mRNA transcribed from the distal D4Z4 unit to a polyadenylation signal in the flanking pLAM region.

The FSHD atrophic myotube phenotype is caused by DUX4 expression.

Background: Facioscapulohumeral muscular dystrophy (FSHD) is linked to deletions in 4q35 within the D4Z4 repeat array in which we identified the double homeobox 4 (DUX4) gene. We found stable DUX4 mRNAs only derived from the most distal D4Z4 unit and unexpectedly extended to the flanking pLAM region that provided an intron and a polyadenylation signal. DUX4 encodes a transcription factor expressed in FSHD but not control primary myoblasts or muscle biopsies.

Facioscapulohumeral muscular dystrophy (FSHD): an enigma unravelled?

Facioscapulohumeral muscular dystrophy (FSHD) is the third most common muscular dystrophy after the dystrophinopathies and myotonic dystrophy and is associated with a typical pattern of muscle weakness. Most patients with FSHD carry a large deletion in the polymorphic D4Z4 macrosatellite repeat array at 4q35 and present with 1-10 repeats whereas non-affected individuals possess 11-150 repeats. An almost identical repeat array is present at 10q26 and the high sequence identity between these two arrays can cause difficulties in molecular diagnosis.

The Krüppel-like factor 15 as a molecular link between myogenic factors and a chromosome 4q transcriptional enhancer implicated in facioscapulohumeral dystrophy.

Facioscapulohumeral muscular dystrophy (FSHD), a dominant hereditary disease with a prevalence of 7 per 100,000 individuals, is associated with a partial deletion in the subtelomeric D4Z4 repeat array on chromosome 4q. The D4Z4 repeat contains a strong transcriptional enhancer that activates promoters of several FSHD-related genes. We report here that the enhancer within the D4Z4 repeat binds the Krüppel-like factor KLF15.

DUX4, a candidate gene for facioscapulohumeral muscular dystrophy, causes p53-dependent myopathy in vivo.

Objective: Facioscapulohumeral muscular dystrophy (FSHD) is associated with D4Z4 repeat contraction on human chromosome 4q35. This genetic lesion does not result in complete loss or mutation of any gene. Consequently, the pathogenic mechanisms underlying FSHD have been difficult to discern.

The helicase-like transcription factor is a strong predictor of recurrence in hypopharyngeal but not in laryngeal squamous cell carcinomas.

Aims: To examine the immunohistochemical expression of helicase-like transcription factor (HLTF) in relation to the prognosis of hypopharyngeal (HSCCs) and laryngeal (LSCCs) squamous cell carcinomas, and to characterize the HLTF protein variants expressed in biopsy specimens of head and neck squamous cell carcinoma (HNSCC) as well as the HeLa cell line.

Methods And Results: HLTF expression was determined by immunohistochemistry on a series of 100 hypopharyngeal (stage IV) and 56 laryngeal SCCs (stages I, II and IV). The HLTF variants were defined using reverse transcriptase-polymerase chain reaction and Western blots in 13 fresh HNSCC biopsies and in HeLa cells.

An isogenetic myoblast expression screen identifies DUX4-mediated FSHD-associated molecular pathologies.

Facioscapulohumeral muscular dystrophy (FSHD) is caused by an unusual deletion with neomorphic activity. This deletion derepresses genes in cis; however which candidate gene causes the FSHD phenotype, and through what mechanism, is unknown. We describe a novel genetic tool, inducible cassette exchange, enabling rapid generation of isogenetically modified cells with conditional and variable transgene expression.

Helicase-like transcription factor exhibits increased expression and altered intracellular distribution during tumor progression in hypopharyngeal and laryngeal squamous cell carcinomas.

The helicase-like transcription factor (HLTF) belongs to the SWI/SNF family of proteins that use the energy from adenosine triphosphate hydrolysis to remodel chromatin during a variety of cellular processes. HLTF is also involved in DNA repair. Using computer-assisted microscopy, the immunohistochemical expression of HLTF was determined using a series of 100 hypopharyngeal and 56 laryngeal squamous cell carcinomas (SCCs) compared to tumor-free epithelia (60 cases) and dysplasias (92 cases).

DUX4, a candidate gene of facioscapulohumeral muscular dystrophy, encodes a transcriptional activator of PITX1.

Facioscapulohumeral muscular dystrophy (FSHD) is an autosomal dominant disorder linked to contractions of the D4Z4 repeat array in the subtelomeric region of chromosome 4q. By comparing genome-wide gene expression data from muscle biopsies of patients with FSHD to those of 11 other neuromuscular disorders, paired-like homeodomain transcription factor 1 (PITX1) was found specifically up-regulated in patients with FSHD. In addition, we showed that the double homeobox 4 gene (DUX4) that maps within the D4Z4 repeat unit was up-regulated in patient myoblasts at both mRNA and protein level.

The DUX4 gene at the FSHD1A locus encodes a pro-apoptotic protein.

Facioscapulohumeral muscular dystrophy (FSHD) patients carry contractions of the D4Z4-tandem repeat array on chromosome 4q35. Decrease in D4Z4 copy number is thought to alter a chromatin structure and activate expression of neighboring genes. D4Z4 contains a putative double-homeobox gene called DUX4.

A new peptidic vector for molecular imaging of apoptosis, identified by phage display technology.

Phosphatidylserine (PS) exposure on the cell surface is an early marker of apoptosis. To select PS binding peptides as vectors of contrast agents to image apoptosis, a phage library has been exposed to perfused mouse livers. Phages not retained on control livers during the first perfusions were used for selections on apoptotic livers in a second series of perfusions.

Relationships between cell division, expression of growth factors and microcirculation in the thyroids of Tg-A2aR transgenic mice and patients with Graves' disease.

Tissue heterogeneity and nodule formation are hallmarks of thyroid growth. This is accounted for by the clonality theory that acknowledges different individual cellular abilities to respond to trophic stimuli. In order to test the hypothesis that functional and mitotic properties of thyrocytes could be influenced by paracrine interactions with neighbour endothelial cells, studies were conducted in both mouse and human goitre models.

Differential patterns of cell cycle regulatory proteins expression in transgenic models of thyroid tumours.

Cell cycle proteins regulate the transitions from G1 to S and G2 to M phases. In higher eukaryotes, their function is controlled by intracellular cascades regulated by extracellular growth factors. We have studied in previously described transgenic mouse models for thyroid proliferative diseases the expression of the key proteins regulating the cell cycle by Western blotting and immunohistochemistry, and have correlated the observations with the known actions of the transgenes on the signal transduction cascades.