1,721,182 research outputs found
Structural and functional alterations of the cell nucleus in skeletal muscle wasting: the evidence in situ.
No full textThe histochemical and ultrastructural analysis of the nuclear components involved in RNA transcription and splicing can reveal the occurrence of cellular dysfunctions eventually related to the onset of a pathological phenotype. In recent years, nuclear histochemistry at light and electron microscopy has increasingly been used to investigate the basic mechanisms of skeletal muscle diseases; the study in situ of nuclei of myofibres and satellite cells proved to be crucial for understanding the pathogenesis of skeletal muscle wasting in sarcopenia, myotonic dystrophy and laminopathies. 
Histochemistry for investigating skeletal muscle under sarcopenic and dystrophic conditions
No full textThe minipaper reports histochemical approaches for investigating skeletal muscle under sarcopenic and dystrophic conditions at fluorescence and transcmission elelctron microscop
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Proximal myotonic myopathy: report on italian families and literature review.
No full textDespite the more recent genetic classification of the novel myotonic dystrophies into at least two distinct myotome dystrophy (DM) loci (DM1, DM2/PROMM/PDM), the clinical characteristics of these dominant myotonic syndromes often blur. The multisystemic nature of these disorders leads to a spectrum of symptoms and signs th.it emphasize the similarities and differences between these diseases. This review focuses en the clinical, laboratory, and genetic findings in 3q-linked and unlinked Italian families with proximal myotonic myopathy (PROMM). From a neuromuscular and cardiac point of view, we present follow-up data fom 25 patients studied serially over a 6-year period. We also present data on central nervous system involvement following neuropsychologic arid neuroimaging studies in this same period of time
Immunological properties of myosin in myotonic dystrophy.
No full textCharacterization study of myosin in myotonic dystroph
Nuclear MBNL1-containing foci increase in size upon cell-cycle exit in fibroblasts from DM2 patients
No full textThe work describes the increase in size of nuclear MBNL1-containing foci upon cell-cycle exit in fibroblasts from DM2 patient
RNA transcription and maturation in skeletal muscle cells are similarly impaired in myotonic dystrophy and sarcopenia: the ultrastructural evidence
No full textIn recent years, histochemistry at light and electron microscopy has increasingly been applied to investigate basic mechanisms of skeletal muscle diseases; in particular, the study in situ of skeletal muscle cell nuclei proved to be crucial for elucidating some pathogenetic mechanisms of skeletal muscle wasting in myotonic dystrophy (DM) and sarcopenia. DM is an autosomal dominant disorder whose multisystemic features originate form nucleotide expansions: (CTG)n in the dystrophy myotonic protein kinase (DMPK) gene on chromosome 19q13 in DM type 1 (DM1), or (CCTG)n in intron 1 of the CNBP gene (previously know as zinc finger 9 gene, ZNF9) on chromosome 3q21 in DM type 2 (DM2). Sarcopenia is an age-related condition characterized by the decline of muscle mass, strength and function, whose causes are still poorly known and probably manifold (e.g., altered levels of anabolic hormones and inflammatory mediators, impairment of proteolytic and autophagic pathways, mitochondrial or neuromuscular dysfunction, loss of satellite cells). Interestingly, skeletal muscles in both DM and sarcopenia show myofibre atrophy, fibre size variability and centrally located nuclei, as well as a reduced satellite cells’ effectiveness. Based on ex vivo and in vitro studies, we have demonstrated that both myofibres and satellite cells of DM and sarcopenic muscles exhibit a massive nuclear rearrangement of the structural and molecular factors responsible for pre-mRNA transcription and maturation: the impairment in the pre-mRNA post-transcriptional pathways would thus account for the aging-reminiscent muscle phenotype of DM patients suggesting that the skeletal muscle wasting observed in DM and sarcopenia may result from similar cellular mechanisms
RNA processing is altered in skeletal muscle nuclei of patients affected by myotonic dystrophy
No full textMyotonic dystrophies (DMs) are characterised by highly variable clinical manifestations consisting of muscle weakness and atrophy, and a wide spectrum of extramuscular manifestations. In both DM1 and DM2 forms, expanded nucleotide sequences cause the accumulation of mutant transcripts in the nucleus, thus deregulating the function of some RNA-binding proteins and providing a plausible explanation for the multifactorial phenotype of DM patients. However, at the skeletal muscle level, no mechanistic explanation for the muscle wasting has so far been proposed. We therefore performed a study in situ by immunoelectron microscopy on biceps brachii biopsies from DM1, DM2 and healthy subjects, providing the first ultrastructural evidence on the distribution of some nuclear ribonucleoprotein (RNP)-containing structures and molecular factors involved in pre-mRNA transcription and maturation in dystrophic myonuclei. Our results demonstrated an accumulation of splicing and cleavage factors in myonuclei of both DM1 and DM2 patients, suggesting an impairment of post-transcriptional pre-mRNA pathways. The transcription of the expanded sequences in DM myonuclei would therefore hamper functionality of the whole splicing machinery, slowing down the intranuclear molecular trafficking; this would reduce the capability of myonuclei to respond to anabolic stimuli thus contributing to muscle wasting
Nuclear ribonucleoprotein-containing foci increase in size in non-dividing cells from patients with myotonic dystrophy type 2
No full textMyotonic dystrophies (DM) are genetically based neuromuscular disorders characterized by the accumulation of mutant transcripts into peculiar intranuclear foci, where different splicing factors (among which the alternative splicing regulator muscleblind-like 1 protein, MBNL1) are ectopically sequestered. The aim of the present investigation was to describe the dynamics of the DM-specific intranuclear foci in interphase nuclei and during mitosis, as well as after the exit from the cell cycle. Primary cultures of skin fibroblasts from DM2 patients were used, as a model system to reproduce in vitro, as accurately as possible, the in vivo conditions. Cycling and resting fibroblasts were investigated by immunocytochemical and morphometric techniques, and the relative amounts of MBNL1 were also estimated by western blotting. MBNL1-containing foci were exclusively found in the nucleus during most of the interphase, while being observed in the cytoplasm during mitosis when they never associate with the chromosomes; the foci remained in the cytoplasm at cytodieresis, and underwent disassembly in early G1 to be reformed in the nucleus at each cell cycle. After fibroblasts had stopped dividing in late-passage cultures, the nuclear foci were observed to progressively increase in size. Interestingly, measurements on muscle biopsies taken from the same DM2 patients at different ages demonstrated that, in the nuclei of myofibers, the MBNL1-containing foci become larger with increasing patient's age. As a whole, these results suggest that in non-dividing cells of DM2 patients the sequestration in the nuclear foci of factors needed for RNA processing would be continuous and progressive, eventually leading to the onset (and the worsening with time) of the pathological traits. This is consistent with the evidence that in DM patients the most affected organs or tissues are those where non-renewing cells are mainly present, i.e., the central nervous system, heart and skeletal muscle
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