Search results for "inclusion bodies"
showing 10 items of 53 documents
ALS-linked FUS mutations confer loss and gain of function in the nucleus by promoting excessive formation of dysfunctional paraspeckles
2019
Mutations in the FUS gene cause amyotrophic lateral sclerosis (ALS-FUS). Mutant FUS is known to confer cytoplasmic gain of function but its effects in the nucleus are less understood. FUS is an essential component of paraspeckles, subnuclear bodies assembled on a lncRNA NEAT1. Paraspeckles may play a protective role specifically in degenerating spinal motor neurons. However it is still unknown how endogenous levels of mutant FUS would affect NEAT1/paraspeckles. Using novel cell lines with the FUS gene modified by CRISPR/Cas9 and human patient fibroblasts, we found that endogenous levels of mutant FUS cause accumulation of NEAT1 isoforms and paraspeckles. However, despite only mild cytoplasm…
Phasor-FLIM analysis of Thioflavin T self-quenching in Concanavalin amyloid fibrils
2020
The formation of amyloid structures has traditionally been related to human neurodegenerative pathologies and, in recent years, the interest in these highly stable nanostructures was extended to biomaterial sciences. A common method to monitor amyloid growth is the analysis of Thioflavin T fluorescence. The use of this highly selective dye, diffused worldwide, allows mechanistic studies of supramolecular assemblies also giving back important insight on the structure of these aggregates. Here we present experimental evidence of self-quenching effect of Thioflavin T in presence of amyloid fibrils. A significant reduction of fluorescence lifetime of this dye which is not related to the propert…
Modification of the major tegument protein pp65 of human cytomegalovirus inhibits virus growth and leads to the enhancement of a protein complex with…
2010
The tegument protein pp65 of human cytomegalovirus (HCMV) is abundant in lytically infected human foreskin fibroblasts (HFF), as well as in virions and subviral dense bodies (DB). Despite this, we showed previously that pp65 is dispensable for growth in HFF. In the process of refining a DB-based vaccine candidate, different HCMV mutants were generated, expressing a dominant HLA-A2-presented peptide of the IE1 protein fused to pp65. One of the mutant viruses (RV-VM1) surprisingly showed marked impairment in virus release from HFF. We hypothesized that analysis of the phenotypic alterations of RV-VM1 would provide insight into the functions of pp65, poorly defined thus far. RV-VM1 infection r…
Gene-Related Protein Surplus Myopathies
2000
Numerous muscular dystrophies, such as dystrophinopathies, sarcoglycanopathies, and emerino- and laminopathies, are marked by the absence or reduction of mutant transsarcolemmal or nuclear proteins. In addition to these recently identified minus-proteinopathies, there are a growing number of plus-proteinopathies among neuromuscular disorders marked by a surplus or excess of endogenous proteins within muscle fibers of different, i.e., nontranssarcolemmal and nonnuclear types. These proteins are often filamentous; for example, desmin and actin accrue in respective desmin-related myopathies, among which are entities marked by mutant desmin, true desminopathies, and actinopathy, the latter ofte…
Congenital myopathies with inclusion bodies: a brief review
1998
Abstract Based on morphological abnormalities, congenital myopathies can be classified into several categories: (1) enzyme histochemically abnormal appearance without structural pathology, e.g. congenital fibre type disproportion or congenital fibre type uniformity; (2) abnormally placed nuclei, e.g. myotubular and centronuclear myopathies; (3) disruption of normal intrinsic structures, largely sarcomeres, e.g. central cores and minicores; (4) abnormal inclusions within muscle fibres. Several such inclusions are derived from pre-existing structures, most notably rods or nemaline bodies. Other derivatives of Z-band material are cytoplasmic bodies and possibly related inclusions as spheroid b…
Ergastoplasmic paracrystalline inclusion bodies in the adipose gonadal envelope and fat body of the glow worm, Lampyris noctiluca (Insecta, Coleopter…
2001
Abstract The gonads of glow worm larvae are enveloped by adipose tissue which represents a specialized fat body. The adipose gonadal envelope, and also to a lesser extent the fat body cells, contain tubular paracrystalline inclusion bodies (PIBs). Cells of other tissues are devoid of such inclusions. The PIBs form in the cisternae of rough ER. In young larvae PIB formation is sparse, but at advanced larval stages PIBs often occur as bundles in stacks of ergastoplasm. Typically, a PIB within a cisterna consists of four to seven parallel tubules. The outer diameter of a tubule is ca 28.8 nm and the width of the tubule lumen ca 12.2 nm. The “wall” of a tubule contains globular protein subunits…
Intramitochondrial crystalloids in rat pinealocytes.
1982
In the present study the rare occurrence of intramitochondrial crystalloid inclusions in the rat pinealocytes is described. They lie within the mitochondrial matrix and consist of a lattice of moderately electron-dense lines. Intersections at regular intervals form rhomboid-like subunits. The significance of these inclusions is not known.
Recent Advances in the Morphology of Myositis
1985
Summary Myositis in man may be divided into infectious and non-infectious forms. The myopathologist more often deals with the latter forms which comprise dermatomyositis/polymyositis, inclusion body myositis, mixed connective tissue disease/collagenoses, and granulomatous myopathies. Modern morphological techniques as enzyme-histochemistry, electron microscopy, immunohistology, and morphometry are of different value in various forms of myositis, but are often indispensable techniques in up-to-date diagnostic work up of a myositis.
Stanley Fahn Lecture 2005: The staging procedure for the inclusion body pathology associated with sporadic Parkinson's disease reconsidered.
2006
The synucleinopathy known as sporadic Parkinson's disease (PD) is a multisystem disorder that severely damages predisposed nerve cell types in circumscribed regions of the human nervous system. A recent staging procedure for the inclusion body pathology associated with PD proposes that, in the brain, the pathological process (formation of proteinaceous intraneuronal Lewy bodies and Lewy neurites) begins at two sites and continues in a topographically predictable sequence in six stages, during which components of the olfactory, autonomic, limbic, and somatomotor systems become progressively involved. In stages 1 to 2, the Lewy body pathology is confined to the medulla oblongata/pontine tegme…
De novo expression of nonhepatocellular cytokeratins in Mallory body formation.
1998
Mallory bodies (MBs) are eosinophilic cytoplasmic inclusions observed predominantly in alcoholic liver disease. Although linked to disease activity, their pathogenesis is still unclear. Since intermediate filaments (cytokeratins) are major components of MBs, their cytokeratin polypeptide composition was analysed with monospecific antibodies for cytokeratins 7, 8, 14, 18, 19, and 20 by immunohistology. MBs were identified by light microscopy and ubiquitin immunostaining. All MBs were positive for cytokeratins 8 and 18. A significant percentage of the MBs was strongly positive for cytokeratins 19 and/or 20, which are not detectable in hepatocytes of normal liver and, in the case of cytokerati…