Auswahl der wissenschaftlichen Literatur zum Thema „Myosin-2 non musculaire“

Current evidence favours the hypothesis that avian muscle fibre-type differentiation is intrinsically programmed during early embryogenesis and proceeds independent of neuronal influences (for review, Miller & Stockdale, 1987; Sanes, 1987). Previous interspecific (chick/quail) and intraspecific (chick/chick) chimaeric studies, involving the heterotopic transplantation of unsegmented somitic mesoderm, indicate that the ability of premyogenic cells to form specific limb muscles is determined by positional cues operative in the host embryo. To determine if similar influences are associated with embryonic fibre-type differentiation, the limb musculature of intraspecific (chick/chick) chimaeras was assessed using differential myosin-ATPase activity. The limb musculature analysed histochemically was derived from donor unsegmented thoracic somitic mesoderm transplanted to replace extirpated brachial somites of a host embryo at 48–52h in ovo. Our results demonstrated that (1) the donor tissue formed, on schedule, an appropriate brachial musculature and (2) the experimental muscles duplicated the fibre- type patterning characteristic of control muscles. Thus, our data suggest that an extramyogenic, non-neural factor(s) operative in the host limb-forming region is associated with both muscle pattern formation and muscle fibre-type pattern formation. Whether or not the same putative factor(s) influences both processes remains to be determined.

Recruitment determines the profile of fibre-type-specific genes expressed across the range of muscle fibres associated with slow, fast fatigue-resistant and fast fatiguable motor units. Downstream signalling pathways activated by neural signalling and mechanical load have been the focus of intensive research in past years. It is now known that Ca2+-dependent calcineurin–nuclear factor of activated T cells and insulin-like growth factor 1 pathways and their downstream mediators contribute to these adaptive responses. These pathways regulate gene expression through muscle-specific (myocyte-enhancing factor 2, myoblast determination protein) and non-specific (nuclear factor of activated T cell 2, GATA-2) transcription factors. Transcriptional signals activated with increased contractile activity result in altered expression of fibre-type specific genes, including the myosin heavy chain isoforms and oxidative and glycolytic enzymes and a net change in muscle fibre-type composition. In contrast, transcriptional signals activated by increased load bearing result in hypertrophy or a growth response, a component of which involves satellite cell recruitment and fusion with existing adult myofibres. Calcineurin has been identified as a key mediator in the hypertrophic response, and the current challenge has been to determine the downstream target genes of this pathway. Exciting new data have emerged, showing that myostatin, a negative regulator of muscle growth, and utrophin, a cytoskeletal protein important in maintaining membrane integrity, are downstream targets of calcineurin signalling. Increased understanding of these mediators of muscle growth may provide strategies for the development of effective therapeutics to counter muscle weakness and muscular dystrophy.

Circular rep-encoding ssDNA (CRESS-DNA) viruses are common constituents of invertebrate viral consortia. Despite their ubiquity and sequence diversity, the effects of CRESS-DNA viruses on invertebrate biology and ecology remain largely unknown. This study assessed the relationship between the transcriptional profile of benthic amphipods of genus Diporeia and the presence of the CRESS-DNA virus, LM29173, in the Laurentian Great Lakes to provide potential insight into the influence of these viruses on invertebrate gene expression. Twelve transcriptomes derived from Diporeia were compared, representing organisms from two amphipod haplotype clades (Great Lakes Michigan and Superior, defined by COI barcode sequencing) with varying viral loads (up to 3 × 106 genome copies organism−1). Read recruitment to de novo assembled transcripts revealed 2,208 significantly over or underexpressed contigs in transcriptomes with above average LM29173 load. Of these contigs, 31.5% were assigned a putative function. The greatest proportion of annotated, differentially expressed transcripts were associated with functions including: (1) replication, recombination, and repair, (2) cell structure/biogenesis, and (3) post-translational modification, protein turnover, and chaperones. Contigs putatively associated with innate immunity displayed no consistent pattern of expression, though several transcripts were significantly overexpressed in amphipods with high viral load. Quantitation (RT-qPCR) of target transcripts, non-muscular myosin heavy chain, β-actin, and ubiquitin-conjugating enzyme E2, corroborated transcriptome analysis and indicated that Lake Michigan and Lake Superior amphipods with high LM29173 load exhibit lake-specific trends in gene expression. While this investigation provides the first comparative survey of the transcriptional profile of invertebrates of variable CRESS-DNA viral load, additional inquiry is required to define the scope of host-specific responses to potential infection.

Abstract MYH-9 related platelet disorders are inherited macrothrombocytopenias. Before the genetic cause was identified, four overlapping syndromes (May-Hegglin, Epstein, Fechtnerand Sebastian syndrome) described the additional clinical manifestations in MYH-9 disorders including renal failure, hearing loss, pre senile cataract and inclusion bodies in leucocytes that are present in different combinations. The MYH-9-gene codes for the cytoplasmic contractile protein non muscular myosin heavy chain IIA, present in several tissues, which explains the additional symptoms. The bleeding tendency is usually mild to moderate but rarely, thrombotic complications are also seen (1). We report on the thrombin generation potential (ETP) in MYH9 patients with and without arterial thrombosis. In the first family (family A) 4 members were evaluated: a 51 year old woman (platelet count 36), her 24 year old daughter (platelet count 46), and the brother of the woman (57 years; platelet count 39) and his 30 year old son (platelet count 44). All four were affected by MYH-9 disorder with macrothrombocytopenia and inclusion bodies in the leucocytes and a 5521G>A mutation, causing Glu1841Lys. 3 of them had a moderate bleeding tendency [ISTH /SSC bleeding scores 9, 13, 4 where <4 is normal) (3)] and in the 51 year old women and her brother, renal insufficiency and hearing loss were already present. Both patients had an arterial thrombosis (myocardial infarction and pons infarction respectively) before 50 year of age. Both showed hyperlipidemia and hyperhomocysteinemia. In the second family (Family B) macrothrombocytopenia and small to medium size inclusion bodies in the leucocytes were found in the mother (38 years; platelet count 36) and the daughter (age15 years, platelet count 46) caused by a c. 4679 T>G mutation resulting in p.Val1560Gly. Their bleeding tendency was mild (bleeding scores 4 and 3 respectively). Thrombelastography (ROTEM) was normal in all five individuals. ETP was seen to be below the normal range in family B. However, in family A, the two members affected by thrombosis had a normal ETP (Fig 1), indicating that other factors compensated for the low platelet count and clinically even led to a breakthrough of arterial thrombosis despite the low platelet count. We suggest that other centers also assess the ETP in their MYH-9 patients according tour protocol to gather data on the potential association of the ETP with the phenotype. References Althaus K, Greinacher A: MYH-9 Related Platelet Disorders: Strategies for Management and Diagnosis. Transfus Med Hemother. 2010 October; 37(5): 260–267. Girolami A , Vettore S, Bonamigo E, Fabris F: Thrombotic events in MYH9 gene-related autosomal macrothrombocytopenias (old May–Hegglin, Sebastian, Fechtner and Epstein syndromes) J Thromb Thrombolysis. 2011 Nov;32(4):474-73. Rodeghiero F, Tosetto A, Abshire T et al.; ISTH/SSC Joint VWF and Perinatal/Pediatric Hemostasis Subcommittees Working Group. ISTH/SSC bleeding assessmenttool: a standardizedquestionnaire and a proposal for a newbleedingscore for inherited bleeding disorders. J Thromb Haemost 2010; 8: 2063–5. Figure 1. Endogenous thrombin potential in two families with MYH-9 related disease Figure 1. Endogenous thrombin potential in two families with MYH-9 related disease Thrombin generation was performed on frozen platelet rich plasma on 5 members from two different families (family A and B) with MYH-9 related disease. Two members in the first family (A:1 and A:2) had a previous arterial thrombosis (pons infarction and myocardial infarction, respectively, marked with a star). Disclosures No relevant conflicts of interest to declare.

Background: Pathogenic mutations in the smooth muscle myosin heavy chain gene, MYH11, cause megacystis megacolon intestinal hypoperistalsis syndrome and other forms of chronic intestinal pseudo-obstruction. Evaluation of intestinal tissues from affected patients is often performed before mutational analysis, but the pathological findings of MYH11-variant visceral myopathy have not been well defined. Methods: Light microscopic, immunohistochemical, and ultrastructural findings from multiple intestinal samples from 2 patients with MYH11-variant visceral myopathy were reviewed, including MYH11-specific immunohistochemistry. The findings were compared with intestinal samples from patients with gamma-smooth muscle actin ( ACTG2)-variant visceral myopathy and non-pseudo-obstruction controls. Results: Apart from non-specific changes (e.g., muscle hypertrophy and distension-related muscularis propria necrosis), no alterations were identified by routine histopathological evaluation or electron microscopy. Immunohistochemistry with antibodies against a battery of smooth muscle proteins, including MYH11, revealed indistinguishable patterns of immunoreactivity in the muscularis propria of both patients and controls. Conclusions: Myopathic morphological or immunohistochemical changes may not be present in intestinal specimens from patients with MYH11-variant visceral myopathy. Molecular genetic studies should be considered for patients with chronic intestinal pseudo-obstruction and normal or non-specific pathology findings.