65 research outputs found
Drosophila Enhancer of Zeste/ESC Complexes Have a Histone H3 Methyltransferase Activity that Marks Chromosomal Polycomb Sites
No full textAbstractEnhancer of Zeste is a Polycomb Group protein essential for the establishment and maintenance of repression of homeotic and other genes. In the early embryo it is found in a complex that includes ESC and is recruited to Polycomb Response Elements. We show that this complex contains a methyltransferase activity that methylates lysine 9 and lysine 27 of histone H3, but the activity is lost when the E(Z) SET domain is mutated. The lysine 9 position is trimethylated and this mark is closely associated with Polycomb binding sites on polytene chromosomes but is also found in centric heterochromatin, chromosome 4, and telomeric sites. Histone H3 methylated in vitro by the E(Z)/ESC complex binds specifically to Polycomb protein
To B or not to B: certification and decertification of benefit corporations
No full textThis study examines drivers of B Corporations (B Corps)that have gone through a decertification process. Using multiple prob it regressions on publicly available data on 4,410 B Corps from 2014 to early 2020, results show that geographic markets, sectors, and firm size are significant drivers. In particular, firms in U.S. markets, service sectors, and SMEs increase the likelihood of decertification. The insights gained through this research have important implications for the literature of B Corps. Additionally, this study can guide B Lab and industry leaders to develop incentives to reduce decertification rates. Finally, limitations and further research avenues are given
Predicting the contribution of novel POLG mutations to human disease through analysis in yeast model
No full textThe yeast Saccharomyces cerevisiae was used to validate the pathogenic significance of eight human mutations in the gene encoding for the mitochondrial DNA polymerase gamma, namely G303R, S305R, R386H, R574W, P625R, D930N, K947R and P1073L, among which three are novel and four are of unclear pathological significance. Mitochondrial DNA extended and point mutability as well as dominance/recessivity of each mutation has been evaluated. The analysis in yeast revealed that two mutations, S305R and R386H, cannot be the sole cause of pathology observed in patients. These data led us to search for a second mutation in compound with S305R and we found a mutation, P1073L, missed in the first genetic analysis. Finally, a significant rescue of extended mutability has been observed for several dominant mutations by treatment with mitochondrial antioxidants. © 2010 Elsevier B.V. and Mitochondria Research Society
Collated mutations in mitochondrial DNA (mtDNA) depletion syndrome (excluding the mitochondrial gamma polymerase, POLG1).
No full textThese tables list both published and a number of unpublished mutations in genes associated with early onset defects in mitochondrial DNA (mtDNA) maintenance including C10orf2, SUCLG1, SUCLA2, TYMP, RRM2B, MPV17, DGUOK and TK2. The list should not be taken as evidence that any particular mutation is pathogenic. We have included genes known to cause mtDNA depletion, excluding POLG1, because of the existing database (http://tools.niehs.nih.gov/polg/). We have also excluded mutations in C10orf2 associated with dominant adult onset disorders
Predicting the contribution of novel POLG mutations to human disease through analysis in yeast model
No full textLong-term survival of neonatal mitochondrial complex III deficiency associated with a novel BCS1L gene mutation
No full textMutations of the BCS1L gene are a recognised cause of isolated respiratory chain complex III deficiency
and underlie several fatal, neonatal mitochondrial diseases. Here we describe a 20-year-old Kenyan
woman who initially presented as a floppy infant but whose condition progressed during childhood
and adolescence with increasing muscle weakness, focal motor seizures and optic atrophy. Muscle biopsy
demonstrated complex III deficiency and the pathogenicity of a novel, homozygous BCS1L mutation was
confirmed by yeast complementation studies. Our data indicate that BCS1L mutations can cause a variable,
neurological course which is not always fatal in childhood
The clinical, histochemical, and molecular spectrum of PEO1 (Twinkle)-linked adPEO
No full textBackground: Mutations in the Twinkle (PEO1) gene are a recognized cause of autosomal dominant progressive external ophthalmoplegia (adPEO), resulting in the accumulation of multiple mitochondrial DNA (mtDNA) deletions and cytochrome c oxidase (COX)–deficient fibers in skeletal muscle secondary to a disorder of mtDNA maintenance. Patients typically present with isolated extraocular muscle involvement, with little apparent evidence of the clinical heterogeneity documented in other mtDNA maintenance disorders, in particular POLG-related disease.Methods: We reviewed the clinical, histochemical, and molecular genetics analysis of 33 unreported patients from 26 families together with all previous cases described in the literature to define the clinical phenotype associated with PEO1 mutations.Results: Ptosis and ophthalmoparesis were almost universal clinical features among this cohort, with 52%(17/33) reporting fatigue and33%(11/33) having mild proximal myopathy. Features consistent with CNS involvement were rarely described; however, in 24% (8/33) of the patients, cardiac abnormalities were reported. Mitochondrial histochemical changes observed in muscle showed remarkablevariability, as did the secondary mtDNA deletions, which in some patients were only detected by PCR-based assays and not Southern blotting. Moreover, we report 7 novel PEO1 variants. Conclusions: Our data suggest a shared clinical phenotype with variable mild multiorgan involvement, and that the contribution of PEO1 mutations as a cause of adPEO may well be underestimated. Direct sequencing of the PEO1 gene should be considered in adPEO patients prior to muscle biopsy
Deficiency of the mitochondrial phosphate carrier presenting as myopathy and cardiomyopathy in a family with three affected children.
No full textIn a family three children presented with severe neonatal lactic acidosis, hypertrophic cardiomyopathy and generalised muscular hypotonia. One child died in infancy, two survived a clinically severe neonatal period. At an age of 9 and 17years, respectively, they present with exercise intolerance, proximal muscle weakness, non-progressive hypertrophic cardiomyopathy and normal mental development. In a muscle biopsy normal activity of respiratory chain enzymes was found; however the amount of the mitochondrial phosphate carrier was decreased. This protein is expressed in two tissue-specific isoforms generated by mutually exclusive alternative splicing of the SLC25A3 gene transcript. We identified a homozygous mutation c.158-9A>G located in the 5'-intron next to exon 3A specific for heart and skeletal muscle. This creates a novel splice site resulting in a more than 95% decrease of the wild type allele
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