217 research outputs found
Fungicide resistance among Cladobotryum spp. – causal agents of cobweb disease of the edible mushroom Agaricus bisporus
A survey of fungicide resistance among isolates of the mushroom pathogens Cladobotryum mycophilum and C. dendroides Types I and II was undertaken, with respect to the active ingredients thiabendazole, carbendazim (benzimidazoles) and prochloraz manganese following an epidemic in Britain and Ireland in 1994/95. The majority of isolates (41/57) were strongly resistant to thiabendazole (ED50 > 200 ppm) and were exclusively C. dendroides Type II. All C. mycophilum and C. dendroides Type I isolates, and four C. dendroides Type II isolates, were weakly resistant to thiabendazole (ED50 1–10 ppm). Thiabendazole-resistant C. dendroides Type II isolates were only weakly resistant to carbendazim (ED50 2–10 ppm) and isolates which were weakly resistant to thiabendazole were carbendazim-sensitive (ED50 < 1 ppm), demonstrating a lack of complete cross resistance between these two benzimidazole fungicides. The ED50 values for all isolates with respect to prochloraz manganese ranged from 0.14 to 7.8 ppm. Benzimidazole resistance was considered to have been an important factor influencing the severity of the 1994/95 cobweb epidemic but 25% of isolates collected were benzimidazole sensitive
Abdominal examination during pregnancy may enhance relationships between midwife, mother and child : a qualitative study of pregnant women's experiences
Background: Abdominal examination is a routine procedure performed by midwives several times during pregnancy to monitor the growth and well-being of the baby. Literature and instructions regarding abdominal examination focus on the technical performance, with limited attention paid to the women’s experience of the examination or the bonding-related aspects between the mother and baby. The aim of the study was to explore how pregnant women experience the abdominal examination and how the examination affects maternal–fetal attachment. Methods: Participant observation and semi-structured interviews with 10 pregnant women. We used thematic analysis to identify themes across the empirical material. Results: We identified the following four central themes: an essential examination, the baby becomes real, the importance of being involved and different senses provide different experiences. These themes describe how the women regarded the abdominal examination as an essential part of the midwifery consultation and considered it the occasion when the baby became real and tangible. Being prepared and involved before and during the examination were pivotal for how the examination was experienced by the women. The abdominal examination was crucial to the pregnant women because it provided them with important sensory aspects that were not obtained from ultrasound examination. Conclusion: The abdominal examination is regarded as essential in midwifery consultations and has the potential for supporting a woman’s bodily sensation of her baby, which is reinforced by the midwife’s manual palpation. Touch can be a way for a pregnant woman to become acquainted with her unborn child, which provides midwives a profound potential to facilitate the process of maternal–fetal attachment
Characterization of Novel Sesquiterpenoid Biosynthesis in Tobacco Expressing a Fungal Sesquiterpene Synthase
POLG2 deficiency causes adult-onset syndromic sensory neuropathy, ataxia and parkinsonism
Objective: Mitochondrial dysfunction plays a key role in the pathophysiology of neurodegenerative disorders such as ataxia and Parkinson's disease. We describe an extended Belgian pedigree where seven individuals presented with adult-onset cerebellar ataxia, axonal peripheral ataxic neuropathy, and tremor, in variable combination with parkinsonism, seizures, cognitive decline, and ophthalmoplegia. We sought to identify the underlying molecular etiology and characterize the mitochondrial pathophysiology of this neurological syndrome.
Methods: Clinical, neurophysiological, and neuroradiological evaluations were conducted. Patient muscle and cultured fibroblasts underwent extensive analyses to assess mitochondrial function. Genetic studies including genome-wide sequencing were conducted.
Results: Hallmarks of mitochondrial dysfunction were present in patients' tissues including ultrastructural anomalies of mitochondria, mosaic cytochrome c oxidase deficiency, and multiple mtDNA deletions. We identified a splice acceptor variant in POLG2, c.970-1G>C, segregating with disease in this family and associated with a concomitant decrease in levels of POLG2 protein in patient cells.
Interpretation: This work extends the clinical spectrum of POLG2 deficiency to include an overwhelming, adult-onset neurological syndrome that includes cerebellar syndrome, peripheral neuropathy, tremor, and parkinsonism. We therefore suggest to include POLG2 sequencing in the evaluation of ataxia and sensory neuropathy in adults, especially when it is accompanied by tremor or parkinsonism with white matter disease. The demonstration that deletions of mtDNA resulting from autosomal-dominant POLG2 variant lead to a monogenic neurodegenerative multicomponent syndrome provides further evidence for a major role of mitochondrial dysfunction in the pathomechanism of nonsyndromic forms of the component neurodegenerative disorders
European admixture on the Micronesian island of Kosrae: lessons from complete genetic information
The architecture of natural variation present in a contemporary population is a result of multiple population genetic forces, including population bottleneck and expansion, selection, drift, and admixture. We seek to untangle the contribution of admixture to genetic diversity on the Micronesian island of Kosrae. Toward this goal, we used a complete genetic approach by combining a dense genome-wide map of 100 000 single-nucleotide polymorphisms (SNPs) with data from uniparental markers from the mitochondrial genome and the nonrecombining portion of the Y chromosome. These markers were typed in ∼3200 individuals from Kosrae, representing 80% of the adult population of the island. We developed novel software that uses SNP data to delineate ancestry for individual segments of the genome. Through this analysis, we determined that 39% of Kosraens have some European ancestry. However, the vast majority of admixed individuals (77%) have European alleles spanning less than 10% of their genomes. Data from uniparental markers show most of this admixture to be male, introduced in the late nineteenth century. Furthermore, pedigree analysis shows that the majority of European admixture on Kosrae is because of the contribution of one individual. This approach shows the benefit of combining information from autosomal and uniparental polymorphisms and provides new methodology for determining ancestry in a population
Clinical, biochemical, and genetic features associated with VARS2-related mitochondrial disease
In recent years, an increasing number of mitochondrial disorders have been associated with mutations in mitochondrial aminoacyl-tRNA synthetases (mt-aaRSs), which are key enzymes of mitochondrial protein synthesis. Bi-allelic functional variants in VARS2, encoding the mitochondrial valyl tRNA-synthetase, were first reported in a patient with psychomotor delay and epilepsia partialis continua associated with an oxidative phosphorylation (OXPHOS) Complex I defect, before being described in a patient with a neonatal form of encephalocardiomyopathy. Here we provide a detailed genetic, clinical, and biochemical description of 13 patients, from nine unrelated families, harboring VARS2 mutations. All patients except one, who manifested with a less severe disease course, presented at birth exhibiting severe encephalomyopathy and cardiomyopathy. Features included hypotonia, psychomotor delay, seizures, feeding difficulty, abnormal cranial MRI, and elevated lactate. The biochemical phenotype comprised a combined Complex I and Complex IV OXPHOS defect in muscle, with patient fibroblasts displaying normal OXPHOS activity. Homology modeling supported the pathogenicity of VARS2 missense variants. The detailed description of this cohort further delineates our understanding of the clinical presentation associated with pathogenic VARS2 variants and we recommend that this gene should be considered in early-onset mitochondrial encephalomyopathies or encephalocardiomyopathies.Peer reviewe
Mutations in ELAC2 associated with hypertrophic cardiomyopathy impair mitochondrial tRNA 3'-end processing
Mutations in either the mitochondrial or nuclear genomes are associated with a diverse group of human disorders characterized by impaired mitochondrial respiration. Within this group, an increasing number of mutations have been identified in nuclear genes involved in mitochondrial RNA metabolism, including ELAC2. The ELAC2 gene codes for the mitochondrial RNase Z, responsible for endonucleolytic cleavage of the 3' ends of mitochondrial pre-tRNAs. Here, we report the identification of sixteen novel ELAC2 variants in individuals presenting with mitochondrial respiratory chain deficiency, hypertrophic cardiomyopathy and lactic acidosis. We provide evidence for the pathogenicity of the novel missense variants by studying the RNase Z activity in an in vitro system. We also modelled the residues affected by missense mutation in solved RNase Z structures, providing insight into enzyme structure and function. Finally, we show that primary fibroblasts from the affected individuals have elevated levels of unprocessed mitochondrial RNA precursors. Our study thus broadly confirms the correlation of ELAC2 variants with severe infantile-onset forms of hypertrophic cardiomyopathy and mitochondrial respiratory chain dysfunction. One rare missense variant associated with the occurrence of prostate cancer (p.Arg781His) impairs the mitochondrial RNase Z activity of ELAC2, suggesting a functional link between tumorigenesis and mitochondrial RNA metabolism
Conceptualising the technical relationship of animal disease surveillance to intervention and mitigation as a basis for economic analysis
<p>Abstract</p> <p>Background</p> <p>Surveillance and intervention are resource-using activities of strategies to mitigate the unwanted effects of disease. Resources are scarce, and allocating them to disease mitigation instead of other uses necessarily involves the loss of alternative sources of benefit to people. For society to obtain the maximum benefits from using resources, the gains from disease mitigation must be compared to the resource costs, guiding decisions made with the objective of achieving the optimal net outcome.</p> <p>Discussion</p> <p>Economics provides criteria to guide decisions aimed at optimising the net benefits from the use of scarce resources. Assessing the benefits of disease mitigation is no exception. However, the technical complexity of mitigation means that economic evaluation is not straightforward because of the technical relationship of surveillance to intervention. We argue that analysis of the magnitudes and distribution of benefits and costs for any given strategy, and hence the outcome in net terms, requires that mitigation is considered in three conceptually distinct stages. In Stage I, 'sustainment', the mitigation objective is to sustain a free or acceptable status by preventing an increase of a pathogen or eliminating it when it occurs. The role of surveillance is to document that the pathogen remains below a defined threshold, giving early warning of an increase in incidence or other significant changes in risk, and enabling early response. If a pathogen is not contained, the situation needs to be assessed as Stage II, 'investigation'. Here, surveillance obtains critical epidemiological information to decide on the appropriate intervention strategy to reduce or eradicate a disease in Stage III, 'implementation'. Stage III surveillance informs the choice, timing, and scale of interventions and documents the progress of interventions directed at prevalence reduction in the population.</p> <p>Summary</p> <p>This article originates from a research project to develop a conceptual framework and practical tool for the economic evaluation of surveillance. Exploring the technical relationship between mitigation as a source of economic value and surveillance and intervention as sources of economic cost is crucial. A framework linking the key technical relationships is proposed. Three conceptually distinct stages of mitigation are identified. Avian influenza, salmonella, and foot and mouth disease are presented to illustrate the framework.</p
Pathogenic variants in HTRA2 cause an early-onset mitochondrial syndrome associated with 3-methylglutaconic aciduria
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