RESUMEN
Mitochondrial DNA mutations cause disease in >1 in 5000 of the population, and approximately 1 in 200 of the population are asymptomatic carriers of a pathogenic mtDNA mutation. Many patients with these pathogenic mtDNA mutations present with a progressive, disabling neurological syndrome that leads to major disability and premature death. There is currently no effective treatment for mitochondrial disorders, placing great emphasis on preventing the transmission of these diseases. An empiric approach can be used to guide genetic counseling for common mtDNA mutations, but many families transmit rare or unique molecular defects. There is therefore a pressing need to develop techniques to prevent transmission based on a solid understanding of the biological mechanisms. Several recent studies have cast new light on the genetics and cell biology of mtDNA inheritance, but these studies have also raised new controversies. Here we compare and contrast these findings and discuss their relevance for the transmission of human mtDNA diseases.
Asunto(s)
ADN Mitocondrial/genética , Enfermedades Genéticas Ligadas al Cromosoma X/genética , Enfermedades Mitocondriales/genética , Mutación/genética , Animales , HumanosRESUMEN
OBJECTIVES: To describe the UK Food Surveillance System (FSS UK) currently in operation in Scotland and Northern Ireland, and being introduced UK-wide, particularly in relation to the development, scope and roll-out of the system. STUDY DESIGN: Pilot questionnaire, followed by pilot information technology (IT)-based study and subsequent roll-out. METHODS: A paper-based trial of data collection was introduced, followed by an IT-based pilot and the subsequent development of an IT-based system and an Internet-based resource. A project working group and specific user groups were formed to assist the dedicated project team to progress the project. The groups' compositions reflect the interests of the various partner organizations, including the involvement of the Food Standards Agency. RESULTS: Following the successful pilot study, Health Protection Scotland was commissioned by the Food Standards Agency to develop and roll-out FSS UK to councils and their partner laboratories throughout the UK within a 3-year period. CONCLUSION: The development of FSS UK provides the opportunity to compare and contrast national food sample data, highlight emerging food-related trends and provide an early warning system for food-related issues.
Asunto(s)
Contaminación de Alimentos/prevención & control , Abastecimiento de Alimentos/normas , Desarrollo de Programa , Microbiología de Alimentos , Salud Pública , Muestreo , Encuestas y Cuestionarios , Reino UnidoRESUMEN
Nanoparticle tracking analysis (NTA) is commonly used to count and size nano-sized particles. A sample loading pump can be used to analyse a larger sample volume, but it is unclear whether accuracy is affected. Using a NanoSight NS300 with the manufacturer-supplied pump, we examined synthetic silica and latex microspheres, liposomes and placental extracellular vesicles at different flow speeds. Analysis at flow speeds of 20 or 50 significantly reduced the measured concentration and mean/modal size of particles, particularly for mono-dispersed samples. We identify sample flow speed as a crucial instrument setting which should be reported in all studies that use NTA.
Asunto(s)
Rastreo Celular , Vesículas Extracelulares/fisiología , Nanopartículas/análisis , Placenta/ultraestructura , Rastreo Celular/métodos , Vesículas Extracelulares/química , Femenino , Citometría de Flujo/métodos , Humanos , Liposomas/análisis , Liposomas/química , Microesferas , Movimiento , Tamaño de la Partícula , Placenta/química , Placenta/citología , Embarazo , Dióxido de Silicio/químicaRESUMEN
AIM/HYPOTHESIS: Pancreatic beta cell function has been shown to decline with age in man. Depletion of mitochondrial DNA (mtDNA) copy number is associated with impaired insulin secretion in pancreatic beta cell lines, and decreased mtDNA copy number has been observed with age in skeletal muscle in man. We investigated whether mtDNA copy number decreases with age in human pancreatic beta cells, which might in turn contribute to the age-related decline in insulin secretory capacity. METHODS: We quantified mtDNA copy number in isolated human islet preparations from 15 pancreas donors aged between 17 and 75 years. Islets (n = 20) were individually hand-picked and pooled from each donor isolate for the quantification of mtDNA copy number and deleted mtDNA (%), which were determined using real-time PCR methods. RESULTS: There was a significant negative correlation between mtDNA copy number and islet donor age (r = -0.53, p = 0.044). mtDNA copy number was significantly decreased in islet preparations from donors aged > or =50 years (n = 8) compared with those aged <50 years (n = 7) (median [interquartile range]: 418 [236-503] vs 596 [554-729] mtDNA copy number/diploid genome; p = 0.032). None of the islet preparations harboured high levels of deleted mtDNA affecting the major arc. CONCLUSION/INTERPRETATION: Given the correlation between mtDNA content and respiratory chain activity, the age-related decrease in mtDNA copy number that we observed in human pancreatic islet preparations may contribute to the age-dependent decline in pancreatic beta cell insulin secretory capacity.