Mitochondrial DNA mutations in individuals occupationally exposed to ionizing radiation

Mutations in a 443-bp amplicon of the hypervariable region HVR1 of the D-loop of mitochondrial DNA (mtDNA) were quantified in DNA extracted from peripheral blood samples of 10 retired radiation workers who had accumulated external radiation doses of .0.9 Sv over the course of their working life and were compared to the levels of mutations in 10 control individuals matched for age and smoking status. The mutation rate in the 10 exposed individuals was 9.92 3 1025 mutations/ nucleotide, and for the controls it was 8.65 3 1025 mutations/ nucleotide, with a procedural error rate of 2.65 3 1025 mutations/ nucleotide. No increase in mtDNA mutations due to radiation exposure was detectable (P 5 0.640). In contrast, chromosomal translocation frequencies, a validated radiobiological technique for retrospective dosimetric purposes, were significantly elevated in the exposed individuals. This suggests that mutations identified through sequencing of mtDNA in peripheral blood lymphocytes do not represent a promising genetic marker of DNA damage after low-dose or low-doserate exposures to ionizing radiation. There was an increase in singleton mutations above that attributable to procedural error in both exposed and control groups that is likely to reflect age-related somatic mutation

Human aging and somatic point mutations in mtDNA: A comparative study of generational differences (grandparents and grandchildren)

The accumulation of somatic mutations in mtDNA is correlated with aging. In this work, we sought to identify somatic mutations in the HVS-1 region (D-loop) of mtDNA that might be associated with aging. For this, we compared 31 grandmothers (mean age: 63 ± 2.3 years) and their 62 grandchildren (mean age: 15 ± 4.1 years), the offspring of their daughters. Direct DNA sequencing showed that mutations absent in the grandchildren were detected in a presumably homoplasmic state in three grandmothers and in a heteroplasmic state in an additional 13 grandmothers; no mutations were detected in the remaining 15 grandmothers. However, cloning followed by DNA sequencing in 12 grandmothers confirmed homoplasia in only one of the three mutations previously considered to be homoplasmic and did not confirm heteroplasmy in three out of nine grandmothers found to be heteroplasmic by direct sequencing. Thus, of 12 grandmothers in whom mtDNA was analyzed by cloning, eight were heteroplasmic for mutations not detected in their grandchildren. In this study, the use of genetically related subjects allowed us to demonstrate the occurrence of age-related (> 60 years old) mutations (homoplasia and heteroplasmy). It is possible that both of these situations (homoplasia and heteroplasmy) were a long-term consequence of mitochondrial oxidative phosphorylation that can lead to the accumulation of mtDNA mutations throughout life

Effect of food concentration and type of diet on Acartia survival and naupliar development

We have performed life table experiments to investigate the effects of different food types and concentrations on the larval development and survival up to adulthood of Acartia tonsa. The food species offered comprised a wide taxonomic spectrum: the pigmented flagellates Isochrysis galbana, Emiliania huxleyi, Rhodomonas sp., Prorocentrum minimum, the diatom Thalassiosira weissflogii, grown on medium offering enriched macronutrient concentrations and the ciliate Euplotes sp. initially cultured on Rhodomonas. For the ciliate species, also the functional response was studied. In order to avoid limitation by mineral nutrients, food algae have been taken from the exponential growth phase of the nutrient replete cultures. The suitability of Rhodomonas as a food source throughout the entire life cycle was not a surprise. However, in contrast to much of the recent literature about the inadequacy or even toxicity of diatoms, we found that also Thalassiosira could support Acartia-development through the entire life cycle. On the other hand, Acartia could not complete its life cycle when fed with the other food items, Prorocentrum having adverse effects even when mixed with Rhodomonas and Thalassiosira. Isochrysis well supported naupliar survival and development, but was insufficient to support further development until reproduction. With Emiliania and Euplotes, nauplii died off before most of them could reach the first copepodite stages. Acartia-nauplii showed a behavioral preference for Euplotes-feeding over diatom feeding, but nevertheless Euplotes was an insufficient diet to complete development beyond the naupliar stages

Pre-microRNA and Mature microRNA in Human Mitochondria

Chantier qualité GAInternational audienceBACKGROUND: Because of the central functions of the mitochondria in providing metabolic energy and initiating apoptosis on one hand and the role that microRNA (miRNA) play in gene expression, we hypothesized that some miRNA could be present in the mitochondria for post-transcriptomic regulation by RNA interference. We intend to identify miRNA localized in the mitochondria isolated from human skeletal primary muscular cells. METHODOLOGY/PRINCIPAL FINDINGS: To investigate the potential origin of mitochondrial miRNA, we in-silico searched for microRNA candidates in the mtDNA. Twenty five human pre-miRNA and 33 miRNA aligments (E-value35) for the smallest RNA input concentration and 204 miRNA for the maximum RNA input concentration. In silico analysis predicted 80 putative miRNA target sites in the mitochondrial genome (E-value<0.05). CONCLUSIONS/SIGNIFICANCE: The present study experimentally demonstrated for the first time the presence of pre-miRNA and miRNA in the human mitochondria isolated from skeletal muscular cells. A set of miRNA were significantly detected in mitochondria fraction. The origin of these pre-miRNA and miRNA should be further investigate to determine if they are imported from the cytosol and/or if they are partially processed in the mitochondria

Hearing and dementia

Hearing deficits associated with cognitive impairment have attracted much recent interest, motivated by emerging evidence that impaired hearing is a risk factor for cognitive decline. However, dementia and hearing impairment present immense challenges in their own right, and their intersection in the auditory brain remains poorly understood and difficult to assess. Here, we outline a clinically oriented, symptom-based approach to the assessment of hearing in dementias, informed by recent progress in the clinical auditory neuroscience of these diseases. We consider the significance and interpretation of hearing loss and symptoms that point to a disorder of auditory cognition in patients with dementia. We identify key auditory characteristics of some important dementias and conclude with a bedside approach to assessing and managing auditory dysfunction in dementia

The Ontogenetic Osteohistology of Tenontosaurus tilletti

Tenontosaurus tilletti is an ornithopod dinosaur known from the Early Cretaceous (Aptian-Albian) Cloverly and Antlers formations of the Western United States. It is represented by a large number of specimens spanning a number of ontogenetic stages, and these specimens have been collected across a wide geographic range (from central Montana to southern Oklahoma). Here I describe the long bone histology of T. tilletti and discuss histological variation at the individual, ontogenetic and geographic levels. The ontogenetic pattern of bone histology in T. tilletti is similar to that of other dinosaurs, reflecting extremely rapid growth early in life, and sustained rapid growth through sub-adult ontogeny. But unlike other iguanodontians, this dinosaur shows an extended multi-year period of slow growth as skeletal maturity approached. Evidence of termination of growth (e.g., an external fundamental system) is observed in only the largest individuals, although other histological signals in only slightly smaller specimens suggest a substantial slowing of growth later in life. Histological differences in the amount of remodeling and the number of lines of arrested growth varied among elements within individuals, but bone histology was conservative across sampled individuals of the species, despite known paleoenvironmental differences between the Antlers and Cloverly formations. The bone histology of T. tilletti indicates a much slower growth trajectory than observed for other iguanodontians (e.g., hadrosaurids), suggesting that those taxa reached much larger sizes than Tenontosaurus in a shorter time

A Ceratopsian Dinosaur from the Lower Cretaceous of Western North America, and the Biogeography of Neoceratopsia

Competing interests: Andrew A. Farke has read the journal's policy and the authors of this manuscript have the following competing interests: Andrew A. Farke is a volunteer section editor and academic editor for PLOS ONE. This does not alter the authors' adherence to PLOS ONE policies on sharing data and materials.Acknowledgments It is a pleasure to offer our most heartfelt thanks to Scott K. Madsen, who found OMNH 34557 and prepared it with consummate skill. We are grateful to James Taylor, Jack Owen, the Keebler family, and the Montana Bureau of Land Management for access to outcrops of the Cloverly Formation. We thank Xu Xing (IVPP) and Hai-Lu You (formerly CAGS-IG) for facilitating access to specimens, Mark Loewen, Joseph Frederickson, Darren Naish, and Leonardo Maiorino for productive discussion and comments, and Roger Burkhalter for assistance in photography. Gary Wisser, from the scientific visualization center at Western University of Health Sciences, is gratefully acknowledged for the high resolution scan of the cranium. Reviews by Peter Makovicky, Hai-Lu You, and editor Peter Wilf improved the manuscript.Author Contributions Conceived and designed the experiments: AAF WDM RLC. Performed the experiments: AAF WDM RLC. Analyzed the data: AAF WDM RLC MJW. Contributed reagents/materials/analysis tools: AAF WDM RLC MJW. Wrote the paper: AAF WDM RLC MJW.The fossil record for neoceratopsian (horned) dinosaurs in the Lower Cretaceous of North America primarily comprises isolated teeth and postcrania of limited taxonomic resolution, hampering previous efforts to reconstruct the early evolution of this group in North America. An associated cranium and lower jaw from the Cloverly Formation (?middle–late Albian, between 104 and 109 million years old) of southern Montana is designated as the holotype for Aquilops americanus gen. et sp. nov. Aquilops americanus is distinguished by several autapomorphies, including a strongly hooked rostral bone with a midline boss and an elongate and sharply pointed antorbital fossa. The skull in the only known specimen is comparatively small, measuring 84 mm between the tips of the rostral and jugal. The taxon is interpreted as a basal neoceratopsian closely related to Early Cretaceous Asian taxa, such as Liaoceratops and Auroraceratops. Biogeographically, A. americanus probably originated via a dispersal from Asia into North America; the exact route of this dispersal is ambiguous, although a Beringian rather than European route seems more likely in light of the absence of ceratopsians in the Early Cretaceous of Europe. Other amniote clades show similar biogeographic patterns, supporting an intercontinental migratory event between Asia and North America during the late Early Cretaceous. The temporal and geographic distribution of Upper Cretaceous neoceratopsians (leptoceratopsids and ceratopsoids) suggests at least intermittent connections between North America and Asia through the early Late Cretaceous, likely followed by an interval of isolation and finally reconnection during the latest Cretaceous.Funding was received from the National Science Foundation (DEB 9401094, 9870173, http://www.nsf.gov); National Geographic Society (5918-97, http://www.nationalgeographic.com/); and American Chemical Society (PRF #38572-AC8, http://www.acs.org). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Yeshttp://www.plosone.org/static/editorial#pee

Metabolic dysregulation in vitamin E and carnitine shuttle energy mechanisms associate with human frailty

Global ageing poses a substantial economic burden on health and social care costs. Enabling a greater proportion of older people to stay healthy for longer is key to the future sustainability of health, social and economic policy. Frailty and associated decrease in resilience plays a central role in poor health in later life. In this study, we present a population level assessment of the metabolic phenotype associated with frailty. Analysis of serum from 1191 older individuals (aged between 56 and 84 years old) and subsequent longitudinal validation (on 786 subjects) was carried out using liquid and gas chromatography-mass spectrometry metabolomics and stratified across a frailty index designed to quantitatively summarize vulnerability. Through multivariate regression and network modelling and mROC modeling we identified 12 significant metabolites (including three tocotrienols and six carnitines) that differentiate frail and non-frail phenotypes. Our study provides evidence that the dysregulation of carnitine shuttle and vitamin E pathways play a role in the risk of frailty