Mitochondrial TERT enhances mitochondria functions in vivo by protecting mitochondrial DNA integrity from oxidative damage : meeting abstract

Mitochondria are essential for respiration and oxidative phosphorylation. Mitochondrial dysfunction due to aging processes is involved in pathologies and pathogenesis of a series of cardiovascular disorders. New results accumulate showing that the enzyme telomerase with its catalytic subunit telomerase reverse transcriptase (TERT) has a beneficial effect on heart functions. The benefit of short-term running of mice for heart function is dependent on TERT expression. TERT can translocate into the mitochondria and mitochondrial TERT (mtTERT) is protective against stress induced stimuli and binds to mitochondrial DNA (mtDNA). Because mtDNA is highly susceptible to damage produced by reactive oxygen species (ROS) which are generated in close proximity to the respiratory chain, the aim of this study was to determine the functions of mtTERT in vivo and in vitro. Therefore, mitochondria from hearts of adult, 2nd generation TERT-deficient mice (TERT -/-) and wt littermates were isolated and state 3 respiration was measured. Strikingly mitochondria from TERT -/- revealed a significantly lower state 3 respiration (TERTwt: 987 +/- 72 pmol/s*mg vs. TERT-/-: 774 +/- 38 pmol/s*mg, p < 0.05, n = 5). These results demonstrated that TERT -/- mice have a so far undiscovered heart phenotype. In contrast mitochondria isolated from liver tissues did not show any differences. To get further insights in the molecular mechanisms, we reduced endogenous TERT levels by shRNA and measured mitochondrial reactive oxygen species (mtROS). mtROS were increased after ablation of TERT (scrambled: 4.98 +/- 1.1% gated vs. shTERT: 2.03 +/- 0.7% gated, p < 0.05, n = 4). We next determined mtDNA deletions, which are caused by mtROS. Semiquantitative realtime PCR of mtDNA deletions revealed that mtTERT protects mtDNA from oxidative damage. To analyze whether mitochondrial integrity is required to protect from apoptosis, vectors with mitochondrially targeted TERT (mitoTERT) and wildtype TERT (wtTERT) were transfected and apoptosis was measured. mitoTERT showed the most prominent protective effect on H2O2 induced apoptosis. In conclusion, mtTERT has a protective role in mitochondria by importantly contributing to mtDNA integrity and thereby enhancing respiration capacity of the heart

Follow-up of vestibular function in bilateral vestibulopathy

Objective: Bilateral vestibulopathy (BV) leads to a bilateral deficit of the vestibulo-ocular reflex and has various aetiologies. The main goal of this study was to determine the frequency and degree of recovery or worsening of vestibular function over time.Methods: 82 patients (59 males, 23 females; mean age at the time of diagnosis 56.3 (SD 17.6) years) were re-examined 51 (36) months after the first examination. All patients underwent a standardised neuro-ophthalmological and neuro-otological examination. Electronystagmography with bithermal caloric irrigation was analysed by measurement of the mean peak slow phase velocity (SPV) of the induced nystagmus. Patients evaluated the course of their disease in terms of balance, gait unsteadiness and health related quality of life.Results: Statistical analysis of the mean peak SPV of caloric induced nystagmus revealed a non-significant worsening over time (initial mean peak SPV 3.0 (3.5)°/s vs 2.1 (2.8)°/s). With respect to subgroups of aetiology, only patients with BV due to meningitis exhibited an increasing, but non-significant SPV (1.0 (1.4)°/s vs 1.9 (1.6)°/s). Vestibular outcome was independent of age, gender, time course of manifestation and severity of BV. Single analysis of all patients showed that a substantial improvement ⩾5°/s occurred in two patients on both sides (idiopathic n = 1, Sjögren's syndrome n = 1) and in eight patients on one side (idiopathic n = 6, meningitis n = 1, Menière's disease n = 1). In 84% of patients there was impairment of their health related quality of life (42% slight, 24% moderate, 18% severe). Forty-three per cent of patients rated the course of their disease as stable, 28% as worsened and 29% as improved.Conclusions: Our data support the view that more than 80% of patients with BV do not improve. Thus the prognosis of BV is less favourable than assumed

Criteria for Blood Vessel Discrimination

Introduction The diagnostic potential of optical coherence tomography (OCT) in neurological diseases is intensively discussed. Besides the sectional view of the retina, modern OCT scanners produce a simultaneous top-view confocal scanning laser ophthalmoscopy (cSLO) image including the option to evaluate retinal vessels. A correct discrimination between arteries and veins (labeling) is vital for detecting vascular differences between healthy subjects and patients. Up to now, criteria for labeling (cSLO) images generated by OCT scanners do not exist. Objective This study reviewed labeling criteria originally developed for color fundus photography (CFP) images. Methods The criteria were modified to reflect the cSLO technique, followed by development of a protocol for labeling blood vessels. These criteria were based on main aspects such as central light reflex, brightness, and vessel thickness, as well as on some additional criteria such as vascular crossing patterns and the context of the vessel tree. Results and Conclusion They demonstrated excellent inter-rater agreement and validity, which seems to indicate that labeling of images might no longer require more than one rater. This algorithm extends the diagnostic possibilities offered by OCT investigations

Prevalence of Potentially Inappropriate Medication Use in Older Adults Using the 2012 Beers Criteria

The Beers list of potentially inappropriate medications (PIMs) provides a key indicator of medication prescribing quality. The criteria were updated in 2012, adding new drugs and assessing evidence strength

Comment former des enseignants pour une éducation à l'environnement et au développement durabl

Nous présentons, dans cette contribution, un atelier de formation proposé à des stagiaires IUFM et l’évaluation qui en a été faite quelques mois plus tard. Cet atelier a été élaboré en référence à une identifi cation des compétences professionnelles nécessaires à la mise en oeuvre d’une Éducation à l’environnement et au développement durable (ÉEDD). Une enquête par questionnaire permet d’évaluer l’impact de cet atelier ainsi que les freins et les motivations des enseignants par rapport aux spécifi cités de l’intégration de l’ÉEDD dans leurs pratiques d’enseignement. L’ensemble des informations recueillies permet d’envisager des propositions d’évolution du dispositif proposé

On Critchfield's proposal: student concerns and recommendations

This is the published version, reproduced here with the publisher's permission. This article is also available electronically from http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3359848/.No abstract available for this item

Massive migration from the steppe is a source for Indo-European languages in Europe

We generated genome-wide data from 69 Europeans who lived between 8,000-3,000 years ago by enriching ancient DNA libraries for a target set of almost four hundred thousand polymorphisms. Enrichment of these positions decreases the sequencing required for genome-wide ancient DNA analysis by a median of around 250-fold, allowing us to study an order of magnitude more individuals than previous studies and to obtain new insights about the past. We show that the populations of western and far eastern Europe followed opposite trajectories between 8,000-5,000 years ago. At the beginning of the Neolithic period in Europe, ~8,000-7,000 years ago, closely related groups of early farmers appeared in Germany, Hungary, and Spain, different from indigenous hunter-gatherers, whereas Russia was inhabited by a distinctive population of hunter-gatherers with high affinity to a ~24,000 year old Siberian6 . By ~6,000-5,000 years ago, a resurgence of hunter-gatherer ancestry had occurred throughout much of Europe, but in Russia, the Yamnaya steppe herders of this time were descended not only from the preceding eastern European hunter-gatherers, but from a population of Near Eastern ancestry. Western and Eastern Europe came into contact ~4,500 years ago, as the Late Neolithic Corded Ware people from Germany traced ~3/4 of their ancestry to the Yamnaya, documenting a massive migration into the heartland of Europe from its eastern periphery. This steppe ancestry persisted in all sampled central Europeans until at least ~3,000 years ago, and is ubiquitous in present-day Europeans. These results provide support for the theory of a steppe origin of at least some of the Indo-European languages of Europe