Assembly-dependent translation of subunits 6 (Atp6) and 9 (Atp9) of ATP synthase in yeast mitochondria

The yeast mitochondrial ATP synthase is an assembly of 28 subunits of 17 types of which 3 (subunits 6, 8, and 9) are encoded by mitochondrial genes, while the 14 others have a nuclear genetic origin. Within the membrane domain (FO) of this enzyme, the subunit 6 and a ring of 10 identical subunits 9 transport protons across the mitochondrial inner membrane coupled to ATP synthesis in the extra-membrane structure (F1) of ATP synthase. As a result of their dual genetic origin, the ATP synthase subunits are synthesized in the cytosol and inside the mitochondrion. How they are produced in the proper stoichiometry from two different cellular compartments is still poorly understood. The experiments herein reported show that the rate of translation of the subunits 9 and 6 is enhanced in strains with mutations leading to specific defects in the assembly of these proteins. These translation modifications involve assembly intermediates interacting with subunits 6 and 9 within the final enzyme and cis-regulatory sequences that control gene expression in the organelle. In addition to enabling a balanced output of the ATP synthase subunits, these assembly-dependent feedback loops are presumably important to limit the accumulation of harmful assembly intermediates that have the potential to dissipate the mitochondrial membrane electrical potential and the main source of chemical energy of the cell

Relatório de estágio em farmácia comunitária

Relatório de estágio realizado no âmbito do Mestrado Integrado em Ciências Farmacêuticas, apresentado à Faculdade de Farmácia da Universidade de Coimbr

Biais attentionnels envers des parties spécifiques du corps : rôle de l'insatisfaction corporelle

Les données de la littérature démontrent que les femmes plus ou moins insatisfaites de leur apparence physique ont tendance à focaliser leur attention sur certaines parties de leur corps. Parallèlement, un certain nombre d'études met en évidence qu'un stimulus pertinent et/ou émotionnel favorise la capture attentionnelle. Ainsi, ces femmes alloueraient leur attention préférentiellement envers des parties de corps jugées pertinentes pour l'image corporelle, créant ainsi des biais. La présente étude a pour but d'investiguer le lien entre ces biais attentionnels et les parties de corps impliquées dans l'insatisfaction corporelle chez 90 femmes. Ce lien sera également exploré en prenant en compte l'importance que ces femmes accordent aux différentes facettes de l'image corporelle. Pour ce faire, les participantes ont effectué une tâche de détection de cible et ont rempli plusieurs questionnaires..

Les troubles de l'attention sélective dans la maladie de Parkinson : étude de cas

Les données de la littérature démontrent que la maladie de Parkinson est une maladie neurodégénérative caractérisée principalement par des symptômes moteurs, affectifs et cognitifs. Plus précisément, au niveau moteur, la triade classiquement retrouvée à la phase état est constituée d’une akinésie, d’une rigidité ou hypertonie extrapyramidale et des tremblements de repos. Concernant les aspects affectifs, l’apparition de troubles de l’humeur et d’une labilité émotionnelle prédominent. Enfin, à propos des facteurs cognitifs, le tableau clinique est souvent composé au premier plan de difficultés exécutives et attentionnelles, touchant particulièrement la sélectivité de l’attention..

Detecting Perfusion Pattern based on the Background Low-frequency Fluctuation in Resting-State Functional MRI Data and its Influence on Resting-State Networks: An Iterative Post-processing Approach

RS-fMRI is based on the assumption that the vascular response and the blood oxygenation level dependent (BOLD) response are homogenous across the entire brain. However, this a priori hypothesis is not consistent with the well-known variability of cerebral vascular territories. In order to explore whether the RS networks are influenced by varied vascular speed in different vascular territories, we assessed the time-shift maps that give an estimate of the local timing of the vascular response and check whether local differences in this timing have an impact on the estimates of RS networks

Personality-related determinants of subtle cognitive decline in old age: a population-based study

Background/Aims: Recent studies of cases with mild cognitive impairment (MCI) suggested that besides Alzheimer disease (AD)-related biomarkers, some personality dimensions are associated with progression to AD. To date, there are no studies addressing the psychological determinants of subtle cognitive decline in healthy elderly controls. Methods: 488 community-dwelling healthy controls were assessed with a detailed neuropsychological battery at baseline and an 18-month follow-up. Personality factors and facets were investigated at baseline using the NEO-Personality Inventory-Revised (NEO-PI-R). Upon follow-up, there were 264 stable controls (sCON) and 224 deteriorating controls (dCON). Their personality data were compared to those of the 102 MCI cases using one-way analysis of variance and logistic regression models. Results: Significantly higher scores of Openness factor (as well as Aesthetics, Ideas and Values facets) were found in sCON than in both dCON and MCI cases. The three groups did not differ in the other NEO-PI-R factor and facet scores. Openess factor (and the same facets) was associated with cognitive preservation in healthy controls (OR: 0.72, 95% CI: 0.59, 0.87). Lower scores in the same factor and facets conferred higher risk to have MCI (OR: 0.61, 95% CI: 0.46, 0.79). Conclusion: Higher openness to new experiences and thoughts may be a protective factor against early cognitive decline in brain aging

Attention and Working Memory-Related EEG Markers of Subtle Cognitive Deterioration in Healthy Elderly Individuals

Future treatments of Alzheimer's disease need the identification of cases at high risk at the preclinical stage of the disease before the development of irreversible structural damage. We investigated here whether subtle cognitive deterioration in a population of healthy elderly individuals could be predicted by EEG signals at baseline under cognitive activation. Continuous EEG was recorded in 97 elderly control subjects and 45 age-matched mild cognitive impairment (MCI) cases during a simple attentional and a 2-back working memory task. Upon 18-month neuropsychological follow-up, the final sample included 55 stable (sCON) and 42 deteriorated (dCON) controls. We examined the P1, N1, P3, and PNwm event-related components as well as the oscillatory activities in the theta (4-7 Hz), alpha (8-13 Hz), and beta (14-25 Hz) frequency ranges (ERD/ERS: event-related desynchronization/synchronization, and ITC: inter-trial coherence). Behavioral performance, P1, and N1 components were comparable in all groups. The P3, PNwm, and all oscillatory activity indices were altered in MCI cases compared to controls. Only three EEG indices distinguished the two control groups: alpha and beta ERD (dCON >  sCON) and beta ITC (dCON <  sCON). These findings show that subtle cognitive deterioration has no impact on EEG indices associated with perception, discrimination, and working memory processes but mostly affects attention, resulting in an enhanced recruitment of attentional resources. In addition, cognitive decline alters neural firing synchronization at high frequencies (14-25 Hz) at early stages, and possibly affects lower frequencies (4-13 Hz) only at more severe stages

HDL and CER-001 Inverse-Dose Dependent Inhibition of Atherosclerotic Plaque Formation in apoE^-/- Mice: Evidence of ABCA1 Down-Regulation

<div><p>Objective</p><p>CER-001 is a novel engineered HDL-mimetic comprised of recombinant human apoA-I and charged phospholipids that was designed to mimic the beneficial properties of nascent pre-ß HDL. In this study, we have evaluated the dose-dependent regulation of ABCA1 expression <i>in vitro</i> and <i>in vivo</i> in the presence of CER-001 and native HDL (HDL3).</p><p>Methods and Results</p><p>CER-001 induced cholesterol efflux from J774 macrophages in a dose-dependent manner similar to natural HDL. A strong down-regulation of the ATP-binding cassette A1 (ABCA1) transporter mRNA (- 50%) as well as the ABCA1 membrane protein expression (- 50%) was observed at higher doses of CER-001 and HDL₃ compared to non-lipidated apoA-I. <i>In vivo</i>, in an apoE^-/- mouse “flow cessation model,” in which the left carotid artery was ligatured to induce local inflammation, the inhibition of atherosclerotic plaque burden progression in response to a dose-range of every-other-day CER-001 or HDL in the presence of a high-fat diet for two weeks was assessed. We observed a U-shaped dose-response curve: inhibition of the plaque total cholesterol content increased with increasing doses of CER-001 or HDL3 up to a maximum inhibition (- 51%) at 5 mg/kg; however, as the dose was increased above this threshold, a progressively less pronounced inhibition of progression was observed, reaching a complete absence of inhibition of progression at doses of 20 mg/kg and over. ABCA1 protein expression in the same atherosclerotic plaque was decreased by-45% and-68% at 50 mg/kg for CER-001 and HDL respectively. Conversely, a-12% and 0% decrease in ABCA1 protein expression was observed at the 5 mg/kg dose for CER-001 and HDL respectively.</p><p>Conclusions</p><p>These data demonstrate that high doses of HDL and CER-001 are less effective at slowing progression of atherosclerotic plaque in apoE^-/- mice compared to lower doses, following a U-shaped dose-response curve. A potential mechanism for this phenomenon is supported by the observation that high doses of HDL and CER-001 induce a rapid and strong down-regulation of ABCA1 both <i>in vitro</i> and <i>in vivo</i>. In conclusion, maximally efficient HDL- or CER-001-mediated cholesterol removal from atherosclerotic plaque is achieved by maximizing macrophage-mediated efflux from the plaque while minimizing dose-dependent down-regulation of ABCA1 expression. These observations may help define the optimal dose of HDL mimetics for testing in clinical trials of atherosclerotic burden regression.</p></div