Substrate metabolism, nutrient balance and obesity development in children and adolescents: a target for intervention?

Obesity results from the organism's inability to maintain energy balance over a long term. Childhood obesity and its related factors and pathological consequences tend to persist into adulthood. A cluster of factors, including high energy density in the diet (high fat intake), low energy expenditure, and disturbed substrate oxidation, favour the increase in fat mass. Oxidation of three major macronutrients and their roles in the regulation of energy balance, particularly in children and adolescents, are discussed. Total glucose oxidation is not different between obese and lean children; exogenous glucose utilization is higher whereas endogenous glucose utilization is lower in obese compared with lean children. Carbohydrate composition of the diet determines carbohydrate oxidation regardless of fat content of the diet. Both exogenous and endogenous fat oxidation are higher in obese than in lean subjects. The influence of high fat intake on accumulation of fat mass is operative rather over a long term. Several future directions are addressed, such that a combination of increased physical activity and modification in diet composition, in terms of energy density and glycemic index, is recommended for children and adolescents.

Development of model observers applied to 3D breast tomosynthesis microcalcifications and masses

The development of model observers for mimicking human detection strategies has followed from symmetric signals in simple noise to increasingly complex backgrounds. In this study we implement different model observers for the complex task of detecting a signal in a 3D image stack. The backgrounds come from real breast tomosynthesis acquisitions and the signals were simulated and reconstructed within the volume. Two different tasks relevant to the early detection of breast cancer were considered: detecting an 8 mm mass and detecting a cluster of microcalcifications. The model observers were calculated using a channelized Hotelling observer (CHO) with dense difference-of-Gaussian channels, and a modified (Partial prewhitening [PPW]) observer which was adapted to realistic signals which are not circularly symmetric. The sustained temporal sensitivity function was used to filter the images before applying the spatial templates. For a frame rate of five frames per second, the only CHO that we calculated performed worse than the humans in a 4-AFC experiment. The other observers were variations of PPW and outperformed human observers in every single case. This initial frame rate was a rather low speed and the temporal filtering did not affect the results compared to a data set with no human temporal effects taken into account. We subsequently investigated two higher speeds at 5, 15 and 30 frames per second. We observed that for large masses, the two types of model observers investigated outperformed the human observers and would be suitable with the appropriate addition of internal noise. However, for microcalcifications both only the PPW observer consistently outperformed the humans. The study demonstrated the possibility of using a model observer which takes into account the temporal effects of scrolling through an image stack while being able to effectively detect a range of mass sizes and distributions.

Development and evaluation of a shaken baby syndrome prevention program.

OBJECTIVE: To evaluate parents' and nurses' opinions regarding the adequacy of an educational program on shaken baby syndrome: the Perinatal Shaken Baby Syndrome Prevention Program (PSBSPP). DESIGN: Qualitative and quantitative assessments in the form of interviews and questionnaires administered in French. SETTING: Two birthing institutions in Montréal, QC, Canada: a university hospital and a regional center. PARTICIPANTS: Two hundred and sixty-three parents (73.8% mothers, 26.2% fathers) received the intervention after the birth of their child, and 69 nurses administered it. METHODS: Parents' and nurses' assessments of the adequacy and relevance of the program and nurses' assessments of the training they received to administer the program were evaluated. RESULTS: Both parents and nurses supported this initiative. Most parents appreciated the usefulness of the information. Nurses believed the program was adequate, and their training to deliver the program was satisfactory. All participants reported that the program was highly relevant, especially for new parents. CONCLUSION: The Perinatal Shaken Baby Syndrome Prevention Program achieves the goals of (a) increasing parents' knowledge about infant crying, anger, and shaken baby syndrome and (b) helping parents identify coping strategies. The relevance of introducing the PSBSPP in all birthing institutions is supported. Future studies should focus on vulnerable and culturally diverse populations, and longitudinal follow-up could help determine if the PSBSPP reduces the incidence of shaken baby syndrome.

Plasma leptin levels in men are not related to the development of lipoatrophy during antiretroviral therapy.

OBJECTIVES: To assess the correlations between the hormone leptin and lipoatrophy in HIV-positive, treatment-naive patients on combination antiretroviral therapy (cART). DESIGN: Case-control study nested in a multicentre cohort of HIV-infected adults. Cases were patients that developed lipoatrophy and controls those who did not. PATIENTS AND METHODS: Clinical parameters and plasma leptin determinations were studied in 97 HIV-1-infected, treatment-naive Caucasian men (10 cases and 87 controls) on an unchanged and virologically successful drug regimen with a zidovudine/lamivudine backbone at baseline and after 2 years of cART. The association of plasma leptin levels and the development of lipoatrophy was investigated. RESULTS: Two years of cART was not associated with a change in plasma leptin levels. Plasma leptin levels remained sensible to changes in body mass index. There was no difference in leptin levels between patients who developed lipoatrophy and controls, neither before nor after cART. The only predictor of development of lipoatrophy was a higher age (P = 0.02). CONCLUSIONS: Leptin as measured in plasma is unlikely to play a major role in the genesis of lipoatrophy.

Sox genes in C. elegans: sox-2 role in postembryonic development

Report for the scientific sojourn carried out at the Columbia University, United States, from 2010 to 2012. Expression of SoxB genes correlates with the commitment of cells to a neural fate; however, the relevance of SoxB proteins in early vertebrate neurogenesis has been difficult to prove genetically due to embryonic lethality and presumed redundant functions. The nematode C. Elegants has only 5 sox genes: sox-2 and sox-3 form the SoxB group while sem-2, sox-4 and egl-13 belong to other Sox groups. Our results show that sox-2 and sem-2 are the sox genes expressed earliest and in a broader manner during embryogenesis, being expressed in several neuronal progenitors. sox-3, sox-4 and egl-13 are expressed in few cells during late embryogenesis, when most neurons are already born. Both sox-2 and sem-2 null mutants are early larval lethal but do not show neuronal specification defects during embryonic development as indicated by quantification of a panneuronal reporter. Potential redundancy or compensatory mechanisms between different sox genes have been ruled out, strongly suggesting that sox genes are not required for specification of embryonically-derived neurons. However, at the first larval stage there are still several blast cells that will give rise to different postembryonic lineages, which generate several neurons amongst other cell types. nterestingly, sox-2 is expressed in many of these progenitor cells. Using mosaic analysis we have so far identified neurons derived from two different postembryonic lineages which fail to be generated in C. elegans sox-2 mutants. These results support the idea that postembryonic progenitor competence is compromised in the absence of sox-2.

Development of a well-defined medium for the in vitro maturation of immature bovine cumulus-oocyte complexes.

PURPOSE: Our purpose was to develop a well-defined medium for the in vitro maturation (IVM) of immature bovine cumulus-oocyte complexes (COC). METHODS: The COC were cultured in the presence of three protein supplementations: fetal bovine serum (FBS), bovine serum albumin, and Synthetic Serum Substitute. The embryos obtained after in vitro fertilization of IVM oocytes were cocultured with Vero cells and their development to the morula and blastocyst stages was studied. RESULTS: When FBS was absent from the IVM medium, a significantly lower fertilization rate was observed, followed by a decrease in the percentage of embryos reaching the blastocyst stage. When FBS was replaced by a defined protein supplementation, the best results were obtained with Synthetic Serum Substitute. CONCLUSIONS: Adequate protein supplementation of the IVM medium optimizes the fertilization rate and the development of bovine IVM oocytes. The implication of these results in the human field is discussed.

"INTERMED": a method to assess health service needs. I. Development and reliability.

The purpose of this paper is to describe the development and to test the reliability of a new method called INTERMED, for health service needs assessment. The INTERMED integrates the biopsychosocial aspects of disease and the relationship between patient and health care system in a comprehensive scheme and reflects an operationalized conceptual approach to case mix or case complexity. The method is developed to enhance interdisciplinary communication between (para-) medical specialists and to provide a method to describe case complexity for clinical, scientific, and educational purposes. First, a feasibility study (N = 21 patients) was conducted which included double scoring and discussion of the results. This led to a version of the instrument on which two interrater reliability studies were performed. In study 1, the INTERMED was double scored for 14 patients admitted to an internal ward by a psychiatrist and an internist on the basis of a joint interview conducted by both. In study 2, on the basis of medical charts, two clinicians separately double scored the INTERMED in 16 patients referred to the outpatient psychiatric consultation service. Averaged over both studies, in 94.2% of all ratings there was no important difference between the raters (more than 1 point difference). As a research interview, it takes about 20 minutes; as part of the whole process of history taking it takes about 15 minutes. In both studies, improvements were suggested by the results. Analyses of study 1 revealed that on most items there was considerable agreement; some items were improved. Also, the reference point for the prognoses was changed so that it reflected both short- and long-term prognoses. Analyses of study 2 showed that in this setting, less agreement between the raters was obtained due to the fact that the raters were less experienced and the scoring procedure was more susceptible to differences. Some improvements--mainly of the anchor points--were specified which may further enhance interrater reliability. The INTERMED proves to be a reliable method for classifying patients' care needs, especially when used by experienced raters scoring by patient interview. It can be a useful tool in assessing patients' care needs, as well as the level of needed adjustment between general and mental health service delivery. The INTERMED is easily applicable in the clinical setting at low time-costs.

Development and validation of AMANDA, a new algorithm for selecting highly relevant regions in Molecular Interaction Fields

Descriptors based on Molecular Interaction Fields (MIF) are highly suitable for drug discovery, but their size (thousands of variables) often limits their application in practice. Here we describe a simple and fast computational method that extracts from a MIF a handful of highly informative points (hot spots) which summarize the most relevant information. The method was specifically developed for drug discovery, is fast, and does not require human supervision, being suitable for its application on very large series of compounds. The quality of the results has been tested by running the method on the ligand structure of a large number of ligand-receptor complexes and then comparing the position of the selected hot spots with actual atoms of the receptor. As an additional test, the hot spots obtained with the novel method were used to obtain GRIND-like molecular descriptors which were compared with the original GRIND. In both cases the results show that the novel method is highly suitable for describing ligand-receptor interactions and compares favorably with other state-of-the-art methods.

Hedgehog signaling governs the development of otic sensory epithelium and its associated innervation in zebrafish

The inner ear is responsible for the perception of motion and sound in vertebrates. Its functional unit, the sensory patch, contains mechanosensory hair cells innervated by sensory neurons from the statoacoustic ganglion (SAG) that project to the corresponding nuclei in the brainstem. How hair cells develop at specific positions, and how otic neurons are sorted to specifically innervate each endorgan and to convey the extracted information to the hindbrain is not completely understood. In this work, we study the generation of macular sensory patches and investigate the role of Hedgehog (Hh) signaling in the production of their neurosensory elements. Using zebrafish transgenic lines to visualize the dynamics of hair cell and neuron production, we show that the development of the anterior and posterior maculae is asynchronic, suggesting they are independently regulated. Tracing experiments demonstrate the SAG is topologically organized in two different neuronal subpopulations, which are spatially segregated and innervate specifically each macula. Functional experiments identify the Hh pathway as crucial in coordinating the production of hair cells in the posterior macula, and the formation of its specific innervation. Finally, gene expression analyses suggest that Hh influences the balance between different SAG neuronal subpopulations. These results lead to a model in which Hh orients functionally the development of inner ear towards an auditory fate in all vertebrate species.

Self-Development of Competences for Social Inclusion Using the TENCompetence Infrastructure

This paper describes a pilot study centred on the technology-enhanced self-development of competences in lifelong learning education carried out in the challenging context of the Association of Participants Àgora. The pilot study shows that the use of the TENCompetence infrastructure, i.e. in this case the Personal Development Planner tool, provides various kinds of benefits for adult participants with low educational profiles and who are traditionally excluded from the use of innovative learning technologies and the knowledge society. The selforganized training supported by the PDP tool aims at allowing the learners to create and control their own learning plans based on their interests and educational background including informal and non-formal experiences. In this sense, the pilot participants had the opportunity to develop and improve their competences in English language (basic and advanced levels) and ICT competence profiles which are mostly related to functional and communicative skills. Besides, the use of the PDP functionalities, such as the self-assessment, the planning and the self-regulating elements allowed the participants to develop reflective skills. Pilot results also provide indications for future developments in the field of technology support for self-organized learners. The paper introduces the context and the pilot scenario, indicates the evaluation methodology applied and discusses the most significant findings derived from the pilot study.

CO2 production of the chick embryo during the first day of post-laying development.

The carbon dioxide production of the chick embryo cultured in vitro has been determined during the first 24 h of post-laying development using a non-invasive conductometric microtechnique. The mean CO2 production of the whole blastoderm (1) increased from 16 nmol/h at laying to 231 nmol/h at early neurulation, (2) became dependent on exogenous glucose and (3) was closely linked to mechanical tension generated in the blastoderm (loosening from vitelline membrane resulted in a decrease of 56%). In our experimental conditions, no significant influence of carbonic anhydrase on the CO2 production has been detected. The value of the respiratory exchange ratio varied from about 3 at pregastrular stages to 1 at neurula stage and CO2 was produced transiently in presence of antimycin A. Such results indicate that the source of CO2 is not exclusively mitochondrial and that the relative proportions of mitochondrial and non-mitochondrial CO2 productions might vary significantly throughout the early development. Our findings confirm that the metabolism of the chick embryo becomes more and more oxidative from laying onwards and suggest that the modifications of metabolism observed during the studied period of development could be associated with functional differentiation.

Supporting life-long competence development using the TENCompetence infrastructure: a first experiment

This paper describes an experiment to explore the effects of the TENCompetence infrastructure for supporting lifelong competence development which is now in development. This infrastructure provides structured, multi-leveled access to learning materials, based upon competences. People can follow their own learning path, supported by a listing of competences and their components, by competence development plans attached to competences and by the possibility to mark elements as complete. We expected the PCM to have an effect on (1) control of participants of their own learning, and (2) appreciation of their learning route, (3) of the learning resources, (4) of their competence development, and (5) of the possibilities of collaboration. In the experiment, 44 Bulgarian teachers followed a distance learning course on a specific teaching methodology for six weeks. Part of them used the TENCompetence infrastructure, part used an infrastructure which was similar, except for the characterizing elements mentioned above. The results showed that in the experimental condition, more people passed the final competence assess-ment, and people felt more in control of their own learning. No differences between the two groups were found on the amount and appreciation of collaboration and on further measures of competence development.

Development of In-Situ Detection Methods for Materials-Related Distress (MRD) in Concrete Pavements, July 2003

The purpose of this research was to summarize existing nondestructive test methods that have the potential to be used to detect materials-related distress (MRD) in concrete pavements. The various nondestructive test methods were then subjected to selection criteria that helped to reduce the size of the list so that specific techniques could be investigated in more detail. The main test methods that were determined to be applicable to this study included two stress-wave propagation techniques (impact-echo and spectral analysis of surface waves techniques), infrared thermography, ground penetrating radar (GPR), and visual inspection. The GPR technique was selected for a preliminary round of “proof of concept” trials. GPR surveys were carried out over a variety of portland cement concrete pavements for this study using two different systems. One of the systems was a state-of-the-art GPR system that allowed data to be collected at highway speeds. The other system was a less sophisticated system that was commercially available. Surveys conducted with both sets of equipment have produced test results capable of identifying subsurface distress in two of the three sites that exhibited internal cracking due to MRD. Both systems failed to detect distress in a single pavement that exhibited extensive cracking. Both systems correctly indicated that the control pavement exhibited negligible evidence of distress. The initial positive results presented here indicate that a more thorough study (incorporating refinements to the system, data collection, and analysis) is needed. Improvements in the results will be dependent upon defining the optimum number and arrangement of GPR antennas to detect the most common problems in Iowa pavements. In addition, refining highfrequency antenna response characteristics will be a crucial step toward providing an optimum GPR system for detecting materialsrelated distress.

Development of the first disease activity index for eosinophilic esophagitis: update on the EEsAI in 2012

Background and Aims: The international E EsAI s tudy g roup is currently d eveloping the first activity index ( EEsAI) specific for E osinophilic Esophagitis (EoE). G oal: T o develop, e valuate and validate the EEsAI. Methods: T he development c omprises three p hases: 1. Selection of c andidate items ( completed); 2. Evaluation of t he activity index i n a first patient cohort (in progress, p atient recruitment completed); and 3. Validation in a s econd EoE patient cohort. F ocus group interviews with patients were used in p hase 1 to g enerate patient r eported outcomes (PRO) according to g uidelines o f regulatory authorities (FDA a nd EMA), whereas the section of biologic items was developed by Delphi rounds o f international E oE experts from E urope and North America. Results: T he EEsAI has a modular c omposition to a ssess the following components o f EoE activity: p atient r eported outcomes, e ndoscopic activity, histologic activity, laboratory activity, a nd quality of l ife (QoL). Definitions for a ll aspects o f endoscopic and histologic appearance were e stablished by consensus r ounds a mong E oE experts. S ymptom a ssessment tools were c reated that t ake into account d ifferent food consistencies as w ell as f ood avoidance and specific processing strategies. The EEsAI i s currently e valuated in a cohort of a dult EoE patients since M arch 2 011 (patient recruitment completed). Conclusions: The EEsAI standardizes outcome assessment in EoE t rials. T he collaboration with i nternational E oE e xperts a s well as f ollowing o f the guidelines f rom regulatory authorities will lead to its wide applicability.

The role of Bmi1 in CNS development and in retinal degeneration

SUMMARY : The present work addresses several aspects of cell cycle regulation, cell fate specification and cell death in the central nervous system (CNS), specifically the cortex and the retina. More precisely, we investigated the role of Bmi1, a polycomb family gene required for stem cell proliferation and self-renewal, in the development of the cerebral cortex, as well as in the genesis of the retina. These data, together with studies published during the last two decades concerning cell cycle re-activation in apoptotic neurons in the CNS, raised the question of a possible link between regulation of the cell cycle during development and during retinal degeneration. 1. The effects of Bmi1 loss in the cerebral cortex : Consistently with our and others' observations on failure of Bmi9-/- stem cells to proliferate and self-renew in vitro, the Bmi9-/- cerebral cortex presented slight defects in proliferation in stem/progenitor cells compartments in vivo. This was in accordance with the pattern of Bmi1 expression in the developing forebrain. The modest proliferation defects, compared to the drastic consequences of Bmi9 loss in vitro, suggest that cell-extrinsic mechanisms may partially compensate for Bmi1 deletion in vivo during cortical histogenesis. Nevertheless, we observed a decreased proliferating activity in neurogenic regions of the adult telencephalon, more precisely in the subventricular zone, showing that Bmi1 controls neural stem/progenitor proliferation during adulthood in vivo. Our data also highlight an increased production of astrocytes at birth, and a generalized gliosis in the adult Bmi9-/- brain. Importantly, glial progenitors and astrocytes retained the ability to proliferate in the absence of Bmi1. 2. The effects of Bmi1 loss in the retina : The pattern of expression of Bmi1 during development and in the adult retina suggests a role for Bmi1 in cell fate specification and differentiation rather than in proliferation. While the layering and the global structure of the retina appear normal in Bmi1 /adult mice, immunohistochemìcal analysis revealed defects in the three major classes of retinal interneurons, namely: horizontal, bipolar and amacrine cells. Electroretinogram recordings in Bmi9-/- mice are coherent with the defects observed at the histological level, with a reduced b-wave and low-profile oscillatory potentials. These results show that Bmi1 controls not only proliferation, but also cell type generation, as previously observed in the cerebellum. 3. Cell cycle events and related neuroprotective strategies in retinal degeneration : In several neurodegenerative disorders, neurons re-express cell cycle proteins such as cyclin dependent kinases (Cdks) prior to apoptosis. Here, we show for the first time that this is also the case during retinal degeneration. Rd1 mice carry a recessive defect (Pdeóbrd/rd) that causes retinal degeneration and serves as a model of retinitis pigmentosa. We found that photoreceptors express Cdk4 and Cdk2, and undergo DNA synthesis prior to cell death. To interfere with the reactivation of Cdk-related pathways, we deleted E2fs or Brni1, which normally allow cell cycle progression. While deleting E2f1 (downstream of Cdk4/6) in Rd1 mice provides only temporary protection, knocking out Bmi1 (upstream of Cdks) leads to an extensive neuroprotective effect, independent of p16ink4a or p19arf, two tumor suppressors regulated by Bmi1. Analysis of Cdks and the DNA repair-related protein Ligase IV showed that Bmi1 acts downstream of DNA repair events and upstream of Cdks in this neurodegenerative mechanism. Expression of Cdks during an acute model of retinal degeneration, light damage-induced photoreceptor death, points to a role for Bmi1 and cell cycle proteins in retinal degeneration. Considering the similarity with the cell cycle-related apoptotic pathway observed in other neurodegenerative diseases, Bmi1 is a possible general target to prevent or delay neuronal death. RESUME : Ce travail aborde plusieurs aspects de la régulation du cycle cellulaire, de la spécification du devenir des cellules et de la mort cellulaire dans le système nerveux centrale (SNC), plus particulièrement dans le cortex cérébral et dans la rétine. Nous nous sommes intéressés au gène Bmi1, appartenant à la famille polycomb et nécessaire à la prolifération et au renouvellement des cellules souches. Nous avons visé à disséquer son rôle dans le développement du cortex et de la rétine. Ces données, ainsi qu'une série de travaux publiés au cours des deux dernières décennies concernant la réactivation du cycle cellulaire dans les neurones en voie d'apoptose dans le SNC, nous ont ensuite poussé à chercher un lien entre la régulation du cycle cellulaire pendant le développement et au cours de la dégénérescence rétinienne. 1. Les effets de l'inactivation de Bmi1 dans le cortex cérébral : En accord avec l'incapacité des cellules souches neurales in vitro à proliférer et à se renouveler en absence de Bmi1, le cortex cérébral des souris Bmi1-/- présente de légers défauts de prolifération dans les compartiments contenant les cellules souches neurales. Ceci est en accord avec le profil d'expression de Bmi1 dans le télencéphale. Les conséquences de la délétion de Bmi1 sont toutefois nettement moins prononcées in vivo qu'in vitro ; cette différence suggère l'existence de mécanismes pouvant partiellement compenser l'absence de Bmi1 pendant la corticogenèse. Néanmoins, l'observation d'une réduction de la prolifération dans la zone sous-ventriculaire, la zone majeure de neurogenèse dans le télencéphale adulte, montre que Bmi1 contrôle la prolifération des cellules souche/progénitrices neurales chez la souris adulte. Nos résultats démontrent par ailleurs une augmentation de la production d'astrocytes à la naissance ainsi qu'une gliose généralisée à l'état adulte chez les souris Bmi1-/-. Les progéniteurs gliaux et les astrocytes conservent donc leur capacité à proliférer en absence de Bmi1. 2. Les effets de l'inactivation de Bmi1 dans la rétine : Le profil d'expression de Bmi1 pendant fe développement ainsi que dans la rétine adulte suggère un rôle de Bmi1 dans la spécification de certains types cellulaires et dans la différentiation plutôt que dans la prolifération. Alors que la structure et la lamination de la rétine semblent normales chez les souris Bmi1-/-, l'analyse par immunohistochimie amis en évidence des défauts au niveau des trois classes d'interneurones rétiniens (les cellules horizontales, bipolaires et amacrines). Les électrorétinogrammes des souris Bmi1-/- sont cohérents avec les défauts observés au niveau histologique et montrent une réduction de l'onde « b » et des potentiels oscillatoires. Ces résultats montrent que Bmi1 contrôle la génération de certaines sous-populations de neurones, comme démontré auparavant au niveau de cervelet. 3. Réactivation du cycle cellulaire et stratégies théraoeutiaues dans les dégénérescences rétiniennes : Dans plusieurs maladies neurodégénératives, les neurones ré-expriment des protéines du cycle cellulaire telles que les kinases cycline-dépendantes (Cdk) avant d'entrer en apoptose. Nous avons démontré que c'est aussi le cas dans les dégénérescences rétiniennes. Les souris Rd1 portent une mutation récessive (Pde6brd/rd) qui induit une dégénérescence de la rétine et sont utilisées comme modèle animal de rétinite pigmentaire. Nous avons observé que les photorécepteurs expriment Cdk4 et Cdk2, et entament une synthèse d'ADN avant de mourir par apoptose. Pour interférer avec la réactivation les mécanismes Cdk-dépendants, nous avons inactivé les gènes E2f et Bmi1, qui permettent normalement la progression du cycle cellulaire. Nous avons mis en évidence que la délétion de E2f1 (en aval de Cdk4/6) dans les souris Rd1 permet une protection transitoire des photorécepteurs. Toutefois, l'inactivation de Bmi1 (en amont des Cdk) est corrélée à une neuroprotection bien plus durable et ceci indépendamment de p16ink4a et p19arf, deux suppresseurs de tumeurs normalement régulés par Bmi1. L'analyse des Cdk et de la ligase IV (une protéine impliquée dans les mécanismes de réparation de l'ADN) a montré que Bmi1 agit en aval des événements de réparation de l'ADN et en amont des Cdk dans la cascade apoptotique dans les photorécepteurs des souris Rd1. Nous avons également observé la présence de Cdk dans un modèle aigu de dégénérescence rétinienne induit par une exposition des animaux à des niveaux toxiques de lumière. Nos résultats suggèrent donc un rôle général de Bmi1 et des protéines du cycle cellulaire dans les dégénérescences de la rétine. Si l'on considère la similarité avec les événements de réactivation du cycle cellulaire observés dans d'autres maladies neurodégénératives, Bmi1 pourrait être une cible thérapeutique générale pour prévenir la mort neuronale.