Versioning Cultural Objects : Digital Approaches

This volume approaches an understanding of the term versioning in the broadest sense, discussing ideas about how versions differ across forms of media, including text, image, and sound. Versions of cultural objects are identified, defined, articulated, and analysed through diverse mechanisms in different fields of research. The study of versions allows for the investigation of the creative processes behind the conception of works, a closer inspection of their socio-political contexts, and promotes investigation of their provenance and circulation. Chapters in this volume include discussion of what a “version” means in different fields, case studies implementing digital versioning techniques, conceptual models for representing versions digitally, and computational and management issues for digital projects

Function of hyperekplexia-causing alpha(1)R271Q/L glycine receptors is restored by shifting the affected residue out of the allosteric signaling pathway

BACKGROUND AND PURPOSE Glycine receptor a1 subunit R271Q and R271L (a1R271Q/L) mutations cause the neuromotor disorder, hereditary hyperekplexia. Studies suggest that the 271 residue is located within the allosteric signalling pathway linking the agonist binding site to the channel gate. The present study aimed to investigate a possible mechanism for restoring the function of the a1R271Q/L glycine receptor

Modulation of Kv3.1b potassium channel level and intracellular potassium concentration in 158N murine oligodendrocytes and BV-2 murine microglial cells treated with 7-ketocholesterol, 24S-hydroxycholesterol or tetracosanoic acid (C24:0)

International audienceLittle is known about K+ regulation playing major roles in the propagation of nerve impulses, as well as in apoptosis and inflammasome activation involved in neurodegeneration. As increased levels of 7-ketocholesterol (7KC), 24S-hydroxycholesterol (24S-OHC) and tetracosanoic acid (C24:0) have been observed in patients with neurodegenerative diseases, we studied the effect of 24 and/or 48 h of treatment with 7KC, 24S-OHC and C24:0 on Kv3.1b potassium channel level, intracellular K+ concentration, oxidative stress, mitochondrial dysfunction, and plasma membrane permeability in 158N oligodendrocytes and BV-2 microglial cells. In 158N cells, whereas increased level of Kv3.1b was only observed with 7KC and 24S-OHC but not with C24:0 at 24 h, an intracellular accumulation of K+ was always detected. In BV-2 cells treated with 7KC, 24S-OHC and C24:0, Kv3.1b level was only increased at 48 h; intracellular K+ accumulation was found at 24 h with 7KC, 24S-OHC and C24:0, and only with C24:0 at 48 h. Positive correlations between Kv3.1b level and intracellular K+ concentration were observed in 158N cells in the presence of 7KC and 24S-OHC, and in 7KC-treated BV-2 cells at 48 h. Positive correlations were also found between Kv3.1b or the intracellular K+ concentration, overproduction of reactive oxygen species, loss of transmembrane mitochondrial potential and increased plasma membrane permeability in 158N and BV-2 cells. Our data support that the lipid environment affects Kv3.1b channel expression and/or functionality, and that the subsequent rupture of K+ homeostasis is relied with oligodendrocytes and microglial cells damages

Docosahexaenoic Acid Attenuates Mitochondrial Alterations and Oxidative Stress Leading to Cell Death Induced by Very Long-Chain Fatty Acids in a Mouse Oligodendrocyte Model

In the case of neurodegenerative pathologies, the therapeutic arsenal available is often directed towards the consequences of the disease. The purpose of this study is, therefore, to evaluate the ability of docosahexaenoic acid (DHA), a molecule present in certain foods and considered to have health benefits, to inhibit the cytotoxic effects of very long-chain fatty acids (C24:0, C26:0), which can contribute to the development of some neurodegenerative diseases. The effect of DHA (50 µM) on very long-chain fatty acid-induced toxicity was studied by several complementary methods: phase contrast microscopy to evaluate cell viability and morphology, the MTT test to monitor the impact on mitochondrial function, propidium iodide staining to study plasma membrane integrity, and DHE staining to measure oxidative stress. A Western blot assay was used to assess autophagy through modification of LC3 protein. The various experiments were carried out on the cellular model of 158N murine oligodendrocytes. In 158N cells, our data establish that DHA is able to inhibit all tested cytotoxic effects induced by very long-chain fatty acids

Modifications peroxysomales associées à l'oxyapoptophagie induite par le 7-cétocholestérol et identification de lipides cytoprotecteurs

Oxidative stress is often increased in several diseases such as age-related diseases (cardiovascular diseases, eye diseases (age-related macular degeneration (AMD) and cataracts), neurodegenerative diseases (Alzheimer's disease, multiple sclerosis), chronic inflammatory diseases (chronic inflammatory bowel disease (IBD)) as well as certain rare genetic diseases (Niemann Pick's disease, X-linked adrenoleukodystrophy (X-ALD)). Oxidative stress can oxidize various molecules, in particular the cholesterol present in lipid membranes, and lead to the formation of oxidized cholesterol derivatives: oxysterols. Some of them, such as 7-ketocholesterol (7KC), are toxic and may be the cause of a type of cell death, oxiapoptophagy, associating an increase in oxidative stress, activation of apoptosis and autophagic criteria. Using 158N murine oligodendrocytes, this work has allowed to better characterize the oxiapoptophagy induced by 7KC. The toxicity of 7KC on cellular organelles such as mitochondria and lysosome was confirmed. This work also shows that oxyapoptophagy is associated with topographic, morphological and functional modifications of the peroxisome. It has been shown that 7KC induces a decrease in the expression and activity of certain peroxisomal transporters (ABCD1, ABCD3) and peroxisomal enzymes (ACOX1, MFP2, catalase) and promotes an accumulation of very long-chain fatty acids (C24:0, C24:1 and C26:0, C26:1) degraded in the peroxisome. It has also been shown that certain lipids (α-tocopherol, α-linolenic acid (ALA), eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), oleic acid (AO), Lorenzo's oil (oleic acid + erucic acid (4: 1)) and sulfo-N-succinimdyl oleate (SSO)) are cytoprotective and strongly attenuate 7KC-induced oxyaptophagy. This makes it possible to envisage the prevention or treatment of diseases associated with high levels of 7KC, in particular certain age-related diseases for which there are no effective treatments.Le stress oxydant est souvent augmenté dans plusieurs maladies comme des maladies liées à l’âge (maladies cardiovasculaires, maladies oculaires (dégénérescence maculaire liée à l’âge (DMLA) et cataracte), des maladies neurodégénératives (Maladie d’Alzheimer, sclérose en plaques), des maladies inflammatoires chroniques (maladies inflammatoires chroniques de l’intestin (MICI)) ainsi que certaines maladies génétiques rares (maladie de Niemann Pick, adrénoleucodystrophie liée à l’X (X-ALD)). Le stress oxydant peut oxyder différentes molécules, notamment le cholestérol présent dans les membranes lipidiques, et conduire à la formation de dérivés oxydés du cholestérol : les oxystérols. Certains d’entre eux, comme le 7-cétocholestérol (7KC), sont toxiques et peuvent être à l’origine d’un type de mort cellulaire, l’oxyapoptophagie, associant une élévation du stress oxydant, une activation de l’apoptose à des critères d’autophagie. En utilisant des oligodendrocytes murins 158N, ce travail a permis de mieux caractériser, l’oxyapoptophagie induite par le 7KC. La toxicité du 7KC sur les organites cellulaires comme la mitochondrie et le lysosome a été confirmée. Ce travail montre aussi que l’oxyapoptophagie est associée à des modifications topographiques, morphologiques et fonctionnelles du peroxysome. Il a été montré que le 7KC induit une diminution de l’expression et de l’activité de certains transporteurs peroxysomaux (ABCD1, ABCD3) et enzymes peroxysomales (ACOX1, MFP2, catalase) et favorise une accumulation d’acides gras à très longue chaine (C24:0, C24:1 et C26:0, C26:1) dégradés au niveau du peroxysome. Il a aussi été démontré que certains lipides (α-tocophérol, acide α-linolénique (ALA), acide éïcosapentaénoïque (EPA), acide docosahéxaénoïque (DHA), acide oléique (AO), huile de Lorenzo (acide oléique + acide érucique (4:1)) et le sulfo-N-succinimdyl oleate (SSO)) sont cytoprotecteurs et atténuent fortement l’oxyapoptophagie induite par le 7KC. Ceci permet d’envisager la prévention ou le traitement les maladies associées à des taux élevés de 7KC, en particulier certaines maladies liées à l’âge qui ne disposent pas de traitements efficaces

peroxisomal changes associated with 7-ketocholesterol-induced oxyapoptophagy and identification of cytoprotective lipids

Le stress oxydant est souvent augmenté dans plusieurs maladies comme des maladies liées à l’âge (maladies cardiovasculaires, maladies oculaires (dégénérescence maculaire liée à l’âge (DMLA) et cataracte), des maladies neurodégénératives (Maladie d’Alzheimer, sclérose en plaques), des maladies inflammatoires chroniques (maladies inflammatoires chroniques de l’intestin (MICI)) ainsi que certaines maladies génétiques rares (maladie de Niemann Pick, adrénoleucodystrophie liée à l’X (X-ALD)). Le stress oxydant peut oxyder différentes molécules, notamment le cholestérol présent dans les membranes lipidiques, et conduire à la formation de dérivés oxydés du cholestérol : les oxystérols. Certains d’entre eux, comme le 7-cétocholestérol (7KC), sont toxiques et peuvent être à l’origine d’un type de mort cellulaire, l’oxyapoptophagie, associant une élévation du stress oxydant, une activation de l’apoptose à des critères d’autophagie. En utilisant des oligodendrocytes murins 158N, ce travail a permis de mieux caractériser, l’oxyapoptophagie induite par le 7KC. La toxicité du 7KC sur les organites cellulaires comme la mitochondrie et le lysosome a été confirmée. Ce travail montre aussi que l’oxyapoptophagie est associée à des modifications topographiques, morphologiques et fonctionnelles du peroxysome. Il a été montré que le 7KC induit une diminution de l’expression et de l’activité de certains transporteurs peroxysomaux (ABCD1, ABCD3) et enzymes peroxysomales (ACOX1, MFP2, catalase) et favorise une accumulation d’acides gras à très longue chaine (C24:0, C24:1 et C26:0, C26:1) dégradés au niveau du peroxysome. Il a aussi été démontré que certains lipides (α-tocophérol, acide α-linolénique (ALA), acide éïcosapentaénoïque (EPA), acide docosahéxaénoïque (DHA), acide oléique (AO), huile de Lorenzo (acide oléique + acide érucique (4:1)) et le sulfo-N-succinimdyl oleate (SSO)) sont cytoprotecteurs et atténuent fortement l’oxyapoptophagie induite par le 7KC. Ceci permet d’envisager la prévention ou le traitement les maladies associées à des taux élevés de 7KC, en particulier certaines maladies liées à l’âge qui ne disposent pas de traitements efficaces.Oxidative stress is often increased in several diseases such as age-related diseases (cardiovascular diseases, eye diseases (age-related macular degeneration (AMD) and cataracts), neurodegenerative diseases (Alzheimer's disease, multiple sclerosis), chronic inflammatory diseases (chronic inflammatory bowel disease (IBD)) as well as certain rare genetic diseases (Niemann Pick's disease, X-linked adrenoleukodystrophy (X-ALD)). Oxidative stress can oxidize various molecules, in particular the cholesterol present in lipid membranes, and lead to the formation of oxidized cholesterol derivatives: oxysterols. Some of them, such as 7-ketocholesterol (7KC), are toxic and may be the cause of a type of cell death, oxiapoptophagy, associating an increase in oxidative stress, activation of apoptosis and autophagic criteria. Using 158N murine oligodendrocytes, this work has allowed to better characterize the oxiapoptophagy induced by 7KC. The toxicity of 7KC on cellular organelles such as mitochondria and lysosome was confirmed. This work also shows that oxyapoptophagy is associated with topographic, morphological and functional modifications of the peroxisome. It has been shown that 7KC induces a decrease in the expression and activity of certain peroxisomal transporters (ABCD1, ABCD3) and peroxisomal enzymes (ACOX1, MFP2, catalase) and promotes an accumulation of very long-chain fatty acids (C24:0, C24:1 and C26:0, C26:1) degraded in the peroxisome. It has also been shown that certain lipids (α-tocopherol, α-linolenic acid (ALA), eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), oleic acid (AO), Lorenzo's oil (oleic acid + erucic acid (4: 1)) and sulfo-N-succinimdyl oleate (SSO)) are cytoprotective and strongly attenuate 7KC-induced oxyaptophagy. This makes it possible to envisage the prevention or treatment of diseases associated with high levels of 7KC, in particular certain age-related diseases for which there are no effective treatments

Paléoenvironnements tropicaux, marins et lagunaires d'un littoral abrité (fonds meubles à bancs coralliens, lagune évaporitique) à l'Oligocène terminal, en Basse-Provence (région d'Aix-en-Provence, Marseille, France)

Distensive phenomena occur ed during the whole of Oligocene, and became more important during the Latest Oligocene, creating the western Mediterranean (rifting) whose shoreline was on the Nerthe chain southern edge. Recent studies show that the "Carry-le-Rouet" marine series and the "Aix-en-Provence" lagunal and lacustrine series belong to the same stratigraphie level, during the Latest Chattian. Hie Carry marine deposits reveal, among others, coral formations (thin-bedded successions of biostromes, coral banks, scattered solitary corals) associated with low energy detrital sedimentary formations. This paleoenvironment agrees with open-sea conditions in a low-energy rift margin, as in some modem fringing reefs in sheltered environments. The essentially carbonated lagunal and lacustrine sediments (laminar and thin-bedded limestones and marls) were deposited under changing environment, ranging from complete fresh water environment to concentration allowing sulfates precipitation. This environment is in agreement with an intermittent tidal marsh. This lagunal and lacustrine environment was alternately closed or open on the open sea through a tectonic shoal (the Nerthe Chain) lifting up or down, during the rifting episodes. Such depositional environments remember some areas of the present-day Red Sea or Persian Gulf shorelines.Les phénomènes distensifs qui ont régné durant tout l'Oligocène prennent à l'Oligocène terminal une ampleur nouvelle, à l'origine de la création de la Méditerranée occidentale (phénomène de rifting) dont le rivage s'établit en bordure méridionale actuelle de la chaîne de la Nerthe. Or, d'après des travaux récents, les niveaux marins de Carry-le-Rouet appartiennent au même niveau stratigraphique que la formation laguno-lacustre à gypse du bassin d'Aix-en-Provence : Chattien terminal. Les dépôts marins de Carry sont constitués, en particulier, de formations coralliennes (successions de biostromes, bancs coralliens de faibles épaisseurs, colonies coralliennes dispersées) associées à des formations sédimentaires détritiques de faible énergie. Ce paléoenvironnement correspond à un contexte de mer ouverte, mais en mode particulièrement calme de bordure de rift, similaire à certains contextes modernes de récifs frangeants en mode calme. Les dépôts laguno-lacustres, essentiellement carbonatés (calcaires et marnes généralement laminaires et en petits bancs), s'effectuent dans un milieu à salinité variable qui peut aller de la dessalure totale à une concentration telle qu'elle permettait la précipitation des sulfates (gypse). Le milieu évoque celui d'un marais maritime intermittent. Ce milieu laguno-lacustre est alternativement séparé ou ouvert sur la mer par l'intermédiaire de passage(s) à travers un seuil d'origine tectonique (massif de la Nerthe), jouant grâce aux mouvements verticaux distensifs associés aux épisodes de rifting. Cette situation n'est pas sans rappeler celle observée aujourd'hui sur certaines portions de littoral de la Mer Rouge ou du Golfe Persique.Barbot, Thomassin Bernard Armand. Paléoenvironnements tropicaux, marins et lagunaires d'un littoral abrité (fonds meubles à bancs coralliens, lagune évaporitique) à l'Oligocène terminal, en Basse-Provence (région d'Aix-en-Provence, Marseille, France). In: Géologie Méditerranéenne. Tome 21, numéro 1-2, 1994. Récifs et plates-formes carbonatées miocènes de Méditerranée / Miocene reefs and carbonate platforms of the Mediterranean. Interim colloquium R.C.M.N.S. (Marseille 3-6 mai 1994) sous la direction de Jean-Paul Saint-Martin et Jean-Jacques Cornée. pp. 95-108

Oxiapoptophagy in Age-Related Diseases. Comment on Ouyang et al. 7-Ketocholesterol Induces Oxiapoptophagy and Inhibits Osteogenic Differentiation in MC3T3-E1 Cells. Cells 2022, 11, 2882

Due to the increase in life span and life expectancy, which can, however, be more or less pronounced depending on the economic, social and cultural context [...

Improved synthesis and in vitro evaluation of the cytotoxic profile of oxysterols oxidized at C4 (4 alpha- and 4 beta-hydroxycholesterol) and C7 (7-ketocholesterol, 7 alpha- and 7 beta-hydroxycholesterol) on cells of the central nervous system

International audienceWhereas the biological activities of oxysterols oxidized at C7 (7-ketocholesterol (71(C), 76-hydroxycholesterol (7 6-0HC), 7 alpha-hydroxycholesterol (7 alpha-OHC)) are well documented, those of oxysterols oxidized at C4 (4 beta-hydroxycholesterol (4 beta-OHC), 4 alpha-hydroxycholesterol (4 alpha-OHC)) are not well known, especially on the cells of the central nervous system. Therefore, an improved methodology has been validated for 4 beta-OHC and 4 alpha-OHC synthesis, and the effects on cell viability and cell growth of these molecules were studied on immortalized, tumoral and normal brain cells (158N, C6 and SK-N-BE cells, and mixed primary cultures of astrocytes and oligodendrocytes). Whereas inhibition of cell growth with 7KC, 7 6-OHC, and 7 alpha-OHC is associated with a decrease of cell viability (cytotoxic activities), our data establish that 4 beta-OHC and 4a-OHC have no effect on cell viability, and no or minor effect on cell growth evocating cytostatic properties. Thus, comparatively to oxysterols oxidized at C7, the toxicity of oxysterols oxidized at C4 is in the following range of order: 7KC > 76-OHC > 7 alpha-OHC > (4 alpha-OHC > 4 alpha-OHC). Interestingly, to date, 4 beta-0HC and 4a-OHC are the only oxysterols identified with cytostatic properties suggesting that these molecules, whereas not cytotoxic, may have some interests to counteract cell proliferation