Eukaryotic DING Proteins Are Endogenous: An Immunohistological Study in Mouse Tissues

BACKGROUND: DING proteins encompass an intriguing protein family first characterized by their conserved N-terminal sequences. Some of these proteins seem to have key roles in various human diseases, e.g., rheumatoid arthritis, atherosclerosis, HIV suppression. Although this protein family seems to be ubiquitous in eukaryotes, their genes are consistently lacking from genomic databases. Such a lack has considerably hampered functional studies and has fostered therefore the hypothesis that DING proteins isolated from eukaryotes were in fact prokaryotic contaminants. PRINCIPAL FINDINGS: In the framework of our study, we have performed a comprehensive immunological detection of DING proteins in mice. We demonstrate that DING proteins are present in all tissues tested as isoforms of various molecular weights (MWs). Their intracellular localization is tissue-dependant, being exclusively nuclear in neurons, but cytoplasmic and nuclear in other tissues. We also provide evidence that germ-free mouse plasma contains as much DING protein as wild-type. SIGNIFICANCE: Hence, data herein provide a valuable basis for future investigations aimed at eukaryotic DING proteins, revealing that these proteins seem ubiquitous in mouse tissue. Our results strongly suggest that mouse DING proteins are endogenous. Moreover, the determination in this study of the precise cellular localization of DING proteins constitute a precious evidence to understand their molecular involvements in their related human diseases

Dietary prevention of visual function and cognitive decline by omega-3 polyunsaturated fatty acids in Senescence Accelerated Mouse P8 (SAM P8)

International audiencePurpose: : Neuronal tissues such as the brain and the retina contain elevated amounts of long-chain omega-3 polyunsaturated fatty acids (PUFAs) and particularly docosahexaenoic acid (DHA). DHA concentrations are known to decrease in the aging brain and are associated with cognitive decline. The senescence-accelerated mouse prone 8 (SAM P8) is a mouse model for aging that exhibits deficits in cognitive performances as well as alterations of retinal functionality (ARVO 2004 E-abstract 797). The aim of this study was to evaluate the effects of a dietary supplementation with DHA on mood, cognition and visual functionality of SAM P8 during aging. Methods: : SAM P8 mice were studied in comparison with SAM resistant 1 control animals (SAM R1). Animals were fed from weaning until 12 months of age with either a control diet balanced in omega-3 and omega-6 PUFAs but without DHA, a diet deficient in omega-3 PUFAs or a diet containing 6% of lipids as DHA. After 5 and 12 months of diet, the scotopic ERG was recorded and working memory and despair behavior were evaluated. The fatty acid composition of the retina and the brain was determined using capillary column gas chromatography. Results: : Dietary supplementation with long-chain omega-3 PUFAs led to significantly higher retinal and cerebral levels of DHA. The incorporation rate was significantly higher in SAM P8 when compared to SAM R1. An age-related diminution of the ERG b-wave amplitude was observed from 5 to 12 months of age in control and deficient SAM P8 when compared to SAM R1. These differences were emphasized in deficient animals. No age-related alteration of the ERG b-wave amplitude was observed in SAM P8 Meanwhile dietary supplementation with DHA reduced the duration of immobility in the forced swimming test in SAM R1 but not in SAM P8. Conclusions: : Dietary supplementation with DHA was efficient in increasing its retinal and cerebral incorporation. DHA successfully prevented the age-related loss of visual function in SAM P8 but did not improve the depression-like symptoms

Concomitant Human Infections with 2 Cowpox Virus Strains in Related Cases, France, 2011

We investigated 4 related human cases of cowpox virus infection reported in France during 2011. Three patients were infected by the same strain, probably transmitted by imported pet rats, and the fourth patient was infected by another strain. The 2 strains were genetically related to viruses previously isolated from humans with cowpox infection in Europe

Couplage et modélisation des flux d'eau et de carbone dans une plantation tropicale pérenne

National audienceLes flux d'énergie, d'eau et de carbone ont été mesurés en continu pendant deux ans dans une plantation tropicale de cocotiers (méthode CARBOEUROFLUX). A l'échelle foliaire, la réponse de la conductance stomatique (Gs) au climat a été mesurée et modélisée (Gsmod, Jarvis, 1976). La réponse de la photosynthèse foliaire (An) a été enregistrée, ainsi que l'effet de la température sur Vcmax et Jmax (Farquhar, 1981). Le modèle complet de photosynthèse foliaire prédit An en fonction des seules variables climatiques et de Gsmod par méthode analytique (Wang and Jarvis, 1993). L'effet du %N sur Vcmax et la distributions de %N dans la canopée est en cours de dépouillement. A l'échelle de l'arbre, les flux de sève mesurés ont été calibrés par des mesures d'évapotranspiration au-dessus et en-dessous de la canopée (eddycorrelation). La conductance de couvert (Gc) a été obtenue en inversant l'équation de Penman-Monteith. On a utilisé un modèle Sun/Shade (de Pury and Farqhuar, 1997) pour calculer la proportion de feuilles d'ombre et de lumière dans la canopée au pas de temps semi-horaire. Le coefficient d'extinction de la plantation a été calculé sur maquette 3D (Dauzat and Eroy, 1995) et le LAI obtenu par destruction. La conductance de couvert modélisée utilise les paramètres de Gsmod (foliaire) et les surfaces calculées respectives des feuilles d'ombre et de lumière. On obtient une bonne correlation entre Gc et Gcmod après ajustement des températures de feuilles (bilans d'énergie et radiatif). La photosynthèse de couvert (Acmod) a été modélisée à l'aide du même modèle Sun/Shade et des paramètres issus du modèle foliaire. La photosynthèse brute du couvert (GPP) est la différence des flux de carbone diurnes de la plantation et de la respiration de l'écosystème mesurée la nuit (Reco, filtrée pour U* et ajustée aux températures diurnes). On obtient une bonne correlation entre GPP et Acmod

Milk polar lipids reduce lipid cardiovascular risk factors in overweight postmenopausal women: towards a gut sphingomyelin-cholesterol interplay

Objectives: Nutritional strategies can play a major role in the management of cholesterolemia, notably in postmenopausal women at risk of CVD. Interest has recently grown on the potential health benefitsof milk polar lipids (MPL).We showed that isolipidic enrichment of the diet with MPL improved several lipid CV risk factors but underlying mechanisms remained unclear. We hypothesized that MPL reduceintestinal cholesterol absorption in humans.Methods:We performed a double-blind randomized controlled trial in 58 postmenopausal women with fasting HDL-cholesterol < 1.6 mM.They were subjected to a 4-week dietary intervention with daily consumption of a cream-cheese containing 12 g of milk fat including either 0 g (control, n = 19), 3 g (n = 19) or 5 g (n = 20) of MPL. Before and after each intervention, blood lipids were measured in the whole cohortwhereas fecal lipids and coprostanol were analyzed in a subgroup (n = 7–9 per group). A proof-of-concept mechanistic crossover study was also carried out in 4 ileostomized subjects who performed 8hpostprandial tests after consuming 0g-, 3g- or 5g-MPL enriched cheese labelled with 2H-cholesterol tracer. Plasma, chylomicrons and ilealefflux were analyzed.Results: Milk fat enriched with 3 to 5 g MPL induced doseresponse reductions in serum total cholesterol (up to −6.8% in 5 g group, p < 0.05), LDL-cholesterol (−8.7%, p < 0.05) and HDL/total-cholesterol ratio (p < 0.001), compared to the control that had no effect. Fecal excretion of coprostanol increased after MPL supplementation (p < 0.05, 3g- and 5g-MPL vs control), and the fecal coprostanol/cholesterol ratio was inversely correlated with serum total- and LDL-cholesterol after intervention (r = −0.5, p < 0.05). In ileostomized subjects, postprandial accumulation of 2Hcholesterol in plasma and chylomicrons was reduced after 3 to 5 g MPL consumption (p < 0.05, vs control). Both cholesterol and milk sphingomyelin increased in ileal efflux after MPL enriched cheeses (p < 0.05).Conclusions: Present results suggest that milk polar lipids decrease cholesterol absorption in humans through interactions with sphingomyelin and by increasing conversion of cholesterol to coprostanol.Funding Sources: ANR (French National Research Agency, VALOBAB project, ANR-11-ALID-007–01), PHRC-I (French Clinical Research Program, 14–007), CNIEL (French Dairy Interbranch Organization)

Autophagy regulates fatty acid availability for oxidative phosphorylation through mitochondria-endoplasmic reticulum contact sites

International audienceAutophagy has been associated with oncogenesis with one of its emerging key functions being its contribution to the metabolism of tumors. Therefore, deciphering the mechanisms of how autophagy supports tumor cell metabolism is essential. Here, we demonstrate that the inhibition of autophagy induces an accumulation of lipid droplets (LD) due to a decrease in fatty acid β-oxidation, that leads to a reduction of oxidative phosphorylation (OxPHOS) in acute myeloid leukemia (AML), but not in normal cells. Thus, the autophagic process participates in lipid catabolism that supports OxPHOS in AML cells. Interestingly, the inhibition of OxPHOS leads to LD accumulation with the concomitant inhibition of autophagy. Mechanistically, we show that the disruption of mitochondria-endoplasmic reticulum (ER) contact sites (MERCs) phenocopies OxPHOS inhibition. Altogether, our data establish that mitochondria, through the regulation of MERCs, controls autophagy that, in turn finely tunes lipid degradation to fuel OxPHOS supporting proliferation and growth in leukemia

Mitochondrial inhibitors circumvent adaptive resistance to venetoclax and cytarabine combination therapy in acute myeloid leukemia

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Appendix D. Patterning of factor relationships with litter decomposability fitted within individual sites in relation to the range of factor variation and sample size at the study sites.

Patterning of factor relationships with litter decomposability fitted within individual sites in relation to the range of factor variation and sample size at the study sites

Appendix B. Near-infrared reflectance spectroscopy calibrations between initial litter spectral properties and (a) litter decomposability and (b) litter quality.

Near-infrared reflectance spectroscopy calibrations between initial litter spectral properties and (a) litter decomposability and (b) litter quality