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31.
Summary The hepatocytes of 15 liver biopsies from 13 patients suffering from nonhemolytic constitutional jaundice were studied with respect to the presence of mitochondria with fibrillary inclusions or with vacuoles and to the presence of «paracrystalline cytoplasmic inclusions».Intramitochondrial fibrillary inclusions were found in all cases in quite various proportions, from 1 to 45% of the observed organelles. Intramitochondrial vacuoles were less frequent: they were observed only in three cases, and in one case only in more than 10% of the organelles. Mugnaini's paracrystalline inclusions, dispersed in the cytoplasm of the hepatocytes without outer membranes, were abundant in two cases.None of these morphological characters could be considered as pathognomonic and their origin is unknown: nevertheless their repartition in human liver in pathological conditions seems worthy of further study.

Travail subventionné par le «Fonds National Suisse de la Recherche Scientifique».  相似文献   
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Highlights? The MRN-CtIP pathway is required for metaphase chromosome alignment in egg extracts ? MRN inhibition interferes with spindle assembly around DNA-coated beads ? MRN inhibition in cells causes a metaphase delay and disrupts the RanGTP gradient ? The MRN complex regulates the stable association of RCC1 to chromatin  相似文献   
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In tropical regions, most primary ecosystems have been replaced by mosaic landscapes in which species must cope with a large shift in the distribution of their habitat and associated food resources. Primates are particularly vulnerable to habitat modifications. Most species persist in small fragments surrounded by complex human-mediated matrices whose structure and connectivity may strongly influence their dispersal and feeding behavior. Behavioral plasticity appears to be a crucial parameter governing the ability of organisms to exploit the resources offered by new matrix habitats and thus to persist in fragmented habitats. In this study, we were interested in the dietary plasticity of the golden-crowned sifaka (Propithecus tattersalli), an endangered species of lemur, found only in the Daraina region in north-eastern Madagascar. We used a DNA-based approach combining the barcoding concept and Illumina next-generation sequencing to (i) describe the species diet across its entire range and (ii) evaluate the influence of landscape heterogeneity on diet diversity and composition. Faeces from 96 individuals were sampled across the entire species range and their contents were analyzed using the trnL metabarcoding approach. In parallel, we built a large DNA reference database based on a checklist of the plant species of the Daraina region. Our results suggest that golden-crowned sifakas exhibit remarkable dietary diversity with at least 130 plant species belonging to 80 genera and 49 different families. We highlighted an influence of both habitat type and openness on diet composition suggesting a high flexibility of foraging strategies. Moreover, we observed the presence of numerous cultivated and naturalized plants in the faeces of groups living in forest edge areas. Overall, our findings support our initial expectation that P. tattersalli is able to cope with the current level of alteration of the landscape and confirm our previous results on the distribution and the dispersal ability of this species.  相似文献   
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Background

Food-based approaches such as biofortification are meant to sustainably address micronutrient deficiencies in poor settings. Knowing more about micronutrient intakes and deficiencies is a prerequisite to designing and evaluating interventions.

Objective

The objectives of the study were to assess biological status and dietary intakes of iron, zinc and vitamin A among women and children aged 36–59 months in rural Burkina Faso and to study relationships between intake and status to better inform future food-based interventions.

Design

A cross-sectional survey was carried out in two rural provinces of Burkina Faso on a random cluster sample of 480 mother-child pairs. Dietary data was obtained by 24-hour recalls repeated on a random sub-selection of 37.5% of subjects to allow calculation of nutrient’s probability of adequacy (PA). Biomarkers were measured on a sub-sample of 180 mother-child pairs. Blood samples were analyzed for hemoglobin, serum ferritin, soluble transferrin receptors (sTfR), C-reactive protein, alpha-1-glycoprotein, serum zinc concentration (SZnC) and retinol. For each micronutrient the relationship between biomarker and dietary intake was investigated by multiple linear regression models accounting for inflammatory biomarkers.

Results

Mean PA for iron, zinc and vitamin A was 0.49, 0.87 and 0.21 among women and 0.61, 0.95 and 0.33 among children, respectively. Prevalence of anemia, corrected low serum ferritin and high sTfR was 37.6%, 4.0% and 77.5% among women and 72.1%, 1.5% and 87.6% among children, respectively. Prevalence of low SZnC and corrected low serum retinol was 39.4% and 12.0% among women and 63.7% and 24.8% among children, respectively. There was a tendency for a positive relationship between vitamin A intakes and serum retinol among women (β = 0.0003, P = 0.06). Otherwise, no link was found between micronutrients biomarkers and intakes.

Conclusion

Our study depicted different images of micronutrient deficiencies when based on dietary intakes or biomarkers results, thus highlighting the need for more suitable biomarkers and more precise measures of absorbable micronutrient intakes at the individual level. It thus points to challenges in the design and evaluation of future biofortification or other food-based interventions in rural areas of Burkina Faso.  相似文献   
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Altered molecular responses to insulin and growth factors (GF) are responsible for late‐life shortening diseases such as type‐2 diabetes mellitus (T2DM) and cancers. We have built a network of the signaling pathways that control S‐phase entry and a specific type of senescence called geroconversion. We have translated this network into a Boolean model to study possible cell phenotype outcomes under diverse molecular signaling conditions. In the context of insulin resistance, the model was able to reproduce the variations of the senescence level observed in tissues related to T2DM's main morbidity and mortality. Furthermore, by calibrating the pharmacodynamics of mTOR inhibitors, we have been able to reproduce the dose‐dependent effect of rapamycin on liver degeneration and lifespan expansion in wild‐type and HER2–neu mice. Using the model, we have finally performed an in silico prospective screen of the risk–benefit ratio of rapamycin dosage for healthy lifespan expansion strategies. We present here a comprehensive prognostic and predictive systems biology tool for human aging.  相似文献   
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The Golgi-associated protein ArfGAP1 has an unusual membrane-adsorbing amphipathic alpha-helix: its polar face is weakly charged, containing mainly serine and threonine residues. We show that this feature explains the specificity of ArfGAP1 for curved versus flat lipid membranes. We built an algorithm to identify other potential amphipathic alpha-helices rich in serine and threonine residues in protein databases. Among the identified sequences, we show that three act as membrane curvature sensors. In the golgin GMAP-210, the sensor may serve to trap small vesicles at the end of a long coiled coil. In Osh4p/Kes1p, which transports sterol between membranes, the sensor controls access to the sterol-binding pocket. In the nucleoporin Nup133, the sensor corresponds to an exposed loop of a beta-propeller structure. Ser/Thr-rich amphipathic helices thus define a general motif used by proteins of various functions for sensing membrane curvature.  相似文献   
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The identification of a highly selective D2 partial agonist, D3 antagonist tool molecule which demonstrates high levels of brain exposure and selectivity against an extensive range of dopamine, serotonin, adrenergic, histamine, and muscarinic receptors is described.  相似文献   
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