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71.
Christine Bernsmeier Diego M. Weisskopf Marlon O. Pflueger Jan Mosimann Benedetta Campana Luigi Terracciano Christoph Beglinger Markus H. Heim Christian Cajochen 《PloS one》2015,10(11)
Background & Aims
Sleep disturbance is associated with the development of obesity, diabetes and hepatic steatosis in murine models. Hepatic triglyceride accumulation oscillates in a circadian rhythm regulated by clock genes, light-dark cycle and feeding time in mice. The role of the sleep-wake cycle in the pathogenesis of human non-alcoholic fatty liver disease (NAFLD) is indeterminate. We sought to detail sleep characteristics, daytime sleepiness and meal times in relation to disease severity in patients with NAFLD.Methods
Basic Sleep duration and latency, daytime sleepiness (Epworth sleepiness scale), Pittsburgh sleep quality index, positive and negative affect scale, Munich Chronotype Questionnaire and an eating habit questionnaire were assessed in 46 patients with biopsy-proven NAFLD and 22 healthy controls, and correlated with biochemical and histological parameters.Results
In NAFLD compared to healthy controls, time to fall asleep was vastly prolonged (26.9 vs. 9.8 min., p = 0.0176) and sleep duration was shortened (6.3 vs. 7.2 hours, p = 0.0149). Sleep quality was poor (Pittsburgh sleep quality index 8.2 vs. 4.7, p = 0.0074) and correlated with changes in affect. Meal frequency was shifted towards night-times (p = 0.001). In NAFLD but not controls, daytime sleepiness significantly correlated with liver enzymes (ALAT [r = 0.44, p = 0.0029], ASAT [r = 0.46, p = 0.0017]) and insulin resistance (HOMA-IR [r = 0.5, p = 0.0009]) independent of cirrhosis. In patients with fibrosis, daytime sleepiness correlated with the degree of fibrosis (r = 0.364, p = 0.019).Conclusions
In NAFLD sleep duration was shortened, sleep onset was delayed and sleep quality poor. Food-intake was shifted towards the night. Daytime sleepiness was positively linked to biochemical and histologic surrogates of disease severity. The data may indicate a role for sleep-wake cycle regulation and timing of food-intake in the pathogenesis of human NAFLD as suggested from murine models. 相似文献72.
73.
Benedetta Gualeni Marcella Facchini Fabio De Leonardis Ruggero Tenni Giuseppe Cetta Manuela Viola Alberto Passi Andrea Superti-Furga Antonella Forlino Antonio Rossi 《Matrix biology》2010,29(6):453-460
Mutations in the sulfate transporter gene, SCL26A2, lead to cartilage proteoglycan undersulfation resulting in chondrodysplasia in humans; the phenotype is mirrored in the diastrophic dysplasia (dtd) mouse. It remains unclear whether bone shortening and deformities are caused solely by changes in the cartilage matrix, or whether chondroitin sulfate proteoglycan undersulfation affects also signalling pathways involved in cell proliferation and differentiation. Therefore we studied macromolecular sulfation in the different zones of the dtd mouse growth plate and these data were related to growth plate histomorphometry and proliferation analysis.A 2-fold increase of non-sulfated disaccharide in dtd animals compared to wild-type littermates in the resting, proliferative and hypertrophic zones was detected indicating proteoglycan undersulfation; among the three zones the highest level of undersulfation was in the resting zone. The relative height of the hypertrophic zone and the average number of cells per column in the proliferative and hypertrophic zones were significantly reduced compared to wild-types; however the total height of the growth plate was within normal values. The chondrocyte proliferation rate, measured by bromodeoxyuridine labelling, was also significantly reduced in mutant mice. Immunohistochemistry combined with expression data of the dtd growth plate demonstrated that the sulfation defect alters the distribution pattern, but not expression, of Indian hedgehog, a long range morphogen required for chondrocyte proliferation and differentiation.These data suggest that in dtd mice proteoglycan undersulfation causes reduced chondrocyte proliferation in the proliferative zone via the Indian hedgehog pathway, therefore contributing to reduced long bone growth. 相似文献
74.
Association of dystrobrevin and regulatory subunit of protein kinase A: a new role for dystrobrevin as a scaffold for signaling proteins 总被引:1,自引:0,他引:1
Ceccarini M Grasso M Veroni C Gambara G Artegiani B Macchia G Ramoni C Torreri P Mallozzi C Petrucci TC Macioce P 《Journal of molecular biology》2007,371(5):1174-1187
The dystrophin-related and -associated protein dystrobrevin is a component of the dystrophin-associated protein complex, which directly links the cytoskeleton to the extracellular matrix. It is now thought that this complex also serves as a dynamic scaffold for signaling proteins, and dystrobrevin may play a role in this context. Since dystrobrevin involvement in signaling pathways seems to be dependent on its interaction with other proteins, we sought new insights and performed a two-hybrid screen of a mouse brain cDNA library using beta-dystrobrevin, the isoform expressed in non-muscle tissues, as bait. Among the positive clones characterized after the screen, one encodes the regulatory subunit RIalpha of the cAMP-dependent protein kinase A (PKA). We confirmed the interaction by in vitro and in vivo association assays, and mapped the binding site of beta-dystrobrevin on RIalpha to the amino-terminal region encompassing the dimerization/docking domain of PKA regulatory subunit. We also found that the domain of interaction for RIalpha is contained in the amino-terminal region of beta-dystrobrevin. We obtained evidence that beta-dystrobrevin also interacts directly with RIIbeta, and that not only beta-dystrobrevin but also alpha-dystrobrevin interacts with PKA regulatory subunits. We show that both alpha and beta-dystrobrevin are specific phosphorylation substrates for PKA and that protein phosphatase 2A (PP2A) is associated with dystrobrevins. Our results suggest a new role for dystrobrevin as a scaffold protein that may play a role in different cellular processes involving PKA signaling. 相似文献
75.
Tettamanti G Grimaldi A Casartelli M Ambrosetti E Ponti B Congiu T Ferrarese R Rivas-Pena ML Pennacchio F Eguileor Md 《Cell and tissue research》2007,330(2):345-359
We have analyzed midgut development during the fifth larval instar in the tobacco budworm Heliothis virescens. In prepupae, the midgut formed during larval instars undergoes a complete renewal process. This drastic remodeling of the
alimentary canal involves the destruction of the old cells by programmed cell-death mechanisms (autophagy and apoptosis).
Massive proliferation and differentiation of regenerative stem cells take place at the end of the fifth instar and give rise
to a new fully functioning epithelium that is capable of digesting and absorbing nutrients and that is maintained throughout
the subsequent pupal stage. Midgut replacement in H. virescens is achieved by a balance between this active proliferation process and cell-death mechanisms and is different from similar
processes characterized in other insects.
This work was supported by FAR 2006 (University of Insubria) to G.T., by a MIUR-FIRB-COFIN grant (no. RBNE01YXA8/2004077251),
and by the Centro Grandi Attrezzature (University of Insubria). 相似文献
76.
Daly-Burns B Alam TN Mackay A Clark J Shepherd CJ Rizzo S Tatoud R O'Hare MJ Masters JR Hudson DL 《Differentiation; research in biological diversity》2007,75(1):35-48
In the normal human prostate, undifferentiated proliferative cells reside in the basal layer and give rise to luminal secretory cells. There are, however, few epithelial cell lines that have a basal cell phenotype and are able to differentiate. We set out to develop a cell line with these characteristics that would be suitable for the study of the early stages of prostate epithelial cell differentiation. We produced a matched pair of conditionally immortalized prostate epithelial and stromal cell lines derived from the same patient. The growth of these cells is temperature dependent and differentiation can be induced following a rise in culture temperature. Three-dimensional co-cultures of these cell lines elicited gland-like structures reminiscent of prostatic acini. cDNA microarray analysis of the epithelial line demonstrated changes in gene expression consistent with epithelial differentiation. These genes may prove useful as markers for different prostate cell types. The cell lines provide a model system with which to study the process of prostatic epithelial differentiation and stromal-epithelial interactions. This may prove to be useful in the development of differentiation-targeted prostate cancer therapies. 相似文献
77.
deltaN-p73 is a transcriptional target of the PML/RARalpha oncogene in myeloid differentiation 总被引:1,自引:0,他引:1
78.
The Internal Transcribed Spacer (ITS) regions of ribosomal DNA are widely used as markers for phylogenetic analyses and environmental
sampling from a variety of organisms including fungi, plants, and animals. In theory, concerted evolution homogenizes multicopy
genes so that little or no variation exists within populations or individuals. However, contrary to theory, ITS variation
has been confirmed in populations and individuals from a diverse range of eukaryotes. The presence of intraspecific and intra-individual
variation in multicopy genes has important implications for ecological and phylogenetic studies, yet relatively little is
known about natural variation of these genes, particularly at the community level. In this study, we examined intraspecific
and intra-sporocarp ITS variation by DNA sequencing from sporocarps and pooled roots from 68 species of ectomycorrhizal fungi
collected at a single site in a Quercus woodland. We detected ITS variation in 27 species, roughly 40% of the taxa examined. Although intraspecific ITS variation
was generally low (0.16–2.85%, mean = 0.74%), it was widespread within this fungal community. We detected ITS variation in
both sporocarps and ectomycorrhizal roots, and variation was present within species of Ascomycota and Basidiomycota, two distantly
related lineages within the Fungi. We discuss the implications of such widespread ITS variability with special reference to
DNA-based environmental sampling from diverse fungal communities.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users. 相似文献
79.
Targeting farnesoid X receptor for liver and metabolic disorders 总被引:3,自引:0,他引:3
The farnesoid X receptor (FXR) is a metabolic nuclear receptor expressed in the liver, intestine, kidney and adipose tissue. By regulating the expression and function of genes involved in bile acid (BA) synthesis, uptake and excretion, FXR has emerged as a key gene involved in the maintenance of cholesterol and BA homeostasis. FXR ligands are currently under clinical investigation for the treatment of cholestasis, dyslipidemic disorders and conditions of insulin resistance in type 2 diabetes and non-alcoholic steatohepatitis (NASH). Because activation of FXR impacts a considerable number of genes, development of FXR modulators that selectively regulate specific pathways will limit potentially undesirable side effects. Interaction of FXR with other BAs and xenobiotics sensors such as the constitutive androstane receptor and the pregnane X receptor might allow the development of combination therapies for liver and metabolic disorders. 相似文献
80.
The Increase in Maternal Expression of axin1 and axin2 Contribute to the Zebrafish Mutant Ichabod Ventralized Phenotype 下载免费PDF全文
Fabio Valenti Jessica Ibetti Yuko Komiya Melissa Baxter Anna Maria Lucchese Lauren Derstine Claudia Covaciu Valeria Rizzo Renza Vento Giuseppe Russo Marcella Macaluso Franco Cotelli Daniele Castiglia Cara J. Gottardi Raymond Habas Antonio Giordano Gianfranco Bellipanni 《Journal of cellular biochemistry》2015,116(3):418-430