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481.
The validity of the conventional Poissonian equation for surviving fraction is examined under the possibility of multi-lesion mechanisms. Alternative multi-lesion formulae are derived which are found to have intrinsic shoulders leading to some interesting consequences in cancer risk models. 相似文献
482.
Emanuela Senatore Francesco Chiuso Laura Rinaldi Daniela Intartaglia Rossella Delle Donne Emilia Pedone Bruno Catalanotti Luciano Pirone Bianca Fiorillo Federica Moraca Giuliana Giamundo Giovanni Scala Andrea Raffeiner Omar TorresQuesada Eduard Stefan Marcel Kwiatkowski Alienke van Pijkeren Manuela Morleo Brunella Franco Corrado Garbi Ivan Conte Antonio Feliciello 《The EMBO journal》2021,40(10)
The primary cilium is a microtubule‐based sensory organelle that dynamically links signalling pathways to cell differentiation, growth, and development. Genetic defects of primary cilia are responsible for genetic disorders known as ciliopathies. Orofacial digital type I syndrome (OFDI) is an X‐linked congenital ciliopathy caused by mutations in the OFD1 gene and characterized by malformations of the face, oral cavity, digits and, in the majority of cases, polycystic kidney disease. OFD1 plays a key role in cilium biogenesis. However, the impact of signalling pathways and the role of the ubiquitin‐proteasome system (UPS) in the control of OFD1 stability remain unknown. Here, we identify a novel complex assembled at centrosomes by TBC1D31, including the E3 ubiquitin ligase praja2, protein kinase A (PKA), and OFD1. We show that TBC1D31 is essential for ciliogenesis. Mechanistically, upon G‐protein‐coupled receptor (GPCR)‐cAMP stimulation, PKA phosphorylates OFD1 at ser735, thus promoting OFD1 proteolysis through the praja2‐UPS circuitry. This pathway is essential for ciliogenesis. In addition, a non‐phosphorylatable OFD1 mutant dramatically affects cilium morphology and dynamics. Consistent with a role of the TBC1D31/praja2/OFD1 axis in ciliogenesis, alteration of this molecular network impairs ciliogenesis in vivo in Medaka fish, resulting in developmental defects. Our findings reveal a multifunctional transduction unit at the centrosome that links GPCR signalling to ubiquitylation and proteolysis of the ciliopathy protein OFD1, with important implications on cilium biology and development. Derangement of this control mechanism may underpin human genetic disorders. 相似文献
483.
Laura Rinaldi Rossella Delle Donne Domenica Borzacchiello Luigi Insabato Antonio Feliciello 《生物化学与生物物理学报:癌评论》2018,1869(2):293-302
Mitochondria are the powerhouse organelles present in all eukaryotic cells. They play a fundamental role in cell respiration, survival and metabolism. Stimulation of G-protein coupled receptors (GPCRs) by dedicated ligands and consequent activation of the cAMP·PKA pathway finely couple energy production and metabolism to cell growth and survival. Compartmentalization of PKA signaling at mitochondria by A-Kinase Anchor Proteins (AKAPs) ensures efficient transduction of signals generated at the cell membrane to the organelles, controlling important aspects of mitochondrial biology. Emerging evidence implicates mitochondria as essential bioenergetic elements of cancer cells that promote and support tumor growth and metastasis. In this context, mitochondria provide the building blocks for cellular organelles, cytoskeleton and membranes, and supply all the metabolic needs for the expansion and dissemination of actively replicating cancer cells. Functional interference with mitochondrial activity deeply impacts on cancer cell survival and proliferation. Therefore, mitochondria represent valuable targets of novel therapeutic approaches for the treatment of cancer patients. Understanding the biology of mitochondria, uncovering the molecular mechanisms regulating mitochondrial activity andmapping the relevant metabolic and signaling networks operating in cancer cells will undoubtly contribute to create a molecular platform to be used for the treatment of proliferative disorders.Here, we will highlight the emerging roles of signaling pathways acting downstream to GPCRs and their intersection with the ubiquitin proteasome system in the control of mitochondrial activity in different aspects of cancer cell biology. 相似文献
484.
Rita Meleddu Serenella Deplano Elias Maccioni Francesco Ortuso Filippo Cottiglia Daniela Secci Alessia Onali Erica Sanna Andrea Angeli Rossella Angius Stefano Alcaro Claudiu T. Supuran Simona Distinto 《Journal of enzyme inhibition and medicinal chemistry》2021,36(1):685
A small library of coumarin and their psoralen analogues EMAC10157a-b-d-g and EMAC10160a-b-d-g has been designed and synthesised to investigate the effect of structural modifications on their inhibition ability and selectivity profile towards carbonic anhydrase isoforms I, II, IX, and XII. None of the new compounds exhibited activity towards hCA I and II isozymes. Conversely, both coumarin and psoralen derivatives were active against tumour associated isoforms IX and XII in the low micromolar or nanomolar range of concentration. These data further corroborate our previous findings on analogous derivatives, confirming that both coumarins and psoralens are interesting scaffolds for the design of isozyme selective hCA inhibitors. 相似文献
485.
Seasonal changes of zinc, copper, and iron in gilthead sea bream (Sparus aurata) fed fortified diets
Emilio Carpeme Rossella Serra Maurizio Manera Gloria Isani 《Biological trace element research》1999,69(2):121-139
Four groups of gilthead sea bream (Sparus aurata) were fed diets with additional metal contents: a basal diet (diet A) contained Zn at 60.9 ± 1.9 mg/kg diet, Cu at 3.9 ±
0.9 mg/kg diet, and Fe at 138.3 ± 6.8 mg/kg diet; the other diets were supplemented with copper (20 mg/kg, diet B), iron (100
mg/kg, diet C), or zinc (300 mg/kg, diet D). Two consecutive year-classes (0+ and 1+ age fish) from the same parent stock were examined. Several fish tissues were analyzed for metal contents in five different
periods of each year in order to determine (1) the sensitivity of certain tissues as indicators of trace element metabolism
and (2) possible seasonal variations. Growth data were similar for gilthead sea bream fed the basal diet and the metal-fortified
diets. Mineral concentrations in tissues were found to be little affected by the dietary supplementation of trace elements,
suggesting an efficient homeostatic control of these three metal concentrations. Tissues involved in metal metabolism (e.g.,
liver, kidney, gills) presented greater variations between minimum and maximum values with respect to other tissues (e.g.,
brain, muscle, eye). Seasonal variations were observed during the 2 yr of this study and were especially evident for zinc
and copper concentrations in the liver. The overall pattern of metal variations showed a decreasing trend during the 2 yr.
Results from this study indicate that (1) trace element concentrations in fish tissues vary with age and life cycle and (2)
trace element requirements may vary in function of age and life cycle. 相似文献
486.
487.
Federico Napolitano Rossella Merone Adele Abbate Virginia Ammendola Emma Horncastle Francesca Lanzaro Marialuisa Esposito Alessandra Maria Contino Roberta Sbrocchi Andrea Sommella Joshua D. Duncan Joseph Hinds Richard A. Urbanowicz Armin Lahm Stefano Colloca Antonella Folgori Jonathan K. Ball Alfredo Nicosia Benjamin Wizel Stefania Capone Alessandra Vitelli 《PLoS neglected tropical diseases》2021,15(4)
488.
489.
Sandro La Vignera Rosita A. Condorelli Rossella Cannarella Ylenia Duca Aldo E. Calogero 《Reproductive biology and endocrinology : RB&E》2018,16(1):108
This article is a review that addresses the following topics, divided by paragraphs. The first paragraph investigates the effects of physical activity on ovarian function, analyzing in particular the changes concerning the serum concentrations of follicle-stimulating hormone, luteinizing hormone, prolactin, growth hormone, thyroid hormones, leptin, ghrelin, neuropeptide Y. The second paragraph analyzes the effects of doping on the hypothalamic-pituitary-ovarian axis. Finally, the last paragraph analyzes the PCOS category, evaluating the effects of hyperandrogenism in relation to athletic performance. 相似文献