461 research outputs found

    Palagruza - The island of Diomedes: Summary excavation report 2002-2008

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    Perspectives of archaeometric analysis on the Hellenistic ware from the East Adriatic coast

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    In this paper, the author discuses about the challenges and perspectives of archaeometric analysis on the Hellenistic ware on the East Adriatic based on hitherto published analysis. Diversity of Hellenistic types of ware – in shapes, colour of coatings and decorations – show differences in technological process, that can be understood through analysis in both archaeological and archaeometric methods. Te archaeometry increasingly plays an important role in the study of archaeological artefacts, and it is necessary to stress out the importance of the integrated archaeological – archaeometric methodological approach. Te author will propose, on the examples of Hellenistic ware production on East Adriatic coast, how to integrate archaeological and archaeometric analysis in researches and studies on ancient pottery production

    Trade route between two Adriatic coasts in 4th and 3rd c. BC.

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    For the last 20 years research on painted pottery, red figured pottery and Gnathia pottery in Southern Italy, which includes defining their chronological framework of production and indentifying the local workshops, provides a better insight into the import painted pottery in the Eastern Adriatic coast in late 4th and 3rd century BC. Most of the imported vessels come from the workshop in Apulia, the Greek colony of Taras on the shores of the Ionian Sea and the native Messapian, Peucetian and Daunian workshops. Although red figured pottery from Apulia are not widely exported outside the home area of production, though examples are found on the Eastern Adriatic, in ancient Issa on the island of Vis and Pharos on the island of Hvar. However, Gnathia pottery, which from the second half of the 4th century BC begins to produce in the workshops in native Apulia, has found a wide market on the Eastern Adriatic. It is interesting to trace the distribution of Canosian (north Apulia) Gnathia products on the East Adriatic, and it is assumed that the potters from Canosa founded the local production of Gnathia pottery in Issa in the middle of the 3rd century. Other than products from the South Italy, on the Eastern Adriatic coast were found and painted Alto Adriatico vessels from the workshops of Northern Italy According to the distribution map of Gnathia and Alto Adriatico vessels on the Eastern Adriatic coast, it is evident that not only the inhabitants of the Greek colonies of Issa and Pharos consumed products of the Italic and Greek ceramics workshop, but the indigenous population has shown a specific interest in such potter

    Real-time prediction with U.K. monetary aggregates in the presence of model uncertainty

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    A popular account for the demise of the U.K.’s monetary targeting regime in the 1980s blames the fluctuating predictive relationships between broad money and inflation and real output growth. Yet ex post policy analysis based on heavily revised data suggests no fluctuations in the predictive content of money. In this paper, we investigate the predictive relationships for inflation and output growth using both real-time and heavily revised data. We consider a large set of recursively estimated vector autoregressive (VAR) and vector error correction models (VECM). These models differ in terms of lag length and the number of cointegrating relationships. We use Bayesian model averaging (BMA) to demonstrate that real-time monetary policymakers faced considerable model uncertainty. The in-sample predictive content of money fluctuated during the 1980s as a result of data revisions in the presence of model uncertainty. This feature is only apparent with real-time data as heavily revised data obscure these fluctuations. Out-of-sample predictive evaluations rarely suggest that money matters for either inflation or real output. We conclude that both data revisions and model uncertainty contributed to the demise of the U.K.’s monetary targeting regime

    The Vasopressin Receptor 2 Mutant R137L Linked to the Nephrogenic Syndrome of Inappropriate Antidiuresis (NSIAD) Signals through an Alternative Pathway that Increases AQP2 Membrane Targeting Independently of S256 Phosphorylation

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    NSIAD is a rare X-linked condition, caused by activating mutations in the AVPR2 gene coding for the vasopressin V2 receptor (V2R) associated with hyponatremia, despite undetectable plasma vasopressin levels. We have recently provided in vitro evidence that, compared to V2R-wt, expression of activating V2R mutations R137L, R137C and F229V cause a constitutive redistribution of the AQP2 water channel to the plasma membrane, higher basal water permeability and significantly higher basal levels of p256-AQP2 in the F229V mutant but not in R137L or R137C. In this study, V2R mutations were expressed in collecting duct principal cells and the associated signalling was dissected. V2R-R137L and R137C mutants had significantly higher basal pT269-AQP2 levels -independently of S256 and PKA-which were reduced to control by treatment with Rho kinase (ROCK) inhibitor. Interestingly, ROCK activity was found significantly higher in V2R-R137L along with activation of the Gα12/13-Rho-ROCK pathway. Of note, inhibition of ROCK reduced the basal elevated osmotic water permeability to control. To conclude, our data demonstrate for the first time that the gain-of-function mutation of the V2R, R137L causing NSIAD, signals through an alternative PKA-independent pathway that increases AQP2 membrane targeting through ROCK-induced phosphorylation at S/T269 independently of S256 of AQP2

    dDAVP Downregulates the AQP3-Mediated Glycerol Transport via V1aR in Human Colon HCT8 Cells

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    Vasopressin (AVP) plays a key function in controlling body water and salt balance through the activation of the vasopressin receptors V1aR and V2R. Abnormal secretion of AVP can cause the syndrome of inappropriate antidiuresis that leads to hyponatremia, which is an electrolyte disorder often observed in the elderly hospitalized and oncologic patients. Beyond kidneys, the colonic epithelium modulates water and salt homeostasis. The water channel AQP3, expressed in villus epithelial cells is implicated in water absorption across human colonic surface cells. Here, the action of dDAVP, a stable vasopressin analog, was evaluated on the AQP3 expression and function using human colon HCT8 cells as an experimental model. Confocal and Western Blotting analysis revealed that HCT8 cells express both V1aR and V2R. Long-term (72 h) treatment with dDAVP reduced glycerol uptake and cell viability. These effects were prevented by SR49059, a synthetic antagonist of V1aR, but not by tolvaptan, a specific V2R antagonist. Of note, the SR49059 action was impaired by DFP00173, a selective inhibitor of AQP3. Interestingly, compared to the normal colonic mucosa, in the colon of patients with adenocarcinoma, the expression of V1aR was significantly decreased. These findings were confirmed by gene expression analysis with RNA-Seq data. Overall, data suggest that dDAVP, through the V1aR dependent pathway, reduces AQP3 mediated glycerol uptake, a process that is reversed in adenocarcinoma, suggesting that the AVP-dependent AQP3 pathway may represent a novel target in colon diseases associated with abnormal cell growth

    Olive Leaf Extract (OLE) impaired vasopressin-induced aquaporin-2 trafficking through the activation of the calcium-sensing receptor

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    Vasopressin (AVP) increases water permeability in the renal collecting duct through the regulation of aquaporin-2 (AQP2) trafficking. Several disorders, including hypertension and inappropriate antidiuretic hormone secretion (SIADH), are associated with abnormalities in water homeostasis. It has been shown that certain phytocompounds are beneficial to human health. Here, the effects of the Olive Leaf Extract (OLE) have been evaluated using in vitro and in vivo models. Confocal studies showed that OLE prevents the vasopressin induced AQP2 translocation to the plasma membrane in MCD4 cells and rat kidneys. Incubation with OLE decreases the AVP-dependent increase of the osmotic water permeability coefficient (Pf). To elucidate the possible effectors of OLE, intracellular calcium was evaluated. OLE increases the intracellular calcium through the activation of the Calcium Sensing Receptor (CaSR). NPS2143, a selective CaSR inhibitor, abolished the inhibitory effect of OLE on AVP-dependent water permeability. In vivo experiments revealed that treatment with OLE increases the expression of the CaSR mRNA and decreases AQP2 mRNA paralleled by an increase of the AQP2-targeting miRNA-137. Together, these findings suggest that OLE antagonizes vasopressin action through stimulation of the CaSR indicating that this extract may be beneficial to attenuate disorders characterized by abnormal CaSR signaling and affecting renal water reabsorption

    In vivo treatment with calcilytic of CaSR knock-in mice ameliorates renal phenotype reversing downregulation of the vasopressin-AQP2 pathway

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    Abstract: High concentrations of urinary calcium counteract vasopressin action via the activation of the Calcium-Sensing Receptor (CaSR) expressed in the luminal membrane of the collecting duct cells, which impairs the trafficking of aquaporin-2 (AQP2). In line with these findings, we provide evidence that, with respect to wild-type mice, CaSR knock-in (KI) mice mimicking autosomal dominant hypocalcaemia, display a significant decrease in the total content of AQP2 associated with significantly higher levels of AQP2 phosphorylation at Ser261, a phosphorylation site involved in AQP2 degradation. Interestingly, KI mice also had significantly higher levels of phosphorylated p38MAPK, a downstream effector of CaSR and known to phosphorylate AQP2 at Ser261. Moreover, ATF1 phosphorylated at Ser63, a transcription factor downstream of p38MAPK, was significantly higher in KI. In addition, KI mice had significantly higher levels of AQP2-targeting miRNA137 consistent with a post-transcriptional downregulation of AQP2. In vivo treatment of KI mice with the calcilytic JTT-305, a CaSR antagonist, increased AQP2 expression and reduced AQP2-targeting miRNA137 levels in KI mice. Together, these results provide direct evidence for a critical role of CaSR in impairing both short-term vasopressin response by increasing AQP2-pS261, as well as AQP2 abundance, via the p38MAPK-ATF1-miR137 pathway. (Figure presented.). Key points: Calcium-Sensing Receptor (CaSR) activating mutations are the main cause of autosomal dominant hypocalcaemia (ADH) characterized by inappropriate renal calcium excretion leading to hypocalcaemia and hypercalciuria. Current treatments of ADH patients with parathyroid hormone, although improving hypocalcaemia, do not improve hypercalciuria or nephrocalcinosis. In vivo treatment with calcilytic JTT-305/MK-5442 ameliorates most of the ADH phenotypes of the CaSR knock-in mice including hypercalciuria or nephrocalcinosis and reverses the downregulation of the vasopressin-sensitive aquaporin-2 (AQP2) expression, providing direct evidence for a critical role of CaSR in impairing vasopressin response. The beneficial effect of calcilytic in reducing the risk of renal calcification may occur in a parathyroid hormone-independent action through vasopressin-dependent inhibition of cAMP synthesis in the thick ascending limb and in the collecting duct. The amelioration of most of the abnormalities in calcium metabolism including hypercalciuria, renal calcification, and AQP2-mediated osmotic water reabsorption makes calcilytic a good candidate as a novel therapeutic agent for ADH

    Male-Produced Sex Pheromone of the Carrion Beetles, Oxelytrum discicolle and its Attraction to Food Sources

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    Abstract Carrion beetles are part of the great diversity of insects collected on cadavers. In Brazil, beetles of the genus Oxelytrum have great forensic importance in post mortem interval (PMI) estimation. We investigated the system of chemical communication in the attraction of these necrophagous beetles. Gas chromatographic analysis (GC) of female and male aeration extracts revealed the presence of two male-specific compounds, produced in a ratio of 94:6. Bioassays showed that the combination of male produced volatiles and the odor of a food source (carcass volatiles) were attractive to females. Mass and infrared spectral analyses of the male-specific compounds suggested that they were both unsaturated hydrocarbons. Several microderivatizations were carried out with the natural products, and the target structures were identified as (Z)-1,8-heptadecadiene (major) and 1-heptadecene (minor). The structure of the minor component was assigned by co-injection with a commercial standard. A seven-step synthesis was developed to synthesize (Z)-1,8-heptadiene, which co-eluted with the major natural product on three different GC stationary phases. Y-tube olfactometer assays showed that the mixture of synthetic standards in the naturally occurring proportion was slightly attractive to females. The results contribute both to the understanding of the chemical ecology of O. discicolle and to its potential to improve the accuracy of PMI estimation

    In vitro and in vivo nutraceutical characterization of two chickpea accessions: Differential effects on hepatic lipid over-accumulation

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    Dietary habits are crucially important to prevent the development of lifestyle-associated diseases. Diets supplemented with chickpeas have numerous benefits and are known to improve body fat composition. The present study was undertaken to characterize two genetically and phenotypically distinct accessions, MG_13 and PI358934, selected from a global chickpea collection. Rat hepatoma FaO cells treated with a mixture of free fatty acids (FFAs) (O/P) were used as an in vitro model of hepatic steatosis. In parallel, a high-fat diet (HFD) animal model was also established. In vitro and in vivo studies revealed that both chickpea accessions showed a significant antioxidant ability. However, only MG_13 reduced the lipid over-accumulation in steatotic FaO cells and in the liver of HFD fed mice. Moreover, mice fed with HFD + MG_13 displayed a lower level of glycemia and aspartate aminotransferase (AST) than HFD mice. Interestingly, exposure to MG_13 prevented the phosphorylation of the inflammatory nuclear factor kappa beta (NF-kB) which is upregulated during HFD and known to be linked to obesity. To conclude, the comparison of the two distinct chickpea accessions revealed a beneficial effect only for the MG_13. These findings highlight the importance of studies addressing the functional characterization of chickpea biodiversity and nutraceutical properties
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