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Transmembrane signalling in cell lines transfected with and expressing both normal human insulin receptors and receptors mutated in their beta-subunit tyrosine kinase domains was investigated. The effect of MA-5, a human-specific monoclonal antibody to the insulin receptor alpha-subunit, on these cell lines was determined. The results suggest that there may be multiple signal transduction pathways for the biological action of insulin. Moreover, some of these pathways may not require the activation of receptor tyrosine kinase.

The hill of Monte Carru (Alghero) has brought to light a necropolis of Roman Empire, (1st-3rd century AD). The necropolis shows different burial rituals with 200 cremations and 150 inhumations. This necropolis can be attributed to the Roman settlement of Carbia, mentioned by the Antoninian Itinerary, a document written during Caracalla's time (212-217 AD), which was probably located in this area but it hasn't been found yet. The aims of the research are the preliminary constitutional and biodemographic reconstruction of this population, through sex and age determination, the reconstruction of the health condition and the lifestyle of the population. The analysis has shown higher percentage of adult individuals (47% males and 36% females) with average age of death of 19/35 years. Important the low percentage of pathologies and a sexual dimorphism in enthesopathies. The paleodiet analysis of bones, performed by XRF of trace elements, showed an almost constant presence of Zinc and Stronzium due to an essentially omnivorous diet. [ABSTRACT FROM AUTHOR]

Abstract Background We previously showed that mice lacking the high mobility group A1 gene (Hmga1-knockout mice) developed a type 2-like diabetic phenotype, in which cell-surface insulin receptors were dramatically reduced (below 10% of those in the controls) in the major targets of insulin action, and glucose intolerance was associated with increased peripheral insulin sensitivity. This particular phenotype supports the existence of compensatory mechanisms of insulin resistance that promote glucose uptake and disposal in peripheral tissues by either insulin-dependent or insulin-independent mechanisms. We explored the role of these mechanisms in the regulation of glucose homeostasis by studying the Hmga1-knockout mouse model. Also, the hypothesis that increased insulin sensitivity in Hmga1-deficient mice could be related to the deficit of an insulin resistance factor is discussed. Results We first show that HMGA1 is needed for basal and cAMP-induced retinol-binding protein 4 (RBP4) gene and protein expression in living cells of both human and mouse origin. Then, by employing the Hmga1-knockout mouse model, we provide evidence for the identification of a novel biochemical pathway involving HMGA1 and the RBP4, whose activation by the cAMP-signaling pathway may play an essential role for maintaining glucose metabolism homeostasis in vivo, in certain adverse metabolic conditions in which insulin action is precluded. In comparative studies of normal and mutant mice, glucagon administration caused a considerable upregulation of HMGA1 and RBP4 expression both at the mRNA and protein level in wild-type animals. Conversely, in Hmga1-knockout mice, basal and glucagon-mediated expression of RBP4 was severely attenuated and correlated inversely with increased Glut4 mRNA and protein abundance in skeletal muscle and fat, in which the activation state of the protein kinase Akt, an important downstream mediator of the metabolic effects of insulin on Glut4 translocation and carbohydrate metabolism, was simultaneously increased. Conclusion These results indicate that HMGA1 is an important modulator of RBP4 gene expression in vivo. Further, they provide evidence for the identification of a novel biochemical pathway involving the cAMP-HMGA1-RBP4 system, whose activation may play a role in glucose homeostasis in both rodents and humans. Elucidating these mechanisms has importance for both fundamental biology and therapeutic implications.

Abstract Background Sodium/iodide symporter (NIS) is a key protein in iodide transport by thyroid cells and this activity is a prerequisite for effective radioiodide treatment of thyroid cancer. In the majority of thyroid cancers, however, iodide uptake is reduced, probably as a result of decreased NIS protein expression. Methods To identify the mechanisms that negatively affect NIS expression in thyroid tumors, we performed electrophoresis mobility shift assays and immunoblot analysis of nuclear protein extracts from normal and tumoral thyroid tissues from 14 unrelated patients. Results Two proteins closely related to the transcription factors AP2 and Sp1 were identified in the nuclear extracts. Expression of both AP2 and Sp1 in nuclear extracts from thyroid tumors was significantly higher than that observed in corresponding normal tissues. Conclusion These observations raise the possibility that NIS expression, and subsequently iodide transport, are reduced in thyroid tumors at least in part owing to alterations in the binding activity of AP2 and Sp1 transcription factors to NIS promoter.

Digital Subtraction Angiography is commonly affected by artifacts due to the patient movements during the acquisition of the images without and with the contrast medium. This paper presents a preliminary study on an angiographic and angio-tomographic technique based on the quasi-simultaneous acquisition of two images, obtained using two different filters at the exit of an X-ray tube. One of the two filters (K-edge filter) contains the same chemical element used as a contrast agent (gadolinium in this study). This filter absorbs more radiation with energy just above the so called K-edge energy of gadolinium than the radiation with energy just below it. The other filter (an aluminium filter in this study) is simply used to suppress the low-energy contribution to the spectrum. Using proper calibration curves, the two images are combined to obtain an image of the contrast agent distribution. In the angio-tomographic application of the proposed technique two images, corresponding to the two filter types, are acquired for each viewing angle of the tomographic scan. From the two tomographic reconstructions, it is possible to obtain a three-dimensional map of the contrast agent distribution. The technique was tested on a sample consisting of a rat skull placed inside a container filled with water. Six small cylinders with 4.7 mm internal diameter containing the contrast medium at different concentrations were placed inside the skull. In the plain angiographic application of the technique, five out of six cylinders were visible, with gadolinium concentration down to 0.96%. In the angio-tomographic application, all six cylinders were visible, with gadolinium concentration down to 0.49%. This preliminary study shows that the proposed technique can provide images of the contrast medium at low concentration without most of the artifacts that are present in images produced by conventional techniques. The results encourage further investigation on the feasibility of a clinical implementation of the technique. [ABSTRACT FROM AUTHOR]

Conventional x-ray transmission tomography provides the spatial distribution of the absorption coefficient inside a sample. Other tomographic techniques, based on the detection of photons coming from fluorescent emission, Compton and Rayleigh scattering, are used for obtaining information on the internal elemental composition of the sample. However, the reconstruction problem for these techniques is generally much more difficult than that of transmission tomography, mainly due to self-absorption effects in the sample. In this article an approach to the reconstruction problem is presented, which integrates the information from the three types of signals. This method provides the quantitative spatial distribution of all elements that emit detectable fluorescent lines (Z≥15 in usual experimental conditions), even when the absorption effects are strong, and the spatial distribution of the global density of the lighter elements. The use of this technique is demonstrated on the reconstruction of a grain of the martian meteorite NWA817, mainly composed of low Z elements not measured in fluorescence and for which this method provides a unique insight. The measurement was done at the ID22 beamline of the European Synchrotron Radiation Facility. [ABSTRACT FROM AUTHOR]