1,721,195 research outputs found
Zinc signalling and subcellular distribution: emerging targets in type 2 diabetes
A finely tuned subcellular distribution of zinc (Zn), through the coordinated action of Zn transporters (ZnTs) and metallothioneins (MTs), is crucial for optimal cell function. Dysfunctions of these proteins might act as key causative or promoting factors in several chronic pathologies. Evidence of their involvement in the pathogenesis of type 2 diabetes (DM2) is emerging. The association of single nucleotide polymorphisms in genes encoding ZnT-8 and MT with DM2 has drawn attention to the relevance of Zn homeostasis for insulin secretory capacity and responsiveness. Here, we propose that potential mechanisms leading to altered subcellular Zn distribution rather than deficiency might be important in DM2. Increasing knowledge of the mechanisms of Zn homeostasis and signalling should promote the development of targeted interventions with the potential to reduce the burden of disease. © 2008
The ROSAT deep cluster survey: The X-ray luminosity function out to z = 0.8
We present the X-ray luminosity function (XLF) of the ROSAT Deep Cluster Survey sample over the redshift range 0.05-0.8. Our results are derived from a complete flux-limited subsample of 70 galaxy clusters, representing the brightest half of the total sample, which have been spectroscopically identified down to the flux limit of 4 x 10(-14) ergs m(-2) s(-1) (0.5-2.0 keV) and have been selected via a serendipitous search in ROSAT PSPC pointed observations. The redshift baseline is large enough that evolutionary effects can be studied within the sample. The local XLF (z less than or equal to 0.25) is found to be in excellent agreement with previous determinations using ROSAT All-Sky Survey data. The XLF at higher redshifts, when combined with the deepest number counts constructed to date (f > 2 x 10(-14) ergs cm(-2) s(-1)), reveals no significant evolution at least out to z = 0.8, over a luminosity range of 2 x 10(42) to 3 x 10(44) ergs s(-1) in the 0.5-2 keV band. These findings extend the study of cluster evolution to the highest redshifts and the faintest fluxes probed so far in X-ray surveys. They complement and do not necessarily conflict with those of the Einstein Extended Medium-Sensitivity Survey, leaving open the possibility of negative evolution of the brightest end of the XLF at high redshifts
Search and analysis of small scale structures in two X-ray clusters of galaxies
We present a refinement of the wavelet analysis technique for the detection and characterisation of small scale features embedded in a strongly varying background. This technique handles with particular care the side effects of nonorthogonality in the wavelet space which can cause spurious detections and lead to a biased estimate of source parameters. This novel technique is applied to two ROSAT PSPC pointed observations of nearby clusters of galaxies, A 1367 and A 194. We find evidence that the case of A 1367 is not unique and that galaxy-scale X-ray emission could be a quite common property of clusters of galaxies. We detect 28 sources in the field of A 1367 and 26 in the field of A 194. Since these numbers are significantly larger than those expected from the log N - log S relation in the field, most of the sources are expected to be associated with the cluster itself and indeed several identifications with galaxies are possible. In addition, CCD observations have revealed that two X-ray sources in the field of A 194, classified as extended by the multi-scale analysis, are very likely associated with two background galaxy clusters at intermediate redshift
Endogenous retroelements in cellular senescence and related pathogenic processes: Promising drug targets in age-related diseases
Endogenous retroelements (ERs) represent nearly half of the human genome. Considered up to recent years as “functionless” DNA sequences, they are now known to be involved in important cellular functions such as stress response and generation of non coding regulatory RNAs. Moreover, an increasing amount of data supports the idea of ERs as key players in cellular senescence and in different senescence-related pathogenic cellular processes, including those leading to inflammation, cancer and major age-related multifactorial diseases. The involvement of ERs in these biological mechanisms can suggest new therapeutic strategies in neoplasms, inflammatory/autoimmune diseases and in different age-related pathologies, such as macular degeneration, diabetes, cardiovascular diseases and major age-related neurodegenerative disorders. The therapeutic approaches which can be suggested range from a set of well-known, common drugs that have been shown to modulate ERs activity, to immune therapy against ER-derived tumor antigens, to more challenging strategies such as those based on anti-ERs RNA interference
Preliminary Comparison of Fractional Absorption of Zinc Sulphate, Zinc Gluconate, and Zinc Aspartate after Oral Supple-Mentation in Healthy Human Volunteers
(1) Background: Zinc is generally used as a nutritional supplement for individuals at nutritional risk, such as older adults. This preliminary study investigated the fractional Zn absorption (FZA) after the supplementation on eight healthy volunteers with three different Zn complexes acquired with milk. (2) Methods: The design was a double-blind, three-period crossover trial. The volunteers were randomly divided into three groups. Each individual consumed 200 mL of bovine milk and rotated through a simultaneous administration of a single oral dose of 70ZnSO4, 70Zn-Gluconate (70Zn-Glu), and 70Zn-Aspartate (70Zn-Asp), equivalent to 2.0 mg 70Zn, followed by 2 weeks of wash-out. An estimation of the FZA for comparative purposes was computed by the isotopic ratio between 66Zn and 70Zn in urine collected before and 48 h after administration. (3) Results: The estimated FZA was found to be significantly higher for 70Zn-Asp when compared to the other forms, while the FZA of 70Zn-Glu was found to be significantly higher than 70ZnSO4. (4) Conclusions: The results of this study suggest that complexing Zn with aspartate in milk could be a useful tool to improve FZA in individuals at risk of Zn deficiency. These results provide a rationale for conducting further studies on Zn-Asp preparations
A first determination of the surface density of galaxy clusters at very low X-ray fluxes
We present the first results of a serendipitous search for clusters of galaxies in deep ROSAT PSPC pointed observations at high Galactic latitude. The survey is being carried out using a wavelet-based detection algorithm which is not biased against extended, low surface brightness sources. A new flux-diameter limited sample of 10 cluster candidates has been created from similar to 3 deg(2) surveyed area. Preliminary CCD observations have revealed that a large fraction of these candidates correspond to a visible enhancement in the galaxy surface density, and several others have been identified from other surveys. We believe these sources to be either low- to moderate-redshift groups or intermediate- to high-redshift clusters. We show X-ray and optical images of some of the clusters identified to date. We present, for the first time, the derived number density of the galaxy clusters to a flux limit of 1 x 10(-14) ergs cm(-2) s(-1) (0.5-2.0 keV). This extends the log N-log S of previous cluster surveys by more than one decade in flux. Results are compared to theoretical predictions for cluster number counts
First Results from the X-Ray and Optical Survey of the Chandra Deep Field South
We present our first results from 120 ks of X-ray observations obtained with the Advanced CCD Imaging Spectrometer on the Chandra X-Ray Observatory. The field of the two combined exposures is 0.096 deg(2) and the detection limit is to a S/N of 2 (corresponding to similar to7 net counts). We reach a flux of 2 x 10(-16) erg s(-1) cm(-2) in the 0.5-2 keV soft band and 2 x 10(-15) erg s(-1) cm(-2) in the 2-10 keV hard band. Our combined sample has 144 soft sources and 91 hard sources, for a total of 159 sources. Fifteen sources are detected only in the hard band, and 68 only in the soft band. For the optical identification, we carried out a survey in V RI with the FORS-1 imaging spectrometer on the Antu telescope (UT-1 at VLT) complete to R less than or equal to 26. This data set was complemented with data from the ESO Imaging Survey (EIS) in the UBJK bands and the ESO Wide Field Imager Survey (WFI) in the B band. The positional accuracy of the X-ray detections is of the order of 1" in the central 6'. Optical identifications are found for similar or equal to 90% of the sources. Optical spectra have been obtained for 12 objects. We obtain the cumulative spectra of the faint and bright X-ray sources in the sample and also the hardness ratios of individual sources. A power-law Dt in the range 2-10 keV using the Galactic value of N-H similar or equal to 8 x 10(19) cm(-2) yields a photon index of Gamma = 1.70 +/- 0.12 and 1.35 +/- 0.20 (errors at 90% confidence level) for the bright and faint samples, respectively, showing a flattening of the spectrum at lower fluxes. Hardness ratio is given as a function of X-ray flux and confirms this result. The spectrum of our sources is approaching the spectrum of the X-ray background (XRB) in the hard band, which has an effective Gamma = 1.4. Correlation function analysis for the angular distribution of the sources indicates that they are significantly clustered on scales as large as 100". The scale dependence of the correlation function is a power law with index gamma similar to 2, consistent with that of the galaxy distribution in the local universe. Consequently, the discrete sources detected by deep Chandra-pointed observations can be used as powerful tracers of the large-scale structure at high redshift. We discuss the log N- log S relationship and the discrete source contribution to the integrated X-ray sky flux. In the soft band, the sources detected in the field at fluxes below 10(-15) erg s(-1) cm(-2) contribute (4.0 +/- 0.3) x 10(-12) erg cm(-2) s(-1) deg(-2) to the total XRB. The flux resolved in the hard band down to the flux limit of 2 x 10(-15) erg s(-1) cm(-2) contributes (1.05 +/- 0.2) x 10(-11) erg cm(-2) s(-1) deg(-2). Once the contribution from the bright counts resolved by ASCA is included, the total resolved XRB amounts to 1.3 x 10(-11) erg cm(-2) s(-1) deg(-2), which is 60%-80% of the total measured background. This result confirms that the XRB is due to the integrated contribution of discrete sources, but shows that there is still a relevant fraction (at least 20%) of the hard XRB to be resolved at fluxes below 10(-15) erg s(-1) cm(-2). We discuss the X-ray flux versus R magnitude relation for the identified sources. We find that similar or equal to 10% of the sources in our sample are not immediately identifiable at R > 26. For these sources, S-x/S-opt whereas most of the ROSAT and Chandra sources have S-x/S-opt <10. We have also found a population of objects with unusually low S-x/S-opt that are identified as galaxies. The R-K versus R color diagram shows that the Chandra sources continue the trend seen by ROSAT. For our 12 spectroscopically studied objects with redshifts, we observe four QSOs, five Seyfert 2 galaxies, one elliptical, and two interacting galaxies. We compare L-x versus z obtained with these measurements and show that Chandra is achieving the predicted sensitivity
Dietary intake and impact of zinc supplementation on the immune functions in elderly: Nutrigenomic approach
Nutrient zinc is a relevant micronutrient involved in maintaining a good integrity of many body homeostatic mechanisms, including immune efficiency, owing to its requirement for the biological activity of many enzymes, proteins, and for cellular proliferation as well as genomic stability. Old people aged 60-65 years and older have zinc intakes below 50 % of the recommended dietary allowances on a given day. Many causes can be involved: among them, impaired intestinal absorption and altered subcellular processes (zinc transporters including Zip and ZnT family, metallothioneins, divalent metal transporter 1) are the most relevant. Zinc supplementation can remodel the immune alterations in elderly leading to healthy ageing. Several zinc trials have been carried out but with contradictory data on immunity, perhaps due to incorrect choice of old subjects who effectively need zinc supplementation. Old subjects with specific metallothioneins and IL-6 polymorphisms are more prone for zinc supplementation. Foods containing zinc (Mediterranean diet) may be enough to restore immunity in other elderly. We report the main causes of low zinc dietary intake in elderly and the impact of zinc supplementation upon the inflammatory/immune response on the basis of individual interleukin-6 and metallothioneins polymorphisms (nutrigenomic approach)
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