Expression of Telomerase and Telomere Length Are Unaffected by either Age or Limb Regeneration in Danio rerio

BACKGROUND:The zebrafish is an increasingly popular model for studying many aspects of biology. Recently, ztert, the zebrafish homolog of the mammalian telomerase gene has been cloned and sequenced. In contrast to humans, it has been shown that the zebrafish maintains telomerase activity for much of its adult life and has remarkable regenerative capacity. To date, there has been no longitudinal study to assess whether this retention of telomerase activity equates to the retention of chromosome telomere length through adulthood. METHODOLOGY/PRINCIPAL FINDINGS:We have systematically analyzed individual organs of zebrafish with regard to both telomere length and telomerase activity at various time points in its adult life. Heart, gills, kidney, spleen, liver, and intestine were evaluated at 3 months, 6 months, 9 months, and 2 years of age by Southern blot analysis. We found that telomeres do not appreciably shorten throughout the lifespan of the zebrafish in any organ. In addition, there was little difference in telomere lengths between organs. Even when cells were under the highest pressure to divide after fin-clipping experiments, telomere length was unaffected. All aged (2 year old) tissues examined also expressed active amounts of telomerase activity as assessed by TRAP assay. CONCLUSIONS/SIGNIFICANCE:In contrast to several other species including humans, the retention of lifelong telomerase and telomeres, as we have reported here, would be necessary in the zebrafish to maintain its tremendous regenerative capacity. The ongoing study of the zebrafish's ability to maintain telomerase activity may be helpful in unraveling the complexity involved in the maintenance (or lack thereof) of telomeres in other species such the mouse or human

MicroRNA profiling reveals that miR-21, miR486 and miR-214 are upregulated and involved in cell survival in Sézary syndrome

Sézary syndrome (SS) is an incurable leukemic variant of cutaneous T-cell lymphoma and its pathogenesis is still unknown. Diagnosis/prognosis may strongly ameliorate the management of SS individuals. Here, we profiled the expression of 470 microRNAs (miRNAs) in a cohort of 22 SS patients, and we identified 45 miRNAs differentially expressed between SS and controls. Using predictive analysis, a list of 19 miRNAs, including miR-21, miR-214, miR-486, miR-18a, miR-342, miR-31 and let-7 members were also found. Moreover, we defined a signature of 14 miRNAs including again miR-21, potentially able to discriminate patients with unfavorable and favorable outcome. We validated our data for miR-21, miR-214 and miR-486 by qRT-PCR, including an additional set of array-independent SS cases. In addition, we also provide an in vitro evidence for a contribution of miR-214, miR-486 and miR-21 to apoptotic resistance of CTCL cell line

Connection between Telomerase Activity in PBMC and Markers of Inflammation and Endothelial Dysfunction in Patients with Metabolic Syndrome

Metabolic syndrome (MS) is a constellation of metabolic derangements associated with vascular endothelial dysfunction and oxidative stress and is widely regarded as an inflammatory condition, accompanied by an increased risk for cardiovascular disease. The present study tried to investigate the implications of telomerase activity with inflammation and impaired endothelial function in patients with metabolic syndrome. Telomerase activity in circulating peripheral blood mononuclear cells (PBMC), TNF-α, IL-6 and ADMA were monitored in 39 patients with MS and 20 age and sex-matched healthy volunteers. Telomerase activity in PBMC, TNF-α, IL-6 and ADMA were all significantly elevated in patients with MS compared to healthy volunteers. PBMC telomerase was negatively correlated with HDL and positively correlated with ADMA, while no association between TNF-α and IL-6 was observed. IL-6 was increasing with increasing systolic pressure both in the patients with MS and in the healthy volunteers, while smoking and diabetes were positively correlated with IL-6 only in the patients' group. In conclusion, in patients with MS characterised by a strong dyslipidemic profile and low diabetes prevalence, significant telomerase activity was detected in circulating PBMC, along with elevated markers of inflammation and endothelial dysfunction. These findings suggest a prolonged activity of inflammatory cells in the studied state of this metabolic disorder that could represent a contributory pathway in the pathogenesis of atherosclerosis

New results on the visco-elastic behaviour of ionomer membranes and relations between T-RH plots and proton conductivity decay of Nafion (R) 117 in the range 50-140 degrees C

The colligative properties of acidic solution inside Nafion (R) 117 membranes have been investigated, in a large temperature range, by two different methods. 1) The matrix counter-pressure index of the ionomer, n(c), was first determined and then its relations with the molar fraction and molality of the inner proton solution were found. 2) In order to calculate the density of the inner proton solutions, a factor F-e proportional to the solution electro-restriction, was experimentally found. The molarity and molality of the inner proton solution, and hence the inner osmotic pressure, were then calculated. The obtained data confirmed the viscous behaviour of Nafion (R) 117 membranes. Furthermore, the comparison between the molality of inner proton solution obtained with the above different methods showed that to consider a solvation shell for the protons (first method) is equivalent to consider an electro-restriction of the solutions (second method). In other words, hydration number and electro-restriction factor are strictly related and the equation relating them is reported. Finally, T-RH plots at constant n(c) values show that the believing concerning the inability of Nafion (R) membranes to be employed in fuel cells at temperature higher than about 80-90 degrees C is not completely true

Cation-conducting ionomers made by ion exchange of sulfonated poly-ether-ether-ketone: Hydration, mechanical and thermal properties and ionic conductivity

The hydration in liquid water of various thermally treated SPEEK membranes was determined and confronted with data in saturated water vapor. Significant differences, which correspond to the so-called Schröder paradox, are observed only in un-crosslinked ionomers with IEC>2. eq/kg. After cation exchange in electrolyte solutions (2 and 0.1. mol/L), the hydration and density of the ionomers was determined and confronted with a physical model. There is no clear correlation with cation properties, such as ionic radius or Robinson-Stokes hydration numbers. The ionic conductivity ranges from 3mS/cm for K, NH4 and Mg-exchanged membranes to 0.6mS/cm for Ca and Zn. Although the latter might be related to ionic cross-linking by the divalent cations, the relatively high conductivity of Mg ions might be useful for electrochemical applications