Aging in Financial Market

We analyze the data of the Italian and U.S. futures on the stock markets and we test the validity of the Continuous Time Random Walk assumption for the survival probability of the returns time series via a renewal aging experiment. We also study the survival probability of returns sign and apply a coarse graining procedure to reveal the renewal aspects of the process underlying its dynamics.Comment: To appear in special issue of Chaos, Solitons and Fractal

Emerging Role of Purine Metabolizing Enzymes in Brain Function and Tumors

The growing evidence of the involvement of purine compounds in signaling, of nucleotide imbalance in tumorigenesis, the discovery of purinosome and its regulation, cast new light on purine metabolism, indicating that well known biochemical pathways may still surprise. Adenosine deaminase is important not only to preserve functionality of immune system but also to ensure a correct development and function of central nervous system, probably because its activity regulates the extracellular concentration of adenosine and therefore its function in brain. A lot of work has been done on extracellular 5'-nucleotidase and its involvement in the purinergic signaling, but also intracellular nucleotidases, which regulate the purine nucleotide homeostasis, play unexpected roles, not only in tumorigenesis but also in brain function. Hypoxanthine guanine phosphoribosyl transferase (HPRT) appears to have a role in the purinosome formation and, therefore, in the regulation of purine synthesis rate during cell cycle with implications in brain development and tumors. The final product of purine catabolism, uric acid, also plays a recently highlighted novel role. In this review, we discuss the molecular mechanisms underlying the pathological manifestations of purine dysmetabolisms, focusing on the newly described/hypothesized roles of cytosolic 5'-nucleotidase II, adenosine kinase, adenosine deaminase, HPRT, and xanthine oxidase

Cytosolic 5′-nucleotidase II silencing in a human lung carcinoma cell line opposes cancer phenotype with a concomitant increase in p53 phosphorylation

Purine homeostasis is maintained by a purine cycle in which the regulated member is a cytosolic 5′-nucleotidase II (cN-II) hydrolyzing IMP and GMP. Its expression is particularly high in proliferating cells, indeed high cN-II activity or expression in hematological malignancy has been associated to poor prognosis and chemoresistance. Therefore, a strong interest has grown in developing cN-II inhibitors, as potential drugs alone or in combination with other compounds. As a model to study the effect of cN-II inhibition we utilized a lung carcinoma cell line (A549) in which the enzyme was partially silenced and its low activity conformation was stabilized through incubation with 2-deoxyglucose. We measured nucleotide content, reduced glutathione, activities of enzymes involved in glycolysis and Krebs cycle, protein synthesis, mitochondrial function, cellular proliferation, migration and viability. Our results demonstrate that high cN-II expression is associated with a glycolytic, highly proliferating phenotype, while silencing causes a reduction of proliferation, protein synthesis and migration ability, and an increase of oxidative performances. Similar results were obtained in a human astrocytoma cell line. Moreover, we demonstrate that cN-II silencing is concomitant with p53 phosphorylation, suggesting a possible involvement of this pathway in mediating some of cN-II roles in cancer cell biology

Cytosolic 5'-Nucleotidase II Is a Sensor of Energy Charge and Oxidative Stress: A Possible Function as Metabolic Regulator

Cytosolic 5'-nucleotidase II (NT5C2) is a highly regulated enzyme involved in the maintenance of intracellular purine and the pyrimidine compound pool. It dephosphorylates mainly IMP and GMP but is also active on AMP. This enzyme is highly expressed in tumors, and its activity correlates with a high rate of proliferation. In this paper, we show that the recombinant purified NT5C2, in the presence of a physiological concentration of the inhibitor inorganic phosphate, is very sensitive to changes in the adenylate energy charge, especially from 0.4 to 0.9. The enzyme appears to be very sensitive to pro-oxidant conditions; in this regard, the possible involvement of a disulphide bridge (C175-C547) was investigated by using a C547A mutant NT5C2. Two cultured cell models were used to further assess the sensitivity of the enzyme to oxidative stress conditions. NT5C2, differently from other enzyme activities, was inactivated and not rescued by dithiothreitol in a astrocytoma cell line (ADF) incubated with hydrogen peroxide. The incubation of a human lung carcinoma cell line (A549) with 2-deoxyglucose lowered the cell energy charge and impaired the interaction of NT5C2 with the ice protease-activating factor (IPAF), a protein involved in innate immunity and inflammation

Performance of Edmonton Frail Scale on frailty assessment: its association with multi-dimensional geriatric conditions assessed with specific screening tools.

BACKGROUND: The aim of this study was to evaluate the performance of Edmonton Frail Scale (EFS) on frailty assessment in association with multi-dimensional conditions assessed with specific screening tools and to explore the prevalence of frailty by gender. METHODS: We enrolled 366 hospitalised patients (women\men: 251\115), mean age 81.5 years. The EFS was given to the patients to evaluate their frailty. Then we collected data concerning cognitive status through Mini-Mental State Examination (MMSE), health status (evaluated with the number of diseases), functional independence (Barthel Index and Activities Daily Living; BI, ADL, IADL), use of drugs (counting of drugs taken every day), Mini Nutritional Assessment (MNA), Geriatric Depression Scale (GDS), Skeletal Muscle Index of sarcopenia (SMI), osteoporosis and functionality (Handgrip strength). RESULTS: According with the EFS, the 19.7% of subjects were classified as non frail, 66.4% as apparently vulnerable and 13.9% with severe frailty. The EFS scores were associated with cognition (MMSE: β = 0.980; p < 0.01), functional independence (ADL: β = -0.512; p < 0.00); (IADL: β = -0.338; p < 0.01); use of medications (β = 0.110; p < 0.01); nutrition (MNA: β = -0.413; p < 0.01); mood (GDS: β = -0.324; p < 0.01); functional performance (Handgrip: β = -0.114, p < 0.01) (BI: β = -0.037; p < 0.01), but not with number of comorbidities (β = 0.108; p = 0.052). In osteoporotic patients versus not-osteoporotic patients the mean EFS score did not differ between groups (women: p = 0.365; men: p = 0.088), whereas in Sarcopenic versus not-Sarcopenic patients, there was a significant differences in women: p < 0.05. CONCLUSIONS: This study suggests that measuring frailty with EFS is helpful and performance tool for stratifying the state of fragility in a group of institutionalized elderly. As matter of facts the EFS has been shown to be associated with several geriatric conditions such independence, drugs assumption, mood, mental, functional and nutritional status

A random telegraph signal of Mittag-Leffler type

A general method is presented to explicitly compute autocovariance functions for non-Poisson dichotomous noise based on renewal theory. The method is specialized to a random telegraph signal of Mittag-Leffler type. Analytical predictions are compared to Monte Carlo simulations. Non-Poisson dichotomous noise is non-stationary and standard spectral methods fail to describe it properly as they assume stationarity.Comment: 13 pages, 3 figures, submitted to PR

On the validity of continuous spectrophotometric assays for adenosine deaminase activity: A critical reappraisal

Kinetic investigations on adenosine deaminase from calf intestinal mucosa by spectrophotometric monitoring of the reaction at 264, 270, or 228 nm show that this method does not produce artifactual inhibition by substrate excess up to 0.7 mm concentration, when either adenosine or 2â\u80²-deoxyadenosine are employed with calf adenosine deaminase. The evaluation of kinetic parameters for this system was carried out both by initial rate measurements and by numerical differentiation of time progress curves according to a recently published method (S. C. Koerber and A. L. Fink, 1987, Anal. Biochem. 165, 75-87). The following results were obtained by the latter method at pH 7.0 and 30°C: for the conversion of adenosine to inosine, kcat= 251 ± 15 s-1, KMs= 29.7 ± 2.8 μm, KMp= 613 ± 62 μm; for the conversion of 2â\u80²-deoxyadenosine to 2â\u80²-deoxyinosine, kcat= 283 ± 17 s-1, KMs= 22.4 ± 2.2 μm, KMp= 331 ± 35 μm. At 285 nm, a slight negative deviation from Beer's law was observed for adenosine at concentrations higher than 0.9 mm. No deviation was found for inosine up to 2.0 mm at the same wavelenth. © 1991