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In accordance with the classification of the International Agency for Research on Cancer, extremely low frequency magnetic fields (ELF-MF) are suspected to promote malignant progression by providing survival advantage to cancer cells through the activation of critical cytoprotective pathways. Among these, the major antioxidative and detoxification defence systems might be targeted by ELF-MF by conferring cells significant resistance against clinically-relevant cytotoxic agents. We investigated whether the hyperproliferation that is induced in SH-SY5Y human neuroblastoma cells by a 50 Hz, 1 mT ELF magnetic field was supported by improved defence towards reactive oxygen species (ROS) and xenobiotics, as well as by reduced vulnerability against both H 2 O 2 and anti-tumor ROS-generating drug doxorubicin. ELF-MF induced a proliferative and survival advantage by activating key redox-responsive antioxidative and detoxification cytoprotective pathways that are associated with a more aggressive behavior of neuroblastoma cells. This was coupled with the upregulation of the major sirtuins, as well as with increased signaling activity of the erythroid 2-related nuclear transcription factor 2 (NRF2). Interestingly, we also showed that the exposure to 50 Hz MF as low as 100 µT may still be able to alter behavior and responses of cancer cells to clinically-relevant drugs.

Population aging results in urgent needs of interventions aimed at ensuring healthy senescence. Exercise often results in healthy aging, yet many molecular mechanisms underlying such effects still need to be identified. We here investigated whether the age-dependent accumulation of oxidative and methylglyoxal- (MG-) related molecular damage could be delayed by moderate exercise in the mouse ovary, an organ that first exhibits impaired function with advancing age in mammals. CD1 female mice underwent two- or four-month treadmill-based running through the transition from adult to middle age, when ovaries show signs of senescence, and markers of protection against reactive oxygen species (ROS) and MG were measured. The long-term exercise reduced the protein oxidative damage in the ovaries (P<0.01), and this was linked to the preservation of the glutathione peroxidase protection against ROS (P<0.001), as well as to the increased glutathione availability (P<0.001). Conversely, even though the age-related deactivation of the MG-targeting systems was partially prevented by the long-term running programme (P<0.001), exercised mice were not protected from the age-dependent glycative burden. In summary, lately initiated regular and moderate exercise limited some changes occurring in the ovaries of middle-aged mice, and this might help to develop nonpharmacological cointerventions to reduce the vulnerability of mammalian ovaries towards redox dysfunctions.

Despite the demonstrated exercise-induced increase in reactive oxygen species (ROS) production, growing epidemiological evidence indicates that habitual, moderate physical activity reduces the incidence of several oxidative stress-based diseases. This apparent paradox can be explained taking into account that ROS produced during repeated exercise bouts may act as mild stressors able to trigger physiological and biomolecular hormetic responses through a number of redox-sensitive transcription pathways. Unfortunately, much more limited information is available from general population-based research, which could better reflect the condition of common people interested in achieving and maintaining good fitness levels. The present work aimed at investigating whether and how exercise-related habits in non-professional regular runners (n=33) can affect the systemic anti-oxidative capacity, and the resting serum levels of typical lipid peroxidation-related by-products and oxidativelydamaged proteins, in comparison with untrained sedentary individuals (n=25). We also analyzed in both groups the redox response elicited by a modified Bruce-based maximal exercise test on the same parameters. Our findings indicated that longterm regular and moderate practice of aerobic physical activity can increase antioxidant defense systems, lower the resting protein oxidation processes and reduce the immediate upregulation of lipid-targeting oxidative stress in response to an acute bout of exercise.

Previously we reported that yeast and Chinese hamster V79 cells cultured under reduced levels of background environmental ionizing radiation show enhanced susceptibility to damage caused by acute doses of genotoxic agents. Reduction of environmental radiation dose rate was achieved by setting up an underground laboratory at Laboratori Nazionali del Gran Sasso, central Italy. We now report on the extension of our studies to a human cell line. Human lymphoblastoid TK6 cells were maintained under identical in vitro culture conditions for six continuous months, at different environmental ionizing radiation levels. Compared to “reference” environmental radiation conditions, we found that cells cultured in the underground laboratories were more sensitive to acute exposures to radiation, as measured both at the level of DNA damage and oxidative metabolism. Our results are compatible with the hypothesis that ultra-low dose rate ionizing radiation, i.e. environmental radiation, may act as a conditioning agent in the radiation-induced adaptive response.

We present the results of an experiment aimed at comparing the effects of different background radiation environments on metabolism and responses to gamma-rays and cycloheximide of cultured mammalian cells. Chinese hamster V79 cells were maintained in exponential growth in parallel for up to 9 months at the Istituto Superiore di Sanità (ISS) and at the INFN-Gran Sasso underground Laboratory (LNGS) where exposure due to gamma-rays and to radon was reduced by factors of about 70 and 25, respectively. After 9 months the cells grown at the LNGS (cumulative gamma dose about 30 microGy, average radon concentration around 5 Bq/m(3)), compared to the cells grown at the ISS (cumulative gamma-ray dose about 2 mGy, average radon concentration around 120 Bq/m(3)), exhibited i). a significant increase of the cell density at confluence, ii). a significantly higher capacity to scavenge organic and inorganic hydroperoxides but a reduced scavenging capacity towards superoxide anions and iii). an increase in both the basal hprt mutation frequency and sensitivity to the mutagenic effect of gamma-rays. The cells grown at the LNGS also showed a greater apoptotic sensitivity starting at the third month of culture, that was no longer detected after 9 months. Overall, these data suggest a role of background ionizing radiation in determining an adaptive response, although they cannot be considered conclusive.

One hundred and three women with a preoperative diagnosis of a pelvic support defect underwent right sacrospinous fixation of the vaginal apex. The procedure was performed either therapeutically (in 63 subjects with vaginal vault eversion) or prophylactically (40 patients with severe uterovaginal prolapse), and was associated with other reconstructive procedures to repair the coexisting cystocele, enterocele or rectocele. Preoperative and postoperative assessments of each vaginal site were compared and the results in the cure of stress urinary incontinence, if present, were evaluated with regard to the type of surgery performed. The overall rate of satisfactory results in the repair of the superior vaginal defect was 94%, and good anatomic results were achieved in the repair of either enterocele or rectocele. Conversely, the repair of the anterior vaginal wall was not as good as in the posterior and superior vaginal sites. Stress urinary incontinence was successfully managed in 72% of the women using different anti-incontinence procedures.[PUBLICATION ABSTRACT]

Tyrosinase is an enzyme having two copper atoms at the reactive site occurring in prokaryotic and eukaryotic organisms. In animals tyrosinase is responsible for pigmentation, in plants for protection of injured tissues or, as in fungi, to harden cell walls. Some of us have previously shown that tyrosinase is involved in truffle development and differentiation. Here we present the purification, the molecular properties and the reversible inhibition of Tuber melanosporum tyrosinase by dimethyl-sulfide and bis[methylthio]methane, the main flavour compounds of black and whitish truffles. The MW r is 39 000. L-3,4-dihydroxyphenylalanine and L-tyrosine stain corresponding bands as expected for a true tyrosinase. Phenylthiourea, diethyldithiocarbamate and mimosine inhibit L-tyrosine and L-3,4-dihydroxyphenylalanine oxidation.

To examine whether a neuronal cell suspension can be held in vitro for a relatively short period without compromising survival rates and functionality, we have set up an experimental protocol planning 24 h of suspension culture in a rotary wall vessel (RWV) bioreactor before plating in a conventional adherent system. Apoptosis measurement and activated caspase-8, -9, and -3 detection have demonstrated that survey of the cells was not affected. The activity of major antioxidant enzymes (AOE), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT), was significantly decreased in RWV-maintained cells. A significant decrease of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) is coupled with a level of activated nuclear factor-κB (NF-κB) protein significantly lower in RVW cells than in the control. On the contrary, the level of IL-6 expression did not change between the test and the control. A significant up-regulation of growth-associated protein-43 (GAP-43), peroxisome proliferator-activated receptor-β/δ (PPARβ/δ), and acyl-CoA synthetase 2 (ACS2) in RWV cells has been detected. We provide the evidence that primary neuronal cells, at an early stage of development, can be maintained in a suspension condition before adherent plating. This experimental environment does not induce detrimental effects but may have an activator role, leading cells to development and maturation in a tridimensional state.

This paper presents evidence that L-tyrosine oxidation products and 5,6-dihydroxyindole, an intermediate of melanin synthesis bind to and modify DNA structure, as tested by extracting cell DNA, using topoisomerase I and denaturation assays. When supercoiled plasmid pCU18 or pBR322 DNAs are treated with 5,6-dihydroxyindole the supercoiled species disappear and are converted to species less mobile in a gel retardation test with respect to relaxed DNA, 5,6-Dihydroxyindole causes an easier acid denaturation of the double helix. The results, that are dose dependent, would point to both intercalation and cross-linking of DNA by 5,6-dihydroxyindole and its oxidation product(s). 3H-L-tyrosine deriving radioactivity, bound to nuclear DNA, is higher at low pH, (5.6) if compared to pH 6.8. The highest radioactivity bound to cell DNA is found during the transition from the amelanotic to the melanotic phenotype in human melanoma cell lines. As a control, the binding of 3H-L-tyrosine radioactivity to human prostate fibroblast DNA was investigated.

This paper models the complex simultaneous localization and mapping (SLAM) problem through a very flexible Markov random field and then solves it by using the iterated conditional modes algorithm. Markovian models allow to incorporate: any motion model; any observation model regardless of the type of sensor being chosen; prior information of the map through a map model; maps of diverse natures; sensor fusion weighted according to the accuracy. On the other hand, the iterated conditional modes algorithm is a probabilistic optimizer widely used for image processing which has not yet been used to solve the SLAM problem. This iterative solver has theoretical convergence regardless of the Markov random field chosen to model. Its initialization can be performed on-line and improved by parallel iterations whenever deemed appropriate. It can be used as a post-processing methodology if it is initialized with estimates obtained from another SLAM solver. The applied methodology can be easily implemented in other versions of the SLAM problem, such as the multi-robot version or the SLAM with dynamic environment. Simulations and real experiments show the flexibility and the excellent results of this proposal.