The Role Of Oxidative Stress In The Pathogenesis Of Epithelial Ovarian Cancer

Ovarian cancer is the leading cause of death from gynecologic malignancies yet the underlying pathophysiology is not clearly established. The disease is usually diagnosed in the advanced stage and carries a poor prognosis. The 5-year survival rate is greater than 75% if diagnosis of the cancer occurs at an early stage; however, this rate drops to 20% when the tumor has spread beyond its origin. Thus, a method for early detection is critically needed, which can help prolong, or even save lives. Currently, an effective screening test for ovarian cancer is lacking. Many tests have been evaluated but have been found to be lacking in sensitivity, specificity, or both. This becomes even more difficult as ovarian cancer is so rare in the general population, with an estimated prevalence of 0.04%. To date, 96% is the highest sensitivity recorded for the early detection of ovarian cancer. However, because of the low prevalence of ovarian cancer, a sensitivity and specificity of 96% would only detect 1 case of cancer per 100 oophorectomies done for positive screens due to the high false positive rate. Clinical and epidemiological investigations have provided evidence supporting the role of reactive oxygen species (ROS) in the prognosis and metastasis of cancer due to exogenous factors that lead to chronic inflammation. In addition, cancer cells are frequently under persistent oxidative stress, which participates in cancer progression as well as in the selection of resistant cells that are unable to be eliminated by apoptosis. A recent novel finding from our laboratory has shown that myeloperoxidase (MPO) is expressed in ovarian cancer cell lines and tissues, with minimal or no expression detected in normal ovarian tissues. Myeloperoxidase is an abundant heme protein, which plays a central role in the formation of reactive oxidant and free radical species. Additionally, under conditions of oxidative stress, MPO serves as a source of free iron. Another source of ROS is the superoxide producing nicotinamide adenine dinucleotide phosphate (NAD(P)H) oxidase, which we observed to be upregulated in ovarian cancer as compared to normal ovarian tissues. It has been reported that mutations in specific regions of NAD(P)H oxidase subunits contribute to the enhancement of the enzyme activity with subsequent increase in superoxide (O2 ●−) production, contributing to enhanced levels of oxidative stress. Therefore, there is compelling eveidence to support the role of oxidative stress in the pathogenesis of ovarian cancer, yet the mechanisms responsible for the dissemination of EOC are not fully understood. The objective of this work is to identify mechanisms of oxidative stress in the pathogenesis of ovarian cancer. The central hypothesis of this study is that ovarian cancer is controlled by mechanisms that emanate from an altered redox balance. To test this hypothesis, the following specific aims have been investigated: Specific Aim I: Determine the oxidative stress profile in epithelial ovarian cancer and determine the effect of the modulation of specific key players of oxidative stress on the persistence of the oncogeneic phenotype. To determine the oxidative stress profile, the expression of the following markers will be evaluated: NAD(P)H oxidase, nitrate/nitrite, glutathione, glutathione reductase, glutathione peroxidase, glutathione s-transferase, inducible nitric oxide synthase, myeloperoxidase, catalase, and superoxide dismutase in epithelial ovarian cancer cells and tissues as compared to their normal counterparts. These markers were selected based on extensive preliminary and published results, utilizing a cell culture model and ovarian cancer tissues. Modulation of key players of oxidative stress will contribute to delineation of the mechanisms of development of ovarian cancer. To achieve this, a combination of knockdown or inhibition of specific pro-oxidants ulizing siRNA or direct inhibition will be performed followed by the assessment of the expression other pro-oxidants as well as the effect on apoptosis. Specific Aim II: To assess the effectiveness of MPO and free iron levels in detection of early stage ovarian cancer. The mechanism by which MPO functions under oxidative stress is not well defined. MPO has been indicated to serve as a source of free iron under oxidative stress. The hypothesis of this aim is that serum MPO and free iron levels can be utilized to distinguish patients with stage I ovarian cancer from those with normal ovaries or benign gynecologic conditions as well as from late state ovarian cancer. MPO and free iron levels will be measured in the sera and tissues of women at the time of ovarian cancer diagnosis as compared to healthy women or those with benign gynecologic disorders respectively. The biological significance of the relationship between serum MPO and free iron, in conjunction with the poor prognosis of ovarian cancer has the potential for future clinical applications. . Specific Aim III: To assess whether a SNP in NAD(P)H oxidase is associated with increased risk of development of ovarian cancer. Single nucleotide polymorphisms (SNPs) are associated with increased risk of several cancers. We evaluated the association of a SNP (rs4673) in the CYBA gene, encoding the p22phox subunit of NAD(P)H oxidase, substituting allele C with T at position 242 located on chromosome 16q24, in high-risk individuals with or without ovarian cancer, with or without a deleterious BRCA1/2 mutation. This SNP is known to be associated an increased activity of the enzyme, resulting in an increase in superoxide production. TaqMan® SNP Genotype analysis and the QuantStudio 12K Flex Real-Time PCR System were utilized to determine the frequency of this SNP in individuals with ovarian cancer as compared to noncancer individuals

MODELING AND OPTMIZATION POWER REQUIREMENTS OF ACTIVE ACOUSTIC LOUVRES

The development of new technologies for ventilated facades is within the context of energy efficiency of buildings , including the compatibility of the dichotomy between natural ventilation and soundproofing in tropical countries . Given this perspective, this work proposes the application of techniques for active noise control in acoustic louvers . One limitation of the spread of technical active noise control in buildings is the energy inherent in the technique. Thus, the proposed system is based on the reduction of structural vibrations of the shutter blades by using piezoelectric actuators . The acoustic transmission loss and energy requirements for active shutters are investigated from numerical modeling . The results suggest their technical feasibility with superior soundproofing to 30 dB and power consumption less than 35 W. Thus , the active noise control using piezoelectric actuators is presented as a promising technology , aligning soundproofing with low energy consumption Type the text of the abstract here, Times New Roman, 9, lower case letters, justified paragraphs, 1.0 line spacing. The abstract should state the objectives, methodology and main conclusions in 200 to 300 words. No not divide into paragraphs

First authentic record of the freshwater turtle mauremys from the upper pliocene of italy, with a new occurrence of the rarely reported ichnotaxon thatchtelithichnus holmani

Nowadays, the living species of the terrapin genus Mauremys (Testudinoidea: Geoemydi-dae) are mostly found in eastern Asia, but three of them inhabit the Western Palearctic ecozone. In Italy, occurrences of living individuals of Mauremys are interpreted as records of alien species; how-ever, a growing fossil record demonstrates that this genus has inhabited Italy as recently as the Late Pleistocene. We report on a new fossil specimen of Mauremys from the Upper Pliocene (Piacenzian) marginal-marine deposits of Tuscany (central Italy). This find, consisting of a partial plastron and a loose neural, represents the second authentic report of Mauremys from the Italian Pliocene, as well as the first one from the Piacenzian of Italy. Therefore, it is a significant fossil that fills a gap in the chro-nostratigraphic distribution of Italian fossil Mauremys, helping – together with the Lower Pliocene holo-type of Mauremys portisi – to bridge the rich Miocene and Pleistocene segments of this record. More-over, two unusual scars observed on the external surface of the studied plastron are here referred to the ichnospecies Thatchtelithichnus holmani. These traces represent one of the few records worldwide of this rarely identified ichnospecies, as well as its geologically youngest published occurrence. Hypo-theses regarding the origin of the Thatchtelithichnus traces are reevaluated, and an origin as attach-ment scars of aquatic ectoparasites (possibly ticks, leeches, or flukes) is reaffirmed as probable in ca-ses of traces occurring on the exterior of the plastral bones of turtles

So close so different: what makes the difference?

The introduction of alien fish species in wetland ecosystems could have a great impact on freshwater communities and ecological processes. Despite fish introduction has been noticed as one of the principal cause of freshwater extinctions, ecosystem processes alteration, and change in aquatic community assemblage, very few data about impact on freshwater reptiles are available. As study model we used two neighbour sub-populations of the endangered Sicilian pond turtle, Emys trinacris, inhabiting two small, close each other and very similar lakes, except for the presence of allocthonous fish, Cyprinus carpio and Gambusia hoolbroki in one of the two. The multi-year study allowed highlighting significant differences in abundance, growth and reproductive output between the two freshwater turtle sub-populations, suggesting their influence on phenotypic plasticity of the studied population. These results are discussed in the light of previous evidence about the impact of these alien species on abundance and assemblage of the invertebrate community with an evident impact on niche width, diet composition and therefore energy intake by Emys trinacris. These data may provide important information to address management strategies and conservation actions of small wetland areas inhabited by pond turtles, pointing out a threats never highlighted up to now

Mirrored images but not silicone models trigger aggressive responses in male common wall lizards

Disentangling the effects of single releasers in animal communication is a demanding task because a releaser often consists of a combination of different key stimuli. Territorial communication in reptiles usually depends on visual, chemical, and acoustic stimuli, but the role of each of them depends on phylogeny. Lacertids are modern lizards that rely mainly on chemical cues for their communication, but they also use aggressive displays based on visual recognition. We experimentally tested the visual stimuli that release an aggressive response in the males of a typical lacertid, the common wall lizard (Podarcis muralis), testing the effects of silicone models and mirrored images in captivity. The response to models and control (a blank sheet) was not significantly different and these stimuli did not release any aggressive behaviour. On the contrary, the reflected image in a mirror caused overt aggression (i.e., bites against it) in 63% of tested individuals. The results clearly demonstrate the role of visual stimuli in territorial communication, but only as a combined effect of shape and motion, differently from other lizard families for which shape is enough to stimulate aggre sive responses. Mirrors can be useful tools to investigate aggression related to physiological and morphological aspects in lacertid lizards

Stable or plastic body shape? Emys orbicularis hatchlings-juveniles growth patterns under different ecological conditions

To test if habitat could shape shell features of freshwater turtles starting from birth, we tested hatchlings of Emys orbicularis, randomly chosen from four clutches of the same locality, under two treatments, stagnant (pond habitat) vs lotic (river habitat) water regimes. Due to mortality at the beginning of the experiment, we finally considered only two clutches. Turtle shells were characterized initially at hatching and then after one year of treatment by means of traditional and geometric morphometrics, and phenotypic trajectories analyses were conducted on both types of data. Carapace growth was isometric both in proportion and shape, while plastron showed an allometric pattern: length increased more than width, while the contour showed an expansion at the rear and a compression of the front. The hydrodynamic conditions during growth did not seem to affect the phenotypic trajectories of the shell proportions or the plastron. On the contrary, a significant effect was found on the phenotypic trajectory of the carapace: the size component (but not the angle one) was positively influenced by the "lentic" treatment, suggesting a different growth rate between the two environmental conditions

Winter activity in a coastal population of Vipera aspis (Reptilia, Viperidae)

L'activité hivernale d'une petite population de Vipera aspis (4 mâles adultes et 3 femelles adultes) a été étudiée au cours de trois hivers à l'aide du radio-pistage. Presque tous les individus sont restés actifs, se cachant simplement sous les feuilles, se déplaçant d'un refuge à l'autre en effectuant des distances d'environ 150 m. Approximativement 50 % des serpents étaient actifs au soleil (29 % du total des journées d'observation). Les domaines vitaux et les zones de principale fréquentation sont statistiquement identiques entre les sexes, bien que légèrement supérieurs chez les mâles. Les tailles observées pour les domaines vitaux sont remarquablement grandes pour des périodes hivernales durant lesquelles l'activité est censée être très réduite. Des déplacements, courts et longs, sont relativement plus fréquents chez les mâles que chez les femelles. Des températures ambiantes favorables liées à la position géographique, et donc à la zone climatique de la zone d'étude, semblent être le stimulus principal pouvant expliquer la forte activité hivernale de la population étudiée

Dimorphisme sexuel, morphométrie et variation phénotypique de la Couleuvre verte et jaune Hierophis viridifl avus dans une région du centre de la Méditerranée

Animal populations living in different environments generally exhibit divergent phenotypic characteristics. In snakes, body size varies greatly among disjunct populations. The European Whip snake, Hierophis viridifl avus, is widely distributed in the western Mediterranean area, and on most of both small and large islands of the Tyrrhenian Sea. We compared biometrical patterns regarding ventral scalation, body size and head size among different samples from mainland, large islands and small islands. Sexual Size Dimorphism was very marked in the species, with males attaining larger body size and larger relative head size than females and a lower number of ventral scales. There was a clear evidence of a strong relationship between ventral scale number and the geographic origin, with smaller island snakes characterized by a signifi cantly higher number of ventral scales. This relationship was true even when considering body size, with insular snakes signifi cantly smaller than mainland ones. Our results clearly indicated a strong differentiation among the considered populations, and provided basis to clarify the relative importance of phenotype variationDimorphisme sexuel, morphométrie et variation phénotypique de la Couleuvre verte et jaune Hierophis viridiflavus dans une région du centre de la Méditerranée. - Généralement les populations animales qui vivent dans des environnements différents divergent dans leurs caractéristiques phénotypiques. Chez les serpents, la taille corporelle varie fortement entre populations disjointes. La Couleuvre verte et jaune Hierophis viridiflavus est largement distribuée en Méditerranée occidentale et sur les îles tant petites que grandes de la mer Tyrrhénienne. Nous avons comparé les patterns biométriques relatifs à l'écaillure ventrale, la taille du corps et de la tête dans divers échantillons provenant du continent, de petites et de grandes îles. Le dimorphisme sexuel est très marqué chez cette espèce, les mâles étant corporellement plus grands, avec une tête plus grosse et moins d'écailles ventrales que les femelles. Une relation forte entre le nombre d'écailles ventrales et l'origine géographique a été clairement mise en évidence, les individus provenant des petites îles étant caractérisés par un nombre significativement élevé d'écailles ventrales. Cette relation se maintient quand on prend en compte la taille corporelle, les individus insulaires étant plus petits que ceux du continent. Nos résultats indiquent clairement une forte différenciation entre les populations étudiées et éclairent l'importance relative de la variation phénotypique

Refinement of the NISECI ecological index reference conditions for Italian freshwater fish communities in the eastern Emilia-Romagna region

Following the Water Framework Directive 2000/60/CE (WFD), each member state of the European Union must monitor compliance of its rivers with ecological quality standards through biological quality indicators. The New Italian Index of the Ecological State of Fish Communities (NISECI) was developed in 2017 for the assessment of fish communities, as directed by the WFD in Italian freshwater habitats. According to the WFD, the general reference conditions (GRCs) of NISECI must be refined on a regional scale through new calculation of its metrics and sub-metrics. In the present study we used environmental and ichthyological data from 457 fish samplings distributed among 299 sampling sites within 84 different water bodies collected from 1995 to 2012 to develop: 1) new lists of expected species for six homogeneous zones identified in the Reno basin (Italy) and in the eastern regional basins of the Emilia-Romagna region; and 2) the threshold values for their species-specific abundance. Results were set as refined reference conditions (RRCs) for two of the metrics used in the application of the NISECI index in the study area (i.e. X1, relating to indigenous species and X2,b, for the abundance of expected species). The RRCs were tested by applying NISECI to 24 monitoring sites of the regional surface water monitoring network (i.e., ARPAE) and comparing the results with the application of NISECI using the GRCs. Furthermore, the analytical power of the refined NISECI was evaluated by relating the findings to three expertbased blind assessments of fish community ecological status. The results confirmed an increase in refined NISECI values and its higher consistency with expert-based assessment, supporting the validity of the presented method for RRC development and its potential for application in other regions

Subjective resource value affects aggressive behavior independently of resource-holding-potential and color morphs in male common wall lizard

AbstractGame theory models predict the outcome of a dyadic contest to depend on opponents' asymmetries in three main traits: resource-holding potential (RHP), resource value (RV) and aggressiveness. Using male common wall lizards Podarcis muralis, a polymorphic species showing three discrete morphs (white, yellow, and red), we investigated how the aggressive behavior varies according to a change in subjective RV and color morphs, while controlling for the asymmetry in RHP (using mirrors). By comparing the aggression of the same individual towards its mirror image in two different arenas (familiar = high subjective RV; novel = low subjective RV), we showed that lizard aggressive behavior was more intense and prolonged in the familiar arena than in the new one, thus supporting the occurrence of a direct relationship between motivation and aggression in this species. We also found the overall aggressiveness to differ from individual to individual, supporting the general hypothesis that aggressiveness is a trait associated with personality. By contrast, no effect of morphs was detected, ruling out the occurrence of morph specific variation in the aggressiveness. Our results highlight that an individual's motivation and personality might be as important as RHP and RV in the resolution of animal contests