Acquired DNA damage in adolescent obesity – a promoter and predictor of cancer?

Introduction Epidemiological evidence linking obesity with increased risk of cancer is steadily growing, although the causative aspects underpinning this association are only partially understood. Obesity coincides with deficiencies in micronutrients such as Vitamin D, a key player in DNA repair processes. As a result, vitamin D deficiency in obesity may have a marked impact on DNA stability and integrity. 8-hydroxyguanosine (8-OHdG) is a well-established marker of oxidative DNA damage that has been identified in higher concentrations in cancer patients. Here we report, preliminary, unpublished findings from our study on acquired DNA damage in childhood obesity. Material and Method Body Mass Index (BMI), Waist to Hip ratio (WHR) and body fat percentage via bioelectrical impedance was assessed in over 70 participants, aged 11-18 and recruited from National Health Service (NHS) obesity clinics and schools in London. A non-invasive, integrated evaluation of urinary 8-OHdG and salivary vitamin D was conducted using ELISA based methods and compared to markers of adiposity. Results and Discussion A BMI percentile >99 was found to be associated with decreased salivary vitamin D and increased urinary 8-OHdG when compared to healthy weight controls (BMI = 5th-85th percentile). Vitamin D levels in saliva were found to be inversely correlated with BMI and body fat percentage. Urinary 8-OHdG positively correlated with body fat percentage and WHR. Most importantly, an inverse correlation between vitamin D in saliva and 8-OHdG in urine was also identified. Recent evidence has suggested vitamin D in obesity to be a consequence of altered behaviour, reduced intestinal absorption, and sequestration of vitamin D into adipose tissue. As a result, DNA repair processes against oxidative DNA damage in obesity may be impaired, resulting in the excess of lesions including 8-OHdG. The effects of excess 8-OHdG lesions have been well researched to include various mutations that can drive carcinogenesis. Conclusion Our results suggest Vitamin D deficiency in obese adolescents may play a significant role in triggering oxidative DNA damage, thus increasing the likelihood of cancer later in life

Genome Instability in Childhood Obesity – a potential role for bariatric surgery in cancer prevention?

Severe paediatric obesity is associated with a range of metabolic complications and is characterised by a chronic meta-inflammatory state. It is postulated that this inflammatory response may result in an excess of systemic reactive oxygen species (ROS) that are well known for inducing DNA damage and reducing the capability of DNA synthesis and repair enzymes. Consequently, chronic inflammation in obesity may promote an accumulation of deleterious DNA mutations, leading to genome instability and driving carcinogenesis. This research aims to accrue evidence to consolidate or refute a causative link between genome instability in childhood obesity and the increased risk of developing cancer at a later stage in life. For the purpose of this study, a novel, non- invasive analytical ‘tool-kit’ for the combined and comprehensive assessment of systemic inflammation and acquired DNA damage has been developed and is being tested on a cohort of severely obese children and healthy weight controls recruited from King’s College Hospital and St George’s NHS trust. Furthermore, this research aims to propose biomonitoring of the genome to inform prioritization and severity of intervention measures based on the suggested reversibility of DNA damage following early surgical weight-loss treatment

Breakups hurt: Party switching and perceived proximity between politicians and their party

What are the effects of party defections on the attitudes of politicians who remain loyal to the party? We answer by combining multiple sources of data into a comprehensive novel data set on parliamentary party switching, to estimate how this affects the perceived distance between a politician and his party. Focusing on the theory of cognitive dissonance and the black sheep effect, we hypothesize that politicians perceive themselves closer to their parties when those parties recently suffered defections. The effect should be greater among incumbent politicians as they directly experience divisions, but also among officials dissatisfied with the leadership as their dissonance should be stronger. Statistical analyses of data from two elite surveys, on a sample of 13,256 politicians belonging to 92 parties that ran in 28 elections held between 2005 and 2015 in 14 countries, provide support for our hypotheses and shed light on the consequences of intra-party defections

Multifractal analysis of radar rainfall fields over the area of Rome

A scale-invariance analysis of space and time rainfall events monitored by meteorological radar over the area of Rome (Italy) is proposed. The study of the scale-invariance properties of intense precipitation storms, particularly important in flood forecast and risk mitigation, allows to transfer rainfall information from the large scale predictive meteorological models to the small scale hydrological rainfall-runoff models. <P style=&quot;line-height: 20px;&quot;> Precipitation events are monitored using data collected by the polarimetric Doppler radar Polar 55C (ISAC-CNR), located 15 km Southeast from downtown. The meteorological radar provides the estimates of rainfall intensity over an area of about 10 000 km² at a resolution of 2&times;2 km² in space and 5 min in time. <P style=&quot;line-height: 20px;&quot;> Many precipitation events have been observed from autumn 2001 up to now. A scale-invariance analysis is performed on some of these events with the aim at exploring the multifractal properties and at understanding their dependence on the meteorological large-scale conditions

The 2.35 year itch of Cyg OB2 #9. II. Radio monitoring

Cyg OB2 #9 is one of a small set of non-thermal radio emitting massive O-star binaries. The non-thermal radiation is due to synchrotron emission in the colliding-wind region. Cyg OB2 #9 was only recently discovered to be a binary system and a multi-wavelength campaign was organized to study its 2011 periastron passage. We report here on the results of the radio observations obtained in this monitoring campaign. We used the Expanded Very Large Array (EVLA) radio interferometer to obtain 6 and 20 cm continuum fluxes. The observed radio light curve shows a steep drop in flux sometime before periastron. The fluxes drop to a level that is comparable to the expected free-free emission from the stellar winds, suggesting that the non-thermal emitting region is completely hidden at that time. After periastron passage, the fluxes slowly increase. We introduce a simple model to solve the radiative transfer in the stellar winds and the colliding-wind region, and thus determine the expected behaviour of the radio light curve. From the asymmetry of the light curve, we show that the primary has the stronger wind. This is somewhat unexpected if we use the astrophysical parameters based on theoretical calibrations. But it becomes entirely feasible if we take into account that a given spectral type - luminosity class combination covers a range of astrophysical parameters. The colliding-wind region also contributes to the free-free emission, which can help to explain the high values of the spectral index seen after periastron passage. Combining our data with older Very Large Array (VLA) data allows us to derive a period P = 860.0 +- 3.7 days for this system. With this period, we update the orbital parameters that were derived in the first paper of this series.Comment: 10 pages, 4 figures, accepted for publication in A&

Synthesis and crystal structure of Bis(2-phenylpyridine-C,N’)-bis(acetonitrile) iridium(III)hexafluorophosphate showing three anion/cation couples in the asymmetric unit

The title compound bis(2-phenylpyridine-C,N’)-bis(acetonitrile)iridium(III)hexafluorophosphate, a six-coordinate iridium(III) complex, crystallizes in the P-1 space group. Iridium is in a distorted octahedral (n = 6) coordination with the N,C’ atoms of two phenylpyridine and the N atoms of two acetonitrile ligands. The peculiarity of this structure is that three independent moieties of the title compound and three PF6− anions, to counterbalance the charge, are observed in the asymmetric unit and this is a rather uncommon fact among the Cambridge Crystallographic Database (CSD) entries. The three couples are almost identical conformers with very similar torsional angles. The packing, symmetry, and space group were accurately analyzed and described also by means of Hirshfeld surface analysis, which is able to underline subtle differences among the three anion/cation couples in the asymmetric unit. The driving force of the packing is the clustering of the aromatic rings and the maximization of acetonitrile:PF6− interactions. The asymmetry of the cluster is the cause of the unusual number of moieties in the asymmetric unit

Evaluating Inflammatory and Genotoxic Consequences of Adiposity in Adolescents: a Non-Invasive Approach

The genome holds a substantial role in maintaining optimal cellular function. There are a variety of well-established genotoxicity tests that can evaluate acquired DNA damage and chromosomal instability. These types of tests can be utilized to inform susceptibility to disorders that are strongly associated with genome damage, such as cancer. A strong correlation has become evident between obesity and over ten different types of cancers. This association may be explained by the increased systemic inflammation and over-generation of reactive oxygen species (ROS) that is characteristic in individuals who possess excess body fat. The mutagenic effects of ROS are well-known and include oxidative base modifications and DNA single and double strand breaks. Emerging evidence indicates a correlation between increased adiposity and markers of oxidative DNA damage. One such marker is 8- OH-2-deoxy Guanosine (8-OHdG), a DNA lesion that is potentially mutagenic. Findings of other biomarkers indicative of DNA strand breaks in obesity include -H2AX foci, micronuclei and comet tails. Telomere attrition marks accelerated ageing and is another phenomenon identified in obese adults and children. Adolescent obesity is expected to rise and lead to morbidity. It is concerning that recent studies have suggested obese children to not only possess a reduced life expectancy, but a pre-disposition to age related disorders, including cancer. We propose biomonitoring of the genome to inform prioritization and severity of intervention measures. A combined laboratory ‘tool-kit’ to allow non-invasive biomonitoring of ‘genome health’ in adolescents and other large epidemiological studies is being developed. This investigation integrates the well-established micronucleus assay in exfoliated buccal epithelial cells, urinary 8-OHdG, salivary telomere length and salivary C-reactive protein to provide a comprehensive assessment of inflammation, cytotoxicity, chromosomal aberrations and DNA damage in a cohort of 11-15 year olds. Correlations of these markers is explored against three different measures of adiposity - waist to hip ratio, body fat percentage and body mass index. Findings from this study aim to establish the applicability of personalized, early detection of acquired DNA damage as a pre-cancerous biomarker in obesity and other pre-pathological conditions

MICROBIAL INDUCED REINFORCED CONCRETE DETERIORATION AND INNOVATIVE PROTECTION TECHNIQUES

Reinforced concrete deterioration due to steel reinforcing bars corrosion is recognized as a serious problem, affecting the durability of various types of civil structures. Many efforts have been dedicated to studying the steel corrosion process induced by chloride penetration, being by far the most frequent cause for reduced durability of reinforced concrete structures. Much less attention has been focused on the microbial degradation of reinforced concrete structures occurring as a consequence of the presence of bacteria involved in the sulfur cycle (Sulfate Reducing Bacteria and Sulphur Oxidizing Bacteria) whose metabolic products react with the cementitious matrix yielding to fast deterioration processes. According to literature, in such field, most of the attentions were focused on concrete deterioration, while if and how bacteria metabolites eventually affect the behaviour of the steel reinforcing bars appears to be still an open issue. The research project aims at filling up the knowledge gap above mentioned, that is: assessing how risky and aggressive a bacterial environment is, especially focusing on corrosion of steel reinforcing bars. On this purpose, abiotic solutions, simulating bacteria metabolic products were used for all tests. While a second part of the work was devoted to the development of a "smart" inhibitive system able to protect steel rebars from the corrosion induced by biogenic acidity that slowly neutralize cement alkalinity. The prolonged protective effect was meant to be achieved by encapsulating the active substances into pH sensitive microbeads, that would release the inhibitor only when reached by the acidification front, thus preventing a premature leaching of the inhibitor. As a common practice in concrete science, investigations were started from the easier system of the steel rebars directly immersed into simulating solutions. Thus, a stable passive layer was growth on the steel surfaces by means of a three days immersion into a saturated Ca(OH)2 solution. Afterwards, samples were moved into sulfides containing alkaline solutions or diluted sulfuric acid, aiming to simulate the metabolic products of SRB and SOB respectively. The acidic conditioning, into diluted sulfuric acid solutions, easily dissolved the passive layer and caused a fast onset of generalized corrosion, whose extension was found to be dependent on the acid concentration as indicated by both gravimetric and electrochemical tests. Conversely, sulfides were proven to induced localized corrosion, their interactions with the steel surface resulted to be significantly affected by the pH of the environment. Actually, for a prevailing of hydroxyl ions over the sulfides ones the steel surface remained protected by the oxide layer, while at lower pH steel-sulfides interaction were promoted, yielding to a porous, conductive, and thus non protective layer of iron sulfides. Once clarified the corrosion mechanisms for steel directly immersed in simulating solutions, reinforced mortar samples were cast, cured, carbonated and then conditioned into two different model media: a sulfides containing solution and diluted sulfuric acid solution. The combination of several electrochemical techniques such as OCP, LPR and EIS pointed out the active behavior of the embedded steel rebars. Visual inspection performed at the end of a 500 days conditioning period confirmed that the acidic conditioning yielded to more severe damages. On the basis of such findings, a "smart" corrosion inhibitor was developed by combining together calcium phosphate and methylene blue dye, being both active compounds in terms of protection of carbon steel from sulfuric acid corrosion. The resulting product was an organic/inorganic hybrid where the organic molecules were entrapped into a porous inorganic matrix, granting their release as a function of a pH drop leading to the dissolution of the latter. Anodic and cathodic potentiodynamic polarizations performed in sulfuric acid solution and in presence of the hybrid inhibitor confirmed that both the anodic and the cathodic processes were hindered as a consequence of the combined effect of methylene blue dye and phosphate ions. The effectiveness of the slow release mechanism was evaluated by means of LPR and EIS monitoring by comparing the responses of the hybrid, its two components singularly used and the free corroding system as a control case. The effect of the organic inhibitor was that of significantly increasing the polarization resistance. Such effect was rapidly lost in the case of methylene blue dye alone, while its slow release, together with the synergic effect of phosphate ions contributed to the prolongation of the protective effect. Finally the interactions of the hybrid and its components with the cementitious matrix were investigated by means of isothermal calorimetry and standard compressive strength tests. The response of both the hydration rate and the strength evolution were found to be independent from the chemical admixtures. Once excluded the onset of negative side effects, reinforced mortar samples containing different amount of the unloaded HAP and the hybrid MBD-HAP were cast and exposed to a sulfuric acid environment for about four months. However such a conditioning period proved not to be long enough to induce the corrosion of the steel reinforcing bars