Fate and Transport of Polycyclic Aromatic Hydrocarbons in Upland Irish Headwater Lake Catchments

Polycyclic aromatic hydrocarbons (PAHs) are a concern due to their carcinogenicity and propensity for transboundary atmospheric transport. Ireland is located on the western periphery of Europe and assumed to receive clean Atlantic air. As such, it has been used as an atmospheric reference for comparison to other regions. Nonetheless, few studies have evaluated concentrations of PAHs within the Irish environment. In the current study, PAHs were measured at five upland (500–800 masl) headwater lake catchments in coastal regions around Ireland, remote from industrial point source emissions. Semipermeable membrane devices were deployed in lakes for a 6-month period in July 2009, and topsoils were sampled from each catchment during October 2010. The concentrations of PAHs were low at most study sites with respect to other temperate regions. Homologue groups partitioned between lake and soil compartments based on their molecular weight were: “lighter” substances, such as Phenanthrene and Fluorene, were found in higher proportions in lakes, whereas “heavier” compounds, such as Chrysene and Benz[a]anthracene, were more prominent in soils. Concentrations of PAHs were highest at the east coast sites, potentially due to contributions from historical transboundary and regional combustion sources

Deoxyuridine triphosphatase (dUTPase) expression and sensitivity to the thymidylate synthase (TS) inhibitorD9331

Uracil DNA misincorporation and misrepair of DNA have been recognized as important events accompanying thymidylate synthase (TS) inhibition. dUTPase catalyses the hydrolysis of dUTP to dUMP, thereby maintaining low intracellular dUTP. We have addressed the relationship between dUTPase expression and cellular sensitivity to TS inhibition in four human lung tumour cell lines. Sensitivity (5-day MTT assay) to the growth inhibitory effects of the non-polyglutamatable, specific quinazoline TS inhibitor ZD9331, varied up to 20-fold (IC 50 3–70 nM). TS protein expression correlated with TS activity (r2= 0.88 P= 0.05). Intracellular concentrations of drug following exposure to ZD9331 (1 μM, 24 h) varied by ~2-fold and dTTP pools decreased by > 80% in all cell lines. No clear associations across the cell lines between intracellular drug concentrations, TS activity/expression, or TTP depletion could be made. dUTPase activity varied 17-fold and correlated with dUTPase protein expression (r2= 0.94 P= 0.03). There was a striking variation in the amount of dUTP formed following exposure to ZD9331 (between 1.3 and 57 pmole 10–6cells) and was in general inversely associated with dUTPase activity. A large expansion in the dUTP pool was associated with increased sensitivity to a 24-h exposure to ZD9331 in A549 cells that have low dUTPase activity/expression. dUTPase expression and activity were elevated (approximately 3-fold) in two variants of a human lymphoblastoid cell line with acquired resistance to TS inhibitors, further suggesting an important role for this enzyme in TS inhibited cells. © 2000 Cancer Research Campaig

The ability to accumulate deoxyuridine triphosphate and cellular response to thymidylate synthase (TS) inhibition

Thymidylate synthase (TS) is an important enzyme catalysing the reductive methylation of dUMP to dTMP that is further metabolized to dTTP for DNA synthesis. Loss of viability following TS inhibition occurs as a consequence of depleted dTTP pools and at least in some cell lines, accumulation of dUTP and subsequent misincorporation of uracil into DNA. The expansion in dUTP pools is largely determined by the expression of the pyrophosphatase, dUTPase. Our previous work has shown that following TS inhibition the ability to accumulate dUTP was associated with an earlier growth inhibitory effect. 3 human lung tumour cell lines and HT29 human colon tumour cells transfected with dUTPase have been used to investigate the relationship between loss of viability following TS inhibition and dUTP accumulation. Cell cycle arrest typical of TS inhibition was an early event in all cell lines and occurred irrespective of the ability to accumulate dUTP or p53 function. However, a large expansion of dUTP pools was associated with mature DNA damage (4 h) and an earlier loss of viability following TS inhibition compared to cells in which dUTP pools were not expanded. In A549 cells damage to mature DNA may have been exacerbated by significantly higher activity of the excision repair enzyme, uracil-DNA glycosylase. Consistent with results using different inhibitors of TS, transfection of dUTPase into HT29 cells significantly reduced the cytotoxicity of a 24 h but not 48 h exposure to ZD9331. Although loss of viability can be mediated through dTTP deprivation alone, the uracil misincorporation pathway resulted in an earlier commitment to cell death. The relevance of this latter pathway in the clinical response to TS inhibitors deserves further investigation. © 2001 Cancer Research Campaign http://www.bjcancer.co

Assessment of inherent fluctuations of mitotic and labelling indices of human tumours.

A method is presented to evaluate the influence of statistical errors and inherent variation on the determination of mitotic and labelling indices of human tumours. In most of the experiments reported here, sufficient cells were counted to yield a statistical error which is small in comparison to the inherent differences in the proliferative indices, both between different sites in the same tumour and between different tumours of the same histological type. These inherent fluctuations are, theefore, a critical factor in cell kinetic studies of human tumours

Identification of the key compounds responsible for Cheddar cheese flavour

End of Project ReportThere is a poor understanding of the relationship between organoleptic assessment of cheese and quantitative analysis of flavour compounds. Further, the contribution of particular cheese-making parameters such as ripening temperature and starter culture has not been fully elucidated. During the ripening of most cheese varieties complex chemical conversions occur within the cheese matrix. In most cheese varieties breakdown of protein is the most important flavour development pathway. The primary cheese protein, casein, is degraded enzymatically to short peptides and free amino acids. The agents primarily responsible for these conversions are the residual rennet that is retained in the cheese curd at the end of the manufacturing phase and the proteinases and peptidases that are associated with the starter bacteria. While the rate and degree of proteolysis are of vital significance for desired flavour development, the direct products of proteolysis do not fully define cheese flavour. Much research is now demonstrating that the further biochemical and chemical conversions of the products of proteolysis, in particular the amino acids, are necessary for full flavour development. The products produced by these pathways are volatile at low boiling points and are thus released during mastication of the cheese in the mouth. Many of these volatile compounds contribute to the flavour sensation experienced by the consumer. A very wide spectrum of such compounds have been isolated from cheese, in excess of two hundred in some cheese varieties. It is now generally accepted that there is no individual compound which defines cheese flavour completely and that the flavour sensation is the result of numerous compounds present in the correct proportions. This has become known as the Component Balance Theory . The application of modern analytical techniques as proposed in this project would provide a greater understanding of the significant flavour compounds in Cheddar cheese and help to identify the impact of specific cheese-making parameters such as starter flora and ripening temperature on the production of volatile flavour compounds. This data would assist the general programme on flavour improvement of cheese which should ultimately benefit the cheese manufacturer. Hence this project set out to develop methods to identify the key flavour compounds in Cheddar cheese. These techniques would then be applied to experimental and commercial cheeses during ripening in an effort to identify key compounds and the influence of starter cultures and ripening temperature on their production.Department of Agriculture, Food and the Marin

Comparison of three methods of feeding sows in gestation and the subsequent effects on lactation performance

A total of 684 sows from breeding groups over six weeks were used to compare three methods of feeding during gestation and to assess the subsequent effects on lactation performance. Control gilts and sows were fed according to body condition based on a scale of 1 to 5, (1=thin, 5=fat). Sows were visually assessed for body condition at breeding and were assigned a daily feed allowance to achieve a body condition score of 3 at farrowing. Sow body condition was evaluated every two weeks throughout gestation, and feed allowance was adjusted as required. Treatment two used feeding levels based on backfat thickness (measured between d 0 and 5 after breeding) and weight at weaning for sows or weight at service for gilts. Feed allowance was calculated to achieve a target backfat of 19 mm at farrowing. Sow feeding level remained constant from d 0 to 101 of gestation. Feed allowances were based on modeled calculations of energy and nutrient requirements to achieve target sow maternal weight and backfat gain. Treatment three was identical to treatment two except that feeding pattern was altered for thin sows and gilts (\u3c15 mm at service) in an attempt to reach 19 mm by d 36 of gestation. Sows were weighed at the previous weaning and gilts at-service and again between d 112 and 114 of gestation. Backfat was measured between d 0 and 5 and again between d 108 and 113 of gestation. Sows on treatments two and three achieved backfat of 19 and 19.1 mm at farrowing, respectively, while control sows numerically tended to have greater backfat at farrowing (20 mm). On average, sows targeted to gain large amounts (6 to 9 mm) of backfat in gestation failed to achieve target gains regardless of feeding method. Feeding sows in gestation based on backfat (treatments two and three) resulted in a higher proportion of sows in the target backfat range of 17 to 21 mm at farrowing and a lower percentage of fat sows (\u3e21 mm) but no difference in the percentage of thin sows (\u3c17 mm) compared to the standard method of feeding based on body condition. Gestation feeding method had no effect on performance during lactation. Feed intake in lactation was lower for high backfat sows (\u3e21 mm) at farrowing compared to sows with \u3c21 mm. The high proportion of sows in the optimum backfat category demonstrates that feeding based on backfat and body weight has potential for facilitating more precise gestation feeding.; Swine Day, 2003, Kansas State University, Manhattan, KS, 200

Dynamic modeling and target loads of sulfur and nitrogen for surface waters in Finland, Norway, Sweden, and the United Kingdom

The target load concept is an extension of the critical load concept of air pollution inputs to ecosystems. The advantage of target loads over critical loads is that one can define the deposition and the point in time (target year) when the critical (chemical) limit is no longer violated. This information on the timing of recovery requires dynamic modelling. Using a well-documented dynamic model, target loads for acidic deposition were determined for 848 surface waters across Finland, Norway, Sweden and the United Kingdom for the target year 2050. In the majority of sites (n = 675), the critical ANC-limit was predicted to be achieved by 2050; however, for 127 sites target loads were determined. In addition, 46 sites were infeasible, i.e., even a deposition reduction to zero would not achieve the limit by 2050. The average maximum target load for sulphur was 38% lower than the respective critical load across the study lakes (n = 127). Target loads on a large regional scale can inform effects-based emission reduction policies; the current assessment suggests that reductions beyond the Gothenburg Protocol are required to ensure surface water recovery from acidification by 2050

Developing mental and physical wellness for looked after young people through a fitness and nutritional guidance programme : a pilot study

This pilot study aimed to explore the suitability of a fitness and nutritional guidance programme (FNGP) for looked after young people and examine changes in physical fitness and mental wellness levels. Fourteen looked after young people took part in a nine-month long FNGP. Reflective feedback was obtained from the therapists and attendance was monitored to examine suitability. Fitness (i.e. body mass index, resting heart rate, lung capacity, aerobic capacity, lower body strength, flexibility) and wellness (i.e. physical indicators of anger, depression, stress and tension) levels were measured at four time points using Fitech V5 Wellness Software. The key strengths of programme were its accessibility for looked after young people, their positive interaction with the fitness therapists and their activity engagement. Attendance rates were high, with 13 participants attending at least one physical activity session per week for nine months. Repeated measures analysis of covariance revealed significant positive changes in the participants' fitness and wellness levels across the nine month period when controlling for alcohol consumption and smoking status. Results provide tentative support for the application of suitable FNGPs for looked after young people. The value of activity engagement for looked after young people in residential care and its effects on health and wellbeing are discussed