Determination of urinary thymidine glycol using affinity chromatography, HPLC and post-column reaction detection : a biomarker of oxidative DNA damage upon kidney transplantation

Reactive oxygen species are generated during ischaemia-reperfusion of tissue. Oxidation of thymidine by hydroxyl radicals (HO) leads to the formation of 5,6-dihydroxy-5,6-dihydrothymidine (thymidine glycol). Thymidine glycol is excreted in urine and can be used as biomarker of oxidative DNA damage. Time dependent changes in urinary excretion rates of thymidine glycol were determined in six patients after kidney transplantation and in six healthy controls. A new analytical method was developed involving affinity chromatography and subsequent reverse-phase high-performance liquid chromatography (RP-HPLC) with a post-column chemical reaction detector and endpoint fluorescence detection. The detection limit of this fluorimetric assay was 1.6 ng thymidine glycol per ml urine, which corresponds to about half of the physiological excretion level in healthy control persons. After kidney transplantation the urinary excretion rate of thymidine glycol increased gradually reaching a maximum around 48 h. The excretion rate remained elevated until the end of the observation period of 10 days. Severe proteinuria with an excretion rate of up to 7.2 g of total protein per mmol creatinine was also observed immediately after transplantation and declined within the first 24 h of allograft function (0.35 + 0.26 g/mmol creatinine). The protein excretion pattern, based on separation of urinary proteins on sodium dodecyl sulphate-polyacrylamide gel electrophorosis (SDS-PAGE), as well as excretion of individual biomarker proteins, indicated nonselective glomerular and tubular damage. The increased excretion of thymidine glycol after kidney transplantation may be explained by ischaemia-reperfusion induced oxidative DNA damage of the transplanted kidney.

Protection by methylproamine of irradiated human keratinocytes correlates with reduction of DNA damage

Purpose: The therapeutic ratio for ionising radiation treatment of tumour is a trade-off between normal tissue side-effects and tumour control. Application of a radioprotector to normal tissue can reduce side-effects. Here we study the effects of a new radioprotector on the cellular response to radiation. Methylproamine is a DNA-binding radioprotector which, on the basis of published pulse radiolysis studies, acts by repair of transient radiation-induced oxidative species on DNA. To substantiate this hypothesis, we studied protection by methylproamine at both clonogenic survival and radiation-induced DNA damage, assessed by γH2AX (histone 2AX phosphorylation at serine 139) focus formation endpoints. Materials and methods: The human keratinocyte cell line FEP1811 was used to study clonogenic survival and yield of γH2AX foci following irradiation (137Cs γ-rays) of cells exposed to various concentrations of methylproamine. Uptake of methylproamine into cell nuclei was measured in parallel. Results: The extent of radioprotection at the clonogenic survival endpoint increased with methylproamine concentration up to a maximum dose modification factor (DMF) of 2.0 at 10 μM. At least 0.1 fmole/nucleus of methylproamine is required to achieve a substantial level of radioprotection (DMF of 1.3) with maximum protection (DMF of 2.0) achieved at 0.23 fmole/nucleus. The γH2AX focus yield per cell nucleus 45 min after irradiation decreased with drug concentration with a DMF of 2.5 at 10 μM. Conclusions: These results are consistent with the hypothesis that radioprotection by methylproamine is mediated by attenuation of the extent of initial DNA damage.

Ecological approaches in planning for sustainable cities : a review of the literature

Rapid urbanization has brought environmentally, socially, and economically great challenges to cities and societies. To build a sustainable city, these challenges need to be faced efficiently and successfully. This paper focuses on the environmental issues and investigates the ecological approaches for planning sustainable cities through a comprehensive review of the relevant literature. The review focuses on several differing aspects of sustainable city formation. The paper provides insights on the interaction between the natural environment and human activities by identifying environmental effects resulting from this interaction; provides an introduction to the concept of sustainable urban development by underlining the important role of ecological planning in achieving sustainable cities; introduces the notion of urban ecosystems by establishing principles for the management of their sustainability; describes urban ecosystem sustainability assessment by introducing a review of current assessment methods, and; offers an outline of indexing urban environmental sustainability. The paper concludes with a summary of the findings.

Pathogenesis of Fallopian tube damage caused by Chlamydia trachomatis infections

Chlamydia trachomatis is the leading cause of bacterial sexually transmitted disease worldwide resulting in 4–5 million new cases of Chlamydia annually and an estimated 100 million cases per annum. Infections of the lower female genital tract (FGT) frequently are asymptomatic so they often remain undiagnosed or untreated. If infections are either not resolved, or are left untreated, chlamydia can ascend to the upper FGT and infect the fallopian tubes (FTs) causing salpingitis that may lead to functional damage of the FTs and tubal factor infertility (TFI). Clinical observations and experimental data have indicated a role for antibodies against C. trachomatis proteins such as the 60 kDa heat-shock protein 60 (cHSP60) in the immunopathogenesis of TFI. When released from infected cells cHSP60 can induce pro-inflammatory immune responses that may functionally impair the FTs leading to fibrosis and luminal occlusion. Chlamydial pathogenesis of irreversible and permanent tubal damage is a consequence of innate and adaptive host immune responses to ongoing or repeated infections. The extracellular matrix (ECM) that is regulated by metalloproteinases (MMPs) may also be modified by chlamydial infections of the FGT. This review will highlight protective and pathogenic immune responses to ongoing and repeated chlamydial infections of the FGT. It will also present two recent hypotheses to explain mechanisms that may contribute to FT damage during a C. trachomatis infection. If Chlamydia immunopathology can be controlled it might yield a method of inducing fibrosis and thus provide a means of non-surgical permanent contraception for women.

Structural damage detection method using frequency response functions

Structural damage detection using measured dynamic data for pattern recognition is a promising approach. These pattern recognition techniques utilize artificial neural networks and genetic algorithm to match pattern features. In this study, an artificial neural network–based damage detection method using frequency response functions is presented, which can effectively detect nonlinear damages for a given level of excitation. The main objective of this article is to present a feasible method for structural vibration–based health monitoring, which reduces the dimension of the initial frequency response function data and transforms it into new damage indices and employs artificial neural network method for detecting different levels of nonlinearity using recognized damage patterns from the proposed algorithm. Experimental data of the three-story bookshelf structure at Los Alamos National Laboratory are used to validate the proposed method. Results showed that the levels of nonlinear damages can be identified precisely by the developed artificial neural networks. Moreover, it is identified that artificial neural networks trained with summation frequency response functions give higher precise damage detection results compared to the accuracy of artificial neural networks trained with individual frequency response functions. The proposed method is therefore a promising tool for structural assessment in a real structure because it shows reliable results with experimental data for nonlinear damage detection which renders the frequency response function–based method convenient for structural health monitoring.

Investigative trends in understanding penalty-kick performance in association football: An ecological dynamics perspective

There have been different approaches to studying penalty-kick performance in association football. In this paper, the authors synthesize key findings within an ecological dynamics theoretical framework. According to this theoretical perspective, information is the cornerstone for understanding the dynamics of action regulation in penalty-kick performance. Research suggests that investigators need to identify the information sources that are most relevant to penalty-kick performance. An important task is to understand how constraints can channel (i.e. change, emphasize or mask) information sources used to regulate upcoming actions and how the influence of these constraints is expressed in players' behavioural dynamics. Due to the broad range of constraints influencing penalty-kick performance, it is recommended that future research adopts an interdisciplinary focus on performance assessment to overcome the current lack of representativeness in penalty-kick experimental designs. Such an approach would serve to capture the information-based control of action of both players as components of this dyadic system in competitive sport.

Ecological and Behavioral Methods for the Study of Bats [2nd. Ed.]

"First published in 1988, Ecological and Behavioral Methods for the Study of Bats is widely acknowledged as the primary reference for both amateur and professional bat researchers. Bats are the second most diverse group of mammals on the earth. They live on every continent except Antarctica, ranging from deserts to tropical forests to mountains, and their activities have a profound effect on the ecosystems in which they live. Despite their ubiquity and importance, bats are challenging to study. This volume provides researchers, conservationists, and consultants with the ecological background and specific information essential for studying bats in the wild and in captivity. Chapters detail many of the newest and most commonly used field and laboratory techniques needed to advance the study of bats, describe how these methods are applied to the study of the ecology and behavior of bats, and offer advice on how to interpret the results of research. The book includes forty-three chapters, fourteen of which are new to the second edition, with information on molecular ecology and evolution, bioacoustics, chemical communication, flight dynamics, population models, and methods for assessing postnatal growth and development. Fully illustrated and featuring contributions from the world’s leading experts in bat biology, this reference contains everything bat researchers and natural resource managers need to know for the study and conservation of this wide-ranging, ecologically vital, and diverse taxon."--Publisher website