The Effects of β-Mercaptoethanol on the Specific Activity of Porphobilinogen Synthase Mutants of the Rhodobacter sphaeroides Protein

The enzyme porphobilinogen synthase (PBGS) catalyzes the conversion of two molecules of δ-aminolevulinic acid (ALA) into porphobilinogen (PBG) in the first common step of the tetrapyrrole biosynthesis pathway. A homology model of the R. sphaeroides PBGS was created by Dr. Eileen K. Jaffe at Fox Chase Cancer Center based on comparison to the crystal structure of Pseudomonas aeruginosa. The proposed structure suggests that there are four cysteines in close proximity to the active site. Three of these cysteines are not present in the highly similar R. capsulatus sequence. Under oxidizing conditions these residues can potentially participate in the formation of disulfide bonds, which would be potential targets for reducing agents, such as β-mercaptoethanol. This is supported by the fact that a number of PBGS enzymes require the addition of β-mercaptoethanol for full activity, including the Rhodobacter sphaeroides enzyme. To test if the three cysteines that are present in the R. sphaeroides enzyme, and not that of R. capsulatus, are responsible for the dependence of R. sphaeroides on a reducing agent (β-mercaptoethanol), site-directed mutagenesis was performed on R. sphaeroides. After the presence of the mutations was confirmed through sequencing, the altered enzymes were isolated and tested for β-mercaptoethanol sensitivity. A decrease in sensitivity is found in all three mutants when compared to wild type. In two mutants of these mutants, C103D and C265V, the difference is very pronounced. A larger goal was to test whether the current structural model is sufficient to serve as a guide for further work on the structure-function relationships in the R. sphaeroides PBGS. Our results indicate that the system is more complicated than anticipated. Further study is needed to clarify the role of cysteine residues

Development of empirical models for pork quality

Pork quality is an important issue for the whole meat chain, from producers, abattoirs, retailers through to costumers and is affected by a web of multi-factorial actions that occur throughout the pork production chain. A vast amount of information is available on how these diverse factors influence different pork quality traits. However, results derived from individual studies often vary and are in some cases even contradictory due to different experimental designs or different pork quality assessment techniques or protocols. Also, individual influencing factors are often studied in isolation, ignoring interacting effects. A suitable method is therefore required to account for a range of interacting factors, to combine the results from different experiments and to derive generic response-laws. The aim of this thesis was to use meta-analyses to produce quantitative, predictive models that describe how diverse factors affect pork quality over a range of experimental conditions

Stationary Regime of Random Resistor Networks Under Biased Percolation

The state of a 2-D random resistor network, resulting from the simultaneous evolutions of two competing biased percolations, is studied in a wide range of bias values. Monte Carlo simulations show that when the external current $I$ is below the threshold value for electrical breakdown, the network reaches a steady state with a nonlinear current-voltage characteristic. The properties of this nonlinear regime are investigated as a function of different model parameters. A scaling relation is found between $/_0$ and $I/I_0$, where $$ is the average resistance, $_0$ the linear regime resistance and $I_0$ the threshold value for the onset of nonlinearity. The scaling exponent is found to be independent of the model parameters. A similar scaling behavior is also found for the relative variance of resistance fluctuations. These results compare well with resistance measurements in composite materials performed in the Joule regime up to breakdown.Comment: 9 pages, revtex, proceedings of the Merida Satellite Conference STATPHYS2

Selecting children for head CT following head injury

OBJECTIVE: Indicators for head CT scan defined by the 2007 National Institute for Health and Care Excellence (NICE) guidelines were analysed to identify CT uptake, influential variables and yield. DESIGN: Cross-sectional study. SETTING: Hospital inpatient units: England, Wales, Northern Ireland and the Channel Islands. PATIENTS: Children (3 years were much more likely to have CT than those <3 years (OR 2.35 (95% CI 2.08 to 2.65)). CONCLUSION: Compliance with guidelines and diagnostic yield was variable across age groups, the type of hospital and region where children were admitted. With this pattern of clinical practice the risks of both missing intracranial injury and overuse of CT are considerable

A comparison of four different imaging modalities - conventional, cross polarized, infra-red and ultra-violet in the assessment of childhood bruising

Background It is standard practice to image concerning bruises in children. We aim to compare the clarity and measurements of bruises using cross polarized, infra-red (IR) and ultra-violet (UV) images to conventional images. Methods Children aged <11 years with incidental bruising were recruited. Demographics, skin and bruise details were recorded. Bruises were imaged by standard protocols in conventional, cross-polarized, IR and UV lights. Bruises were assessed in vivo for contrast, uniformity and diffuseness, and these characteristics were then compared across image modalities. Color images (conventional, cross polarized) were segmented and measured by ImageJ. Bruises of grey scale images (IR, UV) were measured by a ‘plug in’ of ImageJ. The maximum and minimum Feret's diameter, area and aspect ratio, were determined. Comparison of measurements across imaging modalities was conducted using Wilcoxon rank sum tests and modified Bland-Altman graphs. Significance was set at p < 0.05. Results Twenty five children had 39 bruises. Bruises that were of low contrast, i.e. difficult to distinguish from surrounding skin, were also more diffuse, and less uniformity in vivo. Low contrast bruises were best seen on conventional and cross-polarized images and less distinctive on IR and UV images. Of the 19 bruises visible in all modalities, the only significant difference was maximum and minimum Feret's diameters and area were smaller on IR compared to conventional images. Aspect ratios were not affected by the modality. Conclusions Conventional and cross-polarized imaging provides the most consistent bruise measurement, particularly in bruises that are not easily distinguished from surrounding skin visually

Epidemiology of alcohol-related emergency hospital admissions in children and adolescents: an e-cohort analysis in Wales in 2006-2011

Funding: This work was supported by funds from the Economic and Social Research Council, the Medical Research Council and Alcohol Research UK to the ELAStiC Project (ES/L015471/1). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Data Availability: The data used in this study are available in the SAIL databank at Swansea University, Swansea, UK. All proposals to use SAIL data are subject to review by an independent Information Governance Review Panel (IGRP). Before any data can be accessed, approval must be given by the IGRP. The IGRP gives careful consideration to each project to ensure proper and appropriate use of SAIL data. When access has been granted, it is gained through a privacy-protecting safe haven and remote access system referred to as the SAIL Gateway. SAIL has established an application process to be followed by anyone who would like to access data via SAIL https://www.saildatabank.com/application-process.Peer reviewedPublisher PD

Does selective migration alter socioeconomic inequalities in mortality in Wales? : a record-linked total population e-cohort study

Funding for this work was received from Public Health Wales NHS Trust as part of a report on migration and health. Support for the report was also received from the National Centre for Population Health and Wellbeing Research (NCPHWR). Andrea Gartner is funded through the NCPHWR and David Fone, Shantini Paranjothy and Daniel Farewell are members of the NCPHWR team in Cardiff University, School of Medicine. Neither funder bears any responsibility for the analysis or interpretation of the data presented here. We used data from the CHALICE project, which was originally funded by the National Institute for Health Research Public Health Research (NIHR PHR) Programme (project number 09/3007/02). The views and opinions expressed therein are those of the authors and do not necessarily reflect those of the NIHR PHR Programme or the Department of Health. We would like to thank Jenny Morgan for her work on data cleaning and validation of the original dataset.Peer reviewedPublisher PD

Sporadic randomness, Maxwell's Demon and the Poincare' recurrence times

In the case of fully chaotic systems the distribution of the Poincare'recurrence times is an exponential whose decay rate is the Kolmogorov-Sinai(KS) entropy.We address the discussion of the same problem, the connection between dynamics and thermodynamics,in the case of sporadic randomness,using the Manneville map as a prototype of this class of processes. We explore the possibility of relating the distribution of Poincare' recurrence times to `thermodynamics',in the sense of the KS entropy,also in the case of an inverse power law. This is the dynamic property that Zaslavsly [Phys.Today(8), 39(1999)] finds to be responsible for a striking deviation from ordinary statistical mechanics under the form of Maxwell's Demon effect. We show that this way of estabi- lishing a connection between thermodynamics and dynamics is valid only in the case of strong chaos. In the case of sporadic randomness, resulting at long times in the Levy diffusion processes,the sensitivity to initial conditions is initially an inverse pow erlaw,but it becomes exponential in the long-time scale, whereas the distribution of Poincare times keeps its inverse power law forever. We show that a nonextensive thermodynamics would imply the Maxwell's Demon effect to be determined by memory and thus to be temporary,in conflict with the dynamic approach to Levy statistics. The adoption of heuristic arguments indicates that this effect,is possible, as a form of genuine equilibrium,after completion of the process of memory erasure.Comment: 13 pages,two-column,latex-revtex,2 figures(2 files .eps

Mental health selection : common mental disorder and migration between multiple states of deprivation in a UK cohort

Funding Funding for this work was received from Public Health Wales NHS Trust as part of a report on migration and health. Support for the report was also received from the National Centre for Population Health and Wellbeing Research (NCPHWR). The eCATALYsT multiagency dataset and the baseline survey was supported by the Wales Office of Research and Development (SCC99/1/105 and R00/1/017). The follow-up survey was supported by a Welsh Assembly Government/Medical Research Council Health Research Partnership Award (H07-3-030), and the electronic cohort is supported by a National Institute for Social Care and Health Research Welsh Assembly Government Translational Health Research Platform Award (TPR08-020). Data availability statement Data may be obtained from a third party and are not publicly available. The electronic cohort is securely stored and maintained on the Secure Anonymised Information Linkage (SAIL) databank at Swansea University Medical School. The authors welcome general enquiries and ideas for new collaborations. Readers with an interest in further details should contact Professor Shantini Paranjothy, Principal Investigator.Peer reviewedPublisher PD