The toxicity of yellow-wood (Terminalia oblongata) to cattle

Feeding tests were carried out with yellow-wood, which was suspected of poisoning cattle in central Queensland, producing a sub-acute disease characterized by emaciation, photophobia and frequent urination. All animals fed on yellow-wood leaves exhibited symptoms differing only slightly from those observed in natural cases, and yellow-wood is therefore regarded as the cause of the trouble. The main lesion is parenchymatous nephritis

Regulation of protein kinase B and glycogen synthase kinase-3 by insulin and beta-adrenergic agonists in rat epididymal fat cells - Activation of protein kinase B by wortmannin-sensitive and -insensittve mechanisms

Previous studies using L6 myotubes have suggested that glycogen synthase kinase-3 (GSK-3) is phosphoryl ated and inactivated in response to insulin by protein kinase B (PKB, also known as Akt or RAG) (Cross, D, A, E., Alessi, D, R., Cohen, P., Andjelkovic, M., and Hemmings, B, A. (1995) Nature 378, 785-789), In the present study, marked increases in the activity of PKB have been shown to occur in insulin-treated rat epididymal fat cells with a time course compatible with the observed decrease in GSK-3 activity, Isoproterenol, acting primarily through beta(3)-adrenoreceptors, was found to decrease GSK-3 activity to a similar extent (approximately 50%) to insulin, However, unlike the effect of insulin, the inhibition of GSK by isoproterenol was not found to be sensitive to inhibition by the phosphatidylinositol 3'-kinase inhibitors, wortmannin or LY 294002, The change in GSK-3 activity brought about by isoproterenol could not be mimicked by the addition of permeant cyclic AMP analogues or forskolin to the cells, although at the concentrations used, these agents were able to stimulate lipolysis. Isoproterenol, but again not the cyclic AMP analogues, was found to increase the activity of PKB, although to a lesser extent than insulin. While wortmannin abolished the stimulation of PKB activity by insulin, it was without effect on the activation seen in response to isoproterenol, The activation of PKB by isoproterenol was not accompanied by any detectable change in the electrophoretic mobility of the protein on SDS-polyacrylamide gel electrophoresis. It would therefore appear that distinct mechanisms exist for the stimulation of PKB by insulin and isoproterenol in rat fat cells

An analysis of the methyl rotation dynamics in the S0 (X̃ 1A1) and T1 (ã 3A2) states of thioacetone, (CH3)2 CS and (CD 3)2 CS from pyrolysis jet spectra

Jet-cooled, laser-induced phosphorescence excitation spectra (LIP) of thioacetone (CH3)2CS/(CD3)2 CS have been recorded over the region 16 800-18 500 cm-1 using the pyrolysis jet spectroscopic technique. The responsible electronic transition, T 1 ←-S0, ã 3 A ″ ← X̃ 1A1, results from an n → π* electron promotion and gives rise to a pattern of vibronic bands that were attributed to activity of the methyl torsion and the sulphur out-of-plane wagging modes. The intensities of the torsional and wagging progressions in the excitation spectra were interpreted in terms of a C2υ-Cs molecular distortion of the triplet molecule from its singlet ground state equilibrium structure. A complete unrestricted Hartree-Fock (UHF) ab initio molecular orbital (MO) structural optimization of the T1 state predicted that the sulphur was displaced by 27.36° from the molecular plane and the methyl groups were rotated by 10.93° in clockwise-counterclockwise directions. Restricted Hartree-Fock (RHF) calculations were used to generate the F(θ1,θ2) potential surface governing methyl rotation for the S0 state. This was incorporated into a two-dimensional Hamiltonian, symmetrized for the G36 point group and solved variationally for the torsional frequencies. The calculated frequencies of 159.97/118.94 for the ν17 (b1) mode of S0 (CH3)2CS/(CD3)2 CS were found to agree with the experimental values, 153.2/114.7 cm-1. © 1991 American Institute of Physics.The authors are grateful to the Natural Sciences and Engineering Research Council of Canada for financial support of this work. D. J. C. acknowledges the support of the National Science Foundation through Grant No. CHE-8914403.Peer Reviewe

Meningococcal genetic variation mechanisms viewed through comparative analysis of Serogroup C strain FAM18

Copyright @ 2007 Public Library of ScienceThe bacterium Neisseria meningitidis is commonly found harmlessly colonising the mucosal surfaces of the human nasopharynx. Occasionally strains can invade host tissues causing septicaemia and meningitis, making the bacterium a major cause of morbidity and mortality in both the developed and developing world. The species is known to be diverse in many ways, as a product of its natural transformability and of a range of recombination and mutation-based systems. Previous work on pathogenic Neisseria has identified several mechanisms for the generation of diversity of surface structures, including phase variation based on slippage-like mechanisms and sequence conversion of expressed genes using information from silent loci. Comparison of the genome sequences of two N. meningitidis strains, serogroup B MC58 and serogroup A Z2491, suggested further mechanisms of variation, including C-terminal exchange in specific genes and enhanced localised recombination and variation related to repeat arrays. We have sequenced the genome of N. meningitidis strain FAM18, a representative of the ST-11/ET-37 complex, providing the first genome sequence for the disease-causing serogroup C meningococci; it has 1,976 predicted genes, of which 60 do not have orthologues in the previously sequenced serogroup A or B strains. Through genome comparison with Z2491 and MC58 we have further characterised specific mechanisms of genetic variation in N. meningitidis, describing specialised loci for generation of cell surface protein variants and measuring the association between noncoding repeat arrays and sequence variation in flanking genes. Here we provide a detailed view of novel genetic diversification mechanisms in N. meningitidis. Our analysis provides evidence for the hypothesis that the noncoding repeat arrays in neisserial genomes (neisserial intergenic mosaic elements) provide a crucial mechanism for the generation of surface antigen variants. Such variation will have an impact on the interaction with the host tissues, and understanding these mechanisms is important to aid our understanding of the intimate and complex relationship between the human nasopharynx and the meningococcus.This work was supported by the Wellcome Trust through the Beowulf Genomics Initiative

Genome-wide saturation mutagenesis of Burkholderia pseudomallei K96243 predicts essential genes and novel targets for antimicrobial development

This is the final version of the article. Available from the publisher via the DOI in this record.Burkholderia pseudomallei is the causative agent of melioidosis, an often fatal infectious disease for which there is no vaccine. B. pseudomallei is listed as a tier 1 select agent, and as current therapeutic options are limited due to its natural resistance to most antibiotics, the development of new antimicrobial therapies is imperative. To identify drug targets and better understand the complex B. pseudomallei genome, we sought a genome-wide approach to identify lethal gene targets. As B. pseudomallei has an unusually large genome spread over two chromosomes, an extensive screen was required to achieve a comprehensive analysis. Here we describe transposon-directed insertion site sequencing (TraDIS) of a library of over 10(6) transposon insertion mutants, which provides the level of genome saturation required to identify essential genes. Using this technique, we have identified a set of 505 genes that are predicted to be essential in B. pseudomallei K96243. To validate our screen, three genes predicted to be essential, pyrH, accA, and sodB, and a gene predicted to be nonessential, bpss0370, were independently investigated through the generation of conditional mutants. The conditional mutants confirmed the TraDIS predictions, showing that we have generated a list of genes predicted to be essential and demonstrating that this technique can be used to analyze complex genomes and thus be more widely applied. IMPORTANCE: Burkholderia pseudomallei is a lethal human pathogen that is considered a potential bioterrorism threat and has limited treatment options due to an unusually high natural resistance to most antibiotics. We have identified a set of genes that are required for bacterial growth and thus are excellent candidates against which to develop potential novel antibiotics. To validate our approach, we constructed four mutants in which gene expression can be turned on and off conditionally to confirm that these genes are required for the bacteria to survive.This work was partially funded by the Defence Science and Technology Laboratories (DSTL)

Multi-scale modeling of bulk heterojunctions for organic photovoltaic applications

Originally published by InTech, available from http://www.intechopen.com/books/third-generation-photovoltaicsVaruni Dantanarayana, David M. Huang, Jennifer A. Staton, Adam J. Moulé and Roland Falle

Prevalence and microbiological characteristics of clinically infected foot-ulcers in patients with rheumatoid arthritis: A retrospective exploratory study

Background: The prevalence of foot ulcers in patients with rheumatoid arthritis (RA) has been reported at almost 10 %. These foot ulcers often occur at multiple sites and are reoccurring, with the potential risk of infection increased due to RA diagnosis and disease modifying medications. The objective of this study was to estimate the prevalence of clinical infection in foot-ulcers of patients with RA; describe the microbiological characteristics and investigate risk factors. Methods: Retrospective clinical data was collected for all patients attending a rheumatology foot ulcer clinic between 1st May 2012 and 1st May 2013: wound swab data was collected from those with clinical infection. Results: Twenty-eight patients with RA and foot-ulcers were identified; eight of these patients had clinical infection and wound swabs taken (29 %). Of these eight patients there were equal men and women, with median age 74 years, and average disease duration 22 years. Cardiovascular disease/peripheral-vascular disease (CVD/PVD) were reported in six patients, diabetes in two patients. Six patients were treated with disease-modifying anti-rheumatic drugs (DMARDs); three were on biologic medications and two on steroids. Five wound swabs cultured skin flora, one staphylococcus aureus, one had no growth after culture; and one was rejected due to labelling error. Conclusion: Almost a third of people with RA and foot ulcers attending clinic over one year had clinical infection, however microbiological analysis failed to isolate pathogens in six of seven wound swabs. This may be due to inaccurate diagnosis of ulcer infection or to issues with sampling, collection, transport, analysis or reporting. There was insufficient data to relate risk of clinical infection with risk factors. Further research is required to identify the most appropriate techniques for infection diagnosis, wound sampling and processing. Trial registration: Ethical approval was obtained from University of Leeds, Faculty of Medicine and Health (Reference number: SHREC/RP/349)

Synchronous online CPD: empirical support for the value of webinars in career settings

The careers profession in England is facing unprecedented challenges. Initiatives to improve service delivery while keeping costs low are attractive and online training holds the promise of high impact at low cost. The present study employs a qualitative methodology to evaluate a series of online ‘webinars’ conducted with 15 careers advisers. Results showed that the technology itself could impede learning, and participants missed out on the peer-to-peer interaction that takes place in a ‘bricks and mortar’ setting, but overall participants found that access to relevant, good quality training from the convenience of their workplace more than compensated for the challenges. The article offers conceptual support for the viability of online learning through the theory of equivalency, andragogy and transactional distance theory, and makes recommendations for practice

Immunocytochemical determination of the subcellular distribution of ascorbate in plants

Ascorbate is an important antioxidant in plants and fulfills many functions related to plant defense, redox signaling and modulation of gene expression. We have analyzed the subcellular distribution of reduced and oxidized ascorbate in leaf cells of Arabidopsis thaliana and Nicotiana tabacum by high-resolution immuno electron microscopy. The accuracy and specificity of the applied method is supported by several observations. First, preadsorption of the ascorbate antisera with ascorbic acid or dehydroascorbic acid resulted in the reduction of the labeling to background levels. Second, the overall labeling density was reduced between 50 and 61% in the ascorbate-deficient Arabidopsis mutants vtc1-2 and vtc2-1, which correlated well with biochemical measurements. The highest ascorbate-specific labeling was detected in nuclei and the cytosol whereas the lowest levels were found in vacuoles. Intermediate labeling was observed in chloroplasts, mitochondria and peroxisomes. This method was used to determine the subcellular ascorbate distribution in leaf cells of plants exposed to high light intensity, a stress factor that is well known to cause an increase in cellular ascorbate concentration. High light intensities resulted in a strong increase in overall labeling density. Interestingly, the strongest compartment-specific increase was found in vacuoles (fourfold) and in plastids (twofold). Ascorbate-specific labeling was restricted to the matrix of mitochondria and to the stroma of chloroplasts in control plants but was also detected in the lumen of thylakoids after high light exposure. In summary, this study reveals an improved insight into the subcellular distribution of ascorbate in plants and the method can now be applied to determine compartment-specific changes in ascorbate in response to various stress situations