Automated analysis of oxidative metabolites

An automated system for the study of drug metabolism is described. The system monitors the oxidative metabolites of aromatic amines and of compounds which produce formaldehyde on oxidative dealkylation. It includes color developing compositions suitable for detecting hyroxylated aromatic amines and formaldehyde

Automated method for study of drug metabolism

Commercially available equipment can be modified to provide automated system for assaying drug metabolism by continuous flow-through. System includes steps and devices for mixing drug with enzyme and cofactor in the presence of pure oxygen, dialyzing resulting metabolite against buffer, and determining amount of metabolite by colorimetric method

Editorial.

Welcome to the third issue of our journal . We are delighted to feature in this issue two peer-reviewed papers looking in detail at some of the outcomes of the ring-fenced money used for researcher development in the UK under the guise of Roberts funding. In her paper looking at impact of the training provided by this funding on late stage doctoral student researchers, Walsh and colleagues draw our attention to detailed analysis of impact via a variety of evaluation approaches. She also alerts us to the question of whether such development programmes should run alongside the traditional apprenticeship style training of such students. The second paper by Heading and colleagues provides a detailed example of a development programme event in information management and provides further evidence for impact of such training. Bai and Hudson move the focus to the research –teaching nexus and highlight the difficulty for TEFL staff in Chinese HEIs to develop a research strand in their careers. The importance in developing research capacity, providing support and mentoring to such staff is shown to be pivotal in their development. Finally conceptions of research from a variety of viewpoints are analyzed by Pitcher. Pitcher considers how the PhD itself, alongwith how the knowledge and outcomes of PhD research are perceived. In a preliminary survey of students on these matters, Pitcher highlights the importance of alignment with these concepts between student and supervisor thus avoiding difficulties between apprentice and supervisor as the research progresses which might inhibit development

Understanding and addressing mathematics anxiety using perspectives from education, psychology and neuroscience

Mathematics anxiety is a significant barrier to mathematical learning. In this article, we propose that state or on-task mathematics anxiety impacts on performance, while trait mathematics anxiety leads to the avoidance of courses and careers involving mathematics. We also demonstrate that integrating perspectives from education, psychology and neuroscience contributes to a greater understanding of mathematics anxiety in its state and trait forms. Research from cognitive psychology and neuroscience illustrates the effect of state mathematics anxiety on performance and research from cognitive, social and clinical psychology, and education can be used to conceptualise the origins of trait mathematics anxiety and its impact on avoidant behaviour. We also show that using this transdisciplinary framework to consider state and trait mathematics anxiety separately makes it possible to identify strategies to reduce the negative effects of mathematics anxiety. Implementation of these strategies among particularly vulnerable groups, such as pre-service teachers, could be beneficial

Increase of mild disability in Japanese elders: A seven year follow-up cohort study

BACKGROUND: Japan has the highest life expectancy in the world. In a 2002 census government report, 18.5% of Japanese were 65 years old and over and 7.9% were over 75 years old. In this ageing population, the increase in the number of dependent older persons, especially those with mild levels of disability, has had a significant impact on the insurance budget. This study examines the increase of mild disability and its related factors. METHODS: All community-dwelling residents aged 65 and over and without functional decline (n = 1560), of Omishima town, Japan, were assessed in 1996 using a simple illustrative measure, "the Typology of the Aged with Illustrations" to establish a baseline level of function and were followed annually until 2002. The prevalence and incidence of low to severe disability, and their association with chronic conditions present at the commencement of the study, was analyzed. A polychotomous logistic regression model was constructed to estimate the association of each chronic condition with two levels of disability. RESULTS: An increase in mild functional decline was more prevalent than severe functional decline. The accumulation of mild disability was more prominent in women. The major chronic conditions associated with mild disability were chronic arthritis and diabetes in women, and cerebrovascular accident and malignancy in men. CONCLUSION: This study showed a tendency for mild disability prevalence to increase in Japanese elders, and some risk factors were identified. As mild disability increasingly prevalent, these findings will help determine priorities for its prevention in Japanese elders

Integrating the Genetic and Physical Maps of Arabidopsis thaliana: Identification of Mapped Alleles of Cloned Essential (EMB) Genes

The classical genetic map of Arabidopsis includes more than 130 genes with an embryo-defective (emb) mutant phenotype. Many of these essential genes remain to be cloned. Hundreds of additional EMB genes have been cloned and catalogued (www.seedgenes.org) but not mapped. To facilitate EMB gene identification and assess the current level of saturation, we updated the classical map, compared the physical and genetic locations of mapped loci, and performed allelism tests between mapped (but not cloned) and cloned (but not mapped) emb mutants with similar chromosome locations. Two hundred pairwise combinations of genes located on chromosomes 1 and 5 were tested and more than 1100 total crosses were screened. Sixteen of 51 mapped emb mutants examined were found to be disrupted in a known EMB gene. Alleles of a wide range of published EMB genes (YDA, GLA1, TIL1, AtASP38, AtDEK1, EMB506, DG1, OEP80) were discovered. Two EMS mutants isolated 30 years ago, T-DNA mutants with complex insertion sites, and a mutant with an atypical, embryo-specific phenotype were resolved. The frequency of allelism encountered was consistent with past estimates of 500 to 1000 EMB loci. New EMB genes identified among mapped T-DNA insertion mutants included CHC1, which is required for chromatin remodeling, and SHS1/AtBT1, which encodes a plastidial nucleotide transporter similar to the maize Brittle1 protein required for normal endosperm development. Two classical genetic markers (PY, ALB1) were identified based on similar map locations of known genes required for thiamine (THIC) and chlorophyll (PDE166) biosynthesis. The alignment of genetic and physical maps presented here should facilitate the continued analysis of essential genes in Arabidopsis and further characterization of a broad spectrum of mutant phenotypes in a model plant

Arabidopsis HDA6 Regulates Locus-Directed Heterochromatin Silencing in Cooperation with MET1

Heterochromatin silencing is pivotal for genome stability in eukaryotes. In Arabidopsis, a plant-specific mechanism called RNA–directed DNA methylation (RdDM) is involved in heterochromatin silencing. Histone deacetylase HDA6 has been identified as a component of such machineries; however, its endogenous targets and the silencing mechanisms have not been analyzed globally. In this study, we investigated the silencing mechanism mediated by HDA6. Genome-wide transcript profiling revealed that the loci silenced by HDA6 carried sequences corresponding to the RDR2-dependent 24-nt siRNAs, however their transcript levels were mostly unaffected in the rdr2 mutant. Strikingly, we observed significant overlap of genes silenced by HDA6 to those by the CG DNA methyltransferase MET1. Furthermore, regardless of dependence on RdDM pathway, HDA6 deficiency resulted in loss of heterochromatic epigenetic marks and aberrant enrichment for euchromatic marks at HDA6 direct targets, along with ectopic expression of these loci. Acetylation levels increased significantly in the hda6 mutant at all of the lysine residues in the H3 and H4 N-tails, except H4K16. Interestingly, we observed two different CG methylation statuses in the hda6 mutant. CG methylation was sustained in the hda6 mutant at some HDA6 target loci that were surrounded by flanking DNA–methylated regions. In contrast, complete loss of CG methylation occurred in the hda6 mutant at the HDA6 target loci that were isolated from flanking DNA methylation. Regardless of CG methylation status, CHG and CHH methylation were lost and transcriptional derepression occurred in the hda6 mutant. Furthermore, we show that HDA6 binds only to its target loci, not the flanking methylated DNA, indicating the profound target specificity of HDA6. We propose that HDA6 regulates locus-directed heterochromatin silencing in cooperation with MET1, possibly recruiting MET1 to specific loci, thus forming the foundation of silent chromatin structure for subsequent non-CG methylation