Beneficial effect of taurine on hypoxia- and glutamate-induced endoplasmic reticulum stress pathways in primary neuronal culture

Stroke (hypoxia) is one of the leading causes of mortality in the developed countries, and it can induce excessive glutamate release and endoplasmic reticulum (ER) stress. Taurine, as a free amino acid, present in high concentrations in a range of organs in mammals, can provide protection against multiple neurological diseases. Here, we present a study to investigate the potential protective benefits of taurine against ER stress induced by glutamate and hypoxia/reoxygenation in primary cortical neuronal cultures. We found that taurine suppresses the up-regulation of caspase-12 and GADD153/CHOP induced by hypoxia/reoxygenation, suggesting that taurine may exert a protective function against hypoxia/reoxygenation by reducing the ER stress. Moreover, taurine can down-regulate the ratio of cleaved ATF6 and full length ATF6, and p-IRE1 expression, indicating that taurine inhibits the ER stress induced by hypoxia/reoxygenation and glutamate through suppressing ATF6 and IRE1 pathways.     

Common polymorphic variation in the genetically diverse African insulin gene and its association with size at birth

The insulin variable number of tandem repeats (INS VNTR) has been variably associated with size at birth in non-African populations. Small size at birth is a major determinant of neonatal mortality, so the INS VNTR may influence survival. We tested the hypothesis, therefore, that genetic variation around the INS VNTR in a rural Gambian population, who experience seasonal variation in nutrition and subsequently birth weight, may be associated with foetal and early growth. Six polymorphisms flanking the INS VNTR were genotyped in over 2,500 people. Significant associations were detected between the maternally inherited SNP 27 (rs689) allele and birth length [effect size 17.5 (5.2–29.8) mm; P = 0.004; n = 361]. Significant associations were also found between the maternally inherited African-specific SNP 28 (rs5506) allele and post-natal weight gain [effect size 0.19 (0.05–0.32) z score points/year; P = 0.005; n = 728). These results suggest that in the Gambian population studied there are associations between polymorphic variation in the genetically diverse INS gene and foetal and early growth characteristics, which contribute to overall polygenic associations with these traits.     

Efficiency clustering for low-density microarrays and its application to QPCR

Background  

Pathway-targeted or low-density arrays are used more and more frequently in biomedical research, particularly those arrays that are based on quantitative real-time PCR. Typical QPCR arrays contain 96-1024 primer pairs or probes, and they bring with it the promise of being able to reliably measure differences in target levels without the need to establish absolute standard curves for each and every target. To achieve reliable quantification all primer pairs or array probes must perform with the same efficiency.     

Ecophysiological and bioclimatic foundations for a global plant functional classification

Question: What plant properties might define plant functional types (PFTs) for the analysis of global vegetation responses to climate change, and what aspects of the physical environment might be expected to predict the distributions of PFTs? Methods: We review principles to explain the distribution of key plant traits as a function of bioclimatic variables. We focus on those whole‐plant and leaf traits that are commonly used to define biomes and PFTs in global maps and models. Results: Raunkiær's plant life forms (underlying most later classifications) describe different adaptive strategies for surviving low temperature or drought, while satisfying requirements for reproduction and growth. Simple conceptual models and published observations are used to quantify the adaptive significance of leaf size for temperature regulation, leaf consistency for maintaining transpiration under drought, and phenology for the optimization of annual carbon balance. A new compilation of experimental data supports the functional definition of tropical, warm‐temperate, temperate and boreal phanerophytes based on mechanisms for withstanding low temperature extremes. Chilling requirements are less well quantified, but are a necessary adjunct to cold tolerance. Functional traits generally confer both advantages and restrictions; the existence of trade‐offs contributes to the diversity of plants along bioclimatic gradients. Conclusions: Quantitative analysis of plant trait distributions against bioclimatic variables is becoming possible; this opens up new opportunities for PFT classification. A PFT classification based on bioclimatic responses will need to be enhanced by information on traits related to competition, successional dynamics and disturbance.     

The complete genome sequence and comparative genome analysis of the high pathogenicity Yersinia enterocolitica strain 8081

The human enteropathogen, Yersinia enterocolitica, is a significant link in the range of Yersinia pathologies extending from mild gastroenteritis to bubonic plague. Comparison at the genomic level is a key step in our understanding of the genetic basis for this pathogenicity spectrum. Here we report the genome of Y. enterocolitica strain 8081 (serotype 0:8; biotype 1B) and extensive microarray data relating to the genetic diversity of the Y. enterocolitica species. Our analysis reveals that the genome of Y. enterocolitica strain 8081 is a patchwork of horizontally acquired genetic loci, including a plasticity zone of 199 kb containing an extraordinarily high density of virulence genes. Microarray analysis has provided insights into species-specific Y. enterocolitica gene functions and the intraspecies differences between the high, low, and nonpathogenic Y. enterocolitica biotypes. Through comparative genome sequence analysis we provide new information on the evolution of the Yersinia. We identify numerous loci that represent ancestral clusters of genes potentially important in enteric survival and pathogenesis, which have been lost or are in the process of being lost, in the other sequenced Yersinia lineages. Our analysis also highlights large metabolic operons in Y. enterocolitica that are absent in the related enteropathogen, Yersinia pseudotuberculosis, indicating major differences in niche and nutrients used within the mammalian gut. These include clusters directing, the production of hydrogenases, tetrathionate respiration, cobalamin synthesis, and propanediol utilisation. Along with ancestral gene clusters, the genome of Y. enterocolitica has revealed species-specific and enteropathogen-specific loci. This has provided important insights into the pathology of this bacterium and, more broadly, into the evolution of the genus. Moreover, wider investigations looking at the patterns of gene loss and gain in the Yersinia have highlighted common themes in the genome evolution of other human enteropathogens.     

Estimation of the correlation between nutrient intake measures under restricted sampling

Food frequency questionnaires (FFQs) are commonly used to assess dietary intake in epidemiologic research. To evaluate the FFQ reliability, the commonly used approach is to estimate the correlation coefficient between the data given in FFQ and those in food records (for example, 4-day food records [4DFR]) for nutrients of interest. However, in a dietary intervention study, a criterion for eligibility may be to select participants who have baseline FFQ-measured dietary intake of percent energy from fat above a prespecified quantity. Other instruments, such as the 4DFR, may be subsequently administrated only to eligible participants. Under these circumstances, analysis without adjusting for the restricted population will usually lead to biased estimation of correlation coefficients and other parameters of interest. In this paper, we apply likelihood-based and multiple imputation (MI) methods to accommodate such incomplete data obtained as a result of the study design. A simulation study is conducted to examine finite sample performance of various estimators. We note that both the MI estimate and the maximum likelihood (ML) estimate based on a bivariate-normal model are not sensitive to departures from this normality assumption. This led us to investigate robustness properties of the ML estimator analytically. We present some data analyses from a dietary assessment study from the Women's Health Initiative to illustrate the methods.     

Crystal structure of ADP-ribosylated ribosomal translocase from Saccharomyces cerevisiae

The crystal structure of ADP-ribosylated yeast elongation factor 2 in the presence of sordarin and GDP has been determined at 2.6 A resolution. The diphthamide at the tip of domain IV, which is the target for diphtheria toxin and Pseudomonas aeruginosa exotoxin A, contains a covalently attached ADP-ribose that functions as a very potent inhibitor of the factor. We have obtained an electron density map of ADP-ribosylated translation factor 2 revealing both the ADP-ribosylation and the diphthamide. This is the first structure showing the conformation of an ADP-ribosylated residue and confirms the inversion of configuration at the glycosidic linkage. Binding experiments show that the ADP-ribosylation has limited effect on nucleotide binding affinity, on ribosome binding, and on association with exotoxin A. These results provide insight to the inhibitory mechanism and suggest that inhibition may be caused by erroneous interaction of the translation factor with the codon-anticodon area in the P-site of the ribosome.     

BIOME 6000: reconstructing global mid-Holocene vegetation patterns from palaeoecological records

Global change research needs data sets describing past states of the Earth system. Vegetation distributions for specified 'time slices' (with known forcings, such as changes in insolation patterns due to the Earth's orbital variations, changes in the extent of ice-sheets, and changes in atmospheric trace-gas composition) should provide a benchmark for coupled climate-biosphere models. Pollen and macrofossil records from dated sediments give spatially extensive coverage of data on vegetation distribution changes. Applications of such data have been delayed by the lack of a global synthesis. The BIOME 6000 project of IGBP aims at a synthesis for 6000 years bp. Success depends on community-wide participation for data compilation and quality assurance, and on a robust methodology for assigning palaeorecords to biomes. In the method summarized here, taxa are assigned to one or more plant functional types (PFTs) and biomes reconstructed using PFT-based definitions. By involving regional experts in PFT assignments, one can combine data from different floras without compromising global consistency in biome assignments. This article introduces a series of articles that substantially extend the BIOME 6000 data set. The list of PFTs and the reconstruction procedure itself are evolving. Some compromises (for example, restricted taxon lists in some regions) limit the precision of biome assignments and will become obsolete as primary data are put into community data bases. This trend will facilitate biome mapping for other time slices. Co-evolution of climate-biosphere modelling and palaeodata synthesis and analysis will continue.