PPARGC1A sequence variation and cardiovascular risk-factor levels: a study of the main genetic effects and gene x environment interactions in children from the European Youth Heart Study.

AIMS/HYPOTHESIS: The PPARGC1A gene coactivates multiple nuclear transcription factors involved in cellular energy metabolism and vascular stasis. In the present study, we genotyped 35 tagging polymorphisms to capture all common PPARGC1A nucleotide sequence variations and tested for association with metabolic and cardiovascular traits in 2,101 Danish and Estonian boys and girls from the European Youth Heart Study, a multicentre school-based cross-sectional cohort study. METHODS: Fasting plasma glucose concentrations, anthropometric variables and blood pressure were measured. Habitual physical activity and aerobic fitness were objectively assessed using uniaxial accelerometry and a maximal aerobic exercise stress test on a bicycle ergometer, respectively. RESULTS: In adjusted models, nominally significant associations were observed for BMI (rs10018239, p = 0.039), waist circumference (rs7656250, p = 0.012; rs8192678 [Gly482Ser], p = 0.015; rs3755863, p = 0.02; rs10018239, beta = -0.01 cm per minor allele copy, p = 0.043), systolic blood pressure (rs2970869, p = 0.018) and fasting glucose concentrations (rs11724368, p = 0.045). Stronger associations were observed for aerobic fitness (rs7656250, p = 0.005; rs13117172, p = 0.008) and fasting glucose concentrations (rs7657071, p = 0.002). None remained significant after correcting for the number of statistical comparisons. We proceeded by testing for gene x physical activity interactions for the polymorphisms that showed nominal evidence of association in the main effect models. None of these tests was statistically significant. CONCLUSIONS/INTERPRETATION: Variants at PPARGC1A may influence several metabolic traits in this European paediatric cohort. However, variation at PPARGC1A is unlikely to have a major impact on cardiovascular or metabolic health in these children.

A simple model for predicting soil temperature in snow-covered and seasonally frozen soil: model description and testing

Microbial processes in soil are moisture, nutrient and temperature dependent and, consequently, accurate calculation of soil temperature is important for modelling nitrogen processes. Microbial activity in soil occurs even at sub-zero temperatures so that, in northern latitudes, a method to calculate soil temperature under snow cover and in frozen soils is required. This paper describes a new and simple model to calculate daily values for soil temperature at various depths in both frozen and unfrozen soils. The model requires four parameters average soil thermal conductivity, specific beat capacity of soil, specific heat capacity due to freezing and thawing and an empirical snow parameter. Precipitation, air temperature and snow depth (measured or calculated) are needed as input variables. The proposed model was applied to five sites in different parts of Finland representing different climates and soil types. Observed soil temperatures at depths of 20 and 50 cm (September 1981-August 1990) were used for model calibration. The calibrated model was then tested using observed soil temperatures from September 1990 to August 2001. R-2-values of the calibration period varied between 0.87 and 0.96 at a depth of 20 cm and between 0.78 and 0.97 at 50 cm. R-2 -values of the testing period were between 0.87 and 0.94 at a depth of 20cm. and between 0.80 and 0.98 at 50cm. Thus, despite the simplifications made, the model was able to simulate soil temperature at these study sites. This simple model simulates soil temperature well in the uppermost soil layers where most of the nitrogen processes occur. The small number of parameters required means, that the model is suitable for addition to catchment scale models.

Genetic parameters and evaluations from single- and multiple-trait analysis of dairy cow fertility and milk production

Genetic parameters and breeding values for dairy cow fertility were estimated from 62 443 lactation records. Two-trait analysis of fertility and milk yield was investigated as a method to estimate fertility breeding values when culling or selection based on milk yield in early lactation determines presence or absence of fertility observations in later lactations. Fertility traits were calving interval, intervals from calving to first service, calving to conception and first to last service, conception success to first service and number of services per conception. Milk production traits were 305-day milk, fat and protein yield. For fertility traits, range of estimates of heritability (h(2)) was 0.012 to 0.028 and of permanent environmental variance (c(2)) was 0.016 to 0.032. Genetic correlations (r(g)) among fertility traits were generally high ( > 0.70). Genetic correlations of fertility with milk production traits were unfavourable (range -0.11 to 0.46). Single and two-trait analyses of fertility were compared using the same data set. The estimates of h(2) and c(2) were similar for two types of analyses. However, there were differences between estimated breeding values and rankings for the same trait from single versus multi-trait analyses. The range for rank correlation was 0.69-0.83 for all animals in the pedigree and 0.89-0.96 for sires with more than 25 daughters. As single-trait method is biased due to selection on milk yield, a multi-trait evaluation of fertility with milk yield is recommended. (C) 2002 Elsevier Science B.V. All rights reserved.

Genetic diversity and structure of natural and managed populations of Cedrus atlantica (Pinaceae) assessed using random amplified polymorphic DNA

Cedrus atlantica (Pinaceae) is a large and exceptionally long-lived conifer native to the Rif and Atlas Mountains of North Africa. To assess levels and patterns of genetic diversity of this species. samples were obtained throughout the natural range in Morocco and from a forest plantation in Arbucies, Girona (Spain) and analyzed using RAPD markers. Within-population genetic diversity was high and comparable to that revealed by isozymes. Managed populations harbored levels of genetic variation similar to those found in their natural counterparts. Genotypic analyses Of Molecular variance (AMOVA) found that most variation was within populations. but significant differentiation was also found between populations. particularly in Morocco. Bayesian estimates of F,, corroborated the AMOVA partitioning and provided evidence for Population differentiation in C. atlantica. Both distance- and Bayesian-based Clustering methods revealed that Moroccan populations comprise two genetically distinct groups. Within each group, estimates of population differentiation were close to those previously reported in other gymnosperms. These results are interpreted in the context of the postglacial history of the species and human impact. The high degree of among-group differentiation recorded here highlights the need for additional conservation measures for some Moroccan Populations of C. atlantica.

Genetic structure and systematic relationships within the Ophrys fuciflora aggregate (Orchidaceae: Orchidinae): high diversity in Kent and a wind-induced discontinuity bisecting the Adriatic

A recent phylogenetic study based on multiple datasets is used as the framework for a more detailed examination of one of the ten molecularly circumscribed groups identified, the Ophrys fuciflora aggregate. The group is highly morphologically variable, prone to phenotypic convergence, shows low levels of sequence divergence and contains an unusually large proportion of threatened taxa, including the rarest Ophrys species in the UK. The aims of this study were to (a) circumscribe minimum resolvable genetically distinct entities within the O. fuciflora aggregate, and (b) assess the likelihood of gene flow between genetically and geographically distinct entities at the species and population levels. Fifty-five accessions sampled in Europe and Asia Minor from the O. fuciflora aggregate were studied using the AFLP genetic fingerprinting technique to evaluate levels of infraspecific and interspecific genetic variation and to assess genetic relationships between UK populations of O. fuciflora s.s. in Kent and in their continental European and Mediterranean counterparts. The two genetically and geographically distinct groups recovered, one located in England and central Europe and one in south-eastern Europe, are incongruent with current species delimitation within the aggregate as a whole and also within O. fuciflora s.s. Genetic diversity is higher in Kent than in the rest of western and central Europe. Gene flow is more likely to occur between populations in closer geographical proximity than those that are morphologically more similar. Little if any gene flow occurs between populations located in the south-eastern Mediterranean and those dispersed throughout the remainder of the distribution, revealing a genetic discontinuity that runs north-south through the Adriatic. This discontinuity is also evident in other clades of Ophrys and is tentatively attributed to the long-term influence of prevailing winds on the long-distance distribution of pollinia and especially seeds. A cline of gene flow connects populations from Kent and central and southern Europe; these individuals should therefore be considered part of an extensive meta-population. Gene flow is also evident among populations from Kent, which appear to constitute a single metapopulation. They show some evidence of hybridization, and possibly also introgression, with O. apifera.

The role played by the interaction between genetic factors and attachment in the stress response in infancy

Background: The importance of understanding which environmental and biological factors are involved in determining individual differences in physiological response to stress is widely recognized, given the impact that stress has on physical and mental health. Methods: The child-mother attachment relationship and some genetic polymorphisms (5-HTTLPR, COMT and GABRA6) were tested as predictors of salivary cortisol and alpha amylase concentrations, two biomarkers of hypothalamic-pituitary-adrenocortical (HPA) axis and sympathetic adrenomedullary (SAM) system activity, during the Strange Situation (SS) procedure in a sample of more than 100 healthy infants, aged 12 to 18 months. Results: Individual differences in alpha amylase response to separation were predicted by security of attachment in interaction with 5-HTTLPR and GABRA6 genetic polymorphisms, whereas alpha amylase basal levels were predicted by COMT x attachment interaction. No significant effect of attachment, genetics and their interaction on cortisol activity emerged. Conclusions: These results help to disentangle the role played by both genetic and environmental factors in determining individual differences in stress response in infancy. The results also shed light on the suggestion that HPA and SAM systems are likely to have different characteristic responses to stress.

Design, implementation and testing of an intelligent knowledge-based system for the supervisory control of a hot rolling mill

This paper describes the design, implementation and testing of an intelligent knowledge-based supervisory control (IKBSC) system for a hot rolling mill process. A novel architecture is used to integrate an expert system with an existing supervisory control system and a new optimization methodology for scheduling the soaking pits in which the material is heated prior to rolling. The resulting IKBSC system was applied to an aluminium hot rolling mill process to improve the shape quality of low-gauge plate and to optimise the use of the soaking pits to reduce energy consumption. The results from the trials demonstrate the advantages to be gained from the IKBSC system that integrates knowledge contained within data, plant and human resources with existing model-based systems. (c) 2005 Elsevier Ltd. All rights reserved.

Genetic relatedness and phenotypic characteristics of Treponema associated with human periodontal tissues and ruminant foot disease

Treponema have been implicated recently in the pathogenesis of digital dermatitis (DID) and contagious ovine digital dermatitis (CODD) that are infectious diseases of bovine and ovine foot tissues, respectively. Previous analyses of treponemal 16S rDNA sequences, PCR-amplified directly from DID or CODD lesions, have suggested relatedness of animal Treponema to some human oral Treponema species isolated from periodontal tissues. In this study a range of adhesion and virulence-related properties of three animal Treponema isolates have been compared with representative human oral strains of Treponema denticola and Treponema vincentii. In adhesion assays using biotinylated treponemal cells, T denticola cells bound in consistently higher numbers to fibronectin, laminin, collagen type 1, gelatin, keratin and lactoferrin than did T. vincentii or animal Treponema isolates. However, animal DID strains adhered to fibrinogen at equivalent or greater levels than T denticola. All Treponema strains bound to the amino-terminal heparin l/fibrin I domain of fibronectin. 16S rDNA sequence analyses placed ovine strain UB1090 and bovine strain UB1467 within a cluster that was phylogenetically related to T vincentii, while ovine strain UB1466 appeared more closely related to T denticola. These observations correlated with phenotypic properties. Thus, T denticola ATCC 35405, GM-1, and Treponema UB1466 had similar outer-membrane protein profiles, produced chymotrypsin-like protease (CTLP), trypsin-like protease and high levels of proline iminopeptidase, and co-aggregated with human oral bacteria Porphyromonas gingivalis and Streptococcus crista. Conversely, T vincentii ATCC 35580, D2A-2, and animal strains UB1090 and UB1467 did not express CTLP or trypsin-like protease and did not co-aggregate with P. gingivalis or S. crista. Taken collectively, these results suggest that human oral-related Treponema have broad host specificity and that similar control or preventive strategies might be developed for human and animal Treponema-associated infections.

Predicting outcomes following cognitive behavior therapy in child anxiety disorders: the influence of genetic, demographic and clinical information

Background. Within a therapeutic gene by environment (GxE) framework, we recently demonstrated that variation in the Serotonin Transporter Promoter Polymorphism; 5HTTLPR and marker rs6330 in Nerve Growth Factor gene; NGF is associated with poorer outcomes following cognitive behaviour therapy (CBT) for child anxiety disorders. The aim of this study was to explore one potential means of extending the translational reach of G×E data in a way that may be clinically informative. We describe a ‘risk-index’ approach combining genetic, demographic and clinical data and test its ability to predict diagnostic outcome following CBT in anxious children. Method. DNA and clinical data were collected from 384 children with a primary anxiety disorder undergoing CBT. We tested our risk model in five cross-validation training sets. Results. In predicting treatment outcome, six variables had a minimum mean beta value of 0.5: 5HTTLPR, NGF rs6330, gender, primary anxiety severity, comorbid mood disorder and comorbid externalising disorder. A risk index (range 0-8) constructed from these variables had moderate predictive ability (AUC = .62-.69) in this study. Children scoring high on this index (5-8) were approximately three times as likely to retain their primary anxiety disorder at follow-up as compared to those children scoring 2 or less. Conclusion. Significant genetic, demographic and clinical predictors of outcome following CBT for anxiety-disordered children were identified. Combining these predictors within a risk-index could be used to identify which children are less likely to be diagnosis free following CBT alone or thus require longer or enhanced treatment. The ‘risk-index’ approach represents one means of harnessing the translational potential of G×E data.

Genetic structure and linkage disequilibrium in landrace populations of barley in Sardinia

Multilocus digenic linkage disequilibria (LD) and their population structure were investigated in eleven landrace populations of barley (Hordeum vulgare ssp. vulgare L.) in Sardinia, using 134 dominant simple-sequence amplified polymorphism markers. The analysis of molecular variance for these markers indicated that the populations were partially differentiated (F ST = 0.18), and clustered into three geographic areas. Consistent with this population pattern, STRUCTURE analysis allocated individuals from a bulk of all populations into four genetic groups, and these groups also showed geographic patterns. In agreement with other molecular studies in barley, the general level of LD was low (13 % of locus pairs, with P < 0.01) in the bulk of 337 lines, and decayed steeply with map distance between markers. The partitioning of multilocus associations into various components indicated that genetic drift and founder effects played a major role in determining the overall genetic makeup of the diversity in these landrace populations, but that epistatic homogenising or diversifying selection was also present. Notably, the variance of the disequilibrium component was relatively high, which implies caution in the pooling of barley lines for association studies. Finally, we compared the analyses of multilocus structure in barley landrace populations with parallel analyses in both composite crosses of barley on the one hand and in natural populations of wild barley on the other. Neither of these serves as suitable mimics of landraces in barley, which require their own study. Overall, the results suggest that these populations can be exploited for LD mapping if population structure is controlled.