Genome-assisted prediction of a quantitative trait measured in parents and progeny: application to food conversion rate in chickens

Accuracy of prediction of yet-to-be observed phenotypes for food conversion rate (FCR) in broilers was studied in a genome-assisted selection context. Data consisted of FCR measured on the progeny of 394 sires with SNP information. A Bayesian regression model (Bayes A) and a semi-parametric approach (Reproducing kernel Hilbert Spaces regression, RKHS) using all available SNPs (p = 3481) were compared with a standard linear model in which future performance was predicted using pedigree indexes in the absence of genomic data. The RKHS regression was also tested on several sets of pre-selected SNPs (p = 400) using alternative measures of the information gain provided by the SNPs. All analyses were performed using 333 genotyped sires as training set, and predictions were made on 61 birds as testing set, which were sons of sires in the training set. Accuracy of prediction was measured as the Spearman correlation (r¯S) between observed and predicted phenotype, with its confidence interval assessed through a bootstrap approach. A large improvement of genome-assisted prediction (up to an almost 4-fold increase in accuracy) was found relative to pedigree index. Bayes A and RKHS regression were equally accurate (r¯S = 0.27) when all 3481 SNPs were included in the model. However, RKHS with 400 pre-selected informative SNPs was more accurate than Bayes A with all SNPs.     

Trends in aluminium export from a mountainous area to surface waters, from deglaciation to the recent: Effects of vegetation and soil development, atmospheric acidification, and nitrogen-saturation

We reconstructed the history of terrestrial export of aluminium (Al) to Plešné Lake (Czech Republic) since the lake origin 12,600 year BC, and predicted Al export for 2010–2050 on the basis of previously published and new data on mass budget studies, palaeolimnological data, and MAGIC modelling. We focused on three major Al forms; ionic Al (Al_i), organically-bound Al (Al_o), and particulate Al hydroxide [Al(OH)₃]. In early post-glacial time, Plešné Lake received high terrestrial export of Al, but with a minor proportion of Al(OH)₃ (4–25 μM), and concentrations of Al_i and Al_o were negligible. Since the forest and soil development (9900–9000 year BC), erosion has declined and soil organic acids increased export of Al_o from soils. The terrestrial Al_o leaching (7.5 μM) persisted throughout the Holocene until the industrial period. Then, Al_i concentrations continuously increased (up to 28 μM in the mid-1980s) due to atmospheric acidification; the Al_i leaching was mostly associated with sulphate. The proportion of Al_i associated with nitrate has been increasing since the beginning of lake recovery from acidification after 1990 due to reduction in sulphur deposition and nitrogen-saturation of the catchment, leading to persistent nitrate leaching. Currently, nitrate has become the dominant strong acid anion and the major Al_i carrier. Al_o (5.5 μM) is predicted to dominate Al concentrations around 2050, but the predicted Al_i concentrations (4 μM) are uncertain because of uncertainty associated with the future nitrate leaching and its effect on soils.     

Large-scale prediction of long disordered regions in proteins using random forests

Background  

Many proteins contain disordered regions that lack fixed three-dimensional (3D) structure under physiological conditions but have important biological functions. Prediction of disordered regions in protein sequences is important for understanding protein function and in high-throughput determination of protein structures. Machine learning techniques, including neural networks and support vector machines have been widely used in such predictions. Predictors designed for long disordered regions are usually less successful in predicting short disordered regions. Combining prediction of short and long disordered regions will dramatically increase the complexity of the prediction algorithm and make the predictor unsuitable for large-scale applications. Efficient batch prediction of long disordered regions alone is of greater interest in large-scale proteome studies.     

Incomplete posttranslational prohormone modifications in hyperactive neuroendocrine cells

Background  

In black-background-adapted Xenopus laevis, the intermediate pituitary melanotrope cells are hyperactive, producing large amounts of their major secretory cargo proopiomelanocortin (POMC, representing ~80% of all newly synthesised proteins), whereas in white-adapted frogs these cells are only basally active. Here we explored in the hyperactive and basally active melanotrope cells the capacity for posttranslational POMC processing events in the secretory pathway.     

GITR signaling potentiates airway hyperresponsiveness by enhancing Th2 cell activity in a mouse model of asthma

Background

Anxiety and depression are common and treatable risk factors for re-hospitalisation and death in patients with COPD. The degree of lung function impairment does not sufficiently explain anxiety and depression. The BODE index allows a functional classification of COPD beyond FEV₁. The aim of this cross-sectional study was (1) to test whether the BODE index is superior to the GOLD classification for explaining anxious and depressive symptoms; and (2) to assess which components of the BODE index are associated with these psychological aspects of COPD.

Methods

COPD was classified according to the GOLD stages based on FEV_1%predicted in 122 stable patients with COPD. An additional four stage classification was constructed based on the quartiles of the BODE index. The hospital anxiety and depression scale was used to assess anxious and depressive symptoms.

Results

The overall prevalence of anxious and depressive symptoms was 49% and 52%, respectively. The prevalence of anxious symptoms increased with increasing BODE stages but not with increasing GOLD stages. The prevalence of depressive symptoms increased with both increasing GOLD and BODE stages. The BODE index was superior to FEV_1%predicted for explaining anxious and depressive symptoms. Anxious symptoms were explained by dyspnoea. Depressive symptoms were explained by both dyspnoea and reduced exercise capacity.

Conclusion

The BODE index is superior to the GOLD classification for explaining anxious and depressive symptoms in COPD patients. These psychological consequences of the disease may play a role in future classification systems of COPD.     

A new use for synchrotron X‐ray microtomography: three‐dimensional biomechanical modeling of chelicerate mouthparts and calculation of theoretical bite forces

Abstract. We present the first report on the use of the non‐invasive method of synchrotron X‐ray microtomography to model the dynamics and theoretical bite forces of arthropod mouthparts. The nature of the data allowed us to include precise measurements of muscle areas and the spatial geometry of muscle origins and insertions into a biomechanical model of a morphological microstructure. We investigated the functional morphology of the chelicera in the oribatid mite Archegozetes longisetosus (Acari, Oribatida), a model organism for Chelicerata. The chelicera represents a first‐class lever; the intrinsic muscular system consists of a feather‐shaped depressor with six muscle bundles and a bouquet‐shaped levator with 16 bundles. The relative bite forces, as compared with body mass (force/mass^2/3), are 390 N kg^?1 and lie within those known for vertebrates (≤260 N kg^?1) and decapod chelae (≤915 N kg^?1). The dynamics of force transmission and bite forces during the movement of the apotele are calculated. The conserved organization of cheliceral musculature allows broad adaptation of the model to other chelicerate taxa.     

Directed Evolution of Ionizing Radiation Resistance in Escherichia coli

We have generated extreme ionizing radiation resistance in a relatively sensitive bacterial species, Escherichia coli, by directed evolution. Four populations of Escherichia coli K-12 were derived independently from strain MG1655, with each specifically adapted to survive exposure to high doses of ionizing radiation. D₃₇ values for strains isolated from two of the populations approached that exhibited by Deinococcus radiodurans. Complete genomic sequencing was carried out on nine purified strains derived from these populations. Clear mutational patterns were observed that both pointed to key underlying mechanisms and guided further characterization of the strains. In these evolved populations, passive genomic protection is not in evidence. Instead, enhanced recombinational DNA repair makes a prominent but probably not exclusive contribution to genome reconstitution. Multiple genes, multiple alleles of some genes, multiple mechanisms, and multiple evolutionary pathways all play a role in the evolutionary acquisition of extreme radiation resistance. Several mutations in the recA gene and a deletion of the e14 prophage both demonstrably contribute to and partially explain the new phenotype. Mutations in additional components of the bacterial recombinational repair system and the replication restart primosome are also prominent, as are mutations in genes involved in cell division, protein turnover, and glutamate transport. At least some evolutionary pathways to extreme radiation resistance are constrained by the temporally ordered appearance of specific alleles.A survey of bacteria and archaea identifies 11 phyla that contain species with unusually high resistance to the lethal effects of ionizing radiation (IR). These phyla are not closely related to each other and do not share a common lineage, and all include genera that are considered radiosensitive (9). The existence of so many unrelated and isolated radioresistant species in the phylogenetic tree argues that the molecular mechanisms that protect against IR-induced damage evolved independently in these organisms, suggesting that at least some species have the capacity to acquire radioresistance through evolutionary processes if they are subjected to appropriate selective pressure.The first of these species to be discovered, and the best studied to date, is the bacterium Deinococcus radiodurans. The molecular basis of the extraordinary radioresistance of Deinococcus has not been elucidated, but well-constructed proposals abound. Radioresistance has variously been attributed to the condensed structure of the nucleoid (29, 40, 56), the elevated levels of Mn ion present in the cytosol as a mechanism to control protein oxidation (11, 12), a specialized RecA-independent DNA repair process (54), and other species attributes (9). Radioresistance in Deinococcus is probably mechanistically related to desiccation resistance derived from evolution in arid environments (37, 45), although this may not be the origin of the phenotype in all relevant species (9).An understanding of the genetic underpinnings of bacterial radiation resistance holds promise for yielding insights into the mechanistic basis of radiation toxicity, along with the potential for new approaches to facilitate recovery from radiation injury in other organisms, including humans. To better define the genetic, biochemical, and physiological characteristics most important for radioresistance, we employed a strategy to allow the cells to inform us. In brief, we generated radioresistant variants of radiosensitive bacteria and defined the genetic changes underlying the new phenotype.In 1946, Evelyn Witkin established that it was possible to increase the resistance of Escherichia coli B to DNA damage (50). She exposed cultures to high doses of UV light, killing most of the population and selecting for variants better able to tolerate UV. In the 6 decades since the Witkin report, additional investigators have repeated this result, demonstrating that iterative cycles of high-dose exposure to a DNA damaging agent can heritably enhance a culture''s ability to tolerate that DNA damaging agent. Increases in IR resistance have been reported for E. coli (17), Salmonella enterica serovar Typhimurium (14), and Bacillus pumulis (44), organisms that are otherwise considered radiosensitive. Davies and Sinskey (14) showed that for S. enterica serovar Typhimurium LT2, the number of cycles of exposure and recovery correlates with the level of radioresistance achieved. After 84 cycles, they generated a strain displaying inactivation kinetics similar to that of Deinococcus radiodurans, with a D₁₀ value (the dose needed to inactivate 90% of the population) 200-fold higher than that of the parental strain.For this study, we expanded on these earlier studies by independently generating four IR-resistant populations of Escherichia coli K-12 MG1655 (4). Our effort included an important innovation relative to the earlier studies—we characterized the evolved populations with an experimental program that included the complete genomic resequencing of multiple strains purified from three of the populations, taking advantage of new sequencing technologies. The result is an increasingly detailed data set—based on a single robust model system—that allows us to (i) explore the molecular basis of radiation resistance in bacteria and (ii) test current hypotheses and search for novel mechanisms of radiation resistance.