Mapping genetic variants associated with beta-adrenergic responses in inbred mice

β-blockers and β-agonists are primarily used to treat cardiovascular diseases. Inter-individual variability in response to both drug classes is well recognized, yet the identity and relative contribution of the genetic players involved are poorly understood. This work is the first genome-wide association study (GWAS) addressing the values and susceptibility of cardiovascular-related traits to a selective β(1)-blocker, Atenolol (ate), and a β-agonist, Isoproterenol (iso). The phenotypic dataset consisted of 27 highly heritable traits, each measured across 22 inbred mouse strains and four pharmacological conditions. The genotypic panel comprised 79922 informative SNPs of the mouse HapMap resource. Associations were mapped by Efficient Mixed Model Association (EMMA), a method that corrects for the population structure and genetic relatedness of the various strains. A total of 205 separate genome-wide scans were analyzed. The most significant hits include three candidate loci related to cardiac and body weight, three loci for electrocardiographic (ECG) values, two loci for the susceptibility of atrial weight index to iso, four loci for the susceptibility of systolic blood pressure (SBP) to perturbations of the β-adrenergic system, and one locus for the responsiveness of QTc (p<10(-8)). An additional 60 loci were suggestive for one or the other of the 27 traits, while 46 others were suggestive for one or the other drug effects (p<10(-6)). Most hits tagged unexpected regions, yet at least two loci for the susceptibility of SBP to β-adrenergic drugs pointed at members of the hypothalamic-pituitary-thyroid axis. Loci for cardiac-related traits were preferentially enriched in genes expressed in the heart, while 23% of the testable loci were replicated with datasets of the Mouse Phenome Database (MPD). Altogether these data and validation tests indicate that the mapped loci are relevant to the traits and responses studied.

Highly pathogenic adapted HIV-1 strains limit host immunity and dictate rapid disease progression.

OBJECTIVE: The study of HIV-1 rapid progressors has been limited to specific case reports. Nevertheless, identification and characterization of the viral and host factors involved in rapid progression are crucial when attempting to uncover the correlates of rapid disease outcome. DESIGN: We carried out comparative functional analyses in rapid progressors (n = 46) and standard progressors (n = 46) early after HIV-1 seroconversion (≤1 year). The viral traits tested were viral replicative capacity, co-receptor usage, and genomic variation. Host CD8 T-cell responses, humoral activity, and HLA immunogenetic markers were also determined. RESULTS: Our data demonstrate an unusual convergence of highly pathogenic HIV-1 strains in rapid progressors. Compared with standard progressors, rapid progressor viral strains show higher in-vitro replicative capacity (81.5 vs. 67.9%; P = 0.025) and greater X4/DM co-receptor usage (26.3 vs. 2.8%; P = 0.006) in early infection. Limited or absent functional HIV-1 CD8 T-cell responses and neutralizing activity were measured in rapid progressors. Moreover, the increase in common HLA allele-restricted CD8 T-cell escape mutations in rapid progressors acts as a signature of uncontrolled HIV-1 replication and early impairment of adaptive cellular responses. CONCLUSION: Our data support a dominant role for viral factors in rapid progressors. Robust HIV-1 replication and intrinsic viral properties limit host adaptive immune responses, thus driving rapid disease progression.

The Structure and Correlates of Self-Reported DSM-5 Maladaptive Personality Traits: Findings From Two German-Speaking Samples

The authors investigated the structure and correlates of DSM-5 maladaptive personality traits in two samples of 577 students and 212 inpatients using the German self-report form of the Personality Inventory for DSM-5. They found that (a) the factor structure of DSM-5 trait facets is largely in line with the proposed trait domains of Negative Affectivity, Detachment, Antagonism, Disinhibition, and Psychoticism; (b) all DSM-5 trait domains except Psychoticism are highly related to the respective domains of the Five-Factor Model of personality; (c) the trait facets are positively associated with a self-report measure of general personality dysfunction; and (d) the DSM-5 trait facets show differential associations with a range of self-reported DSM-IV Axis I disorders. These findings give further support to the new DSM-5 trait model and suggest that it may generalize to other languages and cul

Grain yield variation and association of major traits in brown-seeded genotypes of tef [Eragrostis tef (Zucc.)Trotter]

Background Tef [Eragrostis tef (Zucc.) Trotter] is the major cereal crop of Ethiopia where it is annually cultivated on more than three million hectares of land by over six million small-scale farmers. It is broadly grouped into white and brown-seeded type depending on grain color, although some intermediate color grains also exist. Earlier breeding experiments focused on white-seeded tef, and a number of improved varieties were released to the farming community. Thirty-six brown-seeded tef genotypes were evaluated using a 6 × 6 simple lattice design at three locations in the central highlands of Ethiopia to assess the productivity, heritability, and association among major pheno-morphic traits. Results The mean square due to genotypes, locations, and genotype by locations were significant (P < 0.01) for all traits studied. Genotypic and phenotypic coefficients of variations ranged from 2.5 to 20.3 % and from 4.3 to 21.7 %, respectively. Grain yield showed significant (P < 0.01) genotypic correlation with shoot biomass and harvest index, while it had highly significant (P < 0.01) phenotypic correlation with all the traits evaluated. Besides, association of lodging index with biomass and grain yield was negative and significant at phenotypic level while it was not significant at genotypic level. Cluster analysis grouped the 36 test genotypes into seven distinct classes. Furthermore, the first three principal components with eigenvalues greater than unity extracted 78.3 % of the total variation. Conclusion The current study, generally, revealed the identification of genotypes with superior grain yield and other desirable traits for further evaluation and eventual release to the farming community.

Simple measures of climate, soil properties and plant traits predict national-scale grassland soil carbon stocks

Soil carbon (C) storage is a key ecosystem service. Soil C stocks play a vital role in soil fertility and climate regulation, but the factors that control these stocks at regional and national scales are unknown, particularly when their composition and stability are considered. As a result, their mapping relies on either unreliable proxy measures or laborious direct measurements. Using data from an extensive national survey of English grasslands, we show that surface soil (0–7 cm) C stocks in size fractions of varying stability can be predicted at both regional and national scales from plant traits and simple measures of soil and climatic conditions. Soil C stocks in the largest pool, of intermediate particle size (50–250 μm), were best explained by mean annual temperature (MAT), soil pH and soil moisture content. The second largest C pool, highly stable physically and biochemically protected particles (0·45–50 μm), was explained by soil pH and the community abundance-weighted mean (CWM) leaf nitrogen (N) content, with the highest soil C stocks under N-rich vegetation. The C stock in the small active fraction (250–4000 μm) was explained by a wide range of variables: MAT, mean annual precipitation, mean growing season length, soil pH and CWM specific leaf area; stocks were higher under vegetation with thick and/or dense leaves. Testing the models describing these fractions against data from an independent English region indicated moderately strong correlation between predicted and actual values and no systematic bias, with the exception of the active fraction, for which predictions were inaccurate. Synthesis and applications. Validation indicates that readily available climate, soils and plant survey data can be effective in making local- to landscape-scale (1–100 000 km2) soil C stock predictions. Such predictions are a crucial component of effective management strategies to protect C stocks and enhance soil C sequestration.

Direct Democracy and Institutional Trust: Relationships and Differences across Personality Traits

Direct democracy plays a prominent role in the explanation of institutional trust. To date, however, empirical findings on the effects of direct democracy remain inconclusive. In this article, we argue that this inconclusiveness can be partly ascribed to the diverse effects direct democracy has on individuals. In other words, direct democracy influences institutional trust, but how and to what degree depends on individuals’ personality traits. Running hierarchical analyses of unique survey data from a random sample of eligible Swiss voters, we document three findings: First, we show that the number of ballot measures is not directly associated with institutional trust. Second, we demonstrate that the Big Five personality traits affect the propensity to trust. Third, some of these traits also alter the relationship between direct democracy and institutional trust, suggesting that certain personality types are more likely to be sensitive to popular votes than others and that not everyone is equally likely to respond to political stimuli, even in highly democratic environments.