146 research outputs found
Positive selection of deleterious alleles through interaction with a sex-ratio suppressor gene in African buffalo: a plausible new mechanism for a high frequency anomaly
Although generally rare, deleterious alleles can become common through genetic drift, hitchhiking or reductions in
selective constraints. Here we present a possible new mechanism that explains the attainment of high frequencies of
deleterious alleles in the African buffalo (Syncerus caffer) population of Kruger National Park, through positive selection of
these alleles that is ultimately driven by a sex-ratio suppressor. We have previously shown that one in four Kruger buffalo
has a Y-chromosome profile that, despite being associated with low body condition, appears to impart a relative
reproductive advantage, and which is stably maintained through a sex-ratio suppressor. Apparently, this sex-ratio
suppressor prevents fertility reduction that generally accompanies sex-ratio distortion. We hypothesize that this bodycondition-
associated reproductive advantage increases the fitness of alleles that negatively affect male body condition,
causing genome-wide positive selection of these alleles. To investigate this we genotyped 459 buffalo using 17 autosomal
microsatellites. By correlating heterozygosity with body condition (heterozygosity-fitness correlations), we found that most
microsatellites were associated with one of two gene types: one with elevated frequencies of deleterious alleles that have a
negative effect on body condition, irrespective of sex; the other with elevated frequencies of sexually antagonistic alleles
that are negative for male body condition but positive for female body condition. Positive selection and a direct association
with a Y-chromosomal sex-ratio suppressor are indicated, respectively, by allele clines and by relatively high numbers of
homozygous deleterious alleles among sex-ratio suppressor carriers. This study, which employs novel statistical techniques
to analyse heterozygosity-fitness correlations, is the first to demonstrate the abundance of sexually-antagonistic genes in a
natural mammal population. It also has important implications for our understanding not only of the evolutionary and
ecological dynamics of sex-ratio distorters and suppressors, but also of the functioning of deleterious and sexuallyantagonistic
alleles, and their impact on population viability.US NIH/NSF Ecology of Infectious Disease Grant GM83863 awarded to WMG.http://www.plosone.orgam201
Spectral and transport properties of doped Mott-Hubbard systems with incommensurate magnetic order
We present spectral and optical properties of the Hubbard model on a
two-dimensional square lattice using a generalization of dynamical mean-field
theory to magnetic states in finite dimension. The self-energy includes the
effect of spin fluctuations and screening of the Coulomb interaction due to
particle-particle scattering. At half-filling the quasiparticles reduce the
width of the Mott-Hubbard `gap' and have dispersions and spectral weights that
agree remarkably well with quantum Monte Carlo and exact diagonalization
calculations. Away from half-filling we consider incommensurate magnetic order
with a varying local spin direction, and derive the photoemission and optical
spectra. The incommensurate magnetic order leads to a pseudogap which opens at
the Fermi energy and coexists with a large Mott-Hubbard gap. The quasiparticle
states survive in the doped systems, but their dispersion is modified with the
doping and a rigid band picture does not apply. Spectral weight in the optical
conductivity is transferred to lower energies and the Drude weight increases
linearly with increasing doping. We show that incommensurate magnetic order
leads also to mid-gap states in the optical spectra and to decreased scattering
rates in the transport processes, in qualitative agreement with the
experimental observations in doped systems. The gradual disappearence of the
spiral magnetic order and the vanishing pseudogap with increasing temperature
is found to be responsible for the linear resistivity. We discuss the possible
reasons why these results may only partially explain the features observed in
the optical spectra of high temperature superconductors.Comment: 22 pages, 18 figure
The model for self-dual chiral bosons as a Hodge theory
We consider (1+1) dimensional theory for a single self-dual chiral boson as
classical model for gauge theory. Using Batalin-Fradkin-Vilkovisky (BFV)
technique the nilpotent BRST and anti BRST symmetry transformations for this
theory have been studied. In this model other forms of nilpotent symmetry
transformations like co-BRST and anti co-BRST which leave the gauge-fixing part
of the action invariant, are also explored. We show that the nilpotent charges
for these symmetry transformations satisfy the algebra of de Rham cohomological
operators in differential geometry. The Hodge decomposition theorem on compact
manifold is also studied in the context of conserved charges.Comment: 19 pages, No figures, Revtex, Final version to appear in EPJ
Incremental prognostic value of coronary computed tomography angiography over coronary calcium scoring for major adverse cardiac events in elderly asymptomatic individuals
Aims Coronary computed tomography angiography (CCTA) and coronary artery calcium score (CACS) have prognostic value for coronary artery disease (CAD) events beyond traditional risk assessment. Age is a risk factor with very high weight and little is known regarding the incremental value of CCTA over CAC for predicting cardiac events in older adults. Methods and results Of 27 125 individuals undergoing CCTA, a total of 3145 asymptomatic adults were identified. This study sample was categorized according to tertiles of age (cut-off points: 52 and 62 years). CAD severity was classified as 0, 1-49, and ≥50% maximal stenosis in CCTA, and further categorized according to number of vessels ≥50% stenosis. The Framingham 10-year risk score (FRS) and CACS were employed as major covariates. Major adverse cardiovascular events (MACE) were defined as a composite of all-cause death or non-fatal MI. During a median follow-up of 26 months (interquartile range: 18-41 months), 59 (1.9%) MACE occurred. For patients in the top age tertile, CCTA improved discrimination beyond a model included FRS and CACS (C-statistic: 0.75 vs. 0.70, P-value = 0.015). Likewise, the addition of CCTA improved category-free net reclassification (cNRI) of MACE in patients within the highest age tertile (e.g. cNRI = 0.75; proportion of events/non-events reclassified were 50 and 25%, respectively; P-value <0.05, all). CCTA displayed no incremental benefit beyond FRS and CACS for prediction of MACE in the lower age tertiles. Conclusion CCTA provides added prognostic value beyond cardiac risk factors and CACS for the prediction of MACE in asymptomatic older adults
Genome-Wide Association Study for Incident Myocardial Infarction and Coronary Heart Disease in Prospective Cohort Studies: The CHARGE Consortium
Background Data are limited on genome-wide association studies (GWAS) for incident coronary heart disease (CHD). Moreover, it is not known whether genetic variants identified to date also associate with risk of CHD in a prospective setting. Methods We performed a two-stageGWAS analysis of incident myocardial infarction (MI) and CHD in a total of 64,297 individuals (including 3898MI cases, 5465 CHD cases). SNPs that passed an arbitrary threshold of 5×10-6 in Stage I were taken to Stage II for further discovery. Furthermore, in an analysis of prognosis, we studied whether known SNPs from former GWAS were associated with totalmortality in individuals who experienced MI during follow-up. Results In Stage I 15 loci passed the threshold of 5×10-6; 8 loci for MI and 8 loci for CHD, for which one locus overlapped and none were reported in previous GWAS meta-analyses. We took 60 SNPs representing these 15 loci to Stage II of discovery. Four SNPs near QKI showed nominally significant association with MI (p-value<8.8×10-3) and three exceeded the genome-wide significance threshold when Stage I and Stage II results were combined (top SNP rs6941513: p = 6.2×10-9). Despite excellent power, the 9p21 locus SNP (rs1333049) was only modestly associated with MI (HR = 1.09, p-value = 0.02) and marginally with CHD (HR = 1.06, p-value = 0.08). Among an inception cohort of those who experienced MI during follow-up, the risk allele of rs1333049 was associated with a decreased risk of subsequent mortality (HR = 0.90, p-value = 3.2×10-3). Conclusions QKI represents a novel locus that may serve as a predictor of incident CHD in prospective studies. The association of the 9p21 locus both with increased risk of first myocardial infarction and longer survival after MI highlights the importance of study design in investigating genetic determinants of complex disorders
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