Multilocus estimation of selfing and its heritability

We describe a new method of estimating the selfing rate (S) in a mixed mating population based on a population structure approach that accounts for possible intergenerational correlation in selfing rate, giving rise to an estimate of the upper limit for heritability of selfing rate (h(2)). A correlation between generations in selfing rate is shown to affect one- and two-locus probabilities of identity by descent. Conventional estimates of selfing rate based on a population structure approach are positively biased by intergenerational correlation in selfing. Multilocus genotypes of individuals are used to give maximum-likelihood estimates of S and h(2) in the presence of scoring artifacts. Our multilocus estimation of selfing rate and its heritability (MESH) method was tested with simulated data for a range of conditions. Selfing rate estimates from MESH have low bias and root mean squared error, whereas estimates of the heritability of selfing rate have more uncertainty. Increasing the number of individuals in a sample helps to reduce bias and root mean squared error more than increasing the number of loci of sampled individuals. Improved estimates of selfing rate, as well as estimates of its heritability, can be obtained with this method, although a large number of loci and individuals are needed to achieve best results.     

Dietary stress does not strengthen selection against single deleterious mutations in Drosophila melanogaster

Stress is generally thought to increase the strength of selection, although empirical results are mixed and general conclusions are difficult because data are limited. Here we compare the fitness effects of nine independent recessive mutations in Drosophila melanogaster in a high- and low-dietary-stress environment, estimating the strength of selection on these mutations arising from both a competitive measure of male reproductive success and productivity (female fecundity and the subsequent survival to adulthood of her offspring). The effect of stress on male reproductive success has not been addressed previously for individual loci and is of particular interest with respect to the alignment of natural and sexual selection. Our results do not support the hypothesis that stress increases the efficacy of selection arising from either fitness component. Results concerning the alignment of natural and sexual selection were mixed, although data are limited. In the low-stress environment, selection on mating success and productivity were concordant for five of nine mutations (four out of four when restricted to those with significant or near-significant productivity effects), whereas in the high-stress environment, selection aligned for seven of nine mutations (two out of two when restricted to those having significant productivity effects). General conclusions as to the effects of stress on the strength of selection and the alignment of natural and sexual selection await data from additional mutations, fitness components and stressors.     

VARIANCE-INDUCED PEAK SHIFTS

The increase in phenotypic variance that occurs in some populations as a result of bottlenecks and founder events can cause a dramatic increase in the probability of a peak shift from one adaptive state to another. Periods of small population size allow drift in the amount of phenotypic variance. Increases in phenotypic variance, coupled with a constant individual fitness function with multiple peaks, can cause the mean fitness landscape to change from bimodal to unimodal, thereby allowing the population's mean phenotype to change deterministically by selection. As the amount of phenotypic variance is returned to an equilibrium state, the multiple peaks reemerge, but the population has moved from one stable state to another. These variance-induced peak shifts allow punctuational evolution from one peak to another at a rate that can be much higher than that predicted by Wright's shifting-balance process alone.     

<Emphasis Type="Italic">TRAF1/C5</Emphasis>polymorphism is not associated with increased mortality in rheumatoid arthritis: two large longitudinal studies

Introduction  

Recently an association between a genetic variation in TRAF1/C5 and mortality from sepsis or cancer was found in rheumatoid arthritis (RA). The most prevalent cause of death, cardiovascular disease, may have been missed in that study, since patients were enrolled at an advanced disease stage. Therefore, we used an inception cohort of RA patients to investigate the association between TRAF1/C5 and cardiovascular mortality, and replicate the findings on all-cause mortality. As TRAF1/C5 associated mortality may not be restricted to RA, we also studied a large cohort of non-RA patients.     

The olfactory placodes of the zebrafish form by convergence of cellular fields at the edge of the neural plate

The primary olfactory sensory system is part of the PNS that develops from ectodermal placodes. Several cell types, including sensory neurons and support cells, differentiate within the olfactory placode to form the mature olfactory organ. The olfactory placodes are thought to arise from lateral regions of the anterior neural plate, which separate from the plate through differential cell movements. We determined the origins of the olfactory placodes in zebrafish by labeling cells along the anterior-lateral edge of the neural plate at times preceding the formation of the olfactory placodes and examining the later fates of the labeled cells. Surprisingly, we found that the olfactory placode arises from a field of cells, not from a discrete region of the anterior neural plate. This field extends posteriorly to the anterior limits of cranial neural crest and is bordered medially by telencephalic precursors. Cells giving rise to progeny in both the olfactory organ and telencephalon express the distal-less 3 gene. Furthermore, we found no localized pockets of cell division in the anterior-lateral neural plate cells preceding the appearance of the olfactory placode. We suggest that the olfactory placodes arise by anterior convergence of a field of lateral neural plate cells, rather than by localized separation and proliferation of a discrete group of cells.     

Pre-steady state transport by erythrocyte band 3 protein: uphill countertransport induced by the impermeant inhibitor H2DIDS.

Pre-steady state Cl- efflux experiments have been performed to test directly the idea that the transport inhibitor H2DIDS (4,4'-diisothiocyanatodihydrostilbene-2,2'-disulfonate) binds preferentially to the outward-facing state of the transporter. Cells were equilibrated with a medium consisting of 150 mM sodium phosphate, pH 6.2, N2 atmosphere, and 80-250 microM 36Cl-. Addition of H2DIDS (10-fold molar excess compared with band 3) induces a transient efflux of Cl-, as expected if H2DIDS binds more tightly to outward-facing than to inward-facing states. The size of the H2DIDS-induced efflux depends on the Cl- concentration and is about 700,000 ions per cell at the highest concentrations tested. The size of the transient efflux is larger than would be expected if the catalytic cycle for anion exchange involved one pair of exchanging anions per band 3 dimer. These results are completely consistent with a ping-pong mechanism of anion exchange in which the catalytic cycle consists of one pair of exchanging anions per subunit of the band 3 dimer.     

Tumor necrosis factor-alpha activation of the c-Jun N-terminal kinase pathway in human neutrophils. Integrin involvement in a pathway leading from cytoplasmic tyrosine kinases apoptosis

The intensity and duration of an inflammatory response depends on the balance of factors that favor perpetuation versus resolution. At sites of inflammation, neutrophils adherent to other cells or matrix components are exposed to tumor necrosis factor-alpha (TNFalpha). Although TNFalpha has been implicated in induction of pro-inflammatory responses, it may also inhibit the intensity of neutrophilic inflammation by promoting apoptosis. Since TNFalpha is not only an important activator of the stress-induced pathways leading to p38 MAPk and c-Jun N-terminal kinase (JNK) but also a potent effector of apoptosis, we investigated the effects of TNFalpha on the JNK pathway in adherent human neutrophils and the potential involvement of this pathway in neutrophil apoptosis. Stimulation with TNFalpha was found to result in beta2 integrin-mediated activation of the cytoplasmic tyrosine kinases Pyk2 and Syk, and activation of a three-part MAPk module composed of MEKK1, MKK7, and/or MKK4 and JNK1. JNK activation was attenuated by blocking antibodies to beta2 integrins, the tyrosine kinase inhibitors, genistein, and tyrphostin A9, a Pyk2-specific inhibitor, and piceatannol, a Syk-specific inhibitor. Exposure of adherent neutrophils to TNFalpha led to the rapid onset of apoptosis that was demonstrated by augmented annexin V binding and caspase-3 cleavage. TNFalpha-induced increases in annexin V binding to neutrophils were attenuated by blocking antibodies to beta2 integrins, and the caspase-3 cleavage was attenuated by tyrphostin A9. Hence, exposure of adherent neutrophils to TNFalpha leads to utilization of the JNK-signaling pathways that may contribute to diverse functional responses including induction of apoptosis and subsequent resolution of the inflammatory response.     

Dioxin-inducible transactivation in a chromosomal setting. Analysis of the acidic domain of the Ah receptor

We analyzed the transactivation function of the acidic segment of the Ah receptor (amino acids 515-583) by reconstituting AhR-defective mouse hepatoma cells with mutants. Our data reveal that both hydrophobic and acidic residues are important for transactivation and that these residues are clustered in two regions of the acidic segment of AhR. Both regions are crucial for function, because disruption of either one substantially impairs transactivation of the chromosomal CYP1A1 target gene. Neither region contains an amino acid motif that resembles those reported for other acidic activation domains. Furthermore, proline substitutions in both regions do not impair transactivation in vivo, a finding that implies that alpha-helix formation is not required for function.     

Vancomycin-Resistant Enterococcus spp. Isolated from Wastewater and Chicken Feces in the United States

Vancomycin-resistant Enterococcus spp. (VRE) were isolated from sewage and chicken feces but not from other animal fecal sources (dog, cow, and pig) or from surface waters tested. VRE from hospital wastewater were resistant to ≥20 μg of vancomycin/ml and possessed the vanA gene. VRE from residential wastewater and chicken feces were resistant to 3 to 5 μg of vancomycin/ml and possessed the vanC gene.