Predicting Carriers of Ongoing Selective Sweeps without Knowledge of the Favored Allele

Methods for detecting the genomic signatures of natural selection have been heavily studied, and they have been successful in identifying many selective sweeps. For most of these sweeps, the favored allele remains unknown, making it difficult to distinguish carriers of the sweep from non-carriers. In an ongoing selective sweep, carriers of the favored allele are likely to contain a future most recent common ancestor. Therefore, identifying them may prove useful in predicting the evolutionary trajectory—for example, in contexts involving drug-resistant pathogen strains or cancer subclones. The main contribution of this paper is the development and analysis of a new statistic, the Haplotype Allele Frequency (HAF) score. The HAF score, assigned to individual haplotypes in a sample, naturally captures many of the properties shared by haplotypes carrying a favored allele. We provide a theoretical framework for computing expected HAF scores under different evolutionary scenarios, and we validate the theoretical predictions with simulations. As an application of HAF score computations, we develop an algorithm (PreCIOSS: Predicting Carriers of Ongoing Selective Sweeps) to identify carriers of the favored allele in selective sweeps, and we demonstrate its power on simulations of both hard and soft sweeps, as well as on data from well-known sweeps in human populations.     

Xylanase and xylosidase activities in avocado fruit

The activities of xylanase and xylosidase were demonstrated in mature avocado (Persea americana Mill.) fruits from different cultivars. When monitored on the day of harvest during the season at 1-month intervals, xylanase activity decreased and xylosidase activity increased between January and February and then remained stable until May. When monitored during the ripening process (January harvest), xylanase activity was constant, and xylosidase activity reached a peak at the climax of ethylene evolution and cellulase activity. Xylanase, which originated from Trichoderma viride and was added to the medium in which avocado discs were incubated, induced ethylene evolution.     

Epidermal growth factor (EGF) stimulates association and kinase activity of Raf-1 with the EGF receptor.

Raf-1 serine- and threonine-specific protein kinase is transiently activated in cells expressing the epidermal growth factor (EGF) receptor upon treatment with EGF. The stimulated EGF receptor coimmunoprecipitates with Raf-1 kinase and mediates protein kinase C-independent phosphorylation of Raf-1 on serine residues. Hyperphosphorylated Raf-1 has lower mobility on sodium dodecyl sulfate gels and has sixfold-increased activity in immunocomplex kinase assay with histone H1 or Raf-1 sequence-derived peptide as a substrate. Raf-1 activation requires kinase-active EGF receptor; a point mutant lacking tyrosine kinase activity in inactive in Raf-1 coupling and association. It is noteworthy that tyrosine phosphorylation of c-Raf-1 induced by EGF was not detected in these cells. These observations suggest that Raf-1 kinase may act as an important downstream effector of EGF signal transduction.     

Adenylate cyclase responses to sucrose stimulation in membranes of pig circumvallate taste papillae.

1. Typical adenylate cyclase (AC) responses to guanine nucleotides were found in membranes of pig circumvallate (CV) taste papillae. 2. Sucrose stimulated AC activity in the CV membranes and this stimulation was GTP dependent and tissue specific. 3. The stimulatory effect of sucrose in the CV membranes was dependent on the concentration of membranes used in the AC assay. 4. This study provides the first biochemical data on cellular transduction of taste in the pig, compares positively to preliminary results in cattle and supports recent suggestions for a role of cAMP in sweet taste transduction.     

EGF receptor-mediated signals are differentially modulated by concanavalin A

NIH 3T3 cells expressing hgh levels of the human epidermal growth factor (EGF) receptor were used to examine the effects of the lectin concanavalin A (Con A) on EGF-mediated signaling events. Proliferation of NIH 3T3 cells expressing high levels of the human EGF receptor was inhibited in a dose-dependent manner by Con A. At the same time, Con A also inhibited both dimerization and tyrosine phosphorylation of the EGF receptor. Tyrosine phosphorylation of the enzyme phospholiphase C-γ, a substrate of the phosphorylated EGF receptor kinase, was also inhibited. In contrast, EGF-stimulated changes in pH, calcium, and levels of inositol phosphates were unaffected by the presence of Con A. These results indicate that certain signals (changes in the levels of intracellular calcium, pH, and inositol phosphates) mediated by EGF binding to its receptor still occur when receptor dimerization and phosphorylation are dramatically decreased, suggesting that multiple independent signals are transmitted by the binding of EGF to its receptor. © 1995 Wiley-Liss, Inc.     

Heterogeneity–diversity relationships in sessile organisms: a unified framework

The hypothesis that environmental heterogeneity promotes species richness by increasing opportunities for niche partitioning is a fundamental paradigm in ecology. However, recent studies suggest that heterogeneity–diversity relationships (HDR) are more complex than expected from this niche‐based perspective, and often show a decrease in richness at high levels of heterogeneity. These findings have motivated ecologists to propose new mechanisms that may explain such deviations. Here we provide an overview of currently recognised mechanisms affecting the shape of HDRs and present a conceptual model that integrates all previously proposed mechanisms within a unified framework. We also translate the proposed framework into an explicit community dynamic model and use the model as a tool for generating testable predictions concerning how landscape properties interact with species traits in determining the shape of HDRs. Our main finding is that, despite the enormous complexity of such interactions, the predicted HDRs are rather simple, ranging from positive to unimodal patterns in a highly consistent and predictable manner.     

Formin-mediated actin polymerization at cell–cell junctions stabilizes E-cadherin and maintains monolayer integrity during wound repair

Cadherin-mediated cell–cell adhesion is required for epithelial tissue integrity in homeostasis, during development, and in tissue repair. E-cadherin stability depends on F-actin, but the mechanisms regulating actin polymerization at cell–cell junctions remain poorly understood. Here we investigated a role for formin-mediated actin polymerization at cell–cell junctions. We identify mDia1 and Fmnl3 as major factors enhancing actin polymerization and stabilizing E-cadherin at epithelial junctions. Fmnl3 localizes to adherens junctions downstream of Src and Cdc42 and its depletion leads to a reduction in F-actin and E-cadherin at junctions and a weakening of cell–cell adhesion. Of importance, Fmnl3 expression is up-regulated and junctional localization increases during collective cell migration. Depletion of Fmnl3 or mDia1 in migrating monolayers results in dissociation of leader cells and impaired wound repair. In summary, our results show that formin activity at epithelial cell–cell junctions is important for adhesion and the maintenance of epithelial cohesion during dynamic processes, such as wound repair.