Disruptive selection and then what?

Disruptive selection occurs when extreme phenotypes have a fitness advantage over more intermediate phenotypes. The phenomenon is particularly interesting when selection keeps a population in a disruptive regime. This can lead to increased phenotypic variation while disruptive selection itself is diminished or eliminated. Here, we review processes that increase phenotypic variation in response to disruptive selection and discuss some of the possible outcomes, such as sympatric species pairs, sexual dimorphisms, phenotypic plasticity and altered community assemblages. We also identify factors influencing the likelihoods of these different outcomes.     

Cloud computing and validation of expandable in silico livers

Background  

In Silico Livers (ISLs) are works in progress. They are used to challenge multilevel, multi-attribute, mechanistic hypotheses about the hepatic disposition of xenobiotics coupled with hepatic responses. To enhance ISL-to-liver mappings, we added discrete time metabolism, biliary elimination, and bolus dosing features to a previously validated ISL and initiated re-validated experiments that required scaling experiments to use more simulated lobules than previously, more than could be achieved using the local cluster technology. Rather than dramatically increasing the size of our local cluster we undertook the re-validation experiments using the Amazon EC2 cloud platform. So doing required demonstrating the efficacy of scaling a simulation to use more cluster nodes and assessing the scientific equivalence of local cluster validation experiments with those executed using the cloud platform.     

Dark and light metabolism of amino acids inChlorella vulgaris

An investigation was made of the suitability of 27 amino acids to serve as source of nitrogen, carbon and energy forChlorella vulgaris in the dark. Only leucine led to profuse growth. Eight other amino acids were moderately effective.In the light, almost all of the amino acids tested proved to be suitable nitrogen sources. Histidine and tryptophane, however, damaged the cells and killed them after a few weeks cultivation in the light, the cultures turning black with histidine and brown with tryptophane. The effect of histidine could be abolished by including pyridoxine or nicotinamide in the culture medium.     

Maternal and paternal contributions to egg size and egg number variation in the blackfin pearl killifish <Emphasis Type="Italic">Austrolebias nigripinnis</Emphasis>

Reproductive effort, egg number and egg size are traditionally considered to be ‘female’ life history traits. However, females often adjust the amount of resources allocated to reproduction depending on their mate, causing male environmental effects on life history traits. If females respond to male traits which are genetically variable, then male environmental effects contain indirect genetic effects. Estimates of how much of the total variation in life history traits originates from female effects versus male environmental effects, seems mostly lacking. We have investigated variation in rates of egg production and in egg size in the annual Argentinian blackfin pearl killifish Austrolebias nigripinnis, in a crossed design where males were exchanged repeatedly between females. Our analysis of phenotypic variance components of reproductive effort, egg size and egg number indicates that the amount of variation contributed by male environmental effects is equal (egg size, reproductive effort) or larger (egg number) than that between females. For egg size and number, we find that male environmental effects consist of a male random effect representing the average response of females to male phenotype, plus a female-male interaction term. This term can be understood as the deviation from the population mean of an individual female’s response. For reproductive effort, we find that the male environmental effect consists of an interaction term only. Random effects on egg size and number additionally vary in magnitude depending on the weekday where we collected eggs, probably due to cyclic variation in experimental conditions. Since we find that both male phenotype and environmental conditions affect egg size and number as determined by females, our results suggest that selection on these life history traits will be frequency-dependent.     

Genome-wide methylation and expression differences in HPV(+) and HPV(?) squamous cell carcinoma cell lines are consistent with divergent mechanisms of carcinogenesis

Oncogenic human papillomaviruses (HPV) are associated with nearly all cervical cancers and are increasingly important in the etiology of oropharyngeal tumors. HPV-associated head and neck squamous cell carcinomas (HNSCC) have distinct risk profiles and appreciate a prognostic advantage compared to HPV-negative HNSCC. Promoter hypermethylation is widely recognized as a mechanism in the progression of HNSCC, but the extent to which this mechanism is consistent between HPV(+) and HPV(−) tumors is unknown. To investigate the epigenetic regulation of gene expression in HPV-induced and carcinogen-induced cancers, we examined genome-wide DNA methylation and gene expression in HPV(+) and HPV(−) SCC cell lines. We used two platforms: the Illumina Infinium Methylation BeadArray and tiling arrays, and confirmed illustrative examples with pyrosequencing and quantitative PCR. These analyses indicate that HPV(+) cell lines have higher DNA methylation in genic and LINE-1 regions than HPV(−) cell lines. Differentially methylated loci between HPV(+) and HPV(−) cell lines significantly correlated with HPV-typed HNSCC primary tumor DNA methylation levels. Novel findings include higher promoter methylation of polycomb repressive complex 2 target genes in HPV(+) cells compared to HPV(−) cells and increased expression of DNMT3A in HPV(+) cells. Additionally, CDKN2A and KRT8 were identified as interaction hubs among genes with higher methylation and lower expression in HPV(−) cells. Conversely, RUNX2, IRS-1 and CCNA1 were major hubs with higher methylation and lower expression in HPV(+) cells. Distinct HPV(+) and HPV(−) epigenetic profiles should provide clues to novel targets for development of individualized therapeutic strategies.Key words: epigenetics, human papillomavirus, HNSCC, DNA methylation, squamous cell carcinoma, gene expression, microarrays, illumina infinium humanmethylation27 beadarray     

Building the perfect parasite: cell division in apicomplexa

Apicomplexans are pathogens responsible for malaria, toxoplasmosis, and crytposporidiosis in humans, and a wide range of livestock diseases. These unicellular eukaryotes are stealthy invaders, sheltering from the immune response in the cells of their hosts, while at the same time tapping into these cells as source of nutrients. The complexity and beauty of the structures formed during their intracellular development have made apicomplexans the darling of electron microscopists. Dramatic technological progress over the last decade has transformed apicomplexans into respectable genetic model organisms. Extensive genomic resources are now available for many apicomplexan species. At the same time, parasite transfection has enabled researchers to test the function of specific genes through reverse and forward genetic approaches with increasing sophistication. Transfection also introduced the use of fluorescent reporters, opening the field to dynamic real time microscopic observation. Parasite cell biologists have used these tools to take a fresh look at a classic problem: how do apicomplexans build the perfect invasion machine, the zoite, and how is this process fine-tuned to fit the specific niche of each pathogen in this ancient and very diverse group? This work has unearthed a treasure trove of novel structures and mechanisms that are the focus of this review.