Host plant quality,selection history and trade-offs shape the immune responses of Manduca sexta

Immune defences are an important component of fitness. Yet susceptibility to pathogens is common, suggesting the presence of ecological and evolutionary limitations on immune defences. Here, we use structural equation modelling to quantify the direct effects of resource quality and selection history, and their indirect effects mediated via body condition prior to an immune challenge on encapsulation and melanization immune defences in the tobacco hornworm, Manduca sexta. We also investigate allocation trade-offs among immune defences and growth rate following an immune challenge. We found considerable variation in the magnitude and direction of the direct effects of resource quality and selection history on immune defences and their indirect effects mediated via body condition and allocation trade-offs. Greater resource quality and evolutionary exposure to pathogens had positive direct effects on encapsulation and melanization. The indirect effect of resource quality on encapsulation mediated via body condition was substantial, whereas indirect effects on melanization were negligible. Individuals in better condition prior to the immune challenge had greater encapsulation; however, following the immune challenge, greater encapsulation traded off with slower growth rate. Our study demonstrates the importance of experimentally and analytically disentangling the relative contributions of direct and indirect effects to understand variation in immune defences.     

Light intensity is a limiting factor to the inland expansion of Cape ivy (<Emphasis Type=Italic>Delairea odorata</Emphasis>)

Cape ivy (Delairea odorata) is a highly invasive climbing perennial vine that is primarily distributed in coastal communities of California and Oregon, with patchy infestations in some inland riparian areas. In this study, we evaluated light as a potential environmental limitation to the spread of Cape ivy into inland regions of the western United States. Cape ivy was collected from four locations representing the north to south range. Plants were grown for 9 to 11 weeks in full sunlight and under two shade regimes (20 and 6% of full sunlight). The experiment was conducted twice at two temperature regimes. Results show some within- and among-population variability, with the southernmost San Diego County population having the highest biomass under the warmer growing conditions and the three northern populations responding most favorably in the cooler growing conditions. Despite the minor differences within and between populations, Cape ivy grew very poorly in full sunlight in both experiments. Although plants growing under 6% light grew better than those in full sunlight, they were far less robust compared to plants growing at 20% light. Our results indicate that while Cape ivy will not persist in areas with prolonged high intensity sunlight, characterized by much of the interior regions of California and Oregon, it is expected to invade and spread in areas with reduced light, including coastal regions frequently exposed to fog or cloudy conditions, or sub-canopy layers of riparian forests or woodlands. These communities should be the target areas for early detection and rapid response programs to prevent further Cape ivy invasion.     

A New Statistic to Evaluate Imputation Reliability

Background

As the amount of data from genome wide association studies grows dramatically, many interesting scientific questions require imputation to combine or expand datasets. However, there are two situations for which imputation has been problematic: (1) polymorphisms with low minor allele frequency (MAF), and (2) datasets where subjects are genotyped on different platforms. Traditional measures of imputation cannot effectively address these problems.

Methodology/Principal Findings

We introduce a new statistic, the imputation quality score (IQS). In order to differentiate between well-imputed and poorly-imputed single nucleotide polymorphisms (SNPs), IQS adjusts the concordance between imputed and genotyped SNPs for chance. We first evaluated IQS in relation to minor allele frequency. Using a sample of subjects genotyped on the Illumina 1 M array, we extracted those SNPs that were also on the Illumina 550 K array and imputed them to the full set of the 1 M SNPs. As expected, the average IQS value drops dramatically with a decrease in minor allele frequency, indicating that IQS appropriately adjusts for minor allele frequency. We then evaluated whether IQS can filter poorly-imputed SNPs in situations where cases and controls are genotyped on different platforms. Randomly dividing the data into “cases” and “controls”, we extracted the Illumina 550 K SNPs from the cases and imputed the remaining Illumina 1 M SNPs. The initial Q-Q plot for the test of association between cases and controls was grossly distorted (λ = 1.15) and had 4016 false positives, reflecting imputation error. After filtering out SNPs with IQS<0.9, the Q-Q plot was acceptable and there were no longer false positives. We then evaluated the robustness of IQS computed independently on the two halves of the data. In both European Americans and African Americans the correlation was >0.99 demonstrating that a database of IQS values from common imputations could be used as an effective filter to combine data genotyped on different platforms.

Conclusions/Significance

IQS effectively differentiates well-imputed and poorly-imputed SNPs. It is particularly useful for SNPs with low minor allele frequency and when datasets are genotyped on different platforms.     

Cholera toxin promotes the induction of regulatory T cells specific for bystander antigens by modulating dendritic cell activation

It has previously been reported that cholera toxin (CT) is a potent mucosal adjuvant that enhances Th2 or mixed Th1/Th2 type responses to coadministered foreign Ag. Here we demonstrate that CT also promotes the generation of regulatory T (Tr) cells against bystander Ag. Parenteral immunization of mice with Ag in the presence of CT induced T cells that secreted high levels of IL-4 and IL-10 and lower levels of IL-5 and IFN-gamma. Ag-specific CD4(+) T cell lines and clones generated from these mice had cytokine profiles characteristic of Th2 or type 1 Tr cells, and these T cells suppressed IFN-gamma production by Th1 cells. Furthermore, adoptive transfer of bone marrow-derived dendritic cells (DC) incubated with Ag and CT induced T cells that secreted IL-4 and IL-10 and low concentrations of IL-5. It has previously been shown that IL-10 promotes the differentiation or expansion of type 1 Tr cells. Here we found that CT synergized with low doses of LPS to induce IL-10 production by immature DC. CT also enhanced the expression of CD80, CD86, and OX40 (CD134) on DC and induced the secretion of the chemokine, macrophage inflammatory protein-2 (MIP-2), but inhibited LPS-driven induction of CD40 and ICAM-I expression and production of the inflammatory cytokines/chemokines IL-12, TNF-alpha, MIP-1alpha, MIP-1beta, and monocyte chemoattractant protein-1. Our findings suggest that CT induces maturation of DC, but, by inducing IL-10, inhibiting IL-12, and selectively affecting surface marker expression, suppresses the generation of Th1 cells and promotes the induction of T cells with regulatory activity.     

RNA sequencing reveals two major classes of gene expression levels in metazoan cells

The expression level of a gene is often used as a proxy for determining whether the protein or RNA product is functional in a cell or tissue. Therefore, it is of fundamental importance to understand the global distribution of gene expression levels, and to be able to interpret it mechanistically and functionally. Here we use RNA sequencing (RNA‐seq) of mouse Th2 cells, coupled with a range of other techniques, to show that all genes can be separated, based on their expression abundance, into two distinct groups: one group comprised of lowly expressed and putatively non‐functional mRNAs, and the other of highly expressed mRNAs with active chromatin marks at their promoters. These observations are confirmed in many other microarray and RNA‐seq data sets of metazoan cell types.     

The Ras-ERK MAPK regulatory network controls dedifferentiation in Caenorhabditis elegans germline

How a committed cell can be reverted to an undifferentiated state is a central question in stem cell biology. This process, called dedifferentiation, is likely to be important for replacing stem cells as they age or get damaged. Tremendous progress has been made in understanding this fundamental process, but its mechanisms are poorly understood. Here we demonstrate that the aberrant activation of Ras-ERK MAPK signaling promotes cellular dedifferentiation in the Caenorhabditis elegans germline. To activate signaling, we removed two negative regulators, the PUF-8 RNA-binding protein and LIP-1 dual specificity phosphatase. The removal of both of these two regulators caused secondary spermatocytes to dedifferentiate and begin mitotic divisions. Interestingly, reduction of Ras-ERK MAPK signaling, either by mutation or chemical inhibition, blocked the initiation of dedifferentiation. By RNAi screening, we identified RSKN-1/P90(RSK) as a downstream effector of MPK-1/ERK that is critical for dedifferentiation: rskn-1 RNAi suppressed spermatocyte dedifferentiation and instead induced meiotic divisions. These regulators are broadly conserved, suggesting that similar molecular circuitry may control cellular dedifferentiation in other organisms, including humans.