Phylogenetic Codivergence Supports Coevolution of Mimetic Heliconius Butterflies

The unpalatable and warning-patterned butterflies _Heliconius erato_ and _Heliconius melpomene_ provide the best studied example of mutualistic Müllerian mimicry, thought – but rarely demonstrated – to promote coevolution. Some of the strongest available evidence for coevolution comes from phylogenetic codivergence, the parallel divergence of ecologically associated lineages. Early evolutionary reconstructions suggested codivergence between mimetic populations of _H. erato_ and _H. melpomene_, and this was initially hailed as the most striking known case of coevolution. However, subsequent molecular phylogenetic analyses found discrepancies in phylogenetic branching patterns and timing (topological and temporal incongruence) that argued against codivergence. We present the first explicit cophylogenetic test of codivergence between mimetic populations of _H. erato_ and _H. melpomene_, and re-examine the timing of these radiations. We find statistically significant topological congruence between multilocus coalescent population phylogenies of _H. erato_ and _H. melpomene_, supporting repeated codivergence of mimetic populations. Divergence time estimates, based on a Bayesian coalescent model, suggest that the evolutionary radiations of _H. erato_ and _H. melpomene_ occurred over the same time period, and are compatible with a series of temporally congruent codivergence events. This evidence supports a history of reciprocal coevolution between Müllerian co-mimics characterised by phylogenetic codivergence and parallel phenotypic change

A systematic analysis of host factors reveals a Med23-interferon-λ regulatory axis against herpes simplex virus type 1 replication

Herpes simplex virus type 1 (HSV-1) is a neurotropic virus causing vesicular oral or genital skin lesions, meningitis and other diseases particularly harmful in immunocompromised individuals. To comprehensively investigate the complex interaction between HSV-1 and its host we combined two genome-scale screens for host factors (HFs) involved in virus replication. A yeast two-hybrid screen for protein interactions and a RNA interference (RNAi) screen with a druggable genome small interfering RNA (siRNA) library confirmed existing and identified novel HFs which functionally influence HSV-1 infection. Bioinformatic analyses found the 358 HFs were enriched for several pathways and multi-protein complexes. Of particular interest was the identification of Med23 as a strongly anti-viral component of the largely pro-viral Mediator complex, which links specific transcription factors to RNA polymerase II. The anti-viral effect of Med23 on HSV-1 replication was confirmed in gain-of-function gene overexpression experiments, and this inhibitory effect was specific to HSV-1, as a range of other viruses including Vaccinia virus and Semliki Forest virus were unaffected by Med23 depletion. We found Med23 significantly upregulated expression of the type III interferon family (IFN-λ) at the mRNA and protein level by directly interacting with the transcription factor IRF7. The synergistic effect of Med23 and IRF7 on IFN-λ induction suggests this is the major transcription factor for IFN-λ expression. Genotypic analysis of patients suffering recurrent orofacial HSV-1 outbreaks, previously shown to be deficient in IFN-λ secretion, found a significant correlation with a single nucleotide polymorphism in the IFN-λ3 (IL28b) promoter strongly linked to Hepatitis C disease and treatment outcome. This paper describes a link between Med23 and IFN-λ, provides evidence for the crucial role of IFN-λ in HSV-1 immune control, and highlights the power of integrative genome-scale approaches to identify HFs critical for disease progression and outcome

Insecticidal Activity of Some Reducing Sugars Against the Sweet Potato Whitefly, Bemisia tabaci, Biotype B

The effects of 16 sugars (arabinose, cellobiose, fructose, galactose, gentiobiose, glucose, inositol, lactose, maltose, mannitol (a sugar alcohol), mannose, melibiose, ribose, sorbitol, trehalose, and xylose) on sweet potato whitefly Bemisia tabaci (Gennadius) (Hemiptera: Aleyrodidae) survival were determined using in vitro bioassays. Of these sugars, arabinose, mannose, ribose, and xylose were strongly inhibitory to both nymphal and adult survival. When 10% mannose was added to the nymphal diet, 10.5%, 1.0%, and 0% developed to the 2nd, 3rd, and 4th instars, respectively. When 10% arabinose was added, 10.8% and 0% of the nymphs molted to the 2nd and 3rd instars, respectively. Addition of 10% xylose or ribose completely terminated B. tabaci development, preventing the molt to the 2nd instar. With decreasing sugar concentrations the inhibitory effect was significantly reduced. In tests using adults, arabinose, galactose, inositol, lactose, maltose, mannitol, mannose, melibiose, ribose, sorbitol, trehalose, and xylose significantly reduced mean day survival. Mortality rates were highest when arabinose, mannitol, mannose, ribose, or xylose was added to the diet. Mean day survival was less than 2 days when adults were fed on diet containing 10% of any one of these five sugars. When lower concentrations of sugars were used there was a decrease in mortality. Mode of action studies revealed that toxicity was not due to the inhibition of alpha glucosidase (converts sucrose to glucose and fructose) and/or trehalulose synthase (converts sucrose to trehalulose) activity. The result of agarose gel electrophoresis of RT-PCR products of bacterial endosymbionts amplified from RNA isolated from whiteflies fed with 10% arabinose, mannose, or xylose indicated that the concentration of endosymbionts in mycetomes was not affected by the toxic sugars. Experiments in which B. tabaci were fed on diets that contained radio-labeled sucrose, methionine or inulin and one or none (control) of the highly toxic sugars showed that radioactivity (expressed in DPM) in the body, in excreted honeydew and/or carbon dioxide, was significantly reduced as compared to controls. Thus, it appears that the ability of insecticidal sugars to act as antifeedants is responsible for their toxicity to B. tabaci

Programmed Death (PD)-1-Deficient Mice Are Extremely Sensitive to Murine Hepatitis Virus Strain-3 (MHV-3) Infection

The inhibitory receptor programmed death-1 (PD-1) has the capacity to maintain peripheral tolerance and limit immunopathological damage; however, its precise role in fulminant viral hepatitis (FH) has yet to be described. Here, we investigated the functional mechanisms of PD-1 as related to FH pathogenesis induced by the murine hepatitis virus strain-3 (MHV-3). High levels of PD-1-positive CD4+, CD8+ T cells, NK cells and macrophages were observed in liver, spleen, lymph node and thymus tissues following MHV-3 infection. PD-1-deficient mice exhibited significantly higher expression of the effector molecule which initiates fibrinogen deposition, fibrinogen-like protein 2 (FGL2), than did their wild-type (WT) littermates. As a result, more severe tissue damage was produced and mortality rates were higher. Fluorescence double-staining revealed that FGL2 and PD-1 were not co-expressed on the same cells, while quantitative RT-PCR demonstrated that higher levels of IFN-γ and TNF-α mRNA transcription occurred in PD-1-deficient mice in response to MHV-3 infection. Conversely, in vivo blockade of IFN-γ and TNF-α led to efficient inhibition of FGL2 expression, greatly attenuated the development of tissue lesions, and ultimately reduced mortality. Thus, the up-regulation of FGL2 in PD-1-deficient mice was determined to be mediated by IFN-γ and TNF-α. Taken together, our results suggest that PD-1 signaling plays an essential role in decreasing the immunopathological damage induced by MHV-3 and that manipulation of this signal might be a useful strategy for FH immunotherapy

Plakophilin-2: a cell-cell adhesion plaque molecule of selective and fundamental importance in cardiac functions and tumor cell growth

Within the characteristic ensemble of desmosomal plaque proteins, the armadillo protein plakophilin-2 (Pkp2) is known as a particularly important regulatory component in the cytoplasmic plaques of various other cell–cell junctions, such as the composite junctions (areae compositae) of the myocardiac intercalated disks and in the variously-sized and -shaped complex junctions of permanent cell culture lines derived therefrom. In addition, Pkp2 has been detected in certain protein complexes in the nucleoplasm of diverse kinds of cells. Using a novel set of highly sensitive and specific antibodies, both kinds of Pkp2, the junctional plaque-bound and the nuclear ones, can also be localized to the cytoplasmic plaques of diverse non-desmosomal cell–cell junction structures. These are not only the puncta adhaerentia and the fasciae adhaerentes connecting various types of highly proliferative non-epithelial cells growing in culture but also some very proliferative states of cardiac interstitial cells and cardiac myxomata, including tumors growing in situ as well as fetal stages of heart development and cultures of valvular interstitial cells. Possible functions and assembly mechanisms of such Pkp2-positive cell–cell junctions as well as medical consequences are discussed

Cloud Computing As a Tool for Enhancing Ecological Goals?

Cloud computing has been introduced as a promising information technology (IT) that embodies not only economic advantages in terms of increased efficiency but also ecological gains through saving energy. The latter has become particularly important in view of the rising energy costs of IT. The present study analyzes whether necessary preconditions for accepting cloud computing as a new infrastructure, such as awareness and perceived net value, exist on the part of the users. The analysis is based on a combined research framework of the theory of reasoned action (TRA) and the technology acceptance model (TAM) in a cloud computing setting. Two consumer surveys, the one to elicit beliefs and the second to gain insight into the ranking of the variables, are employed. This study uses structural equation modeling (SEM) to evaluate the hypotheses. The results indicate support for the proposed research framework. Surprisingly however, the ecological factor does not play a role in forming cloud computing intentions, regardless of prior knowledge or experience. Empirical evidence of this study suggests increasing efforts for informing actual and potential users, particularly in respect to possible ecological advantages through applying the new IT infrastructure

Optimal-Foraging Predator Favors Commensalistic Batesian Mimicry

BACKGROUND:Mimicry, in which one prey species (the Mimic) imitates the aposematic signals of another prey (the Model) to deceive their predators, has attracted the general interest of evolutionary biologists. Predator psychology, especially how the predator learns and forgets, has recently been recognized as an important factor in a predator-prey system. This idea is supported by both theoretical and experimental evidence, but is also the source of a good deal of controversy because of its novel prediction that in a Model/Mimic relationship even a moderately unpalatable Mimic increases the risk of the Model (quasi-Batesian mimicry). METHODOLOGY/PRINCIPAL FINDINGS:We developed a psychology-based Monte Carlo model simulation of mimicry that incorporates a "Pavlovian" predator that practices an optimal foraging strategy, and examined how various ecological and psychological factors affect the relationships between a Model prey species and its Mimic. The behavior of the predator in our model is consistent with that reported by experimental studies, but our simulation's predictions differed markedly from those of previous models of mimicry because a more abundant Mimic did not increase the predation risk of the Model when alternative prey were abundant. Moreover, a quasi-Batesian relationship emerges only when no or very few alternative prey items were available. Therefore, the availability of alternative prey rather than the precise method of predator learning critically determines the relationship between Model and Mimic. Moreover, the predation risk to the Model and Mimic is determined by the absolute density of the Model rather than by its density relative to that of the Mimic. CONCLUSIONS/SIGNIFICANCE:Although these predictions are counterintuitive, they can explain various kinds of data that have been offered in support of competitive theories. Our model results suggest that to understand mimicry in nature it is important to consider the likely presence of alternative prey and the possibility that predation pressure is not constant

“A Hideous Torture on Himself”: Madness and Self-Mutilation in Victorian Literature

This paper suggests that late nineteenth-century definitions of self-mutilation, a new category of psychiatric symptomatology, were heavily influenced by the use of selfinjury as a rhetorical device in the novel, for the literary text held a high status in Victorian psychology. In exploring Dimmesdale’s “self-mutilation” in The Scarlet Letter in conjunction with psychiatric case histories, the paper indicates a number of common techniques and themes in literary and psychiatric texts. As well as illuminating key elements of nineteenth-century conceptions of the self, and the relation of mind and body through ideas of madness, this exploration also serves to highlight the social commentary implicit in many Victorian medical texts. Late nineteenth-century England, like mid-century New England, required the individual to help himself and, simultaneously, others; personal charity and individual philanthropy were encouraged, while state intervention was often presented as dubious. In both novel and psychiatric text, self-mutilation is thus presented as the ultimate act of selfish preoccupation, particularly in cases on the “borderlands” of insanity