Lack of phenotypic and evolutionary cross-resistance against parasitoids and pathogens in Drosophila melanogaster

BackgroundWhen organisms are attacked by multiple natural enemies, the evolution of a resistance mechanism to one natural enemy will be influenced by the degree of cross-resistance to another natural enemy. Cross-resistance can be positive, when a resistance mechanism against one natural enemy also offers resistance to another; or negative, in the form of a trade-off, when an increase in resistance against one natural enemy results in a decrease in resistance against another. Using Drosophila melanogaster, an important model system for the evolution of invertebrate immunity, we test for the existence of cross-resistance against parasites and pathogens, at both a phenotypic and evolutionary level.MethodsWe used a field strain of D. melanogaster to test whether surviving parasitism by the parasitoid Asobara tabida has an effect on the resistance against Beauveria bassiana, an entomopathogenic fungus; and whether infection with the microsporidian Tubulinosema kingi has an effect on the resistance against A. tabida. We used lines selected for increased resistance to A. tabida to test whether increased parasitoid resistance has an effect on resistance against B. bassiana and T. kingi. We used lines selected for increased tolerance against B. bassiana to test whether increased fungal resistance has an effect on resistance against A. tabida.Results/ConclusionsWe found no positive cross-resistance or trade-offs in the resistance to parasites and pathogens. This is an important finding, given the use of D. melanogaster as a model system for the evolution of invertebrate immunity. The lack of any cross-resistance to parasites and pathogens, at both the phenotypic and the evolutionary level, suggests that evolution of resistance against one class of natural enemies is largely independent of evolution of resistance against the other

Non-destructive seed detection in mandarins: comparison of automatic threshold methods FLASH and COMSPIRA MRIs

Here, we review different methods for non-destructive horticultural produce size determination, focusing on electronic technologies capable of measuring fruit volume. The usefulness of produce size estimation is justified and a comprehensive classification system of the existing electronic techniques to determine dimensional size is proposed. The different systems identified are compared in terms of their versatility, precision and throughput. There is general agreement in considering that online measurement of axes, perimeter and projected area has now been achieved. Nevertheless, rapid and accurate volume determination of irregular-shaped produce, as needed for density sorting, has only become available in the past few years. An important application of density measurement is soluble solids content (SSC) sorting. If the range of SSC in the batch is narrow and a large number of classes are desired, accurate volume determination becomes important. A good alternative for fruit three-dimensional surface reconstruction, from which volume and surface area can be computed, is the combination of height profiles from a range sensor with a two-dimensional object image boundary from a solid-state camera (brightness image) or from the range sensor itself (intensity image). However, one of the most promising technologies in this field is 3-D multispectral scanning, which combines multispectral data with 3-D surface reconstruction

Rapid activation of epithelial-mesenchymal transition drives PARP inhibitor resistance in Brca2-mutant mammary tumours

Tumours defective in the DNA homologous recombination repair pathway can be effectively treated with poly (ADP-ribose) polymerase (PARP) inhibitors; these have proven effective in clinical trials in patients with BRCA gene function-defective cancers. However, resistance observed in both pre-clinical and clinical studies is likely to impact on this treatment strategy. Over-expression of phosphoglycoprotein (P-gp) has been previously suggested as a mechanism of resistance to the PARP inhibitor olaparib in mouse models of Brca1/2-mutant breast cancer. Here, we report that in a Brca2 model treated with olaparib, P-gp upregulation is observed but is not sufficient to confer resistance. Furthermore, resistant/relapsed tumours do not show substantial changes in PK/PD of olaparib, do not downregulate PARP1 or re-establish double stranded DNA break repair by homologous recombination, all previously suggested as mechanisms of resistance. However, resistance is strongly associated with epithelial-mesenchymal transition (EMT) and treatment-naïve tumours given a single dose of olaparib upregulate EMT markers within one hour. Therefore, in this model, olaparib resistance is likely a product of an as-yet unidentified mechanism associated with rapid transition to the mesenchymal phenotype

Dog Burials Associated with Human Burials in the West Indies during the Early Pre-Columbian Ceramic Age (500 BC-600 AD)

Across the Caribbean, the widespread presence of canine remains at archaeological sites from the Saladoid period raises questions about the role of “man’s best friend.” Dog (Canis familiaris) remains have been found located in both refuse middens and burials adjacent to human graves in a number of sites in the French Antilles and Barbuda, West Indies. This paper will critically examine dog remains and discuss the varied duality of the dog’s role in the Saladoid world: from food source to lifelong companion. The importance of dogs within Amerindian sites from Saint Martin, the Guadeloupe archipelago, Martinique and Barbuda will be explored from a zooarchaeological perspective, concluding with a critical discussion of changes in cultural patterns, as seen through the decline in dog remains during the Troumassoid and Suazoid period at the sites in the French Antilles. Résumé Sépultures de chiens associées à des sépultures humaines dans les Petites Antilles à l’Âge du Néoindien ancien (500 av. – 600 ap. J.-C.). Dans les Antilles, la présence généralisée de restes de chiens sur les sites de la période céramique ancienne Saladoïde soulève des questions sur le rôle de ce « meilleur ami de l’homme ». En effet, des chiens (Canis familiaris) ont été trouvés aussi bien dans des zones de rejets, qu’enterrés aux côtés de sépultures humaines dans un certain nombre de sites des Petites Antilles. Ce document examinera ces restes de chiens de façon critique et décrira les morphologies particulières des chiens des sites amérindiens de l’île de Saint-Martin, l\u27archipel de la Guadeloupe, la Martinique et de l’île de Barbuda, dans une perspective archéozoologique. Une discussion critique portera sur l\u27évolution des changements des modèles culturels, comme celui de la chute drastique des chiens enterrés pendant les périodes archéologiques plus tardives, Troumassoïde et Suazoïde, des sites des Antilles françaises. Enfin, la discussion portera sur la dualité du rôle du chien dans le monde Saladoïde, à la fois source de nourriture et compagnon de vie

Global analysis of gene expression in NGF-deprived sympathetic neurons identifies molecular pathways associated with cell death

Developing sympathetic neurons depend on nerve growth factor (NGF) for survival and die by apoptosis after NGF withdrawal. This process requires de novo gene expression but only a small number of genes induced by NGF deprivation have been identified so far, either by a candidate gene approach or in mRNA differential display experiments. This is partly because it is difficult to obtain large numbers of sympathetic neurons for in vitro studies. Here, we describe for the first time, how advances in gene microarray technology have allowed us to investigate the expression of all known genes in sympathetic neurons cultured in the presence and absence of NGF

RNA-Seq Differentiates Tumour and Host mRNA Expression Changes Induced by Treatment of Human Tumour Xenografts with the VEGFR Tyrosine Kinase Inhibitor Cediranib.

Pre-clinical models of tumour biology often rely on propagating human tumour cells in a mouse. In order to gain insight into the alignment of these models to human disease segments or investigate the effects of different therapeutics, approaches such as PCR or array based expression profiling are often employed despite suffering from biased transcript coverage, and a requirement for specialist experimental protocols to separate tumour and host signals. Here, we describe a computational strategy to profile transcript expression in both the tumour and host compartments of pre-clinical xenograft models from the same RNA sample using RNA-Seq. Key to this strategy is a species-specific mapping approach that removes the need for manipulation of the RNA population, customised sequencing protocols, or prior knowledge of the species component ratio. The method demonstrates comparable performance to species-specific RT-qPCR and a standard microarray platform, and allowed us to quantify gene expression changes in both the tumour and host tissue following treatment with cediranib, a potent vascular endothelial growth factor receptor tyrosine kinase inhibitor, including the reduction of multiple murine transcripts associated with endothelium or vessels, and an increase in genes associated with the inflammatory response in response to cediranib. In the human compartment, we observed a robust induction of hypoxia genes and a reduction in cell cycle associated transcripts. In conclusion, the study establishes that RNA-Seq can be applied to pre-clinical models to gain deeper understanding of model characteristics and compound mechanism of action, and to identify both tumour and host biomarkers

An Integrated Transcriptomic and Meta-Analysis of Hepatoma Cells Reveals Factors That Influence Susceptibility to HCV Infection

Hepatitis C virus (HCV) is a global problem. To better understand HCV infection researchers employ in vitro HCV cell-culture (HCVcc) systems that use Huh-7 derived hepatoma cells that are particularly permissive to HCV infection. A variety of hyper-permissive cells have been subcloned for this purpose. In addition, subclones of Huh-7 which have evolved resistance to HCV are available. However, the mechanisms of susceptibility or resistance to infection among these cells have not been fully determined. In order to elucidate mechanisms by which hepatoma cells are susceptible or resistant to HCV infection we performed genome-wide expression analyses of six Huh-7 derived cell cultures that have different levels of permissiveness to infection. A great number of genes, representing a wide spectrum of functions are differentially expressed between cells. To focus our investigation, we identify host proteins from HCV replicase complexes, perform gene expression analysis of three HCV infected cells and conduct a detailed analysis of differentially expressed host factors by integrating a variety of data sources. Our results demonstrate that changes relating to susceptibility to HCV infection in hepatoma cells are linked to the innate immune response, secreted signal peptides and host factors that have a role in virus entry and replication. This work identifies both known and novel host factors that may influence HCV infection. Our findings build upon current knowledge of the complex interplay between HCV and the host cell, which could aid development of new antiviral strategies

Common dysregulation of Wnt/Frizzled receptor elements in human hepatocellular carcinoma

Dysregulation of growth factors and their receptors is central to human hepatocellular carcinoma (HCC). We previously demonstrated that the Frizzled-7 membrane receptor mediating the Wnt signalling can activate the β-catenin pathway and promotes malignancy in human hepatitis B virus-related HCCs. Expression patterns of all the 10 Frizzled receptors, and their extracellular soluble autoparacrine regulators (19 Wnt activators and 4 sFRP inhibitors) were assessed by real-time RT–PCR in 62 human HCC of different etiologies and their matched peritumorous areas. Immunostaining was performed to localise Frizzled on cell types in liver tissues. Regulation of three known Frizzled-dependent pathways (β-catenin, protein kinase C, and C-Jun NH2-terminal kinase) was measured in tissues by western blot. We found that eight Frizzled-potentially activating events were pleiotropically dysregulated in 95% HCC and 68% peritumours as compared to normal livers (upregulations of Frizzled-3/6/7 and Wnt3/4/5a, or downregulation of sFRP1/5), accumulating gradually with severity of fibrosis in peritumours and loss of differentiation status in tumours. The hepatocytes supported the Wnt/Frizzled signalling since specifically overexpressing Frizzled receptors in liver tissues. Dysregulation of the eight Frizzled-potentially activating events was associated with differential activation of the three known Frizzled-dependent pathways. This study provides an extensive analysis of the Wnt/Frizzled receptor elements and reveals that the dysregulation may be one of the most common and earliest events described thus far during hepatocarcinogenesis