Adult Drosophila melanogaster evolved for antibacterial defense invest in infection-induced expression of both humoral and cellular immunity genes

<p>Abstract</p> <p>Background</p> <p>While the transcription of innate immunity genes in response to bacterial infection has been well-characterised in the Drosophila model, we recently demonstrated the capacity for such transcription to evolve in flies selected for improved antibacterial defense. Here we use this experimental system to examine how insects invest in constitutive versus infection-induced transcription of immunity genes. These two strategies carry with them different consequences with respect to energetic and pleiotropic costs and may be more or less effective in improving defense depending on whether the genes contribute to humoral or cellular aspects of immunity.</p> <p>Findings</p> <p>Contrary to expectation we show that selection preferentially increased the infection-induced expression of both cellular and humoral immunity genes. Given their functional roles, infection induced increases in expression were expected for the humoral genes, while increases in constitutive expression were expected for the cellular genes. We also report a restricted ability to improve transcription of immunity genes that is on the order of 2-3 fold regardless of total transcription level of the gene.</p> <p>Conclusions</p> <p>The evolved increases in infection-induced expression of the cellular genes may result from specific cross talk with humoral pathways or from generalised strategies for enhancing immunity gene transcription. A failure to see improvements in constitutive expression of the cellular genes suggests either that increases might come at too great a cost or that patterns of expression in adults are decoupled from the larval phase where increases would be most effective. The similarity in fold change increase across all immunity genes may suggest a shared mechanism for the evolution of increased transcription in small, discrete units such as duplication of <it>cis</it>-regulatory elements.</p

Paclitaxel, vinorelbine and 5-fluorouracil in breast cancer patients pretreated with adjuvant anthracyclines

We investigated the activity and toxicity of a combination of vinorelbine (VNB), paclitaxel (PTX) and 5-fluorouracil (5-FU) continuous infusion administered as first-line chemotherapy in metastatic breast cancer patients pretreated with adjuvant anthracyclines. A total of 61 patients received a regimen consisting of VNB 25 mg m−2 on days 1 and 15, PTX 60 mg m−2 on days 1, 8 and 15 and continuous infusion of 5-FU at 200 mg m−2 every day. Cycles were repeated every 28 days. Disease response was evaluated by both RECIST and World Health Organization (WHO) criteria. Objective responses were recorded in 39 of 61 patients (64.0%) assessed by WHO and in 36 of 50 patients (72.0%) assessable by RECIST criteria. Complete remission occurred in 15 (24.6%) and 14 patients (28.0%), respectively. The median time to progression and overall survival of entire population was 10.6 and 27.3 months, respectively, and median duration of complete response was 14.8 months. The dose-limiting toxicity was myelosuppression (leucopenia grade 3/4 in 52.5% of patients). Grade 3/4 nonhaematologic toxicities included mucositis/diarrhoea in 13.1%, skin in 3.3% and cardiac in 1.6% of patients. Grade 2/3 neurotoxicity was observed in five patients (7.2%). The VNB, PTX and 5-FU continuous infusion combination regimen was active and manageable. Complete responses were frequent and durable

Spike Timing Dependent Plasticity Finds the Start of Repeating Patterns in Continuous Spike Trains

Experimental studies have observed Long Term synaptic Potentiation (LTP) when a presynaptic neuron fires shortly before a postsynaptic neuron, and Long Term Depression (LTD) when the presynaptic neuron fires shortly after, a phenomenon known as Spike Timing Dependant Plasticity (STDP). When a neuron is presented successively with discrete volleys of input spikes STDP has been shown to learn ‘early spike patterns’, that is to concentrate synaptic weights on afferents that consistently fire early, with the result that the postsynaptic spike latency decreases, until it reaches a minimal and stable value. Here, we show that these results still stand in a continuous regime where afferents fire continuously with a constant population rate. As such, STDP is able to solve a very difficult computational problem: to localize a repeating spatio-temporal spike pattern embedded in equally dense ‘distractor’ spike trains. STDP thus enables some form of temporal coding, even in the absence of an explicit time reference. Given that the mechanism exposed here is simple and cheap it is hard to believe that the brain did not evolve to use it

Drosophila Microcosms for Ecology and Evolution

International audienc

The Ecology of host-microbe interactions: from the study of model organisms to the protection of crops against pest arthropods - Synthesis of past and current work

Ecole Doctorale GAI

A geometric analysis of the macronutrient needs of Drosophila suzukii larvae

International audienceThe nutritional needs of animals largely depend on their ecology and habitat. Phenotypes and general performance often depend on the synergistic influence of multiple nutrients. These effects are currently studied within the geometric framework of nutrition. Contrary to its close relative Drosophila melanogaster, the invasive Spotted-Wing Drosophila, Drosophila suzukii, attacks fresh, undamaged fruit devoid of microbial growth. Different oviposition habits suggest different nutritional needs by the two species. We investigated the combined influence of carbohydrate and protein concentrations on the larval performance of a D. suzukii population. Proportions of individuals that survived until the adult stage were maximal at intermediate protein and low sugar concentrations. Larval development was shortest under high protein diets. Observations on this population are congruent with what is known of D. suzukii larval ecology, as ripening, undamaged fruit is generally poor in sugars and proteins in comparison to ripe, yeast-colonized fruit. We discuss the limitations of fly nutrition experiments based on laboratory food, such as ours, where the natural dynamics of microbial growth is neglected

Do traits separated by metamorphosis evolve independently? Concepts and methods

International audienceDespite the ubiquity of complex life cycles, we know little of the evolutionary constraints exerted by metamorphosis. Here, we present pitfalls and methods to answer whether animals with a complex life cycle can independently adapt to the environments encountered at each life stage, with a specific focus on the microevolution of quantitative characters. We first discuss challenges associated with study traits and populations. We further emphasize the benefits of using a combination of approaches. We then develop how multivariate methods can limit several issues by revealing genetic patterns that are invisible when only considering trait-by-trait genetic correlations. Finally, we detail how Lande's work on sexual dimorphism can be applied in measuring G matrices across life stages. The methods and tools described here will contribute towards building a predictive framework for trait evolution across life stages