Role of genetic and social factors in modulating the efficiency of division of labour in social insects

Summary : Division of labour is one of the most fascinating aspects of social insects. The efficient allocation of individuals to a multitude of different tasks requires a dynamic adjustment in response to the demands of a changing environment. A considerable number of theoretical models have focussed on identifying the mechanisms allowing colonies to perform efficient task allocation. The large majority of these models are built on the observation that individuals in a colony vary in their propensity (response threshold) to perform different tasks. Since individuals with a low threshold for a given task stimulus are more likely to perform that task than individuals with a high threshold, infra-colony variation in individual thresholds results in colony division of labour. These theoretical models suggest that variation in individual thresholds is affected by the within-colony genetic diversity. However, the models have not considered the genetic architecture underlying the individual response thresholds. This is important because a better understanding of division of labour requires determining how genotypic variation relates to differences in infra-colony response threshold distributions. In this thesis, we investigated the combined influence on task allocation efficiency of both, the within-colony genetic variability (stemming from variation in the number of matings by queens) and the number of genes underlying the response thresholds. We used an agent-based simulator to model a situation where workers in a colony had to perform either a regulatory task (where the amount of a given food item in the colony had to be maintained within predefined bounds) or a foraging task (where the quantity of a second type of food item collected had to be the highest possible). The performance of colonies was a function of workers being able to perform both tasks efficiently. To study the effect of within-colony genetic diversity, we compared the performance of colonies with queens mated with varying number of males. On the other hand, the influence of genetic architecture was investigated by varying the number of loci underlying the response threshold of the foraging and regulatory tasks. Artificial evolution was used to evolve the allelic values underlying the tasks thresholds. The results revealed that multiple matings always translated into higher colony performance, whatever the number of loci encoding the thresholds of the regulatory and foraging tasks. However, the beneficial effect of additional matings was particularly important when the genetic architecture of queens comprised one or few genes for the foraging task's threshold. By contrast, higher number of genes encoding the foraging task reduced colony performance with the detrimental effect being stronger when queens had mated with several males. Finally, the number of genes determining the threshold for the regulatory task only had a minor but incremental effect on colony performance. Overall, our numerical experiments indicate the importance of considering the effects of queen mating frequency, genetic architecture underlying task thresholds and the type of task performed when investigating the factors regulating the efficiency of division of labour in social insects. In this thesis we also investigate the task allocation efficiency of response threshold models and compare them with neural networks. While response threshold models are widely used amongst theoretical biologists interested in division of labour in social insects, our simulation reveals that they perform poorly compared to a neural network model. A major shortcoming of response thresholds is that they fail at one of the most crucial requirement of division of labour, the ability of individuals in a colony to efficiently switch between tasks under varying environmental conditions. Moreover, the intrinsic properties of the threshold models are that they lead to a large proportion of idle workers. Our results highlight these limitations of the response threshold models and provide an adequate substitute. Altogether, the experiments presented in this thesis provide novel contributions to the understanding of how division of labour in social insects is influenced by queen mating frequency and genetic architecture underlying worker task thresholds. Moreover, the thesis also provides a novel model of the mechanisms underlying worker task allocation that maybe more generally applicable than the widely used response threshold models. Resumé : La répartition du travail est l'un des aspects les plus fascinants des insectes vivant en société. Une allocation efficace de la multitude de différentes tâches entre individus demande un ajustement dynamique afin de répondre aux exigences d'un environnement en constant changement. Un nombre considérable de modèles théoriques se sont attachés à identifier les mécanismes permettant aux colonies d'effectuer une allocation efficace des tâches. La grande majorité des ces modèles sont basés sur le constat que les individus d'une même colonie diffèrent dans leur propension (inclination à répondre) à effectuer différentes tâches. Etant donné que les individus possédant un faible seuil de réponse à un stimulus associé à une tâche donnée sont plus disposés à effectuer cette dernière que les individus possédant un seuil élevé, les différences de seuils parmi les individus vivant au sein d'une même colonie mènent à une certaine répartition du travail. Ces modèles théoriques suggèrent que la variation des seuils des individus est affectée par la diversité génétique propre à la colonie. Cependant, ces modèles ne considèrent pas la structure génétique qui est à la base des seuils de réponse individuels. Ceci est très important car une meilleure compréhension de la répartition du travail requière de déterminer de quelle manière les variations génotypiques sont associées aux différentes distributions de seuils de réponse à l'intérieur d'une même colonie. Dans le cadre de cette thèse, nous étudions l'influence combinée de la variabilité génétique d'une colonie (qui prend son origine dans la variation du nombre d'accouplements des reines) avec le nombre de gènes supportant les seuils de réponse, vis-à-vis de la performance de l'allocation des tâches. Nous avons utilisé un simulateur basé sur des agents pour modéliser une situation où les travailleurs d'une colonie devaient accomplir une tâche de régulation (1a quantité d'une nourriture donnée doit être maintenue à l'intérieur d'un certain intervalle) ou une tâche de recherche de nourriture (la quantité d'une certaine nourriture doit être accumulée autant que possible). Dans ce contexte, 'efficacité des colonies tient en partie des travailleurs qui sont capable d'effectuer les deux tâches de manière efficace. Pour étudier l'effet de la diversité génétique d'une colonie, nous comparons l'efficacité des colonies possédant des reines qui s'accouplent avec un nombre variant de mâles. D'autre part, l'influence de la structure génétique a été étudiée en variant le nombre de loci à la base du seuil de réponse des deux tâches de régulation et de recherche de nourriture. Une évolution artificielle a été réalisée pour évoluer les valeurs alléliques qui sont à l'origine de ces seuils de réponse. Les résultats ont révélé que de nombreux accouplements se traduisaient toujours en une plus grande performance de la colonie, quelque soit le nombre de loci encodant les seuils des tâches de régulation et de recherche de nourriture. Cependant, les effets bénéfiques d'accouplements additionnels ont été particulièrement important lorsque la structure génétique des reines comprenait un ou quelques gènes pour le seuil de réponse pour la tâche de recherche de nourriture. D'autre part, un nombre plus élevé de gènes encodant la tâche de recherche de nourriture a diminué la performance de la colonie avec un effet nuisible d'autant plus fort lorsque les reines s'accouplent avec plusieurs mâles. Finalement, le nombre de gènes déterminant le seuil pour la tâche de régulation eu seulement un effet mineur mais incrémental sur la performance de la colonie. Pour conclure, nos expériences numériques révèlent l'importance de considérer les effets associés à la fréquence d'accouplement des reines, à la structure génétique qui est à l'origine des seuils de réponse pour les tâches ainsi qu'au type de tâche effectué au moment d'étudier les facteurs qui régulent l'efficacité de la répartition du travail chez les insectes vivant en communauté. Dans cette thèse, nous étudions l'efficacité de l'allocation des tâches des modèles prenant en compte des seuils de réponses, et les comparons à des réseaux de neurones. Alors que les modèles basés sur des seuils de réponse sont couramment utilisés parmi les biologistes intéressés par la répartition des tâches chez les insectes vivant en société, notre simulation montre qu'ils se révèlent peu efficace comparé à un modèle faisant usage de réseaux de neurones. Un point faible majeur des seuils de réponse est qu'ils échouent sur un point crucial nécessaire à la répartition des tâches, la capacité des individus d'une colonie à commuter efficacement entre des tâches soumises à des conditions environnementales changeantes. De plus, les propriétés intrinsèques des modèles basés sur l'utilisation de seuils conduisent à de larges populations de travailleurs inactifs. Nos résultats mettent en évidence les limites de ces modèles basés sur l'utilisation de seuils et fournissent un substitut adéquat. Ensemble, les expériences présentées dans cette thèse fournissent de nouvelles contributions pour comprendre comment la répartition du travail chez les insectes vivant en société est influencée par la fréquence d'accouplements des reines ainsi que par la structure génétique qui est à l'origine, pour un travailleur, du seuil de réponse pour une tâche. De plus, cette thèse fournit également un nouveau modèle décrivant les mécanismes qui sont à l'origine de l'allocation des tâches entre travailleurs, mécanismes qui peuvent être appliqué de manière plus générale que ceux couramment utilisés et basés sur des seuils de réponse.

Effects of dinner composition on postprandial macronutrient oxidation in prepubertal girls.

OBJECTIVE: To see whether a fat-rich (50%) evening meal promoted fat oxidation and a different spontaneous food intake on the following day at breakfast than a meal with a lower fat content (20%) in 10 prepubertal obese girls. RESEARCH METHODS AND PROCEDURES: The postabsorptive and postprandial (10.5 hours) energy expenditure after a low-fat (LF) (20% fat, 68% carbohydrate, 12% protein) and an isocaloric (2.1 MJ) and isoproteic high-fat (HF; 50% fat, 38% carbohydrate, 12% protein) meal were measured by indirect calorimetry. RESULTS: Fat oxidation was not significantly different after the two meals [LF, 31 +/- 9 vs. HF, 35 +/- 9 g/10.5 hours, p = not significant (NS)]. The girls oxidized 1.8 +/- 0.9 times more fat than that ingested (11.1 grams) with the LF meal vs. 0.3 +/- 0.3 times more fat than that ingested (27.1 grams) with the HF meal (p < 0.001). Carbohydrate oxidation was significantly higher after an LF than an HF meal (39 +/- 12 vs. 29 +/- 9 g/10.5 hours, p < 0,05). At breakfast, the girls spontaneously ingested a similar amount of energy (1.5 +/- 0.7 vs. 1.5 +/- 0.6 MJ, p = NS) and macronutrient proportions (fat, 23% vs. 26%, p = NS; protein, 9% vs. 10%; carbohydrate, 68% vs. 64%,) independently of their having eaten an HF or an LF dinner. DISCUSSION: An HF dinner did not stimulate fat oxidation, and no compensatory effect in spontaneous food intake was observed during breakfast the following morning. Cumulated total fat oxidation after dinner was higher than total fat ingested at dinner, but a much larger negative fat balance was observed after the LF meal. Spontaneous energy and nutrient intakes at breakfast were similar after LF and HF isocaloric, isoproteic dinners. This study points out the lack of sensitivity of short-term fat balance to subsequently readjust fat intake and emphasizes the importance of an LF meal to avoid transient positive fat imbalance.

Macrophage migration inhibitory factor: a regulator of innate immunity.

For more than a quarter of a century, macrophage migration inhibitory factor (MIF) has been a mysterious cytokine. In recent years, MIF has assumed an important role as a pivotal regulator of innate immunity. MIF is an integral component of the host antimicrobial alarm system and stress response that promotes the pro-inflammatory functions of immune cells. A rapidly increasing amount of literature indicates that MIF is implicated in the pathogenesis of sepsis, and inflammatory and autoimmune diseases, suggesting that MIF-directed therapies might offer new treatment opportunities for human diseases in the future.

Comparative population genomics in animals uncovers the determinants of genetic diversity.

Genetic diversity is the amount of variation observed between DNA sequences from distinct individuals of a given species. This pivotal concept of population genetics has implications for species health, domestication, management and conservation. Levels of genetic diversity seem to vary greatly in natural populations and species, but the determinants of this variation, and particularly the relative influences of species biology and ecology versus population history, are still largely mysterious. Here we show that the diversity of a species is predictable, and is determined in the first place by its ecological strategy. We investigated the genome-wide diversity of 76 non-model animal species by sequencing the transcriptome of two to ten individuals in each species. The distribution of genetic diversity between species revealed no detectable influence of geographic range or invasive status but was accurately predicted by key species traits related to parental investment: long-lived or low-fecundity species with brooding ability were genetically less diverse than short-lived or highly fecund ones. Our analysis demonstrates the influence of long-term life-history strategies on species response to short-term environmental perturbations, a result with immediate implications for conservation policies.

Dose reduction of epoetin-alpha in the prevention of chemotherapy-induced anaemia.

INTRODUCTION: Anaemia during chemotherapy is often left untreated. Erythropoiesis-stimulating agents are frequently used to treat overt anaemia. Their prophylactic use, however, remains controversial and raises concerns about cost-effectiveness. Therefore, we assessed the efficacy of a dose-reduction schedule in anaemia prophylaxis. MATERIALS AND METHODS: The study included patients with untreated solid tumours about to receive platinum-based chemotherapy and had haemoglobin (Hb) levels ≥11 g/dL. Epoetin-α was administered at a dose level of 3 × 10,000 U weekly as soon as Hb descended to < 13 g/dL. Dose reductions to 3 × 4,000 U and 3 × 2,000 U weekly were planned in 4-week intervals if Hb stabilised in the range of 11-13 g/dL. Upon ascending to ≥13 g/dL, epoetin was discontinued. Iron supplements of 100 mg intravenous doses were given weekly. Of 37 patients who enrolled, 33 could be evaluated. RESULTS AND DISCUSSION: Their median Hb level was 13.7 (10.9-16.2) g/dL at baseline and descended to 11.0 (7.4-13.8) g/dL by the end of chemotherapy. Anaemia (Hb < 10 g/dL) was prevented in 24 patients (73%). The mean dose requirement for epoetin-α was 3 × 5,866 U per week per patient, representing a dose reduction of 41%. Treatment failed in nine patients (27%), in part due to epoetin-α resistance in four (12%) and blood transfusion in three (9%) patients. CONCLUSION: Dose reduction was as effective as fixed doses in anaemia prophylaxis but reduced the amount of prescribed epoetin substantially.

Monte Carlo simulations of metasomatic enrichment in the lithosphere and implications for the source of alkaline basalts

One hypothesis for the origin of alkaline lavas erupted on oceanic islands and in intracontinental settings is that they represent the melts of amphibole-rich veins in the lithosphere (or melts of their dehydrated equivalents if metasomatized lithosphere is recycled into the convecting mantle). Amphibole-rich veins are interpreted as cumulates produced by crystallization of low-degree melts of the underlying asthenosphere as they ascend through the lithosphere. We present the results of trace-element modelling of the formation and melting of veins formed in this way with the goal of testing this hypothesis and for predicting how variability in the formation and subsequent melting of such cumulates (and adjacent cryptically and modally metasomatized lithospheric peridotite) would be manifested in magmas generated by such a process. Because the high-pressure phase equilibria of hydrous near-solidus melts of garnet lherzolite are poorly constrained and given the likely high variability of the hypothesized accumulation and remelting processes, we used Monte Carlo techniques to estimate how uncertainties in the model parameters (e.g. the compositions of the asthenospheric sources, their trace-element contents, and their degree of melting; the modal proportions of crystallizing phases, including accessory phases, as the asthenospheric partial melts ascend and crystallize in the lithosphere; the amount of metasomatism of the peridotitic country rock; the degree of melting of the cumulates and the amount of melt derived from the metasomatized country rock) propagate through the process and manifest themselves as variability in the trace-element contents and radiogenic isotopic ratios of model vein compositions and erupted alkaline magma compositions. We then compare the results of the models with amphibole observed in lithospheric veins and with oceanic and continental alkaline magmas. While the trace-element patterns of the near-solidus peridotite melts, the initial anhydrous cumulate assemblage (clinopyroxene +/- garnet +/- olivine +/- orthopyroxene), and the modelled coexisting liquids do not match the patterns observed in alkaline lavas, our calculations show that with further crystallization and the appearance of amphibole (and accessory minerals such as rutile, ilmenite, apatite, etc.) the calculated cumulate assemblages have trace-element patterns that closely match those observed in the veins and lavas. These calculated hydrous cumulate assemblages are highly enriched in incompatible trace elements and share many similarities with the trace-element patterns of alkaline basalts observed in oceanic or continental setting such as positive Nb/La, negative Ce/Pb, and similiar slopes of the rare earth elements. By varying the proportions of trapped liquid and thus simulating the cryptic and modal metasomatism observed in peridotite that surrounds these veins, we can model the variations in Ba/Nb, Ce/Pb, and Nb/U ratios that are observed in alkaline basalts. If the isotopic compositions of the initial low-degree peridotite melts are similar to the range observed in mid-ocean ridge basalt, our model calculations produce cumulates that would have isotopic compositions similar to those observed in most alkaline ocean island basalt (OIB) and continental magmas after similar to 0 center dot 15 Gyr. However, to produce alkaline basalts with HIMU isotopic compositions requires much longer residence times (i.e. 1-2 Gyr), consistent with subduction and recycling of metasomatized lithosphere through the mantle. such as a heterogeneous asthenosphere. These modelling results support the interpretation proposed by various researchers that amphibole-bearing veins represent cumulates formed during the differentiation of a volatile-bearing low-degree peridotite melt and that these cumulates are significant components of the sources of alkaline OIB and continental magmas. The results of the forward models provide the potential for detailed tests of this class of hypotheses for the origin of alkaline magmas worldwide and for interpreting major and minor aspects of the geochemical variability of these magmas.

Stress radiography and posterior pathological laxity of knee: comparison between two different techniques.

Stress radiographs have been recommended in order to obtain a better objective quantification of abnormal compartment knee motion. This tool has showed to be superior in quantifying a posterior cruciate ligament (PCL) lesion compared to clinical or arthrometer evaluation. Different radiographic techniques have been described in literature to quantify posterior pathological laxity. In this study we evaluated the total amount of posterior displacement (PTD) and side to side difference (SSD), before and after surgical reconstruction of PCL or PCL and posterolateral complex (PLC), using two different stress radiography techniques (Telos stress and kneeling view). Twenty patients were included in this study. We found a statistical significant difference about both total PTD and SSD among the two techniques preoperatively and at follow-up, with greatest values occurring using the kneeling view. Although stress radiographies has been introduced to allow an objective quantification of laxity in ligamentous injured knee, we believe that further studies on a large numbers of subjects are required to define the relationship between PTD values, measured with stress knee radiography, particularly using kneeling view, and ligamentous knee injury, in order to obtain a real useful tool in the decision making process, as well as to evaluate the outcome after ligamentous surgery.

Intérêt d'une Consultation spécialisée multidisciplinaire en neuro-urologie et urologie fonctionnelle [Benefit of a specialized multidisciplinary clinic in neuro-urology and functional urology].

Functional disorders encounter for a large amount of the medical activity, including in urology. The decreased quality of life due to lower urinary tract symptoms requires a prompt management, with primary assessment undergone in community. Referral to a specialist is required when simple management has failed, and whenever any of these coexists: hematuria, recurrent urinary infection, and neurological condition. The specialized clinic in neurourology and functional urology aim at further investigating the underlying disorder responsible for the urinary symptoms and preventing urinary tract complications. A multidisciplinary team is the key to accurately assess patients with regards to their bother and handicap, therefore offering the most appropriate conservative, medical or surgical management.

Dual role of Bmi1 loss in the preservation of photoreceptor layers in the Rd1 mouse

Purpose: In the Rd1 and Rd10 mouse models of retinitis pigmentosa, a mutation in the Pde6ß gene leads to the rapid loss of photoreceptors. As in several neurodegenerative diseases, Rd1 and Rd10 photoreceptors re-express cell cycle proteins prior to death. Bmi1 regulates cell cycle progression through inhibition of CDK inhibitors, and its deletion efficiently rescues the Rd1 retinal degeneration. The present study evaluates the effects of Bmi1 loss in photoreceptors and Müller glia, since in lower vertebrates, these cells respond to retinal injury through dedifferentiation and regeneration of retinal cells. Methods: Cell death and Müller cell activation were analyzed by immunostaining of wild-type, Rd1 and Rd1;Bmi1-/- eye sections during retinal degeneration, between P10 and P20. Lineage tracing experiments use the GFAP-Cre mouse (JAX) to target Müller cells. Results: In Rd1 retinal explants, inhibition of CDKs reduces the amount of dying cells. In vivo, Bmi1 deletion reduces CDK4 expression and cell death in the P15 Rd1;Bmi1-/- retina, although cGMP accumulation and TUNEL staining are detected at the onset of retinal degeneration (P12). This suggests that another process acts in parallel to overcome the initial loss of Rd1;Bmi1-/- photoreceptors. We demonstrate here that Bmi1 loss in the Rd1 retina enhances the activation of Müller glia by downregulation of p27Kip1, that these cells migrate toward the ONL, and that some cells express the retinal progenitor marker Pax6 at the inner part of the ONL. These events are also observed, but to a lesser extent, in Rd1 and Rd10 retinas. At P12, EdU incorporation shows proliferating cells with atypical elongated nuclei at the inner border of the Rd1;Bmi1-/- ONL. Lineage tracing targeting Müller cells is in process and will determine the implication of this cell population in the maintenance of the Rd1;Bmi1-/- ONL thickness and whether downregulation of Bmi1 in Rd10 Müller cells equally stimulates their activation. Conclusions: Our results show a dual role of Bmi1 deletion in the rescue of photoreceptors in the Rd1;Bmi1-/- retina. Indeed, the loss of Bmi1 reduces Rd1 retinal degeneration, and as well, enhances the Müller glia activation. In addition, the emergence of cells expressing a retinal progenitor marker in the ONL suggests Bmi1 as a blockade to the regeneration of retinal cells in mammals.