Os produtos naturais desempenham fundamental importância na descoberta de novos fármacos. Muitos destes fármacos originaram-se de produtos naturais microbianos o que demonstra uma extrema eficiência na habilidade dos micro-organismos de sintetizar substâncias químicas com elevado potencial biológico. Sabe-se que os insetos sociais estão sujeitos a condições climáticas e populacionais que aumentam sua susceptibilidade a parasitas. Assim, estes insetos desenvolveram um mecanismo de defesa evolutivo que consiste na associação simbiótica a bactérias capazes de biossintetizar produtos antimicrobianos contra os patógenos. Dispondo dessas informações, o presente trabalho contribuiu com o estudo dos produtos naturais biossintetizados pela bactéria Paenibacillus polymyxa ALLI-03-01, provável simbionte da espécie de abelha sem ferrão Melipona scutellaris. Os micro-organismos foram isolados de colônias mantidas no Departamento de Biologia da FFCLRP-USP. Todas as linhagens foram testadas contra dois fungos entomopatogênicos - Beauveria bassiana e Metarhizium anisopliae; os que apresentaram atividade antifúngica tiveram seus extratos em acetato de etila e metanol preparados e foram avaliados em ensaios antiparasitários contra Trypanosoma cruzi e Leishmania donovani. A bactéria ALLI-03-01, isolada do alimento larval, foi escolhida para os estudos químicos, pois apresentou satisfatória atividade antifúngica e proeminente atividade antiparasitária. Este micro-organismo foi identificado pelo sequenciamento do gene 16S rRNA como sendo a bactéria Paenibacillus polymyxa, conhecida pela alta capacidade de produção de metabólitos secundários. Para conhecer seu metabolismo, esta bactéria foi cultivada em meio ISP-2 ágar e líquido e do extrato em acetato de etila do cultivo fermentativo de P. polymyxa ALLI-03-01 foi isolado o ácido L-3-fenil lático. As atividades antifúngicas dos padrões comerciais dos ácidos D-(+)- e L-(-)- 3-fenil lático foram testadas frente ao fungo entomopatogênico B. bassiana e apenas o enantiômero L apresentou atividade antifúngica. Do extrato em metanol do cultivo em meio sólido do mesmo micro-organismo foram identificados em mistura, principalmente por MALDI-TOF MS/MS, nove diferentes ciclolipodepsipeptídeos, da classe das Fusaricidinas. As fusaricidinas são conhecidas por apresentarem alta atividade anti-microbiana, que foi comprovada quando duas frações compostas por diferentes fusaricidinas foram testadas frente ao fungo entomopatogênico Metarhizium anisopliae e contra a bactéria patogênica Paenibacillus larvae. As frações apresentaram resultados satisfatórios de inibição contra ambos os patógenos, dessa maneira as fusaricidinas e a produção seletiva do ácido L-3-fenil lático por esta bactéria podem ser vias de proteção da colônia, evitando que patógenos destruam-na e permitindo o desenvolvimento sadio de larvas. Sendo assim, este trabalho relata pela primeira vez a possível relação simbiótica existente entre o micro-organismo Paenibacillus polymyxa ALLI-03-01 e a colônia de abelhas Melipona scutellaris, bem como a produção por este micro-organismo de compostos com alta atividade antimicrobiana que podem exercer o controle de parasitas dentro da colônia, estabelecendo assim, uma possível relação ecológica entre o micro-organismo destacado e as abelhas Melipona scutellaris. / Natural products play an important role in drug discovery. Several drugs have been discovered or developed from microbial natural products hits and leads showing a great efficiency of microorganisms to synthesize compounds with high biological potential. It is known that social insects are subjected to climate and population conditions that increase their susceptibility to parasites. Therefore, these insects have developed an evolutionary defense mechanism consisting in symbiotic association with bacteria capable of biosynthesize antimicrobial products against pathogens. In this context, this study contributed to the knowledge of natural products biosynthesized by the bacterium Paenibacillus polymyxa ALLI-03-01, a probable symbiont of the stingless bee Melipona scutellaris. Microorganisms were isolated from colonies maintained at the Department of Biology of FFCLRP-USP. All strains were tested against two entomopathogenic fungi - Beauveria bassiana and Metarhizium anisopliae; strains that showed antifungal activity had their ethyl acetate and methanol extracts prepared and evaluated against the parasites Trypanosoma cruzi and Leishmania donovani. The bacterium ALLI-03-01, isolated from larval food, was selected for chemical studies, due to its satisfactory antifungal activity and outstanding antiparasitic activity. This microorganism was identified by gene 16S rRNA sequencing as Paenibacillus polymyxa, a bacterium recognized for its ability of biosynthesize secondary metabolities. This bacterium was cultivated in ISP-2 agar and liquid medium and from the ethyl acetate extract of P. polymyxa ALLI-03-01 cultivated in liquid medium L-3-phenyllactic acid was isolated. The antifungal activity of comercial standards of D-(+)- and L-(-)-phenyllactic acid were tested against entomopathogenic fungus B. bassiana and only the L enantiomer presented antifungal activity. Nine cyclo lipodepsipeptides known as fusaricidins were identified in mixture using MALDI-TOF-MS/MS from the methanol extract of ALLI-03-01. The fusaricidins are recognized for their high antimicrobial activity, which was confirmed when two fractions composed by different fusaricidins were tested against the entomopathogenic fungus Metarhizium anisopliae and the pathogenic bacterium Paenibacillus larvae. The fractions showed satisfactory inhibition against both pathogens. Therefore, fusaricidins and selective production of L-3-phenyllactic acid by the bacterium may be colony protection resources, preventing the action of pathogens and allowing healthy larvae development. Therefore, this study reports for the first time a possible symbiotic relationship between Paenibacillus polymyxa ALLI-03-01 and the colony of M. scutellaris bees, as well as production of compounds with high antimicrobial activity by this microorganism that might act as parasite control agents within the colony, establishing a possible ecological relationship between the bacterium and M. scutellaris bees.

Les interactions interindividuelles permettent la transmission de l’information, la dispersion des pathogènes et la mise en place des comportements dans une population. Cette thèse a permis d’évaluer l’influence des interactions sociales sur le succès de fondation colonial des différents reproducteurs de deux termites européens, l’invasif Reticulitermes flavipes et le natif R. grassei. Les résultats révèlent (i) un meilleur succès de fondation des reproducteurs primaires de R. flavipes, (ii) une organisation biparentale des soins aux jeunes toutes espèces confondues et (iii) une communication et des soins aux oeufs propres aux caractères invasif et natif des espèces d’étude. Pour finir, (iv) une meilleure survie et communication a été observée dans les colonies fondées avec reproducteurs secondaires tandis (v) qu’une communication supérieure et une survie moindre sont observées pour R. flavipes. Les origines évolutives de l’organisation biparentale et des variations de succès de fondations sont discutées. / Individual interactions permit information transmission, pathogen dispersion and shape behavioral strategies in a population. This thesis has permit to explore the influence of social interactions on the colonial foundation success of two European termites, the invasive Reticulitermes flavipes and the native R. grassei. The overall results revealed (i) a better foundation success of primary reproductives of R. flavipes, (ii) a biparental organisation of parental care in both species (iii) a level of communication and egg care reflecting native and invasive status of the two species studied. To finish, (iv) better survival and communication rates were observed in colonies founded with secondary reproductives than in colonies without any and (v) a better communication rate and a weaker survival rate for R. flavipes foundations with or without secondary reproductives. Evolutive origins of biparental care and of the variations of foundation success observed are discussed.

Os produtos naturais desempenham fundamental importância na descoberta de novos fármacos. Muitos destes fármacos originaram-se de produtos naturais microbianos o que demonstra uma extrema eficiência na habilidade dos micro-organismos de sintetizar substâncias químicas com elevado potencial biológico. Sabe-se que os insetos sociais estão sujeitos a condições climáticas e populacionais que aumentam sua susceptibilidade a parasitas. Assim, estes insetos desenvolveram um mecanismo de defesa evolutivo que consiste na associação simbiótica a bactérias capazes de biossintetizar produtos antimicrobianos contra os patógenos. Dispondo dessas informações, o presente trabalho contribuiu com o estudo dos produtos naturais biossintetizados pela bactéria Paenibacillus polymyxa ALLI-03-01, provável simbionte da espécie de abelha sem ferrão Melipona scutellaris. Os micro-organismos foram isolados de colônias mantidas no Departamento de Biologia da FFCLRP-USP. Todas as linhagens foram testadas contra dois fungos entomopatogênicos - Beauveria bassiana e Metarhizium anisopliae; os que apresentaram atividade antifúngica tiveram seus extratos em acetato de etila e metanol preparados e foram avaliados em ensaios antiparasitários contra Trypanosoma cruzi e Leishmania donovani. A bactéria ALLI-03-01, isolada do alimento larval, foi escolhida para os estudos químicos, pois apresentou satisfatória atividade antifúngica e proeminente atividade antiparasitária. Este micro-organismo foi identificado pelo sequenciamento do gene 16S rRNA como sendo a bactéria Paenibacillus polymyxa, conhecida pela alta capacidade de produção de metabólitos secundários. Para conhecer seu metabolismo, esta bactéria foi cultivada em meio ISP-2 ágar e líquido e do extrato em acetato de etila do cultivo fermentativo de P. polymyxa ALLI-03-01 foi isolado o ácido L-3-fenil lático. As atividades antifúngicas dos padrões comerciais dos ácidos D-(+)- e L-(-)- 3-fenil lático foram testadas frente ao fungo entomopatogênico B. bassiana e apenas o enantiômero L apresentou atividade antifúngica. Do extrato em metanol do cultivo em meio sólido do mesmo micro-organismo foram identificados em mistura, principalmente por MALDI-TOF MS/MS, nove diferentes ciclolipodepsipeptídeos, da classe das Fusaricidinas. As fusaricidinas são conhecidas por apresentarem alta atividade anti-microbiana, que foi comprovada quando duas frações compostas por diferentes fusaricidinas foram testadas frente ao fungo entomopatogênico Metarhizium anisopliae e contra a bactéria patogênica Paenibacillus larvae. As frações apresentaram resultados satisfatórios de inibição contra ambos os patógenos, dessa maneira as fusaricidinas e a produção seletiva do ácido L-3-fenil lático por esta bactéria podem ser vias de proteção da colônia, evitando que patógenos destruam-na e permitindo o desenvolvimento sadio de larvas. Sendo assim, este trabalho relata pela primeira vez a possível relação simbiótica existente entre o micro-organismo Paenibacillus polymyxa ALLI-03-01 e a colônia de abelhas Melipona scutellaris, bem como a produção por este micro-organismo de compostos com alta atividade antimicrobiana que podem exercer o controle de parasitas dentro da colônia, estabelecendo assim, uma possível relação ecológica entre o micro-organismo destacado e as abelhas Melipona scutellaris. / Natural products play an important role in drug discovery. Several drugs have been discovered or developed from microbial natural products hits and leads showing a great efficiency of microorganisms to synthesize compounds with high biological potential. It is known that social insects are subjected to climate and population conditions that increase their susceptibility to parasites. Therefore, these insects have developed an evolutionary defense mechanism consisting in symbiotic association with bacteria capable of biosynthesize antimicrobial products against pathogens. In this context, this study contributed to the knowledge of natural products biosynthesized by the bacterium Paenibacillus polymyxa ALLI-03-01, a probable symbiont of the stingless bee Melipona scutellaris. Microorganisms were isolated from colonies maintained at the Department of Biology of FFCLRP-USP. All strains were tested against two entomopathogenic fungi - Beauveria bassiana and Metarhizium anisopliae; strains that showed antifungal activity had their ethyl acetate and methanol extracts prepared and evaluated against the parasites Trypanosoma cruzi and Leishmania donovani. The bacterium ALLI-03-01, isolated from larval food, was selected for chemical studies, due to its satisfactory antifungal activity and outstanding antiparasitic activity. This microorganism was identified by gene 16S rRNA sequencing as Paenibacillus polymyxa, a bacterium recognized for its ability of biosynthesize secondary metabolities. This bacterium was cultivated in ISP-2 agar and liquid medium and from the ethyl acetate extract of P. polymyxa ALLI-03-01 cultivated in liquid medium L-3-phenyllactic acid was isolated. The antifungal activity of comercial standards of D-(+)- and L-(-)-phenyllactic acid were tested against entomopathogenic fungus B. bassiana and only the L enantiomer presented antifungal activity. Nine cyclo lipodepsipeptides known as fusaricidins were identified in mixture using MALDI-TOF-MS/MS from the methanol extract of ALLI-03-01. The fusaricidins are recognized for their high antimicrobial activity, which was confirmed when two fractions composed by different fusaricidins were tested against the entomopathogenic fungus Metarhizium anisopliae and the pathogenic bacterium Paenibacillus larvae. The fractions showed satisfactory inhibition against both pathogens. Therefore, fusaricidins and selective production of L-3-phenyllactic acid by the bacterium may be colony protection resources, preventing the action of pathogens and allowing healthy larvae development. Therefore, this study reports for the first time a possible symbiotic relationship between Paenibacillus polymyxa ALLI-03-01 and the colony of M. scutellaris bees, as well as production of compounds with high antimicrobial activity by this microorganism that might act as parasite control agents within the colony, establishing a possible ecological relationship between the bacterium and M. scutellaris bees.

In order to improve our knowledge of the mechanisms of ageing in animals, the main objective of the thesis was to understand the modulation of such mechanisms by the individual social role, within different social organisations. This objective thus addresses two main questions: i) describing the covariation of the degree of social complexity with ageing patterns; ii) highlighting the underlying cellular and molecular processes. Thanks to complementary and diversified studies (behavioural observations, dosage of the oxidative balance, qPCR measurement of telomere length, proteomics, metabolomics), the present thesis showed that sociality plays a role on ageing at many levels. In the zebra finch, social stress caused by aggression of the conspecifics induces oxidative stress and reduces telomere length in adults. In the sociable weaver, the social environment is of crucial importance during pre- and post-hatch development on the medium term survival of the chicks. Finally, in ants, we were able to show a positive relationship between the degree of sociality and maximum potential life span: this link was caste specific, being only significant for the most social queens. This is inline with a recent review by Lucas and Keller (2020) which concluded that the benefits of sociality are most sensitive for high levels of sociality and particularly in reproductive individuals. With regard to the molecular mechanisms of ageing,we were able to establish a causal chain between social stress, oxidative response and telomere erosion in zebra finches.The role of telomeres as a predictor of offspring survival has been confirmed (over at least 5 years) in the sociable weaver,a cooperative breeder bird. However, this link was not true in queen ants where the longest lived were those with the shortest telomeres. The co-evolution of anti-cancer mechanisms and longevity seems to be conserved since similar strategies are found in taxa as diverse as ants and rodents. On the other hand, and contrary to previous studies conducted on ants, we found that oxidative stress might be a marker of individual ageing. We suggest that the proxies of oxidative stress used so far in ants have been misleading or at least incomplete. Thus, understanding the physiological ageing particularities of ants and other social insects might require finding new relevant and specific markers. Finally, the sirtuins and mTOR signalling pathways, key precursors of which we have detected in ants, are molecular crossroads capable of activating or inhibiting cellular metabolism depending on the cell energy state. According to the studies carried out to date, these signalling pathways are among the first to be able to slow down the effects of ageing and extend life expectancy.However, specific studies need to be carried out to understand their fine regulation and thus assess the universality of these mechanisms in animal ageing. Based on our findings, we propose three points to be further addressed to better understand the mechanisms of ageing in social insects: i) the setup of experiments testing the effectiveness of energy trade-offs involving immunity or digestion metabolism; ii) measuring the telomerase activity among castes of various species in order to explore the telomere and telomere independent roles played by this enzyme in ageing; iii) the need to think about individual longitudinal follow-up and to study wild populations, after the first necessary stages in laboratory. / Doctorat en Sciences / Un résumé grand public en français est disponible au début du manuscrit, juste après les remerciements. / info:eu-repo/semantics/nonPublished

- Extended longevity and high fecundity are two phenomena typical for reproductive castes (queens, eventually kings) of eusocial insects. In my thesis, we explore the hypothesis that the longevity of reproductives in the termite Prorhinotermes simplex is linked with the activation of the telomerase enzyme complex. Telomerase is well known for its life-extension functions, due especially to its capacity to prolong the telomeric ends of chromosomes. Therefore, we studied here the gene expression of: (1) the gene TERT coding for the catalytic subunit of the telomerase and (2) the genes of the main endocrine regulatory pathways, known to be responsible for the control of reproduction and longevity in insects. Expression dynamics of these genes were measured in sterile and reproductive castes of P. simplex during their development and sexual maturation. Based on our results obtained from the TERT expression analyses and their comparison with telomerase enzyme activities, we assume that the telomerase action in the long-lived reproductive individuals is regulated at a post-transcription level. Furthermore, we observed in reproductive castes a simultaneous upregulation of some transcription variants of vitellogenin and the genes for insulin signalling pathways. We can, therefore, conclude that in...

This thesis addresses orchestration of servers amongst multiple co-hosted internet services such as e-Banking, e-Auction and e-Retail in hosting centres. The hosting paradigm entails levying fees for hosting third party internet services on servers at guaranteed levels of service performance. The orchestration of server ensemble in hosting centres is considered in the context of maximising the hosting centre's revenue over a lengthy time horizon. The inspiration for the server orchestration approach proposed in this thesis is drawn from nature and generally classed as swarm intelligence, specifically, sophisticated collective behaviour of social insects borne out of primitive interactions amongst members of the group to solve problems beyond the capability of individual members. Consequently, the approach is self-organising, adaptive and robust. A new scheme for server ensemble orchestration is introduced in this thesis. This scheme exploits the many similarities between server orchestration in an internet hosting centre and forager allocation in a honeybee (Apis mellifera) colony. The scheme mimics the way a honeybee colony distributes foragers amongst flower patches to maximise nectar influx, to orchestrate servers amongst hosted internet services to maximise revenue. The scheme is extended by further exploiting inherent feedback loops within the colony to introduce self-tuning and energy-aware server ensemble orchestration. In order to evaluate the new server ensemble orchestration scheme, a collection of server ensemble orchestration methods is developed, including a classical technique that relies on past history to make time varying orchestration decisions and two theoretical techniques that omnisciently make optimal time varying orchestration decisions or an optimal static orchestration decision based on complete knowledge of the future. The efficacy of the new biomimetic scheme is assessed in terms of adaptiveness and versatility. The performance study uses representative classes of internet traffic stream behaviour, service user's behaviour, demand intensity, multiple services co-hosting as well as differentiated hosting fee schedule. The biomimetic orchestration scheme is compared with the classical and the theoretical optimal orchestration techniques in terms of revenue stream. This study reveals that the new server ensemble orchestration approach is adaptive in a widely varying external internet environments. The study also highlights the versatility of the biomimetic approach over the classical technique. The self-tuning scheme improves on the original performance. The energy-aware scheme is able to conserve significant energy with minimal revenue performance degradation. The simulation results also indicate that the new scheme is competitive or better than classical and static methods.