Les cytokines MIFs (Macrophage Migration Inhibitory Factor) sont des protéines multifonctionnelles qui, chez les mammifères, interviennent dans plusieurs processus majeurs tels que le contrôle du cycle et de la mobilité cellulaire, l’activation de la réponse immunitaire et l’inhibition de l’apoptose. Des travaux récents montrent que les protéines MIFs peuvent également jouer un rôle majeur dans l’immunité des invertébrés, et être utilisées par des organismes parasites d’animaux ou de végétaux pour inhiber les défenses de leurs hôtes respectifs, ce qui soulève la question de leur diversité, de leur histoire évolutive et des potentielles différences fonctionnelles. L’objectif général de ce travail de thèse était d’explorer la diversité et l’histoire évolutive des protéines MIFs à une échelle trans-règne, puis de rechercher leurs éventuelles différences fonctionnelles, en se focalisant sur les systèmes plantes-pathogènes. Nous avons tout d’abord identifié les MIFs chez 803 espèces de plantes, champignons, protistes, et métazoaires, et analysé leur présence/absence et histoire évolutive en fonction des taxa, de l’écologie et du mode de vie (libre ou parasitaire) des espèces. Nous avons montré que l’histoire évolutive des MIFs, chez les eucaryotes, est complexe et implique des duplications ancestrales ainsi que des pertes multiples ou des re-duplications récentes. Les plantes (espèces libres autotrophes) et les parasites de plantes (autres que champignons) possèdent un nombre médian de trois MIFs, alors que les espèces hétérotrophes et les parasites d’animaux ont un nombre de MIF plus faible et/ou plus variable. De plus, les protéines MIFs semblent essentielles et fortement conservées, avec de nombreux résidus sous sélection purifiante, chez certains groupes comme les plantes, alors que dans d’autres groupes, elles semblent facultatives (e.g. champignons) ou présentes en plusieurs copies divergentes (e.g. nématodes, insectes), ce qui suggère de potentielles néofonctionalisations. Nous avons ensuite analysé l’effet des protéines MIFs de plusieurs espèces sur la mort cellulaire en système végétal. Tous les organismes testés (plantes oomycètes, protozoaires, insectes et nématodes), y compris ceux n’ayant pas d’interaction avec les plantes, possèdent au moins une protéine MIF capable d’inhiber cette mort cellulaire. Cela suggère que l’inhibition de la mort cellulaire en plante ne correspond pas à une néofonctionalisation des MIFs de parasites de plantes, mais serait liée à des propriétés structurales et conservées des MIFs. Toutefois, aucun des paramètres étudiés (localisation subcellulaire) ou prédits in silico (présence de motifs, structures 3D, oligomérisation, modifications post-traductionnelles) ne semble lié à cette activité d’inhibition de la mort cellulaire. De futures études fonctionnelles poussées sont nécessaires à l’élucidation des relations structure/fonction de ces protéines complexes. / Macrophage migration inhibitory factors (MIF) are multifunctional proteins regulating major processes in mammals, including control of the cell cycle and migration, activation of innate immune responses, and prevention of p53-mediated apoptosis. MIF proteins also play a role in innate immunity of invertebrate organisms or serve as virulence factors in parasitic organisms, raising the question of their evolutionary history and of a putative differential evolution of structure/function relationships. The general aim of this PhD was to explore the diversity and evolutionary history of MIF proteins accross kingdoms, and to investigate their potential functional differences, with a special emphasis on host-parasite systems. We first performed a broad survey of MIF presence or absence and evolutionary relationships across 803 species of plants, fungi, protists, and animals, and explored a potential relation with the taxonomic status, the ecology, and the lifestyle of individual species. We show that MIF evolutionary history in eukaryotes is complex, involving ancestral duplications, multiple gene losses and recent clade-specific re-duplications. Of note, plants and plant parasites (other than fungi) harbour a median number of three MIFs, while heterotrophic and animal parasite species harbour a lower or/and variable MIF number. Intriguingly, MIFs seem to be essential and highly conserved with many sites under purifying selection in some kingdoms (e.g. plants), while in other kingdoms they appear more dispensable (e.g. in fungi) or present in several diverged variants (e.g. insects, nematodes), suggesting potential neofunctionalizations within the protein superfamily. We then analysed the effect of MIF proteins from selected species on plant cell death. All organisms tested (plant, oomycetes, protozoa, insects, and nematodes) including species that are not in interaction with plants, possess at least one MIF protein showing a significant cell death inhibitory effect. This suggests that plant cell death inhibition does not result from a neofunctionalization of MIF from plant-parasites, and is related to conserved structural features of MIF proteins. However, none of the parameters predicted in silico (sequence motifs, 3D structures, oligomerization, post-traductional modifications) appeared to be related to the cell death inhibitory activity. Future extensive functional studies are necessary to unravel the structure-function relationship of these evolutionarily and functionally complex proteins.

This thesis documents the development and application of a unique database orientated software package, BugsCEP, for environmental and climatic reconstruction from fossil beetle (Coleoptera) assemblages. The software tools are described, and the incorporated statistical methods discussed and evaluated with respect to both published modern and fossil data, as well as the author’s own investigations. BugsCEP consists of a reference database of ecology and distribution data for over 5 800 taxa, and includes temperature tolerance data for 436 species. It also contains abundance and summary data for almost 700 sites - the majority of the known Quaternary fossil coleopteran record of Europe. Sample based dating evidence is stored for a large number of these sites, and the data are supported by a bibliography of over 3 300 sources. Through the use of built in statistical methods, employing a specially developed habitat classification system (Bugs EcoCodes), semi-quantitative environmental reconstructions can be undertaken, and output graphically, to aid in the interpretation of sites. A number of built in searching and reporting functions also increase the efficiency with which analyses can be undertaken, including the facility to list the fossil record of species found by searching the ecology and distribution data. The existing Mutual Climatic Range (MCR) climate reconstruction method is implemented and improved upon in BugsCEP, as BugsMCR, which includes predictive modelling and the output of graphs and climate space maps. The evaluation of the software demonstrates good performance when compared to existing interpretations. The standardization method employed in habitat reconstructions, designed to enable the inter-comparison of samples and sites without the interference of differing numbers of species and individuals, also appears to be robust and effective. Quantitative climate reconstructions can be easily undertaken from within the software, as well as an amount of predictive modelling. The use of jackknifing variants as an aid to the interpretation of climate reconstructions is discussed, and suggested as a potential indicator of reliability. The combination of the BugStats statistical system with an enhanced MCR facility could be extremely useful in increasing our understanding of not only past environmental and climate change, but also the biogeography and ecology of insect populations in general. BugsCEP is the only available software package integrating modern and fossil coleopteran data, and the included reconstruction and analysis tools provide a powerful resource for research and teaching in palaeo-environmental science. The use of modern reference data also makes the package potentially useful in the study of present day insect faunas, and the effects of climate and environmental change on their distributions. The reconstruction methods could thus be inverted, and used as predictive tools in the study of biodiversity and the implications of sustainable development policies on present day habitats. BugsCEP can be downloaded from http://www.bugscep.com

IP25 is a highly branched isoprenoid alkene derived from certain Arctic sea ice diatoms that, when detected in marine sediments, has been used as a proxy for past Arctic sea ice over the last decade. In the current study, the structure of this biomarker was determined following large-scale extraction from sediment material collected from the Canadian Arctic. After purification, the structure of IP25 was confirmed by NMR spectroscopy as being the same as that of a laboratory standard. The purified IP25 was subsequently used to obtain a quantitative (GC-MS) instrumental response factor that could be used to improve the future quantification of IP25 and would help to produce a robust database. IP25, other highly branched isoprenoid (HBI) lipids and some other phytoplanktonic lipids (sterols) were analysed to provide modern and past sediment-based sea ice reconstructions for the Barents Sea. First, a surface sediment study was conducted and biomarker distributions were compared to satellite sea ice records. The occurrence of IP25 was consistent with the presence/absence of seasonal sea ice but there was also evidence of lateral transport of IP25 and other biomarkers in sediments from the southern Barents Sea. In contrast to some previous studies, abundances of IP25, and of those combined with other biomarkers, including sterols, did not show strong quantitative relationships to sea ice concentration. The surface study was used to relate biomarker distributions to recent sea ice and oceanographic conditions and apply this information to long-term sediment records in the eastern and western Barents Sea covering ca. 2 kyr and 11 kyr (Holocene) respectively. IP25 concentrations for the former were found to be very variable and were used to identify the period with maximum sea ice cover occurring from ca. 900 - 400 cal. yr BP where the highest abundances of IP25 and IRD were observed. Similarly, biomarker results from the eastern Barents Sea provided evidence for a dynamic advance of the marginal sea ice zone potentially situated at ca. 78° N (maximum extent) during ca 9.4 – 5.9 cal. kyr BP, to late Holocene and modern day maximum MIZ advance ca. 75° N. Replicate analysis of various biomarkers in individual push-cores collected from a box core obtained from Rijpfjorden (north Svalbard) demonstrated some variability between cores. Variability in individual biomarker concentrations was lowest for HBI lipids and greatest for sterols. These data are consistent with a selective and relatively minor source of the former. In contrast, the somewhat more generic origins of sedimentary sterols likely explain the greater variability in their distributions between cores Finally, the strong abundance relationship between IP25 and a structurally related di-unsaturated HBI (C25:2) was confirmed in all sediments, similar to that found between two tri-unsaturated HBIs, consistent with co-production by certain marine phytoplankton. The progressive use of novel HBIs with two or three degrees of unsaturation (e.g. C25:2 and C25:3) could provide further valuable insights into environmental conditions.

Heaps of fire cracked stones is an apparent feature of the Scandinavian Bronze Age. The heaps are built of stones cracked by fire and then placed in different constructions. The heaps are placed in different contexts in the Bronze Age landscape and for a long time, research neglected this site category owing to that the heaps were not considered important enough to dig. During the 1980s-90s the interest for the heaps of fire cracked stones increased and it became a wellresearched although debated site category. Earlier research has interpreted the heaps to be on the hillslopes in the landscape. This study’s research aims to understand the relation between shorelines and the placement of fire cracked stone heaps. This will be done through a landscape study of Uppland. The study indicates that the pattern in the distribution of heaps of fire cracked stones creates a correlation with the shoreline of the time the heaps were built, through their placement in the landscape. By creating a dynamic shoreline displacement, the essay will be able to look at the landscape in a more detailed way and will be able to investigate the relation between the heaps and the water edge. Through excluding the heaps that are under the waterline it is possible to in general determine the earliest possible production date. The fire cracked stone heaps have earlier been categorised to the Scandinavian Bronze Age but this research argues that some of the heaps should belong to the Neolithic Age as well.

Laboratory mouse is a appropriate experimental model for studies on normal tooth development mechanisms and for understanding of etio-pathogenesis of dental anomalies in humans. Mouse dentition consists of one incisor separated from three molars by toothless diastema in each jaw quadrant. Although an adult mice diastema does not contain teeth, rudimentary tooth primordia (MS, R2) appear here during embryonic development. However, their development stops and consequently functional tooth does not arise here. It is known that in mice with mutations in Spry2 and Spry4 genes, supernumerary teeth arise in antemolar region. The understanding of the temporo-spatial dynamics of signaling centers in Spry2/Spry4 double transgenic mice may help to elucidate the role of these embryonic diastemal buds in supernumerary tooth formation. The research of possible regeneration of dental anomalies in off-spring of crossing Spry4 deficient mice with supernumerary teeth formation with Eda deficient mice with predisposition to reduced dentition could be the way to elucidating of mechanism of dental pathologies development in general. Our aim was to describe temporal and spatial dynamics of Shh signaling domains in Spry2/Spry4 embryos, because Shh is one of the markers of early odontogenesis and determining of...

Ce travail porte sur la croissance épitaxiale et la caractérisation optique de boîtes quantiques d’InAs/InP(001) en faible densité en vue de la réalisation de nouveaux composants nanophotoniques émettant à 1,55 µm. Les propriétés structurales et optiques des îlots ont été corrélés pour différents paramètres de croissance d’un système d’épitaxie par jet moléculaire à sources solides. Nos résultats soulignent l’influence des reconstructions de surface d’InAs sur la forme des îlots. Des boîtes, plutôt que des bâtonnets allongés généralement observés,peuvent être directement formées dans des conditions de croissance adéquates. Une transition de forme de bâtonnets vers des boîtes est également démontrée par des traitements postcroissance sous arsenic. Les faibles densités de boîtes sont obtenues pour des faibles épaisseurs d’InAs déposées. Leur émission est facilement contrôlée à 1,55 µm par une procédure d’encapsulation spécifique appelé « double cap ». Quelques propriétés des boîtes individuelles d’InAs/InP sont ensuite évaluées. Les études de micro-photoluminescence révèlent des pics d’émission très fins et distincts autour de 1,55 µm confirmant les propriétés« quasi-atomiques » de ces boîtes uniques. Enfin, nous proposons pour la première fois une méthode à haute résolution spatiale qui permet d’étudier le transport de charges autour d’une boîte unique grâce à une technique de cathodoluminescence à basse tension d’accélération.Une mesure directe de la longueur de diffusion des porteurs avant capture dans une boîte a été obtenue. Ces résultats ouvrent de nouvelles perspectives quant à l’intégration de ces boîtes uniques dans des microcavités optiques pour la réalisation de sources de lumières quantiques à 1,55 µm. / This thesis focus on the epitaxial growth and optical characterization of diluted InAs/InP(001) quantum dots for the realisation of new nanophotonic devices emitting at 1.55μm. The structural and optical properties of the quantum islands are correlated to different growth parameters of a solid source molecular beam epitaxy system. Our results highlight the influence of InAs surface reconstructions on the island shape. Dots rather than elongated dashes usually observed can be directly formed by adequate growth conditions. Dash to dot shape transition is also demonstrated by post-growth treatments. Low dot densities are obtained for small InAs deposited thickness. Their emission wavelength is easily tuned to1.55 µm using the “double cap” procedure for the growth of the InP capping layer. Optical properties of such single InAs/InP quantum dots are then evaluated. Microphotoluminescence studies reveal sharp and well separated emission lines near 1.55 µm from single dots confirming their atom-like properties. Last, we propose for the first time a highspatial resolution method to study the carrier transport in the vicinity of a single quantum dotusing a low-voltage cathodoluminescence technique. A direct measurement of the carrier diffusion length before capture into one dot has been obtained. These results open the way to the integration of these single dots into optical micro-cavities for the realisation of quantumlight sources at 1.55 µm.

Une des techniques pour obtenir des images de structures hétérogènes ou d'objets enfouis dans un milieu (sol, murs, ...) repose sur la mesure du champ électromagnétique diffracté par les inhomo-généités lorsqu'elles sont soumises à une illumination incidente. Cela nécessite la mise en oeuvre d'un système d'acquisition microonde doté d'un réseau de capteurs linéaire ou plan. Ses critères de conception sont dictés par les algorithmes d'imagerie qui nécessitent le plus souvent des données multifréquences acquises sur une large fenêtre d'observation. Ce travail de thèse repose sur la caractérisation, le calibrage et la validation expérimentale d'un prototype d'imageur multistatique ultra large bande. Un descriptif des systèmes actuels d'imagerie microonde a permis tout d'abord de valider les critères retenus pour le cahier des charges initial et de décrire les considérations associées à un problème de détection subsurface. Le Système d'Imagerie Microonde à Impulsions Synthétiques (SIMIS), dévelopé au LEAT, est caractérisé par ses performances théoriques, et une attention particulière a porté sur l'optimisation de la dynamique de détection. Afin de corriger les erreurs systématiques, le calibrage du radar est accompli sur chaque module successivement, puis, plusieurs études portant sur les erreurs de dérive et les erreurs aléatoires sont proposées. Le système est ensuite utilisé en chambre anéchoïque pour la détection de cibles canoniques (un cylindre métallique et un parallélépipède diélectrique) dans une configuration 2D-TM. La détection des deux objets est confirmée par l'observation d'hyperboles de diffraction sur des images apparentées B-scan. Une modification du système est effectuée et validée afin de réduire le couplage inter-antennes au sein du réseau de transducteurs. Cela permet, le cas échéant, de détecter les cibles à partir de la seule mesure du champ total. Les premiers résultats en imagerie qualitative sont obtenus par la technique du miroir à retournement temporel. Dans le domaine fréquentiel, l'utilisation de la méthode DORT (Décomposition de l'Opérateur de Retournement Temporel) a permis également de détecter les cibles lorsque la longueur d'onde est comparable à leur dimension transverse.

L'infirmité motrice cérébrale (IMC) est une pathologie résultante d'une lésion cérébrale qui atteint environ 4/1000 des nouveau-nés. Cette pathologie consiste en un trouble moteur dû à la contraction continue des muscles (spasticité) qui induit des raideurs musculaires évolutives avec l'âge engendrant des déformations osseuses. L'analyse quantifiée de la marche (AQM) permet d'objectiver et de mieux cibler les traitements orthopédiques. Cette thèse vise à enrichir l'AQM par une modélisation tridimensionnelle personnalisée du squelette et des muscles. L'AQM a été effectuée dans un laboratoire installé au Liban. Une base de données de sujets sains a été établie pour servir de référence à la compréhension des patterns de marche des patients. Une estimation des incertitudes liées aux paramètres de l'AQM a été effectuée, par étude de répétabilité et méthode de Monte Carlo, afin d'objectiver les comparaisons entre patients et sujets sains et entre données pré et post traitement. Une reconstruction 3D personnalisée du squelette en position debout a été effectuée par stéréoradiographie sous le système EOS® chez des enfants sains et IMC pour valider la faisabilité d'une telle technique. Des paramètres quantifiant les vices architecturaux ont été calculés et les incertitudes ont été estimées. Le recalage des structures osseuses durant la marche a été étudié grâce à la mise en place d'une cabine de stéréoradiographie au laboratoire d'analyse de la marche à Beyrouth. Des acquisitions IRM chez des sujets sains et un sujet IMC à Beyrouth ont permis d'explorer la faisabilité de la reconstruction 3D personnalisée des muscles des membres inférieurs en position couchée. La géométrie musculaire a été quantifiée en terme de longueurs, volumes et aires physiologiques. Une première approche de la reconstruction 3D des muscles en position debout a été réalisée en combinant les données de l'IRM et les structures osseuses obtenues par stéréoradiographie, permettant ainsi de calculer les rapports de longueurs entre corps musculaire et partie tendineuse. Ce travail permet d'analyser les anomalies de la marche à la lumière des déformations osseuses et musculaires pour une meilleure prise en charge thérapeutique des enfants IMC.

<p>In quantitative palaeoecology modern species-environmental relationships can be statistically modelled, and recent development has made the calibration models more statistically robust. These models are used to transform fossil assemblages to quantitative estimates of past environmental conditions. The aim of this thesis is to infer Holocene temperatures from fossil pollen data sampled from lakes in central and southern Sweden. This reconstruction is done by using a north-European pollen-climate calibration model, which was extended with 37 modern pollen samples from the southern deciduous vegetation zone in Sweden within this project. A statistical method is used for deriving the pollen-climate calibration model, weighted averaging partial least square (WA-PLS) method. The long term trends in pollen inferred temperatures from this study reflect low, but rapidly rising temperatures in the early-Holocene, a trend that was temporarily interrupted by a cool period about 8500 cal yr BP, but continued after 8000 cal yr BP. A Holocene thermal maximum (HTM) with temperatures roughly 2°C higher than at present was recorded about 7000 cal yr BP and by 4000 cal yr BP pollen inferred temperatures starts to decline. In order to create a more comprehensive picture of past climate patterns in the investigated area inferred temperatures from this study are compared with independent palaeorecords, a stable oxygen isotope record for moisture variability (paper I) and chironomids for summer temperature (paper II). Taken all together, these records reflect a coherent Holocene climate pattern which also is supported by several studies from Scandinavia and the north Atlantic region. Pollen inferred temperatures and the moisture record are indicating markedly dry, continental climate conditions in southern Sweden during the HTM possibly as a result of reorganisations in regional atmosphere circulations. The local observations in this study of regional climate events, such as the cold period at about 8200 cal yr BP and the dry period at about 7000 to 4000 cal yr BP are of particular interest because they suggest that vegetation in the study region has responded sensitively both to long-term climatic trends and more transient climate events.</p>

In quantitative palaeoecology modern species-environmental relationships can be statistically modelled, and recent development has made the calibration models more statistically robust. These models are used to transform fossil assemblages to quantitative estimates of past environmental conditions. The aim of this thesis is to infer Holocene temperatures from fossil pollen data sampled from lakes in central and southern Sweden. This reconstruction is done by using a north-European pollen-climate calibration model, which was extended with 37 modern pollen samples from the southern deciduous vegetation zone in Sweden within this project. A statistical method is used for deriving the pollen-climate calibration model, weighted averaging partial least square (WA-PLS) method. The long term trends in pollen inferred temperatures from this study reflect low, but rapidly rising temperatures in the early-Holocene, a trend that was temporarily interrupted by a cool period about 8500 cal yr BP, but continued after 8000 cal yr BP. A Holocene thermal maximum (HTM) with temperatures roughly 2°C higher than at present was recorded about 7000 cal yr BP and by 4000 cal yr BP pollen inferred temperatures starts to decline. In order to create a more comprehensive picture of past climate patterns in the investigated area inferred temperatures from this study are compared with independent palaeorecords, a stable oxygen isotope record for moisture variability (paper I) and chironomids for summer temperature (paper II). Taken all together, these records reflect a coherent Holocene climate pattern which also is supported by several studies from Scandinavia and the north Atlantic region. Pollen inferred temperatures and the moisture record are indicating markedly dry, continental climate conditions in southern Sweden during the HTM possibly as a result of reorganisations in regional atmosphere circulations. The local observations in this study of regional climate events, such as the cold period at about 8200 cal yr BP and the dry period at about 7000 to 4000 cal yr BP are of particular interest because they suggest that vegetation in the study region has responded sensitively both to long-term climatic trends and more transient climate events.