Frankia est une actinobactérie capable d'établir une symbiose racinaire avec les plantes actinorhiziennes dont le genre Alnus. Seulement certaines souches de Frankia sont capables de sporuler in planta, ce qui est illustré par la présence (Sp+) ou l'absence (Sp–) de sporanges dans les cellules végétales de la nodosité. C’est à notre connaissance un cas unique de sporulation endophyte. Cependant la description et l’interprétation écologique de ce trait d’histoire de vie (THV) original étaient incomplètes. Notre contribution à l’étude de la sporulation in planta des Frankia infectives de l’aulne intègre des approches théorique, descriptive et expérimentale, pour préciser (i) l’influence relative de la souche bactérienne, de l’espèce de la plante-hôte et des conditions pédoclimatiques sur ce THV, (ii) le rôle de la variabilité environnementale sur la distribution, la diversité et la sélection du trait, ainsi que (iii) les coûts et bénéfices associés pour les deux partenaires. Nous avons démontré pour la première fois que la sporulation in planta est un THV (i) spécifique de certaines lignées de Frankia, (ii) majeur pour en comprendre l'histoire évolutive et (iii) significativement corrélé à des caractéristiques génétiques des souches. Nous avons également confirmé que l’occurrence du trait varie selon l’environnement. Nous avons enfin établi un modèle de l'évolution du trait abordant sa valeur adaptative. L’ensemble des réflexions menées et des résultats obtenus nous permet de discuter de la sporulation in planta dans le cadre d’un continuum de stratégies symbiotiques, et plus généralement de discuter de l’écologie évolutive des symbioses entre microorganismes et plantes / Frankia sp. is a telluric actinobacteria able to establish a root symbiosis with actinorhizal plant such as Alnus sp. Only some Frankia strains are able to sporulate in-planta, as spores can be present in (Sp+) or absent from (Sp–) the vegetal cells of the root nodule. It is to our knowledge a unique case of endophytic sporulation. However, the description and the ecological interpretation of this original life-history trait (LHT) were scarce. Our contribution to the study of the in-planta sporulation of Alnus-infective Frankia sp. combines theoretical, descriptive and experimental approaches to precise (i) the relative effect of the bacterial strain, the host-plant species and the pedoclimatic conditions on this LHT, (ii) the effect of the of the environmental variability on the distribution, diversity and selection of the trait, and (iii) the associated costs and benefits for the two symbiotic partners. We demonstrated for the first time that the in-planta sporulation is a LHT (i) specific to some Frankia lineages, (ii) major to understand their evolutionary history and (iii) significantly correlated to particular genetic features. We also shown that the occurrence of the trait varies according to the environment We also proposed a model of the evolution of the trait taking its fitness into account. We bring all the previous considerations and results to discuss the inplanta sporulation trait within a continuum of symbiotic strategies and more generally to discuss the evolutionary ecology of plant-microbe symbioses

Στην παρούσα μεταπτυχιακή εργασία ειδίκευσης περιγράφεται η σύνθεση και ο χαρακτηρισμός νέων μεσοπορωδών βιοενεργών υλικών. Παρουσιάζονται οι συσχετιζόμενες με τα πορώδη/μεσοπορώδη υλικά έννοιες, οι ιδιότητες τους και διάφοροι τρόποι σύνθεσης τους. Εν συνεχεία, αναλύονται θέματα βιουλικών, δίνοντας έμφαση στις βιοϋάλους και τις ιδιότητες τους, και ειδικότερα στη βιονεργότητα, που αποτελεί την πιο χαρακτηριστική ιδιότητα αυτών, ενώ δίνεται έμφαση, επίσης στις διάφορες μεθόδους που χρησιμοποιούνται για την σύνθεση τους. Στην συνέχεια αναλύονται οι τεχνικές που χρησιμοποιήθηκαν για το χαρακτηρισμό των προαναφερθέντων υλικών καθώς και ο τρόπος λειτουργίας της κάθε τεχνικής. Επίσης, γίνεται αναφορά στα διαφορετικά χαρακτηριστικά των υλικών που μπορούν να μελετηθούν για κάθε τεχνική ξεχωριστά. Στο τελευταίο κεφάλαιο παρουσιάζεται αναλυτικά η διαδικασία διεξαγωγής των πειραμάτων, οι διάφοροι τρόποι σύνθεσης που χρησιμοποιήθηκαν, καθώς και σχολιασμός των αποτελεσμάτων. Τέλος, παρουσιάζονται τα συμπεράσματα που προέκυψαν από τα πειραματικά αποτελέσματα για την παρούσα μεταπτυχιακή εργασία. Επίσης γίνεται αναφορά και σε μελλοντικές κατευθύνσεις που περιλαμβάνουν την χρήση αυτών των υλικών σε σύνθετα υλικά για παλμική εναπόθεση με Laser και τεχνικές εναπόθεσης λεπτού υμενίου. / In this master thesis the synthesis and characterization of novel bioactive mesoporous materials is being reported. The notions related to porous/mesoporous materials, their properties and various synthetic methods are being discussed. Subsequently, the notion of “biomaterials” is further analyzed, focusing on bioglasses and their properties. The meaning of bioactivity is also analyzed as the most characteristic feature of bioglasses while various methods used for the synthesis of these are discussed. Following the techniques used to characterize these materials as well as the operating mode of each technique is discussed. In the last chapter, the experimental processes are reported as well as the results are being discussed. Finally, the conclusions of all the experiments and analysis are reported. Also, future directions include the usage of these materials in composite materials for laser ablation and thin film deposition techniques are mentioned.

Medulloblastomas are the most frequent malignant childhood brain tumors, arising in the posterior fossa of children. The overall 5-year survival is 70%, although children often suffer severe long-term side effects from standard medical care. To improve progression-free survival and quality of life for these children, finding new therapeutic targets in medulloblastoma is imperative. Medulloblastoma is divided in to four molecular subgroups (WNT, SHH, Group 3 and Group 4) based on key developmental pathways essential for the initiation and maintenance of tumor development. The MYC family of proto-oncogenes regulates cell proliferation and differentiation in normal brain. Aberrant expression of MYC proteins occurs commonly in medulloblastoma. Our studies on Group 3 medulloblastoma identify the transcription factor SOX9 as a novel target for the E3 ubiquitin ligase FBW7, and show that increased stability of SOX9 confers an increased metastatic potential in medulloblastoma. Moreover, SOX9-positive cells drive distant recurrences in medulloblastoma when combining two regulatable TetON/OFF systems. MYCN depletion leads to increased SOX9 expression in Group 3 medulloblastoma cells, and the recurring tumor cells are more migratory in vitro and in vivo. Segueing to treatment of medulloblastoma, we show that BET bromodomain inhibition specifically targets MYC-amplified medulloblastoma cells by downregulating MYC and MYC-transcriptional targets, and that combining BET bromodomain- and cyclin-dependent kinase- inhibition improves survival in mice compared to single therapy. Combination treatment results in decreased MYC levels and increased apoptosis, and RNA-seq confirms upregulation of apoptotic markers along with downregulated MYC target genes in medulloblastoma cells. This thesis addresses novel findings in transcription factor biology, recurrence and treatment in Group 3 medulloblastoma, the most malignant subgroup of the disease.

The main goal in reversing the allergy epidemic is the development of effective prophylactic strategies. Early life events, such as exposures to microbes, have a major influence on the development of balanced immune responses. Due to their ability to interact with host immune system and to modulate host immune responses probiotics, mainly bifidobacteria and lactobacilli have been used with some success in prevention of allergic disease. In order to be referred to as probiotic, bacterial strain has to undergo rigorous testing. We have selected three new Lactobacillus (L.) strains out of 24 human isolates according to their antagonistic activity against pathogenic bacteria, resistance to low pH and milieu of bile salts. Safety of these strains was proven upon intragastric administration to mice; moreover, we have shown their ability to shift cytokine Th1 - Th2 balance towards non-allergic Th1 response in isolated splenic cells. Allergen specific prophylaxis using probiotics as vehicles for mucosal delivery of recombinant allergen is an attractive concept for development of well-tolerated and effective allergy vaccines. We have shown that neonatal mono-colonization of germ-free mice with the L. plantarum NCIMB8826 strain producing the major birch pollen allergen Bet v 1 attenuates the development of...

This thesis aims to find general principles governing the behaviour of biological systems, with a particular emphasis in the communicational (social) aspect of these systems. Communication between biological entities plays a major role in their evolution, enabling them to exchange information about their environment and thereby improving their chances of survival. Communication also plays a pivotal role in the organisation of populations of organisms, clearly observed in social insects, but present also at least in bacteria, plants, fungi, animals and humans. It is also theorised that the genetic code is a by-product of the establishment of an innovation-sharing protocol between primitive cells [Vetsigian et al., 2006]. This thesis is mainly concerned with identifying necessary conditions for the emergence of communicational codes, and the problems that arise with their establishment. For this purpose, we introduce an information-theoretic framework where species maximise their growth rate by following a Kelly-gambling strategy to bet on environmental conditions. Information theory provides a powerful tool for abstracting away mechanisms and for focusing on hard limits of a system's dynamics which cannot be circumvented. We begin by exploring the relation between information exchange and limited resources. We show that a transition from cooperation to antagonism in the exchange of environmental information follows from a change in the availability of resources, from abundant to scarce. We then assume a non-competitive scenario with abundance of resources, where conflicts in a population occur only at a communicational (informational) level, rather than on the physical level, such as competing for (physical) resources. However, traditional Shannon communication is non-semantic, as opposed to the semantic communication observed in biological systems, which is necessary for capturing conflicts in communication. In the traditional use of information theory, it is assumed that every organism knows how to \interpret" the information offered by other organisms. However, this assumes that one \knows" which other organisms one observes, and thus which code they use. In our model, however, we wish to preclude that: namely, we will do away with the assumption that the identity of the organisms who send the messages and those who receive them is known, and the resulting usable information is therefore influenced by the universality of the code used and by which organisms an organism is \listening" to. We introduce a model which captures semantic communication in information-theoretic terms, where organisms talk to each other in a communication network. We show that, for particular population structures, when organisms cannot identify which other organisms they talk to, the adoption of a universal code emerges as a solution for full interpretation of the shared information. However, the evolution and establishment of universal codes for communication introduces vulnerabilities: organisms can be exploited by parasites. We de ne two types of parasites whose strategies have different levels of complexity and study the co-evolution of a host (the population) and a parasite by optimising their respective objective functions in stages. First, we consider a disruptive parasite (a troll) that inflicts harm in a host by minimising a population's mutual understanding, and then a more complex parasite, which manipulates the members of the population via their codes (the puppetmaster). We show emergent characterisations of both parasites, as well as which host configurations are robust against parasites and show adaptive properties. This thesis introduces a framework which allows the study of informational properties in the host-parasite co-evolution, where the rules of the parasite's habitat, the host, are the outcome of an evolutionary process, and where these very same rules are those that allow the parasite to exploit the host.

Self-reactive CD4+ helper T cells (Th) are key causal agents in the pathogenesis of many autoimmune diseases. Experimental autoimmune encephalomyelitis (EAE) is a CD4+T cell model of the demyelinating autoimmune disease multiple sclerosis (MS). It has been shown that EAE is caused by CD4+ T-cells that produce pro-inflammatory cytokines IFN-γ (Th1) and IL-17 (Th17). As such, understanding how these Th cells are generated and controlled is essential. There is debate as to whether Th1 and Th17 cells act independently in EAE or if there is plasticity between these two subtypes, and whether the capacity to switch from Th1 to Th17 confers pathogenic capacity. T-bet was first described as the master transcription factor for Th1 cells, and is thought to have a critical role in EAE even though IFN-γ, the Th1 archetypal cytokine, has been shown to be redundant. More recent work has shown that T-bet is expressed in multiple immune cell types, and it remains unclear in what cells the expression of T-bet is required for EAE. Considerable efforts have been put into understanding the role of T-bet in EAE pathogenesis, with a view to modulate cells expressing T-bet for therapy. The hypothesis of this work was that T-bet has multifaceted roles in EAE, in initiating and directing an immune response in innate antigen presenting cells such as dendritic cells (DC) as well as programming pathogenic effector CD4+ T cell (Teff) response to antigen. T-bet-/- mice were studied using different models of EAE to dissect the role of T-bet in disease pathogenesis. Active immunisation of C57BL/6 mice with the immunodominant peptide from myelin oligodendrocyte glycoprotein (MOG35-55) showed that T-bet-/- mice developed EAE with an IL-17 dominated profile and critically, T-bet-/- mice were able to produce GM-CSF which has recently been described as a key cytokine for EAE. T-bet-/- cells were not able to transfer EAE in a model of passive transfer EAE, where CD4+ T cells were polarised towards a Th1 profile in vitro. Illustrating that T-bet is required in CD4+ T cells for Th1 mediated EAE. DC driven EAE showed that T-bet-/- DC were able to activate CD4+ T cells in vitro and cause EAE upon co-transfer into host mice with transgenic CD4+ T cells. Thus, it has been shown that T-bet is not required in EAE. This work represents a step further towards understanding the disease mechanisms involved in EAE and suggests T-bet is not an appropriate therapeutic target for the treatment of MS.

The sagebrush (Artemisia spp.) steppe is undergoing rapid ecological change. The degradation of sagebrush steppe rangelands has resulted in the listing of more than 350 animals and plants as species of conservation concern. In addition, there has been a decrease in recreational values, reduced forage production, degraded water resources, and an increase in fire frequency. In the sagebrush steppe, success rates for seeding sagebrush after wildfire are notoriously low. Not only are sagebrush seeds hard to sow due to their small size and associated flower parts, but seedlings are exposed to numerous stresses that lowers their survivability. To improve sowing efficiency and reduce the associated stresses to seedling development we use seed enhancement technologies. In Chapter 1, we explain how a rotary seed coater can be used to agglomerate and apply enhancements to Wyoming big sagebrush (Artemisia tridentata spp. wyomingensis) seed. Using a mix of compost and clay we used a rotary seed coater to create small uniform agglomerates that allowed for enhancements to be applied to the seed. Our study demonstrated that agglomerates have no negative effects on seed germination and increased the overall flow of seed. In Chapter 2, we analyzed the addition of the plant hormone abscisic acid (ABA) in seed coatings. This hormone may delay seed germination and allow seedlings to avoid mortality due to over-winter freezing. We determined effects of different concentrations of ABA on total germination and timing of germination. Using a wet-thermal accumulation model, we estimated germination timing of seeds using soil temperature and water potential data for six different sites in the Great Basin. These models illustrate the variation in germination timing across the Great Basin. From our results we proposed the idea of using ABA to create a bet- hedging strategy in seed mixes to increase the probability that some seeds would germinate when conditions are favorable for seedling success.

An onset coarsening-coalescence event based on the incubation time of cylindrical mesopore formation and a significant decrease of specific surface area by a certain fraction relative to the dry pressed samples was determined by N2 adsorption-desorption hysteresis isotherm for amorphous SiO2 nanoparticles (ca. 40 nm in size). In the temperature range of 1150-1300oC, the nanoparticles with binder (PVA) additive underwent onset sintering coupled with coarsening-coalescence without appreciable crystallization. The apparent activation energy of such a rapid process for amorphous SiO2 nanoparticles was estimated as 177 ¡Ó 31.5 kJ/mol, based on 30% change of specific surface area. As a comparison, in much lower temperature range of 600-900oC, the amorphous Zn2SiO4 nanoparticles underwent onset sintering coupled with coarsening-coalescence accompanied more or less with the formation of ZnO The apparent activation energy of such a rapid process for a amorphous Zn2SiO4 was estimated as 105 ¡Ó 3.8 kJ/mol based on 50% change of specific surface area. The minimum temperatures for sintering/coarsening/coalescence of the amorphous SiO2 and Zn2SiO4 are 1120¢J and 635oC, respectively based on the extrapolation of steady specific surface area reduction rates to null. PLA fragmentation of amorphous and nearly spherical SiO2 nanoparticles (40 nm in size) in water (i.e. PLAL process) with optional NaCl addition was conducted under Q-switch mode (532 nm, 400 mJ per pulse) having laser focal point fixed at ca. 10 mm beneath the water level for an accumulation time of 20 and 30 min at 10 Hz. The 532 nm laser incidence suffered little water absorption and was effective to produce irregular shaped amorphous nanocondensates as small as 10nm~20nm in diameter with accompanied change of medium range order (MRO) as indicated by single rather than two broad x-ray diffractions at low 2theta angle. Whereas the Na+ uptake in the amorphous silica from the salty water account for a lower wave number of FTIR bands. The combined effects of nanosize, MRO change and H+ -signature may cause a lower minimum band gap of the amorphous products (analogous to opal-A) which become partially crystallized as £]-cristobalite (analogous to opal-CT) with additional £\-tridymite when Na+ is present.

The specific surface area reduction and pore size distribution coupled with N2 adsorption-desorption hysteresis isotherm were studied in the temperature range of 1400-1550¢J for periclase MgO powder having 0.1£gm in size and with face-centered cubic structure. The apparent activation energy of such a rapid coarsening-coalescence process for MgO powder was estimated as 181¡Ó3kJ/mol. The minimum temperature for sintering/coarsening/coalescence of submicron MgO particles was estimated to be near 1300¢J based on the extrapolation of steady specific surface area reduction rates to zero. Pulsed laser ablation (PLA) of periclase MgO powders in water was conducted under Q-switch mode and specified water height and water depth (10 mm) for an accumulation time of 5 and 20 minutes at 10 Hz. Such a PLA process has successfully synthesized nanosized and protonated MgO particles from Mg(OH)2 and lamellar precusors, implying the three phases may co-exist at high pressure and temperature conditions upon dynamic shock loading. A significant internal compressive stress up to 10 GPa was built up for the MgO but not the readily relaxed Mg(OH)2 nanocondensates. The lamellae-derived Mg(OH)2 tended to undergo a dehydroxylation process to become MgO following a specific crystallographic relationship, i.e. lamellar basal layer parallel to Mg(OH)2(0001) and MgO(111). The minimum band gap of the colloidal solution of MgO/Mg(OH)2/lamellae was lowered to ca. 5.2eV after the PLA process.

Mesoporous materials attracted great interest due to their huge surface area and adjustable pore sizes. One of the important mesoporous materials is SBA-15 and has larger pore size, hydrothermal stability and thicker walls than other mesoporous materials. In this study, SBA-15 is synthesized by using sol-gel technique and cobalt oxide nanoparticles are incorporated in mesochannels by direct method. SBA-15 was produced from the self-assembly of non-ionic triblock co-polymer (Pluronic 123) and tetra ethyl ortho silicate (TEOS). Then cobalt chloride and cobalt nitrate were added at different loading ratios with two different addition sequences / after polymer and after TEOS. The loading ratios are in Si/Co mols and these ratios are / 15, 10, 5, 3, 1.5, 1 and 0.75 in increasing cobalt amount loaded. Characterization of the produced materials was performed by Powder X-Ray Diffraction (PXRD), Infrared (FTIR) analysis. Nitrogen Phisisorption measurements (BET and BJH Methods) were used to examine the textural properties of produced materials. By means of Transmission Electron Microscopy (TEM) the micro structures of materials were investigated. From the PXRD studies it is observed that the long range order of pores is preserved at even high loading amounts for cobalt chloride addition after TEOS. Co3O4 (JCPDS card no: 42-1467) crystallites are observed for Si/Co mol loading ratios 3, 1.5, 1 and 0.75. Above these loading ratios cobalt oxide is highly dispersed in SBA-15-type structure. FTIR studies revealed the formation of condensed silica network. From the Nitrogen Phisisorption measurements it is observed that addition of cobalt salt decreases the BET surface area of produced materials. All Nitrogen Adsorption-Desorption Isotherms are Type-IV, and has H-1 hysteresis which is a fulfillment of mesoporous structures according to IUPAC classification. BET surface area of samples loaded with cobalt chloride after TEOS possessed higher surface area than other samples. TEM images proved that at loading ratios above 3 there were not any cobalt oxide nanoparticles, cobalt oxide is highly dispersed on silica surface whereas at loading ratios 3 and below there were cobalt oxide nanoparticles embedded in the mesochannels for the samples prepared by addition of cobalt chloride after TEOS.