Malignant glioma have poor prognosis resulting mainly from high level of cell proliferation and invasion and resistance to conventional therapy. Identification of novel targets that are critical elements in gliomagenesis may help improve therapeutic outcome. Using genome-wide explorations of a comprehensive glioma specimen population, we identified whole gain of chromosome 19 as one of the major chromosomal aberrations in high grade glioma that correlates to patients' outcomes. Our analysis revealed for the first time NOTCH3 as one of the most significant gene amplifications mapped to chromosome 19. This amplification is associated with worse outcome compared to tumors with non-amplified locus. NOTCH signaling pathway is essential for cell proliferation, stem cell maintenance and differentiation and its deregulation has been reported in several human cancers. NOTCHs are key positive regulators of cell-cell interactions, angiogenesis, cell adhesion and stem cell niche development which have been shown to play critical roles in gliomagenesis and glioma drug resistance. Our objective is to determine NOTCH3 molecular roles in glioma pathogenesis and aggressiveness. Here we show for the first time that NOTCH3 plays a role in glioma cell proliferation, cell migration, invasion and apoptosis. We also found a NOTCH3 glioma addiction phenomenon. Therefore, our study uncovers, for the first time, the prognostic value and the oncogenic function of NOTCH3 in gliomagenesis and supports NOTCH3 as a promising target of therapy in high grade glioma. Our studies allow the identification of a subset of population that may benefit from GSI-based therapies. This may lead to the design of novel strategies to improve therapeutic outcome of patients with glioma by establishing medical and scientific basis for personalized medicine.

Mountain headwater catchments in the semi-arid Intermountain West are important sources of surface water because these high elevations receive more precipitation than neighboring lowlands. The hydrology of these mountain catchments is especially important as the region faces water shortages and conflicts. Conifer encroachment on aspen stands has been observed across the western US and can result in a decline in water yield. The overall objective of this study was to further our understanding of hillslope-stream connectivity in a headwater catchment of Northern Utah and any observable differences in this connection between aspen and conifer hillslopes. Hillslopes are the fundamental unit of a watershed. Therefore understanding processes at the hillslope scale is pertinent to managing valuable water resources. However, hillslope hydrology is understudied in the snow-driven, semi-arid west, leaving a gap in our knowledge of how watersheds function. This thesis focuses on how and when hillslope water contributes to stream water: hillslope-stream connectivity. Its specific objectives are (1) to compare peak snow accumulation under aspen and conifer stands, (2) to determine if shallow soil moisture shows organized patterns, indicating hillslope-connectivity and compare these patterns between vegetation types, (3) to examine hillslope-stream connectivity within deep layers of the soil profile and compare times of connectivity between vegetation types and (4) to find any thresholds past which hillslope-stream connectivity begins.

Diffuse knapweed (Centaurea diffusa) is an introduced annual or short-lived perennial from Eurasia that has become a threat to native rangelands in the Pacific Northwest. Military training activities on the Yakima Training Center (YTC) increase the likelihood that knapweed will expand its range at YTC. This study, conducted in a major watershed at YTC, focused on: 1) how a variety of environmental variables influences knapweed distribution, 2) the use of Landsat Thematic Mapper (TM) imagery to map existing knapweed populations, and 3) the use of a logistic regression model and geographical information systems (GIS) to create a potential knapweed habitat map. Topographic and climatic factors had the greatest influence on knapweed distribution. Knapweed has a competitive advantage over those which may have some water stress due to increased temperatures (i.e., lower elevations and south slopes). Lower shrub density, greater percent bare ground, and lower percent perennial aerial cover also made for ideal knapweed habitat. Knapweed density decreased as slope steepness, pH, and percent rock cover increased. Using TM imagery to define existing knapweed populations was unsuccessful because most knapweed stands were less than 30 m X 30 m and had little effect on the TM image values. However, the TM imagery was useful in defining potential knapweed habitat along with other variables. Sixty percent of the Selah watershed has the potential to support knapweed. Approximately 68 % of the potential knapweed habitat was infested with knapweed. Denser patches (> 1 plant per m2) were limited to 21% of the potential habitat.

Invasive plant species impact ecosystems by altering native plant community composition and modifying ecosystem properties such as fire and nutrient cycles. We used species distribution models to address both theoretical and applied questions regarding invasive plants in an ecosystem particularly vulnerable to invasion, riparian areas. In our first study, we asked whether a native species is closer to equilibrium than a functionally similar invasive species and determined drivers of invasion for an aggressive invader of riparian areas, Phalaris arundinacea (reed canarygrass). We modeled the presence of P. arundinacea and a comparable native species using four techniques and compared model fit between species and between models with and without dispersal processes incorporated. Non-dispersal model fit for our invasive species was lower than for the native species and improvement in fit with the addition of the dispersal constraint was greater for the invasive species than the native species. These results provide evidence that invasive species are further from equilibrium than native species and suggest that dispersal processes should be considered when modeling invasive species. In our second study, we addressed whether there was a set of site traits that make some sites more prone to invasion by non-native plants than others. We used Random Forests to individually model the presence of 11 invasive plant species that are designated as noxious weeds in our study area. We used model results to identify general patterns of invasion and to provide management recommendations for the study area. We found that a particular site type was more likely to be invaded by the majority of study species: hot, dry sites with high grass or shrub cover near roads with high nutrient levels and high stream baseflow values. Management recommendations to combat invasion by P. arundinacea in particular and invasive species in general are the same: limiting species’ spread along roads, lowering site nutrient levels, and anticipating increased spread with climate change.

Due to the significant threats posed by nonnative fish species worldwide, it is important to understand how life-history strategies of individual species interact with environmental conditions to explain the success or failure of nonnative fish invasions. Brown trout are prolific invaders, but often exhibit upstream distributional limits in Intermountain West streams, potentially due to a maladaptive reproductive life-history strategy influenced by hydrologic conditions in high-elevation areas. We used redd counts, egg survival experiments, and temperature modeling to investigate the reproductive life-history strategy of brown trout and its potential for success along an elevational stream gradient. We documented brown trout spawning in stream reaches at elevations higher than where we typically encounter brown trout during summer electrofishing surveys, indicating the potential for upstream invasion. We observed a decline in egg survival at higher elevation, cooler water sites, but did not document complete recruitment failure at these sites, again indicating the potential for successful invasion at this life-stage. Temperature data indicate that during most years, incubating brown trout eggs would likely fail to emerge from the gravel prior to peak spring flows in these high-elevation stream reaches, suggesting that damaging spring floods may cause significant egg and sac-fry mortality at high elevations, and may determine invasion success in these areas. Our results highlight the importance of identifying specific mechanisms of recruitment failure in order to better predict nonnative fish invasions in the future.

The Staphylococcus aureus two component system (TCS) sae governs expression of numerous virulence factors, including Eap (extracellular adherence protein), which in turn among other functions also mediates invasion of host cells. The sae TCS is encoded by the saePQRS operon, with saeS coding for the sensor histidine kinase (SaeS) and saeR encoding the response regulator (SaeR). The saeRS system is preceded by two additional open reading frames (ORFs), saeP and saeQ, which are predicted to encode a lipoprotein (SaeP) and a membrane protein (SaeQ), respectively. Earlier, we have shown that SDS-containing subinhibitory concentrations of biocides (Perform®) and SDS alone activate sae transcription and increase cellular invasiveness in S. aureus strain Newman. The effect is associated with an amino acid exchange in the N-terminus of SaeS (L18P), specific to strain Newman. In this work, the role of whether the two additional genes, saePQ coding for the accessory proteins SaeP and SaeQ, respectively, are involved in SDS-mediated saeRS was investigated. It could demonstrated that the lack of the SaeP protein resulted in an increased saeRS transcription without SDS stress in both SaeSL/P variants, while the SDS effect was less pronounced on sae and eap expression compared to the Newman wildtype, suggesting that the SaeP protein represses the sae system. Also, SDS-mediated inductions of sae and eap transcription along with enhanced invasion were found to be dependent on presence of the SaeSP variant in Newman wildtype. On the other hand, the study also shows that the saePQ region of the sae operon is required for fully functional two-component system saeRS under normal growth conditions, but it is not involved in SDS-mediated activation of the saeS signaling and sae-target class I gene, eap. In the second approach, the study investigates whether SDS-induced sae expression and host cell invasion is common among S. aureus strains not carrying the (L18P) point mutation. To demonstrate this strain Newman, its isogenic saeS mutants, and various S. aureus isolates were analysed for sae, eap expression and cellular invasiveness. Among the strains tested, SDS exposure resulted only in an increase of sae transcription, Eap production and cellular invasiveness in strain Newman wild type and MRSA strain ST239-635/93R, the latter without an increase in Eap. Interestingly, the epidemic community-associated MRSA strain, USA300 LAC showed a biphasic response in sae transcription at different growth stages, which, however, was not accompanied by increased invasiveness. All other clinical isolates investigated displayed a decrease of the parameters tested. While in strain Newman the SDS effect was due to the saeSP allele, this was not the case in strain ST239-635/93R and the biphasic USA300 strains. Also, increased invasiveness of ST239-635/93R was found to be independent of Eap production. Furthermore, to investigate the global effect of SDS on sae target gene expression, strain Newman wild-type and Newman ∆sae were treated with SDS and analyzed for their transcription profiles of sae target genes using microarray assays. We could show that subinhibitory concentrations of SDS upregulate and downregulate gene expression of several signaling pathways involved in biosynthetic, metabolic pathways as well as virulence, host cell adherence, stress reponse and many hypothetical proteins. In summary, the study sheds light on the role of the upstream region saePQ in SDS-mediated saeRS and eap expression during S. aureus SDS stress. Most importantly, the study also shows that subinhibitory SDS concentrations have pronounced strain-dependent effects on sae transcription and subsequent host cell invasion in S. aureus, with the latter likely to be mediated in some strains by other factors than the known invasin Eap and FnBP proteins. Moreover, there seems to exist more than the saeSP-mediated mechanism for SDS-induced sae transcription in clinical S. aureus isolates. These results help to further understand and clarify virulence and pathogenesis mechanisms and their regulation in S. aureus. / Das Zwei Komponenten-Systems (TCS) Sae in S. aureus reguliert die Expression einer Vielzahl von Virulenzfaktoren, dazu gehört unter anderem das extrazelluläre Adhärenzprotein Eap, welches neben weiteren Funktionen, die Invasion in eukaryotische Wirtszellen vermittelt. Die Gene des sae TCS sind in einem Operon organisiert (saePQRS), wobei saeS für die sensorische Histidinkinase (SaeS) und saeR für den „Response Regulator“ (SaeR) kodieren. Diesen Genen sind zwei weitere Genabschnitte, saeP und saeQ, vorangestellt, wobei saeP vermutlich für ein Lipoprotein (SaeP) und saeQ für ein Membranprotein (RelQ) kodieren. In einer früheren Arbeit konnten wir zeigen, dass SDS-haltige Biozide (Perform©) unter sub- inhibitorischen Konzentrationen, sowie reines SDS, die sae Transkription aktiviert und dadurch zu einer erhöhten Invasion des S. aureus Stamms Newman in Wirtszellen führt. Dieser Effekt ist assoziiert mit einem spezifischen Aminosäureaustausch im N-terminus von SaeS (L18P) des Stamm Newman. In dieser Arbeit soll nun die Beteiligung der zwei zusätzlichen Gene, saeP und saeQ, an der SDS vermittelten transkriptionellen Induktion von saeR/S untersucht werden. Es konnte gezeigt werden, dass ohne SaeP, die saeR/S Transkription in beiden SaeL/P Varianten erhöht war, wobei eine zusätzliche SDS Behandlung hierfür nicht notwendig war. Im Gegenteil, es zeigte sich, dass der SDS Effekt auf die sae und eap Expression in der saeP Mutante deutlich weniger ausgeprägt ist als im Wildtyp Stamm. Das läßt vermuten, dass das Lipoprotein SaeP repremierend auf das sae System einwirkt. Des Weiteren wurde festgestellt, dass die SDS vermittelte transkriptionelle Induktion von sae und eap, zusammen mit der erhöhten Invasion, abhängig vom vorhanden sein der SaeSP Variante im Newman Wildtyp Stamm ist. Die Arbeit zeigt, dass die saePQ Region wichtig ist für die vollständige Funktion des Zwei Komponenten Systems SaeRS unter normalen Wachstumsbedingungen. Jedoch ist diese Region nicht involviert in der Aktivierung von SaeS, mit SDS als Signalgeber, sowie der darauffolgenden Aktivierung des sae Zielgens eap. In einem zweiten Ansatz wurde untersucht, ob die SDS induzierte sae Expression und Wirtszellinvasion auch häufig in S. aureus Stämmen auftritt, welche keine (L18P) Punktmutation besitzen. Dafür wurde Stamm Newman, die isogene saeS Mutante und verschiedene S. aureus Klinikisolate auf ihre sae, eap Expression, sowie zelluläre Invasionsfähigkeit hin analysiert. Von den getesteten Stämmen reagiert nur Wildtyp Stamm Newman und ein MRSA Stamm ST239-635/93R mit gesteigerter sae Transkription, Eap Produktion und zellulärer Invasion. Der MRSA Stamm jedoch ohne erhöhte Eap Produktion. Interessanterweise zeigt der „community- associated“ MRSA Stamm USA300 LAC eine biphasische sae Transkription in verschiedenen Wachstumsphasen, welche jedoch nicht einhergeht mit erhöhter Invasion. Alle anderen Klinikisolate zeigten abnehmende Tendenzen in den getesteten Parametern. Während im Stamm Newman der SDS Effekt auf das saeSP Allel zurückzuführen ist, gilt dies nicht für den Stamm ST239-635/93R, sowie den biphasischen Stamm USA300. Außerdem konnte gezeigt werden, dass die erhöhte Invasion des Stamms ST239-635/93R unabhängig von seiner Eap Produktion ist. Des Weiteren zeigten wir den globalen Effekt von SDS auf die sae Zielgenexpression. Dafür behandelten wir Wildtyp Stamm Newman mit SDS und analysierten die Transkription der sae Zielgene mittels Microarray Analyse. Wir konnten zeigen, dass subinhibitorische SDS Konzentrationen, induzierende als auch repremierende Auswirkungen auf die Genexpression haben. Dabei sind Gene betroffen, die involviert sind in verschiedene Signalwege, Biosynthese/Metabolismus als auch in Virulenz, Wirtzelladhärenz und Stressantwort. Zusammenfassend gibt die Arbeit Aufschluss über die Rolle der „upstream“ Region saePQ hinsichtlich der SDS-abhängigen saeRS und eap Expression in S. aureus. Am wichtigsten ist hierbei die Erkenntnis, das subinhibitorische SDS Konzentrationen einen deutlichen stammabhängigen Effekt auf die sae Transkription und daraus folgernd auf die Wirtszellinvasion von S. aureus haben. Letzteres wird vermutlich in manchen Stämmen durch andere Faktoren als die bekannten Invasinproteine Eap und FnBP vermittelt. Außerdem scheint es in den klinischen S. aureus Isolaten mehr als nur den saeSP abhängigen Mechanismus der sae Induktion durch SDS zu geben. Diese Ergebnisse helfen uns die Virulenz und pathogenen Mechanismen als auch deren Regulation in S. aureus zu verstehen. Die Beobachtungen tragen zu unserem Verständnis bei, wie das sae System Signale der Umgebung detektieren kann. Dies ist bis jetzt eine Fragestellung mit vielen Unbekannten.

Einerseits werden anthropogene Störungen oft genannt, um erfolgreiche Invasionen von invasiven Organismen in ihren neuen Arealen zu erklären. Andererseits sind gängige Theorien pflanzlicher Invasionen häufig für ihren limitierten erklärenden und voraussagenden Wert kritisiert worden, hauptsächlich aus Gründen der ökologisch komplexen Zusammenhänge, die Invasionen zu Grunde liegen. Die ökologische Komplexität eines andauernden Invasionsprozesses zweier invasiver Brassicaceen berücksichtigend, wurde diese Studie durchgeführt, um experimentell die wichtigsten Faktoren zu bestimmen, die den an Feldstandorten zu beobachtenden variablen Dominanz-Mustern der Arten im Vergleich zu vergesellschafteten indigenen Arten zugrunde liegen. Das Vorkommen, die relative Häufigkeit und die Dynamik der genannten Arten in spontanen Beständen stand daher im Zentrum dieser Arbeit. Ziel der Arbeit war es, auf der Basis des erlangten Verständnisses der funktionellen Ökologie der Kodominanzgesellschaften Vorhersagen zum gegenwärtig fortschreitenden Invasionsprozeß zu machen. Die Bestandsentwicklung (Wachstum und Fitneß) der zwei invasiven Arten wurde in Abhängigkeit unterschiedlicher Artenkombination, Etablierungsstadium und anthropogenem Störungsregime in experimenteller Vegetation untersucht. Diese Untersuchungen sind von unmittelbarer Bedeutung für das untersuchte System, weil eine möglichst 'naturgetreue' Artenvergesellschaftung an einem geeigneten Standort gewählt wurde. Darüber hinaus sollte durch die Dauer des Experiments (3 volle Vegetationsperioden) vermieden werden, daß es zu Fehleinschätzungen von Bestandsentwicklungsdynamiken kommt, die aus zu kurzen Beobachtungszeiträumen resultieren können und für prädiktive Aussagen bedeutungslos sind. Die dieser Arbeit zugrunde liegenden Fragen und Hypothesen waren: (?) Werden die invasiven relativ zu den indigenen Arten durch Störungsmanagements gefördert? Führt wiederholte Störung zu einer Verstärkung der Effekte über die Zeit? (!) Hypothese: Die invasiven können relativ zu den indigenen Arten unter dem Einfluß von Störungsmanagements profitieren, wobei die Unterschiede mit der Zeit stärker werden. (.)Die Hypothese wird durch die Ergebnisse bestätigt. Kumulative, durch wiederholte Störungen verursachte Effekte, fördern die Invasiven relativ zu den Indigenen. (?) Unterscheiden sich die unterschiedlichen Störungsregime in ihren Effekten voneinander? (!) Hypothese: Beide invasive Arten reagieren in ähnlicher Weise. Eine zunehmende Störungsintensität (P>M2>M1>K) verstärkt die Effekte. (.)Diese Hypothese wird durch die Ergebnisse teilweise bestätigt. Insgesamt gesehen werden die Invasiven durch eine zunehmende Intensität der Störung stärker gefördert. Allerdings unterscheiden sich die beiden Arten in ihrer Reaktion auf unterschiedliche Störungen erheblich. B. orientalis profitierte nur mäßig, sowohl von Mahd als auch von Bodenabtragung. R. austriaca dagegen wurde von Mahd eher beeinträchtigt und profitierte sehr stark von Bodenabtragung. (?) Wie wirken sich Variationen in der Zusammensetzung von Etablierungsstadien zu Beginn einer Bestandsentwicklung aus? (!)Hypothese: Ein Entwicklungsvorsprung, i.a. ein weiter fortgeschrittenes Etablierungssstadium im Vergleich zu den vergesellschafteten Indigenen, sollte für die Invasiven von Vorteil sein. Im Falle, daß beide Gruppen durch gleiche Etablierungsstadien vertreten sind, sollte die Etablierung aus juvenilen Stadien vorteilhafter sein als jene aus adultem Pflanzenmaterial, weil angenommen wird, daß invasive Arten hohe anfängliche Wachstumsraten juveniler Stadien aufweisen. (.) Auch diese Hypothese kann durch die Ergebnisse nur teilweise bestätigt werden. Ein Etablierungsvorsprung ist für die Invasiven nur zu Beginn der Bestandsentwicklung bedeutend. Darüber hinaus profitiert R. austriaca relativ stärker von der Regeneration aus adultem Pflanzenmaterial. Zurückzuführen ist das auf das enorme Potential dieser Art, aus fragmentierten Pflanzen erfolgreich zu regenerieren. (?) Haben unterschiedliche Artenkombinationen einen Einfluß auf die Reaktion der Invasiven auf die unterschiedlichen Störungsregime und Etablierungsstadien? (!) Hypothese: Ein Unterschied in der Reaktion wird erwartet, aber keine Veränderung der wesentlichen Muster. (.) Der Austausch einer Art (funktioneller Ökotyp) der fünf (sechs) vergesellschafteten Arten in experimenteller Vegetation hatte einen stärkeren Effekt auf die Ergebnisse als erwartet. Es zeigt sich, daß die An- oder Abwesenheit eines funktionellen Ökotyps dafür verantwortlich ist, ob die invasive Art in ihrer Bestandsentwicklung prosperiert oder beeinträchtigt wird. Zusammenfassend läßt sich sagen, daß die Invasiven schwache Konkurrenten sind, aber von anthropogener Störung opportun profitieren. Ihre Entwicklung in den weit verbreiteten 'Co-Dominanzgesellschaften', welche Betrachtungsgegenstand dieser Untersuchung waren, hängt eindeutig mit allen vier untersuchten Faktoren zusammen und ist von diesen abhängig: Artidentität, Art der Störung, Etablierungsstadium und Artkombination. Die Effekte dieser Faktoren interagieren in komplexer Art und Weise. Zieht man die gegenwärtige Art der Landnutzung in der Region in Betracht, muß davon ausgegangen werden, daß beide Arten in mäßig bis stark gestörten krautigen Gesellschaften mit ausreichender Nährstoffversorgung weiter zunehmen werden. Der Invasionserfolg von R. austriaca wird stärker von Bodenstörung und Bodentranslokation abhängen, während für B. orientalis zu erwarten ist, daß sie vor allem an gemähten Standorten mit nicht zu dichtem Bestand an Gräsern weiter expandieren wird. / On the one hand anthropogenic disturbance is often adressed explaining successful invasions of non-indigenous species in their new locations. On the other hand current theories of plant invasion have been criticized for their limited heuristic and predictive value for different reasons referring to their ecological complexity. Including the ecological complexity of an ongoing invasion process of two invasive Brassicaceae, the purpose of this study was to analyse experimentally the most important factors that determine the varied dominance patterns of the invasives as compared to the co-occurring indigenous species that can be observed in the field. Therefore, this study focused on the occurrence, the relative abundance and dynamics of the species in spontaneous stands. The main objective was to predict the further invasion process of the neophytes based on an understanding of the functional ecology of the surveyed co-dominance stands. The development of the stands (growth and fitness) of the two invasives, B. orientalis and R. austriaca, was examined in experimental vegetation in dependence on species association, life stage composition and anthropogenic disturbance regime. These investigations are directly relevant for evaluating the processes in spontaneous field stands that are composed of the same species. The experiment was run over a period of 3 years to avoid misinterpretations by premature results. The underlying questions and hypotheses of this study and the corresponding results were: (?) Do the invasive species profit from anthropogenic disturbance regimes relative to the indigenous species? Do repeated disturbances add up in their effects (cumulative effects)? (!) Hypothesis: the invasive species do profit from disturbances relative to the indigenous species and the differences between the groups will increase if disturbances are repeated. (.) This hypothesis is confirmed by the results. Cumulative effects by repeated distur-bances promote the invasives relative to the indigenous. (?) Do the different disturbance regimes differ from each other in their effects? (!) Hypotheses: both invasive species will benefit in a similar way. A higher disturbance intensity (P>M2>M1>K) will strengthen the effects. (.) These hypotheses are only partly confirmed by the results. On the whole, increased disturbance intensity had a stronger beneficial effect on the invasives. Still, the two species differed strikingly with respect to their response to the various treatments. Whereas B. orientalis profited only moderately by both mowing and soil disruption, R. austriaca rather suffered from mowing but was greatly benefitted by soil disruption. (?) What is the effect of variations in the composition of life stages at the beginning of stand development? (!) Hypotheses: a head start, i.e. an advanced life stage relative to the co-occurring indigenous, should be advantageous for the invasive species. In case both groups co-occur in the same life stage, stand initiation by juveniles should favour the invasives over stand initiation by regeneration of adult plant material because invasive species are supposed to have rapid initial growth. (.) Again, these hypotheses are only partly confirmed by the results. A head start is important for the development of the invasive species, at least initially. However, at least R. austriaca appears to profit relatively more from regeneration by adult plant material. This is due to the enormous regeneration Potential of fragmented plants. (?) Are the responses of the invasive species to the different disturbance regimes and life stage compositions dependent on the association of co-occurring indigenous species? (!) Hypothesis: the responses may vary somewhat but there will be no changes in the major patterns. (.) An exchange of one species (functional type) out of the five (six) species mixed in the experimental stands had a more pronounced effect on the outcome of the results than expected. It appears that the presence or absence of just one functional type (species) in a stand can determine whether the invasive species can thrive under the given site conditions or whether it will be impaired in its development. In sum, the results show that the two invasive species are weak competitors but profit opportunistically from anthropogenic disturbance. Their development in the widespread 'co-dominance stands' that were in the focus of this study is clearly related to and dependent on all four investigated factors, species identity, type of disturbance, life stage composition and species association. The effects of these factors may interact in a complex way. In general, given the present situation of land use in the region, the results suggest that both species will further advance their presence in moderately to intensively disturbed forb communities at sites with sufficient nutrient availability. Invasion success of R. austriaca will be more dependent on soil disruption, transport and deposition while B. orientalis is expected to particularly expand at mown sites that do not have dense cover by meadow grasses.

Mammalian pests are excluded from Maungatautari Ecological Island by an XcluderTM pest-proof fence. Inevitably, the fence integrity will be compromised at some point by mechanisms such as treefall and flood-scour: such events could lead to pest re-invasion. Knowledge of pest activity directly outside the reserve would assist reserve managers in developing optimal breach-response procedures. This thesis described baseline data on the presence, timing of activity and behaviour of mammalian pest animals found directly at the Maungatautari fence. Two seasonal video studies investigated the effects of season (summer and winter), exterior habitat (forest and pasture) and simulated breach type ('tree-fall' and 'flood scour') on the number of pest sightings. Significantly more sightings were recorded in summer (788) than in winter (428), particularly for rodents. Rabbits were sighted significantly more often at pasture sites, but habitat type did not significantly affect sightings of any other species; nor did breach type affect sightings of any species. Ship rats were commonly sighted within the fence hood gutter. Overall, rodent, possum and cat sightings were very high, and mustelid sightings extremely low, in both seasons. Over 95% of non-lagomorph sightings were nocturnal, and the greatest threat of invasion was found to come nocturnally, from mice, and in the summer. A probability model showed that although the cumulative probability of a mammalian pest encountering a fence breach increases dramatically after dark, in reality there is always a threat of encounter, and this is always increasing with time. Over the same two studies, the behaviour of pest mammals sighted was also described. Pests were found to show interest in and enter summer breaches more often than winter breaches (p lt 0.001). Simulated breaches were encountered by pests within the first 24 hours at a very high rate (95% summer, 92.5% winter), and most likely to enter a breach were rodents. Over 7 days, breaches were encountered and entered by increasing numbers of species and possibly by more individuals; all species were shown to be willing to enter. The threat of invasion by ship rats was probably underestimated because of their higher activity within the fence hood than at the fence base; mustelids may also offer a greater threat than the results suggest, because they almost always entered a breach. It was strongly recommended that when the fence integrity is compromised, physical response should be as quick as possible, especially at night. Future research was strongly encouraged, particularly to understand invasion behaviour of animals such as ship rats and stoats, and to describe pest behaviour at real breach events.

Affecting 6-8% of all pregnancies, preeclampsia is the leading cause of maternal morbidity in the western world and is charactensed by hypertension, proteinuria, edema and platelet aggregation. Despite its prevalence and severity, no comprehensive theory or single factor has been suggested to explain the pathophysiology of this multi system disorder of pregnancy, with the only therapies being bed rest, pharmacological symptom management and if necessary early delivery. Oxidative stress plays an important role in the pathophysiology of preeclampsia, resulting from defective trophoblast invasion, reductions in placental perfusion and placental hypoxia/reoxygenation. The inability of endogenous antioxidant systems up regulated in normal pregnancy, to control increased levels of oxidative stress, is suggested as a possible factor in the feed forward generation of reactive oxygen species and placental oxidative stress. That in turn may stimulate increased syncytiotrophoblast apoptosis, endothelial cell activation and the maternal hyper immune response characteristic of preeclampsia. Analysis of the research literature revealed that previous evaluations of placental oxidation and antioxidant enzyme activity in preeclampsia were by no means comprehensive, and exhibited significant inter-study variations. It was the aim of this thesis to clarify the placental oxidative state and the endogenous antioxidant activity of glutathione peroxidase, thioredoxin reductase, thioredoxin and superoxide dismutase in human placentae in an attempt to determine if variations in antioxidant function were due to changes in gene expression or protein oxidation. The findings reported in this thesis indicate the presence of increased levels of oxidative stress in the preeclamptic placenta, associated with significant reductions in antioxidant enzyme capacity. Quantitative real-time PCR analysis of placental samples revealed that deceases in antioxidant capacity in the placenta are more likely to be related to the significant oxidative burden within the tissue rather than reductions in gene expression. A number of animal models exist to investigate components of preeclampsia pathophysiology, however the ability of these models to mimic the oxidative and antioxidant features of preeclampsia remains unclear. The exposure of pregnant rats to N(G)-nitro-L-arginine methyl ester is a widely used model of endothelial cell dysfunction during preeclampsia. It was the aim of this thesis to determine the biochemical characteristics of this model in an attempt to assess its effectiveness in mimicking oxidative changes in the preeclamptic placenta. Although this model is capable of producing a syndiome in rats similar to the disorder in terms of physiology, this is not manifest in terms of placental biochemistry. The importance of selenium in the synthesis of selenobased antioxidants such as glutathione peroxidase and thioredoxin reductase is well documented. Increasing demand for selenium by the developing fetus may be linked to reductions in selenium status during pregnancy. Considering preeclampsia is associated with significant reductions in selenium status it may be hypothesised that reductions in antioxidant function may be linked to selenium inadequacy. The modulation of dietary selenium in pregnant rats was used to determine the importance of selenium during pregnancy and its effect on antioxidant function and placental oxidative stress. The results of this analysis revealed that selenium deficiency causes a pregnancy specific condition similar to preeclampsia. This condition was found to be associated with increased placental oxidative stress and significant reductions in the systemic activity of selenobased antioxidants that could be modified through selenium supplementation. In summary, data obtained in this thesis indicate that placental oxidative stress and reduced antioxidant enzyme activity play a significant role in the pathogenesis of preeclampsia. These studies support the hypothesis that antioxidant sufficiency is crucial in the maintenance of oxidative balance and that antioxidant dysfunction may result in damage to the placenta and the progression of the disease. These novel data further our understanding of the pathophysiology of preeclampsia and provide new insight into the pathogenesis of clinical complications exhibited in this condition, suggesting antioxidant therapy as a possible means for improving the health outcomes of both mother and baby.

This thesis reports on research that examines the early stage invasion process of Asparagus asparagoides (L.) W. Wight (bridal creeper), primarily a bird-dispersed weed, in a remnant vegetation patch. The study site is on Phillip Island, approximately 100 kilometres south east of Melbourne, Victoria. Asparagus asparagoides invasion of the remnant vegetation reserve is a relatively recent phenomenon. Landscape elements that affect bird dispersal and vegetation types that affect seedling establishment may be important factors that limit or enhance the spread of A. asparagoides. A systematic sampling strategy was adopted and data collected for a variety of landscape and vegetative variables including cover and abundance of A. asparagoides and the data were presented in a Geographic Information System (GIS). Preliminary results show that the distribution of A. asparagoides within a remnant vegetation patch is not random. It appears to have entered the reserve from two boundaries, spreading toward the centre, which to date remains sparsely colonised despite the capacity of this weed to spread rapidly over long distances by birds. A number of other outcomes are noted. Asparagus asparagoides establishment is prevented in pasture where sheep and cattle graze, and paddocks subjected to tillage practices. The exclusion of grazing in fenced off vegetation in pastures demonstrates rapid weed establishment and colonisation several hundred metres from main infestation. Field observation and visual inspection of temporal progress of invasion (using above ground weed density with tuber appearance to infer age) appear to suggest that invasion into remnant is associated with the track network. This age/density assumption is strengthened when spatial distribution is examined using a data set where low-density values for A. asparagoides are removed and compared with a data set using all A. asparagoides density values. The mapping of A. asparagoides in fenced off farm remnants suggests that velocity of spread at 191m/yr is a considerable underestimate. Subsequent analysis shows that the spatial distribution of A. asparagoides is not completely spatially random while intensity surface analysis highlights regions of low and high intensity located near track network. Mapping a density surface within GIS provided confirmatory evidence for the establishment of satellite clusters along the track network. The change in the intensity surface observed using the two data sets (lowdensity values and all density values) is also consistent with an expanding invasion occurring between two time periods. Spatial point pattern analysis using K-function statistics shows that xxii the clustering observed using GIS appears to be occurring at two scales or distances (130m- 160m and 195m-205m). The association between tracks and the invasion process observed in the initial stages of the study is examined. There is a change in density as a function of distance from a track where the density of A. asparagoides appears to reduce the further away from the track a site is and this relationship holds regardless of track width. The final stages of the study look at the development of a predictive model. Visual exploration of the data through mapping in a GIS and field observation made during data collection provide the starting point for the development of logistic models to estimate the probability of A. asparagoides presence. Finally the best overall logistic model is applied to a second independent site to determine the general applicability of the model. A number of variables that impact on the presence of A. asparagoides, particularly during the initial stages of the invasion process, are identified. While all the identified variables and the overall model are statistically significant, the model is found to correctly predict presence/absence in only 67% of cases overall. The model however could be expected to correctly predict the presence of A. asparagoides in 74% of cases and has a false positive rate of 40%. The model is applied at a second independent site and found to have an overall percent correct rate of 80% and correctly predicted A. asparagoides presence in 94% of cases. The variables identified as influential in the early stage of invasion are relatively easy to acquire by simple field survey that does not require specialist skills. When considering the model as a tool for the management of remnant vegetation communities, high false positive rates may lead to limited resources being spent on searching sites where there is no weed. However, a high false negative rate would have a larger impact on the management of the weed since the undetected infestations would form sources for new propagules. The model performs well from this point of view in that it provided low false negative rates at both sites. The value of the predictive model is its ability to provide managers with information regarding specific areas to target for weed eradication and management can use the model to assess the effectiveness of any control measures by going back to obtain new cover density data, then using the model to examine the changes over time. The model also provides a starting point for the development of a generic model of A. asparagoides invasion at sites outside of Phillip Island and could also provide the starting point for developing models that could be used for other bird-dispersed fleshy-fruited weed species.