Comparative flux control through the cytoplasmic phase of cell wall biosynthesis

The introduction of antibacterial drugs in the middle of the last century heralded a new era in the treatment of infectious disease. However the parallel emergence of antibiotic resistance and decline in new drug discovery threatens these advances. The development of new antibacterials must therefore be a high priority. The biosynthesis of the bacterial cell wall is the target for several clinically important antibacterials. This extracellular structure is essential for bacterial viability due to its role in the prevention of cell lysis under osmotic pressure. Its principal structural component, peptidoglycan, is a polymer of alternating N-acetyl-glucosamine (GlcNAc) and N-acetyl muramic acid (MurNAc) residues crosslinked by peptide bridges anchored by pentapeptide stems attached to the MurNAc moieties. The biosynthesis of peptidoglycan proceeds in three phases. The first, cytoplasmic, phase is catalysed by six enzymes. It forms a uridine diphosphate (UDP) bound MurNAc residue from UDP-GlcNAc and attaches the pentapeptide stem. This phase is a relatively unexploited target for antibacterials, being targeted by a single clinically relevant antibacterial, and is the subject of this thesis. The Streptococcus pneumoniae enzymes were kinetically characterised and in silico models of this pathway were developed for this species and Escherichia coli. These models were used to identify potential drug targets within each species. In addition the potentially clinically relevant interaction between an inhibitor of and feedback loops within this pathway was investigated. The use of direct parameter estimation instead of more traditional approaches to kinetic characterisation of enzymes was found to have significant advantages where it could be successfully applied. This approach required the theoretical analysis of the models used to determine whether unique parameter vectors could be determined. Such an analysis has been completed for a broad range of biologically relevant enzymes. In addition a relatively new approach to such analysis has been developed

Humanitarianism at home: Exploring practitioners’ perspectives on the relevance of humanitarianism in Australia

Australia has faced various unprecedented challenges in recent years: the extended bushfire season of 2019–20, wide-spread and increasingly severe storms and flooding, and the grave health and socio-economic impacts of the global COVID-19 pandemic. Such events have prompted greater awareness of our shared vulnerability to disasters. They have also exacerbated food insecurity, homelessness, poverty, family violence, and increased the vulnerability of refugees and people seeking asylum in Australia. Where disasters and similar issues are identified in low-income countries, they are typically framed in terms of humanitarian need and may even be the subject of international humanitarian action. Why is it then, that the language and practices of humanitarianism are not ordinarily applied in Australian settings? What indeed is humanitarianism when it is not international? What, if anything, do international experiences of humanitarianism have to offer in Australian contexts? This paper describes a research program that has been prompted by these questions and shares some preliminary findings concerning the perspectives of Australian practitioners on the relevance of humanitarian values, knowledge, and practices in Australia

Equivariant homotopy commutativity for G = Cpqr

We investigate the combinatorial data arising from the classification of equivariant homotopy commutativity for cyclic groups of order G = Cp1···pn for pi distinct primes. In particular, we will prove a structural result which allows us to enumerate the number of N∞-operads for Cpqr, verifying a computational result

The role of omnivory in mediating metacommunity robustness to habitat destruction

Omnivores have long been known to play an important role in determining the stability of ecological communities. Recent theoretical studies have suggested that they may also increase the resilience of their communities to habitat destruction, one of the major drivers of species extinctions globally. However, these outcomes were obtained for minimal food webs consisting of only a single omnivore and its prey species, while much more complex communities can be anticipated in nature. In this study, we undertake a systematic comparative analysis of the robustness of metacommunities containing various omnivory structures to habitat loss and fragmentation using a mathematical model. We observe that, in general, omnivores are better able to survive facing habitat destruction than specialist predators of similar trophic level. However, the community as a whole does not always benefit from the presence of omnivores, as they may drive their intraguild prey to extinction. We also analyze the frequency with which these modules occur in a set of empirical food webs, and demonstrate that variation in their rate of occurrence is consistent with our model predictions. Our findings demonstrate the importance of considering the complete food web in which an omnivore is embedded, suggesting that future study should focus on more holistic community analysis

Trafficking and protection: theorising reintegration and defining success

Grounded upon research in Cambodia, a theory of ‘reintegration’ is proposed for victims of sex-trafficking and benchmarks for assessing success. Drawing upon a cosmopolitan conception of shared vulnerability, it is argued that a life lived with dignity chiefly depends upon access to either modernist or traditional forms of reciprocal recognition

Geotechnical Engineering: Optimum moisture content for compaction of in situ soil at a residential construction site on Five Mile Prairie, WA.

The residential construction site is located at 9117 Scarlet Sky Drive on the southwest margin of Five Mile Prairie, WA. The footprint of the proposed structure overlaps two soils. Near the road is fill material brought in to form the extended roadbed. Further from the access road is the extant soil that formed in place on the prairie. This site is approximately 2,400 feet in elevation, atop basalt. Over time loess and the Glacial Lake Missoula floods shaped the landscape. Grassy, small rolling hills cover the in-situ soil. There is a natural drainage basin below the site that features basalt boulders rimming the edge as a result of many years’ past mass wasting. This study presents results for moisture content and compaction of in-situ soil according to ASTM Standard D698. Compaction prior to construction increases unit weight and shear strength for soil, hence increasing resistance to settling and structural damage

Habitat loss alters effects of intransitive higher-order competition on biodiversity: a new metapopulation framework

Recent studies have suggested that intransitive competition, as opposed to hierarchical competition, allow more species to coexist. Furthermore, it is recognized that the prevalent paradigm, which assumes that species interactions are exclusively pairwise, may be insufficient. More importantly, whether and how habitat loss, a key driver of biodiversity loss, can alter these complex competition structures and therefore species coexistence remain unclear. We thus present a new simple yet comprehensive metapopulation framework which can account for any competition pattern and more complex higher-order interactions (HOIs) among species. We find that competitive intransitivity increases community diversity and that HOIs generally enhance this effect. Essentially, intransitivity promotes species richness by preventing the dominance of a few species unlike hierarchical competition, while HOIs facilitate species coexistence through stabilizing community fluctuations. However, variation in species vital rates and habitat loss can weaken or even reverse such higher-order effects, as their interaction can lead to a more rapid decline in competitive intransitivity under HOIs. Thus, it is essential to correctly identify the most appropriate interaction model for a given system before models are used to inform conservation efforts. Overall, our simple model framework provides a more parsimonious explanation for biodiversity maintenance than existing theory

Habitat heterogeneity mediates effects of individual variation on spatial species coexistence

Numerous studies have documented the importance of individual variation (IV) in determining the outcome of competition between species. However, little is known about how the interplay between IV and habitat heterogeneity (i.e. variation and spatial autocorrelation in habitat quality) affects species coexistence at the landscape scale. Here, we incorporate habitat heterogeneity into a competition model with IV, in order to explore the mechanism of spatial species coexistence. We find that individual-level variation and habitat heterogeneity interact to promote species coexistence, more obviously at lower dispersal rates. This is in stark contrast to early non-spatial models, which predicted that IV reinforces competitive hierarchies and therefore speeds up species exclusion. In essence, increasing variation in patch quality and/or spatial habitat autocorrelation moderates differences in the competitive ability of species, thereby allowing species to coexist both locally and globally. Overall, our theoretical study offers a mechanistic explanation for emerging empirical evidence that both habitat heterogeneity and IV promote species coexistence and therefore biodiversity maintenance

Water quality impacts of the mountain pine beetle infestation in the Rocky Mountain west

November 2014.Includes bibliographical references.The Mountain Pine Beetle (MPB) is the primary cause of insect-induced mortality in pine forests in western North America where some lodgepole forests have experienced more than 90% tree mortality. The implications of MPB infestation on water resources are particularly important in the Rocky Mountains, which serve as the source-water region for more than 60 million people. Two important potential watershed impacts are changes in the hydrologic cycle and water quality. While impacts on the hydrologic cycle have received some attention, the interconnection between these changes and the impacts of the widespread infestation on water quality are not well understood. This study uses a combination of field sample analysis and modeling based in Rocky Mountain National Park to address two potential MPB-driven effects on water quality: increased metal concentrations with ecotoxicological and human health ramifications and the changes in source water contributions to streamflow with possible implications for metal and carbon transport to downstream drinking water supplies. Previous work from the research team at Colorado School of Mines identified increased potential for disinfection byproduct formation at water treatment plants receiving water from heavily MPB-killed forests. These increases exhibited surprising seasonal trends that suggest that the transport of carbon to streams, and thus the flowpaths of water, may be different in MPB-killed forests. The first question was investigated by sequentially extracting trace metals from soils under trees with vary levels of impact, and using geochemical models to identify important process-level drivers of changes in metal mobility. Laboratory results identify redistribution of metals in soils under beetle-killed trees with greater mobilization potential for cadmium, and increases in zinc and copper, likely related to fluxes from needle leachate. Results also align with geochemical models and identify changes in organic carbon inputs as the primary driver of increased metal mobility. The second questions was addressed using a chemical hydrograph separation approach to partition streamwater into the fractions derived from groundwater, rain, and snow. Results demonstrate that fractional late-summer groundwater contributions from impacted watersheds are approximately 30 ± 15% greater after infestation and when compared with a neighboring watershed that experienced earlier and less-severe attack. Water budget analysis compared to published sap flux and remotely sensing studies reveals that this change is consistent with expected increases in groundwater from loss of transpiration across the watershed. A predictive statistical model (calibrated to observations within and around Rocky Mountain National Park) suggests that dissolved organic carbon concentrations in streams will be higher in areas where tree mortality is higher. Although, a strong statistical correlation was not found with the method used. Ultimately, this study identifies process-level hydrologic and biogeochemical changes that improve understanding of the vulnerability of Rocky Mountain water supplies to MPB outbreaks