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Host defence peptides in pregnancy : influences on the microbiome and preterm labourBaker, Tina Louise January 2017 (has links)
Although inflammation is a crucial mechanism in response to injury and pathogen clearance, inappropriate or excessive induction of the inflammatory response in pregnancy can cause initiation of the labour cascade and subsequent preterm delivery. Host Defence Peptides (HDPs) have important anti-microbial properties but are also implicated as multifunctional modulators of immunity and infection. They are predominantly secreted by mucosal epithelial cells and released by leukocytes. The specific HDPs that are the focus of this thesis are Human beta-defensin 3 (hBD3) and Human Cathelicidin (hCAP-18/LL-37). The immunomodulatory effect of HDPs in reproductive tissues in response to infection/inflammation has not been well studied. In a pregnant state, the hypothesis of this thesis is that HDPs have a dual role in preventing ascending infection, but also preventing an exacerbated inflammatory response that can cause preterm birth by initiation of the labour cascade. To explore this I determine whether bacterial stimuli can regulate HDPs expression in pregnancy tissues. I also explore what interactions HDPs have on the production/induction of important cytokines that are vital to the inflammatory response. With the aid of HDP knockout mice, the role of these peptides in infection/inflammation and continuation of pregnancy is investigated in a mouse-model of induced preterm-labour. To understand how ascending infection might be controlled by HDPs in pregnancy, I explore how HDPs regulate commensal and pathogenic bacteria. This is achieved by interrogating the maternal microbiome at mucosal sites in HDP knockout animals, utilising the bacterial 16S rRNA gene and next generation sequencing. Results Placental explants respond to Lipopolysaccharide (LPS) challenge by increasing production of pro-inflammatory cytokines. LL-37 but not hBD3 peptide was able to modulate this inflammation by inhibiting the release of these pro-inflammatory cytokines. To establish whether HDPs are critical in the continuation of pregnancy I use a LPS induced mouse–model of preterm labour in animals lacking the genes for the HDPs, Defb14 (Defb14-/-), or Camp (Camp-/-). Intrauterine injection of LPS induced preterm labour in wildtype mice. However, the Defb14-/- and Camp-/- mice do not have an increased rate of preterm labour. Key inflammatory mediators are increased in response to LPS-induced PTL. Camp-/- animals have a similar inflammatory response to wildtype mice when given LPS during pregnancy. To understand how ascending infection might be controlled by HDPs, I interrogated the maternal microbiome at mucosal sites in HDP knockout animals, utilising the bacterial 16S rRNA gene. I established a workflow for 16S rRNA gene sequencing on next-generation sequencing platforms and a bioinformatic pipeline for data analysis. Using this approach I was able to show the mucosal microbiome of Camp-/- animals were significantly different to that of wildtype controls, showing increased diversity in the microbes present. In murine pregnancy, there were very little global cumulative or progressive shifts in bacteria, with the exception of Candidatus arthromitus, which significantly increases with gestation compared to non-pregnancy This thesis has demonstrated that Host Defence Peptides are expressed in pregnancy tissues and have anti-inflammatory properties in response to bacterial stimuli. It is not clear whether the HDPs, hBD3 and LL-37 are fundamental to the immune defence in pregnancy by preventing excessive inflammation, Although, I have shown LL-37 may have a role in modulation of the maternal microbiota.
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S-nitrosothiols and reactive oxygen species in plant disease resistance and developmentBrzezek, Kerstin January 2014 (has links)
Nitric oxide (NO) as well as reactive oxygen species (ROS) play an important role in defence signalling in plants. After successful recognition of an invading pathogen, an increase in ROS occurs, the ’oxidative burst’; and a ’nitrosative burst’ is also observed. This leads to the induction of defence responses, including the ’hypersensitive response’ (HR), a form of programmed cell death. A balanced production of hydrogen peroxide and NO is crucial for HR induction. In a process called S-nitrosylation, NO can react with cysteine thiols to form S-nitrosothiols, or react with glutathione to form S-nitrosoglutathione (GSNO). The enzyme GNSO reductase (GSNOR) indirectly regulates SNO levels by turning over GNSO. The Arabidopsis thaliana T-DNA insertion mutant atgsnor1-3 shows a complete loss of GNSOR activity and has drastically increased SNO levels, resulting in stunted growth, loss of apical dominance, increased HR, loss of salicylic acid (SA) accumulation and increased susceptibility to avirulent, virulent and non-host pathogens. Two recessive and allelic EMS suppressor mutants in the atgsnor1-3 background were isolated, which showed mostly wild type growth. The mutations were identified by map-based cloning as two different point mutations in At1g20620 or CAT3, one of three catalase genes in Arabidopsis. Catalases break down hydrogen peroxide, with CAT2 being the major catalase in Arabidopsis. All three catalases are structurally very similar, but show temporal and spatial differences in their expression patterns. The suppressor mutants recovered apical dominance, and partially recovered disease resistance to avirulent pathogens, but were still susceptible to virulent pathogens and showed decreased SA levels. The suppressor mutants showed wild type HR in response to different avirulent bacteria. Interestingly, loss-of-function of the other catalase genes as well as loss-of-function of other redox-related genes did not restore apical dominance of atgnsor1-3 plants. This effect seems to be highly specific to CAT3, possibly because of its expression pattern or its expression levels. Further research is needed to fully understand the mechanisms at work here, but these results certainly seem to show a direct connection between redox signalling and S-nitrosylation.
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Identification and characterisation of genes controlling the resistance response to ascochyta blight (Ascochyta rabiei (Pass.) Labrousse) in chickpea (Cicer arietinum L.)Coram, Tristan Edward, n/a January 2006 (has links)
Ascochyta blight, caused by Ascochyta rabiei (Pass.) Labrousse, is one of the most destructive diseases of chickpea (Cicer arietinum L.) worldwide. Despite the existence of highly resistant uncultivated genotypes, attempts to develop cultivars with a high level of durable resistance have been unsuccessful. This study investigated the chickpea defence response to A. rabiei using a functional genomics approach, which has the capacity to improve the overall understanding of the coordinated defence response at a molecular level. An existing cDNA library was used to generate a resource of Expressed Sequence Tags (ESTs) that, after clustering, comprised 516 unigenes. The unigenes were functionally annotated resulting in the identification of 20 specific defence-related unigenes, as well as numerous transcripts with possible involvement in the coordination of defence responses. To explore the expression patterns of the defence-related unigenes in an A. rabiei resistant and susceptible genotype, the unigenes were employed as probes in microarrays. Resulting expression data was analysed to identify differentially expressed unigenes over a time-course after infection. Comparison of the expression profiles from the resistant and susceptible genotype identified three putative genes that were exclusively up-regulated in the resistant genotype, thus may be involved in an effective defence response. Considering that a defence response can involve hundreds of genes, the entire set of chickpea unigenes were used to construct large-scale microarrays. To supplement the chickpea probes, 156 putative defence-related grasspea (Lathyrus sativus L.) ESTs and 41 lentil (Lens culinaris Med.) Resistance Gene Analogs (RGAs) were also included. Expression profiles for three chickpeas and one wild relative were generated over a time course. 97 differentially expressed ESTs were identified using a robust experimental system that included confirmation by quantitative RT-PCR. The results indicated that genes involved in the active defence response were similar to those governed by R-gene mediated resistance, including the production of reactive oxygen species and the hypersensitive response, down-regulation of 'housekeeping' gene expression, and expression of pathogenesis-related proteins. The comparison between resistant and susceptible genotypes identified certain gene expression 'signatures' that may be predictiv e of resistance. To further characterise the regulation of potential defence-related genes, the microarray was used to study expression profiles of the three chickpea genotypes (excluding the wild relative) after treatment with the defence signalling compounds, ethylene (E), salicylic acid (SA), and jasmonate (JA). 425 ESTs were differentially expressed, and comparison between genotypes revealed the presence of a wider range of inducible defence responses in resistant genotypes. Linking the results with the previous microarray results indicated the presence of other pathogen-specific signalling mechanisms in addition to E, SA and JA. The lower arsenal of defence-related gene expression observed in the susceptible genotype may be a result of 'breaks' in the pathways of defence-related gene activation. To draw together the findings of all experiments, a model was constructed for a hypothetical mechanism of chickpea resistance to A. rabiei. The model was synthesised based on the evidence gathered in this study and previously documented defence mechanisms in chickpea, and identified signal transduction as a key to resistance.
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The acquisition of major capital equipment by the Australian Department of Defence : a comparative analysisEarnshaw, Anthany Arthur Paul, n/a January 1994 (has links)
The focus of this thesis is on the acquisition of major capital equipment within Australia's
defence system. For the purposes of this analysis, major capital equipment constitute
selected projects with a total value of at least $200 million.
The projects selected for examination are from each of the three arms of the military
service. These projects are: the Royal Australian Air Force's BLACKHAWK helicopters,
the Army's PERENTIE vehicles, and the Royal Australian Navy's Australian FFG-7
FRIGATES. These projects were chosen because they share similar planning and
management related characteristics. They represent substantial public sector investments.
The technology used in each of the systems is available 'off-the-shelf but the way in
which the systems were ultimately assembled and produced are uniquely Australian: this
adaptation and local innovation involved developmental work. Since each of these
projects is almost complete, a comprehensive analysis of the project has been possible.
The study of these particular projects provides the basis for a comparative analysis of the
acquisition of major defence projects, and facilitates the development of project planning
and management 'lessons'. Since current Australian public (and private) sector policies
seek to maximise the use of leading edge technology by adapting it to meet specific local
requirements; the examination of these three projects provides an objective determination
of the validity of such policies.
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An analysis of the diarchic arrangements of the higher defence organization of AustraliaEarnshaw, A. A. P., n/a January 1990 (has links)
n/a
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Characterisation of the immune response in otitis mediaSaleh, Nadeh S., n/a January 2002 (has links)
Acute otitis media is the most common illness diagnosed during early childhood that
can cause significant morbidity (Brook, 1994) and sometimes can cause irreversible
sequelae such as a hearing defect and subsequent learning difficulties (Klein, 1994). The
aims of the research presented here were to study some aspects of the middle ear
defence mechanisms in both immune and non-immune rats following experimental
otitis media (OM) with two pathogens nontypeable Haemophilus influenzae (NTHi) and
Moraxella catarrhalis (M. catarrhalis). This study also aimed at developing a suitable
technique for preparing immunohistochemical staining of middle ear sections (chapter
2).
A previous study has shown that a regime where rats received an IPP immunisation
combined with an IT boost was effective in enhancing clearance of a middle ear
infection with the same strain of NTHi and also in the presence of a concomitant viral
infection (Moore et al, 2001). Results of this study have shown that for NTHi infection
a distinct cellular influx to the middle ear in the immune rats was accompanied by an
enhanced bacterial clearance compared to the non-immunised rats (chapter 3). This
cellular influx was responsible for the remarkable reduction in the bacterial number.
The sharp decline in PMNs numbers in the NTHi immunised rats that followed
complete bacterial clearance at 72h post infection (Table 3.1) indicate a more
effectively controlled down regulation of this cell infiltrate than the non-immunised rats.
For M. catarrhalis infection, there was no difference in cell infiltrate between immune
and non-immune rats, but enhanced clearance of the bacteria were observed for the
immune animals.
The histopathological changes in the middle ear mucosa of rats with experimentally
induced infection were studied to provide a better understanding about the distribution
of the inflammatory cells and changes in the mucosa during the first 24h post challenge
with NTHi and M. catarrhalis (Chapter 4). These changes have not been previously
studied for the two pathogens at 24h post challenge in rats. Induced infections with the
two pathogens were found to produce similar histopathological changes but more
inflammatory infiltration was observed within the infected mucosa with NTHi than that
seen with M. catarrhalis. The infections were characterized by increased thickness of
the middle ear mucosa, Eustachian tube mucosa, periosteum and tympanic membrane.
There was also an increase in the number and size of small blood vessels at all sites, and
these small blood vessels seem to be the source of the inflammatory infiltration into the
middle ear mucosa and middle ear cavity during the infection. These findings provided
an essential background to the immunohistochemical study.
The effect of mucosal immunisation on the distribution of CD4+T cells and CD8+T
cells has not been investigated previously. Results of the present study (Chapter 5) show
the pattern of distribution of these cells during the first 48h post infection with NTHi in
the rat. The number of CD4+and CD8+T cells peaked at 24h post infection in the nonimmunised
animal and were highest at 48h post-infection in the immunised rats. The
difference in response in the immunised rats may represent regulation of the
inflammatory response by the immune system. The inflammatory response regulation is
indicated by the difference in cellular influx into the immune rats and the response in
the immune rats that corresponds to enhanced bacterial clearance prior to a decrease in
numbers of inflammatory cells once the bacteria was no longer detected (Chapter 3).
This resolution of the inflammatory mass would reduce the opportunity for continued
damage to local tissue. These changes are also supported by the reduction in the
thickness of the middle ear mucosa of the immunised rats especially at 24h and 48h
post-infection (Chapter 5).
This study has shown that there are distinct differences in the rate of bacterial clearance
and cellular changes in the middle ear mucosa and tympanic bulla in immunised rats
during a middle ear infection. Future studies are still required to gain a better
understanding of differences in the inflammatory response for both pathogens, NTHi
and M. catarrhalis.
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Predation and antipredator tactics of nesting black brant and lesser snow geeseArmstrong, William Terry 01 January 1998 (has links)
Coloniality and nest defence were examined in black brant <i>Branta bernicla nigricans</i> and lesser snow geese Chen caerulescens caerulescens. Increased nest density had no effect on nest survival, egg survival, or likelihood of partial clutch predation in snow geese. In brant, nest survival declined as nest density increased in 1992 and with increased distance from shore in 1993. Brant with conspecific nearest neighbours were less likely to suffer partial clutch predation in 1993, but not in 1992. Egg survival in brant increased with nest density in 1993, but decreased as density increased in 1992, however, the decrease occurred only in nests with three or four eggs. Nesting at high densities, in central positions, or far from shorelines commonly travelled by glaucous gulls <i>Larurs hyperboreus</i> and parasitic jaegers <i>Stercorarius parasiticus</i>, the primary egg predators in this study, did not provide geese with a nest or egg survival advantage because effects were lacking in snow geese and were inconsistent and contradictory in brant. Female snow geese had very high nest attendance and both sexes had high territory attendance so snow goose nests were rarely unattended during incubation. Brant had lower nest attendance than snow geese, and due to a lack food near their nests, brant left their territories to feed resulting in lower territory attendance as well. Although male brant were capable of defending the nest from avian predators and usually remained on their territories when females were absent, males were less effective defenders than incubating females. Increased vigilance and decreased resting by female brant as incubation progressed provided support for the prediction, from parental investment theory, that nest guarding effort would increase with offspring age, but there were no changes in male brant or in snow geese. However, declining nest and territory attendance by female brant and males of both species contradicted predictions from parental investment theory but were consistent with an increased need to forage as nutrient reserves declined through incubation as expected due to energetic constraints.
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Not Quite Right2015 September 1900 (has links)
My current area of exploration questions how objects and materials can come together to create fences or barriers. I am attempting to address ideas of boundaries, divisions, and borders, and how areas and spaces are defined. I am interested in how we build them around ourselves, physically and emotionally, as a method of delineation and defence. Through considerations of boundaries the work expands to explore notions of the everyday, materiality and process.
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Continuous performance improvement in the South African National Defence ForceVermaak, JIC, Fourie, L 01 July 2007 (has links)
Abstract:
This article concentrates on the South African National Defence Force
(SANDF), as a South African public sector department, its acceptance of the Batho
Pele principles and the implementation of various organisational performance
improvement programmes. However, despite accepting the principles and the
programmes, it is uncertain whether the SANDF institutionalised them in order to
effect continuous performance improvement.
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Continuous performance improvement in the South African National Defence ForceVermaak, JCI, Fourie, L 07 1900 (has links)
Abstract: This article concentrates on the South African National Defence Force
(SANDF), as a South African public sector department, its acceptance of the Batho
Pele principles and the implementation of various organisational performance
improvement programmes. However, despite accepting the principles and the
programmes, it is uncertain whether the SANDF institutionalised them in order to
effect continuous performance improvement.
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