152,339 research outputs found
Griffith Climate Action Survey 2023: Summary for Policy and Decision Making
No full textGriffith University’s Climate Action Beacon conducted the third of five planned Climate Action Surveys from September to December 2023. The survey discovered what Australians think, feel, and do about climate change and related environmental and climatic events, conditions and issues. This report gives details of the background of the survey, as well as its methods, major findings and potential implications. Comparisons are made with findings from the corresponding 2021 and 2022 surveys.Full Tex
The Griffith Tax Clinic
No full textGriffith University (Queensland) was one of 10 Australian universities chosen to be part of the 2019 National Tax Clinic Project. This project sought to expand the foundational work done by Curtin University (Western Australia) to establish student tax clinics across Australia. The objectives of these clinics were to provide greater access to justice for unrepresented taxpayers, a rich learning environment for students, and greater tax literacy for the community. The Griffith Tax Clinic opened its doors to the public in July 2019. This article reports on the experience of the Griffith Tax Clinic, in its first year of operation, and sets out key learning outcomes and recommendations gleaned from that experience.Full Tex
Going Beyond Counting First Authors in Author Co-citation Analysis
No full textThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Dispelling the Myths Behind First-author Citation Counts
No full textWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
Chronic Inflammation: A Link Between Cardiometabolic and Mood Disorders?
No full textWe live in an age of 'multimorbidity', yet have a rather poor understanding of the impacts of this phenomenon from cellular to organ and system levels. Bi-directional relationships are observed between cardiometabolic (diabetes mellitus, coronary heart disease) and mood disorders (major depressive disorder), each increasing disease risk and frequently co-existing. This cardiometabolic-mood interaction may reflect an under-appreciated commonality of underlying mechanisms across these pathologies. Importantly, comorbid development of these disorders exacerbates the already profound burdens of these individual chronic disorders. Further, psychosocial stress and ageing – increasingly prevalent features of modern societies - may promote these conditions and worsen outcomes. In assessing the intersections of these inter-related disorders, chronic low-grade inflammation is often highlighted and implicated as a common early substrate in cardiometabolic and mood disorders, linking these dominant diseases. Nonetheless, how immunoinflammatory dysregulation drives multimorbidity, and influences 'multifinality' (diverse disease outcomes from common risks/causes), are unclear. Whether immunoinflammatory changes in metabolic vs mood disorders are unique or involve common motifs, and how these interact in dictating cardiometabolic and mental health, remains to be established. Dysregulation of toll-like receptor (TLR) signalling has been specifically implicated in these diseases, potentially presenting a mechanistic nexus in comorbid development of cardiometabolic and mood disorders.
The doctoral work presented in this thesis was designed to address the broad concept of mechanistic intersections contributing to rising multimorbidity. In order to practicably achieve this at a systems level, four major tissues impacted by and contributing to aspects of metabolic and mood disorders were studied: the brain, heart, liver and blood (circulating serum). The brain is an overarching and critical organ, regulating both mood and metabolic homeostasis, and influencing all other organ systems. Cardiac tissue is assessed as it is particularly impacted by type 2 diabetes (T2D); the risk of cardiovascular disease (CVD) is markedly elevated in T2D patients and is the lead cause of death in these patients. Further, CVD is an independent risk factor for both depression and T2D. The liver is fundamental to metabolic homeostasis (the central organ maintaining homeostasis across fed and fasted states via oxidisable substrate storage and release), links the gut to the periphery (gut-liver axis) and contains specialised macrophages which are front-line responders to gut-derived lipopolysaccharides (LPS) (arising with gut permeability changes). Finally, serum was assessed as it is the primary medium for transport of macronutrients, hormones and immunoinflammatory molecules throughout the body.
To avoid the pitfalls of reliance upon gene-modified animal models, non-genetic murine models of type 1 and type 2 diabetes development in early adulthood were studied in Chapter 2 to explore potential changes in TLR-related signalling at the gene level. Somewhat unexpectedly, there was little evidence of shifts in TLR signalling in central nervous system (CNS), hepatic or cardiac tissues in these two conditions. Moreover, while modest elevations in circulating interleukin-6 (IL-6) are observed in T2D animals, tumor necrosis factor alpha (TNF-α) and interleukin-1 beta (IL-1β) levels remained unchanged across models. Together with further analysis of gene expression, these data indicate that the T2D model does not develop an overtly pro-inflammatory phenotype, despite clear evidence of metabolic dysregulation. Given that a well-developed diabetic phenotype was observed (increased body weight, moderate hyperglycaemia, insulin resistance), this work called into question the essential role of TLR4 in the pathogenesis of T2D. Data does reveal marked changes in circulating adipokines and catecholamines, suggesting these endocrine systems may be key to disease progression, independent of inflammation. Surprisingly, assessment of circulating LPS revealed serum levels were decreased (although not significantly) in T2D animals, which casts doubt on whether 12 weeks of feeding with a ‘Western diet’ (30% of total calories from fat) is sufficient to disturb gut physiology and trigger the systemic innate immune response. The majority of animal models employ much higher fat percentages (45-60% calories from fat) in their diabetogenic diets, despite such high fat levels vastly exceeding those in a Western diet (~30%) and raising questions of pathophysiological relevance. Given that little evidence of TLR dysregulation was detected at a physiologically relevant fat percentage, a more chronic model (21-week dietary modification) with an intermediate fat content (43% calories from fat) was developed for subsequent experimentation.
Studies in Chapter 3 demonstrate that a more profound weight gain is achieved with a higher fat content, which still remains below the extreme 60% levels often studied in animal models: this new feeding regime resulted in significantly greater body weight gain although fasting insulin and glucose levels were not altered when compared with the T2D model assessed in Chapter 2. Nonetheless, despite this more pronounced phenotype, limited TLR4-related gene changes were observed in the model. Selective changes to total cellular nuclear factor-kappa B (NF-κB) protein expression were observed in hepatic tissue, although analysis of the nuclear compartment revealed no changes in response to T2D. Thus, while a greater pool of this critical pro-inflammatory factor was evident, this was not necessarily associated with increased nuclear interaction and thus transcriptional control. These data suggest dysregulation of transcriptional control by NF-κB (particularly TLR4 pathway elements) may not be essential in the evolution of T2D in these animals.
Examining a dietary intervention with an omega-3 polyunsaturated fatty acid (n-3 PUFA), α-linolenic acid (ALA), which has been linked to anti-inflammatory outcomes in some chronic disorders, revealed no improvements in the systemic sequalae of T2D. This is consistent with evidence PUFA supplementation may (somewhat paradoxically) have greater influences on metabolic homeostasis in healthy rather than diseased subjects. Unexpected elevations in key inflammatory transcripts were noted with ALA supplementation, potentially reflecting the highly pleiotropic actions of PUFAs. Proteomic profiling of cardiac tissue revealed that a number of inflammatory and related factors beyond TLR-related signalling were impacted by T2D (Serpin-1/PAI-1, leptin, resistin) and/or are sensitive to ALA (IL-10, CD40, VEGF). Data also suggest animal age may be a complicating factor in the protracted disease model, producing apparent independent effects on leptin/insulin expression levels, in turn complicating interpretation of these data. Finally, specific investigation of CNS changes in the model - via analysis of frontal cortex (FC) leptin receptor expression - indicates a sensitivity of central leptin signalling to T2D, which may not only participate in metabolic dysregulation but behavioural outcomes (as suggested in the pathogenesis of depression, for example). This highlights the likely importance of central control and behavioural determinants of disease outcomes.
Investigating central control mechanisms and behaviour in more detail, studies presented in Chapter 4 revealed that the T2D phenotype involves induction of anxiety-related behaviours without impacting on hedonic behaviour. Further, despite evidence from other studies of the benefits of PUFA supplementation in mood disorders, ALA supplementation did not reverse anxiety-related behaviours, though increased locomotion in both healthy and T2D animals. Interestingly, analysis suggests ALA supplementation may confer benefits to locomotive activity independently of disease state, although outcomes are better in healthy controls. Examining elements of central reward pathways, neurotransmission, endocrine and inflammatory control in FC and hippocampus revealed select changes with T2D, including elevated Drd2 (dopamine D2 receptor) and reduced Htr1a (serotonin receptor 1A) in the FC, together with shifts in leptin receptor expression. Surprisingly, hippocampal Il1b gene expression remained similar between groups, though this is consistent with no change in hedonic behaviour. Circulating dopamine and leptin were also sensitive to T2D, with hippocampal dopamine levels selectively elevated in T2D animals supplemented with ALA (although the relevance of this finding is not clear). Overall, these data point to dysregulation of central dopamine and leptin signalling, which may contribute to behavioural disruption in T2D, in turn influencing disease development and outcomes.
In the final studies, CNS responses were explored in greater detail via RNA-sequencing (Chapter 5), more broadly testing whether metabolic and mood disorders share common nervous system changes. Analyses of transcriptome profiles in the FC of the T2D model assessed in Chapter 5 together with a model of chronic social stress (SS) known to induce anxiety/depressive behaviours again provided limited support for an overarching immunoinflammatory dysregulation as a key driver of behavioural changes. These analyses reveal both distinct and common processes (beyond TLR-signalling) that are dysregulated in disease. Comparison between T2D and SS models reveal commonalities in CNS leptin and insulin receptor changes, congruent with evidence of insulin and leptin resistance in the T2D model and their implication in both human major depressive disorder (MDD) and T2D. A majority of over-represented genes were related to cell/tissue development, cell migration and proliferation, suggesting a dominant role for CNS 'remodelling' with both metabolic and mood disorders. Interestingly, down-regulation of ATP metabolic processes and mitochondrial genes was evident in the SS model but not T2D, supporting a more dominant effect of stress on energy production.
Taken together, the findings presented in this doctoral project raise questions regarding the role of dysregulated TLR-signalling in T2D (and stress-related disorders). Despite a clear diabetic phenotype and shifts in behavioural profiles of T2D animals, findings challenge whether TLR-related dysregulation (reported by others) may be a consequence rather than causative factor in disease pathogenesis. Importantly, evidence is presented that insulin, leptin and dopamine signalling (together with other metabolic mediators) may be important linkages between metabolic and mood disorders, and underlie behavioural detriment in T2D. In terms of limiting the development or impacts of disease, n-3 PUFA supplementation resulted in selective benefits in T2D, though these appear unrelated to the metabolic profile of these animals. Finally, shared and unique CNS changes were identified in models of T2D and chronic social stress, supporting structural sensitivity and plasticity with inter-related metabolic and mood disorders.Thesis (PhD Doctorate)Doctor of Philosophy (PhD)School of Medical ScienceGriffith HealthFull Tex
Composing and performing original works for the trombone
No full textThis dissertation explores composing and performing new works for the trombone, and their presentation in a recital designed to demonstrate the potential of the trombone as a soloist instrument. The study builds on the author’s experiences as an orchestral trombonist, as well as his exploration of other styles of trombone playing, including those of brass band and jazz. The author discusses the current repertoire available to trombonists performing recitals, and explores the various qualities of the trombone they demonstrate well. However it goes further to consider what could be done to showcase further its many qualities as a solo instrument. In addition to this artistic research exegesis, the research submission includes the scores of five new compositions by the author featuring a solo trombone, and discusses the process of composing, rehearsing, and performing these works. Their effectiveness in showing off the potential of the trombone as a solo instrument is demonstrated through recordings of live performances of the new works by the author together with colleagues from the Australian National Academy of Music. The research questions posed by the author are addressed through the design and execution of a recital programme that utilises a range of different styles and genres in which the trombone excels. It is proposed that such a programme can potentially showcase more the instrument’s abilities as a solo instrument than is frequently done in traditional trombone recitals.Thesis (Masters)Master of Music Research (MMusRes)Queensland ConservatoriumArts, Education and LawFull Tex
Reinventing Library Research Support Services at Griffith University
No full textGriffith University provides advice and services to researchers around research grants, ethics and integrity, research performance, and publications and outputs. A broad-based researcher education and development program helps inform and upskill researchers and research students. From 2019, Griffith University Library has developed new services to support data-driven, data-intensive research and assist researchers through the entire research lifecycle. This chapter describes the staffing structure and the ideas underpinning a new service catalogue based around key areas, such as data management, open scholarship, and data wrangling. Methods to achieve this included a collaboratively developed knowledge base, the development of new workshops, mapping of research environments and referral pathways, and developing support for researchers for whom there is no established tool for the kinds of research they want to do. A push to establish the library as a vital and valued partner in research projects was a key driver for change.Full Tex
Chemical Investigation of Clerodendrum polycephalum for Anti-Malarial Compounds and its Chemical Diversity with Australian Clerodendrum
No full textThe use of indigenous plants by native healers has been in healthcare system for a long time. It is prevalent in many developing countries because of its wide benefits and rising popularity. But less is known about the chemistry behind the medicinal properties of those indigenous plants. Unraveling the knowledge helps develop drugs based on the indigenous plants and understand their mechanisms of the action. Malaria happens to be a vector borne protozoan parasitic disease which has been reported to affect 229 million people in 2019. Use of indigenous plant for treating malaria is widely practiced and this had led to the development of two anti-malarial drugs, artemisinin, and quinine. Clerodendrum polycephalum, also known as ‘egungun eja’ or ‘ewe agbosa’ or ‘aporo’ by different tribes of Nigeria, is used by native healers as an anti-malarial treatment. However, the anti-malarial effect is not well studied and the chemical compounds responsible for its activity is unknown. The understanding of the chemical composition and their antimalarial activities will provide scientific evidence for its traditional application in malaria treatment. This project was a collaborative research between A/Prof Yunjiang Feng at Griffith Institute for Drug Discovery and Prof. Francis B. Adewoyin at Drug Research and Production Unit, Obafemi Awolowo University, and Prof. Alexander B. Odaibo at Department of Zoology, University of Ibadan; mediated by BIO Ventures for Global Health (BVGH). The Nigerian group analysed the crude extract of Clerodendrum polycephalum based on its traditional use; but lack of expertise in natural product chemistry led to this collaboration. The overall objective was to use bioassay as a guide to isolate antimalarial natural products against Plasmodium falciparum 3D7 drug resistant cell lines. Any novel/new compounds will also be targeted by using 1H NMR guided isolation strategy. Knowing the wide distribution of Clerodendrum around the world, several Australian Clerodendrum sp. were investigated by LC-MS to understand the chemical compositions of samples from different geographic locations. The thesis was started with an introduction chapter which included different concepts such as traditional medicine, malaria, Clerodendrum, bioassay guided fractionation, NMR guided isolation and a brief outline of the project. Traditional medicine (TM) was introduced with a detailed description on African traditional medicine (ATM). It then proceeded with a brief discussion on malaria, its causes, and the current treatment. The chapter then provided a detailed description of genus Clerodendrum, its geographical distribution, traditional use and the biological activity of the plant extract and secondary metabolites. The chapter continued with a brief of bioassay guided fractionation. Finally, the chapter ended with a description of NMR guided isolation of compounds with biological activity. Chapter 2 described detailed experimental procedures involved in this project, including isolation and purification of natural products from the plant species. The chapter also detailed the biological assays as well as the spectroscopic data of the pure compounds. Chapter 3 started with an introduction of Clerodendrum polycephalum, then moved on to the bioassay guided isolation which resulted in four pure compounds, including the new clerodane diterpene lactone A. Considering the difficulties in the isolation process due to the presence of large amount of methyl pheophorbide a, the next batch of crude extract was purified using a revised strategy where the fractionation procedure was modified and 1H NMR was utilized to guide the isolation. This resulted in ten compounds, including four new clerodane diterpene lactone (A-D), one new 12,16-Epoxy-11,14,17-trihydroxy-17(15→16)-abeo- 5,8,11,13,15-abietapentaen-7-one, as well as 5 known compounds, namely, acacetin, methyl pheophorbide a, loliolide, bis (2-ethylhexyl) phthalate and 12,16-Epoxy-6,11,14,17- tetrahydroxy-17(15→16)-abeo-5,8,11,13,15-abietapentaen-7-one. The chemical structures were elucidated by comprehensive analysis of 1D-, 2D-NMR and MS spectroscopic data assisted by density functional theory (DFT) calculated NMR and circular dichroism (CD). The in-vitro activity evaluation against P. falciparum 3D7 revealed that methyl pheophorbide a was active with IC50 values of 4.49 M. The compound showed no cytotoxicity against neonatal foreskin fibroblast (NFF) mammalian cells. Our results provided scientific evidence for the traditional use of Clerodendrum polycephalum in malarial treatment. Chapter 4 aims to investigate whether Clerodendrum sp. collected from different geographic location contain similar chemistry. The chapter started with an introduction of Australian Clerodendrum sp., Griffith University’s NatureBank and the use of LC-MS for screening compounds in plant extracts. Fifteen Australian Clerodendrum were extracted and analyzed by LC-MS. Our results suggested that every compound isolated from Clerodendrum polycephalum was detected in the Australian species. Large scale isolation of Nature Bank sample NB020858 yielded verbascoside, diosmetin-5-o-glucuronide, 4-hydroxywogonin-5-oglucuronide and acacetin-5-o-8-hydroxyglucuronide; among these four compounds verbascoside and an analogue of acacetin-5-o-8-hydroxyglucuronide were also detected in the Nigerian plant extract. Based on the results, we conclude that Clerodendrum plant species from Nigeria and Australia contained same classes of compounds, and chemistry can be used as a tool for plant taxonomic identification.Thesis (Masters)Master of Science (MSc)School of Environment and ScScience, Environment, Engineering and TechnologyFull Tex
Characterisation of the B-Lactamase Gene From Campylobacter Jejuni
No full textThermophilic Campylobacter species such as Campylobacter jejuni and Campylobacter coli are recognised worldwide as major causes of acute gastroenteritis in humans. Campylobacteriosis is frequently a mild to moderate self-limited illness and most cases do not require antimicrobial therapy; antimicrobial therapy is necessary for patients with systemic Campylobacter infections, for patients with severe disease, or for immunosuppressed patients. Antimicrobial susceptibility testing of Campylobacter species using disk diffusion currently is not standardised by the National Committee for Clinical Laboratory Standards (NCCLS), however, in order to monitor the prevalence of antimicrobial resistance in Campylobacter species, there is a need for standardised or calibrated methods of susceptibility testing. Initially, 90 human clinical isolates of thermophilic Campylobacter species from Southeast Queensland, Australia, were screened for resistance to ampicillin, erythromycin and tetracycline using the disk diffusion susceptibility testing method. Levels of resistance were then determined using E test MIC and agar dilution methods to determine the reliability of disk diffusion results. Results of the disk diffusion testing showed 87 (97%) isolates resistant to ampicillin, 14 (16%) isolates were resistant to tetracycline and three (3.4%) isolates were resistant to erythromycin. Results of disk diffusion testing showed 100% correlation (+1 log2 dilution) with agar dilution for erythromycin and tetracycline, and 77% for ampicillin. E test showed 68% correlation with agar dilution for ampicillin, 100% for erythromycin and 64% for tetracycline. These data suggest that disk diffusion susceptibility testing may be used to screen thermophilic Campylobacter spp. for putative resistance to erythromycin and tetracycline and that the incidence of resistance of Campylobacter spp. to erythromycin and tetracycline is low in Southeast Queensland, Australia. Agar dilution remains the most accurate method for determination of ampicillin susceptibility. Numerical analyses of restriction endonuclease (RE) fragment profiles were performed to elucidate relatedness of the antibiotic resistant isolates and the results suggested a high level of isolate variation. The role of the B-lactamase in the resistance of C. jejuni to various B-lactams has been well documented and B-lactamase production in C. jejuni has been reported in 83-93% of strains. The expression and characterisation of the Campylobacter B-lactamase, however, has not been described. In this work, standard cloning techniques utilising a high-copy number E. coli cloning vector and a previously described E. coli-Campylobacter shuttle cloning vector were unsuccessful in isolation and expression of the C. jejuni B-lactamase gene in E. coli, possibly due to a lack of expression of the campylobacter gene in its host or low efficiency of transformation. Therefore, in order to facilitate the isolation, expression and characterisation of the C. jejuni B-lactamase gene, it was necessary to construct a new E.coli-Campylobacter shuttle cloning vector for the purposes of expressing the C. jejuni B-lactamase in Campylobacter. To aid in the construction of the vector, the sequence and genetic organisation of a 4.0-kb cryptic plasmid, termed pCJ419, identified in a human clinical isolate of C. jejuni was determined. Plasmid pCJ419 is a circular molecule of 4013 bp and contains four open reading frames (ORFs), the products of which share significant sequence similarity with putative proteins from known C. jejuni and C. coli plasmids. ORF-1 encodes a putative mobilisation protein (Mob); ORF-2 and ORF-3 encode proteins which have high identity to putative RepA and RepB proteins, respectively, of known C. jejuni and C. coli plasmids. ORF-4 encodes a protein which has high identity to a hypothetical protein of unknown function, Cjp32, previously described in a pVir plasmid of C. jejuni. Tandem repeating sequences typical of a plasmid replication origin (ori) were identified upstream of the DNA sequences encoding putative replication initiation proteins RepA and RepB. An E. coli-Campylobacter shuttle cloning vector, pGU0202, was constructed using plasmid pMW2 which harbours a Campylobacter-derived kanamycin-resistance gene, aphA(3’)-III. The sequences encoding pCJ419 mob, repA and repB were inserted upstream of aphA(3’)-III resulting in a stable construct of 6174 bp that was used successfully to transform both E. coli and Campylobacter. Subsequently, a novel molecular class D ?-lactamase gene, blaOXA-61, from a B-lactamase-positive, ampicillin-resistant (MIC 64 mg l-1), clinical strain of Campylobacter jejuni, strain GC015 was isolated, cloned and characterized using the newly constructed shuttle vector pGU0202. An open reading frame of 774 bp was identified on a ClaI genomic fragment of 2.2 kb and encodes a protein of 257 amino acids. Conserved motifs composed of identical amino acids typical of penicillin-recognising proteins and specific class D motifs were identified. blaOXA-61 was cloned into the shuttle cloning vector pGU0202 and expressed in B-lactamase-negative, ampicillin-susceptible C. jejuni and E. coli. A conserved 122-bp sequence directly upstream of blaOXA-61 was identified and shown to be required in cis for high-level resistance of Campylobacter to the penicillins although blaOXA-61 expressed only at low levels in E.coli. Southern hybridisation analysis demonstrated that the bla gene was chromosomally encoded and present on the same BglII and ClaI-digested genomic DNA fragments from various strains of Campylobacter with ampicillin MICs of between 4 and 64 mg l-1. In addition, DNA fragments encoding two putative zinc-dependent hydrolases from the metallo-B-lactamase superfamily, designated GLX2-1 and GLX2-2, were identified in a clinical isolate of Campylobacter jejuni, strain 012, cloned and sequenced. A strictly conserved motif, -H-X-H-X-D-, characteristic of the metallo- B-lactamase superfamily of proteins, including the class B metallo- B-lactamases, was identified in both proteins although functional B-lactamase could not be expressed in either E. coli or C. coli transformed using the C. jejuni hydrolase-containing shuttle vector pGU0202. Further work is warranted to determine the exact function of these proteins.Thesis (PhD Doctorate)Doctor of Philosophy (PhD)Institute for GlycomicsFull Tex
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