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Search Results: 1 - 10 of 134041 matches for " Andrew T. Slack "
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Analysis of Bordetella pertussis pertactin and pertussis toxin types from Queensland, Australia, 1999–2003
Shane Byrne, Andrew T Slack
BMC Infectious Diseases , 2006, DOI: 10.1186/1471-2334-6-53
Abstract: Forty-six B. pertussis isolates recovered from Queensland patients between 1999 and 2003 were examined by both DNA sequencing and LightCycler? real time PCR to determine their pertactin and pertussis toxin subunit 1 genotypes.Pertactin typing showed that 38 isolates possessed the prn1 allele, 3 possessed the prn2 allele and 5 possessed the prn3 allele. All forty-six isolates possessed the pertussis toxin ptxS1A genotype. Amongst the circulating B. pertussis population in Queensland, 82.5% of the recovered clinical isolates therefore possessed the prn1/ptxS1A genotype.The results of this study compared to historical research on Queensland isolates suggest that B. pertussis pertactin and pertussis toxin variants are not becoming more prevalent in Queensland since the introduction of the acellular vaccines. Current prevalences of pertactin variants are significantly different to that described in a number of other countries with high vaccine coverage. Relative paucity of recovered isolates compared to notified infections, due primarily to non culture based pertussis diagnostics is however a confounding factor in the assessment of variant prevalence.Bordetella pertussis, the etiological agent of 'Whooping Cough' remains prevalent in Australia despite the introduction and wide spread use of pertussis vaccines as part of the childhood immunisation scheme. The Australian standard vaccination schedule for pertussis consists of acellular vaccines given in doses at 2, 4 and 6 months, followed by a fourth dose at 4 years and a booster at 15–17 years of age [1]. Prior to 1999 a local whole cell vaccine was in use beginning in the decade 1936–1945. [2]. An 'Immunise Australia' program established in 1997 has set a target of 90% coverage for pertussis vaccination [2]. In the Australian state of Queensland pertussis vaccine coverage in the 1990s moved from the high 70% to mid 80%, and then rose above the 90% target from 2001 onwards [2-4]. In spite of this high vaccine coverage, i
Development of a Multiple-Locus Variable number of tandem repeat Analysis (MLVA) for Leptospira interrogans and its application to Leptospira interrogans serovar Australis isolates from Far North Queensland, Australia
Andrew T Slack, Michael F Dohnt, Meegan L Symonds, Lee D Smythe
Annals of Clinical Microbiology and Antimicrobials , 2005, DOI: 10.1186/1476-0711-4-10
Abstract: In this study we have searched the available genomic sequence of L. interrogans serovar Copenhageni strain Fiocruz L1-130 for the presence of tandem repeats [1]. These repeats were evaluated against reference strains for diversity. Six loci were selected to create a Multiple Locus Variable Number of Tandem Repeats (VNTR) Analysis (MLVA) to explore the genetic diversity within L. interrogans serovar Australis clinical isolates from Far North Queensland.The 39 reference strains used for the development of the method displayed 39 distinct patterns. Diversity Indexes for the loci varied between 0.80 and 0.93 and the number of repeat units at each locus varied between less than one to 52 repeats. When the MLVA was applied to serovar Australis isolates three large clusters were distinguishable, each comprising various hosts including Rattus species, human and canines.The MLVA described in this report, was easy to perform, analyse and was reproducible. The loci selected had high diversity allowing discrimination between serovars and also between strains within a serovar. This method provides a starting point on which improvements to the method and comparisons to other techniques can be made.Leptospirosis, is the zoonotic disease caused by the spirochete Leptospira. Leptospirosis is characterised either as a febrile illness with sudden onset, or a 'flu like' illness. Patients present with chills, headaches, myalgia, and abdominal pain. In addition, patients may present with renal and pulmonary complications. It is considered an emerging infectious disease with large documented outbreaks occurring world-wide [2]. The majority of isolates detected in Queensland, Australia belong to the genomospecies, L. interrogans, with the dominant serovars being Zanoni or Australis. Typically Leptospirosis infections in Queensland are a result of occupational exposure with the majority of cases occurring in farming or animal based industries [3].The genus Leptospira contains 17 genomospeci
Identification of pathogenic Leptospira species by conventional or real-time PCR and sequencing of the DNA gyrase subunit B encoding gene
Andrew T Slack, Meegan L Symonds, Michael F Dohnt, Lee D Smythe
BMC Microbiology , 2006, DOI: 10.1186/1471-2180-6-95
Abstract: A conventional and real-time PCR methodology was developed and optimised for the amplification of the gyrB from pathogenic Leptospira species. Non pathogenic and opportunistic Leptospira species such as L. fainei and L. broomi were not amplified. The gyrB gene shows greater nucleotide divergence (3.5% to 16.1%) than the 16s rRNA gene (0.1% to 1.4%). Minimum evolution analysis reveals that the gyrB has a different evolution topology for L. kirschneri and L. interrogans. When the two genes were compared for the identification of the 50 unknown isolates there was 100% agreement in the results.This research has successfully developed a methodology for the identification of pathogenic Leptospira using an alternate gene to 16s rRNA. The gyrB encoding gene shows higher nucleotide/evolutionary divergence allowing for superior identification and also the potential for the development of DNA probe based identification.Leptospirosis is the zoonotic disease caused by members of the genus, Leptospira. They are motile helical spirochaetes that metabolise long chain fatty acids as their carbon source. There are 17 species of Leptospira as determined by DNA-DNA hybridisation [1-4]. These species can be further divided into pathogenic, non-pathogenic and opportunistic/possibly pathogenic Leptospira with pathogenic species. The pathogenic Leptospira include; L. interrogans, L. kirschneri, L. santarosai, L. weilii, L. alexanderi, L. borgpetersenii, L. genomospecies 1 and L. noguchii. The non pathogenic Leptospira include: L. biflexa, L. meyeri, L. wolbachii, L. genomospecies 3, L. genomospecies 4, L. genomospecies 5 and opportunistic/intermediate pathogens Leptospira include L. broomi, L. fainei and L. inadai [3]. The grouping of the last three species as opportunistic or possible pathogens is due to the lack of information on the pathogenicity of the species, different phenotypic characteristics compared to the pathogenic Leptospira and also the limited number of reports of these spe
Renal dysfunction in chronic liver disease
Andy Slack, Andrew Yeoman, Julia Wendon
Critical Care , 2010, DOI: 10.1186/cc8855
Abstract: Acute kidney injury (AKI), chronic kidney disease, and the evaluation of numerous exogenous and endogenous measures of kidney function and injury continue to be the focus of much research in different patient populations. The key reason behind this effort is the well described independent association that small changes in kidney function are strongly linked with increased mortality, extending to those with chronic liver disease.The accurate assessment of kidney function and injury is currently affected by the reliance on the measured concentration of serum creatinine, which is significantly affected by the degree of cirrhosis, hyperbilirubinemia, and the nutritional state of the patient. Improved understanding of the pathophysiology of kidney injury and development of more accurate measures of kidney function and injury are necessary to evoke a positive shift in kidney injury diagnosis, treatment, and outcomes. Furthermore, the number of patients with chronic liver disease and chronic kidney disease continues to rise, due to the large numbers of individuals worldwide affected by viral hepatitides, obesity, hypertension, and diabetes. Consequently, preventative health care messages must be louder and further reaching in order to reverse this trend.Chronic liver disease and primary liver cancer account for 1 in 40 (2.5%) deaths worldwide, with hepatitis B the commonest cause in the developing world, followed by alcoholic liver disease and hepatitis C in the Western world [1]. Non-alcoholic steato-hepatitis and non-alcoholic fatty liver disease are increasing causes of chronic liver disease in the general population of Western countries with prevalence rates of 1-5% and 10-24%, respectively [2]. This observation is related to the increasing incidence of obesity in the Western population and the associated metabolic syndrome, consisting of atherosclerotic coronary vascular disease, hypertension, hyperlipidemia, diabetes, and chronic kidney disease. Metabolic syndrome an
A Dominant Clone of Leptospira interrogans Associated with an Outbreak of Human Leptospirosis in Thailand
Janjira Thaipadungpanit,Vanaporn Wuthiekanun,Wirongrong Chierakul,Lee D. Smythe,Wimol Petkanchanapong,Roongrueng Limpaiboon,Apichat Apiwatanaporn,Andrew T. Slack,Yupin Suputtamongkol,Nicholas J. White,Edward J. Feil,Nicholas P. J. Day,Sharon J. Peacock
PLOS Neglected Tropical Diseases , 2007, DOI: 10.1371/journal.pntd.0000056
Abstract: Background A sustained outbreak of leptospirosis occurred in northeast Thailand between 1999 and 2003, the basis for which was unknown. Methods and Findings A prospective study was conducted between 2000 and 2005 to identify patients with leptospirosis presenting to Udon Thani Hospital in northeast Thailand, and to isolate the causative organisms from blood. A multilocus sequence typing scheme was developed to genotype these pathogenic Leptospira. Additional typing was performed for Leptospira isolated from human cases in other Thai provinces over the same period, and from rodents captured in the northeast during 2004. Sequence types (STs) were compared with those of Leptospira drawn from a reference collection. Twelve STs were identified among 101 isolates from patients in Udon Thani. One of these (ST34) accounted for 77 (76%) of isolates. ST34 was Leptospira interrogans, serovar Autumnalis. 86% of human Leptospira isolates from Udon Thani corresponded to ST34 in 2000/2001, but this figure fell to 56% by 2005 as the outbreak waned (p = 0.01). ST34 represented 17/24 (71%) of human isolates from other Thai provinces, and 7/8 (88%) rodent isolates. By contrast, 59 STs were found among 76 reference strains, indicating a much more diverse population genetic structure; ST34 was not identified in this collection. Conclusions Development of an MLST scheme for Leptospira interrogans revealed that a single ecologically successful pathogenic clone of L. interrogans predominated in the rodent population, and was associated with a sustained outbreak of human leptospirosis in Thailand.
Evidence for a Non-β2-Adrenoceptor Binding Site in Human Lung Tissue for a Subset of β2-Adrenoceptor Agonists  [PDF]
Robert J. Slack
Pharmacology & Pharmacy (PP) , 2014, DOI: 10.4236/pp.2014.51006
Abstract:

The aim of this study was to compare the binding profile of a range of β2-adrenoceptor (β2-AR) agonists and antagonists in human lung tissue. Radioligand saturation and competition binding experiments were performed by filtration with a β2-AR antagonist ([3H]propranolol) or agonist ([3H]vilanterol) radioligand and membrane fragments generated from lung parenchyma in the presence of 100 μM guanosine 5’-[β,γ-imido]triphosphate (Gpp(NH)p). In membranes prepared from human lung parenchyma, carmoterol, formoterol, ICI118551, propranolol and salbutamol resulted in inhibition of [3H]vilanterol binding to levels that were significantly different from indacaterol, salmeterol and vilanterol (ANOVA, Bonferroni post-test, P < 0.001 except formoterol vs indacaterol where P < 0.01). Indacaterol and salmeterol resulted in inhibition of [3H]vilanterol binding to levels that were not significantly different from vilanterol (ANOVA, Bonferroni post-test, P > 0.05). Indacaterol, salmeterol and vilanterol resulted in full inhibition of [3H]propranolol binding to levels not significantly different from ICI118551 (ANOVA, Bonferroni post-test, P > 0.05). Indacaterol, salmeterol and vilanterol bind to an additional site in human lung parenchyma membranes that is distinct from the

Job Satisfaction of Employees Undergoing Public Sector Reform in Fiji  [PDF]
Gurmeet Singh, Neale J. Slack
Theoretical Economics Letters (TEL) , 2016, DOI: 10.4236/tel.2016.62035
Abstract: This study analyses job satisfaction in the Maritime Safety Authority of Fiji (MSAF), a public sector entity undergoing reform. Results of this study determine that the level of MSAF employee job satisfaction by dimension was predominantly low; employees had a low level of intrinsic satisfaction, an average level of extrinsic satisfaction, and a low level of general satisfaction; and employees’ level of job satisfaction was significantly lower than the reference group. This research makes its theoretical contribution primarily to the literature on public service job satisfaction, and to the scarce theoretical strands relating to public service safety organisations. A practical outcome of this research is its contribution towards ongoing public sector reforms in Fiji in general and MSAF and the maritime industry in particular.
On the Mechanism of Gene Amplification Induced under Stress in Escherichia coli
Andrew Slack,P. C Thornton,Daniel B Magner,Susan M Rosenberg,P. J Hastings
PLOS Genetics , 2006, DOI: 10.1371/journal.pgen.0020048
Abstract: Gene amplification is a collection of processes whereby a DNA segment is reiterated to multiple copies per genome. It is important in carcinogenesis and resistance to chemotherapeutic agents, and can underlie adaptive evolution via increased expression of an amplified gene, evolution of new gene functions, and genome evolution. Though first described in the model organism Escherichia coli in the early 1960s, only scant information on the mechanism(s) of amplification in this system has been obtained, and many models for mechanism(s) were possible. More recently, some gene amplifications in E. coli were shown to be stress-inducible and to confer a selective advantage to cells under stress (adaptive amplifications), potentially accelerating evolution specifically when cells are poorly adapted to their environment. We focus on stress-induced amplification in E. coli and report several findings that indicate a novel molecular mechanism, and we suggest that most amplifications might be stress-induced, not spontaneous. First, as often hypothesized, but not shown previously, certain proteins used for DNA double-strand-break repair and homologous recombination are required for amplification. Second, in contrast with previous models in which homologous recombination between repeated sequences caused duplications that lead to amplification, the amplified DNAs are present in situ as tandem, direct repeats of 7–32 kilobases bordered by only 4 to 15 base pairs of G-rich homology, indicating an initial non-homologous recombination event. Sequences at the rearrangement junctions suggest nonhomologous recombination mechanisms that occur via template switching during DNA replication, but unlike previously described template switching events, these must occur over long distances. Third, we provide evidence that 3′-single-strand DNA ends are intermediates in the process, supporting a template-switching mechanism. Fourth, we provide evidence that lagging-strand templates are involved. Finally, we propose a novel, long-distance template-switching model for the mechanism of adaptive amplification that suggests how stress induces the amplifications. We outline its possible applicability to amplification in humans and other organisms and circumstances.
Adaptive Amplification and Point Mutation Are Independent Mechanisms: Evidence for Various Stress-Inducible Mutation Mechanisms
P. J. Hastings,Andrew Slack,Joseph F. Petrosino,Susan M. Rosenberg
PLOS Biology , 2012, DOI: 10.1371/journal.pbio.0020399
Abstract: “Adaptive mutation” denotes a collection of processes in which cells respond to growth-limiting environments by producing compensatory mutants that grow well, apparently violating fundamental principles of evolution. In a well-studied model, starvation of stationary-phase lac? Escherichia coli cells on lactose medium induces Lac+ revertants at higher frequencies than predicted by usual mutation models. These revertants carry either a compensatory frameshift mutation or a greater than 20-fold amplification of the leaky lac allele. A crucial distinction between alternative hypotheses for the mechanisms of adaptive mutation hinges on whether these amplification and frameshift mutation events are distinct, or whether amplification is a molecular intermediate, producing an intermediate cell type, in colonies on a pathway to frameshift mutation. The latter model allows the evolutionarily conservative idea of increased mutations (per cell) without increased mutation rate (by virtue of extra gene copies per cell), whereas the former requires an increase in mutation rate, potentially accelerating evolution. To resolve these models, we probed early events leading to rare adaptive mutations and report several results that show that amplification is not the precursor to frameshift mutation but rather is an independent adaptive outcome. (i) Using new high-resolution selection methods and stringent analysis of all cells in very young (micro)colonies (500–10,000 cells), we find that most mutant colonies contain no detectable lac-amplified cells, in contrast with previous reports. (ii) Analysis of nascent colonies, as young as the two-cell stage, revealed mutant Lac+ cells with no lac-amplified cells present. (iii) Stringent colony-fate experiments show that microcolonies of lac-amplified cells grow to form visible colonies of lac-amplified, not mutant, cells. (iv) Mutant cells do not overgrow lac-amplified cells in microcolonies fast enough to mask the lac-amplified cells. (v) lac-amplified cells are not SOS-induced, as was proposed to explain elevated mutation in a sequential model. (vi) Amplification, and not frameshift mutation, requires DNA polymerase I, demonstrating that mutation is separable from amplification, and also illuminating the amplification mechanism. We conclude that amplification and mutation are independent outcomes of adaptive genetic change. We suggest that the availability of alternative pathways for genetic/evolutionary adaptation and clonal expansion under stress may be exploited during processes ranging from the evolution of drug resistance to cancer progression.
On the mechanism of gene amplification induced under stress in Escherichia coli.
Slack Andrew,Thornton P C,Magner Daniel B,Rosenberg Susan M
PLOS Genetics , 2006,
Abstract: Gene amplification is a collection of processes whereby a DNA segment is reiterated to multiple copies per genome. It is important in carcinogenesis and resistance to chemotherapeutic agents, and can underlie adaptive evolution via increased expression of an amplified gene, evolution of new gene functions, and genome evolution. Though first described in the model organism Escherichia coli in the early 1960s, only scant information on the mechanism(s) of amplification in this system has been obtained, and many models for mechanism(s) were possible. More recently, some gene amplifications in E. coli were shown to be stress-inducible and to confer a selective advantage to cells under stress (adaptive amplifications), potentially accelerating evolution specifically when cells are poorly adapted to their environment. We focus on stress-induced amplification in E. coli and report several findings that indicate a novel molecular mechanism, and we suggest that most amplifications might be stress-induced, not spontaneous. First, as often hypothesized, but not shown previously, certain proteins used for DNA double-strand-break repair and homologous recombination are required for amplification. Second, in contrast with previous models in which homologous recombination between repeated sequences caused duplications that lead to amplification, the amplified DNAs are present in situ as tandem, direct repeats of 7-32 kilobases bordered by only 4 to 15 base pairs of G-rich homology, indicating an initial non-homologous recombination event. Sequences at the rearrangement junctions suggest nonhomologous recombination mechanisms that occur via template switching during DNA replication, but unlike previously described template switching events, these must occur over long distances. Third, we provide evidence that 3'-single-strand DNA ends are intermediates in the process, supporting a template-switching mechanism. Fourth, we provide evidence that lagging-strand templates are involved. Finally, we propose a novel, long-distance template-switching model for the mechanism of adaptive amplification that suggests how stress induces the amplifications. We outline its possible applicability to amplification in humans and other organisms and circumstances.
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