Molecular genetic analyses of RFLPs for PCR-amplified growth hormone gene, renal kallikrein gene and atrial natriuretic factor gene in essential hypertension

The present study examined polymorphisms of genes that might be involved in the onset of essential hypertension (HT). These included the (i) growth hormone gene (GH1), whose locus has recently been linked to elevated blood pressure (BP) in the stroke-prone SHR, although recent sib-pair analysis of a polymorphism near the human chorionic somatomammotropin gene (a member of the GH cluster) was unable to show linkage with HT; (ii) renal kallikrein gene (KLK1); and (iii) atrial natriuretic factor gene (ANF), where a primary defect in production or activity of kallikrein or ANF could cause NaCl retention and vasoconstriction. Association analyses were conducted to compare restriction fragment length polymorphisms (RFLPs) of each gene in 85 HT and 95 normotensive (NT) Caucasian subjects whose parents had a similar BP status at age ≥50 years. The frequency of the minor allele of (i) a RsaI RFLP in the promoter of GH1, amplified from leukocyte DNA by the polymerase chain reaction, was 0.15 in the HT group and 0.14 in the NT group (χ1=0.34, P=0.55); (ii) a TaqI RFLP for KLK1 was 0.035 in the HT group and 0.015 in the NT group (χ2=1.5, P=0.21); and (iii) a XhoI RFLP for ANF was 0.50 in HTs and 0.46 in NTs (χ2=0.20, P=0.65). Studies of HT pedigrees found one family in which the ANF locus and HT were not linked, owing to an obligate recombinant. The present data thus provide no evidence for involvement of the growth hormone, renal kallikrein, nor ANF gene in the causation of essential hypertension.

Association and linkage analyses of restriction fragment length polymorphisms for the human renin and antithrombin III genes in essential hypertension

Essential hypertension is a highly hereditable disorder in which genetic influences predominate over environmental factors. The molecular genetic profiles which predispose to essential hypertension are not known. In rats with genetic hypertension, there is some recent evidence pointing to linkage of renin gene alleles with blood pressure. The genes for renin and antithrombin III belong to a conserved synteny group which, in humans, spans the q21.3-32.3 region of chromosome I and, in rats, is linkage group X on chromosome 13. The present study examined the association of particular human renin gene (REN) and antithrombin III gene (AT3) polymorphisms with essential hypertension by comparing the frequency of specific alleles for each of these genes in 50 hypertensive offspring of hypertensive parents and 91 normotensive offspring of normotensive parents. In addition, linkage relationships were examined in hypertensive pedigrees with multiple affected individuals. Alleles of a REN HindIII restriction fragment length polymorphism (RFLP) were detected using a genomic clone, λHR5, to probe Southern blots of HindIII-cut leucocyte DNA, and those for an AT3 Pstl RFLP were detected by phATIII 113 complementary DNA probe. The frequencies of each REN allele in the hypertensive group were 0.76 and 0.24 compared with 0.74 and 0.26 in the normotensive group. For AT3, hypertensive allele frequencies were 0.49 and 0.51 compared with normotensive values of 0.54 and 0.46. These differences were not significant by χ2 analysis (P > 0.2). Linkage analysis of a family (data from 16 family members, 10 of whom were hypertensive), informative for both markers, without an age-of-onset correction, and assuming dominant inheritance of hypertension, complete penetrance and a disease frequency of 20%, did not indicate linkage of REN with hypertension, but gave a positive, although not significant, logarithm of the odds for linkage score of 0.784 at a recombination fraction of 0 for AT3 linkage to hypertension. In conclusion, the present study could find no evidence for an association of a REN HindIII RFLP with essential hypertension or for a linkage of the locus defined by this RFLP in a family segregating for hypertension. In the case of an AT3 Pstl RFLP, although association analysis was negative, linkage analysis suggested possible involvement (odds of 6:1 in favour) of a gene located near the 1q23 locus with hypertension in one informative family.

Assessing the short-term effects of heatwaves on mortality and morbidity in Brisbane, Australia : comparison of case-crossover and time series analyses

Background Heat-related impacts may have greater public health implications as climate change continues. It is important to appropriately characterize the relationship between heatwave and health outcomes. However, it is unclear whether a case-crossover design can be effectively used to assess the event- or episode-related health effects. This study examined the association between exposure to heatwaves and mortality and emergency hospital admissions (EHAs) from non-external causes in Brisbane, Australia, using both case-crossover and time series analyses approaches. Methods Poisson generalised additive model (GAM) and time-stratified case-crossover analyses were used to assess the short-term impact of heatwaves on mortality and EHAs. Heatwaves exhibited a significant impact on mortality and EHAs after adjusting for air pollution, day of the week, and season. Results For time-stratified case-crossover analysis, odds ratios of mortality and EHAs during heatwaves were 1.62 (95% confidence interval (CI): 1.36–1.94) and 1.22 (95% CI: 1.14–1.30) at lag 1, respectively. Time series GAM models gave similar results. Relative risks of mortality and EHAs ranged from 1.72 (95% CI: 1.40–2.11) to 1.81 (95% CI: 1.56–2.10) and from 1.14 (95% CI: 1.06–1.23) to 1.28 (95% CI: 1.21–1.36) at lag 1, respectively. The risk estimates gradually attenuated after the lag of one day for both case-crossover and time series analyses. Conclusions The risk estimates from both case-crossover and time series models were consistent and comparable. This finding may have implications for future research on the assessment of event- or episode-related (e.g., heatwave) health effects.

A Procedural Model for Ontological Analyses

In recent years, there has been a significant increase in the popularity of ontological analysis of conceptual modelling techniques. To date, related research explores the ontological deficiencies of classical techniques such as ER or UML modelling, as well as business process modelling techniques such as ARIS or even Web Services standards such as BPEL4WS, BPML, ebXML, BPSS and WSCI. While the ontologies that form the basis of these analyses are reasonably mature, it is the actual process of an ontological analysis that still lacks rigour. The current procedure is prone to individual interpretations and is one reason for criticism of the entire ontological analysis. This paper presents a procedural model for ontological analysis based on the use of meta models, multiple coders and metrics. The model is supported by examples from various ontological analyses.

Proteomic and other analyses to determine the functional consequences of deregulated kallikrein-related peptidase (KLK) expression in prostate and ovarian cancer

Rapidly developing proteomic tools are improving detection of deregulated kallikrein-related peptidase (KLK) expression, at the protein level, in prostate and ovarian cancer, as well as facilitating the determination of functional consequences downstream. Mass spectrometry (MS)-driven proteomics uniquely allows for the detection, identification and quantification of thousands of proteins in a complex protein pool, and this has served to identify certain KLKs as biomarkers for these diseases. In this review we describe applications of this technology in KLK biomarker discovery, and elucidate MS-based techniques which have been used for unbiased, global screening of KLK substrates within complex protein pools. Although MS-based KLK degradomic studies are limited to date, they helped to discover an array of novel KLK substrates. Substrates identified by MS-based degradomics are reported with improved confidence over those determined by incubating a purified or recombinant substrate and protease of interest, in vitro. We propose that these novel proteomic approaches represent the way forward for KLK research, in order to correlate proteolysis of biological substrates with tissue-related consequences, toward clinical targeting of KLK expression and function for cancer diagnosis, prognosis and therapies.

N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB

Protein N-terminal acetylation (Nt-acetylation) is an important mediator of protein function, stability, sorting, and localization. Although the responsible enzymes are thought to be fairly well characterized, the lack of identified in vivo substrates, the occurrence of Nt-acetylation substrates displaying yet uncharacterized N-terminal acetyltransferase (NAT) specificities, and emerging evidence of posttranslational Nt-acetylation, necessitate the use of genetic models and quantitative proteomics. NatB, which targets Met-Glu-, Met-Asp-, and Met-Asn-starting protein N termini, is presumed to Nt-acetylate 15% of all yeast and 18% of all human proteins. We here report on the evolutionary traits of NatB from yeast to human and demonstrate that ectopically expressed hNatB in a yNatB-Δ yeast strain partially complements the natB-Δ phenotypes and partially restores the yNatB Nt-acetylome. Overall, combining quantitative N-terminomics with yeast studies and knockdown of hNatB in human cell lines, led to the unambiguous identification of 180 human and 110 yeast NatB substrates. Interestingly, these substrates included Met-Gln- N-termini, which are thus now classified as in vivo NatB substrates. We also demonstrate the requirement of hNatB activity for maintaining the structure and function of actomyosin fibers and for proper cellular migration. In addition, expression of tropomyosin-1 restored the altered focal adhesions and cellular migration defects observed in hNatB-depleted HeLa cells, indicative for the conserved link between NatB, tropomyosin, and actin cable function from yeast to human.

Comparative analyses of change orders costs in transportation construction

Transportation construction is substantially different from other construction fields due to widespread use of unit price bidding and competitive contract awarding. Thus, the potential for change orders has been the main source of unbalanced bidding for contractors, which can be described as substantial increases in work quantity or reasonable changes to the initial design provided by the State Highway Agencies (SHAs). It is important to understand the causes of the change orders as cost related issues are the main reason for contract disputes. We have analyzed a large dataset from a major SHA to identify project related and environmental factors that affect the change order costs. The results of the study can be instrumental in assessing the increased costs associated with change orders and better management measures can be taken to mitigate their effects.

Spatial-temporal epidemiological analyses of two sympatric, co-endemic alphaviral diseases in Queensland, Australia

Background: The two most reported mosquito-borne diseases in Queensland, a northern state of Australia, are Ross River virus (RRV) disease and Barmah Forest virus (BFV) disease. Both diseases are endemic in Queensland and have similar clinical symptoms and comparable transmission cycles involving a complex inter-relationship between human hosts, various mosquito vectors, and a range of nonhuman vertebrate hosts, including marsupial mammals that are unique to the Australasian region. Although these viruses are thought to share similar vectors and vertebrate hosts, RRV is four times more prevalent than BFV in Queensland. Methods: We performed a retrospective analysis of BFV and RRV human disease notification data collected from 1995 to 2007 in Queensland to ascertain whether there were differences in the incidence patterns of RRV and BFV disease. In particular, we compared the temporal incidence and spatial distribution of both diseases and considered the relationship between their disease dynamics. We also investigated whether a peak in BFV incidence during spring was indicative of the following RRV and BFV transmission season incidence levels. Results: Although there were large differences in the notification rates of the two diseases, they had similar annual temporal patterns, but there were regional variations between the length and magnitude of the transmission seasons. During periods of increased disease activity, however, there was no association between the dynamics of the two diseases. Conclusions: The results from this study suggest that while RRV and BFV share similar mosquito vectors, there are significant differences in the ecology of these viruses that result in different epidemic patterns of disease incidence. Further investigation is required into the ecology of each virus to determine which factors are important in promoting RRV and BFV disease outbreaks.

Solar evaporator-collectors : analyses and applications

Taking into consideration of growing energy needs and concern for environmental degradation, clean and inexhaustible energy source, such as solar energy, is receiving greater attention for various applications. The use of solar energy system reduces pollution, waste and has little or no harmful effects on the environment. It is appreciated that this source of energy can be complementary rather than being competitive to conventional energy sources. In order to collect and harness energy from the sun, a solar collector is essential. A solar collector is basically a heat exchanger that transforms solar radiant energy into heat or thermal energy. Improvement of performance is essential for commercial acceptance of their use in such applications. Many studies have been undertaken on the enhancement of thermal performance of solar collectors, using diverse materials of various shapes, dimensions and layouts. In the literature, various collector designs have been proposed and tested with the objective of meeting these requirements [1-8]. Omer et al. [1] found the efficiency of a solar collector of about 70% in a solar assisted heat pump system. Traditional solar collectors are single phase collectors, in which the working fluid is either air or water. Different modifications are suggested and applied to improve the heat transfer between the absorber and working fluid in a collector. These modifications include the use of absorber with fins attached [2,3], corrugated absorber [4,5], matrix type absorber [6], V-groove solar air collector [7]. Karim et al. [8] approached a review of design and construction of three types (flat, vee-grooved, and finned) of air collectors. Two-phase collectors, on the other hand, have significant potential for continuous operation round the clock, when used in conjunction with a compressor, as found in a solar assisted heat-pump cycle.

New country market feasibility analyses

Opportunity screening is also known as feasibility testing, which is the process of assessing whether a particular business opportunity is within the capacity of either an entrepreneur or an intrapreneur, and also whether it can create sustainable revenues. As the funnel diagram shows, the number of opportunities diminishes as we move to the right through the diagram. This is because not every idea identified in the opportunity identification stage as potentially interesting, and then framed into a business opportunity in the opportunity development stage, will satisfy the formal and informal screening criteria. The informal screening process occurs in all stages of the development process. For example, not every idea that has been identified will be converted into a business opportunity; similarly, not every business opportunity progresses to a feasibility test. Subsequently, only the best business opportunities are screened, and only the very best of those screened then progress to the business plan step.

In silico analyses reveal common cellular pathways affected by loss of heterozygosity (LOH) events in the lymphomagenesis of Non-Hodgkin’s lymphoma (NHL)

Background The analysis of cellular networks and pathways involved in oncogenesis has increased our knowledge about the pathogenic mechanisms that underlie tumour biology and has unmasked new molecular targets that may lead to the design of better anti-cancer therapies. Recently, using a high resolution loss of heterozygosity (LOH) analysis, we identified a number of potential tumour suppressor genes (TSGs) within common LOH regions across cases suffering from two of the most common forms of Non-Hodgkin’s lymphoma (NHL), Follicular Lymphoma (FL) and Diffuse Large B-cell Lymphoma (DLBCL). From these studies LOH of the protein tyrosine phosphatase receptor type J (PTPRJ) gene was identified as a common event in the lymphomagenesis of these B-cell lymphomas. The present study aimed to determine the cellular pathways affected by the inactivation of these TSGs including PTPRJ in FL and DLBCL tumourigenesis. Results Pathway analytical approaches identified that candidate TSGs located within common LOH regions participate within cellular pathways, which may play a crucial role in FL and DLBCL lymphomagenesis (i.e., metabolic pathways). These analyses also identified genes within the interactome of PTPRJ (i.e. PTPN11 and B2M) that when inactivated in NHL may play an important role in tumourigenesis. We also detected genes that are differentially expressed in cases with and without LOH of PTPRJ, such as NFATC3 (nuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 3). Moreover, upregulation of the VEGF, MAPK and ERBB signalling pathways was also observed in NHL cases with LOH of PTPRJ, indicating that LOH-driving events causing inactivation of PTPRJ, apart from possibly inducing a constitutive activation of these pathways by reduction or abrogation of its dephosphorylation activity, may also induce upregulation of these pathways when inactivated. This finding implicates these pathways in the lymphomagenesis and progression of FL and DLBCL. Conclusions The evidence obtained in this research supports findings suggesting that FL and DLBCL share common pathogenic mechanisms. Also, it indicates that PTPRJ can play a crucial role in the pathogenesis of these B-cell tumours and suggests that activation of PTPRJ might be an interesting novel chemotherapeutic target for the treatment of these B-cell tumours.

Transcriptome analyses of amoebic gill disease-affected atlantic salmon (Salmo salar) tissues reveal localized host gene suppression

The transcriptome response of Atlantic salmon (Salmo salar) displaying advanced stages of amoebic gill disease (AGD) was investigated. Naïve smolt were challenged with AGD for 19 days, at which time all fish were euthanized and their severity of infection quantified through histopathological scoring. Gene expression profiles were compared between heavily infected and naïve individuals using a 17 K Atlantic salmon cDNA microarray with real-time quantitative RT-PCR (qPCR) verification. Expression profiles were examined in the gill, anterior kidney, and liver. Twenty-seven transcripts were significantly differentially expressed within the gill; 20 of these transcripts were down-regulated in the AGD-affected individuals compared with naïve individuals. In contrast, only nine transcripts were significantly differentially expressed within the anterior kidney and five within the liver. Again the majority of these transcripts were down-regulated within the diseased individuals. A down-regulation of transcripts involved in apoptosis (procathepsin L, cathepsin H precursor, and cystatin B) was observed in AGD-affected Atlantic salmon. Four transcripts encoding genes with antioxidant properties also were down-regulated in AGD-affected gill tissue according to qPCR analysis. The most up-regulated transcript within the gill was an unknown expressed sequence tag (EST) whose expression was 218-fold (± SE 66) higher within the AGD affected gill tissue. Our results suggest that Atlantic salmon experiencing advanced stages of AGD demonstrate general down-regulation of gene expression, which is most pronounced within the gill. We propose that this general gene suppression is parasite-mediated, thus allowing the parasite to withstand or ameliorate the host response. © 2008 Springer Science+Business Media, LLC.

Accounting for management costs in sensitivity analyses of matrix population models

Traditional sensitivity and elasticity analyses of matrix population models have been used to inform management decisions, but they ignore the economic costs of manipulating vital rates. For example, the growth rate of a population is often most sensitive to changes in adult survival rate, but this does not mean that increasing that rate is the best option for managing the population because it may be much more expensive than other options. To explore how managers should optimize their manipulation of vital rates, we incorporated the cost of changing those rates into matrix population models. We derived analytic expressions for locations in parameter space where managers should shift between management of fecundity and survival, for the balance between fecundity and survival management at those boundaries, and for the allocation of management resources to sustain that optimal balance. For simple matrices, the optimal budget allocation can often be expressed as simple functions of vital rates and the relative costs of changing them. We applied our method to management of the Helmeted Honeyeater (Lichenostomus melanops cassidix; an endangered Australian bird) and the koala (Phascolarctos cinereus) as examples. Our method showed that cost-efficient management of the Helmeted Honeyeater should focus on increasing fecundity via nest protection, whereas optimal koala management should focus on manipulating both fecundity and survival simultaneously. These findings are contrary to the cost-negligent recommendations of elasticity analysis, which would suggest focusing on managing survival in both cases. A further investigation of Helmeted Honeyeater management options, based on an individual-based model incorporating density dependence, spatial structure, and environmental stochasticity, confirmed that fecundity management was the most cost-effective strategy. Our results demonstrate that decisions that ignore economic factors will reduce management efficiency. ©2006 Society for Conservation Biology.

Biomechanical analyses of the performance of Paralympians: From foundation to elite level

Biomechanical analysis of sport performance provides an objective method of determining performance of a particular sporting technique. In particular, it aims to add to the understanding of the mechanisms influencing performance, characterization of athletes, and provide insights into injury predisposition. Whilst the performance in sport of able-bodied athletes is well recognised in the literature, less information and understanding is known on the complexity, constraints and demands placed on the body of an individual with a disability. This paper provides a dialogue that outlines scientific issues of performance analysis of multi-level athletes with a disability, including Paralympians. Four integrated themes are explored the first of which focuses on how biomechanics can contribute to the understanding of sport performance in athletes with a disability and how it may be used as an evidence-based tool. This latter point questions the potential for a possible cultural shift led by emergence of user-friendly instruments. The second theme briefly discusses the role of reliability of sport performance and addresses the debate of two-dimensional and three-dimensional analysis. The third theme address key biomechanical parameters and provides guidance to clinicians, and coaches on the approaches adopted using biomechanical/sport performance analysis for an athlete with a disability starting out, to the emerging and elite Paralympian. For completeness of this discourse, the final theme is based on the controversial issues on the role of assisted devices and the inclusion of Paralympians into able-bodied sport is also presented. All combined, this dialogue highlights the intricate relationship between biomechanics and training of individuals with a disability. Furthermore, it illustrates the complexity of modern training of athletes which can only lead to a better appreciation of the performances to be delivered in the London 2012 Paralympic Games

Economic analyses of Australia's Sydney rock oyster industry

This thesis provides the first comprehensive assessment of the economic viability of Australia's Sydney rock oyster industry and forms the bases for future policy and industry management recommendations. In the four separate studies of the thesis, the socio-economic profile of the industry, the market price formation dynamics within Australia's oyster market, efficiency and productivity levels and the potential impact of climate change and market dynamics on the industry's future revenue were investigated. Findings of this project suggest, for example, that market dynamics may pose a greater thread to the future development of this industry than direct effect from climate change.