Reduced excision repair cross-complementing 1 expression associates with enhanced papilloma formation and fibroblast transformation after genetic disruption of secreted protein acidic and rich in cysteine

SPARC (secreted protein acidic and rich in cysteine)/ osteonectin/BM-40 is a matricellular protein implicated in development, cell transformation and tumorigenesis. We have examined the role of SPARC in cell transformation induced chemically with 7,12-dimethylbenz[a]anthracene (DMBA) and 12- tetradecanoylphorbol-13-acetate (TPA) in embryonic fibroblasts and in the skin of mice. Embryonic fibroblasts from SPARCnull mice showed increases in cell proliferation, enhanced sensitivity to DMBA and a higher number of DMBA/TPA-induced transformation foci. The number of DMBA-DNA adducts was 9 times higher in SPARCnull fibroblasts and their stability was lower than wild-type fibroblasts, consistent with a reduction in excision repair cross-complementing 1 the nucleotide excision repair enzyme in these cells. The SPARCnull mice showed an increase in both the speed and number of papillomas forming after topical administration of DMBA/TPA to the skin. These papillomas showed reduced growth and reduced progression to a more malignant phenotype, indicating that the effect of SPARC on tumorigenesis depends upon the transformation stage and/or tissue context. These data reinforce a growing number of observations in which SPARC has shown opposite effects on different tumor types/stages.

The Healthy Trends of International Relations Research

As the end of the Cold War approached in 1989, Caroline Thomas argued: “It is important that the discipline [International Relations, IR] should address the issue of disease and more broadly, health, not simply to facilitate containment of disease transmission across international borders but also because central notions of justice, equity, efficiency and order are involved” (1989:273).1 Ten years later, Craig Murphy echoed these sentiments. Murphy (2001: 352) proposed that IR had yet to grapple with the political consequences of growing inequality between the world’s rich and poor, and areas such as health—where these inequalities were most stark—should become the field’s core business. How IR’s theories and methods would approach these issues was less clear. Bettcher and Yach (1998) cautioned that IR would be unable to develop progressive research projects that explored global health diplomacy as a global public good without adopting new perspectives and methods. Others warned that the expansion of security studies into areas such as global health would weaken the intellectual coherency of the field (Walt 1991:213). Taking its cue from the recent Ng and Prah Ruger (2011) study, this paper returns to these concerns to briefly explore key trends and potential future concerns of research in IR on health...

Mapping eQTLs in the Norfolk Island genetic isolate identifies candidate genes for CVD risk traits

Cardiovascular disease (CVD) affects millions of people worldwide and is influenced by numerous factors, including lifestyle and genetics. Expression quantitative trait loci (eQTLs) influence gene expression and are good candidates for CVD risk. Founder-effect pedigrees can provide additional power to map genes associated with disease risk. Therefore, we identified eQTLs in the genetic isolate of Norfolk Island (NI) and tested for associations between these and CVD risk factors. We measured genome-wide transcript levels of blood lymphocytes in 330 individuals and used pedigree-based heritability analysis to identify heritable transcripts. eQTLs were identified by genome-wide association testing of these transcripts. Testing for association between CVD risk factors (i.e., blood lipids, blood pressure, and body fat indices) and eQTLs revealed 1,712 heritable transcripts (p < 0.05) with heritability values ranging from 0.18 to 0.84. From these, we identified 200 cis-acting and 70 trans-acting eQTLs (p < 1.84 × 10(-7)) An eQTL-centric analysis of CVD risk traits revealed multiple associations, including 12 previously associated with CVD-related traits. Trait versus eQTL regression modeling identified four CVD risk candidates (NAAA, PAPSS1, NME1, and PRDX1), all of which have known biological roles in disease. In addition, we implicated several genes previously associated with CVD risk traits, including MTHFR and FN3KRP. We have successfully identified a panel of eQTLs in the NI pedigree and used this to implicate several genes in CVD risk. Future studies are required for further assessing the functional importance of these eQTLs and whether the findings here also relate to outbred populations.

Genetic and phenotypic evidence supports evolutionary divergence of the American flamingo (Phoenicopterus ruber) population in the Galapagos islands

The Galapagos archipelago is characterized by a high degree of endemism across many taxa, linked to the archpelago's oceanic origin and distance from other colonizing land masses. A population of ~ 500 American Flamingos (Phoenicopterus ruber) resides in Galapagos, which is thought to share an historical origin with the American Flamingo currently found in the Caribbean region. Genetic and phenotypic parameters in American Flamingos from Galapagos and from the Caribbean were investigated. Microsatellite and microchondrial DNA markers data showed that the American Flamingo population in Galapagos differs genetically from that in the Caribbean. American Flamingos in Galapagos form a clade which differs by a single common nucleotide substitution from American Flamingos in the Caribbean. The genetic differentiation is also evident from nuclear DNA in that microsatellite data reveal a number of private alleles for the American Flamingo in Galapagos. Analysis of skeletal measurements showed that American Flamingos in Galapagos are smaller than those in the Caribbean primarily due to shorter tarsus length, and differences in body shape sexual dimorphism. American Flamingo eggs from Galapagos have smaller linear dimensions and volumes than those from the Caribbean. The findings are consistent with reproductive isolation of American Flamingo population in Galapagos.

Perturbing event logs to identify cost reduction opportunities: a genetic algorithm-based approach

Organisations are constantly seeking new ways to improve operational efficiencies. This research study investigates a novel way to identify potential efficiency gains in business operations by observing how they are carried out in the past and then exploring better ways of executing them by taking into account trade-offs between time, cost and resource utilisation. This paper demonstrates how they can be incorporated in the assessment of alternative process execution scenarios by making use of a cost environment. A genetic algorithm-based approach is proposed to explore and assess alternative process execution scenarios, where the objective function is represented by a comprehensive cost structure that captures different process dimensions. Experiments conducted with different variants of the genetic algorithm evaluate the approach's feasibility. The findings demonstrate that a genetic algorithm-based approach is able to make use of cost reduction as a way to identify improved execution scenarios in terms of reduced case durations and increased resource utilisation. The ultimate aim is to utilise cost-related insights gained from such improved scenarios to put forward recommendations for reducing process-related cost within organisations.

Beyond Wearables : Experiences and Trends in Design of Portable Medical Devices

The use of Portable Medical Devices (PMDs) has become increasingly widespread over the last few years. A combination of factors; including advances in technology, the pressure to reduce public health costs and the desire to make health solutions accessible to a wider patient base are contributing to the growth in the PMD market. Design has a clear role to play in the current and future context of the PMD landscape. In this paper, we identify emerging trends in the design of PMDs; including changes in the form, purpose and mode of use, and explore how these trends are likely to fundamentally impact the nature of healthcare and the patient experience from an experience design perspective. We conclude by identifying a research opportunity for design within the healthcare and PMD context.

No genetic bottleneck in Plasmodium falciparum wild-type Pfcrt alleles reemerging in Hainan Island, China, following high-level chloroquine resistance

Chloroquine-resistant Plasmodium falciparum was highly prevalent in Hainan, China, in the 1970s. Twenty-five years after cessation of chloroquine therapy, the prevalence of P. falciparum wild-type Pfcrt alleles has risen to 36% (95% confidence interval, 22.1 to 52.4%). The diverse origins of wild-type alleles indicate that there was no genetic bottleneck caused by high chloroquine resistance.

Current trends and challenges for sport and exercise psychology – What now for our discipline?

With an ever changing landscape including National Registration, endorsed areas of practice, establishment of Sport and Exercise Psychology coordinators within National Sporting Organisations, changes to the National and State Sporting Insitutions, this forum looks to explore through collegiate discussion the impacts, current and future implications for our profession across training, supervision, research and applied practice in Australia.

A random key genetic algorithm for live migration of multiple virtual machines in data centers

Live migration of multiple Virtual Machines (VMs) has become an integral management activity in data centers for power saving, load balancing and system maintenance. While state-of-the-art live migration techniques focus on the improvement of migration performance of an independent single VM, only a little has been investigated to the case of live migration of multiple interacting VMs. Live migration is mostly influenced by the network bandwidth and arbitrarily migrating a VM which has data inter-dependencies with other VMs may increase the bandwidth consumption and adversely affect the performances of subsequent migrations. In this paper, we propose a Random Key Genetic Algorithm (RKGA) that efficiently schedules the migration of a given set of VMs accounting both inter-VM dependency and data center communication network. The experimental results show that the RKGA can schedule the migration of multiple VMs with significantly shorter total migration time and total downtime compared to a heuristic algorithm.

Genetic bottlenecks in time and space: reconstructing invasions from contemporary and historical collections

Herbarium accession data offer a useful historical botanical perspective and have been used to track the spread of plant invasions through time and space. Nevertheless, few studies have utilised this resource for genetic analysis to reconstruct a more complete picture of historical invasion dynamics, including the occurrence of separate introduction events. In this study, we combined nuclear and chloroplast microsatellite analyses of contemporary and historical collections of Senecio madagascariensis, a globally invasive weed first introduced to Australia c. 1918 from its native South Africa. Analysis of nuclear microsatellites, together with temporal spread data and simulations of herbarium voucher sampling, revealed distinct introductions to south-eastern Australia and mid-eastern Australia. Genetic diversity of the south-eastern invasive population was lower than in the native range, but higher than in the mid-eastern invasion. In the invasive range, despite its low resolution, our chloroplast microsatellite data revealed the occurrence of new haplotypes over time, probably as the result of subsequent introduction(s) to Australia from the native range during the latter half of the 20th century. Our work demonstrates how molecular studies of contemporary and historical field collections can be combined to reconstruct a more complete picture of the invasion history of introduced taxa. Further, our study indicates that a survey of contemporary samples only (as undertaken for the majority of invasive species studies) would be insufficient to identify potential source populations and occurrence of multiple introductions.

Markers of genetic susceptibility in human environmental hygiene and toxicology : the role of selected CYP, NAT and GST genes

Inherited genetic traits co-determine the susceptibility of an individual to a toxic chemical. Special emphasis has been put on individual responses to environmental and industrial carcinogens, but other chronic diseases are of increasing interest. Polymorphisms of relevant xenobiotic metabolising enzymes may be used as toxicological susceptibility markers. A growing number of genes encoding enzymes involved in biotransformation of toxicants and in cellular defence against toxicant-induced damage to the cells has been identified and cloned, leading to increased knowledge of allelic variants of genes and genetic defects that may result in a differential susceptibility toward environmental toxicants. "Low penetrating" polymorphisms in metabolism genes tend to be much more common in the population than allelic variants of "high penetrating" cancer genes, and are therefore of considerable importance from a public health point of view. Positive associations between cancer and CYP1A1 alleles, in particular the *2C I462V allele, were found for tissues following the aerodigestive tract. Again, in most cases, the effect of the variant CYP1A1 allele becomes apparent or clearer in connection with the GSTM1 null allele. The CYP1B1 codon 432 polymorphism (CYP1B1*3) has been identified as a susceptibility factor in smoking-related head-and-neck squameous cell cancer. The impact of this polymorphic variant of CYP1B1 on cancer risk was also reflected by an association with the frequency of somatic mutations of the p53 gene. Combined genotype analysis of CYP1B1 and the glutathione transferases GSTM1 or GSTT1 has also pointed to interactive effects. Of particular interest for the industrial and environmental field is the isozyme CYP2E1. Several genotypes of this isozyme have been characterised which seem to be associated with different levels of expression of enzyme activity. The acetylator status for NAT2 can be determined by genotyping or by phenotyping. In the pathogenesis of human bladder cancer due to occupational exposure to "classical" aromatic amines (benzidine, 4-aminodiphenyl, 1-naphthylamine) acetylation by NAT2 is regarded as a detoxication step. Interestingly, the underlying European findings of a higher susceptibility of slow acetylators towards aromatic amines are in contrast to findings in Chinese workers occupationally exposed to aromatic amines which points to different mechanisms of susceptibility between European and Chinese populations. Regarding human bladder cancer, the hypothesis has been put forward that genetic polymorphism of GSTM1 might be linked with the occurrence of this tumour type. This supports the hypothesis that exposure to PAH might causally be involved in urothelial cancers. The human polymorphic GST catalysing conjugation of halomethanes, dihalomethanes, ethylene oxide and a number of other industrial compounds could be characterised as a class theta enzyme (GSTT1) by means of molecular biology. "Conjugator" and "non-conjugator" phenotypes are coincident with the presence and absence of the GSTT1 gene. There are wide variations in the frequencies of GSTT1 deletion (GSTT1 *0/0) among different ethnicities. Human phenotyping is facilitated by the GST activity towards methyl bromide or ethylene oxide in erythrocytes which is representative of the metabolic GSTT1 competence of the entire organism. Inter-individual variations in xenobiotic metabolism capacities may be due to polymorphisms of the genes coding for the enzymes themselves or of the genes coding for the receptors or transcription factors which regulate the expression of the enzymes. Also, polymorphisms in several regions of genes may cause altered ligand affinity, transactivation activity or expression levels of the receptor subsequently influencing the expression of the downstream target genes. Studies of individual susceptibility to toxicants and gene-environment interaction are now emerging as an important component of molecular epidemiology.