Investigation of the [−/A]8 and C1236T genetic variations within the human toll-like receptor 3 gene for association with multiple sclerosis

Multiple sclerosis (MS) is a serious cause of neurological disability among young adults. The clinical course remains difficult to predict, and the pathogenesis of the disease is still modestly understood. Autoimmunity is thought to be a key aspect of the disease, with autoreactive T cells thought to mediate central nervous system (CNS) inflammation to some extent. Toll-like receptors are known to mediate cellular recognition of pathogens by way of patterns of molecular presentation. Toll-like receptor 3 is coded by the gene TLR3 and is recognized as an important factor in virus recognition and is known to be involved in the expression of neuroprotective mediators. We set out to investigate two variations within the TLR3 gene, an 8 bp insertion-deletion \[-/A](8) and a single base-pair variation C1236T, in subjects with MS and matched healthy controls to determine whether significant differences exist in these markers in an Australian population. We used capillary gel electrophoresis and TaqMan genotyping assay techniques to resolve genotypes for each marker, respectively. Our work found no significant difference between frequencies for TLR3 \[-/A](8) by genotype (chi(2)=1.03, p=0.60) or allele (chi(2)=1.09, p=0.30). Similarly, we found no evidence for the association of TLR3 C1236T by genotype (chi(2)=0.35, p=0.84) or allele frequency (chi(2)=0.31, p=0.58). This work reveals no evidence to suggest that these markers are associated with MS in the tested population. Although the role of TLR3 and the wider toll-like receptor family remain significant in neurological and CNS inflammatory disorders, our current work does not support a role for the two tested variants in this gene with regard to MS susceptibility.

Legacy of mutiny on the Bounty : founder effect and admixture on Norfolk Island

The population of Norfolk Island, located off the eastern coast of Australia, possesses an unusual and fascinating history. Most present-day islanders are related to a small number of the 'Bounty' mutineer founders. These founders consisted of Caucasian males and Polynesian females and led to an admixed present-day population. By examining a single large pedigree of 5742 individuals, spanning >200 years, we analyzed the influence of admixture and founder effect on various cardiovascular disease (CVD)-related traits. On account of the relative isolation of the population, on average one-third of the genomes of present-day islanders (single large pedigree individuals) is derived from 17 initial founders. The proportion of Polynesian ancestry in the present-day individuals was found to significantly influence total triglycerides, body mass index, systolic blood pressure and diastolic blood pressure. For various cholesterol traits, the influence of ancestry was less marked but overall the direction of effect for all CVD-related traits was consistent with Polynesian ancestry conferring greater CVD risk. Marker-derived homozygosity was computed and agreed with measures of inbreeding derived from pedigree information. Founder effect (inbreeding and marker-derived homozygosity) significantly influenced height. In conclusion, both founder effect and extreme admixture have substantially influenced the genetic architecture of a variety of CVD-related traits in this population.

An investigation of the C77G and C772T variations within the human protein tyrosine phosphatase receptor type C gene for association with multiple sclerosis in an Australian population

Multiple sclerosis (MS) is a common cause of neurological disability in young adults. The disease generally manifests in early to middle adulthood and causes various neurological deficits. Autoreactive T lymphocytes and their associated antigens have long been presumed important features of MS pathogenesis. The Protein tyrosine phosphatase receptor type C gene (PTPRC) encodes the T-cell receptor CD45. Variations within PTPRC have been previously associated with diseases of autoimmune origin such as type 1 diabetes mellitus and Graves' disease. We set out to investigate two variants within the PTPRC gene, C77G and C772T in subjects with MS and matched healthy controls to determine whether significant differences exist in these markers in an Australian population. We employed high resolution melt analysis (HRM) and restriction length polymorphism (RFLP) techniques to determine genotypic and allelic frequencies. Our study found no significant difference between frequencies for PTPRC C77G by either genotype (Χ2 = 0.65, P = 0.72) or allele (Χ2 = 0.48, P = 0.49). Similarly, we did not find evidence to suggest an association between PTPRC C772T by genotype (Χ2 = 1.06, P = 0.59) or allele (Χ2 = 0.20, P = 0.66). Linkage disequilibrium (LD) analysis showed strong linkage disequilibrium between the two tested markers (D' = 0.9970, SD = 0.0385). This study reveals no evidence to suggest that these markers are associated with MS in the tested Australian Caucasian population. Although the PTPRC gene has a significant role in regulating CD4+ and CD8+ autoreactive T-cells, interferon-beta responsiveness, and potentially other important processes, our study does not support a role for the two tested variants of this gene in MS susceptibility in the Australian population.

SHOX gene is expressed in vertebral body growth plates in idiopathic and congenital scoliosis : implications for the etiology of scoliosis in Turner Syndrome

Reduced SHOX gene expression has been demonstrated to be associated with all skeletal abnormalities in Turner syndrome, other than scoliosis (and kyphosis). There is evidence to suggest that Turner syndrome scoliosis is clinically and radiologically similar to idiopathic scoliosis, although the phenotypes are dissimilar. This pilot gene expression study used relative quantitative real-time PCR (qRT-PCR) of the SHOX (short stature on X) gene to determine whether it is expressed in vertebral body growth plates in idiopathic and congenital scoliosis. After vertebral growth plate dissection, tissue was examined histologically and RNA was extracted and its integrity was assessed using a Bio-Spec Mini, NanoDrop ND-1000 spectrophotometer and standard denaturing gel electrophoresis. Following cDNA synthesis, gene-specific optimization in a Corbett RotorGene 6000 real-time cycler was followed by qRT-PCR of vertebral tissue. Histological examination of vertebral samples confirmed that only growth plate was analyzed for gene expression. Cycling and melt curves were resolved in triplicate for all samples. SHOX abundance was demonstrated in congenital and idiopathic scoliosis vertebral body growth plates. SHOX expression was 11-fold greater in idiopathic compared to congenital (n = 3) scoliosis (p = 0.027). This study confirmed that SHOX was expressed in vertebral body growth plates, which implies that its expression may also be associated with the scoliosis (and kyphosis) of Turner syndrome. SHOX expression is reduced in Turner syndrome (short stature). In this study, increased SHOX expression was demonstrated in idiopathic scoliosis (tall stature) and congenital scoliosis.

Understanding the genetic basis of invasiveness

Invasive species provide excellent study systems to evaluate the ecological and evolutionary processes that contribute to the colonization of novel environments. While the ecological processes that contribute to the successful establishment of invasive plants have been studied in detail, investigation of the evolutionary processes involved in successful invasions has only recently received attention. In particular, studies investigating the genomic and gene expression differences between native and introduced populations of invasive species are just beginning and are required if we are to understand how plants become invasive. In the current issue of Molecular Ecology, Hodgins et al. () tackle this unresolved question, by examining gene expression differences between native and introduced populations of annual ragweed, Ambrosia artemisiifolia. The study identifies a number of potential candidate genes based on gene expression differences that may be responsible for the success of annual ragweed in its introduced range. Furthermore, genes involved in stress response are over-represented in the differentially expressed gene set. Future experiments could use functional studies to test whether changes in gene expression at these candidate genes do in fact underlie changes in growth characteristics and reproductive output observed in this and other invasive species.

Allelic variation investigation of the estrogen receptor within an Australian multiple sclerosis population

Multiple Sclerosis (MS) is a central nervous system (CNS) chronic inflammatory demyelinating disease leading to various neurological disabilities. The disorder is more prevalent for women with a ratio of 3:2 female to male. Objectives: To investigate variation within the estrogen receptor 1 (ESR1) polymorphism gene in an Australian MS case-control population using two intragenic restriction fragment length polymorphisms; the G594A located in exon 8 detected with the BtgI restriction enzyme and T938C located in intron 1, detected with PvuII. One hundred and ten Australian MS patients were studied, with patients classified clinically as Relapsing Remitting MS (RR-MS), Secondary Progressive MS (SP-MS) or Primary Progressive MS (PP-MS). Also, 110 age, sex and ethnicity matched controls were investigated as a comparative group. No significant difference in the allelic distribution frequency was found between the case and control groups for the ESR1 PvuII (P = 0.50) and Btg1 (P = 0.45) marker. Our results do not support a role for these two ESR1 markers in multiple sclerosis susceptibility, however other markers within ESR1 should not be excluded for potential involvement in the disorder.

Variation in the vitamin D receptor gene is associated with multiple sclerosis in an Australian population

Multiple Sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system (CNS) resulting in accumulating neurological disability. The disorder is more prevalent at higher latitudes. To investigate VDR gene variation using three intragenic restriction fragment length polymorphisms (Apa I, Taq I and Fok I) in an Australian MS case-control population. One hundred and four Australian MS patients were studied with patients classified clinically as Relapsing Remitting MS (RR-MS), Secondary Progressive MS (SP-MS) or Primary Progressive MS (PP-MS). Also, 104 age-, sex-, and ethnicity-matched controls were investigated as a comparative group. Our results show a significant difference of genotype distribution frequency between the case and control groups for the functional exon 9 VDR marker Taq I (p(Gen) = 0.016) and interestingly, a stronger difference for the allelic frequency (p(All) = 0.0072). The Apa I alleles were also found to be associated with MS (p(All) = 0.04) but genotype frequencies were not significantly different from controls (p(Gen) = 0.1). The Taq and Apa variants are in very strong and significant linkage disequilibrium (D' = 0.96, P < 0.0001). The genotypic associations are strongest for the progressive forms of MS (SP-MS and PP-MS). Our results support a role for the VDR gene increasing the risk of developing multiple sclerosis, particularly the progressive clinical subtypes of MS.

Investigation of the CACNA1A gene as a candidate for typical migraine susceptibility

Typical migraine is a complex neurological disorder comprised of two main subtypes: migraine with (MA) and without aura (MO). The disease etiology is still unclear, but family studies provide strong evidence that defective genes play an important role. Familial hemiplegic migraine (FHM) is a very rare and severe subtype of MA. It has been proposed that FHM and MA may have a similar genetic etiology. Therefore, genetic studies on FHM provide a useful model for investigating the more prevalent types of typical migraine. FHM in some families has been shown to be caused by mutations in a brain-specific P/Q-type calcium channel alpha1 subunit gene (CACNA1A) on chromosome 19p13. There has also been a report of a CACNA1A mutation being associated with MA in a patient from a family with predominant FHM. We have previously demonstrated suggestive linkage of typical migraine in a large Australian family to the FHM region on chromosome 19p13. These findings suggest that CACNA1A may also be implicated in the etiology of typical migraine in this pedigree. To investigate this possibility, we sequenced two patients carrying the critical susceptibility haplotype surrounding CACNA1A. No disease-causing mutations or polymorphisms were revealed in any of the 47 exons screened. To determine whether the CACNA1A gene was implicated in typical migraine susceptibility in the general Caucasian population, we also analyzed 82 independent pedigrees and a large case control group. We did not detect any linkage or association in these groups and conclude that if CACNA1A plays a role in typical migraine, it does not confer a major effect on the disease.

The duration of Chlamydia muridarum genital tract infection and associated chronic pathological changes are reduced in IL-17 knockout mice but protection is not increased further by immunization

IL-17 is believed to be important for protection against extracellular pathogens, where clearance is dependent on neutrophil recruitment and local activation of epithelial cell defences. However, the role of IL-17 in protection against intracellular pathogens such as Chlamydia is less clear. We have compared (i) the course of natural genital tract C. muridarum infection, (ii) the development of oviduct pathology and (iii) the development of vaccine-induced immunity against infection in wild type (WT) BALB/c and IL-17 knockout mice (IL-17-/-) to determine if IL-17-mediated immunity is implicated in the development of infection-induced pathology and/or protection. Both the magnitude and duration of genital infection was significantly reduced in IL-17-/- mice compared to BALB/c. Similarly, hydrosalpinx was also greatly reduced in IL-17-/- mice and this correlated with reduced neutrophil and macrophage infiltration of oviduct tissues. Matrix metalloproteinase (MMP) 9 and MMP2 were increased in WT oviducts compared to IL-17-/- animals at day 7 post-infection. In contrast, oviducts from IL-17-/- mice contained higher MMP9 and MMP2 at day 21. Infection also elicited higher levels of Chlamydia-neutralizing antibody in serum of IL-17-/- mice than WT mice. Following intranasal immunization with C. muridarum Major Outer Membrane Protein (MOMP) and cholera toxin plus CpG adjuvants, significantly higher levels of chlamydial MOMP-specific IgG and IgA were found in serum and vaginal washes of IL-17-/- mice. T cell proliferation and IFNγ production by splenocytes was greater in WT animals following in vitro re-stimulation, however vaccination was only effective at reducing infection in WT, not IL-17-/- mice. Intranasal or transcutaneous immunization protected WT but not IL-17-/- mice against hydrosalpinx development. Our data show that in the absence of IL-17, the severity of C. muridarum genital infection and associated oviduct pathology are significantly attenuated, however neither infection or pathology can be reduced further by vaccination protocols that effectively protect WT mice.

Evidence for allelic association of the dopamine β-hydroxylase gene (DBH) with susceptibility to typical migraine

Migraine is a debilitating neurological disorder characterized by recurrent attacks of severe headache. The disorder is highly prevalent, affecting approximately 12% of Caucasian populations. It is well known that migraine has a strong genetic component, although the type and number of genes involved is not yet clear. However, the calcium channel gene, CACNA1A, on chromosome 19 contains mutations responsible for familial hemiplegic migraine, a rare and severe subtype of migraine. There is also evidence to suggest that serotonin- and dopamine-related genes may be involved in the pathogenesis of migraine. This study employed a linkage and association approach to investigate neurotransmitter-related migraine candidate genes. Polymorphisms within the dopamine beta-hydroxylase (DBH) gene, serotonin transporter gene (SERT), and dopamine receptor gene (DRD2) were tested in 177 unrelated Caucasian migraineurs and 182 control individuals. In addition, an independent sample of 82 families affected with migraine was examined. Unrelated case-control association analysis of a DBH intragenic dinucleotide polymorphism indicated altered allelic distribution between migraine and control groups (L2=16.53, P=0.019). Furthermore, the transmission/disequilibrium test, which was implemented on the family data, also indicated distortion of allele transmission for the same DBH marker (L2=4.44, P=0.035). Together, these results provide evidence for allelic association of the DBH gene with typical migraine susceptibility (Fisher's combined P value=0.006) and indicate that further research into the role of the DBH gene in the etiology of migraine is warranted.

The intervening role of Agreeableness in the relationship between trait emotional intelligence and Machiavellianism : reassessing the potential dark side of EI

Previous research into the potential ‘dark’ side of trait emotional intelligence (EI) has repeatedly demonstrated that trait EI is negatively associated with Machiavellianism. In this study, we reassess the potential dark side of trait EI, by testing whether Agreeableness mediates and/or moderates the relationship between trait EI and Machiavellianism. Hypothesized mediation and moderation effects were tested using a large sample of 884 workers who completed several self-report questionnaires. Results provide support for both hypotheses; Agreeableness was found to mediate and moderate the relationship between trait EI and Machiavellianism. Overall, results indicate that individuals high in trait EI tend to have low levels of Machiavellianism because they generally have a positive nature (i.e. are agreeable) and not because they are emotionally competent per se. Results also indicate that individuals high in ‘perceived emotional competence’ have the potential to be high in Machiavellianism, particularly when they are low in Agreeableness.

A marine reservoir correction for the Houtman-Abrolhos Archipelago, East Indian Ocean, Western Australia

High-precision analysis using accelerator mass spectrometry (AMS) was performed upon known-age Holocene and modern, pre-bomb coral samples to generate a marine reservoir age correction value (ΔR) for the Houtman-Abrolhos Archipelago (28.7°S, 113.8°E) off the Western Australian coast. The mean ΔR value calculated for the Abrolhos Islands, 54 ± 30 yr (1σ) agrees well with regional ΔR values for Leeuwin Current source waters (N-NW Australia-Java) of 60 ± 38. The Abrolhos Islands show little variation with ΔR values of the northwestern and north Australian coast, underlining the dominance of the more equilibrated western Pacific-derived waters of the Leeuwin Current over local upwelling. The Abrolhos Islands ΔR values have remained stable over the last 2896 yr cal BP, being also attributed to the Leeuwin Current and the El Niño Southern Oscillation (ENSO) signal during this period. Expected future trends will be a strengthening of the teleconnection of the Abrolhos Islands to the climatic patterns of the equatorial Pacific via enhanced ENSO and global warming activity strengthening the Leeuwin Current. The possible effect upon the trend of future ΔR values may be to maintain similar values and an increase in stability. However, warming trends of global climate change may cause increasing dissimilarity of ΔR values due to the effects of increasing heat stress upon lower-latitude coral communities.

Sharing the news : Dissemination of links to Australian news sites on Twitter

Social media adoption in Australia, which provides the geographic focus for this chapter, has been rapid and substantial (ABC News, 2010) – possibly because of the considerable dispersal of the Australian population across the continent, as well as the significant distance of the country from many of its closest partner nations. Social media can play an important role in strengthening and maintaining interpersonal and professional relationships in spite of such physical distance; in particular, social media services are now well-recognised as important tools for the dissemination of news across many developed nations. Hermida (2010) and Burns (2010) both speak of Twitter as a medium for “ambient news”, for example: always-on, operating as a steady stream in the background and at the edge of users’ conscious perception. Much as ambient music is designed to do, it comes to the fore when notable events (such as major breaking news) lead to an increase in volume and demand a greater level of attention from users.

Blog research : the 'computational turn' [Blogforschung: Der 'Computational Turn']

ForscherInnen aus Sozial- und Geisteswissenschaften interessieren sich seit nunmehr einem Jahrzehnt für Blogs, Online-Tagebücher und Online-Journale. Auch wenn die Zuwachsrate der Blogosphäre seit der Blütezeit des Bloggens in den 2000ern stagniert, bleiben Blogs doch eines der bedeutendsten Genres der internetgestützten Kommunikation. Tatsächlich ist nach der Massenabwanderung zu Facebook, Twitter und anderen erst in jüngerer Zeit entstandenen Kommunikationsmitteln eine etwas kleinere, aber umso stärker etablierte Blogosphäre von engagierten und eingeschworenen Teilnehmenden übriggeblieben. Blogs werden mittlerweile als Teil einer institutionellen, persönlichen und Gruppen-Kommunikationstrategie akzeptiert. In Stil und Inhalt liegen sie zwischen den statischeren Informationen auf konventionellen Websites und den ständig aktualisierten Facebook- und Twitter-Newsfeeds. Blogs ermöglichen es ihren AutorInnen (und deren KommentatorInnen), bestimmte Themen im Umfang von einigen hundert bis zu einigen tausend Wörtern zu durchdenken, in kürzeren Posts ins Detail zu gehen und ggf. intensiver durchdachte Texte anderswo zu publizieren. Zudem sind sie auch ein sehr flexibles Medium: Bilder, Audio-, Video- sowie andere Materialien können mühelos eingefügt werden - und natürlich auch das grundlegende Instrument des Bloggens: Hyperlinks.

On facilitating regional integration and economic development with collaborative technologies in the South Pacific

The current global economic instability and the vulnerability of small island nations are providing the impetus for greater integration between the countries of the South Pacific region. This exercise is critical for their survival in today’s turbulent economic environment. Past efforts of regional integration in the South Pacific have not been very successful. Reasons attributed to this outcome include issues related to damage of sovereignty, and lack of a shared integration infrastructure. Today, the IT resources with collaborative capacities provide the opportunity to develop a shared IT infrastructure to facilitate integration in the South Pacific. In an attempt to develop a model of regional integration with an IT-backed infrastructure, we identify and report on the antecedents of the current stage of regional integration, and the stakeholders’ perceived benefits of an IT resources backed regional integration in the South Pacific. Employing a case study based approach, the study finds that while most stakeholders were positive about the potential of IT-backed regional integration, significant challenges exist that hinder the realisation of this model. The study finds that facilitating IT-backed regional integration requires enabling IT infrastructure, equitable IT development in the region, greater awareness on the potential of the modern IT resources, market liberalisation of the information and telecommunications sector and greater political support for IT initiatives.