DRD2 C957T and TaqIA genotyping reveals gender effects and unique low-risk and high-risk genotypes in alcohol dependence

AIMS: As recent conflicting reports describe a genetic association between both the C- and the T-alleles of the dopamine D2 receptor (DRD2) C957T polymorphism (rs6277) in alcohol-dependent subjects, our aim was to examine this polymorphism and TaqIA (rs1800497) in Australian alcohol-dependent subjects. METHODS: The C957T polymorphism was genotyped in 228 patients with alcohol dependence (72 females and 156 males) and 228 healthy controls. RESULTS: The C-allele and C/C genotype of C957T was associated with alcohol dependence, whereas the TaqIA polymorphism was not. When analysed separately for C957T, males showed an even stronger association with the C-allele and females showed no association. The C957T and TaqIA haplotyping revealed a strong association with alcohol dependence and a double-genotype analysis (combining C957T and TaqIA genotypes) revealed that the relative risk of different genotypes varied by up to 27-fold with the TT/A1A2 having an 8.5-fold lower risk of alcohol dependence than other genotypes. CONCLUSION: Decreased DRD2 binding associated with the C-allele of the DRD2 C957T polymorphism is likely to be important in the underlying pathophysiology of at least some forms of alcohol dependence, and this effect appears to be limited to males only.

A mitochondrial genome phylogeny of termites (Blattodea: Termitoidae) : robust support for interfamilial relationships and molecular synapomorphies define major clades

Despite their ecological significance as decomposers and their evolutionary significance as the most speciose eusocial insect group outside the Hymenoptera, termite (Blattodea: Termitoidae or Isoptera) evolutionary relationships have yet to be well resolved. Previous morphological and molecular analyses strongly conflict at the family level and are marked by poor support for backbone nodes. A mitochondrial (mt) genome phylogeny of termites was produced to test relationships between the recognised termite families, improve nodal support and test the phylogenetic utility of rare genomic changes found in the termite mt genome. Complete mt genomes were sequenced for 7 of the 9 extant termite families with additional representatives of each of the two most speciose families Rhinotermitidae (3 of 7 subfamilies) and Termitidae (3 of 8 subfamilies). The mt genome of the well supported sister group of termites, the subsocial cockroach Cryptocercus, was also sequenced. A highly supported tree of termite relationships was produced by all analytical methods and data treatment approaches, however the relationship of the termites + Cryptocercus clade to other cockroach lineages was highly affected by the strong nucleotide compositional bias found in termites relative to other dictyopterans. The phylogeny supports previously proposed suprafamilial termite lineages, the Euisoptera and Neoisoptera, a later derived Kalotermitidae as sister group of the Neoisoptera and a monophyletic clade of dampwood (Stolotermitidae, Archotermopsidae) and harvester termites (Hodotermitidae). In contrast to previous termite phylogenetic studies, nodal supports were very high for family-level relationships within termites. Two rare genomic changes in the mt genome control region were found to be molecular synapomorphies for major clades. An elongated stem-loop structure defined the clade Polyphagidae + (Cryptocercus + termites), and a further series of compensatory base changes in this stem loop is synapomorphic for the Neoisoptera. The complicated repeat structures first identified in Reticulitermes, composed of short (A-type) and long (B-type repeats) defines the clade Heterotermitinae + Termitidae, while the secondary loss of A-type repeats is synapomorphic for the non-macrotermitine Termitidae.

Anthropogenic landscape change promotes asymmetric dispersal and limits regional patch occupancy in a spatially structured bird population

1. Local extinctions in habitat patches and asymmetric dispersal between patches are key processes structuring animal populations in heterogeneous environments. Effective landscape conservation requires an understanding of how habitat loss and fragmentation influence demographic processes within populations and movement between populations. 2. We used patch occupancy surveys and molecular data for a rainforest bird, the logrunner (Orthonyx temminckii), to determine (i) the effects of landscape change and patch structure on local extinction; (ii) the asymmetry of emigration and immigration rates; (iii) the relative influence of local and between-population landscapes on asymmetric emigration and immigration; and (iv) the relative contributions of habitat loss and habitat fragmentation to asymmetric emigration and immigration. 3. Whether or not a patch was occupied by logrunners was primarily determined by the isolation of that patch. After controlling for patch isolation, patch occupancy declined in landscapes experiencing high levels of rainforest loss over the last 100 years. Habitat loss and fragmentation over the last century was more important than the current pattern of patch isolation alone, which suggested that immigration from neighbouring patches was unable to prevent local extinction in highly modified landscapes. 4. We discovered that dispersal between logrunner populations is highly asymmetric. Emigration rates were 39% lower when local landscapes were fragmented, but emigration was not limited by the structure of the between-population landscapes. In contrast, immigration was 37% greater when local landscapes were fragmented and was lower when the between-population landscapes were fragmented. Rainforest fragmentation influenced asymmetric dispersal to a greater extent than did rainforest loss, and a 60% reduction in mean patch area was capable of switching a population from being a net exporter to a net importer of dispersing logrunners. 5. The synergistic effects of landscape change on species occurrence and asymmetric dispersal have important implications for conservation. Conservation measures that maintain large patch sizes in the landscape may promote asymmetric dispersal from intact to fragmented landscapes and allow rainforest bird populations to persist in fragmented and degraded landscapes. These sink populations could form the kernel of source populations given sufficient habitat restoration. However, the success of this rescue effect will depend on the quality of the between-population landscapes.

Studies on the surface properties of biodegradable polymer carriers in respiratory delivery of drug from Dry Powder Inhaler formulations

Dry Powder Inhaler (DPI) technology has a significant impact in the treatment of various respiratory disorders. DPI formulations consist of a micronized drug (<5ìm) blended with an inert coarse carrier, for which lactose is widely used to date. DPIs are one of the inhalation devices which are used to target the delivery of drugs to the lungs. Drug delivery via DPI formulations is influenced by the physico-chemical characteristics of lactose particles such as size, shape, surface roughness and adhesional forces. Commercially available DPI formulations, which utilise lactose as the carrier, are not efficient in delivering drug to the lungs. The reasons for this are the surface morphology, adhesional properties and surface roughness of lactose. Despite several attempts to modify lactose, the maximum efficient drug delivery to the lungs remains limited; hence, exploring suitable alternative carriers for DPIs is of paramount importance. Therefore, the objective of the project was to study the performance of spherical polymer microparticles as drug carriers and the factors controlling their performance. This study aimed to use biodegradable polymer microspheres as alternative carriers to lactose in DPIs for achieving efficient drug delivery into the lungs. This project focused on fabricating biodegradable polymer microparticles with reproducible surface morphology and particle shape. The surface characteristics of polymeric carriers and the adhesional forces between the drug and carrier particles were investigated in order to gain a better understanding of their influence on drug dispersion. For this purpose, two biodegradable polymers- polycaprolactone (PCL) and poly (DL-lactide-co-glycolide) (PLGA) were used as the carriers to deliver the anti-asthmatic drug - Salbutamol Sulphate (SS). The first study conducted for this dissertation was the aerosolization of SS from mixtures of SS and PCL or PLGA microparticles. The microparticles were fabricated using an emulsion technique and were characterized by laser diffraction for particle size analysis, Scanning Electron Microscopy (SEM) for surface morphology and X-ray Photoelectron Spectroscopy (XPS) to obtain surface elemental composition. The dispersion of the drug from the DPI formulations was determined by using a Twin Stage Impinger (TSI). The Fine particle Fraction (FPF) of SS from powder mixtures was analyzed by High Performance Liquid Chromatography (HPLC). It was found that the drug did not detach from the surface of PCL microspheres. To overcome this, the microspheres were coated with anti-adherent agents such as magnesium stearate and leucine to improve the dispersion of the drug from the carrier surfaces. It was found that coating the PCL microspheres helped in significantly improving the FPF of SS from the PCL surface. These results were in contrast to the PLGA microspheres which readily allowed detachment of the SS from their surface. However, coating PLGA microspheres with antiadherent agents did not further improve the detachment of the drug from the surface. Thus, the first part of the study demonstrated that the surface-coated PCL microspheres and PLGA microspheres can be potential alternatives to lactose as carriers in DPI formulations; however, there was no significant improvement in the FPF of the drug. The second part of the research studied the influence of the size of the microspheres on the FPF of the drug. For this purpose, four different sizes (25 ìm, 48 ìm, 100 ìm and 150 ìm) of the PCL and PLGA microspheres were fabricated and characterized. The dispersion of the drug from microspheres of different sizes was determined. It was found that as the size of the carrier increased there was a significant increase in the FPF of SS. This study suggested that the size of the carrier plays an important role in the dispersion of the drug from the carrier surface. Subsequent experiments in the third part of the dissertation studied the surface properties of the polymeric carrier. The adhesion forces existing between the drug particle and the polymer surfaces, and the surface roughness of the carriers were quantified using Atomic Force Microscopy (AFM). A direct correlation between adhesion forces and dispersion of the drug from the carrier surface was observed suggesting that adhesion forces play an important role in determining the detachment potential of the drug from the carrier surface. However, no direct relationship between the surface roughness of the PCL or PLGA carrier and the FPF of the drug was observed. In conclusion, the body of work presented in this dissertation demonstrated the potential of coated PCL microspheres and PLGA microspheres to be used in DPI formulations as an alternative carrier to sugar based carriers. The study also emphasized the role of the size of the carrier particles and the forces of interaction prevailing between the drug and the carrier particle surface on the aerosolization performances of the drug.

Insights into historical drainage evolution based on the phylogeography of the chevron snakehead fish (Channa striata) in the Mekong Basin

1. The phylogeography of freshwater taxa is often integrally linked with landscape changes such as drainage re-alignments that may present the only avenue for historical dispersal for these taxa. Classical models of gene flow do not account for landscape changes and so are of little use in predicting phylogeography in geologically young freshwater landscapes. When the history of drainage formation is unknown, phylogeographical predictions can be based on current freshwater landscape structure, proposed historical drainage geomorphology, or from phylogeographical patterns of co-distributed taxa. 2. This study describes the population structure of a sedentary freshwater fish, the chevron snakehead (Channa striata), across two river drainages on the Indochinese Peninsula. The phylogeographical pattern recovered for C. striata was tested against seven hypotheses based on contemporary landscape structure, proposed history and phylogeographical patterns of codistributed taxa. 3. Consistent with the species ecology, analysis of mitochondrial and microsatellite loci revealed very high differentiation among all sampled sites. A strong signature of historical population subdivision was also revealed within the contemporary Mekong River Basin (MRB). Of the seven phylogeographical hypotheses tested, patterns of co-distributed taxa proved to be the most adequate for describing the phylogeography of C. striata. 4. Results shed new light on SE Asian drainage evolution, indicating that the Middle MRB probably evolved via amalgamation of at least three historically independent drainage sections and in particular that the Mekong River section centred around the northern Khorat Plateau in NE Thailand was probably isolated from the greater Mekong for an extensive period of evolutionary time. In contrast, C. striata populations in the Lower MRB do not show a phylogeographical signature of evolution in historically isolated drainage lines, suggesting drainage amalgamation has been less important for river landscape formation in this region.

Serious playground : using Second Life to engage high school students in urban planning

Virtual world platforms such as Second Life have been successfully used in educational contexts to motivate and engage learners. This article reports on an exploratory workshop involving a group of high school students using Second Life for an urban planning project. Young people are traditionally an under-represented demographic when it comes to participating in urban planning and decision making processes. The research team developed activities that combined technology with a constructivist approach to learning. Real world experiences and purposes ensured that the workshop enabled students to see the relevance of their learning. Our design also ensured that play remained an important part of the learning. By conceiving of the workshop as a ‘serious playground’ we investigated the ludic potential of learning in a virtual world.

Analysis of the damping properties of high-transmission-ratio Cycloidal drives

Cycloidal drives are widely used in today’s industries for drives where large reduction ratios are required. Drive-train dynamics plays an important role in their design. This paper presents a new methodology for assessing damping characteristics of Cycloidal drives and compares the natural frequencies obtained from experiments and theoretical/numerical calculations using Fast-Fourier-Transforms.

Delta opioid-receptor function in the dorsal striatum plays a role in high levels of ethanol consumption in rats

Binge-like patterns of excessive drinking during young adulthood increase the propensity for alcohol use disorders (AUDs) later in adult life; however, the mechanisms that drive this are not completely understood. Previous studies showed that the δ-opioid peptide receptor (DOP-R) is dynamically regulated by exposure to ethanol and that the DOP-R plays a role in ethanol-mediated behaviors. The aim of this study was to determine the role of the DOP-R in high ethanol consumption from young adulthood through to late adulthood by measuring DOP-R-mediated [(35)S]GTPγS binding in brain membranes and DOP-R-mediated analgesia using a rat model of high ethanol consumption in Long Evans rats. We show that DOP-R activity in the dorsal striatum and DOP-R-mediated analgesia changes during development, being highest during early adulthood and reduced in late adulthood. Intermittent access to ethanol but not continuous ethanol or water from young adulthood leads to an increase in DOP-R activity in the dorsal striatum and DOP-R-mediated analgesia into late adulthood. Multiple microinfusions of naltrindole into the dorsal striatum or multiple systemic administration of naltrindole reduces ethanol consumption, and following termination of treatment, DOP-R activity in the dorsal striatum is attenuated. These findings suggest that DOP-R activity in the dorsal striatum plays a role in high levels of ethanol consumption and suggest that targeting the DOP-R is an alternative strategy for the treatment of AUDs.

The use of amenities in high density neighbourhoods by older urban Australians residents

Like other major cities, Brisbane (Australia) has adopted policies to increase residential densities to meet the liveability goal of decreasing car dependence. This objective hinges on urban neighbourhoods being amenity-rich spaces, reducing the need for residents to leave their neighbourhood for everyday living. While older people are attracted to urban settings, there has been little empirical evidence linking liveability satisfaction with older people's use of urban neighbourhoods. Using a case study approach employing qualitative (diaries, in-depth interviews) and quantitative (Global Positioning Systems and Geographical Information Systems mapping) methods,this paper explores the effect of the neighbourhood environment and its influence on liveability for older urban people. Reliance on motor vehicles and issues with availability and access to local amenities inhibit local participation for older people. Highlighting these issues furthers our understanding of the landscape planning and design factors that make urban neighbourhoods more liveable for older residents.

Experiences of neighbourhood walkability among older Australians living in high density inner-city areas

Walking as an out-of-home mobility activity is recognised for its contribution to healthy and active ageing. The environment can have a powerful effect on the amount of walking activity undertaken by older people, thereby influencing their capacity to maintain their wellbeing and independence. This paper reports the findings from research examining the experiences of neighbourhood walking for 12 older people from six different inner-city high density suburbs, through analysis of data derived from travel diaries, individual time/space activity maps (created via GPS tracking over a seven-day period and GIS technology), and in-depth interviews. Reliance on motor vehicles, the competing interests of pedestrians and cyclists on shared pathways and problems associated with transit systems, public transport, and pedestrian infrastructure emerged as key barriers to older people venturing out of home on foot. GPS and GIS technology provide new opportunities for furthering understanding of the out-of-home mobility of older populations.

Lateral movements in composite high-rise buildings under seismic action

Daring human nature has already led to the construction of high-rise buildings in naturally challenging geological regions and in worse environments of the world. However; literature review divulges that there is a lag in research of certain generic principles and rules for the prediction of lateral movement in multistorey construction. The present competitive trend orders the best possible used of available construction material and resources. Hence; the mixed used of reinforced concrete with structural steel is gaining prevalence day by day. This paper investigates the effects of Seismic load on composite multistorey building provided with core wall and trusses through FEM modelling. The results showed that increased rigidity corresponds to lower period of vibration and hence higher seismic forces. Since Seismic action is a function of mass and response acceleration, therefore; mass increment generate higher earthquake load and thus cause higher impact base shear and overturning movement. Whereas; wind force depends on building exposed, larger the plan dimension greater is the wind impact. Nonetheless; outriggers trusses noticeably contribute, in improving the serviceability of structure subjected to wind and earthquake forces.

Phenotypic Characterization of Prostate Cancer LNCaP Cells Cultured within a Bioengineered Microenvironment

Biophysical and biochemical properties of the microenvironment regulate cellular responses such as growth, differentiation, morphogenesis and migration in normal and cancer cells. Since two-dimensional (2D) cultures lack the essential characteristics of the native cellular microenvironment, three-dimensional (3D) cultures have been developed to better mimic the natural extracellular matrix. To date, 3D culture systems have relied mostly on collagen and Matrigel™ hydrogels, allowing only limited control over matrix stiffness, proteolytic degradability, and ligand density. In contrast, bioengineered hydrogels allow us to independently tune and systematically investigate the influence of these parameters on cell growth and differentiation. In this study, polyethylene glycol (PEG) hydrogels, functionalized with the Arginine-glycine-aspartic acid (RGD) motifs, common cell-binding motifs in extracellular matrix proteins, and matrix metalloproteinase (MMP) cleavage sites, were characterized regarding their stiffness, diffusive properties, and ability to support growth of androgen-dependent LNCaP prostate cancer cells. We found that the mechanical properties modulated the growth kinetics of LNCaP cells in the PEG hydrogel. At culture periods of 28 days, LNCaP cells underwent morphogenic changes, forming tumor-like structures in 3D culture, with hypoxic and apoptotic cores. We further compared protein and gene expression levels between 3D and 2D cultures upon stimulation with the synthetic androgen R1881. Interestingly, the kinetics of R1881 stimulated androgen receptor (AR) nuclear translocation differed between 2D and 3D cultures when observed by immunofluorescent staining. Furthermore, microarray studies revealed that changes in expression levels of androgen responsive genes upon R1881 treatment differed greatly between 2D and 3D cultures. Taken together, culturing LNCaP cells in the tunable PEG hydrogels reveals differences in the cellular responses to androgen stimulation between the 2D and 3D environments. Therefore, we suggest that the presented 3D culture system represents a powerful tool for high throughput prostate cancer drug testing that recapitulates tumor microenvironment. © 2012 Sieh et al.

The health and cost implications of high body mass index in Australian Defence Force personnel.

BACKGROUND: Frequent illness and injury among workers with high body mass index (BMI) can raise the costs of employee healthcare and reduce workforce maintenance and productivity. These issues are particularly important in vocational settings such as the military, which require good physical health, regular attendance and teamwork to operate efficiently. The purpose of this study was to compare the incidence of injury and illness, absenteeism, productivity, healthcare usage and administrative outcomes among Australian Defence Force personnel with varying BMI. METHODS: Personnel were grouped into cohorts according to the following ranges for (BMI): normal (18.5-24.9 kg/m²; n = 197), overweight (25-29.9 kg/m²; n = 154) and obese (≥30 kg/m²) with restricted body fat (≤28 % for females, ≤24 % for males) (n = 148) and with no restriction on body fat (n = 180). Medical records for each individual were audited retrospectively to record the incidence of injury and illness, absenteeism, productivity, healthcare usage (i.e., consultation with medical specialists, hospital stays, medical investigations, prescriptions) and administrative outcomes (e.g., discharge from service) over one year. These data were then grouped and compared between the cohorts. RESULTS: The prevalence of injury and illness, cost of medical specialist consultations and cost of medical scans were all higher (p <0.05) in both obese cohorts compared with the normal cohort. The estimated productivity losses from restricted work days were also higher (p <0.05) in the obese cohort with no restriction on body fat compared with the normal cohort. Within the obese cohort, the prevalence of injury and illness, healthcare usage and productivity were not significantly greater in the obese cohort with no restriction on body fat compared with the cohort with restricted body fat. The number of restricted work days, the rate of re-classification of Medical Employment Classification and the rate of discharge from service were similar between all four cohorts. CONCLUSIONS: High BMI in the military increases healthcare usage, but does not disrupt workforce maintenance. The greater prevalence of injury and illness, greater healthcare usage and lower productivity in obese Australian Defence Force personnel is not related to higher levels of body fat.

The effect of post-exercise hydrotherapy on subsequent exercise performance and heart rate variability

We investigated the effect of hydrotherapy on time-trial performance and cardiac parasympathetic reactivation during recovery from intense training. On three occasions, 18 well-trained cyclists completed 60 min high-intensity cycling, followed 20 min later by one of three 10-min recovery interventions: passive rest (PAS), cold water immersion (CWI), or contrast water immersion (CWT). The cyclists then rested quietly for 160 min with R-R intervals and perceptions of recovery recorded every 30 min. Cardiac parasympathetic activity was evaluated using the natural logarithm of the square root of mean squared differences of successive R-R intervals (ln rMSSD). Finally, the cyclists completed a work-based cycling time trial. Effects were examined using magnitude-based inferences. Differences in time-trial performance between the three trials were trivial. Compared with PAS, general fatigue was very likely lower for CWI (difference [90% confidence limits; -12% (-18; -5)]) and CWT [-11% (-19; -2)]. Leg soreness was almost certainly lower following CWI [-22% (-30; -14)] and CWT [-27% (-37; -15)]. The change in mean ln rMSSD following the recovery interventions (ln rMSSD(Post-interv)) was almost certainly higher following CWI [16.0% (10.4; 23.2)] and very likely higher following CWT [12.5% (5.5; 20.0)] compared with PAS, and possibly higher following CWI [3.7% (-0.9; 8.4)] compared with CWT. The correlations between performance, ln rMSSD(Post-interv) and perceptions of recovery were unclear. A moderate correlation was observed between ln rMSSD(Post-interv) and leg soreness [r = -0.50 (-0.66; -0.29)]. Although the effects of CWI and CWT on performance were trivial, the beneficial effects on perceptions of recovery support the use of these recovery strategies.

Do high levels of physical activity favor favorable cardiovascular risk factors regardless of sleep?

This study suggests that physical activity is a more important lifestyle modification than sleep to improve cardiovascular risk factors in postmenopausal women; however both lifestyle modifications, including, ensuring sufficient sleep quality and duration and increasing physical activity should be strongly encouraged by menopause practitioners in postmenopausal women care.