Role of the N-terminal region in G protein-coupled receptor functions : negative modulation revealed by 5-HT2B receptor polymorphisms

The putative role of the N-terminal region of rhodopsin-like 7 transmembrane biogenic amine receptors in agonist-induced signaling has not yet been clarified despite recent advances in 7 transmembrane receptor structural biology. Given the existence of N-terminal nonsynonymous polymorphisms (R6G;E42G) within the HTR2B gene in a drug-abusing population, we assessed whether these polymorphisms affect 5-hydroxytryptamine 2B (5-HT2B) receptor in vitro pharmacologic and coupling properties in transfected COS-7 cells. Modification of the 5-HT2B receptor N terminus by the R6G;E42G polymorphisms increases such agonist signaling pathways as inositol phosphate accumulation as assessed by either classic or operational models. The N-terminal R6G;E42G mutations of the 5-HT2B receptor also increase cell proliferation and slow its desensitization kinetics compared with the wild-type receptor, further supporting a role for the N terminus in transduction efficacy. Furthermore, by coexpressing a tethered wild-type 5-HT2B receptor N terminus with a 5-HT2B receptor bearing a N-terminal deletion, we were able to restore original coupling. This reversion to normal activity of a truncated 5-HT2B receptor by coexpression of the membrane-tethered wild-type 5-HT2B receptor N terminus was not observed using a membrane-tethered 5-HT2B receptor R6G;E42G N terminus. These data suggest that the N terminus exerts a negative control over basal as well as agonist-stimulated receptor activity that is lost in the R6G;E42G mutant. Our findings reveal a new and unanticipated role of the 5-HT2B receptor N terminus as a negative modulator, affecting both constitutive and agonist-stimulated activity. Moreover, our data caution against excluding the N terminus and extracellular loops in structural studies of this 7 transmembrane receptor family

Knowledge Transfer in Transnational Programmes : Opportunities and Challenges for the Pacific Region

The globalised world: The current higher education community The last decade has seen rapid changes in the landscape of higher education (HE) throughout the world, largely as a product of globalisation. A major effect has been to propel the interconnectedness between nations and people across the globe (Scholte, 2005). The use of information and communication technology (ICT) has diminished the distance between countries. The world’s economies are becoming more integrated and interrelated through neoliberal economic policies, free trade agreements and open access of goods and services beyond national borders, policies promulgated by organisations such as the World Trade Organization and The World Bank (Marginson & Ordorika, 2011; Mok, 2011). As a consequence, universities are operating at global, national and local levels simultaneously. In the Pacific region, new universities are emerging. For example, Fiji now has one regional and two national universities; Samoa has a national university and Solomon Islands has an institute of higher education. These new players add to regional competition as they open opportunities for global partnerships and transnational programmes. Thus, participating at these multiple levels is inevitable, and no university is immune to these changes (Marginson, Kaur & Sawir, 2011a). Universities are now part of the global HE community that cannot be confined within a nation’s borders. Transitional HE programmes are perhaps one of the most evident demonstrations of the interconnectedness of universities across countries in this global era.

Amanda Gearing Queensland Flood Collection 2011-2012

A collection of oral history recordings, photographs, hand drawn maps, videos and speech notes relating to the 2011 Queensland floods and the major flood event that occurred in Toowoomba and the Lockyer Valley region on 10 January 2011: a flash flood (described as an 'inland tsunami') which devastatingly took 21 human lives. The collection, amassed by Toowoomba-based journalist Amanda Gearing for her Master of Arts degree, includes 86 oral history recordings of flood survivors and rescuers in Spring Bluff, Murphys Creek, Toowoomba, Withcott, Postmans Ridge, Helidon, Carpendale and Grantham as well as digital photographs and videos taken by a number of those interviewed including those taken by Amanda Gearing and other locals. The interviews are very personal and powerful recollections of the experience of the flood event. Some recall feelings of fear and despair and tell of trauma and loss which continues well after the flood event. All are stories of resilience and hope, of rebuilding lives, of lessons learnt, and recommendations in order to avoid the same devastating results in future disasters.

Fine-mapping the HOXB region detects common variants tagging a rare coding allele : evidence for synthetic association in prostate cancer

The HOXB13 gene has been implicated in prostate cancer (PrCa) susceptibility. We performed a high resolution fine-mapping analysis to comprehensively evaluate the association between common genetic variation across the HOXB genetic locus at 17q21 and PrCa risk. This involved genotyping 700 SNPs using a custom Illumina iSelect array (iCOGS) followed by imputation of 3195 SNPs in 20,440 PrCa cases and 21,469 controls in The PRACTICAL consortium. We identified a cluster of highly correlated common variants situated within or closely upstream of HOXB13 that were significantly associated with PrCa risk, described by rs117576373 (OR 1.30, P = 2.62×10(-14)). Additional genotyping, conditional regression and haplotype analyses indicated that the newly identified common variants tag a rare, partially correlated coding variant in the HOXB13 gene (G84E, rs138213197), which has been identified recently as a moderate penetrance PrCa susceptibility allele. The potential for GWAS associations detected through common SNPs to be driven by rare causal variants with higher relative risks has long been proposed; however, to our knowledge this is the first experimental evidence for this phenomenon of synthetic association contributing to cancer susceptibility.

Genetic divergence and echolocation call frequency in cryptic species of Hipposideros larvatus s.l. (Chiroptera : Hipposideridae) from the Indo-Malayan region

The intermediate leaf-nosed bat (Hipposideros larvatus) is a medium-sized bat distributed throughout the Indo-Malay region. In north-east India, bats identified as H. larvatus captured at a single cave emitted echolocation calls with a bimodal distribution of peak frequencies, around either 85 kHz or 98 kHz. Individuals echolocating at 85 kHz had larger ears and longer forearms than those echolocating at 98 kHz, although no differences were detected in either wing morphology or diet, suggesting limited resource partitioning. A comparison of mitochondrial control region haplotypes of the two phonic types with individuals sampled from across the Indo-Malay range supports the hypothesis that, in India, two cryptic species are present. The Indian 98-kHz phonic bats formed a monophyletic clade with bats from all other regional populations sampled, to the exclusion of the Indian 85-kHz bats. In India, the two forms showed 12–13% sequence divergence and we propose that the name Hipposideros khasiana for bats of the 85-kHz phonic type. Bats of the 98-kHz phonic type formed a monophyletic group with bats from Myanmar, and corresponded to Hipposideros grandis, which is suggested to be a species distinct from Hipposideros larvatus. Differences in echolocation call frequency among populations did not reflect phylogenetic relationships, indicating that call frequency is a poor indicator of evolutionary history. Instead, divergence in call frequency probably occurs in allopatry, possibly augmented by character displacement on secondary contact to facilitate intraspecific communication.

Heat maps for aggregating bioacoustic annotations

In our large library of annotated environmental recordings of animal vocalizations, searching annotations by label can return thousands of results. We propose a heat map of aggregated annotation time and frequency bounds, maintaining the shape of the annotations as they appear on the spectrogram. This compactly displays the distribution of annotation bounds for the user's query, and allows them to easily identify unusual annotations. Key to this is allowing zero values on the map to be differentiated from areas where there are single annotations.

A deformable Brodmann area atlas

Functional MRI studies commonly refer to activation patterns as being localized in specific Brodmann areas, referring to Brodmann’s divisions of the human cortex based on cytoarchitectonic boundaries [3]. Typically, Brodmann areas that match regions in the group averaged functional maps are estimated by eye, leading to inaccurate parcellations and significant error. To avoid this limitation, we developed a method using high-dimensional nonlinear registration to project the Brodmann areas onto individual 3D co-registered structural and functional MRI datasets, using an elastic deformation vector field in the cortical parameter space. Based on a sulcal pattern matching approach [11], an N=27 scan single subject atlas (the Colin Holmes atlas [15]) with associated Brodmann areas labeled on its surface, was deformed to match 3D cortical surface models generated from individual subjects’ structural MRIs (sMRIs). The deformed Brodmann areas were used to quantify and localize functional MRI (fMRI) BOLD activation during the performance of the Tower of London task [7].

Functional brain maps of Tower of London performance : a positron emission tomography and functional magnetic resonance imaging study

Regional cerebral blood flow (rCBF) and blood oxygenation level-dependent (BOLD) contrasts represent different physiological measures of brain activation. The present study aimed to compare two functional brain imaging techniques (functional magnetic resonance imaging versus [15O] positron emission tomography) when using Tower of London (TOL) problems as the activation task. A categorical analysis (task versus baseline) revealed a significant BOLD increase bilaterally for the dorsolateral prefrontal and inferior parietal cortex and for the cerebellum. A parametric haemodynamic response model (or regression analysis) confirmed a task-difficulty-dependent increase of BOLD and rCBF for the cerebellum and the left dorsolateral prefrontal cortex. In line with previous studies, a task-difficulty-dependent increase of left-hemispheric rCBF was also detected for the premotor cortex, cingulate, precuneus, and globus pallidus. These results imply consistency across the two neuroimaging modalities, particularly for the assessment of prefrontal brain function when using a parametric TOL adaptation.

Integrating field survey data with satellite image data to improve shallow water seagrass maps : the role of AUV and snorkeller surveys

Repeatable and accurate seagrass mapping is required for understanding seagrass ecology and supporting management decisions. For shallow (< 5 m) seagrass habitats, these maps can be created by integrating high spatial resolution imagery with field survey data. Field survey data for seagrass is often collected via snorkelling or diving. However, these methods are limited by environmental and safety considerations. Autonomous Underwater Vehicles (AUVs) are used increasingly to collect field data for habitat mapping, albeit mostly in deeper waters (>20 m). Here we demonstrate and evaluate the use and potential advantages of AUV field data collection for calibration and validation of seagrass habitat mapping of shallow waters (< 5 m), from multispectral satellite imagery. The study was conducted in the seagrass habitats of the Eastern Banks (142 km2), Moreton Bay, Australia. In the field, georeferenced photos of the seagrass were collected along transects via snorkelling or an AUV. Photos from both collection methods were analysed manually for seagrass species composition and then used as calibration and validation data to map seagrass using an established semi-automated object based mapping routine. A comparison of the relative advantages and disadvantages of AUV and snorkeller collected field data sets and their influence on the mapping routine was conducted. AUV data collection was more consistent, repeatable and safer in comparison to snorkeller transects. Inclusion of deeper water AUV data resulted in mapping of a larger extent of seagrass (~7 km2, 5 % of study area) in the deeper waters of the site. Although overall map accuracies did not differ considerably, inclusion of the AUV data from deeper water transects corrected errors in seagrass mapped at depths to 5 m, but where the bottom is visible on satellite imagery. Our results demonstrate that further development of AUV technology is justified for the monitoring of seagrass habitats in ongoing management programs.

Subtropical values and principles of subtropical design for the South East Queensland region : a report for the Office of Urban Management Queensland Government

The Office of Urban Management recognises that the values which characterise the SEQ region as 'subtropical' are important determinants of form in urban and regional planning. Subtropical values are those qualities on which our regional identity depends. A built environment which responds positively to these values is a critical ingredient for achieving a desirable future for the region. The Centre for Subtropical Design has undertaken this study to identify the particular set of values which characterises SEQ, and to translate theses values into design principals that will maintain and reinforce the value set. The principles not only apply to the overall balance between the natural environment and the built environment, but can be applied by local government authorities to guide local planning schemes and help shape specific built for outcomes.

The future of outsourcing in the Asia-Pacific region: Implications for research and practice—panel report from PACIS 2014

This paper summarizes a panel discussion held at the 18th Pacific Asia Conference on Information Systems (PACIS) in Chengdu, China, 2014, with the same title. The panel discussed the future of outsourcing in the Asia-Pacific region (specifically the importance of outsourcing, new trends, and issues in outsourcing). This paper provides directions for future research that surpasses regional specificity (i.e., the Asia-Pacific region), and contributes to research interests on outsourcing in general.

A Raman and infrared spectroscopic study of the sulphate mineral aluminite Al2(SO4)(OH)4·7H2O

The mineral aluminite has been studied using a number of techniques, including scanning electron microscopy (SEM) with energy dispersive spectroscopy (EDX) and Raman and infrared spectroscopy. Raman spectroscopy identifies multiple sulphate symmetric stretching modes in line with the three sulphate crystallographically different sites. Raman spectroscopy also identifies a low intensity band at 1069 cm−1 which may be attributed to a carbonate symmetric stretching mode, indicating the presence of thaumasite. The observation of multiple bands in this ν4 spectral region offers evidence for the reduction in symmetry of the sulphate anion from Td to C2v or even lower symmetry. The Raman band at 3588 cm−1 is assigned to the OH unit stretching vibration and the broad feature at around 3439 cm−1 to water stretching bands. Water stretching vibrations are observed at 3157, 3294, 3378 and 3439 cm−1. Vibrational spectroscopy enables an assessment of the molecular structure of aluminite to be made.

Anti-tumour effects of antibodies targeting the extracellular cysteine-rich region of the receptor tyrosine kinase EphB4

EphB4 is a membrane-bound receptor tyrosine kinase (RTK) commonly over-produced by many epithelial cancers but with low to no expression in most normal adult tissues. EphB4 over-production promotes ligand-independent signaling pathways that increase cancer cell viability and stimulate migration and invasion. Several studies have shown that normal ligand-dependent signaling is tumour suppressive and therefore novel therapeutics which block the tumour promoting ligand-independent signaling and/or stimulate tumour suppressive ligand-dependent signaling will find application in the treatment of cancer. An EphB4-specific polyclonal antibody, targeting a region of 200 amino acids in the extracellular portion of EphB4, showed potent in vitro anti-cancer effects measured by an increase in apoptosis and a decrease in anchorage independent growth. Peptide exclusion was used to identify the epitope targeted by this antibody within the cysteine-rich region of the EphB4 protein, a sequence defined as a potential ligand interacting interface. Addition of antibody to cancer cells resulted in phosphorylation and subsequent degradation of the EphB4 protein, suggesting a mechanism that is ligand mimetic and tumour suppressive. A monoclonal antibody which specifically targets this identified extracellular epitope of EphB4 significantly reduced breast cancer xenograft growth in vivo confirming that EphB4 is a useful target for ligand-mimicking antibody-based anti-cancer therapies.