A transcriptome resource for the koala (Phascolarctos cinereus) : insights into koala retrovirus transcription and sequence diversity

Background The koala, Phascolarctos cinereus, is a biologically unique and evolutionarily distinct Australian arboreal marsupial. The goal of this study was to sequence the transcriptome from several tissues of two geographically separate koalas, and to create the first comprehensive catalog of annotated transcripts for this species, enabling detailed analysis of the unique attributes of this threatened native marsupial, including infection by the koala retrovirus. Results RNA-Seq data was generated from a range of tissues from one male and one female koala and assembled de novo into transcripts using Velvet-Oases. Transcript abundance in each tissue was estimated. Transcripts were searched for likely protein-coding regions and a non-redundant set of 117,563 putative protein sequences was produced. In similarity searches there were 84,907 (72%) sequences that aligned to at least one sequence in the NCBI nr protein database. The best alignments were to sequences from other marsupials. After applying a reciprocal best hit requirement of koala sequences to those from tammar wallaby, Tasmanian devil and the gray short-tailed opossum, we estimate that our transcriptome dataset represents approximately 15,000 koala genes. The marsupial alignment information was used to look for potential gene duplications and we report evidence for copy number expansion of the alpha amylase gene, and of an aldehyde reductase gene. Koala retrovirus (KoRV) transcripts were detected in the transcriptomes. These were analysed in detail and the structure of the spliced envelope gene transcript was determined. There was appreciable sequence diversity within KoRV, with 233 sites in the KoRV genome showing small insertions/deletions or single nucleotide polymorphisms. Both koalas had sequences from the KoRV-A subtype, but the male koala transcriptome has, in addition, sequences more closely related to the KoRV-B subtype. This is the first report of a KoRV-B-like sequence in a wild population. Conclusions This transcriptomic dataset is a useful resource for molecular genetic studies of the koala, for evolutionary genetic studies of marsupials, for validation and annotation of the koala genome sequence, and for investigation of koala retrovirus. Annotated transcripts can be browsed and queried at http://koalagenome.org

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.

Correlation based method for phase identification in a three phase LV distribution network

Low voltage distribution networks feature a high degree of load unbalance and the addition of rooftop photovoltaic is driving further unbalances in the network. Single phase consumers are distributed across the phases but even if the consumer distribution was well balanced when the network was constructed changes will occur over time. Distribution transformer losses are increased by unbalanced loadings. The estimation of transformer losses is a necessary part of the routine upgrading and replacement of transformers and the identification of the phase connections of households allows a precise estimation of the phase loadings and total transformer loss. This paper presents a new technique and preliminary test results for a method of automatically identifying the phase of each customer by correlating voltage information from the utility's transformer system with voltage information from customer smart meters. The techniques are novel as they are purely based upon a time series of electrical voltage measurements taken at the household and at the distribution transformer. Experimental results using a combination of electrical power and current of the real smart meter datasets demonstrate the performance of our techniques.

Impact of gender-focused human resource management on performance : the mediating effects of gender diversity

Gender-focused human resource policies and practices signal an organization’s perspective on gender diversity. The signal produces perceptions that the organization values gender diversity leading to a gender-diverse workforce. In turn, a gender-diverse workforce provides a firm with a competitive advantage which should result in higher performance. This paper tests the mediating effects of gender diversity (at non-management and management levels) in the relationship between gender-focused policies and practices and performance. The findings indicate that non-management gender diversity partially mediates the relationship between gender-focused policies and practices and productivity, and management gender diversity partially mediates the relationship between gender-focused policies and practices and perceived market performance. The results have several theoretical, research and practical implications.

Bat colony size reduction coincides with clear-fell harvest operations and high rates of roost loss in plantation forest

Clear-fell harvest of forest concerns many wildlife biologists because of loss of vital resources such as roosts or nests, and effects on population viability. However, actual impact has not been quantified. Using New Zealand long-tailed bats (Chalinolobus tuberculatus) as a model species we investigated impacts of clear-fell logging on bats in plantation forest. C. tuberculatus roost within the oldest stands in plantation forest so it was likely roost availability would decrease as harvest operations occurred. We predicted that post-harvest: (1) roosting range sizes would be smaller, (2) fewer roosts would be used, and (3) colony size would be smaller. We captured and radiotracked C. tuberculatus to day-roosts in Kinleith Forest, an exotic plantation forest, over three southern hemisphere summers (Season 1 October 2006–March 2007; Season 2 November 2007–March 2008; and Season 3 November 2008–March 2009). Individual roosting ranges (100% MCPs) post harvest were smaller than those in areas that had not been harvested, and declined in area during the 3 years. Following harvest, bats used fewer roosts than those in areas that had not been harvested. Over 3 years 20.7% of known roosts were lost: 14.5% due to forestry operations and 6.2% due to natural tree fall. Median colony size was 4.0 bats (IQR = 2.0–8.0) and declined during the study, probably because of locally high levels of roost loss. Post harvest colonies were smaller than colonies in areas that had not been harvested. Together, these results suggest the impact of clear-fell harvest on long-tailed bat populations is negative.

Human resource management of Indian call centre representatives

This study examines how call centres adopt different types of human resource practices (involvement and control oriented) to manage frontline employees in Indian call centres. Data were collected from 250 call centre representatives to test the research hypotheses. The research model was analyzed using Mplus software. Findings showed that involvement and control oriented human resource practices resulted in more employee exhaustion and disengagement. Involvement oriented HRM had a positive impact on job satisfaction as well as, a positive relationship between employee exhaustion and disengagement. The findings suggest that, while involvement oriented HRM enhances job satisfaction, its implementation comes with a cost, that is, an increase in employee exhaustion and disengagement at work.

Mining resource profiles from event logs

Human resources are often responsible for the execution of business processes. In order to evaluate resource performance and identify best practices as well as opportunities for improvement, managers need objective information about resource behaviours. Companies often use information systems to support their processes and these systems record information about process execution in event logs. We present a framework for analysing and evaluating resource behaviour through mining such event logs. The framework provides a method for extracting descriptive information about resource skills, utilisation, preferences, productivity and collaboration patterns; a method for analysing relationships between different resource behaviours and outcomes; and a method for evaluating the overall resource productivity, tracking its changes over time and comparing it with the productivity of other resources. To demonstrate the applicability of our framework we apply it to analyse behaviours of employees in an Australian company and evaluate its usefulness by a survey among managers in industry.

An analysis of DNA methylation in human adipose tissue reveals differential modification of obesity genes before and after gastric bypass and weight loss

Background Environmental factors can influence obesity by epigenetic mechanisms. Adipose tissue plays a key role in obesity-related metabolic dysfunction, and gastric bypass provides a model to investigate obesity and weight loss in humans. Results Here, we investigate DNA methylation in adipose tissue from obese women before and after gastric bypass and significant weight loss. In total, 485,577 CpG sites were profiled in matched, before and after weight loss, subcutaneous and omental adipose tissue. A paired analysis revealed significant differential methylation in omental and subcutaneous adipose tissue. A greater proportion of CpGs are hypermethylated before weight loss and increased methylation is observed in the 3′ untranslated region and gene bodies relative to promoter regions. Differential methylation is found within genes associated with obesity, epigenetic regulation and development, such as CETP, FOXP2, HDAC4, DNMT3B, KCNQ1 and HOX clusters. We identify robust correlations between changes in methylation and clinical trait, including associations between fasting glucose and HDAC4, SLC37A3 and DENND1C in subcutaneous adipose. Genes investigated with differential promoter methylation all show significantly different levels of mRNA before and after gastric bypass. Conclusions This is the first study reporting global DNA methylation profiling of adipose tissue before and after gastric bypass and associated weight loss. It provides a strong basis for future work and offers additional evidence for the role of DNA methylation of adipose tissue in obesity.

Kallikrein 4 (hK4) and prostate-specific antigen (PSA) are associated with the loss of E-cadherin and an epithelial-mesenchymal transition (EMT)-like effect in prostate cancer cells

Prostate-specific antigen (PSA) and the related kallikrein family of serine proteases are current or emerging biomarkers for prostate cancer detection and progression. Kallikrein 4 (KLK4/hK4) is of particular interest, as KLK4 mRNA has been shown to be elevated in prostate cancer. In this study, we now show that the comparative expression of hK4 protein in prostate cancer tissues, compared with benign glands, is greater than that of PSA and kallikrein 2 (KLK2/hK2), suggesting that hK4 may play an important functional role in prostate cancer progression in addition to its biomarker potential. To examine the roles that hK4, as well as PSA and hK2, play in processes associated with progression, these kallikreins were separately transfected into the PC-3 prostate cancer cell line, and the consequence of their stable transfection was investigated. PC-3 cells expressing hK4 had a decreased growth rate, but no changes in cell proliferation were observed in the cells expressing PSA or hK2. hK4 and PSA, but not hK2, induced a 2.4-fold and 1.7-fold respective increase, in cellular migration, but not invasion, through Matrigel, a synthetic extracellular matrix. We hypothesised that this increase in motility displayed by the hK4 and PSA-expressing PC-3 cells may be related to the observed change in structure in these cells from a typical rounded epithelial-like cell to a spindle-shaped, more mesenchymal-like cell, with compromised adhesion to the culture surface. Thus, the expression of E-cadherin and vimentin, both associated with an epithelial-mesenchymal transition (EMT), was investigated. E-cadherin protein was lost and mRNA levels were significantly decreased in PC-3 cells expressing hK4 and PSA (10-fold and 7-fold respectively), suggesting transcriptional repression of E-cadherin, while the expression of vimentin was increased in these cells. The loss of E-cadherin and associated increase in vimentin are indicative of EMT and provides compelling evidence that hK4, in particular, and PSA have a functional role in the progression of prostate cancer through their promotion of tumour cell migration.

Sensorineural hearing loss after treatment for head and neck cancer : a review of the literature

Background Definitive cisplatin-based is increasingly delivered as the treatment of choice for patients with head and neck cancer. Sensorineural hearing loss is a significant long term side effect of cisplatin-based chemoradiation and is associated with potential major quality of life issues for patients. Purpose The purpose of this manuscript was to review the mechanism behind sensorineural hearing loss in patients treated with cisplatin-based chemoradiation, including incidence, the contributions of radiotherapy and cisplatin to sensorineural hearing loss and the impact of the toxicity on patient quality of life. Methods Database searches were conducted through PubMed (National Centre for Biotechnology Information) and OvidSP Medline via the Queensland University of Technology Library website. General article searches were conducted through the online search engine Google Scholar. Articles were excluded if the full-text was unavailable, they were not in English or if they were published prior to 1990. Keywords included hearing loss, ototoxicity, cancer, quality of life, cisplatin and radiotherapy. Results/Discussion The total number of journal articles accessed was 290. Due to exclusion criteria, 129 articles were deemed appropriated for review. Findings indicated that sensorineural hearing loss is a significant, long term complication for patients treated with cisplatin-based chemoradiation. Current literature recognises the ototoxic effects of cisplatin and cranial irradiation as separate entities, however the impact of combined modality therapy on sensorineural hearing loss is seldom reported. Multiple risk factors for hearing loss are described, however there are contradictory opinions on incidence and severity and the exact radiation dose threshold responsible for inducing hearing loss in patients receiving combined modality therapy. Sensorineural hearing loss creates a subset of complexities for patients with head and neck cancer and that these patients face significant quality of life impairment. Conclusion The literature review identified that sensorineural hearing loss is a major quality of life issue for patients treated with cisplatin-based chemoradiation for head and neck cancer. Further investigation evaluating the contribution of cisplatin-based chemoradiation to sensorineural hearing loss and the subsequent effect on patient quality of life is warranted.

What determines weight loss behaviour and body weight satisfaction in Australia? Evidence from the HILDA survey

This thesis undertakes an empirical investigation to identify factors that influence the decision to undertake weight loss behaviour using the nationally representative HILDA dataset. Although many factors influenced the decision, the findings suggested that body weight satisfaction was the greatest determinant of weight loss dieting. This thesis therefore conducted a further empirical study to analyse the determinants of body weight satisfaction. A rank-hypothesis was found to better predict variation in body weight satisfaction levels than the absolute value of the individual's Body Mass Index (BMI) or the relative-norm hypothesis, which are commonly reported in the literature.