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.

Temporal and spatial distribution and habitat associations of an urban population of New Zealand long-tailed bats (Chalinolobus tuberculatus)

Two ultrasound survey methods were used to determine the presence and activity patterns of New Zealand long-tailed bats (Chalinolobus tuberculatus) in the city of Hamilton. First, 13 monthly surveys conducted at 18 green spaces found C. tuberculatus in only one urban forest reserve, Hammond Bush, where they were found consistently throughout the year. Bat activity was strongly related to temperature. Second, twice-yearly citywide surveys conducted over 2 years determined the distribution and habitat associations of C. tuberculatus. Bats were found only in the southern part of the city and were strongly associated with the Waikato River. Bat activity was negatively correlated with housing and street light density and positively correlated with topographical complexity. In Hamilton, topographical complexity indicates the presence of gullies. Gullies probably provide foraging and roosting opportunities and connect the river to distant forest patches. These results suggest that urban habitats can be useful for bats if gullies can link these to distant habitat fragments.

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.

Home range and habitat selection by a threatened bat in exotic plantation forest

Individuals' home ranges are constrained by resource distribution and density, population size, and energetic requirements. Consequently, home ranges and habitat selection may vary between individuals of different sex and reproductive conditions. Whilst home ranges of bats are well-studied in native habitats, they are often not well understood in modified landscapes, particularly exotic plantation forests. Although Chalinolobus tuberculatus (Vespertilionidae, Chiroptera) are present in plantation forests throughout New Zealand their home ranges have only been studied in native forest and forest-agricultural mosaic and no studies of habitat selection that included males had occurred in any habitat type. Therefore, we investigated C. tuberculatus home range and habitat selection within exotic plantation forest. Home range sizes did not differ between bats of different reproductive states. Bats selected home ranges with higher proportions of relatively old forest than was available. Males selected edges with open unplanted areas within their home ranges, which females avoided. We suggest males use these edges, highly profitable foraging areas with early evening peaks in invertebrate abundance, to maintain relatively low energetic demands. Females require longer periods of invertebrate activity to fulfil their needs so select older stands for foraging, where invertebrate activity is higher. These results highlight additional understanding gained when data are not pooled across sexes. Mitigation for harvest operations could include ensuring that areas suitable for foraging and roosting are located within a radius equal to the home range of this bat species.

A comparison of the performance of a brand of broad-band and several brands of narrow-band bat detectors in two different habitat types.

The use of bat detectors to monitor bat activity is common. Although several papers have compared the performance of different brands, none have dealt with the effect of different habitats nor have they compared narrow- and broad-band detectors. In this study the performance of four brands of ultrasonic bat detector, including three narrowband and one broad-band model, were compared for their ability to detect a 40 kHz continuous sound of variable amplitude along 100 metre transects. Transects were laid out in two contrasting bat habitat types: grassland and forest. Results showed that the different brands of detector differed in their ability to detect the source in terms of maximum and minimum detectable distance of the source. The rate of sound degradation with distance as measured by each brand was also different. Significant differences were also found in the performance of different brands in open grassland versus deep forest. No significant differences were found within any brand of detector. Though not as sensitive as narrow-band detectors, broad-band models hold an advantage in their ability to identify species where several species are found sympatrically.

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.

Large-scale habitat mapping using vision-based AUVs : experiences, challenges & vehicle design

This paper overviews the development of a vision-based AUV along with a set of complementary operational strategies to allow reliable autonomous data collection in relatively shallow water and coral reef environments. The development of the AUV, called Starbug, encountered many challenges in terms of vehicle design, navigation and control. Some of these challenges are discussed with focus on operational strategies for estimating and reducing the total navigation error when using lower-resolution sensing modalities. Results are presented from recent field trials which illustrate the ability of the vehicle and associated operational strategies to enable rapid collection of visual data sets suitable for marine research applications.

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.

The land hoarding and land inspector dilemma in China : an evolutionary game theoretic perspective

China has experienced considerable economic growth since 1978, which was accompanied by unprecedented growth in urbanization and, more recently, by associated rising urban housing and land banking issues. One such issue is that of land hoarding - where real estate developers purchase land to hold unused in the rising market for a future lucrative sale, often several years later. This practice is outlawed in China, where land use is controlled by increasingly strengthened Government policies and inspectors. Despite this, land hoarding continues apace, with the main culprits being the developers and inspectors working subversively. This resembles a game between two players - the inspector and the developer - which provides the setting for this paper in developing an evolutionary game theory model to provide insights into dealing with the dilemmas faced by the players. The logic and dilemma of land banking strategy and illegal land banking issues are analysed, along with the land inspector’s role from a game theory perspective by determining the replication dynamic mechanism and evolutionary stable strategies under the various conditions that the players face. The major factors influencing the actions of land inspectors, on the other hand, are the costs of inspection, no matter if it is strict or indolent, conflict costs, and income and penalties from corruption. From this, it is shown that, when the net loss for corruption (income from corruption minus the penalties for corruption and cost of strict inspections) is less than the cost of strict inspections, the final evolutionary stable strategy of the inspectors is to carry out indolent inspections. Then, whether penalising developers for hoarding is severe or not, the evolutionary strategy for the developer is to hoard. The implications for land use control mechanisms and associated developer-inspector actions and counteractions are then examined in the light of the model's properties.

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.

Cost-effective biodiversity restoration with uncertain growth in forest habitat quality

This paper develops a dynamic model for cost-effective selection of sites for restoring biodiversity when habitat quality develops over time and is uncertain. A safety-first decision criterion is used for ensuring a minimum level of habitats, and this is formulated in a chance-constrained programming framework. The theoretical results show; (i) inclusion of quality growth reduces overall cost for achieving a future biodiversity target from relatively early establishment of habitats, but (ii) consideration of uncertainty in growth increases total cost and delays establishment, and (iii) cost-effective trading of habitat requires exchange rate between sites that varies over time. An empirical application to the red listed umbrella species - white-backed woodpecker - shows that the total cost of achieving habitat targets specified in the Swedish recovery plan is doubled if the target is to be achieved with high reliability, and that equilibrating price on a habitat trading market differs considerably between different quality growth combinations. © 2013 Elsevier GmbH.

Subpopulation triage: How to allocate conservation effort among populations

Threatened species often exist in a small number of isolated subpopulations. Given limitations on conservation spending, managers must choose from strategies that range from managing just one subpopulation and risking all other subpopulations to managing all subpopulations equally and poorly, thereby risking the loss of all subpopulations. We took an economic approach to this problem in an effort to discover a simple rule of thumb for optimally allocating conservation effort among subpopulations. This rule was derived by maximizing the expected number of extant subpopulations remaining given n subpopulations are actually managed. We also derived a spatiotemporally optimized strategy through stochastic dynamic programming. The rule of thumb suggested that more subpopulations should be managed if the budget increases or if the cost of reducing local extinction probabilities decreases. The rule performed well against the exact optimal strategy that was the result of the stochastic dynamic program and much better than other simple strategies (e.g., always manage one extant subpopulation or half of the remaining subpopulation). We applied our approach to the allocation of funds in 2 contrasting case studies: reduction of poaching of Sumatran tigers (Panthera tigris sumatrae) and habitat acquisition for San Joaquin kit foxes (Vulpes macrotis mutica). For our estimated annual budget for Sumatran tiger management, the mean time to extinction was about 32 years. For our estimated annual management budget for kit foxes in the San Joaquin Valley, the mean time to extinction was approximately 24 years. Our framework allows managers to deal with the important question of how to allocate scarce conservation resources among subpopulations of any threatened species. © 2008 Society for Conservation Biology.