Soluble NSF attachment protein receptor molecular mimicry by a Legionella pneumophila Dot/Icm effector

Upon infection, Legionella pneumophila uses the Dot/Icm type IV secretion system to translocate effector proteins from the Legionella-containing vacuole (LCV) into the host cell cytoplasm. The effectors target a wide array of host cellular processes that aid LCV biogenesis, including the manipulation of membrane trafficking. In this study, we used a hidden Markov model screen to identify two novel, non-eukaryotic soluble NSF attachment protein receptor (SNARE) homologs: the bacterial Legionella SNARE effector A (LseA) and viral SNARE homolog A proteins. We characterized LseA as a Dot/Icm effector of L. pneumophila, which has close homology to the Qc-SNARE subfamily. The lseA gene was present in multiple sequenced L. pneumophila strains including Corby and was well distributed among L. pneumophila clinical and environmental isolates. Employing a variety of biochemical, cell biological and microbiological techniques, we found that farnesylated LseA localized to membranes associated with the Golgi complex in mammalian cells and LseA interacted with a subset of Qa-, Qb- and R-SNAREs in host cells. Our results suggested that LseA acts as a SNARE protein and has the potential to regulate or mediate membrane fusion events in Golgi-associated pathways.

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.

A subexponential construction of graph coloring for multiparty computation

We show the first deterministic construction of an unconditionally secure multiparty computation (MPC) protocol in the passive adversarial model over black-box non-Abelian groups which is both optimal (secure against an adversary who possesses any tsubset is in the possession of the adversary. Unlike the deterministic constructions from Desmedt et al. (2012) our construction has subexponential complexity and is optimal at the same time, i.e., it is secure for any t

Open problem: Shifting experts on easy data

A number of online algorithms have been developed that have small additional loss (regret) compared to the best “shifting expert”. In this model, there is a set of experts and the comparator is the best partition of the trial sequence into a small number of segments, where the expert of smallest loss is chosen in each segment. The regret is typically defined for worst-case data / loss sequences. There has been a recent surge of interest in online algorithms that combine good worst-case guarantees with much improved performance on easy data. A practically relevant class of easy data is the case when the loss of each expert is iid and the best and second best experts have a gap between their mean loss. In the full information setting, the FlipFlop algorithm by De Rooij et al. (2014) combines the best of the iid optimal Follow-The-Leader (FL) and the worst-case-safe Hedge algorithms, whereas in the bandit information case SAO by Bubeck and Slivkins (2012) competes with the iid optimal UCB and the worst-case-safe EXP3. We ask the same question for the shifting expert problem. First, we ask what are the simple and efficient algorithms for the shifting experts problem when the loss sequence in each segment is iid with respect to a fixed but unknown distribution. Second, we ask how to efficiently unite the performance of such algorithms on easy data with worst-case robustness. A particular intriguing open problem is the case when the comparator shifts within a small subset of experts from a large set under the assumption that the losses in each segment are iid.

Superpixel-based appearance change prediction for long-term navigation across seasons

Changing environments pose a serious problem to current robotic systems aiming at long term operation under varying seasons or local weather conditions. This paper is built on our previous work where we propose to learn to predict the changes in an environment. Our key insight is that the occurring scene changes are in part systematic, repeatable and therefore predictable. The goal of our work is to support existing approaches to place recognition by learning how the visual appearance of an environment changes over time and by using this learned knowledge to predict its appearance under different environmental conditions. We describe the general idea of appearance change prediction (ACP) and investigate properties of our novel implementation based on vocabularies of superpixels (SP-ACP). Our previous work showed that the proposed approach significantly improves the performance of SeqSLAM and BRIEF-Gist for place recognition on a subset of the Nordland dataset under extremely different environmental conditions in summer and winter. This paper deepens the understanding of the proposed SP-ACP system and evaluates the influence of its parameters. We present the results of a large-scale experiment on the complete 10 h Nordland dataset and appearance change predictions between different combinations of seasons.

An investigation of the effect of some stable nitroxide antioxidants in prostate cancer cells

The risk of prostate cancer and disease progression may potentially be increased by oxidative stress. This project examined the stability of nitroxide antioxidants and their effects on cell growth, survival and gene regulation in prostate cancer cells. The novel nitroxide, CTMIO, synthesised here at QUT, was found to have minimal toxicity and modulated the expression of a subset of oxidative stress and antioxidant-related genes distinct from those regulated by a related derivative. This study has provided a step forward in our understanding of the mechanism of action of nitroxides within cells.

Proportionality : a valid alternative to correlation for relative data

Relative abundance data is common in the life sciences, but appreciation that it needs special analysis and interpretation is scarce. Correlation is popular as a statistical measure of pairwise association but should not be used on data that carry only relative information. Using timecourse yeast gene expression data, we show how correlation of relative abundances can lead to conclusions opposite to those drawn from absolute abundances, and that its value changes when different components are included in the analysis. Once all absolute information has been removed, only a subset of those associations will reliably endure in the remaining relative data, specifically, associations where pairs of values behave proportionally across observations. We propose a new statistic φ to describe the strength of proportionality between two variables and demonstrate how it can be straightforwardly used instead of correlation as the basis of familiar analyses and visualization methods.

A tale of two solvers: Eager and lazy approaches to bit-vectors

The standard method for deciding bit-vector constraints is via eager reduction to propositional logic. This is usually done after first applying powerful rewrite techniques. While often efficient in practice, this method does not scale on problems for which top-level rewrites cannot reduce the problem size sufficiently. A lazy solver can target such problems by doing many satisfiability checks, each of which only reasons about a small subset of the problem. In addition, the lazy approach enables a wide range of optimization techniques that are not available to the eager approach. In this paper we describe the architecture and features of our lazy solver (LBV). We provide a comparative analysis of the eager and lazy approaches, and show how they are complementary in terms of the types of problems they can efficiently solve. For this reason, we propose a portfolio approach that runs a lazy and eager solver in parallel. Our empirical evaluation shows that the lazy solver can solve problems none of the eager solvers can and that the portfolio solver outperforms other solvers both in terms of total number of problems solved and the time taken to solve them.

Genetic risk score analysis indicates migraine with and without comorbid depression are genetically different disorders

Migraine and major depressive disorder (MDD) are comorbid, moderately heritable and to some extent influenced by the same genes. In a previous paper, we suggested the possibility of causality (one trait causing the other) underlying this comorbidity. We present a new application of polygenic (genetic risk) score analysis to investigate the mechanisms underlying the genetic overlap of migraine and MDD. Genetic risk scores were constructed based on data from two discovery samples in which genome-wide association analyses (GWA) were performed for migraine and MDD, respectively. The Australian Twin Migraine GWA study (N = 6,350) included 2,825 migraine cases and 3,525 controls, 805 of whom met the diagnostic criteria for MDD. The RADIANT GWA study (N = 3,230) included 1,636 MDD cases and 1,594 controls. Genetic risk scores for migraine and for MDD were used to predict pure and comorbid forms of migraine and MDD in an independent Dutch target sample (NTR-NESDA, N = 2,966), which included 1,476 MDD cases and 1,058 migraine cases (723 of these individuals had both disorders concurrently). The observed patterns of prediction suggest that the 'pure' forms of migraine and MDD are genetically distinct disorders. The subgroup of individuals with comorbid MDD and migraine were genetically most similar to MDD patients. These results indicate that in at least a subset of migraine patients with MDD, migraine may be a symptom or consequence of MDD. © 2013 Springer-Verlag Berlin Heidelberg.

Genetic variants underlying risk of endometriosis: Insights from meta-analysis of eight genome-wide association and replication datasets

BACKGROUND Endometriosis is a heritable common gynaecological condition influenced by multiple genetic and environmental factors. Genome-wide association studies (GWASs) have proved successful in identifying common genetic variants of moderate effects for various complex diseases. To date, eight GWAS and replication studies from multiple populations have been published on endometriosis. In this review, we investigate the consistency and heterogeneity of the results across all the studies and their implications for an improved understanding of the aetiology of the condition. METHODS Meta-analyses were conducted on four GWASs and four replication studies including a total of 11 506 cases and 32 678 controls, and on the subset of studies that investigated associations for revised American Fertility Society (rAFS) Stage III/IV including 2859 cases. The datasets included 9039 cases and 27 343 controls of European (Australia, Belgium, Italy, UK, USA) and 2467 cases and 5335 controls of Japanese ancestry. Fixed and Han and Elkin random-effects models, and heterogeneity statistics (Cochran's Q test), were used to investigate the evidence of the nine reported genome-wide significant loci across datasets and populations. RESULTS Meta-analysis showed that seven out of nine loci had consistent directions of effect across studies and populations, and six out of nine remained genome-wide significant (P < 5 × 10(-8)), including rs12700667 on 7p15.2 (P = 1.6 × 10(-9)), rs7521902 near WNT4 (P = 1.8 × 10(-15)), rs10859871 near VEZT (P = 4.7 × 10(-15)), rs1537377 near CDKN2B-AS1 (P = 1.5 × 10(-8)), rs7739264 near ID4 (P = 6.2 × 10(-10)) and rs13394619 in GREB1 (P = 4.5 × 10(-8)). In addition to the six loci, two showed borderline genome-wide significant associations with Stage III/IV endometriosis, including rs1250248 in FN1 (P = 8 × 10(-8)) and rs4141819 on 2p14 (P = 9.2 × 10(-8)). Two independent inter-genic loci, rs4141819 and rs6734792 on chromosome 2, showed significant evidence of heterogeneity across datasets (P < 0.005). Eight of the nine loci had stronger effect sizes among Stage III/IV cases, implying that they are likely to be implicated in the development of moderate to severe, or ovarian, disease. While three out of nine loci were inter-genic, the remaining were in or near genes with known functions of biological relevance to endometriosis, varying from roles in developmental pathways to cellular growth/carcinogenesis. CONCLUSIONS Our meta-analysis shows remarkable consistency in endometriosis GWAS results across studies, with little evidence of population-based heterogeneity. They also show that the phenotypic classifications used in GWAS to date have been limited. Stronger associations with Stage III/IV disease observed for most loci emphasize the importance for future studies to include detailed sub-phenotype information. Functional studies in relevant tissues are needed to understand the effect of the variants on downstream biological pathways.

Enhanced cortisol suppression following administration of low-dose dexamethasone in first-episode psychosis patients

OBJECTIVE Impaired regulation of the hypothalamic-pituitary-adrenal (HPA) axis and hyper-activity of this system have been described in patients with psychosis. Conversely, some psychiatric disorders such as post-traumatic stress disorder (PTSD) are characterised by HPA hypo-activity, which could be related to prior exposure to trauma. This study examined the cortisol response to the administration of low-dose dexamethasone in first-episode psychosis (FEP) patients and its relationship to childhood trauma. METHOD The low-dose (0.25 mg) Dexamethasone Suppression Test (DST) was performed in 21 neuroleptic-naive or minimally treated FEP patients and 20 healthy control participants. Childhood traumatic events were assessed in all participants using the Childhood Trauma Questionnaire (CTQ) and psychiatric symptoms were assessed in patients using standard rating scales. RESULTS FEP patients reported significantly higher rates of childhood trauma compared to controls (p = 0.001) and exhibited lower basal (a.m.) cortisol (p = 0.04) and an increased rate of cortisol hyper-suppression following dexamethasone administration compared to controls (33% (7/21) vs 5% (1/20), respectively; p = 0.04). There were no significant group differences in mean cortisol decline or percent cortisol suppression following the 0.25 mg DST. This study shows for the first time that a subset of patients experiencing their first episode of psychosis display enhanced cortisol suppression. CONCLUSIONS These findings suggest there may be distinct profiles of HPA axis dysfunction in psychosis which should be further explored.

Scoping study into wound management nurse practitioner models of practice

Objectives The primary objective of this research was to investigate wound management nurse practitioner (WMNP) models of service for the purposes of identifying parameters of practice and how patient outcomes are measured. Methods A scoping study was conducted with all authorised WMNPs in Australia from October to December 2012 using survey methodology. A questionnaire was developed to obtain data on the role and practice parameters of authorised WMNPs in Australia. The tool comprised seven sections and included a total of 59 questions. The questionnaire was distributed to all members of the WMNP Online Peer Review Group, to which it was anticipated the majority of WMNPs belonged. Results Twenty-one WMNPs responded (response rate 87%), with the results based on a subset of respondents who stated that, at the time of the questionnaire, they were employed as a WMNP, therefore yielding a response rate of 71% (n≤15). Most respondents (93%; n≤14) were employed in the public sector, with an average of 64 occasions of service per month. The typical length of a new case consultation was 60min, with 32min for follow ups. The most frequently performed activity was wound photography (83%; n≤12), patient, family or carer education (75%; n≤12), Doppler ankle-brachial pressure index assessment (58%; n≤12), conservative sharp wound debridement (58%; n≤12) and counselling (50%; n≤12). The most routinely prescribed medications were local anaesthetics (25%; n≤12) and oral antibiotics (25%; n≤12). Data were routinely collected by 91% of respondents on service-related and wound-related parameters to monitor patient outcomes, to justify and improve health services provided. Conclusion This study yielded important baseline information on this professional group, including data on patient problems managed, the types of interventions implemented, the resources used to accomplish outcomes and how outcomes are measured.

Plant species’ origin predicts dominance and response to nutrient enrichment and herbivores in global grasslands

Exotic species dominate many communities; however the functional significance of species’ biogeographic origin remains highly contentious. This debate is fuelled in part by the lack of globally replicated, systematic data assessing the relationship between species provenance, function and response to perturbations. We examined the abundance of native and exotic plant species at 64 grasslands in 13 countries, and at a subset of the sites we experimentally tested native and exotic species responses to two fundamental drivers of invasion, mineral nutrient supplies and vertebrate herbivory. Exotic species are six times more likely to dominate communities than native species. Furthermore, while experimental nutrient addition increases the cover and richness of exotic species, nutrients decrease native diversity and cover. Native and exotic species also differ in their response to vertebrate consumer exclusion. These results suggest that species origin has functional significance, and that eutrophication will lead to increased exotic dominance in grasslands.

Working the story : News curation in social media as a second save of citizen journalism

For the first decade of its existence, the concept of citizen journalism has described an approach which was seen as a broadening of the participant base in journalistic processes, but still involved only a comparatively small subset of overall society – for the most part, citizen journalists were news enthusiasts and “political junkies” (Coleman, 2006) who, as some exasperated professional journalists put it, “wouldn’t get a job at a real newspaper” (The Australian, 2007), but nonetheless followed many of the same journalistic principles. The investment – if not of money, then at least of time and effort – involved in setting up a blog or participating in a citizen journalism Website remained substantial enough to prevent the majority of Internet users from engaging in citizen journalist activities to any significant extent; what emerged in the form of news blogs and citizen journalism sites was a new online elite which for some time challenged the hegemony of the existing journalistic elite, but gradually also merged with it. The mass adoption of next-generation social media platforms such as Facebook and Twitter, however, has led to the emergence of a new wave of quasi-journalistic user activities which now much more closely resemble the “random acts of journalism” which JD Lasica envisaged in 2003. Social media are not exclusively or even predominantly used for citizen journalism; instead, citizen journalism is now simply a by-product of user communities engaging in exchanges about the topics which interest them, or tracking emerging stories and events as they happen. Such platforms – and especially Twitter with its system of ad hoc hashtags that enable the rapid exchange of information about issues of interest – provide spaces for users to come together to “work the story” through a process of collaborative gatewatching (Bruns, 2005), content curation, and information evaluation which takes place in real time and brings together everyday users, domain experts, journalists, and potentially even the subjects of the story themselves. Compared to the spaces of news blogs and citizen journalism sites, but also of conventional online news Websites, which are controlled by their respective operators and inherently position user engagement as a secondary activity to content publication, these social media spaces are centred around user interaction, providing a third-party space in which everyday as well as institutional users, laypeople as well as experts converge without being able to control the exchange. Drawing on a number of recent examples, this article will argue that this results in a new dynamic of interaction and enables the emergence of a more broadly-based, decentralised, second wave of citizen engagement in journalistic processes.

Architecture for service profiling

Service oriented architecture is gaining momentum. However, in order to be successful, the proper and up-to-date description of services is required. Such a description may be provided by service profiling mechanisms, such as one presented in this article. Service profile can be defined as an up-to-date description of a subset of non-functional properties of a service. It allows for service comparison on the basis of non-functional parameters, and choosing the service which is most suited to the needs of a user. In this article the notion of a service profile along with service profiling mechanism is presented as well as the architecture of a profiling system. © 2006 IEEE.