Strain- and host species-specific inflammasome activation, IL-1β release, and cell death in macrophages infected with uropathogenic Escherichia coli

Uropathogenic Escherichia coli (UPEC) is the main etiological agent of urinary tract infections (UTIs). Little is known about interactions between UPEC and the inflammasome, a key innate immune pathway. Here we show that UPEC strains CFT073 and UTI89 trigger inflammasome activation and lytic cell death in human macrophages. Several other UPEC strains, including two multidrug-resistant ST131 isolates, did not kill macrophages. In mouse macrophages, UTI89 triggered cell death only at a high multiplicity of infection, and CFT073-mediated inflammasome responses were completely NLRP3-dependent. Surprisingly, CFT073- and UTI89-mediated responses only partially depended on NLRP3 in human macrophages. In these cells, NLRP3 was required for interleukin-1β (IL-1β) maturation, but contributed only marginally to cell death. Similarly, caspase-1 inhibition did not block cell death in human macrophages. In keeping with such differences, the pore-forming toxin α-hemolysin mediated a substantial proportion of CFT073-triggered IL-1β secretion in mouse but not human macrophages. There was also a more substantial α-hemolysin-independent cell death response in human vs. mouse macrophages. Thus, in mouse macrophages, CFT073-triggered inflammasome responses are completely NLRP3-dependent, and largely α-hemolysin-dependent. In contrast, UPEC activates an NLRP3-independent cell death pathway and an α-hemolysin-independent IL-1β secretion pathway in human macrophages. This has important implications for understanding UTI in humans.

Compensation or consideration for a statutory right of user?

Section 180 of the Property Law Act 1974 (Qld) makes provision for an applicant to seek a statutory right of user over a neighbour’s property where such right of use is reasonably necessary in the interests of effective use in any reasonable manner of the dominant land. A key issue in an application under s 180 is compensation. Unfortunately, while s 180 expressly contemplates that an order for compensation will include provision for payment of compensation to the owner of servient land there are certain issues that are less clear. One of these is the basis for determination of the amount of compensation. In this regard, s 180(4)(a) provides that, in making an order for a statutory right of user, the court: (a) shall, except in special circumstances, include provision for payment by the applicant to such person or persons as may be specified in the order of such amount by way of compensation or consideration as in the circumstances appears to the court to be just The operation of this statutory provision was considered by de Jersey CJ (as he then was) in Peulen v Agius [2015] QSC 137.

Integrating customer orientation, employee compensation and performance management: A conceptual framework

Compensation systems are an essential tool to link corporate goals such as customer orientation with individual and organisational performance. While some authors demonstrate the positive effects of incorporating nonfinancial measures into the compensation system empirically, companies have encountered problems after linking pay to customer satisfaction. We argue that reasons for this can be attributed to the measurement of customer satisfaction as well as to the missing link between customer satisfaction and customer retention and profitability in theses cases. Hence, there is a strong need for the development of an holistic reward and performance measurement model enabling an organisation to identify cause-and-effect relationships when linking rewards to nonfinancial performance measures. We present a conceptual framework of a success chain driven reward system that enables organisations to systematically derive a customer-oriented reward strategy. In the context of performance evaluation, we propose to rely on integrated and multidimensional measurement methods.

Adaptive aneuploidy protects against thiol peroxidase deficiency by increasing respiration via key mitochondrial proteins

Aerobic respiration is a fundamental energy-generating process; however, there is cost associated with living in an oxygen-rich environment, because partially reduced oxygen species can damage cellular components. Organisms evolved enzymes that alleviate this damage and protect the intracellular milieu, most notably thiol peroxidases, which are abundant and conserved enzymes that mediate hydrogen peroxide signaling and act as the first line of defense against oxidants in nearly all living organisms. Deletion of all eight thiol peroxidase genes in yeast (∆8 strain) is not lethal, but results in slow growth and a high mutation rate. Here we characterized mechanisms that allow yeast cells to survive under conditions of thiol peroxidase deficiency. Two independent ∆8 strains increased mitochondrial content, altered mitochondrial distribution, and became dependent on respiration for growth but they were not hypersensitive to H2O2. In addition, both strains independently acquired a second copy of chromosome XI and increased expression of genes encoded by it. Survival of ∆8 cells was dependent on mitochondrial cytochrome-c peroxidase (CCP1) and UTH1, present on chromosome XI. Coexpression of these genes in ∆8 cells led to the elimination of the extra copy of chromosome XI and improved cell growth, whereas deletion of either gene was lethal. Thus, thiol peroxidase deficiency requires dosage compensation of CCP1 and UTH1 via chromosome XI aneuploidy, wherein these proteins support hydroperoxide removal with the reducing equivalents generated by the electron transport chain. To our knowledge, this is the first evidence of adaptive aneuploidy counteracting oxidative stress.

Single layer lead iodide: Computational exploration of structural, electronic and optical properties, strain induced band modulation and the role of spin-orbital-coupling

Graphitic like layered materials exhibit intriguing electronic structures and thus the search for new types of two-dimensional (2D) monolayer materials is of great interest for developing novel nano-devices. By using density functional theory (DFT) method, here we for the first time investigate the structure, stability, electronic and optical properties of monolayer lead iodide (PbI2). The stability of PbI2 monolayer is first confirmed by phonon dispersion calculation. Compared to the calculation using generalized gradient approximation, screened hybrid functional and spin–orbit coupling effects can not only predicts an accurate bandgap (2.63 eV), but also the correct position of valence and conduction band edges. The biaxial strain can tune its bandgap size in a wide range from 1 eV to 3 eV, which can be understood by the strain induced uniformly change of electric field between Pb and I atomic layer. The calculated imaginary part of the dielectric function of 2D graphene/PbI2 van der Waals type hetero-structure shows significant red shift of absorption edge compared to that of a pure monolayer PbI2. Our findings highlight a new interesting 2D material with potential applications in nanoelectronics and optoelectronics.

Genome sequence of marine bacterium idiomarina sp. strain 28-8, isolated from Korean ark shells

Idiomarina sp. strain 28-8 is an aerobic, Gram-negative, flagellar bacterium isolated from the bodies of ark shells (Scapharca broughtonii) collected from underwater sediments in Gangjin Bay, South Korea. Here, we present the draft genome sequence of Idiomarina sp. 28-8 (2,971,606 bp, with a G+C content of 46.9%), containing 2,795 putative coding sequences.

An exploratory ergonomic study of musculoskeletal disorder prevention in the Queensland Ambulance Service

From 2008-09 to 2012-13, the most prevalent worker compensation claim in the Queensland Ambulance Service (QAS) was musculoskeletal injuries at >80%. This is consistent with literature that shows Musculoskeletal Disorders (MSD) was one of the front runners for workplace injuries among many professions. In an attempt to reduce the injury rate and related claims, the QAS created a selection criterion for their workers based on the Health Related Fitness Test. This method intended to select workers based upon their fitness level, instead of selecting for their ability to perform the tasks or modify the tasks to better suit the workers. With injury rates remaining high, further research produced the Patient Handling Equipment Project Report, which provided the background for the Manual Handling Program Book. The Manual Handling Program Book however lacks in accurately addressing musculoskeletal hazards; actions which cause or avoid injury, correct posture and motion for patient movement, muscular biomechanics, static and dynamic workload including activities causing strain, and equipment use in relation to musculoskeletal hazards. The exploratory research aims to better understand the ambulance service’s perception of Manual Materials Handling (MMH), how it relates to musculoskeletal injuries and how the service has attempted to reduce its prevalence. Based on a literature review and a critical analysis of the QAS Health Related Fitness Test, QAS Patient Handling Equipment Project Report and the QAS Manual Handling Program Book, an understanding of their shortfalls in the prevention of musculoskeletal injuries was gained. This entails understanding the work tasks, workloads, strains and workflow of paramedics. This research creates a starting point for further research into musculoskeletal injuries in paramedics. This study specifically looks at hazards related to musculoskeletal disorders. It identifies work system deficiencies that contribute to the prevalence of musculoskeletal injuries, and possible interventions to avoid them in paramedics.

Shaping development through mechanical strain: The transcriptional basis of diet-induced phenotypic plasticity in a cichlid fish

Adaptive phenotypic plasticity, the ability of an organism to change its phenotype to match local environments, is increasingly recognized for its contribution to evolution. However, few empirical studies have explored the molecular basis of plastic traits. The East African cichlid fish Astatoreochromis alluaudi displays adaptive phenotypic plasticity in its pharyngeal jaw apparatus, a structure that is widely seen as an evolutionary key innovation that has contributed to the remarkable diversity of cichlid fishes. It has previously been shown that in response to different diets, the pharyngeal jaws change their size, shape and dentition: hard diets induce an adaptive robust molariform tooth phenotype with short jaws and strong internal bone structures, while soft diets induce a gracile papilliform tooth phenotype with elongated jaws and slender internal bone structures. To gain insight into the molecular underpinnings of these adaptations and enable future investigations of the role that phenotypic plasticity plays during the formation of adaptive radiations, the transcriptomes of the two divergent jaw phenotypes were examined. Our study identified a total of 187 genes whose expression differs in response to hard and soft diets, including immediate early genes, extracellular matrix genes and inflammatory factors. Transcriptome results are interpreted in light of expression of candidate genesmarkers for tooth size and shape, bone cells and mechanically sensitive pathways. This study opens up new avenues of research at new levels of biological organization into the roles of phenotypic plasticity during speciation and radiation of cichlid fishes.

A Chlamydia trachomatis strain with a chemically generated amino acid substitution (P370L) in the cthtrA gene shows reduced elementary body production

Background Chlamydia (C.) trachomatis is the most prevalent bacterial sexually transmitted infection worldwide and the leading cause of preventable blindness. Genetic approaches to investigate C. trachomatis have been only recently developed due to the organism’s intracellular developmental cycle. HtrA is a critical stress response serine protease and chaperone for many bacteria and in C. trachomatis has been previously shown to be important for heat stress and the replicative phase of development using a chemical inhibitor of the CtHtrA activity. In this study, chemically-induced SNVs in the cthtrA gene that resulted in amino acid substitutions (A240V, G475E, and P370L) were identified and characterized. Methods SNVs were initially biochemically characterized in vitro using recombinant protein techniques to confirm a functional impact on proteolysis. The C. trachomatis strains containing the SNVs with marked reductions in proteolysis were investigated in cell culture to identify phenotypes that could be linked to CtHtrA function. Results The strain harboring the SNV with the most marked impact on proteolysis (cthtrAP370L) was detected to have a significant reduction in the production of infectious elementary bodies. Conclusions This provides genetic evidence that CtHtrA is critical for the C. trachomatis developmental cycle.

Interval training intensity affects energy intake compensation in obese men

Abstract PURPOSE: Compensatory responses may attenuate the effectiveness of exercise training in weight management. The aim of this study was to compare the effect of moderate- and high-intensity interval training on eating behavior compensation. METHODS: Using a crossover design, 10 overweight and obese men participated in 4-week moderate (MIIT) and high (HIIT) intensity interval training. MIIT consisted of 5-min cycling stages at ± 20% of mechanical work at 45%VO(2)peak, and HIIT consisted of alternate 30-s work at 90%VO(2)peak and 30-s rests, for 30 to 45 min. Assessments included a constant-load exercise test at 45%VO(2)peak for 45 min followed by 60-min recovery. Appetite sensations were measured during the exercise test using a Visual Analog Scale. Food preferences (liking and wanting) were assessed using a computer-based paradigm, and this paradigm uses 20 photographic food stimuli varying along two dimensions, fat (high or low) and taste (sweet or nonsweet). An ad libitum test meal was provided after the constant-load exercise test. RESULTS: Exercise-induced hunger and desire to eat decreased after HIIT, and the difference between MIIT and HIIT in desire to eat approached significance (p = .07). Exercise-induced liking for high-fat nonsweet food tended to increase after MIIT and decreased after HIIT (p = .09). Fat intake decreased by 16% after HIIT, and increased by 38% after MIIT, with the difference between MIIT and HIIT approaching significance (p = .07). CONCLUSIONS: This study provides evidence that energy intake compensation differs between MIIT and HIIT.

Role of enhanced vector transmission of a new West Nile virus strain in an outbreak of equine disease in Australia in 2011

Background In 2011, a variant of West Nile virus Kunjin strain (WNVKUN) caused an unprecedented epidemic of neurological disease in horses in southeast Australia, resulting in almost 1,000 cases and a 9% fatality rate. We investigated whether increased fitness of the virus in the primary vector, Culex annulirostris, and another potential vector, Culex australicus, contributed to the widespread nature of the outbreak. Methods Mosquitoes were exposed to infectious blood meals containing either the virus strain responsible for the outbreak, designated WNVKUN2011, or WNVKUN2009, a strain of low virulence that is typical of historical strains of this virus. WNVKUN infection in mosquito samples was detected using a fixed cell culture enzyme immunoassay and a WNVKUN- specific monoclonal antibody. Probit analysis was used to determine mosquito susceptibility to infection. Infection, dissemination and transmission rates for selected days post-exposure were compared using Fisher’s exact test. Virus titers in bodies and saliva expectorates were compared using t-tests. Results There were few significant differences between the two virus strains in the susceptibility of Cx. annulirostris to infection, the kinetics of virus replication and the ability of this mosquito species to transmit either strain. Both strains were transmitted by Cx. annulirostris for the first time on day 5 post-exposure. The highest transmission rates (proportion of mosquitoes with virus detected in saliva) observed were 68% for WNVKUN2011 on day 12 and 72% for WNVKUN2009 on day 14. On days 12 and 14 post-exposure, significantly more WNVKUN2011 than WNVKUN2009 was expectorated by infected mosquitoes. Infection, dissemination and transmission rates of the two strains were not significantly different in Culex australicus. However, transmission rates and the amount of virus expectorated were significantly lower in Cx. australicus than Cx. annulirostris. Conclusions The higher amount of WNVKUN2011 expectorated by infected mosquitoes may be an indication that this virus strain is transmitted more efficiently by Cx. annulirostris compared to other WNVKUN strains. Combined with other factors, such as a convergence of abundant mosquito and wading bird populations, and mammalian and avian feeding behaviour by Cx. annulirostris, this may have contributed to the scale of the 2011 equine epidemic.

Real-time wind speed estimation and compensation for improved flight

This paper presents the development and experimental validation of a prototype system for online estimation and compensation of wind disturbances onboard small Rotorcraft unmanned aerial systems (RUAS). The proposed approach consists of integrating a small pitot-static system onboard the vehicle and using simple but effective algorithms for estimating the wind speed in real time. The baseline flight controller has been augmented with a feed-forward term to compensate for these wind disturbances, thereby improving the flight performance of small RUAS in windy conditions. The paper also investigates the use of online airspeed measurements in a closed-loop for controlling the RUAS forward motion without the aid of a global positioning system (GPS). The results of more than 80 flights with a RUAS confirm the validity of our approach.

Physical mechanisms underlying the strain-rate-dependent mechanical behavior of kangaroo shoulder cartilage

Due to anatomical and biomechanical similarities to human shoulder, kangaroo was chosen as a model to study shoulder cartilage. Comprehensive enzymatic degradation and indentation tests were applied on kangaroo shoulder cartilage to study mechanisms underlying its strain-rate-dependent mechanical behavior. We report that superficial collagen plays a more significant role than proteoglycans in facilitating strain-rate-dependent behavior of kangaroo shoulder cartilage. By comparing the mechanical properties of degraded and normal cartilages it was noted that proteoglycan and collagen degradation significantly compromised strain-rate-dependent mechanical behavior of the cartilage. Superficial collagen contributed equally to the tissue behavior at all strain-rates. This is different to studies reported on knee cartilage and confirms the importance of superficial collagen on shoulder cartilage mechanical behavior. A porohyperelastic numerical model also indicated that collagen disruption would lead to faster damage of the shoulder cartilage than when proteoglycans are depleted.

Investigation of the mechanical behavior of kangaroo humeral head cartilage tissue by a porohyperelastic model based on the strain-rate-dependent permeability

Solid–interstitial fluid interaction, which depends on tissue permeability, is significant to the strain-rate-dependent mechanical behavior of humeral head (shoulder) cartilage. Due to anatomical and biomechanical similarities to that of the human shoulder, kangaroos present a suitable animal model. Therefore, indentation experiments were conducted on kangaroo shoulder cartilage tissues from low (10−4/s) to moderately high (10−2/s) strain-rates. A porohyperelastic model was developed based on the experimental characterization; and a permeability function that takes into account the effect of strain-rate on permeability (strain-rate-dependent permeability) was introduced into the model to investigate the effect of rate-dependent fluid flow on tissue response. The prediction of the model with the strain-rate-dependent permeability was compared with those of the models using constant permeability and strain-dependent permeability. Compared to the model with constant permeability, the models with strain-dependent and strain-rate-dependent permeability were able to better capture the experimental variation at all strain-rates (p<0.05). Significant differences were not identified between models with strain-dependent and strain-rate-dependent permeability at strain-rate of 5×10−3/s (p=0.179). However, at strain-rate of 10−2/s, the model with strain-rate-dependent permeability was significantly better at capturing the experimental results (p<0.005). The findings thus revealed the significance of rate-dependent fluid flow on tissue behavior at large strain-rates, which provides insights into the mechanical deformation mechanisms of cartilage tissues.

Draft genome and plasmid sequences of Chlamydia pneumoniae strain B21 from an Australian endangered marsupial, the western barred bandicoot

Chlamydia pneumoniae is a ubiquitous intracellular pathogen, first associated with human respiratory disease and subsequently detected in a range of mammals, amphibians, and reptiles. Here we report the draft genome sequence for strain B21 of C. pneumoniae, isolated from the endangered Australian marsupial the western barred bandicoot.