Clinical Escherichia coli isolates utilize alpha-hemolysin to inhibit in vitro epithelial cytokine production

Uropathogenic Escherichia coli is the primary cause of urinary tract infections, which affects over 60% of women during their lifetime. UPEC exhibits a number of virulence traits that facilitate colonization of the bladder, including inhibition of cytokine production by bladder epithelial cells. The goal of this study was to identify the mechanism of this inhibition. We observed that cytokine suppression was associated with rapid cytotoxicity toward epithelial cells. We found that cytotoxicity, cytokine suppression and alpha-hemolysin production were all tightly linked in clinical isolates. We screened a UPEC fosmid library and identified clones that gained the cytotoxicity and cytokine-suppression phenotypes. Both clones contained fosmids encoding a PAI II(J96)-like domain and expressed the alpha-hemolysin (hlyA) encoded therein. Mutation of the fosmid-encoded hly operon abolished cytotoxicity and cytokine suppression. Similarly, mutation of the chromosomal hlyCABD operon of UPEC isolate F11 also abolished these phenotypes, and they could be restored by introducing the PAI II(J96)-like domain-encoding fosmid. We also examined the role of alpha-hemolysin in cytokine production both in the murine UTI model as well as patient specimens. We conclude that E. coli utilizes alpha-hemolysin to inhibit epithelial cytokine production in vitro. Its contribution to inflammation during infection requires further study.

Development of immunotherapies and vaccines against visceral leishmaiasis

Visceral leishmaniasis (VL) is a chronic parasitic disease prevalent in tropical and sub- tropical countries. This study focused on the development of immune-based therapy with immune checkpoint inhibitors and/or activators, as well as cytokines as a way to treat VL either alone or in combination with conventional drugs. Since many chronic infectious diseases share mechanisms of immune suppression, these findings have broader implications for other infectious diseases, such as HIV, tuberculosis and malaria.

Quarantine and surveillance strategies for plant pathogen detection and control

Incursions of plant pests and diseases pose serious threats to food security, agricultural productivity and the natural environment. One of the challenges in confidently delimiting and eradicating incursions is how to choose from an arsenal of surveillance and quarantine approaches in order to best control multiple dispersal pathways. Anthropogenic spread (propagules carried on humans or transported on produce or equipment) can be controlled with quarantine measures, which in turn can vary in intensity. In contrast, environmental spread processes are more difficult to control, but often have a temporal signal (e.g. seasonality) which can introduce both challenges and opportunities for surveillance and control. This leads to complex decisions regarding when, where and how to search. Recent modelling investigations of surveillance performance have optimised the output of simulation models, and found that a risk-weighted randomised search can perform close to optimally. However, exactly how quarantine and surveillance strategies should change to reflect different dispersal modes remains largely unaddressed. Here we develop a spatial simulation model of a plant fungal-pathogen incursion into an agricultural region, and its subsequent surveillance and control. We include structural differences in dispersal via the interplay of biological, environmental and anthropogenic connectivity between host sites (farms). Our objective was to gain broad insights into the relative roles played by different spread modes in propagating an invasion, and how incorporating knowledge of these spread risks may improve approaches to quarantine restrictions and surveillance. We find that broad heuristic rules for quarantine restrictions fail to contain the pathogen due to residual connectivity between sites, but surveillance measures enable early detection and successfully lead to suppression of the pathogen in all farms. Alternative surveillance strategies attain similar levels of performance by incorporating environmental or anthropogenic dispersal risk in the prioritisation of sites. Our model provides the basis to develop essential insights into the effectiveness of different surveillance and quarantine decisions for fungal pathogen control. Parameterised for authentic settings it will aid our understanding of how the extent and resolution of interventions should suitably reflect the spatial structure of dispersal processes.

Impact of wildfires and floods on property values: A before and after analysis

One of the most evident casualties of a natural disaster is the property market. The private and social costs from such events run into millions of dollars. In this paper, we use a unique dataset to examine the impact on residential house prices affected by natural disasters using a hedonic property (HP) values approach. For this purpose, we use data before and after a wildfire and floods from Rockhampton in central Queensland, Australia. The data is unique because one suburb was affected by wildfires and another was affected by floods. For the analysis, three suburbs namely Frenchville, Park Avenue and Norman Gardens are used. Frenchville was significantly affected by wildfires in the latter part of 2009 and to a lesser extent in 2012, while Park Avenue was affected by floods at the end of 2010, January 2011–2013. Norman Gardens, which was relatively unaffected, is used as a control site. This enables us to examine the before and after effects on property values in the three suburbs. The results confirm that soon after a natural disaster property prices in affected areas decrease even though the large majority of individual houses remain unaffected. Furthermore, the results indicate that the largely unaffected suburb may gain immediately after a natural disaster but this gain may disappear if natural disasters continue to occur in the area/region due to the stigma created. The results have several important policy decision and welfare implications which are briefly discussed in the paper.

Diaryl dihydropyrazole-3-carboxamides with significant in vivo antiobesity activity related to CB1 receptor antagonism: Synthesis, biological evaluation, and molecular modeling in the homology model

A number of analogues of diaryl dihydropyrazole-3-carboxamides have been synthesized. Their activities were evaluated for appetite suppression and body weight reduction in animal models. Depending on the chemical modification of the selected dihydropyrazole scaffold, the lead compoundsthe bisulfate salt of (±)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic acid morpholin-4-ylamide 26 and the bisulfate salt of (−)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic acid morpholin-4-ylamide 30showed significant body weight reduction in vivo, which is attributed to their CB1 antagonistic activity and exhibited a favorable pharmacokinetic profile. The molecular modeling studies also showed interactions of two isomers of (±)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4,5-dihydro-1H-pyrazole-3-carboxylic acid morpholin-4-ylamide 9 with CB1 receptor in the homology model similar to those of N-piperidino-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-3-pyrazole-carboxamide (rimonabant) 1 and 4S-(−)-3-(4-chlorophenyl)-N-methyl-N‘-[(4-chlorophenyl)-sulfonyl]-4-phenyl-4,5-dihydro-1H-pyrazole-1-carboxamidine (SLV-319) 2.

Assessing vulnerability at the urban interface

House loss during unplanned bushfires is a complex phenomenon where design, configuration, material and siting, can significantly influence the loss. In collaboration with the Bushfire Cooperative Research Centre the CSIRO has developed a tool to assess the vulnerability of a specific house at the urban interface. The tool is based on a spatial profiling of urban assets including their design, material, surrounding objects and their relationship amongst one another. The analysis incorporates both probabilistic and deterministic parameters, and is based on the impact of radiant heat, flame and embers on the surrounding elements and the structure itself. It provides a breakdown of the attributes and design parameters that contribute to the vulnerability level. This paper describes the tool which allows the user to explore the vulnerability of a house to varying levels of bushfire attacks. The tool is aimed at government agencies interested in building design, town planning and community education for bushfire risk mitigation.

Wear Next: An Exploration into the Future of Wearable Technology

Technology is increasingly infiltrating all aspects of our lives and the rapid uptake of devices that live near, on or in our bodies are facilitating radical new ways of working, relating and socialising. This distribution of technology into the very fabric of our everyday life creates new possibilities, but also raises questions regarding our future relationship with data and the quantified self. By embedding technology into the fabric of our clothes and accessories, it becomes ‘wearable’. Such ‘wearables’ enable the acquisition of and the connection to vast amounts of data about people and environments in order to provide life-augmenting levels of interactivity. Wearable sensors for example, offer the potential for significant benefits in the future management of our wellbeing. Fitness trackers such as ‘Fitbit’ and ‘Garmen’ provide wearers with the ability to monitor their personal fitness indicators while other wearables provide healthcare professionals with information that improves diagnosis. While the rapid uptake of wearables may offer unique and innovative opportunities, there are also concerns surrounding the high levels of data sharing that come as a consequence of these technologies. As more ‘smart’ devices connect to the Internet, and as technology becomes increasingly available (e.g. via Wi-Fi, Bluetooth), more products, artefacts and things are becoming interconnected. This digital connection of devices is called The ‘Internet of Things’ (IoT). IoT is spreading rapidly, with many traditionally non-online devices becoming increasingly connected; products such as mobile phones, fridges, pedometers, coffee machines, video cameras, cars and clothing. The IoT is growing at a rapid rate with estimates indicating that by 2020 there will be over 25 billion connected things globally. As the number of devices connected to the Internet increases, so too does the amount of data collected and type of information that is stored and potentially shared. The ability to collect massive amounts of data - known as ‘big data’ - can be used to better understand and predict behaviours across all areas of research from societal and economic to environmental and biological. With this kind of information at our disposal, we have a more powerful lens with which to perceive the world, and the resulting insights can be used to design more appropriate products, services and systems. It can however, also be used as a method of surveillance, suppression and coercion by governments or large organisations. This is becoming particularly apparent in advertising that targets audiences based on the individual preferences revealed by the data collected from social media and online devices such as GPS systems or pedometers. This type of technology also provides fertile ground for public debates around future fashion, identity and broader social issues such as culture, politics and the environment. The potential implications of these type of technological interactions via wearables, through and with the IoT, have never been more real or more accessible. But, as highlighted, this interconnectedness also brings with it complex technical, ethical and moral challenges. Data security and the protection of privacy and personal information will become ever more present in current and future ethical and moral debates of the 21st century. This type of technology is also a stepping-stone to a future that includes implantable technology, biotechnologies, interspecies communication and augmented humans (cyborgs). Technologies that live symbiotically and perpetually in our bodies, the built environment and the natural environment are no longer the stuff of science fiction; it is in fact a reality. So, where next?... The works exhibited in Wear Next_ provide a snapshot into the broad spectrum of wearables in design and in development internationally. This exhibition has been curated to serve as a platform for enhanced broader debate around future technology, our mediated future-selves and the evolution of human interactions. As you explore the exhibition, may we ask that you pause and think to yourself, what might we... Wear Next_? WEARNEXT ONLINE LISTINGS AND MEDIA COVERAGE: http://indulgemagazine.net/wear-next/ http://www.weekendnotes.com/wear-next-exhibition-gallery-artisan/ http://concreteplayground.com/brisbane/event/wear-next_/ http://www.nationalcraftinitiative.com.au/news_and_events/event/48/wear-next http://bneart.com/whats-on/wear-next_/ http://creativelysould.tumblr.com/post/124899079611/creative-weekend-art-edition http://www.abc.net.au/radionational/programs/breakfast/smartly-dressed-the-future-of-wearable-technology/6744374 http://couriermail.newspaperdirect.com/epaper/viewer.aspx RADIO COVERAGE http://www.abc.net.au/radionational/programs/breakfast/wear-next-exhibition-whats-next-for-wearable-technology/6745986 TELEVISION COVERAGE http://www.abc.net.au/radionational/programs/breakfast/wear-next-exhibition-whats-next-for-wearable-technology/6745986 https://au.news.yahoo.com/video/watch/29439742/how-you-could-soon-be-wearing-smart-clothes/#page1

Internet privatization, WikiLeaks, and free expression

In late 2010, the online nonprofit media organization WikiLeaks published classified documents detailing correspondence between the U.S. State Department and its diplomatic missions around the world, numbering around 250,000 cables. These diplomatic cables contained classified information with comments on world leaders, foreign states, and various international and domestic issues. Negative reactions to the publication of these cables came from both the U.S. political class (which was generally condemnatory of WikiLeaks, invoking national security concerns and the jeopardizing of U.S. interests abroad) and the corporate world, with various companies ceasing to continue to provide services to WikiLeaks despite no legal measure (e.g., a court injunction) forcing them to do so. This article focuses on the legal remedies available to WikiLeaks against this corporate suppression of its speech in the U.S. and Europe since these are the two principle arenas in which the actors concerned are operating. The transatlantic legal protection of free expression will be considered, yet, as will be explained in greater detail, the legal conception of this constitutional and fundamental right comes from a time when the state posed the greater threat to freedom. As a result, it is not generally enforceable against private, non-state entities interfering with speech and expression which is the case here. Other areas of law, namely antitrust/competition, contract and tort will then be examined to determine whether WikiLeaks and its partners can attempt to enforce their right indirectly through these other means. Finally, there will be some concluding thoughts about the implications of the corporate response to the WikiLeaks embassy cables leak for freedom of expression online.

Characterisation of the impact of open biomass burning on urban air quality in Brisbane, Australia

Open biomass burning from wildfires and the prescribed burning of forests and farmland is a frequent occurrence in South-East Queensland (SEQ), Australia. This work reports on data collected from 10-30 September 2011, which covers the days before (10-14 September), during (15-20 September) and after (21-30 September) a period of biomass burning in SEQ. The aim of this project was to comprehensively quantify the impact of the biomass burning on air quality in Brisbane, the capital city of Queensland. A multi-parameter field measurement campaign was conducted and ambient air quality data from 13 monitoring stations across SEQ were analysed. During the burning period, the average concentrations of all measured pollutants increased (from 20% to 430%) compared to the non-burning period (both before and after burning), except for total xylenes. The average concentration of O3, NO2, SO2, benzene, formaldehyde, PM10, PM2.5 and visibility-reducing particles reached their highest levels for the year, which were up to 10 times higher than annual average levels, while PM10, PM2.5 and SO2 concentrations exceeded the WHO 24-hour guidelines and O3 concentration exceeded the WHO maximum 8-hour average threshold during the burning period. Overall spatial variations showed that all measured pollutants, with the exception of O3, were closer to spatial homogeneity during the burning compared to the non-burning period. In addition to the above, elevated concentrations of three biomass burning organic tracers (levoglucosan, mannosan and galactosan), together with the amount of non-refractory organic particles (PM1) and the average value of f60 (attributed to levoglucosan), reinforce that elevated pollutant concentration levels were due to emissions from open biomass burning events, 70% of which were prescribed burning events. This study, which is the first and most comprehensive of its kind in Australia, provides quantitative evidence of the significant impact of open biomass burning events, especially prescribed burning, on urban air quality. The current results provide a solid platform for more detailed health and modelling investigations in the future.