Molecular analysis of asymptomatic bacteriuria escherichia coli strain VR50 reveals adaptation to the urinary tract by gene acquisition

Urinary tract infections (UTIs) are among the most common infectious diseases of humans, with Escherichia coli responsible for >80% of all cases. One extreme of UTI is asymptomatic bacteriuria (ABU), which occurs as an asymptomatic carrier state that resembles commensalism. To understand the evolution and molecular mechanisms that underpin ABU, the genome of the ABU E. coli strain VR50 was sequenced. Analysis of the complete genome indicated that it most resembles E. coli K-12, with the addition of a 94-kb genomic island (GI-VR50-pheV), eight prophages, and multiple plasmids. GI-VR50-pheV has a mosaic structure and contains genes encoding a number of UTI-associated virulence factors, namely, Afa (afimbrial adhesin), two autotransporter proteins (Ag43 and Sat), and aerobactin. We demonstrated that the presence of this island in VR50 confers its ability to colonize the murine bladder, as a VR50 mutant with GI-VR50-pheV deleted was attenuated in a mouse model of UTI in vivo. We established that Afa is the island-encoded factor responsible for this phenotype using two independent deletion (Afa operon and AfaE adhesin) mutants. E. coli VR50afa and VR50afaE displayed significantly decreased ability to adhere to human bladder epithelial cells. In the mouse model of UTI, VR50afa and VR50afaE displayed reduced bladder colonization compared to wild-type VR50, similar to the colonization level of the GI-VR50-pheV mutant. Our study suggests that E. coli VR50 is a commensal-like strain that has acquired fitness factors that facilitate colonization of the human bladder.

Determinants of trade in recyclable wastes: Evidence from commodity-based trade of waste and scrap

This paper examines factors that affect the trade of recyclable waste in both exporting and importing countries. To this end, we employ two important elements: first, we adopt a gravity model in our empirical methodology; second, we select five waste and scrap commodities and undertake estimations using commodity-level trade data. We demonstrate that, the higher the wage/per capita GDP/population of an importing country, the more recyclable wastes it imports. This result suggests that the demand for final goods and, accordingly, the demand for materials including recycled material, have strong effects on the import volume of recyclable waste. Moreover, this implies that the imports of a developing country from developed countries increase with expanding industrial activity and economic growth. We find no evidence for a pollution haven for wastes and recycling.

Breakfast at Tiffany's': eBay Inc., trade mark law, and counterfeiting

In an exploration of intellectual property and fashion, this article examines the question of the intermediary liability of online auction-houses for counterfeiting. In the United States, the illustrious jewellery store, Tiffany & Co, brought a legal action against eBay Inc, alleging direct trademark infringement, contributory trademark infringement, false advertising, unfair competition and trademark dilution. The luxury store depicted the online auction-house as a pirate bazaar, a flea-market and a haven for counterfeiting. During epic litigation, eBay Inc successfully defended itself against these allegations in a United States District Court and the United States Court of Appeals for the Second Circuit. Tiffany & Co made a desperate, unsuccessful effort to appeal the matter to the Supreme Court of the United States. The matter featured a number of interventions from amicus curiae — Tiffany was supported by Coty, the Fashion Designer's Guild, and the International Anticounterfeiting Coalition, while eBay was defended by publicly-spirited civil society groups such as Electronic Frontier Foundation, Public Citizen, and Public Knowledge as well as Yahoo!, Google Inc, Amazon.com, and associations representing telecommunications carriers and internet service providers. The litigation in the United States can be counterpointed with the fusillade of legal action against eBay in the European Union. In contrast to Tiffany & Co, Louis Vuitton triumphed over eBay in the French courts — claiming its victory as vindication of the need to protect the commercial interests and cultural heritage of France. However, eBay has fared somewhat better in a dispute with L’Oréal in Great Britain and the European Court of Justice. It is argued that, in a time of flux and uncertainty, Australia should follow the position of the United States courts in Tiffany & Co v eBay Inc. The final part examines the ramifications of this litigation over online auction-houses for trade mark law reform and consumer rights; parallel disputes over intermediary liability and safe harbours in the field of copyright law and the Anti-Counterfeiting Trade Agreement 2010. The conclusion calls for a revision of trade mark law, animated by a respect for consumers’ rights and interests in the electronic marketplace.

LaTeX Template for Writing QUT Thesis (Research Masters and PhD)

A LATEX style file, named qutthesis.sty, is developed, for writing PhD or Research Masters thesis. Developed by Professor Glen Yu-Chu Tian, it tries to fulfill QUT’s Thesis requirements but it is unofficial.

Effects of cold water immersion and active recovery on hemodynamics and recovery of muscle strength following resistance exercise

Cold water immersion (CWI) and active recovery (ACT) are frequently used as post-exercise recovery strategies. However, the physiological effects of CWI and ACT after resistance exercise are not well characterized. We examined the effects of CWI and ACT on cardiac output (Q), muscle oxygenation (SmO2) and blood volume (tHb), muscle temperature (Tmuscle ) and isometric strength after resistance exercise. On separate days, 10 men performed resistance exercise, followed by 10 min CWI at 10°C or 10 min ACT (low-intensity cycling). Q (7.9±2.7 l) and Tmuscle (2.2±0.8ºC) increased, whereas SmO2 (-21.5±8.8%) and tHb (-10.1±7.7 μM) decreased after exercise (p<0.05). During CWI, Q ̇(-1.1±0.7 l) and Tmuscle (-6.6±5.3ºC) decreased, while tHb (121±77 μM) increased (p<0.05). In the hour after CWI, Q ̇and Tmuscle remained low, while tHb also decreased (p<0.05). By contrast, during ACT, Q ̇(3.9±2.3 l), Tmuscle (2.2±0.5ºC), SmO2 (17.1±5.7%) and tHb (91±66 μM) all increased (p<0.05). In the hour after ACT, Tmuscle and tHb remained high (p<0.05). Peak isometric strength during 10 s maximum voluntary contractions (MVCs) did not change significantly after CWI, whereas it decreased after ACT (-30 to -45 Nm; p<0.05). Muscle deoxygenation time during MVCs increased after ACT (p<0.05), but not after CWI. Muscle reoxygenation time after MVCs tended to increase after CWI (p=0.052). These findings suggest firstly that hemodynamics and muscle temperature after resistance exercise are dependent on ambient temperature and metabolic demands with skeletal muscle, and secondly, that recovery of strength after resistance exercise is independent of changes in hemodynamics and muscle temperature.

Infection and cellular defense dynamics in a novel 17beta-estradiol murine model of chronic human group B streptococcus genital tract colonization reveal a role for hemolysin in persistence and neutrophil accumulation

Genital tract carriage of group B streptococcus (GBS) is prevalent among adult women; however, the dynamics of chronic GBS genital tract carriage, including how GBS persists in this immunologically active host niche long term, are not well defined. To our knowledge, in this study, we report the first animal model of chronic GBS genital tract colonization using female mice synchronized into estrus by delivery of 17β-estradiol prior to intravaginal challenge with wild-type GBS 874391. Cervicovaginal swabs, which were used to measure bacterial persistence, showed that GBS colonized the vaginal mucosa of mice at high numbers (106–107 CFU/swab) for at least 90 d. Cellular and histological analyses showed that chronic GBS colonization of the murine genital tract caused significant lymphocyte and PMN cell infiltrates, which were localized to the vaginal mucosal surface. Long-term colonization was independent of regular hormone cycling. Immunological analyses of 23 soluble proteins related to chemotaxis and inflammation showed that the host response to GBS in the genital tract comprised markers of innate immune activation including cytokines such as GM-CSF and TNF-α. A nonhemolytic isogenic mutant of GBS 874391, Δcyle9, was impaired for colonization and was associated with amplified local PMN responses. Induction of DNA neutrophil extracellular traps, which was observed in GBS-infected human PMNs in vitro in a hemolysin-dependent manner, appeared to be part of this response. Overall, this study defines key infection dynamics in a novel murine model of chronic GBS genital tract colonization and establishes previously unknown cellular and soluble defense responses to GBS in the female genital tract.

Pathogens penetrating the central nervous system: Infection pathways and the cellular and molecular mechanisms of invasion

The brain is well protected against microbial invasion by cellular barriers, such as the blood-brain barrier (BBB) and the blood-cerebrospinal fluid barrier (BCSFB). In addition, cells within the central nervous system (CNS) are capable of producing an immune response against invading pathogens. Nonetheless, a range of pathogenic microbes make their way to the CNS, and the resulting infections can cause significant morbidity and mortality. Bacteria, amoebae, fungi, and viruses are capable of CNS invasion, with the latter using axonal transport as a common route of infection. In this review, we compare the mechanisms by which bacterial pathogens reach the CNS and infect the brain. In particular, we focus on recent data regarding mechanisms of bacterial translocation from the nasal mucosa to the brain, which represents a little explored pathway of bacterial invasion but has been proposed as being particularly important in explaining how infection with Burkholderia pseudomallei can result in melioidosis encephalomyelitis.

Dynamic, invivo, real-time detection of retinal oxidative status in a model of elevated intraocular pressure using a novel, reversibly responsive, profluorescent nitroxide probe

Changes to the redox status of biological systems have been implicated in the pathogenesis of a wide variety of disorders including cancer, Ischemia-reperfusion (I/R) injury and neurodegeneration. In times of metabolic stress e.g. ischaemia/reperfusion, reactive oxygen species (ROS) production overwhelms the intrinsic antioxidant capacity of the cell, damaging vital cellular components. The ability to quantify ROS changes in vivo, is therefore essential to understanding their biological role. Here we evaluate the suitability of a novel reversible profluorescent probe containing a redox-sensitive nitroxide moiety (methyl ester tetraethylrhodamine nitroxide, ME-TRN), as an in vivo, real-time reporter of retinal oxidative status. The reversible nature of the probe's response offers the unique advantage of being able to monitor redox changes in both oxidizing and reducing directions in real time. After intravitreal administration of the ME-TRN probe, we induced ROS production in rat retina using an established model of complete, acute retinal ischaemia followed by reperfusion. After restoration of blood flow, retinas were imaged using a Micron III rodent fundus fluorescence imaging system, to quantify the redox-response of the probe. Fluorescent intensity declined during the first 60 min of reperfusion. The ROS-induced change in probe fluorescence was ameliorated with the retinal antioxidant, lutein. Fluorescence intensity in non-Ischemia eyes did not change significantly. This new probe and imaging technology provide a reversible and real-time response to oxidative changes and may allow the in vivo testing of antioxidant therapies of potential benefit to a range of diseases linked to oxidative stress

Multimodal polymer nanoparticles with combined 19F magnetic resonance and optical detection for tunable, targeted, multimodal imagingin vivo

Understanding the complex nature of diseased tissue in vivo requires development of more advanced nanomedicines, where synthesis of multifunctional polymers combines imaging multimodality with a biocompatible, tunable, and functional nanomaterial carrier. Here we describe the development of polymeric nanoparticles for multimodal imaging of disease states in vivo. The nanoparticle design utilizes the abundant functionality and tunable physicochemical properties of synthetically robust polymeric systems to facilitate targeted imaging of tumors in mice. For the first time, high-resolution 19F/1H magnetic resonance imaging is combined with sensitive and versatile fluorescence imaging in a polymeric material for in vivo detection of tumors. We highlight how control over the chemistry during synthesis allows manipulation of nanoparticle size and function and can lead to very high targeting efficiency to B16 melanoma cells, both in vitro and in vivo. Importantly, the combination of imaging modalities within a polymeric nanoparticle provides information on the tumor mass across various size scales in vivo, from millimeters down to tens of micrometers.

Global, regional, and national disability-adjusted life years (DALYs) for 306 diseases and injuries and healthy life expectancy (HALE) for 188 countries, 1990–2013: Quantifying the epidemiological transition

Background The Global Burden of Disease Study 2013 (GBD 2013) aims to bring together all available epidemiological data using a coherent measurement framework, standardised estimation methods, and transparent data sources to enable comparisons of health loss over time and across causes, age–sex groups, and countries. The GBD can be used to generate summary measures such as disability-adjusted life-years (DALYs) and healthy life expectancy (HALE) that make possible comparative assessments of broad epidemiological patterns across countries and time. These summary measures can also be used to quantify the component of variation in epidemiology that is related to sociodemographic development. Methods We used the published GBD 2013 data for age-specific mortality, years of life lost due to premature mortality (YLLs), and years lived with disability (YLDs) to calculate DALYs and HALE for 1990, 1995, 2000, 2005, 2010, and 2013 for 188 countries. We calculated HALE using the Sullivan method; 95% uncertainty intervals (UIs) represent uncertainty in age-specific death rates and YLDs per person for each country, age, sex, and year. We estimated DALYs for 306 causes for each country as the sum of YLLs and YLDs; 95% UIs represent uncertainty in YLL and YLD rates. We quantified patterns of the epidemiological transition with a composite indicator of sociodemographic status, which we constructed from income per person, average years of schooling after age 15 years, and the total fertility rate and mean age of the population. We applied hierarchical regression to DALY rates by cause across countries to decompose variance related to the sociodemographic status variable, country, and time. Findings Worldwide, from 1990 to 2013, life expectancy at birth rose by 6·2 years (95% UI 5·6–6·6), from 65·3 years (65·0–65·6) in 1990 to 71·5 years (71·0–71·9) in 2013, HALE at birth rose by 5·4 years (4·9–5·8), from 56·9 years (54·5–59·1) to 62·3 years (59·7–64·8), total DALYs fell by 3·6% (0·3–7·4), and age-standardised DALY rates per 100 000 people fell by 26·7% (24·6–29·1). For communicable, maternal, neonatal, and nutritional disorders, global DALY numbers, crude rates, and age-standardised rates have all declined between 1990 and 2013, whereas for non–communicable diseases, global DALYs have been increasing, DALY rates have remained nearly constant, and age-standardised DALY rates declined during the same period. From 2005 to 2013, the number of DALYs increased for most specific non-communicable diseases, including cardiovascular diseases and neoplasms, in addition to dengue, food-borne trematodes, and leishmaniasis; DALYs decreased for nearly all other causes. By 2013, the five leading causes of DALYs were ischaemic heart disease, lower respiratory infections, cerebrovascular disease, low back and neck pain, and road injuries. Sociodemographic status explained more than 50% of the variance between countries and over time for diarrhoea, lower respiratory infections, and other common infectious diseases; maternal disorders; neonatal disorders; nutritional deficiencies; other communicable, maternal, neonatal, and nutritional diseases; musculoskeletal disorders; and other non-communicable diseases. However, sociodemographic status explained less than 10% of the variance in DALY rates for cardiovascular diseases; chronic respiratory diseases; cirrhosis; diabetes, urogenital, blood, and endocrine diseases; unintentional injuries; and self-harm and interpersonal violence. Predictably, increased sociodemographic status was associated with a shift in burden from YLLs to YLDs, driven by declines in YLLs and increases in YLDs from musculoskeletal disorders, neurological disorders, and mental and substance use disorders. In most country-specific estimates, the increase in life expectancy was greater than that in HALE. Leading causes of DALYs are highly variable across countries. Interpretation Global health is improving. Population growth and ageing have driven up numbers of DALYs, but crude rates have remained relatively constant, showing that progress in health does not mean fewer demands on health systems. The notion of an epidemiological transition—in which increasing sociodemographic status brings structured change in disease burden—is useful, but there is tremendous variation in burden of disease that is not associated with sociodemographic status. This further underscores the need for country-specific assessments of DALYs and HALE to appropriately inform health policy decisions and attendant actions.