Retrograde transport pathways utilised by viruses and protein toxins

A model has been presented for retrograde transport of certain toxins and viruses from the cell surface to the ER that suggests an obligatory interaction with a glycolipid receptor at the cell surface. Here we review studies on the ER trafficking cholera toxin, Shiga and Shiga-like toxins, Pseudomonas exotoxin A and ricin, and compare the retrograde routes followed by these protein toxins to those of the ER trafficking SV40 and polyoma viruses. We conclude that there is in fact no obligatory requirement for a glycolipid receptor, nor even with a protein receptor in a lipid-rich environment. Emerging data suggests instead that there is no common pathway utilised for retrograde transport by all of these pathogens, the choice of route being determined by the particular receptor utilised

An integrative approach to understanding mussel community structure: Linking biodiversity, environmental context and physiology.

The focus of my third chapter is an integration of the physiology information collected in chapter two to address how species dominance of two distinct thermal guilds (thermally-tolerant and thermally-sensitive) influences gross primary production. I manipulated temperature (15, 25, and 35° C) and species dominance of five mussel species (A. ligamentina, A. plicata and Q. pustulosa, M. nervosa, and O. reflexa) using 1101 re-circulating stream mesocosms housed in an environmentally-controlled room. I quantified individual-based measures of resource acquisition (oxygen consumption, body condition index) and ecosystem services (ammonia and phosphorus excretion rates) for each species. In addition, I quantified gross primary production in the water column, benthos, and the entire stream mesocosm. Gross primary production was highest at 35° C and was positively related to both A. ligamentina and A. plicata dominance with communities. However, species dominance differentially influenced gross primary production of different compartments within the mesocosms with A. plicata (a thermally-tolerant species) positively influencing benthic production, and A. ligamentina (a thermally-sensitive species) positively influencing water column production. Species interactions within treatments were context dependent with A. ligamentina positively influencing A. plicata, M. nervosa, and O. reflexa at 25° C and negatively influencing M. nervosa and O. reflexa at 35° C. In addition to influencing resource acquisition, species dominance also influenced species-specific nutrient excretion rates and subsequently water-column nutrient levels.The research detailed in my second chapter built upon observed patterns of alternating species dominance by asking if different mussel species performed differently under a variety of thermal regimes. To address this question, I acclimated eight mussel species (Lampsilis cardium, Fusconaia flava, Actinonaias ligamentina, Megalonaias nervosa, Amblema plicata, Quadrula pustulosa, Obliquaria reflexa, and Truncilla truncata) to four temperatures (5, 15, 25, and 35° C). I quantified resource acquisition (clearance rate and oxygen consumption), assimilation (glycogen, body condition index, and Q10 rates of anabolism and catabolism), and ecosystem services (ammonia and phosphorus excretion rates, and biodeposition rates) using temperature-controlled respirometers. The results of this experiment demonstrate that although mussels are generally categorized as "filter feeders", there are distinct guilds within this functional group associated with their response to temperature. Megalonaias nervosa, Amblema plicata, Obliquaria reflexa, and Fusconaia flava are thermally-tolerant species assimilating energy at 35° C and increasing the magnitude of services (nutrient excretion, clearance and biodeposition rates) they contribute to ecosystems. Alternatively, A. ligamentina, L. cardium, Q. pustulosa , and Truncilla truncata appear to be thermally-sensitive with increased rates of catabolism at 35° C. However, the functional responses of thermally-sensitive species appeared to differ with some species decreasing filtration activity and increasing rates of nutrient excretion and others increasing both filtration and nutrient excretion rates. Extrapolating these data to real mussel communities highlighted the importance of the relative dominance between thermally-sensitive and tolerant-species under differing environmental contexts. Furthermore, shifts in community structure would be predicted to influence the nature of filtration, biodeposition and nutrient dynamics under current models of climate change.My first chapter integrated biodiversity partitioning techniques with mussel community data across twenty one mussel beds to determine if mussel community biomass could be explained by patterns of species richness or species dominance. This partitioning approach tested the null hypothesis that biomass accrual within mussel beds is equal at all sites. The results of this work demonstrated that mussel biomass is largely explained by complementarity, which indicates that either niche partitioning or facilitation between mussel species is occurring. This conclusion was further supported by the fact that complementarity was highest in species rich, thermally variable mussel beds. In addition, numerically rarer species were in better condition (reduced oxygen consumption rates and higher body condition indices) in species-rich, thermally variable mussel beds which suggests that there is an energetic benefit to living in species rich communities.The research detailed in my dissertation broadens our understanding of the biodiversity-ecosystem function paradigm using long-lived invertebrates in a freshwater ecosystem. Freshwater mussels (Unionoidea) are a globally threatened fauna with 70% of taxa considered threatened, yet little is known concerning their functional role. In addition to species extinctions, the overall biomass of both abundant and rare unionid species is declining in most rivers, and this loss of filter-feeding biomass is predicted to impact river function

Survey of physician knowledge regarding antiretroviral medications in hospitalized HIV-infected patients

<p>Abstract</p> <p>Background</p> <p>Antiretroviral prescribing errors are common among hospitalized patients. Inadequate medical knowledge is likely one of the factors leading to these errors. Our objective was to determine the proportion of hospital physicians with knowledge gaps about prescribing antiretroviral medications for hospitalized HIV-infected patients and to correlate knowledge with length and type of medical training and experience.</p> <p>Methods</p> <p>We conducted an electronic survey comprising of ten clinical scenarios based on antiretroviral-prescribing errors seen at two community teaching hospitals. It also contained demographic questions regarding length and type of medical training and antiretroviral prescribing experience. Three hundred and forty three physicians at both hospitals were asked to anonymously complete the survey between February 2007 and April 2007.</p> <p>Results</p> <p>One hundred and fifty-seven physicians (46%) completed at least one question. The mean percentage of correct responses was 33% for resident physicians, 37% for attending physicians, and 93% for Infectious Diseases or HIV (ID/HIV) specialist physicians. Higher scores were independently associated with ID/HIV specialty, number of outpatients seen per month and physician reported comfort level in managing HIV patients (P < .001).</p> <p>Conclusion</p> <p>Non-ID/HIV physicians had uniformly poor knowledge of common antiretroviral medication regimens. Involvement of ID/HIV specialists in the prescribing of antiretrovirals in hospitalized patients might mitigate prescribing errors stemming from knowledge deficits.</p

Baywide anchovy study sub-program : milestone report no. 4 (2011)

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Marine transport infrastructure development in Moreton Bay: Dredging, monitoring and future directions

Marine infrastructure development throughout southeast Queensland is fast-paced, with the ongoing expansion of our major ports and harbours, airports and road infrastructure. Our cities and regional centres continue to expand along the Queensland coastline and into the marine environment through dredging and land reclamation. These activities are managed from an environmental protection perspective at the local, State and Commonwealth government levels. Here we examine the maintenance and capital dredging works undertaken by the Port of Brisbane Pty Ltd (PBPL), Department of Transport and Main Roads (DTMR) and Brisbane Airport Corporation (BAC), which are necessary for maintaining ports and marina infrastructure, roads and runways. A variety of methods has been adopted over the past few decades for managing potential marine environmental impacts from these dredging activities. This chapter explores the different monitoring tools implemented by the PBPL, DTMR and BAC for managing potential impacts from port and harbour maintenance, capital works programs and operational activities. We consider the regulatory environment and how this influences port and harbour works, road and airport infrastructure development within the Bay. We also explore new technology and approaches to monitoring and the areas of future research and investigation to help contribute towards a sustainable future for Moreton Bay

The secretion inhibitor Exo2 perturbs trafficking of Shiga toxin between endosomes and the trans-Golgi network

The small-molecule inhibitor Exo2 {4-hydroxy-3-methoxy-(5,6,7,8-tetrahydrol[1]benzothieno[2,3-d]pyrimidin-4-yl)hydraz-one benzaldehyde} has been reported to disrupt the Golgi apparatus completely and to stimulate Golgi–ER (endoplasmic reticulum) fusion in mammalian cells, akin to the well-characterized fungal toxin BFA (brefeldin A). It has also been reported that Exo2 does not affect the integrity of the TGN (trans-Golgi network), or the direct retrograde trafficking of the glycolipid-binding cholera toxin from the TGN to the ER lumen. We have examined the effects of BFA and Exo2, and found that both compounds are indistinguishable in their inhibition of anterograde transport and that both reagents significantly disrupt the morphology of the TGN in HeLa and in BS-C-1 cells. However, Exo2, unlike BFA, does not induce tubulation and merging of the TGN and endosomal compartments. Furthermore, and in contrast with its effects on cholera toxin, Exo2 significantly perturbs the delivery of Shiga toxin to the ER. Together, these results suggest that the likely target(s) of Exo2 operate at the level of the TGN, the Golgi and a subset of early endosomes, and thus Exo2 provides a more selective tool than BFA for examining membrane trafficking in mammalian cells