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

The Impact of Turfgrass Pest Management System Techniques on Surface and Ground Water Quality

ReportThe impact of various turfgrass pest management strategies (PMS) on water quality has recently become a concern for many golf course superintendents, sports facilities managers and homeowners. With water quality standards becoming increasingly stringent, management practices have had to follow suit. Uses of alternative control strategies have become increasingly important. This includes the use of biological, cultural and preventative control practices to reduce pest pressure, as well as environmental impacts. Turfgrass is, no doubt, a beneficial addition to most ecosystems, yet when mis-managed can cause harm as well. Mis-management of the turfgrass ecosystem can greatly influence the nitrogen, phosphate and pesticide levels in surface and ground water, causing problems for communities that depend on clean water for consumption as well as recreation. Aquatic ecosystems as well can be severely harmed by increased levels of nitrogen and phosphate, which can cause algal bloom, decreased dissolved oxygen levels, and eutrophication, which in turn has an impact on nearly all ecosystems. Pesticides that find their way into surface or ground water pose a problem to exposed species ranging from fish to humans. When managed correctly, turfgrass provides many positive attributes, including increased UV absorption, CO2 remediation, soil stabilization, ground and surface water filtration, and aesthetic benefits. It is our goal to test the impact of three of the most commonly implemented turfgrass pest management systems, (preventative, IPM, and organic systems) on surface and ground water quality and turfgrass performance. The results will hopefully provide answers on how to produce acceptable turfgrass quality while benefiting the environment

The contribution of constitutional supercooling to nucleation and grain formation

The concept of constitutional supercooling (CS) including the term itself was first described and discussed qualitatively by Rutter and Chalmers in order to understand the formation of cellular structures during the solidification of tin, and then quantified by Tiller et al. On that basis, Winegard and Chalmers further considered 'supercooling and dendritic freezing of alloys' where they described how CS promotes the heterogeneous nucleation of new crystals and the formation of an equiaxed zone. Since then the importance of CS in promoting the formation of equiaxed microstructures in both grain refined and unrefined alloys has been clearly revealed and quantified. This paper describes our current understanding of the role of CS in promoting nucleation and grain formation. It also highlights that CS, on the one hand, develops a nucleation-free zone surrounding each nucleated and growing grain and, on the other hand, protects this grain from readily remelting when temperature fluctuations occur due to convection. Further, due to the importance of the diffusion field that generates CS, recent analytical models are evaluated and compared with a numerical model. A comprehensive description of the mechanisms affecting nucleation and grain formation and the prediction of grain size is presented with reference to the influence of the casting conditions applied during the practical casting of an alloy

The Influence of the effect of solute on the thermodynamic driving force on grain refinement of Al alloys

Grain refinement is known to be strongly affected by the solute in cast alloys. Addition of some solute can reduce grain size considerably while others have a limited effect. This is usually attributed to the constitutional supercooling which is quantified by the growth restriction factor, Q. However, one factor that has not been considered is whether different solutes have differing effects on the thermodynamic driving force for solidification. This paper reveals that addition of solute reduces the driving force for solidification for a given undercooling, and that for a particular Q value, it is reduced more substantially when adding eutectic-forming solutes than peritectic-forming elements. Therefore, compared with the eutectic-forming solutes, addition of peritectic-forming solutes into Al alloys not only possesses a higher initial nucleation rate resulted from the larger thermodynamic driving force for solidification, but also promotes nucleation within the constitutionally supercooled zone during growth. As subsequent nucleation can occur at smaller constitutional supercoolings for peritectic-forming elements, a smaller grain size is thus produced. The very small constitutional supercooling required to trigger subsequent nucleation in alloys containing Ti is considered as a major contributor to its extraordinary grain refining efficiency in cast Al alloys even without the deliberate addition of inoculants.The Australian Research Council (ARC DP10955737)

Recent advances in grain refinement of light metals and alloys

Grain refinement leads, in general, to a decreased tendency to hot tearing, a more dispersed and refined porosity distribution, and improved directional feeding characteristics during solidification. Reduced as-cast grain size can also lead to improved mechanical properties and wrought processing by reducing the recrystallized grain size and achieving a fully recrystallized microstructure. It is now well established that the two key factors controlling grain refinement are the nucleant particles including their potency, size distribution and particle number density, and the rate of development of growth restriction, Q, generated by the alloy chemistry which establishes the undercooling needed to trigger nucleation events and facilitates their survival. The theories underpinning our current understanding of nucleation and grain formation are presented. The application of the latest theories to the light alloys of Al, Mg and Ti is explored as well as their applicability to a range of casting and solidification environments. In addition, processing by the application of physical processes such as external fields and additive manufacturing is discussed. To conclude, the current challenges for the development of reliable grain refining technologies for difficult to refine alloy systems are presented

Mucosal Immunization with the Moraxella Catarrhalis Porin M35 Induces Enhanced Bacterial Clearance from the Lung: A Possible Role for Opsonophagocytosis

Moraxella catarrhalis is a significant cause of respiratory tract infection against which a vaccine is sought. Several outer membrane proteins are currently under investigation as potential vaccine antigens, including the porin M35. We have previously shown that the third external loop of M35 was immunodominant over the remainder of the protein for antibody produced in mice against the refolded recombinant protein. However, as this loop is predicted to fold inside the porin channel we also predicted that it would not be accessible to these antibodies when M35 is expressed on the surface of the bacteria in its native conformation. This study investigated the functional activity of antibodies against M35 and those specific for the loop 3 region of M35 in vitro and in vivo. Antisera from mice immunized with M35 or the loop 3-deletion, M35loop3−, recombinant proteins were not bactericidal but did have enhanced opsonic activity, whereas antibodies raised against the loop 3 peptide were not opsoniszing indicating that the immunodominant loop 3 of M35 was not accessible to antibody as we had previously predicted. Mucosal immunization with M35, M35 that had an antigenically altered loop 3 [M35(ID78)] and M35loop3− enhanced the clearance of M. catarrhalis from the lungs of mice challenged with live M. catarrhalis. The in vivo clearance of bacteria in the mice with the M35-derived protein constructs correlated significantly (p < 0.001) with the opsonic activity assessed an in vitro opsonophagocytosis assay. This study has demonstrated that the immunodominant B-cell epitope to loop 3 of the M. catarrhalis outer membrane protein M35 is not associated with immune protection and that M35-specific antibodies are not bactericidal but are opsoniszing. The opsoniszing activity correlated with in vivo clearance of the bacteria suggesting that opsoniszing antibody may be a good correlate of immune protection

Strategies Employed by Community-Based Service Providers to Address HIV-Associated Neurocognitive Challenges: A Qualitative Study

Background: HIV-associated neurocognitive disorders and other causes of neurocognitive challenges experienced by people living with HIV (PLWH) persist as public health concerns in developed countries. Consequently, PLWH who experience neurocognitive challenges increasingly require social support and mental health services from community-based providers in the HIV sector. Methods: Thirty-three providers from 22 AIDS service organizations across Ontario, Canada, were interviewed to determine the strategies they used to support PLWH experiencing neurocognitive difficulties. Thematic analysis was conducted to determine key themes from the interview data. Results: Three types of strategies were identified: (a) intrapersonal, (b) interpersonal, and (c) organizational. Intrapersonal strategies involved learning and staying informed about causes of neurocognitive challenges. Interpersonal strategies included providing practical assistance, information, counseling, and/or referrals to PLWH. Organizational strategies included creating dedicated support groups for PLWH experiencing neurocognitive challenges, partnering with other organizations with services not available within their own organization, and advocating for greater access to services with expertise and experience working with PLWH. Conclusion: Through concerted efforts in the future, it is likely that empirically investigating, developing, and customizing these strategies specifically to address HIV-associated neurocognitive challenges will yield improved social support and mental health outcomes for PLWH

Quantitative Trait Loci for Vegetative Traits in Perennial Ryegrass (\u3cem\u3eLolium Perenne\u3c/em\u3e L.)

Physiological (EP) research in forage grasses relates traits such as leaf elongation rate (LER), leaf elongation duration (LED), and leaf appearance interval (ALf), to forage yield (Chapman & Lemaire, 1993). This paper reveals preliminary quantitative trait locus (QTL) discovery for eight EP traits in perennial ryegrass. It also investigates the potential role of multivariate analyses such as principal component analysis (PCA) in QTL analysis of EP data

Structure and Metal Binding Properties of ZnuA, a Periplasmic Zinc Transporter from \u3cem\u3eEscherichia coli\u3c/em\u3e

ZnuA is the periplasmic Zn2+-binding protein associated with the high-affinity ATP-binding cassette ZnuABC transporter from Escherichia coli. Although several structures of ZnuA and its homologs have been determined, details regarding metal ion stoichiometry, affinity, and specificity as well as the mechanism of metal uptake and transfer remain unclear. The crystal structures of E. coli ZnuA (Eco-ZnuA) in the apo, Zn2+-bound, and Co2+-bound forms have been determined. ZnZnuA binds at least two metal ions. The first, observed previously in other structures, is coordinated tetrahedrally by Glu59, His60, His143, and His207. Replacement of Zn2+ with Co2+ results in almost identical coordination geometry at this site. The second metal binding site involves His224 and several yet to be identified residues from the His-rich loop that is unique to Zn2+ periplasmic metal binding receptors. Electron paramagnetic resonance and X-ray absorption spectroscopic data on CoZnuA provide additional insight into possible residues involved in this second site. The second site is also detected by metal analysis and circular dichroism (CD) titrations. Eco-ZnuA binds Zn2+ (estimated K d \u3c 20 nM), Co2+, Ni2+, Cu2+, Cu+, and Cd2+, but not Mn2+. Finally, conformational changes upon metal binding observed in the crystal structures together with fluorescence and CD data indicate that only Zn2+ substantially stabilizes ZnuA and might facilitate recognition of ZnuB and subsequent metal transfer