Wheat pathogen Zymoseptoria tritici N-myristoyltransferase inhibitors: on-target antifungal activity and an unusual metabolic defense mechanism

Zymoseptoria tritici is the causative agent of Septoria tritici blotch (STB), which costs billions of dollars annually to major wheat-producing countries in terms of both fungicide use and crop loss. Agricultural pathogenic fungi have acquired resistance to most commercially available fungicide classes, and the rate of discovery and development of new fungicides has stalled, demanding new approaches and insights. Here we investigate a potential mechanism of targeting an important wheat pathogen Z. tritici via inhibition of N-myristoyltransferase (NMT). We characterize Z. tritici NMT biochemically for the first time, profile the in vivo Z. tritici myristoylated proteome and identify and validate the first Z. tritici NMT inhibitors. Proteomic investigation of the downstream effects of NMT inhibition identified an unusual and novel mechanism of defense against chemical toxicity in Z. tritici through the application of comparative bioinformatics to deconvolute function from the previously largely unannotated Z. tritici proteome. Research into novel fungicidal modes-of-action is essential to satisfy an urgent unmet need for novel fungicide targets, and we anticipate that this study will serve as a useful proteomics and bioinformatics resource for researchers studying Z. tritici

Mathematical modelling long-term effects of replacing Prevnar7 with Prevnar13 on invasive pneumococcal diseases in England and Wales

England and Wales recently replaced the 7-valent pneumococcal conjugate vaccine (PCV7) with its 13-valent equivalent (PCV13), partly based on projections from mathematical models of the long-term impact of such a switch compared to ceasing pneumococcal conjugate vaccination altogether. A compartmental deterministic model was used to estimate parameters governing transmission of infection and competition between different groups of pneumococcal serotypes prior to the introduction of PCV13. The best-fitting parameters were used in an individual based model to describe pneumococcal transmission dynamics and effects of various options for the vaccination programme change in England and Wales. A number of scenarios were conducted using (i) different assumptions about the number of invasive pneumococcal disease cases adjusted for the increasing trend in disease incidence prior to PCV7 introduction in England and Wales, and (ii) a range of values representing serotype replacement induced by vaccination of the additional six serotypes in PCV13. Most of the scenarios considered suggest that ceasing pneumococcal conjugate vaccine use would cause an increase in invasive pneumococcal disease incidence, while replacing PCV7 with PCV13 would cause an overall decrease. However, the size of this reduction largely depends on the level of competition induced by the additional serotypes in PCV13. The model estimates that over 20 years of PCV13 vaccination, around 5000–62000 IPD cases could be prevented compared to stopping pneumococcal conjugate vaccination altogether. Despite inevitable uncertainty around serotype replacement effects following introduction of PCV13, the model suggests a reduction in overall invasive pneumococcal disease incidence in all cases. Our results provide useful evidence on the benefits of PCV13 to countries replacing or considering replacing PCV7 with PCV13, as well as data that can be used to evaluate the cost-effectiveness of such a switch

The biogeochemical structure of Southern Ocean mesoscale eddies

Mesoscale eddies play a key role in modulating physical and biogeochemical properties across the global ocean. They also play a central role in cross‐frontal transport of heat, freshwater, and carbon, especially in the Southern Ocean. However, the role that eddies play in the biogeochemical cycles is not yet well constrained, partly due to a lack of observations below the surface. Here, we use hydrographic data from two voyages, conducted in the austral summer and autumn, to document the vertical biogeochemical structure of two mesoscale cyclonic eddies and quantify the role of these eddies in the meridional transport of nutrients across the Subantarctic Front. Our study demonstrates that the nutrient distribution is largely driven by eddy dynamics, yielding identical eddy structure below the mixed layer in both seasons. This result allowed us to relate nutrient content to dynamic height and estimate the average transport by eddies across the Subantarctic Front. We found that relative to Subantarctic Zone waters, long‐lived cold‐core eddies carry nitrate anomalies of 1.6±0.2×1010 moles and silicate anomalies of −5.5±0.7×1010 moles across the fronts each year. This cross‐frontal transport of nutrients has negligible impact on Subantarctic Zone productivity; however, it has potential to modify the nutrient content of mode waters that are exported from the Southern Ocean to lower latitudes

Personality and the creativity of frontline service employees: linear and curvilinear effects

Previous studies have investigated the relationship between the Five Factor model of personality and creativity. As this model has been criticised for providing a limited account of an individual’s personality, this study considers additional personality traits that have recently been investigated in the literature as determinants of employee behaviour. Moreover, we also contribute to the existing body of literature by conducting this study in a services setting, for which we predict personality traits will exert differentiated effects on creativity when compared to other settings. Finally, while past research has focused on linear effects, this study examines the existence of non-linear effects between personality and creativity. The results indicate that personality traits apart from the Five Factor model have an impact on creativity and that the effects of several personality traits on the creativity of frontline service employees differ from those obtained in other settings. Lastly, the findings also show that five of the personality traits have non-linear effects on creativity, and this may be a stimulus for a new stream of research in the human resources literature

Air-sea CO2 exchange in the equatorial Pacific

Author Posting. © American Geophysical Union, 2004. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Journal of Geophysical Research 109 (2004): C08S02, doi:10.1029/2003JC002256.GasEx-2001, a 15-day air-sea carbon dioxide (CO2) exchange study conducted in the equatorial Pacific, used a combination of ships, buoys, and drifters equipped with ocean and atmospheric sensors to assess variability and surface mechanisms controlling air-sea CO2 fluxes. Direct covariance and profile method air-sea CO2 fluxes were measured together with the surface ocean and marine boundary layer processes. The study took place in February 2001 near 125°W, 3°S in a region of high CO2. The diurnal variation in the air-sea CO2 difference was 2.5%, driven predominantly by temperature effects on surface solubility. The wind speed was 6.0 ± 1.3 m s−1, and the atmospheric boundary layer was unstable with conditions over the range −1 < z/L < 0. Diurnal heat fluxes generated daytime surface ocean stratification and subsequent large nighttime buoyancy fluxes. The average CO2 flux from the ocean to the atmosphere was determined to be 3.9 mol m−2 yr−1, with nighttime CO2 fluxes increasing by 40% over daytime values because of a strong nighttime increase in (vertical) convective velocities. The 15 days of air-sea flux measurements taken during GasEx-2001 demonstrate some of the systematic environmental trends of the eastern equatorial Pacific Ocean. The fact that other physical processes, in addition to wind, were observed to control the rate of CO2 transfer from the ocean to the atmosphere indicates that these processes need to be taken into account in local and global biogeochemical models. These local processes can vary on regional and global scales. The GasEx-2001 results show a weak wind dependence but a strong variability in processes governed by the diurnal heating cycle. This implies that any changes in the incident radiation, including atmospheric cloud dynamics, phytoplankton biomass, and surface ocean stratification may have significant feedbacks on the amount and variability of air-sea gas exchange. This is in sharp contrast with previous field studies of air-sea gas exchange, which showed that wind was the dominating forcing function. The results suggest that gas transfer parameterizations that rely solely on wind will be insufficient for regions with low to intermediate winds and strong insolation.This work was performed with the support of the National Science Foundation Grant OCE-9986724 and the NOAA Global Carbon Cycle Program Grants NA06GP048, NA17RJ1223, and NA87RJ0445 in the Office of Global Programs

E-retailing ethics in Egypt and its effect on customer repurchase intention

The theoretical understanding of online shopping behaviour has received much attention. Less focus has been given to the formation of the ethical issues that result from online shopper interactions with e-retailers. The vast majority of earlier research on this area is conceptual in nature and limited in scope by focusing on consumers’ privacy issues. Therefore, the purpose of this paper is to propose a theoretical model explaining what factors contribute to online retailing ethics and its effect on customer repurchase intention. The data were analysed using variance-based structural equation modelling, employing partial least squares regression. Findings indicate that the five factors of the online retailing ethics (security, privacy, non- deception, fulfilment/reliability, and corporate social responsibility) are strongly predictive of online consumers’ repurchase intention. The results offer important implications for e-retailers and are likely to stimulate further research in the area of e-ethics from the consumers’ perspective

Neurophysiologic effects of spinal manipulation in patients with chronic low back pain

<p>Abstract</p> <p>Background</p> <p>While there is growing evidence for the efficacy of SM to treat LBP, little is known on the mechanisms and physiologic effects of these treatments. Accordingly, the purpose of this study was to determine whether SM alters the amplitude of the motor evoked potential (MEP) or the short-latency stretch reflex of the erector spinae muscles, and whether these physiologic responses depend on whether SM causes an audible joint sound.</p> <p>Methods</p> <p>We used transcranial magnetic stimulation to elicit MEPs and electromechanical tapping to elicit short-latency stretch reflexes in 10 patients with chronic LBP and 10 asymptomatic controls. Neurophysiologic outcomes were measured before and after SM. Changes in MEP and stretch reflex amplitude were examined based on patient grouping (LBP vs. controls), and whether SM caused an audible joint sound.</p> <p>Results</p> <p>SM did not alter the erector spinae MEP amplitude in patients with LBP (0.80 ± 0.33 vs. 0.80 ± 0.30 μV) or in asymptomatic controls (0.56 ± 0.09 vs. 0.57 ± 0.06 μV). Similarly, SM did not alter the erector spinae stretch reflex amplitude in patients with LBP (0.66 ± 0.12 vs. 0.66 ± 0.15 μV) or in asymptomatic controls (0.60 ± 0.09 vs. 0.55 ± 0.08 μV). Interestingly, study participants exhibiting an audible response exhibited a 20% decrease in the stretch reflex (p < 0.05).</p> <p>Conclusions</p> <p>These findings suggest that a single SM treatment does not systematically alter corticospinal or stretch reflex excitability of the erector spinae muscles (when assessed ~ 10-minutes following SM); however, they do indicate that the stretch reflex is attenuated when SM causes an audible response. This finding provides insight into the mechanisms of SM, and suggests that SM that produces an audible response may mechanistically act to decrease the sensitivity of the muscle spindles and/or the various segmental sites of the Ia reflex pathway.</p

Observations and models to support the first Marine Ecosystem Assessment for the Southern Ocean (MEASO)

Assessments of the status and trends of habitats, species and ecosystems are needed for effective ecosystem-based management in marine ecosystems. Knowledge on imminent ecosystem changes (climate change impacts) set in train by existing climate forcings are needed for adapting management practices to achieve conservation and sustainabililty targets into the future. Here, we describe a process for enabling a marine ecosystem assessment (MEA) by the broader scientific community to support managers in this way, using a MEA for the Southern Ocean (MEASO) as an example. We develop a framework and undertake an audit to support a MEASO, involving three parts. First, we review available syntheses and assessments of the Southern Ocean ecosystem and its parts, paying special attention to building on the SCAR Antarctic Climate Change and Environment report and the SCAR Biogeographic Atlas of the Southern Ocean. Second, we audit available field observations of habitats and densities and/or abundances of taxa, using the literature as well as a survey of scientists as to their current and recent activities. Third, we audit available system models that can form a nested ensemble for making, with available data, circumpolar assessments of habitats, species and food webs. We conclude that there is sufficient data and models to undertake, at least, a circumpolar assessment of the krill-based system. The auditing framework provides the basis for the first MEASO but also provides a repository (www.SOKI.aq/display/MEASO) for easily amending the audit for future MEASOs. We note that an important outcome of the first MEASO will not only be the assessment but also to advise on priorities in observations and models for improving subsequent MEASOs

Public health and economic impact of vaccination with 7-valent pneumococcal vaccine (PCV7) in the context of the annual influenza epidemic and a severe influenza pandemic

Background: Influenza pandemic outbreaks occurred in the US in 1918, 1957, and 1968. Historical evidence suggests that the majority of influenza-related deaths during the 1918 US pandemic were attributable to bacterial pneumococcal infections. The 2009 novel influenza A (H1N1) outbreak highlights the importance of interventions that may mitigate the impact of a pandemic. Methods: A decision-analytic model was constructed to evaluate the impact of 7-valent pneumococcal conjugate vaccine (PCV7) on pneumococcal disease incidence and mortality during a typical influenza season (13/100) and a severe influenza pandemic (30/100). Outcomes were compared for current PCV7 vaccination practices vs. no vaccination. The model was estimated using published sources and includes indirect (herd) protection of non-vaccinated persons. Results: The model predicts that PCV7 vaccination in the US is cost saving for a normal influenza season, reducing pneumococcal-related costs by $1.6 billion. In a severe influenza pandemic, vaccination would save$7.3 billion in costs and prevent 512,000 cases of IPD, 719,000 cases of pneumonia, 62,000 IPD deaths, and 47,000 pneumonia deaths; 84% of deaths are prevented due to indirect (herd) protection in the unvaccinated. Conclusions: PCV7 vaccination is highly effective and cost saving in both normal and severe pandemic influenza seasons. Current infant vaccination practices may prevent >1 million pneumococcal-related deaths in a severe influenza pandemic, primarily due to herd protection