IL-4 and IL-13 mediated down-regulation of CD8 expression levels can dampen anti-viral CD8⁺ T cell avidity following HIV-1 recombinant pox viral vaccination

We have shown that mucosal HIV-1 recombinant pox viral vaccination can induce high, avidity HIV-specific CD8(+) T cells with reduced interleukin (IL)-4 and IL-13 expression compared to, systemic vaccine delivery. In the current study how these cytokines act to regulate anti-viral CD8(+) T, cell avidity following HIV-1 recombinant pox viral prime-boost vaccination was investigated. Out of a panel of T cell avidity markers tested, only CD8 expression levels were found to be enhanced on, KdGag197-205 (HIV)-specific CD8(+) T cells obtained from IL-13(-/-), IL-4(-/-) and signal transducer and, activator of transcription of 6 (STAT6)(-/-) mice compared to wild-type (WT) controls following, vaccination. Elevated CD8 expression levels in this instance also correlated with polyfunctionality, (interferon (IFN)-γ, tumour necorsis factor (TNF)-α and IL-2 production) and the avidity of HIVspecific CD8(+) T cells. Furthermore, mucosal vaccination and vaccination with the novel adjuvanted IL-13 inhibitor (i.e. IL-13Rα2) vaccines significantly enhanced CD8 expression levels on HIV-specific CD8(+), T cells, which correlated with avidity. Using anti-CD8 antibodies that blocked CD8 availability on CD8(+), T cells, it was established that CD8 played an important role in increasing HIV-specific CD8(+) T cell avidity and polyfunctionality in IL-4(-/-), IL-13(-/-) and STAT6(-/-) mice compared to WT controls, following vaccination. Collectively, our data demonstrate that IL-4 and IL-13 dampen CD8 expression levels on anti-viral CD8(+) T cells, which can down-regulate anti-viral CD8(+) T cell avidity and, polyfunctionality following HIV-1 recombinant pox viral vaccination. These findings can be exploited to, design more efficacious vaccines not only against HIV-1, but many chronic infections where high, avidity CD8(+) T cells help protection.This work was supported by the Australian National Health and Medical Research Council project grant award 525431 (CR) and development grant award APP1000703 (CR), the Australian Centre for Hepatitis and HIV Virology EOI grant 2010/12 (CR&RJ), and Bill and Melinda Gates Foundation GCE Phase I grant OPP1015149 (CR)

Reduced Interleukin-4 Receptor α Expression on CD8+ T Cells Correlates with Higher Quality Anti-Viral Immunity

With the hope of understanding how interleukin (IL)-4 and IL-13 modulated quality of anti-viral CD8(+) T cells, we evaluated the expression of receptors for these cytokines following a range of viral infections (e.g. pox viruses and influenza virus). Results clearly indicated that unlike other IL-4/IL-13 receptor subunits, IL-4 receptor α (IL-4Rα) was significantly down-regulated on anti-viral CD8(+) T cells in a cognate antigen dependent manner. The infection of gene knockout mice and wild-type (WT) mice with vaccinia virus (VV) or VV expressing IL-4 confirmed that IL-4, IL-13 and signal transducer and activator of transcription 6 (STAT6) were required to increase IL-4Rα expression on CD8(+) T cells, but not interferon (IFN)-γ. STAT6 dependent elevation of IL-4Rα expression on CD8(+) T cells was a feature of poor quality anti-viral CD8(+) T cell immunity as measured by the production of IFN-γ and tumor necrosis factor α (TNF-α) in response to VV antigen stimulation in vitro. We propose that down-regulation of IL-4Rα, but not the other IL-4/IL-13 receptor subunits, is a mechanism by which CD8(+) T cells reduce responsiveness to IL-4 and IL-13. This can improve the quality of anti-viral CD8(+) T cell immunity. Our findings have important implications in understanding anti-viral CD8(+) T cell immunity and designing effective vaccines against chronic viral infections.This work was supported by the Australian National Health and Medical Research Council project grant award 525431 (CR) and development grant award APP1000703 (CR) and the Australian Centre for Hepatitis and HIV Virology EOI grant 2010 (CR). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Economic Value of Climate Variability Impacts on Coconut Production in Sri Lanka

This paper assesses the economic value of climate variability, employing a percentile analysis on an array of 31-years national annual coconut production data from 1971 to 2001. Of the production array, 10% and 90% percentiles have been considered respectively as lower and upper production extremes. The 60% of production departures of each year of extremes with respect to the mean production of 10% to 90% percentile were attributed to climate variability because studies show that the 60% of the variation of coconut production is explained by climate. These production deviations were then valued multiplying by free-on-board (FOB) prices of fresh coconuts. Results show that the foregone income from coconuts due to low rainfall varied between US$32 million to US$ 73 million while the incremental coconut income in crop glut extremes due to high rainfall varied between US$42 million and US$ 87 million. Results show that the climate variability causes income losses to the economy estimated at US$32 million to US$ 73 million in years of extreme crop shortage. And in years of extreme crop surplus, the economy realises income gains of US$42 million to US$ 87 million. These indicate the potential for significant economic benefits from investments in adaptations that would reduce variability in nut production which is caused by variations in climate. Further work is however needed to estimate the effectiveness and economic benefits that might be achieved from investments in adaptation

Chesapeake Bay benthic community restoration goals

Benthic macroinvertebrate assemblages have been an integral part of the Chesapeake Bay monitoring program since its inception due to their ecological importance and their value as biological indicators. The condition of benthic assemblages reflects an integration of temporally variable environmental conditions and the effects of multiple types of environmental stresses. As such, benthic assemblages provide a useful complement to more temporally variable chemical and water quality monitoring measures. While assessments using benthic monitoring data have been useful for characterizing changes in environmental conditions at individual sites over time, and for relating the condition of sites to pollution loadings and sources, the full potential of these assessments for addressing larger management questions, such as What is the overall condition of the Bay? or How does the condition of various tributaries compare? has not yet been realized. Regional-scale assessments of ecological status and trends using benthic assemblages are limited by the fact that benthic assemblages are strongly influenced by naturally varying habitat elements, such as salinity, sediment type, and depth. Such natural variability confounds interpretation of differences in the benthic community differences as simple responses to anthropogenic environmental perturbations. An additional limitation is that different sampling methodologies used in various programs often constrain the extent to which the benthic data can be integrated for a unified assessment. The objective of this project was to develop a practical and conceptually sound framework for assessing benthic environmental conditions in Chesapeake Bay that would address the general constraints and limitations just described. This was accomplished by standardizing benthic data from several different monitoring programs to allow their integration into a single, coherent data base. From that data base a set of measures (Chesapeake Bay Benthic Restoration Goals) was developed to describe characteristics of benthic assemblages expected at sites having little evidence of environmental stress or disturbance. Using these goals, benthic data from any part of the Bay could be compared to determine whether conditions at that site met, were above, or were below expectations defined for reference sites in similar habitats

Extreme sea levels at different global warming levels

The Paris agreement focused global climate mitigation policy on limiting global warming to 1.5 or 2 °C above pre-industrial levels. Consequently, projections of hazards and risk are increasingly framed in terms of global warming levels rather than emission scenarios. Here, we use a multimethod approach to describe changes in extreme sea levels driven by changes in mean sea level associated with a wide range of global warming levels, from 1.5 to 5 °C, and for a large number of locations, providing uniform coverage over most of the world’s coastlines. We estimate that by 2100 ~50% of the 7,000+ locations considered will experience the present-day 100-yr extreme-sea-level event at least once a year, even under 1.5 °C of warming, and often well before the end of the century. The tropics appear more sensitive than the Northern high latitudes, where some locations do not see this frequency change even for the highest global warming levels

Natural hazards in Australia : sea level and coastal extremes

The Australian coastal zone encompasses tropical, sub- and extra-tropical climates and accommodates about 80 % of Australia’s population. Sea level extremes and their physical impacts in the coastal zone arise from a complex set of atmospheric, oceanic and terrestrial processes that interact on a range of spatial and temporal scales and will be modified by a changing climate, including sea level rise. This review details significant progress over recent years in understanding the causes of past and projections of future changes in sea level and coastal extremes, yet a number of research questions, knowledge gaps and challenges remain. These include efforts to improve knowledge on past sea level extremes, integrate a wider range of processes in projections of future changes to sea level extremes, and focus efforts on understanding long-term coastline response from the combination of contributing factors

African heritage sites threatened as sea-level rise accelerates

The African coast contains heritage sites of ‘Outstanding Universal Value’ that face increasing risk from anthropogenic climate change. Here, we generated a database of 213 natural and 71 cultural African heritage sites to assess exposure to coastal flooding and erosion under moderate (RCP 4.5) and high (RCP 8.5) greenhouse gas emission scenarios. Currently, 56 sites (20%) are at risk from a 1-in-100-year coastal extreme event, including the iconic ruins of Tipasa (Algeria) and the North Sinai Archaeological Sites Zone (Egypt). By 2050, the number of exposed sites is projected to more than triple, reaching almost 200 sites under high emissions. Emissions mitigation from RCP 8.5 to RCP 4.5 reduces the number of very highly exposed sites by 25%. These findings highlight the urgent need for increased climate change adaptation for heritage sites in Africa, including governance and management approaches, site-specific vulnerability assessments, exposure monitoring, and protection strategies

The Information Geometry of the Ising Model on Planar Random Graphs

It has been suggested that an information geometric view of statistical mechanics in which a metric is introduced onto the space of parameters provides an interesting alternative characterisation of the phase structure, particularly in the case where there are two such parameters -- such as the Ising model with inverse temperature $\beta$ and external field $h$. In various two parameter calculable models the scalar curvature ${\cal R}$ of the information metric has been found to diverge at the phase transition point $\beta_c$ and a plausible scaling relation postulated: ${\cal R} \sim |\beta- \beta_c|^{\alpha - 2}$. For spin models the necessity of calculating in non-zero field has limited analytic consideration to 1D, mean-field and Bethe lattice Ising models. In this letter we use the solution in field of the Ising model on an ensemble of planar random graphs (where $\alpha=-1, \beta=1/2, \gamma=2$) to evaluate the scaling behaviour of the scalar curvature, and find ${\cal R} \sim | \beta- \beta_c |^{-2}$. The apparent discrepancy is traced back to the effect of a negative $\alpha$.Comment: Version accepted for publication in PRE, revtex

The role of intratidal oscillations in sediment resuspension in a diurnal, partially mixed estuary

Using detailed observations of the mean and turbulent properties of flow, salinity and turbidity that spanned 2001/02, we examined the physical mechanisms underpinning sediment resuspension in the low-energy Swan River estuary, Western Australia. In this diurnal tidally-dominated estuary, the presence of intratidal oscillations, a tidal inequality lasting 2 to 3 hours on the flood tide, generated by interactions of the four main diurnal and semidiurnal astronomical constituents, K₁, O₁, M₂, and S₂, played a major role in modifying vertical stratification and mixing. These intratidal oscillations are controlled by phase differences between the tropic and synodic months rather than being temporally-fixed by bed friction, as occurs in semidiurnal estuaries. Intratidal oscillations are largest, at around 0.1 m, near to the Austral solstice when the lunar and solar declination are in-phase. Despite the seemingly small change in water level, shear-induced interfacial mixing caused destratification of the water column with the top-to-bottom salinity (ΔS) difference of 3.5 present early in the flood tide eroded to less than 0.3 by the end of the intratidal oscillation. High turbidity peaks, of 250 nephelometric turbidity units, coincided with these intratidal oscillations and could not be explained by bed friction since shear stress from mean flow did not exceed threshold criteria. High Reynolds stresses of ∼1 Nm⁻² did, however, exceed τcr and together with negative Reynolds fluxes indicate a net downward transport of material. Destratification of the water column induced by shear instabilities resulted in large overturns capable of moving in situ material towards the bed during intratidal oscillations and these turbidities were ∼10 times greater than those from bed-generated resuspension observed later during the flood tide