Background and Aims. The cultivation of grapevines in England is expected to benefit under climate change. Yet assessments of future wine climates remain undeveloped. Accordingly, this study assesses ...how climate change might modify frost risk for Chardonnay in the Southeast England viticulture region. Methods and Results. Cold-bias-corrected climate projections from the UKCP18 Regional (12 km) perturbed parameter ensemble (PPE) climate model under RCP8.5 are applied with phenological models to determine how frost risk and the timing of key grapevine phenophases might alter under climate change. Notwithstanding the uncertainties associated with projections of key viticulture-related bioclimate variables, the last spring frost was found to advance at a greater rate than budburst, indicating a general decrease in frost risk. Conclusions. Although projections point to an improving climate for viticulture across Southeast England, frost will remain a risk for viticulture, albeit at a reduced level compared to the present. Furthermore, the strong cold-bias found for temperature simulations used in this study needs to be given careful consideration when using the UKCP18 projections for viticulture impact assessments of climate change. Significance of the Study. This study highlights the present sensitivity of viticulture to climate variability and the inherent uncertainty associated with making future projections of wine climate under climate change.
The La Niña and El Niño phases of the El Niño-Southern Oscillation (ENSO) have major impacts on regional rainfall patterns around the globe, with substantial environmental, societal and economic ...implications. Long-term perspectives on ENSO behaviour, under changing background conditions, are essential to anticipating how ENSO phases may respond under future climate scenarios. Here, we derive a 7700-year, quantitative precipitation record using carbon isotope ratios from a single species of leaf preserved in lake sediments from subtropical eastern Australia. We find a generally wet (more La Niña-like) mid-Holocene that shifted towards drier and more variable climates after 3200 cal. yr BP, primarily driven by increasing frequency and strength of the El Niño phase. Climate model simulations implicate a progressive orbitally-driven weakening of the Pacific Walker Circulation as contributing to this change. At centennial scales, high rainfall characterised the Little Ice Age (~1450-1850 CE) in subtropical eastern Australia, contrasting with oceanic proxies that suggest El Niño-like conditions prevail during this period. Our data provide a new western Pacific perspective on Holocene ENSO variability and highlight the need to address ENSO reconstruction with a geographically diverse network of sites to characterise how both ENSO, and its impacts, vary in a changing climate.
Why Should We Care About Temporary Waterways? Acuña, V.; Datry, T.; Marshall, J. ...
Science (American Association for the Advancement of Science),
03/2014, Volume:
343, Issue:
6175
Journal Article
Peer reviewed
Intermittently flowing streams and rivers should be recognized, afforded protection, and better managed.
A proposed ruling by the U.S. Environmental Protection Agency (EPA), aimed at clarifying which ...bodies of water that flow intermittently are protected under law (
1
), has provoked conflict between developers and environmental advocates. Some argue that temporary streams and rivers, defined as waterways that cease to flow at some points in space and time along their course (see the figure, left) ( Fig. 1) (
2
), are essential to the integrity of entire river networks. Others argue that full protection will be too costly. Similar concerns extend far beyond the United States. Debate over how to treat temporary waterways in water-policy frameworks is ongoing (
3
), particularly because some large permanent rivers are shifting to temporary because of climate change and extraction of water (
4
). Even without human-induced changes, flow intermittency is part of the natural hydrology for streams and rivers globally.
Governments world-wide increasingly see energy efficiency as an important aspect of sustainability. However, there is a debate in the literature as to whether the impact of improved energy efficiency ...on reducing energy use might be partially, or more than wholly, offset through “rebound” and “backfire” effects. This paper clarifies the theoretical conditions under which such effects would occur and explores their likely significance using a computable general equilibrium (CGE) model of the Scottish economy. We find that for Scotland a general improvement in energy efficiency in the production sectors of the economy initially produces rebound effects that eventually grow into backfire. Energy use ultimately increases in response to an efficiency gain and the ratio of GDP to CO
2 emissions falls. The economic factors underpinning rebound effects are straightforward: energy efficiency improvements result in an effective cut in energy prices, which produces output, substitution, competitiveness and income effects that stimulate energy demands. However, the presence of strong rebound or even backfire does not mean that efficiency-enhancing policies are irrelevant: rather it suggests that such policies operating alone are insufficient to generate environmental improvements. The implication is that a co-ordinated portfolio of energy policies is required.
Identifying and characterizing the enzymes responsible for an observed activity within a complex eukaryotic catabolic system remains one of the most significant challenges in the study of ...biomass-degrading systems. The debranching of both complex hemicellulosic and pectinaceous polysaccharides requires the production of α-l-arabinofuranosidases among a wide variety of coexpressed carbohydrate-active enzymes. To selectively detect and identify α-l-arabinofuranosidases produced by fungi grown on complex biomass, potential covalent inhibitors and probes which mimic α-l-arabinofuranosides were sought. The conformational free energy landscapes of free α-l-arabinofuranose and several rationally designed covalent α-l-arabinofuranosidase inhibitors were analyzed. A synthetic route to these inhibitors was subsequently developed based on a key Wittig–Still rearrangement. Through a combination of kinetic measurements, intact mass spectrometry, and structural experiments, the designed inhibitors were shown to efficiently label the catalytic nucleophiles of retaining GH51 and GH54 α-l-arabinofuranosidases. Activity-based probes elaborated from an inhibitor with an aziridine warhead were applied to the identification and characterization of α-l-arabinofuranosidases within the secretome of A. niger grown on arabinan. This method was extended to the detection and identification of α-l-arabinofuranosidases produced by eight biomass-degrading basidiomycete fungi grown on complex biomass. The broad applicability of the cyclophellitol-derived activity-based probes and inhibitors presented here make them a valuable new tool in the characterization of complex eukaryotic carbohydrate-degrading systems and in the high-throughput discovery of α-l-arabinofuranosidases.
Background
Xenograft rejection of pigs organs with an engineered mutation in the GGTA‐1 gene (GTKO) remains a predominantly antibody mediated process which is directed to a variety of non‐Gal protein ...and carbohydrate antigens. We previously used an expression library screening strategy to identify six porcine endothelial cell cDNAs which encode pig antigens that bind to IgG induced after pig‐to‐primate cardiac xenotransplantation. One of these gene products was a glycosyltransferase with homology to the bovine β1,4 N‐acetylgalactosaminyltransferase (B4GALNT2). We now characterize the porcine B4GALNT2 gene sequence, genomic organization, expression, and functional significance.
Methods
The porcine B4GALNT2 cDNA was recovered from the original library isolate, subcloned, sequenced, and used to identify a bacterial artificial chromosome (BAC) containing the entire B4GALNT2 locus from the Children's Hospital Oakland Research Institute BACPAC Resource Centre (#AC173453). PCR primers were designed to map the intron/exon genomic organization in the BAC clone. A stable human embryonic kidney (HEK) cell line expressing porcine B4GALNT2 (HEK‐B4T) was produced. Expression of porcine B4GALNT2 in HEK‐B4T cells was characterized by immune staining and siRNA transfection. The effects of B4GALNT2 expression in HEK‐B4T cells was measured by flow cytometry and complement mediated lysis. Antibody binding to HEK and HEK‐B4T cells was used to detect an induced antibody response to the B4GALNT2 produced glycan and the results were compared to GTKO PAEC specific non‐Gal antibody induction. Expression of porcine B4GALNT2 in pig cells and tissues was measured by qualitative and quantitative real time reverse transcriptase PCR and by Dolichos biflorus agglutinin (DBA) tissue staining.
Results
The porcine B4GALNT2 gene shares a conserved genomic organization and encodes an open reading frame with 76 and 70% amino acid identity to the human and murine B4GALNT2 genes, respectively. The B4GALNT2 gene is expressed in porcine endothelial cells and shows a broadly distributed expression pattern. Expression of porcine B4GALNT2 in human HEK cells (HEK‐B4T) results in increased binding of antibody to the B4GALNT2 enzyme, and increased reactivity with anti‐Sda and DBA. HEK‐B4T cells show increased sensitivity to complement mediated lysis when challenged with serum from primates after pig to primate cardiac xenotransplantation. In GTKO and GTKO:CD55 cardiac xenotransplantation recipients there is a significant correlation between the induction of a non‐Gal antibody, measured using GTKO PAECs, and the induction of antibodies which preferentially bind to HEK‐B4T cells.
Conclusion
The functional isolation of the porcine B4GALNT2 gene from a PAEC expression library, the pattern of B4GALNT2 gene expression and its sensitization of HEK‐B4T cells to antibody binding and complement mediated lysis indicates that the enzymatic activity of porcine B4GALNT2 produces a new immunogenic non‐Gal glycan which contributes in part to the non‐Gal immune response detected after pig‐to‐baboon cardiac xenotransplantation.
The optimal course of glucocorticoid therapy in anti-neutrophil cytoplasmic autoantibody (ANCA) disease is unknown. This cohort study evaluates effects of glucocorticoid therapy duration on patient ...outcomes and adverse events.
This study assessed 147 patients diagnosed between January 1, 2000 and January 1, 2009 who were treated with glucocorticoids and cyclophosphamide. Patients with end stage kidney disease at presentation, treatment resistance, or who had died within 6 months were excluded. Patients were divided into three groups: 0, 5, or >5 mg prednisone daily at 6 months after therapy initiation. The latter two groups were combined for assessment of adverse events. Wilcoxon rank sum, Kruskal-Wallis, or Fisher's exact tests were used for between-group comparisons. Time to relapse was evaluated by the Kaplan-Meier method with log-rank test for comparison.
There were no differences between groups in ANCA specificity, serum creatinine, frequency of risk factors for relapse, or length of therapy with immunosuppressants. Length of glucocorticoid therapy had no impact on time to relapse (hazard ratio, 0.69 95% confidence interval (CI), 0.23-2.02; 1.01, 95% CI, 0.57-1.81 for the 5-mg and >5-mg groups, respectively), relapse-free survival, end stage kidney disease, or death. Patients receiving glucocorticoids beyond 6 months had significantly higher incidence of infections (0.64 infections per person-year versus 0.39, P<0.0001) and a marginally significant higher frequency of new-onset diabetes mellitus (odds ratio, 2.03; 95% CI, 0.94-4.38).
Glucocorticoid therapy beyond 6 months is associated with a significantly greater risk of infections but not a significantly decreased risk of relapse.
α1,3-Galactosyltransferase gene knockout (GTKO) pigs reduced the significance of antibody to galactose alpha 1,3-galactose (Gal) antigens but did not eliminate delayed xenograft rejection (DXR). We ...hypothesize that DXR of GTKO organs results from an antibody response to a limited number of non-Gal endothelial cell (EC) membrane antigens. In this study, we screened a retrovirus expression library to identify EC membrane antigens detected after cardiac xenotransplantation.
Expression libraries were made from GT:CD46 and GTKO porcine aortic ECs. Viral stocks were used to infect human embryonic kidney cells (HEK) that were selected by flow cytometry for IgG binding from sensitized cardiac heterotopic xenograft recipients. After three to seven rounds of selection, individual clones were assessed for non-Gal IgG binding. The porcine complementary DNA was recovered by polymerase chain reaction amplification, sequenced, and identified by homology comparisons.
A total of 199 and 317 clones were analyzed from GT:CD46 and GTKO porcine aortic EC complementary DNA libraries, respectively. Sequence analysis identified porcine CD9, CD46, CD59, and the EC protein C receptor. We also identified porcine annexin A2 and a glycosyltransferase with homology to the human β1,4 N-acetylgalactosaminyl transferase 2 gene.
The identified proteins include key EC functions and suggest that non-Gal antibody responses may compromise EC functions and thereby contribute to DXR. Recovery of the porcine β1,4 N-acetylgalactosaminyl transferase 2 suggests that an antibody response to a SD-like carbohydrate may represent a new carbohydrate moiety involved in xenotransplantation. The identification of these porcine gene products may lead to further donor modification to enhance resistance to DXR and further reduce the level of xenograft antigenicity.
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