A mechanism for the recently increased interdecadal variability of the Silk Road Pattern

The Silk Road Pattern (SRP) teleconnection manifests in summer over Eurasia, where it is associated with substantial temperature and precipitation anomalies. The SRP varies on interannual and decadal scales; reanalyses show an increase in its decadal variability around the mid-1970s. Understanding what drives this decadal variability is particularly important, because contemporary seasonal prediction models struggle to predict the phase of the SRP. Based on analysis of observations and multiple targeted numerical experiments, this study proposes a mechanism for decadal SRP variability. Causal Effect Network analysis confirms a positive feedback loop between the eastern portion of the SRP pattern and vertical motion over India on synoptic timescales. Anomalies over a larger region of subtropical South Asia can reinforce a background state that projects onto the positive or negative SRP through this mechanism. This effect is isolated and confirmed in targeted numerical simulations. The transition from weak to strong decadal variability in the mid-1970s is consistent with more spatially coherent interannual precipitation variability over subtropical South Asia. Furthermore, results suggest that oceanic variability does not directly force the SRP. Nevertheless, sea surface temperatures in the North Atlantic and the North Pacific may indirectly affect the SRP by modulating South Asian rainfall on decadal timescales

A comprehensive analysis of coherent rainfall patterns in China and potential drivers. Part I: interannual variability

Interannual rainfall variability in China affects agriculture, infrastructure and water resource management. To improve its understanding and prediction, many studies have associated precipitation variability with particular causes for specific seasons and regions. Here, a consistent and objective method, Empirical Orthogonal Teleconnection (EOT) analysis, is applied to 1951–2007 high-resolution precipitation observations over China in all seasons. Instead of maximizing the explained space–time variance, the method identifies regions in China that best explain the temporal variability in domain-averaged rainfall. The EOT method is validated by the reproduction of known relationships to the El Niño Southern Oscillation (ENSO): high positive correlations with ENSO are found in eastern China in winter, along the Yangtze River in summer, and in southeast China during spring. New findings include that wintertime rainfall variability along the southeast coast is associated with anomalous convection over the tropical eastern Atlantic and communicated to China through a zonal wavenumber-three Rossby wave. Furthermore, spring rainfall variability in the Yangtze valley is related to upper-tropospheric midlatitude perturbations that are part of a Rossby wave pattern with its origin in the North Atlantic. A circumglobal wave pattern in the northern hemisphere is also associated with autumn precipitation variability in eastern areas. The analysis is objective, comprehensive, and produces timeseries that are tied to specific locations in China. This facilitates the interpretation of associated dynamical processes, is useful for understanding the regional hydrological cycle, and allows the results to serve as a benchmark for assessing general circulation models

Interannual rainfall variability over China in the MetUM GA6 and GC2 configurations

Six climate simulations of the Met Office Unified Model Global Atmosphere 6.0 and Global Coupled 2.0 configurations are evaluated against observations and reanalysis data for their ability to simulate the mean state and year-to-year variability of precipitation over China. To analyze the sensitivity to air-sea coupling and horizontal resolution, atmosphere-only and coupled integrations at atmospheric horizontal resolutions of N96, N216 and N512 (corresponding to ~200, 90, and 40 km in the zonal direction at the equator, respectively) are analyzed. The mean and interannual variance of seasonal precipitation are too high in all simulations over China, but improve with finer resolution and coupling. Empirical Orthogonal Teleconnection (EOT) analysis is applied to simulated and observed precipitation to identify spatial patterns of temporally coherent interannual variability in seasonal precipitation. To connect these patterns to large-scale atmospheric and coupled air-sea processes, atmospheric and oceanic fields are regressed onto the corresponding seasonal-mean timeseries. All simulations reproduce the observed leading pattern of interannual rainfall variability in winter, spring and autumn; the leading pattern in summer is present in all but one simulation. However, only in two simulations are the four leading patterns associated with the observed physical mechanisms. Coupled simulations capture more observed patterns of variability and associate more of them with the correct physical mechanism, compared to atmosphere-only simulations at the same resolution. However, finer resolution does not improve the fidelity of these patterns or their associated mechanisms. This shows that evaluating climate models by only geographical distribution of mean precipitation and its interannual variance is insufficient. The EOT analysis adds knowledge about coherent variability and associated mechanisms

Helical stability of the GnTV transmembrane domain impacts on SPPL3 dependent cleavage

Signal-Peptide Peptidase Like-3 (SPPL3) is an intramembrane cleaving aspartyl protease that causes secretion of extracellular domains from type-II transmembrane proteins. Numerous Golgi-localized glycosidases and glucosyltransferases have been identified as physiological SPPL3 substrates. By SPPL3 dependent processing, glycan-transferring enzymes are deactivated inside the cell, as their active site-containing domain is cleaved and secreted. Thus, SPPL3 impacts on glycan patterns of many cellular and secreted proteins and can regulate protein glycosylation. However, the characteristics that make a substrate a favourable candidate for SPPL3-dependent cleavage remain unknown. To gain insights into substrate requirements, we investigated the function of a GxxxG motif located in the transmembrane domain of N-acetylglucosaminyltransferase V (GnTV), a well-known SPPL3 substrate. SPPL3-dependent secretion of the substrate’s ectodomain was affected by mutations disrupting the GxxxG motif. Using deuterium/hydrogen exchange and NMR spectroscopy, we studied the effect of these mutations on the helix flexibility of the GnTV transmembrane domain and observed that increased flexibility facilitates SPPL3-dependent shedding and vice versa. This study provides first insights into the characteristics of SPPL3 substrates, combining molecular biology, biochemistry, and biophysical techniques and its results will provide the basis for better understanding the characteristics of SPPL3 substrates with implications for the substrates of other intramembrane proteases

Helical stability of the GnTV transmembrane domain impacts on SPPL3 dependent cleavage

Signal-Peptide Peptidase Like-3 (SPPL3) is an intramembrane cleaving aspartyl protease that causes secretion of extracellular domains from type-II transmembrane proteins. Numerous Golgi-localized glycosidases and glucosyltransferases have been identified as physiological SPPL3 substrates. By SPPL3 dependent processing, glycan-transferring enzymes are deactivated inside the cell, as their active site-containing domain is cleaved and secreted. Thus, SPPL3 impacts on glycan patterns of many cellular and secreted proteins and can regulate protein glycosylation. However, the characteristics that make a substrate a favourable candidate for SPPL3-dependent cleavage remain unknown. To gain insights into substrate requirements, we investigated the function of a GxxxG motif located in the transmembrane domain of N-acetylglucosaminyltransferase V (GnTV), a well-known SPPL3 substrate. SPPL3-dependent secretion of the substrate’s ectodomain was affected by mutations disrupting the GxxxG motif. Using deuterium/hydrogen exchange and NMR spectroscopy, we studied the effect of these mutations on the helix flexibility of the GnTV transmembrane domain and observed that increased flexibility facilitates SPPL3-dependent shedding and vice versa. This study provides first insights into the characteristics of SPPL3 substrates, combining molecular biology, biochemistry, and biophysical techniques and its results will provide the basis for better understanding the characteristics of SPPL3 substrates with implications for the substrates of other intramembrane proteases

Targeted delivery of a vaccine protein to Langerhans cells in the human skin via the C-type lectin receptor Langerin

Human skin is a preferred vaccination site as it harbors multiple dendritic cell (DC) subsets, which display distinct C-type lectin receptors (CLR) that recognize pathogens. Antigens can be delivered to CLR by antibodies or ligands to boost antigen-specific immune responses. This concept has been established in mouse models but detailed insights into the functional consequences of antigen delivery to human skin DC in situ are sparse. In this study, we cloned and produced an anti-human Langerin antibody conjugated to the EBV nuclear antigen 1 (EBNA1). We confirmed specific binding of anti-Langerin-EBNA1 to Langerhans cells (LC). This novel LC-based vaccine was then compared to an existing anti-DEC-205-EBNA1 fusion protein by loading LC in epidermal cell suspensions before coculturing them with autologous T cells. After restimulation with EBNA1-peptides, we detected elevated levels of IFN-γ- and TNF-α-positive CD4+ T cells with both vaccines. When we injected the fusion proteins intradermally into human skin explants, emigrated skin DC targeted via DEC-205-induced cytokine production by T cells, whereas the Langerin-based vaccine failed to do so. In summary, we demonstrate that antibody-targeting approaches via the skin are promising vaccination strategies, however, further optimizations of vaccines are required to induce potent immune responses

On northern-hemisphere wave patterns associated with winter rainfall events in China

During extended winter (November-April) 43% of the intraseasonal rainfall variability in China is explained by three spatial patterns of temporally coherent rainfall. These patterns were identified with Empirical Orthogonal Teleconnection (EOT) analysis of observed 1982-2007 pentad rainfall anomalies and connected to midlatitude disturbances. However, examination of individual strong EOT events shows that there is substantial inter-event variability in their dynamical evolution, which implies that precursor patterns found in regressions cannot serve as useful predictors. To understand the physical nature and origins of the extratropical precursors, the EOT technique is applied to six simulations of the Met Office Unified Model at horizontal resolutions of 200--40 km and with and without air-sea coupling. All simulations reproduce the observed precursor patterns in regressions, indicating robust underlying dynamical processes. Further investigation into the dynamics associated with observed patterns shows that Rossby wave dynamics can explain the large inter-event variability. The results suggest that the apparently slowly evolving or quasi-stationary waves in regression analysis are a statistical amalgamation of more rapidly propagating waves with a variety of origins and properties

Genome-wide association study identifies 30 loci associated with bipolar disorder.

Bipolar disorder is a highly heritable psychiatric disorder. We performed a genome-wide association study (GWAS) including 20,352 cases and 31,358 controls of European descent, with follow-up analysis of 822 variants with P < 1 × 10-4 in an additional 9,412 cases and 137,760 controls. Eight of the 19 variants that were genome-wide significant (P < 5 × 10-8) in the discovery GWAS were not genome-wide significant in the combined analysis, consistent with small effect sizes and limited power but also with genetic heterogeneity. In the combined analysis, 30 loci were genome-wide significant, including 20 newly identified loci. The significant loci contain genes encoding ion channels, neurotransmitter transporters and synaptic components. Pathway analysis revealed nine significantly enriched gene sets, including regulation of insulin secretion and endocannabinoid signaling. Bipolar I disorder is strongly genetically correlated with schizophrenia, driven by psychosis, whereas bipolar II disorder is more strongly correlated with major depressive disorder. These findings address key clinical questions and provide potential biological mechanisms for bipolar disorder

Potential of Airborne LiDAR Derived Vegetation Structure for the Prediction of Animal Species Richness at Mount Kilimanjaro

The monitoring of species and functional diversity is of increasing relevance for the development of strategies for the conservation and management of biodiversity. Therefore, reliable estimates of the performance of monitoring techniques across taxa become important. Using a unique dataset, this study investigates the potential of airborne LiDAR-derived variables characterizing vegetation structure as predictors for animal species richness at the southern slopes of Mount Kilimanjaro. To disentangle the structural LiDAR information from co-factors related to elevational vegetation zones, LiDAR-based models were compared to the predictive power of elevation models. 17 taxa and 4 feeding guilds were modeled and the standardized study design allowed for a comparison across the assemblages. Results show that most taxa (14) and feeding guilds (3) can be predicted best by elevation with normalized RMSE values but only for three of those taxa and two of those feeding guilds the difference to other models is significant. Generally, modeling performances between different models vary only slightly for each assemblage. For the remaining, structural information at most showed little additional contribution to the performance. In summary, LiDAR observations can be used for animal species prediction. However, the effort and cost of aerial surveys are not always in proportion with the prediction quality, especially when the species distribution follows zonal patterns, and elevation information yields similar results