Identification of low-frequency TRAF3IP2 coding variants in psoriatic arthritis patients and functional characterization

Introduction: In recent genome-wide association studies for psoriatic arthritis (PsA) and psoriasis vulgaris, common coding variants in the TRAF3IP2 gene were identified to contribute to susceptibility to both disease entities. The risk allele of p.Asp10Asn (rs33980500) proved to be most significantly associated and to encode a mutant protein with an almost completely disrupted binding property to TRAF6, supporting its impact as a main disease-causing variant and modulator of IL-17 signaling. Methods: To identify further variants, exons 2-4 encoding both known TNF-receptor-associated factor (TRAF) binding domains were sequenced in 871 PsA patients. Seven missense variants and one three-base-pair insertion were identified in 0.06% to 1.02% of alleles. Five of these variants were also present in 931 control individuals at comparable frequency. Constructs containing full-length wild-type or mutant TRAF3IP2 were generated and used to analyze functionally all variants for TRAF6-binding in a mammalian two-hybrid assay. Results: None of the newly found alleles, though, encoded proteins with different binding properties to TRAF6, or to the cytoplasmic tail of the IL-17-receptor α-chain, suggesting that they do not contribute to susceptibility. Conclusions: Thus, the TRAF3IP2-variant p.Asp10Asn is the only susceptibility allele with functional impact on TRAF6 binding, at least in the German population

What drives the recent intensified vegetation degradation in Mongolia - Climate change or human activity?

This study examines the course and driving forces of recent vegetation change in the Mongolian steppe. A sediment core covering the last 55 years from a small closed-basin lake in central Mongolia was analyzed for its multi-proxy record at annual resolution. Pollen analysis shows that highest abundances of planted Poaceae and highest vegetation diversity occurred during 1977–1992, reflecting agricultural development in the lake area. A decrease in diversity and an increase in Artemisia abundance after 1992 indicate enhanced vegetation degradation in recent times, most probably because of overgrazing and farmland abandonment. Human impact is the main factor for the vegetation degradation within the past decades as revealed by a series of redundancy analyses, while climate change and soil erosion play subordinate roles. High Pediastrum (a green algae) influx, high atomic total organic carbon/total nitrogen (TOC/TN) ratios, abundant coarse detrital grains, and the decrease of δ13Corg and δ15N since about 1977 but particularly after 1992 indicate that abundant terrestrial organic matter and nutrients were transported into the lake and caused lake eutrophication, presumably because of intensified land use. Thus, we infer that the transition to a market economy in Mongolia since the early 1990s not only caused dramatic vegetation degradation but also affected the lake ecosystem through anthropogenic changes in the catchment area

Identifying Anode and Cathode Contributions in Li-Ion Full-Cell Impedance Spectra

Measured impedance spectra of Li-ion battery cells are often reproduced with equivalent circuits or physical models to determine losses due to charge transfer processes at the electrodes. The identified model parameters can usually not readily or unambiguously be assigned to the anode and the cathode. A new measurement method is presented that enables the assignment of features of impedance spectra of full cells to single electrodes. To this end, temperature gradients are imprinted perpendicular to the electrode layers of a single-layered Li-ion battery cell while impedance spectra are measured. The method exploits different dependences of the charge transfer processes at the electrodes on temperature. An equivalent circuit model of RC-elements and the effect of temperature on the related electrode properties is discussed to demonstrate the feasibility of the method. A reliable assignment of the change of impedance spectra to the electrode processes is shown to be possible. The assignment can be used to identify if changes in an impedance spectrum originate from the anode or the cathode

Immunopathological properties of the Campylobacter jejuni flagellins and the adhesin CadF as assessed in a clinical murine infection model

Background: Campylobacter jejuni infections constitute serious threats to human health with increasing prevalences worldwide. Our knowledge regarding the molecular mechanisms underlying host-pathogen interactions is still limited. Our group has established a clinical C. jejuni infection model based on abiotic IL-10-/- mice mimicking key features of human campylobacteriosis. In order to further validate this model for unraveling pathogen-host interactions mounting in acute disease, we here surveyed the immunopathological features of the important C. jejuni virulence factors FlaA and FlaB and the major adhesin CadF (Campylobacter adhesin to fibronectin), which play a role in bacterial motility, protein secretion and adhesion, respectively. Methods and results: Therefore, abiotic IL-10-/- mice were perorally infected with C. jejuni strain 81-176 (WT) or with its isogenic flaA/B (ΔflaA/B) or cadF (ΔcadF) deletion mutants. Cultural analyses revealed that WT and ΔcadF but not ΔflaA/B bacteria stably colonized the stomach, duodenum and ileum, whereas all three strains were present in the colon at comparably high loads on day 6 post-infection. Remarkably, despite high colonic colonization densities, murine infection with the ΔflaA/B strain did not result in overt campylobacteriosis, whereas mice infected with ΔcadF or WT were suffering from acute enterocolitis at day 6 post-infection. These symptoms coincided with pronounced pro-inflammatory immune responses, not only in the intestinal tract, but also in other organs such as the liver and kidneys and were accompanied with systemic inflammatory responses as indicated by increased serum MCP-1 concentrations following C. jejuni ΔcadF or WT, but not ΔflaA/B strain infection. Conclusion: For the first time, our observations revealed that the C. jejuni flagellins A/B, but not adhesion mediated by CadF, are essential for inducing murine campylobacteriosis. Furthermore, the secondary abiotic IL-10-/- infection model has been proven suitable not only for detailed investigations of immunological aspects of campylobacteriosis, but also for differential analyses of the roles of distinct C. jejuni virulence factors in induction and progression of disease

Decadal Disruption of the QBO by Tropical Volcanic Supereruptions

The Los Chocoyos (14.6°N, 91.2°W) supereruption happened ∼75,000 years ago in Guatemala and was one of the largest eruptions of the past 100,000 years. It emitted enormous amounts of sulfur, chlorine, and bromine, with multi‐decadal consequences for the global climate and environment. Here, we simulate the impact of a Los Chocoyos‐like eruption on the quasi‐biennial oscillation (QBO), an oscillation of zonal winds in the tropical stratosphere, with a comprehensive aerosol chemistry Earth System Model. We find a ∼10‐year disruption of the QBO starting 4 months post eruption, with anomalous easterly winds lasting ∼5 years, followed by westerlies, before returning to QBO conditions with a slightly prolonged periodicity. Volcanic aerosol heating and ozone depletion cooling leads to the QBO disruption and anomalous wind regimes through radiative changes and wave‐mean flow interactions. Different model ensembles, volcanic forcing scenarios and results of a second model back up the robustness of our results