Mechanistic insights to the effective pathways of global and local climate change in a Baltic Sea seaweed - epiphyte - mesograzer system = Mechanistische Einblicke in die Wirkungspfade von globalen und lokalen Faktoren des Klimawandels auf ein Seetang - Epiphyten - Weidegänger System der Ostsee

Anthropogenic greenhouse gas emissions have been driving global climate change and they will continue to do so over the course of the 21st century. Most of the marine biosphere and especially coastal marine systems have suffered from high anthropogenic pressure per se and it is possible that the novel burden of very rapidly proceeding global climate change triggers shifts to alternative regimes and functioning in marine ecosystems. In the light of this background, my dissertation aims to contribute to the mechanistic understanding of global and local climate change effects on a common coastal marine seaweed (Fucus vesiculosus, Phaeophyceae) system of the Baltic Sea. The results of my experimental studies provide important mechanistic clues about the underlying direct and indirect effective pathways of environmental change in the studied seaweed system. To the best of my knowledge, it is one of the first studies which assess the seasonal variability of the same environmental factors on the same marine system over the course of one year. The detected context-dependency of global climate change effects within one ecosystem clearly shows that our understanding of the basic underlying ecosystem processes and patterns forms a prerequisite for testing, predicting and managing future ecological change in marine systems. Given that grazing forms a crucial ecological force in many coastal vegetated systems, the identified underlying mechanisms of change (top-down and bottom-up control) may allow reference to other similarly structured coastal systems. Importantly my findings point out, that ecological impacts of global climate change may be underestimated if local perturbation is disregarded and, thus, underline the chance and responsibility of local ecosystem management

Warming has stronger direct than indirect effects on benthic microalgae in a seaweed system in spring

Using outdoor mesocosms we investigated the relative importance of the direct and indirect (here: altered grazing) effects of seawater warming on benthic microalgae in a Baltic Sea Fucus vesiculosus (Phaeophyceae) system during the spring season. Seawater warming had a positive main effect on microalgal total biomass accrual and growth rate and on total mesograzer abundance and biomass. Moreover, under the existing resource-replete conditions in spring the direct positive effect of warming on microalgae was stronger than its indirect negative effect through enhanced grazing. The outcome of this study contrasts previous observations from the summer and winter season, where indirect effects of warming mediated by altered grazing were identified as an important driver of primary biomass in the Fucus system. In this context, the results from the spring season add mechanistic information to the overall understanding of the seasonal variability of climate change effects. They suggest that the relative importance of the underlying direct and indirect effective pathways of warming and the overall effect on the balance between production and consumption are influenced by the trophic state of the system, which in temperate regions is related to season

Disentangling different moisture transport pathways over the eastern subtropical North Atlantic using multi-platform isotope observations and high-resolution numerical modelling

Due to its dryness, the subtropical free troposphere plays a critical role in the radiative balance of the Earth’s climate system. But the complex interactions of the dynamical and physical processes controlling the variability in the moisture budget of this sensitive region of the subtropical atmosphere are still not fully understood. Stable water isotopes can provide important information about several of the latter processes, namely subsidence drying, turbulent mixing, dry and moist convective moistening. In this study, we use high-resolution simulations of the isotope-enabled version of the regional weather and climate prediction model of the Consortium for Small-Scale Modelling (COSMO$_{iso}$) to investigate predominant moisture transport pathways in the Canary Islands region in the eastern subtropical North Atlantic. Comparison of the simulated isotope signals with multi-platform isotope observations (aircraft-based in situ measurements, ground-based and space-based remote sensing observations) from a field campaign in summer 2013 shows that COSMO$_{iso}$ can reproduce the observed variability of stable water vapour isotopes on time scales of hours to days, and thus allows studying the mechanisms that control the subtropical free-tropospheric humidity. Changes of isotopic signals along backward trajectories from the Canary Islands region reveal the physical processes behind the short-term isotope variability. We identify four predominant moisture transport pathways of mid-tropospheric air, each with distinct isotopic signatures: (1) Air parcels originating from the convective boundary layer of the Saharan heat low (SHL). These are characterised by a homogenous isotopic composition with a particularly high δD (median mid-tropospheric δD = −122 ‰), which results from dry convective mixing of low-level moisture of diverse origin advected into the SHL. (2) Air parcels originating from the free troposphere above the SHL. Although experiencing the largest changes in humidity and δD during their subsidence over West Africa, these air parcels typically have lower δD values (median δD = −148 ‰) than air parcels originating from the boundary layer of the SHL. (3) Air parcels originating from outside the SHL region, typically descending from tropical upper levels south of the SHL, which are often affected by moist convective injections from mesoscale convective systems in the Sahel. Their isotopic composition is much less enriched in heavy isotopes (median δD = −175 ‰) than those from the SHL region. (4) Air parcels subsiding from the upper-level extratropical North Atlantic. This pathway leads to the driest and most depleted conditions (median δD = −255 ‰) in the middle troposphere near the Canary Islands. The alternation of these transport pathways explains to a large degree the observed high variability in humidity and δD on synoptic time scales. We further show that the four different transport pathways are related to specific large scale-flow conditions. In particular, distinct differences in the location of the North African mid-level anticyclone and of extratropical Rossby wave patterns occur between the four transport pathways. Overall, this study demonstrates that the adopted Lagrangian isotope perspective enhances our understanding of air mass transport and mixing and offers a sound interpretation of the free-tropospheric variability of specific humidity and isotope composition on time scales of hours to days in contrasting atmospheric conditions over the eastern subtropical North Atlantic

Clinical effectiveness of hymenoptera venom immunotherapy

Treatment failure during venom immunotherapy (VIT) may be associated with a variety of risk factors. Our aim was to evaluate the association of baseline serum tryptase concentration (BTC) and of other parameters with the frequency of VIT failure during the maintenance phase. In this observational prospective multicenter study, we followed 357 patients with established honey bee or vespid venom allergy after the maintenance dose of VIT had been reached. In all patients, VIT effectiveness was either verified by sting challenge (n = 154) or patient self-reporting of the outcome of a field sting (n = 203). Data were collected on BTC, age, gender, preventive use of anti-allergic drugs (oral antihistamines and/or corticosteroids) right after a field sting, venom dose, antihypertensive medication, type of venom, side effects during VIT, severity of index sting reaction preceding VIT, and duration of VIT. Relative rates were calculated with generalized additive models. 22 patients (6.2%) developed generalized symptoms during sting challenge or after a field sting. A strong association between the frequency of VIT failure and BTC could be excluded. Due to wide confidence bands, however, weaker effects (odds ratios <3) of BTC were still possible, and were also suggested by a selective analysis of patients who had a sting challenge. The most important factor associated with VIT failure was a honey bee venom allergy. Preventive use of anti-allergic drugs may be associated with a higher protection rate. It is unlikely that an elevated BTC has a strong negative effect on the rate of treatment failures. The magnitude of the latter, however, may depend on the method of effectiveness assessment. Failure rate is higher in patients suffering from bee venom allergy

Lipidation of Pneumococcal Antigens Leads to Improved Immunogenicity and Protection

Streptococcus pneumoniaeinfections lead to high morbidity and mortality rates worldwide.Pneumococcal polysaccharide conjugate vaccines significantly reduce the burden of disease but havea limited range of protection, which encourages the development of a broadly protective protein-basedalternative. We and others have shown that immunization with pneumococcal lipoproteins that lackthe lipid anchor protects against colonization. Since immunity againstS. pneumoniaeis mediatedthrough Toll-like receptor 2 signaling induced by lipidated proteins, we investigated the effects ofa lipid modification on the induced immune responses in either intranasally or subcutaneouslyvaccinated mice. Here, we demonstrate that lipidation of recombinant lipoproteins DacB and PnrAstrongly improves their immunogenicity. Mice immunized with lipidated proteins showed enhancedantibody concentrations and different induction kinetics. The induced humoral immune responsewas modulated by lipidation, indicated by increased IgG2/IgG1 subclass ratios related to Th1-typeimmunity. In a mouse model of colonization, immunization with lipidated antigens led to a moderatebut consistent reduction of pneumococcal colonization as compared to the non-lipidated proteins,indicating that protein lipidation can improve the protective capacity of the coupled antigen. Thus,protein lipidation represents a promising approach for the development of a serotype-independentpneumococcal vaccine

FGFR3 expression in primary and metastatic urothelial carcinoma of the bladder

While fibroblast growth factor receptor 3 (FGFR3) is frequently mutated or overexpressed in nonmuscle-invasive urothelial carcinoma (UC), the prevalence of FGFR3 protein expression and mutation remains unknown in muscle-invasive disease. FGFR3 protein and mRNA expression, mutational status, and copy number variation were retrospectively analyzed in 231 patients with formalin-fixed paraffin-embedded primary UCs, 33 metastases, and 14 paired primary and metastatic tumors using the following methods: immunohistochemistry, NanoString nCounterTM, OncoMap or Affymetrix OncoScanTM array, and Gain and Loss of Analysis of DNA and Genomic Identification of Significant Targets in Cancer software. FGFR3 immunohistochemistry staining was present in 29% of primary UCs and 49% of metastases and did not impact overall survival (P = 0.89, primary tumors; P = 0.78, metastases). FGFR3 mutations were observed in 2% of primary tumors and 9% of metastases. Mutant tumors expressed higher levels of FGFR3 mRNA than wild-type tumors (P < 0.001). FGFR3 copy number gain and loss were rare events in primary and metastatic tumors (0.8% each; 3.0% and 12.3%, respectively). FGFR3 immunohistochemistry staining is present in one third of primary muscle-invasive UCs and half of metastases, while FGFR3 mutations and copy number changes are relatively uncommon

Season affects strength and direction of the interactive impacts of ocean warming and biotic stress in a coastal seaweed ecosystem

The plea for using more “realistic,” community‐level, investigations to assess the ecological impacts of global change has recently intensified. Such experiments are typically more complex, longer, more expensive, and harder to interpret than simple organism‐level benchtop experiments. Are they worth the extra effort? Using outdoor mesocosms, we investigated the effects of ocean warming (OW) and acidification (OA), their combination (OAW), and their natural fluctuations on coastal communities of the western Baltic Sea during all four seasons. These communities are dominated by the perennial and canopy‐forming macrophyte Fucus vesiculosus—an important ecosystem engineer Baltic‐wide. We, additionally, assessed the direct response of organisms to temperature and pH in benchtop experiments, and examined how well organism‐level responses can predict community‐level responses to the dominant driver, OW. OW affected the mesocosm communities substantially stronger than acidification. OW provoked structural and functional shifts in the community that differed in strength and direction among seasons. The organism‐level response to OW matched well the community‐level response of a given species only under warm and cold thermal stress, that is, in summer and winter. In other seasons, shifts in biotic interactions masked the direct OW effects. The combination of direct OW effects and OW‐driven shifts of biotic interactions is likely to jeopardize the future of the habitat‐forming macroalga F. vesiculosus in the Baltic Sea. Furthermore, we conclude that seasonal mesocosm experiments are essential for our understanding of global change impact because they take into account the important fluctuations of abiotic and biotic pressures