@article{WernerWeichKircheretal.2018, author = {Werner, Rudolf A. and Weich, Alexander and Kircher, Malte and Solnes, Lilja B. and Javadi, Mehrbod S. and Higuchi, Takahiro and Buck, Andreas K. and Pomper, Martin G. and Rowe, Steven and Lapa, Constantin}, title = {The theranostic promise for neuroendocrine tumors in the late 2010s - Where do we stand, where do we go?}, series = {Theranostics}, volume = {8}, journal = {Theranostics}, number = {22}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-170264}, pages = {6088-6100}, year = {2018}, abstract = {More than 25 years after the first peptide receptor radionuclide therapy (PRRT), the concept of somatostatin receptor (SSTR)-directed imaging and therapy for neuroendocrine tumors (NET) is seeing rapidly increasing use. To maximize the full potential of its theranostic promise, efforts in recent years have expanded recommendations in current guidelines and included the evaluation of novel theranostic radiotracers for imaging and treatment of NET. Moreover, the introduction of standardized reporting framework systems may harmonize PET reading, address pitfalls in interpreting SSTR-PET/CT scans and guide the treating physician in selecting PRRT candidates. Notably, the concept of PRRT has also been applied beyond oncology, e.g. for treatment of inflammatory conditions like sarcoidosis. Future perspectives may include the efficacy evaluation of PRRT compared to other common treatment options for NET, novel strategies for closer monitoring of potential side effects, the introduction of novel radiotracers with beneficial pharmacodynamic and kinetic properties or the use of supervised machine learning approaches for outcome prediction. This article reviews how the SSTR-directed theranostic concept is currently applied and also reflects on recent developments that hold promise for the future of theranostics in this context.}, subject = {Positronen-Emissions-Tomografie}, language = {en} } @article{BaurOttoStegeretal.2018, author = {Baur, Johannes and Otto, Christoph and Steger, Ulrich and Klein-Hessling, Stefan and Muhammad, Khalid and Pusch, Tobias and Murti, Krisna and Wismer, Rhoda and Germer, Christoph-Thomas and Klein, Ingo and M{\"u}ller, Nora and Serfling, Edgar and Avots, Andris}, title = {The transcription factor NFaTc1 supports the rejection of heterotopic heart allografts}, series = {Frontiers in Immunology}, volume = {9}, journal = {Frontiers in Immunology}, doi = {10.3389/fimmu.2018.01338}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-221530}, year = {2018}, abstract = {The immune suppressants cyclosporin A (CsA) and tacrolimus (FK506) are used worldwide in transplantation medicine to suppress graft rejection. Both CsA and FK506 inhibit the phosphatase calcineurin (CN) whose activity controls the immune receptor-mediated activation of lymphocytes. Downstream targets of CN in lymphocytes are the nuclear factors of activated T cells (NFATs). We show here that the activity of NFATc1, the most prominent NFAT factor in activated lymphocytes supports the acute rejection of heterotopic heart allografts. While ablation of NFATc1 in T cells prevented graft rejection, ectopic expression of inducible NFATc1/αA isoform led to rejection of heart allografts in recipient mice. Acceptance of transplanted hearts in mice bearing NFATc1-deficient T cells was accompanied by a reduction in number and cytotoxicity of graft infiltrating cells. In CD8\(^+\) T cells, NFATc1 controls numerous intracellular signaling pathways that lead to the metabolic switch to aerobic glycolysis and the expression of numerous lymphokines, chemokines, and their receptors, including Cxcr3 that supports the rejection of allogeneic heart transplants. These findings favors NFATc1 as a molecular target for the development of new strategies to control the cytotoxicity of T cells upon organ transplantation.}, language = {en} } @phdthesis{Wohlfart2018, author = {Wohlfart, Christian}, title = {The Yellow River Basin in Transition - Multi-faceted Land Cover Change Analysis in the Yellow River Basin in the Context of Global Change Using Multi-sensor Remote Sensing Imagery}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-163724}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2018}, abstract = {As a cradle of ancient Chinese civilization, the Yellow River Basin has a very long human-environment interrelationship, where early anthropogenic activities re- sulted in large scale landscape modifications. Today, the impact of this relationship has intensified further as the basin plays a vital role for China's continued economic development. It is one of the most densely-populated, fastest growing, and most dynamic regions of China with abundant natural and environmental resources providing a livelihood for almost 190 million people. Triggered by fundamental economic reforms, the basin has witnessed a spectacular economic boom during the last decades and can be considered as an exemplary blueprint region for contemporary dynamic Global Change processes occurring throughout the country, which is currently transitioning from an agrarian-dominated economy into a modern urbanized society. However, this resourcesdemanding growth has led to profound land use changes with adverse effects on the Yellow River social-ecological systems, where complex challenges arise threatening a long-term sustainable development. Consistent and continuous remote sensing-based monitoring of recent and past land cover and land use change is a fundamental requirement to mitigate the adverse impacts of Global Change processes. Nowadays, technical advancement and the multitude of available satellite sensors, in combination with the opening of data archives, allow the creation of new research perspectives in regional land cover applications over heterogeneous landscapes at large spatial scales. Despite the urgent need to better understand the prevailing dynamics and underlying factors influencing the current processes, detailed regional specific land cover data and change information are surprisingly absent for this region. In view of the noted research gaps and contemporary developments, three major objectives are defined in this thesis. First (i), the current and most pressing social-ecological challenges are elaborated and policy and management instruments towards more sustainability are discussed. Second (ii), this thesis provides new and improved insights on the current land cover state and dynamics of the entire Yellow River Basin. Finally (iii), the most dominant processes related to mining, agriculture, forest, and urban dynamics are determined on finer spatial and temporal scales. The complex and manifold problems and challenges that result from long-term abuse of the water and land resources in the basin have been underpinned by policy choices, cultural attitude, and institutions that have evolved over centuries in China. The tremendous economic growth that has been mainly achieved by extracting water and exploiting land resources in a rigorous, but unsustainable manner, might not only offset the economic benefits, but could also foster social unrest. Since the early emergence of the first Chinese dynasties, flooding was considered historically as a primary issue in river management and major achievements have been made to tame the wild nature of the Yellow River. Whereas flooding is therefore largely now under control, new environmental and social problems have evolved, including soil and water pollution, ecological degradation, biodiversity decline, and food security, all being further aggravated by anthropogenic climate change. To resolve the contemporary and complex challenges, many individual environmental laws and regulations have been enacted by various Chinese ministries. However, these policies often pursue different, often contradictory goals, are too general to tackle specific problems and are usually implemented by a strong top-down approach. Recently, more flexible economic and market-based incentives (pricing, tradable permits, investments) have been successfully adopted, which are specifically tailored to the respective needs, shifting now away from the pure command and regulating instruments. One way towards a more holistic and integrated river basin management could be the establishment of a common platform (e.g. a Geographical Information System) for data handling and sharing, possibly operated by the Yellow River Basin Conservancy Commission (YRCC), where available spatial data, statistical information and in-situ measures are coalesced, on which sustainable decision-making could be based. So far, the collected data is hardly accessible, fragmented, inconsistent, or outdated. The first step to address the absence and lack of consistent and spatially up-to-date information for the entire basin capturing the heterogeneous landscape conditions was taken up in this thesis. Land cover characteristics and dynamics were derived from the last decade for the years 2003 and 2013, based on optical medium-resolution hightemporal MODIS Normalized Differenced Vegetation Index (NDVI) time series at 250 m. To minimize the inherent influence of atmospheric and geometric interferences found in raw high temporal data, the applied adaptive Savitzky-Golay filter successfully smoothed the time series and substantially reduced noise. Based on the smoothed time series data, a large variety of intra-annual phenology metrics as well as spectral and multispectral annual statistics were derived, which served as input variables for random forest (RF) classifiers. High quality reference data sets were derived from very high resolution imagery for each year independently of which 70 \% trained the RF models. The accuracy assessments for all regionally specific defined thematic classes were based on the remaining 30 \% reference data split and yielded overall accuracies of 87 \% and 84 \% for 2003 and 2013, respectively. The first regional adapted Yellow River Land Cover Products (YRB LC) depict the detail spatial extent and distribution of the current land cover status and dynamics. The novel products overall differentiate overall 18 land cover and use classes, including classes of natural vegetation (terrestrial and aquatic), cultivated classes, mosaic classes, non-vegetated, and artificial classes, which are not presented in previous land cover studies so far. Building on this, an extended multi-faceted land cover analysis on the most prominent land cover change types at finer spatial and temporal scales provides a better and more detailed picture of the Yellow River Basin dynamics. Precise spatio-temporal products about mining, agriculture, forest, and urban areas were examined from long-trem Landsat satellite time series monitored at annual scales to capture the rapid rate of change in four selected focus regions. All archived Landsat images between 2000 and 2015 were used to derive spatially continuous spectral-temporal, multi-spectral, and textural metrics. For each thematic region and year RF models were built, trained and tested based on a stablepixels reference data set. The automated adaptive signature (AASG) algorithm identifies those pixels that did not change between the investigated time periods to generate a mono-temporal reference stable-pixels data set to keep manual sampling requirements to a minimum level. Derived results gained high accuracies ranging from 88 \% to 98 \%. Throughout the basin, afforestation on the Central Loess Plateau and urban sprawl are identified as most prominent drivers of land cover change, whereas agricultural land remained stable, only showing local small-scale dynamics. Mining operations started in 2004 on the Qinghai-Tibet Plateau, which resulted in a substantial loss of pristine alpine meadows and wetlands. In this thesis, a novel and unique regional specific view of current and past land cover characteristics in a complex and heterogeneous landscape was presented by using a multi-source remote sensing approach. The delineated products hold great potential for various model and management applications. They could serve as valuable components for effective and sustainable land and water management to adapt and mitigate the predicted consequences of Global Change processes.}, subject = {Fernerkundung}, language = {en} } @phdthesis{Hofmann2018, author = {Hofmann, Lukas}, title = {The α-galactosidase A deficient mouse as a model for Fabry disease and the effect of Gb3 depositions on peripheral nociceptive ion channel function}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-158513}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2018}, abstract = {Fabry disease (FD) is an X-linked lysosomal storage disorder with intracellular accumulation of globotriaosylceramide (Gb3) due to α-galactosidase A deficiency. We studied α-galactosidase A knockout mice (GLA KO) as a model for sensory disturbance and pain in FD. Pain associated behavior of young (3 months) and old (≥18 months) GLA KO mice and wildtype (WT) littermates in an inflammatory and a neuropathic pain model was investigated. Furthermore, affective and cognitive behavior was assessed in the na{\"i}ve state and in an inflammatory pain model. Gene and protein expression of pain associated ion channels and Gb3 accumulation in dorsal root ganglion (DRG) neurons was determined. We also performed patch clamp analysis on cultivated DRG neurons and human embryonic kidney 293 (HEK) cells expressing voltage-gated-sodium channel 1.7 (Nav1.7) as an in vitro model of FD. Intracellular Gb3 deposits were modulated using shRNA silencing of α-galactosidase A. After intraplantar injection of complete Freund`s adjuvant (CFA) and chronic constriction injury (CCI) of the right sciatic nerve, old GLA KO mice did not develop heat and mechanical hypersensitivity in contrast to young GLA KO and old WT mice. Additionally, we found no relevant differences between genotypes and age-groups in affective and cognitive behavior in the na{\"i}ve state and after CFA injection. Gene and protein expression analysis provided no explanation for the observed sensory impairment. However, cultured DRG neurons of old GLA KO mice revealed a marked decrease of sodium and Ih-currents compared to young GLA KO and old WT mice. DRG neurons of old GLA KO mice displayed substantial intracellular accumulation of Gb3 compared to young GLA KO and old WT mice. Similar to cultured neurons, sodium currents were also decreased in HEK cells treated with shRNA and consecutively increased intracellular Gb3 deposits compared to the control condition, but could be rescued by treatment with agalsidase-alpha. Our study unveils that, similar to patients with FD, GLA KO mice display age-dependent sensory deficits. However, contrary to patients, GLA KO mice are also protected from hypersensitivity induced by inflammation and nerve lesion due to Gb3-dependent and reversible reduction of neuronal sodium- and Ih-currents. Our data provide evidence for direct Gb3-dependent ion channel impairment in sensory DRG neurons as a potential contributor to sensory dysfunction and pain in FD.}, subject = {Fabry-Krankheit}, language = {en} } @article{BuraBeaupreLegareetal.2018, author = {Bura, Thomas and Beaupr{\´e}, Serge and L{\´e}gar{\´e}, Marc-Andr{\´e} and Ibraikulov, Olzhas A. and Leclerc, Nicolas and Leclerc, Mario}, title = {Theoretical calculations for highly selective Direct Heteroarylation Polymerization: new nitrile-substituted Dithienyl-Diketopyrrolopyrrole-based polymers}, series = {Molecules}, volume = {23}, journal = {Molecules}, number = {9}, issn = {1420-3049}, doi = {10.3390/molecules23092324}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-197648}, pages = {2324}, year = {2018}, abstract = {Direct Heteroarylation Polymerization (DHAP) is becoming a valuable alternative to classical polymerization methods being used to synthesize π-conjugated polymers for organic electronics applications. In previous work, we showed that theoretical calculations on activation energy (Ea) of the C-H bonds were helpful to rationalize and predict the selectivity of the DHAP. For readers' convenience, we have gathered in this work all our previous theoretical calculations on Ea and performed new ones. Those theoretical calculations cover now most of the widely utilized electron-rich and electron-poor moieties studied in organic electronics like dithienyl-diketopyrrolopyrrole (DT-DPP) derivatives. Theoretical calculations reported herein show strong modulation of the Ea of C-H bond on DT-DPP when a bromine atom or strong electron withdrawing groups (such as fluorine or nitrile) are added to the thienyl moiety. Based on those theoretical calculations, new cyanated dithienyl-diketopyrrolopyrrole (CNDT-DPP) monomers and copolymers were prepared by DHAP and their electro-optical properties were compared with their non-fluorinated and fluorinated analogues.}, language = {en} } @phdthesis{Feineis2018, author = {Feineis, Susanne}, title = {Thioether-poly(glycidol) as multifunctional coating system for gold nanoparticles}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-172902}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2018}, abstract = {The aim of this thesis was the development of a multifunctional coating system for AuNPs based on thioether polymers, providing both excellent colloidal stability and a variable possibility to introduce functionalities for biological applications. First, two thioether-polymer systems were synthesised as a systematic investigation into colloidal stabilisation efficacy. Besides commonly used monovalent poly(ethylene glycol) (PEG-SR), its structural analogue linear poly(glycidol) (PG-SR) bearing multiple statistically distributed thioether moieties along the backbone was synthesised. Additionally, respective thiol analogues (PEG-SH and PG-SH) were produced and applied as reference. Successive modification of varyingly large AuNPs with aforementioned thiol- and thioether-polymers was performed via ligand exchange reaction on citrate stabilised AuNPs. An increased stabilisation efficacy of both thioether-polymers against biological and physiological conditions, as well as against freeze-drying compared to thiol analogues was determined. Based on the excellent colloidal stabilisation efficacy and multi-functionalisability of thioether-PG, a plethora of functional groups, such as charged groups, hydrophilic/hydrophobic chains, as well as bio-active moieties namely diazirine and biotin was introduced to the AuNP surface. Moreover, the generic and covalent binding of diazirine-modified PG-SR with biomolecules including peptides and proteins was thoroughly demonstrated. Lastly, diverse applicability and bioactivity of aforementioned modified particles in various studies was displayed, once more verifying the introduction of functionalities. On the one hand the electrostatic interaction of charged AuNPs with hydrogels based on hyaluronic acid was applied to tune the release kinetics of particles from three-dimensional scaffolds. On the other hand the strong complexation of siRNA onto two positively charged AuNPs was proven. The amount of siRNA payload was tuneable by varying the surface charge, ionic strength of the surrounding medium and the N/P ratio. Moreover, the biological activity and selectivity of the biotin-streptavidin conjugation was verified with respectively functionalised particles in controlled agglomeration test and in laser-triggered cell elimination experiments. In the latter, streptavidin-functionalised AuNPs resulted in excellent depletion of biotinylated cells whereas unfunctionalised control particles failed, excluding unspecific binding of these particles to the cell surface.}, subject = {Nanopartikel}, language = {en} } @article{RiquelmeHaarerKammleretal.2018, author = {Riquelme, Paloma and Haarer, Jan and Kammler, Anja and Walter, Lisa and Tomiuk, Stefan and Ahrens, Norbert and Wege, Anja K. and Goecze, Ivan and Zecher, Daniel and Banas, Bernhard and Spang, Rainer and F{\"a}ndrich, Fred and Lutz, Manfred B. and Sawitzki, Birgit and Schlitt, Hans J. and Ochando, Jordi and Geissler, Edward K. and Hutchinson, James A.}, title = {TIGIT\(^+\) iTregs elicited by human regulatory macrophages control T cell immunity}, series = {Nature Communications}, volume = {9}, journal = {Nature Communications}, number = {9}, doi = {10.1038/s41467-018-05167-8}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-226321}, pages = {2858, 1-18}, year = {2018}, abstract = {Human regulatory macrophages (Mreg) have shown early clinical promise as a cell-based adjunct immunosuppressive therapy in solid organ transplantation. It is hypothesised that recipient CD4(+) T cell responses are actively regulated through direct allorecognition of donor-derived Mregs. Here we show that human Mregs convert allogeneic CD4(+) T cells to IL-10-producing, TIGIT(+) FoxP3(+)-induced regulatory T cells that non-specifically suppress bystander T cells and inhibit dendritic cell maturation. Differentiation of Mreg-induced Tregs relies on multiple non-redundant mechanisms that are not exclusive to interaction of Mregs and T cells, including signals mediated by indoleamine 2,3-dioxygenase, TGF-beta, retinoic acid, Notch and progestagen-associated endometrial protein. Preoperative administration of donor-derived Mregs to living-donor kidney transplant recipients results in an acute increase in circulating TIGIT(+) Tregs. These results suggest a feed-forward mechanism by which Mreg treatment promotes allograft acceptance through rapid induction of direct-pathway Tregs.}, language = {en} } @phdthesis{Nuernberger2018, author = {N{\"u}rnberger, Fabian}, title = {Timing of colony phenology and foraging activity in honey bees}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-155105}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2018}, abstract = {I. Timing is a crucial feature in organisms that live within a variable and changing environment. Complex mechanisms to measure time are wide-spread and were shown to exist in many taxa. These mechanisms are expected to provide fitness benefits by enabling organisms to anticipate environmental changes and adapt accordingly. However, very few studies have addressed the adaptive value of proper timing. The objective of this PhD-project was to investigate mechanisms and fitness consequences of timing decisions concerning colony phenology and foraging activity in the honey bee (Apis mellifera), a social insect species with a high degree of social organization and one of the most important pollinators of wild plants and crops. In chapter II, a study is presented that aimed to identify the consequences of disrupted synchrony between colony phenology and the local environment by manipulating the timing of brood onset after hibernation. In a follow-up experiment, the importance of environmental factors for the timing of brood onset was investigated to assess the potential of climate change to disrupt synchronization of colony phenology (Chapter III). Chapter IV aimed to prove for the first time that honey bees can use interval time-place learning to improve foraging activity in a variable environment. Chapter V investigates the fitness benefits of information exchange between nest mates via waggle dance communication about a resource environment that is heterogeneous in space and time. II. In the study presented in chapter II, the importance of the timing of brood onset after hibernation as critical point in honey bee colony phenology in temperate zones was investigated. Honey bee colonies were overwintered at two climatically different sites. By translocating colonies from each site to the other in late winter, timing of brood onset was manipulated and consequently colony phenology was desynchronized with the local environment. Delaying colony phenology in respect to the local environment decreased the capability of colonies to exploit the abundant spring bloom. Early brood onset, on the other hand, increased the loads of the brood parasite Varroa destructor later in the season with negative impact on colony worker population size. This indicates a timing related trade-off and illustrates the importance of investigating effects of climate change on complex multi-trophic systems. It can be concluded that timing of brood onset in honey bees is an important fitness relevant step for colony phenology that is highly sensitive to climatic conditions in late winter. Further, phenology shifts and mismatches driven by climate change can have severe fitness consequences. III. In chapter III, I assess the importance of the environmental factors ambient temperature and photoperiod as well as elapsed time on the timing of brood onset. Twenty-four hibernating honey bee colonies were placed into environmental chambers and allocated to different combinations of two temperature regimes and three different light regimes. Brood onset was identified non-invasively by tracking comb temperature within the winter cluster. The experiment revealed that ambient temperature plays a major role in the timing of brood onset, but the response of honey bee colonies to temperature increases is modified by photoperiod. Further, the data indicate the involvement of an internal clock. I conclude that the timing of brood onset is complex but probably highly susceptible to climate change and especially spells of warm weather in winter. IV. In chapter IV, it was examined if honey bees are capable of interval time-place learning and if this ability improves foraging efficiency in a dynamic resource environment. In a field experiment with artificial feeders, foragers were able to learn time intervals and use this ability to anticipate time periods during which feeders were active. Further, interval time-place learning enabled foragers to increase nectar uptake rates. It was concluded that interval time-place learning can help honey bee foragers to adapt to the complex and variable temporal patterns of floral resource environments. V. The study presented in chapter V identified the importance of the honey bee waggle dance communication for the spatiotemporal coordination of honey bee foraging activity in resource environments that can vary from day to day. Consequences of disrupting the instructional component of honey bee dance communication were investigated in eight temperate zone landscapes with different levels of spatiotemporal complexity. While nectar uptake of colonies was not affected, waggle dance communication significantly benefitted pollen harvest irrespective of landscape complexity. I suggest that this is explained by the fact that honey bees prefer to forage pollen in semi-natural habitats, which provide diverse resource species but are sparse and presumably hard to find in intensively managed agricultural landscapes. I conclude that waggle dance communication helps to ensure a sufficient and diverse pollen diet which is crucial for honey bee colony health. VI. In my PhD-project, I could show that honey bee colonies are able to adapt their activities to a seasonally and daily changing environment, which affects resource uptake, colony development, colony health and ultimately colony fitness. Ongoing global change, however, puts timing in honey bee colonies at risk. Climate change has the potential to cause mismatches with the local resource environment. Intensivation of agricultural management with decreased resource diversity and short resource peaks in spring followed by distinctive gaps increases the probability of mismatches. Even the highly efficient foraging system of honey bees might not ensure a sufficiently diverse and healthy diet in such an environment. The global introduction of the parasitic mite V. destructor and the increased exposure to pesticides in intensively managed landscapes further degrades honey bee colony health. This might lead to reduced cognitive capabilities in workers and impact the communication and social organization in colonies, thereby undermining the ability of honey bee colonies to adapt to their environment.}, subject = {Biene}, language = {en} } @phdthesis{SchenkneeWolf2018, author = {Schenk [n{\´e}e Wolf], Mariela}, title = {Timing of wild bee emergence: mechanisms and fitness consequences}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-161565}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2018}, abstract = {Solitary bees in seasonal environments have to align their life-cycles with favorable environmental conditions and resources. Therefore, a proper timing of their seasonal activity is highly fitness relevant. Most species in temperate environments use temperature as a trigger for the timing of their seasonal activity. Hence, global warming can disrupt mutualistic interactions between solitary bees and plants if increasing temperatures differently change the timing of interaction partners. The objective of this dissertation was to investigate the mechanisms of timing in spring-emerging solitary bees as well as the resulting fitness consequences if temporal mismatches with their host plants should occur. In my experiments, I focused on spring-emerging solitary bees of the genus Osmia and thereby mainly on O. cornuta and O. bicornis (in one study which is presented in Chapter IV, I additionally investigated a third species: O. brevicornis). Chapter II presents a study in which I investigated different triggers solitary bees are using to time their emergence in spring. In a climate chamber experiment I investigated the relationship between overwintering temperature, body size, body weight and emergence date. In addition, I developed a simple mechanistic model that allowed me to unite my different observations in a consistent framework. In combination with the empirical data, the model strongly suggests that solitary bees follow a strategic approach and emerge at a date that is most profitable for their individual fitness expectations. I have shown that this date is on the one hand temperature dependent as warmer overwintering temperatures increase the weight loss of bees during hibernation, which then advances their optimal emergence date to an earlier time point (due to an earlier benefit from the emergence event). On the other hand I have also shown that the optimal emergence date depends on the individual body size (or body weight) as bees adjust their emergence date accordingly. My data show that it is not enough to solely investigate temperature effects on the timing of bee emergence, but that we should also consider individual body conditions of solitary bees to understand the timing of bee emergence. In Chapter III, I present a study in which I investigated how exactly temperature determines the emergence date of solitary bees. Therefore, I tested several variants degree-day models to relate temperature time series to emergence data. The basic functioning of such degree-day models is that bees are said to finally emerge when a critical amount of degree-days is accumulated. I showed that bees accumulate degree-days only above a critical temperature value (~4°C in O. cornuta and ~7°C in O. bicornis) and only after the exceedance of a critical calendar date (~10th of March in O. cornuta and ~28th of March in O. bicornis). Such a critical calendar date, before which degree-days are not accumulated irrespective of the actual temperature, is in general less commonly used and, so far, it has only been included twice in a phenology model predicting bee emergence. Furthermore, I used this model to retrospectively predict the emergence dates of bees by applying the model to long-term temperature data which have been recorded by the regional climate station in W{\"u}rzburg. By doing so, the model estimated that over the last 63 years, bees emerged approximately 4 days earlier. In Chapter IV, I present a study in which I investigated how temporal mismatches in bee-plant interactions affect the fitness of solitary bees. Therefore, I performed an experiment with large flight cages serving as mesocosms. Inside these mesocosms, I manipulated the supply of blossoms to synchronize or desynchronize bee-plant interactions. In sum, I showed that even short temporal mismatches of three and six days in bee-plant interactions (with solitary bee emergence before flower occurrence) can cause severe fitness losses in solitary bees. Nonetheless, I detected different strategies by solitary bees to counteract impacts on their fitness after temporal mismatches. However, since these strategies may result in secondary fitness costs by a changed sex ratio or increased parasitism, I concluded that compensation strategies do not fully mitigate fitness losses of bees after short temporal mismatches with their food plants. In the event of further climate warming, fitness losses after temporal mismatches may not only exacerbate bee declines but may also reduce pollination services for later-flowering species and affect populations of animal-pollinated plants. In conclusion, I showed that spring-emerging solitary bees are susceptible to climate change as in response to warmer temperatures bees advance their phenology and show a decreased fitness state. As spring-emerging solitary bees not only consider overwintering temperature but also their individual body condition for adjusting emergence dates, this may explain differing responses to climate warming within and among bee populations which may also have consequences for bee-plant interactions and the persistence of bee populations under further climate warming. If in response to climate warming plants do not shift their phenologies according to the bees, bees may experience temporal mismatches with their host plants. As bees failed to show a single compensation strategy that was entirely successful in mitigating fitness consequences after temporal mismatches with their food plants, the resulting fitness consequences for spring-emerging solitary bees would be severe. Furthermore, I showed that spring-emerging solitary bees use a critical calendar date before which they generally do not commence the summation of degree-days irrespective of the actual temperature. I therefore suggest that further studies should also include the parameter of a critical calendar date into degree-day model predictions to increase the accuracy of model predictions for emergence dates in solitary bees. Although our retrospective prediction about the advance in bee emergence corresponds to the results of several studies on phenological trends of different plant species, we suggest that more research has to be done to assess the impacts of climate warming on the synchronization in bee-plant interactions more accurately.}, subject = {wild bees}, language = {en} } @article{KlenkeQuastPrelogetal.2018, author = {Klenke, Daniela and Quast, Anja and Prelog, Martina and Holl-Wieden, Annette and Riekert, Maximilian and Stellzig-Eisenhauer, Angelika and Meyer-Marcotty, Philipp}, title = {TMJ pathomorphology in patients with JIA-radiographic parameters for early diagnosis-}, series = {Head \& Face Medicine}, volume = {14}, journal = {Head \& Face Medicine}, doi = {10.1186/s13005-018-0173-5}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-325882}, year = {2018}, abstract = {Background Juvenile idiopathic arthritis (JIA) is often accompanied by pathomorphological changes to the temporomandibular joint (TMJ). By analyzing orthodontical orthopantomograms of JIA patients the aims of the study were a) classification of condyle changes, b) quantification of bony asymmetries of condylar destruction and c) detection of relationships between disease duration and TMJ-involvement. Patients/Methods 46 caucasian JIA-patients (28 female; 18 male; < 16.0 years) were enrolled, each joint (n = 92) was morphologically assessed by means of orthopantomogram, quantitatively analysed and compared with duration of general disease. Condyle morphology was assessed using the Billiau scale for severity of destruction [1]. The quantitative analysis was based on ratios of condyle, ramus and mandible height. Results Patients were divided into groups (Group I - slightly affected, n = 36; Billiau severity 0-2; condyle findings: X-ray normal, condyle erosions, condylar flattening; Group II - severely affected, N = 10; Billiau severity 3-4; condyle findings: condylar flattenings and erosions, unilateral/bilateral complete loss of condyles), based on morphological analysis of condylar destruction. Duration of disease was significantly longer in Group II (8.9 ± 5.2 years) than in Group I (4.6 ± 4.7 years). Asymmetries of condyle, ramus and mandible height, quantitatively analysed by contralateral comparison, were significantly more marked in patients of Group II than of Group I. Conclusions Orthopantomogram imaging can be used in orthodontics clinical routine to detect TMJ-pathologies and is an important reference for monitoring progression of JIA. Classification into severe and slightly affected TMJ is possible by analysis of condylar pathomorphology. An association between degree of destruction, extent of lower jaw asymmetry and disease duration is suggested by the results.}, language = {en} }