@article{VedderAnkenbrandSarmentoCabral2021, author = {Vedder, Daniel and Ankenbrand, Markus and Sarmento Cabral, Juliano}, title = {Dealing with software complexity in individual-based models}, series = {Methods in Ecology and Evolution}, volume = {12}, journal = {Methods in Ecology and Evolution}, number = {12}, doi = {10.1111/2041-210X.13716}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-258214}, pages = {2324-2333}, year = {2021}, abstract = {Individual-based models are doubly complex: as well as representing complex ecological systems, the software that implements them is complex in itself. Both forms of complexity must be managed to create reliable models. However, the ecological modelling literature to date has focussed almost exclusively on the biological complexity. Here, we discuss methods for containing software complexity. Strategies for containing complexity include avoiding, subdividing, documenting and reviewing it. Computer science has long-established techniques for all of these strategies. We present some of these techniques and set them in the context of IBM development, giving examples from published models. Techniques for avoiding software complexity are following best practices for coding style, choosing suitable programming languages and file formats and setting up an automated workflow. Complex software systems can be made more tractable by encapsulating individual subsystems. Good documentation needs to take into account the perspectives of scientists, users and developers. Code reviews are an effective way to check for errors, and can be used together with manual or automated unit and integration tests. Ecological modellers can learn from computer scientists how to deal with complex software systems. Many techniques are readily available, but must be disseminated among modellers. There is a need for further work to adapt software development techniques to the requirements of academic research groups and individual-based modelling.}, language = {en} } @article{LewerentzHoffmannSarmentoCabral2021, author = {Lewerentz, Anne and Hoffmann, Markus and Sarmento Cabral, Juliano}, title = {Depth diversity gradients of macrophytes: Shape, drivers, and recent shifts}, series = {Ecology and Evolution}, volume = {11}, journal = {Ecology and Evolution}, number = {20}, doi = {10.1002/ece3.8089}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-260280}, pages = {13830-13845}, year = {2021}, abstract = {Investigating diversity gradients helps to understand biodiversity drivers and threats. However, one diversity gradient is rarely assessed, namely how plant species distribute along the depth gradient of lakes. Here, we provide the first comprehensive characterization of depth diversity gradient (DDG) of alpha, beta, and gamma species richness of submerged macrophytes across multiple lakes. We characterize the DDG for additive richness components (alpha, beta, gamma), assess environmental drivers, and address temporal change over recent years. We take advantage of yet the largest dataset of macrophyte occurrence along lake depth (274 depth transects across 28 deep lakes) as well as of physiochemical measurements (12 deep lakes from 2006 to 2017 across Bavaria), provided publicly online by the Bavarian State Office for the Environment. We found a high variability in DDG shapes across the study lakes. The DDGs for alpha and gamma richness are predominantly hump-shaped, while beta richness shows a decreasing DDG. Generalized additive mixed-effect models indicate that the depth of the maximum richness (Dmax) is influenced by light quality, light quantity, and layering depth, whereas the respective maximum alpha richness within the depth gradient (Rmax) is significantly influenced by lake area only. Most observed DDGs seem generally stable over recent years. However, for single lakes we found significant linear trends for Rmax and Dmax going into different directions. The observed hump-shaped DDGs agree with three competing hypotheses: the mid-domain effect, the mean-disturbance hypothesis, and the mean-productivity hypothesis. The DDG amplitude seems driven by lake area (thus following known species-area relationships), whereas skewness depends on physiochemical factors, mainly water transparency and layering depth. Our results provide insights for conservation strategies and for mechanistic frameworks to disentangle competing explanatory hypotheses for the DDG.}, language = {en} } @article{Korte2022, author = {Korte, Arthur}, title = {Der Zusammenhang zwischen Genom und Ph{\"a}notyp}, series = {BIOspektrum}, volume = {28}, journal = {BIOspektrum}, number = {3}, issn = {0947-0867}, doi = {10.1007/s12268-022-1765-y}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-324231}, pages = {279-282}, year = {2022}, abstract = {Understanding the causal relationship between genotype and phenotype is a major objective in biology. Genome-wide association studies (GWAS) correlate genetic polymorphisms with trait variation and have already identified causative variants for various traits in many different organisms, from humans to plants. Importantly, many adaptive traits, like the regulation of flowering time in plants, are not regulated by distinct genetic effects, but by more sophisticated gene regulatory networks.}, language = {de} } @phdthesis{Fuellsack2019, author = {F{\"u}llsack, Simone Alexandra}, title = {Die Bedeutung von Todesdom{\"a}ne Adapterproteinen f{\"u}r die Signaltransduktion des TNFR1 und der TRAIL Todesrezeptoren}, doi = {10.25972/OPUS-18451}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-184518}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2019}, abstract = {Die NFκB-Signalwege, Apoptose und Nekroptose sind essentielle Prozesse in der Immunantwort. Außerdem sind diese Signalwege Teil der Regulation von Zelldifferenzierung, -proliferation, -tod und Entz{\"u}ndungsreaktionen. Dabei wird zuerst der Rezeptor (TNFR1 oder TRAILR 1/2) aktiviert, die rekrutierten DD-Adapterproteine TRADD, FADD und RIPK1 leiten dann die entsprechende Signalkaskade weiter und bestimmen durch ihre Zusammenwirkung, ob der NFκB-Signalweg, Apoptose oder Nekroptose induziert wird. TNFR1 und TRAILR 1/2 ben{\"o}tigen die DD-Adapterproteine TRADD, FADD und RIPK1 f{\"u}r die Zelltodinduktion, deren konkrete Bedeutung in Bezug auf Rezeptor-Spezifit{\"a}t, Zusammenwirken und Relevanz allerdings noch unklar ist. Um das Zusammenspiel dieser Proteine besser zu verstehen, wurden in dieser Arbeit Nekroptose-kompetente RIPK3-exprimierende HeLa-Zellen verwendet, bei denen die DD-Adapterproteine FADD, TRADD und RIPK1 einzeln oder in Kombination von zweien ausgeknockt wurden. Es stellte sich heraus, dass RIPK1 essentiell f{\"u}r die TNFR1- und TRAILR 1/2-vermittelte Nekroptose-Induktion ist, doch RIPK1 alleine, d.h. ohne FADD- oder TRADD-Mitbeteiligung, nur bei der TNFR1-Nekroptose-Induktion ausreicht. Wiederum inhibiert TRADD die TNFR1- und TRAILR 1/2-induzierte Nekroptose. RIPK1 und TRADD sind aber unverzichtbar f{\"u}r die NFκB-Aktivierung durch TNFR1 oder TRAILR 1/2 und spielen eine wichtige Rolle bei TNFR1-induzierter Apoptose. Andererseits ist FADD alleine ausreichend f{\"u}r die TRAILR 1/2-bezogene Caspase-8 Aktivierung. Zudem ist FADD notwendig f{\"u}r die TRAIL-induzierte NFκB-Signalaktivierung. In Abwesenheit von FADD und TRADD vermittelt RIPK1 die TNF-induzierte Caspase-8 Aktivierung. FADD wird f{\"u}r die TRAIL-induzierte Nekroptose ben{\"o}tigt, aber gegenl{\"a}ufig wirkt die TNF-induzierte Nektroptose in einer Caspase-8 abh{\"a}ngigen und unabh{\"a}ngigen Weise. Zudem sensitiviert TWEAK die TNF- und TRAIL-induzierte Nekroptose. Zusammenfassend wurde in dieser Arbeit die Auswirkung von TNFR1 und TRAILR 1/2 auf die Aktivierung der unterschiedlichen Signalkaskaden untersucht. Des Weiteren wurde gezeigt, in welcher Weise sich das Zusammenspiel von TRADD, FADD und RIPK1 auf die Induktion von NFκB, Apoptose und Nekroptose auswirkt.}, subject = {Signaltransduktion}, language = {de} } @article{PetersKellerLeonhardt2022, author = {Peters, Birte and Keller, Alexander and Leonhardt, Sara Diana}, title = {Diets maintained in a changing world: Does land-use intensification alter wild bee communities by selecting for flexible generalists?}, series = {Ecology and evolution}, volume = {12}, journal = {Ecology and evolution}, number = {5}, issn = {2045-7758}, doi = {10.1002/ece3.8919}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-312786}, year = {2022}, abstract = {Biodiversity loss, as often found in intensively managed agricultural landscapes, correlates with reduced ecosystem functioning, for example, pollination by insects, and with altered plant composition, diversity, and abundance. But how does this change in floral resource diversity and composition relate to occurrence and resource use patterns of trap-nesting solitary bees? To better understand the impact of land-use intensification on communities of trap-nesting solitary bees in managed grasslands, we investigated their pollen foraging, reproductive fitness, and the nutritional quality of larval food along a land-use intensity gradient in Germany. We found bee species diversity to decrease with increasing land-use intensity irrespective of region-specific community compositions and interaction networks. Land use also strongly affected the diversity and composition of pollen collected by bees. Lack of suitable pollen sources likely explains the absence of several bee species at sites of high land-use intensity. The only species present throughout, Osmia bicornis (red mason bee), foraged on largely different pollen sources across sites. In doing so, it maintained a relatively stable, albeit variable nutritional quality of larval diets (i.e., protein to lipid (P:L) ratio). The observed changes in bee-plant pollen interaction patterns indicate that only the flexible generalists, such as O. bicornis, may be able to compensate the strong alterations in floral resource landscapes and to obtain food of sufficient quality through readily shifting to alternative plant sources. In contrast, other, less flexible, bee species disappear.}, language = {en} } @article{NaglerNaegeleGillietal.2018, author = {Nagler, Matthias and N{\"a}gele, Thomas and Gilli, Christian and Fragner, Lena and Korte, Arthur and Platzer, Alexander and Farlow, Ashley and Nordborg, Magnus and Weckwerth, Wolfram}, title = {Eco-Metabolomics and Metabolic Modeling: Making the Leap From Model Systems in the Lab to Native Populations in the Field}, series = {Frontiers in Plant Science}, volume = {9}, journal = {Frontiers in Plant Science}, number = {1556}, issn = {1664-462X}, doi = {10.3389/fpls.2018.01556}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-189560}, year = {2018}, abstract = {Experimental high-throughput analysis of molecular networks is a central approach to characterize the adaptation of plant metabolism to the environment. However, recent studies have demonstrated that it is hardly possible to predict in situ metabolic phenotypes from experiments under controlled conditions, such as growth chambers or greenhouses. This is particularly due to the high molecular variance of in situ samples induced by environmental fluctuations. An approach of functional metabolome interpretation of field samples would be desirable in order to be able to identify and trace back the impact of environmental changes on plant metabolism. To test the applicability of metabolomics studies for a characterization of plant populations in the field, we have identified and analyzed in situ samples of nearby grown natural populations of Arabidopsis thaliana in Austria. A. thaliana is the primary molecular biological model system in plant biology with one of the best functionally annotated genomes representing a reference system for all other plant genome projects. The genomes of these novel natural populations were sequenced and phylogenetically compared to a comprehensive genome database of A. thaliana ecotypes. Experimental results on primary and secondary metabolite profiling and genotypic variation were functionally integrated by a data mining strategy, which combines statistical output of metabolomics data with genome-derived biochemical pathway reconstruction and metabolic modeling. Correlations of biochemical model predictions and population-specific genetic variation indicated varying strategies of metabolic regulation on a population level which enabled the direct comparison, differentiation, and prediction of metabolic adaptation of the same species to different habitats. These differences were most pronounced at organic and amino acid metabolism as well as at the interface of primary and secondary metabolism and allowed for the direct classification of population-specific metabolic phenotypes within geographically contiguous sampling sites.}, language = {en} } @article{SahlolKollmannsbergerEwees2020, author = {Sahlol, Ahmed T. and Kollmannsberger, Philip and Ewees, Ahmed A.}, title = {Efficient Classification of White Blood Cell Leukemia with Improved Swarm Optimization of Deep Features}, series = {Scientific Reports}, volume = {10}, journal = {Scientific Reports}, number = {1}, doi = {10.1038/s41598-020-59215-9}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-229398}, year = {2020}, abstract = {White Blood Cell (WBC) Leukaemia is caused by excessive production of leukocytes in the bone marrow, and image-based detection of malignant WBCs is important for its detection. Convolutional Neural Networks (CNNs) present the current state-of-the-art for this type of image classification, but their computational cost for training and deployment can be high. We here present an improved hybrid approach for efficient classification of WBC Leukemia. We first extract features from WBC images using VGGNet, a powerful CNN architecture, pre-trained on ImageNet. The extracted features are then filtered using a statistically enhanced Salp Swarm Algorithm (SESSA). This bio-inspired optimization algorithm selects the most relevant features and removes highly correlated and noisy features. We applied the proposed approach to two public WBC Leukemia reference datasets and achieve both high accuracy and reduced computational complexity. The SESSA optimization selected only 1 K out of 25 K features extracted with VGGNet, while improving accuracy at the same time. The results are among the best achieved on these datasets and outperform several convolutional network models. We expect that the combination of CNN feature extraction and SESSA feature optimization could be useful for many other image classification tasks.}, language = {en} } @article{DannhaeuserMrestaniGundelachetal.2022, author = {Dannh{\"a}user, Sven and Mrestani, Achmed and Gundelach, Florian and Pauli, Martin and Komma, Fabian and Kollmannsberger, Philip and Sauer, Markus and Heckmann, Manfred and Paul, Mila M.}, title = {Endogenous tagging of Unc-13 reveals nanoscale reorganization at active zones during presynaptic homeostatic potentiation}, series = {Frontiers in Cellular Neuroscience}, volume = {16}, journal = {Frontiers in Cellular Neuroscience}, issn = {1662-5102}, doi = {10.3389/fncel.2022.1074304}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-299440}, year = {2022}, abstract = {Introduction Neurotransmitter release at presynaptic active zones (AZs) requires concerted protein interactions within a dense 3D nano-hemisphere. Among the complex protein meshwork the (M)unc-13 family member Unc-13 of Drosophila melanogaster is essential for docking of synaptic vesicles and transmitter release. Methods We employ minos-mediated integration cassette (MiMIC)-based gene editing using GFSTF (EGFP-FlAsH-StrepII-TEV-3xFlag) to endogenously tag all annotated Drosophila Unc-13 isoforms enabling visualization of endogenous Unc-13 expression within the central and peripheral nervous system. Results and discussion Electrophysiological characterization using two-electrode voltage clamp (TEVC) reveals that evoked and spontaneous synaptic transmission remain unaffected in unc-13\(^{GFSTF}\) 3rd instar larvae and acute presynaptic homeostatic potentiation (PHP) can be induced at control levels. Furthermore, multi-color structured-illumination shows precise co-localization of Unc-13\(^{GFSTF}\), Bruchpilot, and GluRIIA-receptor subunits within the synaptic mesoscale. Localization microscopy in combination with HDBSCAN algorithms detect Unc-13\(^{GFSTF}\) subclusters that move toward the AZ center during PHP with unaltered Unc-13\(^{GFSTF}\) protein levels.}, language = {en} } @article{KaltdorfSchulzeHelmprobstetal.2017, author = {Kaltdorf, Kristin Verena and Schulze, Katja and Helmprobst, Frederik and Kollmannsberger, Philip and Dandekar, Thomas and Stigloher, Christian}, title = {Fiji macro 3D ART VeSElecT: 3D automated reconstruction tool for vesicle structures of electron tomograms}, series = {PLoS Computational Biology}, volume = {13}, journal = {PLoS Computational Biology}, number = {1}, doi = {10.1371/journal.pcbi.1005317}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-172112}, year = {2017}, abstract = {Automatic image reconstruction is critical to cope with steadily increasing data from advanced microscopy. We describe here the Fiji macro 3D ART VeSElecT which we developed to study synaptic vesicles in electron tomograms. We apply this tool to quantify vesicle properties (i) in embryonic Danio rerio 4 and 8 days past fertilization (dpf) and (ii) to compare Caenorhabditis elegans N2 neuromuscular junctions (NMJ) wild-type and its septin mutant (unc-59(e261)). We demonstrate development-specific and mutant-specific changes in synaptic vesicle pools in both models. We confirm the functionality of our macro by applying our 3D ART VeSElecT on zebrafish NMJ showing smaller vesicles in 8 dpf embryos then 4 dpf, which was validated by manual reconstruction of the vesicle pool. Furthermore, we analyze the impact of C. elegans septin mutant unc-59(e261) on vesicle pool formation and vesicle size. Automated vesicle registration and characterization was implemented in Fiji as two macros (registration and measurement). This flexible arrangement allows in particular reducing false positives by an optional manual revision step. Preprocessing and contrast enhancement work on image-stacks of 1nm/pixel in x and y direction. Semi-automated cell selection was integrated. 3D ART VeSElecT removes interfering components, detects vesicles by 3D segmentation and calculates vesicle volume and diameter (spherical approximation, inner/outer diameter). Results are collected in color using the RoiManager plugin including the possibility of manual removal of non-matching confounder vesicles. Detailed evaluation considered performance (detected vesicles) and specificity (true vesicles) as well as precision and recall. We furthermore show gain in segmentation and morphological filtering compared to learning based methods and a large time gain compared to manual segmentation. 3D ART VeSElecT shows small error rates and its speed gain can be up to 68 times faster in comparison to manual annotation. Both automatic and semi-automatic modes are explained including a tutorial.}, language = {en} } @article{TrinklKaluzaWallaceetal.2020, author = {Trinkl, Moritz and Kaluza, Benjamin F. and Wallace, Helen and Heard, Tim A. and Keller, Alexander and Leonhardt, Sara D.}, title = {Floral Species Richness Correlates with Changes in the Nutritional Quality of Larval Diets in a Stingless Bee}, series = {Insects}, volume = {11}, journal = {Insects}, number = {2}, issn = {2075-4450}, doi = {10.3390/insects11020125}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-200605}, pages = {125}, year = {2020}, abstract = {Bees need food of appropriate nutritional quality to maintain their metabolic functions. They largely obtain all required nutrients from floral resources, i.e., pollen and nectar. However, the diversity, composition and nutritional quality of floral resources varies with the surrounding environment and can be strongly altered in human-impacted habitats. We investigated whether differences in plant species richness as found in the surrounding environment correlated with variation in the floral diversity and nutritional quality of larval provisions (i.e., mixtures of pollen, nectar and salivary secretions) composed by the mass-provisioning stingless bee Tetragonula carbonaria (Apidae: Meliponini). We found that the floral diversity of larval provisions increased with increasing plant species richness. The sucrose and fat (total fatty acid) content and the proportion and concentration of the omega-6 fatty acid linoleic acid decreased, whereas the proportion of the omega-3 fatty acid linolenic acid increased with increasing plant species richness. Protein (total amino acid) content and amino acid composition did not change. The protein to fat (P:F) ratio, known to affect bee foraging, increased on average by more than 40\% from plantations to forests and gardens, while the omega-6:3 ratio, known to negatively affect cognitive performance, decreased with increasing plant species richness. Our results suggest that plant species richness may support T. carbonaria colonies by providing not only a continuous resource supply (as shown in a previous study), but also floral resources of high nutritional quality.}, language = {en} } @article{BerberichKurzReinhardetal.2021, author = {Berberich, Andreas and Kurz, Andreas and Reinhard, Sebastian and Paul, Torsten Johann and Burd, Paul Ray and Sauer, Markus and Kollmannsberger, Philip}, title = {Fourier Ring Correlation and anisotropic kernel density estimation improve deep learning based SMLM reconstruction of microtubules}, series = {Frontiers in Bioinformatics}, volume = {1}, journal = {Frontiers in Bioinformatics}, doi = {10.3389/fbinf.2021.752788}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-261686}, year = {2021}, abstract = {Single-molecule super-resolution microscopy (SMLM) techniques like dSTORM can reveal biological structures down to the nanometer scale. The achievable resolution is not only defined by the localization precision of individual fluorescent molecules, but also by their density, which becomes a limiting factor e.g., in expansion microscopy. Artificial deep neural networks can learn to reconstruct dense super-resolved structures such as microtubules from a sparse, noisy set of data points. This approach requires a robust method to assess the quality of a predicted density image and to quantitatively compare it to a ground truth image. Such a quality measure needs to be differentiable to be applied as loss function in deep learning. We developed a new trainable quality measure based on Fourier Ring Correlation (FRC) and used it to train deep neural networks to map a small number of sampling points to an underlying density. Smooth ground truth images of microtubules were generated from localization coordinates using an anisotropic Gaussian kernel density estimator. We show that the FRC criterion ideally complements the existing state-of-the-art multiscale structural similarity index, since both are interpretable and there is no trade-off between them during optimization. The TensorFlow implementation of our FRC metric can easily be integrated into existing deep learning workflows.}, language = {en} } @article{GuptaOsmanogluMinochaetal.2022, author = {Gupta, Shishir K. and Osmanoglu, {\"O}zge and Minocha, Rashmi and Bandi, Sourish Reddy and Bencurova, Elena and Srivastava, Mugdha and Dandekar, Thomas}, title = {Genome-wide scan for potential CD4+ T-cell vaccine candidates in Candida auris by exploiting reverse vaccinology and evolutionary information}, series = {Frontiers in Medicine}, volume = {9}, journal = {Frontiers in Medicine}, issn = {2296-858X}, doi = {10.3389/fmed.2022.1008527}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-293953}, year = {2022}, abstract = {Candida auris is a globally emerging fungal pathogen responsible for causing nosocomial outbreaks in healthcare associated settings. It is known to cause infection in all age groups and exhibits multi-drug resistance with high potential for horizontal transmission. Because of this reason combined with limited therapeutic choices available, C. auris infection has been acknowledged as a potential risk for causing a future pandemic, and thus seeking a promising strategy for its treatment is imperative. Here, we combined evolutionary information with reverse vaccinology approach to identify novel epitopes for vaccine design that could elicit CD4+ T-cell responses against C. auris. To this end, we extensively scanned the family of proteins encoded by C. auris genome. In addition, a pathogen may acquire substitutions in epitopes over a period of time which could cause its escape from the immune response thus rendering the vaccine ineffective. To lower this possibility in our design, we eliminated all rapidly evolving genes of C. auris with positive selection. We further employed highly conserved regions of multiple C. auris strains and identified two immunogenic and antigenic T-cell epitopes that could generate the most effective immune response against C. auris. The antigenicity scores of our predicted vaccine candidates were calculated as 0.85 and 1.88 where 0.5 is the threshold for prediction of fungal antigenic sequences. Based on our results, we conclude that our vaccine candidates have the potential to be successfully employed for the treatment of C. auris infection. However, in vivo experiments are imperative to further demonstrate the efficacy of our design.}, language = {en} } @article{LopezArboledaReinertNordborgetal.2021, author = {Lopez-Arboleda, William Andres and Reinert, Stephan and Nordborg, Magnus and Korte, Arthur}, title = {Global genetic heterogeneity in adaptive traits}, series = {Molecular Biology and Evolution}, volume = {38}, journal = {Molecular Biology and Evolution}, number = {11}, doi = {10.1093/molbev/msab208}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-270410}, pages = {4822-4831}, year = {2021}, abstract = {Understanding the genetic architecture of complex traits is a major objective in biology. The standard approach for doing so is genome-wide association studies (GWAS), which aim to identify genetic polymorphisms responsible for variation in traits of interest. In human genetics, consistency across studies is commonly used as an indicator of reliability. However, if traits are involved in adaptation to the local environment, we do not necessarily expect reproducibility. On the contrary, results may depend on where you sample, and sampling across a wide range of environments may decrease the power of GWAS because of increased genetic heterogeneity. In this study, we examine how sampling affects GWAS in the model plant species Arabidopsis thaliana. We show that traits like flowering time are indeed influenced by distinct genetic effects in local populations. Furthermore, using gene expression as a molecular phenotype, we show that some genes are globally affected by shared variants, whereas others are affected by variants specific to subpopulations. Remarkably, the former are essentially all cis-regulated, whereas the latter are predominately affected by trans-acting variants. Our result illustrate that conclusions about genetic architecture can be extremely sensitive to sampling and population structure.}, language = {en} } @article{SchilcherHilsmannAnkenbrandetal.2022, author = {Schilcher, Felix and Hilsmann, Lioba and Ankenbrand, Markus J. and Krischke, Markus and Mueller, Martin J. and Steffan-Dewenter, Ingolf and Scheiner, Ricarda}, title = {Honeybees are buffered against undernourishment during larval stages}, series = {Frontiers in Insect Science}, volume = {2}, journal = {Frontiers in Insect Science}, issn = {2673-8600}, doi = {10.3389/finsc.2022.951317}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-304646}, year = {2022}, abstract = {The negative impact of juvenile undernourishment on adult behavior has been well reported for vertebrates, but relatively little is known about invertebrates. In honeybees, nutrition has long been known to affect task performance and timing of behavioral transitions. Whether and how a dietary restriction during larval development affects the task performance of adult honeybees is largely unknown. We raised honeybees in-vitro, varying the amount of a standardized diet (150 µl, 160 µl, 180 µl in total). Emerging adults were marked and inserted into established colonies. Behavioral performance of nurse bees and foragers was investigated and physiological factors known to be involved in the regulation of social organization were quantified. Surprisingly, adult honeybees raised under different feeding regimes did not differ in any of the behaviors observed. No differences were observed in physiological parameters apart from weight. Honeybees were lighter when undernourished (150 µl), while they were heavier under the overfed treatment (180 µl) compared to the control group raised under a normal diet (160 µl). These data suggest that dietary restrictions during larval development do not affect task performance or physiology in this social insect despite producing clear effects on adult weight. We speculate that possible effects of larval undernourishment might be compensated during the early period of adult life.}, language = {en} } @phdthesis{Leidinger2020, author = {Leidinger, Ludwig Klaus Theodor}, title = {How genomic and ecological traits shape island biodiversity - insights from individual-based models}, doi = {10.25972/OPUS-20730}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-207300}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2020}, abstract = {Life on oceanic islands provides a playground and comparably easy\-/studied basis for the understanding of biodiversity in general. Island biota feature many fascinating patterns: endemic species, species radiations and species with peculiar trait syndromes. However, classic and current island biogeography theory does not yet consider all the factors necessary to explain many of these patterns. In response to this, there is currently a shift in island biogeography research to systematically consider species traits and thus gain a more functional perspective. Despite this recent development, a set of species characteristics remains largely ignored in island biogeography, namely genomic traits. Evidence suggests that genomic factors could explain many of the speciation and adaptation patterns found in nature and thus may be highly informative to explain the fascinating and iconic phenomena known for oceanic islands, including species radiations and susceptibility to biotic invasions. Unfortunately, the current lack of comprehensive meaningful data makes studying these factors challenging. Even with paleontological data and space-for-time rationales, data is bound to be incomplete due to the very environmental processes taking place on oceanic islands, such as land slides and volcanism, and lacks causal information due to the focus on correlative approaches. As promising alternative, integrative mechanistic models can explicitly consider essential underlying eco\-/evolutionary mechanisms. In fact, these models have shown to be applicable to a variety of different systems and study questions. In this thesis, I therefore examined present mechanistic island models to identify how they might be used to address some of the current open questions in island biodiversity research. Since none of the models simultaneously considered speciation and adaptation at a genomic level, I developed a new genome- and niche-explicit, individual-based model. I used this model to address three different phenomena of island biodiversity: environmental variation, insular species radiations and species invasions. Using only a single model I could show that small-bodied species with flexible genomes are successful under environmental variation, that a complex combination of dispersal abilities, reproductive strategies and genomic traits affect the occurrence of species radiations and that invasions are primarily driven by the intensity of introductions and the trait characteristics of invasive species. This highlights how the consideration of functional traits can promote the understanding of some of the understudied phenomena in island biodiversity. The results presented in this thesis exemplify the generality of integrative models which are built on first principles. Thus, by applying such models to various complex study questions, they are able to unveil multiple biodiversity dynamics and patterns. The combination of several models such as the one I developed to an eco\-/evolutionary model ensemble could further help to identify fundamental eco\-/evolutionary principles. I conclude the thesis with an outlook on how to use and extend my developed model to investigate geomorphological dynamics in archipelagos and to allow dynamic genomes, which would further increase the model's generality.}, subject = {Inselbiogeografie}, language = {en} } @article{VedderLensMartinetal.2022, author = {Vedder, Daniel and Lens, Luc and Martin, Claudia A. and Pellikka, Petri and Adhikari, Hari and Heiskanen, Janne and Engler, Jan O. and Sarmento Cabral, Juliano}, title = {Hybridization may aid evolutionary rescue of an endangered East African passerine}, series = {Evolutionary Applications}, volume = {15}, journal = {Evolutionary Applications}, number = {7}, doi = {10.1111/eva.13440}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-287264}, pages = {1177-1188}, year = {2022}, abstract = {Abstract Introgressive hybridization is a process that enables gene flow across species barriers through the backcrossing of hybrids into a parent population. This may make genetic material, potentially including relevant environmental adaptations, rapidly available in a gene pool. Consequently, it has been postulated to be an important mechanism for enabling evolutionary rescue, that is the recovery of threatened populations through rapid evolutionary adaptation to novel environments. However, predicting the likelihood of such evolutionary rescue for individual species remains challenging. Here, we use the example of Zosterops silvanus, an endangered East African highland bird species suffering from severe habitat loss and fragmentation, to investigate whether hybridization with its congener Zosterops flavilateralis might enable evolutionary rescue of its Taita Hills population. To do so, we employ an empirically parameterized individual-based model to simulate the species' behaviour, physiology and genetics. We test the population's response to different assumptions of mating behaviour and multiple scenarios of habitat change. We show that as long as hybridization does take place, evolutionary rescue of Z. silvanus is likely. Intermediate hybridization rates enable the greatest long-term population growth, due to trade-offs between adaptive and maladaptive introgressed alleles. Habitat change did not have a strong effect on population growth rates, as Z. silvanus is a strong disperser and landscape configuration is therefore not the limiting factor for hybridization. Our results show that targeted gene flow may be a promising avenue to help accelerate the adaptation of endangered species to novel environments, and demonstrate how to combine empirical research and mechanistic modelling to deliver species-specific predictions for conservation planning.}, language = {en} } @article{MarquardtLandwehrRonchietal.2021, author = {Marquardt, Andr{\´e} and Landwehr, Laura-Sophie and Ronchi, Cristina L. and di Dalmazi, Guido and Riester, Anna and Kollmannsberger, Philip and Altieri, Barbara and Fassnacht, Martin and Sbiera, Silviu}, title = {Identifying New Potential Biomarkers in Adrenocortical Tumors Based on mRNA Expression Data Using Machine Learning}, series = {Cancers}, volume = {13}, journal = {Cancers}, number = {18}, issn = {2072-6694}, doi = {10.3390/cancers13184671}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-246245}, year = {2021}, abstract = {Simple Summary Using a visual-based clustering method on the TCGA RNA sequencing data of a large adrenocortical carcinoma (ACC) cohort, we were able to classify these tumors in two distinct clusters largely overlapping with previously identified ones. As previously shown, the identified clusters also correlated with patient survival. Applying the visual clustering method to a second dataset also including benign adrenocortical samples additionally revealed that one of the ACC clusters is more closely located to the benign samples, providing a possible explanation for the better survival of this ACC cluster. Furthermore, the subsequent use of machine learning identified new possible biomarker genes with prognostic potential for this rare disease, that are significantly differentially expressed in the different survival clusters and should be further evaluated. Abstract Adrenocortical carcinoma (ACC) is a rare disease, associated with poor survival. Several "multiple-omics" studies characterizing ACC on a molecular level identified two different clusters correlating with patient survival (C1A and C1B). We here used the publicly available transcriptome data from the TCGA-ACC dataset (n = 79), applying machine learning (ML) methods to classify the ACC based on expression pattern in an unbiased manner. UMAP (uniform manifold approximation and projection)-based clustering resulted in two distinct groups, ACC-UMAP1 and ACC-UMAP2, that largely overlap with clusters C1B and C1A, respectively. However, subsequent use of random-forest-based learning revealed a set of new possible marker genes showing significant differential expression in the described clusters (e.g., SOAT1, EIF2A1). For validation purposes, we used a secondary dataset based on a previous study from our group, consisting of 4 normal adrenal glands and 52 benign and 7 malignant tumor samples. The results largely confirmed those obtained for the TCGA-ACC cohort. In addition, the ENSAT dataset showed a correlation between benign adrenocortical tumors and the good prognosis ACC cluster ACC-UMAP1/C1B. In conclusion, the use of ML approaches re-identified and redefined known prognostic ACC subgroups. On the other hand, the subsequent use of random-forest-based learning identified new possible prognostic marker genes for ACC.}, language = {en} } @article{SchilcherHilsmannRauscheretal.2021, author = {Schilcher, Felix and Hilsmann, Lioba and Rauscher, Lisa and Değirmenci, Laura and Krischke, Markus and Krischke, Beate and Ankenbrand, Markus and Rutschmann, Benjamin and Mueller, Martin J. and Steffan-Dewenter, Ingolf and Scheiner, Ricarda}, title = {In vitro rearing changes social task performance and physiology in honeybees}, series = {Insects}, volume = {13}, journal = {Insects}, number = {1}, issn = {2075-4450}, doi = {10.3390/insects13010004}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-252305}, year = {2021}, abstract = {In vitro rearing of honeybee larvae is an established method that enables exact control and monitoring of developmental factors and allows controlled application of pesticides or pathogens. However, only a few studies have investigated how the rearing method itself affects the behavior of the resulting adult honeybees. We raised honeybees in vitro according to a standardized protocol: marking the emerging honeybees individually and inserting them into established colonies. Subsequently, we investigated the behavioral performance of nurse bees and foragers and quantified the physiological factors underlying the social organization. Adult honeybees raised in vitro differed from naturally reared honeybees in their probability of performing social tasks. Further, in vitro-reared bees foraged for a shorter duration in their life and performed fewer foraging trips. Nursing behavior appeared to be unaffected by rearing condition. Weight was also unaffected by rearing condition. Interestingly, juvenile hormone titers, which normally increase strongly around the time when a honeybee becomes a forager, were significantly lower in three- and four-week-old in vitro bees. The effects of the rearing environment on individual sucrose responsiveness and lipid levels were rather minor. These data suggest that larval rearing conditions can affect the task performance and physiology of adult bees despite equal weight, pointing to an important role of the colony environment for these factors. Our observations of behavior and metabolic pathways offer important novel insight into how the rearing environment affects adult honeybees.}, language = {en} } @phdthesis{Schmid2024, author = {Schmid, Kerstin}, title = {Integrative, three-dimensional \(in\) \(silico\) modeling of gas exchange in the human alveolus}, doi = {10.25972/OPUS-35182}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-351823}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2024}, abstract = {Die Lunge erf{\"u}llt durch den Austausch von Atemgasen eine {\"u}berlebenswichtige Aufgabe. Der Gasaustausch erfolgt durch einen einfachen, aber entscheidenden passiven Diffusionsprozess. Dieser findet in den Alveolen statt, ballonartigen Strukturen, die an die peripheren Atemwege grenzen. Alveolen sind von einem dichten Netz aus kleinen Kapillaren umgeben. Hier kommt die eingeatmete Luft in unmittelbare N{\"a}he zu dem vom Herzen kommenden sauerstoffarmen Blut und erm{\"o}glicht den Austausch von Sauerstoff und Kohlenstoffdioxid {\"u}ber deren Konzentrationsgradienten. Die Effizienz des Gasaustauschs kann anhand von Indikatoren wie der Sauerstoffdiffusionskapazit{\"a}t der Lunge und der Reaktionshalbzeit gemessen werden. Beim Menschen besteht eine betr{\"a}chtliche Diskrepanz zwischen physiologischen Sch{\"a}tzungen der Diffusionskapazit{\"a}t und der theoretischen Maximalkapazit{\"a}t unter optimalen strukturellen Bedingungen (der morphologischen Sch{\"a}tzung). Diese Diskrepanz wird durch eine Reihe ineinandergreifender Faktoren beeinflusst, darunter strukturelle Elemente wie die Oberfl{\"a}che und die Dicke der Diffusionsbarriere sowie physiologische Faktoren wie die Blutflussdynamik. Um die verschiedenen Rollen dieser Faktoren zu entschl{\"u}sseln, untersuchten wir, wie die morphologischen und physiologischen Eigenschaften der menschlichen alveol{\"a}ren Mikroumgebung kollektiv und individuell den Prozess des Gasaustauschs beeinflussen. Zu diesem Zweck entwickelten wir einen integrativen in silico Ansatz, der 3D morphologische Modellierung und Simulation von Blutfluss und Sauerstofftransport kombiniert. Im Mittelpunkt unseres Ansatzes steht die Simulationssoftware Alvin, die als interaktive Plattform f{\"u}r das zugrundeliegende mathematische Modell des Sauerstofftransports in der Alveole dient. Unser r{\"a}umlich-zeitliches Modell wurde durch die Integration und Erweiterung bestehender mathematischer Modelle entwickelt und liefert Ergebnisse, die mit experimentellen Daten im Einklang stehen. Alvin erm{\"o}glicht eine immersive Auseinandersetzung mit dem simulierten Gasaustausch, indem sie Parameter{\"a}nderungen in Echtzeit und die Ausf{\"u}hrung mehrerer Simulationsinstanzen gleichzeitig erm{\"o}glicht w{\"a}hrend sie ein detailliertes quantitatives Feedback liefert. Die beteiligten morphologischen und physiologischen Parameter wurden mit einem Fokus auf der Mikrovaskulatur weiter untersucht. Durch die Zusammenstellung stereologischer Daten aus der Literatur und geometrischer 3D-Modellierung erstellten wir ein "sheet-flow" Modell als realistische Darstellung des menschlichen alveol{\"a}ren Kapillarnetzwerks. Blutfluss wurde mit Hilfe numerischer Str{\"o}mungsdynamik simuliert. Unsere Ergebnisse stimmen mit fr{\"u}heren Sch{\"a}tzungen {\"u}berein und unterstreichen die entscheidende Rolle von Viskosit{\"a}tsmodellen bei der Vorhersage des Druckabfalls in der Mikrovaskulatur. Dar{\"u}ber hinaus zeigten wir, wie unser Ansatz genutzt werden kann, um strukturelle Details wie die Konnektivit{\"a}t des alveol{\"a}ren Kapillarnetzes mit dem Gef{\"a}ßbaum anhand von Blutflussindizes zu untersuchen. Es ist wichtig zu betonen, dass wir uns bislang auf verschiedene Datenquellen st{\"u}tzten und dass f{\"u}r weitere Fortschritte eine experimentelle Vailidierung erforderlich ist. Die Integration unserer Ergebnisse in Alvin erm{\"o}glichte die Quantifizierung des simulierten Gasaustauschprozesses {\"u}ber die Sauerstoffdiffusionskapazit{\"a}t und die Reaktionshalbzeit. Neben der Bewertung der kollektiven Einfl{\"u}sse der morphologischen und physiologischen Eigenschaften erleichterte unsere interaktive Software auch die Bewertung einzelner Parameter{\"a}nderungen. Die Betrachtung des Blutvolumens und der f{\"u}r den Gasaustausch zur Verf{\"u}gung stehenden Oberfl{\"a}che ergab lineare Korrelationen mit der Diffusionskapazit{\"a}t. Die Blutflussgeschwindigkeit hatte einen positiven, nichtlinearen Effekt auf die Diffusionskapazit{\"a}t. Die Reaktionshalbzeit best{\"a}tigte, dass der Gasaustauschprozess in der Regel nicht diffusionslimitiert ist. Insgesamt lieferte unser Alveolenmodell einen Wert f{\"u}r die Diffusionskapazit{\"a}t, der in der Mitte der fr{\"u}heren physiologischen und morphologischen Sch{\"a}tzung lag. Daraus l{\"a}sst sich schließen, dass Ph{\"a}nomene auf Alveolarebene zu 50\% der Limitierung der Diffusionskapazit{\"a}t beitragen, die in vivo eintreten. Zusammenfassend l{\"a}sst sich sagen, dass unser integrativer in silico Ansatz verschiedene strukturelle und funktionelle Einfl{\"u}sse auf den alveol{\"a}ren Gasaustausch aufschl{\"u}sselt und damit die traditionelle Forschung in der Atemwegsforschung erg{\"a}nzt. Zus{\"a}tzlich zeigen wir seinen Nutzen in der Lehre oder bei der Interpretation ver{\"o}ffentlichter Daten auf. Um unser Verst{\"a}ndnis zu verbessern, sollten k{\"u}nftige Arbeiten vorrangig darauf ausgerichtet sein, einen zusammenh{\"a}ngenden experimentellen Datensatz zu erhalten und ein geeignetes Viskosit{\"a}tsmodell f{\"u}r Blutflusssimulationen zu finden.}, subject = {Gasaustausch}, language = {en} } @article{TooKellerSickeletal.2018, author = {Too, Chin Chin and Keller, Alexander and Sickel, Wiebke and Lee, Sui Mae and Yule, Catherine M.}, title = {Microbial Community Structure in a Malaysian Tropical Peat Swamp Forest: The Influence of Tree Species and Depth}, series = {Frontiers in Microbiology}, volume = {9}, journal = {Frontiers in Microbiology}, doi = {10.3389/fmicb.2018.02859}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-229000}, year = {2018}, abstract = {Tropical peat swamp forests sequester globally significant stores of carbon in deep layers of waterlogged, anoxic, acidic and nutrient-depleted peat. The roles of microbes in supporting these forests through the formation of peat, carbon sequestration and nutrient cycling are virtually unknown. This study investigated physicochemical peat properties and microbial diversity between three dominant tree species: Shorea uliginosa (Dipterocarpaceae), Koompassia malaccensis (legumes associated with nitrogen-fixing bacteria), Eleiodoxa conferta (palm) and depths (surface, 45 and 90 cm) using microbial 16S rRNA gene amplicon sequencing. Water pH, oxygen, nitrogen, phosphorus, total phenolic contents and C/N ratio differed significantly between depths, but not tree species. Depth also strongly influenced microbial diversity and composition, while both depth and tree species exhibited significant impact on the archaeal communities. Microbial diversity was highest at the surface, where fresh leaf litter accumulates, and nutrient supply is guaranteed. Nitrogen was the core parameter correlating to microbial communities, but the interactive effects from various environmental variables displayed significant correlation to relative abundance of major microbial groups. Proteobacteria was the dominant phylum and the most abundant genus, Rhodoplanes, might be involved in nitrogen fixation. The most abundant methanogens and methanotrophs affiliated, respectively, to families Methanomassiliicoccaceae and Methylocystaceae. Our results demonstrated diverse microbial communities and provide valuable insights on microbial ecology in these extreme ecosystems.}, language = {en} }