@phdthesis{Kaymak2019,
  author    = {Kaymak, Irem},
  title     = {Identification of metabolic liabilities in 3D models of cancer},
  doi       = {10.25972/OPUS-18154},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-181544},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2019},
  abstract  = {Inefficient vascularisation of solid tumours leads to the formation of oxygen and nutrient gradients. In order to mimic this specific feature of the tumour microenvironment, a multicellular tumour spheroid (SPH) culture system was used. These experiments were implemented in p53 isogenic colon cancer cell lines (HCT116 p53 +/+ and HCT116 p53-/-) since Tp53 has important regulatory functions in tumour metabolism. First, the characteristics of the cells cultured as monolayers and as spheroids were investigated by using RNA sequencing and metabolomics to compare gene expression and metabolic features of cells grown in different conditions. This analysis showed that certain features of gene expression found in tumours are also present in spheroids but not in monolayer cultures, including reduced proliferation and induction of hypoxia related genes. Moreover, comparison between the different genotypes revealed that the expression of genes involved in cholesterol homeostasis is induced in p53 deficient cells compared to p53 wild type cells and this difference was only detected in spheroids and tumour samples but not in monolayer cultures. In addition, it was established that loss of p53 leads to the induction of enzymes of the mevalonate pathway via activation of the transcription factor SREBP2, resulting in a metabolic rewiring that supports the generation of ubiquinone (coenzyme Q10). An adequate supply of ubiquinone was essential to support mitochondrial electron transport and pyrimidine biosynthesis in p53 deficient cancer cells under conditions of metabolic stress. Moreover, inhibition of the mevalonate pathway using statins selectively induced oxidative stress and apoptosis in p53 deficient colon cancer cells exposed to oxygen and nutrient deprivation. This was caused by ubiquinone being required for electron transfer by dihydroorotate dehydrogenase, an essential enzyme of the pyrimidine nucleotide biosynthesis pathway. Supplementation with exogenous nucleosides relieved the demand for electron transfer and restored viability of p53 deficient cancer cells under metabolic stress. Moreover, the mevalonate pathway was also essential for the synthesis of ubiquinone for nucleotide biosynthesis to support growth of intestinal tumour organoids. Together, these findings highlight the importance of the mevalonate pathway in cancer cells and provide molecular evidence for an enhanced sensitivity towards the inhibition of mitochondrial electron transfer in tumour-like metabolic environments.},
  subject      = {Tumor},
  language  = {en}
}
@phdthesis{KaltdorfgebSchuch2019,
  author    = {Kaltdorf [geb. Schuch], Kristin Verena},
  title     = {Mikroskopie, Bildverarbeitung und Automatisierung der Analyse von Vesikeln in \(C.\) \(elegans\) und anderen biologischen Strukturen},
  doi       = {10.25972/OPUS-16062},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-160621},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2019},
  abstract  = {Thema dieser Thesis ist die Analyse sekretorischer Vesikelpools auf Ultrastrukturebene in unterschiedlichen biologischen Systemen. Der erste und zweite Teil dieser Arbeit fokussiert sich auf die Analyse synaptischer Vesikelpools in neuromuskul{\"a}ren Endplatten (NME) im Modellorganismus Caenorhabditis elegans. Dazu wurde Hochdruckgefrierung und Gefriersubstitution angewandt, um eine unverz{\"u}gliche Immobilisation der Nematoden und somit eine Fixierung im nahezu nativen Zustand zu gew{\"a}hrleisten. Anschließend wurden dreidimensionale Aufnahmen der NME mittels Elektronentomographie erstellt. Im ersten Teil dieser Arbeit wurden junge adulte, wildtypische C. elegans Hermaphroditen mit Septin-Mutanten verglichen. Um eine umfassende Analyse mit hoher Stichprobenzahl zu erm{\"o}glichen und eine automatisierte L{\"o}sung f{\"u}r {\"a}hnliche Untersuchungen von Vesikelpools bereit zu stellen wurde eine Software namens 3D ART VeSElecT zur automatisierten Vesikelpoolanalyse entwickelt. Die Software besteht aus zwei Makros f{\"u}r ImageJ, eines f{\"u}r die Registrierung der Vesikel und eines zur Charakterisierung. Diese Trennung in zwei separate Schritte erm{\"o}glicht einen manuellen Verbesserungsschritt zum Entfernen falsch positiver Vesikel. Durch einen Vergleich mit manuell ausgewerteten Daten neuromuskul{\"a}rer Endplatten von larvalen Stadien des Modellorganismus Zebrafisch (Danio rerio) konnte erfolgreich die Funktionalit{\"a}t der Software bewiesen werden. Die Analyse der neuromuskul{\"a}ren Endplatten in C. elegans ergab kleinere synaptische Vesikel und dichtere Vesikelpools in den Septin-Mutanten verglichen mit Wildtypen. Im zweiten Teil der Arbeit wurden neuromuskul{\"a}rer Endplatten junger adulter C. elegans Hermaphroditen mit Dauerlarven verglichen. Das Dauerlarvenstadium ist ein spezielles Stadium, welches durch widrige Umweltbedingungen induziert wird und in dem C. elegans {\"u}ber mehrere Monate ohne Nahrungsaufnahme {\"u}berleben kann. Da hier der Vergleich der Abundanz zweier Vesikelarten, der „clear-core"-Vesikel (CCV) und der „dense-core"-Vesikel (DCV), im Fokus stand wurde eine Erweiterung von 3D ART VeSElecT entwickelt, die einen „Machine-Learning"-Algorithmus zur automatisierten Klassifikation der Vesikel integriert. Durch die Analyse konnten kleinere Vesikel, eine erh{\"o}hte Anzahl von „dense-core"-Vesikeln, sowie eine ver{\"a}nderte Lokalisation der DCV in Dauerlarven festgestellt werden. Im dritten Teil dieser Arbeit wurde untersucht ob die f{\"u}r synaptische Vesikelpools konzipierte Software auch zur Analyse sekretorischer Vesikel in Thrombozyten geeignet ist. Dazu wurden zweidimensionale und dreidimensionale Aufnahmen am Transmissionselektronenmikroskop erstellt und verglichen. Die Untersuchung ergab, dass hierf{\"u}r eine neue Methodik entwickelt werden muss, die zwar auf den vorherigen Arbeiten prinzipiell aufbauen kann, aber den besonderen Herausforderungen der Bilderkennung sekretorischer Vesikel aus Thrombozyten gerecht werden muss.},
  subject      = {Mikroskopie},
  language  = {de}
}
@phdthesis{Romanov2019,
  author    = {Romanov, Natalie},
  title     = {Characterizing Variation of Protein Complexes and Functional Modules on a Temporal Scale and across Individuals},
  doi       = {10.25972/OPUS-16813},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-168139},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2019},
  abstract  = {A fundamental question in current biology concerns the translational mechanisms leading from genetic variability to phenotypes. Technologies have evolved to the extent that they can efficiently and economically determine an individual's genomic composition, while at the same time big data on clinical profiles and diagnostics have substantially accumulated. Genome-wide association studies linking genomic loci to certain traits, however, remain limited in their capacity to explain the cellular mechanisms that underlie the given association. For most associations, gene expression has been blamed; yet given that transcript and protein abundance oftentimes do not correlate, that finding does not necessarily decrypt the underlying mechanism. Thus, the integration of further information is crucial to establish a model that could prove more accurate in predicting genotypic effects on the human organism. In this work we describe the so-called proteotype as a feature of the cell that could provide a substantial link between genotype and phenotype. Rather than looking at the proteome as a set of independent molecules, we demonstrate a consistent modular architecture of the proteome that is driven by molecular cooperativity. Functional modules, especially protein complexes, can be further interrogated for differences between individuals and tackled as imprints of genetic and environmental variability. We also show that subtle stoichiometric changes of protein modules could have broader effects on the cellular system, such as the transport of specific molecular cargos. The presented work also delineates to what extent temporal events and processes influence the stoichiometry of protein complexes and functional modules. The re-wiring of the glycolytic pathway for example is illustrated as a potential cause for an increased Warburg effect during the ageing of the human bone marrow. On top of analyzing protein abundances we also interrogate proteome dynamics in terms of stability and solubility transitions during the short temporal progression of the cell cycle. One of our main observations in the thesis encompass the delineation of protein complexes into respective sub-complexes according to distinct stability patterns during the cell cycle. This has never been demonstrated before, and is functionally relevant for our understanding of the dis- and assembly of large protein modules. The insights presented in this work imply that the proteome is more than the sum of its parts, and primarily driven by variability in entire protein ensembles and their cooperative nature. Analyzing protein complexes and functional modules as molecular reflections of genetic and environmental variations could indeed prove to be a stepping stone in closing the gap between genotype and phenotype and customizing clinical treatments in the future.},
  subject      = {Proteotype},
  language  = {en}
}
@phdthesis{Schneider2020,
  author    = {Schneider, Felicitas Maria Hannelore},
  title     = {Vergleichende Evaluierung verschiedener Ans{\"a}tze des Memory Enhancement bei neurodegenerativen Prozessen},
  doi       = {10.25972/OPUS-20756},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-207562},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2020},
  abstract  = {Angesichts des dramatischen, weltweiten Anstiegs der Pr{\"a}valenz von Demenzerkrankungen und der aktuellen, unzureichenden Therapieans{\"a}tze ist die Bereitstellung neuer, wirkungsvoller Behandlungsoptionen von gr{\"o}ßter Bedeutung. Technologische, pharmakologische und verhaltensbasierte Verfahren des Memory Enhancement k{\"o}nnten zur L{\"o}sung dieses Problems beitragen: Hierzu z{\"a}hlt die Stammzelltransplantation, die in mehreren Tierstudien zu einer Verbesserung der Ged{\"a}chtnisfunktion f{\"u}hrte. Zudem wird seit L{\"a}ngerem an einer Impfung gegen die Alzheimer-Krankheit mittels β-Amyloid-Antik{\"o}rpern geforscht. Ein weiterer therapeutischer Ansatz f{\"u}r die Alzheimer-Krankheit besteht in der optogenetischen Stimulation spezifischer hippocampaler Engramm-Zellen, durch die bei einem Maus-Modell verloren gegangene Erinnerungen wiederhergestellt werden konnten. Unkonventionelle Pharmazeutika wie Erythropoetin f{\"u}hrten in Tierstudien und bei Patienten mit neuropsychiatrischen Erkrankungen zu einer Verbesserung der kognitiven F{\"a}higkeiten und des Ged{\"a}chtnisses. Eine Modifikation der Ern{\"a}hrung und der Einsatz von Pro- und Pr{\"a}biotika beeinflussen das Ged{\"a}chtnis {\"u}ber eine Manipulation der Darm-Hirn-Achse. Verhaltensbasierte Maßnahmen wie k{\"o}rperliche Aktivit{\"a}t und der Einsatz von Mnemotechniken stellen effektive Ans{\"a}tze des Memory Enhancement dar, welche bereits heute von gesunden Individuen implementiert werden k{\"o}nnen. F{\"u}r die Anwendung von Augmented Reality (AR) konnten kognitionsf{\"o}rdernde Wirkungen beim Lernen neuroanatomischer Themen und dem Zusammenbau von Objekten nachgewiesen werden. Besonders vielversprechend stellt sich die Entwicklung einer Ged{\"a}chtnisprothese dar, durch die vergessene Informationen bei Personen mit stattgehabtem Sch{\"a}del-Hirn-Trauma und apoplektischem Insult reaktiviert werden k{\"o}nnten. Memory Enhancement ist prinzipiell bereits heute bei gesunden und kranken Individuen anwendbar und verspricht wirksame zuk{\"u}nftige Pr{\"a}ventions- und Therapieoptionen. Ein realer Einsatz in der klinischen Praxis ist in naher Zukunft jedoch noch nicht zu erwarten.},
  subject      = {Neurodegeneration},
  language  = {de}
}
@phdthesis{OlivaresBaerwald2020,
  author    = {Olivares-Baerwald, Silvana},
  title     = {Die Rolle von Calcineurin im Nukleus von Kardiomyozyten und ein innovativer Inhibitor als neuer therapeutischer Ansatz bei kardialer Hypertrophie},
  doi       = {10.25972/OPUS-20808},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-208080},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2020},
  abstract  = {Die Calcineurin/NFAT-Signalkaskade spielt eine wichtige Rolle bei der Entwicklung einer kardialen Hypertrophie. Im Zytoplasma von Kardiomyozyten wird die Phosphatase Calcineurin nach Stimulierung der Zellen, z. B. durch Dehnungsreize, Angiotensin II (Ang II) oder Endothelin I (ET-1), und einen daraus folgenden intrazellul{\"a}ren Ca2+-Strom aktiviert. Dies f{\"u}hrt zur Dephosphorylierung von NFAT und zu dessen nukle{\"a}rer Translokation. In fr{\"u}heren Arbeiten von Ritter et al. wurden sowohl eine nukle{\"a}re Lokalisationssequenz (NLS) als auch eine nukle{\"a}re Exportsequenz (NES) innerhalb von Calcineurin identifiziert, die den Transport von Calcineurin zwischen dem Zytoplasma und dem Nukleus erm{\"o}glichen. Basierend auf diesen Ergebnissen wurde das Import Blocking Peptid (IBP) entwickelt. Dieses Peptid entspricht der NLS von Calcineurin und blockiert die Calcineurin-Bindungsstellen des Shuttleproteins (Karyopherins) Importin β1. So wird die Translokation von Calcineurin in den Nukleus unterbunden und die Signalkaskade zur Aktivierung von Hypertrophie-Genen in Kardiomyozyten unterbrochen. Dabei blieb die Phosphatase-Aktivit{\"a}t von Calcineurin unbeeinflusst. Eines der Ziele dieser Arbeit war, IBP weiter zu optimieren und den „proof of principle" auch in vivo zu f{\"u}hren. Hierf{\"u}r wurden u. a. ein geeignetes L{\"o}sungsmittel bestimmt (biokompatibel und an die Peptidcharakteristika angepasst), die Peptidstruktur modifiziert (Erh{\"o}hung der Spezifit{\"a}t/Wirksamkeit) und die erforderliche Dosis weiter eingegrenzt (Belastungs- und Kostenreduktion). Unter Verwendung einer TAMRA-markierten Wirkstoffvariante konnten der Weg des Peptids in M{\"a}usen nachverfolgt und die Ausscheidung quantifiziert werden. Aufbauend auf den Ergebnissen von Burkard et al., die die Entstehung einer konstitutiv-aktiven und nukle{\"a}ren Calcineurin-Isoform nach proteolytischer Spaltung durch Calpain nachwiesen, wurde die Rolle von Calcineurin im Zellkern genauer untersucht. Außerdem sollte die Frage beantwortet werden, wie ({\"u}ber Calcineurin?) die Herzmuskelzelle zwischen Calciumschwankungen im Zuge der Exzitations-Kontraktions-Kopplung (ECC) und vergleichsweise schwachen Calciumsignalen zur Transkriptionsteuerung unterscheidet. Mit Hilfe von nukle{\"a}ren Calcineurin-Mutanten, die einen Defekt in der Ca2+-Bindung aufwiesen, konnte die Bedeutung von Calcineurin als Calciumsensor f{\"u}r die NFAT-abh{\"a}ngige Transkription nachgewiesen werden. Im Mausmodell waren unter Hypertrophie-Bedingungen die Ca2+-Transienten in der nukle{\"a}ren Mikrodom{\"a}ne signifikant st{\"a}rker als im Zytosol, wodurch die Hypothese, dass die Aktivierung der Calcineurin/NFAT-Signalkaskade unabh{\"a}ngig von zytosolischem Ca2+ erfolgt, gest{\"u}tzt wird. Messungen von nukle{\"a}ren und zytosolischen Ca2+-Transienten in IP3-Sponge-M{\"a}usen zeigten im Vergleich zu Wildtyp-M{\"a}usen keine Erh{\"o}hung des Ca2+-Spiegels w{\"a}hrend der Diastole, was auf eine Rolle von Inositoltrisphosphat (IP3) in der Signalkaskade deutet. Außerdem zeigten isolierte Zellkerne ventrikul{\"a}rer adulter Kardiomyozyten eine erh{\"o}hte Expression des IP3-Rezeptors 2 (IP3R2) nach Ang II-Stimulierung. Diese gesteigerte Expression war abh{\"a}ngig von der Calcineurin/NFAT-Kaskade und bestand sogar 3 Wochen nach Entfernung des Ang II-Stimulus fort. Zusammenfassend l{\"a}sst sich sagen, dass nukle{\"a}res Calcineurin als ein Ca2+-Sensor agiert, dass die lokale Ca2+-Freisetzung im Kern {\"u}ber IP3-Rezeptoren detektiert wird und dass dies im Zusammenspiel mit NFAT die Transkription von Hypertrophiegenen initiiert.},
  subject      = {kardiale Hypertrophie},
  language  = {de}
}
@phdthesis{Klepsch2020,
  author    = {Klepsch, Maximilian Andreas},
  title     = {Small RNA-binding complexes in Chlamydia trachomatis identified by Next-Generation Sequencing techniques},
  doi       = {10.25972/OPUS-19974},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-199741},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2020},
  abstract  = {Chlamydia infect millions worldwide and cause infertility and blinding trachoma. Chlamydia trachomatis (C. trachomatis) is an obligate intracellular gram-negative pathogen with a significantly reduced genome. This bacterium shares a unique biphasic lifecycle in which it alternates between the infectious, metabolically inert elementary bodies (EB) and the non-infections, metabolically active replicative reticular bodies (RB). One of the challenges of working with Chlamydia is its difficult genetic accessibility. In the present work, the high-throughput method TagRNA-seq was used to differentially label transcriptional start sites (TSS) and processing sites (PSS) to gain new insights into the transcriptional landscape of C. trachomatis in a coverage that has never been achieved before. Altogether, 679 TSSs and 1067 PSSs were detected indicating its high transcriptional activity and the need for transcriptional regulation. Furthermore, the analysis of the data revealed potentially new non-coding ribonucleic acids (ncRNA) and a map of transcriptional processing events. Using the upstream sequences, the previously identified σ66 binding motif was detected. In addition, Grad-seq for C. trachomatis was established to obtain a global interactome of the RNAs and proteins of this intracellular organism. The Grad-Seq data suggest that many of the newly annotated RNAs from the TagRNA-seq approach are present in complexes. Although Chlamydia lack the known RNA-binding proteins (RBPs), e.g. Hfq and ProQ, observations in this work reveal the presence of a previously unknown RBP. Interestingly, in the gradient analysis it was found that the σ66 factor forms a complex with the RNA polymerase (RNAP). On the other hand, the σ28 factor is unbound. This is in line with results from previous studies showing that most of the genes are under control of σ66. The ncRNA IhtA is known to function via direct base pairing to its target RNA of HctB, and by doing so is influencing the chromatin condensation in Chlamydia. This study confirmed that lhtA is in no complex. On the other hand, the ncRNA ctrR0332 was found to interact with the SNF2 protein ctl0077, a putative helicase. Both molecules co-sedimented in the gradient and were intact after an aptamer-based RNA pull-down. The SWI2/SNF2 class of proteins are nucleosome remodeling complexes. The prokaryotic RapA from E. coli functions as transcription regulator by stimulating the RNAP recycling. This view might imply that the small ncRNA (sRNA) ctrR0332 is part of the global regulation network in C. trachomatis controlling the transition between EBs and RBs via interaction with the SNF2 protein ctl0077. The present work is the first study describing a global interactome of RNAs and proteins in C. trachomatis providing the basis for future interaction studies in the field of this pathogen.},
  language  = {en}
}
@phdthesis{Kurz2020,
  author    = {Kurz, Andreas},
  title     = {Correlative live and fixed cell superresolution microscopy},
  doi       = {10.25972/OPUS-19945},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-199455},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2020},
  abstract  = {Over the last decade life sciences have made an enormous leap forward. The development of complex analytical instruments, in particular in fluorescence microscopy, has played a decisive role in this. Scientist can now rely on a wide range of imaging techniques that offer different advantages in terms of optical resolution, recording speed or living cell compatibility. With the help of these modern microscopy techniques, multi-protein complexes can be resolved, membrane receptors can be counted, cellular pathways analysed or the internalisation of receptors can be tracked. However, there is currently no universal technique for comprehensive experiment execution that includes dynamic process capture and super resolution imaging on the same target object. In this work, I built a microscope that combines two complementary imaging techniques and enables correlative experiments in living and fixed cells. With an image scanning based laser spot confocal microscope, fast dynamics in several colors with low photodamage of the cells can be recorded. This novel system also has an improved resolution of 170 nm and was thoroughly characterized in this work. The complementary technique is based on single molecule localization microscopy, which can achieve a structural resolution down to 20-30 nm. Furthermore I implemented a microfluidic pump that allows direct interaction with the sample placed on the microscope. Numerous processes such as living cell staining, living cell fixation, immunostaining and buffer exchange can be observed and performed directly on the same cell. Thus, dynamic processes of a cell can be frozen and the structures of interest can be stained and analysed with high-resolution microscopy. Furthermore, I have equipped the detection path of the single molecule technique with an adaptive optical element. With the help of a deformable mirror, imaging functions can be shaped and information on the 3D position of the individual molecules can be extracted.},
  subject      = {Einzelmolek{\"u}lmikroskopie},
  language  = {en}
}
@phdthesis{Eidel2020,
  author    = {Eidel, Matthias T. A. M.},
  title     = {Training Effects of a Tactile Brain-Computer Interface System During Prolonged Use by Healthy And Motor-Impaired People},
  doi       = {10.25972/OPUS-20851},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-208511},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2020},
  abstract  = {Background - Brain-Computer Interfaces (BCI) enable their users to interact and communicate with the environment without requiring intact muscle control. To this end, brain activity is directly measured, digitized and interpreted by the computer. Thus, BCIs may be a valuable tool to assist severely or even completely paralysed patients. Many BCIs, however, rely on neurophysiological potentials evoked by visual stimulation, which can result in usability issues among patients with impaired vision or gaze control. Because of this, several non-visual BCI paradigms have been developed. Most notably, a recent study revealed promising results from a tactile BCI for wheelchair control. In this multi-session approach, healthy participants used the BCI to navigate a simulated wheelchair through a virtual apartment, which revealed not only that the BCI could be operated highly efficiently, but also that it could be trained over five sessions. The present thesis continues the research on this paradigm in order to - confirm its previously reported high performance levels and trainability - reveal the underlying factors responsible for observed performance increases - establish its feasibility among potential impaired end-users Methods - To approach these goals, three studies were conducted with both healthy participants and patients with amyotrophic lateral sclerosis (ALS). Brain activity during BCI operation was recorded via electroencephalography (EEG) and interpreted using a machine learning-based linear classifier. Wheelchair navigation was executed according to the classification results and visualized on a monitor. For offline statistical analysis, neurophysiological features were extracted from EEG data. Subjective data on usability were collected from all participants. Two specialized experiments were conducted to identify factors for training. Results and Discussion - Healthy participants: Results revealed positive effects of training on BCI performances and their underlying neurophysiological potentials. The paradigm was confirmed to be feasible and (for a non-visual BCI) highly efficient for most participants. However, some had to be excluded from analysis of the training effects because they could not achieve meaningful BCI control. Increased somatosensory sensitivity was identified as a possible mediator for training-related performance improvements. Participants with ALS: Out of seven patients with various stages of ALS, five could operate the BCI with accuracies significantly above chance level. Another ALS patient in a state of near-complete paralysis trained with the BCI for several months. Although no effects of training were observed, he was consistently able to operate the system above chance level. Subjective data regarding workload, satisfaction and other parameters were reported. Significance - The tactile BCI was evaluated on the example of wheelchair control. In the future, it could help impaired patients to regain some lost mobility and self-sufficiency. Further, it has the potential to be adapted to other purposes, including communication. Once visual BCIs and other assistive technologies fail for patients with (progressive) motor impairments, vision-independent paradigms such as the tactile BCI may be among the last remaining alternatives to interact with the environment. The present thesis has strongly confirmed the general feasibility of the tactile paradigm for healthy participants and provides first clues about the underlying factors of training. More importantly, the BCI was established among potential end-users with ALS, providing essential external validity.},
  subject      = {Myatrophische Lateralsklerose},
  language  = {en}
}
@phdthesis{Seitz2020,
  author    = {Seitz, Nicola},
  title     = {Bee demise and bee rise: From honey bee colony losses to finding measures for advancing entire bee communities},
  doi       = {10.25972/OPUS-18418},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-184180},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2020},
  abstract  = {My dissertation comprises three studies: (1) an assessment of honey bee colony losses in the USA between 2014 and 2015, (2) an exploration of the potential of reclaimed sand mines as bee habitat, and (3) an evaluation of native and non-native pollinator friendly plants in regard to their attraction to bees. While the first study focuses on honey bees, the latter two studies primarily take wild bees or entire bee communities in focus. The study on honey bee colony losses was conducted within the framework of the Bee Informed Partnership (BIP, beeinformed.org) and aligns with the annual colony loss surveys which have been conducted in the USA since the winter of 2006/2007. It was the fourth year for which summer and annual losses were calculated in addition to winter losses. Among participants, backyard beekeepers were the largest group (n = 5690), although sideline (n = 169) and commercial (n = 78) beekeepers managed the majority (91.7 \%) of the 414 267 surveyed colonies. Overall, 15.1 \% of the estimated 2.74 million managed colonies in the USA were included in the study. Total honey bee colony losses (based on the entirety of included colonies) were higher in summer (25.3 \%) than in winter (22.3 \%) and amounted to 40.6 \% for the entire 2014/2015 beekeeping year. Average colony losses per beekeeper or operation were higher in winter (43.7 \%) than in summer (14.7 \%) and amounted to 49 \% for the entire 2014/2015 beekeeping year. Due to the dominance of backyard beekeepers among participants, average losses per operation (or unweighted loss) stronger reflected this smaller type of beekeeper. Backyard beekeepers mainly named colony management issues (e.g., starvation, weak colony in the fall) as causes for mortality, while sideline and commercial beekeepers stronger emphasized parasites or factors outside their control (e.g., varroa, nosema, queen failure). The second study took place at reclaimed sand mines. Sand mines represent anthropogenically impacted habitats found worldwide, which bear potential for bee conservation. Although floral resources can be limited at these habitats, vegetation free patches of open sandy soils and embankments may offer good nesting possibilities for sand restricted and other bees. We compared bee communities as found in three reclaimed sand mines and at adjacent roadside meadows in Maryland, USA, over two years. Both sand mines and roadsides hosted diverse bee communities with 111 and 88 bee species, respectively. Bee abundances as well as richness and Shannon diversity of bee species were higher in sand mines than at roadsides and negatively correlated with the percentage of vegetational ground cover. Species composition also differed significantly between habitats. Sand mines hosted a higher proportion of ground nesters, more uncommon and more 'sand loving' bees similar to natural sandy areas of Maryland. Despite the destruction of the original pre-mining habitat, sand mines thus appear to represent a unique habitat for wild bees, particularly when natural vegetation and open sand spots are encouraged. Considering habitat loss, the lack of natural disturbance regimes, and ongoing declines of wild bees, sand mines could add promising opportunities for bee conservation which has hitherto mainly focused on agricultural and urban habitats. The third study was an experimental field study on pollinator friendly plants. Bees rely on the pollen and nectar of plants as their food source. Therefore, pollinator friendly plantings are often used for habitat enhancements in bee conservation. Non-native pollinator friendly plants may aid in bee conservation efforts, but have not been tested and compared with native pollinator friendly plants in a common garden experiment. In this study, we seeded mixes of 20 native and 20 non-native pollinator friendly plants in two separate plots at three sites in Maryland, USA. For two years, we recorded flower visitors to the plants throughout the blooming period and additionally sampled bees with pan traps. A total of 3744 bees (120 species) were sampled in the study. Of these, 1708 bees (72 species) were hand netted directly from flowers for comparisons between native and non-native plants. Depending on the season, bee abundance and species richness was either similar or lower (early season and for richness also late season) at native plots compared to non-native plots. Additionally, the overall bee community composition differed significantly between native and non-native plots. Furthermore, native plants were associated with more specialized plant-bee visitation networks compared to non-native plants. In general, visitation networks were more specialized in the early season than the later seasons. Four species (Bombus impatiens, Halictus poeyi/ligatus, Lasioglossum pilosum, and Xylocopa virginica) out of the five most abundant bee species (also including Apis mellifera) foraged more specialized on native than non-native plants. Our study showed that non-native plants were well accepted by a diverse bee community and had a similar to higher attraction for bees compared to native plants. However, we also demonstrated alterations in foraging behavior, bee community assemblage, and visitation networks. As long as used with caution, non-native plants can be a useful addition to native pollinator friendly plantings. This study gives a first example of a direct comparison between native and non-native pollinator friendly plants.},
  subject      = {Biene},
  language  = {en}
}
@phdthesis{Redlich2020,
  author    = {Redlich, Sarah},
  title     = {Opportunities and obstacles of ecological intensification: Biological pest control in arable cropping systems},
  doi       = {10.25972/OPUS-17122},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-171228},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2020},
  abstract  = {Modern agriculture is the basis of human existence, a blessing, but also a curse. It provides nourishment and well-being to the ever-growing human population, yet destroys biodiversity-mediated processes that underpin productivity: ecosystem services such as water filtration, pollination and biological pest control. Ecological intensification is a promising alternative to conventional farming, and aims to sustain yield and ecosystem health by actively managing biodiversity and essential ecosystem services. Here, I investigate opportunities and obstacles for ecological intensification. My research focuses on 1) the relative importance of soil, management and landscape variables for biodiversity and wheat yield (Chapter II); 2) the influence of multi-scale landscape-level crop diversity on biological pest control in wheat (Chapter III) and 3) on overall and functional bird diversity (Chapter IV). I conclude 4) by introducing a guide that helps scientists to increase research impact by acknowledging the role of stakeholder engagement for the successful implementation of ecological intensification (Chapter V). Ecological intensification relies on the identification of natural pathways that are able to sustain current yields. Here, we crossed an observational field study of arthropod pests and natural enemies in 28 real-life wheat systems with an orthogonal on-field insecticide-fertilizer experiment. Using path analysis, we quantified the effect of 34 factors (soil characteristics, recent and historic crop management, landscape heterogeneity) that directly or indirectly (via predator-prey interactions) contribute to winter wheat yield. Reduced soil preparation and high crop rotation diversity enhanced crop productivity independent of external agrochemical inputs. Concurrently, biological control by arthropod natural enemies could be restored by decreasing average field sizes on the landscape scale, extending crop rotations and reducing soil disturbance. Furthermore, reductions in agrochemical inputs decreased pest abundances, thereby facilitating yield quality. Landscape-level crop diversity is a promising tool for ecological intensification. However, biodiversity enhancement via diversification measures does not always translate into agricultural benefits due to antagonistic species interactions (intraguild predation). Additionally, positive effects of crop diversity on biological control may be masked by inappropriate study scales or correlations with other landscape variables (e.g. seminatural habitat). Therefore, the multiscale and context-dependent impact of crop diversity on biodiversity and ecosystem services is ambiguous. In 18 winter wheat fields along a crop diversity gradient, insect- and bird-mediated pest control was assessed using a natural enemy exclusion experiment with cereal grain aphids. Although birds did not influence the strength of insect-mediated pest control, crop diversity (rather than seminatural habitat cover) enhanced aphid regulation by up to 33\%, particularly on small spatial scales. Crop diversification, an important Greening measure in the European Common Agricultural Policy, can improve biological control, and could lower dependence on insecticides, if the functional identity of crops is taken into account. Simple measures such as 'effective number of crop types' help in science communication. Although avian pest control did not respond to landscape-level crop diversity, birds may still benefit from increased crop resources in the landscape, depending on their functional grouping (feeding guild, conservation status, habitat preference, nesting behaviour). Observational studies of bird functional diversity on 14 wheat study fields showed that non-crop landscape heterogeneity rather than crop diversity played a key role in determining the richness of all birds. Insect-feeding, non-farmland and non-threatened birds increased across multiple spatial scales (up to 3000 m). Only crop-nesting farmland birds declined in heterogeneous landscapes. Thus, crop diversification may be less suitable for conserving avian diversity, but abundant species benefit from overall habitat heterogeneity. Specialist farmland birds may require more targeted management approaches. Identifying ecological pathways that favour biodiversity and ecosystem services provides opportunities for ecological intensification that increase the likelihood of balancing conservation and productivity goals. However, change towards a more sustainable agriculture will be slow to come if research findings are not implemented on a global scale. During dissemination activities within the EU project Liberation, I gathered information on the advantages and shortcomings of ecological intensification and its implementation. Here, I introduce a guide ('TREE') aimed at scientists that want to increase the impact of their research. TREE emphasizes the need to engage with stakeholders throughout the planning and research process, and actively seek and promote science dissemination and knowledge implementation. This idea requires scientists to leave their comfort zone and consider socioeconomic, practical and legal aspects often ignored in classical research. Ecological intensification is a valuable instrument for sustainable agriculture. Here, I identified new pathways that facilitate ecological intensification. Soil quality, disturbance levels and spatial or temporal crop diversification showed strong positive correlations with natural enemies, biological pest control and yield, thereby lowering the dependence on agrochemical inputs. Differences between functional groups caused opposing, scale-specific responses to landscape variables. Opposed to our predictions, birds did not disturb insect-mediated pest control in our study system, nor did avian richness relate to landscape-level crop diversity. However, dominant functional bird groups increased with non-crop landscape heterogeneity. These findings highlight the value of combining different on-field and landscape approaches to ecological intensification. Concurrently, the success of ecological intensification can be increased by involving stakeholders throughout the research process. This increases the quality of science and reduces the chance of experiencing unscalable obstacles to implementation.},
  language  = {en}
}