@article{BenaventeSchmidtZachmannHuegleDoerretal.1988, author = {Benavente, Ricardo and Schmidt-Zachmann, Marion S. and H{\"u}gle-D{\"o}rr, B. and Reimer, G. and Rose, K. M. and Scheer, Ulrich}, title = {Identification and definition of nucleolus-related fibrillar bodies in micronucleated cells}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-39423}, year = {1988}, abstract = {Small nucleolus-related bodies which occur in the nUcleoplasm of " micronuclei" lacking nucleolar organizers have been studied by immunofluorescence microscopy. These bodies stained specifically with three different antibodies directed against proteins that are normally associated with the dense fibrillar component of functional nucleoli, but not with antibodies specific for certain proteins of the granular component or the fibrillar centers. Our data show that, in the absence of rRNA genes, the various constituent proteins characteristic of the dense fibrillar component spontaneously assemble into spherical entities but that the subsequent fusion of these bodies into larger structures is prevented in these micronuclei. The similarity between these nucleolus-related bodies of micronuclei and the prenucleolar bodies characteristic of early stages of nucleologenesis during mitotic telophase is discussed.}, language = {en} } @article{BenaventeScheerChaly1989, author = {Benavente, Ricardo and Scheer, Ulrich and Chaly, Nathalie}, title = {Nucleocytoplasmic sorting of macromolecules following mitosis: fate of nuclear constituents after inhibition of pore complex function}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-40777}, year = {1989}, abstract = {PtK2 cells in which pore complex-mediated transport is blocked by microinjection early in mitosis of a monoclonal antibody (specific for an Mr 68000 pore complex glycoprotein) or of wheat germ agglutinin (WGA) complete cytokinesis. However, their nuclei remain stably arrested in a telophase-like organization characterized by highly condensed chromatin and the absence of nucleoli, indicating a requirement for pore-mediated transport for the reassembly of interphase nuclei. We have now examined this requirement more closely by monitoring the behavior of individual nuclear macromolecules in microinjected cells using immunofluorescence microscopy and have investigated the effect of microinjecting the antibody or WGA on cellular ultrastructure. The absence of nuclear transport did not affect the sequestration into daughter nuclei of components such as DNA, DNA topoisomerase I and the nucleolar protein fibrillarin that are carried through mitosis on chromosomes. On the other hand, lamins, snRNAs and the p68 pore complex glycoprotein, all cytoplasmic during mitosis, remained largely cytoplasmic in the telophase-arrested cells. Electron microscopy showed the nuclei to be surrounded by a doublelayered membrane with some inserted pore complexes. In addition, however, a variety of membranous structures with associated pore complexes was regularly noted in the cytoplasm, suggesting that chromatin may not be essential for the postmitotic formation of pore complexes. We propose that cellular compartmentalization at telophase is a two-step process. First, a nuclear envelope tightly encloses the condensed chromosomes, excluding non-selectively all macromolecules not associated with the chromosomes. Interphase nuclear organization is then progressively restored by selective pore complex-mediated uptake of nuclear proteins from the cytoplasm.}, subject = {Cytologie}, language = {en} } @article{BenaventeRoseReimeretal.1987, author = {Benavente, Ricardo and Rose, Kathleen M. and Reimer, Georg and H{\"u}gle-D{\"o}rr, Barbara and Scheer, Ulrich}, title = {Inhibition of nucleolar reformation after microinjection of antibodies to RNA polymerase I into mitotic cells}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-33247}, year = {1987}, abstract = {The formation of daughter nuclei and the reformation of nucleolar structures was studied after microinjection of antibodies to RNA polymerase I into dividing cultured cells (PtK2). The fate of several nucleolar proteins representing the three main structural subcomponents of the nucleolus was examined by immunofluorescence and electron microscopy. The results show that the RNA polymerase I antibodies do not interfere with normal mitotic progression or the early steps of nucleologenesis, i.e. , the aggregation of nucleolar material into prenucleolar bodies. However,they inhibit the telophasic coalescence of the prenucleolar bodies into the chromosomal nucleolar organizer regions, thus preventing the formation of new nucleoli. These prenucleolar bodies show a fibrillar organization that also compositionally resembles the dense fibrillar component of interphase nucleoli . We conclude that during normal nucleologenesis the dense fibrillar component forms from preformed entities around nucleolar organizer regions, and that this association seems to be dependent on the presence of an active form of RNA polymerase I.}, language = {en} } @article{BenaventeReimerRoseetal.1988, author = {Benavente, Ricardo and Reimer, Georg and Rose, Kathleen M. and H{\"u}gle-D{\"o}rr, Barbara and Scheer, Ulrich}, title = {Nucleolar changes after microinjection of antibodies to RNA polymerase I into the nucleus of mammalian cells}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-40666}, year = {1988}, abstract = {After microinjection of antibodies against RNA polymerase I into the nuclei of cultured rat kangaroo (PtKz) and rat (RVF-SMC) cells alterations in nucleolar structure and composition were observed. These were detected by electron microscopy and double-label immunofluorescence microscopy using antibodies to proteins representative of the three major components of the nucleolus. The microinjected antibodies produced a progressive loss of the material of the dense fibrillar component (DFC) from the nucleoli which, at 4 h after injection, were transformed into bodies with purely granular component (GC) structure with attached fibrillar centers (FCs). Concomitantly, numerous extranucleolar aggregates appeared in the nucleoplasm which morphologically resembled fragments of the DFC and contained a protein (fibrillarin) diagnostic for this nucleolar structure. These observations indicate that the topological distribution of the material constituting the DFC can be experimentally influenced in interphase cells, apparently by modulating the transcriptional activity of the rRNA genes. These effects are different from nucleolar lesions induced by inhibitory drugs such as actinomycin D-dependent "nucleolar segregation". The structural alterations induced by antibodies to RNA polymerase I resemble, however, the initial events of nucleolar disintegration during mitotic prophase.}, language = {en} } @article{BenaventeDabauvalleScheeretal.1989, author = {Benavente, Ricardo and Dabauvalle, Marie-Christine and Scheer, Ulrich and Chaly, Nathalie}, title = {Functional role of newly formed pore complexes in postmitotic nuclear reorganization}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-40754}, year = {1989}, abstract = {Many nuclear proteins are released into the cytoplasm at prometaphase and are transported back into the daughter nuclei at the end of mitosis. To determine the role of this reentry in nuclear remodelling during early interphase, we experimentally manipulated nuclear protein uptake in dividing cells. Recently we and others have shown that signal-dependent, pore complex-mediated uptake of nuclear protein is blocked in living cells on microinjection of the lectin wheat germ agglutinin (WGA), or of antibodies such as PI1 that are directed against WGA-binding pore complex glycoproteins. In the present study, we microinjected mitotic PtKz cells with WGA or antibody PIt and followed nuclear reorganization of the daughter cells by immunofluorescence and electron microscopy. The inhibitory effect on nuclear protein uptake was monitored by co-injection of the karyophilic protein nucleoplasmin. When injected by itself early in mitosis, nucleoplasmin became sequestered into the daughter nuclei as they entered telophase. In contrast, nucleoplasmin was excluded from the daughter nuclei in the presence of WGA or antibody PI1 . Although PtKz cells with blocked nuclear protein uptake completed cytokinesis, their nuclei showed a telophaselike organization characterized by highly condensed chromatin surrounded by a nuclear envelope containing a few pore complexes. These findings suggest that pore complexes become functional as early as telophase, in close coincidence with nuclear envelope reformation. They further indicate that the extensive structural rearrangement of the nucleus during the telophase-G1 transition is dependent on the influx of karyophilic proteins from the cytoplasm through the pore complexes, and is not due solely to chromosome- associated components.}, language = {en} } @phdthesis{Benadi2013, author = {Benadi, Gita}, title = {Linking specialisation and stability of plant-pollinator networks}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-85288}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2013}, abstract = {In this dissertation, I examine the relationship between specialisation and stability of plant-pollinator networks, with a focus on two issues: Diversity maintenance in animal-pollinated plant communities and robustness of plant-pollinator systems against disturbances such as those caused by anthropogenic climate change. Chapter 1 of this thesis provides a general introduction to the concepts of ecological stability and specialisation with a focus on plant-pollinator systems, and a brief outline of the following chapters. Chapters 2-5 each consist of a research article addressing a specific question. While chapters 2 and 3 deal with different aspects of diversity maintenance in animal-pollinated plant communities, chapters 4 and 5 are concerned with the consequences of climate change in the form of temporary disturbances caused by extreme climatic events (chapter 4) and shifts in phenology of plants and pollinators (chapter 5). From a methodological perspective, the first three articles (chapter 2-4) can be grouped together as they all employ mathematical models of plant-pollinator systems, whereas chapter 5 describes an empirical study of plant-pollinator interactions along an altitudinal gradient in the Alps. The final chapter (6) provides a review of current knowledge on each of the two main themes of this thesis and places the findings of the four research articles in the context of related studies.}, subject = {Theoretische {\"O}kologie}, language = {en} } @phdthesis{Bemm2018, author = {Bemm, Felix Mathias}, title = {Genetic foundation of unrivaled survival strategies - Of water bears and carnivorous plants -}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-157109}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2018}, abstract = {All living organisms leverage mechanisms and response systems to optimize reproduction, defense, survival, and competitiveness within their natural habitat. Evolutionary theories such as the universal adaptive strategy theory (UAST) developed by John Philip Grime (1979) attempt to describe how these systems are limited by the trade-off between growth, maintenance and regeneration; known as the universal three-way trade-off. Grime introduced three adaptive strategies that enable organisms to coop with either high or low intensities of stress (e.g., nutrient deficiency) and environmental disturbance (e.g., seasons). The competitor is able to outcompete other organisms by efficiently tapping available resources in environments of low intensity stress and disturbance (e.g., rapid growers). A ruderal specism is able to rapidly complete the life cycle especially during high intensity disturbance and low intensity stress (e.g., annual colonizers). The stress tolerator is able to respond to high intensity stress with physiological variability but is limited to low intensity disturbance environments. Carnivorous plants like D. muscipula and tardigrades like M. tardigradum are two extreme examples for such stress tolerators. D. muscipula traps insects in its native habitat (green swamps in North and South Carolina) with specialized leaves and thereby is able to tolerate nutrient deficient soils. M. tardigradum on the other side, is able to escape desiccation of its terrestrial habitat like mosses and lichens which are usually covered by a water film but regularly fall completely dry. The stress tolerance of the two species is the central study object of this thesis. In both cases, high througput sequencing data and methods were used to test for transcriptomic (D. muscipula) or genomic adaptations (M. tardigradum) which underly the stress tolerance. A new hardware resource including computing cluster and high availability storage system was implemented in the first months of the thesis work to effectively analyze the vast amounts of data generated for both projects. Side-by-side, the data management resource TBro [14] was established together with students to intuitively approach complex biological questions and enhance collaboration between researchers of several different disciplines. Thereafter, the unique trapping abilities of D. muscipula were studied using a whole transcriptome approach. Prey-dependent changes of the transcriptional landscape as well as individual tissue-specific aspects of the whole plant were studied. The analysis revealed that non-stimulated traps of D. muscipula exhibit the expected hallmarks of any typical leaf but operates evolutionary conserved stress-related pathways including defense-associated responses when digesting prey. An integrative approach, combining proteome and transcriptome data further enabled the detailed description of the digestive cocktail and the potential nutrient uptake machinery of the plant. The published work [25] as well as a accompanying video material (https://www.eurekalert.org/pub_releases/ 2016-05/cshl-fgr042816.php; Video credit: S{\"o}nke Scherzer) gained global press coverage and successfully underlined the advantages of D. muscipula as experimental system to understand the carnivorous syndrome. The analysis of the peculiar stress tolerance of M. tardigradum during cryptobiosis was carried out using a genomic approach. First, the genome size of M. tardigradum was estimated, the genome sequenced, assembled and annotated. The first draft of M. tardigradum and the workflow used to established its genome draft helped scrutinizing the first ever released tardigrade genome (Hypsibius dujardini) and demonstrated how (bacterial) contamination can influence whole genome analysis efforts [27]. Finally, the M. tardigradum genome was compared to two other tardigrades and all species present in the current release of the Ensembl Metazoa database. The analysis revealed that tardigrade genomes are not that different from those of other Ecdysozoa. The availability of the three genomes allowed the delineation of their phylogenetic position within the Ecdysozoa and placed them as sister taxa to the nematodes. Thereby, the comparative analysis helped to identify evolutionary trends within this metazoan lineage. Surprisingly, the analysis did not reveal general mechanisms (shared by all available tardigrade genomes) behind the arguably most peculiar feature of tardigrades; their enormous stress tolerance. The lack of molecular evidence for individual tardigrade species (e.g., gene expression data for M. tardigradum) and the non-existence of a universal experimental framework which enables hypothesis testing withing the whole phylum Tardigrada, made it nearly impossible to link footprints of genomic adaptations to the unusual physiological capabilities. Nevertheless, the (comparative) genomic framework established during this project will help to understand how evolution tinkered, rewired and modified existing molecular systems to shape the remarkable phenotypic features of tardigrades.}, subject = {B{\"a}rtierchen}, language = {en} } @article{BemmBeckerLarischetal.2016, author = {Bemm, Felix and Becker, Dirk and Larisch, Christina and Kreuzer, Ines and Escalante-Perez, Maria and Schulze, Waltraud X. and Ankenbrand, Markus and Van de Weyer, Anna-Lena and Krol, Elzbieta and Al-Rasheid, Khaled A. and Mith{\"o}fer, Axel and Weber, Andreas P. and Schultz, J{\"o}rg and Hedrich, Rainer}, title = {Venus flytrap carnivorous lifestyle builds on herbivore defense strategies}, series = {Genome Research}, volume = {26}, journal = {Genome Research}, number = {6}, doi = {10.1101/gr.202200.115}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-188799}, pages = {812-825}, year = {2016}, abstract = {Although the concept of botanical carnivory has been known since Darwin's time, the molecular mechanisms that allow animal feeding remain unknown, primarily due to a complete lack of genomic information. Here, we show that the transcriptomic landscape of the Dionaea trap is dramatically shifted toward signal transduction and nutrient transport upon insect feeding, with touch hormone signaling and protein secretion prevailing. At the same time, a massive induction of general defense responses is accompanied by the repression of cell death-related genes/processes. We hypothesize that the carnivory syndrome of Dionaea evolved by exaptation of ancient defense pathways, replacing cell death with nutrient acquisition.}, language = {en} } @article{BellDabauvalleScheer1992, author = {Bell, Peter and Dabauvalle, Marie-Christine and Scheer, Ulrich}, title = {In vitro assembly of prenucleolar bodies in Xenopus egg extract}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-34233}, year = {1992}, abstract = {Nuclei assembled in Xenopus egg extract from purified DNA or chromatin resemble their natural counterparts in a number of structural and functional features. However, the most obvious structural element of normal interphase nuclei, the nucleolus, is absent from the in vitro reconstituted nuclei. By EM, cytological silver staining, and immunofluorescence microscopy employing antibodies directed against various nucleolar components we show that nuclei assembled in vitro contain numerous distinct aggregates that resemble prenucleolar bodies (PNBs) by several criteria. Formation of these PNB-like structures requires pore complex-mediated nuclear transport of proteins but is independent of the genetic content of the in vitro nuclei as well as transcriptional and translational events. Our data indicate that nuclei assembled in vitro are capable of initiating early steps of nucleologenesis but that the resulting PNBs are unable to fuse with each other, probably due to the absence of a functional nucleolus organizer. With appropriate modifications, this experimental system should be useful to define and analyze conditions promoting the site-specific assembly of PNBs into a coherent nucleolar body.}, language = {en} } @phdthesis{Beliu2020, author = {Beliu, Gerti}, title = {Bioorthogonale Tetrazin-Farbstoffe f{\"u}r die Lebendzell-Markierung und hochaufgel{\"o}ste Fluoreszenzmikroskopie}, doi = {10.25972/OPUS-18962}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-189628}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2020}, abstract = {Der genetische Code beschreibt die Ver- und Entschl{\"u}sselung der Erb-information f{\"u}r das universelle Prinzip der Proteinbiosynthese aus einzelnen Aminos{\"a}uren. Durch Erweiterung des genetischen Codes lassen sich unna-t{\"u}rliche Aminos{\"a}uren (uAA) mit einzigartigen biophysikalischen Eigenschaf-ten ortsspezifisch in Proteine einf{\"u}hren und erm{\"o}glichen die spezifische Ma-nipulation von Proteinen. Die Click-Reaktion zwischen der unnat{\"u}rlichen Aminos{\"a}ure TCO*-Lysin und Tetrazin besitzt eine außergew{\"o}hnliche Reaktionskinetik (≥800 M-1s-1) und erm{\"o}glicht eine spezifische und bioorthogonale Markierung von Bio- ¬molek{\"u}len unter physiologischen Bedingungen. Im Fokus dieser Arbeit stand zun{\"a}chst die Markierung von Membran- ¬rezeptoren durch Click-Chemie in lebenden Zellen sowie die Untersuchung der Wechselwirkung 22 bekannter und neuartiger Tetrazin-Farbstoff- Konjugate. Dar{\"u}ber hinaus wurde die Anwendbarkeit von bioorthogonalen Click-Reaktionen f{\"u}r die hochaufl{\"o}sende Fluoreszenzmikroskopie untersucht. Durch Erweiterung des genetischen Codes in Proteine aus der Klasse der ionotropen Glutamatrezeptoren (iGluR), TNF-Rezeptoren oder Mikrotubu-li-assoziierten Proteinen (MAP) wurde ortspezifisch die unnat{\"u}rliche Amino-s{\"a}ure TCO*-Lysin eingef{\"u}hrt und dadurch die Fluoreszenzmarkierung durch Tetrazin-Farbstoffe erm{\"o}glicht. Die direkte chemische Kopplung von TCO an Liganden wie Phalloidin und Docetaxel, welche spezifisch das Aktin-Zytoskelett bzw. Mikrotubuli-Filamente binden k{\"o}nnen, erm{\"o}glichte zudem die Click-F{\"a}rbungen von fixierten und lebenden Zellen ohne genetische Ver-{\"a}nderungen der Zielproteine. Des Weiteren wurden die spektroskopischen Eigenschaften von 22 Tetrazin-Farbstoffen, verteilt {\"u}ber den gesamten sichtbaren Wellenl{\"a}ngenbereich, untersucht. Ein charakteristisches Kennzeichen der Click-Reaktion mit Tet-razin-Farbstoffen ist dabei ihre Fluorogenit{\"a}t. Das Tetrazin fungiert nicht nur als reaktive Gruppe w{\"a}hrend der Click-Reaktion mit Alkenen, sondern f{\"u}hrt in vielen Tetrazin-Farbstoff-Konjugaten zur Fluoreszenzl{\"o}schung. W{\"a}hrend bei gr{\"u}n-absorbierenden Farbstoffe vor allem FRET-basierte L{\"o}schprozesse dominieren, konnte photoinduzierter Elektronentransfer (PET) vom angeregten Farbstoff zum Tetrazin als Hauptl{\"o}schmechanismus bei rot-absorbierenden Oxazin- und Rhodamin-Derivaten identifiziert werden. Die effiziente und spezifische Markierung aller untersuchten Tetrazin- Farbstoffe erm{\"o}glichte die Visualisierung von Aktin-Filamenten, Mikrotubuli und Membranrezeptoren sowohl durch konventionelle Fluoreszenzmikrosko-pie als auch durch hochaufl{\"o}sende Verfahren, wie z.B. dSTORM, auf Ein-zelmolek{\"u}lebene. Die unterschiedliche Zellpermeabilit{\"a}t von Tetrazin-Farbstoffen kann dabei vorteilhaft f{\"u}r die spezifische intra- und extrazellul{\"a}re Markierung von Proteinen in fixierten und lebenden Zellen genutzt werden.}, subject = {Hochaufgel{\"o}ste Fluoreszenzmikroskopie}, language = {de} } @article{BeisserGrohmeKopkaetal.2012, author = {Beisser, Daniela and Grohme, Markus A. and Kopka, Joachim and Frohme, Marcus and Schill, Ralph O. and Hengherr, Steffen and Dandekar, Thomas and Klau, Gunnar W. and Dittrich, Marcus and M{\"u}ller, Tobias}, title = {Integrated pathway modules using time-course metabolic profiles and EST data from Milnesium tardigradum}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-75241}, year = {2012}, abstract = {Background: Tardigrades are multicellular organisms, resistant to extreme environmental changes such as heat, drought, radiation and freezing. They outlast these conditions in an inactive form (tun) to escape damage to cellular structures and cell death. Tardigrades are apparently able to prevent or repair such damage and are therefore a crucial model organism for stress tolerance. Cultures of the tardigrade Milnesium tardigradum were dehydrated by removing the surrounding water to induce tun formation. During this process and the subsequent rehydration, metabolites were measured in a time series by GC-MS. Additionally expressed sequence tags are available, especially libraries generated from the active and inactive state. The aim of this integrated analysis is to trace changes in tardigrade metabolism and identify pathways responsible for their extreme resistance against physical stress. Results: In this study we propose a novel integrative approach for the analysis of metabolic networks to identify modules of joint shifts on the transcriptomic and metabolic levels. We derive a tardigrade-specific metabolic network represented as an undirected graph with 3,658 nodes (metabolites) and 4,378 edges (reactions). Time course metabolite profiles are used to score the network nodes showing a significant change over time. The edges are scored according to information on enzymes from the EST data. Using this combined information, we identify a key subnetwork (functional module) of concerted changes in metabolic pathways, specific for de- and rehydration. The module is enriched in reactions showing significant changes in metabolite levels and enzyme abundance during the transition. It resembles the cessation of a measurablemetabolism (e.g. glycolysis and amino acid anabolism) during the tun formation, the production of storage metabolites and bioprotectants, such as DNA stabilizers, and the generation of amino acids and cellular components from monosaccharides as carbon and energy source during rehydration. Conclusions: The functional module identifies relationships among changed metabolites (e.g. spermidine) and reactions and provides first insights into important altered metabolic pathways. With sparse and diverse data available, the presented integrated metabolite network approach is suitable to integrate all existing data and analyse it in a combined manner.}, subject = {Milnesium tardigradum}, language = {en} } @phdthesis{Beisser2011, author = {Beisser, Daniela}, title = {Integrated functional analysis of biological networks}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-70150}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2011}, abstract = {In recent years high-throughput experiments provided a vast amount of data from all areas of molecular biology, including genomics, transcriptomics, proteomics and metabolomics. Its analysis using bioinformatics methods has developed accordingly, towards a systematic approach to understand how genes and their resulting proteins give rise to biological form and function. They interact with each other and with other molecules in highly complex structures, which are explored in network biology. The in-depth knowledge of genes and proteins obtained from high-throughput experiments can be complemented by the architecture of molecular networks to gain a deeper understanding of biological processes. This thesis provides methods and statistical analyses for the integration of molecular data into biological networks and the identification of functional modules, as well as its application to distinct biological data. The integrated network approach is implemented as a software package, termed BioNet, for the statistical language R. The package includes the statistics for the integration of transcriptomic and functional data with biological networks, the scoring of nodes and edges of these networks as well as methods for subnetwork search and visualisation. The exact algorithm is extensively tested in a simulation study and outperforms existing heuristic methods for the calculation of this NP-hard problem in accuracy and robustness. The variability of the resulting solutions is assessed on perturbed data, mimicking random or biased factors that obscure the biological signal, generated for the integrated data and the network. An optimal, robust module can be calculated using a consensus approach, based on a resampling method. It summarizes optimally an ensemble of solutions in a robust consensus module with the estimated variability indicated by confidence values for the nodes and edges. The approach is subsequently applied to two gene expression data sets. The first application analyses gene expression data for acute lymphoblastic leukaemia (ALL) and differences between the subgroups with and without an oncogenic BCR/ABL gene fusion. In a second application gene expression and survival data from diffuse large B-cell lymphomas are examined. The identified modules include and extend already existing gene lists and signatures by further significant genes and their interactions. The most important novelty is that these genes are determined and visualised in the context of their interactions as a functional module and not as a list of independent and unrelated transcripts. In a third application the integrative network approach is used to trace changes in tardigrade metabolism to identify pathways responsible for their extreme resistance to environmental changes and endurance in an inactive tun state. For the first time a metabolic network approach is proposed to detect shifts in metabolic pathways, integrating transcriptome and metabolite data. Concluding, the presented integrated network approach is an adequate technique to unite high-throughput experimental data for single molecules and their intermolecular dependencies. It is flexible to apply on diverse data, ranging from gene expression changes over metabolite abundances to protein modifications in a combination with a suitable molecular network. The exact algorithm is accurate and robust in comparison to heuristic approaches and delivers an optimal, robust solution in form of a consensus module with confidence values. By the integration of diverse sources of information and a simultaneous inspection of a molecular event from different points of view, new and exhaustive insights into biological processes can be acquired.}, subject = {Bioinformatik}, language = {en} } @article{BeierGaetschenbergerAzzamietal.2013, author = {Beier, Hildburg and G{\"a}tschenberger, Heike and Azzami, Klara and Tautz, J{\"u}rgen}, title = {Antibacterial Immune Competence of Honey Bees (Apis mellifera) Is Adapted to Different Life Stages and Environmental Risks}, series = {PLoS ONE}, journal = {PLoS ONE}, doi = {10.1371/journal.pone.0066415}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-96895}, year = {2013}, abstract = {The development of all honey bee castes proceeds through three different life stages all of which encounter microbial infections to a various extent. We have examined the immune strength of honey bees across all developmental stages with emphasis on the temporal expression of cellular and humoral immune responses upon artificial challenge with viable Escherichia coli bacteria. We employed a broad array of methods to investigate defence strategies of infected individuals: (a) fate of bacteria in the haemocoel; (b) nodule formation and (c) induction of antimicrobial peptides (AMPs). Newly emerged adult worker bees and drones were able to activate efficiently all examined immune reactions. The number of viable bacteria circulating in the haemocoel of infected bees declined rapidly by more than two orders of magnitude within the first 4-6 h post-injection (p.i.), coinciding with the occurrence of melanised nodules. Antimicrobial activity, on the other hand, became detectable only after the initial bacterial clearance. These two temporal patterns of defence reactions very likely represent the constitutive cellular and the induced humoral immune response. A unique feature of honey bees is that a fraction of worker bees survives the winter season in a cluster mostly engaged in thermoregulation. We show here that the overall immune strength of winter bees matches that of young summer bees although nodulation reactions are not initiated at all. As expected, high doses of injected viable E.coli bacteria caused no mortality in larvae or adults of each age. However, drone and worker pupae succumbed to challenge with E.coli even at low doses, accompanied by a premature darkening of the pupal body. In contrast to larvae and adults, we observed no fast clearance of viable bacteria and no induction of AMPs but a rapid proliferation of E.coli bacteria in the haemocoel of bee pupae ultimately leading to their death.}, language = {en} } @article{BeetzKrauselJundi2023, author = {Beetz, M. Jerome and Kraus, Christian and el Jundi, Basil}, title = {Neural representation of goal direction in the monarch butterfly brain}, series = {Nature Communications}, volume = {14}, journal = {Nature Communications}, doi = {10.1038/s41467-023-41526-w}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-358073}, year = {2023}, abstract = {Neural processing of a desired moving direction requires the continuous comparison between the current heading and the goal direction. While the neural basis underlying the current heading is well-studied, the coding of the goal direction remains unclear in insects. Here, we used tetrode recordings in tethered flying monarch butterflies to unravel how a goal direction is represented in the insect brain. While recording, the butterflies maintained robust goal directions relative to a virtual sun. By resetting their goal directions, we found neurons whose spatial tuning was tightly linked to the goal directions. Importantly, their tuning was unaffected when the butterflies changed their heading after compass perturbations, showing that these neurons specifically encode the goal direction. Overall, we here discovered invertebrate goal-direction neurons that share functional similarities to goal-direction cells reported in mammals. Our results give insights into the evolutionarily conserved principles of goal-directed spatial orientation in animals.}, language = {en} } @article{BeetzHechavarria2022, author = {Beetz, M. Jerome and Hechavarr{\´i}a, Julio C.}, title = {Neural processing of naturalistic echolocation signals in bats}, series = {Frontiers in Neural Circuits}, volume = {16}, journal = {Frontiers in Neural Circuits}, issn = {1662-5110}, doi = {10.3389/fncir.2022.899370}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-274605}, year = {2022}, abstract = {Echolocation behavior, a navigation strategy based on acoustic signals, allows scientists to explore neural processing of behaviorally relevant stimuli. For the purpose of orientation, bats broadcast echolocation calls and extract spatial information from the echoes. Because bats control call emission and thus the availability of spatial information, the behavioral relevance of these signals is undiscussable. While most neurophysiological studies, conducted in the past, used synthesized acoustic stimuli that mimic portions of the echolocation signals, recent progress has been made to understand how naturalistic echolocation signals are encoded in the bat brain. Here, we review how does stimulus history affect neural processing, how spatial information from multiple objects and how echolocation signals embedded in a naturalistic, noisy environment are processed in the bat brain. We end our review by discussing the huge potential that state-of-the-art recording techniques provide to gain a more complete picture on the neuroethology of echolocation behavior.}, language = {en} } @article{BeerSteffanDewenterHaerteletal.2016, author = {Beer, Katharina and Steffan-Dewenter, Ingolf and H{\"a}rtel, Stephan and Helfrich-F{\"o}rster, Charlotte}, title = {A new device for monitoring individual activity rhythms of honey bees reveals critical effects of the social environment on behavior}, series = {Journal of Comparative Physiology A}, volume = {202}, journal = {Journal of Comparative Physiology A}, number = {8}, doi = {10.1007/s00359-016-1103-2}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-188030}, pages = {555-565}, year = {2016}, abstract = {Chronobiological studies of individual activity rhythms in social insects can be constrained by the artificial isolation of individuals from their social context. We present a new experimental set-up that simultaneously measures the temperature rhythm in a queen-less but brood raising mini colony and the walking activity rhythms of singly kept honey bees that have indirect social contact with it. Our approach enables monitoring of individual bees in the social context of a mini colony under controlled laboratory conditions. In a pilot experiment, we show that social contact with the mini colony improves the survival of monitored young individuals and affects locomotor activity patterns of young and old bees. When exposed to conflicting Zeitgebers consisting of a light-dark (LD) cycle that is phase-delayed with respect to the mini colony rhythm, rhythms of young and old bees are socially synchronized with the mini colony rhythm, whereas isolated bees synchronize to the LD cycle. We conclude that the social environment is a stronger Zeitgeber than the LD cycle and that our new experimental set-up is well suited for studying the mechanisms of social entrainment in honey bees.}, language = {en} } @article{BeerSchenkHelfrichFoersteretal.2019, author = {Beer, Katharina and Schenk, Mariela and Helfrich-F{\"o}rster, Charlotte and Holzschuh, Andrea}, title = {The circadian clock uses different environmental time cues to synchronize emergence and locomotion of the solitary bee Osmia bicornis}, series = {Scientific Reports}, volume = {9}, journal = {Scientific Reports}, doi = {10.1038/s41598-019-54111-3}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-202721}, pages = {17748}, year = {2019}, abstract = {Life on earth adapted to the daily reoccurring changes in environment by evolving an endogenous circadian clock. Although the circadian clock has a crucial impact on survival and behavior of solitary bees, many aspects of solitary bee clock mechanisms remain unknown. Our study is the first to show that the circadian clock governs emergence in Osmia bicornis, a bee species which overwinters as adult inside its cocoon. Therefore, its eclosion from the pupal case is separated by an interjacent diapause from its emergence in spring. We show that this bee species synchronizes its emergence to the morning. The daily rhythms of emergence are triggered by temperature cycles but not by light cycles. In contrast to this, the bee's daily rhythms in locomotion are synchronized by light cycles. Thus, we show that the circadian clock of O. bicornis is set by either temperature or light, depending on what activity is timed. Light is a valuable cue for setting the circadian clock when bees have left the nest. However, for pre-emerged bees, temperature is the most important cue, which may represent an evolutionary adaptation of the circadian system to the cavity-nesting life style of O. bicornis.}, language = {en} } @article{BeerJoschinskiSastreetal.2017, author = {Beer, Katharina and Joschinski, Jens and Sastre, Alazne Arrazola and Krauss, Jochen and Helfrich-F{\"o}rster, Charlotte}, title = {A damping circadian clock drives weak oscillations in metabolism and locomotor activity of aphids (Acyrthosiphon pisum)}, series = {Scientific Reports}, volume = {7}, journal = {Scientific Reports}, number = {14906}, doi = {10.1038/s41598-017-15014-3}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-170020}, year = {2017}, abstract = {Timing seasonal events, like reproduction or diapause, is crucial for the survival of many species. Global change causes phenologies worldwide to shift, which requires a mechanistic explanation of seasonal time measurement. Day length (photoperiod) is a reliable indicator of winter arrival, but it remains unclear how exactly species measure day length. A reference for time of day could be provided by a circadian clock, by an hourglass clock, or, as some newer models suggest, by a damped circadian clock. However, damping of clock outputs has so far been rarely observed. To study putative clock outputs of Acyrthosiphon pisum aphids, we raised individual nymphs on coloured artificial diet, and measured rhythms in metabolic activity in light-dark illumination cycles of 16:08 hours (LD) and constant conditions (DD). In addition, we kept individuals in a novel monitoring setup and measured locomotor activity. We found that A. pisum is day-active in LD, potentially with a bimodal distribution. In constant darkness rhythmicity of locomotor behaviour persisted in some individuals, but patterns were mostly complex with several predominant periods. Metabolic activity, on the other hand, damped quickly. A damped circadian clock, potentially driven by multiple oscillator populations, is the most likely explanation of our results.}, language = {en} } @article{BeerHaertelHelfrichFoerster2022, author = {Beer, Katharina and H{\"a}rtel, Stephan and Helfrich-F{\"o}rster, Charlotte}, title = {The pigment-dispersing factor neuronal network systematically grows in developing honey bees}, series = {The Journal of Comparative Neurology}, volume = {530}, journal = {The Journal of Comparative Neurology}, number = {9}, doi = {10.1002/cne.25278}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-257300}, pages = {1321-1340}, year = {2022}, abstract = {The neuropeptide pigment-dispersing factor (PDF) plays a prominent role in the circadian clock of many insects including honey bees. In the honey bee brain, PDF is expressed in about 15 clock neurons per hemisphere that lie between the central brain and the optic lobes. As in other insects, the bee PDF neurons form wide arborizations in the brain, but certain differences are evident. For example, they arborize only sparsely in the accessory medulla (AME), which serves as important communication center of the circadian clock in cockroaches and flies. Furthermore, all bee PDF neurons cluster together, which makes it impossible to distinguish individual projections. Here, we investigated the developing bee PDF network and found that the first three PDF neurons arise in the third larval instar and form a dense network of varicose fibers at the base of the developing medulla that strongly resembles the AME of hemimetabolous insects. In addition, they send faint fibers toward the lateral superior protocerebrum. In last larval instar, PDF cells with larger somata appear and send fibers toward the distal medulla and the medial protocerebrum. In the dorsal part of the medulla serpentine layer, a small PDF knot evolves from which PDF fibers extend ventrally. This knot disappears during metamorphosis and the varicose arborizations in the putative AME become fainter. Instead, a new strongly stained PDF fiber hub appears in front of the lobula. Simultaneously, the number of PDF neurons increases and the PDF neuronal network in the brain gets continuously more complex.}, language = {en} } @article{BeerHelfrichFoerster2020, author = {Beer, Katharina and Helfrich-F{\"o}rster, Charlotte}, title = {Model and Non-model Insects in Chronobiology}, series = {Frontiers in Behavioral Neuroscience}, volume = {14}, journal = {Frontiers in Behavioral Neuroscience}, issn = {1662-5153}, doi = {10.3389/fnbeh.2020.601676}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-218721}, year = {2020}, abstract = {The fruit fly Drosophila melanogaster is an established model organism in chronobiology, because genetic manipulation and breeding in the laboratory are easy. The circadian clock neuroanatomy in D. melanogaster is one of the best-known clock networks in insects and basic circadian behavior has been characterized in detail in this insect. Another model in chronobiology is the honey bee Apis mellifera, of which diurnal foraging behavior has been described already in the early twentieth century. A. mellifera hallmarks the research on the interplay between the clock and sociality and complex behaviors like sun compass navigation and time-place-learning. Nevertheless, there are aspects of clock structure and function, like for example the role of the clock in photoperiodism and diapause, which can be only insufficiently investigated in these two models. Unlike high-latitude flies such as Chymomyza costata or D. ezoana, cosmopolitan D. melanogaster flies do not display a photoperiodic diapause. Similarly, A. mellifera bees do not go into "real" diapause, but most solitary bee species exhibit an obligatory diapause. Furthermore, sociality evolved in different Hymenoptera independently, wherefore it might be misleading to study the social clock only in one social insect. Consequently, additional research on non-model insects is required to understand the circadian clock in Diptera and Hymenoptera. In this review, we introduce the two chronobiology model insects D. melanogaster and A. mellifera, compare them with other insects and show their advantages and limitations as general models for insect circadian clocks.}, language = {en} }