@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}
}
@phdthesis{Rost2020,
  author    = {Rost, Isabell},
  title     = {Gezielte Anreicherungs- und neue DNA-Sequenzierungsstrategien f{\"u}r die molekulare Analyse von Fanconi-An{\"a}mie-Genen},
  doi       = {10.25972/OPUS-15109},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-151096},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2020},
  abstract  = {Fanconi-An{\"a}mie (FA) ist, mit Ausnahme von Mutationen in FANCR/RAD51, eine autosomal-rezessive oder X-chromosomal vererbte Krankheit, die sich durch eine ausgesprochene klinische als auch genetische Heterogenit{\"a}t auszeichnet. Neben einem fortschreitenden Knochenmarksversagen z{\"a}hlen zu den typischen Merkmalen eine Vielzahl an angeborenen Fehlbildungen, wie beispielsweise Radialstrahlanomalien, Minderwuchs oder Pigmentierungsst{\"o}rungen. Zudem besteht f{\"u}r FA-Patienten ein {\"u}berdurchschnittlich hohes Risiko bereits in jungen Jahren an akuter myeloischer Leuk{\"a}mie oder soliden Tumoren zu erkranken. Bislang konnten in 21 FA-Genen (FANCA, -B, -C, - D1, -D2, -E, -F, -G, -I, -J, -L, -M, -N, -O, -P, -Q, -R, -S, -T, -U oder -V) krankheitsverursachende Mutationen identifiziert werden, deren Proteinprodukte maßgeblich an der Aufrechterhaltung der Genomstabilit{\"a}t beteiligt sind und Komponenten des FA/BRCA-DNA-Reparaturweges darstellen. In der klassischen FA-Mutationsanalyse kommen meist Sanger-Sequenzierungen sowie MLPA- und Immunblot-Analysen zum Einsatz. Da im Wesentlichen keine Genotyp-Ph{\"a}notyp-Korrelation besteht, gestaltet sich, gerade bei seltenen FA-Komplementationsgruppen, der Nachweis von krankheitsverursachenden Mutationen oftmals sehr zeit- und kostenintensiv. W{\"a}hrend der letzten Jahre wurden verschiedene Strategien zur Anreicherung und Sequenzierung entwickelt, welche die parallele Sequenzanalyse einzelner ausgew{\"a}hlter Gene, ganzer Exome oder sogar des gesamten Genoms und somit eine kosten- und zeiteffiziente Mutationsanalyse erm{\"o}glichen. In der vorliegenden Arbeit wurden unterschiedliche Anreicherungsmethoden mit anschließender Hochdurchsatzsequenzierung auf ihre Anwendbarkeit in der molekulargenetischen FA-Diagnostik getestet, um klassische Mutationsanalyse-Methoden zu erg{\"a}nzen oder m{\"o}glicherweise sogar ganz ersetzen zu k{\"o}nnen. Der erste Teil der Arbeit befasste sich mit der Etablierung eines FA-spezifischen Genpanels zur Genotypisierung von FA-Patienten. Nachdem die Methode zun{\"a}chst anhand von FA-Patienten mit bekannten Mutationen optimiert werden musste, erwies sie sich als effizienter Ansatz zum Nachweis krankheitsverursachender Mutationen bei FA-Patienten unbekannter Komplementationsgruppe. Durch die FA-Panelanalyse konnten 37 von 47 unklassifizierten Patienten einer FA-Komplementationsgruppe zugeordnet werden, indem deren kausalen Mutationen bestimmt wurden. In einem weiteren Ansatz sollte die Anwendbarkeit eines kommerziellen Anreicherungspanels zur FA-Diagnostik untersucht werden. Auch hier konnte ein Großteil der krankheitsverursachenden Mutationen von f{\"u}nf bekannten wie auch 13 nicht zugeordneten FA-Patienten detektiert und somit eine molekulargenetische Diagnose bei neun weiteren, zuvor unklassifizierten FA-Patienten, gestellt werden. Ferner wurden sechs ausgew{\"a}hlte Patienten, zus{\"a}tzlich zur Panelanreicherung, per Exomanalyse untersucht. Zum einen konnten Mutationen in bekannten FA-Genen best{\"a}tigt oder neu identifiziert werden. Zum anderen wurden auch potentiell pathogene Mutationen in DNA-Reparaturgenen außerhalb des FA/BRCA-Signalweges bei zwei Patienten mit unbest{\"a}tigter Verdachtsdiagnose FA verifiziert. So wurde bei mehreren Mitgliedern einer Familie mit unterschiedlichen Tumorerkrankungen eine zuvor unbeschriebene homozygote Nonsense-Mutation in der BER-Glykosylase NTHL1 nachgewiesen, f{\"u}r welche bislang erst zwei pathogene Mutationen als Ausl{\"o}ser eines neuen Krebssyndroms bekannt sind. Bei einem weiteren Patienten wurden compound-heterozygote Mutationen in RPA1 detektiert, ein Gen f{\"u}r das bislang noch kein Krankheitsbild bekannt ist. Mit Hilfe der drei verschiedenen Anreicherungsstrategien konnten insgesamt 47 von 60 unklassifizierten FA-Patienten 13 verschiedenen Komplementationsgruppen eindeutig zugeordnet werden. Es zeigte sich dabei ein breites Spektrum an neuen, bislang unbeschriebenen FA-Mutationen. Den gr{\"o}ßten Anteil an der Gesamtzahl der nachgewiesenen Mutationen hatten Spleißmutationen, die auf eine Auswirkung auf das kanonische Spleißmuster untersucht wurden, um einen pathogenen Effekt nachweisen zu k{\"o}nnen. Weiterhin schloss die Arbeit die Charakterisierung einzelner FA-Patienten bzw. Komplementationsgruppen mit ein. Dazu z{\"a}hlen die seltenen Untergruppen FA-T und FA-Q, f{\"u}r die jeweils ein neuer Patient identifiziert werden konnte. Durch die funktionelle Charakterisierung der dritten jemals beschriebenen FA-Q-Patientin konnten Einblicke in das Zusammenspiel der Reparatur von DNA-Quervernetzungen und der Nukleotidexzisionsreparatur gewonnen und die ph{\"a}notypische Variabilit{\"a}t von FA durch die subjektive als auch zellul{\"a}re UV-Sensitivit{\"a}t der Patientin erg{\"a}nzt werden. Dar{\"u}ber hinaus konnte das Mutationsspektrum in FA-I sowie FA-D2 erweitert werden. Eine genauere Untersuchung der Pseudogenregionen von FANCD2 erm{\"o}glichte dabei die gezielte Mutationsanalyse des Gens. Insgesamt konnten die Ergebnisse dieser Arbeit dazu beitragen, das Mutationsspektrum in FA zu erweitern und durch die Identifizierung und Charakterisierung einzelner Patienten neue Einblicke in verschiedene Komponenten des FA/BRCA-Signalweges zu erhalten. Es zeigte sich, dass neue DNA-Sequenzierungsstrategien in der FA-Diagnostik eingesetzt werden k{\"o}nnen, um eine effiziente Mutationsanalyse zu gew{\"a}hrleisten und klassische Methoden in Teilbereichen zu ersetzen.},
  subject      = {Fanconi-An{\"a}mie},
  language  = {de}
}
@phdthesis{Keppler2020,
  author    = {Keppler, Sarah},
  title     = {Characterization of Novel Mutations in Receptor-Tyrosine Kinases in Multiple Myeloma},
  doi       = {10.25972/OPUS-15572},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-155720},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2020},
  abstract  = {Multiple myeloma (MM) is a disease of terminally differentiated B-cells which accumulate in the bone marrow leading to bone lesions, hematopoietic insufficiency and hypercalcemia. Genetically, MM is characterized by a great heterogeneity. A recent next-generation sequencing approach resulted in the identification of a signaling network with an accumulation of mutations in receptor-tyrosine kinases (RTKs), adhesion molecules and downstream effectors. A deep-sequencing amplicon approach of the coding DNA sequence of the six RTKs EPHA2, EGFR, ERBB3, IGF1R, NTRK1 and NTRK2 was conducted in a patient cohort (75 MM samples and 68 corresponding normal samples) of the "Deutsche Studiengruppe Multiples Myelom (DSMM)" to further elucidate the role of RTKs in MM. As an initial approach the detected mutations were correlated with cytogenetic abnormalities and clinical data in the course of this thesis. RTK mutations were present in 13\% of MM patients of the DSMM XI trial and accumulated in the ligand-binding and tyrosine-kinase domain. The newly identified mutations were associated with an adverse patient survival, but not with any cytogenetic abnormality common in MM. Especially rare patient-specific SNPs (single nucleotide polymorphism) had a negative impact on patient survival. For a more comprehensive understanding of the role of rare RTK SNPs in MM, a second amplicon sequencing approach was performed in a patient cohort of the DSMM XII trial that included 75 tumor and 184 normal samples. This approach identified a total of 23 different mutations in the six RTKs EPHA2, EGFR, ERBB3, IGF1R, NTRK1 and NTRK2 affecting 24 patients. These mutations could furthermore be divided into 20 rare SNPs and 3 SNVs (single nucleotide variant). In contrast to the first study, the rare SNPs were significantly associated with the adverse prognostic factor del17p. IGF1R was among the most commonly mutated RTKs in the first amplicon sequencing approach and is known to play an important role in diverse cellular processes such as cell proliferation and survival. To study the role of IGF1R mutations in the hard-to-transfect MM cells, stable IGF1R-knockdown MM cell lines were established. One of the knockdown cell lines (L363-C/C9) as well as a IGF1R-WT MM cell line (AMO1) were subsequently used for the stable overexpression of WT IGF1R and mutant IGF1R (N1129S, D1146N). Overall, an impact on the MAPK and PI3K/AKT signaling pathways was observed upon the IGF1R knockdown as well as upon WT and mutant IGF1R overexpression. The resulting signaling pattern, however, differed between different MM cell lines used in this thesis as well as in a parallel performed master thesis which further demonstrates the great heterogeneity described in MM. Taken together, the conducted sequencing and functional studies illustrate the importance of RTKs and especially of IGF1R and its mutants in the pathogenesis of MM. Moreover, the results support the potential role of IGF1R as a therapeutic target for a subset of MM patients with mutated IGF1R and/or IGF1R overexpression.},
  subject      = {Plasmozytom},
  language  = {en}
}
@phdthesis{Zimmermann2020,
  author    = {Zimmermann, Henriette},
  title     = {Antigenic variation and stumpy development in \(Trypanosoma\) \(brucei\)},
  doi       = {10.25972/OPUS-14690},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-146902},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2020},
  abstract  = {The eukaryotic parasite Trypanosoma brucei has evolved sophisticated strategies to persist within its mammalian host. Trypanosomes evade the hosts' immune system by antigenic variation of their surface coat, consisting of variant surface glycoproteins (VSGs). Out of a repertoire of thousands of VSG genes, only one is expressed at any given time from one of the 15 telomeric expression sites (ES). The VSG is stochastically exchanged either by a transcriptional switch of the active ES (in situ switch) or by a recombinational exchange of the VSG within the active ES. However, for infections to persist, the parasite burden has to be limited. The slender (sl) bloodstream form secretes the stumpy induction factor (SIF), which accumulates with rising parasitemia. SIF induces the irreversible developmental transition from the proliferative sl to the cell cycle-arrested but fly-infective stumpy (st) stage once a concentration threshold is reached. Thus, antigenic variation and st development ensure persistent infections and transmissibility. A previous study in monomorphic cells indicated that the attenuation of the active ES could be relevant for the development of trypanosomes. The present thesis investigated this hypothesis using the inducible overexpression of an ectopic VSG in pleomorphic trypanosomes, which possess full developmental competence. These studies revealed a surprising phenotypic plasticity: while the endogenous VSG was always down-regulated upon induction, the ESactivity determined whether the VSG overexpressors arrested in growth or kept proliferating. Full ES-attenuation induced the differentiation of bona fide st parasites independent of the cell density and thus represents the sole natural SIF-independent differentiation trigger to date. A milder decrease of the ES-activity did not induce phenotypic changes, but appeared to prime the parasites for SIF-induced differentiation. These results demonstrate that antigenic variation and development are linked and indicated that the ES and the VSG are independently regulated. Therefore, I investigated in the second part of my thesis how ES-attenuation and VSG-silencing can be mediated. Integration of reporters with a functional or defective VSG 3'UTR into different genomic loci showed that the maintenance of the active state of the ES depends on a conserved motif within the VSG 3'UTR. In situ switching was only triggered when the telomere-proximal motif was partially deleted, suggesting that it serves as a DNA-binding motif for a telomere-associated protein. The VSG levels seem to be additionally regulated in trans based on the VSG 3'UTR independent of the genomic context, which was reinforced by the regulation of a constitutively expressed reporter with VSG 3' UTR upon ectopic VSG overexpression.},
  subject      = {Trypanosoma brucei},
  language  = {en}
}
@article{KrebsSolimandoKalogirouetal.2020,
  author    = {Krebs, Markus and Solimando, Antonio Giovanni and Kalogirou, Charis and Marquardt, Andr{\´e} and Frank, Torsten and Sokolakis, Ioannis and Hatzichristodoulou, Georgios and Kneitz, Susanne and Bargou, Ralf and K{\"u}bler, Hubert and Schilling, Bastian and Spahn, Martin and Kneitz, Burkhard},
  title     = {miR-221-3p Regulates VEGFR2 Expression in High-Risk Prostate Cancer and Represents an Escape Mechanism from Sunitinib In Vitro},
  series = {Journal of Clinical Medicine},
  volume    = {9},
  journal   = {Journal of Clinical Medicine},
  number    = {3},
  issn      = {2077-0383},
  doi       = {10.3390/jcm9030670},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-203168},
  year      = {2020},
  abstract  = {Downregulation of miR-221-3p expression in prostate cancer (PCa) predicted overall and cancer-specific survival of high-risk PCa patients. Apart from PCa, miR-221-3p expression levels predicted a response to tyrosine kinase inhibitors (TKI) in clear cell renal cell carcinoma (ccRCC) patients. Since this role of miR-221-3p was explained with a specific targeting of VEGFR2, we examined whether miR-221-3p regulated VEGFR2 in PCa. First, we confirmed VEGFR2/KDR as a target gene of miR-221-3p in PCa cells by applying Luciferase reporter assays and Western blotting experiments. Although VEGFR2 was mainly downregulated in the PCa cohort of the TCGA (The Cancer Genome Atlas) database, VEGFR2 was upregulated in our high-risk PCa cohort (n = 142) and predicted clinical progression. In vitro miR-221-3p acted as an escape mechanism from TKI in PC3 cells, as displayed by proliferation and apoptosis assays. Moreover, we confirmed that Sunitinib induced an interferon-related gene signature in PC3 cells by analyzing external microarray data and by demonstrating a significant upregulation of miR-221-3p/miR-222-3p after Sunitinib exposure. Our findings bear a clinical perspective for high-risk PCa patients with low miR-221-3p levels since this could predict a favorable TKI response. Apart from this therapeutic niche, we identified a partially oncogenic function of miR-221-3p as an escape mechanism from VEGFR2 inhibition.},
  language  = {en}
}
@phdthesis{Michel2020,
  author    = {Michel, Konstanze},
  title     = {Die kardiale Bedeutung des Hormons C-Typ natriuretisches Peptid (CNP) und dessen Guanylylcyclase B (GC-B) Rezeptor},
  doi       = {10.25972/OPUS-20021},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-200211},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2020},
  abstract  = {In der vorliegenden Dissertationsarbeit wurden die kardialen Effekte des C-Typ natriuretischen Peptids (CNP) an wildtypischen M{\"a}usen (Studie 1) und an einem neuen genetischen Mausmodell, mit einer Kardiomyozyten-spezifischen Deletion des Guanylyl-Cyclase B (GC-B) Rezeptors (Studie 2) untersucht. In Studie 1 wurden die Wirkungen von exogenem, synthetischem CNP auf eine durch Druckbelastung-induzierte Herzinsuffizienz in wildtypischen M{\"a}usen (C57Bl6 Hintergrund) untersucht. Daf{\"u}r wurde CNP parallel zu einer operativen transversen Aortenkonstriktion (TAC) {\"u}ber osmotische Minipumpen in einer Dosierung von 50 ng/kg/min {\"u}ber 14 Tage appliziert. Die 14 Tage TAC f{\"u}hrten zu einer ausgepr{\"a}gten Linksherzhypertrophie. Diese wurde durch exogenes CNP auf zellul{\"a}rer (verringerte Kardiomyozytenfl{\"a}chen) und molekularer (verringerte BNP mRNA Expression) Ebene signifikant gehemmt. Auch die durch TAC-induzierte linksventrikul{\"a}re Dilatation wurde durch exogenes CNP fast vollst{\"a}ndig verhindert. Diese kardialen protektiven Effekte von CNP traten ohne eine wesentliche Ver{\"a}nderung des arteriellen Blutdrucks auf. M{\"o}gliche mechanistische Ursachen f{\"u}r die sch{\"u}tzende Wirkung von CNP k{\"o}nnte die PKG-abh{\"a}ngige Phosphorylierung des sarkomerischen Proteins Titin sein. Eine gesteigerte Phosphorylierung von Titin an der elastischen N2B-Dom{\"a}ne verringert die Steifigkeit der Kardiomyozyten und verbessert somit deren Relaxationsf{\"a}higkeit (Hudson 2011). Die erh{\"o}hten linksventrikul{\"a}ren Volumina nach TAC (end-diastolische und end-systolische Volumina) wurden m{\"o}glicherweise durch eine erh{\"o}hte Steifigkeit der Kardiomyozyten provoziert. Dies k{\"o}nnte durch den akuten IL-6 mRNA Anstieg nach TAC beg{\"u}nstigt werden, da Kruger et al. einen Zusammenhang zwischen passiver Steifigkeit der Kardiomyozyten und IL-6-Expression postulierten (Kotter 2016, Kruger 2009). Diese Ver{\"a}nderungen wurden durch exogenes CNP verhindert. Es ist wahrscheinlich, dass die CNP-induzierte Phosphorylierung von Titin an Serin 4080 in die Relaxationsf{\"a}higkeit der Kardiomyozyten und somit die diastolische Funktion des linken Ventrikels verbesserte. Aufgrund dieser Beobachtungen wurde in Studie 2 untersucht, ob auch endogenes CNP als parakrines Hormon im Herzen eine TAC-induzierte Herzhypertrophie und die kontraktile Funktion von Kardiomyozyten bei einer hypertensiven Herzerkrankung beeinflussen kann. Daf{\"u}r wurde ein neues genetisches Mausmodell mit einer Kardiomyozyten-spezifischen Deletion des GC-B Rezeptors generiert (CM GC-B KO). Da vorangegangene Studien in unserer Arbeitsgruppe zeigten, dass die basale CNP-Expression im Herzen sehr gering ist, nach 3-t{\"a}giger TAC aber akut ansteigt und nach 14-t{\"a}giger TAC wieder abf{\"a}llt, haben wir CM GC-B KO M{\"a}use und deren Geschwister-Kontrolltiere an beiden Zeitpunkten nach TAC untersucht. Die TAC f{\"u}hrte Genotyp-unabh{\"a}ngig zu einem Anstieg der kardialen Nachlast nach 3 Tagen und weiter nach 14 Tagen. Diese Druckbelastung provozierte eine progressive, signifikante Linksherzhypertrophie. Allerdings reagierten die CM GC-B KO M{\"a}use im Vergleich zu den Kontrolltieren bereits nach 3-t{\"a}giger TAC mit einer ausgepr{\"a}gten Kardiomyozyten-Hypertrophie. Zudem beobachteten wir nach 3-t{\"a}giger TAC in den Knockout-M{\"a}usen eine Abnahme der Ejektionsfraktion und gleichzeitig eine signifikante Zunahme der beiden linksventrikul{\"a}ren Volumina (end-diastolische und end-systolische Volumen). Diese fr{\"u}he linksventrikul{\"a}re Dilatation wurde in den Kontrolltieren nicht beobachtet. Daraus schlussfolgerten wir, dass endogenes kardiales CNP, dessen Expression zu fr{\"u}hen Zeitpunkten nach Druckbelastung ansteigt, das Herz vor kontraktiler Dysfunktion und Dilatation sch{\"u}tzen kann. Um m{\"o}gliche Mechanismen f{\"u}r die protektive Wirkung von endogenem CNP zu erkl{\"a}ren, untersuchten wir die IL-6 mRNA Expression sowie die Titin-Phosphorylierung im Herzen. Der akute Anstieg der IL-6 mRNA Expression nach 3-t{\"a}giger TAC in den CM GC-B KO M{\"a}usen korreliert mit der verminderten Phosphorylierung von Titin an der PGK-spezifischen Phosphorylierungsstelle (Serin 4080). Somit k{\"o}nnte der CNP/GC-B/cGMP-Signalweg zu einer Inhibition pro-inflammatorischer Gene beitragen, da der akute IL-6 mRNA Anstieg in den Kontrollen nicht beobachtet wurde. Auch die gesteigerte NOX4 Expression 3 Tage nach TAC, k{\"o}nnte zu der fr{\"u}hen dilatativen Kardiomyopathie in den Knockout-M{\"a}usen beigetragen haben. Die verringerte STAT3 Aktivierung in den CM GC-B KO M{\"a}usen w{\"u}rde laut Literatur zu vermehrter Apoptose f{\"u}hren, indem pro-apoptotische Gene wie Bcl oder Bax vermehrt transkribiert werden. Auch die erh{\"o}hte Cxcl-1 mRNA Expression in den Knockout-M{\"a}usen deutet zusammen mit dem IL-6 Anstieg auf vermehrte Entz{\"u}ndungsreaktionen 3 Tage nach TAC hin. Zusammengenommen deuten die Ergebnisse dieser Dissertationsarbeit darauf hin, dass der CNP/GC-B/cGMP-Signalweg in fr{\"u}hen Stadien einer erh{\"o}hten kardialen Druckbelastung und der Entstehung einer dilatativen Kardiomyopathie entgegenwirken kann. Die Phosphorylierung des sarkomerischen Proteins Titin und die Hemmung der Expression pro-inflammatorischer Zytokine (speziell IL-6) k{\"o}nnten zu diesem protektiven Effekt beitragen.},
  subject      = {Herzinsuffizienz},
  language  = {de}
}
@phdthesis{Goetz2020,
  author    = {G{\"o}tz, Ralph},
  title     = {Super-resolution microscopy of plasma membrane receptors and intracellular pathogens},
  doi       = {10.25972/OPUS-20716},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-207165},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2020},
  abstract  = {Humans tend to believe in what they can see with their own eyes. Hence, visualization methods like microscopy have always been extremely popular since their invention in the 17th century. With the advent of super-resolution microscopy, the diffraction limit of ~200 - 250 nm could be overcome to enable more detailed insights into biological samples. Especially the single molecule localization microscopy method dSTORM offers the possibility of quantitative bioimaging. Hereby, the repetitive photoswitching of organic dyes in the presence of thiols is exploited to enable a lateral resolution of 20 nm. Another, recently introduced super-resolution method is expansion microscopy (ExM) which physically expands the sample to increase the resolution by the expansion factor from four to even twenty. To enable this, the sample is embedded into a hydrogel, homogenized using an unspecific proteinase and expanded in distilled water. Within this thesis, both methods were used to shed light on plasma membrane receptor distributions and different bacterial and fungal pathogens. In the first part of this thesis dSTORM was used to elucidate the "Receptome", the entirety of all membrane receptors, of the cell line Jurkat T-cells and primary T-cells. Within this project we could successfully visualize and quantify the distribution of the plasma membrane receptors CD2, CD3, CD4, CD5, CD7, CD11a, CD20, CD28, CD45, CD69 and CD105 with receptor densities ranging from 0.8 cluster/µm² in case of CD20 and 81.4 cluster/µm² for the highly abundant CD45 in activated primary T-cells at the basal membrane. Hereby, we could also demonstrate a homogeneous distribution of most receptors, while only few were clustered. In the case of CD3-clusters were detected in Jurkat T-cells and in primary activated T-cells, but not in na{\"i}ve ones, demonstrating the activation of this receptor. This was followed by the application of dSTORM to three different clinical projects involving the receptors CD38, BCMA and CD20 which are immunotherapeutic targets by monoclonal antibodies and CAR T-cells. In the first two projects dSTORM was applied to determine the receptor upregulation upon exposure of various drugs to MM1.S cells or primary multiple myeloma patient cells. This increase in membrane receptor expression can subsequently enhance the efficacy of therapies directed against these receptors. Within the CD20-project, the superior sensitivity of dSTORM compared to flow cytometry could be demonstrated. Hereby, a substantially higher fraction of CD20-positive patient cells was detected by dSTORM than by flow cytometry. In addition, we could show that by dSTORM CD20-positive evaluated cells were eradicated by immunotherapeutic CAR T-cell treatment. These studies were followed by whole cell super-resolution imaging using both LLS-3D dSTORM and 10x ExM to exclude any artifacts caused by interactions with the glass surface. In 10x ExM signal amplification via biotinylated primary antibodies and streptavidin ATTO 643 was essential to detect even single antibodies directed against the heterodimer CD11a with standard confocal microscopes. Albeit probably not quantitative due to the process of gelation, digestion and expansion during the ExM protocol, even some putative dimers of the receptor CD2 could be visualized using 10x ExM-SIM, similar to dSTORM experiments. Within the second part of this thesis, expansion microscopy was established in bacterial and fungal pathogens. ExM enabled not only an isotropic fourfold expansion of Chlamydia trachomatis, but also allowed the discrimination between the two developmental forms by the chlamydial size after expansion into reticulate and elementary bodies. Hereafter, a new α-NH2-ω-N3-C6-ceramide was introduced enabling an efficient fixation and for the first time the use of lipids in both, 4x and 10x ExM, termed sphingolipid ExM. This compound was used to investigate the ceramide uptake and incorporation into the cell membrane of Chlamydia trachomatis and Simkania negevensis. For Chlamydia trachomatis the combined resolution power of 10x ExM and SIM even allowed the visualization of both bacterial membranes within a distance of ~30 nm. Finally, ExM was applied to the three different fungi Ustilago maydis, Fusarium oxysporum and Aspergillus fumigatus after enzymatic removal of the fungal cell wall. In case of Ustilago maydis sporidia this digestion could be applied to both, living cells resulting in protoplasts and to fixed cells, preserving the fungal morphology. This new protocol could be demonstrated for immunostainings and fluorescent proteins of the three different fungi.},
  subject      = {Mikroskopie},
  language  = {en}
}
@phdthesis{Waeldchen2020,
  author    = {W{\"a}ldchen, Sina},
  title     = {Super-Resolution-Mikroskopie zur Visualisierung und Quantifizierung von Glutamatrezeptoren und ADHS-assoziierten Proteinen},
  doi       = {10.25972/OPUS-19283},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-192834},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2020},
  abstract  = {Die Entwicklung hochaufl{\"o}sender Fluoreszenzmikroskopiemethoden hat die Lichtmikroskopie revolutioniert. Einerseits erm{\"o}glicht die h{\"o}here erzielte r{\"a}umliche Aufl{\"o}sung die Abbildung von Strukturen, die deutlich unterhalb der beugungsbedingten Aufl{\"o}sungsgrenze liegen. Andererseits erh{\"a}lt man durch Einzelmolek{\"u}llokalisationsmikroskopiemethoden wie dSTORM (Direct Stochastic Optical Reconstruction Microscopy) Informationen, welche man f{\"u}r quantitative Analysen heranziehen kann. Aufgrund der sich dadurch bietenden neuen M{\"o}glichkeiten, hat sich die hochaufl{\"o}sende Fluoreszenzmikroskopie rasant entwickelt und kommt mittlerweile zur Untersuchung einer Vielzahl biologischer und medizinischer Fragestellungen zum Einsatz. Trotz dieses Erfolgs ist jedoch nicht zu verleugnen, dass auch diese neuen Methoden ihre Nachteile haben. Dazu z{\"a}hlt die Notwendigkeit relativ hoher Laserleistungen, welche Voraussetzung f{\"u}r hohe Aufl{\"o}sung ist und bei lebenden Proben zur Photosch{\"a}digung f{\"u}hren kann. Diese Arbeit widmet sich sowohl dem Thema der Photosch{\"a}digung durch Einzelmolek{\"u}llokalisationsmikroskopie, als auch der Anwendung von dSTORM und SIM (Structured Illumination Microscopy) zur Untersuchung neurobiologischer Fragestellungen auf Proteinebene. Zur Ermittlung der Photosch{\"a}digung wurden lebende Zellen unter typischen Bedingungen bestrahlt und anschließend f{\"u}r 20-24 h beobachtet. Als quantitatives Maß f{\"u}r den Grad der Photosch{\"a}digung wurde der Anteil sterbender Zellen bestimmt. Neben der zu erwartenden Intensit{\"a}ts- und Wellenl{\"a}ngenabh{\"a}ngigkeit, zeigte sich, dass die Schwere der Photosch{\"a}digung auch von vielen weiteren Faktoren abh{\"a}ngt und dass sich Einzelmolek{\"u}llokalisationsmikroskopie bei Ber{\"u}cksichtigung der gewonnenen Erkenntnisse durchaus mit Lebendzellexperimenten vereinbaren l{\"a}sst. Ein weiteres Projekt diente der Untersuchung der A- und B-Typ-Glutamatrezeptoren an der neuromuskul{\"a}ren Synapse von Drosophila melanogaster mittels dSTORM. Dabei konnte eine ver{\"a}nderte Anordnung beider Rezeptortypen infolge synaptischer Plastizit{\"a}t beobachtet, sowie eine absolute Quantifizierung des A-Typ-Rezeptors durchgef{\"u}hrt werden. Im Mittelpunkt eines dritten Projekts standen Cadherin-13 (CDH13) sowie der Glucosetransporter Typ 3 (GluT3), welche beide mit der Aufmerksamkeitsdefizit-Hyperaktivit{\"a}tsst{\"o}rung in Verbindung gebracht werden. CDH13 konnte mittels SIM in serotonergen Neuronen, sowie radi{\"a}ren Gliazellen der dorsalen Raphekerne des embryonalen Mausgehirns nachgewiesen werden. Die Rolle von GluT3 wurde in aus induzierten pluripotenten Stammzellen differenzierten Neuronen analysiert, welche verschiedene Kopienzahlvariation des f{\"u}r GluT3-codierenden SLC2A3-Gens aufwiesen. Die Proteine GluT3, Bassoon und Homer wurden mittels dSTORM relativ quantifiziert. W{\"a}hrend die Deletion des Gens zu einer erwartenden Verminderung von GluT3 auf Proteinebene f{\"u}hrte, hatte die Duplikation keinen Effekt auf die GluT3-Menge. F{\"u}r Bassoon und Homer zeigte sich weder durch die Deletion noch die Duplikation eine signifikante Ver{\"a}nderung.},
  subject      = {Mikroskopie},
  language  = {de}
}
@phdthesis{Hofrichter2020,
  author    = {Hofrichter, Michaela Angelika Hedwig},
  title     = {Charakterisierung von angeborenen H{\"o}rst{\"o}rungen mit Hilfe von Hochdurchsatz-Sequenziermethoden},
  doi       = {10.25972/OPUS-18533},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-185331},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2020},
  abstract  = {Fast 500 Millionen Menschen weltweit sind von einer H{\"o}rst{\"o}rung betroffen. Es wird sogar angenommen, dass diese Anzahl laut der Weltgesundheitsorganisation (WHO) noch steigen und 2050 jeder zehnte Mensch eine H{\"o}rst{\"o}rung aufweisen wird. Mindestens in 50\% aller F{\"a}lle ist die H{\"o}rst{\"o}rung genetisch bedingt. Durch die j{\"u}ngsten Fortschritte der Sequenzierungstechnologien hat die genetische Analyse von H{\"o}rst{\"o}rungen an Bedeutung gewonnen, vor allem hinsichtlich Familienplanung, geeigneter Therapien und zuk{\"u}nftiger m{\"o}glichen Therapieans{\"a}tzen, um das H{\"o}rverm{\"o}gen wiederherzustellen. Die folgende Arbeit stellt 155 famili{\"a}re F{\"a}lle vor, die genetisch untersucht wurden. Diese F{\"a}lle konnten in zwei Kohorten unterteilt werden. Eine Kohorte (n = 74) umfasste Patienten mit kaukasischem Hintergrund, w{\"a}hrend die andere Kohorte (n = 81) Patienten beinhaltete, die aus dem Iran rekrutiert wurden. F{\"u}r die Untersuchung wurde zum einen eine Panel-Analyse mit dem TruSight One Panel (Illumina, San Diego, USA) und zum anderen eine Exom-Sequenzierung durchgef{\"u}hrt. Anschließend wurden die Daten mit Analyse-Programmen wie GensearchNGS (PhenoSystems, Wallonia, Belgien) ausgewertet. Insgesamt konnte f{\"u}r 55\% aller F{\"a}lle eine pathogene oder wahrscheinlich pathogene Variante durch Next Generation Sequencing diagnostiziert werden. Die meisten der gel{\"o}sten F{\"a}lle (ca. 73\%) stammten aus der iranischen Kohorte, was durch elterliche Blutsverwandtschaft und erh{\"o}hte Inzidenz von H{\"o}rst{\"o}rungen im Iran zu erkl{\"a}ren ist. 27\% der gel{\"o}sten F{\"a}lle geh{\"o}rten der zweiten Kohorte an. Mutationen in den Genen MYO15A, LHFPL5, TECTA und SLC26A4 konnten {\"u}berwiegend bei iranischen Patienten identifiziert werden. Varianten im Gen TECTA als auch im Gen SLC26A4 wurden ebenfalls in der kaukasischen Kohorte identifiziert. Beide Ethnien wiesen jeweils ein eigenes Mutationsspektrum auf. Jedoch wurden in beiden Gruppen {\"U}berschneidungen im klinischen Bild durch pathogene Varianten in einer Vielzahl von H{\"o}rst{\"o}rungsgenen, sowie unterschiedliche klinische Ph{\"a}notypen, deren Ursache pathogene Varianten im gleichen H{\"o}rst{\"o}rungsgen zugrunde liegen, und famili{\"a}re Locus-Heterogenit{\"a}t beobachtet.. In dieser Arbeit konnte eine De Novo Mutation im CEACAM16-Gen (DFNA4B) best{\"a}tigt und der Effekt von einer wiederholt betroffenen Aminos{\"a}ure im S1PR2-Gen (DFNB68) beschrieben werden. Dar{\"u}ber hinaus wurden mehrere Patienten mit X-chromosomalem H{\"o}rverlust aufgrund von Defekten im POU3F4-Gen (DFNX2) und Deletionen im SMPX-Gen (DFNX4) diagnostiziert. Zus{\"a}tzlich konnte mit Hilfe einer Exom-basierten Copy Number Variation-Analyse eine Deletion im OTOA-Gen (DFNB22) gefunden werden, welche sich bis in die Tandempseudogenregion erstreckte. Diese Untersuchung zeigt die enormen M{\"o}glichkeiten zur Detektion von Mutationen bei heterogenen Erkrankungen durch Anwendung von Next Generation Sequencing. Weiterhin konnte eine intragenische Deletion im Gen COL9A1 identifiziert werden, die im Zusammenhang mit einer scheinbar isolierten H{\"o}rst{\"o}rung steht und durch den komplexen Umlagerungsmechanismus FoSTeS/MMBIR (Fork Stalling und Template Switching/Microhomology-mediated Break-induced Replication) entstand, der so bei H{\"o}rst{\"o}rungen noch nicht beschrieben wurde. Auf der Suche nach Genen, die bisher noch nicht mit H{\"o}rst{\"o}rungen assoziiert werden konnten, wurden acht Familien in eine Kandidatengenuntersuchung miteinbezogen und eine Exom-weite Analyse durchgef{\"u}hrt. Bei f{\"u}nf Familien konnte noch keine urs{\"a}chliche Variante identifiziert werden. Jedoch wurde bei drei Familien mit einer autosomal dominanten Schwerh{\"o}rigkeit eine genetische Ursache identifiziert und TECTB, ATP11A und THBS2 konnten als Kandidatengene ermittelt werden. Diese Arbeit zeigt, wie wichtig es ist, die kausale Variante bei H{\"o}rst{\"o}rungspatienten zu detektieren. Eine genetische Diagnostik erm{\"o}glicht eine endg{\"u}ltige Diagnose eines Syndroms, ist f{\"u}r die Klassifizierung der H{\"o}rst{\"o}rung notwendig und tr{\"a}gt zu einer zuk{\"u}nftigen Therapie der Patienten bei.},
  subject      = {H{\"o}rst{\"o}rungen},
  language  = {de}
}
@phdthesis{CastilloCajas2020,
  author    = {Castillo Cajas, Ruth},
  title     = {Evolution and diversity of cuticular hydrocarbon profiles of cuckoo wasps},
  doi       = {10.25972/OPUS-17341},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-173418},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2020},
  abstract  = {Cuticular hydrocarbons (CHC) abound on the surface of arthropods. In spite of their simple structure (molecules of carbon and hydrogen atoms), they provide pivotal functions in insects: their hydrophobic properties confer the insects a means to regulate water balance and avoid desiccation, whereas their diversity has enhanced their use as signals and cues in a wide range of communication and recognition processes. Although the study of CHC in insects over the past two decades has provided great insight into the wide range of functions they play, there is still a gap in understanding how they diversify and evolve. In this thesis, I have used members of the family Chrysididae to explore patterns of diversification of CHC. Most of the species of cuckoo wasps in this study are specialized parasitoids or kleptoparasites of mainly solitary hymenopteran hosts. Other hosts of the family include butterflies or stick insects. Cuckoo wasps are a particular interesting model to study the evolution of cuticular hydrocarbons because of their chemical adaptations that allow them to remain unrecognized by their hosts. Chemical insignificance (the reduction of the total amount of CHC on the cuticle) and chemical mimicry (the de novo production of CHC profiles resembling those of their female host) have been described in some representatives of the family and unpublished evidence suggests chemical deception is widespread in Chrysididae (Chapter 2). Nonetheless, to trace the evolution of any trait of interest, a reliable phylogenetic reconstruction of the family is required. Therefore, the first study of this thesis constitutes the largest and to-date most reliable phylogenetic reconstruction of the family Chrysididae, which includes representatives of 186 species of cuckoo wasps. While the results of this phylogenetic reconstruction are consistent with previous ideas on the relationships of subfamilies and tribes, it shows the existence of several non-monophyletic genera (Chapter 3). CHC are involved in intraspecific recognition, often acting as contact sex pheromones. Nevertheless, it is not yet understood to what extent CHC profiles differ between the two sexes and whether some compound classes are more prevalent in one or the other sex. So far, no comparison of CHC profiles of males and females has been done for more than a dozen of related species. In Chapter 4, I describe and compare CHC profiles of females and males of 58 species of cuckoo wasps in order to evaluate whether and to what extent CHC profiles of these species differ between the sexes. I demonstrated that CHC profiles of cuckoo wasps are frequently (more than 90\% of the species analyzed) and strongly dimorphic (both sexes of a given species tend to produce very different CHC compounds). Methyl-branched compounds tend to be more prevalent in males (especially dimethyl-branched compounds) and unsaturated compounds prevail in females. Moreover, a sex-specific pattern in the distribution of the double bond position of alkenes was evident: internal double bond positions (> 11) occur predominantly in males, whereas alkenes with the doubl{\´e} bond at position 9 were more abundant and frequent in females (Chapter4). In Chapter5, I investigated how CHC profiles of cuckoo wasps differ across species. Are CHC profiles of cuckoo wasps species-specific, enabling their use as cues for species recognition? How do CHC profiles resemble phylogenetic relatedness? In Chapter 5, I try to answer these questions by comparing CHC profiles of 59 species of cuckoo wasps. CHC profiles of cuckoo wasps are shown to be species (and sex-) specific. I show that CHC profiles are useful as a complementary tool to help delimiting taxonomically difficult sibling species. Moreover, the evaluation of CHC profiles of five commonly occurring species within a genus, showed little or no geographical variation. However, CHC profiles of closely related species may differ strongly among each other, not being useful to track the evolutionary history of species (Chapter 5). Sexual selection is generally credited for generating striking sexual dimorphism by causing changes in male traits. Most often, sexual selection has a stronger effect on males, who compete for access to and may be selected by females, thus male traits may rapidly evolve. Nevertheless, in cuckoo wasps, it appears that it is the female sex the one evolving faster changes, with females of very closely related species showing extremely divergent profiles. One plausible reason for this disparity is that natural selection acting on female's CHC profiles may be stronger than sexual selection on males (Chapter 6). Since females of cuckoo wasps are most probably engaged in an evolutionary arms race with their female hosts, CHC profiles of female cuckoo wasps are likely rapidly evolving, thus explaining part of the strong observed sexual dimorphism of CHC (Chapter 6). In fact, Chapter 7 shows evidence of a possible ongoing evolutionary arms race between five cuckoo wasps of the genus Hedychrum and their hosts. Hedychrum species parasitize either Coleoptera-hunting or Hymenoptera-hunting digger wasps. Since the coleopteran prey of the former digger wasps is naturally better protected against fungus infestation, these wasps do not embalm their prey with alkene-enriched secretions as do the Hymenoptera-hunting digger wasps. Thus, Coleoptera-hunting digger wasps can apparently diversify their profiles to escape chemical mimicry. Interestingly, only female cuckoo wasps of these hosts have started producing the same compound classes and even the same CHC compounds as those of their hosts. Male cuckoo wasps, however retain an alkene-enriched CHC profile that reflects the molecular phylogeny of the genus (Chapter 7). Whereas, a larger number of parasite-host comparisons may be needed to further conclude that an arms race between cuckoo wasps and their hosts is capable of generating sexual dimorphism of cuckoo wasps, this thesis constitutes the first effort towards this, providing a starting point for further studies. Finally, I provide some methodological tools that may help in speeding up the sometimes cumbersome process of analyzing and identifying CHC profiles. One of the most time-demanding steps in the processing of CHC data is the alignment of CHC chromatograms. This process is often done manually, because alignment programs are mostly designed for metabolomics or are just recently being developed. I analyzed CHC profiles using a combined approach with two freely available programs. I used AMDIS (Automated Mass Spectral Deconvolution and Identification System, http://chemdata.nist.gov/mass-spc/amdis/) to deconvolute and automatically identify all CHC of interest present in a chromatogram. I then developed a series of R scripts to correct for potential, unavoidable errors while processing CHC chromatograms with AMDIS. Chapter 8 explains this procedure. In the next chapter, I developed a program that helps in the identification of one commonly occurring class of hydrocarbons. The limited number of linear alkanes (only one per carbon atom) and their characteristic diagnostic ion allows a rapid and unambigous identification of these substances. In opposition, unsaturated and methyl-branched compounds are more difficult to identify, as a result of the much larger diversity of existing compounds. To identify unsaturated compounds a derivatization is necessary to determine the position of the double bond. Methyl-branched alkanes, however can be identified from the original chromatogram if their diagnostic ions are known. Nonetheless, polymethyl-branched alkanes (e.g., compounds with two or more methyl groups along the chain) are often difficult to identify, because they may appear in mixes (e.g., 3,7 diMeC27 and 3,9 diMeC27), and tables containing the diagnostic ions are not easily available. Therefore, I developed a program that creates a table with all possiblemethyl-branched compounds containing up to 4 methyl groups, and that provides their diagnostic ions and a calculated retention index. This may allow a much faster identification of the methyl-branched compound a researcher is dealing with, without having to lose time in the tedious calculations by hand. The program is able to correctly identify, or at least, greatly reduce the number of possible options for the identification of an unknown methyl-branched compound. Thus, using this tool, most methyl-branched compounds can be readily identified (Chapter 9). This thesis ends with a general discussion (Chapter 10). Overall, this work provides a comprehensive overview of the diversity of cuticular hydrocarbons of cuckoo wasps. The analyses presented here shed light on the emergence and evolution of interspecific diversity and intraspecific sexual dimorphism of CHC profiles. In addition, two technical methods have been developed that could greatly facilitate the CHC analysis of insects.},
  language  = {en}
}
@phdthesis{Tulke2020,
  author    = {Tulke, Moritz},
  title     = {Grundlegende Arbeiten zum bio-artifiziellen renalen Tubulus aus ko-kultivierten adipozyt{\"a}ren mesenchymalen Stammzellen und Endothelzellen auf einer synthetischen Kapillarmembran},
  doi       = {10.25972/OPUS-21689},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-216896},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2020},
  abstract  = {Mit fortschreitender chronischer Niereninsuffizienz kommt es zur Akkumulation von Ur{\"a}mietoxinen und im Endstadium unbehandelt zum Tod im sogenannten Ur{\"a}mischen Syndrom. Die Blutreinigung erfolgt bei der am h{\"a}ufigsten verwendeten Form der Nierenersatztherapie, der H{\"a}modialyse, nur unzureichend. Die Folge ist eine erh{\"o}hte Morbidit{\"a}t und Mortalit{\"a}t der betroffenen Patienten. Bei der H{\"a}modialyse werden nur Ur{\"a}mietoxine bis zu einer Gr{\"o}ße von 20 kDa {\"u}ber die im Dialysator eingesetzten Hohlfaserdialysemembranen diffusiv und konvektiv semiselektiv nach Gr{\"o}ßenausschluss entfernt. Proteingebundene Ur{\"a}mietoxine, deren effektive Gr{\"o}ße durch die Bindung an Transportproteine wie beispielsweise Albumin die Trennsch{\"a}rfe der Dialysemembranen {\"u}bersteigt, werden retiniert. In-vivo werden proteingebundene Ur{\"a}mietoxine im proximalen Tubulus, einem Teil des tubul{\"a}ren Systems des Nephrons, sekretorisch eliminiert. Im Rahmen der vorliegenden Promotionsarbeit wurden die ersten Entwicklungsschritte auf dem Weg zu einem sogenannten bio-artifiziellen Tubulus evaluiert. Der angedachte biohybride Filter sollte aus einer Ko-Kultur funktionaler humaner proximaler Tubuluszellen und humaner Endothelzellen (HUVEC) auf synthetischen Hohlfasermembranen bestehen und k{\"o}nnte w{\"a}hrend der H{\"a}modialyse als zus{\"a}tzlicher Reinigungsschritt angewendet werden, um unter anderem proteingebundene Ur{\"a}mietoxine effektiv durch aktiven Transport aus dem Blut der Patienten zu entfernen. Die Differenzierung der proximalen Tubuluszellen erfolgte dabei aus adulten adipozyt{\"a}ren mesenchymalen Stammzellen (ASC), deren Herkunft eine sp{\"a}tere autologe Behandlung erm{\"o}glicht. Die Ko-Kultur mit Endothelzellen wurde zur potentiellen Steigerung der Sekretion proteingebundener Ur{\"a}mietoxine verwendet. In der vorliegenden Arbeit konnten ASCs durch eine Kombination der l{\"o}slichen Differenzierungsfaktoren All-Trans-Retinoins{\"a}ure (ATRA), Aktivin A und BMP-7 erfolgreich in Zytokeratin 18-exprimierende Zellen differenziert werden, wodurch die erw{\"u}nschte epitheliale Differenzierung best{\"a}tigt wurde. Die Expression funktionaler Proteine, wie das f{\"u}r den Wassertransport relevante Aquaporin 1 oder auch der Na+-/K+-ATPase, konnte in dieser Arbeit bereits vor der Differenzierung nachgewiesen werden. Im n{\"a}chsten Schritt wurde erfolgreich gezeigt, dass eine simultane, qualitativ hochwertige Ko-Kultur von ASCs und HUVECs auf der mit dem extrazellul{\"a}ren Matrixprotein Fibronektin modifizierten Innen- bzw. Außenseite von synthetischen Hohlfasermembranen aus Polypropylen bzw. Polyethersulfon m{\"o}glich ist. Die Viabilit{\"a}t beider Zelltypen wurde dabei durch die Verwendung eines f{\"u}r die Ko-Kultur entwickelten N{\"a}hrmediums erreicht, in welchem die Proliferation von ASCs bei gleichzeitiger Aufrechterhaltung ihrer Stammzelleigenschaften deutlich erh{\"o}ht war. Die in dieser Arbeit erzielten Ergebnisse stellen eine aussichtsreiche Basis f{\"u}r einen bio-artifiziellen renalen Tubulus dar. Weitere Entwicklungsschritte, wie die Differenzierung der ASCs zu proximalen Tubuluszellen im 3D-Bioreaktor einschließlich ihrer funktionalen Charakterisierung anhand Tubulusepithel-spezifischer Transporter, sind erforderlich, be-vor erste funktionale Experimente vor dem „Upscaling" auf klinisch verwendbare Module m{\"o}glich sind.},
  subject      = {Hohlfaserreaktor},
  language  = {de}
}
@phdthesis{Pfann2020,
  author    = {Pfann, Christina},
  title     = {Untersuchungen zu neuen therapeutischen Ans{\"a}tzen zur Beeinflussung der MYC-Expression im kolorektalen Karzinom},
  doi       = {10.25972/OPUS-21668},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-216687},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2020},
  abstract  = {Eine ver{\"a}nderte Expression des Transkriptionsfaktors MYC wird als entscheidender Faktor f{\"u}r Tumorentstehung und -progress im kolorektalen Karzinom gesehen. Somit ist die Hemmung dessen Expression und Funktion ein zentraler Ansatz bei der zielgerichteten Tumortherapie. Als geeignete Strategie, sowohl die Halbwertszeit als auch die Translation von MYC zu verringern, erschien eine duale PI3K-/mTOR-Hemmung durch den small molecule-Inhibitor BEZ235. Gegenteilig ist jedoch unter Behandlung mit BEZ235 eine verst{\"a}rkte MYC-Expression in verschiedenen Kolonkarzinom-Zelllinien zu beobachten. Neben verst{\"a}rkter Transkription, konnte eine verst{\"a}rkte IRES-abh{\"a}ngige Translation von MYC nach Hemmung der mTOR-/5´Cap-abh{\"a}ngigen Translation durch BEZ235, als Ursache der MYC-Induktion nachgewiesen werden. Es konnte gezeigt werden, dass die Induktion von MYC nach PI3K-/mTOR-Hemmung durch eine kompensatorische Aktivierung des MAPK-Signalwegs in Folge einer FOXO-abh{\"a}ngigen Induktion von Rezeptortyrosinkinasen, stattfindet. Eine m{\"o}gliche Strategie, diese Feedback-Mechanismen zu umgehen, ist die direkte Hemmung der Translationsinitiation. Hierf{\"u}r wurden Rocaglamid und dessen Derivat Silvestrol als small molecule-Inhibitoren der eIF4A-Helikase verwendet. Im Gegensatz zur PI3K/mTOR-Hemmung, ist durch eIF4A-Inhibition eine Reduktion der MYC-Proteinexpression in verschiedenen Kolonkarzinom-Zelllinien zu erreichen - ohne einhergehende MAPK-Aktivierung. Anhand der Ergebnisse kann postuliert werden, dass Silvestrol das Potential besitzt, sowohl die Cap-/eIF4F-abh{\"a}ngie als auch die somit eIF4A-abh{\"a}ngige IRES-vermittelte Translation von MYC zu hemmen. Weiterhin kann eine proliferationshemmende Wirkung durch Silvestrol auf Kolonkarzinom-Zellen in vitro, via Zellzyklusarrest und Induktion von Apoptose, gezeigt werden. Dies stellt die Voraussetzung f{\"u}r eine potentielle Eignung als tumorhemmender Wirkstoff in der Therapie des kolorektalen Karzinoms dar.},
  language  = {de}
}
@phdthesis{Fuss2020,
  author    = {Fuß, Antje},
  title     = {Evaluierung des Nachweises von Schistosoma mansoni DNA mittels Real-Time PCR in verschiedenen humanen Proben sowie den Zwischenwirtschnecken in einer Hochpr{\"a}valenzregion am Viktoriasee in Tansania},
  doi       = {10.25972/OPUS-21506},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-215061},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2020},
  abstract  = {Die Schistosomiasis ist nach wie vor eine der h{\"a}ufigsten parasit{\"a}ren Erkrankungen der Welt und verursacht erhebliche gesundheitliche und wirtschaftliche Folgen, insbesondere in {\"a}rmeren, l{\"a}ndlichen Regionen. Durch Immunreaktionen auf die im Wirt abgelegten Eier des Parasiten k{\"o}nnen sich chronische Verlaufsformen manifestieren. Dabei kann es zu irreversiblen Sch{\"a}den kommen. Um dies zu verhindern sind eine fr{\"u}he und sichere Diagnose sowie eine Behandlung mit Praziquantel (PZQ) unabdingbar. Zudem spielt der zuverl{\"a}ssige Nachweis der Schistosomiasis eine Schl{\"u}sselrolle bei der {\"U}berwachung, Pr{\"a}vention und Kontrolle der Erkrankung. In epidemiologischen Studien findet am h{\"a}ufigsten die mikroskopische Kato-Katz (KK)-Methode zum Nachweis von Schistosoma mansoni Eiern im Stuhl Anwendung. Dieses Verfahren ist {\"a}ußerst spezifisch und bietet die M{\"o}glichkeit der Quantifizierung, wodurch die Intensit{\"a}t der vorliegenden Infektion bestimmt werden kann. Die Sensitivit{\"a}t der Testmethode ist jedoch nur moderat, insbesondere bei einer niedrigen Infektionsintensit{\"a}t. Zudem kann eine Infektion erst nach der Pr{\"a}patenzzeit nachgewiesen werden. Der ebenfalls h{\"a}ufig eingesetzte urinbasierte Point-of-Care Circulating Cathodic Antigen (POC-CCA)-Test weist zwar eine h{\"o}here Sensitivit{\"a}t aber geringere Spezifit{\"a}t als das KK-Verfahren auf. Als hochsensitive und sehr spezifische Methode zur Diagnose der Schistosomiasis hat sich der Nachweis von Schistosoma-spezifischer DNA mittels Real-Time PCR herausgestellt. Allerdings wird f{\"u}r die Durchf{\"u}hrung dieser Technik ein gut ausgestattetes Labor ben{\"o}tigt, das sich in der Regel nicht in unmittelbarer N{\"a}he zum Patienten im Feld befindet. Daher ist es besonders wichtig, {\"u}ber praktikable und schnelle Konservierungsmethoden zu verf{\"u}gen, die bevor die Extraktion und Amplifikation der DNA stattfindet, einen einfachen Transport und eine einfache Lagerung des Probenmaterials erm{\"o}glichen. Das Ziel des ersten Teils der vorliegenden Arbeit war, die Sensitivit{\"a}t und Spezifit{\"a}t der klassischerweise verwendeten KK-Methode und des POC-CCA-Tests mit der Real-Time PCR- Methode unter Verwendung von Stuhlproben, Urinproben, Serumproben sowie auf Filterpapier getrocknete Blutproben (dried blood spots - DBSs) zu vergleichen. Zudem wurde die Anwendbarkeit der Real-Time PCR aus Serum- und Urinproben zur Therapiekontrolle {\"u}berpr{\"u}ft. Die dazu notwendigen Studien wurden alle in der Region Mwanza in Tansania durchgef{\"u}hrt, welche als hochendemisch f{\"u}r S. mansoni gilt. F{\"u}r die Untersuchungen zur stuhlbasierten Real-Time PCR wurden als Studienteilnehmer Schulkinder gew{\"a}hlt. Aufgrund der erforderlichen Blutabnahme wurden die anderen Teilstudien nur mit erwachsenen Probanden durchgef{\"u}hrt. Unter Verwendung der KK-Methode als Goldstandard erzielten die Real-Time PCR aus Stuhlproben und der POC-CCA-Test sehr hohe Sensitivit{\"a}ten von 99,5\% bzw. 89,7\%, jedoch nur geringe Spezifit{\"a}ten von 29,55\% und 22,73\%. Die KK-Methode weist bekanntermaßen nur eine geringe bis moderate Sensitivit{\"a}t auf und ist daher nicht gut als Referenz geeignet. Deshalb wurde zus{\"a}tzlich eine latente Klassenanalyse angewandt, um die tats{\"a}chlich Erkrankten zu ermitteln und anhand dieser die diagnostische G{\"u}te der verwendeten Tests zu bestimmen. Hier zeigte der POC-CCA-Test die h{\"o}chste Sensitivit{\"a}t (99,5\%) sowie eine Spezifit{\"a}t von 63,4\%. Der Real-Time PCR-Test hatte eine Sensitivit{\"a}t von 98,7\% und die h{\"o}chste Spezifit{\"a}t (81,2\%). Die Spezifit{\"a}t der KK-Technik betrug 72,8\%, die Sensitivit{\"a}t war signifikant niedriger (89,7\%) als bei den anderen beiden Methoden. Diese Ergebnisse verdeutlichen, dass der POC-CCA-Schnelltest empfindlicher ist als die KK-Methode und zum Screening von S. mansoni-Infektionen eingesetzt werden kann. Die Stuhl-PCR war zwar ebenfalls hochsensitiv und zeigte unter den drei getesteten Diagnoseverfahren die h{\"o}chste Spezifit{\"a}t, aber aufgrund der h{\"o}heren Kosten und der komplizierten Anwendung sollte f{\"u}r epidemiologische Untersuchungen in Hochpr{\"a}valenzregionen der POC-CCA-Test bevorzugt werden. Bei unklaren Diagnosen kann die Real-Time PCR-Methode als Best{\"a}tigungstest Anwendung finden. In der Teilstudie zur serum- und urinbasierten Real-Time PCR in einer endemischen Region vor und nach der Behandlung mit PZQ wurden folgende Ergebnisse erzielt: Unter Verwendung einer kombinierten Referenz aus den Ergebnissen des parasitologischen KK-Tests und / oder der serumbasierten PCR konnte zu Studienbeginn eine Pr{\"a}valenz von S. mansoni von 77,1\% ermittelt werden. In Bezug auf die Sensitivit{\"a}t zeigte der DNA-Nachweis aus Serum (96,3\%) und der POC-CCA-Assay (77,8\%) die h{\"o}chsten Ergebnisse. Die urinbasierte Real-Time PCR zeigte die geringste Empfindlichkeit (33,3\%). Durch die Behandlung mit Praziquantel wurde eine signifikante Reduktion der S. mansoni Pr{\"a}valenz erreicht. Zwanzig Wochen nach Therapie konnte durch die KK-Methode keine, mit dem POC-CCA-Test 33,3\% und mit der serumbasierten Real-Time PCR 58,3\% Infektionen festgestellt werden. Die Analyse der mittels der serumbasierten PCR bestimmten mittleren Ct-Werte im zeitlichen Verlauf zeigte, dass dieser eine Woche nach der Behandlung signifikant abnahm (von 30,3 auf 28) und 20 Wochen sp{\"a}ter {\"u}ber den Basiswert (34,9) anstieg. Der Ct-Wert ist umgekehrt proportional zur DNA-Ausgangsmenge, die in die PCR eingesetzt wurde. Dies deutet darauf hin, dass kurz nach der Therapie ein DNA-Anstieg zu verzeichnen war und 20 Wochen sp{\"a}ter weniger DNA als zu Beginn der Studie nachweisbar war. Dieser DNA-Verlauf l{\"a}sst verschiedene Interpretationsm{\"o}glichkeiten zu. Die Daten zeigen jedoch, dass die serumbasierte Real-Time PCR eine ausgezeichnete diagnostische Genauigkeit aufweist. Da die nachgewiesene DNA jedoch keine R{\"u}ckschl{\"u}sse auf das Parasitenstadium zul{\"a}sst und es sich hierbei auch um DNA aus im Gewebe verbliebenen Eiern oder Reinfektionen handeln k{\"o}nnte, ist diese Methode in Hochpr{\"a}valenz- Regionen nicht zur Therapiekontrolle geeignet. Die Verwendung von Urin zum DNA-Nachweis erzielte keine vielversprechenden Ergebnisse. Die Sensitivit{\"a}t der Real-Time PCR aus DBSs war ebenfalls sehr gering (45,4\%) und kann ohne weitere ausf{\"u}hrliche Testung hinsichtlich Lagertemperatur, Lagerdauer, verschiedener Filterpapierarten und Extraktionsmethoden nicht empfohlen werden. Zusammenfassend zeigten die Ergebnisse dieser Studien, dass sowohl die stuhl- als auch die serumbasierte Real-Time PCR bei der Erkennung und Bewertung der Infektionspr{\"a}valenz, einem wichtigen Aspekt epidemiologischer Studien, deutlich empfindlicher ist als das mikroskopische KK-Verfahren. Aufgrund des hohen Kosten- und Personalaufwandes und der Notwendigkeit eines gut ausgestatteten Labors wird sich diese Methode aber nicht zum Screening in hochendemischen L{\"a}ndern durchsetzen. Sie kann jedoch einen Mehrwert bei der Diagnose der Schistosomiasis bieten, vor allem bei fr{\"u}hen oder leichten Infektionen. Zudem kann diese hochsensitive und spezifische Methode als Best{\"a}tigungstest bei unklaren Diagnosen herangezogen werden. Im zweiten Teil dieser Arbeit wurden malakologische Untersuchungen zur Identifizierung potenzieller {\"U}bertragungsorte f{\"u}r die Schistosomiasis rund um die im Viktoriasee gelegene Insel Ijinga durchgef{\"u}hrt. Diese Analysen fanden innerhalb eines Pilotprojektes zur Eliminierung der Erkrankung auf der Insel Ijinga statt, wobei ein intensiviertes Behandlungsprotokoll, welches die gesamte Inselbev{\"o}lkerung einschloss, Anwendung fand. Die Kontrolle der Praziquanteleffektivit{\"a}t nach mehreren Behandlungsrunden bringt eine Reihe diagnostischer Herausforderungen mit sich. Hier k{\"o}nnte die Beurteilung der Schistosoma-Infektion in den Zwischenwirtschnecken vor und nach der Therapie als Indikator f{\"u}r den Erfolg der Maßnahme dienen. Zu diesem Zweck erfolgte zun{\"a}chst eine Baseline-Untersuchung, bei der Schnecken an Uferregionen gesammelt wurden, an denen die Inselbewohner h{\"a}ufigen Wasserkontakt hatten. Die Schnecken wurden anhand morphologischer Merkmale identifiziert und mithilfe der Real-Time PCR-Methode auf Infektionen mit S. mansoni untersucht. Insgesamt wurden 35,4\% (279/788) S. mansoni- positive Zwischenwirtschnecken (Biomphalaria) detektiert. Dies verdeutlicht, dass an den meisten Wasserkontaktstellen um die Insel Ijinga ein potentielles Risiko f{\"u}r die {\"U}bertragung der Schistosomiasis besteht. Die mithilfe der KK-Methode ermittelte Gesamtpr{\"a}valenz von S. mansoni in der humanen Bev{\"o}lkerung betrug 68,9\%. Nachdem die Bewohner der Insel viermal mit PZQ behandelt wurden, zeigte sich in der kontinuierlich {\"u}berwachten Sentinelgruppe eine Reduktion der Pr{\"a}valenz auf 28,7\%. Zu diesem Zeitpunkt wurde ebenfalls die Analyse der Schnecken wiederholt und es konnten 16,8\% (57/350) Schnecken mit einer S. mansoni Infektion nachgewiesen werden. Die Reduktion der Infektionsh{\"a}ufigkeit in den Schnecken vor und nach der viermaligen Behandlung der Bev{\"o}lkerung war signifikant (χ² = 74.335, p < 0,001). Dies deutet darauf hin, dass die intermedi{\"a}ren Wirtsschnecken zur {\"U}berwachung von Kontrollmaßnahmen verwendet werden k{\"o}nnen.},
  subject      = {Schistosomiasis},
  language  = {de}
}
@article{SteinCoulibalyBalimaetal.2020,
  author    = {Stein, Katharina and Coulibaly, Drissa and Balima, Larba Hubert and Goetze, Dethardt and Linsenmair, Karl Eduard and Porembski, Stefan and Stenchly, Kathrin and Theodorou, Panagiotis},
  title     = {Plant-pollinator networks in savannas of Burkina Faso, West Africa},
  series = {Diversity},
  volume    = {13},
  journal   = {Diversity},
  number    = {1},
  issn      = {1424-2818},
  doi       = {10.3390/d13010001},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-220157},
  year      = {2020},
  abstract  = {West African savannas are severely threatened with intensified land use and increasing degradation. Bees are important for terrestrial biodiversity as they provide native plant species with pollination services. However, little information is available regarding their mutualistic interactions with woody plant species. In the first network study from sub-Saharan West Africa, we investigated the effects of land-use intensity and climatic seasonality on plant-bee communities and their interaction networks. In total, we recorded 5686 interactions between 53 flowering woody plant species and 100 bee species. Bee-species richness and the number of interactions were higher in the low compared to medium and high land-use intensity sites. Bee- and plant-species richness and the number of interactions were higher in the dry compared to the rainy season. Plant-bee visitation networks were not strongly affected by land-use intensity; however, climatic seasonality had a strong effect on network architecture. Null-model corrected connectance and nestedness were higher in the dry compared to the rainy season. In addition, network specialization and null-model corrected modularity were lower in the dry compared to the rainy season. Our results suggest that in our study region, seasonal effects on mutualistic network architecture are more pronounced compared to land-use change effects. Nonetheless, the decrease in bee-species richness and the number of plant-bee interactions with an increase in land-use intensity highlights the importance of savanna conservation for maintaining bee diversity and the concomitant provision of ecosystem services.},
  language  = {en}
}
@article{CavalettoFaccoliMarinietal.2020,
  author    = {Cavaletto, Giacomo and Faccoli, Massimo and Marini, Lorenzo and Spaethe, Johannes and Magnani, Gianluca and Rassati, Davide},
  title     = {Effect of trap color on captures of bark- and wood-boring beetles (Coleoptera; Buprestidae and Scolytinae) and associated predators},
  series = {Insects},
  volume    = {11},
  journal   = {Insects},
  number    = {11},
  issn      = {2075-4450},
  doi       = {10.3390/insects11110749},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-216325},
  year      = {2020},
  abstract  = {Traps baited with attractive lures are increasingly used at entry-points and surrounding natural areas to intercept exotic wood-boring beetles accidentally introduced via international trade. Several trapping variables can affect the efficacy of this activity, including trap color. In this study, we tested whether species richness and abundance of jewel beetles (Buprestidae), bark and ambrosia beetles (Scolytinae), and their common predators (i.e., checkered beetles, Cleridae) can be modified using trap colors different to those currently used for surveillance of jewel beetles and bark and ambrosia beetles (i.e., green or black). We show that green and black traps are generally efficient, but also that many flower-visiting or dark-metallic colored jewel beetles and certain bark beetles are more attracted by other colors. In addition, we show that checkered beetles have color preferences similar to those of their Scolytinae preys, which limits using trap color to minimize their inadvertent removal. Overall, this study confirmed that understanding the color perception mechanisms in wood-boring beetles can lead to important improvements in trapping techniques and thereby increase the efficacy of surveillance programs.},
  language  = {en}
}
@article{BoschertKlenkAbtetal.2020,
  author    = {Boschert, Verena and Klenk, Nicola and Abt, Alexander and Raman, Sudha Janaki and Fischer, Markus and Brands, Roman C. and Seher, Axel and Linz, Christian and M{\"u}ller-Richter, Urs D. A. and Bischler, Thorsten and Hartmann, Stefan},
  title     = {The influence of Met receptor level on HGF-induced glycolytic reprogramming in head and neck squamous cell carcinoma},
  series = {International Journal of Molecular Sciences},
  volume    = {21},
  journal   = {International Journal of Molecular Sciences},
  number    = {2},
  issn      = {1422-0067},
  doi       = {10.3390/ijms21020471},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-235995},
  year      = {2020},
  abstract  = {Head and neck squamous cell carcinoma (HNSCC) is known to overexpress a variety of receptor tyrosine kinases, such as the HGF receptor Met. Like other malignancies, HNSCC involves a mutual interaction between the tumor cells and surrounding tissues and cells. We hypothesized that activation of HGF/Met signaling in HNSCC influences glucose metabolism and therefore substantially changes the tumor microenvironment. To determine the effect of HGF, we submitted three established HNSCC cell lines to mRNA sequencing. Dynamic changes in glucose metabolism were measured in real time by an extracellular flux analyzer. As expected, the cell lines exhibited different levels of Met and responded differently to HGF stimulation. As confirmed by mRNA sequencing, the level of Met expression was associated with the number of upregulated HGF-dependent genes. Overall, Met stimulation by HGF leads to increased glycolysis, presumably mediated by higher expression of three key enzymes of glycolysis. These effects appear to be stronger in Met\(^{high}\)-expressing HNSCC cells. Collectively, our data support the hypothesized role of HGF/Met signaling in metabolic reprogramming of HNSCC.},
  language  = {en}
}
@article{KraussVikukYoungetal.2020,
  author    = {Krauss, Jochen and Vikuk, Veronika and Young, Carolyn A. and Krischke, Markus and Mueller, Martin J. and Baerenfaller, Katja},
  title     = {Epichlo{\"e} endophyte infection rates and alkaloid content in commercially available grass seed mixtures in Europe},
  series = {Microorganisms},
  volume    = {8},
  journal   = {Microorganisms},
  number    = {4},
  issn      = {2076-2607},
  doi       = {10.3390/microorganisms8040498},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-203323},
  pages     = {498},
  year      = {2020},
  abstract  = {Fungal endophytes of the genus Epichlo{\"e} live symbiotically in cool season grass species and can produce alkaloids toxic to insects and vertebrates, yet reports of intoxication of grazing animals have been rare in Europe in contrast to overseas. However, due to the beneficial resistance traits observed in Epichlo{\"e} infected grasses, the inclusion of Epichlo{\"e} in seed mixtures might become increasingly advantageous. Despite the toxicity of fungal alkaloids, European seed mixtures are rarely tested for Epichlo{\"e} infection and their infection status is unknown for consumers. In this study, we tested 24 commercially available seed mixtures for their infection rates with Epichlo{\"e} endophytes and measured the concentrations of the alkaloids ergovaline, lolitrem B, paxilline, and peramine. We detected Epichlo{\"e} infections in six seed mixtures, and four contained vertebrate and insect toxic alkaloids typical for Epichlo{\"e} festucae var. lolii infecting Lolium perenne. As Epichlo{\"e} infected seed mixtures can harm livestock, when infected grasses become dominant in the seeded grasslands, we recommend seed producers to test and communicate Epichlo{\"e} infection status or avoiding Epichlo{\"e} infected seed mixtures.},
  language  = {en}
}
@article{ThornChaoGeorgievetal.2020,
  author    = {Thorn, Simon and Chao, Anne and Georgiev, Konstadin B. and M{\"u}ller, J{\"o}rg and B{\"a}ssler, Claus and Campbell, John L. and Jorge, Castro and Chen, Yan-Han and Choi, Chang-Yong and Cobb, Tyler P. and Donato, Daniel C. and Durska, Ewa and Macdonald, Ellen and Feldhaar, Heike and Fontaine, Jospeh B. and Fornwalt, Paula J. and Hern{\´a}ndez Hern{\´a}ndez, Raquel Mar{\´i}a and Hutto, Richard L. and Koivula, Matti and Lee, Eun-Jae and Lindenmayer, David and Mikusinski, Grzegorz and Obrist, Martin K. and Perl{\´i}k, Michal and Rost, Josep and Waldron, Kaysandra and Wermelinger, Beat and Weiß, Ingmar and Zmihorski, Michal and Leverkus, Alexandro B.},
  title     = {Estimating retention benchmarks for salvage logging to protect biodiversity},
  series = {Nature Communications},
  volume    = {11},
  journal   = {Nature Communications},
  doi       = {10.1038/s41467-020-18612-4},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-230512},
  year      = {2020},
  abstract  = {Forests are increasingly affected by natural disturbances. Subsequent salvage logging, a widespread management practice conducted predominantly to recover economic capital, produces further disturbance and impacts biodiversity worldwide. Hence, naturally disturbed forests are among the most threatened habitats in the world, with consequences for their associated biodiversity. However, there are no evidence-based benchmarks for the proportion of area of naturally disturbed forests to be excluded from salvage logging to conserve biodiversity. We apply a mixed rarefaction/extrapolation approach to a global multi-taxa dataset from disturbed forests, including birds, plants, insects and fungi, to close this gap. We find that 757\% (mean +/- SD) of a naturally disturbed area of a forest needs to be left unlogged to maintain 90\% richness of its unique species, whereas retaining 50\% of a naturally disturbed forest unlogged maintains 73 +/- 12\% of its unique species richness. These values do not change with the time elapsed since disturbance but vary considerably among taxonomic groups. Salvage logging has become a common practice to gain economic returns from naturally disturbed forests, but it could have considerable negative effects on biodiversity. Here the authors use a recently developed statistical method to estimate that ca. 75\% of the naturally disturbed forest should be left unlogged to maintain 90\% of the species unique to the area.},
  language  = {en}
}
@article{BalkenholKaltdorfMammadovaBachetal.2020,
  author    = {Balkenhol, Johannes and Kaltdorf, Kristin V. and Mammadova-Bach, Elmina and Braun, Attila and Nieswandt, Bernhard and Dittrich, Marcus and Dandekar, Thomas},
  title     = {Comparison of the central human and mouse platelet signaling cascade by systems biological analysis},
  series = {BMC Genomics},
  volume    = {21},
  journal   = {BMC Genomics},
  doi       = {10.1186/s12864-020-07215-4},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-230377},
  year      = {2020},
  abstract  = {Background Understanding the molecular mechanisms of platelet activation and aggregation is of high interest for basic and clinical hemostasis and thrombosis research. The central platelet protein interaction network is involved in major responses to exogenous factors. This is defined by systemsbiological pathway analysis as the central regulating signaling cascade of platelets (CC). Results The CC is systematically compared here between mouse and human and major differences were found. Genetic differences were analysed comparing orthologous human and mouse genes. We next analyzed different expression levels of mRNAs. Considering 4 mouse and 7 human high-quality proteome data sets, we identified then those major mRNA expression differences (81\%) which were supported by proteome data. CC is conserved regarding genetic completeness, but we observed major differences in mRNA and protein levels between both species. Looking at central interactors, human PLCB2, MMP9, BDNF, ITPR3 and SLC25A6 (always Entrez notation) show absence in all murine datasets. CC interactors GNG12, PRKCE and ADCY9 occur only in mice. Looking at the common proteins, TLN1, CALM3, PRKCB, APP, SOD2 and TIMP1 are higher abundant in human, whereas RASGRP2, ITGB2, MYL9, EIF4EBP1, ADAM17, ARRB2, CD9 and ZYX are higher abundant in mouse. Pivotal kinase SRC shows different regulation on mRNA and protein level as well as ADP receptor P2RY12. Conclusions Our results highlight species-specific differences in platelet signaling and points of specific fine-tuning in human platelets as well as murine-specific signaling differences.},
  language  = {en}
}
@article{SchlegelSauer2020,
  author    = {Schlegel, Jan and Sauer, Markus},
  title     = {Hochaufgel{\"o}ste Visualisierung einzelner Molek{\"u}le auf ganzen Zellen},
  series = {BIOspektrum},
  volume    = {7},
  journal   = {BIOspektrum},
  issn      = {0947-0867},
  doi       = {10.1007/s12268-020-1501-4},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-232365},
  pages     = {736-738},
  year      = {2020},
  abstract  = {Biological systems are dynamic and three-dimensional but many techniques allow only static and two-dimensional observation of cells. We used three-dimensional (3D) lattice light-sheet single-molecule localization microscopy (dSTORM) to investigate the complex interactions and distribution of single molecules in the plasma membrane of whole cells. Different receptor densities of the adhesion receptor CD56 at different parts of the cell highlight the importance and need of three-dimensional observation and analysis techniques.},
  language  = {de}
}
@article{FofanovProkopovKuhletal.2020,
  author    = {Fofanov, Mikhail V. and Prokopov, Dmitry Yu. and Kuhl, Heiner and Schartl, Manfred and Trifonov, Vladimir A.},
  title     = {Evolution of microRNA biogenesis genes in the sterlet (Acipenser ruthenus) and other polyploid vertebrates},
  series = {International Journal of Molecular Sciences},
  volume    = {21},
  journal   = {International Journal of Molecular Sciences},
  number    = {24},
  issn      = {1422-0067},
  doi       = {10.3390/ijms21249562},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-285230},
  year      = {2020},
  abstract  = {MicroRNAs play a crucial role in eukaryotic gene regulation. For a long time, only little was known about microRNA-based gene regulatory mechanisms in polyploid animal genomes due to difficulties of polyploid genome assembly. However, in recent years, several polyploid genomes of fish, amphibian, and even invertebrate species have been sequenced and assembled. Here we investigated several key microRNA-associated genes in the recently sequenced sterlet (Acipenser ruthenus) genome, whose lineage has undergone a whole genome duplication around 180 MYA. We show that two paralogs of drosha, dgcr8, xpo1, and xpo5 as well as most ago genes have been retained after the acipenserid-specific whole genome duplication, while ago1 and ago3 genes have lost one paralog. While most diploid vertebrates possess only a single copy of dicer1, we strikingly found four paralogs of this gene in the sterlet genome, derived from a tandem segmental duplication that occurred prior to the last whole genome duplication. ago1,3,4 and exportins1,5 look to be prone to additional segment duplications producing up to four-five paralog copies in ray-finned fishes. We demonstrate for the first time exon microsatellite amplification in the acipenserid drosha2 gene, resulting in a highly variable protein product, which may indicate sub- or neofunctionalization. Paralogous copies of most microRNA metabolism genes exhibit different expression profiles in various tissues and remain functional despite the rediploidization process. Subfunctionalization of microRNA processing gene paralogs may be beneficial for different pathways of microRNA metabolism. Genetic variability of microRNA processing genes may represent a substrate for natural selection, and, by increasing genetic plasticity, could facilitate adaptations to changing environments.},
  language  = {en}
}
@article{NaseemOsmanoğluKaltdorfetal.2020,
  author    = {Naseem, Muhammad and Osmanoğlu, {\"O}zge and Kaltdorf, Martin and Alblooshi, Afnan Ali M. A. and Iqbal, Jibran and Howari, Fares M. and Srivastava, Mugdha and Dandekar, Thomas},
  title     = {Integrated framework of the immune-defense transcriptional signatures in the Arabidopsis shoot apical meristem},
  series = {International Journal of Molecular Sciences},
  volume    = {21},
  journal   = {International Journal of Molecular Sciences},
  number    = {16},
  issn      = {1422-0067},
  doi       = {10.3390/ijms21165745},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-285730},
  year      = {2020},
  abstract  = {The growing tips of plants grow sterile; therefore, disease-free plants can be generated from them. How plants safeguard growing apices from pathogen infection is still a mystery. The shoot apical meristem (SAM) is one of the three stem cells niches that give rise to the above ground plant organs. This is very well explored; however, how signaling networks orchestrate immune responses against pathogen infections in the SAM remains unclear. To reconstruct a transcriptional framework of the differentially expressed genes (DEGs) pertaining to various SAM cellular populations, we acquired large-scale transcriptome datasets from the public repository Gene Expression Omnibus (GEO). We identify here distinct sets of genes for various SAM cellular populations that are enriched in immune functions, such as immune defense, pathogen infection, biotic stress, and response to salicylic acid and jasmonic acid and their biosynthetic pathways in the SAM. We further linked those immune genes to their respective proteins and identify interactions among them by mapping a transcriptome-guided SAM-interactome. Furthermore, we compared stem-cells regulated transcriptome with innate immune responses in plants showing transcriptional separation among their DEGs in Arabidopsis. Besides unleashing a repertoire of immune-related genes in the SAM, our analysis provides a SAM-interactome that will help the community in designing functional experiments to study the specific defense dynamics of the SAM-cellular populations. Moreover, our study promotes the essence of large-scale omics data re-analysis, allowing a fresh look at the SAM-cellular transcriptome repurposing data-sets for new questions.},
  language  = {en}
}
@article{DollKolbSchnappetal.2020,
  author    = {Doll, Julia and Kolb, Susanne and Schnapp, Linda and Rad, Aboulfazl and R{\"u}schendorf, Franz and Khan, Imran and Adli, Abolfazl and Hasanzadeh, Atefeh and Liedtke, Daniel and Knaup, Sabine and Hofrichter, Michaela AH and M{\"u}ller, Tobias and Dittrich, Marcus and Kong, Il-Keun and Kim, Hyung-Goo and Haaf, Thomas and Vona, Barbara},
  title     = {Novel loss-of-function variants in CDC14A are associated with recessive sensorineural hearing loss in Iranian and Pakistani patients},
  series = {International Journal of Molecular Sciences},
  volume    = {21},
  journal   = {International Journal of Molecular Sciences},
  number    = {1},
  issn      = {1422-0067},
  doi       = {10.3390/ijms21010311},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-285142},
  year      = {2020},
  abstract  = {CDC14A encodes the Cell Division Cycle 14A protein and has been associated with autosomal recessive non-syndromic hearing loss (DFNB32), as well as hearing impairment and infertile male syndrome (HIIMS) since 2016. To date, only nine variants have been associated in patients whose initial symptoms included moderate-to-profound hearing impairment. Exome analysis of Iranian and Pakistani probands who both showed bilateral, sensorineural hearing loss revealed a novel splice site variant (c.1421+2T>C, p.?) that disrupts the splice donor site and a novel frameshift variant (c.1041dup, p.Ser348Glnfs*2) in the gene CDC14A, respectively. To evaluate the pathogenicity of both loss-of-function variants, we analyzed the effects of both variants on the RNA-level. The splice variant was characterized using a minigene assay. Altered expression levels due to the c.1041dup variant were assessed using RT-qPCR. In summary, cDNA analysis confirmed that the c.1421+2T>C variant activates a cryptic splice site, resulting in a truncated transcript (c.1414_1421del, p.Val472Leufs*20) and the c.1041dup variant results in a defective transcript that is likely degraded by nonsense-mediated mRNA decay. The present study functionally characterizes two variants and provides further confirmatory evidence that CDC14A is associated with a rare form of hereditary hearing loss.},
  language  = {en}
}
@article{StojanovićFuchsFiedleretal.2020,
  author    = {Stojanović, Stevan D. and Fuchs, Maximilian and Fiedler, Jan and Xiao, Ke and Meinecke, Anna and Just, Annette and Pich, Andreas and Thum, Thomas and Kunz, Meik},
  title     = {Comprehensive bioinformatics identifies key microRNA players in ATG7-deficient lung fibroblasts},
  series = {International Journal of Molecular Sciences},
  volume    = {21},
  journal   = {International Journal of Molecular Sciences},
  number    = {11},
  issn      = {1422-0067},
  doi       = {10.3390/ijms21114126},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-285181},
  year      = {2020},
  abstract  = {Background: Deficient autophagy has been recently implicated as a driver of pulmonary fibrosis, yet bioinformatics approaches to study this cellular process are lacking. Autophagy-related 5 and 7 (ATG5/ATG7) are critical elements of macro-autophagy. However, an alternative ATG5/ATG7-independent macro-autophagy pathway was recently discovered, its regulation being unknown. Using a bioinformatics proteome profiling analysis of ATG7-deficient human fibroblasts, we aimed to identify key microRNA (miR) regulators in autophagy. Method: We have generated ATG7-knockout MRC-5 fibroblasts and performed mass spectrometry to generate a large-scale proteomics dataset. We further quantified the interactions between various proteins combining bioinformatics molecular network reconstruction and functional enrichment analysis. The predicted key regulatory miRs were validated via quantitative polymerase chain reaction. Results: The functional enrichment analysis of the 26 deregulated proteins showed decreased cellular trafficking, increased mitophagy and senescence as the major overarching processes in ATG7-deficient lung fibroblasts. The 26 proteins reconstitute a protein interactome of 46 nodes and miR-regulated interactome of 834 nodes. The miR network shows three functional cluster modules around miR-16-5p, miR-17-5p and let-7a-5p related to multiple deregulated proteins. Confirming these results in a biological setting, serially passaged wild-type and autophagy-deficient fibroblasts displayed senescence-dependent expression profiles of miR-16-5p and miR-17-5p. Conclusions: We have developed a bioinformatics proteome profiling approach that successfully identifies biologically relevant miR regulators from a proteomics dataset of the ATG-7-deficient milieu in lung fibroblasts, and thus may be used to elucidate key molecular players in complex fibrotic pathological processes. The approach is not limited to a specific cell-type and disease, thus highlighting its high relevance in proteome and non-coding RNA research.},
  language  = {en}
}
@article{HesselbachSeegerSchilcheretal.2020,
  author    = {Hesselbach, Hannah and Seeger, Johannes and Schilcher, Felix and Ankenbrand, Markus and Scheiner, Ricarda},
  title     = {Chronic exposure to the pesticide flupyradifurone can lead to premature onset of foraging in honeybees Apis mellifera},
  series = {Journal of Applied Ecology},
  volume    = {57},
  journal   = {Journal of Applied Ecology},
  number    = {3},
  doi       = {10.1111/1365-2664.13555},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-212769},
  pages     = {609-618},
  year      = {2020},
  abstract  = {1.Honeybees Apis mellifera and other pollinating insects suffer from pesticides in agricultural landscapes. Flupyradifurone is the active ingredient of a novel pesticide by the name of 'Sivanto', introduced by Bayer AG (Crop Science Division, Monheim am Rhein, Germany). It is recommended against sucking insects and marketed as 'harmless' to honeybees. Flupyradifurone binds to nicotinergic acetylcholine receptors like neonicotinoids, but it has a different mode of action. So far, little is known on how sublethal flupyradifurone doses affect honeybees. 2. We chronically applied a sublethal and field-realistic concentration of flupyradifurone to test for long-term effects on flight behaviour using radio-frequency identification. We examined haematoxylin/eosin-stained brains of flupyradifurone-treated bees to investigate possible changes in brain morphology and brain damage. 3. A field-realistic flupyradifurone dose of approximately 1.0 μg/bee/day significantly increased mortality. Pesticide-treated bees initiated foraging earlier than control bees. No morphological damage in the brain was observed. 4. Synthesis and applications. The early onset of foraging induced by a chronical application of flupyradifurone could be disadvantageous for honeybee colonies, reducing the period of in-hive tasks and life expectancy of individuals. Radio-frequency identification technology is a valuable tool for studying pesticide effects on lifetime foraging behaviour of insects.},
  language  = {en}
}
@article{SajkoGrishkovskayaKostanetal.2020,
  author    = {Sajko, Sara and Grishkovskaya, Irina and Kostan, Julius and Graewert, Melissa and Setiawan, Kim and Tr{\"u}bestein, Linda and Niederm{\"u}ller, Korbinian and Gehin, Charlotte and Sponga, Antonio and Puchinger, Martin and Gavin, Anne-Claude and Leonard, Thomas A. and Svergun, Dimitri I. and Smith, Terry K. and Morriswood, Brooke and Djinovic-Carugo, Kristina},
  title     = {Structures of three MORN repeat proteins and a re-evaluation of the proposed lipid-binding properties of MORN repeats},
  series = {PLoS One},
  volume    = {15},
  journal   = {PLoS One},
  number    = {23},
  doi       = {10.1371/journal.pone.0242677},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-231261},
  year      = {2020},
  abstract  = {MORN (Membrane Occupation and Recognition Nexus) repeat proteins have a wide taxonomic distribution, being found in both prokaryotes and eukaryotes. Despite this ubiquity, they remain poorly characterised at both a structural and a functional level compared to other common repeats. In functional terms, they are often assumed to be lipid-binding modules that mediate membrane targeting. We addressed this putative activity by focusing on a protein composed solely of MORN repeats-Trypanosoma brucei MORN1. Surprisingly, no evidence for binding to membranes or lipid vesicles by TbMORN1 could be obtained either in vivo or in vitro. Conversely, TbMORN1 did interact with individual phospholipids. High- and low-resolution structures of the MORN1 protein from Trypanosoma brucei and homologous proteins from the parasites Toxoplasma gondii and Plasmodium falciparum were obtained using a combination of macromolecular crystallography, small-angle X-ray scattering, and electron microscopy. This enabled a first structure-based definition of the MORN repeat itself. Furthermore, all three structures dimerised via their C-termini in an antiparallel configuration. The dimers could form extended or V-shaped quaternary structures depending on the presence of specific interface residues. This work provides a new perspective on MORN repeats, showing that they are protein-protein interaction modules capable of mediating both dimerisation and oligomerisation.},
  language  = {en}
}
@article{KraussVikukYoungetal.2020,
  author    = {Krauss, Jochen and Vikuk, Veronika and Young, Carolyn A. and Krischke, Markus and Mueller, Martin J. and Baerenfaller, Katja},
  title     = {Correction: Krauss, J., et al. Epichlo{\"e} endophyte infection rates and alkaloid content in commercially available grass seed mixtures in Europe. Microorganisms 2020, 8, 498},
  series = {Microorganisms},
  volume    = {8},
  journal   = {Microorganisms},
  number    = {10},
  issn      = {2076-2607},
  doi       = {10.3390/microorganisms8101616},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-216254},
  year      = {2020},
  abstract  = {No abstract available.},
  language  = {en}
}
@article{BaurNietzerKunzetal.2020,
  author    = {Baur, Florentin and Nietzer, Sarah L. and Kunz, Meik and Saal, Fabian and Jeromin, Julian and Matschos, Stephanie and Linnebacher, Michael and Walles, Heike and Dandekar, Thomas and Dandekar, Gudrun},
  title     = {Connecting cancer pathways to tumor engines: a stratification tool for colorectal cancer combining human in vitro tissue models with boolean in silico models},
  series = {Cancers},
  volume    = {12},
  journal   = {Cancers},
  number    = {1},
  issn      = {2072-6694},
  doi       = {10.3390/cancers12010028},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-193798},
  pages     = {28},
  year      = {2020},
  abstract  = {To improve and focus preclinical testing, we combine tumor models based on a decellularized tissue matrix with bioinformatics to stratify tumors according to stage-specific mutations that are linked to central cancer pathways. We generated tissue models with BRAF-mutant colorectal cancer (CRC) cells (HROC24 and HROC87) and compared treatment responses to two-dimensional (2D) cultures and xenografts. As the BRAF inhibitor vemurafenib is—in contrast to melanoma—not effective in CRC, we combined it with the EGFR inhibitor gefitinib. In general, our 3D models showed higher chemoresistance and in contrast to 2D a more active HGFR after gefitinib and combination-therapy. In xenograft models murine HGF could not activate the human HGFR, stressing the importance of the human microenvironment. In order to stratify patient groups for targeted treatment options in CRC, an in silico topology with different stages including mutations and changes in common signaling pathways was developed. We applied the established topology for in silico simulations to predict new therapeutic options for BRAF-mutated CRC patients in advanced stages. Our in silico tool connects genome information with a deeper understanding of tumor engines in clinically relevant signaling networks which goes beyond the consideration of single drivers to improve CRC patient stratification.},
  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}
}
@article{BaeHeidrichLevicketal.2020,
  author    = {Bae, Soyeon and Heidrich, Lea and Levick, Shaun R. and Gossner, Martin M. and Seibold, Sebastian and Weisser, Wolfgang W. and Magdon, Paul and Serebryanyk, Alla and B{\"a}ssler, Claus and Sch{\"a}fer, Deborah and Schulze, Ernst-Detlef and Doerfler, Inken and M{\"u}ller, J{\"o}rg and Jung, Kirsten and Heurich, Marco and Fischer, Markus and Roth, Nicolas and Schall, Peter and Boch, Steffen and W{\"o}llauer, Stephan and Renner, Swen C. and M{\"u}ller, J{\"o}rg},
  title     = {Dispersal ability, trophic position and body size mediate species turnover processes: Insights from a multi-taxa and multi-scale approach},
  series = {Diversity and Distribution},
  volume    = {27},
  journal   = {Diversity and Distribution},
  number    = {3},
  doi       = {10.1111/ddi.13204},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-236117},
  pages     = {439-453},
  year      = {2020},
  abstract  = {Aim: Despite increasing interest in β-diversity, that is the spatial and temporal turnover of species, the mechanisms underlying species turnover at different spatial scales are not fully understood, although they likely differ among different functional groups. We investigated the relative importance of dispersal limitations and the environmental filtering caused by vegetation for local, multi-taxa forest communities differing in their dispersal ability, trophic position and body size. Location: Temperate forests in five regions across Germany. Methods: In the inter-region analysis, the independent and shared effects of the regional spatial structure (regional species pool), landscape spatial structure (dispersal limitation) and environmental factors on species turnover were quantified with a 1-ha grain across 11 functional groups in up to 495 plots by variation partitioning. In the intra-region analysis, the relative importance of three environmental factors related to vegetation (herb and tree layer composition and forest physiognomy) and spatial structure for species turnover was determined. Results: In the inter-region analysis, over half of the explained variation in community composition (23\% of the total explained 35\%) was explained by the shared effects of several factors, indicative of spatially structured environmental filtering. Among the independent effects, environmental factors were the strongest on average over 11 groups, but the importance of landscape spatial structure increased for less dispersive functional groups. In the intra-region analysis, the independent effect of plant species composition had a stronger influence on species turnover than forest physiognomy, but the relative importance of the latter increased with increasing trophic position and body size. Main conclusions: Our study revealed that the mechanisms structuring assemblage composition are associated with the traits of functional groups. Hence, conservation frameworks targeting biodiversity of multiple groups should cover both environmental and biogeographical gradients. Within regions, forest management can enhance β-diversity particularly by diversifying tree species composition and forest physiognomy.},
  language  = {en}
}
@article{JessenKressBaluapurietal.2020,
  author    = {Jessen, Christina and Kreß, Julia K. C. and Baluapuri, Apoorva and Hufnagel, Anita and Schmitz, Werner and Kneitz, Susanne and Roth, Sabine and Marquardt, Andr{\´e} and Appenzeller, Silke and Ade, Casten P. and Glutsch, Valerie and Wobser, Marion and Friedmann-Angeli, Jos{\´e} Pedro and Mosteo, Laura and Goding, Colin R. and Schilling, Bastian and Geissinger, Eva and Wolf, Elmar and Meierjohann, Svenja},
  title     = {The transcription factor NRF2 enhances melanoma malignancy by blocking differentiation and inducing COX2 expression},
  series = {Oncogene},
  volume    = {39},
  journal   = {Oncogene},
  issn      = {0950-9232},
  doi       = {10.1038/s41388-020-01477-8},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-235064},
  pages     = {6841-6855},
  year      = {2020},
  abstract  = {The transcription factor NRF2 is the major mediator of oxidative stress responses and is closely connected to therapy resistance in tumors harboring activating mutations in the NRF2 pathway. In melanoma, such mutations are rare, and it is unclear to what extent melanomas rely on NRF2. Here we show that NRF2 suppresses the activity of the melanocyte lineage marker MITF in melanoma, thereby reducing the expression of pigmentation markers. Intriguingly, we furthermore identified NRF2 as key regulator of immune-modulating genes, linking oxidative stress with the induction of cyclooxygenase 2 (COX2) in an ATF4-dependent manner. COX2 is critical for the secretion of prostaglandin E2 and was strongly induced by H\(_2\)O\(_2\) or TNFα only in presence of NRF2. Induction of MITF and depletion of COX2 and PGE2 were also observed in NRF2-deleted melanoma cells in vivo. Furthermore, genes corresponding to the innate immune response such as RSAD2 and IFIH1 were strongly elevated in absence of NRF2 and coincided with immune evasion parameters in human melanoma datasets. Even in vitro, NRF2 activation or prostaglandin E2 supplementation blunted the induction of the innate immune response in melanoma cells. Transcriptome analyses from lung adenocarcinomas indicate that the observed link between NRF2 and the innate immune response is not restricted to melanoma.},
  language  = {en}
}
@article{IsaacsMikasiObasaetal.2020,
  author    = {Isaacs, Darren and Mikasi, Sello Given and Obasa, Adetayo Emmanuel and Ikomey, George Mondinde and Shityakov, Sergey and Cloete, Ruben and Jacobs, Graeme Brendon},
  title     = {Structural comparison of diverse HIV-1 subtypes using molecular modelling and docking analyses of integrase inhibitors},
  series = {Viruses},
  volume    = {12},
  journal   = {Viruses},
  number    = {9},
  issn      = {1999-4915},
  doi       = {10.3390/v12090936},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-211170},
  year      = {2020},
  abstract  = {The process of viral integration into the host genome is an essential step of the HIV-1 life cycle. The viral integrase (IN) enzyme catalyzes integration. IN is an ideal therapeutic enzyme targeted by several drugs; raltegravir (RAL), elvitegravir (EVG), dolutegravir (DTG), and bictegravir (BIC) having been approved by the USA Food and Drug Administration (FDA). Due to high HIV-1 diversity, it is not well understood how specific naturally occurring polymorphisms (NOPs) in IN may affect the structure/function and binding affinity of integrase strand transfer inhibitors (INSTIs). We applied computational methods of molecular modelling and docking to analyze the effect of NOPs on the full-length IN structure and INSTI binding. We identified 13 NOPs within the Cameroonian-derived CRF02_AG IN sequences and further identified 17 NOPs within HIV-1C South African sequences. The NOPs in the IN structures did not show any differences in INSTI binding affinity. However, linear regression analysis revealed a positive correlation between the Ki and EC50 values for DTG and BIC as strong inhibitors of HIV-1 IN subtypes. All INSTIs are clinically effective against diverse HIV-1 strains from INSTI treatment-na{\"i}ve populations. This study supports the use of second-generation INSTIs such as DTG and BIC as part of first-line combination antiretroviral therapy (cART) regimens, due to a stronger genetic barrier to the emergence of drug resistance.},
  language  = {en}
}
@article{LealSchwebsBriggsetal.2020,
  author    = {Leal, Andrea Zurita and Schwebs, Marie and Briggs, Emma and Weisert, Nadine and Reis, Helena and Lemgruber, Leondro and Luko, Katarina and Wilkes, Jonathan and Butter, Falk and McCulloch, Richard and Janzen, Christian J.},
  title     = {Genome maintenance functions of a putative Trypanosoma brucei translesion DNA polymerase include telomere association and a role in antigenic variation},
  series = {Nucleic Acids Research},
  volume    = {48},
  journal   = {Nucleic Acids Research},
  number    = {17},
  doi       = {10.1093/nar/gkaa686},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-230579},
  pages     = {9660-9680},
  year      = {2020},
  abstract  = {Maintenance of genome integrity is critical to guarantee transfer of an intact genome from parent to off-spring during cell division. DNA polymerases (Pols) provide roles in both replication of the genome and the repair of a wide range of lesions. Amongst replicative DNA Pols, translesion DNA Pols play a particular role: replication to bypass DNA damage. All cells express a range of translesion Pols, but little work has examined their function in parasites, including whether the enzymes might contribute to host-parasite interactions. Here, we describe a dual function of one putative translesion Pol in African trypanosomes, which we now name TbPolIE. Previously, we demonstrated that TbPolIE is associated with telomeric sequences and here we show that RNAi-mediated depletion of TbPolIE transcripts results in slowed growth, altered DNA content, changes in cell morphology, and increased sensitivity to DNA damaging agents. We also show that TbPolIE displays pronounced localization at the nuclear periphery, and that its depletion leads to chromosome segregation defects and increased levels of endogenous DNA damage. Finally, we demonstrate that TbPolIE depletion leads to deregulation of telomeric variant surface glycoprotein genes, linking the function of this putative translesion DNA polymerase to host immune evasion by antigenic variation.},
  language  = {en}
}
@article{StieglervonHoermannMuelleretal.2020,
  author    = {Stiegler, Jonas and von Hoermann, Christian and M{\"u}ller, J{\"o}rg and Benbow, M. Eric and Heurich, Marco},
  title     = {Carcass provisioning for scavenger conservation in a temperate forest ecosystem},
  series = {Ecosphere},
  volume    = {11},
  journal   = {Ecosphere},
  number    = {4},
  doi       = {10.1002/ecs2.3063},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-218054},
  year      = {2020},
  abstract  = {Carrion plays an essential role in shaping the structure and functioning of ecosystems and has far-reaching implications for biodiversity conservation. The change in availability and type of carcasses throughout ecosystems can involve negative effects for scavenging communities. To address this issue, there have been recent conservation management measures of carrion provision in natural systems. However, the optimal conditions under which exposing carcasses to optimize conservation outcomes are still limited. Here, we used camera traps throughout elevational and vegetational gradients to monitor the consumption of 48 deer carcasses over a study period of six years by evaluating 270,279 photographs resulting out of 15,373 trap nights. We detected 17 species visiting carcass deployments, including five endangered species. Our results show that large carcasses, the winter season, and a heterogeneous surrounding habitat enhanced the frequency of carcass visits and the species richness of scavenger assemblages. Contrary to our expectations, carcass species, condition (fresh/frozen), and provision schedule (continuous vs single exposure) did not influence scavenging frequency or diversity. The carcass visitation frequency increased with carcass mass and lower temperatures. The effect of large carcasses was especially pronounced for mesopredators and the Eurasian lynx (Lynx lynx). Lynx were not too influenced in its carrion acquisition by the season, but exclusively preferred remote habitats containing higher forest cover. Birds of prey, mesopredators, and top predators were also positively influenced by the visiting rate of ravens (Corvus corax), whereas no biotic or abiotic preferences were found for wild boars (Sus scrofa). This study provides evidence that any ungulate species of carrion, either in a fresh or in previously frozen condition, attracts a high diversity of scavengers especially during winter, thereby supporting earlier work that carcass provisions may support scavenger communities and endangered species.},
  language  = {en}
}
@article{NaseemOthmanFathyetal.2020,
  author    = {Naseem, Muhammad and Othman, Eman M. and Fathy, Moustafa and Iqbal, Jibran and Howari, Fares M. and AlRemeithi, Fatima A. and Kodandaraman, Geema and Stopper, Helga and Bencurova, Elena and Vlachakis, Dimitrios and Dandekar, Thomas},
  title     = {Integrated structural and functional analysis of the protective effects of kinetin against oxidative stress in mammalian cellular systems},
  series = {Scientific Reports},
  volume    = {10},
  journal   = {Scientific Reports},
  doi       = {10.1038/s41598-020-70253-1},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-231317},
  year      = {2020},
  abstract  = {Metabolism and signaling of cytokinins was first established in plants, followed by cytokinin discoveries in all kingdoms of life. However, understanding of their role in mammalian cells is still scarce. Kinetin is a cytokinin that mitigates the effects of oxidative stress in mammalian cells. The effective concentrations of exogenously applied kinetin in invoking various cellular responses are not well standardized. Likewise, the metabolism of kinetin and its cellular targets within the mammalian cells are still not well studied. Applying vitality tests as well as comet assays under normal and hyper-oxidative states, our analysis suggests that kinetin concentrations of 500 nM and above cause cytotoxicity as well as genotoxicity in various cell types. However, concentrations below 100 nM do not cause any toxicity, rather in this range kinetin counteracts oxidative burst and cytotoxicity. We focus here on these effects. To get insights into the cellular targets of kinetin mediating these pro-survival functions and protective effects we applied structural and computational approaches on two previously testified targets for these effects. Our analysis deciphers vital residues in adenine phosphoribosyltransferase (APRT) and adenosine receptor (A2A-R) that facilitate the binding of kinetin to these two important human cellular proteins. We finally discuss how the therapeutic potential of kinetin against oxidative stress helps in various pathophysiological conditions.},
  language  = {en}
}
@article{GeorgievChaoCastroetal.2020,
  author    = {Georgiev, Kostadin B. and Chao, Anne and Castro, Jorge and Chen, Yan-Han and Choi, Chang-Yong and Fontaine, Joseph B. and Hutto, Richard L. and Lee, Eun-Jae and M{\"u}ller, J{\"o}rg and Rost, Josep and Żmihorski, Michal and Thorn, Simon},
  title     = {Salvage logging changes the taxonomic, phylogenetic and functional successional trajectories of forest bird communities},
  series = {Journal of Applied Ecology},
  volume    = {57},
  journal   = {Journal of Applied Ecology},
  number    = {6},
  doi       = {10.1111/1365-2664.13599},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-214887},
  pages     = {1103 -- 1112},
  year      = {2020},
  abstract  = {Salvage logging following natural disturbances may alter the natural successional trajectories of biological communities by affecting the occurrences of species, functional groups and evolutionary lineages. However, few studies have examined whether dissimilarities between bird communities of salvaged and unsalvaged forests are more pronounced for rare species, functional groups and evolutionary lineages than for their more common counterparts. We compiled data on breeding bird assemblages from nine study areas in North America, Europe and Asia, covering a 17-year period following wildfire or windstorm disturbances and subsequent salvage logging. We tested whether dissimilarities based on non-shared species, functional groups and evolutionary lineages (a) decreased or increased over time and (b) the responses of rare, common and dominant species varied, by using a unified statistical framework based on Hill numbers and null models. We found that dissimilarities between bird communities caused by salvage logging persisted over time for rare, common and dominant species, evolutionary lineages and for rare functional groups. Dissimilarities of common and dominant functional groups increased 14 years post disturbance. Salvage logging led to significantly larger dissimilarities than expected by chance. Functional dissimilarities between salvaged and unsalvaged sites were lower compared to taxonomic and phylogenetic dissimilarities. In general, dissimilarities were highest for rare, followed by common and dominant species. Synthesis and applications. Our research demonstrates that salvage logging did not decrease dissimilarities of bird communities over time and taxonomic, functional and phylogenetic dissimilarities persisted for over a decade. We recommend resource managers and decision makers to reserve portions of disturbed forest to enable unmanaged post-disturbance succession of bird communities, particularly to conserve rare species found in unsalvaged disturbed forests.},
  language  = {en}
}
@article{KablauBergRutschmannetal.2020,
  author    = {Kablau, Arne and Berg, Stefan and Rutschmann, Benjamin and Scheiner, Ricarda},
  title     = {Short-term hyperthermia at larval age reduces sucrose responsiveness of adult honeybees and can increase life span},
  series = {Apidologie},
  volume    = {51},
  journal   = {Apidologie},
  issn      = {0044-8435},
  doi       = {10.1007/s13592-020-00743-8},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-232462},
  pages     = {570-582},
  year      = {2020},
  abstract  = {Honeybees are very sensitive to their breeding temperature. Even slightly lower temperatures during larval development can significantly affect adult behavior. Several devices which are employed for killing the honeybee ectoparasite Varroa destructor rely on short-term hyperthermia in the honeybee hive. The device used here applies 43.7 °C for 2 h, which is highly effective in killing the mites. We study how short-term hyperthermia affects worker brood and behavior of emerging adult bees. Sucrose responsiveness was strongly reduced after treatment of larvae early or late of larval development. Hyperthermia significantly enhanced life span, particularly in bees receiving treated early in larval development. To ask whether increased life span correlated with foraging performance, we used radio frequency identification (RFID). Onset and offset of foraging behavior as well as foraging trip duration and lifetime foraging effort were unaffected by hyperthermia treatment as prepupa.},
  language  = {en}
}
@article{MayrPetersEardleyetal.2020,
  author    = {Mayr, Antonia V. and Peters, Marcell K. and Eardley, Connal D. and Renner, Marion E. and R{\"o}der, Juliane and Steffan-Dewenter, Ingolf},
  title     = {Climate and food resources shape species richness and trophic interactions of cavity-nesting Hymenoptera},
  series = {Journal of Biogeography},
  volume    = {47},
  journal   = {Journal of Biogeography},
  number    = {4},
  doi       = {10.1111/jbi.13753},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-208101},
  pages     = {854-865},
  year      = {2020},
  abstract  = {Aim: Temperature, food resources and top-down regulation by antagonists are considered as major drivers of insect diversity, but their relative importance is poorly understood. Here, we used cavity-nesting communities of bees, wasps and their antagonists to reveal the role of temperature, food resources, parasitism rate and land use as drivers of species richness at different trophic levels along a broad elevational gradient. Location: Mt. Kilimanjaro, Tanzania. Taxon: Cavity-nesting Hymenoptera (Hymenoptera: Apidae, Colletidae, Megachilidae, Crabronidae, Sphecidae, Pompilidae, Vespidae). Methods: We established trap nests on 25 study sites that were distributed over similar large distances in terms of elevation along an elevational gradient from 866 to 1788 m a.s.l., including both natural and disturbed habitats. We quantified species richness and abundance of bees, wasps and antagonists, parasitism rates and flower or arthropod food resources. Data were analysed with generalized linear models within a multi-model inference framework. Results: Elevational species richness patterns changed with trophic level from monotonically declining richness of bees to increasingly humped-shaped patterns for caterpillar-hunting wasps, spider-hunting wasps and antagonists. Parasitism rates generally declined with elevation but were higher for wasps than for bees. Temperature was the most important predictor of both bee and wasp host richness patterns. Antagonist richness patterns were also well predicted by temperature, but in contrast to host richness patterns, additionally by resource abundance and diversity. The conversion of natural habitats through anthropogenic land use, which included biomass removal, agricultural inputs, vegetation structure and percentage of surrounding agricultural habitats, had no significant effects on bee and wasp communities. Main conclusions: Our study underpins the importance of temperature as a main driver of diversity gradients in ectothermic organisms and reveals the increasingly important role of food resources at higher trophic levels. Higher parasitism rates at higher trophic levels and at higher temperatures indicated that the relative importance of bottom-up and top-down drivers of species richness change across trophic levels and may respond differently to future climate change.},
  language  = {en}
}
@article{PetersClassenMuelleretal.2020,
  author    = {Peters, Marcell K. and Classen, Alice and M{\"u}ller, J{\"o}rg and Steffan‑Dewenter, Ingolf},
  title     = {Increasing the phylogenetic coverage for understanding broad-scale diversity gradients},
  series = {Oecologia},
  volume    = {192},
  journal   = {Oecologia},
  issn      = {0029-8549},
  doi       = {10.1007/s00442-020-04615-x},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-232519},
  pages     = {629-639},
  year      = {2020},
  abstract  = {Despite decades of scientific effort, there is still no consensus on the determinants of broad-scale gradients of animal diver-sity. We argue that general drivers of diversity are unlikely to be found among the narrowly defined taxa which are typically analyzed in studies of broad-scale diversity gradients because ecological niches evolve largely conservatively. This causes constraints in the use of available niche space leading to systematic differences in diversity gradients among taxa. We instead advocate studies of phylogenetically diverse animal communities along broad environmental gradients. Such multi-taxa communities are less constrained in resource use and diversification and may be better targets for testing major classical hypotheses on diversity gradients. Besides increasing the spatial scale in analyses, expanding the phylogenetic coverage may be a second way to achieve higher levels of generality in studies of broad-scale diversity gradients},
  language  = {en}
}
@article{ThornSeiboldLeverkusetal.2020,
  author    = {Thorn, Simon and Seibold, Sebastian and Leverkus, Alexandro B and Michler, Thomas and M{\"u}ller, J{\"o}rg and Noss, Reed F and Stork, Nigel and Vogel, Sebastian and Lindenmayer, David B},
  title     = {The living dead: acknowledging life after tree death to stop forest degradation},
  series = {Frontiers in Ecology and the Environment},
  volume    = {18},
  journal   = {Frontiers in Ecology and the Environment},
  number    = {9},
  doi       = {10.1002/fee.2252},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-218575},
  pages     = {505 -- 512},
  year      = {2020},
  abstract  = {Global sustainability agendas focus primarily on halting deforestation, yet the biodiversity crisis resulting from the degradation of remaining forests is going largely unnoticed. Forest degradation occurs through the loss of key ecological structures, such as dying trees and deadwood, even in the absence of deforestation. One of the main drivers of forest degradation is limited awareness by policy makers and the public on the importance of these structures for supporting forest biodiversity and ecosystem function. Here, we outline management strategies to protect forest health and biodiversity by maintaining and promoting deadwood, and propose environmental education initiatives to improve the general awareness of the importance of deadwood. Finally, we call for major reforms to forest management to maintain and restore deadwood; large, old trees; and other key ecological structures.},
  language  = {en}
}
@article{Prieto‐GarciaHartmannReisslandetal.2020,
  author    = {Prieto-Garcia, Cristian and Hartmann, Oliver and Reissland, Michaela and Braun, Fabian and Fischer, Thomas and Walz, Susanne and Sch{\"u}lein-V{\"o}lk, Christina and Eilers, Ursula and Ade, Carsten P. and Calzado, Marco A. and Orian, Amir and Maric, Hans M. and M{\"u}nch, Christian and Rosenfeldt, Mathias and Eilers, Martin and Diefenbacher, Markus E.},
  title     = {Maintaining protein stability of ∆Np63 via USP28 is required by squamous cancer cells},
  series = {EMBO Molecular Medicine},
  volume    = {12},
  journal   = {EMBO Molecular Medicine},
  number    = {4},
  doi       = {10.15252/emmm.201911101},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-218303},
  year      = {2020},
  abstract  = {The transcription factor ∆Np63 is a master regulator of epithelial cell identity and essential for the survival of squamous cell carcinoma (SCC) of lung, head and neck, oesophagus, cervix and skin. Here, we report that the deubiquitylase USP28 stabilizes ∆Np63 and maintains elevated ∆NP63 levels in SCC by counteracting its proteasome-mediated degradation. Impaired USP28 activity, either genetically or pharmacologically, abrogates the transcriptional identity and suppresses growth and survival of human SCC cells. CRISPR/Cas9-engineered in vivo mouse models establish that endogenous USP28 is strictly required for both induction and maintenance of lung SCC. Our data strongly suggest that targeting ∆Np63 abundance via inhibition of USP28 is a promising strategy for the treatment of SCC tumours.},
  language  = {en}
}
@article{GrohRoessler2020,
  author    = {Groh, Claudia and R{\"o}ssler, Wolfgang},
  title     = {Analysis of Synaptic Microcircuits in the Mushroom Bodies of the Honeybee},
  series = {Insects},
  volume    = {11},
  journal   = {Insects},
  number    = {1},
  issn      = {2075-4450},
  doi       = {10.3390/insects11010043},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-200774},
  year      = {2020},
  abstract  = {Mushroom bodies (MBs) are multisensory integration centers in the insect brain involved in learning and memory formation. In the honeybee, the main sensory input region (calyx) of MBs is comparatively large and receives input from mainly olfactory and visual senses, but also from gustatory/tactile modalities. Behavioral plasticity following differential brood care, changes in sensory exposure or the formation of associative long-term memory (LTM) was shown to be associated with structural plasticity in synaptic microcircuits (microglomeruli) within olfactory and visual compartments of the MB calyx. In the same line, physiological studies have demonstrated that MB-calyx microcircuits change response properties after associative learning. The aim of this review is to provide an update and synthesis of recent research on the plasticity of microcircuits in the MB calyx of the honeybee, specifically looking at the synaptic connectivity between sensory projection neurons (PNs) and MB intrinsic neurons (Kenyon cells). We focus on the honeybee as a favorable experimental insect for studying neuronal mechanisms underlying complex social behavior, but also compare it with other insect species for certain aspects. This review concludes by highlighting open questions and promising routes for future research aimed at understanding the causal relationships between neuronal and behavioral plasticity in this charismatic social insect.},
  language  = {en}
}
@article{FleischmannGrobRoessler2020,
  author    = {Fleischmann, Pauline N. and Grob, Robin and R{\"o}ssler, Wolfgang},
  title     = {Kompass im Kopf : wie W{\"u}stenameisen lernen heimzukehren},
  series = {Biologie in unserer Zeit},
  volume    = {50},
  journal   = {Biologie in unserer Zeit},
  number    = {2},
  issn      = {1521-415X},
  doi       = {10.1002/biuz.202010699},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-219260},
  pages     = {100-109},
  year      = {2020},
  abstract  = {Erfolgreiche r{\"a}umliche Orientierung ist f{\"u}r viele Tiere eine allt{\"a}gliche Herausforderung. Cataglyphis-W{\"u}stenameisen sind bekannt f{\"u}r ihre Navigationsf{\"a}higkeiten, mit deren Hilfe sie nach langen Futtersuchl{\"a}ufen problemlos zum Nest zur{\"u}ckfinden. Wie aber nehmen naive Ameisen ihre Navigationssysteme in Betrieb? Nach mehrw{\"o}chigem Innendienst im dunklen Nest werden sie zu Sammlerinnen bei hellem Sonnenschein. Dieser Wechsel erfordert einen drastischen Wandel im Verhalten sowie neuronale Ver{\"a}nderungen im Gehirn. Erfahrene Ameisen orientieren sich vor allem visuell, sie nutzen einen Himmelskompass und Landmarkenpanoramen. Daher absolvieren naive Ameisen stereotype Lernl{\"a}ufe, um ihren Kompass zu kalibrieren und die Nestumgebung kennenzulernen. W{\"a}hrend der Lernl{\"a}ufe blicken sie wiederholt zum Nesteingang zur{\"u}ck und pr{\"a}gen sich so ihren Heimweg ein. Zur Ausrichtung ihrer Blicke nutzen sie das Erdmagnetfeld als Kompassreferenz. Cataglyphis-Ameisen besitzen hierf{\"u}r einen Magnetkompass, der bislang unbekannt war.},
  language  = {de}
}
@article{BiscottiCarducciBaruccaetal.2020,
  author    = {Biscotti, Maria Assunta and Carducci, Federica and Barucca, Marco and Gerdol, Marco and Pallavicini, Alberto and Schartl, Manfred and Canapa, Adriana and Contar Adolfi, Mateus},
  title     = {The transcriptome of the newt Cynops orientalis provides new insights into evolution and function of sexual gene networks in sarcopterygians},
  series = {Scientific Reports},
  volume    = {10},
  journal   = {Scientific Reports},
  doi       = {10.1038/s41598-020-62408-x},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-227326},
  year      = {2020},
  abstract  = {Amphibians evolved in the Devonian period about 400 Mya and represent a transition step in tetrapod evolution. Among amphibians, high-throughput sequencing data are very limited for Caudata, due to their largest genome sizes among terrestrial vertebrates. In this paper we present the transcriptome from the fire bellied newt Cynops orientalis. Data here presented display a high level of completeness, comparable to the fully sequenced genomes available from other amphibians. Moreover, this work focused on genes involved in gametogenesis and sexual development. Surprisingly, the gsdf gene was identified for the first time in a tetrapod species, so far known only from bony fish and basal sarcopterygians. Our analysis failed to isolate fgf24 and foxl3, supporting the possible loss of both genes in the common ancestor of Rhipidistians. In Cynops, the expression analysis of genes described to be sex-related in vertebrates singled out an expected functional role for some genes, while others displayed an unforeseen behavior, confirming the high variability of the sex-related pathway in vertebrates.},
  language  = {en}
}
@article{RuedenauerRaubenheimerKessnerBeierleinetal.2020,
  author    = {Ruedenauer, Fabian A. and Raubenheimer, David and Kessner-Beierlein, Daniela and Grund-Mueller, Nils and Noack, Lisa and Spaethe, Johannes and Leonhardt, Sara D.},
  title     = {Best be(e) on low fat: linking nutrient perception, regulation and fitness},
  series = {Ecology Letters},
  volume    = {23},
  journal   = {Ecology Letters},
  number    = {3},
  doi       = {10.1111/ele.13454},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-208709},
  pages     = {545-554},
  year      = {2020},
  abstract  = {Preventing malnutrition through consuming nutritionally appropriate resources represents a challenge for foraging animals. This is due to often high variation in the nutritional quality of available resources. Foragers consequently need to evaluate different food sources. However, even the same food source can provide a plethora of nutritional and non-nutritional cues, which could serve for quality assessment. We show that bumblebees, Bombus terrestris , overcome this challenge by relying on lipids as nutritional cue when selecting pollen. The bees 'prioritised' lipid perception in learning experiments and avoided lipid consumption in feeding experiments, which supported survival and reproduction. In contrast, survival and reproduction were severely reduced by increased lipid contents. Our study highlights the importance of fat regulation for pollen foraging bumblebees. It also reveals that nutrient perception, nutrient regulation and reproductive fitness can be linked, which represents an effective strategy enabling quick foraging decisions that prevent malnutrition and maximise fitness.},
  language  = {en}
}
@article{LeverkusGustafssonLindenmayeretal.2020,
  author    = {Leverkus, Alexandro B and Gustafsson, Lena and Lindenmayer, David B and Castro, Jorge and Rey Benayas, Jos{\´e} Mar{\´i}a and Ranius, Thomas and Thorn, Simon},
  title     = {Salvage logging effects on regulating ecosystem services and fuel loads},
  series = {Frontiers in Ecology and the Environment},
  volume    = {18},
  journal   = {Frontiers in Ecology and the Environment},
  number    = {7},
  doi       = {10.1002/fee.2219},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-216111},
  pages     = {391 -- 400},
  year      = {2020},
  abstract  = {Salvage logging, or logging after natural disturbances such as wildfires, insect outbreaks, and windstorms, is carried out to recover some of a forest's natural and/or economic capital. However, trade-offs between management objectives and a lack of consensus on the ecological consequences of salvage logging impair science-based decision making on the management of forests after natural disturbances. We conducted a global meta-analysis of the impacts of salvage logging on regulating ecosystem services and on fuel loads, as a frequent post-disturbance objective is preventing subsequent wildfires that could be fueled by the accumulation of dead trunks and branches. Salvage logging affected ecosystem services in a moderately negative way, regardless of disturbance type and severity, time elapsed since salvage logging, intensity of salvage logging, and the group of regulating ecosystem services being considered. However, prolonging the time between natural disturbance and salvage logging mitigated negative effects on regulating ecosystem services. Salvage logging had no overall effect on surface fuels; rather, different fuel types responded differently depending on the time elapsed since salvage logging. Delaying salvage logging by ~2-4 years may reduce negative ecological impacts without affecting surface fuel loads.},
  language  = {en}
}
@article{YangHeydarianKozjakPavlovicetal.2020,
  author    = {Yang, Tao and Heydarian, Motaharehsadat and Kozjak-Pavlovic, Vera and Urban, Manuela and Harbottle, Richard P. and Rudel, Thomas},
  title     = {Folliculin Controls the Intracellular Survival and Trans-Epithelial Passage of Neisseria gonorrhoeae},
  series = {Frontiers in Cellular and Infection Microbiology},
  volume    = {10},
  journal   = {Frontiers in Cellular and Infection Microbiology},
  number    = {422},
  issn      = {2235-2988},
  doi       = {10.3389/fcimb.2020.00422},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-211372},
  year      = {2020},
  abstract  = {Neisseria gonorrhoeae, a Gram-negative obligate human pathogenic bacterium, infects human epithelial cells and causes sexually transmitted diseases. Emerging multi-antibiotic resistant gonococci and increasing numbers of infections complicate the treatment of infected patients. Here, we used an shRNA library screen and next-generation sequencing to identify factors involved in epithelial cell infection. Folliculin (FLCN), a 64 kDa protein with a tumor repressor function was identified as a novel host factor important for N. gonorrhoeae survival after uptake. We further determined that FLCN did not affect N. gonorrhoeae adherence and invasion but was essential for its survival in the cells by modulating autophagy. In addition, FLCN was also required to maintain cell to cell contacts in the epithelial layer. In an infection model with polarized cells, FLCN inhibited the polarized localization of E-cadherin and the transcytosis of gonococci across polarized epithelial cells. In conclusion, we demonstrate here the connection between FLCN and bacterial infection and in particular the role of FLCN in the intracellular survival and transcytosis of gonococci across polarized epithelial cell layers.},
  language  = {en}
}
@article{AuerHuegelschaefferFischeretal.2020,
  author    = {Auer, Daniela and H{\"u}gelsch{\"a}ffer, Sophie D. and Fischer, Annette B. and Rudel, Thomas},
  title     = {The chlamydial deubiquitinase Cdu1 supports recruitment of Golgi vesicles to the inclusion},
  series = {Cellular Microbiology},
  volume    = {22},
  journal   = {Cellular Microbiology},
  number    = {5},
  doi       = {10.1111/cmi.13136},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-208675},
  pages     = {e13136},
  year      = {2020},
  abstract  = {Chlamydia trachomatis is the main cause of sexually transmitted diseases worldwide. As obligate intracellular bacteria Chlamydia replicate in a membrane bound vacuole called inclusion and acquire nutrients for growth and replication from their host cells. However, like all intracellular bacteria, Chlamydia have to prevent eradication by the host's cell autonomous system. The chlamydial deubiquitinase Cdu1 is secreted into the inclusion membrane, facing the host cell cytosol where it deubiquitinates cellular proteins. Here we show that inactivation of Cdu1 causes a growth defect of C. trachomatis in primary cells. Moreover, ubiquitin and several autophagy receptors are recruited to the inclusion membrane of Cdu1-deficient Chlamydia . Interestingly, the growth defect of cdu1 mutants is not rescued when autophagy is prevented. We find reduced recruitment of Golgi vesicles to the inclusion of Cdu1 mutants indicating that vesicular trafficking is altered in bacteria without active deubiquitinase (DUB). Our work elucidates an important role of Cdu1 in the functional preservation of the chlamydial inclusion surface.},
  language  = {en}
}
@article{WhisnantJuergesHennigetal.2020,
  author    = {Whisnant, Adam W. and J{\"u}rges, Christopher S. and Hennig, Thomas and Wyler, Emanuel and Prusty, Bhupesh and Rutkowski, Andrzej J. and L'hernault, Anne and Djakovic, Lara and G{\"o}bel, Margarete and D{\"o}ring, Kristina and Menegatti, Jennifer and Antrobus, Robin and Matheson, Nicholas J. and K{\"u}nzig, Florian W. H. and Mastrobuoni, Guido and Bielow, Chris and Kempa, Stefan and Liang, Chunguang and Dandekar, Thomas and Zimmer, Ralf and Landthaler, Markus and Gr{\"a}sser, Friedrich and Lehner, Paul J. and Friedel, Caroline C. and Erhard, Florian and D{\"o}lken, Lars},
  title     = {Integrative functional genomics decodes herpes simplex virus 1},
  series = {Nature Communications},
  volume    = {11},
  journal   = {Nature Communications},
  doi       = {10.1038/s41467-020-15992-5},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-229884},
  year      = {2020},
  abstract  = {The predicted 80 open reading frames (ORFs) of herpes simplex virus 1 (HSV-1) have been intensively studied for decades. Here, we unravel the complete viral transcriptome and translatome during lytic infection with base-pair resolution by computational integration of multi-omics data. We identify a total of 201 transcripts and 284 ORFs including all known and 46 novel large ORFs. This includes a so far unknown ORF in the locus deleted in the FDA-approved oncolytic virus Imlygic. Multiple transcript isoforms expressed from individual gene loci explain translation of the vast majority of ORFs as well as N-terminal extensions (NTEs) and truncations. We show that NTEs with non-canonical start codons govern the subcellular protein localization and packaging of key viral regulators and structural proteins. We extend the current nomenclature to include all viral gene products and provide a genome browser that visualizes all the obtained data from whole genome to single-nucleotide resolution. Here, using computational integration of multi-omics data, the authors provide a detailed transcriptome and translatome of herpes simplex virus 1 (HSV-1), including previously unidentified ORFs and N-terminal extensions. The study also provides a HSV-1 genome browser and should be a valuable resource for further research.},
  language  = {en}
}
@article{HabensteinAminiGruebeletal.2020,
  author    = {Habenstein, Jens and Amini, Emad and Gr{\"u}bel, Kornelia and el Jundi, Basil and R{\"o}ssler, Wolfgang},
  title     = {The brain of Cataglyphis ants: Neuronal organization and visual projections},
  series = {Journal of Comparative Neurology},
  volume    = {528},
  journal   = {Journal of Comparative Neurology},
  number    = {18},
  doi       = {10.1002/cne.24934},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-218212},
  pages     = {3479 -- 3506},
  year      = {2020},
  abstract  = {Cataglyphis ants are known for their outstanding navigational abilities. They return to their inconspicuous nest after far-reaching foraging trips using path integration, and whenever available, learn and memorize visual features of panoramic sceneries. To achieve this, the ants combine directional visual information from celestial cues and panoramic scenes with distance information from an intrinsic odometer. The largely vision-based navigation in Cataglyphis requires sophisticated neuronal networks to process the broad repertoire of visual stimuli. Although Cataglyphis ants have been subjected to many neuroethological studies, little is known about the general neuronal organization of their central brain and the visual pathways beyond major circuits. Here, we provide a comprehensive, three-dimensional neuronal map of synapse-rich neuropils in the brain of Cataglyphis nodus including major connecting fiber systems. In addition, we examined neuronal tracts underlying the processing of visual information in more detail. This study revealed a total of 33 brain neuropils and 30 neuronal fiber tracts including six distinct tracts between the optic lobes and the cerebrum. We also discuss the importance of comparative studies on insect brain architecture for a profound understanding of neuronal networks and their function.},
  language  = {en}
}
@article{BoetzlSchueleKraussetal.2020,
  author    = {Boetzl, Fabian A. and Schuele, Maren and Krauss, Jochen and Steffan-Dewenter, Ingolf},
  title     = {Pest control potential of adjacent agri-environment schemes varies with crop type and is shaped by landscape context and within-field position},
  series = {Journal of Applied Ecology},
  volume    = {57},
  journal   = {Journal of Applied Ecology},
  number    = {8},
  doi       = {10.1111/1365-2664.13653},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-218265},
  pages     = {1482 -- 1493},
  year      = {2020},
  abstract  = {Increasing natural pest control in agricultural fields is an important aim of ecological intensification. Combined effects of landscape context and local placement of agri-environmental schemes (AES) on natural pest control and within-field distance functions of natural pest control agents have rarely been addressed but might affect the distribution of biocontrol providers. Importantly, it is currently unknown whether ecosystem services provided by adjacent AES are consistent for different crop types during crop rotation. In this study, we assessed whether crop rotation from oilseed rape to cereals altered within-field distance functions of ground-dwelling predators from adjacent agri-environmental fields along a gradient in landscape context. Additionally, we recorded crop pests, predation rates, parasitoids as well as crop yields on a total of 30 study sites. Distance functions varied between trophic levels: Carabid richness decreased while densities of carabid beetles, staphylinid beetles as well as crop yields increased towards the field centres. Distance functions of parasitoids and pests were modulated by the amount of semi-natural habitat in the surrounding landscape, while the effects of adjacent AES were limited. Distance decay functions found for ground-dwelling predators in oilseed rape in the previous year were not always present in cereals. Increasing distance to the field edge also increased effects of crop rotation on carabid beetle assemblages, indicating a source habitat function of field edges. Synthesis and applications. Distance functions of natural pest control are not universal and the effects of agri-environmental schemes (AES) in different adjacent crops during crop rotation vary and depend on ecological contrasts. A network of semi-natural habitats and spatially optimized AES habitats can benefit pest control in agricultural landscapes, but constraints as a result of crop type need to be addressed by annually targeted, spatially shifting agri-environment schemes for different crops.},
  language  = {en}
}
@article{LapuenteArandjelovicKuehletal.2020,
  author    = {Lapuente, Juan and Arandjelovic, Mimi and K{\"u}hl, Hjalmar and Dieguez, Paula and Boesch, Christophe and Linsenmair, K. Eduard},
  title     = {Sustainable Peeling of Kapok Tree (Ceiba pentandra) Bark by the Chimpanzees (Pan troglodytes verus) of Como{\´e} National Park, Ivory Coast},
  series = {International Journal of Primatology},
  volume    = {41},
  journal   = {International Journal of Primatology},
  issn      = {0164-0291},
  doi       = {10.1007/s10764-020-00152-9},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-232581},
  pages     = {962-988},
  year      = {2020},
  abstract  = {Primates often consume either bark or cambium (inner bark) as a fallback food tocomplete their diet during periods of food scarcity. Wild chimpanzees exhibit greatbehavioral diversity across Africa, as studies of new populations frequently reveal.Since 2014, we have been using a combination of camera traps and indirect signs tostudy the ecology and behavior of wild chimpanzees (Pan troglodytes verus) in Como{\´e}National Park, Ivory Coast, to document and understand the behavioral adaptations thathelp them to survive in a savanna-forest mosaic landscape. We found that Como{\´e}chimpanzees peel the bark of the buttresses of kapok tree (Ceiba pentandra) trees to eatthe cambium underneath. Individuals of all sex/age classes across at least six neigh-boring communities peeled the bark, but only during the late rainy season andbeginning of the dry season, when cambium may represent an important fallback food.Baboons (Papio anubis) also target the same trees but mainly eat the bark itself. Mostof the bark-peeling wounds onCeibatrees healed completely within 2 years, seeminglywithout any permanent damage. We recorded chimpanzees visiting trees in early stagesof wound recovery but leaving them unpeeled. Only 6\% of peeled trees (N= 53) werereexploited after a year, suggesting that chimpanzees waited for the rest of the trees toregrow the bark fully before peeling them again, thus using them sustainably. Manyhuman groups of hunter-gatherers and herders exploited cambium sustainably in thepast. The observation that similar sustainable bark-peeling behavior evolved in bothchimpanzees and humans suggests that it has an important adaptive value in harshenvironments when other food sources become seasonally scarce, by avoiding thedepletion of the resource and keeping it available for periods of scarcity.},
  language  = {en}
}
@article{FlemmingHankirErnestusetal.2020,
  author    = {Flemming, S. and Hankir, M. and Ernestus, R.-I. and Seyfried, F. and Germer, C.-T. and Meybohm, P. and Wurmb, T. and Vogel, U. and Wiegering, A.},
  title     = {Surgery in times of COVID-19 — recommendations for hospital and patient management},
  series = {Langenbeck's Archives of Surgery},
  volume    = {405},
  journal   = {Langenbeck's Archives of Surgery},
  issn      = {1435-2443},
  doi       = {10.1007/s00423-020-01888-x},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-231766},
  pages     = {359-364},
  year      = {2020},
  abstract  = {Background The novel coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2), has escalated rapidly to a global pandemic stretching healthcare systems worldwide to their limits. Surgeonshave had to immediately react to this unprecedented clinical challenge by systematically repurposing surgical wards. Purpose To provide a detailed set of guidelines developed in a surgical ward at University Hospital Wuerzburg to safelyaccommodate the exponentially rising cases of SARS-CoV-2 infected patients without compromising the care of emergencysurgery and oncological patients or jeopardizing the well-being of hospital staff. Conclusions The dynamic prioritization of SARS-CoV-2 infected and surgical patient groups is key to preserving life whilemaintaining high surgical standards. Strictly segregating patient groups in emergency rooms, non-intensive care wards andoperating areas prevents viral spread while adequately training and carefully selecting hospital staff allow them to confidentlyand successfully undertake their respective clinical duties.},
  language  = {en}
}
@article{StelznerWinklerLiangetal.2020,
  author    = {Stelzner, Kathrin and Winkler, Ann-Cathrin and Liang, Chunguang and Boyny, Aziza and Ade, Carsten P. and Dandekar, Thomas and Fraunholz, Martin J. and Rudel, Thomas},
  title     = {Intracellular Staphylococcus aureus Perturbs the Host Cell Ca\(^{2+}\) Homeostasis To Promote Cell Death},
  series = {mBio},
  volume    = {11},
  journal   = {mBio},
  doi       = {10.1128/mBio.02250-20},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-231448},
  year      = {2020},
  abstract  = {The opportunistic human pathogen Staphylococcus aureus causes serious infectious diseases that range from superficial skin and soft tissue infections to necrotizing pneumonia and sepsis. While classically regarded as an extracellular pathogen, S. aureus is able to invade and survive within human cells. Host cell exit is associated with cell death, tissue destruction, and the spread of infection. The exact molecular mechanism employed by S. aureus to escape the host cell is still unclear. In this study, we performed a genome-wide small hairpin RNA (shRNA) screen and identified the calcium signaling pathway as being involved in intracellular infection. S. aureus induced a massive cytosolic Ca\(^{2+}\) increase in epithelial host cells after invasion and intracellular replication of the pathogen. This was paralleled by a decrease in endoplasmic reticulum Ca\(^{2+}\) concentration. Additionally, calcium ions from the extracellular space contributed to the cytosolic Ca2+ increase. As a consequence, we observed that the cytoplasmic Ca\(^{2+}\) rise led to an increase in mitochondrial Ca\(^{2+}\) concentration, the activation of calpains and caspases, and eventually to cell lysis of S. aureus-infected cells. Our study therefore suggests that intracellular S. aureus disturbs the host cell Ca\(^{2+}\) homeostasis and induces cytoplasmic Ca\(^{2+}\) overload, which results in both apoptotic and necrotic cell death in parallel or succession. IMPORTANCE Despite being regarded as an extracellular bacterium, the pathogen Staphylococcus aureus can invade and survive within human cells. The intracellular niche is considered a hideout from the host immune system and antibiotic treatment and allows bacterial proliferation. Subsequently, the intracellular bacterium induces host cell death, which may facilitate the spread of infection and tissue destruction. So far, host cell factors exploited by intracellular S. aureus to promote cell death are only poorly characterized. We performed a genome-wide screen and found the calcium signaling pathway to play a role in S. aureus invasion and cytotoxicity. The intracellular bacterium induces a cytoplasmic and mitochondrial Ca\(^{2+}\) overload, which results in host cell death. Thus, this study first showed how an intracellular bacterium perturbs the host cell Ca\(^{2+}\) homeostasis."},
  language  = {en}
}
@article{SarukhanyanShityakovDandekar2020,
  author    = {Sarukhanyan, Edita and Shityakov, Sergey and Dandekar, Thomas},
  title     = {Rational drug design of Axl tyrosine kinase type I inhibitors as promising candidates against cancer},
  series = {Frontiers in Chemistry},
  volume    = {7},
  journal   = {Frontiers in Chemistry},
  number    = {920},
  issn      = {2296-2646},
  doi       = {10.3389/fchem.2019.00920},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-199505},
  year      = {2020},
  abstract  = {The high level of Axl tyrosine kinase expression in various cancer cell lines makes it an attractive target for the development of anti-cancer drugs. In this study, we carried out several sets of in silico screening for the ATP-competitive Axl kinase inhibitors based on different molecular docking protocols. The best drug-like candidates were identified, after parental structure modifications, by their highest affinity to the target protein. We found that our newly designed compound R5, a derivative of the R428 patented analog, is the most promising inhibitor of the Axl kinase according to the three molecular docking algorithms applied in the study. The molecular docking results are in agreement with the molecular dynamics simulations using the MM-PBSA/GBSA implicit solvation models, which confirm the high affinity of R5 toward the protein receptor. Additionally, the selectivity test against other kinases also reveals a high affinity of R5 toward ABL1 and Tyro3 kinases, emphasizing its promising potential for the treatment of malignant tumors.},
  language  = {en}
}
@article{RoemerCosarinskyRoces2020,
  author    = {R{\"o}mer, Daniela and Cosarinsky, Marcela I. and Roces, Flavio},
  title     = {Selection and spatial arrangement of building materials during the construction of nest turrets by grass-cutting ants},
  series = {Royal Society Open Science},
  volume    = {7},
  journal   = {Royal Society Open Science},
  doi       = {10.1098/rsos.201312},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-230458},
  year      = {2020},
  abstract  = {Ants build complex nest structures by reacting to simple, local stimuli. While underground nests result from the space generated by digging, some leaf- and grass-cutting ants also construct conspicuous aboveground turrets around nest openings. We investigated whether the selection of specific building materials occurs during turret construction in Acromyrmex fracticornis grass-cutting ants, and asked whether single building decisions at the beginning can modify the final turret architecture. To quantify workers' material selection, the original nest turret was removed and a choice between two artificial building materials, thin and thick sticks, was offered for rebuilding. Workers preferred thick sticks at the very beginning of turret construction, showed varying preferences thereafter, and changed to prefer thin sticks for the upper, final part of the turret, indicating that they selected different building materials over time to create a stable structure. The impact of a single building choice on turret architecture was evaluated by placing artificial beams that divided a colony's nest entrance at the beginning of turret rebuilding. Splitting the nest entrance led to the self-organized construction of turrets with branched galleries ending in multiple openings, showing that the spatial location of a single building material can strongly influence turret morphology.},
  language  = {en}
}
@article{MarkertSkoruppaYuetal.2020,
  author    = {Markert, Sebastian M. and Skoruppa, Michael and Yu, Bin and Mulcahy, Ben and Zhen, Mai and Gao, Shangbang and Sendtner, Michael and Stigloher, Christian},
  title     = {Overexpression of an ALS-associated FUS mutation in C. elegans disrupts NMJ morphology and leads to defective neuromuscular transmission},
  series = {Biology Open},
  volume    = {9},
  journal   = {Biology Open},
  doi       = {10.1242/bio.055129},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-230662},
  year      = {2020},
  abstract  = {The amyotrophic lateral sclerosis (ALS) neurodegenerative disorder has been associated with multiple genetic lesions, including mutations in the gene for fused in sarcoma (FUS), a nuclear-localized RNA/DNA-binding protein. Neuronal expression of the pathological form of FUS proteins in Caenorhabditis elegans results in mislocalization and aggregation of FUS in the cytoplasm, and leads to impairment of motility. However, the mechanisms by which the mutant FUS disrupts neuronal health and function remain unclear. Here we investigated the impact of ALS-associated FUS on motor neuron health using correlative light and electron microscopy, electron tomography, and electrophysiology. We show that ectopic expression of wild-type or ALS-associated human FUS impairs synaptic vesicle docking at neuromuscular junctions. ALS-associated FUS led to the emergence of a population of large, electron-dense, and filament-filled endosomes. Electrophysiological recording revealed reduced transmission from motor neurons to muscles. Together, these results suggest a pathological effect of ALS-causing FUS at synaptic structure and function organization.},
  language  = {en}
}
@article{RoesingSalvadorGuentzeletal.2020,
  author    = {R{\"o}sing, Nils and Salvador, Ellaine and G{\"u}ntzel, Paul and Kempe, Christoph and Burek, Malgorzata and Holzgrabe, Ulrike and Soukhoroukov, Vladimir and Wunder, Christian and F{\"o}rster, Carola},
  title     = {Neuroprotective Effects of Isosteviol Sodium in Murine Brain Capillary Cerebellar Endothelial Cells (cerebEND) After Hypoxia},
  series = {Frontiers in Cellular Neuroscience},
  volume    = {14},
  journal   = {Frontiers in Cellular Neuroscience},
  issn      = {1662-5102},
  doi       = {10.3389/fncel.2020.573950},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-215013},
  year      = {2020},
  abstract  = {Ischemic stroke is one of the leading causes of death worldwide. It damages neurons and other supporting cellular elements in the brain. However, the impairment is not only confined to the region of assault but the surrounding area as well. Besides, it also brings about damage to the blood-brain barrier (BBB) which in turn leads to microvascular failure and edema. Hence, this necessitates an on-going, continuous search for intervention strategies and effective treatment. Of late, the natural sweetener stevioside proved to exhibit neuroprotective effects and therapeutic benefits against cerebral ischemia-induced injury. Its injectable formulation, isosteviol sodium (STVNA) also demonstrated favorable results. Nonetheless, its effects on the BBB have not yet been investigated to date. As such, this present study was designed to assess the effects of STVNA in our in vitro stroke model of the BBB.The integrity and permeability of the BBB are governed and maintained by tight junction proteins (TJPs) such as claudin-5 and occludin. Our data show increased claudin-5 and occludin expression in oxygen and glucose (OGD)-deprived murine brain capillary cerebellar endothelial cells (cerebEND) after STVNa treatment. Likewise, the upregulation of the transmembrane protein integrin-αv was also observed. Finally, cell volume was reduced with the simultaneous administration of STVNA and OGD in cerebEND cells. In neuropathologies such as stroke, the failure of cell volume control is a major feature leading to loss of cells in the penumbra as well as adverse outcomes. Our initial findings, therefore, point to the neuroprotective effects of STVNA at the BBB in vitro, which warrant further investigation for a possible future clinical intervention.},
  language  = {en}
}
@article{MemmelSisarioZimmermannetal.2020,
  author    = {Memmel, Simon and Sisario, Dmitri and Zimmermann, Heiko and Sauer, Markus and Sukhorukov, Vladimir L. and Djuzenova, Cholpon S. and Flentje, Michael},
  title     = {FocAn: automated 3D analysis of DNA repair foci in image stacks acquired by confocal fluorescence microscopy},
  series = {BMC Bioinformatics},
  volume    = {21},
  journal   = {BMC Bioinformatics},
  doi       = {10.1186/s12859-020-3370-8},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-229023},
  year      = {2020},
  abstract  = {Background Phosphorylated histone H2AX, also known as gamma H2AX, forms mu m-sized nuclear foci at the sites of DNA double-strand breaks (DSBs) induced by ionizing radiation and other agents. Due to their specificity and sensitivity, gamma H2AX immunoassays have become the gold standard for studying DSB induction and repair. One of these assays relies on the immunofluorescent staining of gamma H2AX followed by microscopic imaging and foci counting. During the last years, semi- and fully automated image analysis, capable of fast detection and quantification of gamma H2AX foci in large datasets of fluorescence images, are gradually replacing the traditional method of manual foci counting. A major drawback of the non-commercial software for foci counting (available so far) is that they are restricted to 2D-image data. In practice, these algorithms are useful for counting the foci located close to the midsection plane of the nucleus, while the out-of-plane foci are neglected. Results To overcome the limitations of 2D foci counting, we present a freely available ImageJ-based plugin (FocAn) for automated 3D analysis of gamma H2AX foci in z-image stacks acquired by confocal fluorescence microscopy. The image-stack processing algorithm implemented in FocAn is capable of automatic 3D recognition of individual cell nuclei and gamma H2AX foci, as well as evaluation of the total foci number per cell nucleus. The FocAn algorithm consists of two parts: nucleus identification and foci detection, each employing specific sequences of auto local thresholding in combination with watershed segmentation techniques. We validated the FocAn algorithm using fluorescence-labeled gamma H2AX in two glioblastoma cell lines, irradiated with 2 Gy and given up to 24 h post-irradiation for repair. We found that the data obtained with FocAn agreed well with those obtained with an already available software (FoCo) and manual counting. Moreover, FocAn was capable of identifying overlapping foci in 3D space, which ensured accurate foci counting even at high DSB density of up to similar to 200 DSB/nucleus. Conclusions FocAn is freely available an open-source 3D foci analyzer. The user-friendly algorithm FocAn requires little supervision and can automatically count the amount of DNA-DSBs, i.e. fluorescence-labeled gamma H2AX foci, in 3D image stacks acquired by laser-scanning microscopes without additional nuclei staining.},
  language  = {en}
}
@article{RequierJowanowitschKallniketal.2020,
  author    = {Requier, Fabrice and Jowanowitsch, Kim K. and Kallnik, Katharina and Steffan-Dewenter, Ingolf},
  title     = {Limitation of complementary resources affects colony growth, foraging behavior, and reproduction in bumble bees},
  series = {Ecology},
  volume    = {101},
  journal   = {Ecology},
  number    = {3},
  doi       = {10.1002/ecy.2946},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-211891},
  pages     = {e02946},
  year      = {2020},
  abstract  = {Resource availability in agricultural landscapes has been disturbed for many organisms, including pollinator species. Abundance and diversity in flower availability benefit bee populations; however, little is known about which of protein or carbohydrate resources may limit their growth and reproductive performance. Here, we test the hypothesis of complementary resource limitation using a supplemental feeding approach. We applied this assumption with bumble bees (Bombus terrestris), assuming that colony growth and reproductive performance should depend on the continuous supply of carbohydrates and proteins, through the foraging for nectar and pollen, respectively. We placed wild-caught bumble bee colonies along a landscape gradient of seminatural habitats, and monitored the colonies' weight, foraging activity, and reproductive performance during the whole colony cycle. We performed supplemental feeding as an indicator of landscape resource limitation, using a factorial design consisting of the addition of sugar water (carbohydrate, supplemented or not) crossed by pollen (protein, supplemented or not). Bumble bee colony dynamics showed a clear seasonal pattern with a period of growth followed by a period of stagnation. Higher abundance of seminatural habitats resulted in reducing the proportion of pollen foragers relative to all foragers in both periods, and in improving the reproductive performance of bumble bees. Interestingly, the supplemental feeding of sugar water positively affected the colony weight during the stagnation period, and the supplemental feeding of pollen mitigated the landscape effect on pollen collection investment. Single and combined supplementation of sugar water and pollen increased the positive effect of seminatural habitats on reproductive performance. This study reveals a potential colimitation in pollen and nectar resources affecting foraging behavior and reproductive performance in bumble bees, and indicates that even in mixed agricultural landscapes with higher proportions of seminatural habitats, bumble bee populations face resource limitations. We conclude that the seasonal management of floral resources must be considered in conservation to support bumble bee populations and pollination services in farmlands.},
  language  = {en}
}
@article{BeerHelfrichFoerster2020,
  author    = {Beer, Katharina and Helfrich-F{\"o}rster, Charlotte},
  title     = {Post-embryonic Development of the Circadian Clock Seems to Correlate With Social Life Style in Bees},
  series = {Frontiers in Cell and Developmental Biology},
  volume    = {8},
  journal   = {Frontiers in Cell and Developmental Biology},
  issn      = {2296-634X},
  doi       = {10.3389/fcell.2020.581323},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-216450},
  year      = {2020},
  abstract  = {Social life style can influence many aspects of an animal's daily life, but it has not yet been clarified, whether development of the circadian clock in social and solitary living bees differs. In a comparative study, with the social honey bee, Apis mellifera, and the solitary mason bee, Osmia bicornis, we now found indications for a differentially timed clock development in social and solitary bees. Newly emerged solitary bees showed rhythmic locomotion right away and the number of neurons in the brain that produce the clock component pigment-dispersing factor (PDF) did not change during aging of the adult solitary bee. Honey bees on the other hand, showed no circadian locomotion directly after emergence and the neuronal clock network continued to grow after emergence. Social bees appear to emerge at an early developmental stage at which the circadian clock is still immature, but bees are already able to fulfill in-hive tasks.},
  language  = {en}
}
@article{ClassenEardleyHempetal.2020,
  author    = {Classen, Alice and Eardley, Connal D. and Hemp, Andreas and Peters, Marcell K. and Peters, Ralph S. and Ssymank, Axel and Steffan-Dewenter, Ingolf},
  title     = {Specialization of plant-pollinator interactions increases with temperature at Mt. Kilimanjaro},
  series = {Ecology and Evolution},
  volume    = {10},
  journal   = {Ecology and Evolution},
  number    = {4},
  doi       = {10.1002/ece3.6056},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-235959},
  pages     = {2182-2195},
  year      = {2020},
  abstract  = {Aim: Species differ in their degree of specialization when interacting with other species, with significant consequences for the function and robustness of ecosystems. In order to better estimate such consequences, we need to improve our understanding of the spatial patterns and drivers of specialization in interaction networks. Methods: Here, we used the extensive environmental gradient of Mt. Kilimanjaro (Tanzania, East Africa) to study patterns and drivers of specialization, and robustness of plant-pollinator interactions against simulated species extinction with standardized sampling methods. We studied specialization, network robustness and other network indices of 67 quantitative plant-pollinator networks consisting of 268 observational hours and 4,380 plant-pollinator interactions along a 3.4 km elevational gradient. Using path analysis, we tested whether resource availability, pollinator richness, visitation rates, temperature, and/or area explain average specialization in pollinator communities. We further linked pollinator specialization to different pollinator taxa, and species traits, that is, proboscis length, body size, and species elevational ranges. Results: We found that specialization decreased with increasing elevation at different levels of biological organization. Among all variables, mean annual temperature was the best predictor of average specialization in pollinator communities. Specialization differed between pollinator taxa, but was not related to pollinator traits. Network robustness against simulated species extinctions of both plants and pollinators was lowest in the most specialized interaction networks, that is, in the lowlands. Conclusions: Our study uncovers patterns in plant-pollinator specialization along elevational gradients. Mean annual temperature was closely linked to pollinator specialization. Energetic constraints, caused by short activity timeframes in cold highlands, may force ectothermic species to broaden their dietary spectrum. Alternatively or in addition, accelerated evolutionary rates might facilitate the establishment of specialization under warm climates. Despite the mechanisms behind the patterns have yet to be fully resolved, our data suggest that temperature shifts in the course of climate change may destabilize pollination networks by affecting network architecture.},
  language  = {en}
}
@article{MatthesDiersSchlegeletal.2020,
  author    = {Matthes, Niels and Diers, Johannes and Schlegel, Nicolas and Hankir, Mohammed and Haubitz, Imme and Germer, Christoph-Thomas and Wiegering, Armin},
  title     = {Validation of MTL30 as a quality indicator for colorectal surgery},
  series = {PLoS One},
  volume    = {15},
  journal   = {PLoS One},
  number    = {8},
  doi       = {10.1371/journal.pone.0238473},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-230530},
  year      = {2020},
  abstract  = {Background Valid indicators are required to measure surgical quality. These ideally should be sensitive and selective while being easy to understand and adjust. We propose here the MTL30 quality indicator which takes into account 30-day mortality, transfer within 30 days, and a length of stay of 30 days as composite markers of an uneventful operative/postoperative course. Methods Patients documented in the StuDoQ|Colon and StuDoQ|Rectal carcinoma register of the German Society for General and Visceral Surgery (DGAV) were analyzed with regard to the effects of patient and tumor-related risk factors as well as postoperative complications on the MTL30. Results In univariate analysis, the MTL30 correlated significantly with patient and tumor-related risk factors such as ASA score (p<0.001), age (p<0.001), or UICC stage (p<0.001). There was a high sensitivity for the postoperative occurrence of complications such as re-operations (p<0.001) or subsequent bleeding (p<0.001), as well as a significant correlation with the CDC classification (p<0.001). In multivariate analysis, patient-related risk factors and postoperative complications significantly increased the odds ratio for a positive MTL30. A negative MTL30 showed a high specify for an uneventful operative and postoperative course. Conclusion The MTL30 is a valid indicator of colorectal surgical quality.},
  language  = {en}
}
@article{VoulgariKokotaSteffanDewenterKeller2020,
  author    = {Voulgari-Kokota, Anna and Steffan-Dewenter, Ingolf and Keller, Alexander},
  title     = {Susceptibility of Red Mason Bee Larvae to Bacterial Threats Due to Microbiome Exchange with Imported Pollen Provisions},
  series = {Insects},
  volume    = {11},
  journal   = {Insects},
  number    = {6},
  issn      = {2075-4450},
  doi       = {10.3390/insects11060373},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-207948},
  year      = {2020},
  abstract  = {Solitary bees are subject to a variety of pressures that cause severe population declines. Currently, habitat loss, temperature shifts, agrochemical exposure, and new parasites are identified as major threats. However, knowledge about detrimental bacteria is scarce, although they may disturb natural microbiomes, disturb nest environments, or harm the larvae directly. To address this gap, we investigated 12 Osmia bicornis nests with deceased larvae and 31 nests with healthy larvae from the same localities in a 16S ribosomal RNA (rRNA) gene metabarcoding study. We sampled larvae, pollen provisions, and nest material and then contrasted bacterial community composition and diversity in healthy and deceased nests. Microbiomes of pollen provisions and larvae showed similarities for healthy larvae, whilst this was not the case for deceased individuals. We identified three bacterial taxa assigned to Paenibacillus sp. (closely related to P. pabuli/amylolyticus/xylanexedens), Sporosarcina sp., and Bacillus sp. as indicative for bacterial communities of deceased larvae, as well as Lactobacillus for corresponding pollen provisions. Furthermore, we performed a provisioning experiment, where we fed larvae with untreated and sterilized pollens, as well as sterilized pollens inoculated with a Bacillus sp. isolate from a deceased larva. Untreated larval microbiomes were consistent with that of the pollen provided. Sterilized pollen alone did not lead to acute mortality, while no microbiome was recoverable from the larvae. In the inoculation treatment, we observed that larval microbiomes were dominated by the seeded bacterium, which resulted in enhanced mortality. These results support that larval microbiomes are strongly determined by the pollen provisions. Further, they underline the need for further investigation of the impact of detrimental bacterial acquired via pollens and potential buffering by a diverse pollen provision microbiome in solitary bees.},
  language  = {en}
}
@article{CosarinskyRoemerRoces2020,
  author    = {Cosarinsky, Marcela I. and R{\"o}mer, Daniela and Roces, Flavio},
  title     = {Nest Turrets of Acromyrmex Grass-Cutting Ants: Micromorphology Reveals Building Techniques and Construction Dynamics},
  series = {Insects},
  volume    = {11},
  journal   = {Insects},
  number    = {2},
  issn      = {2075-4450},
  doi       = {10.3390/insects11020140},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-200680},
  year      = {2020},
  abstract  = {Acromyrmex fracticornis grass-cutting ants construct conspicuous chimney-shaped nest turrets made of intermeshed grass fragments. We asked whether turrets are constructed by merely piling up nearby materials around the entrance, or whether ants incorporate different materials as the turret develops. By removing the original nest turrets and following their rebuilding process over three consecutive days, age-dependent changes in wall morphology and inner lining fabrics were characterized. Micromorphological descriptions based on thin sections of turret walls revealed the building behaviors involved. Ants started by collecting nearby twigs and dry grass fragments that are piled up around the nest entrance. Several large fragments held the structure like beams. As a net-like structure grew, soil pellets were placed in between the intermeshed plant fragments from the turret base to the top, reinforcing the structure. Concomitantly, the turret inner wall was lined with soil pellets, starting from the base. Therefore, the consolidation of the turret occurred both over time and from its base upwards. It is argued that nest turrets do not simply arise by the arbitrary deposition of nearby materials, and that workers selectively incorporate large materials at the beginning, and respond to the developing structure by reinforcing the intermeshed plant fragments over time.},
  language  = {en}
}
@article{DoerflerCadotteWeisseretal.2020,
  author    = {Doerfler, Inken and Cadotte, Marc W. and Weisser, Wolfgang W. and M{\"u}ller, J{\"o}rg and Gossner, Martin M. and Heibl, Christoph and B{\"a}ssler, Claus and Thorn, Simon and Seibold, Sebastian},
  title     = {Restoration-oriented forest management affects community assembly patterns of deadwood-dependent organisms},
  series = {Journal of Applied Ecology},
  volume    = {57},
  journal   = {Journal of Applied Ecology},
  number    = {12},
  doi       = {10.1111/1365-2664.13741},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-217918},
  pages     = {2429 -- 2440},
  year      = {2020},
  abstract  = {Land-use intensification leads to loss and degradation of habitats and is thus a major driver of biodiversity loss. Restoration strategies typically focus on promoting biodiversity but often neglect that land-use intensification could have changed the underlying mechanisms of community assembly. Since assembly mechanisms determine the diversity and composition of communities, we propose that evaluation of restoration strategies should consider effects of restoration on biodiversity and community assembly. Using a multi-taxon approach, we tested whether a strategy that promotes forest biodiversity by restoring deadwood habitats also affects assembly patterns. We assessed saproxylic (i.e. deadwood-dependent) beetles and fungi, as well as non-saproxylic plants and birds in 68 beech forest plots in southern Germany, 8 years after the commencement of a restoration project. To assess changes in community assembly, we analysed the patterns of functional-phylogenetic diversity, community-weighted mean (CWM) traits and their diversity. We hypothesized that restoration increases habitat amount and heterogeneity of deadwood and reduces canopy cover and thereby decreases the strength of environmental filters imposed by past silvicultural intensification, such as a low amount in deadwood. With the restoration of deadwood habitats, saproxylic beetle communities became less functionally-phylogenetically similar, whereas the assembly patterns of saproxylic fungi and non-saproxylic taxa remained unaffected by deadwood restoration. Among the traits analysed, deadwood diameter niche position of species was most strongly affected indicating that the enrichment of large deadwood objects led to lower functional-phylogenetical similarity of saproxylic beetles. Community assembly and traits of plants were mainly influenced by microclimate associated with changes in canopy cover. Synthesis and applications. Our results indicate that the positive effects of deadwood restoration on saproxylic beetle richness are associated with an increase in deadwood amount. This might be linked to an increase in deadwood heterogeneity, and therefore decreasing management-induced environmental filters. Deadwood enrichment can thus be considered an effective restoration strategy which reduces the negative effects of intense forest management on saproxylic taxa by not only promoting biodiversity but also by decreasing the environmental filters shaping saproxylic beetle communities, thus allowing the possibly for more interactions between species and a higher functional diversity.},
  language  = {en}
}
@article{FazeliBeerGeisenhofetal.2020,
  author    = {Fazeli, Gholamreza and Beer, Katharina B. and Geisenhof, Michaela and Tr{\"o}ger, Sarah and K{\"o}nig, Julia and M{\"u}ller-Reichert, Thomas and Wehman, Ann M.},
  title     = {Loss of the Major Phosphatidylserine or Phosphatidylethanolamine Flippases Differentially Affect Phagocytosis},
  series = {Frontiers in Cell and Developmental Biology},
  volume    = {8},
  journal   = {Frontiers in Cell and Developmental Biology},
  issn      = {2296-634X},
  doi       = {10.3389/fcell.2020.00648},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-208771},
  year      = {2020},
  abstract  = {The lipids phosphatidylserine (PtdSer) and phosphatidylethanolamine (PtdEth) are normally asymmetrically localized to the cytosolic face of membrane bilayers, but can both be externalized during diverse biological processes, including cell division, cell fusion, and cell death. Externalized lipids in the plasma membrane are recognized by lipid-binding proteins to regulate the clearance of cell corpses and other cell debris. However, it is unclear whether PtdSer and PtdEth contribute in similar or distinct ways to these processes. We discovered that disruption of the lipid flippases that maintain PtdSer or PtdEth asymmetry in the plasma membrane have opposite effects on phagocytosis in Caenorhabditis elegans embryos. Constitutive PtdSer externalization caused by disruption of the major PtdSer flippase TAT-1 led to increased phagocytosis of cell debris, sometimes leading to two cells engulfing the same debris. In contrast, PtdEth externalization caused by depletion of the major PtdEth flippase TAT-5 or its activator PAD-1 disrupted phagocytosis. These data suggest that PtdSer and PtdEth externalization have opposite effects on phagocytosis. Furthermore, externalizing PtdEth is associated with increased extracellular vesicle release, and we present evidence that the extent of extracellular vesicle accumulation correlates with the extent of phagocytic defects. Thus, a general loss of lipid asymmetry can have opposing impacts through different lipid subtypes simultaneously exerting disparate effects.},
  language  = {en}
}
@article{RothZoderZamanetal.2020,
  author    = {Roth, Nicolas and Zoder, Sebastian and Zaman, Assad Ali and Thorn, Simon and Schmidl, J{\"u}rgen},
  title     = {Long-term monitoring reveals decreasing water beetle diversity, loss of specialists and community shifts over the past 28 years},
  series = {Insect Conservation and Diversity},
  volume    = {13},
  journal   = {Insect Conservation and Diversity},
  number    = {2},
  doi       = {10.1111/icad.12411},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-214905},
  pages     = {140 -- 150},
  year      = {2020},
  abstract  = {Lentic freshwater organisms are influenced by a multitude of factors, including geomorphology, hydrology, anthropogenic impacts and climate change. Organisms that depend on patchy resources such as water beetles may also be sensitive to anthropogenic habitat degradation, like pollution, eutrophication, water level or management alteration. To assess composition and ecological trends in the water beetle communities of Central Europe, we sampled water beetles (Dytiscidae, Haliplidae, Noteridae) in 33 water bodies in Southern Germany from 1991 to 2018. We used manual, time-standardised capture during three periods: between 1991 and 1995, 2007 and 2008, and 2017 and 2018. During the 28-year survey period, we captured a total of 81 species. We found annual declines in both species number (ca -1\%) and abundance (ca -2\%). Also, community composition showed significant changes over time. The significant impact of pH on the community composition suggests that the recorded changes through time partly reflect natural succession processes. However, a pronounced decline of beetle species belonging to the moor-related beetle associations indicated that Central European water beetles are also threatened by non-successional factors, including desiccation, increased nitrogen input and/or mineralisation, and the loss of specific habitats. This trend to physiographical homogenisation resulted in corresponding community composition shifts. To effectively protect endangered species, conservation strategies need to be aimed at regularly creating new water bodies with mineralic bottom substratum, and maintenance of moor water bodies that represent late successional stages.},
  language  = {en}
}
@article{KunzGoetzGaoetal.2020,
  author    = {Kunz, Tobias C. and G{\"o}tz, Ralph and Gao, Shiqiang and Sauer, Markus and Kozjak-Pavlovic, Vera},
  title     = {Using Expansion Microscopy to Visualize and Characterize the Morphology of Mitochondrial Cristae},
  series = {Frontiers in Cell and Developmental Biology},
  volume    = {8},
  journal   = {Frontiers in Cell and Developmental Biology},
  issn      = {2296-634X},
  doi       = {10.3389/fcell.2020.00617},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-208296},
  year      = {2020},
  abstract  = {Mitochondria are double membrane bound organelles indispensable for biological processes such as apoptosis, cell signaling, and the production of many important metabolites, which includes ATP that is generated during the process known as oxidative phosphorylation (OXPHOS). The inner membrane contains folds called cristae, which increase the membrane surface and thus the amount of membrane-bound proteins necessary for the OXPHOS. These folds have been of great interest not only because of their importance for energy conversion, but also because changes in morphology have been linked to a broad range of diseases from cancer, diabetes, neurodegenerative diseases, to aging and infection. With a distance between opposing cristae membranes often below 100 nm, conventional fluorescence imaging cannot provide a resolution sufficient for resolving these structures. For this reason, various highly specialized super-resolution methods including dSTORM, PALM, STED, and SIM have been applied for cristae visualization. Expansion Microscopy (ExM) offers the possibility to perform super-resolution microscopy on conventional confocal microscopes by embedding the sample into a swellable hydrogel that is isotropically expanded by a factor of 4-4.5, improving the resolution to 60-70 nm on conventional confocal microscopes, which can be further increased to ∼ 30 nm laterally using SIM. Here, we demonstrate that the expression of the mitochondrial creatine kinase MtCK linked to marker protein GFP (MtCK-GFP), which localizes to the space between the outer and the inner mitochondrial membrane, can be used as a cristae marker. Applying ExM on mitochondria labeled with this construct enables visualization of morphological changes of cristae and localization studies of mitochondrial proteins relative to cristae without the need for specialized setups. For the first time we present the combination of specific mitochondrial intermembrane space labeling and ExM as a tool for studying internal structure of mitochondria.},
  language  = {en}
}
@article{ThornChaoBernhardtRoemermannetal.2020,
  author    = {Thorn, Simon and Chao, Anne and Bernhardt-R{\"o}mermann, Markus and Chen, Yan-Han and Georgiev, Kostadin B. and Heibl, Christoph and M{\"u}ller, J{\"o}rg and Sch{\"a}fer, Hanno and B{\"a}ssler, Claus},
  title     = {Rare species, functional groups, and evolutionary lineages drive successional trajectories in disturbed forests},
  series = {Ecology},
  volume    = {101},
  journal   = {Ecology},
  number    = {3},
  doi       = {10.1002/ecy.2949},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-212378},
  pages     = {e02949},
  year      = {2020},
  abstract  = {Following natural disturbances, additional anthropogenic disturbance may alter community recovery by affecting the occurrences of species, functional groups, and evolutionary lineages. However, our understanding of whether rare, common, or dominant species, functional groups, or evolutionary lineages are most strongly affected by an additional disturbance, particularly across multiple taxa, is limited. Here, we used a generalized diversity concept based on Hill numbers to quantify the community differences of vascular plants, bryophytes, lichens, wood-inhabiting fungi, saproxylic beetles, and birds in a storm-disturbed, experimentally salvage logged forest. Communities of all investigated species groups showed dissimilarities between logged and unlogged plots. Most species groups showed no significant changes in dissimilarities between logged and unlogged plots over the first seven years of succession, indicating a lack of community recovery. In general, the dissimilarities of communities were mainly driven by rare species. Convergence of dissimilarities occurred more often than divergence during the early stages of succession for rare species, indicating a major role in driving decreasing taxonomic dissimilarities between logged and unlogged plots over time. Trends in species dissimilarities only partially match the trends in dissimilarities of functional groups and evolutionary lineages, with little significant changes in successional trajectories. Nevertheless, common and dominant species contributed to a convergence of dissimilarities over time in the case of the functional dissimilarities of wood-inhabiting fungi. Our study shows that salvage logging following disturbances can alter successional trajectories in early stages of forest succession following natural disturbances. However, community changes over time may differ remarkably in different taxonomic groups and are best detected based on taxonomic, rather than functional or phylogenetic dissimilarities.},
  language  = {en}
}
@article{FerberGerhardsSaueretal.2020,
  author    = {Ferber, Elena and Gerhards, Julian and Sauer, Miriam and Krischke, Markus and Dittrich, Marcus T. and M{\"u}ller, Tobias and Berger, Susanne and Fekete, Agnes and Mueller, Martin J.},
  title     = {Chemical Priming by Isothiocyanates Protects Against Intoxication by Products of the Mustard Oil Bomb},
  series = {Frontiers in Plant Science},
  volume    = {11},
  journal   = {Frontiers in Plant Science},
  issn      = {1664-462X},
  doi       = {10.3389/fpls.2020.00887},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-207104},
  year      = {2020},
  abstract  = {In Brassicaceae, tissue damage triggers the mustard oil bomb i.e., activates the degradation of glucosinolates by myrosinases leading to a rapid accumulation of isothiocyanates at the site of damage. Isothiocyanates are reactive electrophilic species (RES) known to covalently bind to thiols in proteins and glutathione, a process that is not only toxic to herbivores and microbes but can also cause cell death of healthy plant tissues. Previously, it has been shown that subtoxic isothiocyanate concentrations can induce transcriptional reprogramming in intact plant cells. Glutathione depletion by RES leading to breakdown of the redox potential has been proposed as a central and common RES signal transduction mechanism. Using transcriptome analyses, we show that after exposure of Arabidopsis seedlings (grown in liquid culture) to subtoxic concentrations of sulforaphane hundreds of genes were regulated without depletion of the cellular glutathione pool. Heat shock genes were among the most highly up-regulated genes and this response was found to be dependent on the canonical heat shock factors A1 (HSFA1). HSFA1-deficient plants were more sensitive to isothiocyanates than wild type plants. Moreover, pretreatment of Arabidopsis seedlings with subtoxic concentrations of isothiocyanates increased resistance against exposure to toxic levels of isothiocyanates and, hence, may reduce the autotoxicity of the mustard oil bomb by inducing cell protection mechanisms.},
  language  = {en}
}
@article{UrbanRemmeleDittrichetal.2020,
  author    = {Urban, Lara and Remmele, Christian W. and Dittrich, Marcus and Schwarz, Roland F. and M{\"u}ller, Tobias},
  title     = {covRNA: discovering covariate associations in large-scale gene expression data},
  series = {BMC Reserach Notes},
  volume    = {13},
  journal   = {BMC Reserach Notes},
  doi       = {10.1186/s13104-020-04946-1},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-229258},
  year      = {2020},
  abstract  = {Objective The biological interpretation of gene expression measurements is a challenging task. While ordination methods are routinely used to identify clusters of samples or co-expressed genes, these methods do not take sample or gene annotations into account. We aim to provide a tool that allows users of all backgrounds to assess and visualize the intrinsic correlation structure of complex annotated gene expression data and discover the covariates that jointly affect expression patterns. Results The Bioconductor package covRNA provides a convenient and fast interface for testing and visualizing complex relationships between sample and gene covariates mediated by gene expression data in an entirely unsupervised setting. The relationships between sample and gene covariates are tested by statistical permutation tests and visualized by ordination. The methods are inspired by the fourthcorner and RLQ analyses used in ecological research for the analysis of species abundance data, that we modified to make them suitable for the distributional characteristics of both, RNA-Seq read counts and microarray intensities, and to provide a high-performance parallelized implementation for the analysis of large-scale gene expression data on multi-core computational systems. CovRNA provides additional modules for unsupervised gene filtering and plotting functions to ensure a smooth and coherent analysis workflow.},
  language  = {en}
}
@article{GromaHorstDasetal.2020,
  author    = {Groma, Michaela and Horst, Sarah A. and Das, Sudip and Huettel, Bruno and Klepsch, Maximilian and Rudel, Thomas and Medina, Eva and Fraunholz, Martin},
  title     = {Identification of a Novel LysR-Type Transcriptional Regulator in Staphylococcus aureus That Is Crucial for Secondary Tissue Colonization during Metastatic Bloodstream Infection},
  series = {mbio},
  volume    = {11},
  journal   = {mbio},
  number    = {4},
  doi       = {10.1128/mBio.01646-20},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-230473},
  year      = {2020},
  abstract  = {Staphylococcus aureus is a common cause of bacteremia that can lead to severe complications once the bacteria exit the bloodstream and establish infection in secondary organs. Despite its clinical relevance, little is known about the bacterial factors facilitating the development of these metastatic infections. Here, we used an S. aureus transposon mutant library coupled to transposon insertion sequencing (Tn-Seq) to identify genes that are critical for efficient bacterial colonization of secondary organs in a murine model of metastatic bloodstream infection. Our transposon screen identified a LysR-type transcriptional regulator (LTTR), which was required for efficient colonization of secondary organs such as the kidneys in infected mice. The critical role of LTTR in secondary organ colonization was confirmed using an isogenic mutant deficient in the expression of LTTR. To identify the set of genes controlled by LTTR, we used an S. aureus strain carrying the LTTR gene in an inducible expression plasmid. Gene expression analysis upon induction of LTTR showed increased transcription of genes involved in branched-chain amino acid biosynthesis, a methionine sulfoxide reductase, and a copper transporter as well as decreased transcription of genes coding for urease and components of pyrimidine nucleotides. Furthermore, we show that transcription of LTTR is repressed by glucose, is induced under microaerobic conditions, and required trace amounts of copper ions. Our data thus pinpoints LTTR as an important element that enables a rapid adaptation of S. aureus to the changing host microenvironment. IMPORTANCE Staphylococcus aureus is an important pathogen that can disseminate via the bloodstream and establish metastatic infections in distant organs. To achieve a better understanding of the bacterial factors facilitating the development of these metastatic infections, we used in this study a Staphylococcus aureus transposon mutant library in a murine model of intravenous infection, where bacteria first colonize the liver as the primary infection site and subsequently progress to secondary sites such as the kidney and bones. We identified a novel LysR-type transcriptional regulator (LTTR), which was specifically required by S. aureus for efficient colonization of secondary organs. We also determined the transcriptional activation as well as the regulon of LTTR, which suggests that this regulator is involved in the metabolic adaptation of S. aureus to the host microenvironment found in secondary infection sites.},
  language  = {en}
}
@article{PetrovGentschevVyalkovaetal.2020,
  author    = {Petrov, Ivan and Gentschev, Ivaylo and Vyalkova, Anna and Elashry, Mohamed I. and Klymiuk, Michele C. and Arnhold, Stefan and Szalay, Aladar A.},
  title     = {Canine Adipose-Derived Mesenchymal Stem Cells (cAdMSCs) as a "Trojan Horse" in Vaccinia Virus Mediated Oncolytic Therapy against Canine Soft Tissue Sarcomas},
  series = {Viruses},
  volume    = {12},
  journal   = {Viruses},
  number    = {7},
  doi       = {10.3390/v12070750},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-236007},
  year      = {2020},
  abstract  = {Several oncolytic viruses (OVs) including various human and canine adenoviruses, canine distemper virus, herpes-simplex virus, reovirus, and members of the poxvirus family, such as vaccinia virus and myxoma virus, have been successfully tested for canine cancer therapy in preclinical and clinical settings. The success of the cancer virotherapy is dependent on the ability of oncolytic viruses to overcome the attacks of the host immune system, to preferentially infect and lyse cancer cells, and to initiate tumor-specific immunity. To date, several different strategies have been developed to overcome the antiviral host defense barriers. In our study, we used canine adipose-derived mesenchymal stem cells (cAdMSCs) as a "Trojan horse" for the delivery of oncolytic vaccinia virus Copenhagen strain to achieve maximum oncolysis against canine soft tissue sarcoma (CSTS) tumors. A single systemic administration of vaccinia virus-loaded cAdMSCs was found to be safe and led to the significant reduction and substantial inhibition of tumor growth in a CSTS xenograft mouse model. This is the first example that vaccinia virus-loaded cAdMSCs could serve as a therapeutic agent against CSTS tumors.},
  language  = {en}
}
@phdthesis{Glaab2020,
  author    = {Glaab, Sabine},
  title     = {Green classroom at the wildlife park: Aspects of environmental, instructional and conceptual education of primary school children concerning the European wildcat.},
  doi       = {10.25972/OPUS-16949},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-169496},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2020},
  abstract  = {To foster sustainable environmentally friendly behavior in children it is important to provide an effective form of environmental education. In this context we studied three important factors: Attitude towards nature, environmental knowledge and advanced expert knowledge. Concerning attitude towards nature our first question was: "Is it possible to affect primary school children's environmental values during a one-day visit at a wildlife park?" As a control, the program was also conducted in schools, leading to two different learning settings- wildlife park and school. Regarding environmental knowledge, in our second question we wanted to know, if our modified teaching approach "guided learning at workstations" (G) combining instructional and constructivist elements would lead to good cognitive learning results of primary school children. Additionally, we compared it to a stronger teacher-centered (T) as well as to a stronger student-centered (S) approach. The third question we asked was "Is it possible to convey fascinating expert knowledge on a more advanced subject to primary school children using conceptual change theory?" After gathering primary school children's preconceptions, we defined different groups due to the heterogeneity of their pre-existing conceptions and the change in conceptions. Based on this research we designed a program along with an instrument to measure the impact of the conceptual change teaching method. After years of building a strong cooperation between the section Didactics of Biology at the Julius-Maximilians University W{\"u}rzburg, the nearby schools and the wildlife park "Wild-Park Klaushof" near Bad Kissingen in northern Bavaria it was time to evaluate the environmental education programs prepared and applied by undergraduate university students. As a model species we chose the European wildcat (Felis silvestris silvestris) which represents endangered wildlife in Europe and the need for human interaction for the sake of preserving a species by restoring or recreating the habitat conditions needed while maintaining current infrastructure. Drawing from our own as well as teachers' and university students' experiences, we built, implemented and evaluated a hands-on program following several workstations between the wildcat enclosure and the wildlife park's green classroom. The content of our intervention was presented as a problem-oriented lesson, where children were confronted with the need for human interaction in order to preserve the European wildcat. Not only on a theoretical basis, but very specific to their hometowns they were told where and when nature conservation groups met or where to donate money. 692 Bavarian third grade primary school children in 35 classes participated in the one-day intervention that took place between the months of april, 2014 and november, 2015 in the wildlife park or in their respective classrooms. The ages varied between 8 and 11 years with the mean age being 8.88 ± 0.56 years old. 48.6 \% of them were boys, 51.4 \% were girls. (1) To measure primary school children's environmental attitudes a questionnaire on two major environmental values- preservation and utilization of nature- was administered in a pre, post- and retention test design. It was possible to affect primary school children's environmental preservation values during our one-day program. This result could be found not only at the wildlife park but unexpectedly also in school, where we educated classes for control purposes. We also found this impact consistent in all used teaching approaches and were surprised to see the preservation values change in a way we did not expect from higher tendency towards preservation of nature to a lower one. We presume that children of this age group reflected on the contents of our intervention. This had an influence on their own values towards preservation which led to a more realistic marking behavior in the questionnaire. We therefore conclude that it is possible to affect primary school children's environmental values with a one-day program on environmental content. (2) We were interested in conveying environmental knowledge about the European wildcat; its morphology, ecology and behavior. We designed and applied a knowledge questionnaire also in a pre-, post- and retention test design, to find out, whether different forms of instruction made a difference in learning success of primary school children. We used two approaches with a teacher in the role of a didactic leader- our modified guided approach (G) as well as a stronger teacher-centered one (T) with a higher focus on instruction. The third approach was presented as a strong student-centered learning at workstations (S) without a didactic leader we also called "free learning at workstations". Overall, all children's knowledge scores changed significantly from pre- to post-test and from pre- to retention test, indicating learning success. Differences could only be found between the posttest values of both approaches with a didactic leader (G, T) in comparison to the strong student-centered (S) form. It appears that these primary school children gained knowledge at the out of school learning setting regardless of the used teaching approach. On the subject of short-term differences, we discuss, that the difference in learning success might have been consistent from post to retention test if a consolidation phase had been added in the days following the program as should be common practice after a visit to an out-of- school learning setting but was not part of our intervention. When comparing both approaches with a didactic leader (G, T), we prefer our modified guided learning at workstations (G) since constructivist phases can be implemented without losses concerning learning success. Moreover, the (at least temporary) presence of a teacher in the role of a didactic leader ensures maintained discipline and counteracts off-task behavior. To make sure, different emotional states did not factor in our program, we measured children's situational emotions directly after the morning intervention using a short scale that evaluated interest, wellbeing and boredom. We found, that these emotions remained consistent over both learning settings as well as different forms of instruction. While interest and wellbeing remained constantly high, boredom values remained low. We take this as a sign of high quality designing and conducting the intervention. (3) In the afternoon of the one-day intervention, children were given the opportunity to investigate the wildcat further, this time using the conceptual change theory in combination with a more complex and fascinating content: cats' vision in dusk and dawn. Children were confronted with their preconceptions which had been sampled prior to the study and turned into three distinctive topics reflected in a special questionnaire. In a pre-, post and retention test design we included the most common alternative conceptions, the scientifically correct conceptions as well as other preconceptions. We gathered a high heterogeneity of preconceptions and defined three groups based on conceptual change literature: "Conceptual change", "Synthetic Models" and "Conceptual Growth". In addition to these we identified two more groups after our data analysis: "Knowledge" and "Non-addressed Concepts". We found that instruction according to the conceptual change theory did not work with primary school children in our intervention. The conceptual change from the addressed alternative conceptions as well as from other preconceptions towards the scientifically correct conceptions was successfully achieved only on occasion. In our case and depending on the topic only one third to one fourth of the children actually held the addressed conception while the rest was not targeted by the instruction. Moreover, we conclude children holding other conceptions were rather confused than educated by the confrontation. We assume that children of this age group may be overchallenged by the conceptual change method.},
  subject      = {Biologie},
  language  = {en}
}
@article{DollVonaSchnappetal.2020,
  author    = {Doll, Julia and Vona, Barbara and Schnapp, Linda and R{\"u}schendorf, Franz and Khan, Imran and Khan, Saadullah and Muhammad, Noor and Alam Khan, Sher and Nawaz, Hamed and Khan, Ajmal and Ahmad, Naseer and Kolb, Susanne M. and K{\"u}hlewein, Laura and Labonne, Jonathan D. J. and Layman, Lawrence C. and Hofrichter, Michaela A. H. and R{\"o}der, Tabea and Dittrich, Marcus and M{\"u}ller, Tobias and Graves, Tyler D. and Kong, Il-Keun and Nanda, Indrajit and Kim, Hyung-Goo and Haaf, Thomas},
  title     = {Genetic Spectrum of Syndromic and Non-Syndromic Hearing Loss in Pakistani Families},
  series = {Genes},
  volume    = {11},
  journal   = {Genes},
  number    = {11},
  issn      = {2073-4425},
  doi       = {10.3390/genes11111329},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-219293},
  year      = {2020},
  abstract  = {The current molecular genetic diagnostic rates for hereditary hearing loss (HL) vary considerably according to the population background. Pakistan and other countries with high rates of consanguineous marriages have served as a unique resource for studying rare and novel forms of recessive HL. A combined exome sequencing, bioinformatics analysis, and gene mapping approach for 21 consanguineous Pakistani families revealed 13 pathogenic or likely pathogenic variants in the genes GJB2, MYO7A, FGF3, CDC14A, SLITRK6, CDH23, and MYO15A, with an overall resolve rate of 61.9\%. GJB2 and MYO7A were the most frequently involved genes in this cohort. All the identified variants were either homozygous or compound heterozygous, with two of them not previously described in the literature (15.4\%). Overall, seven missense variants (53.8\%), three nonsense variants (23.1\%), two frameshift variants (15.4\%), and one splice-site variant (7.7\%) were observed. Syndromic HL was identified in five (23.8\%) of the 21 families studied. This study reflects the extreme genetic heterogeneity observed in HL and expands the spectrum of variants in deafness-associated genes.},
  language  = {en}
}
@phdthesis{Lakovic2020,
  author    = {Lakovic, Milica},
  title     = {Evolution of animal dispersal: Putting timing in perspective},
  doi       = {10.25972/OPUS-15452},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-154522},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2020},
  abstract  = {Dispersal is a life-history trait affecting dynamics and persistence of populations; it evolves under various known selective pressures. Theoretical studies on dispersal typically assume 'natal dispersal', where individuals emigrate right after birth. But emigration may also occur during a later moment within a reproductive season ('breeding dispersal'). For example, some female butterflies first deposit eggs in their natal patch before migrating to other site(s) to continue egg-laying there. How breeding compared to natal dispersal influences the evolution of dispersal has not been explored. To close this gap we used an individual-based simulation approach to analyze (i) the evolution of timing of breeding dispersal in annual organisms, (ii) its influence on dispersal (compared to natal dispersal). Furthermore, we tested (iii) its performance in direct evolutionary contest with individuals following a natal dispersal strategy. Our results show that evolution should typically result in lower dispersal under breeding dispersal, especially when costs of dispersal are low and population size is small. By distributing offspring evenly across two patches, breeding dispersal allows reducing direct sibling competition in the next generation whereas natal dispersal can only reduce trans-generational kin competition by producing highly dispersive offspring in each generation. The added benefit of breeding dispersal is most prominent in patches with small population sizes. Finally, the evolutionary contests show that a breeding dispersal strategy would universally out-compete natal dispersal.},
  language  = {en}
}
@article{WeissSchlegelTerpitzetal.2020,
  author    = {Weiss, Esther and Schlegel, Jan and Terpitz, Ulrich and Weber, Michael and Linde, J{\"o}rg and Schmitt, Anna-Lena and H{\"u}nniger, Kerstin and Marischen, Lothar and Gamon, Florian and Bauer, Joachim and L{\"o}ffler, Claudia and Kurzai, Oliver and Morton, Charles Oliver and Sauer, Markus and Einsele, Hermann and Loeffler, Juergen},
  title     = {Reconstituting NK Cells After Allogeneic Stem Cell Transplantation Show Impaired Response to the Fungal Pathogen Aspergillus fumigatus},
  series = {Frontiers in Immunology},
  volume    = {11},
  journal   = {Frontiers in Immunology},
  issn      = {1664-3224},
  doi       = {10.3389/fimmu.2020.02117},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-212581},
  year      = {2020},
  abstract  = {Delayed natural killer (NK) cell reconstitution after allogeneic stem cell transplantation (alloSCT) is associated with a higher risk of developing invasive aspergillosis. The interaction of NK cells with the human pathogen Aspergillus (A.) fumigatus is mediated by the fungal recognition receptor CD56, which is relocated to the fungal interface after contact. Blocking of CD56 signaling inhibits the fungal mediated chemokine secretion of MIP-1α, MIP-1β, and RANTES and reduces cell activation, indicating a functional role of CD56 in fungal recognition. We collected peripheral blood from recipients of an allograft at defined time points after alloSCT (day 60, 90, 120, 180). NK cells were isolated, directly challenged with live A. fumigatus germ tubes, and cell function was analyzed and compared to healthy age and gender-matched individuals. After alloSCT, NK cells displayed a higher percentage of CD56\(^{bright}\)CD16\(^{dim}\) cells throughout the time of blood collection. However, CD56 binding and relocalization to the fungal contact side were decreased. We were able to correlate this deficiency to the administration of corticosteroid therapy that further negatively influenced the secretion of MIP-1α, MIP-1β, and RANTES. As a consequence, the treatment of healthy NK cells ex vivo with corticosteroids abrogated chemokine secretion measured by multiplex immunoassay. Furthermore, we analyzed NK cells regarding their actin cytoskeleton by Structured Illumination Microscopy (SIM) and flow cytometry and demonstrate an actin dysfunction of NK cells shown by reduced F-actin content after fungal co-cultivation early after alloSCT. This dysfunction remains until 180 days post-alloSCT, concluding that further actin-dependent cellular processes may be negatively influenced after alloSCT. To investigate the molecular pathomechansism, we compared CD56 receptor mobility on the plasma membrane of healthy and alloSCT primary NK cells by single-molecule tracking. The results were very robust and reproducible between tested conditions which point to a different molecular mechanism and emphasize the importance of proper CD56 mobility.},
  language  = {en}
}
@article{SiegerHovestadt2020,
  author    = {Sieger, Charlotte Sophie and Hovestadt, Thomas},
  title     = {The degree of spatial variation relative to temporal variation influences evolution of dispersal},
  series = {Oikos},
  volume    = {129},
  journal   = {Oikos},
  number    = {11},
  doi       = {10.1111/oik.07567},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-239049},
  pages     = {1611 -- 1622},
  year      = {2020},
  abstract  = {In the face of ongoing global climate and land use change, organisms have multiple possibilities to cope with the modification of their environment. The two main possibilities are to either adapt locally or disperse to a more suitable habitat. The evolution of both local adaptation and dispersal interacts and can be influenced by the spatial and temporal variation (of e.g. temperature or precipitation). In an individual based model (IBM), we explore evolution of phenotypes in landscapes with varying degree of spatial relative to global temporal variation in order to examine its influence on the evolution of dispersal, niche optimum and niche width. The relationship between temporal and spatial variation did neither influence the evolution of local adaptation in the niche optimum nor of niche widths. Dispersal probability is highly influenced by the spatio-temporal relationship: with increasing spatial variation, dispersal probability decreases. Additionally, the shape of the distribution of the trait values over patch attributes switches from hump- to U-shaped. At low spatial variance more individuals emigrate from average habitats, at high spatial variance more from extreme habitats. The comparatively high dispersal probability in extreme patches of landscapes with a high spatial variation can be explained by evolutionary succession of two kinds of adaptive response. Early in the simulations, extreme patches in landscapes with a high spatial variability act as sink habitats, where population persistence depends on highly dispersive individuals with a wide niche. With ongoing evolution, local adaptation of the remaining individuals takes over, but simultaneously a possible bet-hedging strategy promotes higher dispersal probabilities in those habitats. Here, in generations that experience extreme shifts from the temporal mean of the patch attribute, the expected fitness becomes higher for dispersing individuals than for philopatric individuals. This means that under certain circumstances, both local adaptation and high dispersal probability can be selected for for coping with the projected environmental changes in the future.},
  language  = {en}
}
@article{BoffHenriqueFriedeletal.2020,
  author    = {Boff, Samuel and Henrique, Jessica Amaral and Friedel, Anna and Raizer, Josu{\´e}},
  title     = {Disentangling the path of pollinator attraction in temporarily colored flowers},
  series = {International Journal of Tropical Insect Science},
  volume    = {41},
  journal   = {International Journal of Tropical Insect Science},
  doi       = {10.1007/s42690-020-00323-4},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-235402},
  pages     = {1305-1311},
  year      = {2020},
  abstract  = {Plants may use different strategies to attract pollinators in long distance (e.g. floral display) and in short distance (e.g. ratio between differentially colored flowers) scales. The Verbenaceae Lantana canescens Kunth is a wide spread species in open sites of the Brazilian Pantanal wetland. Individuals of this generalist species can produce a variable number of open inflorescences with yellow and white flowers that are organized in whorls. In this study we tested the hypothesis that increased floral display (long distance attraction) and the ratio between yellow and white flowers (short distance attraction) enhances the number of pollinator species and individuals. We observed flower visitors and calculated floral parameters in 38 plots of 1 m2 each, that contained a varying number of flowering L. canescens individuals. Non-metric multidimensional scaling and Bray-Curtis distances were used to account for flower visitor composition and the relative visitation rate, respectively. We used a structural equation model to test the power of each predictor variable on the visitation rate and a covariance analysis to disentangle the effect of each independent variable on the frequency of plant-pollinator interactions. We found that the number of flower visitors and the visitation rate increased with increasing number of inflorescences. Disentangling long and short distance attraction indicated that the number of inflorescences (per plot) and the number of yellow flowers (yellowing effect) contributed most to flower visitation at long and short distance, respectively.},
  language  = {en}
}
@phdthesis{Kaltdorf2020,
  author    = {Kaltdorf, Martin Ernst},
  title     = {Analyse von regulatorischen Netzwerken bei Zelldifferenzierung und in der Infektionsbiologie},
  doi       = {10.25972/OPUS-19852},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-198526},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2020},
  abstract  = {Das zentrale Paradigma der Systembiologie zielt auf ein m{\"o}glichst umfassendes Ver-st{\"a}ndnis der komplexen Zusammenh{\"a}nge biologischer Systeme. Die in dieser Arbeit angewandten Methoden folgen diesem Grundsatz. Am Beispiel von drei auf Basis von Datenbanken und aktueller Literatur rekonstruier-ten Netzwerkmodellen konnte in der hier vorliegenden Arbeit die G{\"u}ltigkeit analyti-scher und pr{\"a}diktiver Algorithmen nachgewiesen werden, die in Form der Analy-sesoftware Jimena angewandt wurden. Die daraus resultierenden Ergebnisse sowohl f{\"u}r die Berechnung von stabilen Systemzust{\"a}nden, der dynamischen Simulation, als auch der Identifikation zentraler Kontrollknoten konnten experimentell validiert wer-den. Die Ergebnisse wurden in einem iterativen Prozess verwendet werden um das entsprechende Netzwerkmodell zu optimieren. Beim Vergleich des Verhaltens des semiquantitativ ausgewerteten regulatorischen Netzwerks zur Kontrolle der Differenzierung humaner mesenchymaler Stammzellen in Chondrozyten (Knorpelbildung), Osteoblasten (Knochenbildung) und Adipozyten (Fett-zellbildung) konnten 12 wichtige Faktoren (darunter: RUNX2, OSX/SP7, SOX9, TP53) mit Hilfe der Berechnung der Bedeutung (Kontrollzentralit{\"a}t der Netzwerkknoten identifi-ziert werden). Der Abgleich des simulierten Verhaltens dieses Netzwerkes ergab eine {\"U}bereinstimmung mit experimentellen Daten von 47,2\%, bei einem widerspr{\"u}chlichen Verhalten von ca. 25\%, dass unter anderem durch die tempor{\"a}re Natur experimentel-ler Messungen im Vergleich zu den terminalen Bedingungen des Berechnung der stabilen Systemzust{\"a}nde erkl{\"a}rt werden kann. Bei der Analyse des Netzwerkmodells der menschlichen Immunantwort auf eine Infek-tion durch A. fumigatus konnten vier Hauptregulatoren identifiziert werden (A. fumi-gatus, Blutpl{\"a}ttchen, hier Platelets genannt, und TNF), die im Zusammenspiel mit wei-teren Faktoren mit hohen Zentralit{\"a}tswerten (CCL5, IL1, IL6, Dectin-1, TLR2 und TLR4) f{\"a}hig sind das gesamte Netzwerkverhalten zu beeinflussen. Es konnte gezeigt werden, dass sich das Aktivit{\"a}tsverhalten von IL6 in Reaktion auf A. fumigatus und die regulato-rische Wirkung von Blutpl{\"a}ttchen mit den entsprechenden experimentellen Resultaten deckt. Die Simulation, sowie die Berechnung der stabilen Systemzust{\"a}nde der Immunantwort von A. thaliana auf eine Infektion durch Pseudomonas syringae konnte zeigen, dass die in silico Ergebnisse mit den experimentellen Ergebnissen {\"u}bereinstimmen. Zus{\"a}tzlich konnten mit Hilfe der Analyse der Zentralit{\"a}tswerte des Netzwerkmodells f{\"u}nf Master-regulatoren identifiziert werden: TGA Transkriptionsfaktor, Jasmons{\"a}ure, Ent-Kaurenoate-Oxidase, Ent-kaurene-Synthase und Aspartat-Semialdehyd-Dehydrogenase. W{\"a}hrend die ersteren beiden bereits lange als wichtige Regulatoren f{\"u}r die Gib-berellin-Synthese bekannt sind, ist die immunregulatorische Funktion von Aspartat-Semialdehyd-Dehydrogenase bisher weitgehend unbekannt.},
  subject      = {Netzwerksimulation},
  language  = {de}
}
@article{FlorenvonRintelenHerbertetal.2020,
  author    = {Floren, Andreas and von Rintelen, Thomas and Herbert, Paul D. N. and de Araujo, Bruno Cancian and Schmidt, Stefan and Balke, Michael and Narakusumo, Raden Pramesa and Peggie, Djunijanti and Ubaidillah, Rosichon and von Rintelen, Kristina and M{\"u}ller, Tobias},
  title     = {Integrative ecological and molecular analysis indicate high diversity and strict elevational separation of canopy beetles in tropical mountain forests},
  series = {Scientific Reports},
  volume    = {10},
  journal   = {Scientific Reports},
  doi       = {10.1038/s41598-020-73519-w},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-230565},
  year      = {2020},
  abstract  = {Tropical mountain forests contribute disproportionately to terrestrial biodiversity but little is known about insect diversity in the canopy and how it is distributed between tree species. We sampled tree-specific arthropod communities from 28 trees by canopy fogging and analysed beetle communities which were first morphotyped and then identified by their DNA barcodes. Our results show that communities from forests at 1100 and 1700 m a.s.l. are almost completely distinct. Diversity was much lower in the upper forest while community structure changed from many rare, less abundant species to communities with a pronounced dominance structure. We also found significantly higher beta-diversity between trees at the lower than higher elevation forest where community similarity was high. Comparisons on tree species found at both elevations reinforced these results. There was little species overlap between sites indicating limited elevational ranges. Furthermore, we exploited the advantage of DNA barcodes to patterns of haplotype diversity in some of the commoner species. Our results support the advantage of fogging and DNA barcodes for community studies and underline the need for comprehensive research aimed at the preservation of these last remaining pristine forests.},
  language  = {en}
}
@article{GoetzKunzFinketal.2020,
  author    = {G{\"o}tz, Ralph and Kunz, Tobias C. and Fink, Julian and Solger, Franziska and Schlegel, Jan and Seibel, J{\"u}rgen and Kozjak-Pavlovic, Vera and Rudel, Thomas and Sauer, Markus},
  title     = {Nanoscale imaging of bacterial infections by sphingolipid expansion microscopy},
  series = {Nature Communications},
  volume    = {11},
  journal   = {Nature Communications},
  doi       = {10.1038/s41467-020-19897-1},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-231248},
  year      = {2020},
  abstract  = {Expansion microscopy (ExM) enables super-resolution imaging of proteins and nucleic acids on conventional microscopes. However, imaging of details of the organization of lipid bilayers by light microscopy remains challenging. We introduce an unnatural short-chain azide- and amino-modified sphingolipid ceramide, which upon incorporation into membranes can be labeled by click chemistry and linked into hydrogels, followed by 4x to 10x expansion. Confocal and structured illumination microscopy (SIM) enable imaging of sphingolipids and their interactions with proteins in the plasma membrane and membrane of intracellular organelles with a spatial resolution of 10-20nm. As our functionalized sphingolipids accumulate efficiently in pathogens, we use sphingolipid ExM to investigate bacterial infections of human HeLa229 cells by Neisseria gonorrhoeae, Chlamydia trachomatis and Simkania negevensis with a resolution so far only provided by electron microscopy. In particular, sphingolipid ExM allows us to visualize the inner and outer membrane of intracellular bacteria and determine their distance to 27.6 +/- 7.7nm. Imaging of lipid bilayers using light microscopy is challenging. Here the authors label cells using a short chain click-compatible ceramide to visualize mammalian and bacterial membranes with expansion microscopy.},
  language  = {en}
}
@article{DiersWagnerBaumetal.2020,
  author    = {Diers, J. and Wagner, J. and Baum, P. and Lichthardt, S. and Kastner, C. and Matthes, N. and Matthes, H. and Germer, C.-T. and L{\"o}b, S. and Wiegering, A.},
  title     = {Nationwide in-hospital mortality rate following rectal resection for rectal cancer according to annual hospital volume in Germany},
  series = {BJS Open},
  volume    = {4},
  journal   = {BJS Open},
  number    = {2},
  doi       = {10.1002/bjs5.50254},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-212878},
  pages     = {310 -- 319},
  year      = {2020},
  abstract  = {Background The impact of hospital volume after rectal cancer surgery is seldom investigated. This study aimed to analyse the impact of annual rectal cancer surgery cases per hospital on postoperative mortality and failure to rescue. Methods All patients diagnosed with rectal cancer and who had a rectal resection procedure code from 2012 to 2015 were identified from nationwide administrative hospital data. Hospitals were grouped into five quintiles according to caseload. The absolute number of patients, postoperative deaths and failure to rescue (defined as in-hospital mortality after a documented postoperative complication) for severe postoperative complications were determined. Results Some 64 349 patients were identified. The overall in-house mortality rate was 3·9 per cent. The crude in-hospital mortality rate ranged from 5·3 per cent in very low-volume hospitals to 2·6 per cent in very high-volume centres, with a distinct trend between volume categories (P < 0·001). In multivariable logistic regression analysis using hospital volume as random effect, very high-volume hospitals (53 interventions/year) had a risk-adjusted odds ratio of 0·58 (95 per cent c.i. 0·47 to 0·73), compared with the baseline in-house mortality rate in very low-volume hospitals (6 interventions per year) (P < 0·001). The overall postoperative complication rate was comparable between different volume quintiles, but failure to rescue decreased significantly with increasing caseload (15·6 per cent after pulmonary embolism in the highest volume quintile versus 38 per cent in the lowest quintile; P = 0·010). Conclusion Patients who had rectal cancer surgery in high-volume hospitals showed better outcomes and reduced failure to rescue rates for severe complications than those treated in low-volume hospitals.},
  language  = {en}
}
@article{PolidoriBallesterosWurdacketal.2020,
  author    = {Polidori, Carlo and Ballesteros, Yolanda and Wurdack, Mareike and As{\´i}s, Josep Daniel and Tormos, Jos{\´e} and Ba{\~n}os-Pic{\´o}n, Laura and Schmitt, Thomas},
  title     = {Low host specialization in the cuckoo wasp, Parnopes grandior, weakens chemical mimicry but does not lead to local adaption},
  series = {Insects},
  volume    = {11},
  journal   = {Insects},
  number    = {2},
  issn      = {2075-4450},
  doi       = {10.3390/insects11020136},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-200651},
  year      = {2020},
  abstract  = {Insect brood parasites have evolved a variety of strategies to avoid being detected by their hosts. Few previous studies on cuckoo wasps (Hymenoptera: Chrysididae), which are natural enemies of solitary wasps and bees, have shown that chemical mimicry, i.e., the biosynthesis of cuticular hydrocarbons (CHC) that match the host profile, evolved in several species. However, mimicry was not detected in all investigated host-parasite pairs. The effect of host range as a second factor that may play a role in evolution of mimicry has been neglected, since all previous studies were carried out on host specialists and at nesting sites where only one host species occurred. Here we studied the cuckoo wasp Parnopes grandior, which attacks many digger wasp species of the genus Bembix (Hymenoptera: Crabronidae). Given its weak host specialization, P. grandior may either locally adapt by increasing mimicry precision to only one of the sympatric hosts or it may evolve chemical insignificance by reducing the CHC profile complexity and/or CHCs amounts. At a study site harbouring three host species, we found evidence for a weak but appreciable chemical deception strategy in P. grandior. Indeed, the CHC profile of P. grandior was more similar to all sympatric Bembix species than to a non-host wasp species belonging to the same tribe as Bembix. Furthermore, P. grandior CHC profile was equally distant to all the hosts' CHC profiles, thus not pointing towards local adaptation of the CHC profile to one of the hosts' profile. We conducted behavioural assays suggesting that such weak mimicry is sufficient to reduce host aggression, even in absence of an insignificance strategy, which was not detected. Hence, we finally concluded that host range may indeed play a role in shaping the level of chemical mimicry in cuckoo wasps.},
  language  = {en}
}
@article{RablAlonsoRodriguezBrehmetal.2020,
  author    = {Rabl, Dominik and Alonso-Rodr{\´i}guez, Aura M. and Brehm, Gunnar and Fiedler, Konrad},
  title     = {Trait variation in moths mirrors small-scaled ecological gradients in a tropical forest landscape},
  series = {Insects},
  volume    = {11},
  journal   = {Insects},
  number    = {9},
  issn      = {2075-4450},
  doi       = {10.3390/insects11090612},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-213016},
  year      = {2020},
  abstract  = {Along environmental gradients, communities are expected to be filtered from the regional species pool by physical constraints, resource availability, and biotic interactions. This should be reflected in species trait composition. Using data on species-rich moth assemblages sampled by light traps in a lowland rainforest landscape in Costa Rica, we show that moths in two unrelated clades (Erebidae-Arctiinae; Geometridae) are much smaller-sized in oil palm plantations than in nearby old-growth forest, with intermediate values at disturbed forest sites. In old-growth forest, Arctiinae predominantly show aposematic coloration as a means of anti-predator defense, whereas this trait is much reduced in the prevalence in plantations. Similarly, participation in M{\"u}llerian mimicry rings with Hymenoptera and Lycidae beetles, respectively, is rare in plantations. Across three topographic types of old-growth forests, community-weighted means of moth traits showed little variation, but in creek forest, both types of mimicry were surprisingly rare. Our results emphasize that despite their mobility, moth assemblages are strongly shaped by local environmental conditions through the interplay of bottom-up and top-down processes. Assemblages in oil palm plantations are highly degraded not only in their biodiversity, but also in terms of trait expression.},
  language  = {en}
}
@article{ScheinerStraussThammetal.2020,
  author    = {Scheiner, Ricarda and Strauß, Sina and Thamm, Markus and Farr{\´e}-Armengol, Gerard and Junker, Robert R.},
  title     = {The bacterium Pantoea ananatis modifies behavioral responses to sugar solutions in honeybees},
  series = {Insects},
  volume    = {11},
  journal   = {Insects},
  number    = {10},
  issn      = {2075-4450},
  doi       = {10.3390/insects11100692},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-216247},
  year      = {2020},
  abstract  = {1. Honeybees, which are among the most important pollinators globally, do not only collect pollen and nectar during foraging but may also disperse diverse microbes. Some of these can be deleterious to agricultural crops and forest trees, such as the bacterium Pantoea ananatis, an emerging pathogen in some systems. P. ananatis infections can lead to leaf blotches, die-back, bulb rot, and fruit rot. 2. We isolated P. ananatis bacteria from flowers with the aim of determining whether honeybees can sense these bacteria and if the bacteria affect behavioral responses of the bees to sugar solutions. 3. Honeybees decreased their responsiveness to different sugar solutions when these contained high concentrations of P. ananatis but were not deterred by solutions from which bacteria had been removed. This suggests that their reduced responsiveness was due to the taste of bacteria and not to the depletion of sugar in the solution or bacteria metabolites. Intriguingly, the bees appeared not to taste ecologically relevant low concentrations of bacteria. 4. Synthesis and applications. Our data suggest that honeybees may introduce P.ananatis bacteria into nectar in field-realistic densities during foraging trips and may thus affect nectar quality and plant fitness.},
  language  = {en}
}
@article{VenjakobLeonhardtKlein2020,
  author    = {Venjakob, Christine and Leonhardt, Sara and Klein, Alexandra-Maria},
  title     = {Inter-individual nectar chemistry changes of field scabious, Knautia arvensis},
  series = {Insects},
  volume    = {11},
  journal   = {Insects},
  number    = {2},
  issn      = {2075-4450},
  doi       = {10.3390/insects11020075},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-200866},
  year      = {2020},
  abstract  = {Nectar is crucial to maintain plant-pollinator mutualism. Nectar quality (nutritional composition) can vary strongly between individuals of the same plant species. The factors driving such inter-individual variation have however not been investigated closer. We investigated nectar quality of field scabious, Knautia arvensis in different grassland plant communities varying in species composition and richness to assess whether nectar quality can be affected by the surrounding plant community. We analyzed (with high performance liquid chromatography) the content of carbohydrates, overall amino acids, and essential amino acids. Amino acid and carbohydrate concentrations and proportions varied among plant individuals and with the surrounding plant community but were not related to the surrounding plant species richness. Total and individual carbohydrate concentrations were lowest, while proportions of the essential amino acids, valine, isoleucine, leucine (all phagostimulatory), and lysine were highest in plant species communities of the highest diversity. Our results show that K. arvensis nectar chemistry varies with the composition of the surrounding plant community, which may alter the taste and nutritional value and thus affect the plant's visitor spectrum and visitation rate. However, the strong inter-individual variation in nectar quality requires additional studies (e.g., in semi-field studies) to disentangle different biotic and abiotic factors contributing to inter-individual nectar chemistry in a plant-community context.},
  language  = {en}
}
@article{JahedKavousiFarashianietal.2020,
  author    = {Jahed, Razieh Rafiei and Kavousi, Mohammad Reza and Farashiani, Mohammad Ebrahim and Sagheb-Talebi, Khosro and Babanezhad, Manoochehr and Courbaud, Benoit and Wirtz, Roland and M{\"u}ller, J{\"o}rg and Larrieu, Laurent},
  title     = {A comparison of the formation rates and composition of tree-related microhabitats in beech-dominated primeval Carpathian and Hyrcanian forests},
  series = {Forests},
  volume    = {11},
  journal   = {Forests},
  number    = {2},
  issn      = {1999-4907},
  doi       = {10.3390/f11020144},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-200849},
  year      = {2020},
  abstract  = {Primeval forests in the temperate zone exist only as a few remnants, but theses serve as important reference areas for conservation. As key habitats, tree-related microhabitats (TreMs) are of intense interest to forest ecologists, but little is known about their natural composition and dynamics in different tree species. Beech forms a major part of the temperate forests that extend from Europe, home to European beech Fagus sylvatica L. (Fs), eastward to Iran, where Oriental beech Fagus orientalis Lipsky (Fo) is the dominant species. In this study, we compared TreMs in primeval forests of both species, using data from Fo growing in 25 inventory plots throughout the Hyrcanian forest belt in Iran and from Fs growing in a 9 ha permanent plot in the Uholka Forest of Ukraine. TreMs based on 47 types and 11 subgroups were recorded. Beech trees in the Hyrcanian forest had a higher mean diameter at breast height (dbh) than beech trees in Uholka and contained twice as many TreMs per hectare. Although the mean richness of TreMs per TreM bearing tree was similar in the two species, on the basis of the comparison single trees in two groups (n = 405 vs. 2251), the composition of the TreMs clearly differed, as the proportions of rot holes, root-buttress concavities, and crown deadwood were higher in the Hyrcanian Forest, and those of bark losses, exposed heartwood, and burrs and cankers higher in Uholka Forest. Estimates of TreMs dynamics based on dbh and using Weibull models showed a significantly faster cumulative increase of TreMs in Fo, in which saturation occurred already in trees with a dbh of 70-80 cm. By contrast, the increase in TreMs in Fs was continuous. In both species, the probability density was highest at a dbh of about 30 cm, but was twice as high in Fo. Because of limitations of our study design, the reason behind observed differences of TreM formation and composition between regions remains unclear, as it could be either result of the tree species or the environment, or their interaction. However, the observed differences were more likely the result of differences in the environment than in the two tree species. Nevertheless, our findings demonstrate that the Hyrcanian Forest, recently designated as a natural heritage site in Iran, is unique, not only as a tertiary relict or due to its endemic trees, herbs and arthropods, but also because of its TreMs, which form a distinct and rich habitat for associated taxa, including endemic saproxylic species.},
  language  = {en}
}
@article{OelschlaegelWeissSadanSalpeteretal.2020,
  author    = {Oelschlaegel, Diana and Weiss Sadan, Tommy and Salpeter, Seth and Krug, Sebastian and Blum, Galia and Schmitz, Werner and Schulze, Almut and Michl, Patrick},
  title     = {Cathepsin inhibition modulates metabolism and polarization of tumor-associated macrophages},
  series = {Cancers},
  volume    = {12},
  journal   = {Cancers},
  number    = {9},
  issn      = {2072-6694},
  doi       = {10.3390/cancers12092579},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-213040},
  year      = {2020},
  abstract  = {Stroma-infiltrating immune cells, such as tumor-associated macrophages (TAM), play an important role in regulating tumor progression and chemoresistance. These effects are mostly conveyed by secreted mediators, among them several cathepsin proteases. In addition, increasing evidence suggests that stroma-infiltrating immune cells are able to induce profound metabolic changes within the tumor microenvironment. In this study, we aimed to characterize the impact of cathepsins in maintaining the TAM phenotype in more detail. For this purpose, we investigated the molecular effects of pharmacological cathepsin inhibition on the viability and polarization of human primary macrophages as well as its metabolic consequences. Pharmacological inhibition of cathepsins B, L, and S using a novel inhibitor, GB111-NH\(_2\), led to changes in cellular recycling processes characterized by an increased expression of autophagy- and lysosome-associated marker genes and reduced adenosine triphosphate (ATP) content. Decreased cathepsin activity in primary macrophages further led to distinct changes in fatty acid metabolites associated with increased expression of key modulators of fatty acid metabolism, such as fatty acid synthase (FASN) and acid ceramidase (ASAH1). The altered fatty acid profile was associated with an increased synthesis of the pro-inflammatory prostaglandin PGE\(_2\), which correlated with the upregulation of numerous NF\(_k\)B-dependent pro-inflammatory mediators, including interleukin-1 (IL-1), interleukin-6 (IL-6), C-C motif chemokine ligand 2 (CCL2), and tumor necrosis factor-alpha (TNFα). Our data indicate a novel link between cathepsin activity and metabolic reprogramming in macrophages, demonstrated by a profound impact on autophagy and fatty acid metabolism, which facilitates a pro-inflammatory micromilieu generally associated with enhanced tumor elimination. These results provide a strong rationale for therapeutic cathepsin inhibition to overcome the tumor-promoting effects of the immune-evasive tumor micromilieu.},
  language  = {en}
}
@article{LeonhardtLihoreauSpaethe2020,
  author    = {Leonhardt, Sara D. and Lihoreau, Mathieu and Spaethe, Johannes},
  title     = {Mechanisms of nutritional resource exploitation by insects},
  series = {Insects},
  volume    = {11},
  journal   = {Insects},
  number    = {9},
  issn      = {2075-4450},
  doi       = {10.3390/insects11090570},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-211161},
  year      = {2020},
  abstract  = {Insects have evolved an extraordinary range of nutritional adaptations to exploit other animals, plants, bacteria, fungi and soils as resources in terrestrial and aquatic environments. This special issue provides some new insights into the mechanisms underlying these adaptations. Contributions comprise lab and field studies investigating the chemical, physiological, cognitive and behavioral mechanisms that enable resource exploitation and nutrient intake regulation in insects. The collection of papers highlights the need for more studies on the comparative sensory ecology, underlying nutritional quality assessment, cue perception and decision making to fully understand how insects adjust resource selection and exploitation in response to environmental heterogeneity and variability.},
  language  = {en}
}
@article{SchmidtDenkWiegering2020,
  author    = {Schmidt, Stefanie and Denk, Sarah and Wiegering, Armin},
  title     = {Targeting protein synthesis in colorectal cancer},
  series = {Cancers},
  volume    = {12},
  journal   = {Cancers},
  number    = {5},
  issn      = {2072-6694},
  doi       = {10.3390/cancers12051298},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-206014},
  year      = {2020},
  abstract  = {Under physiological conditions, protein synthesis controls cell growth and survival and is strictly regulated. Deregulation of protein synthesis is a frequent event in cancer. The majority of mutations found in colorectal cancer (CRC), including alterations in the WNT pathway as well as activation of RAS/MAPK and PI3K/AKT and, subsequently, mTOR signaling, lead to deregulation of the translational machinery. Besides mutations in upstream signaling pathways, deregulation of global protein synthesis occurs through additional mechanisms including altered expression or activity of initiation and elongation factors (e.g., eIF4F, eIF2α/eIF2B, eEF2) as well as upregulation of components involved in ribosome biogenesis and factors that control the adaptation of translation in response to stress (e.g., GCN2). Therefore, influencing mechanisms that control mRNA translation may open a therapeutic window for CRC. Over the last decade, several potential therapeutic strategies targeting these alterations have been investigated and have shown promising results in cell lines, intestinal organoids, and mouse models. Despite these encouraging in vitro results, patients have not clinically benefited from those advances so far. In this review, we outline the mechanisms that lead to deregulated mRNA translation in CRC and highlight recent progress that has been made in developing therapeutic strategies that target these mechanisms for tumor therapy.},
  language  = {en}
}
@article{KannKunzHansenetal.2020,
  author    = {Kann, Simone and Kunz, Meik and Hansen, Jessica and Sievertsen, J{\"u}rgen and Crespo, Jose J. and Loperena, Aristides and Arriens, Sandra and Dandekar, Thomas},
  title     = {Chagas disease: detection of Trypanosoma cruzi by a new, high-specific real time PCR},
  series = {Journal of Clinical Medicine},
  volume    = {9},
  journal   = {Journal of Clinical Medicine},
  number    = {5},
  issn      = {2077-0383},
  doi       = {10.3390/jcm9051517},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-205746},
  year      = {2020},
  abstract  = {Background: Chagas disease (CD) is a major burden in Latin America, expanding also to non-endemic countries. A gold standard to detect the CD causing pathogen Trypanosoma cruzi is currently not available. Existing real time polymerase chain reactions (RT-PCRs) lack sensitivity and/or specificity. We present a new, highly specific RT-PCR for the diagnosis and monitoring of CD. Material and Methods: We analyzed 352 serum samples from Indigenous people living in high endemic CD areas of Colombia using three leading RT-PCRs (k-DNA-, TCZ-, 18S rRNA-PCR), the newly developed one (NDO-PCR), a Rapid Test/enzyme-linked immuno sorbent assay (ELISA), and immunofluorescence. Eighty-seven PCR-products were verified by sequence analysis after plasmid vector preparation. Results: The NDO-PCR showed the highest sensitivity (92.3\%), specificity (100\%), and accuracy (94.3\%) for T. cruzi detection in the 87 sequenced samples. Sensitivities and specificities of the kDNA-PCR were 89.2\%/22.7\%, 20.5\%/100\% for TCZ-PCR, and 1.5\%/100\% for the 18S rRNA-PCR. The kDNA-PCR revealed a 77.3\% false positive rate, mostly due to cross-reactions with T. rangeli (NDO-PCR 0\%). TCZ- and 18S rRNA-PCR showed a false negative rate of 79.5\% and 98.5\% (NDO-PCR 7.7\%), respectively. Conclusions: The NDO-PCR demonstrated the highest specificity, sensitivity, and accuracy compared to leading PCRs. Together with serologic tests, it can be considered as a reliable tool for CD detection and can improve CD management significantly.},
  language  = {en}
}
@article{GrundMuellerRuedenauerSpaetheetal.2020,
  author    = {Grund-Mueller, Nils and Ruedenauer, Fabian A. and Spaethe, Johannes and Leonhardt, Sara D.},
  title     = {Adding amino acids to a sucrose diet is not sufficient to support longevity of adult bumble bees},
  series = {Insects},
  volume    = {11},
  journal   = {Insects},
  number    = {4},
  issn      = {2075-4450},
  doi       = {10.3390/insects11040247},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-203866},
  year      = {2020},
  abstract  = {Dietary macro-nutrients (i.e., carbohydrates, protein, and fat) are important for bee larval development and, thus, colony health and fitness. To which extent different diets (varying in macro-nutrient composition) affect adult bees and whether they can thrive on nectar as the sole amino acid source has, however, been little investigated. We investigated how diets varying in protein concentration and overall nutrient composition affected consumption, longevity, and breeding behavior of the buff-tailed bumble bee, Bombus terrestris (Hymenoptera: Apidae). Queenless micro-colonies were fed either natural nutrient sources (pollen), nearly pure protein (i.e., the milk protein casein), or sucrose solutions with low and with high essential amino acid content in concentrations as can be found in nectar. We observed micro-colonies for 110 days. We found that longevity was highest for pure pollen and lowest for pure sucrose solution and sucrose solution supplemented with amino acids in concentrations as found in the nectar of several plant species. Adding higher concentrations of amino acids to sucrose solution did only slightly increase longevity compared to sucrose alone. Consequently, sucrose solution with the applied concentrations and proportions of amino acids or other protein sources (e.g., casein) alone did not meet the nutritional needs of healthy adult bumble bees. In fact, longevity was highest and reproduction only successful in micro-colonies fed pollen. These results indicate that, in addition to carbohydrates and protein, adult bumble bees, like larvae, need further nutrients (e.g., lipids and micro-nutrients) for their well-being. An appropriate nutritional composition seemed to be best provided by floral pollen, suggesting that pollen is an essential dietary component not only for larvae but also for adult bees.},
  language  = {en}
}